1503

Algorithms in
PEDIATRICS
Algorithms in
PEDIATRICS
Editors
Anand S Vasudev DNB D Ped DCP MNAMS MICP (USA) FIAP FIMSA
Senior Consultant, Pediatric Nephrologist
Indraprastha Apollo and Max Hospital
New Delhi, India
Nitin K Shah MD DCH DNB

Professor and Consultant Pediatrician
PD Hinduja National Hospital and
Medical Research Centre
Honorary Hematoncologist
BJ Wadia Hospital for Children
Lions Hospital
Mumbai, Maharashtra, India
Foreword
Pramod Jog
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Algorithms in Pediatrics / Anand S Vasudev, Nitin K Shah
First Edition: 2017

ISBN: 978-93-5152-160-0
Contributors
EDITORS
Anand S Vasudev DNB D Ped DCP MNAMS MICP (USA) FIAP FIMSA Nitin K Shah MD DCH DNB
Senior Consultant, Pediatric Nephrologist Professor and Consultant Pediatrician
Indraprastha Apollo and Max Hospital PD Hinduja National Hospital and Medical Research Centre
New Delhi, India Honorary Hematoncologist
BJ Wadia Hospital for Children
Lions Hospital
SECTION EDITORS
Piyali Bhattacharya DCH MD FCCM Pankaj V Deshpande MRCP MD DCH FCPS PICU Mediclinic City Hospital
PGDMLS Consultant Dubai, UAE
Specialist Department of Nephrology
Sanjay Gandhi Post Graduate Institute of PD Hinduja National Hospital and Vikas Kohli MD FAAP FACC
Medical Sciences Medical Research Centre Fetal, Neonatal, Pediatric Cardiologist
Lucknow, Uttar Pradesh, India Mumbai, Maharashtra, India Director
Delhi Child Heart Center
Amar J Chitkara MD DNB Anaita Udwadia Hegde MD MRCPCH New Delhi, India
Head Consultant
Department of Pediatrics Department of Pediatric Neurology Anurag Krishna MCh FAMS
Max Superspeciality Hospital Jaslok Hospital and Research Center Director
New Delhi, India Breach Candy Hospital Trust Department of Pediatrics and
Bai Jerbai Wadia Hospital for Children Pediatric Surgery
Rajesh R Chokhani MD DCH FRCPCH Mumbai, Maharashtra, India Max Institute of Pediatrics,
Consultant Max Healthcare
Mumbai, Maharashtra, India Vaman V Khadilkar MD DNB MRCP DCH New Delhi, India
Pediatric Endocrinologist
Jaydeep Choudhury DNB MNAMS Jehangir Hospital Shyam Kukreja
Associate Professor Pune, Maharashtra, India Head
Department of Pediatrics Bombay Hospital Department of Pediatrics
Institute of Child Health Mumbai, Maharashtra, India Max Superspeciality Hospital
Kolkata, West Bengal, India New Delhi, India
Praveen Khilnani MD FICCM FSICCM
Neelu A Desai MD DNB FAAP FCCM Anjali Kulkarni MD FRCPCH
Consultant Director Head
Department of Pediatric Neurology Pediatric Critical Care Services and Department of Pediatrics and
PD Hinduja National Hospital and Fellowship Program Neonatology
Medical Research Centre BLK Superspeciality Hospital Sir HN Reliance Foundation Hospital
Mumbai, Maharashtra, India New Delhi, India Mumbai, Maharashtra, India
Algorithms in Pediatrics
Ashish Mehta MD DCH Usha Pratap MD MRCP Varinder Singh MD FRCPCH

Consultant and Director Senior Consultant Director Professor
Arpan Newborn Care Centre Pvt Ltd Department of Pediatric Cardiology Department of Pediatrics
Ahmedabad, Gujarat, India Deenanath Mangeshkar Hospital Lady Hardinge Medical College and
Pune, Maharashtra, India Kalawati Saran Children’s Hospital
Rujuta Mehta MS DNB New Delhi, India
Consultant Girish Raheja MS
Balabhai Nanavati Hospital Senior Consultant and Academic Tanu Singhal MD MSc
Jaslok Hospital and Research Centre Coordinator Consultant, Department of Pediatrics
Shushrusha Hospital Indraprastha Apollo Hospital Kokilaben Dhirubhai Ambani Hospital
Head New Delhi, India Mumbai, Maharashtra, India
Department of Pediatric Orthopedics
ATK Rau MD DHA Soonu Udani MD
Bai Jerbai Wadia Hospital for Children
Professor and Incharge Pediatric Intensivist
Department of Pediatrics Section Head Pediatrics
Vibhu Mendiratta MD MS Ramaiah Medical College PD Hinduja National Hospital and
Consultant and Professor Bangalore, Karnataka, India Medical Research Centre
Department of Dermatology and STD
GR Sethi MD
Lady Hardinge Medical College and
Formerly Head Vrajesh Udani MD
Associated Hospitals
Department of Pediatrics Consultant
New Delhi, India
Maulana Azad Medical College Department of Pediatric Neurology
Taral V Nagda MS DNB DOrth New Delhi, India PD Hinduja National Hospital and
Medical Research Centre
Consultant Rasik S Shah MCh Mumbai, Maharashtra, India
Department of Pediatric Orthopedics Section Incharge
PD Hinduja National Hospital and Department of Pediatric Surgery Shashi Vashisht MS
Medical Research Centre, Saifee PD Hinduja National Hospital and Professor and Head
Hospital, Jupiter Hospital Medical Research Centre Department of Ophthalmology
Mumbai, Maharashtra, India Mumbai, Maharashtra, India Dr Ram Manohar Lohia Hospital
New Delhi, India
MKC Nair Anand K Shandilya MD DCH FRCPCH
Professor and Vice Chancellor Consultant Anju Virmani MD DNB
Kerala University of Health Sciences and Department of Pediatrics Senior Consultant, Apollo, Max,
Founder Director Dr Anand’s Hospital For Children Pentamed and Sundar Lal Jain Hospital
Child Development Centre Mumbai, Maharashtra, India New Delhi, India
Thrissur, Kerala, India
Anupam Sibal MD FIMSA FIAP FRCP FRCP Surender K Yachha MD DM
Priyankar Pal MD Senior Consultant Professor and Head
Associate Professor and Head Department of Pediatric Department of Pediatric Gastroenterology
Department of Pediatrics Gastroenterology and Hepatology Sanjay Gandhi Postgraduate Institute of
Institute of Child Health Indraprastha Apollo Hospitals Medical Sciences
Kolkata, West Bengal, India New Delhi, India Lucknow, Uttar Pradesh, India
vi
Contributors
CONTRIBUTING AUTHORS
Kochurani Abraham DCH Satish K Aggarwal MS MCh Vibha S Bafna MD DCH
Senior Registrar Senior Consultant Senior Consultant
Department of Pediatrics Department of Pediatric Surgery Department of Pediatrics
Jehangir Hospital Sir Ganga Ram Hospital Jehangir Hospital
Pune, Maharashtra, India New Delhi, India Pune, Maharashtra, India
Mohan K Abraham MS MCh Atul Ahuja MS Arvind S Bais MS FIMSA

Professor and Head Senior Consultant Senior Consultant
Department of Pediatric Surgery Department of ENT and Department of ENT
Amrita Institute of Medical Sciences Head and Neck Surgery Indian Spinal Injury Hospital
Kochi, Kerala, India Indraprastha Apollo Hospital New Delhi, India
New Delhi, India
Bharat Agarwal MD DCh Naveen Bajaj DM MD
Head Ira E Almeida DCH MD DNB PG-DAP Consultant, Department of Neonatology
Department of Hemato-Oncology Senior Pediatrician Deep Hospital
BJ Wadia Children Hospital Department of Pediatrics Ludhiana, Punjab, India
Mumbai, Maharashtra, India Hospicio Hospital
Margao, Goa, India Anurag Bajpai MD FRACP
Gautam S Agarwal MCh Consultant, Department of Pediatric and
Principal Consultant Parmanand GK Andankar DCH DNB Adolescent Endocrinology
Department of Pediatric Surgeon Pediatric Intensivist Regency Hospital Limited
Max Super Speciality Hospital Wadia Children Hospital Kanpur, Uttar Pradesh, India
New Delhi, India Consultant Pediatric and Neonatal
Intensivist Minu Bajpai MS MCh PhD FRCS
Manjari Agarwal MD Jupiter and Bethany Hospital Professor
Attending Consultant Thane, Maharashtra, India Department of Pediatric Surgery
Department of Pediatric Rheumatology All India Institute of Medical Sciences
Institute of Child Health Alaric J Aroojis MS DNB FCPS New Delhi, India
Sir Ganga Ram Hospital Consultant
New Delhi, India Department of Pediatric Orthopedics Chandra S Bal
Kokilaben Dhirubhai Ambani Hospital Professor
Mridul Agarwal MD FNB and Bai Jerbai Wadia Hospital for Department of Nuclear Medicine
Consultant Children All India Institute of Medical Sciences
Department of Pediatric Cardiac Mumbai, Maharashtra, India New Delhi, India
Sciences, Sir Ganga Ram Hospital
New Delhi, India Priyanka Arora MS Padma Balaji MD
Assistant Professor Junior Consultant
Mandar Agashe MS Department of Ophthalmology Kanchi Kamakoti Childs Trust and
Consultant, Centre for Pediatric Dayanand Medical College and Childs Trust Medical Foundation
Orthopedic Care, Dr Agashe’s Hospital Hospital Chennai, Tamil Nadu, India
Mumbai, Maharashtra, India Ludhiana, Punjab, India
Suma Balan MD MRCP CH CCST
Anju Aggarwal MD FIAP Shreedhara Avabratha K MD DNB Consultant
Associate Professor Professor Department of Pediatrics
Department of Pediatrics Department of Pediatrics Amrita Institute of Medical Sciences
University College of Medical Sciences Father Muller Medical College Kochi, Kerala, India
and Guru Tegh Bahadur Hospital Mangalore, Karnataka, India
New Delhi, India Indira Banerjee MD DNB MRCPCH
Sanjay M Bafna MD Trainee, Department of Pediatric
Neeraj Aggarwal MD FNH Senior Consultant and Head Cardiology, Rabindranath Tagore
Consultant, Department of Pediatric Department of Pediatrics International Institute of Cardiac
Cardiac Sciences, Sir Ganga Ram Hospital Jehangir Hospital Sciences vii
New Delhi, India Pune, Maharashtra, India Kolkata, West Bengal, India
Sushmita Banerjee DCH MSc MRCPI Jasodhara Chaudhuri MD MRCPCH Arjun A Dhawale MS DNB MRCSEd
FRCPCH RMO-cum-Clinical Tutor Surgeon, Department of Orthopedics
Consultant Department of Pediatric Medicine and Spine Surgery
Department of Pediatric Nephrology Medical College Sir HN Reliance Foundation Hospital and
Calcutta Medical Research Institute Kolkata, West Bengal, India BJ Wadia Hospital For Children
Kolkata, West Bengal, India Mumbai, Maharashtra, India
Hitesh B Chauhan MS
Rahul P Bhamkar DNB DCH MNAMS Pediatric Orthopedic Surgeon Dhulika Dhingra MD
Department of Pediatric Orthopedic Assistant Professor
Associate Consultant
Rainbow Superspeciality Hospital and Department of Pediatrics
Department of Pediatrics
Children’s Orthopedic Centre Chacha Nehru Bal Chikitsalaya
Sir HN Reliance Foundation Hospital
Ahmedabad, Gujarat, India New Delhi, India
Deepak Chawla MD DM Vinod Gunasekaran MD FIAP
Vidyut Bhatia MD Clinical Assistant, Institute of Child Health
Associate Professor
Consultant Department of Pediatrics Sir Ganga Ram hospital
Department of Pediatric Government Medical College Hospital New Delhi, India
Gastroenterology and Hepatology Chandigarh, India
Indraprastha Apollo Hospitals Vikram Gagneja DNB FNB FCCM
New Delhi, India Harshika Chawla MBBS Consultant Pediatrician and Intensivist
Gagneja Speciality Clinic
Postgraduate Resident
Veereshwar Bhatnagar MS MCh Department of Ophthalmology
New Delhi, India
Professor Postgraduate Institute of Medical Suma Ganesh MS DNBE
Department of Pediatric Surgery Education and Research and
Consultant and Head
All India Institute of Medical Sciences Dr Ram Manohar Lohia Hospital
Department of Pediatric Ophthalmology
New Delhi, India New Delhi, India
and Strabismus
Dr Shroff’s Charity Eye Hospital
Sagar Bhattad MD Dinesh K Chirla MD DM MRCPCH
New Delhi, India
Senior Resident Consultant
Department of Pediatrics Department of Neonatology Niti Gaur MD
Postgraduate Institute of Rainbow Children’s Hospital Senior Resident
Medical Education and Research Hyderabad, Telangana, India Department of Dermatology
Chandigarh, India Lady Hardinge Medical College and
Sushma P Desai DCH MD PGDAP Associated Hospitals
Reeta Bora MD DM Counseller New Delhi, India
Associate Professor and Incharge of Gopi Children and Orthopedic Hospital
Neonatal Unit and Adolescent Speciality Clinic Paula Goel MD PGDAP PGDMLS
Department of Pediatrics Surat, Gujarat, India Consultant and Director
Assam Medical College Fayth Clinic
Dibrugarh, Assam, India Vaishali R Deshmukh DCH DNB Mumbai, Maharashtra, India
PGD-AP
Consultant and In-Charge Anju Gupta MD
Sudha R Chandrashekhar MD ESPE
Nine-to-Nineteen Clinic Associate Professor
Professor Deenanath Mangeshkar Hospital and Department of Pediatrics
Department of Pediatrics Research Center Postgraduate Institute of Medical
Bai Jerbai Wadia Hospital for Children Pune, Maharashtra, India Education and Research
and Seth GS Medical College Chandigarh, India
Mumbai, Maharashtra, India Taru Dewan MS FRCSEd
Associate Professor Sailesh G Gupta MD DCH
Anirban Chatterjee MS DNB MNAMS Department of Ophthalmology Consultant
Senior Consultant Postgraduate Institute of Medical Department of Pediatrics and
Department of Orthopedics Education and Research and Neonatology, Ashna Childrens Hospital
Medica Superspecialty Hospital Dr Ram Manohar Lohia Hospital and Arushee Childcare Hospital
viii Kolkata, West Bengal, India New Delhi, India Mumbai, Maharashtra, India
Contributors
Shalu Gupta MD Aspi J Irani MD DCH Nachiket M Joshi MBBS

Professor, Department of Pediatrics Pediatrician, Department of Pediatrics Resident
Lady Hardinge Medical College and Nanavati Super Speciality Hospital Department of General Surgery
Kalawati Saran Children’s Hospital Mumbai, Maharashtra, India PD Hinduja National Hospital and
New Delhi, India Medical Research Centre
Nurul Islam MD DNB Mumbai, Maharashtra, India
Supriya Phanse Gupte MD PDCC Consultant, Pediatric Cardiology
Leeds Royal Infirmary Mission Hospital Nandkishor S Kabra DM MD DNB MSc
United Kingdom Durgapur, West Bengal, India Director, Department of Neonatology
Surya Mother and Child Care
Omkar P Hajirnis MD DNB MRCPCH Barath Jagadisan MD PDCC Mumbai, Maharashtra, India
Pediatric Neurologist Associate Professor
Department of Pediatric Neurology Department of Pediatrics Veena Kalra
Bhaktivedanta Hospital and Research Jawaharlal Institute of Postgraduate Consultant
Centre, Dr LH Hiranandani Hospital Medical Education and Research Department of Pediatric Neurology
Rajiv Gandhi Medical College and Pondicherry, India All India Institute of Medical Sciences
CSM Hospital New Delhi, India
Mumbai, Maharashtra, India Ashish Jain MD DNB DM
Assistant Professor Akshay Kapoor MD
Manisha Halkar MD DNB Department of Neonatology Consultant
Consultant, Department of Neonatology Maulana Azad Medical College Department of Pediatric
Meenakshi Hospitals New Delhi, India Gastroenterology and Hepatology
Bangalore, Karnataka, India Indraprastha Apollo Hospitals
Naveen Jain DM New Delhi, India
Aru C Handa Coordinator, Department of Neonatology
Senior Consultant Kerala Institute of Medical Sciences Gauri Kapoor MD PhD
Department of ENT and Head Neck Trivandrum, Kerala, India Director
Surgery Medanta Medicity Department of Pediatric Hematology
Shikha Jain MS
Gurgaon, Haryana, India Oncology
Medical Officer
Rajiv Gandhi Cancer Institute and
Kumud K Handa MS DNB MNAMS Department of Ophthalmology
Research Centre
Dr Ram Manohar Lohia Hospital
Director and Head New Delhi, India
New Delhi, India
Department of ENT and Head Neck
Surgery Dasmit S Khokar MS MCh FIAPS
Manisha Jana
Medanta Medicity Professor
Assistant Professor
Gurgaon, Haryana, India Department of Pediatric Surgery
Department of Radiodiagnosis
BJ Medical College and
Rashna D Hazarika MD All India Institute of Medical Sciences
Sassoon General Hospitals
New Delhi, India
Senior Consultant and Chief Pune, Maharashtra, India
Department of Pediatrics, Pediatric and Kana R Jat MD FCCP MNAMS
Neonatal Intensive Care Assistant Professor
Vinayan KP MD DCH DNB DM
Midland Hospital and Rigpa Children’s Department of Pediatrics Professor and Head
Clinic All India Institute of Medical Sciences Department of Neurology
Guwahati, Assam, India New Delhi, India Amrita Institute of Medical Sciences
Kochi, Kerala, India
Ira J Holla MBBS Nameet Jerath MD
Junior Resident Senior Consultant, Department of Venkatadass Krishnamoorthy MS DNB
Department of Pediatrics Pediatric Critical Care and Pulmonology, Consultant, Department of Orthopedics
Lok Nayak Jai Prakash Narayan Hospital Indraprastha Apollo Hospital Ganga Hospital
New Delhi, India New Delhi, India Coimbatore, Tamil Nadu, India
Ram G Holla MD DM Ganesh S Jevalikar MD DNB PDCC Rakesh Kumar

Senior Consultant Consultant, Department of Professor
Department of Neonatology and Endocrinology and Diabetes Department of Nuclear Medicine
ix
Pediatrics, Adiva Hospitals Medanta The Medicity All India Institute of Medical Sciences
New Delhi, India Gurgaon, Haryana, India New Delhi, India
Rashmi Kumar John Matthai DCH MD FAB FIAP Uday Monga MS FAGE
Professor and Head Professor and Head Senior Resident
Department of Pediatrics Department of Pediatrics Department of Otorhinolaryngology
King George Hospital PSG Institute of Medical Sciences and Head Neck Surgery
Lucknow, Uttar Pradesh, India Coimbatore, Tamil Nadu, India Uday ENT Hospital
New Delhi, India
Sathish Kumar MD DCH Puthezhath SN Menon MD MNAMS
Professor and Consultant FIAP FIMSA Sangeeta S Mudaliar DNB MRCPCH
Department of Pediatrics Consultant and Head Consultant
Christian Medical College Department of Pediatrics Department of Hemato-Oncology
Vellore, Tamil Nadu, India Jaber Al-Ahmed Armed Forces Hospital B J Wadia Children Hospital
Kuwait, Kuwait Mumbai, Maharashtra, India
Ritabrata Kundu MD FIAP
Professor, Department of Pediatrics Bhavesh M Mithiya MD Surpreet BS Nagi DCH
Dip (Pediatrics)
Institute of Child Health Consultant
Kolkata, West Bengal, India Consultant Department of Pediatrics
Department of Pediatrics Dr Anands Hospital for Children
PA M Kunju MD DM Jupiter Hospital Mumbai, Maharashtra, India
Professor and Head Kotagiri Medical Fellowship Hospital
Department of Pediatric Neurology Thane, Maharashtra, India Premal Naik MS DNB
Government Medical College Hon. Orthopedic Surgeon
Trivandrum, Kerala, India Aparajita Mitra MCh NHL Municipal Medical College
Senior Resident Director, Rainbow Superspeciality
Lokesh Lingappa MD DM MRCPCH Department of Pediatric Surgery Hospital
Consultant, Department of Pediatric All India Institute of Medical Sciences Ahmedabad, Gujarat, India
Neurology, Rainbow Children’s Hospital New Delhi, India
Hyderabad, Telangana, India Ruchi Nanawati MD
Monjori Mitra DCH DNB FIAP Professor and Head, Department iof
Gaurav Mandhan MD FIAP Associate Professor Neonatology, Seth GS Medical College
Associate Consultant Department of Pediatrics Medicine and KEM Hospital
Department of Neonatology Institute of Child Health Mumbai, Maharashtra, India
Max Super Specialty Hospital Kolkata, West Bengal, India
New Delhi, India Narendra R Nanivadekar MD DCH DNB
Rakesh Mondal MD DNB PDSR MNAMS Consultant, Department of Pediatrics
Mamta V Manglani MD DCH MRCPCHI
Aster Aadhar Hospital
Professor and Head Professor Kolhapur, Maharashtra, India
Department of Pediatrics Department of Pediatric Medicine
Lokmanya Tilak Municipal Medical Medical College Kolkata Nikita MD DNB
College and General Hospital Kolkata, West Bengal, India Senior Resident
Mumbai, Maharashtra, India Department of Dermatology and STD
Jayashree A Mondkar MD DCH Lady Hardinge Medical College and
Mukta Mantan MD DNB Professor and Head Associated Hospitals
Professor, Department of Pediatrics Department of Neonatology New Delhi, India
Maulana Azad Medical College Lokmanya Tilak Municipal General
New Delhi, India Hospital and Lokmanya Tilak Somashekhar M Nimbalkar MD
Municipal Medical College Professor
Manoj G Matnani MD PGDVES PGDMDPN Mumbai, Maharashtra, India Department of Pediatrics
PGDVIH PGDCH Pramukhswami Medical College
Consultant Anil K Monga MS DORL FCPS Karamsad, Gujarat, India
Department of Pediatric Nephrology Senior Consultant
KEM Hospital, Jehangir Hospital Department of Otorhinolaryngology Raghupathy Palany BSc MD DCH FRCP
Pune, Maharashtra, India and Head Neck Surgery Professor
Bombay Hospital Sir Ganga Ram Hospital Indira Gandhi Institute of Child Health
Mumbai, Maharashtra, India New Delhi, India Bangalore, Karnataka, India
x
Contributors
Nitin Pant MS MCh Baldev S Prajapati MD DPed FIAP Arun G Roy MD DM

Assistant Professor FICMCH MNAMS Professor
Department of Pediatric Surgery Professor Department of Neurology
Kalawati Saran Children’s Hospital Department of Pediatrics Amrita Institute of Medical Sciences
Lady Hardinge Medical College GCS Medical College, Hospital and Kochi, Kerala, India
New Delhi, India Research Centre
Ahmedabad, Gujarat, India Tapas K Sabui MD
Ankit Parakh MD DNB MNAMS Professor
Consultant Rajal B Prajapati MD DPed Department of Pediatric Medicine
Department of Pediatric Pulmonology Professor RG Kar Medical College
Dr BL Kapur Memorial Hospital Department of Pediatrics Kolkata, West Bengal, India
New Delhi, India Sheth V S General Hospital and
AMC MET Medical College Anupam Sachdeva MD DCH
Ketan P Parikh MS MCh Ahmedabad, Gujarat, India Chariman, Institute of Child Health
Consultant Pediatric Surgeon Sir Ganga Ram Hospital
Department of Pediatric Surgery Prema Raghunathan DNB PGDAP
New Delhi, India
Jaslok Hospital Professor
Mumbai, Maharashtra, India Department of Pediatrics Abhijeet Saha MD IMS BHU
Rajarajeswari Medical College Associate Professor
Mandar B Patil DCH DNB Bangalore, Karnataka, India Department of Pediatrics
Assistant Professor Post Graduate Institute of Medical
Dr DY Patil Medical College Sarbani S Raha MD
Education and Research
Kolhapur, Maharashtra, India Consultant
Dr Ram Manohar Lohia Hospital
Child Neurology and
Sandeep A Patwardhan MS Orth D Orth New Delhi, India
Epilepsy Clinic
Professor Vadodara, Gujarat, India Bhaskar Saikia MD
Department of Pediatric Orthopedics
Devinder Rai MS Consultant
Sancheti Institute
Max Superspeciality Hospital
Pune, Maharashtra, India Vice Chairman
New Delhi, India
Department of ENT
Sarah Paul DCH MD Sir Ganga Ram Hospital VK Sairam AB (Ped) AB (Ped. Neph)
Professor New Delhi, India
Pediatric Nephrologist
Department of Pediatrics
Anand P Rao MD DNB Kanchi Kamacoti Childs
PSG Institute of Medical Sciences
Consultant Trust Hospital
Coimbatore, Tamil Nadu, India
Department of Pediatric Chennai, Tamil Nadu, India
Ranjan K Pejaver FRCP FRCPCH FIAP FNNF Rheumatology
Professor, Department of Neonatology Manipal Hospital
Dilip Samal
Kempegowda Institute of Medical Bengaluru, Karnataka, India Senior Resident, Department of ENT and
Sciences Head Neck Surgery Medanta Medicity
Chief Neonatologist, Meenakshi Narendra Rathi MD DNB MNAMS FIAP Gurgaon, Haryana, India
Hospitals Consultant, Department of Pediatrics
Bangalore, Karnataka, India Smile Institute of Child Health Jayanth S Sampath MSc FRCSEd
Akola, Maharashtra, India Consultant and Director
Preetham K Poddutoor Dch DNB Bangalore Institute of Movement
Consultant, Department of Intensive Aarathi R Rau MD Research and Analysis
Care, Rainbow Children’s Hospital Professor, Department of Pathology Bangalore, Karnataka, India
Hyderabad, Telangana, India MS Ramaiah Medical College
Bangalore, Karnataka, India Viraj V Sanghi MD DNB
Suhas V Prabhu MD DCH MNAMS Consultant, Department of Neurology
Visiting Consultant Suyodhan A Reddy MCh DNB Bombay Hospital and
Department of Pediatrics Associate Professor Medical Research Centre
PD Hinduja Hospital and Medical Department of Pediatric Surgery Saifee Hospital
Research Centre BJ Wadia Hospital for Children Ika Children’s Centre
Mumbai, Maharashtra, India Mumbai, Maharashtra, India Mumbai, Maharashtra,India xi
Sarita Sanke MD Ira Shah MD DCH FCPS DNB DPID Sirisharani Siddaiahgari MD DNB
Postgraduate Associate Professor MRCPCH
Department of Dermatology and STD Bai Jerbai Wadia Hospital for Children Consultant, Department of Pediatric
Lady Hardinge Medical College Consultant, Department of Pediatric Hematology Oncology
New Delhi, India Infectious Diseases and Pediatric Rainbow Children’s Hospital
Hepatology, Nanavati Hospital Hyderabad, Telangana, India
Naveen Sankhyan Mumbai, Maharashtra, India
Assistant Professor Aashim Singh MBBS
Department of Pediatric Neurology Mehul A Shah MD DCH MD DABPN Junior Resident
Postgraduate Institute of Medical Consultant, Department of Pediatric Department of Dermatology
Education and Research Nephrology, Apollo Health City Lady Hardinge Medical College and
Chandigarh, India Hyderabad, Telangana, India Associated Hospitals
New Delhi, India
Vijaya Sarathi MD DM Raju C Shah MD DPed FIAP
Assistant Professor Professor, Department of Pediatrics Manav D Singh MS
Department of Endocrinology Ankur Institute of Child Health Associate Professor
Vydehi Institute of Medical Sciences and Ahmedabad, Gujarat, India Department of Ophthalmology
Research Center Postgraduate Institute of Medical
Bengaluru, Karnataka, India Jyoti Sharma MD DNB Education and Research and Dr Ram
Consultant Manohar Lohia Hospital
Moinak S Sarma MD DM Department of Pediatric Nephrology New Delhi, India
Senior Research Associate King Edward Memorial Hospital
Department of Pediatric Pune, Maharashtra, India Preeti Singh MD
Gastroenterology Assistant Professor
Sanjay Gandhi Postgraduate Institute of Pradeep K Sharma MD Department of Pediatrics
Medical Sciences Consultant Lady Hardinge Medical College and
Lucknow, Uttar Pradesh, India Sri Balaji Action Medical Institute associated Hospitals
New Delhi, India New Delhi, India
Kiran P Sathe DCH DNB
Associate Consultant, Department of Sangeetha Shenoy MD Noopur Singhal MD
Pediatrics and Pediatric Nephrology Associate Professor Senior Resident
Sir HN Reliance Foundation Hospital Department of Pediatrics Department of Pediatrics
Mumbai, Maharashtra, India MS Ramaiah Medical College Post Graduate Institute of Medical
Bangalore, Karnataka, India Education and Research
Veeraraja B Sathenahalli MD Dr Ram Manohar Lohia Hospital
Assistant Professor Viraj Shingade MS DNB New Delhi, India
Department of Pediatrics, Jagadguru Director
Jayadeva Murugarajendra Medical Children Orthopedic Care Institute Pratibha D Singhi MD
College Pravira Hospital Professor, Department of Pediatrics
Davanagere, Karnataka, India Nagpur, Maharashtra, India Post Graduate Institute of Medical
Education and Research
Malathi Sathiyasekaran MD DCH Roli M Srivastava DCH PGDAP Chandigarh, India
MNAMS DM Research Officer
Consultant Department of Obstetrics and Anshu Srivastava MD DM
Department of Gastroenterology Gynecology Additional Professor
Kanchi Kamakoti CHILDS Trust Hospital Ganesh Shankar Vidyarthi Memorial Department of Pediatric
and Sundaram Medical Foundation Medical College Gastroenterology
Chennai, Tamil Nadu, India Kanpur, Uttar Pradesh, India Sanjay Gandhi Postgraduate Institute of
Medical Sciences
Tulika Seth MD ABP Poonam Sidana MD Lucknow, Uttar Pradesh, India
Additional Professor Senior Consultant
Department of Hematology Department of Pediatrics Anurag M Srivastava MS
All India Institute of Medical Sciences Max Super Specialty Hospital Consultant, Rockland Hospital
New Delhi, India New Delhi, India New Delhi, India
xii
Contributors
Nidhi Sugandhi MS MCh Soumya Tiwari MD M Vijayakumar MD DCH DM FIAP

Assistant Professor Assistant Professor Consultant
Department of Pediatric Surgery Department of Pediatrics Department of Pediatric Nephrology
Dr Ram Manohar Lohia Hospital and Kalawati Saran Children’s hospital Mehta Children’s Hospital
Post Graduate Institute of Medical Lady Hardinge Medical College Chennai, Tamil Nadu, India
Education and Research New Delhi, India
New Delhi, India Vijay Viswanathan DNB DCH
Alpana A Utture Dch MD DM Consultant, Sandhi Children’s Clinic
Balasubramanian Sundaram MD DCH Associate Professor Jupiter Hospital
MAMS FIAP FRCPCH MGM Hospital
Department of Neonatology
Senior Consultant, Department of Dr Yewale’s Multispecialty Centre
Seth Gordhandas Sunderdas Medical
Pediatrics, Kanchi Kamakoti Childs Trust Mumbai, Maharashtra, India
College and King Edward Memorial
Hospital and The Child’s Trust Medical
Hospital
Research Foundation V Viswanathan DCH MRCP PhD
Chennai, Tamil Nadu, India Mumbai, Maharashtra, India
Senior Consultant
Jayakumar Vaikundam MD DCH DM Department of Pediatric Neurology
Deepti Suri MD DNB Kanchi Kamakoti Childs Trust Hospital
Associate Professor Senior Consultant and Chairman
Apollo Children’s Hospital
Department of Pediatrics JK Institute of Neurology
Chennai, Tamil Nadu, India
Postgraduate Institute of Medical Madurai, Tamil Nadu, India
Education and Research Sanjay Wazir DM
Chandigarh, India
Kiran SK Vaswani MD DCH PGD-AP Dip
Director - NICU, Department of Pediatrics
counselling
Cloudnine Hospital
Rhishikesh P Thakre DM MD DNB DCH Consultant Gurgaon, Haryana, India
FCPS PULSE Child Care Clinic
Professor Mumbai, Maharashtra, India Pravesh Yadav MD
Department of Pediatrics Senior Resident
MGM College and Hospital Anoop K Verma MD FIAP FIAMS Department of Dermatology and STD
Director, Neonatology Division Pediatrician Lady Hardinge Medical College and
Neo Clinic and Hospital Swapnil Nursing Home Associated Hospitals
Aurangabad, Maharashtra, India Raipur, Chhattisgarh, India New Delhi, India
S Thangavelu MD DCH DNB MRCP Madhava Vijayakumar MD DCH DNB M Zulfikar Ahamed MD DM
Senior Consultant and Director Additional Professor Professor and Head
Department of Pediatrics Department of Pediatrics Department of Pediatric Cardiology
Mehta Children’s Hospitals Government Medical College Government Medical College
Chennai, Tamil Nadu, India Kozhikode, Kerala, India Thiruvananthapuram, Kerala, India
xiii
Foreword
Pramod Jog MD DNB FIAP

Professor of Pediatrics
DY Patil Medical College
President, Indian Academy of Pediatrics (IAP), 2016
Member, Standing Committee, International Pediatric Association (IPA)
Pune, Maharashtra, India
Publication of any book is a process as laborious as the process of delivering a baby. Maturity (contents and the quality),
weight gain (number of pages), and intact survival (final copy) all have to be carefully looked after. More so for a book with
156 chapters running in 19 sections with every chapter having at least one algorithm!
Algorithms in Pediatrics have gone through all these laborious processes and have come out as an exclusive book
for pediatricians, giving instant guidelines for treatment, bringing uniformity in management, and training minds for
protocolized thinking. With each protocol, the book provides concise, precise, and up-to-date information which shall help
standardize care in pediatric practice.
When a practitioner is confronted with a clinical problem, he can rarely turn to a textbook for help. What he needs at
that time is not a recounting of a long list of differential diagnosis, but practical guidelines as to how to arrive at a particular
diagnosis and how to proceed further.
This book on algorithms intends to enable the pediatrician to recognize many disorders in a simplified manner and give
practical suggestions in their management, a learning experience in a structured manner.
To put it in the words of Henry David Thoreau, “Our lives are frittered away by detail; simplify, simplify”.
Practicing pediatricians are often faced with clinical problems for which they have been rather inadequately trained
during their medical curriculum. Textbooks published from the medically advanced countries do not focus enough
attention on the prevailing problems and circumstances in the developing countries such as India. The algorithms in this
book have been formed keeping in mind the situations prevailing in India, especially the constraints under which the
clinicians here have to practice. The main emphasis has been to provide clear-cut guidelines as to how to make a diagnosis
on clinical grounds with minimal investigations and to choose the most rational therapy.
Although, prepared specifically to meet the needs of practicing doctors or those who intend to practice in near future,
even pediatric residents would find the book extremely useful while preparing for their viva voce at the diploma or MD
exams. The book covers most of those aspects which are practically never taught in the curriculum but are nevertheless
expected to be known by pediatric postgraduates. It will also assist the students, house officers, and clinicians in the
evaluation of common pediatric signs and symptoms in clinical practice.
With the help of history, focused examination, and minimum investigations, pediatricians in office practice can reach a
working diagnosis and lay down immediate priorities in management.
There is rarely a single acceptable approach to any given problem, and not all diagnoses can fit neatly into an algorithm.
Even though the protocols cannot be considered all-inclusive, the goal is to facilitate a logical and efficient stepwise
approach to reasonable differential diagnoses for the common clinical problems. The algorithmic format provides a rapid
and concise stepwise approach to a diagnosis. Moreover, it would train the brain to approach a problem.
The explosion of knowledge in pediatrics is phenomenal and fast. If the medical advances and good clinical practice get
coupled with effective advocacy, our increasing knowledge will benefit child care in our country.
I am sure that the algorithms will enhance the capabilities of pediatricians, guiding them towards optimal utilization of
available investigative and therapeutic resources.
xvi
Preface
It gives us immense pleasure to present to you the 1st edition of “Algorithms in Pediatrics”. Pediatrics is rapidly advancing
with the growth of its subspecialties. At times, it becomes difficult for busy pediatricians, whether in practice, in teaching
institutions, or pursuing their postgraduation, to read through lengthy texts of different subspecialties. Keeping this in
mind, we thought of bringing forth this concise book on algorithms, which deals with common and practical topics of
everyday requirements in different pediatric specialties.
The book has been designed with a practical approach in mind, with an algorithm for each topic, along with a concise
text to use the algorithms. The text has been kept simple and easily comprehendible. The book can be consulted rapidly in
the emergency room, wards, outpatient departments, or in busy clinics.
The book contains 19 subspecialty sections, with 8–10 chapters in each, a total of 156 chapters. This was an immense
work, which could not have been possible without the help and coordination of the section editors. We are very thankful
to all the section editors.
A large number of luminaries and experts in the field of pediatrics and its subspecialties have contributed their mind
and might in bringing out this book. We are thankful to all these contributors.
We are also thankful to Jaypee Brothers Medical Publishers (P) Ltd. for publishing this book.
We are also grateful to our respective spouses for being tolerant and supportive of us in this endeavor.
Anand S Vasudev
Nitin K Shah
Contents
Section 1: Neonatology 13. Neonatal Seizures 50

Sanjay Wazir
Section Editors: Anjali Kulkarni, Ashish Mehta
14. Neonatal Sepsis 54
1. Neonatal Resuscitation 1 Rahul P Bhamkar, Anjali Kulkarni
Rhishikesh P Thakre
15. Approach to Congenital Heart Disease 58
2. Apnea 5 Dinesh K Chirla, Preetham K Poddutoor
Naveen Jain
16. First Golden Hour Management of Preterm 63
3. Respiratory Distress in Newborn 8 Naveen Bajaj
Reeta Bora 17. Perinatal Hypoxia 67
4. Respiratory Support in Newborns 13 Ashish Jain, Veeraraja B Sathenahalli
Jayashree A Mondkar, Alpana A Utture
5. Persistent Pulmonary Section 2: Adolescence

Hypertension of the Newborn 20
Section Editors: MKC Nair, Piyali Bhattacharya
Ram G Holla, Ira J Holla
18. Teen Pregnancy and Contraception 71
6. Bronchopulmonary Dysplasia 23 Prema Raghunathan
Naveen Bajaj, Ruchi Nanawati
19. HEEADSSS Assessment of
7. Patent Ductus Arteriosus 28 the Adolescent Child 76
Kiran P Sathe, Anjali Kulkarni Piyali Bhattacharya
8. Neonatal Shock 31 20. Adolescent Anemia 79

Ranjan K Pejaver, Manisha Halkar Vaishali R Deshmukh
9. Anemia in Neonate 34 21. Academics and Career Choices in

Nandkishor S Kabra Adolescents: Approach in
the Pediatric Office Setting 84
10. Bleeding Neonate 39 Ira E Almeida
Deepak Chawla
22. Polycystic Ovarian Syndrome and
11. Neonatal Hyperbilirubinemia Menstrual Problems in Adolescents 87
(Unconjugated) 43 Roli M Srivastava
Poonam Sidana, Gaurav Mandhan
23. Approach to a Case of
12. Hypoglycemia 47 Sexual Abuse in Children/Adolescent 94
Sailesh G Gupta Sushma P Desai
24. Adolescent Depression/Suicidal 38. Approach to Burns in Children 175

Tendency and Its Management 101 Vibha S Bafna
Paula Goel
39. Approach to Envenomation 181
25. Teen Aggression: Steps in Management 110 Mandar B Patil
Kiran SK Vaswani
Section 5: Intensive Care

Section 3: Immunization
Section Editors: Praveen Khilnani, Soonu Udani
Section Editors: Amar J Chitkara, Jaydeep Choudhury
40. Recognition and Assessment of
26. Immunization in Childhood 115 Critically Ill Child 188
Monjori Mitra Praveen Khilnani
27. Missed Immunization 121 41. Septic Shock 195

Ritabrata Kundu Vikram Gagneja, Praveen Khilnani
28. Animal Bites 123 42. Status Epilepticus 201

Jaydeep Choudhury Soonu Udani
29. Adverse Event Following Immunization 127 43. Cardiogenic Shock 204
Amar J Chitkara Nameet Jerath, Praveen Khilnani
44. Head Injury in Infants and Children 209

Section 4: Office Emergencies Bhaskar Saikia, Praveen Khilnani
Section Editors: Anand Shandilya, Rajesh R Chokhani 45. Trauma in Children 213
30. Approach to Respiratory Distress in Children 130 Soonu Udani
Narendra R Nanivadekar 46. Poisoning in Children 217
31. Recognition of Child in Shock 135 Pradeep K Sharma, Praveen Khilnani
Kiran SK Vaswani
47. Snakebite Envenomation 223
32. Croup 139 Soonu Udani, Narendra Rathi
Bhavesh M Mithiya
48. Initial Approach to a Comatose Child 226
33. Approach to a Child with Soonu Udani
Acute Febrile Encephalopathy 144
Surpreet BS Nagi
Section 6: Infectious Diseases
34. Management of a Child
with Respiratory Distress 157 Section Editors: Shyam Kukreja, Tanu Singhal
Sanjay M Bafna, Kochurani Abraham
49. Fever without Focus in Infants
35. Hypovolemic Shock 162 Less than 3 Months of Age 228
Parmanand GK Andankar Balasubramanian Sundaram
36. Approach to Fever in Children 166 50. Acute Viral Encephalitis 231
Rhishikesh P Thakre Jaydeep Choudhury
37. Approach to Poisoning in Children 170 51. Acute Osteomyelitis 235

Somashekhar M Nimbalkar Baldev S Prajapati, Rajal B Prajapati
xx
Contents
52. Algorithmic Approach to Short Section 8: Pulmonology

Duration Fever without Focus
in Older Infants and Children 241 Section Editors: GR Sethi, Varinder Singh
Suhas V Prabhu
66. Approach to a Child with
53. Fever with Rash 243 Respiratory Distress 303
Ritabrata Kundu Soumya Tiwari
54. Approach to Managing New Onset 67. Assessing and Managing

Fever in the Intensive Care Unit 246 a Child with Stridor 308
Tanu Singhal Dhulika Dhingra, Varinder Singh
55. Infant Born to Human Immunodeficiency 68. Recurrent Wheezing in

Virus Infected Mother 250 Infants and Preschool Children 312
Ira Shah Ankit Parakh, Varinder Singh
56. Fever of Unknown Origin 253 69. Managing Acute Severe Asthma 317
Raju C Shah, Tanu Singhal Ankit Parakh, Shalu Gupta, Varinder Singh
70. Management of Bronchiolitis 322

Section 7: Hematology/Oncology Preeti Singh, Varinder Singh
Section Editors: Nitin K Shah, ATK Rau 71. Management of Bronchiectasis 327
Kana R Jat
57. A Mass in the Abdomen:
The Way to Diagnosis 256
Gauri Kapoor Section 9: Cardiology
58. Approach to a Child with Persistent Anemia 260 Section Editors: Vikas Kohli, Usha Pratap
Mamta V Manglani
72. Management of Congestive Heart
59. Algorithmic Approach to Failure in Infants and Children:
Thrombocytopenia in Children 269 An Algorithmic Approach 332
ATK Rau, Shreedhara Avabratha K M Zulfikar Ahamed
60. Algorithmic Laboratory Approach to 73. Approach to a Child with Chest Pain 338
a Child with Anemia 272 Vikas Kohli, Neeraj Agarwal
Aarathi R Rau
74. Systemic Hypertension 343
61. Recurrent Unusual Infections in a Child: Nurul Islam
The Way Forward 277
Tulika Seth 75. Pediatrician’s Perspective for
Postoperative Follow-up of a Child 348
62. Approach to Persistent Fever with Vikas Kohli, Mridul Agarwal
Hepatosplenomegaly in a Child 283
Anupam Sachdeva, Vinod Gunasekaran
Section 10: Gastroenterology
63. Approach to a Bleeding Child 287
Nitin K Shah Section Editors: Surender K Yachha, Anupam Sibal
64. Clinic Pathological Approach 76. Chronic Diarrhea in Children
to Coagulation Disorder 294 Less than 3 Years of Age 352
Sangeeta S Mudaliar, Bharat Agarwal Moinak S Sarma, Surender K Yachha
65. Algorithmic Approach to 77. Chronic Diarrhea in Children

Eosinophilia in Children 299 More than 3 Years of Age 358 xxi
ATK Rau, Sangeetha Shenoy Surender K Yachha, Moinak S Sarma
78. Approach to Upper Gastrointestinal 94. Approach to Pediatric Movement Disorders 448
Bleed in Children 366 PA M Kunju, Anoop K Verma
Anshu Srivastava
95. Afebrile Encephalopathy: Bedside
79. Management of Lower Approach to Diagnosis and Management 458
Gastrointestinal Bleed 373 Lokesh Lingappa, Sirisharani Siddaiahgari
Malathi Sathiyasekaran
80. Acute Liver Failure 380 Section 12: Nephrology

Vidyut Bhatia, Anupam Sibal, Akshay Kapoor
Section Editors: Anand S Vasudev, Pankaj V Deshpande
81. Corrosive Injury in Children 384
Barath Jagadisan 96. Approach to Rickets in Children 463
S Thangavelu, M Vijayakumar
82. Chronic Abdominal Pain 389
Sarah Paul, John Matthai 97. Disorders of Sodium and Potassium 469
Sushmita Banerjee
Section 11: Neurology 98. Acute Glomerulonephritis 473

Noopur Singhal, Abhijeet Saha
Section Editors: Neelu A Desai, Anaita Udwadia Hegde,
Vrajesh Udani 99. Approach to Hematuria in Children 480
Mukta Mantan, Anand S Vasudev
83. Approach to Global Developmental Delay 392
Pratibha D Singhi, Naveen Sankhyan 100. Approach to Urinary Tract Infection 485
Pankaj V Deshpande
84. Approach to Psychomotor
Regression in Children 396 101. Antenatal Renal Anomalies:
Anaita Udwadia Hegde, Omkar P Hajirnis Outcome and Postnatal Management 491
Mehul A Shah
85. Approach to a Child with First Seizure 404
Anju Aggarwal, Anaita Udwadia Hegde 102. Acute Kidney Injury 497
VK Sairam
86. Medical Management of Epilepsy 408
Veena Kalra, Omkar P Hajirnis 103. Enuresis 500
Jyoti Sharma
87. Approach to Refractory Epilepsies 414
Neelu A Desai, Vrajesh Udani 104. Approach to Renal
Tubular Disorders in Children 504
88. Acute Flaccid Paralysis 419 Manoj G Matnani
V Viswanathan, Padma Balaji
105. Nephrotic Syndrome in Children 510
89. Approach to Floppy Infant 423 Mukta Mantan, Anand S Vasudev
Vrajesh Udani, Sarbani S Raha
90. Approach to Ataxia 427 Section 13: Endocrinology

Jayakumar Vaikundam
Section Editors: Vaman V Khadilkar, Anju Virmani
91. Acute Hemiplegia in Children:
An Algorithm for Diagnosis and Treatment 435 106. Approach to Short Stature 514
Viraj V Sanghi Vaman V Khadilkar, Supriya Phanse Gupte
92. Approach to a Child with Spastic Paraplegia 440 107. Childhood Obesity 520
Arun G Roy, Vinayan KP Anurag Bajpai
xxii 93. Acute Febrile Encephalopathy 444 108. An Approach to Hyperglycemia 526
Rashmi Kumar Aspi J Irani
Contents
109. Gynecomastia in Children 532 Section 15: Pediatric Surgery

Raghupathy Palany
Section Editors: Anurag Krishna, Rasik S Shah
110. Precocious Puberty 535
125. Empyema Thoracis: Management Algorithm 609
Puthezhath SN Menon, Madhava Vijayakumar
Rasik S Shah, Suyodhan A Reddy
111. Persistent Hypoglycemia
in Newborns and Infants 542 126. Evaluation of Acute
Abdominal Pain in Children 615
Ganesh S Jevalikar
Ketan P Parikh
Disorder of Sex Development 549 127. Management of Undescended
Testis: Cryptorchidism 622
Vijaya Sarathi
Rasik S Shah, Suyodhan A Reddy, Nachiket M Joshi
113. Approach to Thyroid Disorders
in Children 556 128. Acute Scrotum 629
Anju Virmani Mohan K Abraham
114. Endocrine Hypertension in Children 560 129. Per-rectal Bleeding 632

Sudha R Chandrashekhar Dasmit S Khokar
130. Inguinal Hernia 637

Satish K Aggarwal, Nitin Pant
Section 14: Rheumatology
131. Antenatal Hydronephrosis 642
Section Editor: Priyankar Pal Anurag Krishna
115. Approach to Oligoarthritis 564 132. Management of Vesicoureteric Reflux 646
Vijay Viswanathan Minu Bajpai, Aparajita Mitra, Manisha Jana,
Rakesh Kumar, Chandra S Bal
116. Approach to Polyarthritis 568
Rashna D Hazarika 133. Intussusception 651
Gautam S Agarwal, Anurag Krishna
117. Fever with Arthritis:
An Algorithmic Approach 573 134. Neonatal Jaundice: Surgical Perspective 655
Sathish Kumar Nidhi Sugandhi, Veereshwar Bhatnagar
118. Childhood Vasculitis 578

Indira Banerjee, Rakesh Mondal Section 16: Dermatology
119. Kawasaki Disease 584 Section Editor: Vibhu Mendiratta
Anju Gupta
135. Atopic Dermatitis 661
120. Henoch-Schönlein Purpura 589 Vibhu Mendiratta, Nikita, Sarita Sanke
Anand P Rao
121. Systemic Lupus Erythematosus 592 Hypopigmented Macules 664
Suma Balan Vibhu Mendiratta, Pravesh Yadav
122. Approach to Juvenile Dermatomyositis 598 137. Pediatric Acne 667

Deepti Suri, Sagar Bhattad Vibhu Mendiratta, Niti Gaur, Aashim Singh
123. Acute Osteoarticular Infections 601 138. Approach to Congenital Melanocytic Nevus 670
Jasodhara Chaudhuri, Tapas K Sabui Vibhu Mendiratta, Pravesh Yadav
124. Eye Involvement: Beyond Infections 605 139. Seborrheic Dermatitis 672
Vibhu Mendiratta, Nikita, Sarita Sanke
xxiii
Manjari Agarwal
Section 17: Ophthalmology 149. Stridor in Children 723

Arvind S Bais
Section Editor: Shashi Vashisht
150. Upper Airway Obstruction and
140. Approach to Red Eye in Children 675 Sleep Related Breathing Disorders 727
Suma Ganesh, Priyanka Arora Girish Raheja
141. Compensatory Head Posture 680

Manav D Singh Section 19: Orthopedics
142. Pediatric Epiphora 687 Section Editors: Taral V Nagda, Rujuta Mehta
Shashi Vashisht
151. Septic Arthritis 733
143. Deviation of Eyes 691 Viraj Shingade, Mandar Agashe
Taru Dewan, Harshika Chawla
152. Angular and Rotational
144. Decreased Vision in Children 696 Deformities in Children 739
Shikha Jain Taral V Nagda, Venkatadass Krishnamoorthy
153. Approach to a Child with a Limp 746

Section 18: Ear, Nose, and Throat Sandeep A Patwardhan, Anirban Chatterjee,
Arjun A Dhawale
Section Editor: Girish Raheja
154. Pulled Elbow, Growing Pains, and Flatfoot 751
145. Hearing Screening and Premal Naik, Hitesh B Chauhan
Management in Newborn 699
Atul Ahuja 155. Clubfoot Treatment: Current Concepts 755
Rujuta Mehta, Alaric J Aroojis
146. Hoarseness in Pediatric Age Group 704
Kumud K Handa, Aru C Handa, Dilip Samal 156. Developmental Dysplasia of the Hip 761
Jayanth S Sampath, Rujuta Mehta
147. Otitis Media with Effusion 709
Anurag M Srivastava, Anil K Monga, Uday Monga
Index 767
148. Pediatric Sinusitis 717
Devinder Rai
xxiv
Section 1: Neonatology
Chapter 1
Neonatal Resuscitation
Rhishikesh P Thakre
INTRODUCTION Identifying High Risk Delivery

Birth of newborn is a potential medical emergency. Up to half Focused questions (help prepare and anticipate problems
of newborns who require resuscitation have no identifiable during resuscitation) include: (1) What is the gestational
risk factors before birth. Preparation and anticipation is the age? (2) Is the amniotic fluid clear? (3) How many babies are
key. All babies need assessment for resuscitation at birth. Up expected? (4) Are there any additional risk factors?
to 10% of babies need some resuscitation and less than 1%
need major resuscitation. ASSESSMENT AT BIRTH
Need for resuscitation can generally be identified by a rapid
STANDARD PRECAUTIONS assessment by asking “Is the infant breathing or crying?” If the
All resuscitation should be conducted under strict asepsis. baby is breathing or crying, the newborn does not require any
All resuscitation apparatus should be clean and sterile, further resuscitation. Early skin-to-skin contact with mother
and where indicated, disposable. Suction catheters, mucus be practiced and newborn assessed for breathing, color, and
activity.
extractor, umbilical catheters, syringes, needles, endotracheal
If the baby is not breathing or crying, a series of steps may be
(ET) tubes, feeding tubes should be single use, sterile, and
needed to establish breathing sequentially performing initial
disposable.
steps, PPV, CC, intubation, and/or administration of drugs.
Assessing the breathing is by observing the baby’s chest
PREPARATION PRIOR TO BIRTH movements. Breathing is adequate if a baby is vigorously
crying or has good regular chest movements with no pauses
Equipment Check or indrawing with associated good tone. Gasping or labored
• All equipment should be available in various sizes for breathing should not be mistaken for normal breathing.
different gestation
• A checklist should be used to ensure that the equipment is CORD CLAMPING
functional
All babies who establish spontaneous respiration at birth
• Following equipment are “desirable” for resuscitation:
should have cord clamping delayed for more than 1 minute.
compressed air, blender, continuous positive airway
It is a safe procedure in term, preterm, and low birth weight
pressure (CPAP), pulse oximeter + probe and plastic wrap.
(LBW) babies with improved iron status, higher blood pressures
during stabilization, and a lower incidence of intraventricular
Personnel hemorrhage (IVH) and fewer blood transfusions in preterms.
• At every delivery, there should be at least one person whose
primary responsibility is the baby and who is capable of
initiating resuscitation positive pressure ventilation (PPV)
STEPS IN NEONATAL RESUSCITATION
and chest compression (CC). Skilled personnel for complete A baby who is not breathing or crying at birth should undergo
resuscitation be readily available, if needed following steps of resuscitation with ongoing assessment and
• Two persons or more are required in “high risk” delivery. reassessment at every step (Algorithm 1).
ch-01.indd 1 11/18/2016 4:55:34 PM

Algorithm 1
Indian Academy of Pediatrics Neonatal Resuscitation Program First Golden Minute algorithm for neonatal resuscitation
*In meconium stained depressed neonates after oral suction, endotracheal suction may be considered.
#Endotracheal intubation may be considered at several steps.
CPAP, continuous positive airway pressure, HR, heart rate; ET, endotracheal; IV, intravenous; NICU, neonatal intensive care unit.
Initial Steps for air entry and chest movement. If not, take corrective
measures for ventilation—mask reposition, reposition airway,
A baby who is not breathing or crying should be received in
suction, open mouth and ventilate, pressure increase, and
dry, prewarmed cloth with immediate cord clamping and
consider alternate airway measures (MRSOPA). Heart rate is
placed under a heat source. The head, trunk, and the limbs
assessed every 30 seconds. Consider inserting orogastric tube
should be dried firmly and quickly. Suction of mouth followed
if ventilation is prolonged.
by nose may be done if there is obvious obstruction to airway.
Positive pressure ventilation is discontinued if there
Stimulation is done by rubbing the back or flicking the soles.
is rise in HR greater than 100 beats per minute and onset of
The newborn is repositioned and simultaneous assessment of
spontaneous respiration. If despite adequate PPV, there is no
respiration and heart rate (HR) is done.
desired response, one may consider intubation or initiate CC if
Response to resuscitation is best judged by increasing HR
HR is less than 60 beats per minute.
and later by establishment of spontaneous breathing. The HR
is easiest and quickest assessed by palpating at the base of
umbilical cord, but auscultation of precordium is most reliable.
Intubation
Intubation is considered if ventilation is ineffective, newborn
Positive Pressure Ventilation is nonvigorous with meconium stained liquor, need for CC,
administration of drugs, or suspected congenital diaphragmatic
Positive pressure ventilation is indicated if the newborn has
hernia. Intubation is performed in time limit of 30 seconds.
apnea or gasping respiration, HR less than 100 beats per
There is no role of cuffed ET tubes. Two common and serious
minute or SpO2 below target values despite supplemental
errors of ET intubation are malplacement of the ET tube and
oxygen being increased to 100%. A flow-inflating bag, a self-
the use of the wrong sized tubes.
inflating bag, or a pressure-limited T-piece resuscitator can
be used for PPV. Call for help and ask assistant to apply pulse
oximeter, if available, to right hand/wrist of the newborn. In Chest Compression
all newborns (term or preterm), PPV should be started with Heart rate less than 60 beats per minute despite adequate
room air. Provide breaths at a rate of 40–60 per minute using ventilation is indication to start CC. One should ensure
“breathe–two-three” and assess for efficacy after 5–10 breaths. that assisted ventilation is being delivered optimally before
2 Check for rise in HR and oximetry. If there is no HR rise, check starting CCs. Consider intubation if CC is to begin. The
ch-01.indd 2 11/18/2016 4:55:35 PM

Chapter 1: Neonatal Resuscitation
2 thumb encircling hands technique may generate higher respiratory efforts, good muscle tone, and a HR greater than
peak systolic and coronary perfusion pressure than the 2 finger 100 beats per minute, and needs no intervention.
technique, hence the 2 thumb encircling hands technique is A nonvigorous infant needs immediate intubation,
recommended for performing CCs in newly born infants. The under vision tracheal suction skipping the initial steps of
2 finger method should be reserved only for brief applications resuscitation. If tracheal intubation is unsuccessful or there is
while an emergent umbilical venous catheter is established severe bradycardia, then proceed to PPV.
and then should be converted back to the 2 thumb method. A
ratio of three CC to one ventilation is delivered in 2 seconds Role of Oxygen
for uninterrupted 45–60 seconds compressing the 1/3 Need for oxygen is based on oximetry. Pulse oximeter
anteroposterior diameter of the chest and HR is checked every working on a “signal extraction technique” that is designed
45–60 seconds. to reduce movement artifact with a neonatal probe is ideal.
If the HR less than 60 beats per minute, CC with intubation Administration of supplementary oxygen should be regulated
is continued with administration of adrenaline; if the HR by blending oxygen and air, and the concentration delivered
is 60–100 beats per minute, CC is stopped and ventilation is guided by oximetry. Healthy infants born at term may take
continued and if the HR is greater than 100 beats per minute more than 10 minutes to achieve a preductal oxygen saturation
with spontaneous breathing, PPV is discontinued. greater than 95% and nearly 1 hour to achieve postductal
saturation greater than 95%. If the saturation is less than
Medications desired, start supplemental oxygen. Use 100% oxygen if the
Bradycardia in the newborn infant is usually the result of newborn needs CC. Minute specific oxygen saturation targets
inadequate lung inflation or profound hypoxemia, and for newborns are provided in table 1.
establishing adequate ventilation is the most important step to
correct it. Medications are indicated if the HR is less than 60 Pneumothorax
beats per minute despite 45–60 seconds of adequate CC and Transillumination using a cold light source may be used for
ventilation. The preferred mode of drug delivery is umbilical diagnosing pneumothorax bedside, if facility exists. In absence
venous route. Epinephrine is administered in 1:10,000 of cold light source, use a butterfly with a three way and syringe
concentration at dose of 0.1–0.3 mL/kg, IV (ET: 0.5–1 mL/ to tap in the second intercostal space on the suspected side.
kg) as fast as possible. Heart rate is assessed after 1 minute of
adrenaline administration. Therapeutic Hypothermia
Volume expanders, normal saline or ringer lactate, Currently, therapeutic hypothermia is not defined as
10 mL/kg over 5–10 minutes may be administered if there is standard of care in India. However, if facility exists, such
no response to resuscitation and signs of poor peripheral therapy may be used but only after taking informed consent
perfusion or history suggestive of blood loss. There is no role of from parents.
naloxone in delivery room. Endotracheal drug administration
does not give reliable effects. Resuscitation of Babies
Outside Hospital/Home Delivery
PRETERM RESUSCITATION Special attention should be paid to maintaining normal
Additional personnel and equipment are required. Preterm/ temperature of the baby by closing the windows to prevent
LBW babies not requiring resuscitation at birth can be kept draughts, use dry warm cloth, baby cap, and skin-to-skin
on mother’s chest in skin-to-skin contact for thermoregulation. contact. Resuscitation can also be performed keeping baby on
Ensure the area is preheated using a warmer or portable pad. mother’s abdomen. Baby should be transferred to facility in
Food grade, clean, plastic wrapping may be done before drying skin-to-skin contact with mother.
in less than 32 weeks’ gestation as soon as the baby is born to
ensure thermal care. If preterm is breathing spontaneously To Resuscitate or Not
with labored respiration or is cyanotic or low SpO2, consider The decision of when not to resuscitate or how much to
initiating CPAP. Gentle handling, avoiding head-down position, resuscitate is complex. Such decisions are best made with
avoiding excess pressures of PPV or CPAP, administering
surfactant after stabilization, using pulse oximeter as a Table 1: Target oxygen saturation
guide to oxygenation and avoiding rapid infusions are good
Time (min) Preductal SpO2 after birth
resuscitation practices.
1 60–65%
2 65–70%
SPECIAL CIRCUMSTANCES 3 70–75%
4 75–80%
Meconium Stained Liquor
5 80–85%
The resuscitation is based on whether the newborn is vigorous
or not. A vigorous infant is defined as one who has strong 10 85–95% 3
ch-01.indd 3 11/18/2016 4:55:35 PM

an understanding of the relevant neonatal data and ethical

issues, including the rights of the newborn and the parents. Clinical Pearls
The ideal situation is one where the healthcare team and • Failing to prepare is preparing to fail. Personnel and equipment
family come together and make the best possible decision for preparation is essential
all involved. • Discontinuation of resuscitative efforts may be appropriate if
resuscitation of an infant with cardiac arrest does not result in
spontaneous circulation within 10 minutes
Postresuscitation Care
• Use of pulse oximetry is desirable in following conditions:
The postresuscitation care has been described in table 2. anticipated need for resuscitation, positive pressure ventilation,
supplemental oxygen, continuous positive airway pressure,
Harmful Practices In evaluation of cyanosis
• Free-flow oxygen can be delivered by holding tube near the
Newborn Resuscitation nostrils, using face mask and flow-inflating bag. It cannot be
• Routine suction of mouth and nose delivered by self-inflating bag.
• Routine stomach-wash of the baby
• Prolonged flicking the soles or rubbing or slapping the
back when baby is depressed Key points
• Putting the baby upside down for postural drainage.
))
Rapid assessment for need for resuscitation and initial
steps should be performed within 30 seconds and positive
Table 2: Postresuscitation care
pressure ventilation initiated not later than 60 seconds of life
Routine care Observational Postresuscitation constitutes the “golden minute”
care care ))
The most sensitive measure of response to resuscitation is
prompt improvement in heart rate
When? For all Post initial Post positive
))
The most important and effective step in resuscitation is
spontaneous steps or brief pressure ventilation
ventilation
breathing positive pressure (>1 min), need for
newborns ventilation chest compressions, ))
Initiate resuscitation with room air for all newborns
not requiring (<1 min) intubation or drugs ))
Cord clamping should be delayed for atleast 1 minute in
resuscitation babies not requiring resuscitation.
Where? Mother Supervised in Neonatal intensive

nursery care unit suggested readings
1. NRP Addendum. Consensus document by IAP NNF NRP India Task Force (2012).
Care? Assess Observe for Sick newborn care
2. Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L, Goldsmith JP,
for color, temperature, and monitoring
et al. Part 11: neonatal resuscitation: 2010 International Consensus on
activity, and respiration, heart
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
breathing rate, blood sugar With Treatment Recommendations. Circulation. 2010;122 (Suppl 2):S516-38.
ch-01.indd 4 11/18/2016 4:55:35 PM

Chapter 2
Apnea
Naveen Jain
INTRODUCTION Clinical Pearls

Apnea is a common problem in clinical practice of pediatricians
• Is the baby completely well after the apnea (apnea of
managing preterm babies. It is a symptom of serious concern prematurity likely)
as timely intervention may be necessary to prevent death/
• Or does the baby still need oxygen to saturate, has poor
serious hypoxia and associated morbidities. Many apnea
sensorium or activity, hypo-/hyperthermia, poor perfusion,
events or a single serious apnea event may lead the clinician to
abnormal sugars—look for a cause and treat.
investigate extensively and initiate empirical therapies ranging
from antibiotics to treatment for reflux. A clinical approach
guideline may optimize interventions.
Common Causes Of Apnea
Cessation of breathing lasting long enough (defined as
>20 seconds, but time never measured in clinical practice!) to • Pneumonia, sepsis, necrotizing enterocolitis
cause hypoxia (saturation <80%), bradycardia [heart rate (HR) • Central causes: perinatal asphyxia, seizures, birth trauma,
<100 beats per minute] or poor perfusion or poor tone. meningitis, intracranial hemorrhage [intraventricular
hemorrhage (IVH), subdural hemorrhage], periventricular
leukomalacia (PVL), and hydrocephalus
CLINICAL EVALUATION
• Hypoglycemia
Apnea is always a life-threatening emergency and treatment • Dyselectrolytemia: hyponatremia, hypocalcemia, hypo
(resuscitation) precedes evaluation. In practice, good obser kalemia
vation is possible only after resuscitation. Classical description • Anemia
of apnea has been central/obstructive and mixed based on • Hypo- and hyperthermia
whether baby is breathing or not at the time of apnea. • Airway obstruction
However, it is more useful to classify babies as: • Drug toxicity, e.g., phenobarbitone
• Well preterm baby with apnea: possibly apnea of • Cardiac causes: patent ductus arteriosus (PDA).
prematurity (AOP)
• Sick baby with apnea: one who has low saturations and
Differential Diagnosis
needs oxygen to saturate even after effective breathing
is established and has either poor sensorium or tone, • Periodic breathing (cessation of breathing with no cyanosis
poor perfusion, abnormalities of glucose, temperature or bradycardia)
instability, or feed intolerance. Apnea in this circumstance • Subtle seizures
is usually secondary to a cause, i.e., symptomatic apnea • Gastroesophageal reflux disease (GERD)
and needs specific investigation and treatment.
Apnea of prematurity needs only stimulation of respiratory
INVESTIGATIONS
center with xanthines. Symptomatic apnea may also benefit
with the xanthines/continuous positive airway pressure (CPAP)/ Based on the expected cause, investigations should be planned:
nasal intermittent mandatory ventilation (NIMV), but treatment • Blood sugar, serum electrolytes, and serum calcium
of primary cause is more important. Recurrent and severe apnea • Sepsis screen including blood culture
may require intubation and ventilation in both situations. • Hemoglobin for anemia
ch-02.indd 5 11/18/2016 4:56:09 PM

• Ultrasonography head to rule out IVH, PVL, and hydro • Methylxanthines (caffeine and aminophylline): these are
cephalus adenosine receptor antagonists and are primarily used
• Echocardiography to rule out PDA in AOP
• Chest X-ray for pneumonia {{ Caffeine (Standard dose regime) 10 mg/kg of caffeine
• Serum phenobarbitone level base as loading dose over 30 minutes followed by

• Arterial blood gas. 5 mg/kg/day of caffeine base in once a day dose regimen
reduces apnea. To be continued till baby is apnea free
for 7 days or more than 34 weeks postconceptional
MANAGEMENT (Algorithm 1) age. Caffeine may also be used in periextubation
• Emergency: period to reduce the need for reintubation in very low
{{ Warmth, airway, position to semiextension of neck, birth weight babies. High dose up to 20 mg/kg/day
and suction of oronasopharynx has not been reported to have any adverse effects on
{{ Gentle stimulation of sole or rubbing back followed by neurodevelopment
positive pressure ventilation (PPV) if no respiration after {{ Aminophylline (Loading dose) 8 mg/kg intravenous
simulation (as in Neonatal Resuscitation Program) infusion over 30 minutes followed by 1.5–3 mg/kg per
• Oxygen, if baby is hypoxic, to maintain SpO2 in the range dose every 8–12 hourly. Caffeine is the preferred drug
of 90–95% because of higher therapeutic safety, more reliable
• Temporarily withhold feeds enteral absorption, less fluctuation of plasma levels
• Right lateral position with head elevated in suspected owing to its long half-life, ease of administration
GERD (once daily), and few peripheral side effects like
Algorithm 1
Management of newborn with apnea
CPAP, continuous positive airway pressure; HR, heart rate; AOP, apnea of prematurity; NIMV, nasal intermittent mandatory ventilation; AF, anterior fontanelle;
IVH, intraventricular hemorrhage; IEM, inborn error of metabolism; CBC, complete blood count; CRP, C-reactive protein; KMC, kangaroo mother care; ABG, arterial
blood gas; PCV, packed cell volume.
6
ch-02.indd 6 11/18/2016 4:56:10 PM

Chapter 2: Apnea
tachycardia and feed intolerance as compared to • Supportive care:

aminophylline {{ Transfusion of packed red blood cells: if packed cell
{{ Use of caffeine in babies less than 1,250 g or less than volume less than 30% and no other evident cause of
28 weeks of gestation has been shown to decrease apnea
bronchopulmonary dysplasia and survival with {{ Antibiotics should be initiated in all sick babies with
better neurodevelopmental outcome at 18 months apnea, and pending reports of blood culture.
of corrected age. There is no role of prophylactic use
of either aminophylline or caffeine in the prevention
AREAS OF UNCERTAINTY IN
of AOP. Caffeine may have action for days after
stopping, and babies must be monitored in hospital for CLINICAL PRACTICE
recurrence of apnea for 5–7 days after stopping caffeine • The duration and frequency of apneas that can be safely
tolerated
Clinical Pearls • Effect of treated and untreated apneas on neuro
development.
• Caffeine/aminophylline may decrease incidence and severity
of apnea episodes; this must not delay investigating for a
cause or planning for continuous positive airway pressure/ Key points
ventilation
))
It is important to differentiate if the baby looks well or not
• Aminophylline is similar in effectiveness; close monitoring
for tachycardia and feed intolerance may be required (most ))
A well baby is likely to have apnea of prematurity
centers are not monitoring drug levels in India) if cost limits ))
Investigations are required in a sick baby to find other causes
use of caffeine. of apnea.
• Continuous positive airway pressure: continuous positive

airway pressure should be used in apnea if xanthines fail. SUGGESTED READINGs
Continuous positive airway pressure is the preferred mode 1. Butcher-Puech MC, Henderson-Smart DJ, Holley D, Lacey JL, Edwards DA.
of treatment if baby has retractions or need for oxygen in Relation between apnoea duration and type and neurological status of preterm
addition to apnea. Postextubation CPAP reduces chances infants. Arch Dis Child. 1985;60(10):953-8.
of extubation failure due to apnea 2. Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in
• High flow nasal cannula: flow of gases greater than 2 L/min preterm infants. Cochrane Database Syst Rev. 2010;(12):CD000140.
produces CPAP like benefit. The mixture of air and oxygen 3. Henderson-Smart DJ, De Paoli AG. Prophylactic methylxanthine for pre
vention of apnoea in preterm infants. Cochrane Database Syst Rev. 2010;(12):
should be warmed and humidified
CD000432.
• Noninvasive ventilation with nasal prongs in the form of 4. Henderson-Smart DJ, Steer PA. Caffeine versus theophylline for apnea in preterm
NIMV and synchronized NIMV infants. Cochrane Database Syst Rev. 2010;20(1):CD000273.
• Intubation and ventilation: if the baby has frequent apnea
on CPAP and NIMV, intubation and mechanical ventilation
should be considered
ch-02.indd 7 11/18/2016 4:56:10 PM

Chapter 3
Respiratory Distress in Newborn
Reeta Bora
INTRODUCTION • Surgical causes: pneumothorax, congenital malformation

like tracheoesophageal fistula, diaphragmatic hernia,
Respiratory distress is a common problem in newborn and choanal atresia, Pierre-Robin syndrome.
is encountered in almost 6–7% of neonates. The clinical
presentation of respiratory distress in the newborn includes Term Baby
tachypnea (respiratory rate of >60 breaths per min), retraction
of chest (intercostals, subcostal, or supraclavicular), grunting, • Pulmonary:
{{ Transient tachypnea of newborn
cyanosis, inspiratory stridor, and nasal flaring. However,
{{ Meconium aspiration syndrome (MAS)
conventionally, presence of any two out of retraction, grunt,
{{ Congenital and acquired pneumonia
and tachypnea is defined as respiratory distress. There are
many conditions in newborn which can lead to respiratory • Cardiac, central nervous system, metabolic, and surgical
distress and many of them are preventable. Some of them last causes are similar to those of preterm babies.
for few hours only while some may be persistent and if not
managed urgently, may lead to death. Early recognition and
APPROACH TO A NEONATE
management is necessary to prevent mortality and to decrease
morbidity. WITH RESPIRATORY DISTRESS
History
COMMON CAUSES OF
A detailed good history is very important to come to a diagnosis.
RESPIRATORY DISTRESS IN NEWBORN
It is important to know if the baby is a term (>37 completed
weeks of gestational age) or a preterm baby (<37 weeks of
Preterm Baby
gestation). If preterm, the exact gestational age helps us to
• Pulmonary: assess the risk of RDS or hyaline membrane disease. It is
{{ Respiratory distress syndrome (RDS) (hyaline mem
important to know in case of preterm baby whether antenatal
brane disease) steroid has been received or not. If there is history of prolonged
{{ Congenital pneumonia
rupture of membrane, congenital pneumonia should be
{{ Aspiration pneumonia
suspected. History of diabetes mellitus in mother in a preterm,
{{ Transient tachypnea of newborn (TTNB)
late preterm, or term baby may be indicator of hyaline
• Cardiac: membrane disease; similarly, history of meconium stained
{{ Congenital heart disease
liquor with poor Apgar score and distress soon after birth
{{ Myocardial dysfunction
would indicate MAS. The importance of determining the time
• Central nervous system: of onset of distress needs to be emphasized, as this may vary
{{ Asphyxia
depending upon the etiology. Respiratory distress syndrome,
{{ Intraventricular hemorrhage
TTNB, and MAS are some conditions which would present in a
• Metabolic: neonate soon after birth. If feeding problems are present, such
{{ Hypoglycemia
as choking or aspiration during a feed, and distress occurred
{{ Acidosis
after some duration after birth, aspiration pneumonia may
{{ Hypothermia
be thought of as a cause. Congenital heart disease usually
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Chapter 3: Respiratory Distress in Newborn
manifests with symptoms like respiratory distress after some neutrophil count, estimation of C-reactive protein level, band
duration after birth; acquired pneumonias will also manifest cell count and micro-erythrocyte sedimentation rate, and
later than 48 hours after birth. blood culture needs to be done. Shake test should be done
if RDS is suspected. Shake test is a simple bedside test and
Clinical Examination should be done in preterm babies with respiratory distress,
especially if there is no history of administration of antenatal
The neonate should then be assessed for severity of
steroid. The gastric aspirate (0.5 mL) is mixed with 0.5 mL of
respiratory distress, any associated neurological signs like
absolute alcohol in test tube. This is shaken for 15 seconds
level of alertness, bulged fontanelle, tone anomaly, etc. One
and allowed to stand for 15 minutes. A negative shake test,
should also look for any signs suggestive of cardiac problem
i.e., no bubbles or bubbles covering less than one-third of the
like prolonged capillary refill time, poor pulse volume, a
rim indicates a high risk of developing RDS and the presence
hepatomegaly, presence of any murmur, and any abnormality
of bubbles at more than two-third of the rim indicates lung
in blood pressure. Any signs indicating presence of sepsis
maturity and decreased risk of developing RDS. A chest
should be looked for. If malformations are present in any
X-ray helps to differentiate different conditions like RDS,
part of body, it may indicate a surgical cause or a cardiac
TTNB, MAS, pneumonia, and different surgical conditions
cause as the possibility for respiratory distress. Excessive
like tracheoesophageal fistula and diaphragmatic hernia
frothing with inability to pass a feeding tube may indicate
(Figs 1 to 5). Cardiomegaly in chest X-ray may indicate cardiac
presence of tracheoesophageal fistula while deterioration of
abnormality as a cause of respiratory distress. An arterial blood
a baby on bag and mask ventilation and associated scaphoid
gas (ABG) helps further in establishing diagnosis.
shape of abdomen would indicate presence of diaphragmatic
hernia. In a dehydrated baby, metabolic acidosis may be the
cause. History of meconium stained liquor, and on clinical MANAGEMENT (Algorithm 1)
examination, meconium staining of nails, skin, umbilicus, etc.
with a hyperinflated chest would indicate MAS. General Management
Irrespective of cause, the principles of supportive therapy
Clinical Pearl for respiratory distress in newborn is same and crucial in
all. All babies with respiratory distress would need constant
• A detailed history and clinical examination is very important to monitoring. The parameters to be monitored to find whether
find the cause of respiratory distress in a newborn. baby is improving or deteriorating with any indication for
respiratory support are the respiratory rate, presence of
The Downes’ score is commonly used for assessing severity grunting, chest indrawing, or any episode of apnea. Babies
of respiratory distress objectively in a newborn as well as to should be assessed for Downes’ score at intervals to access
assess whether baby is improving or deteriorating later on improvement or deterioration. Monitoring should be
(Table 1).
A score of 6 or more indicates severe respiratory distress
and impending failure with need for respiratory support. A
score of less than 6 indicates respiratory distress and may
indicate oxygen supplementation with a hood and a score
of 4–6 indicates moderate respiratory distress with need for
support with continuous positive airway pressure (CPAP).
Investigations
Based on probable diagnosis reached after thorough history
and clinical examination, investigations need to be planned to
confirm diagnosis. If history of prolonged rupture of membrane
is present in a neonate with respiratory distress, sepsis screen
which includes estimation of total leukocyte count, absolute
Table 1: Score for respiratory distress (Downes’ score)

Score 0 1 2
Respiratory rate <60 60–80 >80 Fig. 1: Chest X-ray anteroposterior view of a premature baby showing
respiratory distress syndrome, with bilateral lung fields showing ground
Central cyanosis None None with 40% FiO2 Need >40% FiO2
glass appearance (RDS) with air bronchogram. If a preterm baby has
Retractions None Mild Severe respiratory distress within the first 6 hours of birth and is cyanosed
Grunting None Minimal Obvious or needs oxygen to maintain oxygen saturation, the diagnosis is RDS
unless proved otherwise. X-ray findings would be a reticulogranular
Air entry Good Decreased Very poor pattern in mild disease and a “white out” picture in severe disease. 9
ch-03.indd 9 11/18/2016 4:56:45 PM

Fig. 2: Chest X-ray showing hyperinflation of lung fields, bilateral Fig. 4: Patchy opacities with intermittent hyperlucent areas suggestive
streaky opacities radiating from hilum and fluid in the horizontal of air entrapment are seen in MAS. Babies born through meconium
fissure of right lung suggestive of transient tachypnea of newborn. stained liquor could have meconium aspiration syndrome (MAS) and
Transient tachypnea of the newborn is a benign condition usually aspiration may occur in utero, during delivery or immediately after
seen in term babies born by cesarean section. These babies are well birth. Thick meconium could block air passages and cause atelectasis
and have only tachypnea with rates as high as 80–100breaths per and air leak syndromes.
minute. The breathing is shallow and rapid without any significant
chest retractions. It occurs because of delayed clearance of lung fluid.
Management is supportive and prognosis is excellent. or nasal cannula for achieving appropriate oxygen saturation
(88–92% in preterm and 90–93% in term). Oxygen when given
therapeutically should always be warmed and humidified.
When oxygen hood is used for administering oxygen, oxygen
flow rate should be 5–6 L/min. Flow rate less than 3 L/min is not
appropriate as may lead to carbon dioxide rebreathing. If an
oxygen hood is used with all side ports closed and flow rate of 5
L/min, the baby would receive around 80% oxygen, if one side
port is kept open with same flow rate, baby would receive 60%
oxygen while baby would receive 40% oxygen if both side ports
are kept open. The percentage of oxygen needed by baby can
be determined by oxygen saturation reading shown in pulse
oximeter. The aim should be to maintain oxygen saturation
in the range of 90–94%. Another useful method of providing
oxygen is nasal prongs. Appropriate sized prongs which fit into
neonate’s nostrils should be used. If baby’s oxygen saturation is
acceptable, we can slowly wean off oxygen.
Fig. 3: Chest X-ray showing infiltrates in right lower lung which is

asymmetrical bilaterally with history of prolonged rupture of membrane, Clinical Pearl
suggesting congenital pneumonia. In developing countries, pneumonias
account for more than 50% cases of respiratory distress in newborn. • During oxygen therapy, percentage of oxygen needed should
In congenital pneumonia, respiratory distress is noticed soon after be determined in a neonate by oxygen saturation reading in
birth or during first 24 hours. Auscultatory signs may be nonspecific. a pulse oximeter. Oxygen is a drug and overdose should be
The newborn may die from pneumonia without manifesting distress. avoided. Target SpO2 should be 90–94% in neonates.
Neonates may develop pneumonia postnatally as a consequence of
septicemia, aspiration of feeds, and ventilation for respiratory failure. The body temperature of the neonate should be maintained
in normal range (36.5–37.5°C). Fluid and electrolyte balance
continued till baby no longer requires oxygen for at least a should be maintained. If baby is having moderate-to-severe
minimum period of 24 hours. respiratory distress, baby can be maintained on intravenous
Based on severity of respiratory distress, baby would fluid. If mild respiratory distress is there, as assessed by Downes’
require oxygen (Downes’ score 1–3), continuous positive score, baby can be fed expressed breast milk by tube feeding.
pressure ventilation (Downes’ 4–6), or mechanical ventilation Blood sugar should be monitored and kept in normal range
10 (Downes’ score >6). Oxygen can be provided with oxygen hood (40–125 mg/dL). If baby has apnea, baby should be stimulated
ch-03.indd 10 11/18/2016 4:56:45 PM

Chapter 3: Respiratory Distress in Newborn
A B
Fig. 5: Showing presence of pneumothorax on chest X-ray A, Right sided pneumothorax and B, bilateral pneumothorax. Pneumothorax in
neonates could be spontaneous but is more often due to meconium aspiration syndrome or staphylococcal pneumonia. It is important to recognize
pneumothorax because quick recognition and prompt treatment could be life-saving. The distress is usually sudden in onset and heart sounds
become less distinct. Immediate management in hemodynamically unstable neonate is by a needle aspiration and later chest tube drainage.
Algorithm 1
Management of neonatal respiratory distress
MAS, meconium aspiration syndrome; RDS, respiratory distress syndrome; TTNB, transient tachypnea of newborn; CPAP, continuous positive airway pressure;
NICU, neonatal intensive care unit.
by providing tactile stimulation or positive pressure ventilation respiratory distress is persistent or risk factors for sepsis are
by bag and mask. Repeated episodes might indicate need for present, antibiotics should be started after taking cultures. If
CPAP or mechanical ventilation, if severe. Such babies would cultures come negative and clinically baby does not seem to
need transfer to centers with facility for CPAP or mechanical have infection, antibiotics can be stopped.
ventilation if these are not available locally. Continuous positive airway pressure is indicated for
All babies with respiratory distress do not need antibiotics. neonates with respiratory distress if Downes’ score is 4–6. 11
Babies with TTNB do not need antibiotics. However, if Experience is required for the successful application of CPAP,
ch-03.indd 11 11/18/2016 4:56:46 PM

especially with short binasal prongs. Single prong method may If CPAP fails or Downes’ score is more than 6, there is need
be beneficial for nurseries who have less experience with short for mechanical ventilation.
binasal prongs or when application of short binasal prongs
is problematic. While commencing CPAP, it can be given at a Specific Management
pressure of 6–8 cm of water with sufficient oxygen to maintain
In case of pneumonia, antibiotic is indicated. Antibiotic
target saturation. An orogastric tube needs to be passed to
of choice should be based on local antibiotic sensitivity
decompress the stomach. While baby is on CPAP, continuous pattern. In case of hyaline membrane disease, surfactant
monitoring of saturation, heart rate, respiratory rate is replacement therapy is indicated. If pneumothorax occurs,
indicated. Blood gases are indicated when pressures or oxygen needle decompression or chest tube drainage may be
percentage are changed or patient’s condition shows some required. Small pneumothoraces can be treated in term
change. The circuit integrity should be checked periodically. infants without invasive management through nitrogen
washout. Administration of 100% oxygen can accelerate the
Clinical Pearl resolution of the pneumothorax as readily absorbed oxygen
replaces nitrogen in the extrapulmonary space. Neonates
• Downes’ score of 4–6 is an indication for continuous positive
with respiratory distress due to surgical conditions, like
airway pressure. A score of greater than 6 is an indication for
tracheoesophageal fistula, diaphragmatic hernia, etc., would
mechanical ventilation.
need surgical intervention. Respiratory distress due to cardiac
failure would need management of cardiac failure.
Baby’s improvement would be indicated by reduction
in respiratory rate, stabilization or reduction of oxygen
requirement to maintain saturation of 92–95%, reduction in Key points
sternal and intercostal retraction, reduction in grunt, and
improved ABG reports. The need for CPAP for acute lung ))
Respiratory distress occurs in 6–7% of all neonates
conditions usually lasts for 1–3 days. ))
Early identification and appropriate and timely management
Weaning is commenced when saturation is more than 96%, is the key to success in management
retraction, grunt disappears, and respiratory rate stabilizes ))
Oxygen saturation in pulse oximeter should be maintained at
with normal blood gas reports. While weaning, initially FiO2 90–94%
is brought down and then pressure is reduced by 1–2 cm/h ))
Oxygen should be used judiciously and overdose should be
until a pressure of 5 cm is reached. When neonate is stabilized avoided
in 21% oxygen and 5 cm H2O, ceasing CPAP is considered. ))
Antibiotic use is not indicated in all patients with respiratory
However, recommencing CPAP may be needed at times if work distress.
of breathing is increased or oxygen requirement increases.
Complications of CPAP, like pneumothorax, must be excluded
in such babies. SUGGESTED READINGS
Continuous positive airway pressure is said to be failed if 1. Facility based care of sick neonate at referral health facility. Participant’s manual.
there is rapid rise for oxygen requirement, respiratory acidosis National Neonatology Forum and UNICEF, 2008.
or partial pressure of carbon dioxide greater than 60 mmHg, 2. Frey B, Shan F. Oxygen administration in infants. Arch Dis Child Fetal Neonatal Ed.
2003;88:F84-8.
recurrent apnea and increased work of breathing indicated by
3. Hein HH, Ely JW, Lofgren MA. Neonatal respiratory distress in the community
excessive retraction grunt and retraction, or if agitation is not hospital: when to transport, when to keep. J Fam Pract. 1998;46:284-9.
relieved. 4. Hermansen CL, Lorah KM. Respiratory distress in newborn. Am Fam Physician.
There can be at times complications of CPAP like pneumo 2007;76:987-94.
thorax, nasal trauma or CPAP belly, i.e., distension of abdomen.
12
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Chapter 4
Respiratory Support in Newborns
Jayashree A Mondkar, Alpana A Utture
INTRODUCTION COMMON CLINICAL

Respiratory disorders are one of the commonest reasons INDICATIONS FOR RESPIRATORY
for admission to the neonatal unit. Innovations in neonatal SUPPORT IN Neonatal Intensive Care Unit
respiratory care over the past few decades resulting in the
availability of a number of noninvasive and invasive modalities Pulmonary Disorders
of therapy have revolutionized the management of babies • Respiratory distress syndrome (RDS)
with respiratory disorders, especially the very low birth weight • Meconium aspiration syndrome (MAS)
(VLBW) group. • Congenital pneumonia
The aims of respiratory support are to maintain adequate • Community acquired pneumonia
oxygenation and ventilation, to reduce respiratory work and to • Persistent pulmonary hypertension of the newborn
prevent lung injury. • Air leak syndromes
The modalities of respiratory support commonly available • Chronic lung disease
in our neonatal intensive care units (NICUs) include: • Pleural effusion
• Pulmonary hypoplasia
Oxygen Therapy • Upper airway disorders.
• As a standalone therapy or
• As part of all respiratory support modalities mentioned Surgical Respiratory Disorders
below. • Esophageal atresia with tracheoesophageal fistula
• Congenital diaphragmatic hernia (CDH)
Noninvasive Modes of Respiratory Support • Congenital cystic adenomatoid malformation of the lung
• Continuous positive airway pressure (CPAP) • Congenital lung cysts, bronchogenic cysts.
• Heated, humidified high flow nasal cannula
• Nasal intermittent positive pressure ventilation (NIPPV). Cardiopulmonary Disorders
• Neonatal septic shock
Invasive Ventilation • Cardiogenic shock associated with structural cardiac
• Conventional ventilation using a variety of modes defects.
• High frequency ventilation.
Central Nervous System Disorders
Respiratory Adjuncts • Perinatal asphyxia and hypoxic ischemic encephalopathy
• Surfactant therapy • Apnea of prematurity
• Adjuncts for persistent pulmonary hypertension of the • Neonatal encephalopathy
newborn (PPHN): nitric oxide, sildenafil. • Neuromuscular disorders.
ch-04.indd 13 11/24/2016 12:15:57 PM

OXYGEN THERAPY Mechanism of Action

• Alveolar stabilization and maintenance of functional
Indications residual capacity (FRC)
Oxygen therapy is indicated for hypoxemia resulting from • Facilitates gas exchange by preventing collapse of the
alveoli at end expiration
reduced alveolar oxygen content, low ventilation-perfusion
• Decreases the work of breathing as the pressure required
ratio, reduced diffusion capacity, or extrapulmonary right-to-
to overcome the collapsing forces generated by surface
left shunts. The aim of therapy is to achieve adequate tissue tension is reduced when the alveolus is partially inflated.
oxygenation without creating oxygen toxicity and oxidative • Conserves surfactant
stress. Strategies to “normalize” oxygenation with use of high • Decreased ventilation-perfusion mismatch
FiO2 result in high rates of retinopathy of prematurity, chronic • Helps maintain upper airway stability by stenting the
lung disease, brain, and other organ injury, especially in the airway and decreasing obstruction
premature infant. • Lowers airway resistance to gas flow in patients with
obstructive lung disease and apnea
• Augments stretch receptors and decreases diaphragmatic
Clinical Pearl fatigue
• Reduces intracardiac left-to-right shunt.
• Oxygen therapy should be used judiciously and blended air-
oxygen mixture using a blender preferably with an oxygen Indications
analyzer should be used at all times to target oxygen saturation
• Any respiratory distress with or without low FRC and not
between 90 and 95%.
because of listed contraindication
• Postextubation
Oxygen is usually administered: • Meconium aspiration syndrome
• By means of a head box, mask, nasal cannula. Here, an • Tracheomalacia, bronchomalacia with terminal airway
external air-oxygen blender should be used to titrate collapse
the fraction of oxygen delivered. It is used for mild-to- • Some congenital heart defect with increased pulmonary
moderately severe respiratory disorders in term babies blood flow
without evidence of respiratory failure • Partial paralysis of diaphragm.
It is important to note that in preterm with RDS, there is
little role for standalone oxygen therapy as the priority is Contraindications
to recruit adequate lung volume by early use of continuous • Pneumothorax
distending airway pressure • Choanal atresia
• As part of assisted therapy: CPAP or mechanical ventilation • Cleft lip or palate
wherein supplemental oxygen is administered by the • Congenital diaphragmatic hernia
mixture of air and oxygen in the ventilator or CPAP device. • Tracheoesophageal fistula
• Cardiac failure or hemodynamic instability.
Clinical Pearl Types of Continuous Positive
• Gas warming and humidification is essential to avoid drying Airway Pressure Delivery Systems
of the airways and secretions as well as to avoid convective • Continuous flow CPAP system: continuous flow CPAP
heat losses when using head box, nasal cannulas, or assisted consists of gas flow generated at a source and directed
ventilation. against the resistance of the expiratory limb of the circuit.
Ventilator derived CPAP and bubble or underwater CPAP
are examples of continuous flow devices
NONINVASIVE RESPIRATORY SUPPORT • Ventilator based CPAP: ease of use, pressure stability, and
Noninvasive respiratory support has become the mainstay an effective alarm system. Ventilator CPAP is typically used
of respiratory therapy in the NICU so as to reduce complications for infant extubated from mechanical ventilator
of invasive mechanical ventilation like ventilator associated • Bubble CPAP: In this system of delivery, short binasal
pneumonias and chronic lung disease. prongs are attached to a circuit with a gas source providing
blended, warm, humidified gas at flow rate of 5–8 L/min;
the expiratory limb is partly submerged under water. The
Continuous Positive Airway Pressure height of the submerged water column in centimeters
Continuous positive airway pressure is the application of represents CPAP pressure in centimeters. The benefits of
continuous distending pressure to the airways of spontaneously bubble CPAP are ease of setup and low cost. However, as
breathing baby. Current evidence strongly supports the role of there is no audible pressure disconnect alarm, no warning
early use of CPAP to reduce the need for intubation, invasive occurs even when there are leaks in the system. Visual
14 ventilation, and surfactant therapy for extremely low birth alarm of “no bubbling” and clinical observations of the
weight (ELBW) babies by 50%. patient are essential to maintaining patient safety
ch-04.indd 14 11/24/2016 12:15:57 PM

Chapter 4: Respiratory Support in Newborns
• Variable flow CPAP: variable flow CPAP represents a Continuous Positive Airway Pressure Failure
sophisticated technology of CPAP delivery with visual and • Oxygen requirement greater than 60% to maintain
audible alarms. The major benefit is a decrease in the work saturation 91–95% and CPAP greater than 8 cm H2O
of breathing due to the variable flow. However, it requires • A respiratory acidosis, pH less than 7.20 with partial
specific equipment such as flow drivers, generators, and pressure of carbon dioxide greater than 60 mmHg
circuits that are expensive. Although data suggests that • Recurrent apneic episodes
some of these systems are superior to others, in clinical • Increased work of breathing (sternal and intercostal
practice, the stability of the nasal interface is probably the recession/grunt/tachypnea).
most important factor determining the success or failure of
this form of respiratory support.
Clinical Pearl
Clinical Pearl • Before using alternative mode of ventilation for continuous
positive airway pressure failure, quickly go through check
• Endotracheal continuous positive airway pressure should list to ensure adequate flow delivery, adequate pressure, and
never be used as it significantly increases the work of breathing. position of interface.
It is like breathing through a straw.
Complications
Interface Used for Delivery of Pneumothorax: incidence varies between 0.5 and 2% though
Continuous Positive Airway Pressure the Continuous Positive Airway Pressure or Intubation at Birth
Short binasal prongs are most effective due to reduced airway (COIN) study showed a higher incidence of 9%. In this trial,
resistance. Nasal masks are also finding favor as a CPAP CPAP pressure of 8 cm H2O was used compared to conventional
interface. 5–6 cm of NCPAP.
Continuous Positive Airway Pressure belly: benign gaseous
Initiating Continuous Positive Airway Pressure abdominal distention that can be minimized by evacuating the
• Continuous positive airway pressure should be initiated gas in the stomach routinely every 3 hours and by maintaining
soon after birth in infants who have sufficient respiratory an open-to-air orogastric tube while on CPAP
drive and evidence of respiratory distress, especially in
ELBW babies. More than 50% of ELBW infants who are not Nasal septum damage: this occurs due to care-related problems
depressed at birth can be managed successfully with nasal and is preventable with proper prong size and position,
continuous positive airway pressure (NCPAP), avoiding the minimizing tubing torque, gentle intermittent cleansing, and
use of invasive ventilation. For any preterm with RDS, CPAP proper heating and humidification.
should be promptly instituted if the Silverman Anderson
score is greater than or equal to 3 or the FiO2 requirement Clinical Pearl
is greater than or equal to 30%
• Place the baby supine with a slight head extension • Advantage of noninvasive respiratory support outweighs
• Choose the appropriate sized short binasal prongs size 0 or complications related to it.
1. Avoid pressure of the prongs against the nasal septum
• Start with a CPAP of 5–6 cm H2O, flow of 5–7 L/min of Heated Humidified High Flow Nasal Cannula
blended, warm, humidified gas
• Use appropriate FiO2 to maintain SaO2 between 90 and 95% The heated and humidified high flow nasal cannula (HH-
• Titrate CPAP pressure till the grunting and retractions are HFNC) is a simple, noninvasive method of oxygen delivery
relieved or till a maximum of 8 cm H2O that can produce positive pressure in the airways. The system
• If FiO2 requirement is greater than or equal to 0.4, consists of delivery of heated and humidified, blended air-
administer surfactant as early rescue therapy by intubation- oxygen gas delivered to the baby by nasal cannula with short
surfactant-extubation (INSURE) technique. binasal prongs. Blended gas administered at flow rates of
more than 1 L/min produces distending airway pressure. The
distending pressure generated depends on the size of the nasal
Clinical Pearls cannula, and the flow rate. Generally, flow rates of 3–6 L/min
• Any kind of noninvasive support demands same vigilance as are used. Care should be taken to ensure that the nasal prongs
invasive support do not fit the nares tightly as very high distending pressure can
be generated.
• Adequacy of flow is decided by bubbling at expiratory
The benefits of HH-HFNC are the simplicity of use, less
limb; adequacy of oxygenation is decided by SpO2 on pulse
oximeter; and adequacy of pressure is decided by chest risk of damage to the nares and nasal septum, and comfort for
retractions. more mature babies with RDS. The risk of using HH-HFNC lies
in the inability to effectively measure distending pressure.
15
ch-04.indd 15 11/24/2016 12:15:57 PM

Noninvasive Positive Pressure Ventilation • Respiratory failure characterized by:

{{ PaO less than 50 mmHg on FiO of 100%
2 2
This is a method of assisted ventilation without an endotracheal
{{ PaCO greater than 55–60 mmHg with pH less than 7.25
2
(ET) tube in the trachea, and using either nasal prongs or nasal
• Continuous positive airway pressure failure
mask as the interface. The ventilator delivers peak inspiratory
• Shock.
pressure (PIP), positive end-expiratory pressure (PEEP) at the
set inspiratory time, rate, and FiO2.
The common methods of delivery used are: Clinical Pearl
• Nasal intermittent positive pressure ventilation
• Synchronized nasal intermittent positive pressure venti • Decision to provide ventilatory support should not be
lation (SNIPPV). exclusively based on blood gas.
Mechanism of Action
Modes of Ventilation
Like CPAP, nasal intermittent positive pressure ventilation
expands the lung, increases FRC, prevents alveolar collapse, Conventional ventilation is time-cycled pressure-limited.
and improves ventilation-perfusion mismatch. Currently, patient triggered modes of ventilation like
Synchronized NIPPV results in a higher tidal volume synchronized intermittent mandatory ventilation (SIMV)
compared to NCPAP breaths and nonsynchronized NIPPV. and assist control are preferred. Pressure support ventilation
Whether synchronized or not, NIPPV improves thoraco (PSV) is a mode of ventilation in which patient’s spontaneous
abdominal asynchrony and chest wall stabilization, resulting breaths are augmented by supplemental inspiratory pressure.
in a decreased work of breathing. This may be used along with SIMV or CPAP. It is particularly
useful in weaning off ventilation.
Indications for Use Flow cycling is increasingly being used wherein the breath
• Postextubation support: several randomized controlled is terminated not at a set inspiratory time but when inspiratory
trials have demonstrated a reduction in extubation failure flow is reduced to 30% of the peak flow.
using synchronized nasal ventilation compared to CPAP Flow cycling gives inspiratory as well as expiratory
but not when nonsynchronized NIPPV was used synchrony.
• Apnea of prematurity: NIPPV has been found to be more
effective than NCPAP Controls in Ventilation
• Respiratory distress syndrome as primary support: few Although pressure controlled ventilation has been used
small studies have reported improved carbon dioxide traditionally, volume targeting to reduce volutrauma, the
removal, reduced apnea, and shorter duration of major factor implicated in BPD is increasingly being preferred.
ventilation in the NIPPV group. A significant reduction This can be delivered by using volume controlled ventilation
in bronchopulmonary dysplasia (BPD) has been or in the pressure limited mode with volume guarantee,
reported when NIPPV is used as respiratory support after volume limit, or hybrid modes like pressure regulated volume
extubation or as a primary mode for RDS. It appears that control. The tidal volume is set, and once reached, the breath
nonsynchronized early NIPPV seems to be beneficial for is terminated. Set tidal volume 4–6 mL/kg for preterm and
slightly mature and heavier infants when compared with 6–8 mL/kg for term infants.
NCPAP. However, SNIPPV presents potential advantages
over NCPAP and NIPPV, but more studies are needed for Ventilation Strategies
generalization Ventilator-associated lung injury has been traditionally
Potential drawbacks include the likelihood of gastro thought to result from high pressures and barotruma.
intestinal complications due to the additional pressure, risk However, studies have shown that it is the high volumes
for air leaks, and nasal damage as seen for CPAP therapy. and volutrauma responsible for major lung damage. Lung
injury is also caused by repeated collapse and reopening
Clinical Pearl of the alveoli which occurs with very low end-expiratory
pressures.
• So far, evidences that favor noninvasive ventilation are mainly
related to its use in postextubation neonates. Respiratory distress syndrome
• Provide adequate PEEP to avoid atelectasis 5–6 cm
• Provide PIP enough to achieve adequate oxygenation and
MECHANICAL VENTILATION ventilation.
Conventional Ventilation Meconium aspiration syndrome

Due to the risk of hyperinflation, low PEEP 4–5 cm, moderate
Indications pressure, and rapid rates are often needed. Analgesia and
16 • Apnea sedation may also be required.
ch-04.indd 16 11/24/2016 12:15:57 PM

Bronchopulmonary dysplasia • Pneumothorax may be diagnosed by auscultation, trans

Moderate pressure required, may require longer inspiratory illumination, or chest X-ray. An emergency thoracentesis
time of 0.4–0.5 seconds. may be required
• Reset ventilator by settings used during hand ventilation.
Management after Initiating Ventilation
Weaning
• Check adequacy of mechanical breaths: good air entry
• Once the patient is clinically stable, blood gases have
heard over both sides of the chest, chest rise, and synchro
normalized, and X-ray shows improvement, the ventilator
nization. Chest wall expansion must be just adequate and
settings are gradually decreased keeping in mind the
not excessive
progress of disease process
• Maintain saturation between 91 and 95%; reduce FiO2
• Improvement of lung compliance on the pressure volume
clinically on the pulse oximeter
loops and tidal volume scalers is a good indicator for
• If retractions persist after breaths are synchronized: PEEP/
considering weaning
PIP need to be adjusted
• Diuresis in preterm is also a good indicator of improving
• Monitor pulses, noninvasive blood pressure, capillary refill
lung function. Decrease the most damaging parameters,
time
i.e., FiO2 and PIP first
• After stabilizing the baby, check an arterial blood gas (ABG)
• Changes are accomplished in small decrements (PIP 2 cm
• Do a chest X-ray: look for position of the ET tube.
H2O, FiO2 5%, rate 5 beats per min).
Ventilator Adjustments
• To improve oxygenation: increase FiO2, mean airway
Algorithm 1
pressure (MAP), inspiratory time, respiratory rate
• To improve ventilation and decrease PaCO2: increase MAP Algorithm for management of respiratory distress syndrome
or respiratory rate.
Sudden Deterioration
• Look for inadvertent extubation, malposition of ET tube
(right mainstem) or ET tube occlusion
• Suction the ET to remove secretions
• Auscultate for air entry. Remove from ventilator and
stabilize by bag and tube ventilation
• Rule out ventilator malfunction
• Do an ABG and chest X-ray. Emergency reintubation may
be needed
Table 1: Suggested initial settings on ventilator

Settings Normal lung RDS MAS
PIP (cm H2O) 12–14 16–18 16–18
PEEP (cm H2O) 3–4 5–7 4–5
FiO2 10% higher than head box or CPAP FiO2
Rates (per min) 25–30 40–60 40–60
Flow (L/min) 8–10 8–10 8–10
Inspiratory time (s) 0.36–0.40 0.36–0.40 0.36–0.38
RDS, respiratory distress syndrome; MAS, meconium aspiration syndrome;
PIP, peak inspiratory pressure; PEEP, positive end-expiratory pressure; CPAP,
continuous positive airway pressure.
Table 2: Target blood gases

Preterm Term
pH 7.25–7.35 7.35–7.45
PaO2 50–70 60–80
PaCO2 45–55 35–45 NCPAP, nasal continuous positive airway pressure; RDS, respiratory distress
syndrome; ABG, arterial blood gas; PDA, patent ductus arteriosus; FiO2, fraction
PaO2, partial pressure of arterial oxygen, PaCO2, partial pressure of arterial of inspired oxygen; SaO2, arterial oxygen saturation; PaCO2, partial pressure of
carbon dioxide arterial carbon dioxide; INSURE, intubatio-surfactant-extubation; LR, labor room. 17
ch-04.indd 17 11/24/2016 12:15:58 PM

Algorithm 2 • Failure of conventional ventilation in the term infant:

Management of meconium aspiration syndrome persistent pulmonary hypertension of the newborn, MAS
• Air leak syndromes [pneumothorax, pulmonary interstitial
emphysema (PIE)]
• Congenital diaphragmatic hernia: certain centers use
HFOV as a primary modality of respiratory therapy for
CDH
• Failure of conventional ventilation in the preterm infant
(severe RDS, PIE, pulmonary hypoplasia) or to reduce
barotrauma when conventional ventilator settings are high.
Initial Settings on High

Frequency Oscillatory Ventilation
On an HFOV ventilator, the oxygenation is controlled by
changing the MAP also called Paw or by the FiO2.
Ventilation is controlled by the amplitude (δP) and the
frequency.
In contrast to conventional ventilation, decreasing the
frequency increases the tidal volume delivered, thereby
increasing the carbon dioxide washout.
Initial settings: aim is to maximize recruitment of alveoli:
• Set MAP 2–3 cm H2O above the MAP on conventional
ventilation
• Set frequency to 8–10 Hz for term babies and 10–12 Hz for
preterms
• Generally, the frequency is set at 10 Hz, inspiratory time at
33%, and rarely require change throughout the course of
ventilation
• Set amplitude to get good vibrations (wobble) of chest,
abdomen, and upper thighs.
Ventilator Setting Adjustments on

High Frequency Oscillatory Ventilation
MSAF, meconium stained amniotic fluid; MAS, meconium aspiration syndrome;
ABG, arterial blood gas; HFOV, high frequency oscillatory ventilation; iNO, Table 3 describes ventilator adjustments on high frequency
inhaled nitric oxide; PPHN, persistent pulmonary hypertension of the newborn.
oscillatory ventilation.
Extubation Criteria Chest X-ray

• 12–14 cm H2O (larger babies may be extubated with PIP 14) Follow-up chest radiograph in 4–6 hours is recommended to
• Respiratory rate of 20–25 beats per minute assess the expansion.
• FiO2 requirement less than 40% Thereafter, repeat chest radiography with acute changes in
• Extubation to nasal CPAP/NIPPV is especially useful in patient condition.
VLBW babies
• Postextubation, periodic suctioning as needed, gentle
chest physiotherapy, and nebulization with ipratropium Table 3: Ventilator adjustments on high frequency oscillatory
help stabilization. ventilation
Poor oxygenation Over Under Over
High Frequency Oscillatory Ventilation
oxygenation ventilation ventilation
High frequency oscillatory ventilation (HFOV) is a type
Increase FiO2 Decrease FiO2 Increase Decrease
of mechanical ventilation that uses a constant distending
amplitude amplitude
pressure (MAP) with pressure variations (δP) oscillating
around the MAP at very high rates (up to 900 cycles per min). Increase MAP (Paw)* Decrease MAP Decrease Increase
This creates small tidal volume, often less than the dead space. (1–2 cm H2O) (1–2 cm H2O) frequency frequency
by 1–2 Hz by 1–2 Hz
Indications *Pressure airway.
18 At present, HFOV is generally used as a rescue therapy. MAP, mean airway pressure.
ch-04.indd 18 11/24/2016 12:15:58 PM

Suctioning
Key points
• Suction is indicated for diminished chest wall movement
(chest wobble), elevated carbon dioxide, and/or ))
Decision to provide respiratory support to neonate is never
worsening oxygenation suggesting airway or ET tube solely based on blood gas
obstruction, or if there are visible/audible secretions in ))
Noninvasive support is a preferable modality to avoid lung
the airway injury
• Avoid in the first 24 hours of HFOV unless clinically ))
So far, no continuous positive airway pressure machine has
indicated shown superiority over other as far as outcome is concerned
• Press the “stop” button briefly while quickly inserting and ))
Irrespective of the mode being used, always adjust ventilator
withdrawing suction catheter (PEEP is maintained). settings, keeping in mind pathophysiology of the disease state
))
High frequency ventilator has proven role as a rescue ventilator.
Weaning It is not a panacea of all respiratory problems of neonate.
• Reduce FiO2 to less than 40% gradually
• Reduce MAP when chest radiograph shows evidence of
overinflation (>9 ribs) or hyperoxemia on ABG SUGGESTED READINGs
• Reduce MAP by 1–2 cm H2O to 8–10 cm H2O 1. Boost II collaborative groups. Oxygen saturation and outcomes in preterm
• In air leak syndromes, reducing MAP takes priority over infants. N Engl J Med. 2013;368:2094-104.
weaning the FiO2 2. Donn SM, Sinha SK. Assisted ventilation and its complications. In: Martin
• Wean the amplitude in 2–4 cm H2O decrements based RJ, Fanaroff AA, Walsh MC (Eds). Fanaroff and Martin’s Neonatal-perinatal
on PaCO2 Medicine: Diseases of the Fetus and Infant, 9th edition. Philadelphia: Mosby/
• Discontinue HFOV when MAP 8–10 cm H2O and amplitude Elsevier; 2011.
3. Goldsmith J, Karotkin E. Assisted Ventilation of the Neonate, 5th edition. Saunders
20–25
publication; 2010.
• If infant is stable, oxygenating well and blood gases are
4. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB. COIN Trial
satisfactory, then infant could be extubated to CPAP or Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J
switched to conventional ventilation. Med. 2008;358(7):700-8.
19
ch-04.indd 19 11/24/2016 12:15:58 PM

Chapter 5
Persistent Pulmonary
Hypertension of the Newborn
Ram G Holla, Ira J Holla
INTRODUCTION lung function and growth. The developing lung is subject

to multiple genetic, pathological, and/or environmental
The fetal circulation is characterized by two parallel circu influences that can adversely affect lung adaptation,
lations, with a high pulmonary vascular resistance (PVR) and development, and growth, leading to pulmonary hypertension.
right-to-left shunting at the levels of the ductus arteriosus
and foramen ovale. At birth, there is a fall in the PVR due to
lung expansion and a simultaneous rise in systemic vascular Clinical Pearl
resistance (SVR). Humoral mediators released in response to • Persistent pulmonary hypertension of the newborn is caused
elevated arterial oxygen content and pH further constrict the by failure of pulmonary pressures to fall after birth leading to
ductus. This transforms the fetal circulation, characterized right-to-left shunting, hypoxemia, acidosis, and shock.
by pulmonary and systemic circuits in series to the adult
circulation, in which the two circuits function in parallel.
Failure to achieve or sustain the normal decrease in PVR
at birth, results in persistent pulmonary hypertension of the
CLINICAL MANIFESTATIONS
newborn (PPHN). OF PERSISTENT PULMONARY
Persistent pulmonary hypertension of the newborn is HYPERTENSION OF THE NEWBORN
a clinical syndrome characterized by sustained elevation
in PVR at birth, with resulting shunting from right to left Profound Hypoxemia and Labile Oxygenation
through persistent fetal channels.
• Hypoxemia out of proportion to the degree of parenchymal
lung disease. The outstanding feature of PPHN is central
MECHANISMS LEADING cyanosis that responds poorly to near 100% oxygen given
TO PERSISTENT PULMONARY by hood, but may respond to oxygen by ventilation
HYPERTENSION OF THE NEWBORN (TABLE 1) • Symptoms generally begin at birth, but definitely before 12
hours
Normal pulmonary vascular development in infancy requires • Differential saturation: preductal oxygen saturation may be
maintenance of low PVR after birth and is necessary for normal 10% higher (or more) than postductal saturation. Arterial
Table 1: Mechanisms leading to pulmonary hypertension in the newborn

Abnormally constricted blood Structurally abnormal pulmonary Hypoplastic pulmonary Functional obstruction to
vessels vasculature vasculature pulmonary flow
• Acute perinatal hypoxia • Placental insufficiency • Diaphragmatic hernia • Polycythemia
• Meconium aspiraton • Prolonged gestation • Lung dysgenesis • Hyperfibrinogenemia
• Sepsis or pneumonia • In utero closure of ductus • Pleural effusion
• Respiratory distress syndrome arteriosus: aspirin, nonsteroidal • Congential lung hypoplasia
• Hypoventilation anti-inflammatory drugs • Potter syndrome
• Central nervous system depression • Idiopathic • Thoracic dystrophies
• Hypothermia
• Hypoglycemia
ch-05.indd 20 11/24/2016 1:55:28 PM

Chapter 5: Persistent Pulmonary Hypertension of the Newborn
blood gas may show similar findings (PaO2 >20 mm, higher In all cases, response to treatment, particularly changes in
in the preductal sample). A subset of infants may have right- cardiac output and direction of ductal shunting, should be
to-left shunting only at the level of the foramen ovale and not assessed by repeated echocardiographic assessments
at the ductus, and may fail to show differential cyanosis. • Hyperoxia test: hyperoxia with or without hyperventilation
Respiratory symptoms are related to the underlying can help to predict the presence and reversibility of
disease, distress being the most severe in meconium aspiration pulmonary hypertension. Details are given in algorithm 1.
syndrome, diaphragmatic hernia, respiratory distress syndrome,
pneumonia, etc.
MANAGEMENT
DIFFERENTIAL DIAGNOSIS Management of a neonate with PPHN (Algorithm 2) constitutes
a medical emergency in which correction of hypoxia is
Primary pulmonary disease without elevated PVR and important for reversal of pulmonary hypertension, limitation of
structural heart disease associated with right-to-left shunting shunting, establishment of systemic perfusion, and prevention
should be excluded before a diagnosis of PPHN can be made. of end-organ damage.
• General measures:
Clinical Pearl {{ Correct underlying metabolic/hematological derange
ments:
• Differential oxygenation: SpO2 10% higher, PaO2 20 mmHg –– Correct acidosis, hypoglycemia, hypocalcemia,
higher in preductal than postductal samples. polycythemia, hypothermia
–– Treatment directed at the specific disorder causing
PPHN, e.g., congenital diaphragmatic hernia
Clinical Signs Favoring Cyanotic {{ Monitoring:
Congenital Cardiac Disease over Persistent –– Blood pressure—preferably intra-arterial
Pulmonary Hypertension of the Newborn –– Pulse oximetry (both pre- and postductal)
• Cardiomegaly –– Transcutaneous oxygen/carbon dioxide
• Weak pulses –– End-tidal CO2
• Active precordium –– Frequent postductal blood gas assessments
• Pulse differential between upper and lower extremities –– Monitoring of blood gas should be accompanied by
• Pulmonary edema charting of trends in PaO2, PaCO2, alveolar-arterial
• Grade 3+ murmur oxygen gradient (AaDO2), and oxygenation index
• Persistent pre- and postductal arterial oxygen tension (see appendix ‘A’)
{{ Sedation/paralysis: the hyper-reactive pulmonary circu
(PaO2) at or less than 40 mmHg.
lation is highly sensitive to catecholamines leading to
increased PVR. Stress should be blocked by silence,
Investigations and Diagnosis
avoidance of disturbance, gentle handling, and sedation
• Chest X-ray usually shows the underlying pulmonary –– Fentanyl (2–5 µg/kg/h)
disease or may be normal. The cardiac silhouette is usually –– Morphine (5–10 µg/kg/h) infused continuously
normal. Pulmonary blood flow may be diminished –– Very agitated or unstable neonates, particularly
• The electrocardiogram is usually normal for age if breathing out of phase, may be paralyzed with
• An echocardiography must be performed in every baby with pancuronium (0.1 mg/kg/dose; every 1–4 h PRN)
PPHN for diagnosis and exclusion of cardiac disease. The or vecuronium
size, direction, and location of shunt should be assessed. {{ Maintain hematocrit above 45%
Algorithm 1
Hyperoxia/hyperventilation test
21
PaO2, partial pressure of arterial oxygen; PaCO2, partial pressure of arterial carbon dioxide; PPHN, persistent pulmonary hypertension of the newborn.
ch-05.indd 21 11/24/2016 1:55:28 PM

Algorithm 2 {{ Nitric oxide: nitric oxide relaxes the vascular smooth

Outline of management of persistent pulmonary muscle and causes pulmonary vasodilation. Inhaled
hypertension of the newborn nitric oxide (iNO) is administered by conventional
or high frequency ventilation in doses of 5–20 ppm,
diffuses into ventilated alveoli, causes localized
vasodilatation and improves oxygenation, in addition
to decreasing PVR
• Extracorporeal membrane oxygenation (ECMO): ECMO
often is lifesaving therapy for infants with PPHN who fail
conventional management and/or iNO treatment.
Ligation or pharmacological closure of the duct is not useful
and may be detrimental. There is insufficient data to justify the
use of other proposed medical therapies including sildenafil,
magnesium sulfate, calcium channel blockers, adenosine,
inhaled prostacyclin, ethyl nitrite, bosentan (endothelin
NIBP, noninvasive blood pressure; PaCO2, partial pressure of arterial carbon
dioxide. receptor antagonist), and inhaled or intravenous tolazoline.
• Ventilation: optimize lung recruitment and reduce

Appendix
ventilation-perfusion mismatch: specific approaches to
[(Barometric pressure – Partial pressure of
respiratory support and mechanical ventilation vary. A
water vapor) × FiO2 ] – PaCO2
gentle approach that maintains adequate oxygenation 1. PaO2 =
and mild hyperventilation (PaCO2 35–45 mmHg, and pH RQ
at 7.35–7.45), generally lowers the PVR to the extent of [(760 – 47) × 0.21] – 40
abolishing right-to-left shunting. The state of the underlying = 0.8
lung should dictate the specific respiratory management
strategy, keeping always in mind that high intrathoracic = 150 – 50 = 100 (approximately)
pressure may worsen the situation by impeding cardiac
output and elevating PVR. High frequency oscillatory Alveolar to arterial oxygen gradient = PaO2 – PAO2
ventilation (HFOV) is often useful in treating infants whose Where RQ indicates respiratory quotient; PaO2, alveolar oxygen
PPHN is associated with severe pulmonary parenchymal gradient; PAO2, arterial oxygen gradient; and PaCO2, partial pressure
disease. Neonates with PPHN are unstable in their of CO2.
cardiopulmonary status and weaning from ventilation
(MAP × FiO2 × 100)
should be done very gradually to prevent reversal. 2. Oxygenation index:
Surfactant therapy should be used where applicable PaO2
• Optimize cardiac output and left ventricular function,
maintenance of systemic blood pressure: the aim of
Key points
cardiovascular management is to optimize systemic
blood pressure to levels above the pulmonary pressure in ))
Persistent pulmonary hypertension of the newborn (PPHN) is
order to minimize or eliminate right-to-left shunt. Target more common in term and post-term newborns
mean blood pressure levels would be 45–55 mmHg. Low ))
Assessment of pre- and postductal saturations helps in early
blood pressure may be normalized by the use of: diagnosis
{{ Volume expansion: especially in hypovolemic conditions ))
Congenital heart disease should always be ruled out in a
(e.g., hemorrhage, hydrops, capillary leak) or decreased patient having clinical features of PPHN
SVR (e.g., septic shock) or systemic hypotension ))
High frequency oscillatory ventilation and inhaled nitric
{{ Vasopressors: dopamine, dobutamine, and/or adrenaline oxide have revolutionized the treatment of PPHN.
often are necessary to achieve adequate cardiac
output. Dopamine in doses more than 10 µg/kg/min
and adrenaline increase SVR through stimulation of SUGGESTED READINGs
α- and β-receptors. High doses of both may stimulate 1. Baquero H, Sloiz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with
pulmonary α-receptors, leading to increased PVR. When persistent pulmonary hypertension of the newborn: a pilot randomized blinded
cardiac function is poor, cardiotonic medications, such study. Pediatrics. 2006;117(4):1071-83.
as milrinone that both enhance cardiac output and lower 2. Konduri GG, Solimano A, Sokol GM, Singer J, Ehrenkranz RA, Singhal N, et al.
PVR, might be useful A randomized trial of early versus standard inhaled nitric oxide therapy in term
and near-term newborn infants with hypoxic respiratory failure. Pediatrics.
• Decrease PVR: 2004;113:559-64.
{{ Alkalinization: alkalosis reduces PVR. Alkalosis 3. Steinhorn RH, Farrow KN. Pulmonary hypertension in the neonate. Neo Reviews.
can be achieved by gentle hyperventilation and/or 2007;8:e14-21.
22 conservative use of metabolic therapy with sodium 4. Wood BR. Physiological principles. In: Goldsmth JP, Karotkin EH (Eds). Assisted
bicarbonate, aiming for a pH of 7.35–7.45 ventilation of the neonate, 4th ed. Philadelphia: WB Saunders; 2003. pp. 19-46.
ch-05.indd 22 11/24/2016 1:55:28 PM

Chapter 6
Bronchopulmonary Dysplasia
Naveen Bajaj, Ruchi Nanawati
INTRODUCTION Table 1: National Institute of Health definition: broncho

pulmonary dysplasia diagnostic criteria
Chronic lung disease (CLD) or bronchopulmonary dysplasia
(BPD) is a clinical syndrome following very preterm delivery Gestational age <32 weeks >32 weeks
that results in decreased oxygenation, an increased work of Time point of 36 weeks PMA or >28 days but <56 days
breathing, and lung abnormalities that persist into childhood. assessment discharge to home postnatal age or
In very low birth weight (VLBW) babies, overall incidence is whichever comes first discharge to home
22% and is inversely related to gestational age and birth weight. whichever comes first
Although it can occur in full term infants, it is uncommon in Treatment with oxygen >21% for at least 28 days PLUS
infants born after 32 weeks.
Mild BPD Breathing room air Breathing room air at
at 36 weeks PMA or 56 days postnatal age
Clinical Pearl discharge, whichever or discharge, whichever
comes first comes first
• Bronchopulmonary dysplasia mainly occurs in very low birth
weight babies. Moderate BPD Need for <30% Need for <30% oxygen
oxygen at 36 weeks at 56 days postnatal age
PMA or discharge, or discharge, whichever
DEFINITION whichever comes first comes first
Severe BPD Need for ≥30% Need for ≥30% oxygen
Bronchopulmonary dysplasia has been defined by different
oxygen and/or and/or positive pressure
authors as the need of supplemental oxygen either at 28 days positive pressure (PPV/NCPAP) at 56
of life or at 36 weeks of postconceptional age. The most recent (PPV/NCPAP) at days postnatal age or
National Institute of Health (NIH) consensus definition is 36 weeks PMA or discharge, whichever
described in table 1. discharge, whichever comes first
The more specific old term BPD instead of more recent comes first
term CLD is preferred, because this disease is clearly distinct BPD, bronchopulmonary dysplasia; PMA, postmenstrual age; NCPAP, nasal
from the multiple CLDs of later life. continuous positive airway pressure; PPV, positive pressure ventilation.
Old and New Bronchopulmonary Dysplasia

PATHOGENESIS
In recent years, with improved survival of extreme premature
infants, the clinical and X-ray findings that define BPD has Bronchopulmonary dysplasia is caused by multiple adverse
changed and a milder clinical disease called “new BPD” has events during pre- and postnatal period (Algorithm 1).
emerged (Table 2).
Predisposing Factors
Clinical Pearl • High intermittent positive pressure ventilation/oxygen
requirement
• New bronchopulmonary dysplasia (BPD), a milder form of
• Barovolutrauma
disease is more common than old BPD nowadays.
• High initial fluid intake
ch-06.indd 23 11/18/2016 4:59:22 PM

Table 2: Old versus new bronchopulmonary dysplasia CLINICAL FEATURES

Old BPD (Classic BPD) New BPD (Atypical BPD) Bronchopulmonary dysplasia usually develops in premature
Infants at risk Larger, more mature Very low birth weight neonates being treated with oxygen and positive pressure
ventilation for respiratory failure, most commonly due to RDS.
Airway injury Severe Mild-to-none It is often anticipated when mechanical ventilation or oxygen
Fibrosis Severe Minimal dependence extend beyond 10–14 days. Common clinical
pointers are:
Alveoli Develop in regions Uniform arrested • Preterm on ventilator, failure to wean, extubation failures
without fibrosis development
• Persistent or increased oxygen requirement
Causes Oxygen, ventilation Interference with • Signs of respiratory distress
development • Barrel shaped chest
X-ray Overinflation and Diffuse haziness or fine, • Severe bronchospasm
cystic emphysema lacy pattern • Cardiomegaly, hypertension, and cor pulmonale
• Copious secretions, tracheo- and bronchomalacia
BPD, bronchopulmonary dysplasia.
• Feed intolerance, failure to thrive.
• Respiratory distress syndrome (RDS), patent ductus

arteriosus (PDA), pulmonary interstitial emphysema
Clinical Pearl
• Chorioamnionitis: fetal inflammatory response syndrome • Ventilatory or oxygen dependency beyond 2 weeks of life is an
• Nosocomial infections early suspicious sign of bronchopulmonary dysplasia.
• Colonization with Ureaplasma urealyticum
• Genetic predisposition.
Chest X-ray
Clinical Pearl Northway originally described the four stages of radiographic
appearances in BPD (Table 3). The new BPD on X-ray only
• Prematurity, respiratory distress syndrome, ventilation, and
shows diffuse haziness, occasionally, infiltrates or segmental
infections are common predisposing factors.
atelectasis.
Algorithm 1
Bronchopulmonary dysplasia pathogenesis
24
ch-06.indd 24 11/18/2016 4:59:22 PM

Chapter 6: Bronchopulmonary Dysplasia
Table 3: X-ray staging and appearance of bronchopulmonary Algorithm 2

dysplasia Management strategies for bronchopulmonary dysplasia
Stage Day X-ray appearance
Stage I (mild) 2–3 days Identical to respiratory distress
syndrome
Stage II 4–10 days Pulmonary parenchymal opacities
(moderate)
Stage III 10–20 Radiolucent cysts giving bubbly lung
(severe) days appearance
Stage IV 30 days Marked hyperinflation,
(advanced) emphysematous lung, fibrous streaks,
and cardiomegaly
Pulmonary Functions
• Increased airway hyper-reactivity, high airway resistance,
and decreased compliance results in markedly increase
work of breathing, hypoventilation, and hypercapnia
• Airway resistance increases markedly during active
expiratory efforts such as in physical agitation
• Flow volume loops: ski slope sign in severe cases BPD, bronchopulmonary dysplasia; CPAP, continuous positive airway pressure;
• Functional residual capacity is initially normal or low but PTV, patient triggered ventilation; TPN, total parenteral nutrition; PDA, patent
ductus arteriosus; ELBW, extremely low birth weight; SpO2, blood oxygen
increases in advanced stages. saturation level.
Echocardiography
Table 4: Ventilatory strategy and arterial blood gas targets in
Pulmonary hypertension may be seen in established BPD and
bronchopulmonary dysplasia
reflects the severity of disease.
Ventilatory strategy Target arterial blood gas values
DIFFERENTIAL DIAGNOSIS Slow rates: 20–40/min pH: 7.25–7.3
• Bacterial or viral pneumonia Lowest possible PIP: 15–20 PaO2: 60–80 mmHg
• Pulmonary lymphangiectasia cm H2O
• Recurrent aspirations Moderate PEEP: 5–6 cm H2O PaCO2: 55–60 mmHg
• Total anomalous pulmonary venous connections. Inspiratory time: 0.3–0.5 s SpO2: 89–94%
Tidal volume: 5–8 mL/kg PaCO2 levels can be ignored if pH
TREATMENT STRATEGIES FOR SUSPECTED >7.25
BRONCHOPULMONARY DYSPLASIA PIP, peak inspiratory pressure; PEEP, positive end-expiratory pressure; Ti,
inspiratory time, SpO2, blood oxygen saturation level; PaO2, partial pressure of
Though there is no single magical therapy for BPD, but multiple arterial oxygen; PaCO2, partial pressure of arterial carbon dioxide.
“best practices” result in better outcome of these infants. These
include multidisciplinary preventive and treatment strategies.
Algorithm 2 depicts the timeline and management strategies Clinical Pearl
of BPD.
• Gentle ventilation, early extubation, and use of noninvasive
Respiratory support: gentle ventilation to maintain adequate ventilation are the goals.
gas exchange while minimizing ventilator induced lung
injury. The aim is to ventilate for the shortest possible time,
Delivery of oxygen: warm humidified oxygen by nasal cannula
wean gradually, use methylxanthines (caffeine preferred than
or hood to maintain SpO2 between 89 and 94%. Infants with
aminophylline) for apneas and in periextubation period, and
no other medical problem can be given home oxygen therapy
extubate to nasal continuous positive airway pressure (CPAP)
by nasal cannula from a portable oxygen cylinder/oxygen
as early as possible. The ventilator strategy and the targets used
concentrator. Monitor oxygen requirement and weight gain.
in these cases are summarized in table 4.
Postextubation physiotherapy is helpful in managing Desaturation during and after feeding: managed by increasing
segmental collapse and increased airway secretions. the inspired oxygen concentration.
25
ch-06.indd 25 11/18/2016 4:59:23 PM

Bronchopulmonary dysplasia spells: BPD spells which are Preventive Strategies

sudden episodes of cyanosis and desaturation due to expiratory
Avoidance of factors that predispose to lung injury is
flow limitation may require sedation and paralysis.
cornerstone of management of BPD. Some of the proven
Fluid and nutrition: even though these neonates have an strategies in the management of BPD are as follows:
augmented metabolic demand requiring higher intake of • Antenatal steroids
calories (120–160 kcal/kg/day) to sustain growth, they cannot • Early surfactant therapy
tolerate increased fluid volumes. Hence, fluids are restricted • Ventilation strategies: aim is to minimize lungs injury by
to 120–150 mL/kg/day. Neonates who cannot be fed should optimizing the ventilator strategies which includes:
be given parenteral nutrition. Those on oral feeds may be {{ Early institution of CPAP
fed calorie-dense feeds (24–30 kcal/oz) by fortification of {{ Use of intubation-surfactant-extubation (INSURE)
expressed breast milk with human milk fortifier or by using technique followed by CPAP
high calorie formula. Supplementation with medium chain {{ Use of patient triggered ventilation: more physiological
triglyceride oil is another option. Adequate intake of calcium, {{ Permissive hypercapnia: accepting PCO levels as high
2
phosphorus, vitamins, and iron should be ensured. as 55 mmHg with pH greater than or equal to 7.25
Treatment of infections: bacterial or fungal infections are {{ Avoidance of hyperoxia: target SpO : 85–92% in acute
2
frequent in BPD infants and worsen the lung damage and phase of ventilation
should be investigated and treated. {{ High frequency oscillation: less injurious to lungs, but
no evidence for its benefits in routine use.

Drug treatment (Table 5): before a drug is initiated in a case • Early use of caffeine therapy: within first 72 hours,
of BPD, one should always revisit the decision and seriously preferably as early as feasible
consider if that drug is required.
• Low fluid intake
Follow these principles of a drug therapy: • Aggressive nutrition strategies
• All drugs have adverse effects • Prevention of nosocomial infections
• Anticipate that a drug may have no therapeutic effect • Aggressive treatment of PDA
• If you start a drug, be willing to stop it. • Vitamin A: essential for lung development and differen
tiation. Its use in extremely low birth weight (ELBW) babies
Clinical Pearl as 5,000 IU IM three times/week for 4 weeks reduces risk
of BPD
• Avoid using drug, especially steroids. Use steroids only in • Inhaled nitric oxide: proven role yet to be established
ventilator dependent babies who are more than 1 week of life, • Corticosteroids: not recommended.
in smallest possible dose and for shortest duration.
Table 5: Drug dosage

Drug Dosage Side effects
Caffeine • Loading: 20–25 mg/kg IV over 30 min or PO • Restlessness, vomiting, and
(equivalent to 10–12.5 mg/kg caffeine base). tachycardia
• Maintenance: 5–10 mg/kg of caffeine citrate IV
or PO once daily
Diuretics
Furosemide • IV: 1–2 mg/kg/dose q 12–24 hourly • Hypercalciuria
• Oral: 2–6 mg/kg q 6–8 hourly • Nephrocalcinosis
Chlorthiazides • 10–20 mg/kg q 12 hourly • Ototoxicity
Spironolactone • 0.5–1.5 mg/kg q 12 hourly • Hypokalemia, alkalosis
Bronchodilators Inhalation
Salbutamol • 0.1–0.5 mg/kg q 2–6 hourly
• Tachycardia, tremors
Ipratropium • 0.025 mg/kg q 8 hourly
Dexamethasone
Use minimal possible dose and for minimum • 0.15 mg/kg/day x 3 days • Hyperglycemia, hypertension,
duration of 3–7 days and only in infants who • 0.1 mg/kg/day x 2 days gastrointestinal hemorrhage, and
are >7 days old and cannot be weaned off from • 0.05 mg/kg/day x 2 days in two divided doses perforation
mechanical ventilation • Poor neurodevelopment outcome
26 IV, intravenous; PO, per os.
ch-06.indd 26 11/18/2016 4:59:23 PM

Chapter 6: Bronchopulmonary Dysplasia
• Long-term neurodevelopmental sequelae

Clinical Pearl • Recurrent hospitalization.
• Respiratory strategies aim to minimize lung injury and
early use of caffeine reduces the chances of developing Key points
bronchopulmonary dysplasia..
))
Bronchopulmonary dysplasia (BPD) is mainly a disease
of extreme preterm and very low birth weight babies,
INFANT STIMULATION contributing to morbidities like neurodevelopment impair
ment, recurrent respiratory illnesses, and growth failure
AND PARENTAL SUPPORT ))
Prematurity, severity of respiratory disease, and ventilation are
Infants with severe BPD may be ventilator dependent the main risk factors
for many weeks or months and thus, deprived of normal ))
Preventive strategies like antenatal steroids, early use of
parental stimulation. A well-organized stimulation program surfactants, gentle ventilation, early and aggressive use
and parental participation helps in reducing infant’s neuro of continuous positive airway pressure, and early caffeine
developmental delays and allaying parental anxiety. therapy reduce the incidence of BPD
))
Early extubation should be the goal for all preterm babies
requiring mechanical ventilation
DISCHARGE PLANNING ))
Systemic steroids should be used only in selective cases
Usually, oxygen can be discontinued in before discharge. ))
Nutrition, early stimulation, and parental anxiety should be
However, home oxygen therapy is a safe alternative to long- addressed timely
term hospitalization in selected cases: ))
Use of anti-inflammatory agents like inhaled nitric oxide,
• Stable babies with no other medical illness late use of surfactant and antioxidants may be promising
• Stable oxygen requirement therapies in the future.
• Parents prepared and trained
• Follow-up is ensured.
SUGGESTED READINGs
OUTCOME 1. Bancalari EH, Walsh MC. Bronchopulmonary dysplasia. In: Martin RJ, Fanaroff AA,
Walsh MC (Eds). Fanaroff and Martin’s Neonatal-Perinatal Medicine Disease of
The outcome has improved because of better management and the Fetus and Infant, 9th ed. Elsevier; 2011. pp. 1179-91.
milder form of the disease. 2. Davis JM, Rosenfield WN. Bronchopulmonary dysplasia. In: MacDonald MG, Seshia
Mortality is low; however, when it occurs is usually because MMK, Mullett MD (Eds). Avery’s Neonatology Pathophysiology and Management
of the Newborn, 6th ed. Lippincott Williams and Wilkins; 2005. pp. 568-99.
of respiratory failure, infections, pulmonary hypertension, and
3. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med.
cor pulmonale. Infants with severe BPD are at higher risk of: 2001;163:1723-9.
• Growth failure 4. Korones Sheldon B. Complications. In: Goldsmith JP, Karotkin EH (Eds). Assisted
• Feeding problems and gastroesophageal reflux Ventilation of the Neonate, 5th ed. Saunders; 2011. pp. 389-425.
• Recurrent chest infections 5. Patel RM, Leong T, Carlton DP, Vyas-Read S. Early caffeine therapy and clinical
• Hyper-reactive airway disease outcomes in extremely preterm infants. J Perinatol. 2013;33(2):134-40.
27
ch-06.indd 27 11/18/2016 4:59:23 PM

Chapter 7
Patent Ductus Arteriosus
Kiran P Sathe, Anjali Kulkarni
INTRODUCTION
It is the abnormal persistence of the normal fetal vessel
joining the pulmonary trunk to the descending aorta. It is one
of the commonest congenital cardiac anomaly in neonatal
period especially in the preterm neonates. It may result in
altered hemodynamics and can complicate the clinical course
in the inital days of life in sick neonates.
INCIDENCE
Vermont Oxford Network (2006) of nearly 40,000 preterm
infants with a birthweight 501–1,500 g showed the overall
Fig. 1: Normal flow of blood through the ductus during the fetal
incidence of patent ductus arteriosus (PDA) to be 37.2%. The
life (marked by solid arrows) compared to the flow during the
incidence of PDA in infants with gestational ages of 24, 25, extrauterine life (marked by dotted arrows)
and 26 weeks was 76.9, 69.5, and 61.5%, respectively. Although
spontaneous permanent ductus arteriosus closure occurs • Intravenous fluid overload
in nearly 34% of extremely low birth weight neonates 2–6 • Perinatal asphyxia
days postnatally and in the majority of very low birth weight • Congenital syndromes
neonates within the first year of life, 60–70% of preterm infants • High altitude.
of less than 28 weeks’ gestation receive medical or surgical
therapy for a PDA. Clinical Pearl
• Patency or closure of ductus depends on the balance between
PATHOPHYSIOLOGY vasodilator and vasoconstrictive factors. Oxygen therapy
During fetal life, ductus arteriosus helps to shunt blood away in preterm neonates has a vasoconstricting effect while
from the high resistance pulmonary circulation (Fig. 1). prostaglandins (PGE2) have vasodilator effect.
Postdelivery, the pulmonary vascular resistance falls with
increase in the oxygen tension. This coupled with increase in
systemic vascular resistance following clamping of the cord, CLINICAL PRESENTATION
results in reversal of the ductal shunt, eventually resulting in Clinical presentation of PDA has been discussed in detail in
closure of the ductus. While functional closure occurs within algorithm 1.
first 4 days of life, anatomical closure occurs by second week of In one study, pulse quality (43%) and murmur (42%) had
life. Failure of the ductal closure results in PDA. the highest mean sensitivities. Corresponding specificities
were 74% for pulse volume and 87% for murmur. The
Predisposing Factors combination of a cardiac murmur with an abnormal pulse
• Prematurity less than 34 weeks volume had the highest positive predictive value (77%). The
• Respiratory distress syndrome and surfactant adminis radiological examination did not improve the observers’ ability
tration to distinguish between patients with and without PDA.
ch-07.indd 28 11/18/2016 5:00:42 PM

Chapter 7: Patent Ductus Arteriosus
Algorithm 1
Clinical presentation of patent ductus arteriosus
PDA, patent ductus arteriosus; HMD, hyaline membrane disease; CLD, chronic lung disease.
Algorithm 2
Clinical Pearls
Management of patent ductus arteriosus
• Increase in the pulmonary fluid in an infant with previously
improving or stable respiratory status should raise a suspicion
of underlying patent ductus arteriosus (PDA)
• Similar findings can occur with other cardiac lesions, such as
aortic-pulmonary window or an arteriovenous fistula
• Clinical signs are very unreliable for diagnosis of PDA in preterm
infants. Echocardiography should always be used for diagnosis.
INVESTIGATIONS
Two-dimensional echocardiography with Doppler ultra
sound: identifies of PDA, associated cardiac defects and
direction of flow with cardiac contractility. Signs of hemo • Was practiced earlier but no longer recommended as
dynamically significant duct on echocardiography are: associated with side effects like increased broncho
• Left atrium-to-aortic root diameter ratio of greater than or pulmonary dysplasia (BPD) in those who never developed
equal to 1.4 in the parasternal long axis view PDA and the fact that most PDAs don’t require treatment.
• Ductus arteriosus diameter of greater than or equal to
1.4 mm/kg body weight Conservative Treatment
• Holodiastolic flow reversal in the descending aorta
Managing PDAs with supportive therapies as discussed in
• Pulse wave Doppler main pulmonary artery demonstrates
the chapter and waiting for a spontaneous closure as can
turbulent systolic and diastolic flow and abnormally high
happen in approximately 30% cases in first week and many can
antegrade diastolic flow (≥0.5 m/s).
close spontaneously in the first year.
Clinical Pearls Symptomatic Treatment
• Always rule out a duct dependent lesion on echocardiogram • Treatment only when the PDA is causing significant
in case the facility is available before starting pharmacotherapy morbidity and not responding to treatment
• Duct dependent pulmonary or systemic blood flow should be • Indications:
{{ Hemodynamically significant PDA on ventilator
identified on echocardiography, as patent ductus arteriosus
closure is contraindicated in such patients. beyond first week of life and not improving despite
supportive treatment
{{ Hemodynamically significant PDA with necrotizing
MANAGEMENT (ALGORITHM 2) enterocolitis (NEC) or renal failure (in such cases

ibuprofen or surgery is preferred over indomethacin
Prophylactic Treatment • Second course may be used in case the baby remains on
• Treatment either medical or surgical closure of PDA before ventilator despite the use of one course of pharmacotherapy. 29
the symptoms began The reported closure rate with the second dose is 40%.
ch-07.indd 29 11/18/2016 5:00:42 PM

reports of persistent pulmonary hypertension of the

Clinical Pearl newborn with ibuprofen use and nonstatistical increase in
• Not all patent ductus arteriosus require closure. The optimal the incidence of chronic lung disease with its use
current management approach is not known as there is • Dose: 10 mg/kg first dose followed by 5 mg/kg for two more
paucity of large randomized controlled trials comparing the doses 24 hours apart
three approaches in the current era of neonatal practice. • Intravenous formulations mostly tried but since this one is
not available in India at present, one should use the oral
form despite the paucity of literature on the same.
Supportive Treatment
• Thermoneutral environment Paracetamol
• Maintenance of hematocrit >35% to increase the pulmonary • Mainly observational data, no randomized controlled trial
vascular resistance available at present
• High positive end-expiratory pressure and lower inspiratory • Dose 60 mg/kg/day in four divided doses for 2–5 days
time • Indications: failure to respond to or contraindication to use
• No loop diuretics: results in increased ductal patency of cyclooxygenase (COX) inhibitors
because of vasodilatory prostaglandin E2 release and • Safety not established at present
increased incidence of side effects. If required, use thiazide • Not currently recommended.
diuretics
• Moderate fluid restriction: 110–130 mL/kg/day
Surgical Ligation
• Monitoring of weight at least twice daily
• Serum electrolytes and renal functions are to be monitored • Indications: failure of two courses or contraindication for
twice daily use of COX inhibitors who have a large PDA and on high
• Daily ultrasonography (USG) head. ventilator settings
• Increased adverse effects with ligation, hence not preferred
Clinical Pearl • Postoperative: risk of significant brain injury due to intra
operative compromise or postoperative hemo dynamic
• Feeding during treatment with pharmacotherapy can instability. Use of functional echocardiography after
continue with enteral trophic feeds preferably human milk. surgery should be considered to manage shock.
• Coil or device closure for symptomatic PDA with normal
Agents Used for Pharmacotherapy pulmonary artery pressure in children with more than 3 kg.
Indomethacin
Key points
• Dose: 0.2 mg/kg/dose every 12 hours for three doses
• Targeted treatment: discontinuing treatment when the ))
Patent ductus arteriosus (PDA) is the persistence of normal
sequential echoes show closure even before the full course. fetal vessel and usually complicates preterm deliveries
Similar closure rates comparable to full course are there ))
Nonspecific clinical presentation mandates echocardiographic
but a nonstatistical trend toward higher intraventricular evaluation to conclusively diagnose PDA and assess for any
hemorrhage (IVH) in the targeted group does not warrant associated cardiac comorbidities
using this approach till further trials ))
Nonjudicious use of oxygen therapy in preterm babies can be
• Long course: 0.1–0.2 mg/kg/dose once a day for 5 days is harmful and can inadvertently lead to ductus closure in cases
not recommended now as although the closure rates were with duct dependent lesions
similar, the incidence of NEC was increased ))
Therapeutic closure of ductus is not warranted except in
• Side effects: decreased blood flows to different organs symptomatic cases
resulting in cerebral ischemia, renal failure, and NEC. ))
Medical closure is easier, effective, safer, and preferred over
There is also increased risk of intestinal perforation in surgical closure.
those with concomitant use of hydrocortisone
• Contraindications:
{{ Blood urea greater than 60 mg/dL SUGGESTED READINGs
{{ Serum creatinine greater than 0.8 mg/dL
1. Hermes-DeSantis ER, Clyman RI. Patent ductus arteriosus: pathophysiology and
{{ Urine output less than 1 mL/kg/h management. J Perinatol. 2006;26:S14-8.
{{ Platelet count less than 50,000/mm3 2. McNamara PJ, Sehgal A. Towards rational management of the patent ductus
{{ Necrotizing enterocolitis arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal.
{{ Active bleeding 2007;92(6):F424-7.
{{ Intraventricular hemorrhage grade III/IV or if prog 3. Niu MC, Mallory GB, Justino H, Ruiz FE, Petit CJ. Treatment of severe pulmonary
ression of IVH is demonstrated in earlier cranial USG. hypertension in the setting of the large patent ductus arteriosus. Pediatrics.
2013;131(5):e1643-9.
4. Sasi A, Deorari A. Patent ductus arteriosus in preterm infants. Indian Pediatr.
Ibuprofen 2011;48:301-8.
30 • Similar efficacy as compared to indomethacin with lesser 5. Sekar KC, Corff KE. Treatment of patent ductus arteriosus: indomethacin or
NEC and renal dysfunction. There is, however, few case ibuprofen? J Perinatol. 2008; 28(1):S60-2.
ch-07.indd 30 11/18/2016 5:00:42 PM

Chapter 8
Neonatal Shock
Ranjan K Pejaver, Manisha Halkar
INTRODUCTION Continued
The term “shock” denotes a complex clinical syndrome {{ Sequestered blood

characterized by acute failure of the circulatory system to {{ Accidental or incorrect removal of arterial lines
{{ Iatrogenic causes such as iatrogenic laboratory blood outs
maintain adequate tissue and organ perfusion which leads
to inadequate oxygen and nutrient substrate delivery to body • Plasma or fluid losses
{{ Effusions (erythroblastosis fetalis, nonimmune hydrops)
tissues and compromised metabolic waste product removal.
{{ Break in skin integrity
{{ Myelomeningocele, gastroschisis
INCIDENCE • Dehydration
{{ Emesis or diarrhea, insensible water loss or repeated discarding
Shock is a common morbidity which presents as a neonatal of the gastrointestinal residuals
emergency. As it is a multi factorial disorder the true incidence Cardiogenic shock
is difficult to estimate. • Left ventricular outflow tract obstruction
{{ Hypoplastic left heart syndrome, critical aortic stenosis or
coarctation of aorta
PATHOPHYSIOLOGY OF SHOCK • Large left-to-right shunts
{{ Ventricular septal defect
The pathophysiology of shock has been outlined in algorithm 1.
{{ Atrial septal defect
{{ Patent ductus arteriosus

Algorithm 1
• Infective myocarditis
Pathophysiology of shock {{ Enterovirus
{{ Herpes simplex virus-2
• Cardiomyopathy
{{ Dilated cardiomyopathy
{{ Hypertrophic cardiomyopathy (infant of diabetic mother)
• Dysrhythmia
{{ Prolonged, unrecognized supraventricular tachycardia
ETIOLOGY OF SHOCK {{ Bradyarrhythmias
{{ Complete heart block (systemic lupus erythematosus in mother)

Box 1 describes etiology of different types of shock. {{ Intrapartum or postpartum asphyxia
{{ Metabolic acidosis
Box 1: Etiology of shock {{ Severe hypoglycemia, hypocalcemia
Hypovolemic shock {{ Inborn error of metabolism (glycogen storage disease, muco
• Acute and/or chronic blood loss polysaccharidoses, disorders of fatty acid metabolism)
{{ Placental abruption or placenta previa • Distributive shock
{{ Uterine/umbilical cord rupture {{ Sepsis
{{ Difficult delivery leading to trauma and/or hypoxia • Obstructive shock

{{ Maternal-fetal transfusion {{ Tension pneumothorax
{{ Twin-to-twin transfusion {{ Congenital diaphragmatic hernia
Continued
ch-08.indd 31 11/18/2016 5:02:01 PM

Clues on History Suggesting Etiology transducer or indirectly through noninvasive techniques

which include manual oscillometric techniques and
• Significant blood loss from placental anomalies; hypo
automated Doppler techniques.
volemic shock
• Maternal chorioamnionitis; septic shock
• Hydrops fetalis; distributive shock Clinical Pearl
• Maternal history of systemic lupus erythematosus or
• Noninvasive methods may overestimate the blood pressure in
Sjögren's syndrome; cardiogenic shock
hypotensive infants.
• Prior maternal history of stillbirth
• Foul smelling or meconium stained amniotic fluid; septic
shock
INVESTIGATIONS IN NEONATAL SHOCK
• Antenatal asphyxia with abnormal heart rate pattern;
cardiogenic shock Investigations to be done in neonatal shock have been enlisted
• Congenital heart disease detected by prenatal ultrasound; in table 3.
cardiogenic shock
Table 3: Investigations in neonatal shock
DIAGNOSIS For determining the cause of For management of shock
shock
• Neonates with shock present with diverse signs and
symptoms Sepsis screen and blood culture: Blood gas to alter ventilation
rule out sepsis and look for acidosis
• In clinical practice, the reference range blood pressure
limits are defined as the gestational and postnatal age Echocardiography if cardiogenic Serum lactate: serial monitoring
dependent blood pressure values between the 5th (or 10th) shock is suspected to gauge the progress
and 95th (or 90th) percentiles Chest X-ray to rule out Functional echo: to study the
• However, by the third day of life, most preterm infants, even pneumothorax or other superior vena cava flow and
with 24–26 weeks’ gestation, have a mean blood pressure of respiratory pathologies and study the right ventricular and
30 mmHg or greater (Table 1) cardiac disease left ventricular output
• As a rough rule of thumb, the lower limit of normal mean Kleihauer-Betke test to rule out Ionized calcium: correcting
blood pressure in mmHg on the day of birth is appro fetomaternal hemorrhage hypocalcemia may improve
ximately equal to the gestational age in weeks (Table 2) cardiac contractibility
• Measurement of neonatal blood pressure can be completed Ultrasonography head to rule Serum cortisol to correct
directly through invasive techniques, i.e., direct manometry out intraventricular hemorrhage relative adrenal insensitivity
using an arterial catheter or use of an in-line pressure
Serum biochemistry
Table 1: Blood pressure range in preterm infants by age
Day Systolic range (mmHg) Diastolic range (mmHg) Clinical Pearl
1 48–63 25–35
• Use of functional echocardiography aids assessment of
2 54–63 30–39 cardiac output and may help choice of inotropes.
3 53–67 31–43
4 57–71 32–45
MANAGEMENT OF NEONATAL SHOCK
5 56–72 33–47
Management of neonatal shock has been outlined in
6 57–71 32–47
algorithm 2.
7 61–74 34–46
Clinical Pearls
Table 2: Blood pressure ranges in term infants
• Low blood pressure in a preterm baby may not need to be
Age Systolic (mmHg) Diastolic (mmHg) Mean (mmHg) treated unless associated with signs of poor perfusion
1h 70 44 53 • Since dopamine and dobutamine have a half-life of 2 minutes,
12 h 66 41 50 any change in their concentration would result in steady state
in 10 minutes, and hence, changes in their dosage should be
Day 1 71 ± 9 43 ± 10 55 ± 9
made every 15 minutes till the blood pressure stabilizes.
Day 3 77 ± 12 49 ± 10 63 ± 13
Day 6 76 ± 10 49 ± 11 62 ± 12
Vasoactive Agents Used in Neonatal Shock
Week 2 78 ± 10 50 ± 9 –
Vasoactive agents used in neonatal shock have been discussed
32 Week 4 85 ± 10 46 ± 9 –
in table 4.
ch-08.indd 32 11/18/2016 5:02:01 PM

Chapter 8: Neonatal Shock
Algorithm 2
Management of neonatal shock
SBF, skin blood flow; PDA, patent ductus arteriosus; PPHN, persistent pulmonary hypertension of the newborn.
Table 4: Vasoactive agents used in neonatal shock

Agent type Agent Dosage Comments
Volume Isotonic sodium chloride solution 10–20 mol/kg IV Hypovolemic shock, readily available
expanders Plasma 10–20 mL/kg IV Disseminated intravascular coagulation, expensive
Whole blood products 10–20 mL/kg IV Hypovolemic due to blood loss
Reconstituted blood products 10–20 mL/kg IV Use O negative
Vasoactive Dopamine 5–20 µg/kg/min IV Inotropic sympathomimetic amine acting on α and β
drugs dopaminergic receptors. Lower doses myocardial contractility
and higher doses peripheral vasoconstriction
Dobutamine 5–20 µg/kg/min IV Inotropic sympathomimetic amine acting on α and β receptors.
Increases myocardial contractility and peripheral vaso
dilatation suitable for hypotension associated with myocardial
dysfunction and low cardiac output
Epinephrine 0.05–1 µg/kg/min IV Stimulates α1, α2, β1, β2; vasodilatation at low doses, inotropic
action, significant vasoconstriction at higher doses. Treatment
of refractory hypotension
Norepinephrine 0.05–1 µg/kg/min IV Used in refractory hypotension. Stimulates β1- and α-adrenergic
receptors, increasing cardiac muscle contractility and heart rate,
as well as vasoconstriction
Milrinone 75 µg/kg over 60 min; Selective phosphodiesterase inhibitor, inotrope, and vasodilator
Maintenance infusion
0.5–0.75 µg/kg/min
2. Haque KN. Understanding and optimizing outcome in neonates with sepsis and
Key points septic shock. In: Yearbook of intensive care and emergency medicine. London:
Springer; 2007. pp. 55-68.
))
Neonatal shock can present with varied signs and symptoms 3. Kourembanas S. Shock. In: Cloherty JP, Eichenwald EC, Stark AR (Eds). Manual of
))
It is important to differentiate cardiac causes of shock to Neonatal Care, 6th ed. Philadelphia: Lippincott; 2008. p. 176.
enable prompt treatment of the cause 4. Lee J, Rajadurai VS, Tan KW. Blood pressure standards for very low birthweight
))
Repeated volume replacements are not indicated in infants during the first day of life. Arch Dis Child Fetal Neonatal Ed. 1999;81:
newborns as it may lead to fluid overload and associated F168-70.
complications. One should have a low threshold for starting 5. Nuntnarumit P, Yang W, Bada-Ellzey HS. Blood pressure measurements in the
vasopressor drugs newborn. Clin Perinatol. 1999;26:981-96.
6. Seri I, Evans J. Controversies in the diagnosis and management of hypotension in
))
Shock must be corrected before it becomes irreversible the newborn infant. Curr Opin Pediatr. 2001;13(2):116-23.
causing multiorgan failure. 7. Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates.
Clin Perinatol. 2010;37(2):439-79.
SUGGESTED READINGs 8. Zubrow AB, Hulman S, Kushner H, Falkner B. Determinants of blood pressure in
infants admitted to neonatal intensive care units: a prospective multicenter study. 33
1. Al-Aweel I, Pursley DM, et al. Variations in prevalence of hypotension, Philadelphia Neonatal Blood Pressure Study Group. J Perinatol. 1995;15(6):
hypertension, and vasopressor use in NICUs. J Perinatol. 2001;21(5):272-8. 470-9.
ch-08.indd 33 11/18/2016 5:02:01 PM

Chapter 9
Anemia in Neonate
Nandkishor S Kabra
INTRODUCTION {{ Obstetrical causes: placental abruption, placenta

previa, trauma to placenta or umbilical cord during
Anemia is one of the common hematological abnormalities delivery, and rupture of anomalous placental vessels
in newborn. Normal erythropoiesis in newborn is influenced {{ Fetomaternal transfusion: 8% of normal pregnancies
by several factors, especially erythropoietin. Erythropoietin have some admixture
stimulates maturation of red blood cell (RBC) precursors. {{ Fetoplacental transfusion due to positioning of infant
It is defined as hemoglobin or hematocrit value that is above level of placenta after delivery, partial cord
more than 2 standard deviations below the mean for age (Table occlusion (e.g., with nuchal or prolapsed cord).
1 and 2). {{ Twin-twin transfusion: occurs only with monochorionic
(i.e., monozygotic) twins and when there are placental
vessels which allow shunting of blood from one twin to
ETIOLOGY
the other. Donor will have anemia of variable severity and
Three general causes include blood loss, increased RBC recipient will have polycythemia of variable severity
destruction, and decreased RBC production. {{ Internal hemorrhage such as intracranial hemorrhage
1. Blood loss, the commonest cause of neonatal anemia, (ICH), intraventricular periventricular hemorrhage,
includes: subgaleal hemorrhage, cephalohematoma, adrenal
hemorrhage, subcapsular hematoma of liver, or
ruptured viscus (e.g., spleen)
Table 1: Normal hematological values in full term infants {{ Iatrogenic blood loss secondary to sampling of blood
for laboratory tests. This is the commonest cause of
Age (days) Hb (g/dL) PCV (%) Reticulocyte
anemia (and transfusion) in small premature infants.
count (%)
1 19.0 ± 2.2 61 ± 7 3.2 ± 1.4 Table 2: Normal hemoglobin levels (g/dL) in preterms
2 19.0 ± 1.9 60 ± 6 3.2 ± 1.3
Birth Postnatal age (weeks)
3 18.7 ± 3.4 62 ± 9 2.8 ± 1.7
weight
2 4 6 8 10
4 18.6 ± 2.1 57 ± 8 1.8 ± 1.1 (g)
5 17.6 ± 1.1 57 ± 7 1.2 ± 0.2 800– 16.0 10.0 8.7 8.0 8.0
6 17.4 ± 2.2 54 ± 7 0.6 ± 0.2 1,000 (14.8–17.2) (16.8–13.2) (7.0–10.2) (7.1–9.8) (6.9–10.2)
7 17.9 ± 2.5 56 ± 9 0.5 ± 0.4 1,001– 16.4 12.8 10.5 9.1 8.5
Age (weeks) 1,200 (14.1–18.7) (7.8–15.3) (7.2–12.3) (7.8–10.4) (7.0–10.0)
1–2 17.3 ± 2.3 54 ± 8 0.5 ± 0.3 1,201– 16.2 13.4 10.9 9.9 9.8
2–3 15.6 ± 2.6 46 ± 7 0.8 ± 0.6 1,400 (13.6–18.8) (8.8–16.2) (8.5–13.3) (8.0–11.8) (8.4–11.3)
3–4 14.2 ± 2.1 43 ± 6 0.6 ± 0.3 1,401– 15.6 11.7 10.5 9.8 9.9
4–5 12.7 ± 1.6 36 ± 5 0.9 ± 0.8 1,500 (13.4–17.8) (9.7–13.7) (9.1–11.9) (8.4–12.0) (8.4–11.4)
5–6 11.9 ± 1.5 36 ± 6 1.0 ± 0.7 1,501– 15.6 11.0 9.6 9.8 10.1
PCV, packed cell volume; Hb, hemoglobin. 2,000 (13.5–17.7) (9.6–14.0) (8.8–11.5) (8.4–12.0) (8.6–11.8)
ch-09.indd 34 11/18/2016 5:03:27 PM

Chapter 9: Anemia in Neonate
2. Increased RBC destruction: increase in oxygen requirements, lethargy, poor feeding,

{{ Intrinsic causes: hereditary RBC disorders (rare), hepatosplenomegaly (hemolytic disease), jaundice, wide pulse
including RBC enzyme defects (e.g., glucose-6- pressure, hypotension, metabolic acidosis.
phosphate dehydrogenase (G6PD) deficiency, hexo
kinase deficiency, pyruvate kinase deficiency), RBC CLINICAL APPROACH
membrane defects (e.g., hereditary spherocytosis,
elliptocytosis, stomatocytosis), hemoglobinopathies History
(e.g., α-thalassemia) • Family history: anemia, jaundice, gallstones, splenectomy,
{{ Extrinsic causes: immune hemolysis (Rh incom
ethnicity
patibility, ABO incompatibility, minor blood group • Maternal history: anemia, blood group and Rh type,
incompatibility, e.g., Kell, Duffy). transfusions, viral exanthematous illness during pregnancy,
{{ Acquired hemolysis: infection, disseminated intra per vaginal bleeding, multiple gestation: twin-to-twin
vascular coagulation, drugs transfusion, type of delivery (instrumental), complications
3. Decreased RBC production: of labor and delivery
{{ Anemia of prematurity due to transient deficiency of • Neonatal history: age at onset, physical findings, to know
erythropoietin the cause of anemia (Table 3).
{{ Aplastic or hypoplastic anemia (e.g., Diamond-Blackfan)
{{ Bone marrow suppression (e.g., with rubella or Physical Examination

parvovirus B19 infection) • Look for cephalohematoma, subgaleal bleed, petechiae,
{{ Nutritional anemia (e.g., iron deficiency), usually after
and overt bleeding from gastrointestinal tract and umbilical
neonatal period. cord
• Pallor with prolong capillary refill time: tachycardia and
Clinical Pearl hypotension: acute blood loss
• Pallor without signs of decompensation: chronic blood loss
• Anemia in neonates is the commonest hematologic abnormality. • Pallor, jaundice, hepatosplenomegaly: chronic hemolysis
• Failure to thrive may be a manifestation of chronic anemia
• Examination of placenta: for evidence of hematoma,
CLINICAL FINDINGS retroplacental clots, infection, and arteriovenous anasto
mosis in monochorionic placenta.
This will vary with the severity of anemia and other associated
conditions. The major physiologic impact of anemia is
decreased oxygen delivery to tissues, resulting in compensatory Clinical Pearl
responses and acute/chronic consequences. There may be
• A systemic approach is required to identify exact cause of
no signs with mild anemia. With more severe anemia, exami
anemia and a protocol base management is must to correct it.
nation findings include: pallor, tachycardia, tachypnea, apnea,
Table 3: Classification of anemia in the newborn

Reticulocytes Bilirubin Coombs test RBC morphology Diagnostic possibilities
Normal or ↓ Normal Negative • Normal • Physiologic anemia of infancy or prematurity; congenital
hypoplastic anemia; other causes of decreased production
Normal or ↑ Normal Negative • Normal • Acute hemorrhage (fetomaternal, placental, umbilical
cord, or internal hemorrhage)
↑ ↑ Positive • Hypochromic microcytes • Chronic fetomaternal hemorrhage
• Spherocytes • Immune hemolysis (blood group incompatibility or
maternal autoantibody)
Normal or ↑ ↑ Negative • Spherocytes • Hereditary spherocytosis
• Elliptocytes • Hereditary elliptocytosis
• Hypochromic microcytes • a- or g-thalassemia syndrome
• Spiculated RBCs • Pyruvate kinase deficiency
• Schistocytes and RBC fragments • Disseminated intravascular coagulation; other
• Bite cells (Heinz bodies with microangiopathic processes
supravital stain) • Glucose-6-phosphate dehydrogenase deficiency
• Normal • Infections; enclosed hemorrhage (cephalohematoma)
RBC, red blood cell.
Source: Christou HA. Anemia. In: Cloherty JP, Eichenwald EC, Hanson AR, Stark AR, editors. Manual of Neonatal Care. 7th ed (South Asian Edition). Philadelphia: Wolters 35
Kluwer, LWW; 2012. p. 563-71.
ch-09.indd 35 11/18/2016 5:03:27 PM

INVESTIGATIONS (ALGORITHM 1) Clinical Pearl

• Complete hemogram with peripheral smear and
reticulocyte count and RBC indices • In preterm and term infants, packed red blood cells
transfusion should be considered if an immediate need for
• Blood group and direct Coombs test
increased oxygen delivery to tissues is clinically desired.
• Serum bilirubin: increased levels of indirect bilirubin
suggestive of chronic hemolysis
• Kleihauer-Betke test of mother’s blood: estimation of fetal Red Blood Cell Transfusion
blood lost into maternal circulation can be made by using
the formula 2400 × fetal/maternal cells = mL of fetal blood,
Guidelines for Premature Infants
e.g., 1/600 red cells in mother’s circulation is fetal, then Consider RBC transfusions in the following conditions:
2,400 × 1/600 = 4 mL of fetal blood in maternal circulation • For infants requiring significant mechanical ventilation,
• Thick and thin peripheral smear for malarial parasites defined as FiO2 greater than 40% and/or pressor support if the
• Urine for hematuria central hematocrit is less than 40% (hemoglobin <11 g/dL)
• Stool for occult blood • For infants requiring minimal mechanical ventilation, with
• TORCH screen (toxoplasma, rubella, cytomegalovirus, FiO2 less than 35%, if the central hematocrit is less than
herpes, parvovirus B19, coxsackie): baby and mother 35% (hemoglobin <10 g/dL)
• Ultrasound skull for evidence of ICH/intraventricular • For infants on supplemental oxygen who are not requiring
hemorrhage minimal mechanical ventilation, with FiO2 less than 25%, if
• Test for G6PD deficiency the central hematocrit is less than 25% (hemoglobin
• Bone marrow examination, if indicated. <8 g/dL), one or more of the following is present:
{{ More than 24 hours of tachycardia (heart rate >180/min)
or tachypnea (respiratory rate >80 breaths per min)

MANAGEMENT {{ An increased oxygen requirement from the previous
• Fluid resuscitation: normal saline push followed by packed 48 hours, define as greater than fourfold increase in
cell transfusion: acute blood loss nasal cannula flow (i.e., 0.25–1 L/min) or an increase
• Treat the underlying cause, e.g., treatment of sepsis and in nasal continuous positive airway pressure (CPAP)
toxoplasmosis more than 20% from the previous 48 hours (i.e.,
• Iron therapy: 6 mg/kg/day for 3 months: chronic blood loss. 5–6 cm H2O)
Algorithm 1
Approach to anemia in newborn
36
DIC, disseminated intravascular coagulation; MCV, mean corpuscular volume; G6PD, glucose-6-phosphate dehydrogenase.
ch-09.indd 36 11/18/2016 5:03:28 PM

Chapter 9: Anemia in Neonate
{{ Weight gain less than 10 g/kg/day over the previous {{ Babies more than 1500 g = 2–3 mg/kg/day starting at
4 days while receiving more than 100 kcal/kg/day 2 weeks of life.
{{ An increase in the number or severity of apnea and
bradycardia (in general >10 spells or >3 spells requiring Clinical Pearl
bag and mask ventilation; however, absolute number is
up to individual interpretation) • Delay the cord clamping at birth in preterm infants to improve
{{ Infant undergoing surgery hemoglobin levels and reduce future transfusion needs.
• For infants without any symptoms, if the central hematocrit
is less than 20% hemoglobin (<7 g/dL) and the absolute • Use of recombinant human erythropoietin (rhEPO)
reticulocyte count is less than 3% {{ Indication: prevention of anemia of prematurity in
• For infants with a cumulative blood loss of 10% or more VLBW
of blood volume in 72-hour period when infant has {{ Dose: 100–300 IU/kg/dose subcutaneously on alternate
significant cardiorespiratory illness, if further blood
day for 6 weeks (start at 2 weeks of age)
sampling is anticipated. Stable infants are not transfused
{{ Supplement with iron (6 mg/kg/day)
only to replace blood lost through phlebotomy. If an
{{ In exclusively breastfed preterm infants, vitamin E
erythrocyte transfusion is not given, “blood out” may
supplementation is not indicated.
be replaced mL for mL with 0.9% saline when 10–15 mL
of blood per kg body weight is reached, in order to avoid
hypovolemia. In addition to the saline used for the above AREAS OF UNCERTAINTY
indication, clinicians may administer additional albumin,
fresh frozen plasma, platelet transfusions as they deem • When infants are transfused at lower hemoglobin values
clinically indicated. Whenever possible, RBC transfusion for the gestational age, postnatal age, and the need for
should be given as 10–20 mL/kg, intravenously, infused assisted respiratory support (oxygen, CPAP, mechanical
slowly over 3–4 hours under cardiorespiratory monitoring. ventilation), it is considered as restricted transfusion
Packed RBCs volume may be restricted to 10 mL/kg in approach. The use of restrictive as compared to liberal
infants perceived to be at risk of necrotizing enterocolitis hemoglobin thresholds in infants of VLBW results in
(NEC). Few studies have demonstrated that preterm very modest reductions in exposure to transfusion and in
low birth weight (VLBW) infant if kept nil by mouth during hemoglobin levels. Restrictive practice does not appear to
the period of transfusion reduce the risk of transfusion have a significant impact on death or major morbidities at
related NEC. Small packs (triple and penta packs) of blood first hospital discharge or at follow-up. However, given the
should be made available through blood bank for blood uncertainties of these conclusions, it would be prudent to
transfusion. avoid hemoglobin levels below the lower limits tested in
clinical studies
Complications Associated • Early administration of rhEPO (started before 8 days
of age) reduces the use one or more red blood cell
with Blood Transfusions transfusions, the volume of RBC transfused, and the
• Immunologic reactions: number of donors and transfusions the infant is exposed
{{ Acute hemolytic reactions to following study entry. The small reductions are of
{{ Delayed hemolytic reactions limited clinical importance.
{{ Transfusion associated acute lung injury
{{ Allergic reaction
{{ Graft versus host disease Key points

• Infections: human immunodeficiency virus, hepatitis B ))
Anemia in neonates is the commonest hematologic abnormality
and C, cytomegalovirus, malaria, syphilis
• Volume overload
))
Causes of anemia include blood loss, increased red blood cell
(RBC) destruction and decreased RBC production
• Transfusion related acute gut injury in premature infants
• Hypocalcemia ))
While investigating a newborn with anemia, a systematic
• Transfusion with adult packed RBCs may theoretically approach as depicted in algorithm 1 is desirable
increase the release of oxygen and may cause hyperoxemia ))
Delay the cord clamping at birth in preterm infants to improve
and toxicity hemoglobin levels and reduce future transfusion needs
• Hypothermia, if large quantity of cold blood is used. ))
Use laboratory tests judiciously
))
Monitor phlebotomy losses
Prevention of Anemia of Prematurity ))
Start oral iron therapy in preterm infants by 2 weeks of age as
• Maintain record of phlebotomy losses: transfuse the infant is established on full enteral feeds
babies to replace phlebotomy losses, if exceeding 10% of ))
Consider for erythropoietin therapy from first week of life in
blood volume in 72 hours (only in babies with significant extremely low birth weight infants
cardiorespiratory illness) ))
In preterm and term infants, packed RBCs transfusion should
• Prophylactic iron therapy: be considered if an immediate need for increased oxygen
{{ Babies less than 1500 g = 3–4 mg/kg/day starting at 37
delivery to tissues is clinically desired.
2 weeks of life
ch-09.indd 37 11/18/2016 5:03:28 PM

SUGGESTED READINGs controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for
extremely low birth weight infants. J Pediatr. 2006; 149:301-07.
1. Aher S, Ohlsson A. Early versus late erythropoietin for preventing red blood cell 6. Mentzer WC, Glader BE. Erythrocyte disorders in infancy. In: Taeusch HW, Ballard
transfusion in preterm and/or low birth weight infants. Cochrane Database Syst RA, Gleason CA, (Editors). Avery’s Diseases of the Newborn, 8th ed. Philadelphia:
Rev. 2012 Oct 17; 10:CD004865. Saunders; 2004. pp. 1180-214.
2. Aher S, Ohlsson A. Late erythropoietin for preventing red blood cell transfusion in 7. Ohlsson A,. Aher SM. Early erythropoietin for preventing red blood cell transfusion
preterm and/or low birth weight infants. Cochrane Database Syst Rev. Cochrane in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2012
Database Syst Rev. 2012 Sep 12;9:CD004868. Sep 12; 9:CD004863.
3. Blanchette V, Dror Y, Chan A. Hematology. In: McDonald MG, Mullet MD, Seshia 8. Paul DA, Leef KH, Locke RG, Stefano JL. Transfusion volume in infants with very
MMK, (Editors). Avery’s Neonatology, Pathophysiology and Management of the low birth weight: a randomized trial of 10 versus 20 ml/kg. J Pediatr Hematol
Newborn, 6th ed. (Indian edition). Philadelphia: Lippincott Williams and Wilkins; Oncol. 2002; 24:43-6.
2005. pp. 1169-234. 9. Roberts IAG, Murray NA., Hematology. In: Rennie JM, (Editors). Robertson’s
4. Christou HA. Anemia. In: Cloherty JP, Eichenwald EC, Hanson AR, Stark AR , Textbook of Neonatology, 4th ed. Philadelphia: Elsevier Churchill Livingstone;
(Editors). Manual of Neonatal Care, 7th ed. (South Asian Edition)., Philadelphia: 2011. pp. 739-72.
Wolters Kluwer, LWW;, 2012. pp. 563-71. 10. Whyte R, Kirpalani H. Low versus high haemoglobin concentration threshold for
5. Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA, et blood transfusion for preventing morbidity and mortality in very low birth weight
al. The Premature Infants in Need of Transfusion (PINT) study: a randomized, infants. Cochrane Database Syst Rev. 2011 Nov 9; 11:CD000512.
38
ch-09.indd 38 11/18/2016 5:03:28 PM

Chapter 10
Bleeding Neonate
Deepak Chawla
INTRODUCTION and endothelium (Algorithm 1). In neonates, there is

decreased activity of procoagulant system which is balanced
Bleeding is an alarming symptom at any age, more so in a by decreased activity of coagulation inhibitors and fibrinolytic
young infant. Loss of blood from intravascular space may system so that a healthy term neonate does not develop
manifest as overt bleeding like upper or lower gastrointestinal bleeding or thrombosis despite passing through birth canal
bleeding or pulmonary hemorrhage or as covert bleeding like and undergoing postnatal extracellular fluid constriction
intracranial hemorrhage. In addition, a neonate may manifest (Table 1).
bleeding tendency by development of facial purpura after
birth, prolonged bleeding from venipuncture sites and oozing
from umbilical cord. Objective of this chapter is to delineate an Clinical Pearl
approach to diagnose underlying cause and plan treatment of
• Laboratory values of coagulant factors in neonates should
a bleeding neonate.
be based on gestation- and postnatal-age-based reference
values.
HEMOSTASIS IN NEONATE
Knowledge of components of hemostatic system and their
physiological variation in term and preterm neonates is
CAUSES OF BLEEDING IN NEONATES
essential to develop understanding of causes of bleeding Bleeding in neonates may result from decreased number or
and to correctly interpret results of laboratory investigations. function of platelets and specific deficiencies of coagulation
Components of hemostatic system include procoagulant factors (Table 2). Some systemic disorders can cause more
factors, inhibitors of coagulation, fibrinolytic system, platelets, widespread disturbance in hemostatic mechanism.
Algorithm 1
Coagulation factors (solid boxes) and their inhibitors (dashed boxes)
ch-10.indd 39 11/24/2016 12:28:56 PM

Table 1: Hemostatic system in a neonate in comparison to adults passage of antibodies from a mother affected by autoimmune
thrombocytopenia or systemic lupus erythematosus.
Component of Alteration
Thrombocytopenia is common but rarely severe to cause
hemostatic system
bleeding in neonates born to pregnancies complicated by
Platelets • Platelet count comparable to adults gestational hypertension; intrauterine growth restriction, or
• Smaller and more immature mega hemolysis, elevated liver enzyme levels, and a low platelet
karyocytes count syndrome. History must be sought for systemic disorders
• Lower thrombopoietin levels in which can cause disseminated intravascular coagulation like
thrombocytopenic neonates birth asphyxia and neonatal sepsis. Inherited deficiencies
Fibrinogen, factor V and • Comparable to adults of coagulation factors can be suspected if parents have a
factor VIII consanguineous marriage or previous siblings are affected.
Hemophilia A and B are X-linked recessive disorders while
von Willebrand factor • Increased
von Willebrand factor deficiency can be autosomal dominant
Other coagulation factors • Decreased (by 50% as compared to or recessive. Presence of skeletal abnormalities like absent
adults) thumb or absent radius bone indicates Fanconi anemia or
Antithrombin III, • Decreased thrombocytopenia-absent radius syndrome. Chromosomal
protein C and protein S disorders like trisomy 13, 18, or 21 can be associated with
Plasminogen • Decreased thrombocytopenia.
Clinical Pearl
Table 2: Common causes of bleeding in neonates
Platelets Coagulation factors • Detailed family history should be taken to rule out inherited or
maternal causes of bleeding in a neonate.
Early onset (within 72 h of birth) • Vitamin K deficiency
• Pregnancy complications {{ Early (within 24 h)
Gestation at birth, age at onset of bleeding, and site
(gestational hypertension, {{ Classical (24 h to 7 days)
intrauterine growth restriction) of bleeding can indicate underlying cause. Bleeding in an

{{ Late (2–12 weeks)
otherwise healthy term or late preterm neonate indicates
• Early-onset sepsis • Hemophilia A (classical either coagulation factor deficiency or NAIT. Early-onset
• Neonatal alloimmune hemophilia due to factor thrombocytopenia (within 72 h of birth) in a preterm neonate
thrombocytopenia VIII deficiency)
is most commonly due to maternal illness while late-onset
• Neonatal autoimmune • Hemophilia B (factor IX thrombocytopenia (after 72 h of birth) is most commonly
thrombocytopenia deficiency)
due to sepsis or necrotizing enterocolitis. Intracranial bleed
• TORCH infections • Disseminated intravascular without significant birth trauma indicates presence of
Late onset (after 72 h of birth) coagulation
underlying bleeding disorder. Subdural hemorrhage is more
• Late-onset sepsis • Liver disease common with hemophilia while intraparenchymal bleed is
• Necrotizing enterocolitis more common with thrombocytopenia (e.g., NAIT). Other
• TORCH infections common sites of bleeding in coagulation factor deficiency
TORCH, toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, include oozing from umbilical stump, prolonged bleeding from
cytomegalovirus and herpes infections. venipuncture or heel stick sites, large caput succedaneum, or
large cephalhematoma without birth trauma. Mucosal bleeds,
e.g., from oral mucosa or gastrointestinal bleeds, are more
Clinical Pearl commonly observed in thrombocytopenia.
• Pregnancy complications are the most common underlying

cause of early-onset thrombocytopenia. Systemic infections Clinical Pearl
are most common underlying cause of late-onset thrombo
• Intracranial bleed in a term neonate should raise suspicion of
cytopenia.
coagulation dysfunction. Mucosal bleed is most commonly
due to platelet disorders.
APPROACH TO A BLEEDING NEONATE

History should be sought about maternal intake of
medications and administration of vitamin K at birth.
History and Physical Examination Maternal intake of antitubercular or antiepileptic drugs
Detailed maternal history should be taken to rule out thrombo may be associated with development of early onset vitamin
cytopenia due to immune causes. Neonatal alloimmune K deficiency bleeding (VKDB) which presents within first
thrombocytopenia (NAIT) is frequently suspected if there is 24 hours of birth. Neonates not receiving the recommended
history of bleeding or thrombocytopenia in previous siblings. dose of vitamin K at birth may develop classical (24 h to 7 days
40 Thrombocytopenia can also develop due to transplacental after birth) or late onset (2–12 weeks) VKDB.
ch-10.indd 40 11/24/2016 12:28:56 PM

Chapter 10: Bleeding Neonate
Laboratory Investigations neonate may be because of congenital infections for which

Essential laboratory investigations which should be done in appropriate diagnostic test should be done. Conversely,
neonates with bleeding include platelet count, prothrombin mild early-onset transient thrombocytopenia in a small-for-
time (PT), activated partial thromboplastin time (APTT) gestation neonate may be because of gestational hypertension
and fibrinogen levels (Algorithm 2). Prothrombin time is in mother and no further investigations are needed.
prolonged in deficiency of vitamin K dependent coagulation
factors (II, VII, IX, and X). Activated partial thromboplastin MANAGEMENT
time is prolonged in deficiency of vitamin K dependent
coagulation factors and deficiency of contact factors (XI, XII, Thrombocytopenia
prekallikrein, and high molecular weight kininogen). If PT,
APTT, and platelets counts are normal, bleeding may occur Management of thrombocytopenia consists of treating
because of decreased factor XIII, a2-antiplasmin activity underlying cause and if needed giving platelet transfusion.
or abnormal platelet functions. In a sick neonate, more In case of NAIT, platelet transfusion is indicated if platelet
widespread derangement of the laboratory markers indicates counts are below 30,000/µL. In case of active bleeding, platelet
decreased synthesis due to liver disorder or consumption transfusion can be given if platelet count is below 50,000/µL.
If available, single donor platelets which are human platelet
coagulopathy.
antigen compatible with the neonate are preferred. If these
are not available without delay, random donor platelets can be
Clinical Pearl transfused. Administration of intravenous immunoglobulin (1
g/kg for 2 days or 0.4 g/kg/day for 5 days) may increase platelet
• Initial workup in a bleeding neonate should include platelet
count in immune thrombocytopenia. Platelet counts need to
count, prothrombin time, activated partial thromboplastin
time, and fibrinogen levels. be monitored for first 10–14 days after birth.
Due to lack of demonstrable efficacy in preventing serious
hemorrhages, threshold platelet count below which platelet
Specific factor assay can be done on clinical suspicion. transfusion is given has become more stringent with time.
However, results need to be interpreted carefully in view of Most of neonates with platelet count above 20,000/µL will not
altered levels in neonates. Levels of factor VIII are comparable develop a serious bleed. Therefore, this cutoff may be used in
to adults. Therefore, classical hemophilia can be diagnosed in otherwise healthy neonates with thrombocytopenia. Higher
neonates. On the other hand, levels of factor IX are about 15% cutoff of 30,000/µL may be used in neonates at higher risk of
of adult level and, therefore, hemophilia B can be diagnosed bleeding which include extremely low birthweight neonates
only by 6–12 months of age, when levels reach the adult range. in their first week after birth, unstable blood pressure records,
Prothrombin time and APTT are influenced by ratio of blood previously existing grade 3 or 4 intraventricular hemorrhage,
and citrate in the sample; therefore, care must be taken while current minor bleeds, coexisting coagulopathy or before
withdrawing the sample. exchange transfusion or surgery. In case of active major
Additional laboratory investigations may be warranted bleeding, platelet count may be maintained above 50,000/µL.
as per clinical suspicion. For example, severe early-onset Platelets can be obtained by pooling from multiple donors
thrombocytopenia (platelet count <50,000/µL) in a preterm (platelet concentrate) or by apheresis from a single donor
Algorithm 2
Laboratory investigations in a bleeding neonate
PT, prothrombin time; APTT, activated partial thromboplastin time; DIC, disseminated intravascular coagulation.
41
ch-10.indd 41 11/24/2016 12:28:56 PM

(apheresis unit). It is stored at room temperature and has a

shelf-life of 5 days. A dose of 10 mL/kg is usually sufficient to Key points
increase the platelet count above therapeutic threshold. ))
In neonates, coagulation cascade remains same as pediatric
patients, while causes for bleeding differ. It involves factors
related to maternal causes and intrapartum insults
Clinical Pearl ))
Laboratory values of coagulation factors are different than
• Platelet count should be maintained above 50,000/µL in adults
a neonate with active bleeding and above 30,000/µL in a ))
Platelet and component therapy should be used very
neonate without active bleeding. judiciously. Clinical status need be considered while planning
for the transfusions.
Coagulopathy
SUGGESTED READINGs
Vitamin K deficiency can be treated by administration of
vitamin K by subcutaneous or intravenous route. Effect of 1. Bussel JB, Sola-Visner M. Current approaches to the evaluation and management
of the fetus and neonate with immune thrombocytopenia. Semin Perinatol.
parenteral vitamin K starts within 4 hours. In case of active
2009;33:35-42.
bleeding, fresh frozen plasma (FFP) can be administered. 2. Moskowitz NP, Karpatkin M. Coagulation problems in the newborn. Curr Paediatr.
In case of classical hemophilia, treatment of choice is 2005;15:50-6.
administration of factor VIII concentrate. If not available, 3. Poterjoy BS, Josephson CD. Platelets, frozen plasma, and cryoprecipitate: what
cryoprecipitate or FFP can be given. Dose of cryoprecipitate is the clinical evidence for their use in the neonatal intensive care unit? Semin
is 2 mL/kg or I unit/7 kg. Fresh frozen plasma can be Perinatol. 2009;33:66-74.
administered in a dose of 10-20 mL/kg. Specific deficiencies 4. Sola-Visner M. Platelets in the neonatal period: developmental differences
in platelet production, function, and hemostasis and the potential impact of
of other coagulation factors are rare and can be managed by
therapies. Hematology Am Soc Hematol Educ Program. 2012;2012:506-11.
administration of cryoprecipitate or FFP. 5. te Pas AB, Lopriore E, van den Akker ES, Oepkes D, Kanhai HH, Brand A, et al.
Supportive and specific care for underlying systemic Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the
causes of bleeding like sepsis and NEC should be given. role of matched platelet transfusion and IVIG. Eur J Pediatr. 2007;166:1057-63.
42
ch-10.indd 42 11/24/2016 12:28:57 PM

Chapter 11
Neonatal Hyperbilirubinemia
(Unconjugated)
Poonam Sidana, Gaurav Mandhan
INTRODUCTION Table 1: Differentiating points for various categories of un

conjugated hyperbilirubinemia
Unconjugated neonatal hyperbilirubinemia (NNH) is one of
the commonest problems faced by pediatricians attending to Physiological jaundice Pathological jaundice
neonates. Incidence is reported as 60% in term and around • Appears at >24 h and • Appears within 24 h of life
80% in preterm neonates. Incidence and severity are inversely <72 h • Increases >5 mg/dL/24 h OR
related to gestational age at birth. It is a benign condition which • Peak level of 12–15 mg/dL >0.5 mg/dL/h
resolves by itself in most of the cases. However, neurotoxic is seen at 3–5 day of life • Peak level crosses 95th centile
potential of the unconjugated bilirubin which can result in in term and 5–7 day in for age in hours/in intervention
permanent neurodevelopmental sequelae in some neonates is preterm zone
well known. Hence, it is necessary that all those neonates who • Usually, needs no • Persists >14 days in term
are at high risk are identified and managed appropriately. intervention • Conjugated serum bilirubin
• Disappears without >2 mg/dL
Clinical Pearl intervention by 7th and 14th • Process may be delayed/
day in term and preterm prolonged in preterm neonate;
• There is no single level of serum bilirubin which applies to neonates respectively peak levels may be higher
all the babies. Instead, various nomograms are available to • Needs intervention
evaluate risk and decide intervention for a particular neonate.
• Gestational age less than 38 weeks

Unconjugated hyperbilirubinemia may be categorized
• ABO/Rh incompatibility setting
as physiological/pathological or exaggerated physiological.
• Predischarge serum bilirubin in intermediate/high risk
For a clinician, it is important to know how to differentiate
between these categories. Also it is extremely important to zone
decide which babies are at risk of developing NNH level that • Previous sibling with jaundice
may need investigations and/or intervention. Table 1 lists • Extraneous blood source: cephalohematoma, bruising
some important differentiating points for various categories. • Infant of diabetic mother, exclusive but inadequate breast
feeding/poor feeder, race glucose-6-phosphate dehydro
genase.
EXAGGERATED PHYSIOLOGICAL JAUNDICE
Time of appearance and rate of rise does not match that of Risk Factors for Neurotoxicity
pathological jaundice. However, absolute total serum bilirubin
• Isoimmune hemolytic disease
value tends to be higher than that expected for physiological
• Glucose-6-phosphate dehydrogenase deficiency
jaundice. Investigations do not reveal any specific cause.
• Perinatal asphyxia
Following groups of neonates are more prone to develop
• Sepsis
significant NNH.
• Acidosis
• Serum albumin <3.0 mg/dL.
Risk Factors For Pathological In order to plan appropriate investigations, one needs to
Neonatal Hyperbilirubinemia know the causes of NNH presenting at various neonatal ages.
• Jaundice noted before 24 hours/after 72 hours Common causes of pathological NNH are given in table 2.
ch-11.indd 43 11/18/2016 5:05:12 PM

Table 2: Common causes of pathological neonatal hyper • Glucose-6-phosphate dehydrogenase level in a male
bilirubinemia neonate in high prevalence areas
• Sepsis workup in sick neonate
<24 hours 24–72 hours >72 hours
• Thyroid profile
Hemolytic disease Physiological Sepsis • Investigations for rare causes as applicable.
of newborn: ABO/
Rh incompatibility
MANAGEMENT PLAN
G6PD/pyruvate Sepsis Extraneous blood like
kinase deficiency, cephalohematoma or
FOR A JAUNDICED NEONATE
membrane defects IVH or bruising • History and examination
Infections • Polycythemia • Neonatal hepatitis/ • Serum bilirubin level
• Extraneous blood extrahepatic biliary • Risk assessment based on total serum bilirubin, history
like cephalo atresia and examination
hematoma or IVH • Breastfeeding/milk • Physiological or pathological
or bruising jaundice • Investigate as needed
• Poor feeding • Metabolic causes • Decide need to follow up or intervene.
G6PD, glucose-6-phosphate dehydrogenase; IVH, intraventricular hemorrhage.
TREATMENT
In an ideal situation, treatment guidelines should be based
Clinical Pearl on epidemiological data collected from a local population. In
India, in view of paucity of any national database on neonatal
• All infants discharged at less than 72 hours should be seen jaundice, American Academy of Pediatrics (AAP) guidelines
within 2 days of discharge to ensure diagnosis of pathological (2004) for NNH management have been followed for the last
jaundice. many years. These guidelines do not address treatment of
newborns born less than 35 weeks of gestation.
Recently published guidelines by National Institute for
INVESTIGATIONS Health and Clinical Excellence (NICE) in 2010 are more
The following investigations may be done, in the order of inclusive, as they have evaluated data from diverse sources,
priority, depending on clinical evaluation: including AAP 2004 guidelines and few Indian studies also.
• Serum bilirubin, total and conjugated, can use trans These guidelines are applicable to neonates born from 23 weeks’
cutaneous bilirubin if baby >35 weeks/>24 h/not under gestation onward, till term. There are graphs available for each
phototherapy gestation outlining phototherapy and exchange thresholds
• Blood group of the baby and the mother from birth itself. Management of jaundice appearing within
• Direct Coombs test in Rh isoimmunized/ABO in first 24 hours of life has been addressed clearly.
compatibility Tables 3 and 4 and algorithm 1 represent the adaptations
• Hemogram, reticulocyte count, peripheral smear for from NICE guidelines 2010 for the management of neonatal
hemolysis/red blood cell morphology jaundice.
Table 3: Guidelines for treatment of jaundice in preterm neonates 27–32 weeks

Postnatal 27 weeks 28 weeks 29 weeks 30 weeks 31 weeks 32 weeks
age (h) Photo Exchange Photo Exchange Photo Exchange Photo Exchange Photo Exchange Photo Exchange
0 2.3 4.7 2.3 4.7 2.3 4.7 2.3 4.7 2.3 4.7 2.3 4.7
6 2.9 5.6 2.9 5.6 3.2 5.8 2.9 5.8 3.2 5.8 3.2 5.8
12 3.5 6.7 3.8 6.7 3.8 6.7 4.1 6.7 4.1 7.0 4.1 7.0
18 4.1 7.3 4.4 7.6 4.4 7.6 4.7 7.9 4.7 8.2 5.0 8.2
24 4.7 8.5 5.0 8.5 5.3 8.8 5.6 9.1 5.8 9.4 5.8 9.4
30 5.6 9.4 5.8 9.4 6.1 9.6 6.1 9.9 6.4 50.2 6.7 50.5
36 6.1 10.0 6.4 11.0 6.7 10.8 7.0 11.1 7.3 11.4 7.6 12.3
42 6.7 11.0 7.0 11.0 7.6 11.7 7.9 12.3 8.2 12.6 8.5 12.9
48 7.6 12.0 7.9 12.0 8.2 12.9 8.5 13.2 9.1 11.5 9.4 14.0
54 8.2 13.0 8.5 13.0 9.1 14.0 9.4 14.3 9.9 14.0 10.7 15.2
60 8.8 14.0 9.4 15.0 9.9 14.9 10.2 15.5 10.8 15.8 11.1 16.4
66 9.4 15.0 9.9 15.0 11.0 15.8 11.1 16.4 11.4 17.0 12.0 17.5
44 72 9.9 16.0 11.0 16.0 11.0 17.0 11.7 17.5 17.3 18.1 12.9 18.7
ch-11.indd 44 11/18/2016 5:05:13 PM

Chapter 11: Neonatal Hyperbilirubinemia (Unconjugated)
Table 4: Guidelines for treatment of jaundice in neonates 33 to more than 38 weeks

Postnatal 33 weeks 34 weeks 35 weeks 36 weeks 37 weeks >38 weeks
age (h) Photo Exchange Photo Exchange Photo Exchange Photo Exchange Photo Exchange Photo Exchange
0 2.3 4.7 2.3 4.7 2.3 4.7 2.3 4.7 2.3 4.7 5.8 5.8
6 3.2 5.8 3.2 5.8 3.2 5.8 3.5 5.8 3.5 5.8 7.3 8.8
12 4.1 7.0 4.4 7.0 4.4 7.3 4.7 7.3 4.7 7.6 8.8 11.7
18 5.3 8.2 5.6 8.2 5.3 8.5 5.6 8.8 5.8 8.8 10.2 14.6
24 6.1 9.4 6.1 9.6 6.4 9.9 6.7 9.9 7.0 10.2 11.7 17.5
30 7.0 10.5 7.0 11.1 7.3 11.1 7.6 11.4 7.9 11.7 12.4 20.5
36 7.9 11.7 8.2 12.3 8.5 12.4 8.8 12.9 9.1 13.2 11.2 23.4
42 8.8 11.2 8.8 13.5 9.6 14.0 9.9 14.0 10.2 14.6 11.9 26.1
48 9.6 14.3 10.2 14.6 10.5 15.2 10.8 15.5 11.1 10.2 14.6 26.3
54 10.5 15.8 11.1 15.8 11.7 16.4 12.0 17.9 12.6 17.5 15.3 26.3
60 11.7 17.0 12.3 17.5 12.6 17.8 13.2 18.4 11.5 18.7 16.1 26.3
66 12.6 18.1 13.2 18.7 13.5 19.3 14.0 19.6 14.6 20.2 16.8 26.3
72 13.5 19.3 14.0 19.9 14.6 20.5 15.2 21.1 15.8 21.6 17.5 26.3
78 13.5 19.3 14.0 19.9 14.6 20.5 15.2 21.1 15.8 21.6 18.2 26.3
84 13.5 19.3 14.0 19.9 14.6 20.5 15.2 21.1 15.8 21.6 19.0 26.3
90 13.5 19.3 14.0 19.9 14.6 20.5 15.2 21.1 15.8 21.6 19.7 26.3
96 13.5 19.3 14.0 19.9 14.6 20.5 15.2 21.1 15.8 21.6 20.5 26.1
Algorithm 1
Management of unconjugated neonatal hyperbilirubinemia
PT, phototherapy; SPT, single phototherapy; MPT, multiple phototherapy; IVIG, intravenous immunoglobulin.
45
*Monitoring pattern: 24 h/exchange zone—6–12 hourly; rest 12–24 h or later as per postnatal age and risk factors.
#Investigsations: blood groups of mother and baby; DCT, Hb/PCV, retics smear for hemolysis if indicated; sepsis profile, G6PD and the thyroid profile if indicated.
ch-11.indd 45 11/18/2016 5:05:13 PM

Clinical Pearl SUGGESTED READINGs

1. Available from: https://www.nice.org.uk/guidance/cg98/evidence.
• While interpreting National Institute for Health and Clinical
2. Evidence Based Clinical Practice Guidelines by National Neonatology Forum,
Excellence charts, following conversion needs to be applied: India, October 2010.
1 mg/dL of serum bilirubin = 17.1 µm/L of bilirubin. 3. Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF.
Hyperbilirubinemia in the newborn infant ≥35 weeks’ gestation: an update with
clarifications. Pediatrics. 2009;124:1193-8.
Key points 4. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of
gestation. Pediatrics. 2004;114:297-316.
))
All neonates being discharged from hospital should be 5. Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin’s Neonatal-perinatal
examined for jaundice. Based on risk assessment, a follow-up Medicine Diseases of the Fetus and Infant. 8th ed.; 2006.
plan needs to be decided and explained to the parents clearly 6. Narang A, Gathwala G, Kumar P. Neonatal jaundice: an analysis of 551 cases.
))
Use total bilirubin for all decisions. Do not subtract conjugated Indian Pediatr. 1997;34:429-32.
bilirubin 7. Taeusch HW, Ballard RA, Gleason CA, editors. Avery’s Diseases of Newborn.
8th ed.; 2005.
))
Appropriate feeding, hydration, blood sugar level, and electro
lyte balance must be maintained for babies requiring treatment
))
A neonate presenting in exchange range or suspected to be
having bilirubin encephalopathy is a medical emergency.
Treatment should be started without any delay.
46
ch-11.indd 46 11/18/2016 5:05:13 PM

Chapter 12
Hypoglycemia
Sailesh G Gupta
INTRODUCTION METHODS OF GLUCOSE ESTIMATION

There is no universal definition for hypoglycemia. The normal Important point in BG estimation is whole blood sugar is
range of blood glucose (BG) is variable and depends upon 10–15% lower than the plasma glucose. Glucose oxidase and
factor like birthweight, gestational age, body store, feeding glucose electrode method are two most commonly used
status, as well as the presence or absence of the disease. method for BG estimation in laboratory which are accurate
Operational threshold has been defined as that and reliable. Samples should be analyzed quickly as BG values
concentration of plasma or whole BG at which clinician drops by 14–18 mg/dL/h of storage.
should consider intervention based on the currently available
literature. Operational threshold has been defined as BG level MANAGEMENT OF
less than 40 mg/dL (plasma glucose level <45 mg/dL). SYMPTOMATIC HYPOGLYCEMIA
• All symptomatic hypoglycemia infants should be treated
SCREENING OF BABIES (WHO ARE AT RISK) with intravenous fluids
• Preterm infants • A bolus of 2 mL/kg of 10% dextrose is given intravenously
• Small for gestational age after sending a lab sample for confirmation of diagnosis
• Large for gestational age • Following a bolus of 10% dextrose continuous glucose
• Infant of diabetic mother infusion should be started at glucose infusion rate (GIR) of
• Sick infants (e.g., sepsis, birth asphyxia, shock, poly 6 mg/kg/min
cythemia, etc.) • Blood glucose should be checked 15–30 minutes after
• Infants on intravenous fluids and total parenteral nutrition giving intravenous 10% dextrose bolus. If it stays greater
• Mother receiving drugs like, b-blocker, oral hypoglycemic, than 50 mg/dL then decrease frequency of monitoring
and received intrapartum glucose infusion. from every hour to 4–6 hourly
• If BG is less than 50 mg/dL then GIR should be increased
in the increment of 2 mg/kg/min every 15–30 minutes until
SCREENING SCHEDULE BG is greater than 50 mg/dL or GIR reaches 12 mg/kg/min
Screening schedule is given in table 1 • After BG values stabilized for greater than 50 mg/dL for at
least 24 hours, then only tapering of GIR should be started
Table 1: Screening schedule at 2 mg/kg/min every 6 hourly with BG monitoring. It
should be accompanied by concomitant increase in oral
Condition Timing
feeds. Once GIR of 4 mg/kg/min is achieved and infant is
Infant of diabetic mother 2, 6, 12, 24, 48, and 72 h tolerating oral feeds and BG is greater than 50 mg/dL then
Other at risk neonates 2, 6, 12, 24, 48 (or until glucose values only glucose infusion should be stopped.
become normal) • Do not stop glucose infusion abruptly as it can cause
Babies on IVF and TPN 6 hourly for the first 72 h then once/ rebound hypoglycemia. Maximum 12.5% dextrose can
twice a day be given through peripheral line due to risk of thrombo
IVF, intravenous fluids; TPN, total parenteral nutrition. phlebitis.
ch-12.indd 47 11/24/2016 12:30:05 PM

MANAGEMENT OF MANAGEMENT OF
ASYMPTOMATIC HYPOGLYCEMIA REFRACTORY HYPOGLYCEMIA
Often low blood glucose level (BGL) may not manifest clinically
and maybe without any symptoms. Asymptomatic hypo Definitions
glycemia is defined as a condition with BGL of <45 mg/dL Unable to achieve normal BG despite giving glucose infusion at
(confirmed in laboratory) with the infant not manifesting 12 mg/kg/min or hypoglycemia remains for more than 7 days
clinical features. Unanimous opinion does not exist for the need then it’s considered to be refractory hypoglycemia.
to treat asymptomatic infants with low BGL. Management of Important causes
asymptomatic hypoglycemia is summarized in table 2. • Hyperinsulinemic states
• Congenital hypopituitarism
tABLE 2: Management plan of infants with asymptomatic hypo • Adrenal insufficiency
glycemia
• Metabolic disorders like galactosemia, fatty acid oxidation
Condition Timing defects, organic acidemias, etc.
Blood sugar Try oral feeds (expressed breast milk or infant
20–45 mg/dL formula) and repeat BGL after 1 hr:
Critical Sample in
• If BGL >45 mg/dL, then provide 2 h oral feeds Management of Refractory Hypoglycemia
and measure BGL 6 h for 48 h. Aim to maintain • Serum insulin level
BGL between 50 mg/dL and 120 mg/dL • Serum cortisol
• If BGL <45 mg/dL, start IV dextrose infusion • Serum ammonia
and manager as per protocol for symptomatic • Serum ketone bodies
hypoglycemia
• Serum lactate.
Blood sugar Start IV Dextrose at 6 mg/kg/min. Subsequently Other secondary investigations can be done according to
<20 mg/dL manage as symptomatic hypoglycemia
the etiology suspected.
BGL, blood glucose level.
Algorithm 1
Algorithm for management of neonatal hypoglycemia
IV, intravenous; GIR, gluscose infusion rate.

48
ch-12.indd 48 11/24/2016 12:30:06 PM

Chapter 12: Hypoglycemia
Drugs for the Treatment reached. The dextrose infusion should be tapered gradually
of Refractory Hypoglycemia only after BGL stabilizes above 50 mg/dL for 24 hours. Abrupt
• Hydrocortisone 5 mg/kg/day intravenous or oral in two cessation of infusion can cause rebound hypoglycemia
divided doses ))
Hypoglycemia without clinical manifestations should be
• Diazoxide 10–25 mg/kg/day orally in three divided doses treated with IV dextrose infusion if BGL <25 mg/dL. With BGL
• Glucagon 100 mg/kg subcutaneous/intramuscular maximum >25 mg/dL, oral feeding of milk is followed 30 min later, by
three doses BGL measurement. If BGL >45 mg/dL, oral feeding and 6 h
BGL monitoring are done. If BGL <45 mg/dL, a dextrose bolus
• Octreotide 2–10 mg/kg/day subcutaneous two to three
of 10% at 2 ml/kg is given and followed up with management
times a day.
as for symptomatic hypoglycemia
))
Inability of achieve BGL >50 mg/dL after dextrose infusion
rate of 12 mg/Kg/min, or hypoglycemia lasting over a week
Key points is labeled as refractory. Causes should be explored, and
treatment may include the use of drugs appropriate to the
))
A BGL <40 mg/dL or plasma GL <45 mg/dL is considered the
cause of refractory hypoglycemia.
operational threshold for management of Hypoglycemia in a
Newborn
))
Newborns ‘at risk’ for Hypoglycemia should be screened
clinically and by measurement of BGL to diagnose
asymptomatic and symptomatic hypoglycemia Suggested readings
))
All symptomatic hypoglycemia should be treated with
1. Cornblath M, Ichord R. Hypoglycemia in neonates. Semin Perinatol. 2000;24:
Intravenous bolus of 10% dextrose followed by dextrose 136-49.
infusion at the rate 6 mg/Kg/min, and frequent monitoring 2. Cornblath M, Schwartz R. Outcome of neonatal hypoglycemia. Br Med J. 1999;
of BGL. For BGL <50 mg/dL, the infusion rate is increased 318:194.
by 2 mg/Kg/min, until an infusion rate of 12 mg/Kg/min is 3. Mitanchez D. Glucose regulation in preterm newborn infants. Horm Res. 2007;
68:265-71.
49
ch-12.indd 49 11/24/2016 12:30:06 PM

Chapter 13
Neonatal Seizures
Sanjay Wazir
INTRODUCTION Table 1: Etiology of neonatal seizures based on timing after

birth
Neonatal seizures represent one of the major challenges
for the clinician working in nursery because of difficulty in Age Etiology
diagnosis and lack of effective evidence based treatment First 24 h • Hypoxic ischemic encephalopathy
scheme. Incidence of neonatal seizures is inversely • Meningitis/sepsis
proportional to the birthweight with incidence of approxi • Subdural/subarachnoid/interventricular
mately 60 per 1,000 at less than 1,500 g and 3 per 1,000 at more hemorrhage intrauterine infection
than 2,500 g at birth. • Trauma
• Pyridoxine dependency
RISK FACTORS FOR NEONATAL SEIZURES • Drug effect/withdrawal
24–72 h • Meningitis/sepsis
Maternal • In premature infants: intraventricular hemorrhage
• Advancing maternal age more than 40 years • In full-term infants: infarction, venous thrombosis
• Preexisting/gestational diabetes mellitus • Cerebral dysgenesis
• Intrapartum evidence of fetal distress 72 h to • Above causes
• Placental abruption, cord prolapse, prolonged second stage 1 week • Inborn errors of metabolism
• Maternal pyrexia, chorioamnionitis. • Hypocalcemia
• Familial neonatal seizures
Infant
1 week to • Above causes
• Lower gestational age 4 weeks • Herpes simplex virus
• Low birthweight
• Post-term more than 42 weeks 1. Hypoxic ischemic encephalopathy
• Male sex. 2. Intracranial infections: bacterial, viral, fungal, intrauterine
3. Cerebral malformations
Clinical Pearl 4. Intracranial hemorrhage
5. Metabolic: hypocalcemia, hypomagnesemia, hypo
• Half of the seizures in newborns are subclinical and one-third glycemia, hypo- or hypernatremia
of seizures do not have an electroencephalogram correlate. 6. Bilirubin encephalopathy
7. Drug withdrawl: chronic maternal use of drugs
8. Inborn errors of metabolism: nonketotic hyperglycinemia,
ETIOLOGY OF NEONATAL SEIZURES (TABLE 1) pyridoxine-dependent epilepsy, folinic acid-responsive
First four causes constitute approximately 85% of all causes seizures, pyruvate dehydrogenase deficiency, glucose
of neonatal seizures. It is important to find out the cause as the transporter deficiency, biotinidase deficiency, Leigh
prognosis is dependent on the etiology of seizure. disease, sulfite oxidase deficiency
ch-13.indd 50 11/18/2016 5:13:41 PM

Chapter 13: Neonatal Seizures
9. Epilepsy syndromes: benign idiopathic neonatal Table 3: Differential diagnosis of movement disorders in
convulsions, benign familial neonatal seizures, benign neonates
nonfamilial (idiopathic) neonatal seizures, early infantile
Phenomenon Characteristics
epileptic encephalopathy with burst suppression pattern
(Ohtahara syndrome), early myoclonic encephalopathy. Jitteriness • Rhythmic character with equal forward and
backward movement
• Can be restrained and is stimulus sensitive
Clinical Pearl • No eye movements
• Sixty percent of the causes of seizures are due to hypoxic Benign sleep • Myoclonic activity confined to sleep
ischemic encephalopathy and 20% are related to stroke. myoclonus • Occurs in the first few weeks of life
• Spontaneous resolution by 2–3 months
• No autonomic movements or eye movements
TYPES OF SEIZURES Hyperekplexia • Triad of generalized stiffness while awake,
Types of seizures are given in table 2. (stiff baby nocturnal myoclonus and exaggerated startle
syndrome) reflex
Table 2: Types of seizures • Resolved by manual flexion of the neck or hips
• Clonazepam is helpful
Apnea Pedaling
Nonconvul- • Not associated with eye movements
Subtle • Eye deviation (term) sive apnea • Tachycardia is not seen
• Blinking, fixed stare (preterm)
Sandifer • Caused by acid reflux
• Repetitive mouth and tongue movements syndrome • Intermittent paroxysmal spells of generalized
• Apnea pedaling, tonic posturing of limbs stiffness and opisthotonic posturing
Tonic • Maybe focal or generalized • Usually occur within 30 min of meal
• Tonic extension or flexion of limbs (often signals Neonatal • Fixed contraction of muscles
severe intracranial hemorrhage in preterm infants) dystonia • Usually in severe brain lesion or in drug
Clonic • Maybe focal or multifocal overdose like metoclopramide
• Clonic limb movements (synchronous or
asynchronous, localized or often with no anatomic
order to progression) Table 4: List of antiepileptics and their doses
• Consciousness maybe preserved
Drug Loading dose Maintenance dose
• Often signals focal cerebral injury
Phenobarbital 20 mg/kg IV 3–5 mg/kg per 24 h IV
Myoclonic • Focal, multifocal, or generalized maximum 40 mg/kg or PO
• Lightning-like jerks of extremities (upper > lower)
Phenytoin 20 mg/kg IV (infusion 3–4 mg/kg per 24 h IV
rate
DIFFERENTIAL DIAGNOSIS OF 1 mg/kg/min)
MOVEMENT DISORDERS IN NEONATES Midazolam 0.05 mg/kg IV 0.15 mg/kg/h
(in 10 min)
Differential diagnosis of movement disorders in neonates is
given in table 3. Lidocaine 2 mg/kg IV • 6 mg/kg/h IV
• After 24 h of treatment:
4 mg/kg/h
INVESTIGATIONS • After 36 h: 2 mg/kg/h
• Clinical history and examination • After 48 h: Stop
• Blood sugar Clonazepam 0.15 mg/kg IV repeat 0.1 mg/kg per 24 h
• Serum calcium and magnesium 1x or 2x
• Blood gas
Pyridoxine 50–100 mg 50–100 mg
• Urea and electrolytes
• Blood culture IV, intravenous; PO, per os.
• Cerebrospinal fluid
• Electroencephalogram (EEG): Obtain EEG if possible
• Ultrasonography. Clinical Pearl
• The data regarding the efficacy of older antiepileptics is not
ANTIEPILEPTICS AND THEIR DOSES very convincing but newer drugs have hardly any; hence,
phenobarbitone remains the first choice in neonatal seizures.
List of antiepileptics and their doses is given in table 4.
51
ch-13.indd 51 11/18/2016 5:13:41 PM

PROGNOSIS • Status epilepticus

• Neurologic examination at the time of seizures
Dependent on the cause of seizures, e.g., in case of late-onset • Number of drugs required to treat seizures
hypocalcemia, the outcome is 100% normal and in case of • Findings on neuroimaging
cerebral malformation, nearly all would have a bad prognosis. • Conceptional age (term versus preterm)
Some of the outcomes are listed in table 5. • Birthweight.
Predictive Variables
Multiple rather than single factors appear to be most Algorithm 1
accurate in predicting outcome. However, all these variables Treatment for neonatal seizures
ultimately are related to the degree of brain injury at the time
of seizure occurrence, and, in turn, the seizure etiology.
• Features of the interictal EEG from one or serial recordings
• Features of the ictal EEG
• Seizure burden, including the number of sites of seizure
onset and seizure duration
Table 5: Long term outcome of neonatal seizures

Outcome Incidence (%)
Early death 20–30
Developmental delay 55
Mental retardation 20–40
Cerebral palsy 25–40
No neurological abnormalities 22–35
Postnatal epilepsy 20–30
ABC, airway, breathing, and circulation.
Algorithm 2
Weaning protocol for neonatal seizures
52 EEG, electroencephalogram.
ch-13.indd 52 11/18/2016 5:13:42 PM

Chapter 13: Neonatal Seizures
Key points SUGGESTED READINGs

1. Clancy RR. Summary proceedings from the neurology group on neonatal
))
Neonatal period is the most common time in one’s life to get
seizures. Pediatrics. 2006;117(3 Pt 2):S23-7.
seizures
2. Glass HC, Sullivan JE. Neonatal seizures. Curr Treat Options Neurol. 2009;
))
Preferably, all neonatal seizures should have an EEG 11(6):405-13.
record available to differentiate between the nonepileptic 3. Okumura A. The diagnosis and treatment of neonatal seizures. Chang Gung Med
phenomenon and seizures J. 2012;35(5):365-72.
))
Antiepileptics may have toxic effects on the brain; hence, one 4. Zupanc ML. Neonatal seizures. Pediatr Clin North Am. 2004;51(4):961-78.
should try to stop as soon as possible
))
Further studies are needed regarding new and more
efficacious treatments and their impact on the outcome of
different neonatal seizure types.
53
ch-13.indd 53 11/18/2016 5:13:42 PM

Chapter 14
Neonatal Sepsis
Rahul P Bhamkar, Anjali Kulkarni
INTRODUCTION Table 2: Risk factors for sepsis
Neonatal sepsis is the commonest cause of mortality and Early onset sepsis Late onset sepsis
morbidity in newborns in our country. It can be divided into Maternal factors • Neonatal intensive
two categories based on the onset. • Prolonged rupture of membranes care unit admission
>18 h* • Poor hygiene
• Intrapartum maternal fever >38°C • Low and very low
CLASSIFICATION within 15 days* birthweight babies
Etiology-wise, sepsis can be classified as bacterial and fungal • Foul smelling liquor* • Poor cord care
sepsis. • Chorioamnionitis* • Prematurity
• Bacterial sepsis: presents both as early onset sepsis (EOS) • Unclean vaginal examination • Bottle feeding
and late onset sepsis (LOS) • Maternal leukocytosis (WBC >15000) • Invasive procedure
• Fungal sepsis: presents commonly as LOS. • Prolonged rupture of membrane >12 h • Superficial infection
The difference between early and late onset sepsis is given • Frequent (>3) per vaginal examination (pyoderma,
in labor umbilical sepsis)
in table 1.
• Vaginal positive swab for group B • Fungal sepsis:
streptococcus exposure to broad-
Table 1: Classification of sepsis Fetal factors spectrum antibiotics
• Fetal distress: sustained fetal causing alteration of
Early onset sepsis (<72 h) Late onset sepsis (>72 h) normal flora
tachycardia >160/min*
• Caused by organisms • Caused by organisms
• APGAR <5
acquired before or acquired from hospital or
immediately after birth community • Low birth weight (<1500 g)
(vertical infection) • Prematurity <34 weeks
• Varied presentation
• Predominantly respiratory *Major risk factors
presentation
SIGNS AND SYMPTOMS
ASSOCIATED WITH NEONATAL SEPSIS
RISK FACTORS FOR SEPSIS
Risk factors for sepsis are given in table 2. Early Signs
• Respiratory distress that ranges from mild tachypnea to
respiratory failure
ORGANISMS IN NEONATAL SEPSIS
• Increase in ventilatory support in the mechanically
According to the National Neonatal Perinatal Database data ventilated patient
2002–2003, K. pneumoniae was the commonest (30.1%), • Lethargy or hypotonia
followed by S. aureus (16.2%), E. coli (13%) and Pseudomonas sp. • Increase in apnea
(9.3%). The organisms are similar in both EOS and LOS in Indian • Feeding intolerance
scenario according to this report. • Temperature instability
ch-14.indd 54 11/24/2016 12:30:50 PM

Chapter 14: Neonatal Sepsis
• Hypotension or evidence of poor perfusion TREATMENT

• Increase in heart rate
Supportive Care
Late Signs
• Oxygen/ventilation
• Sclerema
• Volume expansion/maintaining blood pressure with
• Shock
crystalloids, colloids, use of inotropes
• Disseminated intravascular coagulation (DIC)
• Treatment of anemia, thrombocytopenia, DIC
• Pulmonary hemorrhage.
• Temperature maintenance
• Treatment of hypoglycemia/hyperglycemia/hypocalcemia
Clinical Pearl
• Since the signs of neonatal sepsis are very nonspecific, any
Specific Treatment
acute deterioration in a neonate should be assumed to be All babies with presence of risk factors and/or with signs and
because of septicemia in Indian scenarios unless there are symptoms of sepsis should be screened for sepsis and blood
definite indications of alternative pathology. culture should be collected. Pending blood culture report
babies should be judiciously started on antibiotics.
DIAGNOSTIC WORKUP Antibiotics
• Complete blood count: leukocytosis (>20,000) or leuko For practical purpose, antibiotics can be classified as:
penia (<6,000), persistent thrombocytopenia • First-line antibiotics: ampicillin plus gentamicin
• Immature to total neutrophil ratio: increase in immature to • Second-line antibiotics: third or fourth generation cep
total white cell ratio greater than 0.3 is 85% sensitive and halosporin/piperacillin plus tazobactum plus amikacin
specific, particularly for EOS • Third-line antibiotics: carbapenams plus amikacin
• C-reactive protein: rises approximately 12 hours after onset • Fourth-line antibiotics: polymyxin/colistin/vancomycin/
of sepsis and returns to normal within 2–7 days. Greater than linezolid.
1 mg/dL indicates sepsis. Sensitivity 85% and specificity 90%. Choice of antibiotics should be judiciously decided
C-reactive protein has low negative predictive value in EOS (Table 3). For suspected LOS, it is justified to start directly on
• Procalcitonin: greater than 0.25–2 ng/L suggests sepsis; second-line antibiotics. In EOS if high vaginal swab positive,
greater than 2 ng/mL, strong suspicion of sepsis neonate should be treated with specific antibiotics as per
• Blood culture: gold standard in diagnosis till date culture and sensitivity report. If mother is positive for group
• Chest X-ray if respiratory distress B streptococcus then double dose of ampicillin should be
• Lumber puncture: should be performed when index of used.
suspicion of meningitis is high in EOS and in all cases of LOS.
Clinical Pearls Clinical Pearl

• Consideration of fungal sepsis should be given for very
• Blood culture should always be obtained before starting low birthweight babies, especially with central lines who
antibiotic therapy, but inability to obtain blood culture should deteriorate on antibiotics. Fluconazole prophylaxis in such
not delay starting of treatment. babies has shown to reduce the incidence of invasive fungal
• Neutropenia in face of confirmed sepsis indicate that baby is sepsis. In babies with pending culture report, it is justified to
extremely unwell. start antifungal treatment..
Table 3: Antimicrobial dosage with spectrum and schedule

Antibiotic/antifungal Spectrum Dose
Ampicillin Listeria monocytogenes, E. coli, Enterococcus, • Mild/moderate infection: 100 mg/kg/dose
group B streptococcus • Meningitis: 400 mg/kg/day (interval: Table 4)
Cefotaxime Gram-negative enteric bacteria, meningitis • 50 mg/kg/dose (interval: Table 4)
Ceftriaxone* Gram negative bacteria and gonococcal • Sepsis: 50 mg/kg (Table 4)
infection • Meningitis: 80–100 mg/kg
Cefepime Covers both Gram-positive and -negative • <28 days: 30 mg/kg/dose 12 hourly
organism especially P. aeruginosa • >28 days: 50 mg/kg/dose 12 hourly
• Meningitis: 50 mg/kg/dose 8 hourly
Piperacilline + tazobactum Gram-positive, Gram-negative anaerobic, e.g., • 50–100 mg/kg/dose (interval: Table 4)
Enterococcus, Proteus 55
Continued
ch-14.indd 55 11/24/2016 12:30:51 PM

Continued
Antibiotic/antifungal Spectrum Dose
Amikacin Gram-negative enteric bacteria, e.g., Serratia • <29 weeks
{{ 0–7 days: 18 mg/kg/dose 48 hourly
{{ >29 days: 15 mg/kg/dose 24 hourly
• 30–34 weeks
{{ >8 days: 15 mg/kg/dose 24 hourly
• >35 weeks:
{{ 15 mg/kg/dose 24 hourly
Gentamicin Gram-negative bacteria • <32 week

• >32 week
Carbapenems Multiresistant Klebsiella pneumoniae, • 20–25 mg/kg/dose (interval: Table 4)

Enterobacteriaceae, anaerobes
Colistin Pseudomonas aeruginosa • 50,000–75,000 units/kg/day divided 8 hourly
Vancomycin Methicillin-resistant S. aureus • <29 week
{{ 0–14 days: 10–15 mg/kg/dose 18 hourly
{{ >14 days: 10–15 mg/kg/dose 12 hourly
• 30–42 week
{{ 0–14 days: 10–15 mg/kg/dose 12 hourly
{{ >14 days: 10–15 mg/kg/dose 8 hourly
• >42 weeks
{{ 10–15 mg/kg/dose 6 hourly
Linezolid Methicillin-resistant S. aureus refractory to • <34 weeks: 10 mg/kg/dose 12 hourly

vancomycin • >34 weeks: 10 mg/kg/dose 8 hourly
Fluconazole Candida spp. • Prophylaxis: 3 mg/kg/dose twice weekly
• Therapeutic:
{{ <29 week:
–– 0–14 days: 6 mg/kg/dose 48 hourly

–– >14 days: 6 mg/kg/dose 24 hourly
{{ >30 weeks
–– 0–7 days: 6 mg/kg/dose 28 hourly

–– >7 days: 6 mg/kg/dose 24 hourly
Liposomal amphotericin B Fluconazole-resistant Candida spp. • 2.5–7 mg/kg/day as continuous infusion over 1 h 24 hourly
*Not recommended for use in neonates with hyperbilirubinemia, concurrent administration with calcium-containing product contraindicated.
Table 4: Dosing interval chart Management of Early Onset Sepsis

Gestational age Postnatal age Interval Management of early onset sepsis is represented in algorithm 1.
Asymptomatic neonate with minor risk factors should be
<29 weeks 0–28 days 12 h observed, pending blood culture and septic screen and
>28 days 8h treatment should be started if baby becomes symptomatic or
30–36 weeks 0–14 days 12 h screening results are positive, whereas neonates with major
>14 days 8h risk factors should be started on antibiotics pending the sepsis
screen results. All symptomatic neonates where alternative
>37 weeks 0–7 days 12 h diagnosis is not possible should be started on antibiotics.
>7 days 8h
Clinical Pearl
• About 90% of the early onset sepsis would present with
Clinical Pearl respiratory involvement.
• Irrational use of antibiotics should be avoided in neonatal
intensive care unit. Clinically evaluate and consider other Management of Late Onset Sepsis
56 clinical diagnosis in the absence of positive laboratory
Management of late onset sepsis is represented in algorithm 2.
parameters and symptomatic baby.
All severely symptomatic infants should be started on anti
ch-14.indd 56 11/24/2016 12:30:51 PM

Chapter 14: Neonatal Sepsis
Algorithm 1 Algorithm 2
Management of early onset sepsis Management of late onset sepsis
*Lumber puncture, all symptomatic infant except in premature baby with RDS
CSF, cerebrospinal fluid.
Algorithm 3
Stopping antibiotics
biotics pending sepsis screen, blood culture, and cerebrospinal • Intravenous immunoglobulin, pentoxifylline (immuno
fluid examination and culture reports. Babies with minor modulator)
symptoms should be started on treatment based on the sepsis • Colony-stimulating factor
screen results. • Blood exchange transfusion
Clinical Pearls Key points

• A sepsis screen is not warranted in neonates with a high ))
Sepsis is the commonest cause of mortality and morbidity in
probability for sepsis. Instead, these neonates should be the neonatal period
directly started on antibiotics pending blood culture ))
We should have a high index of suspicion for diagnosis, and
• Lumbar puncture should be done in all cases of late onset antibiotics must be used judiciously where required along
sepsis. with the appropriate supportive therapy.
Stopping Antibiotics SUGGESTED READINGs

Guidelines for stopping antibiotics are illustrated in 1. Benitz WE, Han MY, Madan A, Ramachandra P. Serial serum C-reactive protein
algorithm 3. Duration of antibiotics depends upon clinical levels in the diagnosis of neonatal infection. Pediatrics. 1998;102:E41.
condition of the infant and organism identified. If septic screen 2. Martin RJ, Fanaroff AA, Walsh MC, editors. Fanaroff and Martin’s Neonatal-
and blood culture is negative and baby is asymptomatic or Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed. Maryland Heights,
symptoms resolved, antibiotics can be stopped after 48 hours. Missouri: Elsevier; 2010.
If blood culture is negative and clinical suspicion is high, 3. Kliegman RM, Stanton BM, Geme JS, Schor NF, Behrman RE, editors. Nelson
Textbook of Pediatrics. 19th ed. Maryland Heights, Missouri: Elsevier; 2011.
repeat blood culture and CRP; continue antibiotics for 7–10
4. Neonatology Clinical Guidelines. King Edward Memorial Hospital, Perth, Western
days till infective indices have normalized. For proven sepsis Australia. Feb 2010.
with normal cerebrospinal fluid findings, treatment should be 5. Remington JS, Klein JO. Infectious Diseases of the Fetus and Newborn Infant. 7th
at least 10–14 days and for meningitis, treatment should be for ed. Maryland Heights, Missouri: Elsevier; 2010.
21 days. For fungal sepsis, treatment duration is 3–6 weeks or 6. Segar JL, Patel CA, Tierney SB. Recommended Antimicrobial Dosage Schedules
21 days after first negative blood culture. for Neonates. Available from: https://www.uichildrens.org/uploadedFiles/
UIChildrens/Health_Professionals.
7. Singh SA, Dutta S, Narang A. Predictive clinical scores for diagnosis of late onset
Adjunctive Therapies in Sepsis neonatal septicemia. J Trop Pediatr. 2003;49:235-9.
The following treatments have been tried with varying results but 8. Young TE, Magnum B. Neofax: A manual of drugs used in neonatal care. 23rd ed.
there is no evidence-based recommendation for any of these. Columbus, Ohio: Ross Laboratories; 2010.
57
ch-14.indd 57 11/24/2016 12:30:51 PM

Chapter 15
Approach to
Congenital Heart Disease
Dinesh K Chirla, Preetham K Poddutoor
INTRODUCTION Table 2: Causes and frequency of congenital heart disease
Congenital heart disease (CHD) is found in 7–8 per 100 live Causes Frequency Common cardiac
births. It may occur as an isolated defect or in association with (%) abnormalities
other malformations such as esophageal atresia, anorectal Chromosomal disorder
malformation, exomphalos, and skeletal defects. Trisomy 21 30–40% Atrioventricular septal
About 10–15% have complex lesion with more than one defect, VSD
cardiac abnormality and 10–15% have noncardiac abnormality. Trisomy 18 and 13 60–80% Complex (VSD, PDA)
The most common congenital anomalies are given in table 1.
Turners (45XO) 15% Aortic valve stenosis,
coarctation of aorta
Clinical Pearl Chromosome 22q — Aortic arch anomalies,
• The nine most common congenital anomalies account for deletion tetralogy of Fallot
80% of all lesions. Maternal drugs
Warfarin therapy 5% Pulmonary valve stenosis,
Congenital heart disease is particularly common in PDA
chromosomal disorders and with some maternal conditions. Fetal alcohol syndrome 25% ASD, VSD, tetralogy of Fallot
A neonate should be suspected and evaluated for CHD in the
Maternal disorders
following conditions (Table 2 and Algorithm 1).
Newborn with CHD presents if there is: Rubella infection 30–35% Peripheral pulmonary
• Unfavorable transitional circulation where the circulation stenosis, PDA
is parallel instead of being in series Systemic lupus 35% Complete heart block
• Obstruction of series circulation and patent ductus erythematosus (SLE)
arteriosus closes Diabetes mellitus 2% Increased incidence
• Fall in pulmonary vascular resistance and shunting and overall (VSD, transposition,
mixing occurs. hypertrophied septum)
Initial evaluation would include assessment of perfusion, VSD, ventricular septal defect; VSD, ventricular septal defect; PDA, patent
oxygen saturation, pulses, and blood pressure measurements. ductus arteriosus.
Table 1: The most common congenital heart lesion

ANTENATAL DIAGNOSIS
Acyanotic Outflow obstruction Cyanotic
Checking the anatomy of fetal heart has become a routine
VSD 30% Pulmonary stenosis 7% Tetralogy of Fallot 5%
part of the fetal anomaly scan (targeted imaging for fetal
PDA 12% Aortic stenosis 5% TGA 5% anomalies) at 18–20 weeks in most of the fetal medicine units.
ASD 7% Coarctation of aorta 5% AVSD 2% If an abnormality is detected, detailed fetal echocardiography
TGA, transposition of the great arteries; VSD, ventricular septal defect; AVSD, is performed by pediatric cardiologists (Algorithm 2).
atrioventricular septal defect; PDA, patent ductus arteriosus. Unfortunately, these services are available only in few tertiary
ch-15.indd 58 11/24/2016 12:33:08 PM

Chapter 15: Approach to Congenital Heart Disease
Algorithm 1
Algorithm 2 The following features of murmurs are associated with

When to do fetal echocardiography structural heart disease:
• Murmur intensity grade 3 or higher
• Harsh quality
• Pansystolic duration
• Loudest at upper left, upper right sternal border, or apex
• Abnormal S2.
Clinical Pearl
• The features of an innocent murmur can be remembered as
the four S’s: Soft, Systolic, aSymptomatic, and left Sternal edge.
Cyanosis
Much more threatening than a murmur is the presence of
cyanosis. Peripheral cyanosis may occur when a neonate is cold
or unwell from any cause. Central cyanosis is seen on tongue.
Cyanosis without pulmonary disease is almost invariably
the result of a serious cardiac abnormality. Clinically, it is
CHD, congenital heart disease; SLE, systemic lupus erythematosus. sometimes difficult to identify cyanosis differentiating between
cardiac and pulmonary cyanosis see (Table 3); always check
oxygen saturation with pulse oximetry. Those with left-sided
units or perinatal centers in India. Depending on diagnosis,
obstructive lesions present with inadequate systemic perfusion
some choose termination of pregnancy in complex CHD;
and shock, whereas those with right-sided lesions present with
majority can continue with pregnancy and have neonates
cyanosis because of inadequate blood reaching the lungs. In
management planned antenatally.
neonatal period, cardiac cyanosis may be caused by:
• Reduced pulmonary blood flow
Clinical Pearl {{ Critical pulmonary stenosis
{{ Tetralogy of Fallot
• Neonates with duct-dependent lesion are likely to need
{{ Tricuspid atresia/Ebstein’s
treatment in the first 2 days.
• Poor mixing/separate parallel systemic and pulmonary
circulation
Pathologic Murmurs {{ Transposition of great vessels
The intensity and quality of the murmur and associated • Common mixing of systemic venous and pulmonary
findings differentiate innocent murmurs from those associated venous blood
with heart disease. {{ TAPVR, truncus arteriosus, double outlet ventricle. 59
ch-15.indd 59 11/24/2016 12:33:08 PM

Table 3: Clinical features helpful in distinguishing respiratory from cardiac cyanosis

Respiratory cyanosis Cardiac cyanosis
History Prematurity, meconium liquor/below Family history of congenital heart disease
cords, risk of infection
Respiration Marked respiratory distress Little or no respiratory distress unless shocked or metabolic
disorders
Cardiovascular examination Normal May have clear signs
Response to oxygen Cyanosis likely to improve Cyanosis unlikely to improve dramatically
Chest X-ray Obvious respiratory pathology No respiratory pathology, abnormal heart shadow or lung
Normal cardiothoracic ratio vasculature may be seen
Electrocardiogram Normal May be normal, may be helpful
Blood gases Hypercapnia Hypo- or normocapnia
Heart rate ++ +++
Respiratory rate +++ ++
Grunt ++ 0/+
Murmur 0 0/+/++/+++
Congestive heart failure 0 0/+/++/+++
Abnormal pulses 0 0/+
Response to O2 +++ 0/+
Note that all categories have overlap between respiratory and cardiac causes.
The diagnosis of cyanotic CHD can be confirmed by Algorithm 3

hyperoxia test if detailed echocardiography is not available. Neonate with cardiogenic shock
Heart Failure
Heart failure in neonatal period usually results from left heart
obstruction, e.g., coarctation of aorta. If the obstruction is severe
then arterial perfusion is predominantly via arterial duct (right
to left flow) so called duct-dependent systemic circulation.
Congenital Heart Disease:

Presenting as Cardiac Failure
• Neonate—obstructed systemic circulation (duct-dependent): TGA, transposition of the great arteries; HCM, hypertrophic cardiomyopathy;
DCM, dilated cardiomyopathy.
presents with shock
{{ Hypoplastic left heart syndrome • In lesions with parallel pulmonary and systemic
{{ Critical aortic valve stenosis circulations (e.g., transposition of the great arteries with
{{ Severe coarctation of aorta intact ventricular septum), mixing between the two
{{ Interruption of aortic arch circulations is decreased, leading to hypoxia and metabolic
• Infants acidosis, which results in failure and shock
{{ Ventricular septal defect • Cardiogenic shock must be differentiated from other
{{ Atrioventricular septal defect causes of shock, such as sepsis. In newborns who present
{{ Large patent ductus arteriosus. with shock, cardiomegaly is a helpful finding indicating a
cardiac etiology.
Shock
A variety of mechanisms can lead to cardiogenic shock SYSTEMATIC ASSESSMENT OF
in newborns with duct-dependent CHD when the ductus
arteriosus closes (Algorithm 3):
THE INFANT WITH SUSPECTED
• In left heart obstructive lesions (e.g., hypoplastic left heart CONGENITAL HEART DISEASE
syndrome, critical aortic stenosis, coarctation of the aorta,
and interrupted aortic arch), systemic perfusion is lost History
• In right-sided obstructive lesions (e.g., total anomalous • Birth details (peripartum asphyxia)
pulmonary venous connection, tricuspid atresia and mitral • Maternal illness or drug ingestion, anticonvulsant, warfarin,
60 atresia), restricted pulmonary blood flow results in reduced lithium
systemic blood flow, which may result in shock • Family history.
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Chapter 15: Approach to Congenital Heart Disease
Symptoms in Baby • Peripheral perfusion and temperature

• Blood pressure of all four limbs.
• Cyanosis
• Poor feeding
• Breathlessness
Diagnosis
• Excess weight gain. If CHD is suspected, a chest X-ray and electrocardiography
should be performed. Echocardiography combined with
Examination Doppler ultrasound will be able to diagnose all causes of CHD.
Cardiac catheterization is seldom needed.
• Color (cyanosis or pallor), oxygen saturation
• Respiratory rate
• Heart rate Clinical Pearl
• Peripheral pulses: • A normal chest X-ray and electrocardiography does not
{{ Inequality of volume between right and left brachial
exclude congenital heart disease.
pulse
{{ Weak femoral pulses
{{ Pulses weak or bounding Specific Treatment

• Cardiac impulse (right or left ventricular prominence) Individual treatment options for common acyanotic con
• Heart sounds genital heart diseases are given in table 4 and those with
• Murmur: timing, nature, duration, loudness, site, and outflow obstruction in a well child are given in table 5 and
radiation for a sick child in table 6. The principles of management of
• Hepatomegaly congenital heart disease are given in algorithm 4 and 5, and
• Edema the management of heart failure is given in algorithm 6.
Table 4: Acyanotic heart disease : Left-to-right shunts

Lesion Symptoms Signs Management
ASD-secundum None Ejection systolic murmur Catheter device closure (3–5 years)
AVSD-partial None, heart failure Fixed split S2 Surgery at 3 years
VSD-small (80–90%) None Pansystolic murmur None
VSD-large (10–20%) Heart failure Active precordium Diuretics, captopril, surgery at 3–6 months
PDA-term None Continuous murmur Coil or device closure
PDA-preterm None, heart failure Systolic murmur + bounding pulses Fluid restriction, brufen or indomethacin,
surgical closure
ASD, atrial septal defect; AVSD, atrioventricular septal defect; VSD, ventricular septal defect.
Table 5: Outflow obstruction in the well child

Lesion Signs Management
Aortic stenosis Murmur, upper right sternal edge, carotid thrill Balloon dilatation
Pulmonary stenosis Murmur, upper left sternal edge, no carotid thrill Balloon dilatation
Coarctation of aorta Systemic hypertension, radiofemoral delay Surgery
Table 6: Left heart outflow obstruction in the sick child—duct-dependent lesion

Lesion Signs Management
Coarctation of aorta and prostaglandin Heart murmur, heart failure Maintain ABC, immediately start
Interrupted aortic arch Weak or absent femoral pulses
Blood pressure arms > leg
Hypoplastic left heart syndrome Circulatory collapse Maintain ABC, immediately start PGE
All peripheral pulses weak or absent Surgery (complex) Norwood
ABC, airway, blood, circulation; PGE, prostaglandin E.
61
ch-15.indd 61 11/24/2016 12:33:09 PM

Algorithm 4
TAPVC, total anomalous pulmonary venous connection; DOV, double outlet ventricle; DIV, double inlet ventricle; TGA, transposition of the great
arteries; IVSD, inlet ventricular septal defect; AVSD, atrioventricular septal defect; PDA, patent ductus arteriosus.
Algorithm 5
CHF, congestive heart failure; CCHD, critical congenital heart disease; ABC, airway, breathing, circulation; BP, blood pressure; ECG, echocardiogram.
Algorithm 6
Key points
Management of heart failure
))
Congenital heart disease may present as a neonatal emergency
))
Acyanotic left-to-right shunts are the commonest anomalies
))
Congenital heart disease is an important differential diagnosis
in a neonate presenting with respiratory distress
))
Occasionally, congenital heart disease may be asymptomatic;
hence, it is essential to check saturation and blood pressure in
all four limbs in all the newborns prior to discharge.
SUGGESTED READINGs
1. Dolbec K, Mick NW. Congenital Heart Disease. Emerg Med Clin N Am.
2011;29:811-27.
2. Yee L. Cardiac emergencies in the first year of life. Emerg Med Clin N Am.
2007;25:981-1008.
3. Yates R. Cardiovascular disease. Rennie & Roberton’s Textbook of Neonatology;
62 2012.
ch-15.indd 62 11/24/2016 12:33:09 PM

Chapter 16
First Golden Hour
Management of Preterm
Naveen Bajaj
INTRODUCTION Clinical Pearl

The term “golden hour” has been taken from the adult trauma
• Consistencies in golden hour stabilization practices improve
treatment arena in which the best time frame to prevent
neonatal outcome in preterm and very low birth weight
irreversible internal damage and optimize the chance of
babies.
survival is the first hour of management. Neonates especially
very low birth weight (VLBW) and preterm babies of less
than or equal to 32 weeks of gestation are highly vulnerable
to many disease in the first hours of life when adaptation is BASIC PRINCIPLES
critical and timing of care affects survival and long-term • Lung protection
outcome. Delivery room management that focuses on • Brain protection
adaptation of these infants, as well as early interventions in • Minimize damage to other organs
first hour of life that improve long-term outcomes, emphasize • Early nutrition.
the importance of this ‘golden hour’” of care in this extremely Techniques included in the golden hour stabilization
vulnerable population of preterms and VLBW babies. practices are:
• Thermoregulation
SPECIAL CONSIDERATIONS • Resuscitation as per Neonatal Resuscitation Program
IN PRETERM NEONATES guidelines
• Poor thermal control • Respiratory management
{{ Oxygen targeting
• Poor energy stores
{{ Administering positive end-expiratory pressure (PEEP)
• Poor respiratory drive
{{ Continuous positive airway pressure (CPAP) venti
• Surfactant deficiency
• Susceptibility to intraventricular hemorrhage and lation
periventricular leukomalacia {{ Nasal ventilator strategies to an infant in the delivery
• Often born after a complication of pregnancy like room to reduce intubations

antepartum hemorrhage, intrauterine growth restriction, {{ Early identifications of those infants who need
infection, etc. surfactant and mechanical ventilation

• Stressed family. • Fluid and nutrition
• Treatment and prevention of infections
AIM OF GOLDEN HOUR • Developmentally supportive care
• Family centered care.
• To optimize the survival free of disability in preterm infants
(≤32 weeks) and VLBW by providing optimal interventions
in the first few hours of life Clinical Pearl
• To undertake all nursing and medical procedures as quickly
• Thermoregulation, respiratory, and nutrition practices
and with as little disturbance to the infant as possible,
constitute the most important aspect of first golden hour.
usually within 1 hour of admission.
ch-16.indd 63 11/18/2016 5:19:23 PM

PRINCIPLES OF GOLDEN HOUR Thermoregulation

CARE (Figure 1 and Algorithm 1) Thermal instability has a detrimental effect on infants’
transition to extrauterine life.
Delivery Room Practices

• Maintain delivery room temperature greater than 25–26°C
• Radiant warmer on 30 minutes prior to delivery
• Prewarmed blankets/hat
• Polyethylene bag in less than 29 weeks of gestation
• Heated and humidified gas during resuscitation and
transport (preferable)
• Transport in a prewarmed incubator.
Neonatal Intensive Care Unit (NICU) Practices

• Radiant warmer/incubator on 30 minutes prior to expected
Fig. 1 : The golden hour triad arrival of baby
Algorithm 1
NICU, neonatal intensive care unit; ET, endotracheal tube; FiO2, fraction of inspired oxygen; CPAP, continuous positive airway pressure; SpO2, pulse oxygen
64 saturation; MV, mechanical ventilation; UVC, umbilical venous catheter; UAV, umbilical arterial catheter; PICC, peripherally inserted central catheter; TPN, total
parenteral nutrition.
ch-16.indd 64 11/18/2016 5:19:24 PM

Chapter 16: First Golden Hour Management of Preterm
• On admission to NICU, weigh infant in the polyethylene bag • Intubation and prophylactic surfactant is the best
• Use incubator in less than or equal to 28 week baby, supported approach to the initial respiratory management
and remove bag on admission regardless of admission of the most preterm infants of less than 26 weeks
temperature • Infants of greater than or equal to 26–28 weeks may be
• If using radiant warmer and admission temperature best managed with prophylactic surfactant and rapid
less than 37°C, leave in bag until procedures such as line extubation to nasal CPAP or early elective nasal CPAP with
insertion is completed and then remove bag. If using selective surfactant treatment depending upon institution
radiant heat source and admission temperature is greater policy
than or equal to 37°C, remove bag. Place a skin temperature • More mature preterm infants of greater than 28 weeks
probe to avoid extremes in temperature. may be best managed with early elective nasal CPAP
with selective surfactant treatment, If a preterm infant is
Clinical Pearl managed initially with nasal CPAP, surfactant is given if
fraction of inspired oxygen (FiO2) requirement increases
• In extreme preterms, additional measures like use of polythene to 0.30–0.40 with X-ray showing respiratory distress
bag in delivery room and transportation of infant in incubator syndrome
is desired to prevent hypothermia in early hour. • Acceptable oxygen saturations in preterm newborns in
delivery room are given in table 1
Respiratory Support (Algorithm 2) • In NICU, maintain pulse oxygen saturation SpO2 88–92%
• Acceptable arterial blood gas: pH = 7.25–7.35; partial
Goals of treatment is to use the least amount of intervention pressure of arterial carbon dioxide (PaCO2) = 40–50 mmHg;
necessary to support normal gas exchange while minimizing partial pressure of arterial oxygen (PaO2) = 50–70 mmHg.
lung injury by early intervention, optimizing lung recruitment
by using high PEEP and avoiding lung overdistention (low tidal
volume 5–6 mL/kg). Clinical Pearl
• Use air/oxygen blender for resuscitation
• Prophylactic/early surfactant and nasal continuous positive
• Use pulse oximetry and target saturations to guide to
airway pressure practices are aimed to minimize lung injury.
inspired oxygen concentration
Algorithm 2
Golden hour respiratory practices
65
PEEP, positive end-expiratory pressure; CPAP, continuous positive airway pressure; FiO2, fraction of inspired oxygen.
ch-16.indd 65 11/18/2016 5:19:24 PM

Table 1: Acceptable oxygen saturations in preterm newborns • Establish contact between the family and members of the
in delivery room • Neonatal intensive care unit team and/or other support
Time from birth in minutes Acceptable right wrist or hand
individuals before the birth of the infant
saturation • Maintain infant-family contact throughout the admission
process
1 60
• Ensure that the family is fully informed of their infant’s
2 65 condition
3 70 • Welcome the family to the NICU.
4 75
5 80
Clinical Pearl
10 85 • Parental stress needs to be addressed by the treating physician.
Fluids and Nutrition INVESTIGATION

The goal is to prevent hypoglycemia but also fluid overload. Take blood tests from umbilical arterial catheter or peripheral
• Start fluids 60–100 mL/kg depending upon the gestational line once inserted and record amount of blood withdrawn.
age • Blood glucose
• Start D10% with amino acids [total parenteral nutrition • Arterial blood gas
(TPN) starter bag] as the first fluid • Complete and differential blood counts
• Prevent hypoglycemia and hyperglycemia • Blood culture, C-reactive protein
• Monitor electrolytes and correct acidosis • Blood group Consider coagulation screen if severe
• Avoid volume overload chorioamnionitis/sepsis
• If hypotensive, start dopamine after one fluid bolus of • X-ray chest.
10 mL/kg
• Start trophic feeds as early as possible.
Key points
Developmentally Supportive Care ))
Golden hour is critical short period of time at birth where
• Considerable stress response has been associated with appropriate interventions (or the lack thereof ) can make a
normal birth and high risk (preterm) neonates may be difference in neonatal mortality and morbidity
particularly susceptible to stressors because of frequent ))
Thermoregulation, neuroprotection, respiratory, and nutrition
painful procedures and constant exposure to noxious practices constitute the most important aspect of first golden
sensory inputs which are auditory, visual, tactile, and hour care
chemosensory in nature in NICU. ))
Strong communication, teamwork, clinical skills and evidence-
• Sound based practices are essential in delivering best care to these
{{ Minimize unnecessary conversation high risk neonates consistently
{{ Keep voices low
))
Parental counseling is important in allaying the anxiety and
{{ Silence or keep alarms at low volume
stress of the family.
• Light
{{ Use lowest light level necessary
{{ Shield baby’s eyes SUGGESTED READINGS

• Chemosensory
1. Davis PG, Lemyre B, de Paoli AG. Nasal intermittent positive pressure ventilation
{{ Allow alcohol based swabs to dry away from nose
(NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm
• Tactile neonates after extubation. Cochrane Database Syst Rev. 2001;3:CD003212.
{{ Receive baby in bag or warmed, soft blanket
2. Rojas-Reyes MX, Morley CJ, Soll R. Prophylactic versus selective use of surfactant
{{ Dry and handle gently in preventing morbidity and mortality in preterm infants. Cochrane Database Syst
{{ Use “nesting” Rev. 2012;3:CD000510.
{{ Minimize pain 3. Stevens TP, Blennow M, Myers EH, Soll R. Early surfactant administration with
{{ Umbilical lines/peripherally inserted central catheter brief ventilation vs. selective surfactant and continued mechanical ventilation
line for preterm infants with or at risk for respiratory distress syndrome. Cochrane
{{ Premedication for intubation
Database Syst Rev. 2007;4:CD003063.
4. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research
{{ Sucrose for painful procedures
Network, Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, et al. Early CPAP versus
{{ Skin-to-skin with parent if possible.
surfactant in extremely preterm infants. N Engl J Med. 2010;362(21):1970-9.
5. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal
Family Involvement Research Network, Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, et al.
Birth of a high risk neonate is highly anxiety-provoking for Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med.
2010;362(21):1959-69.
families.
6. Vaucher YE, Peralta-Carcelen M, Finer NN, Carlo WA, Gantz MG, Walsh MC, et al.
66 • Provide neonatology consultation or repeat consultation
Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial. N Engl
before the birth of the infant J Med. 2012;367(26):2495-504.
ch-16.indd 66 11/18/2016 5:19:24 PM

Chapter 17
Perinatal Hypoxia
Ashish Jain, Veeraraja B Sathenahalli
INTRODUCTION CLINICAL EVALUATION

Perinatal hypoxia/asphyxia is a common major health problem Subsequent to the resuscitation of the baby, the post-
causing morbidity and mortality in neonates. According to asphyxiated newborn should undergo a detailed clinical evalua
National Neonatal-Perinatal Database, perinatal hypoxia is tion, as this neonate is prone for multiorgan dysfunction as
the most common cause of stillbirth accounting up to 45% of perinatal hypoxia virtually affects every organ system. Further
cases and is one among the three leading causes of neonatal management and outcome varies on the severity of organ
mortality. This denotes the magnitude of this serious clinical dysfunction. There are several scoring systems that have being
condition. Cautious monitoring and management of a neonate used. A scoring system that can be specifically followed for that
with perinatal hypoxia is an area of importance. Guidelines on setting should be used. Some of the scoring system would need
clinical approach and management may help in improving the an electroencephalography (EEG) and other investigations on
outcome. The management of perinatal hypoxia is evolving the baby. The most commonly used systems are:
day by day with better understanding of its pathophysiology. • Sarnat and Sarnat staging system—a descriptive staging
system
DEFINITIONS • Levene staging system—a simpler, practical staging system
• Thompson scoring system.
The definitions of perinatal hypoxia vary from context to context.
The babies who have mild stage of the disease (Thompson
Thus, there is no single definition of perinatal hypoxia.
score <10) are almost free of any neurodevelopmental
National Neonatal-Perinatal Database defines perinatal
sequelae, however, the babies with moderate and severe
hypoxia/asphyxia as moderate when there is slow/gasping
stage of encephalopathy (Thompson score >10 and >15) may
breathing or an Apgar score of 4–6 at 1 minute and severe if no
have a neurodevelopmental impairment in 25% and 95% of
breathing or an Apgar score of 0–3 at 1 minute of age.
cases, respectively. A non-progressing score is also reassuring
American Academy of Pediatrics and American College of
and has a better outcome; hence the serial examination is
Obstetrics and Gynecology require presence of all of following
criteria to define perinatal asphyxia: important on day to day basis for the first 7 days.
• Profound metabolic or mixed acidemia (pH <7.0) in
umbilical cord blood Clinical Pearls
• Persistence of low Apgar scores less than 3 for more than • Staging/scoring system is vital in management of hypoxic-
5 minutes ischemic encephalopathy. Blood gas and electroencep
• Signs of neonatal neurologic dysfunction (e.g., seizures, halogram should be done wherever the facility is available
encephalopathy, tone abnormalities) • These systems though vital in management, a single time
• Evidence of multiple organ involvement (such as that of finding should not be used as criteria to prognosticate
kidneys, lungs, liver, heart, and intestine). parents about baby. It is suggested to serially follow up and
prognosticate about the baby accordingly.
Clinical Pearl
• No definition of perinatal asphyxia is complete, all the MONITORING
definitions have limitations. The definition which is feasible
Neonates with moderate and severe encephalopathy are to
and sensitive should be used.
be shifted to neonatal intensive care unit (NICU) for further
ch-17.indd 67 11/18/2016 5:24:21 PM

Table 1: Suggested monitoring in moderate to severe cases of perinatal asphyxia

Organ system Possible dysfunctions Monitoring recommended
Temperature Temperature dysregulation Continuous monitoring of temperature, avoid
hyperthermia of any degree
CNS HIE, intracranial hemorrhage, seizures, long-term Staging system of HIE, aEEG monitoring where facilities are
neurological sequelae available
Cardiac Myocardial dysfunction, valvular dysfunction, rhythm Heart rate, ECG monitoring, SpO2 monitoring, invasive BP
abnormalities, congestive cardiac failure monitoring when required
Renal Hematuria, acute tubular necrosis, renal vein thrombosis Urine output measurement, urine routine examination,
renal parameters, and serum electrolytes
Pulmonary Delayed adaptation, respiratory failure, meconium aspiration, ABG monitoring, regular adjustments and monitoring of
surfactant depletion, primary pulmonary hypertension the ventilator settings
GI tract Necrotizing enterocolitis, hepatic dysfunction Abdominal girth monitoring, see for aspirates if distention
present
Hematological Thrombocytopenia, coagulation abnormalities Complete blood counts with platelets and PT, especially if
bleeding
Others Metabolic acidosis, hypoglycemia, hypocalcemia, Regular monitoring of the blood sugar, calcium, and
hyponatremia electrolyte
HIE, hypoxic ischemic encephalopathy; CNS, central nervous system; aEEG, amplitude-integrated electroencephalography; ECG, electrocardiogram; SpO2, pulse
oxygen saturation; BP, blood pressure; ABG, arterial blood gas; GI, gastrointestinal; PT, prothrombin time.
Table 2: Levene staging system for hypoxic ischemic encephalopathy

Features Mild Moderate Severe
Consciousness Irritable Lethargy Comatose
Tone Hypotonia Marked hypotonia Severe hypotonia
Seizures No Yes Prolonged
Sucking/respiration Poor suck Unable to suck Unable to sustain spontaneous respiration
management. However, neonates with mild encephalopathy frequently for the next 48–72 hours for development of any
should be monitored at regular intervals for signs of advanced features of HIE (Table 2).
stages of hypoxic ischemic encephalopathy (HIE). The clinical
features of HIE vary over time. The window period between Management in Neonatal Intensive Care Unit
these stages can be used for therapeutic intervention. Strict
clinical monitoring will help in management of these neonates. Management of moderate to severe hypoxia consists of
Perinatal hypoxia affects virtually every organ system mainly clinical, lab monitoring at regular intervals, and maintaining
renal, central nervous system and cardiac. The clinical features the physiology, viz., temperature, oxygenation, fluid, and
of organ dysfunction should be looked for. Organ system electrolyte status. Any complications like seizures are promptly
dysfunction seen in perinatal hypoxia is given in table 1. managed. Clinical parameters like heart rate, respiratory
rate, pulse oxygen saturation (SpO2), temperature, blood
pressure, capillary refill time, urine output, and neurological
MANAGEMENT
examinations for the signs of HIE should be monitored at
The management is mainly supportive and comprises of regular intervals. Laboratory parameters to be monitored
cardiac, respiratory, metabolic, and neurological support in include blood sugar, blood gas, urine osmolality, serum
the form of maintaining optimum saturation, perfusion, blood electrolytes, and renal function tests at regular intervals. Other
sugar, calcium levels, and control of seizures. parameters like electrocardiogram, and chest X-ray should be
done in clinically indicated babies.
Delivery Room Management Important management guidelines for care in NICU are
discussed below.
Maintain appropriate temperature, airway, and serially record
Apgar score. Collect umbilical arterial cord blood for analysis.
A neonate with moderate to severe hypoxia is resuscitated Supportive Therapy
as per the Neonatal Resuscitation Program guidelines and • Maintain normal temperature and avoid hyperthermia
transferred to NICU for further management. A neonate with • Maintain adequate ventilation and oxygenation. The
68 mild hypoxia is transferred to mother’s side and monitored oxygen saturations should be targeted between 90 and 95%.
ch-17.indd 68 11/18/2016 5:24:21 PM

Chapter 17: Perinatal Hypoxia
Table 3: Thompson score

Signs 0 1 2 3
Tone Normal Hyper Hypo Flaccid
LOC Normal Hyperalert, stare Lethargic Comatose
Fits None <3 per day > 2 per day Refractory
Posture Normal Fisting, cycling Strong distal flexion Decerebrate
Moro Normal Partial Absent –
Grasp Normal Poor Absent –
Suck Normal Poor Absent ± bites –
Respiration Normal Hyperventilation Brief apnea IPPV
Fontanel Normal Full, not tense Tense –
LOC, level of consciousness; IPPV, intermittent positive pressure ventilation.
Assisted ventilation should be provided in case of apnea Benzodiazepines are third-line drugs. Lorazepam is
or respiratory distress causing inadequate respiration. advised in doses of 0.05–0.1 mg/kg/dose intravenously. In
Permissive hypercarbia is allowed refractory cases, consider use of investigations like EEG,
• Maintain fluid and electrolyte status by judicious use cranial ultrasonography, computed tomography scan, and
of fluids. Where tissue perfusion is poor, consider fluid magnetic resonance imaging brain to evaluate for neural
bolus and inotrope support (dopamine and dobutamine). injuries.
Dobutamine is a better choice as the peripheral vascular Long-term seizure management: it is based on clinical exam
resistance in these babies is already high. Restricted and EEG. If clinical exam and EEG are normal, anticonvulsant
fluid administration as a routine is not advised as it can be weaned. If on more than one anticonvulsant, the last
may predispose the baby to hypotension. Restrict fluid anticonvulsant is weaned first. If any of the two are found to
only if there is hyponatremia (sodium <120 mg/dL) due be abnormal, then the anticonvulsant is continued for 1 month
to syndrome of inappropriate antidiuretic hormone and baby reassessed at 1 month. Newborns with neurological
secretion and in cases of acute renal failure. Hypoxia deficit/sequelae and abnormal EEG are at risk of recurrent
may cause injury to heart affecting its contractility. This seizures and may require long-term anticonvulsant therapy.
can be assessed using echocardiography and managed • Cardiac support: fluid bolus and inotrope are advised to
accordingly maintain adequate perfusion
• Maintain normal metabolic milieu by frequent monitoring • It is advised to withhold feeds until all parameters are
of blood sugar. Serum calcium is monitored regularly. It is stable
recommended to administer calcium in maintenance dose • Hematologic, hepatic, and pulmonary derangements are
to all severely hypoxic for 2 days so as to maintain calcium managed accordingly.
in normal range
• Seizures are serious manifestation of HIE (Stage II HIE). Therapeutic Hypothermia
Hypoxic seizures usually occur in the first 12–24 hours. This is now emerging as a novel therapy in babies with peri
These may be subtle or evident prominently. Electro natal asphyxia to prevent the death and neurodevelopmental
encephalogram recording will help to identify subclinical impairment. This mode is used in infants of 36 weeks gestation
seizures. Any metabolic disturbances like hypoglycemia, or more with moderate to severe encephalopathy. It consists
hyponatremia, and hypocalcemia should be corrected. of moderate use of therapeutic hypothermia (33–34°C) within
4 hours of life. It has shown reduction in combined outcome
Specific Therapy of mortality or major neurodevelopmental sequelae within
Treatment of seizures: phenobarbitone is the initial drug of 6 hours of life and continued for 72 hours of age.
choice. Loading dose of 20 mg/kg followed by 2 additional
boluses of 10 mg/kg if seizures continue. Maintenance dose of Clinical Pearls
3–5 mg/kg/day is started after 24 hours. Monitor for respiratory
• Metabolic cause should be ruled out while managing seizures
depression during loading doses.
in a neonate with perinatal hypoxia
Phenytoin is added to seizures uncontrolled by pheno
• Monitoring and management of multisystems is a key factor in
barbitone. Loading dose is 15–20 mg/kg and maintenance
prognosis of the baby.
dose is 4–8 mg/kg/day. 69
ch-17.indd 69 11/18/2016 5:24:21 PM

Algorithm 1
Algorithm for management of an asphyxiated baby
PPV, positive pressure ventilation; NRP, Neonatal Resuscitation Program; NNPD, National Neonatal-Perinatal Database; HIE, hypoxic ischemic encephalopathy;
EEG, electroencephalography; NICU, neonatal intensive care unit; SIADH, syndrome of inappropriate antidiuretic hormone secretion; ARF, acute renal failure;
GIR, glucose infusion rate.
Key points
SUGGESTED READINGS
1. Blackmon LR, Stark AR; American Academy of Pediatrics Committee on Fetus
))
Good antenatal care and prompt neonatal resuscitation are and Newborn. Hypothermia: a neuroprotective therapy for neonatal hypoxic
essential for prevention of perinatal hypoxia. However, in the ischemic encephalopathy. Pediatrics. 2006;117;942-8.
event of a baby suffering from hypoxia at birth, adequate 2. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for
supportive care and specific management can reduce the newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev.
mortality and long-term morbidity provided there is least 2013;1:CD003311.
possible delay in starting the treatment 3. Levene MI. The asphyxiated newborn infant. In: Levene MI, Lilford RJ , editors.
))
A system of staging like Levene staging system, a practical and Fetal and neonatal neurology and neurosurgery. Edinburgh: Churchill Livingstone;
easy to use system or others, like Thompson score, should be 1995. pp. 405-25.
used in every case for better management and prognostication 4. National Neonatal Perinatal Database report (National Neonatology Forum, India);
2003.
))
Therapeutic hypothermia is an emerging mode of therapy in
5. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A
the management of an asphyxiated baby with better long-
clinical and encephalographic study. Arch Neurol. 1976;33:696-705.
term outcome
6. Thompson CM, Puterman AS, Linley LL, Hann FM, van der Elst CW, Molteno
))
The early prediction of the complications and supportive CD, et al. The value of a scoring system for hypoxic ischemic encephalopathy in
management forms the cornerstone in the management of predicting neurodevelopmental outcome. Acta Paediatr. 1997;86;757-61.
a baby with perinatal asphyxia.
70
ch-17.indd 70 11/18/2016 5:24:22 PM

Section 2: Adolescence
Chapter 18
Teen Pregnancy and
Contraception
Prema Raghunathan
Introduction American College of Obstetricians and Gynecologists

stipulate that a routine pelvic examination with Pap smear
Adolescents compromise about 26% of Indian population. be initiated 3 years after onset of sexual activity and annual
According to National Family Health Survey-3, 16% of women screening for sexually transmitted infections (STIs).
in age group 15–19 years have at least one child ever born. The various contraceptive methods are broadly classified
Only 8% of women and 15% of men know about emergency into hormonal (Table 1), nonhormonal (Table 2), and emergency
contraception. Among this, a significant number is contributed contraception. The nonhormonal methods are barrier methods,
by married adolescents in India, most other teens have sexual spermicides, and intrauterine devices (IUDs). The hormonal
relationships due to peer pressure or impulsivity. Teen methods are combination pills or progesterone-only pills.
pregnancies are higher in India than even in United Kingdom
(UK), United States (US). The rate of birth among adolescents Nonhormonal Methods
in US is about 13% of all births. Adolescents have limited
education on sexuality, even if they are sexually active. Barrier Method
The increasing rates of teen pregnancies and abortion Condoms: it prevents sperms from being deposited in the
causes increased medical expenditure as most of these vagina (Fig 1). The advantages are:
pregnancies are unplanned. They are also mostly seen in • There are no major side effects
underprivileged society. Teen pregnancies push an adolescent • Risk of STIs reduced (acquired immunodeficiency
to become school dropout, face lot of stress, and can succumb to syndrome and human papillomavirus)
psychological trauma. Hence, clinicians caring for adolescents • Low cost, easy availability
should step in to provide sexual education (safe sex) and • Little need for advanced planning.
contraceptive counseling as part of reproductive health. A female condom is second choice over male condom due
to its complexity of properly using device, its low typical efficacy
CONTRACEPTION rate, and lack of studies on effectiveness in STIs. Diaphragm
and cervical caps are messy and less used by teenagers.
Contraception counseling is an important aspect of teen
care. The first step is to identify adolescent who are sexually Spermicides
active (maintain confidentiality) and the ones who follow
These are available as foam, cream, films, or effervescent
abstinence. The caregivers, parents, adolescent specialist
vaginal suppositories containing nonoxynol-9. They must be
should support adolescents who follow abstinence as
placed in vaginal cavity shortly before intercourse.
“abstinence is the best method of contraception”. If the teen
is sexually active, contraceptive counseling should be given Combination Methods
to understand the adolescent’s perception and misperception
about contraceptives, risks of unprotected intercourse, Use of condom by male and spermicidal foam by female
educate regarding real risks, and contraindications for various adolescent is extremely effective and failure rate is 2%.
methods available. Once the contraceptive method is chosen
by the adolescent, the provider must discuss the common side Hormonal Methods
effects, realistic expectation for failure, a contingency plan for Estrogenic substances in combination with a progestin or a
that possibility, and strategies for close follow-up. progestin alone are used in these methods. The mechanism
ch-18.indd 71 11/24/2016 12:34:33 PM

Table 1: List of hormonal contraceptives

Methods Available as Potential Side effects Comments
Commonly used methods
Oral contraceptive pills • Mala D Breakthrough bleeding, nausea, • Decreased burden: Menstrual blood loss
• Mala N headaches, breast tenderness dysmenorrhea, acne
• Pelvic inflammatory disease
Progestin only Mini pills Irregular bleeding, breast, tenderness, Used among breast feeding teens
depression
Contraceptive injections- • Depo-Provera– • Weight again Not used for more than one year, preferred
progestin-only injection 3 monthly • Acne among married teens
• NET-EN-2 monthly • Depression
• Irregular bleeding or amenorrhea
Rarely used methods
Vaginal ring NuvaRing Vaginal irritation and discharge Decreases dysmenorrhea, acne, pelvic
inflammatory disease
Transdermal patch Weekly Allergic reaction at skin site, breast Not freely available in India
tenderness, breakthrough bleeding
Implant Implanon Weight gain, local insertion • High efficacy
complications • Acceptability, Decreases dysmenorrhea
Table 2: List of nonhormonal methods

Commonly used methods
Methods Potential Side effects Comments
Male condom Latex allergy • Prevents sexually transmitted diseases and human immunodeficiency
virus risk
• Failure rate reduced if used with other hormonal contraceptive method
Female condom Vaginal discomfort Not available in India, needs proper education for perfect use
Intrauterine device Excessive menstrual blood loss Nonhormonal, used among parous teens
copper-containing
Spermicides urinary tract infections, Allergy to Should be used by teenage girls along with partner using condoms for
ingredients maximum contraception
that prevents sperm penetration. They also cause stromal

edema, regression of endometrial glands, and produce static
endometrial hypoplasia. These hormones are steroidal
contraceptives, can be used orally, parenterally or as devices:
intrauterine and vaginal. The oral combination pills typically
contain ethinyl estradiol and a progestin. The typical failure,
i.e., pregnancy rates are under 1 per woman years of use.
Exogenous estrogen use can cause serious side effects
rarely like thrombophlebitis, myocardial infarction, hepatic
adenoma, and carbohydrate intolerance. The more commonly
seen adverse effects are nausea, weight gain, acne in certain
progestin pills which can be reduced by using estrogen
containing pills which suppresses activity of sebaceous glands.
The advantage, of estrogen are relief of dysmenorrhea, short
menstrual cycle; estrogen containing pills have higher levels
of cardioprotective high density lipoproteins. A few extended
cyclic pills are being released which can cause amenorrhea
Fig. 1: Female condoms for 3 months to 1 year. However, the major disadvantages of
those pills is compliance as adolescents do not take pills every
of action of both (the hormones) estrogen and progesterone day and may lead to increased failure rates and breakthrough
combination and progesterone-only pills is to prevent bleeding. The recommendations for missing pills are given
luteinizing hormone (LH) surge and as a result to inhibit in box 1. The most commonly used pill in India is Mala-D
72 ovulation, they also thicken cervical mucous in such a way (norethisterone acetate + ethinyl estradiol), Mala-N (norgestrel
ch-18.indd 72 11/24/2016 12:34:33 PM

Chapter 18: Teen Pregnancy and Contraception
+ ethinyl estradiol) which is also supplied by Government Contraindications of Combined Hormonal

of India. Other oral contraceptive pills (OCPs) are Ovral-L, Contraceptives
Novelon, Femilon, and Loette.
Other combination methods are transdermal patch (Fig. 2) Absolute contraindications (class 4 in the World Health
and vaginal contraceptive ring. The transdermal patch releases Organization classification)
20 μg ethinyl estradiol and 150 μg norelgestromin daily. This • Pregnancy
method is not popular among adolescents as patch can get partial • Undiagnosed genital bleeding
or fully detached. The vaginal contraceptive ring (NuvaRing) is a • Breast cancer
flexible, transparent, colorless ring which is inserted into vagina • Past or present circulatory disease
by self and remains for 3 weeks where it releases 15 μg of ethinyl • Thrombophilia
estradiol and 120 μg of etonogestrel/day. • Pill induced hypertension
In situations where estrogens are contraindicated, • Migraine with aura
progestin-only pills can be used. These are called “mini pills” • Active liver disease
and are less reliable in inhibiting ovulation, compliance is • Systemic lupus erythematosus
poor among adolescents. The injectable progestin, medroxy • Hemolytic-uremic syndrome
progesterone acetate, is highly effective as deep intramuscular • Thrombotic thrombocytopenic purpura.
(IM) injection 150 μg (Depo-Provera). Bone mineral density
loss which is reversible side effect should be kept in mind. The Relative contraindications (class 2 or 3 in
progestin-only drug can also be used as subcutaneous implant. the World Health Organizationclassification)
• Smoker aged over 35 years
Box 1: Guidelines for missed OCPS • Hypertension (blood pressure >140/90 mmHg)
• Diabetes
OCP–missed pill rules
• Hyperprolactinemia
• If the teen has missed taking OCP ask her to resume her usual pill • Gallbladder disease
taking schedule as early as possible. (she may take two pills on
• Migraine without aura
the same day)
• Osteosclerosis
• If pills are missed in week 1 (Days 1–7), emergency contraception
should be considered • Sickle-cell disease.
• If the missed pills are in week 3 she should omit the pill free
interval Clinical Pearl
• Abstinence or condoms should be used as backup method if the
following number of pills are missed • Abstinence is the best contraception for teens.
{{ Two for twenty (if two or more 20 µg ethinyl estradiol pills are
missed)
{{ Three for thirty (if three or more 30–35 µg ethinyl estradiol pills Emergency Contraception
are missed
Pregnancy risk with unprotected intercourse (in midcycle) is
• Emergency contraception: if you have had unprotected sex
20–30%. The risk can be reduced if emergency contraception
in the previous 7 days and you have missed two or more pills
is used within 72 hours; these emergency contraceptive
(i.e., more than 48 hours late) in the first week of a pack, you may
need emergency contraception. pills are combination of ethinyl estradiol and norgestrel/
levonorgestrel. This helps by disrupting luteal phase and
hormone pattern, makes cervix unstable, and unsuitable
uterine lining for implantation. They also blunt LH surge and
impair ovulation in midcycle. The important side effects are
nausea and vomiting.
Potential Indications for

Use of Emergency Contraception
• Lack of contraceptive use during coitus
• Mechanical failure of male condom (breakage, slippage, or
leakage)
• Dislodgment, breakage, or incorrect use of diaphragm,
cervical cap, or female condom
• Failure of spermicide tablet or film to melt before
intercourse
• Error in practicing withdrawal (coitus interruptus)
• Missed combined oral contraceptives (any two consecutive
Fig. 2: Transdermal patch pills) 73
ch-18.indd 73 11/24/2016 12:34:34 PM

• Missed progestin-only oral contraceptive (one or more) ADOLESCENT PREGNANCY

• Expulsion or partial expulsion of an IUD
• Exposure to potential teratogen (such as isotretinoin or By providing good education including sexual education to our
thalidomide while not using effective contraception) teens, counseling them regarding abstinence, and providing
• Late injection of injectable contraceptive (>2 weeks life skills, teen pregnancies can be avoided. Still there are lots
delay of a progestin-only formulation, such as depot of pregnancies being reported. As one sector of them could
medroxyprogesterone acetate) be early marriages from rural population and sexual abuse.
• Two or more days delay in starting new vaginal ring or patch Among Indian studies, teenage pregnancy varies from 5.1% to
cycle as high as 21.12%.
• Rape. The adolescent caregivers should always suspect preg
nancy when there is secondary amenorrhea as most
INTRAUTERINE DEVICES teens may be reluctant to give history of sexual activity.
The methods to diagnose pregnancy are urine pregnancy
Intrauterine devices are small flexible plastic objects intro test, which is sensitive by 5 days of missed cycles by 98%.
duced in uterine cavity through cervix. They contain copper Ultrasound scan detects pregnancy and can also rule out an
(Cu) or progesterone. Cu-T 380A IUD renders endometrium ectopic pregnancy.
unsuitable for implantation, the levonorgestrel IUD acts by The next step after diagnosing is addressing psycho
thickening of cervical mucosa, inhibiting sperm survival and social, emotional, and medical aspects. The options of
suppresses endometrium (Fig. 3). This method of contraception elective termination of pregnancy or raising the child by
is used among teens who are highly sexually active but they friends/family/option of adoption can be given to family.
should take measures to prevent STIs (Algorithm 1). Complications due to teen pregnancy could be medical
or psychosocial (Algorithm 2). Most teen pregnancies do
not have major medical complications. The pregnancy
termination rate is about 33% in Indian statistics.
Miscarriages/stillbirth rate is about 15%. Teen mothers have
higher rate of anemia, pregnancy induced hypertension,
eclampsia, poor weight gain, increased STIs, increased
abuse, violence, and depression. The babies of teen mothers
Fig. 3: Intrauterine devices have behavioral problems in preschool years, poor scholastic
performance, learning difficulties; these could be attributed
Algorithm 1 to poverty, negative parenting styles, and higher possibilities
Approach to teen contraception of abuse and neglect.
There are lot of educational programs for youth in
various countries to educate teens about abstinence,
contraception, STIs; this education and life skills training
Algorithm 2
PIH, pregnancy induced hypertension; STI, sexually transmitted infection;

IUDs, intrauterine device; OCPs, oral contraceptive pills. IUGR, intrauterine growth retardation; SIDS, sudden infant death syndrome.
74
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Chapter 18: Teen Pregnancy and Contraception
given at schools and adolescents clinics, health clinics, and/ SUGGESTED READINGS
or, youth organizations have to be geared up to tackle this
problem in India. 1. Parthasarathy A, Nair MK, Menon PS, Bhave SY. Bhave’s Textbook of Adolescent
Medicine, 1st edition. New Delhi, India: Jaypee Brothers Medical Publishers; 2006.
2. Brooks RL, Shrier LA. An update on contraception for adolescents. Adolesc Med.
1999;10(2):211-9.
Key points 3. Brown RT, Braveman PK. Contraception and adolescents. Adolesc Med Clin.
2005;16(3):15-16.
))
Adolescents need sexual education 4. Greydanus DE, Senanayake P, Gains MJ. Reproductive health: an international
))
Encourage and support abstinence perspective. Indian J Pediatr. 1999;66(3):415-24.
))
Provide contraceptive counseling for sexually active teens 5. World Health Organization (WHO). (2000). Improving access to quality care
in family planning: medical eligibility criteria for contraceptive use. [online]
))
Encourage dual protection for pregnancy and sexually trans Available from extranet.who.int/iris/restricted/bitstream/10665/61086/1/WHO_
mitted infections. RHR_00.02.pdf. [Accessed November, 2015].
75
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Chapter 19
HEEADSSS Assessment of the
Adolescent Child
Piyali Bhattacharya
Young people are resources to be developed, not problems to be • Respond openly to adolescent’s initial reactions and
solved. feelings
Pittman • Give clear introductions: yourself, your role, what you will
be doing and why, e.g., “to get a better understanding of
different areas of your life and how these might affect your
INTRODUCTION
health, I would like to ask you a few questions if it is okay
The HEEADSSS (Home, Education and employment, Eating with you”
and exercise, Activities and peer relationships, Drugs, Suicide {{ Reassure the young person about confidentiality.
and depression, Sexuality and Safety) assessment is a screening However, three exceptions must be made clear to the
tool for conducting a comprehensive psychosocial history young person and their caregivers:
and health risk assessment of an adolescent (Algorithm 1). It 1. Harm to self
provides an ideal platform for a preventive health check and 2. Harm to others
information about the young one’s functioning in key areas of 3. Others harming you.
their life. {{ Start with less sensitive areas of a young person’s life
and move towards more sensitive areas using a “third

BUILD A RELATIONSHIP person” approach, e.g., “Some young people of your
age are starting to experiment with drugs or alcohol (or
• Confidently welcome the adolescent sex). Have any of your friends tried these? How about
yourself?”
Algorithm 1 {{ Perform a risk assessment and screen for specific risk
Algorithm depicts points for interviewing and behaviors which occur in clusters.
risk assessment in an adolescent child
INTERVIEWING THE ADOLESCENT
Home
• How is it at home at the moment? Who lives with you?
Where do you live?
• Do you have your own space? Who do you get along best
with? Could you talk to them if you were worried about
anything? Is there anyone new at home? Has someone left
recently?
• Have you moved recently?
• Have you ever had to live away from home? (Why?)
HEEADSSS, Home, Education and employment, Eating and exercise, Activities • Have you ever run away? (Why?)
and peer relationships, Drugs, Suicide and depression, Sexuality and Safety. • Is there any physical violence at home?
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Chapter 19: HEEADSSS Assessment of the Adolescent Child
Education and Employment • Have any of your relationships ever been sexual
relationship? Are your sexual activities enjoyable?
• What are your favorite subjects and least favorite subjects
• Are you interested in boys? Girls? Both?
at school? • Have you ever been forced or pressured into doing
• How are your grades? Any recent changes? Have you something sexual that you did not want to do?
changed schools in the past few years? • Have you ever been touched sexually in a way that you did
• Have you ever had to repeat a class? Have you ever had not want?
to repeat a grade? What are your future education/ • Have you ever been raped, on a date or any other time?
employment plans/goals? Are you working? Where? How • How many sexual partners have you had altogether?
long? • Have you ever been pregnant or worried that you may be
• Tell me about your friends at school. Is your school a safe pregnant? (females)
place? • Have you ever gotten someone pregnant or worried that
• Have you ever been suspended? Expelled? Have you ever that might have happened? (males) What does the term
considered dropping out? “safe sex” mean to you?
• How well do you get along with the people at school or • What do you know about contraception?
work?
• Do you feel connected to your school? Do you feel as if you Suicide and Depression
belong?
• Do you feel sad or down more than usual? Do you find
• Are there adults at school you feel you could talk to about
yourself crying more than usual? Are you “bored” all the
something important? (Who?)
time? Are you having trouble getting to sleep?
• Does it seem that you have lost interest in things that you
Eating and Exercise used to really enjoy? Do you ever feel so down that life is
• Has your weight changed recently? Are you worried about not worth living?
it? Have you ever dieted? • Do you find yourself spending less and less time with
• How much exercise do you get? How much exercise do you friends? Would you rather just be by yourself most of the
get in an average day/week? time?
• What do you think would be a healthy diet? How does that • Have you ever thought a lot about hurting yourself or
compare to your current eating patterns? someone else?
• Do you worry about your weight? How often? • Have you ever had to hurt yourself (e.g., by cutting yourself )
• Do you eat in front of the television? Computer? What to calm down or feel better?
would it be like if you gained/lost 10 pounds? • Have you started using alcohol or drugs to help you relax,
calm down, or feel better?
Activities and Hobbies
Safety and Abuse
• What do you do to relax? What do you and your friends do
• Have you ever been seriously injured? Do you always wear
for fun? (With whom, where, and when?)
a seatbelt in the car?
• What do you and your family do for fun? (With whom,
• Have you ever ridden with a driver who was drunk or high?
where, and when?)
When? How often?
• Do you participate in any sports or other activities?
• Do you use safety equipment for sports and/or other physical
• Do you regularly attend a club, or other organized activity?
activities (e.g., helmets for biking or skateboarding)?
• Do you have any hobbies? • Is there any violence in your home? Does the violence ever
• Do you read for fun? (What?) get physical?
• How much television do you watch in a week? How about • Is there a lot of violence at your school? In your
video games? What music do you like to listen to? neighborhood? Among your friends?
• Have you ever been physically or sexually abused? Have
Drugs, Alcohol, and Tobacco you ever been raped, on a date or at any other time? (If not
• Lots of teenagers try smoking/alcohol, have you ever tried asked previously)
it? • Have you ever been in a car or motorcycle accident? (What
• Have you been offered drugs? Is it hard for you to say no in happened?)
this situation? • Have you ever been picked on or bullied? Is that still a
• Is there any history of alcohol or drug problems in your problem?
family? Does anyone at home use tobacco? • Have you gotten into physical fights in school or your
• Do you ever drink or use drugs when you are alone? neighborhood? Are you still getting into fights?
• Have you ever felt that you had to carry a knife, gun, or
other weapon to protect yourself? Do you still feel that way?
Sex and Relationships • All communication should be with: open-ended questions,
• Have you ever been in a romantic relationship? Tell me affirmations, reflective listening and summary statements
about your dates (OARS). 77
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WRAPPING UP THE SESSION • Based on the level of risk: decrease risk factors or increase
protective factors
At the end of the HEEADSSS assessment, the pediatrician • Possible foci: environment and social context, family,
should compliment the young person on their strengths and individual.
areas in their life where they are doing well. He should: A pediatrician must seek a collaborative approach and
• Identify areas for intervention and prevention facilitate access to psychological and specialist counseling
• Identify and discuss any issues of concern psychosocial services once a problem has been identified.
health
• Identify the overall level of risk of the young person and
specific risk factors in their lives, as well as protective Clinical Pearl
factors and strengths
• Identify areas for intervention and follow-up • Specific risk behaviors usually occur in clusters. Risk assessment,
• Provide health education about particular health issues or therefore, must be done continuously throughout the whole
risk behaviors. interview of the adolescent in order to identify associated
The HEEADSSS assessment is not simply an information factors.
gathering exercise; listen carefully to the young person’s verbal
and nonverbal responses. Adolescents may present with minor
complaints but exploring beyond the presenting complaint SUGGESTED READINGS
may detect underlying health concerns and risk factors, thereby
1. Goldenring JM, Rosen DS. Getting into adolescent heads: an essential update.
providing timely intervention and preventive education.
Contemp Pediatr. 2004;21:64-90.
2. Sanci L. Adolescent Health Care Principles. Melbourne, Australia: The Centre for
PRINCIPLES OF INTERVENTION Adolescent Health, The Royal Australian College of General Practitioners; 2001.
3. SERU. Improving Young People’s Access to Health Care Through General Practice:
• Allow time to finish, provide a brief summary, give A Guide for General Practitioners and Divisions of General Practice. Melbourne,
opportunity for questions Australia: Access SERU, Department of General Practice and Public Health,
• Discuss options and help the adolescent make choices University of Melbourne; 1999.
78
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Chapter 20
Adolescent Anemia
Vaishali R Deshmukh
Introduction Clinical Pearl

Anemia is a major public health problem in India. It has a
special significance in adolescents as it affects final height, The World Health Organization Global Database:
cognition, and reproductive health. • Prevalence of anemia in south-east Asia: 57%
Most of the hereditary or congenital anemias present • Global prevalence in school-aged children: 25.4% (305 million)
before the age of adolescence (exceptions: congenital dys
• Overall prevalence in India: 74.3%.
erythropoietic anemia, milder forms of hemolytic anemia).
Since nutritional anemia, especially iron deficiency anemia, is
the most commonly found anemia in adolescents in India as Table 1: The World Health Organization guidelines for severity
well as all over the world, it will be discussed here in detail. of anemia
Anemia is not a specific entity. It is a condition, which Age No anemia Mild Moderate Severe
results from an underlying pathologic process.
12–14 years >12 g/dL 11.0–11.9 g/dL 8.0–10.9 g/dL <8 g/dL
Surprisingly, in a gradually developing anemia, hardly
any symptoms are apparent until hemoglobin reaches a level Nonpregnant >12 g/dL 11.0–11.9 g/dL 8.0–10.9 g/dL <8 g/dL
>15 years girls
of 8 g/dL or lower because, the body adjusts for anemia in the
initial stages by various adaptive mechanisms. Men >13 g/dL 11.0–12.9 g/dL 8.0–10.9 g/dL <8 g/dL
The normal lifespan of red blood cells (RBCs) is 110–120 Source: Guidelines for treatment of iron deficiency anemia - MoHFW, Govt. of
days. Adult RBCs do not have a nucleus. This makes them a better India.
oxygen vehicle but gives them a definite lifespan. Adolescents, The functional definition of anemia is “an insufficient
beyond the age of 12 years, have hematologic ranges similar to RBC mass to adequately deliver oxygen to peripheral tissues”
those of adults. At puberty, hemoglobin concentration reaches (Table 1).
adult level as a result of effect of androgens on erythropoiesis.
Severe Anemia
PREVALENCE Severe anemia is defined clinically as a low hemoglobin
According to the World Health Organization Global Database, concentration leading to cardiac decompensation, that is, to
the prevalence of anemia is very high in India putting it in the point that the heart cannot maintain adequate circulation
severe public health problem category. of the blood. There is extreme pallor. If the hemoglobin or
According to National Family Health Survey-3, the hematocrit can be determined, cutoffs of hemoglobin below
prevalence of anemia in Indian adolescent girls is 56–68% and 7.0 g/dL or hematocrit below 20% should be used to define
boys is 56–68% and 30%, respectively. severe anemia.
Clinical Pearl
DEFINITION
• Anemia is caused by either reduced or ineffective production
Anemia is defined as reduction in the number of RBCs or of red blood cells (RBCs), blood loss, or increased destruction
reduced packed cell volume (hematocrit) or low hemoglobin, of RBCs.
all below the lower limit for the age norm.
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Mechanism of Anemia of Chronic Diseases SPECIAL FEATURES OF ANEMIA IN

In a chronic disease, anemia is caused either due to decreased ADOLESCENTS
production or increased destruction of RBCs. The mechanism is
Various unique factors contribute to the cause and effect of
as follows:
anemia in adolescence.
• Reduced erythropoietin
• Moderate decrease in RBC lifespan
• Increased RBC destruction by the hyperactive reticulo
Clinical Pearl
endothelial system • The most common anemia in adolescents all over the world is
• Relative failure of bone marrow response iron deficiency anemia.
• Defective release of iron from tissues into plasma
• Increased levels of tumor necrosis factor causing suppressed Gender difference between normal ranges of hematocrit
erythroid response. starts becoming apparent at adolescence. The sudden growth
spurt (the third and the last spurt after intrauterine life and
Etiology of Anemia (Algorithm 1) gestation) leads to relative deficiency of nutrients and occult
deficiencies become apparent. Hormones like testosterone,
Nutritional Anemia which affect erythropoiesis, peak during adolescence.
By definition, it is the anemia caused by dietary deficiency • In adolescent boys, the rapidly increasing muscle mass
of one or more nutrients required for hemoglobin synthesis. demands high amount of iron. In addition, the blood
The most common deficiency is that of iron followed by folate volume increases in short span
and vitamin B12. This deficiency is usually compounded by • Menstrual losses contribute to iron deficiency in adolescent
intestinal parasites (helminthiasis) and malaria. girls
Iron deficiency anemia typically shows three phases with • In girls, the beginning of menstruation, i.e., menarche, leads
increasing severity: to significant loss of blood on a regular basis. The menstrual
1. Prelatent phase of iron deficiency: reduced serum ferritin, flow may be heavier in the initial period of menarche. Add
reduced iron stores without reduction in serum iron to this the increased demand for iron due to rapid growth
2. Latent phase: iron stores are exhausted but hemoglobin and the result is significant anemia in adolescent girls.
levels are normal. Some symptoms such as fatigue, malaise Teenage pregnancy makes the physiological anemia of
but no anemia. Increase in total iron binding capacity, pregnancy much more severe
reduction in transferrin saturation • Intergenerational effect of anemia: low maternal
3. Iron deficiency anemia: pallor, pica, low hemoglobin, hemoglobin and weight is a major cause of intrauterine
presence of microcytes. growth restriction and high maternal mortality
• Changes in thinking patterns and lifestyle lead to food fads,
Other Causes of Anemia in Adolescents consumption of junk food, and irregular eating habits
Other causes of anemia in adolescents are as follows: The changing lifestyle and the peculiar temperament of
• Thalassemia adolescents are responsible for this. They eat a lot of junk
• Sickle-cell anemia food due to irregular timings and peer pressure. The sense
• Pernicious anemia of newly acquired freedom and the need to stay away from
• Hemorrhagic causes home necessitates them to eat outside food
• Chronic disease • Socioeconomic status of the family, traditional eating
• Bone marrow infiltration. habits of the region, the fear of gaining weight, and irregular
Algorithm 1
Approach to anemia
80
PBS, peripheral blood smear; RBC, red blood cell; MCV, mean corpuscular volume; C/o, complaints of.
ch-20.indd 80 11/18/2016 5:36:46 PM

Chapter 20: Adolescent Anemia
eating habits are of great importance in development of producing noncognitive disturbances, and limiting activity
adolescent anemia and work capacity
• Adolescents have poor compliance to treatment Iron supplementation among iron deficient anemic
• “I do not care” attitude causes difficulty in convincing them children benefits learning processes as measured by the school
of consequences achievement test scores:
• Occasional or no visits to doctors prevent early detection. • Poor physical growth
• High maternal mortality
Clinical Effects of Anemia • Gastrointestinal: symptoms of underlying disorder
(duodenal ulcer, cancer, hiatus hernia).
• In a gradually developing anemia, patient may remain
asymptomatic until hemoglobin reaches a level of 8 g/dL
or lower. The symptoms depend upon the magnitude and INVESTIGATIONS (ALGORITHM 2)
the rate of reduction in oxygen carrying capacity of blood
• Hemogram with peripheral blood smear (PBS): to
and the capacity of the pulmonary and the cardiovascular
determine the severity of anemia, affection of other cell
system to compensate for anemia. The symptomatology
lines, RBC morphology, hematocrit level, and presence of
also reflects the symptoms of the underlying disease
parasites such as malaria
• Normally, the body adjusts for anemia in the initial stages
• Reticulocyte count: to assess bone marrow response
by various adaptive mechanisms. The cardiac output
increases to increase the oxygen delivery to the tissues. • Stool for parasites and occult blood
The production of 2,3-diphosphoglycerate in the RBCs • Hemoglobin electrophoresis
increases leading to reduced affinity of hemoglobin to • Serum bilirubin and serum iron studies
oxygen. This causes shift of oxygen dissociation curve to • Investigations to rule out underlying diseases.
the left causing release of oxygen to tissues faster. This is
also seen at high altitudes. Production of erythropoietin MANAGEMENT
increases too, leading to stimulation of bone marrow and
increased RBC output Treatment Program (Algorithm 3)
• A striking feature of iron deficiency anemia is pica. This
desire to consume unusual things is very peculiar to iron International Nutritional Anemia Consultative Group has
deficiency anemia, the reason is not clear, especially seen recommended the following treatment program:
is pagophagia, i.e., urge to eat unusual amounts of ice • Mild anemia: 60 mg of elemental iron daily for 3 months
• Skin and mucosa: the hair texture worsens leading to lack after which hemoglobin estimation is done
of luster, premature graying, and thinning of hair. This • Moderate anemia: it is investigated for complete blood
effect can be used to counsel the adolescents as this may count, PBS, malarial parasites, and stool for occult blood
appeal to them and treated in the same way as mild anemia
• Neuromuscular symptoms: headache, vertigo, tinnitus, • Severe anemia: investigate and treat with 120 mg iron +
faintness, lack of concentration, drowsiness, restlessness, 400 µg folic acid daily for 3 months.
muscular weakness; in pernicious anemia, paresthesias
• Behavioral and cognitive problems: iron deficiency Indications for Blood Transfusion
adversely affects behavior by impairing cognitive functions, • All children with hemoglobin less than or equal to 4 g/dL
Algorithm 2
Diagnosis of anemia
MCV, mean corpuscular volume; e/o, evidence of. 81
ch-20.indd 81 11/18/2016 5:36:47 PM

Algorithm 3
Treatment of anemia
• Children with hemoglobin 4–6 g/dL with complications, made for prophylactic iron and folic acid supplementation to
such as dehydration, shock, impaired consciousness, heart children, adolescents, and pregnant women.
failure, deep and labored breathing, very high parasitemia All adolescent boys as well as girls (10–19 years) are given
(>10% of RBC) weekly tablets containing 100 mg elemental iron and 500 μg of
• If packed cells are available, give 10 mL/kg over folic acid along with biannual deworming:
3–4 hours preferably. If not, give whole blood 20 mL/kg • Diet: increased consumption of food rich in iron, such as
over 3–4 hours with close monitoring and diuretics. animal proteins, green leafy vegetables, jaggery, etc. Using
iron pots for cooking
Prevention (Fig. 1) • Biannual deworming of all school-going children with
albendazole
Due to its prevalence across all age groups all over the world, • Malaria control
prevention plays a major role in the management of iron • Treatment of underlying condition
deficiency anemia • Reproductive and obstetric interventions: preventing
• Increased awareness about the magnitude of anemia and adolescent pregnancies, reducing the total number of
its far-reaching consequences among the masses will go a pregnancies and increasing the time between pregnancies
long way to reduce its incidence will contribute to the control of iron deficiency anemia in
• School and college based awareness programs to reduce women. Pregnancy creates a large demand for iron, which
consumption of junk food and to encourage healthy is needed to develop the fetus and placenta and to expand
dietary habits a woman’s blood volume. Additional iron is lost with blood
• Food based interventions: fortification of commonly lost at delivery. When the iron demands of pregnancy are
consumed food, such as salt, milk, or atta with iron combined with the iron demands of adolescent growth, girls
• Screening for anemia in adolescents and other high risk enter adulthood at great risk of iron deficiency.
groups to tap cases of anemia in presymptomatic stage
• Regular supplementation of iron-folic acid tablets to CONCLUSION
adolescents and pregnant women.
Anemia is a major public health problem in India. In adolescent
National Iron plus Initiative: this is a proposed lifecycle iron- age group, iron deficiency anemia is the most common
folic acid supplementation program by Ministry of Health anemia. It is of particular significance due to its major effects
and Family Welfare, where age specific recommendations are on growth, development, productivity, maternal mortality, and
intergenerational effects. Regular screening, prophylaxis, early
detection and treatment, food fortification, and public awareness
programs are needed to control iron deficiency anemia.
Key points
))
Iron deficiency anemia is the most common type of anemia in
adolescents all over the world
))
Due to the unique stage of growth, adolescent anemia has
a significant impact on growth, cognition, reproduction, and
general productivity
))
Prevention is the best method of managing iron deficiency
82 anemia.
Fig. 1: Prevention of anemia
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Chapter 20: Adolescent Anemia
SUGGESTED READINGS from www.pbnrhm.org/docs/iron_plus_guidelines.pdf. [Accessed November,

2015].
1. Means RT, Glader B. Anemia: general considerations. In: Greer JP (Ed). Wintrobe’s 6. Chellan R, Paul L. Prevalence of iron-deficiency anemia in India: Results from a
Clinical Hematology, 12th edition. Philadelphia, PA, USA: Lippincott Williams & large nationwide survey. J Population Social Studies. 2010;19(1):59-80.
Wilkins; 2009. pp. 779-807. 7. Lozoff B. Behavioral alterations in iron deficiency. Adv Pediatr. 1988;35:331‑59.
2. de Benoist B, McLean E, Egli I, Cogswell M (Eds). Worldwide Prevalence of 8. Soemantri AG, Pollitt E, Kim I. Iron deficiency anemia and educational
Anemia 1993-2005: WHO Global Database on Anaemia. Geneva, Switzerland: achievement. Am J Clin Nutr. 1985;42(6):1221-8.
World Health Organization; 2008. 9. Işık Balcı Y, Karabulut A, Gürses D, Ethem Çövüt I. Prevalence and risk factors of
3. Kliegman RM, Stanton BM, Geme JS, Schor N, Behrman RE. Nelson’s Textbook of anemia among adolescents in Denizli, Turkey. Iran J Pediatr. 2012;22(1):77-81.
Pediatrics, 19th edition. Philadelphia, PA, USA: Saunders-Elsevier; 2011. 10. Daniel WA. Hematocrit: maturity relationship in adolescence. Pediatrics.
4. Parthasarathy A, Nair MK, Menon PS, Bhave SY. Bhave’s Textbook of Adolescent 1973;52(3):388-94.
Medicine, 1st edition. New Delhi, India: Jaypee Brothers Medical Publishers; 11. Stoltzfus RJ, Dreyfuss ML (Eds). (1998). Guidelines for the Use of Iron
2006. Supplements to Prevent and Treat Iron Deficiency Anemia. International
5. Adolescent Division, Ministry of Health and Family Welfare, Government of India. Nutritional Anemia Consultative Group (INACG). [online] Available from www.who.
(2013). Guidelines for Control of Iron Deficiency Anaemia: National Iron plus int/nutrition/publications/micronutrients/guidelines_for_Iron_supplementation.
Initiative (Towards infinite potential in an anaemia free India). [online] Available pdf. [Accessed November, 2015].
83
ch-20.indd 83 11/18/2016 5:36:47 PM

Chapter 21
Academics and Career Choices in Adolescents:
Approach in the Pediatric Office Setting
Ira E Almeida
INTRODUCTION for a day or more can be helpful. If the child is undecided,

aptitude testing and workshops on career options are useful.
For parents whose health concerns about their wards have been An approach to help the pediatrician in office practice to
addressed by the pediatrician for so many years, there is no leap guide and refer appropriately with regard to academics and
of faith in expecting that the same doctor must have something career choices is represented in algorithm 1.
in a bottle or book that addresses their biggest anxiety during
their child’s adolescence academic performance. Most
children enter high school and adolescence at the same time School and Performance
in India—it becomes a time fraught with stress by definition The greater difficulty is when the child presents with under
alone. In most government schools, high school is the first time achievement. For the pediatrician, one needs to evaluate study
children can fail a grade and have to repeat it—in such schools, skills, examine parental expectations, and check performance
government policy mandates that children get promoted to the reports. Medical problems like hypothyroidism, iron, iodine, or
next grade regardless of competence in taught skills right up to vitamin deficiencies must be looked into. Checking for specific
grade VII. It is not surprising that pediatric practices face large learning disability, attention deficit hyper activity disorder,
numbers of adolescents presenting with academic difficulties. emotional problems, physical problems, and substance abuse
A pediatric practice must stretch its role to point parents and becomes imperative. Specific learning disability usually
their adolescent children presenting with such difficulties presents with the child doing well orally, but doing dis
in the correct direction, whether with a direct solution or by proportionally badly in written work. Emotional problems
referring the child to appropriate assessors. which can affect self-esteem, concentration, and application
A seemingly innocuous statement made by a mother should be considered. Below normal intelligence could be due
“my child does not study well; give him a tonic”, can cause a to perinatal causes like TORCH [toxoplasmosis, other (syphilis,
great deal of anxiety in the pediatrician. However, this is not varicella-zoster, parvovirus B19), rubella, cytomegalovirus, and
as simple as it sounds. Besides, doctors often feel helpless herpes] infections, prematurity, meningoencephalitis, or an
when the parents ask them to advise career choices for their underlying chromosomal disorder like Klinefelter’s syndrome,
wards (often they also hope that they will inspire their kids to Fragile X, Turner’s syndrome, etc.
become doctors).
In the conventional system of education in India, we have
Clinical Pearl
those who are academic and those who are not. For those who
are academic achievers, the paths that most parents wish for • Anemia in adolescent girls and iodine deficiency in hilly areas
their children are those that will take them to professional are often missed and are easily correctable causes of poor
courses like medicine and engineering and if not successful, school performance.
allied fields like physiotherapy, audiology, diplomas in
technical courses, etc. are acceptable. For the creative types Physical problems like visual disability (uncorrected
who fall off this path, many interesting fields like photography, refractive errors, squint, or more serious conditions like
design, advertising, media, communication, and event chorioretinitis, retinal detachment, etc.), hearing disability,
management are now available. (congenital or acquired) need a thorough evaluation. Children
If the child has made up his mind as to what he/she wants with Down syndrome, mild cerebral palsy, hemiplegic
to do, encouraging them to shadow a professional in the field syndromes may also have writing difficulties and would
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Chapter 21: Academics and Career Choices in Adolescents: Approach in the Pediatric Office Setting
Algorithm 1
Academics and career choices
SLD, specific learning disability; ADHD, attention deficit hyperactivity disorder; IQ, intelligence quotient; TV, television.
benefit from technological alternatives like tablets. Substance College and Careers
abuse should be looked into if there are any tell-tale signs like
red eyes, inappropriate use of sunglasses, long sleeves, and Career counseling tests may not be always accurate though they
unexplained need for pocket money or parental suspicion. may help to clear the confusion in the child’s mind and give the
An excessive amount of screen time can affect academic parents the satisfaction that they are doing something. Asking
performance, especially online addiction to pornography. the child how they see themselves 10 years from now and 85
ch-21.indd 85 11/18/2016 5:39:17 PM

working backwards may help. More often the child knows what SUGGESTED READINGS
they do not want to do, before they know what they want to.
Taking into consideration their interests, personality, 1. Karande S, Kulkarni M. Poor school performance. Indian J Pediatr. 2005;72(11):
life goals, and values besides their academic strengths and 961-7.
2. Shapiro BK, Gallico RP. Learning disabilities. Pediatr Clin North Am. 1993;40(3):491-
aptitude makes it easier to zero in on a career. Most career
505.
guidance centers are able to provide information regarding 3. Elkind D. All Grown Up and No Place To Go: Teenagers in Crisis. MA, USA:
eligibility and entrance procedures for career options both in Addison-Wesley; 1998.
India and abroad. 4. American Psychiatric Association. Diagnostic Criteria for ADHD DSM-4:
Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA, USA:
Clinical Pearl American Psychiatric Association, 2013.
5. Academic underachievement among the gifted: Students perception of factors
• Children with borderline mental retardation should be put in that reverse the pattern. Gifted Child Quarterly (NAGC). 2004;36(3):140-6.
skill programs/apprenticeships as early as possible, i.e., after 6. Klegman RM, Stanton BM, St. Geme J, Schor NF, editors. Neurodevelopment
middle school. function and dysfunction in the school age child. Nelson Textbook of Paediatrics.
20th ed. Philadelphia: Elsevier; 2016. pp. 192-99.
Key points Websites for Parents

• www.careerchoices.com
))
Be alert to learning difficulties, which should be evaluated • www.talkitover.in
and managed promptly, to prevent the child getting into a • www.onestepup.in
cycle of low esteem, worthlessness, dropping out of school, • www.nos.org
and failure • www.careerage.com
))
Guide parents of children with specific learning difficulties • www.careerplanning.about.com.
to seek remediation with a special educator. If detected late,
accommodation with concessions and the National Open
School, are the options
))
The plethora of career choices is confusing. Work with parents
to access career information and career guidance centers
))
Be a catalyst in enabling children reach their full potential. Your
role could make difference between a child being independent
and being isolated, depressed, and unproductive.
86
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Chapter 22
Polycystic Ovarian Syndrome and
Menstrual Problems in Adolescents
Roli M Srivastava
POLYCYSTIC OVARIAN SYNDROME • Hirsutism: the growth of coarse hair on a woman in a male
pattern (upper lip, chin, chest, upper abdomen, back, etc.)
The condition “polycystic ovarian syndrome (PCOS)” was • Acne: pubertal acne in general is twice as prevalent in
first described in 1935 by Dr Stein and Dr Leventhal; hence adolescent males versus females and males are more likely
its original name Stein-Leventhal syndrome is characterized to have severe disease. Thus, an adolescent female with
by an imbalance of hormones in women which can affect moderate-to-severe acne should be investigated for PCOS
menstrual periods and ovulation. Women are often very • Virilization: clitoromegaly, deepening voice, increased
embarrassed by some of the symptoms associated with this musculature, or rapidly progressive hirsutism or alopecia),
condition, such as excessive hair growth, acne, obesity, and however, is not a feature of PCOS, but instead of more
the development of small cysts on the ovaries. Because of these severe hyperandrogenism.
distressing symptoms, women may also experience feelings
of depression and anxiety. It is one of the most common
Chronic Anovulation
female endocrine disorders affecting approximately 5–10% of
women of reproductive age and is one of the leading causes It may result in:
of infertility. It is a very common problem amongst young • Oligomenorrhea
women and teenage girls, sometimes even affecting girls as • Amenorrhea
young as 11 years of age. If not treated early, serious health • Dysfunctional uterine bleeding
complications, such as diabetes and cardiovascular disease, • Infertility.
can develop and so, the management of the PCOS patient However, around 20% of patients with PCOS may have
often will vary over time as the patient enters different stages of normal menstrual cycles. Often, menstrual abnormalities
life with different goals. In contrast, because of the long-term are long-standing, even since menarche although primary
health implications of insulin resistance (IR), the importance amenorrhea very rare (Box 1).
of lifestyle modification towards weight management and
maintaining adequate physical activity should be the one POLYCYSTIC OVARIAN
constant in the management of these patients.
SYNDROME DIAGNOSTIC CRITERIA
Polycystic ovarian syndrome includes a wide spectrum of
DIAGNOSIS is BY CLINICAL EXAMination,
clinical symptoms and signs. Three different diagnostic
ULTRASOUND, and LABORATORY classifications had been proposed to define this disease
Polycystic ovarian syndrome is most simply clinically defined till November 2015. The first one was published in 1990,
as the presence of: and is known as the “National Institute of Health criteria”.
• Hyperandrogenism (clinically and/or biochemically) Later, in 2003, an expert panel met in Rotterdam and added
• Chronic anovulation in the absence of specific adrenal
and/or pituitary disease.
Box 1: Clinical features of polycystic ovarian syndrome
Hyperandrogenism • Oligomenorrhea/amenorrhea • Hirsutism
• Acne • Acanthosis nigricans
Hyperandrogenism may present clinically as hirsutism, acne,
and male-pattern alopecia. • Obesity • Male-pattern alopecia
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NIH, National Institute of Health;PCOS, polycystic ovarian syndrome; PCO, polycystic ovaries on ultrasound.
Fig. 1: 1990 National Institute of Health consensus versus 2003 Rotterdam consensus
Table 1: Polycystic ovarian syndrome diagnostic criteria
NH 1990 Rotterdam 2003 AE-PCOS Society 2006 AACE/ACE and AES Society
2015
• Chronic anovulation • Oligo- and/or anovulation • Clinical and/or biochemical signs • Chronic anovulation
• Clinical and/or biochemical signs of • Clinical and/or biochemical of hyperandrogenism • Hyperandrogenism
hyperandrogenism (with exclusion signs of hyperandrogenism • Ovarian dysfunction (Oligo- (clinical/biologic)
of other etiologies, e.g., congenital • Polycystic ovaries (Two of anovulation and/or polycystic • Polycystic ovaries (one of
adrenal hyperplasia) (Both criteria three criteria needed) ovarian morphology) (Both the above three criteria)
needed) criteria needed)
NIH, National Institute of Health; AACE, American Association of Clinical Endocrinologists; ACE, American College of Endocrinology; AES, Androgen Excess and PCOS
Society.
Algorithm 1 symptoms. The number of follicles and ovary volume are both
important in the ultrasound evaluation.
RADIOGRAPHIC FEATURES
Ovaries may show sonographic features of polycystic ovaries
(Fig. 2), bilateral enlarged ovaries with multiple small follicles:
17-OH progesterone, 17-hydroxyprogesterone; TSH, thyroid-stimulating 50%
hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone. • Increased ovarian size (>10 cc)
• 12 or more follicles measuring 2–9 mm
to the previous criteria the presence of polycystic ovarian • Follicles of similar size
morphology detected by transvaginal ultrasonography (Fig. 1). • Peripheral location of follicles: gives a string of pearl
Then, the Androgen Excess Society, published in 2006, gave appearance
the new diagnostic criteria being applied till late and finally • Hyperechoic central stroma.
latest in November 2015, the American Association of Clinical
Endocrinologists, American College of Endocrinology, and
Androgen Excess Society released new guidelines in the PATHOPHYSIOLOGY OF POLYCYSTIC
evaluation and treatment of PCOS (Table 1). OVARIAN SYNDROME
As PCOS is an umbrella of various signs and symptoms, Polycystic ovaries develop, when the ovaries are stimulated
certain diseases with nearly same presenting features, to produce androgens, either through excess of luteinizing
especially irregular cycles and androgenic features, have to be
ruled out to reach the diagnosis (Algorithm 1).
Clinical Pearl
DIAGNOSIS AND DIFFERENTIAL • Polycystic ovarian syndrome (PCOS) should be considered
DIAGNOSIS (TABLE 2) and appropriate assessment should be undertaken before
commencement of the oral contraceptive pills in adolescents
Not all women with PCOS have polycystic ovaries, nor do
with irregular periods, i.e., irregular cycles (≥35 days or <21 days),
all women with ovarian cysts have PCOS; although a pelvic
2 years following menarche. Other causes of irregular cycles,
ultrasound is a major diagnostic tool, it is not the only one. such as thyroid dysfunction or hyperprolactinemia, need to be
The diagnosis is straightforward using the Rotterdam criteria, considered and excluded prior to the diagnosis of PCOS.
88 even when the syndrome is associated with a wide range of
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Chapter 22: Polycystic Ovarian Syndrome and Menstrual Problems in Adolescents
Table 2: Diagnosis and differential diagnosis

Differential diagnosis Test Comments
Hypothalamic amenorrhea: weight loss, exercise, Low FSH LH: FSH >2 is suggestive of PCOS
anxiety, chronic illness
Pituitary adenoma: galactorrhea may be present High prolactin Mild transient hyperprolactinemia: (check for hypothyroidism)
prolactin is generally only 50% above the upper limit of normal
Hypothyroidism: cold dry skin, constipation High TSH
Late-onset congenital adrenal hyperplasia: rare, High 17-OH A morning, fasting, level of <200 ng/dL in the follicular phase
mimics PCOS in all regards. The classic forms progesterone excludes late-onset 21-hydroxylase deficiency. Oral contraceptives
presents in newborn girls as ambiguous genitalia and glucocorticoids can affect values
Premature ovarian failure High FSH
Cushing’s syndrome hypertension, purple abdominal High cortisol Mild elevations can be seen in PCOS values ≥2 times the upper
striae, prominent dorsal cervical fat pads, and a limit of normal (Cushing’s syndrome). Oral contraceptive pills
rounded, plethoric face should be discontinued before dynamic testing
Adrenal tumor: extensive signs of virilization Very high TT TT values may be normal in PCOS. Oral contraceptive pills lower TT,
3 months off OCPs best to get true value. Most testosterone values
in PCOS will be ≤150 ng/dL, i.e., mild elevation, testosterone values
of ≥200 ng/dL suggest ovarian or adrenal tumor
FSH, follicle-stimulating hormone; LH, luteinizing hormone; PCOS, polycystic ovarian syndrome; TSH, thyroid-stimulating hormone; 17-OH progesterone,
17-hydroxyprogesterone; TT, total testosterone; OCPs, oral contraceptive pills.
A B
Fig. 2: Characteristic string of pearls sign seen: A, left ovary and B, right ovary
hormone (LH) or through hyperinsulinemia in women whose hirsutism and virilization) and estrogens [which inhibits
ovaries are sensitive to this stimulus. Multiple ovarian cysts are follicle-stimulating hormone (FSH) via negative feedback].
seen in ultrasound. These “cysts” are actually immature follicles Also, hyperinsulinemia increases gonadotropin-releasing
whose development has arrested at an early-antral stage due hormone (GnRH) pulse frequency, LH over FSH dominance,
to the disturbed ovarian function. Polycystic ovarian syndrome increased ovarian androgen production, decreased follicular
is characterized by a complex set of symptoms, and research maturation and decreased sex hormone-binding globulin
to date suggests that IR could be a leading cause. Polycystic (SHBG) binding; all these steps lead to the development
ovarian syndrome may also have a genetic predisposition. of PCOS. Insulin resistance is a common finding among
A majority of patients with PCOS have IR and/or are obese. patients of normal weight as well as those overweight patients
Their elevated insulin levels contribute to the abnormalities (Algorithm 2).
seen in the hypothalamic-pituitary-ovarian axis that lead
to PCOS. Adipose tissue possesses aromatase that converts
POLYCYSTIC OVARIAN SYNDROME
androstenedione to estrone and testosterone to estradiol. The
excess of adipose tissue in obese patients creates the paradox Health consequences of polycystic ovarian syndrome are given
of having both excess androgens (which are responsible for in box 2 and table 3. 89
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Algorithm 2
Pathophysiology of polycystic ovarian syndrome
IR, insulin resistance; LH, luteinizing hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone;
SHBG, sex hormone-binding globulin; CV, cardiovascular.
Box 2: Polycystic ovarian syndrome: health consequences MANAGEMENT OF

• Reproductive • Cardiometabolic POLYCYSTIC OVARIAN SYNDROME
{{ Infertility {{ Diabetes hypertension
The overall aims of treatment are to:
{{ Increased risk of miscarriage {{ Dyslipidemia
• Correct the high androgen levels and adverse metabolic
{{ Increased risk of gestational {{ Increased
effects
diabetes/preeclampsia inflammation
{{ Increased risk of endometrial {{ Increased
• Restore menstrual regularity
cancer cardiovascular disease • Manage the cosmetic symptoms and signs
• Psychosocial risk • Restore fertility if desired
{{ Depression and anxiety {{ Non-alcoholic • Long-term health: chronic disease prevention
{{ Cosmetic concerns steatohepatitis • Diabetes prevention
(hyperandrogenic symptoms) {{ Sleep apnea • Cardiovascular disease risk reduction
{{ Increased risk of type 2 • Cancer prevention
diabetes The medical management of PCOS can be broken into:
• Chronic management
• Acute management (Algorithm 3).
Table 3: The spectrum of features of polycystic ovarian
syndrome and associated menstrual problems
Clinical Endocrinal Probable complications
HIRSUTISM
Obesity Increased insulin Dyslipidemaia The decision to treat should be based on the patient’s perception
of the excess terminal hair growth. It can be managed in two
Menstrual Decreased sex LDL increased
disturbance hormone binding ways (Algorithm 5):
globulin • Treatment of hirsutism:
{{ Cosmetic: shaving, waxing, electrolysis, etc.
Oligomenorrhoea – HDL increased
• Medical management of hirsutism:
Amenorrhoea – Triglycerides increased {{ Decreasing the amount
Regular cycle – – {{ Blocking action of androgens.
Hyper Testosterone Diabetese mellitus

androgenism Increased Mechanical
Infertility LH increased CV Disease, hypertension • Plucking is best avoided as it can lead to folliculitis and
Asymptomatic Prolactin increased Endometrial carcinoma scarring
LH, luteinizing hormone; LDL, low-density lipoprotein; HDL, high-density
• Shaving is likely to be the cheapest and simplest
lipoprotein; CV, cardiovascular. • Electrolysis involves electrocoagulation of the hair follicle
90
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Algorithm 3
IR, insulin resistance; PCOS, polycystic ovarian syndrome.
Algorithm 4
Acute management: Control of irregular menses
OCPs, oral contraceptive pills.
Algorithm 5 Testosterone Production (Algorithm 3)

Management of hirsutism • Oral contraceptive pills: gonadotropin production (as
testosterone is predominantly ovarian in nature and is
caused by both LH and by effect of hyperinsulinemia at the
ovary and SHBG
• Metformin
• Lifestyle modification/weight loss.
Medical Management of
Hirsutism (Algorithm 6)
Testosterone Action
• Antiandrogens (spironolactone):
{{ Aldosterone antagonist
{{ Antihypertensive agent also has a 67% relative affinity for
the testosterone receptors (SHBG by insulin sensitivity):

–– Spironolactone: 50 mg twice a day 6–12 months
–– Increase to 100 mg twice a day if required
–– Side effects: menstrual irregularity, nausea.
Management of Infertility
• Laser treatment involves causing selective thermal It is rarely required in adolescents. It is very difficult to cover
damage to the hair follicle. It may lead to erythema, edema, its intricacies; therefore, just a brief word on clomiphene,
blistering and/or temporary hyper- or hypopigmentation. metformin, and lifestyle modifications is being taken up.
• Eflornithine hydrochloride 13.9% cream: approved for the Polycystic ovarian syndrome accounts for 75% of anovulatory
treatment of unwanted facial hair. It slows the growth, but infertility. Additionally, when pregnancies do occur, the first
does not remove hair. trimester miscarriage rate is as high as 30–50% (Table 4). 91
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Table 4: Management of infertility

Clomiphene Lifestyle modification/weight loss Metformin
• Obese women do not respond to • Lifestyle modification needs to be • Start at 500 mg twice a day and increased to thrice
low doses at the rate of 50 mg dose stressed a day if ovulation did not occur by 6 weeks, and add
• The degree of obesity correlates • 3–6 month trial of aggressive lifestyle clomiphene 6 weeks later
with the dose of clomiphene modification may be a prudent first • Use improves the outcome of other infertility therapies
needed to induce ovulation step before considering an insulin • Improves fertilization and pregnancy rates
• The higher doses may cause side sensitizer • In the setting of infertility, metformin therapy should
effects and can increase the rate likely be continued for as long as fertility efforts are
of multiple gestations, given in ongoing, even if it “fails” initially
combination with metformin • Reduces risk of early pregnancy loss; no birth defects
occurred
Algorithm 6 • The pattern of dyslipidemia in PCOS is in keeping with

IR, increased triglycerides, low high density lipoprotein
cholesterol.
Assessment of Cardiometabolic Risk

(Fig. 3 and Table 5)
• Screen all PCOS for following: obesity, lack of physical
activity, cigarette smoking, dyslipidemia, hypertension
and impaired glucose tolerance test
• All women with PCOS should be assessed for excess weight
at every visit. Age appropriate and gender appropriate
body mass index should be considered.
LIFESTYLE MANAGEMENT FOR WOMEN

WITH POLYCYSTIC OVARY SYNDROME
DIABETES RISK AND LONG-TERM Lifestyle management (single or combined approaches of
MANAGEMENT OF INSULIN RESISTANCE IN diet, exercise and/or behavioral interventions) for weight
POLYCYSTIC OVARIAN SYNDROME loss, prevention of weight gain, or for general health benefits
should be recommended in women with PCOS (Box 3).
Most PCOS patients are inherently IR with the obesity seen
Although first-line monotherapy in adolescent age group
in many, with a substantial proportion of patients have
includes metformin and/or combination therapy with oral
abnormalities on the oral glucose tolerance test.
contraceptive agents and antiandrogen agents.
Lifestyle modification:
It is hoped that early and proper diagnosis, will allow
• 20 minutes of brisk walking
more women to be managed properly for their presenting
• Daily metformin is found to be useful for significant
symptoms (hirsutism, irregular menses, etc.), but also to be
improvement in insulin sensitivity; causes reduction in the
educated and managed for the continuing health risk of IR
development of type 2 diabetes mellitus.
throughout their lives.
Cardiovascular Risk Factors and
Disease in Polycystic Ovarian Syndrome Box 3: Lifestyle management
• Prevalence of diagnosed hypertension or higher ambula • Face to face, tailored dietary advice, including education,
tory blood pressure in PCOS behavioral change techniques and ongoing emotional support
should be provided to women with PCOS and a BMI ≥25 kg/m2
Signs of insulin resistance Best test for insulin resistance (overweight/obese)
• Upper-body obesity • Best test for insulin resistance is • Exercise recommendations
• Acanthosis nigricans 2 hour oral glucose tolerance test • 150 min/week or 20 minutes/day
• However, only 35–50% • Interpretation: • Of this, 90 min/week should be aerobic activity at moderate-to-
of polycystic ovarian {{ Impaired glucose high intensity (60–90% of maximum heart rate)
syndrome patients are tolerance:140–199 mg/dL
PCOS, polycystic ovarian syndrome; BMI, body mass index.
obese {{ Diabetic: ≥200 mg/dL
92
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A B
Fig 3: A, Metabolic syndrome and B, metabolic syndrome marker for cardiovascular disease
Table 5: Assessment of cardiometabolic risk

Diabetes status Blood pressure monitoring Lipid profile measurement
Prediabetes and/or type 2 diabetes should be Blood pressure should be measured Complete lipid profile
assessed
Oral GTT should be performed Annually: in PCOS with BMI 18.5 kg/m2 Every 2 years: PCOS with normal lipid profile
Every 2nd year in all women with PCOS Every visit: in PCOS with BMI Every year: PCOS with abnormal lipid profiles
≥25 kg/m2 and/or excess weight
Annually: in those with additional risk factors The ideal daytime blood pressure should A lipid profile should include: total
for type 2 diabetes, e.g., features of IR not exceed 135/85 mmHg cholesterol, LDL-C, HDL-C, and triglycerides
GTT, glucose tolerance test; PCOS, polycystic ovarian syndrome; IR, insulin resistance; BMI, body mass index; LDL-C, low density lipoprotein cholesterol; HDL-C, high
density lipoprotein cholesterol.
3. Broekmans FJ, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser BC.
Key points PCOS according to the Rotterdam consensus criteria: Change in prevalence
among WHO-II anovulation and association with metabolic factors. BJOG.
))
Polycystic ovarian syndrome (PCOS) is the most common 2006;113(10):1210-7.
endocrine disorder among young women affecting approxi 4. Dunaif A, Thomas A. Current concepts in the polycystic ovary syndrome. Annu
mately 5–10% Rev Med. 2001;52:401-19.
))
One of the leading causes of infertility 5. Farah L, Lazenby AJ, Boots LR, Azziz R. Prevalence of polycystic ovary syndrome in
))
There is not a single diagnostic test for PCOS women seeking treatment from community electrologists. Alabama Professional
))
Associated with a range of metabolic abnormalities which Electrology Association Study Group. J Reprod Med. 1999;44(10):870-4.
can lead to long-term health problems 6. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the
))
Lifestyle changes play an important role in management of polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2002;26(7):883-96.
the syndrome 7. http://e-hmr.org/ViewImage.php?Type=F&aid=264837&id=F2&afn=130_
))
Management should be individually tailored for each patient HMR_32_4_197&fn=hmr-32-197-g002_0130HMR
depending on the type of symptoms and clinical features 8. http://www.aafp.org/afp/2006/0415/p1374.html
found 9. http://www.jarrettfertility.com/PCOS%20patient%20handout.pdf
10. http://www.managingpcos.org.au/pcos-evidence-based-guidelines/algorithms
))
Prevent weight gain and address weight loss if needed as
11. http://www.managingpcos.org.au/pcos-evidence-based-guidelines/algorithms
body mass index >30 limits fertility
12. Rebar R, Judd HL, Yen SS, Rakoff J, Vandenberg G, Naftolin F. Characterization
))
About 5–10% weight loss will greatly assist in symptom control
of the inappropriate gonadotropin secretion in polycystic ovary syndrome.
))
Women with PCOS have increased risk of endometrial cancer J Clin Invest. 1976;57(5):1320-9.
with prolonged amenorrhea; aim for >4 periods/year unless 13. Sheehan MT. Polycystic ovarian syndrome: diagnosis and management. Clin Med
on contraception. Res. 2004;2(1):13-27.
14. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries.
Am J Obstet Gynecol. 1935;29:181-91.
SUGGESTED READINGS 15. Stein IF, Leventhal ML. Amenorrhoea associated with bilateral polycystic ovaries.
1. Artini PG, Di Berardino OM, Simi G, Papini F, Ruggiero M, Monteleone P, et al. Am J Obstet Gynecol. 1935;29:181-91.
Best methods for identification and treatment of PCOS. Minerva Ginecol. 16. Teede HJ, Misso ML, Deeks AA, Moran LJ, Stuckey BG, Wong JL, et al.
2010;62(1):33-48. Assessment and management of polycystic ovary syndrome: summary of an
2. Atiomo WU, Pearson S, Shaw S, Prentice A, Dubbins P. Ultrasound criteria in evidence-based guideline. Med J Aust. 2011;195(6):S65-112.
the diagnosis of polycystic ovary syndrome (PCOS). Ultrasound Med Biol. 17. Weissleder R, Wittenberg J, Harisinghani MG, Chen JW, editors. Primer of
2000;26(6):977-80. Diagnostic Imaging. 5th ed. St. Louis, MO: Mosby; 2011. 93
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Chapter 23
Approach to a Case of
Sexual Abuse in Children/Adolescent
Sushma P Desai
WHAT IS CHILD/ • An adult persuading a child or adolescent to engage in

ADOLESCENT SEXUAL ABUSE sexual activity.
If an older adolescent manifest such a behavior to a child it
Definition of adolescent sexual abuse as provided by many will also constitute child sexual abuse.
working in the field of child abuse, it is “any sexual behavior
directed at the dependent developmentally immature child Clinical Pearl
and adolescent that they do not comprehend fully, to which
they are unable to give informed consent. It involves the • The United Nations Children’s Fund: “Child marriage represents
exposure of a child to sexual contact, activity, or behavior the most prevalent form of sexual abuse and exploitation of
and may include invitation to sexual touching, intercourse, girls”.
or other forms of exploitation such as juvenile prostitution or
pornography”.
AGE OF CONSENSUAL SEX
Clinical Pearl Age of consensual sex in India is 16 year of age. Age of simple
majority is 18 years and legal age of consent for marriage is 21
• Under the law, child sexual abuse is an umbrella term
years in boy and 18 years in girls.
describing criminal and civil offenses in which adult engages in
sexual activity with a minor or exploits a minor for the purpose
of sexual gratification. It can never be considered normal or PEDOPHILE
socially acceptable behavior.
Usually, it has an unidentifiable sexual preference with regard
to prepubertal children and will frequent locations that attract
The World Health Organization defines an adolescent as children.
being between 10 and 19 years.
Incest (Intrafamilial Child Abuse/Child

SEXUAL ABUSE BEHAVIOR DEFINITION
Incestuous Abuse)
• An adult exposing his/her genitals to or persuading a child
Traditionally “incest” is defined as sexual relations between
or adolescent to do the same
people classed as being too closely related to marry each other.
• An adult touching a child or adolescent’s genitals or making
a child or adolescent touch the adult’s genitalia
• An adult involving a child or adolescent in pornography, Clinical Pearl
either by exposing a child or adolescent to create
pornographic material • Incest between a child/adolescent and a related adult has
been identified as the most widespread form of child sexual
• An adult having oral, vaginal, and anal intercourse with a
abuse with a huge capacity for the damage to a child. It leads
child or adolescent
to serious type of long-term psychological trauma, especially
• Any verbal or other sexual suggestion made to a child or
in case of parental incest.
adolescent by an adult
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Chapter 23: Approach to a Case of Sexual Abuse in Children/Adolescent
Most often reported form of incest is father-daughter and • Mentally and physically: challenged/retarded children and
stepfather-daughter incest, mother/stepmother-daughter form adolescents
contributes to a small portion of the remaining incest. Sibling • Unloved, uncared children, and adolescent
incest may also be as common as or more common than other • Violence in community.
types of incest. Prevalence of parental incest is difficult to assess
due to secrecy and privacy. Statistics show that about 30% of
all perpetrators are related to the sexual victim, 60% are family
PROFILE OF THE ADULT SEX OFFENDER
acquaintances, and 10% are strangers. • Children and adolescents living in parents homes are more
likely to be abused by adults from within the family or
Commercial Sexual known friend circle. In 80% of the cases, the perpetrator is
either related or known to the victim
Exploitation of Children
• Children on streets or observation homes are more likely to
Commercial sexual exploitation of children is defined as be abused by strangers
“Sexual abuse by an adult accompanied by remuneration • The offender has a special ability to identify vulnerable
in cash or in kind to the child or to the third person(s). children, to use that vulnerability to sexually abuse the child
Commercial sexual exploitation of children usually take • The systematically desensitize children to touch
the form of child prostitution or child pornography and is • They use adult authority to isolate the victim from others
often facilitated by child sex tourism (also internet child and enforce their victim’s silence including threats, force,
pornography)”. It is particularly a problem of developing bribery, acts of cruelty.
countries of Asia.
Types TYPES OF OFFENDERS

Child sexual abuse includes a variety of sexual offenses, There are two groups:
including: • Situational: does not prefer children, but offend under
• Sexual assault: an adult uses a minor for the purpose of certain circumstances. They can be:
sexual gratification, e.g., rape (including sodomy) and {{ Regressed: typically has a relationship with the adults,
sexual penetration with an object
but a stressor causes them to seek children as a
• Sexual exploitation: offenses in which an adult victimizes
substitute
a minor for advancement, sexual gratification, or profit,
{{ Morally indiscriminate: all-round sexual deviant, who
e.g., prostituting a child and creating or trafficking in child
may commit other sexual offenses unrelated to children
pornography
{{ Naïve/inadequate: often mentally disabled in some
• Sexual grooming: it defines a social conduct of a potential
way, finds children less threatening
child sex offender who seeks to make a minor more
accepting of their advances, e.g., in an online chat room. • Preferential: has true sexual interest in children
{{ Mysoped: sadistic and violent, target strangers more
often than acquaintances

VULNERABLE SITUATIONS (RISK FACTORS) {{ Fixated: little or no activity with own age, described as
• Children and adolescents of single parent: due to lack of “overgrown child”.

adequate supervision
• Children and adolescents with low self-esteem: due STATISTICS OF CHILD SEXUAL
to failure in academic life. If parents persistently keep
ABUSE IN INDIA
comparing them with the achievers; this results in low self-
esteem and as rebellion they may involve in sexual activity Global prevalence: study in 2009 shows (65 studies from 22
considering it as an achievement countries) 19.7% of female children and 7.9% male, highest in
• Attraction to city life: children and adolescents get induced Africa 34.4%, lowest in Europe 9.2%, Asia 23.9%.
by middlemen and easy access to money/comforts of life
• Lack of education: children and adolescents due to lack of India: the Ministry of Women and Child Development
education lack of being well-informed may get induced to published the Study on Child Abuse: India 2007. Its main
sexual activities by strangers easily findings included 53.22% of children reported having faced
• Children and adolescence education on sex and sexual sexual abuse. About 52.9% were boys and 47.06% girls.
parts will help them take care of their private parts and Andhra Pradesh, Bihar, Assam, and Delhi reported highest
sexual life incidence. Children on streets, at work, and in institutional
• Poverty: high risk of getting sexually abused because of care reported higher incidence. The study also reported 50%
poor socioeconomic conditions of the abusers are known to the child or are in a position of
• Parental factors: loss of job and substance abuse like trust and responsibility. Most children had not reported the
alcoholism. Drug addiction matter to anyone.
95
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symptoms are often the only way to recognize sexual

Clinical Pearls abuse
• About 40% of girls and 25% of boys are sexually abused before • There is no specific symptom/syndrome
they reach 16 years of age. • Most important element of the diagnosis is the disclosure,
• One-tenth children is being sexually abused at any given point which depends on our ability to speak with children
of time. • Children need support and stress-reducing resources after
disclosure of sexual abuse. Negative social reactions to the
disclosure have been found to be harmful to the survivor’s
well-being.
EFFECTS
Clinical Pearl
Psychological Effects
• Children who receive supportive responses after disclosure
Clinical Pearl have less traumatic symptoms and are abused for a shorter
period of time.
• About 51–79% of sexually abused children exhibit psycho
logical symptoms. • American Academy of Child and Adolescent Psychiatry
provides guidelines for what to say to the victim and what
The child sexual abuse can lead to both long- and short-term to do following the disclosure.
harm, including psychopathology in later life. The common
effects are anxiety, depression, eating disorders, poor self EXAMINATION OF
esteem, somatization, sleep disturbances, dissociative disorder, A CASE OF SEXUAL ABUSE
and posttraumatic stress disorder. Children may manifest
regressive disorders like thumb sucking and bed wetting. History
Clinical Pearl • Look for risk factors of victimization/vulnerability for
sexual abuse in adolescents like:
• The strongest indicator of sexual abuse is inappropriate sexual {{ Female sex
knowledge and interest. {{ Going alone in lonely places at odd times
{{ Going to a friend’s house for exchanging notes
{{ Parties (especially night parties)

The victim may withdraw from school and normal social
{{ Dating
activities and exhibit learning and behavioral problem, cruelty
{{ Crowded places (e.g., buses, trains, fair, etc.)
to animals, attention deficit hyperactivity disorder, conduct
{{ “Immoral” neighborhood
disorder, and oppositional defiant disorder.
{{ Families with a person of personality disorder (sex
Adolescent victims show risky sexual behavior. Self-inflicted
harm and teenage pregnancy is one of the important effects. maniac)
{{ Single parent/broken homes
Increased rates of crime in sexually abused teen are observed.
{{ Both parents working and child alone at home
{{ Children on foster care, i.e., parents or elders are out

Physical Effects
and some relative/friend is staying at home
• Injury: depending on age and the size of the child and the {{ Drinking/watching pornography/movie with friends
degree of force used. Internal laceration, bleeding, and {{ Heart breaks, failure, and other situations needing
damage to internal organs and even death emotional support
• Infection: sexually transmitted infections, human immuno {{ History of past abuse
deficiency virus/acquired immunodeficiency syndrome • How to identify sex abuse/flag signs for the adolescent
• Neurological damage: traumatic stress, including stress specialist:
caused by sexual abuse, causes notable changes in brain {{ Fear of being bathed
functioning and development. Increased likelihood of {{ Having a great deal of knowledge about sex at a very
“ictal temporal lobe epilepsy-like symptoms”. Short-term young age or sexual behavior that seems beyond his or
memory impairment and lowering of the score of math her age
scholastic aptitude test. {{ Feeling depressed
{{ Anxiety, low-self esteem
{{ Sudden avoidance to visit a particular place or a

DIAGNOSIS/DISCLOSURE
particular person, decreased desire of interaction with
• Victims are often unable to speak due to different reasons peers
such as threat, fear, shame, guilt {{ Poor interest in academics
• Therefore, indirect nonverbal clues, behavioral distur {{ Fondling with one’s genitalia too often
96 bances, psychosomatic, psychiatric, and seldom physical {{ Drug or alcohol abuse.
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Physical Examination Table 1: Sexual abuse signs in sodomy

• Points to remember: Chronic Recent
{{ Ensure patient privacy
Proctitis Tear
{{ Prepare the child by explaining the examination and
showing equipment; this has been shown to diminish Hypotonic sphincters Bleeding
fears and anxiety Anal fistula Bruising
{{ Ask whom he/she would like in the room for support
during the examination Anal and perianal skin changes Semen

• The examination should include: Chondylomata, warts, chancre Gonorrhea
{{ Mental maturity—by asking questions like age, time,
etc.
{{ Physical maturity—with the help of growth parameters
Age Determination
{{ Nutrition status It has a great medicolegal importance as the justice and
{{ Look—vacant/starry/slating/fearful punishment to the abuser is directly related to the age of the
{{ Mental status—confused/clear/apprehensive victim. The age determination of an adolescent can be done
{{ Clothing—any evidence struggle/trace evidence like from a comprehensive examination of the following four
hair and stains of forensic importance aspects:
{{ Oral hygiene and personal hygiene
1. General physical features
{{ Physical indicator of sexual assault and injuries
2. Secondary sexual character: Tanner’s staging
• Indicators of child sexual abuse: 3. Appearance of teeth: orthopantomogram is helpful
{{ Sure indicators:
4. Ossification of bones.
–– Venereal diseases
–– Pregnancy
Collection of Forensic Samples
–– Presence of semen The following samples are required to be collected in sexual
–– Gonococcal infection of pharynx, urethra, rectum, abuse cases:
vagina • Blood (blood grouping, testing drug intoxication)
{{ Probable indicators: • Urine (to test for suspected pregnancy, drug testing)
–– Genital herpes • Seminal stain (blood grouping)
–– Trichomonas • Nail scraping (from under the nails, to look for epithelium
–– Recurrent urinary tract infection of the assailant)
–– Horizontal hymen opening in relation to age. • Hair (to look for seminal stain, foreign hair)
{{ Near indicators:
• Vaginal swabs (vulva, low vaginal, high vaginal): it is
–– Abdominal pains stressed here that it should be made a routine
–– Leaking vagina or anus • Microscopic examination of vaginal slides (motile and
immotile sperm).
–– Difficult walking
–– Sudden withdrawal from normal activities
–– Sudden change in appetite TREATMENT
–– Unusual sexual knowledge
The initial approach depends upon following factors:
–– Mood variation without any obvious reasons
• Age at the time of presentation
–– Depression or depersonalization
• Circumstances of presentation for treatment
–– Irritation unprovoked or easily induced
• Comorbid conditions.
–– Suicide attempts or threats The goal of management is:
–– Lack of attachment to parents • To treat current issues
–– Torn clothing and/or stained with blood or semen • To prevent future abuse/untoward incidences.
• Detail examination of the genitalia: There are three modalities of therapy:
{{ Genital injuries in adolescents:
1. Family therapy
–– Scratches over the thigh, genitalia, or body 2. Group therapy
–– Bruising of the vulva 3. Individual therapy.
–– Swelling in the genital area Treatment of young children requires strong parental
–– Minor tears in the hymen involvement and can benefit from family therapy. Adolescents
–– Minor lacerations tend to be more independent, they respond well to individual
–– Bleeding or group therapy. The modalities also shift during the course of
–– Laceration of large size in case of age incompatibility therapy, e.g., group therapy is rarely used in initial stages as the
• Sexual abuse signs in sodomy (Table 1). subject matter is very personal and/or embarrassing.
97
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PHARMACOLOGICAL MANAGEMENT FOLLOW-UP AND REHABILITATION

• Follow-up care must be given to assess the late compli
Prophylaxis of Sexually Transmitted Diseases cations, especially the psychosocial problems
Incidence of sexually transmitted diseases from sexual assault • Parental support is very important for the rehabilitation.
without prophylaxis is: Adolescents can be taken care of at home environment in
• Condyloma: 1 in 4 a better way
• Chlamydia: 1 in 10 • If parents cannot support their adolescent children,
• Gonorrhea: 1 in 30 especially in rural areas, supportive social and legal
• Human immunodeficiency virus: 1 in 1,000 networks should be developed for them to prevent suicidal
• Syphilis: 1 in 1,000 attempts or fall into flesh trade.
• Hepatitis B/herpes simplex virus: uncertain.
PREVENTION
Gonorrhea and Chlamydia
• Adults (parents, families, community, and teachers)
• Nonpregnant victims:
must help children through nonthreatening and age-
{{ Doxycycline 300 mg orally, stat, followed by 100 mg
appropriate means to participate in their own protection
twice a day for 3 days (patient >8 years old)
• Personal safety curriculum is designed to:
• Alternative: {{ Protect children/adolescents from abuse, specifically
{{ Floxacin 400 mg twice a day for 7 days (patient >16 years
sexual abuse
old) {{ Empower children/adolescent to take part in their own
{{ Azithromycin 2 g orally, single dose
protection by giving them age appropriate information,
• Pregnancy and adolescent victims: erythromycin 1.5 g skills, and self-esteem
orally stat, followed by 500 mg four times a day. {{ Teach children/adolescent that their body belongs
only to them and nobody has the right to touch them

Syphilis in a way they do not like or understand, give them
Benzathine penicillin 2.4 million units (adults), in children knowledge of sexual organs and function
not usually given because of a low incidence of risk of syphilis, {{ Children not to keep secret
instead a follow-up rapid plasma reagent test is done at {{ To be bold to make friends—but when it comes to sex
6–12 weeks. If seroconversion has occurred therapy is given at learn to say no
that time. {{ Teach children/adolescent that only the offender is to
blame for any inappropriate sexual touch

Human Papillomavirus {{ Teach assertiveness skills, helping children to stand up
Not known prophylactic regimen. Human papillomavirus for their own right without violating the right of others
vaccine is recommended for all adolescent girls and quadri {{ Build the support system of each child including the
valent vaccine for adolescent boys above age of 9 years. family, school, community, and friends.
Human Immunodeficiency Virus HOW TO HELP THE SURVIVOR

The risk of transmission is very less, risk-benefit ratio should be
When a survivor tells us that she/he has been sexually abused,
weighed before giving the drugs.
she/he is entrusting you with a part of the life that is painful,
• Triple-drug therapy including zidovudine, lamivudine
frightening, and vulnerable.
(3TC) and famotidine.
The following guidelines can help us honor that trust and
assist their healing:
Herpes Simplex Virus
• Believe the survivor
• Acyclovir 40 mg/kg. • Be clear that abuse is never a child or young adolescent’s fault
• Do not sympathize with the abuser
Trichomonas
• Express your compassion
• Metronidazole 2 g orally (single dose). • Validate the survivor’s feeling and join with the survivor in
validating the damage
Pregnancy Prophylaxis • Encourage the survivor to get support
Incidence of pregnancy in rape/sexual assault is 1 per 100. • Seek expert’s help if the survivor is suicidal
• Levonorgestrel 0.75 mg 2 tablets stat or ethinyl estradiol • Respect the time and space taken to heal
0.05 mg 2 tablet stat, followed by 2 tablet after 12 hours. • Resist seeing the survivor as a victim.
98
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SEXUAL ABUSE AND EXISTING LEGAL SYSTEM International Law

• It is necessary to give recognition to child abuse as an Child sexual abuse is outlawed nearly everywhere in the world,
offence against innocence and, therefore, the law against generally with severe criminal penalties including in some
child rape needs to be more stringent jurisdiction, life imprisonment, or capital punishment. An
• Since sexual abuse of minors has its own characteristics, it adult’s sexual intercourse with a child below the age of legal
needs to be addressed separately from the offence of sexual consent is defined as statutory rape, based on the principle
assault on an adult person that a child is not capable of consent and that any apparent
• Ironically, existing rape/sexual abuse laws make no consent by a child is not considered to be legal consent. The
distinction between rape of a minor and that of an adult. United Nations Conventions on the Rights of the Child (CRC)
is an international treaty that legally obliges states to protect
Clinical Pearl children’s rights in November 2008, 193 countries are bound by
the CRC, including every member of United Nations except the
• The “Protection of Children Against Sexual Offense Bill 2011”
was passed in the Indian Parliament on May 22, 2012 which
United States and Somalia (Algorithm 1).
came into force from November 14, 2012.
Algorithm 1
An algorithmic approach to a case of child/adolescent sexual abuse
99
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Key points
))
Sexual abuse is rampant and universal as children and adolescents are vulnerable and most often not in a position to voice their protest
against the heinous offense against their body/their complains are not taken seriously and many times silenced
))
About 40% of girls and 25% of boys suffer from sexual abuse before they reach 16 years of age. Majority of them are not surfaced
))
Contrary to the common belief, majority of the offenders are known to the victim
))
Child sexual abuse is one of the most fundamental violations of children’s human rights which lead to tremendous psychological trauma
having many long-term and short-term effects on their overall development adversely affecting them throughout their life
))
As the survivors are often not able to reveal, high index of suspicion based on nonverbal clues, psychosomatic symptoms and seldom
physical signs are helpful to come to the diagnosis
))
Important aspects of management are helping the survivor in disclosure with the help of counseling and strong psychosocial support.
Pharmacological therapy is aimed at prevention of pregnancy and prophylaxis against sexually transmitted infection
))
There is a great need to find ways to prevent child/adolescent sexual abuse and to ensure the safety from victimization of any form
))
Self-defense training for every girl has an important role in prevention of victimization. Schools have the potential to teach protective
behaviors effectively, including teaching the parents
))
There is a need for incorporation of child sexual abuse in Indian Penal Code, including incest, sexual abuse of boys, and nonpenetrative
sexual abuse.
SUGGESTED READINGS 10. Parthasarathy A, Nair MK, Menon PS, Bhave SY. Bhave’s Textbook of Adolescent
Medicine, 1st ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ldt.; 2006.
1. Aggarwal A. (2000). Age estimation in the living: some medicolegal considerations. 11. Pereda N, Guilera G, Forns M, Gómez-Benito J. Prevalence of child sexual
[online] Available from: anilaggrawal.com/ij/vol_001_no_002/ug001.html. abuse in community and student samples: a meta-analysis. Clin Psychol Rev.
[Accessed November, 2015]. 2009;29(4):328-38.
2. American Academy of Child and Adolescent Psychiatry. (2014). Responding to 12. Teicher MH. Scars that won’t heal: the neurobiology of child abuse. Sci Am.
child sexual abuse. [online] Available from: www.aacap.org/AACAP/Families_ 2002;286(3):68-75.
and_Youth/Facts_for_Families/FFF-Guide/Responding%20To-Child-Sexual- 13. The Ministry of Women and Child Development, the Government of India. (2007).
Abuse-028.aspx. [Accessed November, 2015]. Study on Child Abuse: India - 2007. [online] Available from: www.savethechildren.
3. American Academy of Pediatrics and Adolescent Psychiatry. Factsheet on Child in/custom/recent-publication/Study_on_Child_Abuse_India_2007.pdf.
Sexual abuse. [Accessed November, 2015].
4. American Psychological Association. (2011). Understanding child sexual abuse: 14. The sexual exploitation of children. Chart 1: Definition of terms associated with
education, prevention, and recovery. [online] Available from: www.apa.org/pi/about/ the sexual exploitation of children, University of Pennsylvania, Centre of Youth
Policy Studies, US National Institute of Justice; August 2001.
newsletter/2011/12/sexual-abuse.aspx. [Accessed November, 2015].
15. Tulir: Center for Treatment of Child Sexual Abuse, Chennai, India.
5. Amnesty International USA. United Nations Convention on the Rights of the Child:
Frequently Asked Questions. 2008. 16. Widom CS. Posttraumatic stress disorder in abused and neglected children
grown up. Am J Psychiatry. 1999;156(8):1223-9.
6. Child Marriage. Available from: http://www.unicef.org/chinese/protection/files/
17. World Health Organization (WHO). (2000). Violence and injury prevention:
Child marriage.pdf.
Guidelines for medico-legal care for victims of sexual violence. [online]
7. Child sexual abuse: consequences and implications. J Paediatr Health Care. Available from: www.who.int/violence_injury_prevention/publications/violence/
2009;24(6):385-64. med_leg_guidelines/en/. [Accessed November, 2015].
8. Department of child protection, UNICEF, DWCD, Government of India/Manual 18. World Health Organization. (2002). Understanding and addressing violence
for Medical Officer dealing with medicolegal cases of victims of trafficking for against women: Sexual violence. [online] Available from: apps.who.int/iris/
commercial sexual exploitation and child sexual abuse. bitstream/10665/77434/1/WHO_RHR_12.37_eng.pdf. [Accessed November,
9. Medline plus, US National Library of Medicine. Child Sexual Abuse. 2008-04-02. 2015].
100
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Chapter 24
Adolescent Depression/
Suicidal Tendency and Its Management
Paula Goel
Introduction CLINICAL FEATURES

Every year about 2 million adolescents (1 in every 12) suffer Presence of following symptoms for more than 2 weeks
an episode of depression; 1 in 5 adolescents experience (Diagnostic and Statistical Manual of Mental Disorders Fourth
depression before they reach adulthood. Depression affects Edition Text Revision):
3.5% of children at any given time, impeding healthy psycho • Depressed mood: feels sad, empty, bored, appears tearful,
social development. Diminished self-worth, academic irritable mood
struggles, and difficulties in social relations with family and • Markedly decreased interest or pleasure in almost all
peers exert a heavy toll on youth who are often unable to activities most of the day, nearly every day
communicate the nature of their experience. It is a common • Significant weight loss or weight gain with increase or
and serious problem. It increases the risk for suicide, the third decrease in appetite nearly every day
leading cause of death in this age-group. • Poor sleep, insomnia, or hypersomnia nearly every day
Often, it leads to more poor academic achievement, greater • Psychomotor agitation or retardation almost daily:
absenteeism, strained relationships with family and friends, restlessness, pacing, tapping of fingers, abruptly starting
interference with extracurricular activities, and substance and stopping tasks, meaninglessly moving objects around.
abuse. Clinical depression during adolescence represents Fatigue or loss of energy
the strongest risk factor for teenager suicide and is linked to • Feelings of worthlessness or excessive or inappropriate
significant psychosocial impairment in adulthood. guilt nearly daily
Periodic screening of children presenting—for any reason— • Diminished ability to think or concentrate on academics/
to primary care physicians can improve clinical recognition of indecisiveness almost daily
these disorders and result in improved rates of treatment. • Recurrent thoughts of death or suicidal ideation
The importance of detecting and treating depression in • Clinically significant distress or impairment in social,
adolescents is being increasingly recognized. occupational, or other important areas of functioning
Prevalence is related to age, gender, and social class (about • Symptoms persist for more than 2 months or are
1% between 10 years and 14 years of age and 25% among late characterized by morbid preoccupation with feelings of
teens). worthlessness, suicidal ideation, psychotic symptoms,
marked functional impairment.
PREDISPOSING FACTORS Clinical features can also be classified as:
• Affective: depressed mood and feelings of worthlessness or
• Biological factors guilt
• Endocrinal factors • Behavioral symptoms: social withdrawal and agitation.
• Social factors Feelings of restlessness, grouchiness, aggression, sulkiness
• Structural factors in brain • Cognitive symptoms or problems in thinking including
• Environmental factors: socioeconomic status, level of difficulty in concentration or making decisions, school
family conflict, abuse or neglect, and parental separation difficulties
or divorce • Somatic symptoms: insomnia or hypersomnia
• Family history of depression. • Prepubertal children: somatic symptoms
ch-24.indd 101 11/18/2016 5:49:21 PM

• Adolescents: affective and behavioral symptoms {{ Little coordination typically occurs between primary
• Highly intelligent, academically strong children com care and mental health specialties
pensate for mood disorders with increased attention to • The challenge
academics {{ The burden of adolescent depression prevention and
• Comorbidities: conduct disorder, defiant disorder, panic management falls squarely on primary care
disorder, attention deficit hyperkinetic disorder, anxiety {{ Most pediatricians and family practitioners believe it is
disorders, and disruptive disorders. their responsibility to identify depression, but relatively
The US Preventive Services Task Force now recommends few believe it is their responsibility to treat it
screening adolescents (12–18 years) for major depressive {{ Most do not feel equipped to manage adolescent
disorder when systems are in place to assure accurate depression, and their office systems are not set up to
diagnosis, psychotherapy (cognitive-behavioral or inter handle it
personal) and follow-up. {{ Adolescent depression is different than adult depression
The American Academy of Pediatrics also strengthened due to developmental issues, responses to treatment,
their recommendations for mental health screening and issues in psychotherapy, risks of medications, family
counseling in the latest Bright Futures Guidelines. dynamics
The Guidelines for Adolescent Depression in Primary Care • Steps to integrate care:
{{ Assess the practice: adolescent patient load, prevalence
(GLAD-PC) were published in 2007 and have been updated in
2010. Guidelines for Adolescent Depression in Primary Care of mental health issues
{{ Determine the role you want to play and services to
provides provide a roadmap for enhancing care. This time
tool presents important elements from the 2010 GLAD-PC for provide for adolescent depression
{{ Build a network of local resources: therapists, peer
the identification, assessment, and treatment of adolescent
depression in the office setting. counseling, group programs, etc.
{{ Determine relation with mental health resources:
• Systems must be in place to allow effective triage (safety/
consultation, colocation, collaboration
placement) for:
{{ Provide training where needed: screening/assessing,
{{ Identification of high risk cases
{{ Screening
record keeping, confidentiality (state law), staff
roles, insurance coverage including preapprovals
{{ Assessment and intervention
or preauthorizations for referrals; counseling/
{{ A predetermined “go-to” list of providers and facilities
psychotherapy training for designated staff
to refer for care when indicated.
{{ Assure systems are in place to allow effective triage
• The good news:
(safety/placement) that includes a “go-to” list of
{{ Screening is simple, effective, and well received by
providers and facilities to send patients as needed
patients, parents, and providers {{ Follow guideline recommendations
{{ A two-question screening can identify the need for
• Guide to the office visit: mental health or emotional issues
more in depth screening as chief complaint, or positive screen on Patient Health
{{ Adolescents prefer to have their depression addressed
Questionnaire-2
in primary care • Staff: preparation for visit.
{{ Most adolescents see their primary doctor at least
annually; an estimated 45% of suicide victims

reportedly saw their primary doctor in the month prior IDENTIFY Risk Status
to the suicide • Assistant: Perform chart review to ensure:
{{ Most depressed adolescents can be treated in primary
{{ Forms/assessments to be completed by patient in chart
care {{ Score instrument in chart for clinician.
{{ There are effective treatments and guidelines for using
them in primary care

• The bad news ASSESS for Depression
{{ Only about 1 of 3 adolescents with depression is identi • Review symptom assessment and scoring
fied (American College of Preventive Medicine, 2011) • Interview with patient and family/caregiver to identify
{{ Fewer than half of primary care clinicians inquire contributing factors
about depression with adolescents; fewer yet use a • Collect collateral information and family history to help
standardized instrument to assess depression distinguish adjustment disorders and family relationship
{{ Fewer than half of adolescents who are diagnosed are issues
treated appropriately • Assess for safety/suicide risk and appropriate level of care
{{ Severe cases should be treated by mental health • Refer to crisis or emergency services if necessary.
specialists, but there is a severe shortage of child
psychiatrists—few of these severe cases are seen by
DIAGNOSE and Rate Severity
specialists
{{ Reimbursement policies are often a disincentive to Provide diagnosis; rate severity: mild, moderate, or severe
102 treating depression in primary care [based on number of symptoms present].
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Chapter 24: Adolescent Depression/Suicidal Tendency and Its Management
EDUCATE {{ Discuss more serious adverse effects, especially

suicidal ideation; emphasize careful monitoring due to
• Depression is an illness, not a weakness; very common, increased risk earlier in treatment
no one’s fault, usually involves genetic and environmental • Develop safety plan for acute crisis, deterioration of
factors symptoms
• Functional impairment in various domains can be • Consider ongoing mental health consultation
manifestations of the illness • Evaluate response at 6–8 weeks (American College of
• Depression can be a recurrent illness—recovery may take
Preventive Medicine, 2011).
a while
• Key to overcoming depression is staying with the treatment
plan long term FOLLOW-UP MANAGEMENT
• Stress in the parent-child relationship, if present, may be (AT 6–8 WEEK VISIT)
part of the problem
• Ask adolescent about future goals—if none, be wary of Mild depression:
suicidal ideation. • If persistent: institute treatment as moderate cases or refer
to mental health
Initial Management • If improved: continue monitoring monthly for 6 months,
• Discuss limits of confidentiality regular follow-up for 2 years after resolution of symptoms.
• Emphasize monitoring symptoms, especially changes Moderate or severe:
reflecting increasing suicidal ideation. • If not improved
{{ Reassess the diagnosis
{{ Consider adding a medication, increasing the dosage,

Primary Care
or changing medications if already on maximum
• Offer referral for peer/family support, community resources, dosage
etc. {{ Add psychotherapy if not already using, or intensifying
• Facilitate parental and patient self-management; provide current therapy
written materials and websites for more information. {{ Consider referral to mental health
{{ Provide further education, review safety plan, continue

CONSIDER CONSULTATION ongoing monitoring
With mental health specialist: recommended for severe or {{ Evaluate response again at 6–8 weeks
complicated depressions, or for interventions not within scope • If partially improved:

of the pediatric practice: {{ Consider adding a medication or increasing the dosage
• Decide to treat in practice or refer to trusted network of {{ Add psychotherapy if not already using, or intensifying
mental health providers current therapy

• If referred, designate case coordination responsibilities; {{ Consider referral to mental health
follow-up plan {{ Provide further education, review safety plan, continue
• Maintain contact with mental health specialist as long as ongoing monitoring

such treatment continues. {{ Evaluate response again at 6–8 weeks
• If improved:
{{ Continue prescribed medication for 1 year after
TREATMENT PLAN
symptom resolution
If treating in practice: {{ Continue monthly monitoring for 6 months
• Include family: set specific goals for key areas of {{ Provide regular follow-up for 2 years after resolution of
functioning—home, peer relationships, school and work. symptoms.
Mild depression:
• Active support and monitoring for 6–8 weeks, contact every Final Thoughts
1–2 weeks
Moderate or severe: Adolescent depression challenges everyone—from the affected
• Initiate shared decision discussion about therapy: young person to the parents and providers, and the entire
{{ Psychotherapy and/or antidepressants healthcare system. The fragmented care and lack of support
{{ Review benefits and risks of each option including for primary care undermines early identification and timely
the black box warning regarding selective serotonin treatment.
reuptake inhibitors (SSRIs) and suicide risk • Routine screening and diagnosis:
• Discuss preferences and plan for chosen treatment: {{ Periodically screen children and youth for early signs of
{{ Emphasize importance of finding a therapist one feels depression and/or anxiety. Record these results in the
comfortable with for psychotherapy patient’s problem list
• Discuss common medication side effects: {{ Ask questions of the child (or parent where applicable)
{{ Emphasizing temporary nature and importance of not when there are red flags including unexplained somatic
stopping medication without calling first complaints, unexplained behavioral changes, teenage 103
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Algorithm 1
Treatment protocol for management of depression
pregnancy, school absences, and family members with not effect a significant improvement, it is appropriate
depression, anxiety, alcohol, or other substance abuse to refer to a specialist or to the child and youth mental
• Suggested questions health team for treatment (Algorithms 1–4).
{{ Do you find yourself sad, irritable, or worried a lot?
{{ Is the child withdrawing from or avoiding their usual
activities? Algorithm 2
{{ Family involvement is invaluable for assisting with and
Management of children and youth with anxiety or depression
monitoring treatments as well as providing assurance
and emotional support for the child or youth. Assure
the family that the questions and fact-finding is not to
assign blame but to better understand the situation
{{ Choose an appropriate diagnostic questionnaire
available for download on the internet. If the screen

indicates a possible problem then either begin or
schedule time to begin a detailed inquiry about anxiety
or depressive symptoms, evaluate severity, and the
potential for self-harm
{{ Consider that there may be more than one psychiatric
disorder when screening because anxiety and

depressive disorders are highly comorbid in children
and adolescents. All youth, with mood or anxiety
disorders should be screened for alcohol or drug use
{{ Note red flags for risk of bipolar depression: family
history, psychotic depression, mania with SSRIs,

hypersexuality, risk-taking behavior, and prepubertal
depression. Consider referral if bipolar disorder is
suspected. Manage the patient while waiting for
referral and provide follow-up
• Diagnosis
{{ Take a medical history and do a physical examination
with attention to conditions that may mimic anxiety

or depressive disorders. Consider indications for
diagnostic tests such as thyroid-stimulating hormone.
Consider the family situation and social stressors
{{ Investigations: clinical basis, identify hypothyroidism
and anemia
• Attempt nonpharmacological management strategies first:
{{ Nonpharmacological approaches are essential first line
104 treatments for both anxiety and depression. If physician CBT, cognitive behavioral therapy; IPT, interpersonal psychotherapy; OCD,
counseling, parental involvement, and use of books does obsessive compulsive disorder.
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Algorithm 3 at lower doses (e.g., 25–50 mg sertraline), obsessive

Pharmacotherapy of major depressive disorder compulsive disorder (OCD) (100–200 mg sertraline),
generally start low and increase slowly. Dosing example: 10
mg daily fluoxetine for an adolescent. For an anxious 6 year
old, start with 5 mg daily and use increments of 5 mg every
2 weeks if needed
• Depression: the response often requires full doses for youth
and the response to medication is slower. Example: start
the first week with 10 mg daily of fluoxetine and increase to
20 mg daily as soon as tolerated. Increase again up 30 mg
daily if not improved after 6 weeks to a maximum of 40 mg
daily. If not responding after 10–12 weeks, refer to specialist.
Adverse effects: in children, SSRIs and other new anti
depressants produce a higher rate of behavioral and emotional
adverse effects (such as agitation, disinhibition, irritability, and
occasionally thoughts of self-harm). The largest drug-placebo
difference in the number of cases of suicidal ideation and
behavior is greatest for the under-24 age group. For all ages,
the risk is highest during the first few months of drug therapy,
therefore, monitor patients closely during this time
• Monitoring: request assistance of the family and/or
teenager, to monitor both symptoms and functions
• Continuation: for both anxiety and depression, the usual
length of treatment is 6–12 months before a trial of tapering
MDD, major depressive disorder; SSRIs, selective serotonin reuptake inhibitors; • Discontinuation: anxious patients are very sensitive to
TCAs, tricyclic antidepressants; NaSSAs, noradrenergic and specific sero
tonergic antidepressants; SNRIs, serotonin-norepinephrine reuptake inhibitors. physical sensations during discontinuation. So, taper off
particularly slowly over 1–2 months by approximately 5 mg
per reduction.
INDICATIONS FOR PHARMACOTHERAPY
Indications for pharmacotherapy include persistent depression Antidepressants Commonly Used in
and/or a comorbid anxiety disorder which have not responded Treatment of Major Depressive Disorders (Table 1)
to psychosocial interventions. • Selective serotonin reuptake inhibitors (sertraline,
Depression: psychotherapy can be effective for treating paroxetine, etc.): these medications are somewhat less
depression, particularly in adolescents. If unavailable, toxic in overdosage. As compared to adults, adolescents
medications may be indicated: are a bit more likely to become agitated or to develop a
• The drug most often used is fluoxetine mania while they are taking an SSRI. These medications
can decrease libido in both adolescents and adult.
• If bipolar vulnerability, start with a shorter-acting SSRI
Fluoxetine, sertraline, citalopram, and escitalopram are
(e.g., sertraline)
commonly used as an initial medication. Fluoxetine now
• If comorbid anxiety, fluvoxamine or sertraline are possible
has Food and Drug Administration (FDA) approval for the
alternatives.
treatment of depression in children and adolescents. The
Spontaneous remission in community diagnosed adoles
other SSRI medications do not as of yet have FDA approval
cent depression is 50% within 2 months. However, those not
for depression in children. These last two have fewer
remitting in this time period have a high risk of chronicity.
interactions with other medications.
Refer to a specialist.
• Bupropion (Wellbutrin): this medication can be helpful for
depression and attention deficit hyperactivity disorder but
Medication Dosing and is less effective for comorbid anxiety. It does not seem to
Follow-up for Anxiety and Depression cause weight gain.
• Tricyclics (imipramine, desipramine, nortriptyline): these
General Dosing Suggestions medications are still used if the SSRIs and bupropion
Start with one-fourth or half of the adult dose and wait at least 1 do not work. As the tricyclics are more likely to cause
week to increase dosages. For adolescents, the maximum dose rhythm changes in children, baseline and periodic electro
can be similar to adults, while the dose is less than the adult cardiograms (ECGs) should be considered. Side effects
dose for children may include dry mouth, dry eyes (problem if contact
• Anxiety: children who are anxious are sensitive to physical wearer) dizziness, and ECG, pulse, and rhythm changes.
sensations. Provide support, reassurance, and monitor Clomipramine (anafranil) is quite effective in individuals
frequently. Generalized anxiety disorder may respond with OCD. 105
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Algorithm 4
Major depression (nonpsychotic)
SSRI, selective serotonin reuptake inhibitor; BUP, bupropion; SNRIs, serotonin-norepinephrine reuptake inhibitors; MRT, mirtazapine; TCAs, tricyclic antidepressants;
NEF, nefazodone; MAOI, monoamine oxidase inhibitors; ECT, electroconvulsive therapy.
Table 1: Antidepressants commonly used in treatment of major Prevalence of anxiety disorders in children aged 5–17 is
depressive disorders 6.4%. The debilitating nature of these disorders is routinely
underestimated and the need for help may not be realized
Class Drugs
until serious impairment in social and academic functioning
Selective serotonin reuptake Citalopram, escitalopram, has occurred. Untreated anxiety disorders in children and
inhibitors fluoxetine, fluvoxamine, adolescents are associated with higher rates of comorbid
paroxetine, sertraline, vilazodone
depression and substance abuse (Algorithm 5).
Serotonin-norepinephrine Desvenlafaxine, duloxetine,
reuptake inhibitors venlafaxine
SUICIDE
Monoamine oxidase Isocarboxazid, phenelzine,
inhibitors selegiline, tranylcypromine Death due to suicide is more common in boys than girls.
Most acts of suicide are preceded by an expression of death
Tricyclic antidepressants Amitriptyline, desipramine,
doxepin, imipramine, nortriptyline wish either to friends or to a trustworthy adult in the previous
24 hours. May be made impulsively without much forethought
106 Miscellaneous Bupropion, mirtazapine or can be premeditated. Emotional development is at its peak
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Algorithm 5
Major depressive disorder
CBT, cognitive behavior therapy; IPT, interpersonal therapy; FT, family therapy; SSRI, selective serotonin reuptake inhibitors.
during middle adolescence, the control of emotions is still How:

incomplete due to evolving and immature prefrontal lobes. • Was the plot to suicide conceived
• How were the steps planned
Predisposing Factors • Any previous attempts?
• Adolescents with poor coping skills and problem solving When and where:
skills. Low levels of serotonin and its major metabolite • Was the suicidal action planned
5-hydroxyindoleacetic acid (5-HIAA) • Where was the place chosen
• Chaotic childhood with problems during child rearing, • Where was the place where the suicidal note if any was
domestic violence, abusive adults planned to be placed. Significant life events are chosen for
• High achiever adolescent may resort to suicide when suicide.
humiliated for perceived failure. Adolescents with other Why:
coexisting mental illnesses may resort to suicide as they are • Psychological details are probed
vulnerable to stressors much more than normal population. • Feelings of worthlessness, helplessness, emotional pain,
humiliation, emptiness, rejection, abandonment, fear of
Approach to an Adolescent with Suicide Behavior death, fear of mental breakdown, self hatred, guilt.
Adolescents should be posed directly about the existence Adolescents with multiple attempts usually take care to
of suicide ideation. They may not have confided in parents, execute the next in a manner which is difficult to intervene.
hence parental history may not be reliable. Questions should Single attempters usually equip themselves with coping skills
be developmentally appropriate as it helps in devising with time.
management strategies in form of cognitive behavior therapy Suicide prevention can be primary, secondary, or tertiary:
and interpersonal therapy. All suicide ideation should be taken • Primary suicide prevention aims to reduce the number of
seriously and evaluated thoroughly and repeatedly. new cases of suicide in the general population
What, when, where, how, and why aspects of suicidal • Secondary suicide prevention aims to decrease the
behavior should be explored and evaluated. likelihood of a suicide attempt in high risk patients
What: • Tertiary suicide prevention occurs in response to
• Was the action completed suicides and attempts to diminish suicide
• Was the thoughts about life after death contagion (clusters of suicides in a geographical area that
• The adolescent expect to happen on completion of suicide occur predominantly among teenagers and young adults)
• Any alternative plans thought to accomplish the objective. and copy cat suicides. 107
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Risk Factors for Suicide serotonin metabolite) and HPA axis dysregulation as indicated
• Biological risk factors for suicide include: by dexamethasone nonsuppression.
{{ Low cerebrospinal fluid 5-HIAA levels
{{ Hypothalamic-pituitary-adrenal axis dysregulation What are the Most Effective

{{ Low blood cholesterol levels Secondary Suicide Prevention Strategies?
{{ Medical or neurological illnesses (such as multiple
In a recent systematic review of suicide prevention strategies,
sclerosis, stroke, Huntington disease and epilepsy) Mann et al., found evidence of effectiveness in five secondary
{{ Cigarette smoking
suicide prevention methods:
• Psychological risk factors include: 1. Pharmacological interventions
{{ Acceptability of suicide
2. Psychological interventions
{{ A childhood history of physical or sexual abuse
3. Follow-up care
{{ Discouraged help-seeking behavior
4. Reduced access to lethal means
{{ Aggressive/impulsive traits
5. Responsible media reporting of suicide (Algorithms 6
{{ Pessimism
and 7).
{{ Hopelessness
{{ Low self-esteem
{{ Poor access to psychiatric treatment

Clinical Pearls
{{ Relationship problems
• Counselors and clinicians should actively use specialize tools
{{ Financial troubles
such as patient health questionnaire
{{ A family or personal history of suicide
• An algorithm of nonpharmacological intervention makes it
{{ Major depression
easier to manage depression
{{ Substance use.
• Pharmacological management, when necessary, should follow
correct doses as per body weight and side effects have to be
Rating Scales for Suicide Behavior and monitored
Related Mental Health Conditions • Treatment of adolescent depression/suicidal tendency is a
The most widely used scales for rating suicidal behaviors include: long-term process with regular monitoring and follow up as
• The Scale for Suicidal Ideation has good reported reliability small social and psychological trigger factors can produce
and validity and measures three major factors: (i) active sudden relapse.
suicidal desire, (ii) specific plans for suicide, and (iii)
passive suicidal desire
• The Suicide Intent Scale measures the degree of suicide Algorithm 6
intent Treatment of bipolar I depression
• The Risk-Rescue Rating Scale is an interviewer-adminis
tered measure that assesses the lethality and intent of a
suicide attempt
• The Columbia-Suicide Severity Rating Scale assesses
severity of suicidal ideation and tracks suicidal events
• The Beck Hopelessness Scale is a self-report inventory
designed to measure three major aspects of hopelessness:
feelings about the future, loss of motivation, and expectations
• The Hamilton Depression Rating Scale is a clinician-
applied scale rating dimensions of depression
• The Beck Depression Inventory is a multiple choice self-
report inventory that measures the severity of depression.
The Search for Biological Markers for Suicide

Many researchers have been trying to find biological markers
related to suicidal behavior that could improve secondary
suicide prevention. Several biological features related to
failures in neurotransmitter and neuroendocrine systems,
such as the serotonergic, noradrenergic, dopaminergic, and
hypothalamic-pituitary-adrenocortical (HPA) systems, have
been proposed, e.g., considerable evidence accrued using
various research approaches suggests a potentially causal
association between suicidal behavior and the serotonin
neurotransmission system.
108 To date, the most promising biological predictors of
suicidal behavior are low cerebrospinal fluid 5-HIAA (the main
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Algorithm 7 SUGGESTED READINGs

Treatment of bipolar II depression
1. Andersen UA, Andersen M, Rosholm JU, Gram LF. Contacts to the health care
system prior to suicide: A comprehensive analysis using registers for general and
psychiatric hospital admissions, contacts to general practitioners and practicing
specialists and drug prescriptions. Acta Psychiatr Scand. 2000;102.
2. Beck AT, Kovacs M, Weissman A. Assessment of suicidal intention: the Scale for
Suicide Ideation. J Consult Clin Psychol. 1979;47(2):343-52.
3. Jacobs DG, Baldessarini RJ, Conwell Y, Fawcett JA, Horton L, Meltzer H, et al.
(2003). Practice Guideline for the Assessment and Treatment of Patients with
Suicidal Behaviors. [online] Available from: psychiatryonline.org/pb/assets/
raw/sitewide/practice_guidelines/guidelines/suicide.pdf. [Accessed November,
2015].
4. Johansson L, Lindqvist P, Eriksson A. Teenage suicide cluster formation and
contagion: implications for primary care. BMC Fam Pract. 2006;7:32.
5. Lönnqvist JK, Henriksson MM, Isometsä ET, Marttunen MJ, Heikkinen ME, Aro
HM, et al. Mental disorders and suicide prevention. Psychiatry Clin Neurosci.
1995;49(Suppl 1):S111-6.
6. Mann JJ, Apter A, Bertolote J, Beautrais A, Currier D, Haas A, et al. Suicide
prevention strategies: a systematic review. JAMA. 2005;294(16):2064-74.
7. Murphy GE. The prediction of suicide: why is it so difficult? Am J Psychother.
1984;38(3):341-9.
8. Oquendo MA, Galfalvy H, Russo S, Ellis SP, Grunebaum MF, Burke A, et al.
Prospective study of clinical predictors of suicidal acts after a major depressive
episode in patients with major depressive disorder or bipolar disorder. Am J
Psychiatry. 2004;161(8):1433-41.
9. Pignone MP, Gaynes BN, Rushton JL, Burchell CM, Orleans CT, Mulrow CD, et
al. Screening for depression in adults: a summary of the evidence for the US
Preventive Services Task Force. Ann Intern Med. 2002;136(10):765-76.
10. Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification
Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in
Key points the FDA’s pediatric suicidal risk analysis of antidepressants. Am J Psychiatry.
2007;164(7):1035-43.
))
Adolescent depression is a common and serious problem 11. Sher L, Oquendo MA, Mann JJ. Risk of suicide in mood disorders. Clin Neurosci
increasing the risk of suicide Res. 2001;1:337-44.
))
Early detection and treatment is key to effective management 12. Sher L. Preventing suicide. QJM. 2004;9(10):677-80.
))
Behavioral changes at home, amongst peers and at school 13. Van Heeringen K. The neurobiology of suicide and suicidality. Can J Psychiatry.
should be noticed and acted upon 2003;48(5):292-300.
))
Both nonpharmacological and pharmacological methods 14. World Health Organization. (2003). World Health Report 2003: Shaping the
Future. [online] Available from: www.who.int/whr/2003/en/whr03_en.pdf.
have to be used in stepwise integrated approach involving
[Accessed November, 2015].
family members and school staff
))
Suicidal ideation needs to be identified early by psychological
profiling and the necessary corrective actions have to be
initiated.
109
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Chapter 25
Teen Aggression:
Steps in Management
Kiran SK Vaswani
INTRODUCTION Box 1: Three pathways/clusters

Aggression aimed at harming others and/or self, with many • “Authority conflict” (avoidance/conflict): stubborn-disobedience-
negative outcomes, like violence, delinquency, substance avoidance (truancy/running away from home)
use, scholastic problems, is common in adolescence. It may • “Covert” (property loss): sneaky acts—stealing, vandalism
be the first sign/manifestation of childhood psychiatric progressing to fraud and serious theft
disorders or organic diseases. Therefore, it is imperative for • “Overt” (physical harm): starts with annoying, bullying, then
the primary caregiver to recognize aggression and intervene physical fighting to forced sex
early. Approximately 3–7% of school children have signs of
aggression. Aggression is “any behavior intended to harm another
The objective of this chapter is to understand the following person who is motivated to avoid the harm”. Clusters of
aspects of teen aggression: aggression, a disruptive behavior, are as shown in box 1.
• Definition, subtypes, and related term anger Aggression by definition is intentional, thus an autistic
• Normative development teen’s aggression is not primary disruptive behavior.
• Risk and protective factors
• Related comorbidities
Proactive and Reactive/Affective Aggression
• Prevention and parent support
• Assessment and intervention: algorithm. Aggression can be proactive or reactive (affective), features of
these are summarized in table 1.
Definition, Subtypes, Disruptive Behavior Disorders

and Related Term Anger
Disruptive behavior disorders (DBD) are characterized by
Anger is defined as a person’s response to a threat actual or predominance of oppositional, defiant, or antisocial behaviors,
perceived, against an individual or group (Lazarus, 1991). range from the milder oppositional defiant disorder (ODD) to
It may be adaptive or when uncontrolled, associated with the more serious conduct disorder (CD). Features of DRD are
aggression. given in table 2.
Table 1: Features of proactive and reactive/affective aggression

Features Proactive (premeditated) aggression Reactive/affective (impulsive) aggression
Purpose • Obtain specific rewards/goals • Learned behavioral response to abuse; perceive threat/
• Establish social dominance provocation in neutral/friendly situations
Relation to anger • Calculated/cold-blooded • Emotionally driven/hot-blooded
• No significant display of anger • Visible display of anger
Peer relations • Leadership skills and a sense of humor • Peer rejection/victimization
Clinical implications and • Externalizing behavior/subsequent criminal • Common psychotic symptoms/need lithium or
prognosis behavior uncommon neuroleptics
Intervention implications • Systematic interventions • Cognitive behavioral therapy and medications
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Chapter 25: Teen Aggression: Steps in Management
Table 2: Diagnostic features of disruptive behavior disorders

Features Oppositional defiant disorder Conduct disorder
American Psychiatric Association’s Ongoing symptoms of “negativistic, defiant, “A repetitive and persistent pattern of behavior
Diagnostic and Statistical Manual of disobedient, and hostile behaviors toward in which the basic rights of others or major age
Mental Disorders Fourth Edition authority figures” appropriate social rules are violated”
Onset Mainly <8 years/early adolescence Child onset: <10 years
Adolescent onset: >10 years, rarely >16 years
Symptoms • Trouble with authority • Significant aggression towards others
• Breaks school rules • Animal cruelty
• Angry/argumentative • Destruction of property/theft/setting fires
• Noncompliant • Law breaking/serious violation of rules
• Blame others for their errors • Substance abuse
• Have not broken major societal rules • Poor school performance
• Have broken major societal rules; suspended from
school or have police involvement
Duration of symptoms for diagnosis For at least 6 months More than three incidents within the last 12 months,
and at least one in past 6 months
Intermittent Explosive Disorder Box 2: Risk factors

This manifests in late adolescence as discrete episodes of • Age at onset of aggression: important risk factor for conduct
aggression, unrelated to stressors, remits spontaneously with disorder (CD). Children displaying aggression are at the highest
no impulsivity; unexplained by personality disorders/attention risk for conduct related problems as adults
deficit hyperactivity disorder (ADHD)/substance intoxication, • Psychological maltreatment: neglect (infancy), humiliation,
is probably an epileptoid state with aura, postictal-like changes rejection, witnessing intimate partner violence
in sensorium, responding to anticonvulsants, β-blockers, and • Physically and sexually abused: likely to become seriously
calcium channel inhibitors. delinquent and violent juveniles
• Physical discipline by parents, models aggression as coping tool
• Media violence and internet addiction, extensively studied,
Normative Development
significant role in shaping the developing brain/“wired” for
Aggression, a normal and highly frequent behavior in kids/ aggression
teens, facilitates competence in social assertiveness, games, • Vicious cycle exists between substance use and violence
and developing autonomy. It is mostly directed towards peers, • Associating with delinquent peers and gangs; peer group
and very little towards adult caregivers. rejection and victimization; females tend to be with the gang for
a refuge and belong to more troubled families
• Easy access to weapons
Risk and Protective Factors • Related psychiatric disorders: 65–95% of boys with CD have
attention deficit hyperactivity disorder:
Insight of these factors helps in prevention of and intervention {{ Girls have depression with CD:
in aggression. Risk factors are depicted in figure 1 and box 2.
–– Look for comorbid conditions, especially suicidal attempts,
Protective factors contributing to a significant reduction in in girls with antisocial behavior as they are at a great risk
antisocial behavior are listed in box 3.
–– Other associations: anxiety, autism spectrum disorder,
intellectual disability, language deficits, bipolar disorder
Prevention of aggression • Social cognitive risk factor: aggressive children misread inter
personal cues and interpret ambiguous/prosocial communi
Parent support and other factors that contribute to prevention cation as hostile and react aggressively
of aggression are listed in box 4.
Box 3: Protective factors: contribute to significant reduction

in antisocial behavior
• A good relationship with at least one parent
• Consistent parental discipline
• A caring relationship with competent adult
• School and family connectedness
• Prosocial peers
• Normal/above: normal intelligence
• Good work habits, extracurricular activities 111
Fig. 1: Aggression risk factors
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Box 4: Prevention and parent support Box 5: Assessment

• Kids/teens with several risk factors demonstrating intense Parent interview
anger/loss of temper, extreme irritability/impulsiveness, or easy • Child’s temperament as an infant and young child
frustration need to be evaluated/intervened • Development history and assessment, including language
• Studies show aggression can be decreased/prevented by: • Details of disturbing behavior-onset, psychosocial stressors
{{ Violence leads to violence, therefore, reduce exposure to (death/separation/crisis/loss of pet) at the onset
violence at home/community/media • Frequency, intensity, duration of an episode, triggers/trends,
{{ Prevention of child abuse. Victim identification, care and degree of disruption
support programs • Parenting styles, expectations, strategies for dealing with stress
{{ Reducing availability and harmful use of alcohol
• Media exposure
{{ Reducing access to lethal means: weapons/pesticides
• Aggressive neighborhood
{{ Promoting gender equality, sex education, and parenting
Adolescent interview
program for teens
• Opportunity to observe:
{{ Developing life skills in kids/teens
{{ Evidence of anxiety, hyperactivity
{{ Changing cultural/social environment supporting violence
{{ Motivation for change
{{ Promoting Alternative Thinking Strategies (PATHS): 3-steps to
• HEEADDSS assessment:
calm down:
{{ Home: family dynamics, abuse, and neglect
–– Stop
{{ Education: peer activities, acceptance, bullying
–– Take a deep breath
{{ Activities: hobbies, media use, leisure, sleep
–– Identify problem and your feelings
{{ Drugs: substance abuse
{{ Depression/suicide
{{ Sexual health: sexuality, sexual activity/abuse
Clinical Pearls {{ Safety: possession of arms, vehicle driving
Teacher interview
• Teens with childhood onset of aggression are more likely to • Behavior details
manifest delinquent activity during adolescence, persisting • Academic performance
into adulthood compared to those with adolescent onset
Peer interview
• Aggression in a child at any age needs to be evaluated/
• Behavior details
intervened and not dismissed as “child will grow out of it”
• Academic performance
• Physically/sexually abused children and adolescents are more • Bullying, participation in peer activities
likely to become seriously delinquent and violent juveniles
Standardized Rating Scales: completed by teens, parents,
• Child neglect in infancy is associated with aggressive behavior teachers
in childhood • Help in assessing: depression, anxiety, aggression, withdrawal,
• Media and aggression: children watching violent shows are inattention, hyperactivity, delinquent behavior, suicide ideation
“more likely to strike out at playmates, argue, and disobey • Based on others’ opinions
authority and less willing to wait for things” Gerbner • Used in combination with other data
• Look for comorbid conditions, especially suicide ideation and • The Youth Self Report, Child Behavior Checklist, Direct and
attempts in girls with antisocial behavior Indirect Aggression Scale: commonly used
• Inquire and counsel for possible abuse Eliminate other diagnoses
• Teens with symptoms of both attention deficit hyperactivity • Mood disorders: major depression, bipolar disorder
and conduct disorders have poor outcomes. • Anxiety disorders: post-traumatic stress disorder, generalized
anxiety disorder, panic attack
• Psychotic disorders: with active delusions or hallucinations
Assessment • Substance use: active phase or withdrawal
• Developmental disorders: autism, mental retardation
Evaluate: • Temporal lobe epilepsy, endocrinal disorders, intracranial space
• Development related: short-lived, without significant/ occupying lesions, megaloblastic anemia
persistent dysfunction
• Context of action: better prognosis when impulsive/on
peers’ encouragement than when planned and individually
Intervention
executed
• Behavior details • Effective strategies: group intervention—time and cost-
• Comorbid conditions effective
• Eliminate other diagnoses • Take necessary precautions to keep “self” safe
• Protective and risk factors • Targeting teens: cognitive behavioral therapy to change
• Perception of the issue and motivation for change. Box 5 social cognitive distortions involves practising alternative
112 briefly enumerates the process of assessment. ways of dealing with conflicts
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Chapter 25: Teen Aggression: Steps in Management
• Limitations: lack of motivation, immature cognition, and • Develop critical viewing skills to make kids/teens less
language deficits susceptible to negative messages of media
• Problem-solving skills training by role-playing, practising, • Monitor television viewing habits
and homework assignments • Role-model: limit time and content
• Glick’s aggression replacement therapy: • Discuss media contents and deconstruct:
{{ Learning social skills through structured learning {{ Does it resemble any person/situation in real life?
training has 4 steps: {{ Was there a problem/conflict and how was it solved?
1. Shows behavior (saying thank you/sorry/asking for Can we adopt these methods? Given a choice what
permission) would have been your strategy?
2. Try the skill by role-playing {{ What are victim’s feelings? Was it possible to avoid
3. Practise hurting/harming them? How?
4. Use in actual situations Risk factors and comorbidities: identify and treat appropriately:
{{ Anger control training: identify triggers, cues, self-talk,
• Medication: as an adjunct to behavioral therapy
use reducers (deep-breathing), and self-evaluation • Mainly for comorbid conditions: depression, anxiety,
{{ Moral education: justice, personal rights/responsi
selective serotonin reuptake inhibitors, fluoxetine
bilities • No specific antiaggressive agents, mood stabilizers, anti
• Parent involvement (parent management training): epileptic drugs—valproate, or atypical antipsychotics used
parents trained to observe, teach prosocial behavior by
• Risperidone in severe aggression affecting function
role-playing, practising, and feedback
• Selective serotonin reuptake inhibitors useful in irritable
• Adolescent transition program: parenting skills, improved
depressed/anxious.
family relationships and communication, limit-setting,
and problem-solving
• Family therapy to improve communication, reduce Clinical Pearls
blaming
• Behavioral interventions are the mainstay of treatment
Tips for parents (and teachers) to deal with an aggressive
adolescent are listed in table 3. • Effective strategies include all stakeholders in management:
the teen, parents, school, peers, and the community
Teens and parents inclusive interventions (most effective):
• Schools: prosocial peers • Medication has a limited role in management of aggression.
• Life skills programs
• Utilize mental health professionals to train teachers, Prompt referral to the expert:
counsel teens and parents involve in school and community • Escalating behavior, from vandalism to harming
activities • Multiple domains of involvement: mood, substance,
Media literacy and deconstruction exercises: psychotic, suicide ideation/attempts.
Table 3: Tips for dealing with an aggressive adolescent for parents and teachers (gatekeepers)
No child is always bad Attend/praise positive behaviors
Respect Let the adolescent know that you care and respect him and do not like the inappropriate behaviors and (not
the individual)
Do not ignore Inappropriate aggression
Be positive Remain calm and model positive problem-solving
Behavior contracts Target behaviors: stated as positive behaviors dos and not don’ts, e.g., if he often argues, target behavior:
discuss things calmly
Effective commands One at a time, avoid question commands/vague/chained: multiple requests/much explanation
House rules Clearly stated
Communication Increase ongoing communication and cohesion
Problem-solving Model effective problem solving: identify problem, generate alternative responses, evaluate these, and plan
implementing
Relaxation Quick, effective techniques (deep breathing/counting to 10)
Coping statements Develop a list
Perspective talking Understanding others’ thinking/feelings
Negotiating Less likely to use defiance/aggression to meet needs
Autonomy Value and encourage positive ideas/independent-thinking/decision-making
Monitoring Caring/not violating privacy 113
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Algorithm 1
Steps in management of teens aggression
ODD, oppositional defiant disorder; CD, conduct disorder; CBT, cognitive behavioral therapy; PTSD, post-traumatic stress disorder.
3. National Association of School Psychologists. [online] Available from: http://www.

Key points nasponline.org/resources/principals/nasp_aggression.pdf.
))
Behavioral and mental health concerns are common in 4. Oppositional and aggressive behaviors. [online] Available from: http://www.
brightfutures.org/mentalhealth/pdf/bridges/oppositional.pdf.
pediatrician’s office practice, and aggression is both a
challenging and significant concern 5. Rappaport N, Thomas C. Recent research findings on aggressive and violent
behavior in youth: implications for clinical assessment and intervention.
))
Aggression may represent a normal developmental stage J Adolesc Health. 2004;35(4):260-77.
or indicate a serious mental health disorder, and has grave
6. Sadock BJ, Sadock VA. Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral
implications for both the individual and his family and also Sciences/clinical Psychiatry, 9th edition. Philadelphia, PA, USA: Lippincott
community at large Williams & Wilkins; 2003.
))
As clinicians, we need to identify those with multiple risk 7. Sexson SB. Child and Adolescent Psychiatry: Blackwell’s Neurology and
factors, and suggest interventions before the behavior Psychiatry Access Series, Second Edition. Wiley. 2005
becomes chronic, severe, and frequent 8. Sharma MK, Marimuthu P. Prevalence and psychosocial factors of aggression
))
Identify comorbidities and deal with them among youth. Indian J Psychol Med. 2014;36(1):48-53.
))
Consider medical causes of aggression 9. Working with aggressive adolescents. (1998). [online] Available from: http://
www.practicenotes.org/vol3_no2/working_with_adolescents.htm. [Accessed
))
Effective strategies of management involve teens, parents,
March, 2016].
and schools.
10. World Health Organization (WHO). (2010). Violence prevention the evidence:
Series of briefings on violence prevention. [online] Available from www.who.
int/violence_injury_prevention/violence/4th_milestones_meeting/evidence_
SUGGESTED READINGS briefings_all.pdf. [Accessed November, 2015].
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental 11. Yadav A. MEDIA VIOLENCE and Aggression among Adolescents: Media Literacy
Disorders Fourth Edition Text Revision (DSM-IV-TR). Washington, DC, USA: as an Intervention. [online] Available from ciet.nic.in/MediaClub/pdf/Media_
American Psychiatric Association; 2000. pp. 645-50. Violence_Media_Literacy.pdf. [Accessed November, 2015].
2. National Association of School Psychologists. [online] Available from: http://www. 12. Zahrt DM, Melzer-Lange MD. Aggressive behavior in children and adolescents.
nasponline.org/publications/booksproducts/nas-cbiii-05-1001-009-r02.pdf Pediatr Rev. 2011;32(8):325-32.
114
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Chapter 26
Immunization in Childhood
Monjori Mitra
INTRODUCTION immunity and neutralizing antibodies (e.g., live, attenuated

virus vaccines) usually can induce prolonged immunity, even
Along with the routine vaccines in national immunization if antibody titers decline over time. Subsequent exposure to
program, Indian Academy of Pediatrics recommends routine such viruses usually results in a rapid anamnestic antibody
vaccination to prevent other vaccine-preventable diseases that response without viremia.
occur in infants, children, and adolescents. Approximately, 90–95% of recipients of a single dose
There has been a constant surveillance of the various of certain live vaccines administered by injection at the
vaccine-preventable diseases and the outcome has prompted recommended age (i.e., measles, rubella, and yellow fever
the various advisory bodies to reschedule the vaccination vaccines) develop protective antibodies, generally within 14
program based on the reports. days of the dose. For varicella and mumps vaccines, 80–85%
The schedule recommended is based on the best of vaccines are protected after a single dose. However, because
seroprotective outcome of the vaccines which are being a limited proportion (5–15%) of measles, mumps, and rubella
continuously studied in various environmental settings. The (MMR) or varicella vaccines fails to respond to first dose, a
vaccination providers should try to influence the community second dose is recommended to provide another opportunity
or the individual to follow the same to get the best protective to develop immunity. Of those who do not respond to the
efficacy for individual and community. first dose of MMR or varicella vaccine, 97–99% responds to a
Optimal response to a vaccine depends on multiple factors, second dose.
including the type of vaccine, age of the recipient, and immune
status of the recipient. Recommendations for the age at which
vaccines are administered are influenced by age-specific
COMBINATION VACCINES AND DRUG
risks for disease, age-specific risks for complications, age- CONTROLLER GENERAL OF INDIA LICENSURE
specific responses to vaccination, and potential interference Only combination vaccines licensed by Drug Controller
with the immune response by passively transferred maternal General of India (DCGI) should be used. Vaccination providers
antibodies. Vaccines are recommended for members of the should not combine separate vaccines into the same syringe to
youngest age group at risk for experiencing the disease for administer together unless mixing is indicated for the patient’s
which efficacy and safety have been demonstrated. age and is explicitly specified on the DCGI-approved product
Certain products, including inactivated vaccines, toxoids, label inserts. Only two combination vaccines [diphtheria,
recombinant subunit vaccines, polysaccharide conjugate tetanus, pertussis, polio, and Haemophilus influenzae
vaccines, and live vaccines, require two doses or more to type b (DTaP-IPV/Hib) vaccine] contain separate antigen
elicit an adequate antibody response. Tetanus and diphtheria components for which DCGI approves mixing by the user.
toxoids require booster doses to maintain protective antibody The safety, immunogenicity, and effectiveness of unlicensed
concentrations. Unconjugated polysaccharide vaccines do combinations are unknown and should not be used.
not induce T-cell memory, and additional doses (although
they elicit the same or a lower antibody concentration)
might increase the level of protection. Conjugation with a
INTERCHANGEABILITY OF FORMULATIONS
protein carrier improves the effectiveness of polysaccharide Regulatory body generally licenses a combination vaccine
vaccines by inducing T-lymphocyte-dependent immunologic based on studies demonstrating that the product’s immuno
function. Many vaccines that stimulate both cell-mediated genicity (or efficacy) and safety are comparable or equivalent
ch-26.indd 115 11/19/2016 12:47:29 PM

to monovalent or combination products licensed previously. • Oral polio vaccine: at 6 months with hepatitis B and at
The combination vaccine may be used interchangeably with 9 months with measles
monovalent formulations and other combination products {{ Additional doses of OPV on all national immunization
with similar component antigens produced by the same days and subnational immunization days
manufacturer to continue the vaccination series. For example, • Booster dose: 18 months with first booster
DTaP, DTaP/Hib, and future DTaP vaccines that contain similar {{ Inactivated polio vaccine: two instead of three doses
acellular pertussis antigens from the same manufacturer may can also be used if primary series started at 8 weeks
be used interchangeably, if licensed and indicated for the {{ Inactivated polio vaccine catch-up schedule: two doses
patient’s age. at 2 months apart followed by a booster after 6 months.

Ideally, the doses of vaccine in a series should be from the
same manufacturer; however, if this is not possible or if the Catch-up Vaccination
manufacturer of doses given previously is unknown, providers • Inactivated polio vaccine catch-up schedule: two doses
should administer the vaccines that are available. at 2 months apart followed by a booster after 6 months of
previous dose.
VACCINATION ALGORITHM
Diphtheria, Tetanus Toxoids,
Bacillus Calmette-Guérin Vaccine and Pertussis Vaccine
• This should be given at birth before discharge from the Routine Vaccination
hospital or at first contact
• Catch-up may be given up to 5 years. • Minimum age: 6 weeks
• The first booster (fourth dose) may be administered as
early as age 12 months, provided at least 6 months have
Hepatitis B Vaccine elapsed since the third dose
• Minimum age of administration is at birth. Administer • Diphtheria, tetanus, and acellular pertussis (DTaP)
monovalent hepatitis B vaccine to all newborns before vaccine/combinations should preferably be avoided for
hospital discharge. Hepatitis B vaccine may also be given the primary series
in any of the following schedules: • Diphtheria, tetanus, and acellular pertussis may be preferred
{{ At birth, 1, and 6 months to Diphtheria, tetanus, and whole-cell pertussis (DTwP) in
{{ At birth, 6, and 14 weeks children with history of severe adverse effects after previous
{{ At 6, 10, and 14 weeks dose/s of DTwP or children with neurologic disorders
{{ At birth, 6, 10, and 14 weeks, etc. • First and second boosters may also be of DTwP. However,
• Monovalent hepatitis B vaccine should be used for doses considering a higher reactogenicity, DTaP can be consi
administered before age of 6 weeks dered for the boosters
• Administration of a total of four doses of hepatitis B vaccine • If any “acellular pertussis” containing vaccine is used, it
is permissible when a combination vaccine containing must at least have three or more components in the product
hepatitis B is administered after the birth dose • No need of repeating/giving additional doses of whole-
• Infants who did not receive a birth dose should receive cell pertussis vaccine to a child who has earlier completed
three doses of a hepatitis B containing vaccine starting as their primary schedule with acellular pertussis vaccine-
soon as feasible containing products.
• The ideal minimum interval between first and second dose
is 4 weeks, and between second and third dose is 8 weeks Catch-up Vaccination
• Ideally, the final (third or fourth) dose in the hepatitis B • Catch-up schedule: the second childhood booster is not
vaccine series should be administered not earlier than the required if the last dose has been given beyond the age of
age of 24 weeks and at least 16 weeks after the first dose. 4 years
• Catch-up below 7 years: DTwP/DTaP at 0, 1, and 6 months
Catch-up Vaccination • Catch-up above 7 years: Tdap, Td, and Td at 0, 1, and
• Administer the three-dose series to those not previously 6 months, respectively.
vaccinated
• In catch-up vaccination, use 0, 1, and 6 months schedule. Haemophilus influenzae Type B Conjugate Vaccine
Minimum age: 6 weeks as combination with DTwP/DTaP.
Poliovirus Vaccines: Oral Polio Vaccine/ Primary series includes Hib conjugate vaccine at ages 6, 10,
Inactivated Polio Vaccine and 14 weeks with a booster at age 12 through 18 months.
• Birth dose: oral polio vaccine (OPV) before discharge from
hospital Catch-up
{{ Inactivated polio vaccine (IPV): 6, 10, and 14 weeks. • In 6–12 months: two doses, 1 month apart and one booster
Oral polio vaccine in place of IPV. If IPV is unaffordable • In 12–15 months: one primary and one booster
116 or unavailable • Above 15 months: single dose.
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Chapter 26: Immunization in Childhood
If the first dose was administered at age 7 through (including sickle cell disease), HIV infection, cochlear
11 months, administer the second dose at least 4 weeks later implant, or cerebrospinal fluid leak
and a final dose at age 12–18 months at least 8 weeks after the • An additional dose of PPSV should be administered after
second dose. 5 years to children with anatomic/functional asplenia or an
immunocompromising condition
Pneumococcal Vaccines • Pneumococcal polysaccharide vaccine should never be
used alone for prevention of pneumococcal diseases
Routine Vaccination amongst high risk individuals
• Minimum age: 6 weeks • Children with following medical conditions for which
• Both PCV10 and PCV13 are licensed for children from PPSV23 and PCV13 are indicated in the age group 24–
6 weeks to 5 years of age (although the exact labeling 71 months:
details may differ by country). Additionally, PCV13 is {{ Immunocompetent children with chronic heart
licensed for the prevention of pneumococcal diseases in disease (particularly cyanotic congenital heart disease
adults >50 years of age and cardiac failure); chronic lung disease (including
• Primary schedule (for both PCV10 and PCV13): three asthma if treated with high dose oral corticosteroid
primary doses at 6, 10, and 14 weeks with a booster at age therapy); diabetes mellitus; cerebrospinal fluid leaks;
12–15 months. or cochlear implant
{{ Children with anatomic or functional asplenia
Catch-up Vaccination (including sickle cell disease and other hemoglobino
• Administer one dose of PCV13 or PCV10 to all healthy pathies, congenital or acquired asplenia, or splenic
children aged 24–59 months who are not completely dysfunction)
{{ Children with immunocompromising conditions:
vaccinated for their age
• For PCV13, catch-up in 6–12 months—two doses 4 weeks HIV infection, chronic renal failure and nephrotic
apart and one booster; 12–23 months—two doses 8 weeks syndrome, diseases associated with treatment with
apart; 24 months and above—single dose immunosuppressive drugs or radiation therapy,
• For PCV10, catch-up in 6–12 months—two doses 4 weeks including malignant neoplasms, leukemias, lympho
apart and one booster; 12 months to 5 years—two doses mas, and Hodgkin disease; or solid organ trans
8 weeks apart plantation, congenital immunodeficiency.
• Vaccination of persons with high risk conditions:
{{ Pneumococcal vaccines and pneumococcal poly Rotavirus Vaccines
saccharide vaccine (PPSV) both are used in certain • Minimum age: 6 weeks for both Rotavirus (RV)-1 (Rotarix)
high risk group of children. and RV-5 (RotaTeq)
{{ For children aged 24–71 months with certain under • Only two doses of RV1 are recommended at present and
lying medical conditions, administer one dose of PCV13 three doses for RV5
if three doses of PCV were received previously, or • The maximum age for the first dose in the series is 14 weeks,
administer two doses of PCV13 at least 8 weeks apart if 6 days; and 8 months, 0 days for the final dose in the series
fewer than three doses of PCV were received previously • Vaccination should not be initiated for infants aged
{{ A single dose of PCV13 may be administered to
15 weeks, 0 days, or older and should not cross 32 weeks.
previously unvaccinated children aged 6–18 years who
have anatomic or functional asplenia (including sickle Catch-up Vaccination
cell disease), HIV infection or an immunocompro
• The maximum age for the first dose in the series is 14 weeks,
mising condition, cochlear implant, or cerebrospinal
6 days
fluid leak
• Vaccination should not be initiated for infants aged
{{ Administer PPSV23 at least 8 weeks after the last dose
15 weeks, 0 days or older
of PCV to children aged 2 years or older with certain
• The maximum age for the final dose in the series is
underlying medical conditions.
8 months, 0 days.
Pneumococcal Polysaccharide Measles, Mumps, and Rubella Vaccine

Vaccine (PPSV23)
• Minimum age: 2 years
Routine Vaccination
• Not recommended for routine use in healthy individuals. • Minimum age: 9 months or 270 completed days.
Recommended only for the vaccination of persons with • Administer the first dose of MMR vaccine at age 9–12
certain high-risk conditions months, and the second dose at age 15–18 months.
• Administer PPSV at least 8 weeks after the last dose of PCV • The second dose must follow in second year of life. However,
to children aged 2 years or older with certain underlying it can be given at anytime 4–8 weeks after the first dose
medical conditions like anatomic or functional asplenia • No need to give stand alone measles vaccine 117
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Catch-up Vaccination • Live attenuated H2-strain Hepatitis A vaccine: single dose

• Ensure that all school aged children and adolescents have starting at 12 months and through 23 months of age.
had two doses of MMR vaccine; the minimum interval
between the two doses is 4 weeks
Catch-up Vaccination
• One dose if previously vaccinated with one dose • Either of the two vaccines can be used in ‘catch-up’
• Stand alone measles/measles containing vaccine can be schedule beyond 2 years of age
administered to infants aged 6–8 months during outbreaks. • Administer two doses for killed vaccine at least 6 months
However, this dose should not be counted. apart to unvaccinated persons
• Only single dose of live attenuated H2-strain vaccine
Varicella Vaccine • For catch-up vaccination, prevaccination screening for
hepatitis A antibody is recommended in children older
• Minimum age: 12 months than 10 years as at this age the estimated seropositive rates
• The risk of breakthrough varicella is lower if given exceed 50%.
15 months onwards
• The second dose may be administered before the age of
4 years, provided at least 3 months have elapsed since the
Typhoid Vaccine
first dose Routine Vaccination
• For children aged 1–12 years, the recommended minimum • Both Vi-PS conjugate and Vi-PS (polysaccharide) vaccines
interval between doses is 3 months. However, if the second are available
dose was administered at least 4 weeks after the first dose, • Minimum ages:
it can be accepted as valid {{ Vi-PS (Typbar-TCV ): 6 months;
• Children greater than 13 years should receive two doses, {{ Vi-PS (polysaccharide) vaccines: 2 years
4–8 weeks apart. • Vaccination schedule:
• Typhoid conjugate vaccines (Vi-PS): single dose at 9–12
Catch-up Vaccination through 23 months and a booster during second year of life
• Ensure that all persons aged 7–18 years without ‘evidence • Vi-PS (polysaccharide) vaccines: single dose at 2 years;
of immunity’ have two doses of the vaccine revaccination every 3 years
• For children aged 12 months to 12 years, the recommended • Currently, two typhoid conjugate vaccines, Typbar-TCV
minimum interval between doses is 3 months. However, if and PedaTyph available in Indian market
the second dose was administered at least 4 weeks after the • An interval of at least 4 weeks with the MMR vaccine should
first dose, it can be accepted as valid be maintained while administering Typbar-TCV vaccine
• For persons aged 13 years and older, the minimum interval • Primary dose of conjugate vaccine should follow a booster
between doses is 4 weeks at 2 years of age
• For persons without evidence of immunity, administer two • Either Typbar-TCV or Vi-polysaccharide (Vi-PS) can be
doses if not previously vaccinated or the second dose if employed as booster
only one dose has been administered • Typhoid revaccination every 3 years, if Vi-polysaccharide
• Evidence of immunity to varicella includes any of the vaccine is used
following: • No evidence of hyporesponsiveness on repeated
{{ Documentation of age appropriate vaccination with a revaccination of Vi-polysaccharide vaccine so far
varicella vaccine • Need of revaccination following a booster of Typbar-TCV
{{ Laboratory evidence of immunity or laboratory not yet determined.
confirmation of disease
{{ Diagnosis or verification of a history of varicella disease Catch-up Vaccination
by a healthcare provider • Recommended throughout the adolescent period, i.e.,
{{ Diagnosis or verification of a history of herpes zoster by 18 years.
a health-care provider
• Postexposure prophylaxis: vaccine is 90% effective in Human Papilloma Virus Vaccine
preventing or modifying the disease if given within 3 days
of exposure and 70% effective in preventing if given within Routine Vaccination
5 days and in both the situation, modification occurs 100%. • Minimum age: 9 years
• Human papilloma virus (HPV)-4 [Gardasil] and HPV2
Hepatitis A Vaccine vaccines [Cervarix] are licensed and available
• Only two doses of either of the two HPV vaccines (HPV4 and
Routine Vaccination HPV2) for adolescent/preadolescent girls aged 9–14 years
• Minimum age: 12 months • For girls 15 years and older, and immunocompromised
• Killed hepatitis A vaccine: start the two dose hepatitis A individuals three doses are recommended
vaccine series for children aged 12–23 months; separate • For two-dose schedule, the minimum interval between
118 the two doses by 6–18 months doses should be 6 months
ch-26.indd 118 11/19/2016 12:47:29 PM

Chapter 26: Immunization in Childhood
• Either HPV4 (0, 2, and 6 months) or HPV2 (0, 1, and {{ As of today, quadrivalent conjugate and polysaccharide
6 months) is recommended in a three-dose series for vaccines are recommended only for children 2 years
females aged 15 years and older and above. Monovalent group A conjugate vaccine,
• Human papilloma virus 4 can also be given in a three-dose PsA–TT can be used in children above 1 year of
series for males aged 11 or 12 years, but not yet licensed for age. Revaccination only once after 3 years in those
use in males in India at continued high risk for polysaccharide vaccine,
• The vaccine series can be started beginning at age 9 years conjugate vaccine as of now no booster required.
• For three-dose schedule, administer the second dose
1–2 months after the first dose and the third dose 6 months Cholera Vaccine
after the first dose (at least 24 weeks after the first dose).
• Minimum age: 1 year; killed whole cell Vibrio cholerae
vaccine (Shanchol)
Catch-up Vaccination • Not recommended for routine use in healthy individuals;
• Administer the vaccine series to females (either HPV2 or recommended only for the vaccination of persons residing
HPV4) at age 13–45 years if not previously vaccinated in highly endemic areas and traveling to areas where risk of
• Use recommended routine dosing intervals (see above) for transmission is very high
vaccine series catch-up. • Two doses 2 weeks apart for greater than 1 year.
Influenza Vaccine Japanese Encephalitis Vaccine

• Minimum age: 6 months for trivalent inactivated influenza Routine Vaccination
vaccine • Recommended only for individuals living in endemic areas
• Recommended only for the vaccination of persons with • The vaccine should be offered to the children residing in
certain high-risk conditions rural areas only and those planning to visit endemic areas
{{ First time vaccination: 6 months to below 9 years—
(depending upon the duration of stay)
two doses 1 month apart; 9 years and above—annual • Three types of new generation Japanese encephalitis
revaccination with single dose (JE) vaccines are licensed in India: one, live attenuated,
{{ Dosage [trivalent influenza vaccine (TIV)]: aged
cell culture derived SA 14-14-2, and two inactivated JE
6–35 months 0.25 mL; 3 years and above 0.5 mL vaccines, namely vero cell culture-derived SA 14-14-2 JE
{{ For children aged 6 months through 8 years:
vaccine (JEEV) and vero cell culture-derived, 821564XY,
administer two doses (separated by at least 4 weeks) JE vaccine (JENVAC)
to children who are receiving influenza vaccine for • Live attenuated, cell culture derived SA 14-14-2:
the first time {{ Minimum age: 8 months
{{ All the currently available TIVs in the country contain
{{ Two dose schedule, first dose at 9 months along with
the swine flu or A (H1N1) antigen; no need to vaccinate measles vaccine and second at 16–18 months along
separately with DTP booster
• For children aged 6 months to below 9 years: for the {{ Not available in private market for office use
2012 season, administer two doses (separated by at least • Inactivated cell culture derived SA 14-14-2 (JEEV):
4 weeks) to those who did not receive at least one dose of {{ Minimum age: 1 year (United States Food and Drug
the 2010–11 vaccine. Those who received at least one dose Administration: 2 months)
of the 2012–13 vaccine require one dose for the 2013–14 {{ Primary immunization schedule: two doses of 0.25 mL
season each administered intramuscularly on days 0 and 28
• Best time to vaccinate: as soon as the new vaccine is for children aged more than or equal to 1 year to less
released and available in the market and just before the than or equal to 3 years
onset of rainy season. {{ Two doses of 0.5 mL for children aged more than
3 years and adults aged 18 years and above

Meningococcal Vaccine {{ Need of boosters still undetermined
• Meningococcal conjugated and polysaccharide vaccines • Inactivated Vero cell culture-derived Kolar strain,
are available 821564XY, JE vaccine (JENVAC)
• Minimum age: 2 years for both the vaccines {{ Minimum age: 1 year
{{ Recommended only for certain high risk group of {{ Primary immunization schedule: two doses of 0.5 mL
children, during outbreaks, and international travelers, each administered intramuscularly at 4 weeks interval
including students going for study abroad and travelers {{ Need of boosters still undetermined.
to Hajj and sub-Sahara Africa

{{ Conjugate vaccines are preferred over polysaccharide
Catch-up Vaccination
vaccines due to their potential for herd protection • All susceptible children up to 15 years should be
and their increased immunogenicity, particularly in administered during disease outbreak/ahead of anticipated
children <2 years of age outbreak in campaigns. 119
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Rabies Vaccine • Meningococcal vaccine

• Japanese encephalitis vaccine
• Practically all children need vaccination against rabies
• Cholera vaccine
• Following two situations included in high risk category
• Rabies vaccine
of children for rabies vaccination and should be offered
preexposure prophylaxis: • Yellow fever vaccine
{{ Children having pets in home
• Pneumococcalpolysaccharide vaccine (PPSV23).
{{ Children perceived with higher threat of being bitten
High risk category of children:
by dogs such as hostellers, risk of stray dog menace • Congenital or acquired immunodeficiency (including
while going outdoor human immunodeficiency virus infection)
• Only modern tissue culture vaccines and intramuscular • Chronic cardiac, pulmonary (including asthma if
routes are recommended for both postexposure and treated with prolonged high dose oral corticosteroids),
preexposure prophylaxis in office practice hematologic, renal (including nephrotic syndrome), liver
• Postexposure prophylaxis (PEP) is recommended following disease, and diabetes mellitus
a significant contact with dogs, cats, cows, buffaloes, • Children on long-term steroids, salicylates, immuno
sheep, goats, pigs, donkeys, horses, camels, foxes, jackals, suppressive, or radiation therapy
monkeys, mongoose, squirrel, bears, and others. Domestic • Diabetes mellitus, cerebrospinal fluid leak, cochlear
rodent (rat) bites do not require postexposure prophylaxis implant, malignancies
in India • Children with functional/anatomic asplenia/hyposplenia
• Postexposure prophylaxis: • During disease outbreaks
{{ Modern tissue culture vaccines are recommended for • Laboratory personnel and healthcare workers
all category II and III bites • Travelers.
{{ Dose: 1.0 mL intramuscular in anterolateral thigh or
deltoid (never in gluteal region) for human diploid

cell vaccine, purified chick embryo cell vaccine, Clinical Pearls
purified duck embryo vaccine; 0.5 mL for purified
vero cell vaccine. Intradermal administration is not • Constant surveillance is maintained of the various vaccine
recommended in individual practice preventable diseases
{{ Schedule: 0, 3, 7, 14, and 30 with day ‘0’ being the day of • Vaccine schedule is formulated as per the epidemiology of the
commencement of vaccination. A sixth dose on day 90 disease, need of that particular vaccine, and feasibility
is optional and may be offered to patients with severe • Optimal response to a vaccine depends on multiple factors,
debility or those who are immunosuppressed including the type of vaccine, age of the recipient, and
{{ Rabies immunoglobin (RIG) along with rabies vaccines immune status of the recipient.
are recommended in all category III bites
{{ Equine RIG (dose 40 U/kg) can be used if human rabies
immunoglobin is not available

• Preexposure prophylaxis: Key points
{{ Three doses are given intramuscularly in deltoid/
))
Certain vaccines are given free of cost to all children in India
anterolateral thigh on days 0, 7, and 28 (day 21 may be under National Immunization Program
used if time is limited but day 28 preferred)
{{ For reexposure at any point of time after completed
))
Indian Academy of Pediatrics has formulated immunization
schedule for guiding the members about the available
(and documented) pre- or postexposure prophylaxis,
vaccines
two doses are given on days 0 and 3
{{ Rabies immunoglobin is not required during ))
All the children should be immunized as per the guidelines at
reexposure therapy. specified time and age.
INDIAN ACADEMY OF PEDIATRICS SUGGESTED READINGS

RECOMMENDED VACCINES FOR HIGH RISK
1. Plotkin SA, Orenstein WA, Offit PA. Vaccine, 5th ed. Philadelphia: WB Saunders;
CHILDREN (VACCINES UNDER SPECIAL 2008.
CIRCUMSTANCES) 2. Vijay Yewale, Panna Choudhury, Naveen Thacker (Eds). IAP Guide Book on
Immunization. IAP Committee on Immunization 2009-2011. Mumbai: Indian
Indian Academy of Pediatrics recommended vaccines for high Academy of Pediatrics; 2011.
risk children (vaccines under special circumstances) are as 3. IAP Immunization Timetable 2014-Figure with range and Footnotes. Available
follows: from: http://acvip.org/professional/columns/pdf/IAP%20Immunization%20
• Influenza vaccine Timetable%202014-Figure%20with%20range%20&%20Footnotes.docx.
120
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Chapter 27
Missed Immunization
Ritabrata Kundu
Introduction Table 1: Vaccination in a child presenting at the age between 6

months and 1 year
Vaccine regimen for children whose vaccine has been missed
or delayed should preferably be individualized, but certain Vaccine Interval between doses
general principles should be followed. As vaccines produce Hepatitis B • First dose on presentation
immunological memory, any delay between recommended • Second dose after 4 weeks
• Third dose 6 months after first dose
doses does not require reinitiation of the entire vaccine
DTaP/DTwP • First dose on presentation
series. Administrations of vaccine at intervals shorter than
• Second dose after 4 weeks
recommended minimal interval produce poor immunological • Third dose after 8 weeks
response and should be avoided. • Fourth dose at 15–18 months
Two or more live injectable vaccines, administered at • Fifth dose at 4–6 years
shorter intervals, inhibits immunological response to the • There should be gap of at least 6 months
second or later dose. Whereas oral live virus vaccines do not between third and fourth dose and same
between fourth and fifth dose
interfere with injectable live vaccines administered at any
Hib • First dose on presentation
time interval. Hence, two or more live injectable vaccines • Second dose after 4 weeks
can either be given simultaneously or 4 weeks minimal • Third dose after 8 weeks
interval is needed between doses. Inactivated vaccines and • Fourth dose at 12–15 months
live vaccines can be administered simultaneously or at any • If the first dose is administered at 7–11 months
interval between the doses. then second dose 4 weeks later, and final dose
12–15 months of age
If live vaccines are inadvertently administered at an
interval of less than 4 weeks, revaccination with the second IPV • First dose on presentation
vaccine should be done. • Third dose after 8 weeks
Simultaneous administration of several vaccines may be • Fourth dose at 12–15 months
needed at the same sitting, if the chances of the child’s return PCV • First dose on presentation
to the vaccine facility are minimal. If more than one injection • Second dose after 4 weeks
has to be given in the same limb, thigh is preferred for its large • Third dose after 8 weeks
muscle mass, but 1–2 inches gap between two injection sites • Forth dose at 12–15 months
• If the first dose is administered at 7–11 months,
should be maintained to prevent overlapping of local reaction.
then second dose after 8 weeks and third dose at
Tables 1, 2, and 3 shows different vaccine schedules in three 12–15 months
age groups, namely between 6 months and 1 year, at 3 years Measles • At 9 months or before 1 year
and at 5 years respectively.. Rest of the vaccines, like varicella and hepatitis A at specified age
Child with unknown or undocumented immunization
DTaP, diphtheria, tetanus, and pertussis; DTwP, diphtheria, tetanus toxoids and
states should be considered as unimmunized and should be whole-cell pertussis; Hib, Haemophilus influenzae type b; IPV, inactivated polio
vaccinated accordingly. vaccine; PCV, pneumococcal conjugate vaccine.
ch-27.indd 121 11/19/2016 12:48:26 PM

Table 2: Vaccination in a child presenting at the age of 3 years

Clinical Pearls
Vaccine Interval between dose
Hepatitis B • First dose on presentation • Two or more live injectable vaccine, administered at shorter
intervals, inhibits immunological response to the later dose
• Second dose after 1 month
• Live injectable vaccines are given either simultaneously or at
• Third dose after 6 months from first dose
4 weeks interval
DTaP/DTwP • First dose on presentation
• Simultaneous administration of several vaccines may be given
• Second dose after 4 weeks from first dose
at the same sitting.
• Third dose 6 months after second dose
Hib Single dose at presentation
IPV • First dose on presentation Key points
• Third dose after 6 months from first dose ))
Certain general principles should be followed for children
PCV • Single dose at presentation who has missed vaccine regimen
MMR • First dose at presentation ))
Child with unknown or undocumented immunization state
should be considered as unimmunized.
• Second dose between 4–6 years of age
Hepatitis A • First dose at presentation
• Second dose 6 months after first dose SUGGESTED READINGS
Varicella • First dose at presentation
1. Plotkin SA, Orenstein WA, Offit PA. Vaccine, 5th edition. Philadelphia: WB
• Second dose 3 months after first dose Saunders; 2008.
DTaP, diphtheria, tetanus, and pertussis; DTwP, diphtheria, tetanus toxoids and 2. Vijay Yewale, Panna Choudhury, Naveen Thacker (Eds). IAP Guide Book on
whole-cell pertussis; Hib, Haemophilus influenzae type b; IPV, inactivated polio Immunization. IAP Committee on Immunization 2009-2011. Mumbai: Indian
vaccine; PCV, Pneumococcal conjugate vaccine; MMR, measles, mumps, and Academy of Pediatrics; 2011.
rubella.
Table 3: Vaccination in a child presenting at the age of 5 years
Vaccine Interval between dose

Hepatitis B • Same as in 3 years
DTaP • Same as in 3 years
MMR • First dose at presentation
• Second dose 8 weeks after the first dose
Hepatitis A • Same as in 3 years
Varicella • Same as in 3 years
DTaP, diphtheria, tetanus, and pertussis; MMR, measles, mumps, and rubella.
122
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Chapter 28
Animal Bites
Jaydeep Choudhury
INTRODUCTION • As children have soft skin, even minor scratches and trivial
bites may result in category III exposures.
Rabies is a fatal encephalitis. It is a zoonotic disease and
transmission to humans occurs by bite of an infected animal.
In India, the transmitting animal is dog in more than 95% cases. POSTEXPOSURE PROPHYLAXIS
Though rabies is fatal, once symptoms of the disease develop,
In rabies endemic country like India, every animal bite is
it is almost 100% preventable if prophylactic measures are
potentially suspected as a rabid animal bite; the treatment
instituted soon after the exposure.
should be started immediately. Rabies has long incubation
period. Prophylactic postexposure treatment should be started
PROBLEMS OF at the earliest to ensure that the individual will be immunized
RABIES INFECTION IN CHILDREN before the rabies virus reaches the nervous system. The
classification of animal bite for postexposure prophylaxis
In India and other developing countries, 50–60% of all rabies
(PEP) has been based on these World Health Organization
deaths occur in children (<15 years of age). There are several
recommendations (Table 1).
reasons as to why children are more susceptible:
• Children play in the streets and are more prone for dog Vaccination status of the biting animal: history of rabies
bites. Because of their playful nature, they also tend to vaccination in an animal is not always a guarantee that the
tease dogs and in consequence, dogs attack them biting animal is not rabid. Animal vaccine failures may occur
• Because of their short stature, bites on heads, neck, and because of improper administration or poor quality of the
upper parts of the body are more common and bites tend vaccine, poor health status of the animal, and the fact that one
to be severe. This results in greater risk for infection with vaccine dose does not always provide long-lasting protection
relatively shorter incubation period. Because of their short against infection in dogs.
stature, even bites on lower parts of the body may result in
shorter incubation period Observation of biting animal: the treatment should always
• Many times, because of the fear of painful injections that be started immediately after animal bite. The treatment may
may be given, they even tend to hide the fact that they were be modified if animal involved (dog or cat) remains healthy
bitten throughout an observation period of 10 days by converting
Table 1: Type of contact, exposure, and recommended postexposure prophylaxis

Category Type of contact Type of exposure Recommended postexposure prophylaxis
I • Touching or feeding of animals None None, if reliable case history is available
• Licks on intact skin
II • Nibbling of uncovered skin Minor Wound management + antirabies vaccine
• Minor scratches or abrasions without bleeding
III • Single or multiple transdermal bites or scratches, licks on Severe Wound management + rabies
broken skin immunoglobulin + antirabies vaccine
• Contamination of mucous membrane with saliva (i.e., licks)
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PEP to preexposure vaccination by skipping the vaccine dose A properly immunized child can only take one dose of tetanus
on day 14 and administering it on day 28 while using Essen toxoid if there is a lapse of a period of 5 years from the last dose
schedule. The observation period is valid for dogs and cats of tetanus toxoid.
only. The natural history of rabies in mammals other than To prevent sepsis in the wound, a suitable course of an
dogs or cats is not fully understood and therefore the 10-day antibiotic may be recommended.
observation period is not applicable.
Rabies Immunoglobulin
Approach to Postexposure Prophylaxis The RIG provides passive immunity to tide over the initial
The PEP consists of three parameters and should be done phase of the infection.
simultaneously as per the category of the bites: Two types of RIGs are available:
1. Management of animal bite wound(s) 1. Equine rabies immunoglobulin (ERIG): it is of hetero
2. Passive immunization: rabies immunoglobulins (RIGs) logous origin raised by hyperimmunization of horses. The
3. Active immunization: antirabies vaccines (ARVs). currently manufactured ERIGs are highly purified and
enzyme refined, with these preparations, the occurrence of
Management of Animal Bite Wound adverse reaction has been significantly reduced.
Wound toilet: since the rabies virus enters the human body 2. Human rabies immunoglobulins (HRIGs): as it is
through a bite or scratch, it is imperative to remove as much homologous, HRIG is free from the side effects encountered
saliva as possible. Since the rabies virus can persist and even in a serum of heterologous origin, and because of their
multiply at the site of bite for a long time, wound toilet must be longer half-life, are given in half the dose of equine
performed even if the patient reports late (Table 2). antirabies serum.
Prompt and gentle thorough washing with soap or Dose of rabies immunoglobulins:
detergent and flushing the wound with running water for 10 • The dose of ERIG is 40 IU/kg body weight of patient and
minutes can do this. is given after testing for sensitivity, up to a maximum of
The application of irritants is unnecessary and damaging. 3,000 IU. The ERIG produced in India contains 300 IU/mL
In case irritants have been applied on the wound, enough • The dose of the HRIG is 20 IU/kg body weight (maximum
gentle washing with soap or detergent to remove the extraneous 1,500 IU). HRIG does not require any prior sensitivity
material, especially oil, should be done followed by flushing testing. HRIG preparation is available in concentration of
with copious amount of water for 10 minutes immediately. 150 IU/mL.
Application of antiseptic: after thorough washing and Administration of immunoglobulins: as much of the calculated
drying the wound, any one of the available chemical agents dose of RIG as is anatomically feasible should be infiltrated
should be applied, viz.: povidone iodine (solution), alcohol, into and around the wounds. Remaining, if any, after all
chloroxylenol, chlorhexidine gluconate, and cetrimide solution wounds have been infiltrated, should be administered by deep
in appropriate recommended dilution. intramuscular (IM) injection at an injection site distant from
the vaccine injection site. The total recommended dose of
Local infiltration of RIGs: in category III bites, RIG should be immunoglobulin must not be exceeded as it may suppress the
infiltrated in the depth and around the wound to inactivate the antibody production by the vaccine.
locally present virus as described below. If immunoglobulin was not administered when vaccination
was begun, it can be administered up to the seventh day after
Suturing of wound: it should be avoided as far as possible. If
the administration of the first dose of vaccine.
surgical intervention is unavoidable, minimum loose sutures
In circumstances where no immunoglobulins are available,
should be applied after adequate local treatment along with
greater emphasis should be given to proper wound toileting
proper infiltration of RIGs.
followed by Essen schedule of cell-culture vaccine (CCV) with
Tetanus toxoid injection (anti-tetanus prophylaxis): this should double dose on day 0 at two different sites intramuscularly
be given to those children who had not received a booster dose. (0 day: 2 doses on left and right deltoid, following the single
Table 2: Do’s and don’ts of wound management

Step of wound management Purpose
Do’s
Physical wash under running tap water for at least 10 minutes Mechanical removal of virus from
the wound
Chemical washing the wound with soap and water, dry, and apply disinfectant Inactivation of the virus
Biological infiltration of immunoglobulins in the depth and around the wound in category III exposures Neutralization of the virus
Don’ts
Touch the wound with bare hand
124 Apply irritants like soil, chilies, oil, herbs, chalk, betel leaves, etc.
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Chapter 28: Animal Bites
dose on each day, i.e., day 3, 7, 14, and 28). It is emphasized {{ Updated Thai Red Cross Schedule (2-2-2-0-2): this
that doubling the first dose of CCV is not a replacement to involves injection of 0.1 mL of reconstituted vaccine
RIG. A full course of vaccine should follow thorough wound per ID site and on two such ID sites per visit (one
cleansing and passive immunization. on each deltoid area, an inch above the insertion of
deltoid muscle) on day 0, 3, 7, and 28. The day 0 is the
Antirabies Vaccines day of first-dose administration of intradermal rabies
Active immunization is achieved by administration of safe and vaccines (IDVR) (ID inoculation of ARV) and may not
potent CCVs or purified duck embryo vaccines (PDEV). The be the day of rabies exposure/animal bite
dosage schedule of cell culture rabies vaccine (CCV/CCRV) is {{ Antirabies treatment centers which meet the following
same irrespective of the body weight or age of the children. criteria may use ID administration:
• Storage and transportation: it is recommended that these –– Have adequately trained staff to give IDRV
vaccines should be kept and transported at a temperature –– Can maintain cold chain for vaccine storage
range of 2–8°C. Freezing does not damage the lyophilized –– Ensure adequate supply of suitable syringes and
vaccine but there are chances of breakage of ampoule needles for ID administration
containing the diluent. Liquid vaccines should never be –– Are adequately well versed in management of open
frozen vial and safe storage practices.
• Reconstitution and storage: the lyophilized vaccine should
be reconstituted with the diluent provided with the vaccine Postexposure Therapy for Previously Vaccinated
immediately prior to use. In case of unforeseen delay it Children
should be used within 6–8 hours of reconstitution.
Children who have previously received full PEP or preexposure
Intramuscular regimen: the currently available vaccines and
vaccination (either by IM or ID routes) with a potent CCV
regimens in India for IM administration are described below.
should now be given only two booster doses: IM (0.5 mL/1 mL)/
• Antirabies vaccines:
ID (0.1 mL at 1 site) on day 0 and 3 irrespective of the duration
{{ Cell-culture vaccines:
of previous vaccination. Proper wound toilet should be done.
–– Human diploid cell vaccine: produced locally in
Treatment with RIG is not necessary.
private sector
–– Purified chick embryo cell vaccine: produced
locally in private sector
Preexposure Vaccination of Children
–– Purified vero-cell rabies vaccine: imported and As rabies is a 100% fatal disease and children constitute a
produced locally in public and private sectors special risk for getting the infection, it may be advisable to
{{ Purified duck embryo vaccine: vaccinate children after they attain the age of 3 years and start
–– Produced locally in private sector. playing in the streets and may come in contact with street or
Note: All CCRVs and purified duck embryo vaccine used for pet dogs.
PEP should have potency (antigen content) greater than
2.5 IU/dose. Schedule of Preexposure Vaccination
• Regimen: • Intramuscular: 3 doses of any CCVs (1 mL or 0.5 mL
{{ Essen schedule (5-dose IM regimen): the course for depending on the brand) administered on the anterolateral
PEP should consist of IM administration of 5 injections thigh on day 0, 7, and 28
on day 0, 3, 7, 14, and 28. Day 0 indicates date of first • Intradermal: the dose is same for all vaccine brands and
injection 0.1 mL is administered ID over the deltoid on day 0, 7,
{{ Site of inoculation: the anterolateral thigh region is and 28.
ideal for the inoculation of these vaccines in infants The management of children exposed to animal bites is
and younger children, whereas the older children shown in algorithm 1.
can take in deltoid regions. Gluteal region is not
recommended because the fat present in this region
Clinical Pearls
retards the absorption of antigen and hence impairs
the generation of optimal immune response. • The transmitting animal of rabies is dog in more than 95%
Intradermal (ID) regimens: it consists of administration of cases
a fraction of IM dose of CCVs on multiple sites in the layers • Rabies is fatal once symptoms of the disease develop, but
of dermis of skin. The use of ID route leads to considerable it is almost 100% preventable if prophylactic measures are
savings in terms of total amount of vaccine needed for full instituted soon after the exposure
pre- or postexposure vaccination, thereby reducing the cost
• Intradermal rabies vaccination is given in state run rabies
of active immunization. In ID route, small amount (0.1 mL) of clinics, where many people come for rabies vaccine daily
rabies vaccines/antigen is deposited in the layers of the skin at
• Rabies immunoglobulins is not needed for person who have
two or more sites:
received full course of rabies vaccine.
• Intradermal vaccine regimen:
125
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Algorithm 1
Key points
Algorithm for management of children exposed to animal bites
))
In rabies endemic country like India, every animal bite is
potentially suspected as a rabid animal bite the treatment
should be started immediately
))
Children have soft skin, therefore, even minor scratches and
trivial bites may result in category III exposures
))
Prompt and gentle thorough washing with soap or detergent
and flushing the wound with running water for 10 minutes
))
Children above 3 years of age may be routinely given
preexposure prophylaxis of antirabies vaccines.
SUGGESTED READINGS
1. Sudarshan MK. (2003). Assessing burden of rabies in India: WHO sponsored
National Multi-centric Rabies Survey. [online] Available from: rabies.org.in/rabies-
journal/rabies-06/SpecialArticle1.htm. [Accessed November, 2015].
2. Sudarshan MK. Rabies. In: Parthasarathy A, Kundu R, Agrawal R, et al. (Eds).
Textbook of Pediatric Infectious Diseases, 1st edition. New Delhi, India: Jaypee
Brothers Medical Publishers; 2013.
3. World Health Organization. WHO Expert Consultation on Rabies: First Report.
Technical Report Series 931. Geneva, Switzerland: World Health Organization;
2005.
4. World Health Organization. WHO Recommendations on Rabies Post-exposure
ARV, antirabies vaccines; PEP, postexposure prophylaxis; RIG, rabies immuno Treatment and the Correct Technique of Intra-dermal Immunization against
globulins. Rabies. Geneva, Switzerland: World Health Organization; 1997.
126
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Chapter 29
Adverse Event Following
Immunization
Amar J Chitkara
INTRODUCTION Algorithm 1
World Health Organization: Causality assessment of serious
Childhood morbidity and mortality has witnessed tre adverse event following immunizations
mendous decrease following widespread immunization in
the last 30–40 years across the globe. Many new vaccines
are being developed and introduced in both the public and
private sectors. Though the vaccines are of documented safety
and efficacy, yet infrequently have adverse events. These
adverse events can be a strong deterrent to the acceptability
of vaccines; hence it is imperative to have a comprehensive
surveillance system to address these concerns, especially
with the introduction of many new vaccines/products
and that too in a country with 27 million births per year
and an extensive expanded program of immunization
with constraints of medical care access. The adverse event
following immunization (AEFI) is defined as “a medical
incident that takes place after immunization, causes concern,
and is believed to be caused by the immunization”.
with the World Health Organization (WHO)/National Polio
WHY REPORT ADVERSE Surveillance Project, India. Operational guidelines were
EVENT FOLLOWING IMMUNIZATION? developed and disseminated widely across the country in
the public sector by organizing multiple workshops. The
Vaccines are always administered to healthy infants and program was further strengthened in 2010 with the highest
children to provide protection against dreadful diseases, hence AEFI reports during the year. The initiative by the Indian
any alteration in health with a temporal association with the Academy of Pediatrics (IAP) to collaborate with the national
vaccine be it fever, erythema, local pain and swelling, or a program has been a welcome step. The detailed operational
major event leading to disability, hospitalization, or death, guidelines and standard operating procedures are available in
erodes the confidence of the caregivers in the program and the public domain as well as print. The cases are then taken
any nonacceptance can have serious outcomes as regards up for causality assessment as per the standard WHO protocol
morbidity and mortality by vaccine preventable deaths (VPDs). (Algorithm 1).
Ironically, with widespread vaccination, the disease burden
decreases and even mild AEFI become noticeable.
WHAT TO REPORT
NATIONAL ADVERSE EVENT Serious AEFI, such as death, disability, and hospitalization,
need to be reported immediately while minor AEFI, such
FOLLOWING IMMUNIZATION PROGRAM
as fever, local reactions, etc., are reported through monthly
Though started along with Universal Immunization Program reports in the public health. The reporting hierarchy and the
in 1985, the real thrust started only in 2005 in collaboration timelines are given in algorithm 2. From the programmatic
ch-29.indd 127 11/24/2016 12:36:29 PM

Table 1: Types of adverse event following immunizations reaches the concerned district immunization officer (DIO),
state immunization officer, and Ministry of Health and Family
Types of adverse event Examples
Welfare (MoHFW) for appropriate action. Also, the fear and
Vaccine reaction High grade fever following diphtheria, anxiety of IAP members in reporting has been allayed to a
pertussis, and tetanus toxoids great extent by official communication and talks with MoHFW
vaccination, anaphylaxis
in this regard. The doctors can also report to their district
Program error Bacterial abscess due to unsterile immunization officers, medical officer, of nearest primary
injection/wrong diluent health center directly. The event is then investigated by DIO
Coincidental Pneumonia after oral polio vaccine and the local AEFI committee; however, the reporting physician
is expected to cooperate. The keyword remains creating
Injection reaction Fainting spell after immunization awareness about utility of AEFI reporting and allaying fears
Unknown – associated with reporting. An increased collaboration with
the various AEFI committees and nominating the practicing
purpose, the AEFIs are classified into five broad categories of physicians to these committees can further augment national
AEFI: (i) programmatic error, (ii) vaccine reaction, (iii) injection AEFI program.
reactions, (iv) coincidental, and (v) unknown (Table 1).
Clinical Pearl
REPORTING FROM PRIVATE SECTOR • Report adverse event following immunization and feel safe.
It has been estimated that about 9% of the national population
gets vaccinated at private facilities and there exists a
considerable heterogeneity varying from 10 to 30%, especially
THE WAY FORWARD
being high in urban and metros across the country. The • Collaboration with all professional bodies who vaccinate
AEFI reporting from private sector has been exceptionally their patient’s across all ages to report AEFI
low because of a fear of reporting and harassment following • Create awareness amongst medical fraternity about the
the event. It should also be noted that since all new vaccines strengths of AEFI reporting to evaluate safety aspects of
evolve from the private sector, the AEFI from this sector has a vaccines used and available currently. This can be achieved
very high potential for assessing the safety of these vaccines. by a concerted effort through the continuing medical
Since 2011, IAP has taken an initiative to collaborate with educations, conferences, and print publications of various
national AEFI program to encourage reporting. The infectious professional organizations
disease surveillance, a web and SMS-based surveillance of • National, state, and district AEFI committees to have
VPDs has a built in portal of reporting AEFI that follows the representatives from private sector to instill confidence
standard operating procedures. The information automatically amongst reporting physicians
Algorithm 2
Reporting framework and timelines
AEFI, adverse event following immunizations; Pvt, private; CSF, cerebrospinal fluid; AC, assistant commissioner; UIP, Universal Immunization Program; MoHFW,
128 Ministry of Health and Family Welfare; GoI, Government of India.
ch-29.indd 128 11/24/2016 12:36:29 PM

Chapter 29: Adverse Event Following Immunization
• Creating user friendly reporting network, especially an 4. World Health Organization. Surveillance of Adverse Events following Immunization:
E-network like IDSURV.org and promoting public private Field Guide for Managers of Immunization Programs. Geneva, Switzerland: World
partnership towards achieving this Health Organization; 1997.
• Inculcate confidence amongst practicing doctors in 5. World Health Organization. Aide Memoir on AEFI investigation. Geneva,
Switzerland: World Health Organization; 2005.
reporting AEFI by strong assurance from the MoHFW
6. Chen RT, Rastogi SC, Mullen JR, Hayes SW, Cochi SL, Donlon JA, et al. The vaccine
and state health departments regarding no harassment
adverse event reporting system (VAERS). Vaccine. 1994;12(6):542-50.
following these reports.
7. Ministry of Health and Family Welfare (MoHFW), Government of India (GoI).
Adverse Events Following Immunization: Surveillance and Response Operational
SUGGESTED READINGS Guidelines. 2006.
1. World Health Organization (WHO), United Nations Children’s Fund (UNICEF), World 8. Ministry of Health and Family Welfare (MoHFW), Government of India (GoI).
Bank. State of World Vaccines and Immunization. 3rd ed. Geneva, Switzerland: Adverse Events Following Immunization: surveillance and response operational
World Health Organization; 2009. guidelines. 2010.
2. Centers for Disease Control and Prevention (CDC). Global routine vaccine 9. Ministry of Health and Family Welfare, Government of India (GoI). Adverse
coverage, 2010. MMWR Morb Mortal Wkly Rep. 2011;60(44):1520-2. Events Following Immunization: surveillance and response Standard operating
3. Black RE, Counsens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, procedures. 2010.
regional, and national causes of child mortality in 2008: a systematic analysis. 10. Ministry of Health and Family Welfare (MoHFW), Government of India (GoI). Multi
Lancet. 2010;375(9730):1969-87. Year Strategic Plan (MYP) for UIP of India 2005-10. 2010.
129
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Section 4: Office Emergencies
Chapter 30
Approach to Respiratory
Distress in Children
Narendra R Nanivadekar
INTRODUCTION Primary Assessment

Respiratory distress is one of the most common complaints Primary assessment is a hands-on evaluation of airway,
presenting to the pediatric emergency department. It requires breathing, circulation, disability, and exposure, which, includes
a rapid yet systematic assessment to facilitate diagnosis and vital signs and pulse oximetry.
quick efficient management, because many conditions causing
respiratory distress have the potential to lead to respiratory Airway
failure. Thus, a systematic approach can help us to recognize Airway patency can be checked by looking for the movement of
respiratory distress sufficiently early, even before it progresses the chest and abdomen and listening for the air movement and
to respiratory failure, and initiate appropriate supportive and breath sounds (Table 2).
specific management which can dramatically improve the A child with a foreign body airway obstruction may
outcome. require an advanced airway technique like laryngoscopy or
bronchoscopy. Increased inspiratory effort with retractions,
APPROACH abnormal inspiratory sounds (snoring or high-pitched stridor)
suggests that the child has upper airway obstruction (UAO).
This section discusses the diagnostic approach to respiratory Episodes where no airway or breath sounds are present despite
distress. Management of respiratory distress is dealt with in
respiratory effort may suggest complete airway obstruction.
another section subsequently.
Breathing
Initial Impression
Evaluation of breathing is helpful to diagnose majority of
The first step is a quick audiovisual assessment done within causes of respiratory distress. Evaluation includes:
seconds of establishing contact with the child. The aim is to • Respiratory rate
identify the need for cardiopulmonary resuscitation (CPR), • Effort
and prioritize interventions before proceeding further with a • Chest expansion and air movement
detailed systematic assessment (Table 1).
This is followed by detailed evaluation which consists of Table 2: Assessment of the airway
primary, and secondary assessments and diagnostic tests. This
helps us to identify the type and severity of the problem. Observation Inference Implication
(airway status)
Table 1: Initial impression Normal chest Clear Open and
Initial impression movement and silent unobstructed
breathing
Consciousness Level of consciousness (e.g., unresponsive,
irritable, alert) Stridor, gurgling, Partially Maintained by
Breathing Increased work of breathing, absent/decreased snoring +/− obstructed/ simple measures like
respiratory effort, or abnormal sounds heard suprasternal retractions maintainable position, suction, etc.
without auscultation No chest movement or Complete Needs advanced
Color Abnormal skin color such as cyanosis, mottling, breath sounds obstruction/not measures like
pallor maintainable intubation
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Chapter 30: Approach to Respiratory Distress in Children
• Lung and airway sounds children and also indicates that the patient is getting fatigued
• O2 saturation by pulse oximetry. fast and needs urgent intervention.
Respiratory rate should be evaluated before the hands-on
Chest wall expansion: decreased or asymmetric chest wall
evaluation as anxiety and agitation will make it difficult to assess.
expansion can be due to inadequate effort, airway obstruction,
Children with respiratory distress are typically tachypneic.
atelectasis, pneumothorax, hemothorax, pleural effusion,
Though the normal respiratory rate varies with age, for
mucus plug, or foreign, body aspiration. By and large the
practical purposes, at any age respiratory rate greater than 60
diseased side would be moving less.
indicates abnormality. Though nonspecific, it is the first sign of
respiratory distress. Quiet tachypnea (with normal respiratory Air movement: while normal inspiratory sounds will be soft
effort) may be due to nonpulmonary causes like fever, anemia, quiet noises with observed inspiratory effort, expiration may
pain, sepsis, congestive cardiac failure, or mild metabolic be short and quiet, at times inaudible. Presence of abnormal
acidosis. Bradypnea may be due to either neuromuscular sounds along with respiratory distress often gives clue to the
weakness primarily or after persistent tachypnea leading diagnosis.
to fatigue secondarily. Either way it is an ominous sign. Pulse oximeter can be considered as another vital sign
Occasionally, it may be due to central causes. Any respiratory which may indicate hypoxia long before cyanosis or bradycardia
rate below 10 per minute requires further evaluation. is evident. Preferably it should be done continuously during
stabilization of the patient.
Clinical Pearl
Circulation
• Bradycardia when associated with other signs of decreased Circulation assessment consists of evaluation of heart rate
perfusion, most commonly indicates hypoxia, and is an and rhythm, pulses (both central and peripheral), capillary
ominous sign demanding urgent action. refill time, skin color and temperature, and blood pressure.
This needs to be done to complete the overall evaluation
Respiratory effort: usually, a child with respiratory distress of the patient and to categorize whether the child also has a
will have increased effort. Increased effort will be seen as circulatory disorder which may be secondary to the respiratory
nasal flaring, use of other accessory muscles, retractions, insufficiency or may be coexisting.
head bobbing or see-saw respirations. Additionally, we may
encounter prolonged inspiration or expiration, open mouth Disability
breathing, or gasping. Grunting indicates that the child has The aim is to assess the neurological perfusion/function, either
severe respiratory distress. by the alert, voice, pain, unresponsive (AVPU scale) or the
Nasal flaring will be seen commonly in infants and younger Glasgow Coma Scale.
children. Subcostal, substernal, or intercostal retractions
indicate mild distress whereas supraclavicular, suprasternal, Exposure
or sternal retractions suggest severe distress. The type of This will give an idea about the presence of bruises, petechiae,
retractions may also vary with the site of disease—predominant and the body temperature of the child.
suprasternal retractions are seen in UAO, intercostal retractions
in parenchymal lung disease, and subcostal retractions in Secondary Assessment
lower airway obstruction (LAO) (Table 3).
This is to be done after primary assessment is completed and
Head bobbing is a sign of respiratory failure and warrants
appropriate interventions have been instituted to stabilize the
an early intervention. Similarly see-saw respiration is
child. It comprises of a focused history and focused physical
characteristic of neuromuscular weakness in infants and
examination. The focused history can be best remembered
by the mnemonic SAMPLE: Signs and symptoms, Allergies,
Medications, Past medical history, Last meal, Events. This can
Table 3: Abnormal sounds and their explanation
be followed with a focused physical examination. This should
Stridor An inspiratory, coarse, Upper airway obstruction include careful assessment of the primary area of concern of
high-pitched sound (extrathoracic) the illness or injury.
Grunting Expiratory short and Smaller airway collapse,
low-pitched sound alveolar collapse, or both Diagnostic Tests
Wheezing Musical sound Lower airway obstruction, These are performed to confirm the diagnosis or to determine
heard chiefly during chiefly smaller airways the severity of illness. They are chiefly laboratory evaluation
expiration. (intrathoracic) like complete blood count, arterial blood gas, biochemistry,
and radiology like X-ray, computed tomography scan, etc.
Crackles Sharp, crackling Wet in a lung tissue disease
sounds like pneumonia or pulmonary
At any point of time, if a life-threatening situation is
edema or dry as in atelectasis encountered, one must initiate CPR (Table 4).
or interstitial lung disease In view of the potential life-threatening situation, a detailed
history taking may be done only after the child is stabilized
Gurgling Coarser sounds Secretions, vomitus, or blood
(Table 5). 131
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Table 4: Signs of life-threatening illness in a child with Table 6: Categorization by type and severity
respiratory distress
Type Severity
Airway Complete or severe airway obstruction Respiratory • Upper airway obstruction • Respiratory
Breathing Apnea/bradypnea, markedly increased work of distress • Lower airway obstruction distress
breathing • Lung tissue disease • Respiratory
Circulation Absence of detectable pulse, poor perfusion, • Disordered control of breathing failure
hypotension, bradycardia
Disability Unresponsiveness Respiratory Distress
Exposure Significant hypothermia or bleeding, petechiae or
Respiratory distress is a clinical state characterized by
purpura consistent with septic shock
abnormal respiratory rate or effort. It is commonly charac
terized by tachypnea and increased respiratory effort
Table 5: Additional diagnostic evaluation that may help in (increased work of breathing). Thus, it is a physiological state
respiratory distress in which the child is trying to maintain adequate gas exchange
History Time frame Acute, recurrent, or chronic nature of despite a respiratory pathology, by increasing the rate and
progression effort. However, in the absence of effective intervention, a
point may be reached at which adequate gas exchange can no
Associated Cough, fever, rash, chest pain
symptoms longer be maintained in spite of the increased rate and effort.
When this happens, the child is said to have progressed into
Preceding Choking, foreign body inhalation,
the state of respiratory failure.
events trauma, exposure to chemical or
During this progression, at times, the respiratory rate and
environmental irritants
effort may actually fall secondary to respiratory fatigue; thus, at
Family history Exposure to infections, tuberculosis, times, severe respiratory distress is clinically evident in the form
atopy
of hypoventilation, and is an indication of respiratory failure.
Diagnostic Direct If upper airway obstruction is
workup laryngoscopy detected/suspected Respiratory Failure
X-rays Chest, lateral neck, and decubitus Respiratory failure is defined as inadequate oxygenation,
Arterial blood Hypoxia (PaO2 <60 mmHg) ventilation, or both. Since respiratory distress and respiratory
gas Hypercarbia (PaCO2 >40 mmHg) and failure represent a continuum, respiratory failure can be
SaO2 monitoring identified clinically by recognizing definite clinical signs
Acidosis (pH <7.3), alkalosis (pH >7.5) of hypoxemia or hypercarbia, in addition to the signs of
Sepsis Blood counts and culture studies respiratory distress (Table 7).
workup Though neurological illnesses can lead to “breathlessness”,
PaO2, partial pressure of arterial oxygen; PaCO2, partial pressure of carbon
they are unlikely to present with breathlessness as the only/
dioxide; SaO2, saturated oxygen of arterial blood. chief complaint. Whether the neurological illness is acute
(head injury, encephalitis, or meningitis) or subacute/
chronic (Guillain-Barré syndrome, or spinal muscular
GENERAL APPROACH TO atrophy) there will usually be a prominent history of the
A CHILD IN RESPIRATORY DISTRESS initiating/primary events which will suggest the possible
cause of hypo/hyperventilation. It is important to note that
Children, who present with breathlessness to the emergency
alteration of sensorium in a child with hypo/hyperventilation
department, are likely to be suffering from respiratory, cardiac,
or metabolic conditions. The history is extremely useful in does not necessarily mean a primary neurological illness; it
deciding the probable etiology of breathlessness. A careful
Table 7: Clinical signs of respiratory distress and failure
evaluation of what the chief complaint/s is/are, as well as the
onset, duration, and progress of the same, provide valuable Respiratory distress Respiratory failure
clues. Specific findings on physical examination can further • Tachypnea • (Early) Marked tachypnea/
suggest the probable diagnosis. tachycardia
• Tachycardia
The most common causes of breathlessness are • (Late) Bradypnea, apnea/bradycardia
• Increased respiratory
“respiratory”. If one identifies the problem to be primarily
effort • Increased/decreased/no respiratory
respiratory, after the assessment one should be able to decide
• Abnormal airway effort
the physiological type of the problem and the severity of the
sounds • Cyanosis agitation, incessant
respiratory problem in the patient, which may help us in
• Pale cool skin crying, fighting the oxygen mask or
initiating a specific treatment. combativeness, diaphoresis
Based on the severity, respiratory problems can be classified • Changes in mental
status • Stupor/coma
into respiratory distress and respiratory failure (Table 6).
132
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Chapter 30: Approach to Respiratory Distress in Children
could be the end result of any progressive cardiorespiratory

pathology as well. Similarly, though see-saw respiration is Clinical Pearl
classically seen in neuromuscular weakness, it could be seen
as a preterminal event in any severe respiratory pathology. • In general, management of respiratory distress does not require
Therefore, as mentioned above, the history is crucial. an immediate chest radiograph; most conditions are apparent
If the clinical signs suggest that the type of respiratory clinically and waiting for radiography to initiate treatment can
problem is “lung tissue disease”, the more common causes waste precious time.
are pneumonia, acute respiratory distress syndrome (ARDS),
and cardiac causes. The detection of cardiac failure, shock, or Approach to a child with breathing difficulty is represented in
cyanosis may suggest a cardiac cause of breathlessness (Table 8). algorithm 1.
Table 8: Diagnostic clues to the cause of breathlessness

“Type” of Specific features Common causes and their additional clues
problem
Upperairway • Stridor, a change in voice, e.g., hoarseness, • Supraglottic—Epiglottitis, retropharyngeal abscess
obstruction the presence of a barking cough, drooling, • Glottic—Acute laryngotracheobronchitis
suprasternal retractions • Infraglottic—Bacterial tracheitis
Lowerairway • Wheezing, a particularly increased expiratory • Asthma—Acute onset, episodic/intermittent breathlessness;
obstruction effort, subcostal retractions fever +/−, prominent cough. Bronchiolitis—infant, prodrome,
seasonality, fever +/−
Lung tissue • Grunting, crackles, diminished breath sounds • Pneumonia—high fever, chest pain +/−
disease • Pulmonary edema, ARDS (both usually secondary to other causes)
Disordered • History of primary illness, significant alteration of • Neurological illnesses
control of sensorium, variable respiratory rate (tachypnea
breathing alternating with bradypnea), and poor respiratory
effort (shallow breathing, see-saw breathing)
RP, retropharyngeal; ARDS, acute respiratory distress syndrome.
Algorithm 1
Approach to a child with breathing difficulty
133
ARDS, acute respiratory distress syndrome; ILD, interstitial lung disease; GBS, Guillain-Barré syndrome.
Ch-30.indd 133 11/19/2016 12:56:34 PM

Key points
SUGGESTED READINGS
1. Hazinski MF, Gonzals L, O’Neill L (Eds). BLS for Healthcare Providers. American
))
Initial assessment: appearance, work of breathing, circulation Heart Association; 2006.
))
Manage/restore airway, breathing, circulation 2. Manual For GEM Course. Indian Academy of Paediatrics.
))
Provide high flow oxygen 3. Mathew JL, Singhi SC. Approach to a child with breathing difficulty. Indian J
Pediatr. 2011;78:118-26.
))
Immediate management of specific clinical condition 4. Mathew JL. Examination of respiratory system. In: Gupta P (Ed). Clinical Methods
))
Detailed clinical assessment to localize illness to respiratory in Paediatrics. New Delhi; 2009. pp. 183-218.
system (upper airway obstruction, lower airway obstruction, 5. Meyburg J, Bernhard M, Hoffmann GF, Motsch J. Principles of emergency
and parenchymal illness), cardiovascular system or neuro medical care. Dtsch Arztebl Int. 2009;106:739-47.
logical illness 6. PALS Providers Manual, American Heart Association; 2011.
))
X-ray chest is not mandatory in the initial stage in majority of 7. Rajesh VT, Singhi S, Kataria S. Tachypnoea is a good predictor of hypoxia in
acutely ill infants under 2 months. Arch Dis Child. 2000;82:46-9.
the cases
8. Schuh S, Lalani A, Allen U, Manson D, Babyn P, Stephens D, et al. Evaluation of the
))
Specific investigations and treatment should be based on the utility of radiography in acute bronchiolitis. J Paediatr. 2007:150;429-33.
likely cause identified on clinical evaluation 9. Singhi S, Mathew JL. Acute respiratory distress. In: Singh M (Ed). Medical
))
Start cardiopulmonary resuscitation at any point a life- Emergencies in Children, 4th edition. New Delhi: Sagar Publications; 2007. pp.
threatening event is encountered 352-72.
134
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Chapter 31
Recognition of Child in Shock
Kiran SK Vaswani
INTRODUCTION RECOGNITION OF SHOCK

Shock is a common cause of morbidity and mortality in For prompt and proper management of ill children, it is
children. Early recognition of shock and prompt intervention important to recognize:
remains the cornerstone of intact survival. The objective of this • Shock is present
chapter is: • Type of shock
• Early recognition of shock, by evaluating clinical signs of • Severity of shock.
systemic perfusion and compensation
• To ascertain the type of shock: hypovolemic, distributive, Recognizing Shock
cardiogenic, or obstructive.
Simple clinical evaluation of airway, breathing, circulation,
• To assess the severity of shock, whether compensated or
disability, exposure (ABCDE) of a patient gives sufficient clues
hypotensive
to recognition of shock and also type and severity of shock.
• Respiratory rate, effort, and sounds: tachypnea, a breathing
DEFINITION rate that is more rapid than normal for age with or without
Shock is a critical condition that results from inadequate tissue signs of increased work of breathing, decreased air entry,
delivery of oxygen and nutrients to meet tissue metabolic asymmetrical chest rise, and crackles (crepitations), need
demand, often, but not always characterized by inadequate to be looked for, along with pulse oximetry
peripheral and end-organ perfusion. • Heart rate and pulse quality: tachycardia is a resting
Lactic acid and waste products accumulate in the tissues heart rate that is faster than the normal range for a child’s
as a result of anaerobic metabolism when oxygen delivery is age. Tachycardia is body’s first response and the main
compromised and a vicious cycle sets in as illustrated in the compensatory mechanism especially in infants.
figure 1 below.
Clinical Pearl
• Tachycardia should not be ignored though it does not always
indicate shock.
Evaluation of pulses, both central and peripheral, gives vital

information regarding perfusion (Table 1). Vasoconstriction
Table 1: Easily palpable central and peripheral pulses

Central pulses Peripheral pulses
• Femoral • Radial
• Brachial (in infants) • Dorsalis pedis
• Carotid (in older children) • Posterior tibial
Fig. 1: Shock cycle • Axillary
Ch-31.indd 135 11/19/2016 1:41:33 PM

results in weak peripheral pulses while a low systemic vascular An increase in the output reflects improved kidney
resistance (SVR) and increased blood flow to the skin in perfusion. It is important to remember that initial urine
distributive shock results in bounding pulses. output is not a reliable indicator of present status.
Bradycardia, weak central pulses are relatively late features • Exposure: exposing one area at a time, avoiding discomfort
and sinister signs implying exhaustion of physiological and hypothermia, look for core temperature, fever and,
compensatory mechanisms. evidence of trauma, burns, petechiae, purpura, rashes of
• Systolic blood pressure and pulse pressure: systolic blood “allergy”, acute surgical emergencies like acute abdomen,
pressure measured appropriately helps in assessing the torsion of testis (including one in an undescended testis),
severity of shock. It is important to realize that a normal or and poisoning.
low systolic pressure is not a criterion to recognize shock. A focused medical history, easy to recall by the mnemonic
An observed decrease in systolic blood pressure of 10 mm SAMPLE (Signs and symptoms, Allergies, Medicines given,
Hg from baseline should prompt to evaluate further and Past medical history, Last meal, Events leading to the present
identify shock illness) gives valuable information regarding the cause or
• Pulse-pressure: vasoconstriction manifests as narrow other comorbid conditions to help tailor intervention strategy.
pulse pressure, less than 25% of systolic pressure in cold For example, history of diarrhea, trauma, known allergies to
shock and a low SVR as wide-pulse pressure food or medicines, premature birth, recent travel, a known
• End-organ perfusion case of congenital heart disease or arrhythmias, seizures,
{{ Brain: level of consciousness is assessed on AVPU scale neuromuscular disease, diabetes, renal disease, or last
–– A- Alert menstrual period in an adolescent girl, can help identify the
–– V- Responsive to voice type of shock or need to modify drugs or dosages.
–– P- Responsive to pain Certain laboratory tests can be crucial in recognition
–– U- Unresponsive and management of shock. These include rapid bedside
Pupillary size and response to light, muscle tone, glucose, arterial blood gas, venous blood gas, hemoglobin
and seizures give vital clues to cerebral and brain-stem concentration, arterial lactate, central venous or invasive
perfusion and function. arterial pressure monitoring, chest X-ray, electrocardiogram,
{{ Skin: skin perfusion is assessed by examining three echocardiogram, and abdominal ultrasound.
parameters—color, refill time, and temperature of skin
(CRT)
TYPES
–– Color: look for changes in skin color, pallor,
cyanosis and, mottling (an irregular and patchy Shock can be categorized into four basic types:
discoloration of skin) 1 Hypovolemic
–– Refill time: capillary refill time (CRT) is the time 2 Distributive
it takes for blood to return to tissue blanched 3 Cardiogenic
by pressure. It increases in a neutral thermal 4 Obstructive.
environment, as skin perfusion decreases. Normal Shock can result from a variety of clinical causes, like
CRT is less than 2 seconds. It may be very rapid, decreased blood volume resulting from blood or fluid loss,
flash, as in warm shock cardiac-pump dysfunction, maldistribution of blood as in sepsis
or anaphylaxis, and/or physical obstruction to blood flow.
Clinical Pearl
Clinical Pearls
• Though a sluggish (color, refill time, and temperature of skin)
may be a feature of shock, a normal or rapid CRT does not rule • Hypovolemic shock is characterized by “quiet tachypnea”
out shock. A rising fever or a cold environment will result in a • Increased respiratory effort distinguishes cardiogenic from
prolonged CRT. hypovolemic shock
• Children with cardiogenic shock may demonstrate retractions,
–– Temperature: skin temperature should be normal grunting, and use of accessory muscles.
and consistent over the trunk and extremities. • Treatment of obstructive shock is cause-specific; however, the
With decreased skin perfusion, skin becomes cool, most critical task is prompt recognition
hands and feet getting affected first. A temperature • Without early recognition and immediate treatment,
difference between “toe and tummy” indicates obstructive shock rapidly progresses to cardiopulmonary
decreased perfusion. As the condition worsens, failure and cardiac arrest.
even trunk temperature drops. Temperature of
skin also helps in monitoring improvement, as
perfusion improves the line of demarcation moves SEVERITY
distally
{{ Kidneys: urine output is a simple and essential para Compensated and Hypotensive Shock
136 meter to assess kidney perfusion. Children with shock Compensated shock is characterized by maintenance of
have decreased urine output, less than 1 mL/kg/hr. systolic blood pressure within the normal range with signs of
Ch-31.indd 136 11/19/2016 1:41:33 PM

Chapter 31: Recognition of Child in Shock
inadequate tissue perfusion. The compensatory mechanisms Table 2: Definition of hypotension by systolic blood pressure
try to maintain blood flow to the heart and brain, when oxygen and age
delivery is limited.
Age Blood pressure
Hypotensive shock represents failure or exhaustion of
physiological responses to maintain systolic blood pressure Term neonates <60 mmHg
and perfusion, that is, hypotension with poor perfusion. It is a
Infants (1–12 months) <70 mmHg
late finding in most types of shocks and may signal impending
cardiac arrest but can occur early in septic shock as a result of Children 1–10 years <70 mmHg + (child’s age in years × 2)
vasodilation by mediators. of age mmHg
Hypotension is defined by systolic blood pressure and age Children >10 years <90 mmHg
(Table 2).
Table 3: Clinical features characteristic of type of shock

Clinical signs Hypovolemic shock Distributive shock Cardiogenic shock Obstructive shock
Patency Airway open and maintainable/not maintainable
Respiratory rate Increased
Respiratory effort Normal to increased Labored
Breath sounds Normal Normal/crackles Crackles, grunting
Heart rate Increased
Peripheral pulse quality Weak Bounding or weak Weak
Systolic blood pressure Compensated → Hypotensive
Pulse pressure Narrow Variable Narrow
Skin color Pale Pale/flushed Pale
Capillary refill Delayed Variable Delayed
Peripheral temperature Cool Warm or cool Cool
Sensorium • Irritable early
• Lethargic late
Urine output Decreased
Table 4: Comprehensive table showing clinical examples, characteristic features and compensatory mechanisms in the course of
different types of shock
Type of shock Clinical examples Characteristic features and compensatory Special features/remarks
mechanisms
Hypovolemic • Diarrhea, vomiting, large • Absolute deficiency of intravascular volume— • Most common cause of shock
shock burns, hemorrhage, osmotic ↓preload leading to ↓ stroke volume and cardiac in children.
diuresis—DKA, third space output • “Cold shock”
losses • Tachycardia, ↑SVR, ↑cardiac contractility
Distributive • Severe infections—caused by • Inappropriate distribution • Early in the course:
shock organisms or endotoxins of blood volume • ↓SVR and ↑blood flow to the skin results in warm
• Septic shock • Anaphylaxis • Pulmonary extremities and bounding peripheral pulses, wide
• Anaphylactic vasoconstriction pulse pressure—“warm shock”
shock • High cervical spine injury • Loss of vascular tone • Late phase:
• Neurogenic • Inability to ↑ HR in • Hypovolemia and/or myocardial dysfunction result in
shock response to ↓BP ↓COP
• SVR can then ↑, resulting in
• ↓blood flow to skin, cold extremities and weak pulses,
narrow pulse pressure—“cold shock”
• Septic shock most common distributive shock
Cardiogenic • Congenital heart disease, • Myocardial dysfunction • Marked • ↑LV afterload
shock myocarditis, arrhythmias, tachycardia, ↑SVR, • ↓renal flow with fluid retention
sepsis, poisoning/drug toxicity ↓COP • ↑respiratory effort
Obstructive • Cardiac tamponade, tension • Cardiac output is impaired • Signs of systemic or pulmonary venous congestion
shock pneumothorax, massive by physical obstruction to not consistent with hypovolemic shock and
pulmonary emboli blood flow ↑respiratory effort 137
DKA, diabetic ketoacidosis; SVR, systemic vascular resistance; HR, heart rate; BP, blood pressure; COP, colloid osmotic pressure; LV, left ventricular.
Ch-31.indd 137 11/19/2016 1:41:33 PM

Algorithm 1
Recognition of shock
Though different types of shock are shown in this algorithm, it is impotant to realize that a given child may not present with any of these in isolation. One type of shock
may progress to another type as condition progresses, as has been illustrated in tables 3 and 4.
RR, respiratory rate; HR, heart rate; CRT, capillary refill time; BP, blood pressure; DKA, diabetic ketoacidosis; CHF, congestive heat failure
It is important to realize that these threshold values were

established in normal, resting children; and children with Key points
injury or serious illness would have increased blood pressure. ))
The presence of shock and the type of shock can be
So a low-normal range is abnormal in a seriously ill child. recognized by simple, systematic clinical examination
At times, with poor perfusion and feeble distal pulse and ))
Shock can exist and should be diagnosed even in the presence
cool extremities, blood pressure recording may not be feasible. of normal blood pressure; the presence of hypotension only
Change in the level of consciousness, progressive tachypnea, helps to categorize the severity of shock
and tachycardia indicate worsening status. Bradycardia and ))
It is crucial to recognize shock before hypotension develops,
weak central pulses in a child with signs of shock are signs of so that prompt treatment can be instituted
impending cardiac arrest. ))
Majority of patients presenting to us in shock have, fortunately,
It is crucial to recognize the shock in the compensated “normal” blood pressure, giving us a window period to revive
stage and manage promptly. Though shock progression them
is un predictable, it may take hours to deteriorate from ))
Tachycardia should not be ignored; though it does not always
compensated to hypotensive shock but only minutes for indicate shock
hypotensive shock to end up in cardiopulmonary failure and ))
In acute illnesses, cold extremities demand prompt action.
cardiac arrest.
SUGGESTED READINGs
Clinical Pearl 1. Goldenhour Emergency Management (GEM) Course Manual. Indian Academy of
Pediatrics. 2013.
• Shock can be categorized but not diagnosed by blood pressure. 2. Indian Pediatrics. Principles of Pediatric and Neonatal Emergencies, 3rd edition.
New Delhi: Jaypee Brothers Medical Publishers; 2011.
Shock can be categorised but not identified or defined by 3. PALS Provider Manual. American Academy of Paediatrics and American Heart
blood pressure. Association. 2011.
138
Ch-31.indd 138 11/19/2016 1:41:33 PM

Chapter 32
Croup
Bhavesh M Mithiya
INTRODUCTION Stridor is common and this abnormal sound alarms

parents enough to visit healthcare facility.
Croup is a common, primarily pediatric viral respiratory Stridor is an audible harsh, high-pitched sound produced
tract illness. As its alternative names (laryngotracheitis/ by turbulent airflow through a partially obstructed upper
laryngotracheobronchitis) indicate, croup generally affects the airway (at the level of supraglottis, glottis, subglottis, and/or
larynx and trachea with the maximal narrowing occurring in trachea).
the upper, extrathoracic trachea, although this illness may also During inspiration, airways that are easily collapsible (e.g.,
extend to the bronchi. supraglottic region) are suctioned closed because of negative
It is the most common etiology for hoarseness, cough, intraluminal pressure and are forced open during expiration.
and onset of acute stridor in febrile children. As with all viral Stridor can be heard in inspiration, expiration, or it can be
infections, the severity ranges widely, with the vast majority biphasic (inspiratory and expiratory).
recovering without consequences or sequelae; however, it can Inspiratory stridor suggests a laryngeal obstruction,
be life threatening. whereas expiratory stridor suggests tracheobronchial obstruc
tion. Biphasic stridor indicates either a subglottic or glottic
EPIDEMIOLOGY anomaly.
It is most common in monsoon and early winter but may occur

at any time of year. It is commonly seen in age group of 1–3
years, with peak during 2nd year of life. Boys are more affected
than girls (2:1). Around 15% of children experience at least one
episode, and 5% of children experience more than one episode.
ETIOLOGY
Parainfluenza viruses are the most common amongst all
viruses, responsible for as many as 80% of croup cases, though
it can be caused by many other viruses.
CLINICAL FEATURES
Croup begins with nonspecific respiratory symptoms, like
rhinorrhea, sore throat, cough, and generally low grade fever
(38–39°C); however in next 1–2 days, the characteristic signs
of hoarseness, barking cough, and inspiratory stridor develop,
often suddenly, along with a variable degree of respiratory
distress. “Absence of drooling of saliva” clinically confirms
presence of edema below the glottic area (which differentiates
croup from supraglottic causes like epiglottis/retropharyngeal Fig. 1: Location of airway obstruction in epiglottitis, croup, and
abscess) (Figs 1 to 3). bronchilolitis
Ch-32.indd 139 11/19/2016 1:48:51 PM

SEVERITY OF CROUP
While most have only “barking” cough and hoarse cry, few
have stridor on activity/agitation, and very few have audible
stridor at rest with respiratory distress. Paradoxically, a severely
affected child may have “quiet” stridor secondary to a greater
degree of airway obstruction.
Various croup scores have been developed to assess the
degree of respiratory compromise, but for practical purposes,
it can be divided into mild, moderate, and severe disease.
A clinically useful croup severity assessment table has been
developed by the Alberta Clinical Practice Guideline Working
Group (Table 1).
DIFFERENTIAL DIAGNOSIS
Though certain conditions like congenital structural
Fig. 2: Croup: inflammatory edema below the glottic area (subglottic malformations can present with stridor, they are not acute.
edema) When a child presents with acute stridor, one needs to
differentiate retropharyngeal (RP) abscess/epiglottitis from
acute laryngotracheobronchitis (ALTB) by the presence of
drooling of saliva in the former. Recurrent stridor is usually
allergic and may occasionally be due to gastroesophageal
reflux (GER).
INVESTIGATIONS
Croup is essentially a clinical diagnosis, based on presenting
history/physical examination, and investigations rarely
contribute. The complete blood count (CBC) is nonspecific.
Identifying the specific viral etiology is typically not
necessary and also not available to most.
Arterial blood gas (ABG) measurements are unnecessary
(unless respiratory fatigue), in fact it may worsen the airway
obstruction due to excessive crying.
Typically X-ray is not needed to confirm the diagnosis of
croup, and if at all, it is done to exclude other causes mimicking
Fig. 3: Epiglottitis: inflammatory edema above the glottic area croup such as a radio-opaque foreign body, or an RP abscess.
(supraglottic edema) If done, X-ray (AP) of the soft tissues of the neck classically
reveals a steeple sign (also known as a pencil-point sign),
An acute onset of marked inspiratory stridor is one of the

hallmarks of croup. The child with croup typically does not Table 1: Croup severity assessment
appear toxic. Mild Occasional barking cough, no audible stridor at
severity rest, and either no or mild suprasternal and/or
Clinical Pearls intercostal retractions
Upper airway obstruction Moderate Frequent barking cough, easily audible stridor at
• Interferes mainly with inspiration severity rest, and suprasternal and sternal wall retractions at
rest, with no or minimal agitation
• Inspiratory stridor
• Severe retractions Severe Frequent barking cough, prominent inspiratory
severity (and occasionally expiratory) stridor, marked sternal
• Croupy/brassy cough
wall retractions, significant agitation and distress
Lower airway obstruction
• Interferes mainly with expiration Impending Barking cough (often not prominent), audible
respiratory stridor at rest, sternal wall retractions may not be
• Expiratory wheeze
failure marked, lethargy or decreased consciousness, and
• Mild retractions + prolonged expiration often dusky appearance without supplemental
140 • Repetitive cough. oxygen support
Ch-32.indd 140 11/19/2016 1:48:51 PM

Chapter 32: Croup
which signifies subglottic narrowing, whereas the lateral neck TREATMENT

view may reveal a distended hypopharynx (ballooning) during
inspiration (see the images below) (Figs 4 and 5). However, The current cornerstones of treatment are corticosteroids and
these findings may not be seen in upto 50% cases. nebulized epinephrine.
A steeple sign may also be observed in patients without • Nebulized epinephrine (adrenaline):
{{ It is used for children with moderate-to-severe respira
croup, such as epiglottitis, thermal injury, angioedema, or
bacterial tracheitis. tory distress. Effectiveness of standard epinephrine
Laryngoscopy and/or bronchoscopy are indicated only in 1:1,000 (which is available in India) is the same as
unusual circumstances (e.g., the course of illness is not typical racemic epinephrine, when given in dose of 0.5 mL/kg
or recurrent croup to rule out an underlying anatomic or (maximum 5 mL)
{{ Epinephrine stimulates α- and β2-receptors causing
congenital disorder).
constrictions of precapillary arterioles thereby
decreasing capillary hydrostatic pressure which
leads to fluid resorption from the interstitium, thus
decreasing airway edema
{{ Its effectiveness is immediate with evidence of
therapeutic benefit within the first 30 minutes and

then, lasts from 1.5 hours to 2 hours; hence after
nebulized epinephrine, patient should be observed for
at least 3 hours to monitor for a rebound worsening.
Patients can be discharged home if they demonstrate
good color, adequate air entry, baseline consciousness,
and no stridor at rest and have received a dose of
A
corticosteroids
• Corticosteroids: they act through anti-inflammatory action,
whereby decreasing mucosal edema and also decreasing
the need for nebulized epinephrine. It may be warranted
even in those children who present with mild symptoms.
In moderate to severe disease, it improves croup scores
within 12–24 hours and decrease hospitalization rates. All
different routes of administration (oral/IM/nebulized) are
shown to be efficacious
{{ Dexamethasone: a single dose of dexamethasone has
been shown to be effective in reducing the overall

severity of croup, if used within the first 4–24 hours
of onset. Most trials have used dexamethasone IM or
oral (with equal efficacy) at 0.6 mg/kg/dose (with a
maximum daily dose of 10 mg). It is 6.67 times potent
than prednisone and has a long half-life of 36–56 hours.
B Also, patients treated with single dose of prednisolone
Fig. 4: A steeple sign (also known as a pencil-point sign), which (1 mg/kg) were found to require more follow-up visits
signifies subglottic narrowing than with dexamethasone (0.15 mg/kg)
–– Even though dexamethasone dosed at 0.15 mg/kg
is as effective as 0.3 mg/kg or 0.6 mg/kg, still dose
of 0.6 mg/kg is advocated as it is more effective for
patients diagnosed with severe croup and remains
optimal for safety and benefit
{{ Inhaled budesonide:
–– It has been shown in several studies to be equi

valent to oral dexamethasone. Dose is 2–4 mg.
Using inhaled corticosteroids (budesonide) along
with systemic steroid does not provide additional
benefit
–– Usage of steroids has no significant adverse effects;
however, it should be carefully evaluated for children
with diabetes/immunocompromised state, recently
diagnosed with varicella or tuberculosis. Urgent care
Fig. 5: A distended hypopharynx (ballooning) during inspiration of croup depends on the degree of severity 141
Ch-32.indd 141 11/19/2016 1:48:52 PM

• Cool-mist therapy: Randomized studies with moderate-to- Pulmonary edema, pneumothorax, lymphadenitis, and
severe croup revealed no difference in outcome otitis media have also been reported in croup. Poor ability to
• Antibiotics are not needed, as etiology is viral infection maintain adequate oral intake plus increased insensible fluid
• Heliox:Currently, the evidence is not sufficient to losses can lead to dehydration.
establish the beneficial effect of heliox in pediatric croup
management (Table 2).
PROGNOSIS
The prognosis for croup is excellent, and recovery is usually
COMPLICATIONS
complete. The majority of patients are managed successfully as
Complications in croup are rare. In most series, less than 5% outpatients, without the need for hospitalization.
of children needed hospitalization and less than 2% of those
who were hospitalized were intubated. Death occurred in
SPASMODIC CROUP
approximately 0.5% of intubated patients.
A secondary bacterial infection may rarely result in Spasmodic croup (laryngismus stridulus) may be a non
pneumonia or bacterial tracheitis, a life-threatening infection. infectious variant of the disorder, with a clinical presentation
This manifests as, mild-to-moderate illness for 2–7 days, similar to that of the acute disease but with less coryza.
followed by severe symptoms with toxic appearance and does In spasmodic croup, subglottic edema occurs without the
not respond well to nebulized epinephrine. inflammation typical in viral disease.
Table 2: Management of croup (as per severity)

Mild Moderate-to-severe Impeding respiratory failure
• Reassurance, education • 100% humidified oxygenation • 100% humidified oxygenation
regarding course of disease and • Avoid agitation • Avoid agitation
monitoring at home • Position of comfort • Nebulized epinephrine
• Avoid agitation • Nill orally • Dexamethasone IM/IV
• Position of comfort in parent’s • Nebulized epinephrine • Ventilation support, if needed, initially with a bag and mask
lap
• Dexamethasone/inhaled budesonide • Endotracheal intubation* (with tube 0.5–1 mm smaller
• Avoid unnecessary painful than predicted) if respiratory fatigue/worsening
procedures • Observe for at least 2 hours after
giving nebulised epinephrine (to see hypercarbia
• Consider dexamethasone no recurrence of stridor) • Prepare for surgical airway if needed
*Endotracheal intubation with upper airway obstruction is a high risk procedure and should be performed by a team with airway expertise.
Algorithm 1
Algorithm for croup
142 To decide severity, refer Table 1.
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Chapter 32: Croup
Spasmodic croup (recurrent croup) typically presents at 10. Chun R, Preciado DA, Zalzal GH, Shah RK. Utility of bronchoscopy for recurrent
night with the sudden onset of “croupy” cough and stridor. The croup. Ann Otol Rhinol Laryngol. 2009;118(7):495-9.
child may have had mild upper respiratory complaints prior 11. Donnelly BW, McMillan JA, Weiner LB. Bacterial tracheitis: report of eight new
cases and review. Rev Infect Dis. 1990;12(5):729-35.
to this, but more often has behaved and appeared completely
12. Edwards KM, Dundon MC, Altemeier WA. Bacterial tracheitis as a complication of
well prior to the onset of symptoms.
viral croup. Pediatr Infect Dis. 1983;2(5):390-1.
Allergic factors may cause recurrent croup, due to the 13. Fifoot AA, Ting JY. Comparison between single-dose oral prednisolone and oral
patient becoming sensitized to viral antigens. Another dexamethasone in the treatment of croup: a randomized, double-blinded clinical
diagnostic consideration is GER. Studies of children presenting trial. Emerg Med Australas. 2007;19(1):51-8.
with recurrent croup have reported relief of their respiratory 14. Geelhoed GC. Budesonide offers no advantage when added to oral dexamethasone
symptoms when treated for reflux. in the treatment of croup. Pediatr Emerg Care. 2005;21(6):359-62.
15. Guidelines for the diagnosis and management of croup. 2008 update. Alberta
Medical Association; 2011.
Key points 16. Hoa M, Kingsley EL, Coticchia JM. Correlating the clinical course of recurrent
croup with endoscopic findings: a retrospective observational study. Ann Otol
))
It is a viral (parainfluenza) infection with subglottic airway
Rhinol Laryngol. 2008;117(6):464-9.
obstruction, in age 1–3 years
17. Huang CC, Shih SL. Images in clinical medicine. Steeple sign of croup. N Engl J
))
Presents with upper respiratory infection days, then hoarse Med. 2012;367(1):66.
voice, barking cough, inspiratory stridor, distress 18. Jones R, Santos JI, Overall JC. Bacterial tracheitis. JAMA. 1979;242(8):721-6.
))
Absence of drooling and nontoxic patient helps to 19. Kairys SW, Olmstead EM, O’Connor GT. Steroid treatment of laryngotracheitis: a
differentiate it from supraglottic pathology meta-analysis of the evidence from randomized trials. Pediatrics. 1989;83(5):
))
Diagnosis is almost always clinical and no role of laboratory/ 683-93.
radiological investigations 20. Kirks DR. The respiratory system. Practical Pediatric Imaging: Diagnostic
Radiology of Infants and Children, 3rd edition. Philadelphia, Pa: Lippincott-Raven;
))
Assessment of severity is clinical, which decides treatment
1998. pp. 651-3.
))
Nebulized epinephrine and steroids are the cornerstone 21. McGee DL, Wald DA, Hinchliffe S. Helium-oxygen therapy in the emergency
treatment of croup department. J Emerg Med. 1997;15(3):291-6.
))
Recovery is seen within 12–24 hours of steroid and prognosis 22. Russell K, Wiebe N, Saenz A, Ausejo SM, Johnson D, Hartling L, et al.
is excellent. Glucocorticoids for croup. Cochrane Database Syst Rev. 2004;(1):CD001955.
23. Russell KF, Liang Y, O’Gorman K, Johnson DW, Klassen TP. Glucocorticoids for
croup. Cochrane Database Syst Rev. 2011;(1):CD001955.
SUGGESTED READINGs 24. Scolnik D, Coates AL, Stephens D, Da Silva Z, Lavine E, Schuh S. Controlled
delivery of high vs low humidity vs mist therapy for croup in emergency
1. [Guideline] Alberta Medical Association. Guideline for the diagnosis and
departments: a randomized controlled trial. JAMA. 2006;295(11):1274-80.
management of croup. Alberta Clinical Practice Guidelines 2005 Update.
2. American Academy of Pediatrics. Parainfluenza viral infections. In: Pickering 25. Sparrow A, Geelhoed G. Prednisolone versus dexamethasone in croup: a
LK (Ed). Red Book: 2003 Report of the Committee on Infectious Diseases, 26th randomised equivalence trial. Arch Dis Child. 2006;91(7):580-3.
edition. Elk Grove Village, IL: American Academy of Pediatrics; 2003. pp. 479-81. 26. Sung JY, Lee HJ, Eun BW, Kim SH, Lee SY, Lee JY, et al. Role of human
3. Beckmann KR, Brueggemann WM. Heliox treatment of severe croup. Am J Emerg coronavirus NL63 in hospitalized children with croup. Pediatr Infect Dis J.
Med. 2000;18(6):735-6. 2010;29(9):822-6.
4. Benson BE, Baredes S, Schwartz RA. (2015). Stridor. [online] Available from http:// 27. Terregino CA, Nairn SJ, Chansky ME, Kass JE. The effect of heliox on croup: a
emedicine.medscape.com/article/995267-overview. [Accessed December, pilot study. Acad Emerg Med. 1998;5(11):1130-3.
2015]. 28. Vorwerk C, Coats T. Heliox for croup in children. Cochrane Database Syst Rev.
5. Bernstein T, Brilli R, Jacobs B. Is bacterial tracheitis changing? A 14-month experience 2010;(2):CD006822.
in a pediatric intensive care unit. Clin Infect Dis. 1998;27(3):458-62. 29. Vorwerk C, Coats TJ. Use of helium-oxygen mixtures in the treatment of croup: a
6. Bjornson C, Russell KF, Vandermeer B, Durec T, Klassen TP, Johnson DW. systematic review. Emerg Med J. 2008;25(9):547-50.
Nebulized epinephrine for croup in children. Cochrane Database Syst Rev. 30. Wald EL. Croup: common syndromes and therapy. Pediatr Ann. 2010;39(1):
2011;(2):CD006619. 15-21.
7. Bjornson CL, Klassen TP, Williamson J, Brant R, Mitton C, Plint A, et al. A 31. Weber JE, Chudnofsky CR, Younger JG, Larkin GL, Boczar M, Wilkerson
randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J MD, et al. A randomized comparison of helium-oxygen mixture (Heliox) and
Med. 2004;351(13):1306-13. racemic epinephrine for the treatment of moderate to severe croup. Pediatrics.
8. Cetinkaya F, Tufekci BS, Kutluk G. A comparison of nebulized budesonide, and 2001;107(6):E96.
intramuscular, and oral dexamethasone for treatment of croup. Int J Pediatr 32. Williams JV, Harris PA, Tollefson SJ, Halburnt-Rush LL, Pingsterhaus JM, Edwards
Otorhinolaryngol. 2004;68(4):453-6. KM, et al. Human metapneumovirus and lower respiratory tract disease in
9. Chub-Uppakarn S, Sangsupawanich P. A randomized comparison of dexa otherwise healthy infants and children. N Engl J Med. 2004;350(5):443-50.
methasone 0.15 mg/kg versus 0.6 mg/kg for the treatment of moderate to 33. Zoorob R, Sidani M, Murray J. Croup: an overview. Am Fam Physician. 2011;83(9):
severe croup. Int J Pediatr Otorhinolaryngol. 2007;71(3):473-7. 1067-73.
143
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Chapter 33
Approach to a Child with
Acute Febrile Encephalopathy
Surpreet BS Nagi
INTRODUCTION Acute Febrile Encephalopathy

A child presenting with fever and altered sensorium is a common Acute febrile encephalopathy is a clinical diagnosis and is
pediatric emergency. Acute febrile encephalopathy (AFE) is a described as a syndrome of altered sensorium associated with
clinical term used to describe an altered mental state that either fever of less than 1 week duration, and altered consciousness
accompanies or follows a short febrile illness and is characterized of more than 12-hours duration, with or without seizures in a
by a diffuse and nonspecific brain insult manifested by a previously normal child.
combination of coma, seizures, and/or decerebration.
Encephalopathy is a diffuse disease affecting the brain that Encephalitis
alters its structure or function and may be caused due to diverse Encephalitis means inflammation of the brain. It is strictly a
etiology like infective, metabolic, toxic, ischemic, nutritional pathological diagnosis; but surrogate clinical/imaging markers
causes or trauma. In febrile illnesses, encephalopathy may may provide evidence of inflammation.
result from pathogenic mechanisms affecting the nervous
system directly or systemic complications like hypoglycemia,
hypovolemia, hyperpyrexia, hypoxia, anemia, hepatic or renal
Acute Encephalitis Syndrome
failure, toxins, vasculitis, and bleeding. Clinically, a case of acute encephalitis syndrome (AES) is
Central nervous system (CNS) infections are the most defined as a person of any age, at any time of year with the
common cause of AFE in children. Various causes such as viral acute onset of fever and a change in mental status (including
encephalitis, cerebral malaria, bacterial meningitis, Reye’s symptoms such as confusion, disorientation, coma, or inability
syndrome, and inflammatory encephalopathies including to talk) and/or new onset of seizures (excluding simple febrile
acute disseminated encephalomyelitis (ADEM), etc. have been seizures). Other early clinical findings may include an increase
implicated in the etiology; and the proportionate contribution in irritability, somnolence, or abnormal behavior greater than
of each varies according to the geographical area. In tropical that seen with usual febrile illness.
countries like India, cerebral malaria, Japanese encephalitis
(JE), herpes simplex encephalitis (HSE), and bacterial PATHOPHYSIOLOGY
meningitis are the common causes of AFE, while tuberculous
meningitis (TBM) usually presents with a subacute or chronic The pathophysiology of AFE usually is multifactorial and varies
history. Even after a detailed diagnostic workup, one may not be according to the etiology. Encephalopathy generally results
able to arrive at a definitive diagnosis in many cases. Neverthe from cytotoxic injury or disruption of neurotransmission.
less, a detailed examination and workup is warranted, because However, the final pathway is common, which is interruption
many conditions like cerebral malaria and HSE are treatable. of the polysynaptic pathways and altered excitatory-inhibitory
amino acid balance, leading to cerebral edema. All forms
of acute toxic metabolic encephalopathy interfere with the
SOME DEFINITIONS function of the ascending reticular activating system and/or its
projections to the cerebral cortex, thus leading to impairment
Encephalopathy of arousal and/or awareness, and/or seizures. Despite a
Encephalopathy describes a clinical syndrome of altered wide array of pathophysiologic mechanisms, the clinical
mental status, manifesting as reduced consciousness or altered manifestations tend to be very similar because of the common
behavior, without any inflammation of the brain. final mechanism.
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Chapter 33: Approach to a Child with Acute Febrile Encephalopathy
ETIOLOGY {{Impaired heat dissipation: Heat stroke, anticholinergic

toxicity
The etiology of AFE varies from infectious etiologies to {{ Structural lesions: Hypothalamic lesion, brainstem
noninfectious metabolic disorders (Table 1). The following are lesions, and intraventricular and subarachnoid
some of the common causes of AFE: hemorrhage
• Infections: • Miscellaneous:
{{ Meningoencephalitis: due to viruses like herpes
{{ Plant toxins like Cassia occidentalis
simplex virus (HSV) 1 and 2, human herpes virus {{ Reye’s syndrome
6, Epstein-Barr virus (EBV), varicella zoster virus, {{ Infectious or postinfectious ADEM.
cytomegalovirus, adenovirus, influenza, enterovirus,
poliovirus, measles, mumps, rubella, rabies, dengue
virus, chikungunya, arboviruses (JE, West Nile virus), EVALUATION
and retrovirus [human immunodeficiency virus (HIV)] Patients presenting with an AFE can be broadly divided into
{{ Bacterial infections like pyogenic meningitis, and
three categories (Table 2).
other organisms like Mycobacterium tuberculosis, A detailed history and physical examination is essential to
Mycoplasma pneumoniae, Listeria, Borrelia burgdorferi categorize the patient into one of these groups. At the outset,
(Lyme disease), Leptospira, Brucella, and Salmonella it is important to differentiate infective from non-infective
typhi causes, because infection mandates prompt antimicrobial
{{ Rickettsial infections, fungal infections due to crypto
therapy. There are no distinguishing clinical or radiological
coccosis, histoplasmosis, coccidioidomycosis, and
features to differentiate the various causes of viral encephalitis.
candidiasis
The clinical and the radiological findings in encephalitis should
{{ Cerebral malaria due to Plasmodium, and infection
be interpreted in the geographical and other epidemiological
with other parasites like Toxoplasma gondii and
background.
Schistosoma
{{ Brain abscess, subdural, or epidural empyema
{{ Sepsis with disseminated intravascular coagulation or APPROACH TO ACUTE FEBRILE

thrombotic thrombocytopenic purpura ENCEPHALOPATHY (ALGORITHM 1)
• Noninfective causes:
{{ Overproduction of heat: Neuroleptic malignant Step 1: Initiate Resuscitation and Assess
syndrome, malignant hyperthermia, non-convulsive Neurological Status
status epilepticus (NCSE), and thyrotoxic encephalo
pathy As in any emergency, one needs to quickly evaluate the
airway, breathing, and circulation (ABC’s). It is during this
assessment that alteration of sensorium is first recognized
Table 1: Etiology of acute febrile encephalopathy (or confirmed). Initial neurological examination includes only
Diagnosis Number of cases (%) a survey of vital signs, including respiratory patterns, Glasgow
Coma Scale (GCS) score, pupillary response, and extraocular
Suspected viral etiology 57 (37.3) muscle examination. The common goal in the treatment of a
Pyogenic meningitis 51 (33.8) patient with encephalopathy is to prevent secondary injury
Tubercular meningitis 12 (7.9) by maintaining oxygen delivery and supply of nutrients to the
brain. Thus, the ABC’s of basic life support supersede all other
Cerebral malaria 08 (5.2) interventions.
Dyselectrolytemia 06 (4) If the initial assessment suggests that the child is unstable,
Hepatic encephalopathy 03 (2) then the management priorities should be directed to ensuring
DKA 03 (2) Table 2: Categories of patients presenting with an acute febrile

ADEM 02 (1.3) encephalopathy
Septicemia 02 (1.3) Category Common causes

Reye’s syndrome 03 (2) Primary CNS infections Meningitis, encephalitis (HSV, JE), TBM,
and brain abscess
Shigellosis 01 (0.67)
Systemic infections Shigella, typhoid, malaria, dengue, and
Enteric fever 01 (0.67) rickettsial infections
Prolonged coma after seizure 01 (0.67) Noninfectious causes ADEM, Reye’s syndrome, and
IC bleed due to aplastic anemia 01 (0.67) mitochondrial and other IEMs, drugs and
toxins, SOLs
Total 151 (100)
CNS, central nervous system; HSV, herpes simplex virus; JE, Japanese
DKA, diabetic ketoacidosis; ADEM, acute disseminated encephalomyelitis; IC, encephalitis; ADEM, acute disseminated encephalomyelitis; IEMs, inborn errors
intracranial. of metabolism; SOLs, space occupying lesions; TBM, tuberculous meningitis. 145
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Algorithm 1
Approach to a child with acute febrile encephalopathy
ABC’s, airway, breathing, and circulation; GCS, Glasgow Coma Scale; ICP, intracranial pressure; NS, normal saline; CBC, complete blood
count; ABG, arterial blood gas; LFT, liver function test; CT, computed tomography; MRI, magnetic resonance imaging; ICU, intensive care unit;
AVPU, alert, voice, pain, and unresponsive scale; XRC, X-ray chest.
146
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adequacy of airway, breathing, and circulatory function, (PaCO2 <30 mmHg) are only justified in patients with
irrespective of the etiology. Depending on the degree of transtentorial herniation.
instability, this initial management may actually precede the Attempt should be made to maintain the cerebral
assessment of the degree of impairment of consciousness; perfusion pressure (CPP), which is the major factor that
though usually, both are carried out nearly simultaneously. affects cerebral blood flow and hence, adequate oxygenation.
The depth of coma can be assessed by the GCS or the AVPU Cerebral perfusion pressure depends on the mean arterial
scale (Wherein A-Alert, V-Response to Voice, P-Response to pressure (MAP) and the ICP (CPP = MAP − ICP). Cerebral
Pain and U-Unresponsive). A modified GCS should be used perfusion pressure can reduce as a result of reduced MAP or
for infants and young children. In case of any confusion about raised ICP or a combination of these two. Therefore, adequate
the assessment, it is preferable to err on the side of recording a MAP should be maintained. If the ICP rises, the blood pressure
lower score initially, since it is easier to withdraw treatment in (BP) rises as a compensatory phenomenon in order to try and
a child who is improving, rather than to resuscitate a child who maintain the cerebral perfusion. However, there is a limit to
is deteriorating. such compensation, beyond which the cerebral perfusion
Assessment of the airway and need for intubation is may suffer. Cerebral ischemia is the single-most important
of paramount importance as the children with impaired determinant that decides the outcome of such patients.
consciousness are at a high risk for aspiration (Box 1). These Once the airway and breathing have been addressed,
children have loss of tone of the oropharyngeal muscles circulation must be evaluated. This involves assessment of
causing the tongue to fall back and obstruct the airway, and the cardiac output. Symptoms of shock include tachycardia,
pooling of secretions (leading to aspiration). Measures should cool extremities, delayed capillary refill time, mottled or pale
be taken to secure the airway. If the child shows signs of skin, and effortless tachypnea. Hypotension is a late finding in
airway obstruction, repositioning of the head with the chin lift shock. Vascular access is necessary for volume resuscitation
maneuver may alleviate the obstruction. If cervical spine injury in patients with impaired circulation. While establishing an
is suspected, a jaw thrust maneuver is preferable and the neck intravenous access, samples should be drawn for various
immobilized while securing the airway. An oral airway may be investigations. If there is evidence of circulatory failure, fluid
inserted if required and secretions cleared using a large-bore- bolus (20 mL/kg of normal saline; maximum 60 mL/kg)
suction cannula. should be administered. If there is evidence of septic shock,
Once the airway patency has been established, the larger volumes (60–80 mL/kg) may be needed to correct the
adequacy of breathing should be evaluated. Auscultation of shock. Once an intervention is performed, the clinician must
the lung fields should assess for air entry, symmetry of breath reassess the patient. Raised ICP is not a contraindication for
sounds, and presence of adventitious breath sounds such as fluid administration for the correction of shock. Effective
crackles or wheezes. Pulse oximetry can be used to evaluate circulation through intravenous isotonic fluid administration
oxygenation. Oxygen should be administered to all seriously- and inotropes, if necessary, is essential to deliver oxygen
ill children via non-rebreathing face mask. Adequacy of and metabolic substrates to the brain and remove toxic
ventilation should be assessed by examination and arterial metabolites. Hypotonic fluids like 5% or 10% dextrose can lead
blood gases. If the airway is patent but the child’s respiratory to cerebral edema in children with raised ICP and should not
effort is deemed inadequate, positive pressure ventilation be administered. Aim should be to maintain the BP at around
should be initiated. The airway interventions should be the 95th percentile in order to maintain CPP in the face of an
instituted as nontraumatically as possible, as they may elevated ICP.
cause spikes in intracranial pressure (ICP). Rapid-sequence Raised ICP is a common cause of death in children with
intubation is preferred. Moderate hyperventilation (target AFE. It is important to recognize and promptly manage signs
PaCO2 30–35 mmHg) to produce arterial constriction and of raised ICP (Box 2). A common mistake in the emergency
lower ICP should only be initiated for patients with signs of departments is to mistake decerebrate posturing for seizures,
increased ICP. Extreme hyperventilation has been associated and inappropriately treat with antiepileptic drugs. Almost
with brain ischemia; the risks of aggressive hyperventilation all cases of non-traumatic coma have an element of raised
ICP. Signs of raised ICP should be picked up early. A careful
examination of the fundus is mandatory in all children with
Box 1: Recommendations for intubation
• GCS <12, or deteriorating GCS scores
• Impaired airway reflexes Box 2: Signs of raised intracranial pressure
• Abnormal respiratory pattern (Respiratory depression)
• Worsening Glasgow Coma Scale despite correction of airway,
• Neurogenic hyperventilation breathing, and circulation
• Signs of raised intracranial pressure • Persistence of abnormal posturing
• Evidence of herniation • Abnormal breathing patterns
• Asymmetric or dilated pupils • Abnormal pupillary response
• Oxygen saturation <92% despite high flow oxygen • Doll’s eye reflex
• Fluid refractory shock • Cushing’s triad (late sign)
GCS, Glasgow Coma Scale. • Papilledema 147
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altered sensorium. Acute elevation of ICP will not cause case of refractory seizures. Subtle seizures (NCSE) should
papilledema in the acute stages. Hence, its absence must be identified and treated appropriately, as unrecognized
not be taken as a reassuring sign. Neither, will a computed seizure activity increases the ICP and could precipitate
tomography (CT) pick up raised ICP in the acute stage. herniation. Non convulsive status epilepticus manifests, as
If there are features of raised ICP, measures to decrease an abnormal and fluctuating impairment of consciousness,
ICP should be rapidly instituted. Early interventions to reduce diminished responsiveness; and may be picked up on an
ICP include treating fever, maintaining the head in the midline electroencephalogram (EEG), and often showing a delayed
with an elevation of 15–30° above the horizontal and moderate response (4–5 days in some patients) to anticonvulsant
hyperventilation (target PaCO2 30–35 mmHg). Mannitol medications.
should be given in a dose of 0.25–0.5 g/kg intravenously over Agitation may increase ICP, interfere with respiratory
15 minutes, and repeated every 4–6 hourly; only if required. support, and increase the risk of injury. Efforts should be
It should not be administered round the clock and is unlikely taken to provide pain relief and sedation during painful
to be effective after 48–72 hours. Furosemide is often used in procedures. Significant sedation, however, may obscure the
conjunction with mannitol. Hypertonic saline (3%) may be neurologic examination, may contribute to hypotension and
preferred in hypotensive or hypoperfused patients for reducing hypoventilation, and should be administered only when the
the ICP while maintaining the MAP and CPP. A neurosurgical benefits of relieving agitation outweigh the need for close
consultation should be asked for. neurologic monitoring by examination.
Clinical Pearls Key points

• Airway, breathing and circulation of basic life support Initial steps in resuscitation
supersede all other interventions
))
Assess airway, breathing and circulation and stabilize
• Initial management may actually precede the assessment of the
degree of impairment of consciousness in an unstable child ))
Assess level of consciousness (modified Glasgow Coma Scale
or Alert, Voice, Pain Unresponsive Scale)
• Preferable to record a lower glasgow coma scale score initially
• Airway interventions should be instituted as nontraumatically ))
Secure airway, oxygenation, and ventilation, rapid sequence
as possible intubation preferred, maintain cerebral perfusion pressure
• Maintain cerebral perfusion pressure ))
Secure vascular access, isotonic fluids, inotropes
• Reassess after every intervention ))
Assess and treat for immediately correctable causes (glucose,
• Almost all cases of nontraumatic coma have an element of electrolytes, acid-base abnormalities)
raised intracranial pressure ))
Assess and treat raised intracranial pressure: Head 15–30º,
• Normal fundus or normal neuroimaging does not rule out a midline, mild hyperventilation, mannitol, furosemide, 3%
raised intracranial pressure. normal saline
))
In case of signs of herniation—sedation, paralysis, intubation,
Treatment of associated conditions is of paramount ventilation
importance. Normothermia should be maintained. The use ))
Identify and treat aggravating factors—seizures, noncon
of therapeutic hypothermia (32–34°C) may be appropriate vulsive status epilepticus, fever, pain, anxiety
for children with out-of-hospital arrest and persistent coma ))
Continuous monitoring of heart rate, respiratory rate, blood
or those with ventricular fibrillation or pulseless ventricular pressure, temperature, oxygen saturations, electrocardiogram,
tachycardia. Acid-base and electrolyte abnormalities should Glasgow Coma Scale.
be corrected.
If hypoglycemia is present, intravenous glucose bolus
should be administered. In a neonate, 2 mL/kg of 10% Step 2: Take History and
IV dextrose bolus; and in an older child 5 mL/kg of 10% Perform Focused Examination
IV dextrose bolus should be given. Thereafter, the sugar
levels should be monitored and the glucose infusion rates History (Table 3)
modified accordingly. Hyperglycemia resulting from stress is The patient’s history may hold the most important and
a more common finding in these conditions. Hypoglycemia sometimes the only clue to a correct diagnosis. A careful
damages the brain immediately and needs urgent correction. history should be taken with special emphasis on the onset and
Hyperglycemia, on the other hand, is associated with a higher duration of encephalopathy and the type and degree of fever.
morbidity and mortality if not treated; and hence tight glycemic The child, who has been apparently well prior to the onset of
control should be the aim. encephalopathy and has an acute onset of illness, may have
If the child is having seizures, or there is history of a seizure suffered from poisonings, drug overdose, metabolic disorders
preceding the encephalopathy, anticonvulsants (intravenous or child abuse, as the probable causes. Central nervous system
benzodiazepine followed by phenytoin loading 20 mg/kg or infections, on the other hand, would present with complaints
fosphenytoin) should be administered. The standard protocol evolving over a few days associated with a history of fever or
148 for the management of status epilepticus may be followed in recent illness. Disorders in which encephalopathy may be
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Table 3: Important clues in the history of acute febrile Table 4: Important clues in general examination in acute febrile
encephalopathy encephalopathy
History Probable etiology Clinical finding Probable etiology
Geographic area or residence of the Endemic for JE, malaria Pallor Cerebral malaria, typhoid,
child intracranial bleed
Recent travel Malaria, dengue, typhus, Icterus Leptospirosis, cerebral malaria
arbovirus
Generalized lymph EBV, leptospirosis, HIV
Similar illness in the family or locality Epidemic of AES, HSV, JE adenopathy
Prodromal symptoms like a URI, flu- H1N1, enterovirus, polio Skin rashes Meningococcemia, arboviruses,
like illness or diarrhea varicella, rickettsia, dengue,
Congenital heart disease, chronic Brain abscess measles, enterovirus
ear infections, sinusitis, orbital Petechiae Meningococcemia, dengue, viral
cellulitis, or dental infection hemorrhagic fevers
Dog bite Rabies Erythema nodosum Tuberculosis, histoplasmosis
Insect or mosquito bite Rickettsial infection, Parotid swelling and orchitis Mumps
malaria, dengue, JE
Mucous membrane lesions Herpes simplex virus
Contamination with dirty water Leptospirosis and shallow ulcers
Contact with tuberculosis TBM Abnormal odor of breath Diabetic ketoacidosis, hepatic
Recent immunizations ADEM coma
Treatment history prior to the Partially-treated bacterial Myalgia, arthralgia Leptospirosis, dengue
presentation meningitis
Hypotension, shock Dengue, leptospirosis, cerebral
Exposure to drugs or toxins at home Poisoning, nonaccidental malaria
trauma
Organomegaly EBV, dengue, leptospirosis, HIV
Past history of similar episodes IEM
EBV, Epstein-Barr virus; HIV, human immunodeficiency virus.
JE, Japanese encephalitis; AES, acute encephalitis syndrome; HSV, herpes
simplex virus; URI, upper respiratory infection; TBM, tuberculous meningitis;
ADEM, acute disseminated encephalomyelitis; IEM, inborn error of metabolism. children. The degree of fever, the presence of tachycardia out-
of-proportion to the fever, and the presence of tachypnea and
preceded by a febrile illness include ADEM, Reye’s syndrome, hypotension, when present, are ominous signs.
mitochondrial and other inborn errors of metabolism. The presence of fever suggests an infective process (sepsis,
The associated symptoms may indicate the focus of pneumonia, meningitis, encephalitis, or brain abscess); but
infection. Symptoms such as headache, nausea and vomiting, may also indicate heat stroke or abnormality of hypothalamic
irritability, seizures, focal deficits, rash, and joint pain temperature regulatory mechanisms. Tachycardia may be a
should be enquired into in depth. Other concurrent systemic result of fever, hypovolemic or septic shock, heart failure, or
illnesses, e.g., jaundice (hepatic failure), pneumonia (hypoxic arrhythmias. Bradycardia may result from raised ICP or a result
encephalopathy), diarrhea (dyselectrolytemia), and dysentery of myocardial injury (myocarditis, hypoxia, sepsis, or toxins).
(shigella encephalopathy) need to be elicited in the history. Tachypnea with respiratory distress indicates lung pathology
Nonaccidental trauma should always be considered in a (pneumonia, pneumothorax, empyema, or asthma). Quiet
lethargic infant. tachypnea is indicative of acidosis which may be present in
Other history which may offer some aid in the diagnosis: diabetic ketoacidosis (DKA), uremia, or some poisonings.
• History of trauma, recent illness, or surgery (splenectomy, Hypotension may be seen in sepsis, cardiac dysfunction,
neurosurgery) toxic ingestion, or adrenal insufficiency, and may lead to
• Family history of seizure disorders or previous child deaths poor cerebral perfusion, resulting in diffuse or watershed
• Comorbid conditions like congenital heart disease, hypoxic-ischemic injury. Hypertension may be the cause of
diabetes, chronic liver, or renal diseases altered sensorium in hypertensive encephalopathy or may be
• Premorbid developmental or neurological status of the a compensatory mechanism to maintain cerebral perfusion in
child children with increased ICP or stroke.
• Immunosuppressive states (HIV), chemotherapy, and A thorough systemic examination should be performed
prolonged steroids. to look for a source of sepsis. Systemic examination must be
performed to look for hepatosplenomegaly (infections or
Examination liver disease), pulmonary involvement such as pneumonia,
pleural effusions, and empyema, skin and bone lesions and
General examination (Table 4) cardiac involvement such as myocarditis or a pre-existing
The general examination may provide helpful etiological clues. congenital or rheumatic heart disease (which may predispose
Vital signs are often overlooked but are valuable in assessing ill to endocarditis and subsequently intracranial abscess). 149
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Detailed neurological examination The presence of oculocephalic (doll’s eye), oculovestibular,

The neurological examination is targeted to document corneal, cough, and gag reflexes must be looked for to check
the level and localization of brain dysfunction. It may for brainstem function. Brainstem dysfunction is an important
also provide information about the potential causes. This feature in some causes of viral encephalitis such as enterovirus
includes assessment of the level of consciousness, patterns 71, mumps, and rabies and in all causes when the ICP has risen
progressively.
of respiration, and signs of meningeal irritation, fundus and
Fundus examination must be performed to look for
pupillary examination, signs of cranial nerve involvement,
papilledema and retinal hemorrhages. Retinal hemorrhages
presence of focal deficits, signs of raised ICP, brainstem signs
are an important clue for cerebral malaria in endemic setting,
and autonomic signs.
being present in nearly a quarter of the patients.
The level of consciousness must be recorded in the form of
an objective scale, such as the GCS or the AVPU score. While
the GCS allows efficient, standardized communication of a
Clinical Pearl
child’s state, a more detailed description of the child’s clinical
• Unilateral pupillary dilatation in the comatose patient should
findings is often more useful for relaying detailed information be considered as evidence of oculomotor nerve compression
and detecting changes over time. from ipsilateral uncal herniation, unless proved otherwise.
Respiratory pattern abnormalities signify either a metabolic
derangement or a neurological insult (Table 5).
Motor examination (Table 6)
Pupils Assessment of muscle strength, tone, and tendon reflexes
Pupillary size, shape, symmetry, and response to light provide should be done for normality and symmetry. The trunk,
valuable clues to brainstem and third nerve dysfunction. The limb position, spontaneous movements, and response to
presence or absence of the pupillary reaction to light is one stimulation must be observed to look for any focal deficits
of the most important differentiating features to distinguish (suggestive of postictal Todd’s palsy or structural abnormality),
between structural and metabolic disorders as metabolic and posturing (decerebrate or decorticate).
disturbances affect the pupillary pathways late. Usually in Special attention should be given to posturing because it
metabolic disorders leading to altered level of consciousness, often signals a brainstem herniation syndrome.
• Decorticate posturing: Flexion of upper limbs and
pupils remain reactive in the initial stages. But in structural
extension of the lower limbs. It suggests involvement of the
disorders with increased ICP, signs of herniation syndrome
cerebral cortex and preservation of brainstem function
will appear. Topical administration of mydriatics must
• Decerebrate posturing: Rigid extension of both arms and
be avoided, but if done, should be documented to avoid
legs indicative of cortical and brainstem dysfunction
confusion in interpretation. Abnormalities of eye position
• Opisthotonus: Neck is hyperextended and the teeth are
and movement may provide some clues. Conjugate clenched; the arms are adducted and hyperextended; and
lateral deviation of the eyes is a sign either of an ipsilateral the legs are extended with feet plantar flexed. It indicates
hemisphere lesion, a contralateral hemisphere seizure focus, severe brainstem dysfunction
or damage involving the contralateral pontine horizontal • The flaccid patient with no response to painful stimuli
gaze center (parapontine reticular formation). Lateral gaze indicates deep brainstem dysfunction
palsy may signal central herniation with compression of • Monoplegia or hemiplegia, except when in postictal phase,
bilateral sixth nerves. Tonic upward gaze has been associated suggests a structural disturbance of the contralateral
with bilateral hemispheric damage. hemisphere (herniation across falx).
Table 5: Types of abnormal respiratory patterns

Pattern Lesion Presentation Conditions
Cheyne-Stokes Deep hemispheric Hyperpnea alternates with apnea Strokes, traumatic brain injuries, brain tumors, carbon
respiration or diencephalic dioxide poisoning, metabolic encephalopathy, high
dysfunction altitude sickness, normal side effect of IV morphine
administration
Central neurogenic Midbrain dysfunction Sustained, deep, regular, and rapid Strokes, traumatic brain injuries. Increasing irregularity
hyperventilation respiration of this respiratory pattern generally is a sign that the
patient will enter into coma
Apneustic Damage to the pons Inspiratory pauses, lasting 2–3 Strokes, trauma, pontine infarction, anoxic
or upper medulla seconds, alternating with end- encephalopathy, and ketamine (temporary)
expiratory pauses
Ataxic Damage to the Completely irregular breathing Trauma, stroke, opioid use
medulla oblongata pattern with irregular pauses and This respiratory pattern indicates a very poor prognosis
150 unpredictable periods of apnea
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Table 6: Important clues in neurological examination in acute Table 7: Clinical recognition of herniation syndromes
febrile encephalopathy
Type of herniation Clinical manifestations
CNS signs Probable etiology Uncal • Unilateral ptosis
Abnormal behavior or HSV, NCSE • Unilateral fixed dilated pupil
psychosis • Minimal deviation of eyes on
Meningeal signs Meningitis, TBM, encephalitis, ADEM oculocephalic/oculovestibular testing
hemiparesis
Ataxia ADEM, varicella, enterovirus
Asymmetric signs and TBM, encephalitis, ADEM Diencephalic • Small or midpoint pupils reactive to light
symptoms • Full deviation of eyes on oculocephalic/
oculovestibular testing
Papilledema SOL, hydrocephalus in TBM
• Flexor response to pain and/or decorticate
Opisthotonus JE, autoimmune encephalitis posturing
Cranial nerve palsies TBM, encephalitis, JE, vasculitis • Cheyne-Stokes respiration
Bowel and bladder ADEM • Hypertonia and/or hyperreflexia with
dysfunction extensor plantars
Visual loss Optic neuritis, ADEM, HT Midbrain • Midpoint pupils, fixed to light
encephalopathy
Upper pontine • Minimal deviation of eyes on
Rapidly changing CNS signs JE oculocephalic/oculovestibular testing
Acute flaccid paralysis Enterovirus, poliomyelitis, ADEM • Extensor response to pain and/or
Seizures JE, cerebral malaria, TBM, meningitis decerebrate posturing
Dystonia or extrapyramidal JE, TBM • Hyperventilation
movements Lower pontine • Midpoint pupils, fixed to light
Myoclonic jerks Enterovirus • No response on oculocephalic/
CNS, central nervous system; HSV, herpes simplex virus; NCSE, nonconvulsive oculovestibular testing
status epilepticus; TBM, tuberculous meningitis; ADEM, acute disseminated • No response to pain or flexion of legs only
encephalomyelitis; SOL, space occupying lesion; JE, Japanese encephalitis; HT, • Flaccidity with extensor plantars
hypertensive.
• Shallow or ataxic respiration
Medullary • Pupils dilated, fixed to light
Presence of signs of meningeal irritation (neck rigidity,
Kernig’s sign, and Brudzinski’s sign) must be looked for. • Slow, irregular, or gasping respiration
Kernig’s sign involves flexion of the hip to 90° with subsequent • Respiratory arrest with inadequate cardiac
output
pain on extension of the leg; Brudzinski’s sign involves
involuntary flexion of the knees and hips after passive flexion
of the neck while supine. In younger children, Kernig’s and
Brudzinski’s signs are not consistently present; especially with The various herniation syndromes can be recognized
an open fontanel. Signs of meningeal irritation may be present clinically. The importance lies in recognition and prompt
in meningitis, encephalitis, and subarachnoid hemorrhage. treatment, before the damage becomes irreversible. Treatment
Neck rigidity is present in meningitis, tonsillar herniation, or of herniation involves removal of the etiologic mass and
craniocervical trauma. surgical decompression in the form of external ventricular
The commonly seen focal signs are hemiparesis, ataxia, drainage and hemicraniectomy may be indicated (Table 7).
aphasia, pyramidal signs, and involuntary movements
(myoclonus, dystonia, tremors). Cranial neuropathies of the Step 3: Send Basic Investigations
ocular, oculomotor, abducens, facial, and auditory nerve
should be looked for. Basic Investigations
Signs of increased intracranial tension in children range Basic workup like complete blood count with platelet count,
from headache, vomiting to herniation. It is best to suspect peripheral smear, blood culture, blood glucose, liver and renal
raised ICP and start treating it, on clinical grounds alone. Raised profile, coagulation parameters, and electrolytes should be
ICP, when untreated, can also lead to herniation of the brain, obtained in all patients presenting with an AFE. An arterial
which causes direct mechanical damage as well as ischemia blood gas, chest X-ray, serum ammonia, and serum lactate
and hemorrhage secondary to vascular distortion. Brain tissue should be sent if required.
deforms intracranially and moves from higher to lower pressure All patients with febrile encephalopathy should undergo
when there is asymmetric, unilateral, or generalized increased blood cultures. Relative lymphocytosis in the peripheral
ICP. This gives rise to the various herniation syndromes. These blood is common in viral encephalitis. Leukopenia and
syndromes, in this order (from higher to lower pressures), thrombocytopenia are noted in viral hemorrhagic fevers and
signify a progression in severity. Changes from one syndrome rickettsial infections. Typhoid fever and cerebral malaria may
to the next, signifies progressive worsening. be associated with severe anemia and thrombocytopenia. 151
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Hypoglycemia and electrolyte imbalance are usually associated Table 9: Diagnostic criteria used for some common etiologies
with CNS infection and they may contribute to altered of acute febrile encephalopathy
sensorium. Serum creatinine and blood urea are helpful to
Diagnosis Criteria
assess the renal function and serum bilirubin, transaminases
and prothrombin time are indicated if jaundice is present. HSV encephalitis • Nonspecific prodrome, exanthem ±
An X-ray chest may show changes suggestive of tuberculosis, • Fever with altered sensorium, focal signs +,
mycoplasma, or legionellosis. neck signs +
In endemic areas, look for malaria (peripheral smear • CSF cytology (predominant lymphocytes),
and rapid detection tests), dengue (serology and NS1 Ag), CSF PCR and serology
Leptospira (antibody tests), enteric fever (blood culture), • EEG: Periodic lateralized epileptiform
typhus (antibody test), and JE (antibody in serum and CSF) as discharges
the probable etiology. • MRI/CT: Frontotemporal pathology
Japanese • Disorientation and delirium → somnolence,
encephalitis then progressing to coma
Table 8: Specific therapy according to the etiology of acute • Rapidly changing central nervous system
febrile encephalopathy signs, seizures
• CSF pleocytosis, PCR, antigen tests
Diagnosis Specific therapy
• Albuminuria
Herpes simplex virus Acyclovir-DOC, valacyclovir, foscarnet
Pyogenic • Fever with altered sensorium, no focal
Varicella zoster Acyclovir meningitis signs, neck signs +
Human herpes virus 6 Foscarnet, ganciclovir • CSF cytology (predominant neutrophils)
• MRI/CT: Meningeal enhancement
Cytomegalovirus Ganciclovir
Tubercular • Stage 1: nonspecific signs, stage 2—neck
Enterovirus Pleconaril
meningitis signs, signs of ↑ ICP, cranial nerve palsies,
Rickettsia Doxycycline, erythromycin focal signs, stage 3—coma, decorticate/
decerebrate posturing
Mycoplasma Azithromycin
• CSF compatible with TBM, isolation of AFB,
Leptospirosis Penicillin ADA ↑
Tuberculosis Antitubercular drugs • MRI/CT: hydrocephalus, basal exudates,
tuberculoma
Pyogenic meningitis Ceftriaxone + vancomycin
Cerebral malaria • Fever with altered sensorium ± focal signs,
ADEM Steroids, IVIG frequent seizures hypoglycemia
ADEM, acute disseminated encephalomyelitis; IVIG, intravenous immuno • Peripheral smear +, rapid antigen test +
globulin; DOC, drug of choice.
ADEM • Fever much earlier than the onset of
encephalopathy
• Cranial nerve palsies, visual loss, ataxia,
Key points motor and sensory deficits, bladder/bowel
dysfunction, and spinal cord demyelination
Baseline investigations recommended in acute febrile
• CSF compatible (↑ proteins, N sugars,
encephalopathy
N cytology)
))
Complete blood count with platelets, peripheral smear • EEG: Generalized slowing, occipital
))
Blood glucose epileptiform discharges
))
Blood culture, urine examination • MRI: Diffuse white matter changes
))
Liver function tests, renal function tests, electrolytes Sepsis associated • Underlying sepsis syndrome
))
Coagulation parameters, chest X-ray encephalopathy • CSF and imaging normal
(SAE)
))
Arterial blood gas measurement, lactate, ammonia.
HSV, herpes simplex virus; CSF, cerebrospinal fluid; PCR, polymerase chain
Tests which may be done in endemic areas reaction; EEG, electroencephalogram; MRI, magnetic resonance imaging; CT,
))
Malaria (peripheral smear and rapid antigen test) computed tomography; ICP, intracranial pressure; TBM, tuberculous meningitis;
AFB, acid-fast bacilli; ADA, adenosine deaminase activity.
))
Dengue (serology and nonstructural protein 1 antigen)
))
Leptospira (antibody tests)
))
Enteric fever (blood culture) Lumbar Puncture
))
Typhus (antibody test) Urgent evaluation of CSF is required when there is a suspected
))
Japanese encephalitis (antibody in serum and cerebrospinal infection of the CNS; provided the patient is hemodynamically
fluid). stable, and has no features of raised ICP. A lumbar puncture
152 is recommended in all patients with suspected CNS infections
Ch-33.indd 152 11/19/2016 1:50:52 PM

Box 3: Contraindications of lumbar puncture

scan may give valuable information such as presence of a
bleed, and basal exudates and hydrocephalus in tubercular
Lumbar puncture should be deferred in patients with meningitis. The presence of diffuse edema on CT scan may
• Abnormal breathing patterns • Abnormal doll’s eye suggest an underlying parenchymal involvement and focal
• Shock movement hypodensities in temporal lobe and basal ganglia or thalamus
• Bradycardia (HR <60) • Dilated pupils may point towards a possible diagnosis of viral encephalitis
th • Impaired pupillary reaction (HSV or JE). Computed tomography may also show brain
• Hypertension (BP >95
percentile) to light herniation, effacement of cisterns, and infective collections
• Abnormal posture such as brain abscesses and subdural empyema. Computed
• GCS <8 or deteriorating GCS
tomography should be performed immediately when the
• Convulsive SE or NCSE • Features of raised ICP
examination suggests increased ICP (papilledema, bulging
HR, heart rate; BP, blood pressure; GCS, Glasgow Coma Scale; SE, status fontanel in infants, or bradycardia with hypertension) or a
epilepticus; NCSE, non-convulsive status epilepticus; ICP, intracranial transtentorial herniation syndrome (Box 4).
pressure.
Magnetic resonance imaging (MRI): If possible, an MRI
who are febrile, have a GCS less than 12, and are less than an should be obtained, as soon as the patient is stable. Magnetic
year old [probably with an open atrial fibrillation (AF)], and resonance imaging is known to be superior in picking up
those who are clinically stable to undergo the procedure. In subtle changes and is likely to be more helpful in establishing
patients who are not stable, a neuroimaging study should be a diagnosis by picking up characteristic pattern of gray
obtained prior to the lumbar puncture (Box 3). matter involvement and meningeal enhancement. Magnetic
Cerebrospinal fluid should be examined for pressure, gross resonance imaging is more sensitive for early evidence of viral
examination for turbidity, cytology, biochemistry, Gram’s encephalitis and may show frontotemporal pathology in HSV
stain, Ziehl-Neelsen stain for acid fast bacilli, bacterial culture, infection, thalamic involvement in JE, and midbrain and pons
latex agglutination, polymerase chain reaction (PCR) for HSV involvement in enterovirus infection. It also picks up infarction,
1 and 2, and IgM antibodies for JE and for dengue virus (if diffuse axonal injury from head injury, petechial hemorrhages,
suspected), and additional cultures based on clinical suspicion cerebral venous thrombosis and necrotizing lesions in acute
(fungal or tubercular). Concurrent blood sugar must also be necrotizing encephalopathy. Magnetic resonance imaging is
measured to look for the CSF to blood sugar ratio. also useful for diagnosing alternative etiologies such as ADEM
Usual CSF findings in viral encephalitis include lymphocytic (evident as demyelination on MRI), and antibody associated
pleocytosis, mild to moderately elevated protein, and normal encephalopathies. Magnetic resonance imaging may also offer
CSF sugar. Similar findings may occur in tubercular meningitis information regarding prognosis in patients with anoxic or
and partially-treated pyogenic meningitis; however, the traumatic coma.
CSF sugar is likely to be low in these situations. Neutrophilic Magnetic resonance imaging is not needed if the etiology
predominance is seen in pyogenic meningitis with high protein is clear by other investigations, e.g., cerebral malaria, pyogenic
levels, and a Gram’s stain, latex agglutination test or culture meningitis; or if suggestive changes are seen on CT; or in
may clinch the diagnosis. epidemic situations where the likely etiology is already
Empirical treatment should be started pending the results known. In all other patients, MRI provides useful information
of lumbar puncture and/or neuroimaging studies. The CSF regarding the etiology and alternative diagnoses. However,
analysis is an important investigation in children with AES. the availability, cost, and difficulties in transporting sick and
unstable patients for MRI may be limiting factors (Box 5).
Neuroimaging
Decision for imaging should not delay the empiric therapy. CT
Box 4: Indications of computed tomography
scan of the brain is of limited value in a patient with AFE, since
it does not definitely indicate either meningeal or parenchymal • Intracranial bleed
involvement; however, it may be the only possible option • Basal exudates and hydrocephalus (tuberculous meningitis)
available in an emergency. It is known that CT scan is likely to • Herniation syndromes
be normal in many cases of viral encephalitis, especially in the • Brain abscess
early stages and is more likely to pick up abnormality in the
• Subdural empyema
later stages when the pathology is well established. Magnetic
resonance imaging is more likely to pick up early lesions in
patients with AFE and should be the radiological investigation Box 5: Indications of magnetic resonance imaging
of choice in such patients as soon as it is available.
• Frontotemporal lesions (herpes simplex virus)
Computed tomography (CT): If the child is afebrile and deeply • Thalamic involvement (Japanese encephalitis)
comatose and/or has focal signs, it is preferable to do a CT • Midbrain and pons (enterovirus)
scan prior to a lumbar puncture. Focal seizures and presence
• Demyelination (acute disseminated encephalomyelitis)
of focal neurological deficits indicate a localized lesion and are
expected to be picked up by CT scan. Computed tomography • Infarction, cerebral venous thrombosis 153
Ch-33.indd 153 11/19/2016 1:50:52 PM

infections (Weil-Felix test, and rickettsial serology) must be

Clinical Pearls performed. HIV testing should be performed in children with
• Empirical treatment should be started pending the results of unexplained encephalitis, as rarely, meningoencephalitis may
lumbar puncture be a presenting feature of primary HIV infection.
Additional studies may be indicated if there are clinical
• Decision for imaging should not delay the therapy
clues suggestive of particular infections. These may include
• Magnetic resonance imaging is preferable to computed
HSV whole blood PCR in suspected cases of disseminated
tomography, if available and affordable.
HSV infection and serologic testing for measles, mumps,
arboviruses, varicella, EBV, syphilis, and Lyme disease.
Identifiable causes like DKA and hypertensive encephalo
Step 4: Initiate Empiric Therapy
pathy should be treated according to the recommended
Empiric antimicrobial treatment is recommended when the protocols. The clinician should always be alert to the possibility
diagnosis of bacterial meningitis or herpes encephalitis is of child abuse in an infant/toddler with sudden unexplained
strongly suspected, as early treatment improves prognosis altered consciousness.
of these conditions. Treatment may impair the diagnostic In suspected cases of opioid ingestion, naloxone should
sensitivity of CSF cultures but should not affect other tests be administered; atropine and pralidoxime should be given
(total cell count, Gram’s stain, or PCR). The recommended in suspected organophosphorus poisoning and flumazenil
empiric therapy in a case of AFE is a combination of a third- should be given for benzodiazepine overdose. Antivenom is
generation cephalosporin, acyclovir and an antimalarial. recommended in cases of envenomation.
A broad-spectrum antibiotic such as ceftriaxone must be
given in a dose of 100 mg/kg/day, which can be stopped if no Other Tests
evidence of bacterial meningitis is evident in the subsequent
An EEG must be performed in all children with unexplained
CSF analysis or imaging.
altered sensorium to look for suspected NCSE. Periodic
Acyclovir must be started according to age-specific doses,
epileptiform discharges may occur in NCSE but also in
in all cases of suspected viral encephalitis, as HSE is a treatable
underlying brain injury without seizures. Diffuse theta
disease, and can be stopped if the HSV PCR in CSF is negative
and delta activity, absence of faster frequencies, and inter
or the MRI findings are not suggestive of the same. Children
mittent rhythmic delta activity are characteristic of severe
beyond the neonatal group should be treated with intravenous
encephalopathies. Periodic lateralized epileptiform discharges
acyclovir in a dose of 10 mg/kg every 8 hours given as a 1-hour
suggest herpes encephalitis or infarction. Multifocal or
infusion. A positive MRI scan and EEG have 95% sensitivity
generalized periodic discharges can also be seen with
in the diagnosis of HSE. However, if the CSF PCR for HSV or
metabolic and infectious etiologies and are characteristic
MRI have been performed very early after the symptom onset
of subacute sclerosing panencephalitis. Triphasic waves
(within 48 hours), these may be falsely negative. Hence, these
indicate a hepatic or uremic encephalopathy. Nonepileptiform
studies should be repeated before stopping acyclovir if the
features of the EEG, such as slowing or asymmetry, are largely
clinical suspicion of HSE continues to be high.
nonspecific findings, but can sometimes provide diagnostic
Empirical antimalarials must be started if there is a
or prognostic information. Continuous EEG can be used to
suspicion of cerebral malaria. The recommended antimalarial
assess and titrate the depth of sedation in patients placed
therapy is an artemisinin-based combination therapy
under anesthesia for control of status epilepticus or increased
consisting of artesunate + sulfadoxine-pyrimethamine or
ICP. Electrocardiogram may also be helpful in patients with
artemether + lumefantrine. Alternatively, quinine may be used
subtle and doubtful seizures, to guide antiepileptic drug
with strict monitoring of blood sugar levels and ECG. This
management.
should be stopped if the peripheral smear and rapid diagnostic
In cases of suspected metabolic abnormalities and
tests are negative.
unexplained or recurrent encephalopathy, blood ammonia,
urine and blood samples for amino and organic acid disorders,
Key points free fatty acid and carnitine levels should be obtained before
starting treatment and stopping feeds. Hyperammonemia
Recommended Empiric therapy for AFE
may be caused by some inborn errors of metabolism, Reye’s
))
Ceftriaxone + Acyclovir + Antimalarial. syndrome, liver failure, or valproate toxicity. Blood tandem mass
spectroscopy, urine gas chromatography-mass spectroscopy
can detect common causes of intoxication and drug abuse, and
Step 5: Send Specific
specific drug levels (suspected antiepileptic toxicity) should be
Investigations and Treat the Cause obtained if specific ingestions are suspected. In selected cases,
When the etiology is not clear, other microbiological a urine toxicology screen, thyroid function tests and thyroid
investigations must be obtained. These samples include urine, autoantibodies (Hashimoto’s encephalopathy), cortisol levels,
throat swab, nasopharyngeal aspirate, serum, and swab from carboxyhemoglobin levels (carbon monoxide poisoning),
vesicles or rash, if present. In patients having unexplained autoimmune screen (cerebral vasculitis), and coagulation
154 encephalopathy with fever and rash, testing for rickettsial studies (coagulopathy) are recommended.
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Step 6: Supportive Care and behavioral disturbances are commonly seen after viral
CNS infections. Visual disturbances due to chorioretinopathy
After stabilization of the airway, breathing, and circulation,
and peripheral amblyopia may also be seen. Myocarditis and
other supportive care measures must be instituted along
pulmonary edema are important complications of enteroviral
with the empirical treatment as mentioned above. Timely
encephalitis. Subdural effusions develop in 10–30% of patients
and appropriate supportive care is of paramount importance
with meningitis. Other complications include seizures, raised
to reduce the mortality and morbidity associated with viral
ICP, cranial nerve palsies, stroke, herniation syndromes, and
encephalitis. Patients with GCS less than 8, having features
thrombosis of the dural venous sinuses. Pericarditis or arthritis
of raised ICP, status epilepticus, and shock should ideally be
may occur in patients being treated for meningitis, especially
managed in an intensive care unit. Full sedation, controlled
that caused by Neisseria meningitidis.
ventilation, and minimal handling with elevation of the head
Rifampicin chemoprophylaxis is recommended for all close
end of the bed at 30°, should be maintained during transport
contacts of patients with meningococcal and H. influenzae B
of the child.
meningitis. Vaccination for H. influenzae B is recommended
Maintenance Intravenous Fluids for all children, and meningococcal and pneumococcal
vaccine should be given to the high-risk groups. Vaccination
Fluid therapy should be targeted to maintain euvolemia and for polio, measles, mumps, rubella and varicella should also
normoglycemia, and to prevent hyponatremia. Children with be instituted. Control of insect vectors by suitable spraying
acute viral encephalitis should receive fluids at the normal methods and eradication of insect breeding sites reduces the
daily requirement. Increased fluids and fluid boluses may be incidence of arboviral infections and malaria.
indicated for dehydration and hypotension. Serum sodium Regular posture change must be done to prevent the
should be monitored, and abnormalities of serum sodium development of bed sores. The patient should be started
should be corrected slowly. Rapid correction of hyponatremia on early physiotherapy, to prevent the development of
may lead to central pontine myelinolysis. contractures. Neurodevelopmental and audiologic evaluations
should be a part of the routine follow-up of children who have
Other Drugs
recovered from viral meningoencephalitis. Metabolic causes
Corticosteroids: Steroids are indicated in meningococcemia may need long-term dietary treatment. Psychological support
with shock, enteric encephalopathy, ADEM, Hashimoto’s needs to be rendered to the patient and family.
encephalopathy, and autoimmune encephalitis. The role of
corticosteroids in the treatment of viral encephalitis is not
established. However, corticosteroids may be considered along PROGNOSIS
with acyclovir in patients with marked cerebral edema, brain The outcome of a child with an AFE depends on the etiology,
shift or raised ICP. Dexamethasone is recommended prior and the depth and duration of impaired consciousness,
to antibiotics in H. influenzae B meningitis, as it reduces the the specific cause and the age of the child. Prolonged coma
incidence of deafness and neurological handicap. However, after a hypoxic-ischemic insult carries a poor prognosis.
this benefit is not certain for meningitis due to other organisms Most children surviving infectious encephalopathies have a
like Pneumococcus. comparatively better outcome, often surviving with mild or
If metabolic causes have been identified, e.g., DKA, hepatic moderate difficulties only. Outcome has been shown to be
encephalopathy, uremia, or hyperammonemia, these should worse for patients who were younger, had a lower GCS score
be treated appropriately. Concurrent bacterial infections like on presentation, or had absent brainstem reflexes, poor motor
pneumonia should be appropriately treated. Haloperidol responses, hypothermia, or hypotension. These children
and phenergan may be used to combat the abnormal or should be followed up for early identification of developmental
psychotic behavior. Dopamine receptor blocking agents are disabilities, learning and behavior problems, as well as other
used to control the choreoathetosis, and muscle relaxants and neurological sequelae such as motor, visual, or hearing deficit
anticholinergics may help in the management of dystonia. and seizure disorder. Acute complications like motor deficits
and cortical blindness improve with time.
Step 7: Prevention/Treatment of
Complications and Rehabilitation
CONCLUSION
The clinical course of the child should be monitored closely
and documented on a daily basis. Particular attention should Diagnostic approach to a child presenting with an AFE poses a
be paid to changing level of consciousness, fever, seizures, real challenge, especially when the history is not reliable and
autonomic nervous system dysfunction, increased ICP, and the clinical findings are not contributory towards a specific
speech and motor disturbances. etiology. A high index of suspicion should be maintained
Supportive and rehabilitative efforts are very important after for a diagnosis in these patients as time is the essence in the
patients recover. Nosocomial infections, aspiration pneumonia, management strategy. A systematic approach to the history,
and coagulation disturbances may occur as complications, thorough physical examination and appropriate investigations
and should be detected and treated promptly. Motor aimed at recognition of the etiology could aid in the diagnosis.
incoordination, convulsive disorders, total or partial deafness, Early stabilization and institution of nonspecific-supportive 155
Ch-33.indd 155 11/19/2016 1:50:52 PM

measures remain the cornerstone of management, and 15. Kneen R, Michael BD, Menson E, Mehta B, Easton A, Hemingway C, et al.
identification of the cause and its appropriate treatment need Management of suspected viral encephalitis in children - Association of British
to be instituted in order to ensure the survival and also to Neurologists and British Pediatric Allergy Immunology and Infection Group
National Guidelines. J Infect. 2012;64:449-77.
prevent long-term sequelae, neurological or otherwise.
16. Koelfen W, Freund M, Gückel F, Rohr H, Schultze C. MRI of encephalitis in
children: Comparison of CT and MRI in the acute stage with long-term follow-up.
Neuroradiology. 1996;38:73-9.
Key points 17. Kothari VM, Karnad DR, Bichile LS. Tropical infections in the ICU. J Assoc
))
Acute febrile encephalopathy is an altered mental state Physicians India. 2006;54:291-8.
18. Logan SA, MacMahon E. Viral meningitis. BMJ. 2008;336:36-40.
manifested by fever, coma, seizures, and/or decerebration
19. Mikati MA. Status epilepticus. In: Kliegman RM, Stanton BM, St. Geme J, Schor
))
Central nervous system infections are the most common N, Behrman RE (Eds). Nelson Textbook of Pediatrics, 19th ed. Saunders Elsevier;
cause of acute febrile encephalopathy in children 2011. p. 2038.
))
A definitive diagnosis may not be possible even after a 20. Modi A, Atam V, Jain N, Gutch M, Verma R. The etiological diagnosis and outcome
detailed diagnostic workup in patients of acute febrile encephalopathy: A prospective observational study at
tertiary care center. Neurol India. 2012;60:168-73.
))
Early recognition, efficient decision making and institution of
21. Murthy SN, Faden HS, Cohen ME, Bakshi R. Acute disseminated encephalomyelitis
therapy can be lifesaving.
in children. Pediatrics. 2002;110:e21.
22. Parke JT. Acute encephalopathies. In: McMillan JA, Feigin RD, DeAngelis C,
Jones MD (Eds). Oski’s Pediatrics: Principles and Practice, 4th ed. Philadelphia:
SUGGESTED READINGS Lippincott Williams & Wilkins; 2006. p. 2258.
23. Prober CG, Le Dyner L. Acute bacterial meningitis beyond the neonatal period.
1. American Heart Association. 2005 American Heart Association (AHA) guidelines In: Nelson Textbook of Pediatrics, 19th ed. Saunders Elsevier; 2011:595:2087-
for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care 2095.
(ECC) of pediatric and neonatal patients: pediatric basic life support. Pediatrics. 24. Sankhyan N, Vykunta Raju KN, Sharma S, Gulati S. Management of raised
2006;117:e989-e1004. intracranial pressure. Indian J Pediatr. 2010;77:1409-16.
2. Bansal A, Singhi S, Singhi P, Khandelwal N, Ramesh N. Non traumatic coma. 25. Saunders M, Gorelick MH. Evaluation of the sick child in the office and clinic.
Indian J Pediatrics. 2005;72:467-73. In: Kliegman RM, Stanton BM, St. Geme J, Schor N, Behrman RE (Eds). Nelson
3. Bauer T. Non-convulsive status epilepticus and coma. Epilepsia. 2010;51:177-90. Textbook of Pediatrics, 19th ed. Saunders Elsevier; 2011. pp. 275-8.
4. Bhalla A, Suri V, Singh P, Varma S, Khandelwal NK. Imaging in adult patients with 26. Schor NF. Acute disseminated encephalomyelitis (ADEM). In: Kliegman RM,
acute febrile encephalopathy. Journal of Acute Disease. 2012;1:7-12. Stanton BM, St. Geme J, Schor N, Behrman RE (Eds). Nelson Textbook of
5. Bhalla A, Suri V, Varma S, Sharma N, Mahi S, Singh P, et al. Acute febrile encephalo Pediatrics, 19th ed. Saunders Elsevier; 2011. pp. 2079-80.
pathy in adults from Northwest India. J Emerg Trauma Shock. 2010;3:220-4. 27. Sharma S, Kochar GS, Sankhyan N, Gulati S. Approach to the child with coma.
6. Chandran A, Herbert H, Misurski D, Santosham M. Long-term sequelae of Indian J Pediatr. 2010;77:1279-87.
childhood bacterial meningitis. Pediatr Infect Dis J. 2011;30:3-6. 28. Sharma S, Mishra D, Aneja S, Kumar R, Jain A. For the expert group on
7. Charles G. Prober,LauraLe Dyner: Viral Meningoencephalitis. In: Kliegman Encephalitis, Indian Academy of Pediatrics: Consensus Guidelines on Evaluation
RM, Stanton BM, St. Geme J, Schor N, Behrman RE (Eds). Nelson Textbook of and Management of Suspected Acute Viral Encephalitis in Children in India.
Pediatrics, 19th ed. Saunders Elsevier; 2011. pp. 2095-7. Indian Pediatrics. 2012;49:897-910.
8. Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B, Cossen CK, et al. 29. Shaw DW, Cohen WA. Viral infections of the CNS in children: imaging features.
Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Am J Roentgenol. 1993;160:125-33.
Infect Dis. 2006;43:1565-77. 30. Singh RR, Chaudhary SK, Bhatta NK, Khanal B, Shah D. Clinical and etiological
9. Grimwood K, Andersen P, Andersen V, Tan L, Nolan T. Twelve year outcomes profile of acute febrile encephalopathy in eastern Nepal. Indian J Pediatr.
following bacterial meningitis: Further evidence for persisting effects. Arch Dis 2009;76:1109-11.
Child. 2000;83:111-6. 31. Stevens RD, Bhardwaj A. Approach to the comatose patient. Crit Care Med.
10. Hazarika D. Approach to a child with fever and altered sensorium. Indian J Pract 2006;34:31-41.
Pediatr. 2011;13:193-206. 32. Taylor DA, Ashwal S. Impairment of consciousness and coma. In: Swaiman KF,
11. Karmarkar SA, Aneja S, Khare S, Saini A, Seth A, Chauhan BK. A study of acute Ashwal S, Ferriero DM (Eds). Pediatric Neurology: Principles and Practice, 4th ed.
febrile encephalopathy with special reference to viral etiology. Indian J Pediatr. Philadelphia: Elsevier Publications; 2006. p. 1379.
2008;75:801-5. 33. Tenembaum S, Chitnis T, Ness J, Hahn JS. Acute disseminated encephalomyelitis.
12. Kirkham FJ. Non traumatic coma in children. Arch Dis Child. 2001;85:303-12. Neurology. 2007;68:S23-S36.
13. Klig JE, O’Malley PJ. Pediatric office emergencies. Curr Opin Pediatr. 2007;19: 34. Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, et al.
591-6. Practice guideline for the management of bacterial meningitis. Clin Infect Dis.
14. 0Kneen R, Jakka S, Mithyantha R, Riordan A, Solomon T. The management of 2004;39:1267-84.
infants and children treated with acyclovir for suspected viral encephalitis. Arch 35. Yeolekar ME, Trivedi TH. Febrile encephalopathy: challenges in management. J
Dis Child. 2010;95:100-6. Assoc Physicians India. 2006;54:845-7.
156
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Chapter 34
Management of a
Child with Respiratory Distress
Sanjay M Bafna, Kochurani Abraham
INTRODUCTION INITIAL EVALUATION AND STABILIZATION

Respiratory distress (RD) is a manifestation of variety The first priority is evaluation and stabilization of airway,
of pulmonary and extrapulmonary conditions. Prompt breathing, and circulation.
recognition and early intervention prevent progression of RD
to respiratory failure (RF) and cardiorespiratory arrest. Airway
This chapter describes general management approach
The airway is assessed to see if it is patent or obstructed. This
to RD with main focus on emergency room management.
Detailed specific management of conditions causing RD is is done by “look, listen, and feel” for air movement. Abnormal
discussed elsewhere in the book. airway sounds and/or poor air entry may indicate obstructed
airway.
The airway can be clear, maintainable or not maintainable.
DEFINITIONS
Respiratory distress is a clinical state characterized by Clear Airway
abnormal respiratory rate or effort. It commonly manifests as Allow the child position of comfort.
tachypnoea and increased work of breathing.
Maintainable airway
A child with neurological illness usually has abnormal
pattern of respiration and/or bradypnoea. This essentially means that the airway may be partially
Respiratory failure is defined as a clinical state of obstructed but is maintainable by simple maneuvers like
inadequate oxygenation or ventilation or both. It is often the positioning, suctioning, removal of foreign body, or use of
end stage of RD. airway adjuncts.
• Head tilt/chin lift: if the airway is blocked by the falling
back of the tongue, it may be opened by this maneuver.
PATHOPHYSIOLOGY The rescuer places one hand on the forehead and applies
Most important function of respiratory system is oxygenation pressure to tilt the head back gently, to achieve neutral
and ventilation. Impaired oxygenation in lungs results in position in an infant and sniffing position in a child. Two
hypoxemia. This may occur due to alveolar hypoventilation, to three fingers of the other hand should then be placed
V/Q mismatch or right to left shunt. under the chin to lift it upwards. The thumb of this hand
Tissue oxygenation depends on oxygenation in lungs, may be used to part the lips to keep the mouth open
cardiac output, hemoglobin concentration, and tissue perfusion. • Jaw thrust: this is used in suspected cervical spine injury
Impairment of any of these would result in tissue hypoxia. as head tilt-chin lift is contraindicated. This is achieved by
Inadequate ventilation is seen in airway disease, lung placing two or three fingers under the angle of the mandible
parenchymal disease, and central hypoventilation. This results bilaterally, and lifting the jaw upwards.
in hypercarbia.
Conditions causing tissue hypoxia or hypercarbia result in Not maintainable airway
RD as a compensatory mechanism to maintain adequate gas It may need one of the following advanced airway interventions:
exchange. • Endotracheal intubation
When these compensations fail, child develops RF. • Laryngeal mask airway in unconscious patient
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• Application of continuous positive airway pressure (CPAP) Table 1: Initial management of respiratory distress/respiratory
• Cricothyrotomy/tracheostomy failure
• Endoscopic removal of foreign body. Evaluate Interventions
Airway • Support an open airway or if necessary, open the
Breathing airway with
This can be supported by administration of oxygen or by {{ Head tilt-chin lift
assisted ventilation. It is important to differentiate RD from RF {{ Jaw thrust without head tilt if cervical spine
at initial evaluation. Child with RF has features of hypoxemia injury is suspected. If this maneuver does not
and hypercarbia. open the airway, use the head tilt-chin lift or
jaw thrust with gentle head extension.
Clinical Pearl • Clear the airway if indicated by suctioning or
removal of visualized foreign body
• Respiratory failure is a clinical diagnosis. Arterial blood gas is • Consider an oropharyngeal airway (OPA) or
done for confirmation and monitoring. nasopharyngeal airway (NPA)
Breathing • Monitor O2 saturation
In a child with RD, maintenance of airway, administration • Provide humidified O2. Use a high concentration
of oxygen, etiological management, and monitoring may delivery device like nonrebreathing mask for
suffice. But in a child with RF, one must take total control of treatment of severe respiratory distress
airway and breathing. • Administer inhaled medication (e.g., salbuterol,
epinephrine) as needed
Oxygen Delivery • Assist ventilation with bag mask device and
In a child with RD, proper administration of high concen supplementary O2 if needed
tration of oxygen is the mainstay of therapy. Oxygen is given in • Prepare for endotracheal intubation if indicated
a nonthreatening manner to a child with RD, avoiding agitation Circulation • Monitor heart rate, rhythm and blood pressure
as far as possible, as this increases the work of breathing and • Establish vascular access
makes the flow of air turbulent thereby increasing the resistance
to air flow. Taking the mothers help to provide oxygen goes a
long way in decreasing the child’s agitation. Nasal prongs and Type
a simple face mask do not provide a high concentration of Respiratory problem is categorized as one of the following:
oxygen and are unreliable for use in the emergency room. The • Upper airway obstruction (UAO)
devices which can be used are a nonrebreathing mask with a • Lower airway obstruction (LAO)
flow rate of 10–12 L/m, an oxygen hood in infants with a flow of • Lung tissue disease
10–15 L/m or a flow inflating bag with a flow rate of three times • Disordered control of breathing.
minute ventilation.
Assisted Ventilation TARGETED INTERVENTIONS

Child with severe RD or RF will need advanced airway measures Targeted intervention includes:
and assisted ventilation. Assisted ventilation can be provided • General measures as per the type of respiratory problem
by bag-mask ventilation (BMV), noninvasive ventilation or • Specific measures as per the etiology.
endotracheal intubation and mechanical ventilation. Following sections describe important emergency room
In most emergencies, effective BMV usually provides measures in a child with RD. The specific measures depend on
adequate oxygenation and ventilation until definite control of the underlying etiology, which are mentioned here briefly. The
airway can be achieved. BMV can be as effective as ventilation detailed description is given elsewhere in this book.
through endotracheal (ET) tube for short periods of time and
may be safer when provider is inexperienced in insertion of
advanced airway.
UPPER AIRWAY OBSTRUCTION
Table 1 summarizes the initial management of child Acute UAO is an obstruction of large airways outside the thorax.
with RD.
General Management
ASSESSMENT TO DETERMINE THE SEVERITY The most important priority in UAO is to open and maintain a
AND TYPE OF RESPIRATORY PROBLEM patent airway. The measures needed to do so are described in
table 1.
• When UAO is severe, call for help of a person with expertise
Severity in airway management
Once oxygenation and ventilation are stabilized, the severity is • In less severe UAO, children may benefit from insertion
158 identified as respiratory distress or failure. of an oropharyngeal airway (OPA) or nasopharyngeal
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Chapter 34: Management of a Child with Respiratory Distress
airway (NPA), which may relieve the obstruction caused • More than 1 year: heimlich maneuver (abdominal thrust)
by the tongue One of the given outcomes may follow:
• Use OPA only in comatose child • Relief from obstruction: evaluation
• A child with intact gag reflex may tolerate an NPA • Incomplete obstruction: managed as above
• Child with redundant tissues or tissue edema may benefit • Child becomes unresponsive: start cardiopulmonary
from application of CPAP. resuscitation (CPR). Before you deliver a breath, look into
the mouth. If you a see a foreign body that can be easily
Clinical Pearl removed, remove it.
• Failure to aggressively treat a partial upper airway obstruction Angioneurotic Edema

can lead to complete airway obstruction and cardiac arrest.
Steps in management of anaphylaxis are summarized in box 1.
Specific Management Clinical Pearl

Apart from initial interventions mentioned in table 1, additional • Hyperacute onset of breathlessness in an alert child should
measures as per etiology focus on relieving the obstruction. arouse suspicion of foreign body aspiration or anaphylaxis.
Table 2 summarizes the clinical features of various UAO
Foreign Body Aspiration Acute Laryngotracheobronchitis

Management depends upon degree of obstruction. Treatment of child with acute laryngotracheobronchitis
depends upon severity as described in table 3.
Incomplete obstruction
(Child is breathing, coughing, and able to make sounds).
• Position of comfort Box 1: Management of anaphylaxis
• Supplemental oxygen • Administer adrenaline 1:1,000 IM 0.01 mL/kg, repeated every
• Rigid bronchoscopy. 10–15 minutes as needed
• Treat bronchospasm with salbutamol metered-dose inhaler or
nebulization
Clinical Pearl
• For severe respiratory distress, anticipate further airway swelling
• Do not perform blind finger sweep, it may push the foreign and prepare for endotracheal intubation
body further into the airway. • To treat hypotension:
{{ Place the child in Trendelenburg position as tolerated
{{ Administer normal saline bolus 20 mL/kg (repeat as needed)

Complete obstruction
{{ Consider adrenaline drip for hypotension unresponsive to
(No sound, unable to cough, and unable to breathe adequately).
above measures
Perform following maneuvers:
• Administer diphenhydramine and H2 blocker
• Less than 1 year: five back blows followed by five chest
thrusts • Administer methylprednisolone or equivalent corticosteroid IV
Table 2: Differential diagnosis of acute upper airway obstruction

Etiology Fever Cough Voice Stridor Dysphagia Others
Epiglottitis +++ Ineffective Hot potato Soft + Drooling of saliva
Thumb sign on X-ray
Diphtheria ± − Normal to In laryngeal + Pseudomembrane, toxicity
hoarse involvement
Retropharyngeal +++ Ineffective Muffled Soft + Drooling of saliva,
abscess neck stiffness, soft tissue swelling on X-ray
Foreign body − Sudden Hoarse Depends upon ± −
choking level of obstruction
ALTB +/− Brassy Hoarse Harsh − Steeple sign on X-ray
Angioedema − Dry staccato Hoarse Varies ± Swelling of lip, tongue, mucous membrane
Bacterial tracheitis +++ Brassy Hoarse Harsh − Purulent tracheal secretions
ALTB, acute laryngotracheobronchitis. 159
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Table 3: Management of croup Table 4: Management of acute asthma

Mild • Careful observation, monitoring. Asthma severity Interventions
• Consider oral dexamethasone. Mild to • Salbutamol MDI with spacer +/− mask or
Moderate • Administer humidified oxygen moderate nebulized salbutamol every 20 minutes—
total three doses.
• Administer nebulized epinephrine
• Administer oral prednisolone
• (1:1,000 solution at a dose of 0.5 mL/kg—max 5 mL)
Moderate to • Hospitalize and start oxygen
• Administer dexamethasone oral/IM/IV
severe • Continue salbutamol nebulization 1–4 hourly
• (0.15–3 mg/kg) or budesonide 2 mg nebulization
or continuously
• Observe for at least 2 hours after nebulized • Administer steroids PO/IV
epinephrine to ensure continued improvement.
• Add ipratropium bromide nebulization
Severe • Administer high concentration of oxygen every 20 minutes for three times followed by
• Assist ventilation if necessary 6 hourly
• Administer dexamethasone IV/IM • Consider magnesium sulfate
• Perform endotracheal intubation if indicated • Perform diagnostic tests
• Prepare for surgical airway if needed. Impending • Consider adding following measures:
respiratory {{ Start on terbutaline infusion and/or
failure aminophylline infusion

{{ In case of poor response or red flag signs:
Clinical Pearl –– Consider BiPAP in alert child

–– ET intubation and mechanical ventilation
• In upper airway obstruction with signs of severe obstruction,
place an advanced airway early even if SpO2 is normal, as it MDI, metered-dose inhaler; BiPAP, biphasic positive airway pressure; ET,
endotracheal.
drops much later.
• Hypertonic saline, steroids, ribavirin: conflicting reports,
variable response. None have proven benefit.
LOWER AIRWAY OBSTRUCTION Table 4 summarizes acute asthma treatment in emergency
room.
General Management
• The most important priority is to maintain adequte LUNG TISSUE DISEASE
oxygention and ventilation
• The aim is to maintain SpO2 above 94% Common causes of lung tissue disease are:
• Pneumonia
• Use appropriate oxygen delivery device with optimum
• Cardiogenic pulmonary edema
flow rate
• Acute respiratory distress syndrome (ARDS).
• In severe RD, administer oxygen by nonrebreathing mask
to provide 100% oxygen
General Management
• If assissted ventilation is required, perform BMV at
relatively slow rate. Initial interventions are listed in table 1.
In children with refractory hypoxemia, consider CPAP,
noninvasive ventilation or mechanical ventilation with positive
Clinical Pearl end-expiratory pressure (PEEP).
• Ventilating at slow rate in lower airway obstruction reduces the
risk of air trapping and complications of high airway pressure. Clinical Pearl
Specific Management • Saturated oxygen of arterial blood less than 90% on 100%
oxygen is an indication for assisted ventilation.
Common causes of LAO are asthma and bronchiolitis.
Management of Bronchiolitis Specific Management

• Management is mainly supportive Acute Infectious Pneumonia
• Administer humidified O2 • Perform diagnostic tests—e.g., complete blood count
• IV fluids (CBC), chest X-ray (CXR), blood culture, etc. as indicated
• Suction oral and nasal secretions • Administer antibiotic therapy
• Trial of bronchodilators: continue only if favorable • Treat wheezing with bronchodilators
response is noted • Consider using CPAP or noninvasive ventilation. Severe
• Severe cases need intensive care unit (ICU) care. Assess cases need intubation and mechanical ventilation
160 and provide ventilatory support if needed • Supportive measures: antipyretics, IV fluids, etc.
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Chapter 34: Management of a Child with Respiratory Distress
Algorithm 1
Step-wise management of a child with respiratory distress
RD, respiratory distress; RF, respiratory failure.
Cardiogenic Pulmonary Edema

Key points
The most common cause of acute cardiogenic pulmonary
edema in children is left ventricular myocardial dysfunction. ))
The first priority in the management of a child with respiratory
• Provide ventilatory support as needed distress (RD) is to stabilize airway, breathing and circulation
• Consider diuretics to reduce left atrial pressure ))
As this is being done, simultaneously the child is assessed to
• Inotropic infusions and afterload-reducing agents to determine the severity and type of respiratory problem
improve myocardial function ))
Subsequently, detailed evaluation (including investigations) is
• Obtain expert consultation. required to determine the underlying etiology of RD
))
Treatment of RD consists of general measures depending
Acute Respiratory Distress Syndrome upon the type of the problem and specific-targeted inter
Early recognition and treatment of bacteremia, shock and RF vention as per the etiology
may help prevent progression to ARDS. ))
Early recognition and a systematic approach to management
• Obtain laboratory studies—CBC, ABG, serum electrolytes, are crucial for better outcome.
blood culture etc. as indicated
• Provide ventilatory support as needed
• Indications for ventilator support: SUGGESTED READINGs
{{ Worsening clinical and radiological lung disease
1. Agarwal R, Singh V, Yewale V (Eds). RTI facts; bugs, drugs and you. IAP Consensus
{{ Hypoxemia refractory to high concentrations of fraction
Guidelines on Rational Management of Respiratory Tract Infections in Children.
of inspired oxygen. IAP Action Plan, 2012.
2. Everald ML. Acute bronchiolitis and croup. Pediatr Clin North Am. 2009;56:119-31.
3. Global Strategy for Asthma Management and Prevention—revised 2012. [online]
DISORDERED CONTROL OF BREATHING Accessed from www.ginasthma.org. [Accessed December, 2015].
It results from affection of central control of respiration or 4. Helfaer MA, Nichols DG (Eds). Roger’s Handbook of Pediatric Intensive Care, 4th
neuromuscular weakness. edition. Lippincott Williams & Wilkins; 2010.
5. PALS Provider Manual. American Academy of Pediatrics and American Heart
Important Aspects of Treatment Association. 2011.
6. Subramanyam L. Essentials of Paediatric Pulmonology, 3rd edition. PPFI; 2008.
• Airway management 7. Wilmott RW, Boat TF, Bush A, Chernick V, Deterding RR, Ratjen F (Eds). Kendig and
• Management of raised intracranial pressure (ICP) Chernick’s Disorders of the Respiratory Tract in Children, 8th edition. Saunders;
• Treatment of the cause. 2012.
161
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Chapter 35
Hypovolemic Shock
Parmanand GK Andankar
INTRODUCTION sive nasogastric/fistula/enterostomy losses, sodium-losing

nephropathy, and diuretic therapy are usually associated with
Circulatory shock is a common emergency encountered low, plasma-protein losses.
in pediatric practice. Shock has been defined as a patho
physiological state in which there is an inadequate supply or
Clinical Pearl
inappropriate use of metabolic substrate (particularly oxygen)
by peripheral tissues. It is often classified as hypovolemic, • Hemorrhage can be concealed in the abdominal or thoracic
cardiogenic, obstructive, or distributive. spaces, in retroperitoneal tissues or in tissues surrounding
bony fractures.
CAUSES (BOX 1)
Hypovolemic shock is caused by a loss of intravascular fluid CLINICAL FEATURES
which is usually whole blood or plasma.
The clinical features of hypovolemic shock are the same as those
Whole blood loss (hemorrhagic): Blood loss may occur from an of shock (in general), i.e. tachycardia, poor peripheral pulses,
open wound or from concealed hemorrhage in the abdominal delayed capillary refill time, cool extremities, pallor, and poor
or thoracic spaces (e.g., hemothorax, lacerated liver, spleen urine output. In addition, the child may have hypotension,
or kidney, gastrointestinal hemorrhage), in retroperitoneal dyspnea, and change in sensorium.
tissues (with ruptured aorta or coagulation abnormality) or in It is the history which provides specific clues to the shock
tissues surrounding bony fractures. being hypovolemic.
Plasma loss (nonhemorrhagic): Intravascular volume deple
tion due to excessive extracellular fluid loss with or without INVESTIGATIONS
loss of plasma protein. For example, pancreatitis, peritonitis,
Complete blood count, electrolyte levels (Na+, K+, Cl−, HCO3−),
burns, crush syndrome, and anaphylaxis tend to have a high
blood urea nitrogen, creatinine, glucose levels, prothrombin
plasma protein loss, whereas vomiting, diarrhea, exces
time, activated partial thromboplastin time, arterial blood
gases, and urinalysis.
Box 1: Hemorrhagic and nonhemorrhagic causes of hypo Blood should be typed and cross-matched.
volemic shock
Hemorrhagic Nonhemorrhagic
TREATMENT AND MANAGEMENT
• Gastrointestinal bleeding • Heat stroke/water deprivation
• Surgery • Vomiting/diarrhea
Prehospital Care
• Trauma • Pharmacologic (e.g., diuretics)
• Hepatic or splenic rupture • Burns • Prevent further injury
• Major vessel injury • Nephrotic syndrome • Transport the patient to the hospital as rapidly as possible
• Intracranial bleeding • Pancreatitis • In patients with acute gastroenteritis with dehydration,
• Long bone fractures • Diabetes mellitus start oral rehydration solution at home and during
• Diabetes insipidus transport for hospitalization.
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Chapter 35: Hypovolemic Shock
Prevention of Further Injury What fluids?

• Cervical spine must be immobilized Three randomized controlled trials compared the use of
• Splinting of fractures. colloid to crystalloid resuscitation in children with dengue
shock. No difference was shown in mortality between those
General Shock Management resuscitated with colloid or crystalloid. Similarly, there were
no differences in outcome (new organ failure, duration of
Position of Child ventilation, renal replacement therapy, or length of stay)
Stable: Allow to remain with caregiver in a position of comfort. and mortality after albumin administration (versus saline).
Unstable: If hypotensive, place in Trendelenburg position Albumin and normal saline were equally effective for fluid
unless breathing is compromised. resuscitation [Saline versus Albumin Fluid Evaluation (SAFE)
Study]. Thus, isotonic crystalloid solutions are as effective as
Airway colloid solutions for the majority of patients with hypovolemic
• Open, clear, maintained shock (Table 1).
• Consider intubation. Dutch Pediatric Society evidence-based clinical practice
guidelines recommend that in neonates and children with
Breathing hypovolemia the first-choice fluid for resuscitation should be
• To optimize arterial O2 content isotonic saline.
• Start oxygen by nonrebreathing mask at flow rate 10–15 L/min If loss of protein containing fluids is documented or sus
• Assist ventilation if required pected (clue: low albumin), or if resuscitation is not responding
• When in doubt, ventilate. to crystalloids, only then should colloids be administered.
In patients with crystalloid refractory hemorrhagic shock,
Circulation PRBC 10 mL/kg should be administered promptly.
• Establish venous access or intraosseous access or central
line How much fluid?
• Replace fluid Surviving sepsis guideline suggests that initial resuscitation
• Give an isotonic fluid (crystalloid) bolus of 20 mL/kg to begin with infusion of crystalloids with boluses of 20 mL/kg
restore blood pressure and tissue perfusion over 5–10 minutes. The amount of fluid necessary to restore
• For trauma and hemorrhage, administer packed red blood effective circulating blood volume depends on amount of fluid
cells (PRBCs). lost and rate of ongoing losses. The volume of fluid required
for resuscitation can be 40–60 mL/kg or higher. However,
Monitor a child with nonhemorrhagic hypovolemic shock should
• Mental status generally respond to 40 mL/kg of crystalloid solution; if a child
• Heart rate is unresponsive to this amount of fluid resuscitation, the child
• Respiration must be evaluated for complicating factors causing refractory
• Blood pressure shock, such as unrecognized pneumothorax or pericardial
• Electrocardiogram effusion, intestinal ischemia, sepsis, myocardial dysfunction,
• Arterial oxygen saturation adrenocortical insufficiency, and pulmonary hypertension.
• Temperature
• Urine output. Table 1: Crystalloids versus colloids
Crystalloids Colloids
Clinical Pearl
• Includes 0.9% normal • 5% albumin, dextran,
• If peripheral access is not readily obtained, intraosseous access saline and RL hydroxyethyl starch, and blood
may be established quickly and reliably in patients of any age. products
Advantages
Fluid Therapy • Availability, low cost, and • Maintain or increase oncotic
lack of exposure to blood pressure
Initiate fluid resuscitation as quickly as possible.
products • Significant increase of
Reasons for fluid therapy intravascular volume
• Preserve oxygen delivery to tissues • Stays in the intravascular
• Correct hypovolemia compartment longer
• Maintain cardiac output—Colloids + red blood cells • Better perfusion
• Optimize gas exchange • Less tissue edema
• Replace electrolytes and water—Crystalloids
Disadvantage
• Maintain urine output
• Identify the goal and choose the fluid which best achieves • Large volumes required • Pulmonary edema can occur
the goal. RL, Ringer’s lactate. 163
Ch-35.indd 163 11/24/2016 12:40:17 PM

How fast? When to start inotrope?

As fast as possible (5–10 minutes). Fluid administration should be stopped and inotropes should
be started when the ventricular filling pressure (CVP and 2D
How long? Echo) rises, without evidence of improvement in cardiovascular
It has been reported that up to 60 mL/kg of fluids may be given performance.
in first hour of therapy in shock without increasing risk of
pulmonary edema. The rate of fluid administration should be Additional/Special Considerations during
reduced substantially when there are clinical signs of adequate
cardiac filling with hemodynamic improvement. The end point Management of Hypovolemic Shock
of fluid resuscitation is when there is normalization of arterial in Trauma Patients (Table 2)
blood pressure, pulse pressure, and heart rate, and adequate Even as the primary assessment is being performed,
urine output and decrease in metabolic acidosis. • Organize trauma team
If shock persists, while one may continue with aggressive • Call the surgeon
fluid resuscitation in aliquots of 20 mL/kg, one needs to • Notify the blood bank.
carefully monitor vital parameters, and also more aggressive
monitoring like continuous central venous pressure (CVP), for During Primary Assessment
response of therapy.
In a hypotensive patient with a CVP of less than 10 mm Hg, Airway
in absence of pulmonary edema, more fluids can be given to • Protect the airway, use adjuncts as required; if unstable—
achieve the desired preload. secure airway early
Inspite of this, if there is no improvement in blood pressure, • Protect cervical spine.
peripheral perfusion or urine output, the patient’s diagnosis
should be re-evaluated, and a probable cause of ongoing
Breathing
depletion should be sought. The child must be evaluated Provide high flow oxygen, assist ventilation as needed.
for complicating factors causing refractory shock such as
Circulation
unrecognized pneumothorax or pericardial effusion, intestinal
ischemia, sepsis, myocardial dysfunction, adrenocortical • Secure two separate venous access with large bore cannula
insufficiency, and pulmonary hypertension. • Send blood for grouping, cross matching
If CVP is greater than 10 mmHg and shock persists, consider • Control external bleeding.
2D echocardiography to rule out cardiac dysfunction. Disability
In hemorrhagic hypovolemic shock, blood must be
transfused if hypotension persists despite adequate crystalloid Assess neurological status—alert, voice, pain, unresponsive
infusion. It must be noted that hematocrit is a poor indicator scale.
of severity of hemorrhage, because it does not decline in the Exposure
setting of hemorrhagic shock.
Undress patient to look for additional injuries.
Clinical Pearl
During Tertiary Assessment
• Hematocrit is a poor indicator of severity of hemorrhage, Additional radiology: X-ray chest, pelvis, cervical spine
because it does not decline in the setting of hemorrhagic shock. (lateral).
Table 2: Identification of source of hemorrhage and interventions

Identify the source of hemorrhage
External Long bones Chest Abdomen Retroperitoneum
Careful visual inspection Careful visual Chest X-ray Diagnostic peritoneal Pelvic X-ray
inspection tap/(FAST)
Interventions
Apply direct pressure, Splint, reduce fractures ICD Emergency laparotomy Externally stabilize pelvis
suture lacerations
FAST, focused abdominal sonography in trauma.
164
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Chapter 35: Hypovolemic Shock
Algorithm 1
Algorithm for management of hypovolemic shock
ABC, Airway, Breathing and Circulation; IO, intraosseous; VBG, venous blood gas; CBC, complete blood count; IPCU, Intensive Psychiatric Care Unit; HR, heart
rate; RR, respiratory rate; IV, intravenous; ORS, oral rehydration solution; CVP, central venous pressure; AGE, acute gastroenteritis; MAP, mean arterial pressure.

))
The clinical signs of hypovolemic shock are the same as those 1. Fuhrman BP, Zimmerman JJ (Eds). Pediatric Critical Care, 4th edition. Elsevier;
of shock in general. It is the history which provides specific 2011.
clues to the shock being hypovolemic 2. Management of Shock, Pediatric Advanced Life Support.
3. Shaffner DH, Nichols DG (Eds). Roger’s Textbook of Pediatric Intensive Care, 5th
))
While the need for fluids is obvious, one must administer
edition. Wolters Kluwer Health; 2015.
oxygen to optimize arterial oxygen content
4. Wills BA, Nguyen MD, Ha TL, Dong TH, Tran TN, Le TT, et al. Comparison of
))
Isotonic crystalloid solutions are as effective as colloid three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med.
solutions for the majority of patients with hypovolemic shock 2005;353(9):877-89.
))
One may need up to 40 mL/kg of fluid before a child with 5. Worthley LI. Shock: a review of pathophysiology and management. Part I. Crit
hypovolemic shock (nonhemorrhagic) responds; additional Care Resusc. 2000;2(1):55-65.
needs beyond this amount should prompt a review of other
possibilities/complications
))
There are additional/special considerations during the
165
management of hypovolemic shock in trauma patients.
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Chapter 36
Approach to Fever in Children
Rhishikesh P Thakre
INTRODUCTION whether the child is getting better or worse, history of exposure

to sick contacts, use of antipyretics or antibiotics (with their
Fever is one of the most common distressing signs of childhood doses) taken or previous diagnostic tests done and their results.
illness. In majority, the cause is usually viral, self-limited, and All efforts should be made to enquire about the oral intake,
benign, but in few it is due to serious underlying illness. The fluid losses, urination, recent travel, prior hospitalization, and
clinician’s responsibility is to establish a correct diagnosis vaccination status (Table 1).
in reasonable time and initiate treatment, if indicated. This
chapter focuses on approach to acute fever. Table 1: Key points on history
Note Comment
RECOGNIZING FEVER Onset High fever from the very onset usually suggests
viral infection, malaria, or localized bacterial
The first step is to reliably document fever by measuring infection at the site of entry of organisms
axillary temperature using digital thermometer. Use of oral and (tonsillitis/UTI)
rectal routes is not recommended. A temperature above 38°C
Duration Persistent fever beyond day 3 without localizing
or 100.4°F is considered as fever.
signs calls for laboratory tests
Progress Gradually- improving fever by day 3 or 4
Identifying “High Risk” for Serious Illness suggests self-limiting viral infection, while
One should be alert to and identify immediately any life- bacterial infections peak by day 3 or 4
threatening features, including compromise of the airway, Interfebrile Children suffering from viral infection or malaria
breathing, or circulation, and decreased level of consciousness state appear normal between fever spikes. If the
(Box 1). This identifies seriously-ill children in need for urgent child continues to appear sick even between
referral or treatment. fever spikes, the cause is likely to be a bacterial
infection
ASSESSMENT OF FEVER Response to Poor response to optimum doses of paracetamol

antipyretic or ibuprofen may suggest severe bacterial
The main goal of evaluation of febrile children is to distinguish infection
those with mild self-limiting illness from those with serious Accompanying Bacterial infection usually presents with localiza-
bacterial infection (SBI). symptoms tion to a part of a system (such as tonsillitis or
An enquiry should be made about the nature of fever, pneumonia) while viral infection usually affects
defining when was the child last well, activity, sleep pattern, the entire system or multiple systems (such as
respiratory and gastrointestinal system)
Box 1: Assessing “danger signs” in febrile children Contact with Family member with similar illness suggests
similar illness airborne viral infection.
• A—Arousal, alertness, activity
Past history of Device (shunt, implant), underlying anomaly
• B—Breathing difficulty
infective focus (CHD, VUR) predispose to early complication and
• C—Color and Circulation need urgent evaluation
• D—Decreased intake and urine output UTI, urinary tract infection; CHD, congenital heart defect; VUR, vesicoureteral reflux.
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Chapter 36: Approach to Fever in Children
EXAMINATION Table 4: Pointers to serious bacterial infections in a febrile child
The purpose of examination is directed at locating a source Fast respiration (>60/min), chest indrawing, grunt Pneumonia
for fever, with specific attention to potential SBI and resultant Neck stiffness, bulging fontanel, decreased level Meningitis
complications. Ill-appearing children are more likely than of consciousness, convulsive status epilepticus
well-appearing children to have SBI, and most well-appearing Unexplained vomiting, poor feeding, lethargy, Urinary tract
children do not have SBI. irritability, abdominal pain or tenderness, urinary infections
In addition to temperature one should record the heart frequency or dysuria
rate, respiratory rate and capillary refill time as part of the Disproportionate tachycardia, cool extremities, Septicemia
routine assessment (Table 2). prolonged capillary refill (>3 seconds), core
axillary mismatch, altered sensorium, oliguria
suggests systemic inflammatory response
ASSESSMENT FOR LOCALIZING SIGNS causing shock
Presence of associated symptoms or signs gives clue to Nonblanching rash, particularly with one or more Meningococ-
underlying focus of infection (Table 3). Examination of the of the following: an ill-looking child, lesions larger cemia
throat and ear is important and often missed. A systematic than 2 mm in diameter (purpura, capillary refill
examination should then be conducted, including the skin time of ≥3 seconds, and neck stiffness
and nails, head and neck, and the cardiovascular, respiratory, Swelling of a limb or joint, not using an extremity, Septic arthritis/
abdominal, musculoskeletal, and neurological systems. One nonweight bearing osteomyelitis
should be aware that classical signs of meningitis like neck
stiffness are classically seen in older children and are often An attempt must be made to ensure that possibility of SBI
absent in infants with bacterial meningitis. Hence, one has to has been ruled out on clinical grounds.
have a high index of suspicion and look for subtle signs like At times noninfective causes do present with short-
bulging fontanel, irritability, high pitched cry, or any other duration fever and one should have a high index of suspicion
indicator of altered sensorium (Table 4). for them (e.g., Kawasaki disease, leukemia).
Table 2: Key points on general examination

INVESTIGATIONS
Look for Note
Many infections can be identified by history and examination
Appearance Well or sick based on alertness, interaction, tone, alone, but some infections may be occult. The most common
cry, activity, and look. Lack of alertness indicates
SBIs in infants that may not be clinically apparent are
encephalopathy and underlying serious illness
bacteremia, urinary tract infection (UTI), and pneumonia.
Breathing Normal or abnormal, apnea, type of breathing—rate Tempo and complexity of workup is decided by the pace of
and work of breathing. Breathing difficulty with illness. Investigations must be done on all sick children and in
altered sensorium indicates serious illness those without localization by 72 hours.
Color Pink color of extremities is assuring. Mottling, cyanosis, • Complete hemogram: A white blood cell (WBC) count
and ashen complexion indicate serious illness of greater than 15,000/mm3 or less than 5,000/mm3, a
Temperature Degree and severity band-to-neutrophil ratio ≥0.2 is considered abnormal.
An abnormality is a relatively poor surrogate marker for
Heart rate Proportionate or disproportionate to temperature
bacteremia (Table 5)
Hydration Assess the sensorium, skin turgor, eyes, mucous • Urinalysis (dipstick, urinalysis, microscopy, Gram’s stain,
membrane, and urine pattern culture) must be considered in presence of fever without
localization, particularly in younger children or when UTI
Table 3: Common causes of fever is suspected. A urine dipstick test positive for nitrite or
leukocyte esterase or a finding of greater than 10 WBCs/hpf
Fever with localization (<7 days) Probable diagnosis or organisms seen on Gram’s stain is considered abnormal
Watery nasal discharge Viral URI • Chest X-ray is useful in children with respiratory
Purulent nasal discharge, follicles/ Bacterial URI localization. Chest film should be considered in an infant
exudates on tonsils, petechiae on with an unexplained WBC count of greater than 20,000, or
palate with prolonged fever or cough
Tachypnea with chest signs Pneumonia • In children with no definitive diagnosis beyond day 3 or
Watery stools Viral AGE
where antibiotic is to be initiated, blood culture must be
done. It is the gold standard for the diagnosis of bacterial
Blood-mucus in stools, tenesmus Bacterial AGE
infection
Urinary complaints UTI • Cerebrospinal fluid (CSF) examination (cytology, Gram’s
Splenohepatomegaly Malaria, typhoid, hepatitis, stain and culture) is mandatory in every suspected case of
or infectious mononucleosis meningitis and also in all sick infants without localization.
URI, upper respiratory infection; AGE, acute gastroenteritis; UTI, urinary tract CSF fluid with greater than 8 WBC/mm3 or organisms on 167
infection. Gram’s stain is considered abnormal.
Ch-36.indd 167 11/24/2016 12:42:35 PM

Table 5: Interpreting hemogram

Hemoglobin Total leukocyte count Polymorphs Lymphocytes Eosinophils Platelets Disease
Normal +++ +++ − 0 Normal Acute bacterial infection
Normal +++ +++ − + High Systemic infection
Low +++ + +++ − Low ALL
Normal ++ ++ − 0 Normal/low Acute viral infection
Normal Low − ++ 0 Normal/low Typhoid
Low +/− − − + Low Malaria
High + − ++ − Low Capillary leak
Normal + − ++ + Normal Tuberculosis, chronic infection
No combination of clinical assessment and diagnostic MANAGEMENT OF

testing will successfully identify all patients who have serious FEBRILE CHILD (Algorithm 1)
infection at the time of initial presentation; therefore, the
importance of timely reassessment with good history, • Supportive treatment: supportive treatment of fever is
systematic confident clinical examination and intelligent symptomatic. Not all fevers need treatment. Primary goal
use of laboratory tests, a rational approach cannot be overe of treating the febrile child should be to improve the child’s
mphasized. overall comfort rather than focus on the normalization of
body temperature.
Cooling: involves nursing in cool environment and
INDICATIONS FOR HOSPITALIZATION unbundling the child. Sponging is reserved for patients
Most infants and children who have fever and are otherwise with hyperthermia (temperature more than 38.5°C) after
healthy, who are well appearing with no localization can be 30 minutes of antipyretic dose.
managed on an outpatient basis. The degree of illness should Antipyretics: the use of antipyretics should be indi
be determined through the child’s interactions with the vidualized and based on the child’s well-being, not
environment; observing their alertness, playfulness and feeding temperature alone. Antipyretics should be used as
pattern with appearance of any new symptoms (Box 2). ‘‘therapy’’ for fever rather than ‘‘control”. Treatment
for fever with antipyretic is indicated if the child has
discomfort, i.e., irritable, drowsy, greater than 40°C, pain,
Box 2: Indications for hospitalization or excessive crying. Both paracetamol (10–15 mg/kg, 4–6
• Febrile neonate hourly) and ibuprofen (5–10 mg/kg, 6 hourly) are effective
• Toxic child antipyretics.
• Presence of “danger signs” Hydration should be ensured for all febrile children by
• Admission for period of observation increasing oral intake as for every 1°C rise in temperature
• Pre-existing medical problem (congenital heart defect, the fluid requirement increases by 10%.
immunodeficiency, malnutrition)
Empiric treatment: empiric treatment is not routinely
• Parental preference
recommended. It is justified only in toxic children and
Algorithm 1
Algorithm for acute fever
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Chapter 36: Approach to Fever in Children
neonates and that too, only after sending relevant investi

gations. It is directed towards the probable underlying Clinical Pearls
cause of illness and most probable organism.
• Uncommon manifestations of common diseases are more
Specific treatment: specific therapy should be directed
likely than are rare diseases
towards the specific cause identified on evaluation like
• Clues to the diagnosis are frequently present in the history and
UTI, pneumonia, etc.
physical examination but are not elicited or unappreciated.
• Follow-up: not all febrile children have a focus identified
Therefore, thoroughness and repetition are vitally important.
on first evaluation. All such children should be followed
up on outpatient department basis continuing with
symptomatic treatment at home. Parents should be
made aware about the danger signs and asked to report Key points
immediately if there are any concerns or appearance of
))
All febrile children should have periodic assessment for
new symptoms.
“danger signs”; presence of these should lead to prompt
interventions
SPECIAL CIRCUMSTANCES: ))
Fever without focus in a well child should be treated
FEVER IN NEWBORN (<30 DAYS) symptomatically on OPD basis. Such children should be
periodically evaluated. Empiric antibiotics should be avoided
Physical examination has marked limitations to predict ))
The emphasis should be on the child and not his temperature.
accurately a serious infection in neonates. All febrile newborns Counseling parents about fever phobia is mus
should be screened for complete blood count, CSF study and ))
Decision-making in fever should take into consideration the
for culture of urine and blood. X-ray chest should be done if child’s age, general well-being, facilities, ease and reliability for
a respiratory cause is suspected. Febrile neonates should be follow-up.
hospitalized regardless of the results of laboratory studies and
given intravenous antibiotics till infection is ruled out.
SUGGESTED READINGs
PARENT EDUCATION: FEVER PHOBIA 1. Chiappini E, Principi N, Longhi R, Tovo PA, Becherucci P, Bonsignori F, et al.
Management of fever in children: summary of the Italian Pediatric Society
Parents should be made aware that fever is a symptom and not
Guidelines. Clin Ther. 2009;31:1826-43.
an illness. The severity of fever does not necessarily correlate 2. Rapid approach to common symptoms. Standardization of pediatric office
with seriousness of illness. Child’s well-being is more important practice. Fever, 13-16. Indian Academy of Pediatrics; 2005.
than the height of the fever. The risk of febrile convulsion is less 3. Section on Clinical Pharmacology and Therapeutics; Committee on Drugs, Sullivan
than 5% and it is a benign event. JE, Farrar HC. Fever and antipyretic use in children. Pediatrics. 2011;127;580-7.
169
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Chapter 37
Approach to
Poisoning in Children
Somashekhar M Nimbalkar
INTRODUCTION MANAGEMENT OF POISONING

Data regarding poison exposure is not well maintained in
India; but based on global trends it can be assumed with fair Initial Assessment and
approximation that the poison exposure in children in India Emergency Management
would range above 8 million at the least.
In a responsive patient, initial management in all patients
presenting to the emergency is focused on airway, breathing,
ETIOPATHOGENESIS and circulation.
Common causes of poisoning in India vary geographically
Airway
and are dependent on access to various agents. Healthcare
providers should be familiar with common poisonings in Presence of abnormal sounds like stridor, gurgling sounds,
their area. or noisy breathing may indicate that the airway is partially
obstructed. Altered sensorium indicates that the child’s airway
is at risk. In such cases, measures to manage airway should
CLINICAL PRESENTATION be initiated. These may include positioning, oropharyngeal
Most children present with nonspecific symptoms such as airways, laryngeal mask airways, or endotracheal intubation.
nausea, vomiting, or altered sensorium. However, there are Caustic agents, angiotensin converting enzyme inhibitors, and
certain toxidromes, which, on recognition, can give us a clinical plants containing calcium oxalate crystals can predispose to
diagnosis (Tables 1 and 2). airway edema and obstruction.
Table 1: Clinical manifestations of selected toxic ingestions

Ingestion Clinical findings
Acetaminophen • Early: nausea, vomiting, anorexia; jaundice and liver failure occur later
Antihistamines • Initially CNS depression but stimulation in higher doses (tremors, hyperactivity, hallucinations, seizures)
Aspirin • Tachypnea, respiratory alkalosis, metabolic acidosis, coagulopathies, slurred speech, tinnitus, seizures
β-blockers • Bradycardia, hypotension, coma, convulsions, hypoglycemia, bronchospasm
Calcium channel blockers • Hypotension, bradycardia, junctional arrhythmias, hyperglycemia, metabolic acidosis
Caustics • Coagulation necrosis with acids or liquefaction necrosis with alkali; burning, scarring/strictures, dysphagia,
glottic edema
Digoxin • Nausea, vomiting, visual disturbances, lethargy, electrolyte imbalance, hyperkalemia, prolonged AV
dissociation and heart block
Disk batteries • Can cause corrosion if there is contact with mucosal surfaces
Continued
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Chapter 37: Approach to Poisoning in Children
Continued
Ingestion Clinical findings
Ethanol • Early: nausea and vomiting, stupor, anorexia; late: coma, hypothermia, hypoglycemia
• Life-threatening: cardiorespiratory depression if levels above 400–500 mg/dL
Ethylene glycol • CNS depression, metabolic acidosis, convulsions and coma, renal failure, hypocalcemia, anion gap metabolic
acidosis, osmolal gap, oxalaturia
Hypoglycemic agents • Hypoglycemia, seizures, coma
Iron • Hemorrhagic necrosis of GI mucosa, hypotension, hepatotoxicity, metabolic acidosis, shock, seizure, coma
Isopropyl alcohol • Altered mental status, gastritis, hypotension, osmolal gap elevated, ketonuria without metabolic acidosis or
hypoglycemia
Lead • Abdominal pain, constipation, anorexia, listlessness, encephalopathy (peripheral neuropathy), microcytic
anemia
Methanol • CNS depression, delayed metabolic acidosis, optic disturbances, anion gap metabolic acidosis, osmolal gap
Tricyclic antidepressants • Lethargy, disorientation, ataxia, urinary retention, decreased GI motility, seizures, coma
• Cardiovascular alterations: sinus tachycardia, widened QRS complex; may progress to hypotension, ventricular
dysrhythmias, cardiovascular collapse
CNS, central nervous system; AV, asterioventricular; GI, gasteointestinal.
Table 2: Toxidromes
Mental status Heart rate BP RR Pupils Laboratory and electrocardiographic findings
Acetaminophen Early: nausea, vomiting – – – – Elevated aspartate transaminase, alanine transaminase,
Late: confusion, stupor, bilirubin after 24 h
coma
Salicylates Disorientation, ↑ – ↑ – Respiratory alkalosis, progressive anion gap metabolic
lethargy, convulsions, acidosis, hyperglycemia or hypoglycemia, electrolyte
coma imbalances
Anticholinergics Delirium, psychosis, ↑ ↑ – Large, Sinus tachycardia (tricyclic antidepressants increase QRS
seizure, coma sluggish interval)
Benzodiazepines Drowsy, lethargy, coma ↓ – ↓ – –
Calcium channel Drowsy, confusion ↓ ↓ – – Heart block, metabolic acidosis, hyperglycemia
blockers
Stimulants Agitation, delirium, ↑ ↑ ↑ Large, –
psychosis, convulsions reactive
Narcotics Drowsy, coma ↓ ↓ ↓ Pinpoint Respiratory acidosis
Organophosphates Confusion, coma ↓ ↓ ↑ Small –
Sedative/hypnotics Somnolence, coma ↓ ↓ ↓ Variable –
with respiratory abnormalities or shock should receive high-

Clinical Pearls flow oxygen through a nonrebreathing mask. Children with
• Abnormal sounds suggest partial airway obstruction decreased consciousness and reduced respiratory effort should
• If the patient has altered sensorium, the airway should be receive bag-mask ventilation with 100% oxygen. Bag-Mask
managed immediately. ventilation should be done even with adequate saturation as
children may have high levels of CO2.
Breathing Circulation
Respiratory rate, effort of breathing, retractions, breath sounds, Cardiovascular system is assessed by heart rate, pulse volume,
chest expansion, and abdominal excursions are noted for the capillary refill, blood pressure, coolness of skin, sensorium,
adequacy of breathing and ventilation. Children presenting and urine output. Crystalloids should be given to manage 171
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hypovolemia, followed by inotropes and specific antitoxins and ecstasy. An enlarged anion gap greater than 18 is found
as these can correct hypotension rapidly. In some poisonings, in ethanol, iron, methanol, salicylates, and ethylene glycol.
inotropes can worsen hypotension. In a similar fashion, Hypokalemia is seen in beta agonist and theophylline
arrhythmias should be managed with specific antidotes, poisoning, while hyperkalemia is seen in digoxin ingestion.
crystalloids, and antiarrhythmics.
Clinical Pearls
Disability
Neurological function is assessed by measuring conscious • Interpretation of drug concentrations and enzymes in
ness, pupillary size, posture, and presence of convulsive neonates differs from children
movements. Level of consciousness can be measured by • Activated charcoal does not absorb iron, metals, lithium,
using the AVPU scale. Poisoning with opiates, sedatives, cyanides, petroleum distillates, and alcohol.
antihistamines, and hypoglycemic agents should be considered
in children with lower level of consciousness. Large pupils
suggest amphetamines, ecstasy, theophylline and tricyclic- Poison Elimination
antidepressant poisoning (all of these cause hypertonia) Minimizing toxin exposure: this step is especially helpful in
while small pupils suggest opiates and organophosphorus cases of topical and inhaled toxin exposure. External toxin
poisonings. Convulsions can be treated by lorazepam or decontamination prevents ongoing toxicity to the child
midazolam. Trial of naloxone should be considered in and also protects staff from exposure. The child needs to be
suspected opiate poisoning. disrobed including removal of jewelry, watches, etc. and the
entire body or exposed area washed, preferably in a suitable
Exposure area in the emergency room. Ocular exposures should be
The core temperature of the child should be recorded. managed by irrigating the eye with copious isotonic saline
Salicylates, anticholinergics, sympathomimetics, cocaine, and (such as normal saline or lactated ringers) for at least half-an-
dissociative drugs such as ketamine can cause a fever. Anti hour or till normal ocular pH is obtained. Prior use of ocular
pyretics are not effective and external and internal cooling anesthetics such as tetracaine will ensure better irrigation.
measures should be used to reduce the core temperature to
less than 39°C. Benzodiazepines, dantrolene, or paralysis and Toxin Elimination
mechanical ventilation should be used to reduce excessive The evidence for toxin elimination from the gastrointestinal
heat production due to agitation or muscle rigidity. tract is inconclusive, yet it continues to be used in certain
circumstances. In asymptomatic children with nontoxic
Monitoring and Investigations ingestions, it is not required. However, if the ingestion is
Monitoring includes pulse oximetry, continuous ECG recent, the child symptomatic, or there is a possibility of
monitoring, noninvasive blood pressure monitoring, and core delayed toxicity, then decontamination by various methods is
temperature monitoring. Blood investigations should include recommended.
arterial blood gases and blood glucose.
Complete blood count, urinalysis, and tests of hepatic and Activated Charcoal
renal function are done. If facilities exist then plasma drug Activated charcoal has a surface area of 1,000 m2/g, is safe and
concentrations of a few drugs such as paracetamol, salicylates, can be used in the dose of 1 g/kg per dose and is capable of
iron, lithium, theophylline, methanol, digoxin, ethylene glycol, binding a number of poisonous substances without being
anticonvulsants, methaemoglobin, and carboxyhemoglobin systematically absorbed. It, however, does not absorb iron,
should be done. However, they should not be part of the general metals, lithium, cyanides, petroleum distillates, and alcohol.
screen; rather they should be done only when suspected, for The dose is generally 10 times the estimated poison dose, and
confirmation of the diagnosis. Usually the results are available generally children are given 25–50 g. Repeated doses can be
later and do not impact initial management. Additionally, used in aspirin, barbiturates, and theophylline as they promote
interpretation of results should be carefully done in neonates drug reabsorption from the circulation into the bowel and thus
as levels of cholinesterase and carboxyhemoglobin may differ interrupt enterohepatic cycling. Charcoal is unpalatable and
from children. A strip of the child’s ECG should be studied, hence flavoring may be necessary. This does reduce charcoal’s
especially if arrhythmias are suspected, and a chest x-ray activity. Aspirated charcoal can cause lung damage. Usefulness
should be done if there is clinical suspicion of aspiration or of activated charcoal beyond 1 hour of ingestion is limited but
pulmonary edema. can be considered, if delayed gut absorption is expected.
Results of investigations can assist in identifying drugs
that may have caused the poisoning. Metabolic acidosis is Emesis
seen with carbon monoxide, iron, methanol, ethylene glycol, Emesis by administration of ipecac syrup is not recommended
tricyclic antidepressants, salicylates, tricyclic antidepressants, for gastrointestinal decontamination.
172
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Chapter 37: Approach to Poisoning in Children
Gastric Lavage Table 3: Antidotes and management of selected toxic exposures

Lavage is not routinely recommended for decontamination Ingestion Potential antidote/Other management
due to variable results, lack of evidence of improved outcomes,
Acetaminophen N-acetylcysteine, activated charcoal within 4 h
and significant adverse effects. Gastric lavage is initiated in
children who present within 1 hour. It is contraindicated Antihistaminics Activated charcoal or whole bowel
in poisonings by most hydrocarbons, alkalis, and acids. In irrigation if extended-release formulations,
anticonvulsants, physostigmine
children, additional difficulty is encountered as the small
size of the lavage tube makes it difficult to remove the toxin. Benzodiazepine Flumazenil
Children often need to be intubated to facilitate the procedure, β-blockers Glucagon, activated charcoal if early after
especially if they have altered sensorium. Most commonly it ingestion, whole bowel irrigation for delayed-
is effectively used in iron over ingestion and the usual fluid release formulations, atropine, IVF, pressors
is water or isotonic solution, in aliquots of 10–20 mL/kg. To Calcium channel Calcium, activated charcoal if early after
perform lavage, the child is placed on its left side and a lavage blockers ingestion, whole bowel irrigation for delayed-
tube is passed into the stomach. Fluid is aspirated and small release formulations, atropine, IVF, pressors,
aliquots of fluid are instilled and reaspirated. This process is insulin/glucose
continued till the aspirate is clear. After lavage, the tube can be Cholinesterase Atropine, pralidoxime
used for instilling specific antidote or activated charcoal. inhibitors
Whole-Bowel Irrigation Digoxin Digoxin immune fab, activated charcoal,

electrolyte management
This is not routinely indicated but is used in poisoning by
sustained-release or enteric-coated drugs, metals such as Iron Deferoxamine, whole bowel irrigation,
hemodynamic support, monitor for possible
iron and lithium, and drug packets that have long absorption
GI bleed, treat acidosis, hypoglycemia, and
time or are not bound by charcoal. A large volume (>1 L) hypotension
polyethylene glycol electrolyte solution is administered at
a fast rate, via nasogastric tube. Effectiveness is seen until Isoniazid Pyridoxine
about 4 hours after ingestion of enteric-coated tablets and Opioids Naloxone
sometimes even until about 12–16 hours after administration Salicylates Correct electrolyte imbalance, fluid therapy,
of some sustained-release medications. It causes formation urine alkalinizers, hemodialysis
of liquid stools and reduces transit time of intestinal contents.
Sulfonylurea Dextrose, octreotide
Cathartics Tricyclic Activated charcoal, sodium bicarbonate to
These are of equivocal efficacy. Saccharide (Sorbitol) and antidepressants reduce cardiotoxicity, pressor support
saline (magnesium citrate) cathartics have been administered Cyanide Ensure airway, breating, circulation, 100%
as a single dose. oxygen inhalation, sodium nitrite/sodium
thiosulfate or hydroxocobalamin
Clinical Pearls Carbon monoxide 100% oxygen inhalation or hyperbaric oxygen
Caustic agents Ensure airway, breating, circulation, steroid
• Ipecac syrup is not recommended for gastrointestinal deconta
use in esophageal burns is controversial;
mination hospitalize the patient to monitor for
• Cathartics are of unknown efficacy. mediastinitis, pneumonitis, and peritonitis
Disk batteries Removal if in esophagus; if below esophagus,
watch for 3 days for passage with stools, if not
Other Methods of Elimination
passed out, consider surgical removal
Urinary alkalinization by the administration of sodium
Ethanol Respiratory management, correction of
bicarbonate, effectively increases the elimination of drugs
hypoglycemia, temperature control, thiamine
with a low pH such as salicylates and chlorpropamide. (in chronic alcoholism)
Alkalinization increases the ionized fraction of the drug in the
tubular lumen, preventing its reabsorption. Hemodialysis is Ethylene glycol Ethanol or 4-methylpyrazole if level
and methanol >20 mg/dL, sodium bicarbonate, calcium,
used for salicylates, toxic alcohols, lithium, and theophylline.
pyridoxine, thiamine, folate, hemodialysis
Charcoal hemoperfusion, plasmapheresis, exchange trans
fusion and continuous ultrafiltration techniques may also Lead Chelation with edetate calcium disodium,
be used. 2,4-dimercaptopropanol, succimer, and
anticonvulsants if required
Specific Antitoxins Agents causing Methylene blue
In some poisonings, antidotes which can counter the poison methemo
globinemic
may be available (Table 3). 173
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Algorithm 1
Management of poisoning
ECG, electrocardiography OPA,oropharyngeal airway; LMA, laryngeal mask airway; CBC, complete blood count; NIBP, noninvasive blood pressure; ABG, arterial
blood gas; RFT, renal function test; LFT, liver function test; CAB, compressions, airway, breathing.
Key points
SUGGESTED READINGs
1. Abbruzzi G, Stork CM. Pediatric toxicologic concerns. Emerg Med Clin North Am.
))
Providers should be aware of most common poisonings that 2002;20(1):223-47.
occur in the area they work 2. Clinical Practice Guidelines: Paracetamol Poisoning from The Royal Children’s
))
Stabilization of the child is of prime importance Hospital accessed at http://www.rch.org.au/clinicalguide/guideline_index/Para
cetamol_Poisoning/ on 12 Oct 2013.
))
Awareness of toxidromes will enhance ability to manage 3. Florin TA, Ludwig S. Poisoning. In: Florin T, Ludwig S, Aronson P, Werner H (Eds).
complex poisonings Netter’s Pediatrics. Philadelphia, PA: Elseiver/Saunders; 2011. pp. 56-61.
))
Investigations should be tailored to suspected toxins 4. Jepsen F, Mary R. Poisoning in children. Current Paediatrics. 2005;15(7):563-8.
5. Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE. Poisonings. In:
))
Consultation with a toxicologist is recommended. Kliegman RM, Stanton BF, St. Geme III JW, Schor NF, Behrman RE (Eds). Nelson
Textbook of Pediatrics, 19th ed. Philadelphia, PA: Elsevier/Saunders; 2011. pp.
250-70.
6. Penny L, Tony M. Poisoning in children. Continuing Education in Anaesthesia.
Critical Care & Pain. 2009;9(4):109-13.
7. Punja M, Hoffman RJ. Approach to poisoning. Critical Care Emergency Medicine.
Acknowledgement 2011. p. 409.
8. Rezaiyan T. Poisonings. In: Tschudy M, Arcara K (Eds). The Harriet Lane Handbook:
The author would like to thank Dr Satvik Bansal for drawing the a Manual for Pediatric House Officers, 19th ed. Philadelphia, PA: Mosby; 2011.
algorithms and Dr Shikha Kothari for editing the manuscript. pp. 19-56.
174
Ch-37.indd 174 11/24/2016 12:43:43 PM

CHAPTER 38
Approach to Burns in Children
Vibha S Bafna
INTRODUCTION ESTIMATION OF BURNT BODY SURFACE AREA

Burn injuries are third leading cause of unintentional deaths in Appropriate burn charts like the Barlow’s or Lund and Browder
children. Around 90% of these burns are caused by household chart, for different age groups should be used to estimate the
accidents mostly in the kitchen and mainly by scald injuries. extent of body surface area burnt (Table 2).
Adolescents are often involved in flame burns, firecracker
injuries, and high voltage electrical injuries. Clinical Pearls
This chapter deals with:
• Accurate estimation of the burnt surface area and depth is
• Modern burn classification system
required for fluid resuscitation and prediction of eventual
• Estimation of burnt body surface area morbidity and mortality
• First aid measures
• In small burns, less than10% burnt surface area (BSA), the rule
• The initial triage and management strategy
of palm may be used, especially in outpatient settings. The
• Further treatment
palm of the child is roughly 1% of the child’s BSA.
• Prevention.
MODERN BURNS CLASSIFICATION FIRST AID MEASURES

Older descriptions of the burn injuries have now been replaced • Remove the child from the harmful environment. Extinguish
by superficial, partial thickness (superficial and deep) and full flames by rolling the child on ground, cover him with a
thickness burn injuries (Table 1) (Figs 1 to 4). blanket or a carpet
TABLE 1: Categories of burn depth

Criteria 1st degree burn 2nd degree, or partial thickness burn 3rd degree, or full thickness burn
(superficial) (superficial and deep)
Surface • Dry, no blisters • Moist blebs, blisters • Dry, leathery eschar
appearance • Minimal or no edema • Underlying tissue is mottled, pink and white, fair • Mixed white, waxy, khaki, mahogany, soot
• Erythematous capillary refill stained
• Blanches, bleeds • Bleeds • No blanching or bleeding
Pain • Very painful • Very painful • Insensate
Histological • Epidermal layers only • Epidermis, papillary, and reticular layers of dermis • Down to and may include fat, sub
depth • May include domes of subcutaneous layers cutaneous tissue, fascia, muscle, and bone
Healing • 2–5 days with no • Superficial: 5–21 days with no grafting • Large areas require grafting
time scarring • Deep partial: 21–35 days with no infection • Small areas may heal from the edges after
• If infected: converts to full thickness burn weeks
SECTION 4: Office Emergencies
Fig. 1: Superficial partial thickness burn
Fig. 4: Depth and level of burn
• Remove smoldering clothing or clothes saturated with hot

fluids. Remove all jewelery, especially rings and bracelets
to prevent constriction and vascular compromise
• In case of scalds, wash the area with copious water and
cover it with cold wet compresses
• In case of chemical injury, brush off any remaining
chemical and wash the affected area with water. Consider
using a neutralizing agent
• In case of electrical burns, shut off the current before
touching the victim yourself
• Administer analgesic medications as feasible
• Arrange for quick and safe transport to nearest adequately
equipped medical facility.
Fig. 2: Deep partial thickness burns INITIAL TRIAGE AND

MANAGEMENT STRATEGIES
Rapidly review the cardiovascular and pulmonary status.
Document pre-existing conditions like asthma, chronic heart,
renal, or hepatic disease, etc.
Airway and Breathing

Ensure and maintain adequate airway and provide humidified
oxygen. Endotracheal intubation may be required in patients
with facial burns or burns in an enclosed space which can
cause inhalational injury leading to laryngeal edema. Hypoxia
or carbon monoxide poisoning is treated with 100% oxygen.
Circulation
Children with burns more than 15% of body surface area (BSA)
require intravenous fluid resuscitation to maintain adequate
perfusion. Ringer lactate 10–20 mL/kg/h is initially infused
until proper fluid replacement can be calculated. All high
176 Fig. 3: Full thickness burns tension electrical burns require forced alkaline diuresis to
CHAPTER 38: Approach to Burns in Children
TABLE 2: Barlow chart for estimating the percentage of burn area

Body part 0–1 yr 1–4 yr 5–9 yr 10–14 yr 15–18 yr Adult
Head 19 17 13 11 9 7
Neck 2 2 2 2 2 2
Anterior trunk 13 13 13 13 13 13
Posterior trunk 13 13 13 13 13 13
Right buttock 2.5 2.5 2.5 2.5 2.5 2.5
Left buttock 2.5 2.5 2.5 2.5 2.5 2.5
Genitalia 1 1 1 1 1 1
Right upper arm 4 4 4 4 4 4
Left upper arm 4 4 4 4 4 4
Right lower arm 3 3 3 3 3 3
Left lower arm 3 3 3 3 3 3
Right hand 2.5 2.5 2.5 2.5 2.5 2.5
Left hand 2.5 2.5 2.5 2.5 2.5 2.5
Right thigh 5.5 6.5 8 8.5 9 9.5
Left thigh 5.5 5.5 8 8.5 9 9.5
Right leg 5 5 5.5 6 6.5 7
Left leg 5 5 5.5 6 6.5 7
Right foot 3.5 3.5 3.5 3.5 3.5 3.5
Left foot 3.5 3.5 3.5 3.5 3.5 3.5
177
avoid renal damage due to myoglobinuria caused by muscle Box 1: Indications for hospitalization for burns
injury. There is high risk of arrhythmias in electrical burns, so
cardiac monitoring should be started immediately on arrival • Burns affecting >15% body surface area
and cardiopulmonary resuscitation should be instituted • Full thickness or third degree burns
promptly if indicated. • Electrical burns caused by high tension wiring or lightening
• Chemical burns
Associated Injuries • Inhalational burns
Evaluate the child for associated internal or external injuries. • Inadequate home or social environment
Cervical-spine injury precautions should be observed until it • Suspected child abuse or neglect
is ruled out. • Burns to face, hands, feet, genitalia, perineum, or major joints
• Burns in patient with significant pre-existing medical conditions
Extent and the Depth of Burns
• Associated injuries like fractures
Assess with the help of appropriate charts.
Nil by Mouth • First 24 hours:

{{ 4 mL/kg/% of BSA burn of ringer lactate. The first half is
Children with more than 15% burns should not receive oral
fluids initially to avoid gastric distension. A nasogastric tube infused over 8 hours and the rest is given over the next
should be inserted to avoid aspiration. 16 hours from the time of burn and not from the time
of hospitalization
{{ In addition routine maintenance fluids are continued.
Catheterization
• Second 24 hours:
A Foley’s catheter should be inserted to monitor urine output {{ Half of the first day’s fluid is infused as ringer lactate in
in all children who require fluid resuscitation. 5% dextrose
{{ Decrease sodium concentration in fluids in infants if
Wound Care urinary sodium is rising
All wounds should be wrapped with sterile towels till further {{ The choice of fluids as colloids or crystalloids is
plans of treatment are finalized. presently controversial. Colloids may be preferred

in burns more than 85% BSA, to be started after
Clinical Pearl 8–24 hours of injury.
• Emergency room management of burns focuses on airway, Assessment and Monitoring

breathing, and fluid resuscitation. Monitor: vitals, urine output, mental status, acid-base balance,
hematocrit, and serum proteins. Adjust fluids according to
patient’s response.
FURTHER TREATMENT
Catheterization: it should be done in all children needing fluid
Outpatient Management of Minor Burns resuscitation or those with genital/buttock or upper-thigh
burns.
First and second degree burns of less than 10% of BSA can be
treated on an outpatient basis. They do not require tetanus IV access: in case of major burns, an adequate central venous
vaccine except if they are unimmunized. Blisters should access must be secured for fluid replacement and for central
be left intact and dressed with silver sulfadiazine cream. venous pressure monitoring in patients with hemodynamic
Debridement of the devitalized skin is required after the instability. Consider arterial line in patients needing frequent
blisters have ruptured. blood gas monitoring.
Initial investigations: hemogram, urine routine, electrolytes,
INPATIENT MANAGEMENT blood sugar level, renal function test, serum proteins, other tests
(arterial blood gas, prothrombin time, partial thromboplastin
OF BURNS (BOX 1)
time and cultures, etc. are done as indicated.
This includes fluid and electrolyte management, adminis
tration of blood products, antibiotics, wound care, pain relief, Electrolytes
and nutrition.
Sodium: supplementation may be required for children with
more than 20% burns, if 0.5% silver nitrate solution is used
Fluid Resuscitation as topical antibacterial burn dressing. Oral sodium chloride,
Modified Parkland formula is most commonly used to calculate 4 g/m² BSA/day is given in 4–6 divided doses to maintain
the initial fluid requirement. sodium above 130 mEq/L.
178
CHAPTER 38: Approach to Burns in Children
Potassium: Maintain levels above 3 mEq/L. Potassium losses silver) and biobrane (bilaminate membrane with an outer layer
are increased with 0.5% silver nitrate solution or in patients on of silicone and an inner layer of a nylon mesh impregnated with
aminoglycosides, diuretics, or amphotericin. collagen, induces epithelization and neovascularization) are
newer options used in extensive burns. Accuzyme ointment is
Subsequent Fluids and Feeding a topical enzymatic debridement agent useful in deep second
degree wounds to remove dead tissue and aid early healing.
Oral feeding may be started as early as 48 hours after a burn
Deep 2nd degree and 3rd degree burns should be excised
injury with the help of a nasogastric feeding tube. IV fluids are
early and grafted. Sequential excision and grafting is often
decreased according to the oral feeds tolerated so as to keep
required in deep burns.
the total fluid intake constant.
Blood Products: Indications Clinical Pearl

Packed red blood cells are infused for Hb of less than 8 g/dL. • Second and third degree burns need immediate surgical referral.
Consider transfusion in patients with Hb less than 10 g/dL
with systemic infection, hemoglobinopathy, cardiopulmonary Prompt excision and wound closure is achieved with
disease, or anticipated (or ongoing) blood loss when repeated autografts. Alternatives for wound closure include allograft,
grafting is needed. xenografts, and other synthetic skin coverings which may be
useful in extensive burns to limit fluid, electrolyte, heat and
Albumin: 5% albumin is infused to maintain a serum albumin protein loss, and to reduce pain.
level above 2 g/dL. Following amount is infused over 24 hours
starting on second day.
Pain Relief
Body surface area (BSA) 30–50% 50–70% 70–100% Adequate analgesia, anxiolytics, and psychologic support is
necessary to reduce early metabolic stress and long-term post-
Albumin (mL/kg/% BSA) 0.3 mL 0.4 mL 0.5 mL
traumatic stress disorders. Opiate analgesics like morphine
Fresh frozen plasma: it is indicated for a deranged prothrombin and anxiolytics like lorazepam can be used in conjunction
time (>1.5 times) or activated partial thromboplastin time for synergistic effect. Procedures like dressing change and
(>1.2 times) in children who are bleeding or scheduled for debridement will require adequate sedation and pain relief
a procedure that could result in blood loss of more than half with same agents used by IV route. Ketamine is another good
blood volume. option for procedural sedation.
Nutritional Support
Prevention of Infection/Role of Antibiotics
The burn injury produces a hypermetabolic response causing
The use of prophylactic antibiotics is controversial. Children
protein and fat catabolism. Energy expenditure can be
with more than 30% burns should be treated in a bacteria-
curtailed by early excision and grafting, controlling ambient
controlled segregated unit.
temperature and humidity, thus avoiding cold stress, treating
Mortality related to burn injury results from metabolic and
anxiety and pain, and allowing appropriate sleep intervals.
bacterial consequences of large open wound, reduction of host
High calorie support consisting of 1,800 cal/m2/day plus
defense and malnutrition. Specific sites of infection include
2,200 cals/m2 of burn/day and high proteins, i.e., 3–4 g/kg/day
wound infection, pneumonia, urinary tract infection and
reduces metabolic stress. Multivitamins, especially B group,
blood stream infection.
vitamin C, and A, and zinc are also essential.
Fever alone may not be indicative of infection as it may
Alimentation should be started as soon as possible,
result from hypermetabolic response. Serial evaluation
parenterally or enterally to meet the high caloric needs.
of burn wound and close monitoring of vitals and other
Parenteral nutrition should be changed to enteral as soon as
parameters is crucial for early detection of infection. Sepsis
practical, to decrease infectious complications.
screen includes blood cultures, wound swabs, throat swab,
sputum, urine, and stool.
An attempt should be made to isolate the organism before INHALATIONAL INJURY
starting empirical therapy. Broad spectrum antibiotic with
It should be suspected in case of: (1) exposure to direct heat—
Gram-positive coverage (staphylococci) should be used.
e.g., steam burns. (2) Child with acute asphxia. (3) Carbon
monoxide (CO) poisoning. (4) Exposure to toxic fumes—e.g.,
Wound Care and Surgical Management cyanides from combustible plastics.
Wound treatment and prevention of wound infection promote The consequences of burns with inhalational injury can be:
early healing and improve aesthetic and functional outcomes. • Early CO poisoning, airway obstruction, pulmonary edema
Topical treatment of burns can be done with silver nitrate, • Acute respiratory distress syndrome usually evident at 24–
silver sulfadiazine, or mafenide acetate. These agents can 48 hours, although it can occur even later
penetrate tissue and prevent infection. Wound coverings like • Late complications (days to weeks)—pneumonia and
Aquacel-Ag (absorptive hydrofiber dressing impregnated with pulmonary emboli. 179
ALGORITHM 1 the hospital stay. Services of child therapists may be required

to ease the early and long-term psychological problems of the
child and his care providers.
PREVENTION OF BURNS
Pediatricians can play a major role in preventing the most
common burns by educating parent and caregivers.
KEY POINTS
))
Appropriate first aid and initial emergency evaluation and
treatment are the keystones in successful management of
burn injury
))
The key areas of indoor management of large burns are—fluid
and electrolytes balance, wound management, prevention
ABC, airway, breathing, circulation.
and treatment of infection, pain relief, and adequate nutrition
))
A large number of burns in children can be prevented by simple
and effective measures. Education of parents and other care
Treatment providers plays a very important role in prevention of burn
• Maintaining a patent airway by prompt intubation and injuries.
adequate ventilation and oxygenation
• Beta-agonist aerosols and inhaled corticosteroids are
helpful in cases with wheezing SUGGESTED READINGS
• Carbon monoxide poisoning is treated with 100% oxygen
but severe cases may require hyperbaric oxygen therapy 1. Antoon AY, Donovan MK. Burn injuries. In: Kliegman, Stanton, St. Geme, Schor and
• Patients with severe inhalational injury not responding Behrman (Eds). Nelson Textbook of Pediatrics, 19th ed. Elsevier, Saunders.
to conventional ventilation may require high-frequency 2. Chugh K (Ed). Management of Burns in Children in Manual of Pediatric Intensive
ventilation, nitric oxide inhalation and finally extra Care & Emergency Medicine, 2nd ed.
3. Gupta RK, Gupta R. Approach to a child with burns. In: Gupte S (Ed). Recent
corporeal membrane oxygenation.
Advances in Pediatrics. Neonatal & Pediatric Intensive Care. New Delhi: Jaypee
Brothers; 2011.
RECONSTRUCTION AND REHABILITATION 4. Lund CC, Browder NC. The estimation of area of burn. Surg Gynecol Obstet.
1944;79:352.
Occupational and physical therapy should begin as soon as the 5. Papinir HS. Initial management of a major burn II; assessment and resuscitation.
initial salvage measures are over and continued throughout BMJ. 2004:329;101-3.
180
CHAPTER 39
Approach to Envenomation
Mandar B Patil
INTRODUCTION TABLE 1: Differences between a poisonous and nonpoisonous

snake (Fig. 1)
Certain reptiles and arthropods secrete and introduce
poisonous fluids into the body of their victims by stings and Poisonous snake Nonpoisonous snake
bites. This is known as envenomation. Head is triangular-shaped with small Head is rounded with
The most common envenomation encountered is due to scales large scales
snakes and scorpion bites followed less commonly by bee and Pit between the eye and nostril No pit
wasp sting and rarely by lizards. (pit viper)
Jaw scales: –
APPROACH TO SNAKE BITE • Third labial touches eye and nasal
shields (cobra, king cobra, coral snake)
India is inhabited by about 244 species of snakes of which 57 are
• Central row of vertebral scales enlarged
poisonous or harmful. The commonly encountered poisonous
• Four large infralabial scales (krait)
snakes in this region include cobra (Naja naja), common krait,
Russell’s viper, saw-scaled viper, and less commonly sea snakes. Fangs are long and grooved Short and solid
Teeth have two long fangs Several small teeth
How to Identify Venomous Snake Belly scales are large and cover entire Small or large scales
Diagnosis of the species of the bitten snake is important for breadth but do not cover the
optimal clinical management. This is achieved by examining entire breadth
the dead snake or by the clinical examination of the victim. Tail is compressed Not much compressed
Commonly encountered poisonous snakes include (Fig. 2):
Usually nocturnal habits Not necessarily
• Naja naja: it is the commonest Indian cobra. It is identified
by the famous spectacle mark on the hood. When
challenged, cobras rear up, spread a hood, hiss, and make The under surface is white with brown speckles. When
repeated strikes towards the aggressor challenged, the grating rasp is both a warning as well as an
• Common krait: it is smooth bluish-black with a rounded identifying sound.
head slightly distinct form the neck. There are normally
about 40 thin white cross bands. The under surface is white
CLINICAL FEATURES (ALGORITHM 1)
• Russell’s viper: the scales are very rough. The pupil of the
eye is distinctly vertical. The body has black edged almond Clinical features suggestive of nonvenomous snake bite are
shaped marks. The best recognition characters are the (also seen in a poisonous snake bite without envenomation or
short, fat body, the triangular shaped head and a very bite through clothing or leather boots) (Fig. 2):
regular chain-like pattern. When threatened, it makes a • Universal fear—a state of shock
loud and characteristic hissing sound • Multiple teeth impressions at bite site
• Saw-scaled viper: the scales are rough and heavily keeled, • Absence of significant local swelling or pain
eyes are large, and the head is wider than the neck. The • Anxious victims may overbreathe and develop tingling and
body is brown-greyish with a darker zigzag pattern mark numbness in the limbs, stiffness or tetany of hands and
on the back and a distinct or lance mark on the head. feet, and dizziness.
Clinical features suggestive of envenomation:

• Elapidae (cobra, krait): neurotoxic
{{ Minimum local features at bite site
{{ Inability to open mouth
{{ Vomiting—earliest symptom
{{ Inability to protrude tongue
{{ Blurred vision
{{ Inability to speak or swallow
{{ Ptosis
{{ Respiratory paralysis
{{ Ophthalmoplegia
• Viperidae (vipers):
{{ Local:
–– Pain
–– Blistering
–– Swelling
–– Necrosis
–– Bruising
–– Lymphangitis and lymphadenitis
{{ Systemic (coagulopathy):
–– Spontaneous bleeding from gums, nose, skin,

gastrointestinal tract, and central nervous system
–– Cardiac arrhythmias
–– Persistent shock or hypotension
–– Nephrotoxicity
–– Disseminated intravascular coagulation
–– Abdominal pain
• Hydrophiidae (banded sea krait): myotoxic
{{ Rhabdomyolysis: myoglobinemia, hypercalcemia, and
renal failure
{{ Trismus, muscle pain, tenderness with progressive
paralysis
• Crotalidae (pit viper):
{{ Pain swelling, blistering, and regional lymphadenopathy
{{ Headache, nausea, vomiting, abdominal pain and

Fig. 1: Examination of bitten snake; poisonous versus nonpoisonous chest pain
snake {{ Coagulopathy
ALGORITHM 1
Diagnosis of the snake responsible for the bite
182
CHAPTER 39: Approach to Envenomation
ALGORITHM 2
Management of snake envenomation
Fig. 2: Poisonous snakes: Cobra, common Krait, Rusell’s Viper and

Saw- scaled Viper
Clinical Pearls
• Venomous snake bite is identified primarily by the clinical
20 WBCT, 20-minute whole blood cloting test.
signs of envenomation in the victim, although dead snake, if
brought and identified, can add to the diagnosis
• Cobra and krait envenomation result in neurotoxicity ■■ Repeat dose of ASV:
• Viper envenomation causes coagulopathy. ǅǅ Hemorrhagic bites: After initial 10 vials
of ASV, no dose is given for next 6 hours.
Then, 20-minute whole blood cloting test
MANAGEMENT OF SNAKE (20 WBCT) is done every 6 hours, and if
positive, a repeat dose of 10 vials is given.
ENVENOMATION (ALGORITHM 2)
Occasionally, multiple doses may be
• First aid: Traditional first aid measures such as incision required
over bite marks, suction of venom, tourniquets, and local ǅǅ Neurotoxic bites: If the victim does not
ice packs should be discouraged improve (or worsens) after first dose of ASV
Recommended first-aid measures are: and neostigmine over 1–2 hours, another
{{ Reassurance to the victim dose of 10 vials is given. After this, the victim
{{ Immobilization of the bitten limb with a splint or sling will either recover or require mechanical
{{ To avoid interference with the bite wound to prevent ventilation
introduction of the infection ■■ Management of anaphylaxis due to ASV:
{{ Pressure immobilization is recommended only for ǅǅ ASV can result in anaphylaxis
bites by neurotoxic elapid snakes, including sea snakes ◆◆ Stop ASV infusion
but not for viper bites ◆◆ Epinephrine 0.01 mg/kg intramuscularly
• In hospital: (IM)
{{ Rapid assessment and resuscitation: ◆◆ Hydrocortisone hemisuccinate 2 mg/kg
–– Rapid assessment of airway, breathing, circulation, intravenous (IV)
and level of consciousness ◆◆ Diphenhydramine 0.2 mg/kg IV
–– If required, urgent resuscitation for prolonged hypo ◆◆ After complete recovery, reintroduce
tension and shock, terminal respiratory failure, ASV, initially slow and then with a
sudden or rapid deterioration and cardiac arrest normal drip rate
{{ Specific therapy: ■■ 20-minute whole blood clotting test:
–– Polyvalent antisnake venom (ASV): ǅǅ Between 2–5 mL of victim’s blood is taken
■■ Dose of ASV: in a new glass test tube and left undisturbed
ǅǅ The dose of the ASV is not determined by for 20 minutes
the severity of symptoms of envenomation ǅǅ The tube is tilted to see if the blood is still
ǅǅ 10 vials of ASV are dissolved in 200 mL of NS liquid (indicating consumption coagulo
and infused over 1 hour pathy) 183
ǅǅ This test is done to assess effectiveness of

ASV and deciding its subsequent doses
–– Neostigmine:
■■ It is used in victims of postsynaptic type of
neuromuscular junction block caused by neuro
toxic snake (cobra) bite. Dose is 25–50 µg/kg IM
every 4 hourly with 0.05 mg/kg atropine IV till
complete neurological recovery
–– Mechanical ventilation:
■■ It is life-saving in victims of respiratory paralysis
due to neurotoxicity by cobra and krait
–– Blood transfusion (including component), volume
expanders, and peritoneal dialysis are indicated
depending upon the clinical situation
■■ The bitten limb is nursed in the most comfortable
position, preferably slightly elevated Fig. 4: Indian black scorpion
■■ Fasciotomy for compartment syndrome.
Note: If dead snake is not brought, snake species could not be withdrawal—this is the diagnostic sign of sting called “TAP
identified, directly look for sign of envenomation. sign”. Severe pain without systemic involvement is suggestive
of nonvenomous sting.
APPROACH TO SCORPION STING Systemic Manifestations
Scorpion sting is an acute life-threatening, time-limiting Characteristic autonomic storm is divided into four phases:
medical emergency among children, usually in villages. 1. Cholinergic phase
Out of 89 species of scorpions in India, only two are of 2. Adrenergic-inotropic phase
medical importance. They are Mesobuthus tamulus (Indian 3. Adrenergic-hypokinetic phase:
red scorpion) (Fig. 3) and Palamnaeus swammerdami (Indian {{ Left-ventricular dysfunction leading to cardiogenic
black scorpion) (Fig. 4). pulmonary edema
4. Recovery phase.
Clinical Features (Fig. 5 and Algorithm 3) Other features:
The envenomation is classically characterized by “autonomic • Central nervous system (encephalopathy, stroke, seizures)
storm”. • Disseminated intravascular coagulation (DIC)
• Rarely acute pancreatitis and acute renal failure.
Local Manifestations
Soon after sting, the victim experiences severe excruciating
Investigations
radiating pain from sting site, usually toes and fingers. Sudden • X-ray chest:
tap at and around the site of sting induces severe pain and {{ For evidence of pulmonary edema
• Electrocardiogram (ECG):
{{ Sinus tachycardia (most common)
{{ Sinus bradycardia
{{ Supraventricular tachycardia
{{ Peaked (tented) T waves
{{ Myocardial infarction pattern
{{ Conduction block.
Note: Low voltage complexes throughout the record and left-

anterior hemiblock indicate a poor prognosis. All victims with
systemic involvement show abnormal ECG.
• Echocardiography:
{{ Left-ventricular dilatation
{{ Regional-wall motion abnormality
{{ Decreased left-ventricular ejection fraction and

shortening fraction
• Prothrombin time, activated partial thromboplastin time
and fibrinogen degradation products (FDP) with D-dimer
184 Fig. 3: Red scorpion for evidence of DIC.
*Aggressive supportive measure may reduce mortality.

DIC, disseminated intravascular coagulation.
Fig. 5: Clinical features (according to time frame) and outcome of Mesobuthus tamulus scorpion sting in Indian children
ALGORITHM 3
Management of scorpion sting
ASV, antiscorpion venom; SNP, sodium nitroprusside; NTG, nitroglycerine.
Management (Algorithm 3) Scorpion antivenom (SAV):

• Monospecific Fab2 SAV is available for therapeutic use
Local pain: • Intravenous route
• Mild tolerable pain need not be treated • Administer as early as possible—preferably within first
• Severe pain: oral NSAIDs, local ice pack application and 6 hours of sting
xylocaine (local anesthesia). • Dose: 30–100 mL (3–10 vials).
Fluid therapy: Prazosin:
• Correction and maintenance of fluid and electrolyte • Alpha-adrenoreceptor antagonist
balance. • A dose of 30 µg/kg/dose orally or through tube feed 185
• It is repeated in the same dose at the end of 3 hours and The most well-known allergic reaction is the type I
according to the clinical response and later every 6 hours anaphylactic or immediate hypersensitivity reaction.
till the extremities are warm, dry, and peripheral veins are Type III (serum sickness) reactions occur 3–14 days
easily visible after the sting and present with fever, headache, urticaria,
• The time lag between the sting and administration of lymphadenopathy, polyarthritis, and polyarthralgias.
prazosin determines the outcome.
Mass Stinging Events
Note: Previously used therapies like atropine, steroids, morphine,
lytic cocktail, nifedipine, and captopril have proven harmful or Toxicity from massive honeybee envenomation occurs
deleterious and potentiate the effects of scorpion venom, hence directly from the systemic effects of the venom, as opposed
should be avoided. to immune-mediated anaphylaxis. Mass envenomations
usually occur when stinging insects respond to an intruder as
a threat to their colony.
Clinical Pearls • Generalized edema
• Confusion, coma, seizures
• Scorpion envenomation is characterized by autonomic storm
• Hemolysis, thrombocytopenia, DIC
• Prazosin—an α-adrenoreceptor antagonist is antidote to • Fever
envenomation • Rapidonset diarrhea
• Time interval between the sting and administration of prazosin • Rhabdomyolysis, acute renal failure
for autonomic storm determines the outcome. • Nausea and vomiting
• Tachycardia and hypotension
• Hepatotoxicity
APPROACH TO ENVENOMATION
BY BEES AND WASPS Management (Algorithm 4)
Bees and wasps are stinging insects belonging to the order • Removal of stinger from the site of sting in case of bee sting
Hymenoptera. as quickly as possible. Delays in stinger removal cause
more venom to enter the wound
Allergic Reactions and Anaphylaxis • Bee venom is acidic. Hence, neutralize it by applying
• Hives alkaline solution like soda or methylene blue. Wasp venom
• Loss of consciousness is alkaline. Hence, it is neutralized by applying vinegar or
• Pruritis lemon juice
• Heart palpitations • Mild local reactions of pain and erythema are managed
• Dyspnea with cold compresses and analgesics. Moderate to severe
• Upper airway obstruction. local reactions are managed with oral or paranteral
ALGORITHM 4
Bee and wasp sting management
186
IM, intramuscular; IV, intravenous; PO, per os.
antihistaminics (diphenhydramine 1 mg/kg IV up to SUGGESTED READINGS

50 mg or hydroxyzine 0.5 mg/kg orally up to 50 mg) and
corticosteroids 1. Bahloul M, Chaari A, Dammak H, Samet M, Chtara K, Chelly H, et al. Pulmonary edema
• Anaphylaxis: IM or SC epinephrine 0.01 mg/kg (maximum following scorpion envenomation: mechanisms, clinical manifestations, diagnosis and
treatment. Int J Cardiol. 2013;162(2):86-91.
dose 0.5 mg) of the 1:1,000 dilution of epinephrine intra 2. Bahloul M, Chabchoub I, Chaari A, Chatara K, Jallel H, Dammak H, et al. Scorpion
muscularly), IV Diphenhydramine, IV hydrocortisone (or envenomation among children: clinical manifestations and outcome (analysis of 685
methylprednisolone) and adequate IV fluid resuscitation cases). Am J Trop Med Hyg. 2010;83:1984-92.
• Treat hypotension and shock with crystalloids, dopamine, 3. Bawaskar HS, Bawakar PH. Efficacy and safety of scorpion antivenom plus Prazosin
and dobutamine compared with prazosin alone for venomous scorpion (Mesobuthgus Tamulus) sting:
randomized open label clinical trial. BMJ. 2011;342:c7136.
• Respiratory failure is managed by mechanic ventilation
4. Bawaskar HS, Bawaksar PH. Cardiovascular manifestations of severe scorpion sting
• Mass stinging: supportive care (correction of hypotension, in India (Review of 34 children). Annal Trop Pediat. 1991;11:481-88.
coagulopathy, and acute renal failure, etc.), no specific 5. Bawaskar HS, Bawaskar PH. Indian scorpion envenoming. Indian J Pediatr.
antidote or allergy treatment. 1998;65:383-91.
6. Bawaskar HS, Bawaskar PH. Scorpion sting: update. J Ass Phys India. 2012;60:
46-55.
KEY POINTS 7. Bawaskar HS. Scorpion sting. In: Shah SN (Ed). API Textbook of Medicine. 7th ed.
The Association of Physicians of India: Mumbai; 2003. pp. 1282-84.
))
The most common envenomation encountered is due to 8. Feng SY, Godo C. Hymenoptera envenomation: bees, wasps & ants. In: Strother C
snakes and scorpion bites followed less commonly by bee (Ed). Pediatric Emergency Medicine Practice. EB Medicine: 2008;5(6).
and wasp sting 9. Kulkarni ML, Anees S. Snake venom poisoning: experience with 633 cases. Indian
Pediatr. 1994;31:1239-43.
))
The commonly encountered poisonous snakes in this region 10. Kulkarni ML. Bee and wasp sting. In: Kulkarni ML, Kulkarni AS, Reddy Pradeep P,
include cobra, common krait, Russell’s viper, saw-scaled viper, Vijay NCD, Kulkarni PM (Eds). Pediatric Toxicology, 1st ed. Hyderabad: Paras Medical
and less commonly sea snakes Publisher; 2011. pp. 131-53.
))
Venomous snake bite is identified primarily by the clinical 11. Kulkarni ML. Scorpion sting. In: Kulkarni ML, Kulkarni AS, Reddy Pradeep P, Vijay
NCD, Kulkarni PM (Eds). Pediatric Toxicology, 1st ed. Hyderabad: Paras Medical
signs of envenomation in the victim, although dead snake, if Publisher; 2011. pp. 131-53.
brought and identified, can add to the diagnosis 12. Kulkarni ML. Snake bite. In: Kulkarni ML, Kulkarni AS, Reddy Pradeep P, Vijay NCD,
))
Cobra and Krait envenomation result in neurotoxicity. Viper Kulkarni PM (Eds). Pediatric Toxicology, 1st ed. Hyderabad: Paras Medical Publisher;
envenomation causes coagulopathy 2011. pp. 131-53.
13. Lovrcchio F, Cannon RD, Algier J, Ruha AM, Curry SC, Wallace KL, et al. Bee swarming
))
Polyvalent antisnake venom (ASV) is the specific treatment for in children. Am J Emerg Med. 2007;25:931-3.
snake envenomation. The dose of ASV is not determined by 14. Natu VS, Kamerkar SB, Geeta K, Vidya K, Natu V, Sane S, et al. Efficacy of antiscorpion
severity of symptoms venom serum over prazosin in the management of severe scorpion envenomation.
J Postgrad Med. 2010;56:275-80.
))
Scorpion envenomation is classically characterized by
15. Paul V, Pratibha S, Prahlad KA, Earali J, Francis S, Lewis F. High-dose anti-snake
“autonomic storm” venom versus low-dose anti-snake venom in the treatment of poisonous snake
))
Prazosin is antidote to scorpion envenomation bites—a critical study. J Assoc Phys India. 2004;52:14-7.
16. Pramanik S, Banerjee S. Wasp stings with multi-system Dysfunction. Indian Pediatr.
))
Mass honeybee envenomation usually occurs when stinging
2007;44:788-90.
insects respond to an intruder as a threat to their colony 17. Simpson ID. The pediatric management of snake bite: the national protocol. Indian
))
Mass stinging is treated with supportive care (correction of Pediatr. 2007;44:173-6.
hypotension, coagulopathy, acute renal failure, etc.). There is 18. Warrell D. Snake bite. Lancet. 2010;375:77-88.
no specific antidote or allergy treatment. 19. Warrell DA. World Health Organization. WHO/SEARO guidelines for the management
of snake-bites. Regional office for South-East Asia, New Delhi; 2010.
187
Chapter 40
Recognition and
Assessment of Critically Ill Child
Praveen Khilnani
INTRODUCTION
In outpatient practice, pediatric specialist as well as general
practitioner comes across common pediatric illnesses freq
uently. It is important to recognize potentially life-threatening
conditions as well as conditions requiring immediate inter
vention and transfer to a higher-level medical facility.
Besides accidental trauma, poisoning, insect bites, and
allergic reactions, common medical problems that bring the
child to medical attention are fever, cough, respiratory distress,
cyanosis, earache, poor feeding, vomiting, diarrhea, irritability,
lethargy, convulsions, and unresponsiveness. Common
conditions that require immediate attention are respiratory Fig. 1: Action related to pediatric assessment and intervention
distress, shock, lethargy, and coma.
Since our main goal as a medical practitioner is to prevent Algorithm 1
unnecessary mortality and morbidity by prompt and early
Common conditions precipitating cardiac arrest
recognition of potential problems leading to respiratory or
cardiorespiratory arrest, it is important to pay attention to
the following during history and physical examination done
simultaneously.
• Listen carefully to the mother.
• Do not ignore, it will not get better if something is not done.
EVALUATE, IDENTIFY, AND INTERVENE

A carefully performed clinical assessment, including obser
vation, history, and physical examination, will detect serious
illness with 90% sensitivity. Each component of the evaluation
is effective in identifying serious illness (Fig. 1 and Algorithm 1).
The assessment of a seriously unwell child involves the
following:
• Diagnostic tests:
• Pediatric assessment triangle (initial impression) (Fig. 2) {{ Laboratory and radiological.
• Primary assessment: Airway, breathing, circulation, dis
ability, exposure (ABCDE) assessment
• Secondary assessment: Initial Impression
{{ Vital signs It is the rapid assessment of a child with an emergency
{{ Focused history condition through visual and auditory evaluation of the child’s
{{ Detailed physical examination consciousness, work of breathing, and color. It is “from the
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Chapter 40: Recognition and Assessment of Critically Ill Child
Airway
The goal is to assess if the airway is patent or if there are signs
of obstruction (e.g., stridor, dyspnea, and hoarse voice). If
the child is unresponsive and cannot talk, cry, or cough,
evaluate for possible airway obstruction. Is the airway noisy
(e.g., snoring, stridor, wheeze, grunting, or hoarse speech)?
Determine if the airway is patent, and able to be maintained
with positioning and suction, or not. If cervical spine injury is
suspected, manually stabilize the head and neck in a neutral,
inline position (jaw thrust without head tilt maneuver to open
Fig. 2: Pediatric assessment triangle (initial impression) the airway).
Look in the mouth for blood, broken teeth, gastric contents,
door” observation to be completed within seconds and no and foreign objects. If solid material is visualized, remove it with
equipment is required. The initial assessment of the child’s a gloved finger covered in gauze under direct vision. If a foreign
overall condition is of crucial importance. If the child exhibits body is suspected but not visualized, a combination of back
abnormal findings, proceed immediately to the primary blows and chest thrusts is recommended in infants. In an older
assessment part of evaluation. child back blows in a forward leaning position is recommended.
Abdominal thrusts in children are not recommended as their
Consciousness effectiveness and safety have not been established.
• Reflects the adequacy of ventilation, oxygenation, brain Insert an airway adjunct (e.g., oropharyngeal or naso
perfusion, body homeostasis, and central nervous system pharyngeal airway, or laryngeal mask airway) as needed
function to maintain a patent airway. If airway patency cannot be
• What is the child’s state of consciousness: unresponsive, maintained, perform tracheal intubation. Rapid sequence
irritable, alert? intubation should be considered in all patients, except those in
• Does the child look ill? cardiac arrest, to provide optimum conditions and to minimize
the potential for aspiration. Cricothyrotomy or emergency
Work of Breathing tracheostomy can be done as a last resort to maintain airway
patency. Not many pediatricians would be familiar with
• Assess body position, visible movements of chest/
performing these procedures, therefore, in anticipation a
abdomen, and breathing pattern
consult should be obtained from an airway expert such as
• Listen for abnormal audible airway sounds (snoring,
anesthesia or an ear, nose, throat consultant.
hoarse speech, grunting, and wheezing)
• Look for visual signs of increased work of breathing such Breathing
as abnormal position or posture (i.e., sniffing position,
tripod position, head bobbing), retractions, nasal flaring, The goal in assessing breathing is to determine whether there is
grunting, gasping, and tachypnea adequate gas exchange.
• Reflects the adequacy of airway, oxygenation, and • Will the child lie flat? Is he in the tripod or “sniffing” position?
ventilation. Are the airways obstructed? Is the child short • Are accessory muscles being used (head bobbing in
of breath? infants)? Or is there minimal movement of the chest wall?
• Is there sternal, supraclavicular, substernal, or intercostal
Coloration of Skin recession present?
• Is nasal flaring present?
• Assess skin color
• Is the respiratory rate fast, slow, or normal?
• Look at the skin and mucus membranes for abnormal color
• Is cyanosis present?
(pallor, mottling, and cyanosis)
• Is air movement audible on auscultation?
• Reflects the adequacy of cardiac output and perfusion
• What is the oxygen saturation (SpO2)?
of vital organs. Is the skin unusually pale, mottled, or
Place your cheek near the child’s face and mouth and
cyanotic?
feel/listen for air movement and look at the chest/abdomen
The initial impression will help decide if the child problem
for respiratory movement. The child with breathing difficulty
is life-threatening or not.
often has a respiratory rate outside the normal limits for their
age. Normal respiratory rate values according to age are listed
Primary Assessment in table 1. Initially, the child becomes tachypneic, and as
It uses an ABCDE approach. During the evaluation, primary fatigue begins and hypoxia worsens, the child may progress
assessment and management occur simultaneously. The to respiratory failure and bradypnea. On auscultation with a
primary assessment should be periodically repeated, parti stethoscope over the mid axillary line, try to hear abnormal
cularly after major intervention or when a change in the lung sounds (e.g., wheeze, crackles, and snoring). Palpate the
patient’s condition is detected (evaluate, identify, intervene) chest for tenderness, instability and crepitations. Table 2 shows
(Algorithms 2 and 3). types and severity of retractions indicating breathing difficulty. 189
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Algorithm 2
Approach to sick child
GCS, Glasgow Coma Scale; ET, endotracheal; CPR, cardiopulmonary resuscitation; PICU, pediatric intensive care unit; IV, intravenous.
Intervention assessing ABCD with no other abnormal findings. If breathing

All children with breathing difficulties should receive high is absent or the child is hypoventilating (slow respiratory rate
flow oxygen through a face mask oxygen as soon as the airway or weak effort), respiration should be supported with oxygen
has been assessed and demonstrated to be adequate. Pulse via bag-valve-mask device and an airway adjunct needs to be
oximetry is an excellent tool to use in assessing a child’s inserted (e.g., laryngeal mask airway, and endotracheal tube).
breathing. A pulse oximetry reading above 94% indicates
that oxygenation is probably adequate. A reading below 90% Circulation
in a child with 100% mask oxygen could be an indication for The goals are to assess adequate cardiovascular function and
assisted ventilation. tissue perfusion, ensure effective circulating volume, and in
If the child is breathing adequately but is unresponsive, trauma, control of bleeding. Look for following points:
190 place the patient in recovery position (lateral recumbent) after • Is skin color normal, or is it pale or mottled?
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Algorithm 3
Approach to collapsed child
AED, automated external defibrillator; CPR, cardiopulmonary resuscitation; PALS, pediatric advanced life support.
Table 1: Normal respiratory rates* Table 2: Severity of retractions

Age Respiratory rates (breaths per minute) Breathing difficulty Location of Description
Infant (<1 year) 30–60 retraction
Mild-to-moderate Subcostal • Abdominal
1–3 years 24–40
• Retractions below
4–5 years 22–34 • Rib cage
6–12 years 18–30 Substernal • Abdominal
Adolescent (13–18) year 12–16 • Retractions below
• The sternum
*>60/min in all ages is abnormal.
Intercostal • Retractions
• Beetween the ribs
• Is there an increased respiratory rate without increased
work of breathing? Severe (may Supraclavicular • Reatractions in the
include retractions neck ablove the clavicle
• Is it cool peripherally but warm centrally?
of mild to moderate
• Is the pulse rate fast, slow, or normal? Suprasternal • Restractions just
breathings
• Is the pulse volume weak or strong? • Above the sternum
difficulty)
• Is the capillary refill time (CRT) normal or prolonged? Sternal • Inward retractions of
It is important to determine the heart rate, pulse quality, sternum towards 191
skin temperature, CRT, and blood pressure. Normal heart rate • The anterior spine
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varies with age (as noted in table 3); tachycardia can be an Blood pressure trends are useful in determining the child’s
early sign of hypoxia or low perfusion, but it can also reflect less condition and response to treatment.
serious conditions (e.g., fever, anxiety, and pain). Bradycardia
(rate <60/min in children or <100/min in newborns) indicates Disability (Mental Status)
serious illness and poor myocardial perfusion. Assess the patient by looking at appearance as part of initial
Pulse quality reflects the adequacy of peripheral perfusion. impression and at level of consciousness with the AVPU (Alert,
A weak central pulse may indicate decompensated shock, and response to Verbal stimuli, response to Pain, Unresponsive)
a peripheral pulse that is difficult to find, weak or irregular scale (Table 6). The pediatric Glasgow Coma Scale (GCS) is a
suggests poor peripheral perfusion and may be a sign of shock. second option (Table 7).
Check the femoral pulse in infants and young children, or Evaluate the brainstem by checking the responses in each
the carotid pulse in an older child or adolescent. If no pulse pupil to a direct beam of light. A normal pupil will constrict
is felt, and there are no, or minimal signs of life, commenced after a light stimulus. Evaluate the motor activity by looking for
cardiopulmonary resuscitation. symmetrical movement of the extremities, seizures, posturing,
Next, evaluate the CRT, skin color, and temperature. Normal or flaccidity.
CRT is less than 2 seconds. The CRT should be done centrally • What is the child’s AVPU score?
(e.g., on the chest) to minimize the impact of environmental • Is the child mobile? Or is there limited movement with
factors. Blood pressure determination and interpretation can poor muscle tone?
be difficult. Normal blood pressure values in children vary • If the child is crying or speaking, is this strong or weak?
according to age and are difficult to remember. Table 4 can be • If crying, can the child be consoled?
very useful in clinical practice. A low blood pressure indicates • Does the child fix their gaze on the carer(s), or does he/she
decompensated shock. have a glazed appearance?
An easy formula for determining the lower limit of • Is the child’s behavior normal for their developmental age?
acceptable blood pressure is: minimal systolic blood pressure • Is the child having convulsions, is he stiff or floppy?
= 70 + (2 × age in years) (Table 5). With knowledge of the child’s appearance from the initial
appearance and AVPU scale, if the disability assessment
Table 3: Normal heart rates (per minute) by age
demonstrates altered level of consciousness, begin with general
Age Awake rates Mean Sleeping rate life support/monitoring with oxygen, cardiac monitoring, and
New born to 3 months 85–205 140 80–160 pulse oximetry. Intubation should be considered if GCS is less
than 8.
3 months to 2 years 100–190 130 75–160
2 years to 10 years 60–140 80 60–90 Exposure
>10 years 60–100 75 50–90 Proper exposure of the child is necessary for completing
the initial physical assessment. The initial impression using
Table 4: Normal blood pressure in children by age pediatric assessment triangle requires removal of part of the
child’s clothing to allow careful observation. Be careful to avoid
Age Systolic blood Diastolic blood
rapid heat loss, especially in infants and children in a cold
pressure (mmHg) pressure (mmHg)
environment.
Female Male Female Male • Is there fever?
Neonates (1st day) 60–74 60–74 31–45 31–44 • Is there a nonblanching rash present?
Neonates (4th day) 76–83 68–84 37–53 35–53
Infant (1 month) 73–91 74–94 36–56 37–55 Secondary Assessment
Infant (3 months) 78–100 81–103 44–63 45–65 The secondary assessment focuses on advanced life-support
Infant (6 months) 82–102 87–105 46–66 48–68 interventions and management. It is important to per
form an additional assessment with a focused history and
Infant (1 years) 68–104 67–103 22–60 20–58
Child (2 year) 71–105 70–106 27–65 25–63
Table 6: AVPU
Child (7 years) 79–113 79–115 39–77 38–78
Adolescent (5 years) 93–127 95–131 47–85 45–85 A Alert The chils is awake, active and appropriately
responsive to parents and external stimuli,
*Appropriate response is assessed in terms of
Table 5: Definition of hypotension by age
the anticipated response based on the child's
Age Systolic blood pressure (mmHg) age and the setting on situation.
Term neonates (0–28 days) <60 V Voice The child responds only when the parents or
you call the child's name of speakloudly
Infants (1–2 months) <70
Children (1–10 years) 70 + (age × 2) P Painful The child responds only a painful stimulus,
such as pinching the nail bed
192 Children >10 years <90
U Unresponsive The child does not respond to any stimulus
Hypertension with hemorrhage: >2–25% acute blood loss.
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Table 7: Glosgow coma scale for adults and modified Glosgow coma scale for infants and children*
Response Adults Child Infants Coded value
Eye opening Spontaneous Spontaneous Spontaneous 4
To speech To speech To speech 3
To pain To pain To pain 2
None None None 1
Best value Oriented Oriented Coss and babies 5
Confused Confused Irritable, cries 4
Inappropriate words Inappropriate words Cries in response to pain 3
Incomprehensible Incomprehensible words or Moans in response to pain 2
sound nonspecific sounds
None None None 1
†
Best motor response Obeys Obeys commands Moves spontaneously and purposely 6
Localizes Localizes painful stimulus Withdraws in response to pain 5
Withdraws Withdraws in response to pain Withdraws in response to pain 4
Abnormal flexion Flexion in response to pain Decorticate posturing (abnormal flexion) 3
Extensor response Extension to response to pain Decerebrate posturing (abnormal ectension 2
in response to pain)
None None None
Total score 3–15
†
If the patient is intubated, unconscious or preverbal, the most important part of this scale in motor response. Providers should carefully evaluate this components.
physical examination in stable patients. Generally, the initial Categorization by Severity

assessment is aimed at detecting immediate life-threatening
problems that can compromise basic life functions, as in the Respiratory Distress
primary survey. • Tachypnea
The secondary survey is intended to detect less immediate • Tachycardia
threats to life and has several specific objectives: • Increased respiratory effort
• Obtaining a complete history including mechanism • Abnormal airway sounds
of injury or circumstances of the illness. The SAMPLE • Pale cool skin
mnemonic can be helpful: • Changes in mental status
{{ Signs and symptoms
{{ Allergies
Respiratory Failure
{{ Medications • Early: marked tachypnea/tachycardia
{{ Past medical history • Late: bradypnea, apnea/bradycardia
{{ Last oral intake • Increased/decreased/no respiratory effort
{{ Events leading to the injury or illness
• Cyanosis
• Performing a detailed physical examination • Stupor/coma.
Shock
Laboratory and Radiological
Diagnostic Testing Compensated
• Establishing a clinical diagnosis: obtain a quick random • Tachycardia
blood sugar • Cool pale diaphoretic skin
• Performing laboratory investigations and imaging. • Delayed CRT (>2 s)
• Weak peripheral pulses
• Narrow pulse pressure
Ongoing Assessment
• Oliguria.
Always reassess the patient; the purpose is to assess the
effectiveness of the emergency interventions provided and Hypotensive
identify any missed injuries or conditions. This should be • All features of compensated shock and blood pressure
performed in every patient after the detailed physical exami below the 5th percentile 193
nation and after ensuring completion of critical interventions. • Change in mental status.
Ch-40.indd 193 11/19/2016 2:47:00 PM

Initial Stabilization • Anticonvulsants: if convulsions, use diazepam IV/rectal,

lorazepam, or midazolamiv (caution: respiratory depres
Things required at all practice locations (hospital or private
sion/arrest)
practice clinic):
{{ Phenytoin/phenobarbitone intravenously
• Oxygen source and mask
• Fever control
• Bag valve mask device (Ambubag)
• Analgesics, if severe pain: nonsteroidal anti-inflammatory
• Laryngeal mask airway
agents/narcotics as necessary
• Intubating equipment
• Antiemetics: if vomiting
• Intraosseous needle
• Antiallergics: if allergic reaction/anaphylaxis
• Intravenous cannula, IV fluids
• Subcutaneous adrenaline, antihistaminics, steroids.
• Suction
• Pulse oximeter
• Nebulizer.
Transport
After initial stabilization and ensuring airway, breathing,
Common Initial Interventions and circulation under reasonable control with established IV
Once the critically ill child is recognized, do not waste time in access, transfer/transport to a higher-level facility needs to be
detailed investigations and diagnosis. arranged.
Do the following regardless of diagnosis:
• Start oxygen Clinical Pearls
• If respiratory distress
{{ Ensure airway open by head tilt, chin lift, jaw thrust • Cardiac arrest can be prevented in most children if respiratory
{{ If not maintainable, intubate distress is assessed and treated
{{ If cannot intubate, ventilate with bag and mask. • Early rapid cardiopulmonary assessment saves life
{{ If cannot intubate or ventilate, then use laryngeal mask • Fluid therapy and antibiotic dose alone can do 80% of the job
airway and call the best expert in airway management. in a septic child.
Foreign Body Obstruction

If known foreign body obstruction:
Key points
• Then back blows, chest thrust, and Heimlich maneuver
• Nebulize as required (adrenaline or b2 stimulant). ))
Solve immediate problem
Monitor oxygen saturation if pulse oximeter is available. ))
Do not waste time in establishing precise diagnosis
))
Recognize critical illness
Shock
))
Stabilize
Establish intravenous/intraosseous access. ))
Arrange transfer to a pediatric intensive care unit
• Do not waste more than 90 seconds trying for intravenous
))
Ensure continued stabilization measures until care is handed
access or wasting time with attempting to place a central
over.
line
• Intraosseous access can be used in all age groups
• Push fluid bolus 20 mL/kg up to 60–80 mL/kg of isotonic
fluid (Normal saline/Ringers lactate). SUGGESTED READINGs
After each intervention, reassess airway breathing and 1. de Caen AR, Berg MD, Chameides L, et al. Part 12: Pediatric Advanced Life
circulation (capillary refill, color, heart rate, pulse, blood Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary
pressure, mental status, urine output). Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S526.
2. Kleinman ME, de Caen AR, Chameides L, et al. Pediatric basic and advanced
Other Supportive Therapy life support: 2010 International Consensus on Cardiopulmonary Resuscitation
and Emergency Cardiovascular Care Science with Treatment Recommendations.
• First dose of antibiotic Pediatrics. 2010;126:e1261.
194
Ch-40.indd 194 11/19/2016 2:47:00 PM

Chapter 41
Septic Shock
Vikram Gagneja, Praveen Khilnani
INTRODUCTION Box 1: Diagnostic criteria for sepsis

Severe sepsis or septic shock remains a major cause of Infection (documented or suspected), and some of the following:
morbidity and mortality among children, mainly due to • General variables
{{ Fever (>38.5°C)
acute hemodynamic compromise and associated multiple
{{ Hypothermia (core temperature <35°C)
organ dysfunctions. Emphasis has been on early recognition
{{ Heart rate more than two standard deviation (SD) above the
and early goal-directed therapy of severe sepsis and septic
shock by means of aggressive fluid resuscitation (somewhat normal value for age
{{ Tachypnea
guarded in malnourished children), use of catecholamines,
{{ Altered mental status
early antibiotics, and other adjuvant drugs, widely considered
{{ Significant edema or positive fluid balance (>20 mL/kg over
of pivotal importance to improve the short- and long-term
24 h)
outcome of these patients. Severe sepsis (septic shock) is {{ Hyperglycemia (plasma glucose >140 mg/dL or 7.7 mmol/L) in
defined as sepsis plus sepsis-induced organ dysfunction or the absence of diabetes
tissue hypoperfusion (Boxes 1 and 2) as per Surviving Sepsis • Inflammatory variables
Campaign 2012. Sepsis-induced hypotension is defined as {{ Leukocytosis (WBC count >12,000 μL–1)
blood pressure less than two standard deviation below normal {{ Leukopenia (WBC count <4,000 μL–1)
for age with no other causes of hypotension. Normal ranges for {{ Normal WBC count with greater than 10% immature forms
pediatric age group are given in table 1. {{ Plasma C-reactive protein more than two SD above the normal
value
{{ Plasma procalcitonin more than two SD above the normal value
MANAGEMENT • Hemodynamic variables
{{ Arterial hypotension less than two SD below normal for age
Airway, Breathing, and Circulation {{ Organ dysfunction variables
{{ Arterial hypoxemia (PaO /FiO <300)

Patient should be given 100% oxygen by facemask if airway 2 2
{{ Acute oliguria (urine output <0.5 mL/kg/h for at least 2 h
is maintainable or high flow nasal cannula/nasopharyngeal
continuous positive airway pressure (CPAP) if there is despite adequate fluid resuscitation)
{{ Creatinine increase >0.5 mg/dL or 44.2 μmol/L
increase work of breathing to maintain their functional
{{ Coagulation abnormalities (international normalized ratio
residual capacity. The decision to intubate and ventilate is
>1.5 or activated partial thromboplastin time >60 s)
based on clinical assessment of increased work of breathing, {{ Ileus (absent bowel sounds)
hypoventilation, or impaired mental status. Waiting for {{ Thrombocytopenia (platelet count <100,000 μL–1)
confirmatory laboratory tests is discouraged. However, during {{ Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or
intubation and mechanical ventilation, increased intrathoracic 70 μmol/L)
pressure and drugs used for sedation can reduce venous return • Tissue perfusion variables
and lead to worsening shock if the patient is not adequately {{ Hyperlactatemia (>1 mmol/L)
volume-loaded. Mechanical ventilation should be done using {{ Decreased capillary refill or mottling (normal filling in early
lung protective strategies (tidal volume 4–6 mL/kg of ideal warm shock)
body weight, plateau pressure ≤30). Appropriate sedation
Ch-41.indd 195 11/19/2016 2:58:10 PM

Box 2: Severe sepsis

pulses, normal blood pressure for age, sensorium, and urine
output. Thereafter, central venous oxygen saturation (ScvO2)
Any of the is following thought to be due to infection: greater than or equal to 70% and cardiac index between 3.3
• Sepsis-induced hypotension and 6.0 L/min/m2 should be targeted, if facilities for such
• Lactate above upper limits laboratory normal monitoring are available. Fluid responsiveness techniques can
• Urine output <0.5 mL/kg/h for more than 2 h despite adequate be applied wherein fluid administration is continued as long as
fluid resuscitation
there is hemodynamic improvement either based on dynamic
• Acute lung injury with PaO2/FiO2 <250 in the absence of
(e.g., change in pulse pressure, stroke volume variation) or
pneumonia as infection source
static (e.g., arterial pressure, heart rate) variables. Noninvasive
• Acute lung injury with PaO2/FiO2 <200 in the presence of
pneumonia as infection source measures, such as echocardiography, may be utilized to assess
• Creatinine >2.0 mg/dL (176.8 μmol/L) for adequacy of fluid resuscitation by assessing inferior vena
• Bilirubin >2 mg/dL (34.2 μmol/L) cava collapse.
• Platelet count <100,000 μL
• Coagulopathy (international normalized ratio >1.5) Fluid Refractory Shock
If despite of 60 mL/kg of fluid, therapeutics endpoints like
CRT less than 2 seconds, threshold heart rates, normal pulses
and analgesia should be provided to a patient on mechanical
with no differential between the quality of the peripheral and
ventilation.
central pulses, warm extremities, urine output more than
Getting intravenous access may be difficult early in the
1 mL/kg/hour, normal mental status, and blood pressure more
course of shock especially in small children, rapid use of
than fifth centile for age are not met, shock is defined as fluid
intraosseous access should be utilized which can be used
refractory and child should be shifted to pediatric intensive
to give any type of medication. Time should not be wasted
care unit (PICU) for further monitoring. Vasoactive drugs
in attaining central line. Rapid fluid boluses of 20 mL/kg
can be started through peripheral or intraosseous line till the
(isotonic crystalloid or colloids) can be administered by push
central line is established. Shock is further defined into warm
or rapid infusion device (pressure bag) while observing for
or cold shock, catecholamine resistant, and refractory shock as
signs of fluid overload (i.e., the development of increased
shown in table 2. Further management of septic shock in PICU
work of breathing, rales, gallop rhythm or hepatomegaly). In
is guided as per algorithm 1.
the absence of these clinical findings, repeated fluid boluses
can be administered. Children commonly require 40–60 mL/
kg in the first hour (some children may require 180–200 mL/ Antibiotics and Source Control
kg). Each fluid bolus should be followed by quick assessment Broad-spectrum antibiotics should be administered early
of clinical parameters like improvement in heart rate as per age preferably within first hour of therapy after taking appropriate
(Table 1), capillary refill time (CRT) (normal CRT <2 s), normal cultures but should not delay therapy, as each passing hour
pulses with no differential between peripheral and central increase chances of mortality. Antimicrobials can be given
Table 1: Heart rates and systolic blood pressure and perfusion pressure (MAP-CVP) for age
Age group Heart rate (bpm) Systolic blood pressure (mmHg), 5th percentile
(Range 5th-95th percentile) (Perfusion pressure = MAP-CVP)
Up to one month 140 (120–180) <60 (55)
2 months to 1 year 130 (80–180) <70 (60)
1–5 years 80 (60–140) <70 + [2× age in years] (65)
6–10 years 80 (60–130) <70 + [2× age in years] (65)
>10 years 75 (90–100) <90 (65)
Fifth percentile is the minimum acceptable. MAP (mean arterial pressure) = diastolic pressure + 1/3 pulse pressure (mmHg)
Table 2: Hemodynamic definitions of shock as per American College of Critical Care Medicine
Cold or worm shock Decreased perfusion manifested by altered decreased mental statue, capillary refill >2 s (cold shock) or
flash capillary refill (warm shock), diminished (cold shock) or bounding (warm shock) peripheral pulses,
mottled cool extremities (cold shock), or decreased urine output <1 mL/kg/h
Fluid-refractory/dopamine- Shock persists despite ≥60 mL/kg fluid resuscitation (when appropriate) and dopamine infusion to
resistant shock 10 mg/kg/min
Catecholamine-resistant shock Shock persists use of the direct-acting catecholamines; epinephrine or norepinephrine
Refractory shock Shock persists despite goal-directed use of inotropic agents, vasopressors, vasodilators, and maintenance
196 of metabolic (glucose and calcium) and hormonal (thyroid, hydrocortisone, insulin) homeostasis
Ch-41.indd 196 11/19/2016 2:58:10 PM

Chapter 41: Septic Shock
Algorithm 1
Algorithm for time sensitive, goal-directed stepwise management of hemodynamic support in infants and children. Proceed to next step
if shock persists. 1) First hour goals—Restore and maintain heart rate thresholds, capillary refill ≤2 seconds, and normal blood pressure in
the first hour/emergency department. Support oxygenation and ventilation as appropriate. 2) Subsequent intensive care unit goals—If
shock is not reversed, intervene to restore and maintain normal perfusion pressure (mean arterial pressure-central venous pressure) for
age, central venous oxygen saturation >70%, and CI >3.3, <6.0 L/min/m2 in pediatric intensive care unit.
CI, cardiac index; FATD, femoral arterial thermodilution; Hb, hemoglobin; IM, intramuscular; IO, interosseous; IV, intravenous; PIV, peripheral intravenous; PICCO,
pulse contour cardiac output; CVP, central venous pressure; MAP, mean arterial pressure.
intramuscularly or orally (if tolerated) until intravenous and intravenous immunoglobulin in refractory toxic shock
line access is available. Antibiotics should be chosen based syndrome may be considered. Any site of localized pus
on suspected community acquired or hospital-acquired collection or any other source of infection should be taken care
infection, local resistance pattern of organism, site of infection, of once child is stable enough for procedure. Antibiotics may
and whether immune-compromised or immune-competent de-escalated later according to culture sensitivity report.
and past history of chronic illness. The choice of empiric drugs
should also take into consideration the ongoing epidemic and Steroid Therapy
endemic (e.g., H1N1, methicillin-resistant Staphylococcus If a child is at risk of suspected or proven absolute adrenal
aureus, chloroquine-resistant malaria, and penicillin-resistant insufficiency (random cortisol level <18 µg/dL) or adrenal 197
pneumococci). Clindamycin, to decrease toxin production pituitary axis failure (e.g., purpura fulminans, congenital
Ch-41.indd 197 11/19/2016 2:58:10 PM

adrenal hyperplasia, prior recent steroid exposure, hypo Deep Vein Thrombosis and
thalamic/pituitary abnormality) and remains in shock despite Stress Ulcer Prophylaxis
epinephrine or norepinephrine infusion, then hydrocortisone
can be administered. Hydrocortisone may be administered as There is no role of deep vein thrombosis and stress ulcer
an intermittent or continuous infusion (preferable in view of prophylaxis in prepubertal children with severe sepsis.
decrease incidence of hyperglycemia and hyponatremia) at However, stress ulcer prophylaxis is commonly used in children
a dosage of 50 mg/m2/24 h titrated to reversal of shock and who are mechanically ventilated and high risk for bleeding
tapered once vasopressor support is not required. with H2-blockers or proton pump inhibitors, although its effect
is not known.
Glycemic Control
Diuretics and Renal Replacement Therapy
Hypoglycemia should be prevented by providing appropriate
glucose delivery rate to the child. Associations have been Fluid overload in severe sepsis has been associated with
reported between hyperglycemia and an increased risk of increased risk of mortality, so effort to reverse fluid overload
death and longer length of hospital stay. Two consecutives with diuretics when shock has resolved and if unsuccessful,
values of more than or equal to 180 mg/dL should be then continuous venovenous hemofiltration or intermittent
managed with insulin infusion in addition to glucose to avoid dialysis to prevent greater than 10% of total body weight fluid
hypoglycemic episodes. overload has met with improved survival in severe sepsis.
Blood Products and Plasma Therapies Extracorporeal Membrane Oxygenation

Packed cell transfusion may be given to maintain hemoglobin Extracorporeal membrane oxygenation may be used to
of 10 gm/dL if child is hemodynamically unstable (ScvO2 <70% support children and neonates with septic shock or sepsis-
during resuscitation) and target of 7–9 g/dL is reasonable associated respiratory failure. The survival of septic patients
after stabilization and recovery from shock and hypoxemia. supported with ECMO is 73% for newborns and 39% for older
Fresh-frozen plasma may be used as infusion not as bolus, children, and is highest in those receiving venovenous ECMO.
if international normalized ratio is prolonged and bleeding Forty-one percent of children with a diagnosis of sepsis
tendency is present. In patients with severe sepsis, platelets requiring ECMO for respiratory failure survive to hospital
be administered prophylactically when counts are less discharge. Venoarterial ECMO is also useful in children
than or equal to 10,000/mm3 (10 × 109/L) in the absence of with refractory septic shock, with one center reporting 74%
apparent bleeding, as well when counts are less than or equal survival to hospital discharge using central cannulation via
to 20,000/mm3 (20 × 109/L) if the patient has a significant sternotomy. ECMO has been used successfully in critically ill
risk of bleeding. Higher platelet counts (≥50,000/mm3 [50 × H1N1 pediatric patients with refractory respiratory failure.
109/L]) are advised for active bleeding, surgery or invasive
procedures. CONCLUSION
Nutrition Optimum treatment of severe sepsis or septic shock is a
dynamic and evolving process. Early diagnosis, allowing
Providing early enteral nutrition to maintain gut integrity and
rapid therapeutic intervention, is essential in improving the
to prevent gut translocation of bacteria should be the goal
outcome of these patients. Current treatment includes early
once hemodynamic stability is achieved. Partial or complete
fluid resuscitation, early appropriate antibiotics, tailored use of
total parenteral nutrition can be given, where enteral feeding
inotropes and vasopressors, lung protective strategy for acute
cannot be established.
respiratory distress syndrome, and use of adjuvant treatments
such as low-dose hydrocortisone (Table 5). Early recognition
Protein C and Activated Protein Concentrate of organ failure and supportive therapy especially renal
No benefit of recombinant human activated protein C in replacement therapy to prevent further injury helps in reversal
patients with septic shock. of organ dysfunction.
Table 5: Summary of pediatric recommendations of surviving sepsis guidelines 2012

A. Initial resuscitation • For respiratory distress and hypoxemia, start with face mask oxygen, or if needed and available, high flow
nasal cannula oxygen or nasopharyngeal continuous positive airway pressure. For improved circulation,
peripheral intravenous access or intraosseous access can be used for fluid resuscitation and inotrope infusion
when a central line is not available. If mechanical ventilation is required then cardiovascular instability during
intubation is less likely after appropriate cardiovascular resuscitation
• Initial therapeutic endpoints of resuscitation of septic shock: capillary refill of ≤2 s, normal blood pressure for
age, normal pulses with no differential between peripheral and central pulses, warm extremities, urine output
>1 mL/kg/h, and normal mental status. Central venous oxygen saturation ≥70% and cardiac index between
198 3.3 and 6.0 L/min/m2 should be targeted thereafter
Continued
Ch-41.indd 198 11/19/2016 2:58:10 PM

Chapter 41: Septic Shock
Continued
• Follow American College of Critical Care Medicine-Pediatric Life Support guidelines for the management of
septic shock
• Evaluate for and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with
refractory shock
B. Antibiotics and source • Empiric antibiotics be administered within 1 h of the identification of severe sepsis. Blood cultures should be
control obtained before administering antibiotics when possible but this should not delay administration of antibiotics.
The empiric drug choice should be changed as epidemic and endemic ecologies dictate (e.g., H1N1, MRSA,
chloroquine resistant malaria, penicillin-resistant pneumococci, recent ICU stay, and neutropenia)
• Clindamycin and antitoxin therapies for toxic shock syndromes with refractory hypotension
• Early and aggressive source control (grade 1D)
• Clostridium difficile colitis should be treated with enteral antibiotics if tolerated. Oral vancomycin is preferred
for severe disease
C. Fluid resuscitation • In the industrialized world with access to inotropes and mechanical ventilation, initial resuscitation of
hypovolemic shock begins with infusion of isotonic crystalloids or albumin with boluses of up to 20 mL/kg
crystalloids (or albumin equivalent ) over 5–10 minutes, titrated to reversing hypotension, increasing urine
output, and attaining normal capillary refill, peripheral pulses, and level of consciousness without inducing
hepatomegaly or rales. If hepatomegaly or rales exists then inotropic support should be implemented, not
fluid resuscitation. In nonhypotensive children with severe hemolytic anemia (severe malaria or sickle cell
crises) blood transfusion is considered superior to crystalloid or albumin bolusing
D. Inotropes/ • Begin peripheral inotropic support until central venous access can be attained in children who are not
vasopressors/ responsive to fluid resuscitation
vasodilators • Patients with low cardiac output and elevated systemic vascular resistance states with normal blood pressure
be given vasodilator therapies in addition to inotropes
E. Extracorporeal • Consider ECMO for refractory pediatric septic shock and respiratory failure
membrane oxygenation
(ECMO)
F. Corticosteroids • Timely hydrocortisone therapy in children with fluid refractory, catecholamine resistant shock, and suspected
or proven absolute (classic) adrenal insufficiency
G. Protein C and activated No recommendation as no longer available
protein concentrate
H. Blood products and • Similar hemoglobin targets in children as in adults. During resuscitation of low superior vena cava oxygen
plasma therapies saturation shock (<70%), hemoglobin levels of 10 g/dL are targeted. After stabilization and recovery from
shock and hypoxemia, a lower target >7.0 g/dL can be considered reasonable
• Platelet transfusion targets as described in text
• Use plasma therapies in children to correct sepsis-induced thrombotic purpura disorders, including
progressive disseminated intravascular coagulation, secondary thrombotic microangiopathy, and thrombotic
thrombocytopenic purpura
I. Mechanical ventilation • Lung-protective strategies during mechanical ventilation
J. Sedation/analgesia/ • We recommend use of sedation with a sedation goal in critically ill mechanically ventilated patients with sepsis
drug toxicities • Monitor drug toxicity labs because drug metabolism is reduced during severe sepsis, putting children at
greater risk of adverse drug-related events
K. Glycemic control • Control hyperglycemia using a similar target as in adults ≤180 mg/dL. Glucose infusion should accompany
insulin therapy in newborns and children because some hyperglycemic children make no insulin whereas
others are insulin resistant
L. Diuretics and renal • Use diuretics to reverse fluid overload when shock has resolved, and if unsuccessful then continuous
replacement therapy venovenous hemofiltration or intermittent dialysis to prevent >10% total body weight fluid overload
M. Deep vein thrombosis • No recommendation on the use of deep vein thrombosis prophylaxis in prepubertal children with severe
prophylaxis sepsis
N. Stress ulcer • No recommendation on the use of stress ulcer prophylaxis in prepubertal children with severe sepsis
prophylaxis
O. Nutrition • Enteral nutrition given to children who can be fed enterally, and parenteral feeding in those who cannot
199
Ch-41.indd 199 11/19/2016 2:58:11 PM

Clinical Pearls SUGGESTED READINGS

1. Amado VM, Vilela GP, Queiroz A Jr, Amaral AC. Effect of a quality improvement
• Septic patients may have warm shock or cold shock with or intervention to decrease delays in antibiotic delivery in pediatric febrile
without respiratory distress neutropenia: A pilot study. J Crit Care. 2011;26:103.e9-12.
2. Aneja RK, Carcillo JA. Differences between adult and pediatric septic shock.
• Source control (debridement, drainage) should be considered
Minerva Anestesiol. 2011;77:986-92.
in all septic patients.
3. Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, Jefferson LS, Loftis LL. Fluid
• Isotonic solution such as normal saline or Ringers lactate for all overload is associated with impaired oxygenation and morbidity in critically ill
initial fluid therapy children. Pediatr Crit Care Med. 2012;13(3):253-8.
• First dose of antibiotics to be stored in outpatient department 4. Branco RG, Garcia PC, Piva JP, Casartelli CH, Seibel V, Tasker RC. Glucose
and emergency areas level and risk of mortality in pediatric septic shock. Pediatr Crit Care Med.
2005;6(4):470-2.
• If persistent hypotension despite fluids and inotropes, one
5. Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, et al. Clinical
should look for mechanical causes, such as tamponade due to practice parameters for hemodynamic support of pediatric and neonatal septic
raised intra-abdominal pressure, pleural or pericardial effusion, shock: 2007 update from the American College of Critical Care Medicine. Crit
or tension pneumothorax. Care Med. 2009;37:666-88.
6. Dellinger R, Levy M, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving
sepsis campaign: international guidelines for management of severe sepsis and
septic shock: 2012. Crit Care Med. 2013;41(2):580-637.
Key points 7. Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard ML,
et al. Fluid overload before continuous hemofiltration and survival in critically ill
))
Early fluid resuscitation, early appropriate antibiotics, tailored children: A retrospective analysis. Crit Care Med. 2004;32:1771-6.
use of inotropes and vasopressors, use of hydrocortisone in 8. Goldstein B, Giroir B, Randolph A; International Consensus Conference on
catecholamine resistant shock, known adrenal insufficiency Pediatric Sepsis, International pediatric sepsis consensus conference: Definitions
(chronic steroid therapy, example nephrotic syndrome, for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2‑8.
autoimmune disorders) 9. Khilnani P, Singhi S, Lodha R, Santhanam I, Sachdev A, Chugh K, et al. Pediatric
))
Lung protective strategy for acute respiratory distress sepsis guidelines: summary for resource-limited countries. Indian J Crit Care
syndrome should be used Med. 2010;14(1):41-52.
10. Khilnani P. The pediatric BUS has arrived: Is bedside ultrasound in the pediatric
))
Early recognition of fluid overload, organ failure, and intensive care unit a feasible option? Pediatr Crit Care Med. 2011;12(6)681-3.
supportive therapy, especially renal replacement therapy 11. Pizarro CF, Troster EJ, Damiani D, Carcillo JA. Absolute and relative adrenal
to minimize fluid overload and further injury helps should insufficiency in children with septic shock. Crit Care Med. 2005;33:855-9.
be considered in all patients with every sepsis once 12. Randolph AG. Management of acute lung injury and acute respiratory distress
hemodynamic stability has been achieved syndrome in children. Crit Care Med. 2009;37:2448-54.
))
Inborn errors of metabolism can mimic sepsis, therefore, 13. Skinner SC, Iocono JA, Ballard HO, Turner MD, Ward AN, Davenport DL, et al.
anion gap and urine metabolic screen should be considered Improved survival in venovenous vs venoarterial extracorporeal membrane
oxygenation for pediatric noncardiac sepsis patients: a study of the Extracorporeal
especially in infants.
Life Support Organization registry. J Pediatr Surg. 2012;47:63-7.
200
Ch-41.indd 200 11/19/2016 2:58:11 PM

Chapter 42
Status Epilepticus
Soonu Udani
INTRODUCTION • Lorazepam, 0.1 mg/kg IV (maximum, 5 mg) over 1 min,

(diazepam can be substituted)
Status Epilepticus (SE) is a brain damaging emergency that • Allow 5 minutes to determine whether seizure
needs prompt and targeted therapy in a protocolised manner terminates
if good outcome is to be expected. Several algorithms may be • Give oxygen; stabilize airway, respiration, and hemo
available and units must make one most suitable for their dynamics as needed
setting. • Obtain IV access
• Check bedside glucose
DEFINITION • Begin electrocardiogram (ECG) monitoring
• Repeat benzodiazepine administration.
A seizure is a paroxysmal change in motor activity and or 2. Administer fosphenytoin (PHT) 20 mg/kg phenytoin
behavior that results from abnormal electrical activity in the equivalent IV at 2–3 mg/kg/min (maximum, 150 mg/min)
brain. There are several proposed definitions for SE. (phenytoin needs to be given slower) (Phenobarbitone at
The classic one is: seizures or repeated seizures lasting for more 20 mg/kg can be substituted here)
than 30 minutes without recovering consciousness between • If the patient’s age is less than 2 years, consider
seizures. pyridoxine 100 mg IV push
Recent definition states: status greater than 5 minutes or a • Testings:
continuous seizures or two or more discrete seizure between {{ Bedside glucose complete blood count cultures
which there is incomplete recovery of consciousness. {{ Electrolytes, calcium, magnesium, phosphorus,
For practical purposes: any child that is brought convulsing to liver function test, and toxicology if indicated
the hospital is said to be in SE. (serum, urine preserve till consultant orders)
Defining status in this way allows us to recognize short {{ Antiepileptic drug (AED) levels, prothrombin time,
lasting seizures as relatively benign events not necessarily thromboplastin time
requiring emergent treatment and gives us strong grounds to {{ Support airway, respiration, hemodynamics as
treat longer lasting seizures aggressively as true emergencies needed
necessitating strong pharmacologic intervention. {{ Continuous vital sign and ECG monitoring.
3. If seizures persist for more than 10 min, repeat dose of PHT

10–20 mg/kg; wait for 10 min if still have seizures
MANAGEMENT OF status epilepticus
This is now the stage of established SE as two primary drugs
Current management of SE emphasizes a more aggressive have failed.
approach—initiating first line therapy more rapidly (the longer 4. Administer levetiracetam (LEV) 20 mg/kg IV at 5 mg/kg/
one waits the longer the seizure takes to come under control). min (maximum 3 g), continue at 40 mg/kg/day in two to
If the patient is out of hopistal, has no intravenous access, three divided doses.
or casualty, consider buccal midazolam 0.3 mg/kg or rectal If contraindication to LEV and no specific concern regarding
diazepam 0.3 mg/kg. liver/metabolic/mitochondrial disease, then administer:
1. Intravenous (IV) benzodiazepines: early use gives best • Valproate (VPA) 30 mg/kg at 5 mg/kg/min
results OR
Ch-42.indd 201 11/19/2016 2:59:36 PM

• Phenobarbital (PB) 20 mg/kg over 5–10 min. Algorithm 1

If seizures persist after 10 min, established RSE and admit Algorithm of seizure
to pediatric intensive care unit (PICU).
In patients who had failed first line therapy, additional
second and third line therapy adds only marginal benefit (2.3–
5%). Given the observation that intermediate steps are time
consuming with limited added value and also with increased
awareness of the importance of early treatment of seizure, a
change to accelerated protocol has been proposed. Lorazepam
and phenytoin are given simultaneously, followed by
pharmacologic coma (omit phenobarbitone). The application
of such treatment has to be balanced with available expertise
and infrastructure.
Prepare to secure airway, mechanically ventilate, and
obtain central venous access and continuous hemodynamic
monitoring through an arterial line.
5. Initiate coma with midazolam 0.2 mg/kg bolus (maximum
10 mg) over 2 minutes, and then initiate infusion at 0.1 mg/
kg/h.
If seizures persist for five more minutes after an additional
midazolam bolus of 0.2 mg/kg bolus, increase the dose by 0.02
every 5–10 minutes.
One or two extra boluses can be given but they should not
be repeated for every increase in infusion rate.
The patient would almost always need intubation and
ventilatory support by now. Vasopressor support with
norepinephrine (NE) by the central line should be considered
If seizures persist at maximum midazolam (generally
2 mg/kg/h) or midazolam infusion or till hypotension, cardiac
instability is seen.
If seizures still persist, with reassessment of cardio
vascular status, which may include an echocardiography for
contractility, the next step should be pentobarbital coma.
An electroencephalogram (EEG)—preferably continuous—
should be obtained at this stage, especially if no clinical seizure
activity is visible.
6. Thiopental 4 mg/kg load and 1–2 mg/kg/h
• Increase only on advice of consultant and EEG for burst
suppression IV, intravenous; IO, intraosseous; PICU, pediatric intensive care unit.
• Warning: cardiodepressive; especially after 3–4 days of
continuous use
• Propofol is another option however, it is not approved If no clinical or electrographic seizures, then wean off.
in children for use for more than 24 h The patient should be monitored for levels of PB, PHT, and
• General anesthesia requires the expertise of an VPA when used. The child would be on two to three AEDs by
anesthetist and the machine for gas delivery; most now and these should not be stopped immediately. The rest of
PICUs are ill-equipped for the system. the management would depend on the cause and recovery.
7. Weaning: after a minimum of 24 hours of electrical seizure- Magnetic resonance imaging and etiology seeking tests (as
free activity, reduce midazolam by 0.05 mg/kg/h every 3 in encephalopathy) should be performed even with the patient
hour, with frequent EEG review. on ventilation.
Similar weaning should be done for thiopental, unless When the patient does not respond, other advanced
abrupt stoppage is required because of severe hypotension therapies may be called for which are beyond this discussion.
uncontrolled by NE. Hypotension will reduce cerebral
perfusion pressure and aggravate central nervous injury. Clinical Pearls
If clinical or subclinical seizures occur, reinstitute coma
with midazolam for 24 hours. Similarly for thiopental. • Prolonged status injures the brain
• Accelerated protocol saves 20–30 minutes
Note: Midazolam does not cause burst suppression, the end point is
• Treat within the facility’s capabilities and transfer early.
202 loss of seizure activity.
Ch-42.indd 202 11/19/2016 2:59:36 PM

Chapter 42: Status Epilepticus
Key points
SUGGESTED READINGs
1. Abend NS, Dlugos DJ. Treatment of refractory status epilepticus: literature review
))
Attention to airway, breathing, and circulation simultaneously
and a proposed protocol. Pediatr Neurol. 2008;38(6):377-90.
while treating seizures
2. Abou Khaled KJ, Hirsch LJ. Advances in the management of seizures and status
))
Early treatment aborts status faster and prevents benzo epilepticus in critically ill patients. Crit Care Clin. 2006;22(4):637-59.
diazepine resistance 3. Shearer P, Riviello J. Generalized convulsive status epilepticus in adults
))
Do not forget glucose and calcium and children: treatment guidelines and protocols. Emerg Med Clin N Am.
2011;29(1):51-64.
))
Strict attention to hemodynamics especially in the stage of
refractory status
))
Get expert help as newer drugs and advanced treatments
options may exist.
203
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Chapter 43
Cardiogenic Shock
Nameet Jerath, Praveen Khilnani
INTRODUCTION rate (HR) and stroke volume, and the stroke volume itself is
dependent on preload, contractility, and afterload of the heart.
Children with congenital heart disease, cardio myopathy, The oxygen content of blood is dependent on the
various arrhythmias, viral myocardititis,post cardiac surgery hemoglobin concentration and its oxygen saturation (SpO2).
or severe sepsis can have severe myocardial dysfunction and Preload, contractility, afterload, hemoglobin, SpO2, and to
cardiogenic shock. It is a commonly encountered problem some extent, HR can be optimized with drugs or other inter
in pediatric age group and early diagnosis and initiation ventions and help tilting the metabolic balance back to normal.
of treatment can prevent mortality and severe morbidity. As the shock progresses, body’s compensatory mechanisms,
This chapter covers algorhithmic approach to a child with like increase in systemic vascular resistance (SVR) and HR start
cardiogenic shock with systematic differential diagnosis and to kick in. These compensatory responses can be detrimental
broad management of various etiologies leading to cardiogenic and can worsen the cardiogenic shock by increasing afterload
shock. and worsening cardiac output. As the critical point is reached,
patient can switch from a “warm” state of adequate perfusion
DEFINITION to a “cold” state. Patients now show signs of poor cardiac
output and are tachycardic, hypotensive, diaphoretic, oliguric,
Shock is a state of imbalance between the metabolic supply and acidotic, and poorly perfused. Extremities are cool and mental
demands of the body. Cardiogenic shock is the subset when the status is altered. Hepatomegaly, jugular venous distension,
cardiac function is responsible for the failure of cardiovascular rales, and peripheral edema may be observed.
system to meet the metabolic demands of the body.
Shock on presentation has similar signs and symptoms, like Diastolic Dysfunction
tachycardia, tachypnea, poor perfusion, and decreased urine
output with or without drop in blood pressure (hypotension), Diastolic dysfunction is poorly understood and often over
and it may be impossible to identify shock to be cardiogenic on looked. It can be associated with normal systolic ventricular
presentation. function. Impaired myocardial relaxation during diastole
The initial management of any child who presents with increases left ventricular end diastolic pressure (LVEDP). This
shock, irrespective of the etiology, remains the same. The aim is transmitted to the lung and results in pulmonary edema and
is quick identification of shock status and an early appropriate dyspnea. Elevated LVEDP reduces the perfusion pressure in
response to improve outcomes. the coronaries which further hampers cardiac perfusion and
Cardiac function can be depressed in patients with any type function.
of shock, even of noncardiac origin. Myocardial dysfunction
could be responsible for worsening of shock state as in massive Recognition of Cardiogenic Shock
sepsis. We shall restrict ourselves to only the cardiac causes of There are often subtle clues to suggest that the shock could be
cardiogenic shock in this chapter (Algorithm 1). cardiogenic and it is important to identify such patients, as their
management plan would differ from the routine management
of shock.
PATHOPHYSIOLOGY Though there are often overlap of symptoms with other
It pays to remember the determinants of substrate delivery to noncardiogenic conditions, the following symptoms should
the tissues (Algorithm 2). Cardiac output is dependent on heart alert one to the possibility of cardiogenic origin of shock:
Ch-43.indd 204 11/19/2016 3:02:13 PM

Chapter 43: Cardiogenic Shock
Algorithm 1
Cardiogenic shock management according to cause
SVT, supraventricular tachycardia; ARVD, arrhythmogenic right ventricular dysplasia; CO2, carbon dioxide; SpO2, saturation of peripheral oxygen;
HR, heart rate; BP, blood pressure; RR, respiratory rate; PGE1, prostaglandin E1; CXR, chest X-ray; Echo, echocardiography; CVP, central
venous pressure; CVO2, central venous oxygen saturation; ECMO, extracorporeal membrane oxygenation.
Algorithm 2 • Breathlessness while feeding

Pathophysiology of cardiogenic shock • History of fast breathing at all times
• Dramatic, sudden onset of illness
• Any shock state in an infant
• Central cyanosis.
Often clues towards cardiogenic shock can be found
on careful monitoring and trend of vitals and response to
interventions during resuscitation. The response to a fluid
bolus should be improvement of the HR and improvement
in blood pressure as the venous return [and central venous
pressure (CVP)] improves. Contrary to expectation, if the HR
starts rising and/or the blood pressure drops in response to
a fluid bolus, one should be alerted and cautiously review
the scenario. Excessive and too fast fluid bolus in a child with
cardiogenic shock could worsen the hemodynamic state. Such
children may still be hypovolemic and require fluid boluses but
• Insignificant fevers compared to the distress, illness these should be slower and in smaller aliquots. The importance
• Excessive sweating of assessment and reassessment after each intervention cannot
• Excessive irritability be overemphasized.
205
Ch-43.indd 205 11/19/2016 3:02:13 PM

Causes of Cardiogenic Shock {{ Intubation and mechanical ventilation

{{ Reduce agitation, anxiety with judicious sedation
• Arrhythmias: supraventricular tachycardia (SVT), arrhy
{{ Blood transfusion
thmogenic right ventricular dysplasia
• Improve myocardial function
• Myocarditis/cardiomyopathy: hypoxia, infectious, meta
{{ Optimize preload
bolic, toxic, neuromuscular disorders
{{ Augment contractility
• Congenital heart diseases
{{ Reduce afterload (think of ventilation as a modality)
• Postoperative low cardiac output state (LCOS)
{{ Correct rhythm disturbances
• Trauma.
Neonatal period undergoes significant transitions in • Think of duct dependent states: prostaglandin E1 (PGE1)
pulmonary and systemic circulations immediately to a infusion.
few weeks after birth. Congenital heart diseases with duct
dependent circulations can present dramatically with collapse.
General Measures
Any newborn who presents in shock should be suspected to The initial management of shock remains the same as outlined
have a duct dependent circulation. in the guidelines elsewhere, as many times it is impossible
Congenital heart diseases are a significant group of patients to discern the cause of shock on presentation. The history,
who can present in shock. A chest X-ray can help group them clinical features, and response to resuscitation efforts often
into either well, overly or poorly perfused lung fields. Lesions have enough clues to primary cardiac involvement. Once
with generous pulmonary blood flows (like large ventricular cardiogenic shock has been identified, the management
septal defect) present with tachypnea and respiratory distress should be tailored to the suspected condition.
and need measures to restrict the pulmonary blood flow. Fluid boluses should be carefully given in small aliquots of
5–10 mL/kg. Most children will have concomitant dehydration
Investigations too because of poor oral intake, respiratory losses, and
sometimes associated diarrhea and vomiting, and will benefit
After initial stabilization, laboratory investigations that may
from fluid boluses. At any stage, if the desired hemodynamic
be ordered include complete blood count, arterial blood
response is not seen, no more fluid boluses should be
gas, electrolytes including ionized calcium, renal and liver
functions, serum lactate, and cardiac enzymes if indicated. administered.
Once a central venous line is in place, measurement of Maintain normal sugar levels, temperature, and a calm
central venous oxygen saturation (CVO2) is a good marker of state by judicious use of sedation to reduce the metabolic
cardiac output. Central venous oxygen saturation measured demands of the body. The electrolytes including magnesium
from superior vena cava reflects the adequacy of oxygen and calcium should be normalized.
delivery, and therefore, cardiac output (Fick’s Principle). Ventilation should be thought of early in patients with
cardiogenic shock. It has the advantages of reducing metabolic
Chest Radiography demands of the body by reducing the work of breathing,
allowing sedation and muscle relaxation, and by reducing
The chest radiograph should be evaluated for the size of heart
afterload. Ventilated patients should be targeted to normal pH
and pulmonary vasculature, both of which provide essential
and CO2 with adequate oxygenation.
information regarding the possible causes of shock.
Monitoring is a vital part of management of cardiogenic
Electrocardiography shock. Most such children will require invasive arterial
pressure monitoring and central venous lines for CVP and for
An electrocardiogram can be diagnostic in certain conditions infusion of vasoactive drugs.
like anomalous origin of left coronary artery from pulmonary
artery. The rhythm on the monitor should be carefully assessed.
Long-standing SVT, ventricular tachycardia, atrial fibrillation, CARDIOGENIC SHOCK IN A NEWBORN
or atrioventricular block could be the reason of shock. The newborn period presents a specific subgroup as this is a
period of transition from fetal to extrauterine circulation. Many
Echocardiography duct dependent lesions can present with dramatic shock with
This is the most effective way of a comprehensive assessment of the closure of the patent ductus arteriosus. All circulatory
cardiac structure and function. It also helps in the calculation shocks in newborns should be treated as duct dependent
of cardiac output and systemic vascular resistance index. A lesion unless proven otherwise and efforts should be targeted
quick, limited assessment should be in the armamentarium of to keep the duct patent by PGE1 infusion (0.05–0.1 mg/kg/min).
each critical care specialist.
More specialized tests, like cardiac catheterization or Preload
magnetic resonance imaging, are sometimes needed for
Preload assessment and titrating fluid management can be very
detailed assessment and management of certain conditions.
challenging. The idea is to optimize preload to help the cardiac
output by shifting up on the Frank-Starling curve. Judicious small
Management volume fluid boluses are recommended, sometimes as small as
206 Principles of management: 5 mL/kg with subsequent fluid being guided by hemodynamic
• Minimize myocardial oxygen demands response. Crystalloids remain the fluid of choice.
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Chapter 43: Cardiogenic Shock
In a fluid overloaded child with stable blood pressure, should be avoided as monotherapy in acute early phase of
diuretics may be judiciously used later on in the course of the shock due to the risk of uncontrolled hypotension. They are
management. sometimes used together with an inotrope.
Myocardial Contractility, Inotropic Agents SPECIFIC THERAPY

The choice of vaso-cardioactive drugs will depend on the
Intravenous immunoglobulin is often used in patients with
clinical state and no one prescription fits all.
myocarditis to modulate the immune response. There is not
Dopamine and adrenaline are good inotropic agents and
enough literature support for this practice though.
increase the contractile force of the heart pump and increase
Postoperative LCOS is the state of low cardiac output after
the SVR. They thus increase the cardiac output and the blood
cardiac surgeries because of many factors including tissue
pressure. Both also increase the metabolic demands of the
edema, cytokine release, cardiac stun, etc. This needs careful
heart.
monitoring and management on the lines described above.
Dobutamine and milrinone are inodilators that improve
Most carefully managed hearts will start showing improvement
the pump function and also cause dilation of systemic vessels
in about 48 hours.
[reduced SVR and hence blood pressure (BP)]. The combined
effects of improved contractility and reduction in afterload
improves cardiac output albeit with some drop in BP. Milrinone Surgical Correction
and to smaller extent dobutamine has excellent lusitropic Some congenital heart diseases may need urgent surgical
effect, which allows for relaxation of heart, improving the correction. Cardiac lesions with torrential pulmonary blood
diastolic dysfunction. flow benefit from pulmonary artery banding procedures.
Noradrenaline and vasopressin are primarily vaso
constrictors and their use alone in a failing heart is not Extracorporeal Cardiac Support
appropriate. They both increase blood pressure but with
Cardiogenic shock refractory to the above mentioned therapies
increased workload (afterload) for the heart. They can help
can be supported on extracorporeal support systems, like
improve coronary perfusion.
ventricular assist devices (e.g., Berlin Heart, Thoratec) or
extracorporeal membrane oxygenation. These are used as
Vasoactive Drugs
temporary measures while awaiting spontaneous recovery or
The clinical effects and recommended doses of few vasoactive as a bridge to transplant.
drugs are given in table 1.
Diastolic Blood Pressure CARDIAC TRANSPLANT

The left heart gets its perfusion through coronary arteries Heart transplant is the last option for refractory and terminal
during diastole across a pressure gradient (diastolic blood heart failure. Organ supply remains the biggest hurdle in our
pressure–LVEDP). Maintenance of adequate diastolic blood country for this option to be exercised.
pressure is, therefore, necessary to maintain the coronary
perfusion to fuel the heart.
Clinical Pearls
Afterload Reduction • Cardiogenic shock in children can present as respiratory distress
Positive end expiratory pressure in a child with adequate • Newborns cardiogenic shock due to congenital heart disease
venous filling has the effects of reducing afterload making present when ductus closes, as a corollary prostaglandin drip
it easier for the heart to pump. This, amongst others, is an to keep ductus open may be life-saving
important reason to consider early ventilation of such children. • Metabolic/endocrine problems, such as hypoglycemia, hypo
Inodilators (dobutamine, milrinone, amrinone) or pure calcemia, and hypothyroidism, can present as cardiogenic shock
vasodilators (nitroprusside, nitroglycerine) will reduce
• Septic shock is an important cause of cardiogenic shock.
afterload and may be used to augment cardiac output. They
Table 1: Vasoactive drugs

Drug Dose Clinical effect
Dopamine 5–20 mg/kg/min ↑ contractility, vasoconstricts, ↑ heart rate
Dobutamine 5–20 mg/kg/min ↑ contractility, vasodilates
Adrenaline 0.01–1 mg/kg/min ↑ contractility, vasoconstricts, ↑ heart rate
Noradrenaline 0.01–1 mg/kg/min Vasoconstricts+++, ↑ contractility, heart rate
Milrinone 0.25–0.75 mg/kg/min ↑ contractility, lusitropic
Vasopressin 0.0001–0.008 U/kg/min Vasoconstricts +++ 207
Ch-43.indd 207 11/19/2016 3:02:13 PM

Key points
SUGGESTED READINGS
1. Arikan AA, Citak A. Pediatric shock. Signa Vitae. 2008;3(1):13-23.
))
Tachycardia and worsening of blood pressure in response to 2. Lincoln S Smith, Lynn J Hernan. Shock states. In: Fuhrman BP, Zimmerman JJ
a fluid bolus in any child with shock should alert to a likely (Eds). Pediatric Critical Care. 4th ed. Philadelphia: Elsevier Saunders; 2011. p.
cardiogenic cause 364.
))
Central venous oxygenation is a good surrogate for cardiac 3. Reynolds HR, Hochman JS. Cardiogenic shock: current concepts and improving
output assessment outcomes. Circulation. 2008;117(5):686-97.
))
Fluid bolus of 5-10 mL/kg should be cautiously used in 4. Rossano JW, Price JF, Nelson DP. Treatment of heart failure in infants and
children suspected to have cardiogenic shock children: Medical management. In: Nichols DG (Ed). Rogers’ Textbook of Pediatric
Intensive Care. Lippincott Williams and Wilkins; 2008. p. 1093.
))
Echocardiography is invaluable in diagnosis of cardiac lesions/
5. Smith KA, Bigham MT. Cardiogenic shock. The Open Pediatric Medicine Journal.
conditions
2013;7(Suppl 1: M5):19-27.
))
All newborns with shock should be suspected to have a duct- 6. Woods WA, McCulloch MA. Cardiovascular emergencies in the pediatric patient.
dependent lesion Emerg Med Clin North Am. 2005;23(4):1233-49.
))
Early ventilation should be considered in cardiogenic shock.
208
Ch-43.indd 208 11/19/2016 3:02:13 PM

Chapter 44
Head Injury in
Infants and Children
Bhaskar Saikia, Praveen Khilnani
INTRODUCTION Neurological deficit may be transient after an impact such

as a short seizure. If the child presents with coma, deficit cannot
Traumatic brain injury in children is prevalent universally with be assessed, a previous observation by parents or doctor is
potentially poor outcomes. Domestic accidents, motor vehicle noted and needs to be followed closely.
accidents, recreational injuries, and sports mishaps are the The AVPU (Alert, Responds to Verbal commands, Responds to
common causes; however, child abuse must be kept in mind pain, Unresponsive) scale can provide valuable information.
in children, especially in toddlers. The reported mortality in
developed countries in hospital setting is 9–35%.
Glasgow Coma Scale
The incidence in developing countries is poorly docu
mented, however, mortality is higher in developing countries. The Glasgow Coma Scale (GCS) is used to assess the depth of
Primary brain injury is the direct result of the physical coma after head injury in adults and children above 5 years
trauma. It may result in uncomplicated concussion with quick of age. In those below 5 years, modified GCS should be used
recovery and no residual deficit or in serious hemorrhage, (Table 1).
contusion or hematomas. While these are all visible on a Classification of head injury using GCS
computed tomography (CT) scan, diffuse axonal injury can • 13–15: mild
be a severe condition where the initial CT scan may look • 9–12: moderate
deceptively benign. Secondary brain injury may occur after • 3–8: severe.
the primary event due to potentially preventable causes like Clinical criteria for discharge from emergency room after 2
hypoxia, hypoperfusion, hypercarbia, and hematoma. hours of observation:
• No loss of consciousness
• No vomiting
MANAGEMENT • No amnesia
Management of head injury and control of intracranial • Normal mental status
pressure (ICP) (Algorithm 1) or maintenance of cerebral • No focal neurological deficit
perfusion pressure (CPP) is to be started right from the site • No neurological deterioration
of accident to include prevention of hypotension by active • No post-traumatic seizure including impact seizure
control of bleeding and fluid therapy. Immediate stabilization • No otorrhea or rhinorrhea or bleeding
of the airway, breathing, and circulation (ABC) with cervical • No shock or other organ involvement that would preclude
spine immobilization should be done followed by detailed discharge
evaluation of the following: • No anticoagulant, anti-inflammatory drug, or bleeding
• Mode of injury diathesis
• Time of injury • No suspicion of child abuse, no matter how trivial the injury
• Neurological condition of the child • Radiological criteria for minor head injury
• Seizures may occur immediately or soon after the injury. • No intracranial abnormality related to the head injury on
Loss of consciousness of more than 5 minutes warrants CT scan.
imaging and evaluation. Recovery from early loss of conscious Skull fractures are acceptable except:
ness with a secondary lapse may be indicative of extradural • Those that cross the middle meningeal artery
hematoma. • Those that cross the dural sinuses
Vomiting after even trivial head injury is not uncommon in • Those that are depressed more than the thickness of the
children, but observation for this is usually advisable. adjacent skull.
Ch-44.indd 209 11/19/2016 3:03:43 PM

Algorithm 1
Pediatric head trauma
PICU, pediatric intensive care unit; LOC, loss of consciousness; CT, computed tomography; MRI, magnetic resonance imaging; ICP, intracranial pressure; CPP,
cerebral perfusion pressure; BP, blood pressure; RL/NS, Ringer’s lactate/normal saline; GCS, Glasgow Coma Scale; PEEP, positive end-expiratory pressure;
PaCO2, partial pressure of carbon dioxide.
In children fulfilling the above criteria for minor head drainage. All unnecessary touch, rough handling, moving,
injury, delayed deterioration is extremely uncommon and can and noise should be controlled or kept to minimum. Severe
be safely discharged. All other patient should be admitted. hyperglycemia greater than 180 mg/dL and hypoglycemia
should be avoided.
Care upon Admission Orotracheal intubation is preferred as it is quicker,
requiring less manipulation of the neck, avoids aggravating any
Tracheal intubation is indicated for children with GCS ≤8. anterior basilar skull fracture, or introducing infection into the
Children with multi-trauma, inhalation injury, airway/facial anterior cranial vault.
injury, and shock with inaccessible head injury should be All patients should be presumed to be full stomach. The
intubated, especially if at risk for increased ICP from pain and jaw thrust maneuver is used during bag mask ventilation and
agitation. The cervical spine must be protected. head tilt and chin lift maneuver should be avoided. Common
Pain, fever, and retention of urine should be treated medications used during intubation include thiopentone
immediately. Constrictive cervical collar or large-bore internal and lidocaine. It should be emphasized that even comatose
jugular catheter should be avoided. Supine position with the patients must have good sedation and muscle relaxant during
210 head end elevated to 30° is preferred for adequate venous intubation to avoid sudden rise in ICP.
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Chapter 44: Head Injury in Infants and Children
Table 1: Modified Glasgow Coma Scale in pediatrics It is not necessary to repeat a scan after 24–48 hours if there
is no clinical deterioration or change in the GCS.
Eye opening Score
A quick cross table lateral X-ray can help to visualize at least
Spontaneous 4
the top three vertebrae. Cervical spine should also be scanned
To verbal stimuli 3 during the CT head to avoid repeated radiation exposure.
To pain 2 Other associated injuries should be ruled out and should
None 1 be treated simultaneously if required. The following conditions
Verbal response Score warrant early surgical intervention:
Nonverbal children Best verbal response • Acute extra-axial hematomas of 1 cm or more in thickness
Smiles, oriented to sounds, Oriented and converses 5 • Subdural or epidural hematomas of more than 5 mm in
follows objects, interacts thickness with midline shift
Consolable when crying and Disoriented and 4 • Hematomas more than 5 mm with midline shift in patients
interacts inappropriately converses with moderate brain injury with effacement of the basal
Inconsistently consolable and Inappropriate words 3 cisterns
moans; makes vocal sounds • Depressed skull fractures.
Cerebrospinal fluid rhinorrhea and otorrhea need
Inconsolable irritable and Incomprehensible 2
conservative approach avoiding packing of ears and nose.
restless; cries sounds
Almost all cases resolve spontaneously over 7–10 days.
None None 1
Cerebrospinal fluid leaks less likely to heal are:
Motor response Score • Developing after days or weeks
Obeys commands 6 • Postsurgical repair or accidental trauma
Localizes pain 5 • Massive leaks immediately after surgery
Flexion withdrawal 4 • Gunshot injury
Abnormal flexion (decorticate rigidity) 3 • With normal CSF pressure.
Extension (decerebrate rigidity) 2 Antibiotic prophylaxis remains controversial.
None 1
Intracranial Pressure
Hypotension is common and blood loss should never be Intracranial vault is a closed compartment—although with
attributed to the head injury alone. some potential for expansion in the infant, follows the Monro-
A diligent search should be made for the source of bleeding. Kellie doctrine hypothesis. Intracranial pressure should be
Scalp and head trauma can cause hypotension only in monitored in facilities are available. Brief increases in ICP for
children below 2 years of age. Rapid and aggressive treatment is less than 5 minutes are not associated with significant damage.
needed to prevent secondary damage from hypoxic-ischemic Sustained increases of more than 20 mmHg that do not return
injury. A low blood pressure at the time of presentation is to base line in 5 minutes probably require attention. Most of the
associated with poor prognosis. Hypotension of neurogenic evidences in adults and children set the acceptable high ICP
origin is rare and indicates severe brainstem or cervical spine level at 20 mmHg. In a study by Esparza, an ICP more than 40
injury. Hypertension as part of Cushing’s triad—hypertension, mmHg was associated with a 100% mortality and those between
bradycardia, and hypoventilation—are more common. This 20–40 mmHg had a 28% mortality, and with 0–20 mmHg had
indicates raised ICP. Hypertension may mask hypovolemia, 7% mortality or disability. The current recommendation is to
therefore, blood pressure measurement alone should not be keep the ICP less than 20 mmHg.
accepted as a sign of normovolemia. Normal saline is the best
choice for initial resuscitation.
Cerebral Perfusion Pressure
Radiological Investigations This is the critical determinant of cerebral blood flow (CBF)
and brain perfusion. It is defined as the difference between
There is no real role for skull X-ray in head injury as far as mean arterial pressure and the ICP. Studies showing outcomes
prognostication or severity of injury is concerned. Normal at various CPP levels confirm that a higher CPP level usually
ultrasound cranium in an infant may give false sense of above 60 mmHg is associated with worse outcome. However,
security as it will miss details. Computed tomography scan is there does not seem to be difference of outcome in 40–60
very helpful and threshold should be low for ordering a CT in mmHg. Guidelines for the acute medical management of severe
patients with: traumatic brain injury in infants, children, and adolescents
• Any focal deficit (2012) recommended CPP of 40 mmHg as the threshold for
• Any history of loss of consciousness more than 5 minutes infants and younger children and 50 mmHg for older children.
• GCS persistent less than 13
• Unable to examine the patient because of sedation,
paralysis, or intubation for other reasons
Monitoring Devices
• Pupillary inequality Intraventricular catheter, intrap
arenchymal pressure trans
• Cerebrospinal fluid (CSF) leak ducer, and subdural bolt can be used as invasive devices 211
• Depressed skull fracture and transcranial Doppler can be used as noninvasive device.
• Vomiting more than three times. Advanced monitoring like jugular venous oxygenation and
Ch-44.indd 211 11/19/2016 3:03:44 PM

brain tissue oxygenation are technologies measuring the Delayed lethargy and behavioral changes may be seen
adequacy of oxygen delivery to the brain directly. Regional after head injury in a child with normal CT scan and normal
oxygenation can be noninvasively measured with near infrared neurological examination known as postconcussive syndrome.
spectroscopy if available.
Steroids have no benefit in head injury as the edema is Clinical Pearls
cytotoxic in nature.
Hypocapnia reduces the CBF by vasoconstriction and • Vomiting, migraine, and cortical blindness can occur with
hence reduces ICP. However, it will also reduce CBF to the concussion with complete recovery in most cases of closed
point of reducing CPP and cause ischemia. Hyperventilation head injury
for a brief period of less than 10 minutes may be employed in • Jaw thrust should be used for cervical spine protection
the setting of a sudden rise in ICP or impending herniation
• Bleeding or clear fluid (cerebrospinal fluid) from ear or nose
preferably under ICP and CPP monitoring. The goal of therapy indicates fracture base of skull
is to maintain eucapnia with PaCO2 of 32–35 mmHg.
• Persistent hypotension in multitrauma patient may not be
Mannitol 0.25–1 g/kg is still the most commonly used
due to head injury; look for other causes such as long bone
agent by reducing the blood viscosity reduces the cerebral
fracture, and abdominal bleeding due to visceral injury.
vasoconstriction, improves the cerebral blood flow, and
prevents stasis. This action is immediate and last about
75 minutes. It takes 15 minutes to 6 hours for osmotic reduction
of brain water in an intact blood-brain barrier. It may also get Key points
deposited in injured brain cells after prolonged use for less
))
All patients with head injuries with loss of consciousness
than 48 hours, resulting in rebound edema.
should be admitted for observation
Three to seven percent saline has been successfully used
in the treatment of traumatic brain injury. The hyperosmolar ))
Computed tomography head is the investigation of choice in
state induced is more sustained and the reduction in ICP tends patients with loss of consciousness or neurological symptoms
to be more sustained with fewer peaks requiring intermittent following head injury
measures. The exact dosage is still unclear and bolus doses ))
Glasgow Coma Scale less than 8 is an indication for intubation
from 6.5 mL–10 mL/kg have been advocated followed by ))
Hypotension must be treated by control of bleeding and fluid
an infusion of 0.1–2.5 mL/kg/h. Serum sodium levels up to therapy.
160 mmol/L have been reported with no side effects. Serum
osmolarity rather than sodium level should be monitored for
effect, with a target osmolarity of 340–360 mOsm/kg. Gradual
SUGGESTED READINGs
tapering of about 10% every 6 hours is required if continuous
infusion is used for more than 48–72 hours. 1. Adelson PD, Bratton S, Carney NA, Chesnut RM, du Coudray HE, Goldstein B, et al.
Barbiturates are used for reducing the metabolic activity Guidelines for the acute medical management of severe traumatic brain injury in
of the brain, thereby its oxygen consumption. Short-acting infants, children and adolescents. Pediatr Crit Care Med. 2003;4(Suppl. 3):S72-5.
barbiturates like thiopentone in a loading dose of 4 mg/kg 2. Coles JP, Minhas PS, Fryer TD, Smielewski P, Aigbirihio F, Donovan T, et al.
Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical
followed by 2–4 mg/kg/h as an infusion is most commonly relevance and monitoring correlates. Crit Care Med. 2002;30(9):1950-9.
used. Significant side effect includes hypotension in 54% 3. Hutchinson JS, Ward RE, Lacroix J, Hebert PC, Barnes MA, Bohn DJ, et al.
requiring fluids and vasopressors, anergy, pneumonia, sepsis, Hypothermia therapy after traumatic brain injury in children. N Engl J Med.
and hyponatremia. 2008;358(23):2447-56.
Moderate hypothermia with a core temperature of 32–34°C 4. Ichai C, Armando G, Orban JC, Berthier F, Rami L, Samat-Long C, et al. Sodium
may be useful but did not improve outcome in children. lactate versus mannitol in the treatment of intracranial hypertensive episodes in
A seizure does worsen ICP and the severe head injury patient severe traumatic brain-injured patients. Intensive Care Med. 2009;35(3):471-9.
has a high incidence of early symptomatic seizure; prophylactic 5. Jagannathan J, Okonkwo DO, Dumont AS, Ahmed H, Bahari A, Prevedello DM,
medication like fosphenytoin, valproate or levetiracetam should et al. Outcome following decompressive craniectomy in children with severe
traumatic brain injury: a 10-year single-center experience with long-term follow
be administered. Seizures may occur even in minor trauma. up. J Neurosurg. 2007;106(Suppl. 4):268-75.
Immediate seizure may occur on impact or within the first 24 6. Kochanek PK, Carney N, Adelson PD, Ashwal S, Bell MJ, Bratton S, et al.
hours. Most seizures appear within the first 3 hours, are short- Guidelines for the acute medical management of severe traumatic brain injury
lived, generalized, and without any CT scan abnormality. in infants, children and adolescents—Second edition. Pediatr Crit Care Med.
They do not predict future epilepsy, require no treatment, and 2012;13(Suppl. 1):S1-82.
bear a good prognosis. If the seizure is complex, prolonged, or 7. McHugh GS, Engel DC, Butcher I, Steyerberg EW, Lu J, Mushkudiani N, et al.
localized, further observation and treatment is warranted. Prognostic value of secondary insults in traumatic brain injury: results from the
Decompressive craniectomy may be required for severe IMPACT study. J Neurotrauma. 2007;24(2):287-93.
head injury and medically refractory intracranial hypertension 8. Muizelaar JP, Marmarou A, Ward JD, Kontos HA, Choi SC, Becker DP, et al.
Adverse effect of prolonged hyperventilation in patients with severe head injury:
in conditions like: a randomized control trial. J Neurosurg. 1991;75(5):731-9.
• Diffuse cerebral swelling on cranial CT imaging 9. Muizelaar JP, Wei EP, Kontos HA, Becker DP. Mannitol causes compensatory
• Sustain ICP more than 40 mmHg before surgery cerebral vasoconstriction and vasodilation in response to blood viscosity changes.
• Glasgow Coma Scale 3 at some point of subsequent to injury J Neurosurg. 1983;59(5):822-8.
212 • Secondary clinical deterioration 10. Wakai A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury.
• Evolving cerebral herniation syndrome. Cochrane Database Syst Rev. 2007;24(1):CD001049.
Ch-44.indd 212 11/19/2016 3:03:44 PM

Chapter 45
Trauma in Children
Soonu Udani
INTRODUCTION • D—disability
• E—exposure
Polytrauma is defined as trauma to more than one area of the
body and the term is usually reserved for moderate to severe Airway
injury requiring multiple interventions; e.g., head ± orthopedics
± abdominal ± plastic surgery- and includes burns. • Priority → choking will kill faster than anything else
The length should be used for the rapid determination of • Assess for obstruction due to position, injury, blood, teeth,
weight for appropriate drug doses and equipment size. vomitus, and foreign object
{{ Level of consciousness
BE PREPARED !!!
{{ Maxillofacial injury
{{ Stridor or cyanosis.
UNIQUE ANATOMY of PEDIATRIC PATIENTS Hemodynamics → initial fluids: normal saline (NS).
Packed cell transfusions if hypotension persists after 2–3
• Cranium is larger relatively → more space between brain
boluses. Attempt to control hemorrhage by bandages.
and bone, hence bridging veins have less support
• Thinner musculature and padding, thus less protection to
organs
Breathing Assessment
• Ribs are more flexible, hence less dissipation of energy and • Rate
lung contusion can occur • Chest wall movement: paradoxical breathing; flail segment
• Solid organs are comparatively larger than adults, so, less • Oxygen status
protected by the rib cage • Percussion note
• Kidney more mobile, hence more commonly injured • Tracheal deviation
• Larger surface area relative to volume predisposes children • Crepitus
to thermal evaporative loss. Result is hypothermia and • Open wounds.
dehydration. Management will be specific to the findings:
• Warm humidified oxygen
• Gastric decompression
PRIMARY SURVEY (ALGORITHM 1) • Appropriate mechanical ventilation → avoid barotrauma
and volutrauma
Goals of primary survey are:
• Chest tube(s) if indicated.
• Identify immediate/potential threats to life and initiate
treatment
• Identify the disposition of the patient (e.g., operating room, Circulation/Hemodynamics
intensive care unit, trauma facility) • Blood volume = 70–90 mL/kg
• Continuous reassessment is essential. • Systolic blood pressure (SBP) = 70 + 2 (age in years); In
Stabilize and transfer/triage only after the following: years old, will be 70 + 10 = 80 mmHg
• A—airway • Diastolic blood pressure = 2/3 SBP
• B—breathing Pediatric vasculature readily constricts and increases
• C—circulation systemic vascular resistance to maintain perfusion.
Ch-45.indd 213 11/19/2016 3:05:14 PM

Algorithm 1
Primary survey meant to discover life-threatening conditions and stabilize patient
HR, heart rate; BP, blood pressure; GCS, Glasgow Coma Scale; pRBC, packed red blood cells.
Tachycardia and poor skin perfusion may be the only keys • Maximal flow rate: 25 mL/min
to hypovolemia. • Contraindicated at site of fractures or devitalized limb
Hypotension in a child = decompensated shock and • Fluid resuscitation:
{{ 20 mL/kg warmed NS = first line therapy
estimated blood loss >/= 45% and may be abruptly followed by
{{ Recall the 3:1 rule of crystalloid resuscitation
bradycardia.
• Consider packed red blood cells (pRBCs) if
{{ Obvious exsanguination injury
Circulation with Hemorrhage Control
{{ Initiating third bolus (10 mL/kg of type specific or
• Heart rate (HR) O negative warmed pRBCs).
• Systolic blood pressure and pulse pressure
• Peripheral pulses
Box 1: Structure of the pediatric airway
• Skin condition/perfusion/capillary refill
• Sensorium • Passive flexion due to large occiput → airway obstruction
• Potentially “deadly” bleeding checks. • Relatively larger tongue → airway obstruction
After initial resuscitation done → reassess • Mass of adenoidal tissues → nasopharyngeal (NP) airways
difficult to pass
Check for the following:
• U-shaped, floppy epiglottis → may necessitate use of a straight
• Cervical spine must be stabilized
blade
• Chest has to be reassessed
• Anterior and cephalad larynx → visualization more difficult
• Fractures long bones and pelvis
• Airway narrowest at the cricoid ring → uncuffed tubes up to
• Abdominal injuries 6 mm or ~ 8 years
• Bleeding from the ear and nose • Narrow tracheal diameter and distance between the rings →
• Glasgow Coma Scale (GCS) for improvement or needle cricothyroidotomy over surgical for a difficult airway
deterioration. • Short tracheal length (4 cm NB; 8 cm toddler) → RMS intubation
No child should die from lack of vascular access. and dislodgement
214 • More narrow large airways → greater airway resistance (R = 1/r4)
Intraosseous access: anything can be given for this site.
Ch-45.indd 214 11/19/2016 3:05:14 PM

Chapter 45: Trauma in Children
Box 2: Indications for a definitive airway

• Placement of Foley catheter with inflatable retaining device
only when child > 5 kg
• Lack of a patent/protected airway • Secondary survey continued
• Impending loss of the airway • Review labs
• Comatose patient Glasgow Coma Scale <9 • Radiology: focused assessment sonography in trauma
• Inability to oxygenate ultrasound
• Inability to ventilate {{ Chest, pelvis, lateral c-spine if not done with primary
• Full/impending cardiac arrest survey

• Head injury {{ Additional images on the basis of threat to life/limb
• Tetanus toxoid
• Antibiotics
• Analgesia (systemic and local)
Box 3: Repeatedly check for optimal response to resuscitation • Continuous reassessment; tracking of vitals and urine
• Slowing of heart rate output.
• Increased pulse pressure (>20 mmHg)
Head Trauma
• Normal skin perfusion
• Leading cause of death
• Improvement in level of consciousness
• Results in significant morbidity
• Systolic blood pressure >80 mmHg (age based) • Hypotension and hypoxia from concurrent injury adversely
• Urine output = 1–2 mL/kg/h affect the outcome from intracerebral injury.
Spinal Cord Injury without

Disability Assessment Radiological Abnormality
• Alert/verbal/painful/unresponsive (AVPU)/modified GCS • If spinal cord injury is suspected on the basis of mechanism
• Pupil size and reactivity or clinical examination, do not be dissuaded by normal
• Extremity movement and tone X-rays
• Posturing • A normal X-ray and initial exam is not enough
• Reflexes. • Be aware of: local pain, torticollis.
Management:
Management: Address findings in keeping with increased • Avoid secondary and iatrogenic injury
intracranial pressure and/or spinal cord injury without • Corticosteroids are currently not recommended.
radiological abnormality.
Chest and Abdomen
Exposure with Environmental Control Pliable chest wall so lung contusions may occur without
• Logroll to examine back obvious external injury.
• Look under hair, collar, and splints. Clinical examination improved with gastric and bladder
• Survey repeatedly. decompression. Clinical findings may underestimate problems.
Therefore, diagnostic adjuncts:
• Computed tomography: less sensitive for bowel, spleen,
Secondary Survey
early pancreas, liver
This commences once the injured child is stabilized. • Ultrasound: good for hepatic and splenic injury.
Goals to identify any new/potential threats to life organ Visceral injuries specific to the pediatric population:
and limb are discussed in box 4. • Pancreatic injury
• Identify injuries that may impact the child later (e.g., minor • Small bowel perforation (ligament of treitz)
fractures, dislocations, and lacerations) • Mesenteric and small bowel avulsion
• Obtain a more complete history • Duodenal hematoma
• Continuous monitoring (HR, blood pressure, T, SaO2 ± • Spleen, liver, and kidney disruption
etCO2) • Bladder injury.
• Achieved through a well organized head to toe examination Missed abdominal trauma is the leading cause of
preventable morbidity and mortality.
Clinical findings associated with intra-abdominal injury:
Box 4: Check these areas for potential threats to other organs • Initial Hct less than 30%
• Maxillofacial and head • Abdomen, perineum, rectum, • Abdominal tenderness
vagina • Femur fracture
• Cervical spine and neck
• Neurological.
• AST more than 200 U/L and/or ALT more than 125 U/L
• Chest • Urine with more than 5 RBCs/hpf. 215
Ch-45.indd 215 11/19/2016 3:05:14 PM

Indications for Surgery Key points

• Hemodynamic instability despite maximal resuscitative
))
Trauma is leading cause of morbidity and mortality in
measures +/– a positive diagnostic study
developed world
• Falling hematocrit
• Transfusion of greater than 50% of total blood volume ))
Blunt trauma is most common mechanism of injury in children
• Radiographic evidence of pneumoperitoneum, intra ))
ABCDE sequence of initial assessment should be followed in
peritoneal bladder rupture, grade V renovascular injury. every child with multiple trauma
• Peritonitis or the development to peritoneal signs ))
Continuous monitoring following initial resuscitation is
• Evisceration of intraperitoneal contents mandatory to detect further deterioration
• Evidence of fecal or bowel contamination on diagnostic ))
Fatal: Pediatric Trauma Score <0, transport to nearest facility.
peritoneal lavage.
Nonoperative approach mandates pediatric intensive care
unit accessibility. SUGGESTED READINGs
1. Nichols DG (Ed). Roger’s Textbook of Pediatric Intensive Care, 4th edition.
Clinical Pearls Philadelphia: Lippincott Williams & Wilkins; 2008.
2. The International ATLS working Group. Tchorz, KM. Advanced Trauma Life
• Cervical spine should be always taken care of in a child with Support (ATLS®): The Ninth Edition. The Journal Of Trauma And Acute Care
polytrauma Surgery. 2013;74(5):1363.
• Patients with persistent shock despite initial resuscitation
may have neurogenic shock, cardiac contusion, or cardiac
tamponade
• Multidisciplinary approach with one team leader.
216
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Chapter 46
Poisoning in Children
Pradeep K Sharma, Praveen Khilnani
INTRODUCTION its amount, time of ingestion, circumstances preceding,

smells or unusual items, occupation of those in home, and
Various Indian studies report kerosene (30–50%), drugs queries regarding the presence of a suicide note is pivotal to
(11%), pesticides (11%), snakebites (10–20%), corrosives, management. Obtaining an accurate history in adolescent
and household cleaning products as the common substance is especially challenging due to the potential use of multiple
causing poisonings. Certain household items often ingested
substances, possible drug abuse, prolonged time between
by children are proven to be nontoxic and harmless (Box 1).
ingestion and presentation, and attempts at concealing
However, ingestion of excessive amount of these substances
information. Additional information includes the maximum
may lead to toxicity.
amount of toxin available and the minimum amount per
kilogram that produces symptoms. Quantity of liquid toxins
EVALUATION OF CHILDREN swallowed can be estimated as 5–10 mL in a young child and
WITH SUSPECTED TOXIN INGESTION 10–15 mL in an adolescent. Product containers or medication
labels are helpful to identify specific toxic contents. A number
The acute management generally begins in the emergency
of medications have been determined to be potentially lethal
department with triage and the determination of appropriate
to a child who weighs 10 kg and ingests just one tablet, capsule,
decontamination and treatment regimens. Immediate
or teaspoonful (Table 1).
attention to the patient’s airway, breathing, and circulation
(ABC) should be done and following the establishment
of lifesaving supportive care, a detailed evaluation can be PHYSICAL EXAMINATION
performed (Algorhithm 1).
A comprehensive physical examination is crucial in
determining the involved agents and allows for specific
HISTORY initial treatment. The signs and symptoms that suggest
specific classes of poisoning are generally grouped into
A comprehensive history may be obtained from witnesses,
syndromes and referred to as toxidromes (Table 2). A vitals
family members, and friends. Nature of substance ingested,
recording also helps in determining the particular toxidrome
(Table 3).
Box 1: Nontoxic substances
• Silica gel • Shaving cream and lotions
• Ball pen inks • Soaps and detergents SYSTEMIC EXAMINATION
• Candle • Bath oils Frequent neurologic examination is especially important,
• Modeling clay • Thermometer mercury as many toxins can depress the consciousness. Symmetrical
• Crayons • Saccharin pupillary changes are typical of toxic exposures, with
• Lipstick • Water colors
asymmetry most commonly evidencing a structural or focal
• Shampoo • Petroleum jelly
neurologic abnormality. Detailed general physical and
• Chalk • Toothpaste
systemic examinations help in pointing to a specific toxin as
• Pencil lead
shown in table 4.
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Algorithm 1
Approach to a child with poisoning
Table 1: Toxicity levels of selected medication and medication classes

Agents Minimum lethal dose Potential maximum available Dose potentially fatal units in a 10 kg child
Antimalarial
Chloroquine 20 mg/kg 500 mg 1
Hydroxychloroquine 20 mg/kg 200 mg 1
Camphor 100 mg/kg 200 mg/mL 5 mL
Imidazolines
Clonidine 0.01 mg/kg 0.3 mg, 7.5 mg/patch 1
Tetrahydrozoline 2.5–5 mL 0.1% 2.5–5 mL
Methyl salicylates 150–200 mg/kg 1400 mg/mL 1.1–1.4 mL
Sulfonylureas
Glipizide 0.1 mg/kg 5 mg 1
Glyburide 0.1 mg/kg 10 mg 1
Table 2: Toxidromes and agents

Toxidrome Agents Clinical manifestations
Sympatho • Albuterol; amphetamines; caffeine; catecholamines; • Agitation; seizures; mydriasis; tachycardia • Pallor
mimetic cocaine; ephedrine; ketamine; lysergic acid • Hypertension • Cool skin
toxidrome* diethylamide; methamphetamine; phencyclidine; • Diaphoresis • Fever
phenylephrine; phenylpropanolamine;
pseudoephedrine; terbutaline; theophylline
218
Continued
Ch-46.indd 218 11/19/2016 3:06:32 PM

Chapter 46: Poisoning in Children
Continued
Toxidrome Agents Clinical manifestations

Cholinergic • Organophosphate and carbamates • Muscarinic effects (dumbbells) • Weakness
toxidrome • Pesticides, nicotine • Diarrhea • Paralysis
• Urinary incontinence • Tachycardia
• Miosis • Hypertension
• Bradycardia • Agitation
• Bronchorrhea • Central effects
• Emesis • Lethargy
• Lacrimation • Coma
• Salivation • Agitation
• Nicotinic effects • Seizures
• Fasciculations
Anticho • Antihistamines—diphenhydramine, hydroxyzine • Agitation Associated
linergic • Atropine • Delirium expressions
toxidrome* • Benztropine mesylate • Coma • “Mad as a hatter”
• Carbamazepine • Mydriasis • “Blind as a bat”
• Cyclic antidepressants • Dry mouth • “Red as a beet”
• Cyclobenzaprine • Warm, dry, flushed skin • “Hot as a hare”
• Hyoscyamine • Tachycardia
• Jimsonweed • Hypertension
• Oxybutynin • Fever
• Phenothiazines • Urinary retention
• Scopolamine • Decreased bowel sounds
• Trihexyphenidyl
Opioid • Morphine, methadone, dextromethorphan, • Central nervous system depression,
toxidrome fentanyl, pentazocine, heroin, codeine respiratory depression, coma, miosis,
hypothermia, bradycardia, constipation
*Both have almost similar clinical features except diaphoresis, cool skin, and hyperactive bowel sounds in sympathomimetic toxidrome and warm, dry skin and
diminished bowel sounds in anticholinergic toxidrome.
Table 3: Common clinical findings in toxidrome

Physical Findings Sympathomimetic Anticholinergic Cholinergic Opioid Sedative-hypnotic
Pulse rate Increased Increased Decreased Decreased Decreased
Respiratory rate Increased No change No change Normal/decreased Normal/decreased
Body temperature Increased Increased No change Normal/decreased Normal/decreased
Blood pressure Increased No change/increased No change Normal/decreased Normal/decreased
Mental state Agitated Agitation/delirium Depressed Depressed Depressed
Pupils Mydriasis Mydriasis Miosis Miosis Normal
Mucous membranes Wet Dry Wet Normal Normal
Skin Diaphoretic Dry Diaphoretic Normal Normal
LABORATORY EVALUATION MUDPILES: methanol, uremia, diabetic ketoacidosis, para

ldehyde and phenformin, isoniazid and iron, lactic acidosis,
The laboratory generally confirms a diagnosis and also based ethanol and ethylene glycol, salicylates.
upon quantitative drug or toxin levels helps in deciding about Electrocardiogram is invaluable in detecting dysrhy
therapy. The drug or toxin levels are available for acetaminophen, thmias and conduction abnormalities. Increased serum
ethanol, methanol, ethylene glycol, lithium, salicylates, iron, osmolality is seen with methanol, ethanol, ethylene glycol,
lead, mercury, arsenic, phenobarbital, carbon monoxide, acetone, and isopropanol. Complete blood cell count
methemoglobin, and theophylline. A negative toxicology screen with platelets and leukocyte differential, prothrombin
by no means excludes the possibility of toxic exposure. time, partial thromboplastin time, liver function tests, and
Arterial blood gas analysis evaluates acid-base status and electroencephalogram may prove useful. Urine color may
anion gap metabolic acidosis. Agents with elevated anion gap be helpful in the identification of a number of toxins. It is
can be summarized by the mnemonic MUDPILES as given important to obtain urine pregnancy tests on patient of
below. childbearing age.
219
Ch-46.indd 219 11/19/2016 3:06:32 PM

Table 4: Clinical manifestations of poisoning Continued

Clinical Suspected toxins Clinical Suspected toxins
manifestations manifestations
Skin Miosis Narcotics (except demerol and lomotil),
Cyanosis un Nitrates, nitrites, phenacetin, benzocaine phenothiazines, organophosphates, diazepam,
responsive to barbiturates, mushrooms (muscarine types)
oxygen Mydriasis Anticholinergics, sympathomimetics, cocaine,
Red flush Carbon monoxide, cyanide, boric acid, TCAs, methanol, glutethimide, LSD
anticholinergics Blindness, optic Methanol
Sweating Amphetamines, LSD, organophosphates, atrophy
cocaine, barbiturates Fasciculation Organophosphates
Dry Anticholinergics Nystagmus Diphenylhydantoin, barbiturates,
Bullae Barbiturates, carbon monoxide carbamazepine, PCP, carbon monoxide,
glutethimide, ethanol
Jaundice Acetaminophen, mushrooms, carbon
Hypertonia Anticholinergics, strychnine, phenothiazines
Purpura Aspirin, warfarin, snakebite
Myoclonus, Anticholinergics, phenothiazines, haloperidol
Temperature rigidity
Hypothermia Sedative hypnotics, ethanol, carbon monoxide, Delirium, Anticholinergics, sympathomimetics, alcohol,
phenothiazines, TCAs, clonidine psychosis phenothiazines, PCP, LSD, marijuana, cocaine,
Hyperthermia Anticholinergics, salicylates, phenothiazines, heroin, methaqualone, heavy metals
TCAs, cocaine, amphetamines, theophylline Coma Alcohols, anticholinergics, sedative hypnotics,
Blood pressure narcotics, carbon monoxide, tricyclic
Hypertension Sympathomimetics (especially phenylpropa antidepressants, salicylates, organophosphates,
nolamine in over-the-counter cold remedies), barbiturates
organophosphates, amphetamines, PCP Weakness, Organophosphates, carbamates, heavy metals
Hypotension Narcotics, sedative hypnotics, TCAs, paralysis
phenothiazines, clonidine, β-blockers, calcium Gastrointestinal symptoms
channel blockers Vomiting, Iron, phosphorus, heavy metals, lithium,
Pulse rate diarrhea, pain mushrooms, fluoride, organophosphates,
Bradycardia Digitalis, sedative hypnotics, β-blockers, arsenic
ethchlorvynol, calcium channel blockers Constipation Lead, narcotics, botulism
Tachycardia Anticholinergics, sympathomimetics, Hematemesis Aminophylline, corrosives, iron, lead, salicylates
amphetamines, alcohol, aspirin, theophylline,
LSD, lysergic acid diethylamide; PCP, phencyclidine; TCA, tricyclic antidepressant.
cocaine, TCAs
Arrhythmia Anticholinergics, TCAs, organophosphates,
phenothiazines, digoxin, β-blockers, carbon
monoxide, cyanide, theophylline RADIOLOGIC IMAGING
Mucous membranes Radiographic evaluation is useful for certain foreign bodies,
Dry Anticholinergics radiopaque drugs, metals, and chemicals. Serial chest/
Salivation Organophosphates, carbamates abdominal X-rays identify the movement of the disc batteries
Oral lesions Corrosives, paraquat, lacrimation through the gastrointestinal (GI) tract. Radiopaque compounds
may be grouped by the mnemonic “COINS”: chloral hydrate
Lacrimation Caustics, organophosphates, irritant gases
and cocaine packets, opiate packets, iron and heavy metals
Respiration (lead, arsenic and mercury), neuroleptics, and sustained-
Depressed Alcohol, narcotics, barbiturates, sedative/ release or enteric coated tablets.
hypnotics
Tachypnea Salicylates, amphetamines, carbon monoxide
Kussmaul Methanol, ethylene glycol, salicylates
MANAGEMENT
Pneumonia Hydrocarbons The approach includes:
Pulmonary Aspiration, salicylates, narcotics, • Emergency stabilization
edema sympathomimetics • Decontamination
Central nervous system • Enhanced elimination
• Antidote and poison specific therapy.
Seizures TCAs, cocaine, phenothiazines, amphetamines,
camphor, lead, salicylates, isoniazid,
organophosphates, antihistamines, Emergency Stabilization
propoxyphene, strychnine
220 This begins with checking the ABC and stabilization. Because
Continued the patient’s status can change rapidly, it is essential to
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Chapter 46: Poisoning in Children
reassess the patient often and monitor the need for ventilator the intestinal tract. Multiple doses should not include sorbitol
support. Blood glucose should be obtained from patient because of possible electrolyte and fluid abnormalities.
with ingestion of oral hypoglycemic agents, alcohol, and
with altered sensorium. Symptoms of hypoglycemia may Whole-bowel Irrigation
be rapidly reversed with intravenous dextrose. Intravenous Whole-bowel irrigation (WBI) involves administration
thiamine (10 mg for infants, 10–25 mg for children) should of large volumes of polyethylene glycol solution orally to
be given before dextrose administration to prevent Wernicke decontaminate the GI tract. The pediatric dose is 25 mL/
encephalopathy. Although altered mental status in a child kg/h, up to 500 mL/h in young children and up to 1 L/h in
may be presumed to be from poisoning, traumatic head injury adolescents. It may be useful when a drug or toxicant does not
should also be considered. Any child with coma, altered have an antidote or treatment and the substance ingested is
sensorium, seizures, agitation, impaired vital parameter— an enteric pill, sustained release preparation, or agents poorly
tachycardia/bradycardia, arrhythmia, hypotension/hyper adsorbed by AC. Examples are lithium, iron, and lead. Adverse
tension, respiratory distress or depression, and organ failure effects of WBI include vomiting, abdominal cramps, bloating,
should be managed in pediatric intensive care unit. and rarely, aspiration pneumonitis.
Decontamination Surgical Decontamination

Decontamination may be individualized, depending upon Surgical intervention is usually indicated for mechanical bowel
the type and amount of substance ingested, potential toxicity, obstruction or bowel ischemia due to heroin or cocaine drug
time elapsed since ingestion, and the symptoms exhibited. packets and also for massive iron ingestion with failure to
evacuate the GI tract.
Gastric Lavage
A mainstay of gastric decontamination, involves insertion Enhanced Elimination
of a large-bore orogastric tube into the stomach, followed by
Active elimination techniques should be considered only
repeated administration and aspiration of 10–15 mL/kg saline
in ingestion of a potentially lethal dose of toxin, progressive
until aspirates is clear. This can be particularly traumatizing
clinical deterioration refractory to aggressive supportive care,
to a young child. Contraindications include compromised
and blood concentrations that indicate serious intoxication
upper airway protection, ingestion of corrosive substances
and impaired organ function. Hemodialysis (HD) is useful for
or hydrocarbons, and patients at risk for GI perforation or
drugs with small volume of distribution, poor plasma protein
hemorrhage. Possible complications are aspiration, respiratory
binding, low molecular weight, and weak lipid solubility,
compromise, mechanical injury/perforation, and electrolyte
e.g., atenolol, ethylene glycol, methanol, and salicylates.
imbalances. The American Academy of Clinical Toxicology
Hemoperfusion, using a charcoal filter in a HD machine, can
(AACT) and European Association of Poison Centers and
remove toxins with high molecular weight, e.g., barbiturates,
Clinical Toxicologists discourage its routine use unless
carbamazepine, chloral hydrate, dapsone, isoniazid, pro
performed within 1 hour of the ingestion.
cainamide, organophosphates, and diphenhydramine.
Exchange transfusion is an alternative procedure for a
Syrup of Ipecac small group of children who are not eligible for HD. Beneficial
In 2003, the American Academy of Pediatrics released a policy effects are seen with salicylate, theophylline, phenobarbital,
statement advising that syrup of ipecac should no longer chloramphenicol, lithium, aniline, chloral hydrate, salicylate,
be used. quinine, and methemoglobinemia. Extracorporeal membrane
oxygenation has been used for hydrocarbon-induced lung
Activated Charcoal injury, bupropion, amiodarone, calcium channel blocker
It works by adsorbing the toxin and preventing enterohepatic overdose, and a severe ibuprofen poisoning.
and enteroenteric recirculation. A charcoal/drug ratio of
10:1 is recommended (1–2 g/kg). Activated charcoal (AC) is Diuresis
helpful in carbamazepine, dapsone, phenobarbital, quinine,
Drug elimination may be facilitated by ensuring adequate
theophylline, salicylates, phenytoin, or valproic acid ingestion.
renal flow 2–5 mL/kg/h. Elimination of drugs with pKa
AC is unpalatable, messy, and poorly accepted by young
values of 3.0–7.2 may be enhanced by alkalinizing the urine,
children often causing vomiting. AC does not bind well with
e.g., salicylate, phenobarbital, chlorpropamide, and the
xenobiotics that are highly ionized (e.g., metals, electrolytes,
chlorophenoxy herbicides. Complications are fluid overload,
acids, and alkali). In addition, AC is contraindicated in patients
with cerebral edema, pulmonary edema, and hyponatremia.
who have ingested corrosives or hydrocarbons, in those with
bowel obstruction or perforation, and in patients with a
depressed level of consciousness. Toxin-specific Treatments
The AACT discourages the routine use except within 1 If physical examination or laboratory findings suggest a specific
hour of ingestion. The first dose is often given with a cathartic toxidrome, then consider toxin specific treatments, such as an
agent, such as sorbitol, to improve taste and transit through antidote (Table 5). Antidotes are usually given after the patient 221
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Table 5: Selected antidotes exposed to potentially lethal drugs and toxins. The evaluation
of a child presumed to have been exposed to a toxic
Antidote Toxin
substance should include a precise history of the exposure, a
Atropine Organophosphate, carbamate poisoning, physical examination, and knowledge of current ingestions
bradydysrhythmias and recreational practices. Poison centers and medical
Calcium (chloride or Calcium channel blocker overdose, toxicologists should be consulted to assist with the diagnosis
gluconate) hydrofluoric acid ingestion/exposure and management of medicinal/drug overdoses.
Cyanide antidote Cyanide, acetonitrile (artificial nail
package, Amyl nitrite, remover), amygdalin (peach, apricot pits),
Sodium nitrite, nitroprusside (thiosulfate only)
Clinical Pearls
Sodium thiosulfate
• Common toxidromes can identify many poisonous substances
Deferoxamine Iron (Tables 2 and 3)
Digoxin-specific Digoxin, digitoxin, natural cardiac • Causes of high anion gap—MUDPILES: methanol, uremia,
antibody glycosides (e.g., oleander, red squill, Bufo diabetic ketoacidosis, paraldehyde and phenformin, isoniazid
toad venom) and iron, lactic acidosis, ethanol and ethylene glycol, salicylates.
Flumazenil Benzodiazepines
Fomepizole Toxic alcohols (ethylene glycol, methanol)
Glucagon Calcium channel blocker, β-blocker toxicity Key points
Glucose (dextrose) Sulfonylureas, insulin, hypoglycemia ))
Precise history is very important in all cases of poisonings
(multiple toxins)
))
Management of most poisonings is supportive
Hydroxocobalamin Cyanide, acetonitrile, amygdalin, ))
Induction of vomiting (syrup ipecac) is no longer recom
(vitamin B12) nitroprusside
mended due to risk of aspiration in comatose patients and all
Insulin (high dose) Calcium channel blocker, β-blocker toxicity patients with suspected hydrocarbon ingestion
Methylene blue Methemoglobinemia ))
Poison control centers are helpful in guiding therapy and
N-acetylcysteine Acetaminophen, pennyroyal oil, carbon
observation period
tetrachloride ))
All unknown poisonings or unknown causes of coma are
medicolegal cases.
Naloxone Opioid toxicity
Octreotide Sulfonylurea toxicity
Physostigmine Antimuscarinic delirium (as a diagnostic SUGGESTED READINGs
tool only) 1. American Academy of Pediatrics Committee on Injury, Violence, and Poison
Pralidoxime Organophosphate poisoning (insecticides, Prevention. Policy statement: poison treatment in the home. American Academy
nerve agents) of Pediatrics Committee on Injury, Violence, and Poison Prevention. Pediatrics.
2003;112(5):1182-5.
Protamine sulfate Heparins 2. Bronstein AC, Spyker DA, Cantilena LR, Rumack BH, Dart RC. 2011 Annual
Pyridoxine Isoniazid, Gyromitra mushrooms report of the American Association of Poison Control Centers’ National Poison
Data System (NPDS): 29th Annual Report. Clin Toxicol (Phila). 2012;50(10):911-
Thiamine Deficiency states (e.g., alcoholism,
1164.
anorexia nervosa)
3. Gupta SK, Peshin SS, Srivastava A, Kaleekal T. A study of childhood poisoning at
Sodium bicarbonate Sodium channel blocking cardiotoxins, National Poisons Information Centre, All India Institute of Medical Sciences, New
salicylates Delhi. J Occup Health. 2003;45(3):191-6.
4. McGregor T, Parkar M, Rao S. Evaluation and management of common childhood
poisonings. Am Fam Physician. 2009;79(5):397-403.
is stable, preferably within a few hours of ingestion and may
5. National Poisons Information Centre (NPIC), All India Institute of Medical sciences.
require multiple doses because of short durations of action.
[online] available from http://www.aiims.edu/aiims/departments/pharmacology/
NPIC/home.htm [Accessed December, 2015].
CONCLUSION 6. Nichols DG, Ackerman AD, Argent AC, et al. (Eds). Rogers’ Textbook of Pediatric
Intensive Care, 4th edition. Philadelphia: Lipincott Williams and Wilkins; 2008.
Poison prevention remains a challenge and a necessity to 7. Rathore S, Verma AK, Pandey A, Kumar S. Pediatric poisoning trend in Lucknow
prevent the most vulnerable population from becoming District, India. J Forensic Res. 2013;4:179.
222
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Chapter 47
Snakebite Envenomation
Soonu Udani, Narendra Rathi
INTRODUCTION • Neurotoxic and hemorrhage effects. Timing of onset can be

variable.
A victim of a snakebite needs to be treated appropriately Local signs: Viper versus cobra
and rapidly. The outcome can be excellent if a protocolized • Pain, wheal, swelling, bullae. Regional lymphadenopathy
approach is used. develops rather rapidly
First aid: many old practices are known to do more harm • Blood filled bullae—viper
than good. • Necrosis, gangrene, and anaerobic infections are common.
• No—incision, suction, ice packs, washing wound, tourniquet
• Reassurance important though neglected step. The Neurotoxic Effects
sympathetic storm caused by fear and anxiety with pain, is
deleterious to the hemodynamics of the patient • Neuromuscular blockade: flaccid paralysis
• Immobilize bitten part/victim by a splint. Bandage the part • Ptosis (earliest): inability to look up, external ophthalmo
by starting distal to the bite and going above the joint plegia
• Palate, jaw, tongue, larynx, neck, deglutition: ask the child
• Carry the child
to open mouth and protrude tongue
• Lateral decubitus to prevent aspiration, if weakness should
• Accumulation of secretions: bulbar palsy
set in and compromise the airway.
• Flaccid quadriplegia.
It lasts 2–4 days and recover over next 2–5 days, but the
TYPE AND SEVERITY OF THE BITE timings can be variable and effects may last for several days.
[anti-snake venom (ASV) will have no effect on already fixed
• Identifying species is not vital as the venom available is
toxin].
trivalent for krait, viper, and cobra
• Take it seriously! Small snake, second bite, severed head
are all equally dangerous
Hemorrhagic Effects
• Number of bites. The more the bites, the more the enveno • Bleeding from fang marks and injection sites.
mation • Blood filled bullae locally
• Amount of venom injected for size of patient. The snake • Bleeding gums
injects the same amount of venom and the smaller the size • Epistaxis
of the patient, the higher the dose • Gastrointestinal tract bleed
• Intracranial hemorrhage.
The 20-minute whole blood clotting time (WBCT), a simple,
Box 1: Identifying species clinically if possible
bedside, reliable method to diagnose hemorrhagic effects,
• Cobra: local signs + neurotoxic monitor ASV effectiveness, and control its adminis tration.
• Krait: no local signs + neurotoxic Also, helps hemorrhagic effects of venom from disseminated
• Viper: local signs + coagulopathy intravascular coagulopathy from sepsis.
• Sea snake: no local signs + myotoxic Put 2–5 mL blood into a dry, clean, new test tube, leave
undisturbed for 20 minutes and check for clotting by gentle
• “Every snakebite does not need anti-snake venom”
movement.
• “Every poisonous snakebite does not need anti-snake venom”
Test to be done on admission and 6 hourly.
Ch-47.indd 223 11/19/2016 3:08:08 PM

Treatment • Select the objective measure of impairment like single

breath count or length of time upward gaze can be
Supportive Therapy maintained and establish the value
• Give intramuscular (IM) neostigmine 25–50 µg/kg with
• Rapid assessment of airway, breathing, and circulation
0.05 mg/kg atropine IV every 10 minutes till the objective
• Open airway, oxygenate if needed
measure is reassessed
• Cardiopulmonary resuscitation, if needed
• Improvement should become evident after 20 minutes.
• Tetanus toxoid
Hemorrhagic: repeat 20-minute WBCT after 6 hours, if positive
• Intravenous (IV) fluids, antibiotics with anaerobic coverage
give second dose of ASV.
• Blood components readied
Support with fresh frozen plasma (FFP), platelets and
• Mechanical ventilation.
packed red blood cells as needed. Dialysis may be needed for
Specific Therapy renal failure.
It includes ASV and neostigmine. Anti-snake venom administration: Only IV, not IM/SC
Indications of ASV: • No sensitivity testing is advocated. As soon as possible,, if
• Signs of local envenomation signs of envenomation
{{ Swelling involving greater than ½ bitten limb • Not useful to prevent local tissue necrosis, so there should
{{ Rapid extension of swelling beyond joint be no local infiltration
{{ Regional lymphadenopathy • 8–10 vials dissolved in 200 mL normal saline over 1 hour.
• In absence of tourniquet Repeat in 2–6 hours. (hematotoxin requires more dosing
• Signs of systemic envenomation than neurotoxin as it is in the circulation and can be
{{ Neurotoxic signs neutralized).
{{ Hemorrhagic signs
If anaphylaxis occurs:
{{ Cardiovascular: shock, arrhythmia, electrocardiogram
• Stop immediately if pruritus, urticaria, fever, vomiting,
abnormalities diarrhea, hypotension, bronchospasm
{{ Acute renal failure
• Intramuscular adrenaline (epinephrine) (0.01 mg/kg)
{{ Hemoglobinuria, myoglobinuria
• Intravenous hydrocortisone (2 mg/kg)
{{ Polymorphonuclear leukocytosis.
• Intravenous antihistamine (avil 0.2 mg/kg)
Anti-snake venom dose: symptomatology is not useful for • Second dose of epinephrine if no improvement/
dose. The same dose applies to adults and children as it is to deterioration in 15 minutes → starts an infusion
neutralize the poison and that quantity remains the same. • Restart ASV: after complete recovery, slow infusion for
Table 1 shows the dose relationship and the rationale of using a 15 minutes, close supervision, after 15 minutes, resume
standard 8–10 + 5–10 vial dosage regimen. normal drip rate.
Mechanical ventilation: even when ASV not available,
Neurotoxic: if no response to first dose of ASV and neostigmine
mechanical ventilation is life saving.
in 2 hours, then second dose of ASV is to be used. If there is no
response to the second dose, then start/continue ventilation. Indication: respiratory paralysis, inability to handle secretions.
Local therapy, like debridement and incision drainage,
Neostigmine: it is useful for neuromuscular junction
should be done only after
blockade caused by neurotoxic snakebites. It is useful only
• ASV is given
for postsynaptic type of blockade (occurring with cobra bites)
• Do not underestimate the necrosis that can occur—the
and not for presynaptic block (krait bites cause both pre- and
need for amputation is not uncommon
postsynaptic blockade).
• Elevation of bitten part
• Aspiration of bullae, only if tense.
Debridement, dressing, grafting: avoid fasciotomy as it may
Table 1: Snakes with venom yield, lethal dose, and antivenom spread the venom again.
neutralizing dose
Snakes Venom yield Lethal dose 1 mL of antivenom Clinical Pearls
per bite (g) for man (g) neutralized (mg)
• Snakebite is like poisoning
Cobra 0.2 0.12 0.6 • Call up an expert or check the books for details
Krait 0.022 0.06 0.45 • Do not transport unstable patients
Russell’s viper 0.15 0.15 0.6 • Supportive management can save a life even without anti-
Saw-scaled viper 0.0046 0.08 0.45 snake venom, especially in neurotoxic bites.
224
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Chapter 47: Snakebite Envenomation
Algorithm 1
ABC, airway, breathing, and circulation; ASV, anti-snake venom; inj., injection; 20-min WBCT, 20-minute whole blood clotting test; IV, intravenous.
Key points
SUGGESTED READINGS
1. Bawaskar HS, Bawaskar PH. Profile of snakebite envenoming in western
))
History of snakebite and fang marks are not a must to
Maharashtra, India. Trans R Soc Trop Med Hyg. 2002;96(1):79-84.
diagnose snake envenomation (e.g., kraits and sea snakes)
2. Philip E. Snake bite and scorpion sting. In: Srivastava RN (Ed). Pediatric and
))
In areas known for krait bites, when a perfectly normal person Neonatal Emergency Care. New Delhi: Jaypee Brothers Medical Publishers;
sleeping on floor reports early morning with vomiting, 1994. pp. 227-34.
abdominal pain, and bulbar palsy, it should be diagnosed as 3. Simpson ID. The pediatric management of snakebite the national protocol. Indian
krait envenomation, unless proved otherwise Pediatr. 2007;44(3):173-6.
))
All snakebites do not need anti-snake venom (ASV). Dose 4. WHO/SEARO guidelines for the clinical management of snake bites in the Southeast
remains the same for all Asian region. Southeast Asian J Trop Med Public Health. 1999;30(Supp 1):1-85.
))
The 20-minute whole blood clotting test is simple, cheap,
reliable, and bedside tool in hands of clinician for diagnosing
coagulopathy of viper bites
))
Endotracheal intubation and mechanical ventilation are of
utmost important in saving a child with neurotoxic respiratory
paralysis in isolation and in combination with ASV
))
Do not ignore bite by small snakes, bite after eating prey, or
bite after several strikes—all such bites are capable of severe
envenomation.
225
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Chapter 48
Initial Approach to
a Comatose Child
Soonu Udani
INTRODUCTION Overzealous hyperventilation → CO2 too low → danger

of hypoperfusion and drop in cerebral perfusion.
Whatever the initiating event that results in altered sensorium, Cerebral perfusion pressure = Mean arterial pressure
it is the “secondary injury” (which results from hypoxia and
– Intracranial pressure
hypoperfusion), that has huge impact on the eventual outcome.
• Target mean arterial pressures (MAP) to 70 mmHg
The approach to a child with altered sensorium, therefore,
minimum considering a target CPP of 50 mmHg
focuses on the efforts to prevent or limit this secondary injury,
• Isotonic fluids, inotropes [maintain blood pressure (BP) =
while trying to offer specific treatment.
Rapidly evaluate the appearance, breathing, and 95th centile
circulation. Confirm the altered sensorium and proceed with • When monitoring of ICP/MAP unavailable, avoid hypo
further assessment only if the child is stable. If the child is osmolar/hyperosmolar fluids—no role of fluid restriction
unstable, “the initial management priorities are to stabilize and • High BP at presentation → effect/cause—reduce slowly
support the airway, breathing, and circulation, irrespective of after ICP ruled out
the etiology”. • Glycemic control less than 180 mg/dL.
Every patient of altered sensorium/coma should be
treated as having increased intracranial pressure (ICP) until BEWARE HYPOGLYCEMIA
proved otherwise: an unstable airway leads to hypoxia →
cerebral vasodilation → increase in cerebral blood flow → Worsening Glasgow Coma Scale despite
increase in ICP.
Open with “jawthrust” or “chin lift” method if the spine is
correction of Airway, Breathing,
deemed unaffected. and Circulation (Box 2)
Indications for intubation with full and proper sedation
and muscle relaxant with premedication with lidocaine is Box 2: Signs of raised intracranial pressure in coma
illustrated in Box 1. • Abnormal posturing
Focus on • Abnormal breathing pattern
• Oxygenation: partial pressure of oxygen (PaO2) less than 60
• Abnormal oculocephalic (doll’s eye) or oculovestibular reflex
mmHg (> 95% SpO2)
• Ventilation: partial pressure of carbon dioxide (PaCO2) → • Abnormal pupillary response
mid-30s • Cushing’s triad
Box 1: Indications for intubation Chasing the cause: the list is exhaustive; a meticulous, “obvious
• Glasgow Coma Scale ≤12 or AVPU [A (alert) V (responds to voice) causes” can be remembered by the “mnemonic COMA”:
P (responds to pain) U (unresponsive)] C: Convulsions (status epilepticus)
• Features of herniation O; O2 depriving events—resuscitation following episodes like
• Abnormal respiration drowning, electrocution, foreign body
M: Major illnesses, e.g., diabetes, hypertension (secondary),
• Asymmetric or dilated pupils
viral hepatitis, etc.
• Inability to handle secretions (absent gag, gurgling sounds) A: Accidents (trauma).
Ch-48.indd 226 11/19/2016 3:10:17 PM

Chapter 48: Initial Approach to a Comatose Child
Table 1: Quick guide to causes of coma Algorithm 1
Febrile Afebrile Simplified approach to Coma
Bacterial meningitis Well child: poisoning

Tuberculous meningitis Metabolic
Herpes meningoencephalitis Child abuse
Malaria Sick child: tumor
Dengue Hypertension
Immune mediated (ADEM) Diabetic ketoacidosis
Onset in hours—drugs, poisoning –
Onset in days—CNS infections –
Onset in weeks—tumor, DKA, HTN –
ADEM, acute disseminated encephalomyelitis; DKA, diabetic ketoacidosis; CNS,
central nervous system; HTN, hypertension.
When the cause is not very clear, consider the following

(Table 1):
INVESTIGATIONS
• Complete blood count, peripheral smear for malarial
parasites (MP), cultures, blood sugar, blood urea nitrogen,
electrolytes, liver function test, ammonia, lactate, arterial
blood gas: keep extra samples for further tests
• Prioritize as per working diagnosis
• Imaging: if signs of raised ICP, no lumbar puncture—
magnetic resonance imaging preferable. If not, computed
tomography to check edema and impending herniation.
PaCO2, partial carbon dioxide pressure: BP, bllod pressure; GCS, glasgow
coma scale; AVPU, alert, voice, pain, unresponsive; ICP, intracranial pressure;
Immediate Treatment NCS, nonconvulsive seizures; LP, lumbar puncture; CT, computed tomography;
MRI, magnetic resonance
• Treatment for raised ICP: mannitol 1.25–2 mL/kg. Hypertonic
saline to osmolarity of 310–360 mmol/L. Controlled
ventilation and supportive nursing management. Key points
• Specific treatment, if cause is known
• More broad based treatment covering meningitis, herpes, ))
Neuroprotective strategies should be employed from the
malaria, and other treatable infections, if cause is not time of first contact
known or till results are available. ))
Supportive care is as important as specific treatment
))
Repeated assessment is important
Clinical Pearls ))
Prevention and rapid treatment of aggravating causes
))
Institute early rapid empirical treatment of probable causes
• Every patient of altered sensorium/coma should be treated ))
Eye on good outcome, not only on survival.
as having increased intracranial pressure (ICP) until proved
otherwise
• Raised ICP should be presumed until proven otherwise SUGGESTED READINGs
• Overzealous hyperventilation → CO2 too low → danger of
hypoperfusion and drop in cerebral perfusion 1. Kirkham FJ. Non-traumatic coma in children. Arch Dis Child. 2001;85(4):303-12.
• Hypertonic saline replaces mannitol as the osmolar agent of 2. Udani S. Advances in neurocritical care. Indian J Pediatr. 2015;82(3):272-6.
choice 3. Udani S. The comatose child. In: Udani S, Chugh K, Ugra D, Khilnani P (Eds). IAP
• No role of fluid restriction. Specialty Series Textbook on Pediatric Intensive Care, 2nd edition. New Delhi:
Jaypee Brothers Medical Publishers (P) Ltd;2013. pp. 341-451.
227
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Chapter 49
Fever without Focus in Infants
Less than 3 Months of Age
Balasubramanian Sundaram
INTRODUCTION EPIDEMIOLOGY
The differential diagnosis involving fever in neonates and Risk of SBI varies with age. Risk is greatest during the immediate
young infants 29–60 days of age includes both infectious and neonatal period and through the first month (and is heightened
non-infectious causes. Although self-limited viral infections in the infant born prematurely). Even among neonates, only
are the most common cause of fever, the incidence of serious 7% of those who have fever without focus have an SBI.
bacterial infections (SBIs) may be higher in this population
compared to older children; neonates have been shown to
LABORATORY DIAGNOSIS
be at particularly high risk. SBIs include bacteremia (e.g.,
sepsis), cellulitis, osteomyelitis, septic arthritis, meningitis, Various diagnostic tests to quantify the risk of bacteremia
pneumonia, and urinary tract infection (UTI). and its complications have been assessed including the white
Among these, UTI is the most common type of SBI. Among blood cells count and differential, microscopic examination of
bacterial pathogens causing SBI in infants less than 90 days buffy coat of blood, erythrocyte sedimentation rate, C-reactive
of age, Gram-negative bacteria such as E. coli and Klebsiella protein, procalcitonin serum levels, morphologic changes
are most frequently identified. Other common pathogens in peripheral blood neutrophils, and quantitative cultures of
are Streptococcus pneumoniae, Haemophilus influenzae, blood. In addition, clinical scales have been developed to help
Neisseria meningitidis, S. aureus and less commonly Group B identify the febrile child with a serious illness.
streptococcus and Listeria monocytogenes. Neonatal herpes The outcome of primary concern is not occult bacteremia
simplex virus (HSV) is an important consideration in infants but meningitis. An ideal diagnostic test would specifically
0–28 days of age. Neonates with cutaneous vesicles, seizures, identify febrile children at risk of a serious complication,
and/or elevated transaminases present a high index of because many focal infections after bacteremia (e.g., most
suspicion for HSV infection; however, it is rare for a neonate cases of either pneumonia or cellulitis) can be treated when
with HSV to present with fever of uncertain source (FUS). they become apparent and are not usually associated with
Because the clinical examination alone is unable to serious sequelae. Unfortunately, there is no such test. Lowering
reliably predict serious illness in infants less than 60 days of the risk of serious complications by preventing infections
age with FUS and culture results are not immediately available, through use of conjugate vaccines has proven to be the most
clinicians must often approach management of patients effective strategy.
with fever by relying on a combination of history, physical
examination findings, and diagnostic screening tests.
MANAGEMENT
There is general agreement that febrile children who are
DEFINITION “very young” (variably considered to be younger than 3, 2, or
The term fever without focus or fever without localizing Signs 1 month of age) should be managed differently from the way
or FUS is defined as an acute febrile illness in which the in which older children are managed (Algorithm 1). Some
etiology of the fever is not apparent after a thorough history clinicians adhere to a protocol of treating all young infants
and physical examination. A rectal temperature higher than with fever and no apparent focus of infection with broad-
38ºC (100.4ºF) has been defined as fever in literature. spectrum antimicrobial agents administered intravenously
Ch-49.indd 228 11/24/2016 12:46:59 PM

Chapter 49: Fever without Focus in Infants Less than 3 Months of Age
in the hospital until the results of cultures of the blood, urine generally sufficient for initial empiric therapy in most infants
and cerebrospinal fluid (CSF) are known. Although sometimes with community acquired infection.
perceived as the “safe” approach, such management
incurs considerable financial cost and risk of iatrogenic PITFALLS AND PEARLS IN
complications and of diagnostic misadventures associated
with hospitalization.
ASSESSMENT AND DIAGNOSIS
These risks include errors in the type and dosage of drugs, 1. Parental report of fever via palpation is unreliable as a sole
complications of venous cannulation (such as phlebitis and method of determining fever.
sloughing of the skin), and nosocomial infections. many experts 2. Practice guidelines recommend that if a neonate has had
believe that febrile infants from 2 to 3 months of age with no a fever recorded at home by a reliable parent, the patient
apparent focus of infection who appear well and/or who have should be treated as a febrile neonate.
a laboratory-documented viral infection can be managed 3. If excessive clothing and blankets encasing the infant
without either additional laboratory tests or hospitalization, are suspected of falsely elevating the body temperature,
provided that careful follow-up is ensured. then the excessive coverings should be removed and the
If an antimicrobial agent is to be administered, cultures of temperature retaken in 15–30 minutes. If body temperature
the blood, urine and CSF should be obtained first. Rapid tests is normal after the covers are removed, then the infant is
for specific viral pathogens, which now are widely available, considered afebrile.
may aid decisions about managing patients and may reduce 4. A response to antipyretic medication does not change the
the need for and/or the duration of hospitalization. likelihood of an infant having an SBI.
Febrile infants at low risk of SBI for whom adequate 5. Clinical assessment include a thorough history and
home observation and follow-up cannot be ensured should physical examination (include questions about recent
be hospitalized and can be observed without antimicrobial symptoms, vaccinations, exposure to sick contacts, and the
treatment. Doing so (if the child appears well) is reasonable child’s birth history in the patient history).
and avoids the adverse side effects of antimicrobial agents 6. The large majority of children with fever without localizing
and intravenous cannulation, shortens the duration of signs in the 1–3 months age group likely have a viral
hospitalization, and saves money without placing the child at syndrome.
significant risk of complications. 7. Ill-appearing (toxic) febrile infants less than or equal
Most febrile infants with no apparent focus of infection to 3 months of age require prompt hospitalization and
who are younger than 1 month should be hospitalized and immediate parenteral antimicrobial therapy after cultures
treated with antimicrobial therapy. The choice of antibiotic of blood, urine, and CSF are obtained. It is recommended
would depend on local epidemiological data and antibiotic that the following laboratory studies be performed in
susceptibility patterns in the area of practice. A third neonates with FUS, complete blood count, differential,
generation cephalosporin with an aminoglycoside would be blood culture urinalysis and urine culture. cerebrospinal
fluid studies:
i. Tube 1: protein and glucose
Algorithm 1 ii. Tube 2: culture, sensitivity, Gram stain
Management algorithm
iii. Tube 3: cell count and differential
iv. Tube 4: hold for additional studies. Stool culture if
diarrhea is present.
8. Well-appearing infants 1–3 months of age can be managed
safely using low-risk laboratory and clinical criteria if
reliable parents are involved and close follow-up is assured
(Table 1).
9. Among SBIs, pyelonephritis is the most common and
may be seen in well-appearing infants who have fever
without a focus or in those who appear ill. Urinalysis
may be negative in infants less than 2 months of age with
pyelonephritis.
10. Analysis of CSF for HSV using polymerase chain reaction
(PCR) may be considered in neonates with CSF pleocytosis
and a negative Gram stain.
11. Delaying or omitting a lumbar puncture for CSF analyses
may be considered in young infants 29–60 days of age
OPD, outpatient department; CBC, complete blood count; CRP, c-reactive with FUS who meet all applicable low-risk clinical and
protein; IV, intravenous; LP, lumbar puncture; WBC, white blood cell. laboratory criteria (Box 1).
229
Ch-49.indd 229 11/24/2016 12:47:00 PM

Box 1: Low-risk criteria for infants with fever 1–3 months of Key points
age
Low-risk clinical criteria • Complete blood count
))
Although controversy remains as how to best manage
acutely febrile infants and children, there are several areas of
• Well-appearing {{ WBC 5,000 to 15,000/mm3 near consensus
• Previously healthy {{ ≤1,500 band cells/mm3 ))
Infants aged less than or equal to 60 days continue to have
• No focal source of infection • Chest radiograph (if obtained) the highest rates of serious bacterial infections (SBIs) and
Low-risk laboratory criteria {{ No evidence of discrete pose a challenge to practitioners attempting to determine
infiltrate how extensive an evaluation to perform in a non-toxic
• Urinalysis appearing child
• Stool smear (when diarrhea is
{{ ≤10 WBC/hpf ))
Urinary tract infections (UTIs) are the most common SBIs in
present)
{{ No bacteria on Gram’s all age groups
{{ Negative for blood
stain ))
Assessment for UTI should be part of any evaluation for all but
{{ ≤5 WBC/hpf
the lowest-risk patients (i.e., circumcised boys)
WBC, white blood cell
))
New technologies can more rapidly diagnose common viral
and bacterial infections and recommendations to simplify the
management of these febrile infants and children are needed.
12. If antimicrobial therapy will be initiated in infants who
meet low-risk criteria, CSF specimens need to be collected
prior to treatment. SUGGESTED READINGs
13. A chest X-ray may be performed in neonates and young
1. Huppler AR, Eickhoff JC, Wald ER. Performance of low-risk criteria in the
infants 29–60 days of age who manifest one or more of
evaluation of young infants with fever: review of the literature. Pediatrics.
the following clinical findings: tachypnea more than 2010;125(2):228-33.
60 breaths/min, crackles in the chest, retractions, nasal 2. Jhaveri R, Byington CL, Klein JO, Shapiro ED. Management of the non-toxic-
flaring, cyanosis or oxygen saturation less than 95%. appearing acutely febrile child: a 21st century approach. The Journal of
14. In patients who are not responding to antimicrobial therapy, Pediatrics, 2011;159(2):181-5.
the clinician should consider additional evaluation and 3. Kramer, Michael S, Steven G. Rothrock, Andy Jagoda.“The young febrile child:
evidence-based diagnostic and therapeutic strategies” An Evidence-Based
treatment options, including: alternative antimicrobial
Approach to Infectious Disease.(2015.
therapy for resistant organisms (in neonates only) CSF HSV 4. Olaciregui I, Hernández U, Muñoz JA, Emparanza JI, Landa JJ. Markers that
PCR (if not completed previously) and empiric treatment predict serious bacterial infection in infants under 3 months of age presenting
with acyclovir. with fever of unknown origin. Arch Dis Child. 2009;94(7):501-5.
230
Ch-49.indd 230 11/24/2016 12:47:00 PM

Chapter 50
Acute Viral Encephalitis
Jaydeep Choudhury
Introduction a focal seizure or paralysis of any part of body is encephalitis.

Presence of rash on body excludes Japanese encephalitis.
Acute viral encephalitis is an important cause of mortality and AES with symmetrical signs and fever is likely to be cerebral
morbidity in children. Most of the times acute viral encephalitis malaria.
is a clinical diagnosis and laboratory confirmation is not A suspected case that meets the clinical case definition
possible due to lack of availability of diagnostic testing for most for AES may be classified in one of the following four ways as
of the agents. A period of up to 14 days is considered to define shown in algorithm 1.
“acute”. Acute encephalitis syndrome (AES) including Japanese • Laboratory-confirmed JE: a suspected case that has been
B encephalitis (JE) is a group of clinically similar neurologic laboratory-confirmed as JE
manifestation caused by several different viruses, bacteria, • Probable JE: a suspected case that occurs in close
fungus, parasites, spirochetes, chemical/toxins, etc. There is geographic and temporal relationship to laboratory-
seasonal and geographical variation in the causative organism. confirmed case of JE, in the context of an outbreak
It may be sporadic like herpes simplex encephalitis (HSE) or • Acute encephalitis syndrome (due to agent other than JE):
epidemic such as JE. The outbreak of JE usually coincides with a suspected case in which diagnostic testing is performed
the monsoon and post-monsoon period when the density of and an etiological agent other than JE virus is identified
mosquitoes increases while encephalitis due to other viruses • Acute encephalitis syndrome (due to unknown agent): a
especially enteroviruses occurs throughout the year as it is suspected case in which no diagnostic testing is performed
water borne disease. For surveillance purposes, all the acute or in which testing was performed but no etiological
encephalitis cases to be reported under the heading of acute agent was identified or in which the test results were
encephalitis. indeterminate.
The case fatality rate of AES is very high and those who
survive may suffer with various neurological sequelae.
Children are at risk of highest attack rates because of lack of CLINICAL MANIFESTATIONS
cumulative immunity due to natural infection. Encephalitis, A case of viral encephalitis including JE presents with a
usually caused by a virus, cannot be treated with antibiotics. prodrome of fever, headache, nausea, diarrhea, vomiting,
A good clinical management is important to reduce the risk of and myalgia lasting for 1–5 days. It is followed by irritability,
disability or death from the disease. altered behavior, convulsions, and coma. The progression of
Clinically, a case of AES is defined as a person of any age, disease is rapid. Features of raised intracranial tension are
at any time of year with the acute onset of fever and a change commonly present in acute stage of illness. The patient may
in mental status (including symptoms such as confusion, develop difficulty of speech and other neurological deficits
disorientation, come, or inability to talk) and/or new onset like ocular palsies, hemiplegia, quadriplegia and may have
of seizures (excluding simple febrile seizures). Other early extrapyramidal signs in the form of dystonia, choreoathetosis,
clinical findings may include an increase in irritability, and coarse tremors.
somnolence or abnormal behavior greater than that seen All the cases of AES should be reported as they have
with usual febrile illness. similar clinical manifestations. Their case management
It is important to note that in an epidemic situation fever usually follows a common protocol along with situation
with altered sensorium persisting for more than 2 hours with specific treatment.
Ch-50.indd 231 11/19/2016 3:15:18 PM

Algorithm 1
Causes of acute encephalitis syndrome
VEE, venezuelan equine encephalitis; JE, japanese B encephalitis; WNE, west nile encephalitis; TBM, tuberculous meningitis; RNA, ribonucleic acid.
MANAGEMENT • Temperature: fever and hypothermia should be treated

• Ongoing seizures: benzodiazepine, followed by phenytoin
Acute encephalitis syndrome is a medical emergency and it loading if required.
requires immediate consideration of vital functions including
life support, identification of cause and institution of specific
therapy if available. Management of AES including Japanese
Step II: Clinical Evaluation:
encephalitis is essentially symptomatic. To reduce severe History and Examination
morbidity and mortality, it is important to identify early The following are the important aspects in history and
warning signs and refer patients to health facility. examination. The approach to a suspected case of AES is
The step-wise management of AES is as follows. shown in algorithm 2.
• Fever, headache, vomiting, seizures, abnormal posturing
Step I: Rapid Assessment and Stabilization • Altered behavior, cognition, personality changes, altered
• Establish and maintain airway: The child has to be intubated consciousness
if glasgow coma scale (GCS) less than 8, there is impaired • Prodromal symptoms, flu-like illness, diarrhea
airway reflexes, abnormal respiratory pattern, signs of • Rash, vesicles, past history of chicken pox
raised intracranial pressure (ICP), oxygen saturation less • Residence: rural/urban, endemic for cerebral malaria, any
than 92% despite high flow oxygen and fluid refractory epidemic of AES in neighborhood
shock • History of animal contact, insect bite, dog bite
• Ventilation, adequate oxygenation • Drug or toxin exposure
• Circulation: intravenous (IV) access has to be established, • Recent history of travel
samples to be collected for investigation (complete blood • History of trauma
count, blood sugar, liver function test, renal function test, • Personal or family history of seizure disorder
electrolytes, blood gas, lactate, peripheral smear and rapid • Recent immunizations
diagnostic test for malarial parasite, serology for viruses). • History of recurrent episodes of encephalopathy: These are
Fluid bolus to be given if in circulatory failure (20 mL/kg characteristic of some inborn errors of metabolism (urea
0.9% NaCl), inotropes if required cycle defects, organic acidemias, and fatty acid oxidation
• Signs of cerebral herniation or raised ICP should be defects). It may also be present in migraine, epilepsy and
232 identified substance abuse
Ch-50.indd 232 11/19/2016 3:15:18 PM

Chapter 50: Acute Viral Encephalitis
Algorithm 2
Approach to a child with acute encephalitis syndrome
CSE, cerebrospinal fluid; IgM, immunoglobulin M; JE, Japanese B encephalitis; AES, acute encephalitis syndrome.
• Other concurrent systemic illness, e.g., jaundice (hepatic Neuroimaging is not needed if the etiology is clear by
failure), pneumonia (hypoxic encephalopathy), diarrhea other investigations, e.g., cerebral malaria, pyogenic
(dyselectrolytemia), dysentery (shigella encephalopathy) meningitis. Suggestive MRI findings are present in some
• Past medical illness: diabetes, congenital heart disease, conditions of viral encephalitis such as HSE, JE, and
chronic kidney or liver disease enterovirus encephalitis
• Family history of previous infant/child deaths • Throat swab, nasopharyngeal swab.
• Pre-morbid developmental/neurological status of the child
• Risk factors for immunodeficiency: HIV risk factors, cancer Step IV: Empirical Treatment
treatment and steroid/immunosuppressant treatment. Empirical treatment must be started, pending the results of
investigations.
Step III: Investigation/ • Ceftriaxone: a broad spectrum antibiotic, such as
Samples to Be Collected ceftriaxone must be given, which can be stopped if there is
no evidence of bacterial meningitis
• Cerebrospinal fluid (CSF): in hemodynamically stable • Acyclovir (should be started in all suspected sporadic
patients without any features of raised intracranial pressure, viral encephalitis). Dose of acyclovir 3 months to 12 years
lumbar puncture should be performed. Cerebrospinal is 500 mg/m2 8 hourly. In children above 12 years
fluid should be examined for cytology, biochemistry, Gram 10 mg/kg 8 hourly. Duration of treatment in confirmed
stain, Ziehl–Neelsen stain for acid fast bacilli, bacterial cases should be 14–21 days intravenous treatment and
culture, latex agglutination, polymerase chain reaction minimum 21 days for those aged 3 months to 12 years
for herpes simplex virus 1 and 2, and immunoglobulin • Artemether combination therapy: in cerebral malaria.
M antibodies for JE and for dengue virus depending on
clinical suspicion. Usual CSF findings in viral encephalitis Step V: Supportive Care and Treatment
include lymphocytic pleocytosis, mild to moderately
• Euglycemia should be maintained, fever should be
elevated protein, and normal CSF sugar. Similar findings
controlled and hydration maintained
may occur in tubercular meningitis and partially treated
• Raised ICP to be treated with mild head-end elevation
pyogenic meningitis; however, the CSF sugar is likely to be
by 15–30°. Mannitol 20% IV 5 mL/kg over 30 min as first
low in these situations
dose then 2.5 mL/kg at 6 hourly intervals up to 48 hours.
• Blood/serum, urine: complete blood count including
Injection furosemide IV 1 mg/kg up to 40 mg can be given
platelet count, blood glucose, serum electrolytes, liver and
• Seizures: anticonvulsant to be given if history of seizures or
kidney function tests, blood culture, arterial blood gas and
if GCS less than 8, or child has features of raised ICP
lactate. Peripheral smear for malarial parasite and rapid
• Steroids: pulse steroids (methylprednisolone or dexa
diagnostic test for malaria should be obtained. Chest X-ray
methasone) to be given in children with suspected acute
should also be obtained
disseminated encephalomyelitis.
• Neuroimaging: magnetic resonance imaging (MRI) or
computed tomography scan may give valuable information
Step VI: Prevention/Treatment of Complications
such as presence of bleed, cerebral edema, temporal
lobe hypodensities in HSE, thalamic abnormalities in and Rehabilitation
JE, and basal exudates and hydrocephalus in tubercular • Physiotherapy, posture change, prevention of bed sores,
meningitis. Computed tomography may also show brain and exposure keratitis
herniation, effacement of cisterns, infective collections • Complications like aspiration pneumonia, nosocomial
such as brain abscesses and subdural empyema. infections, and coagulation defects to be treated accordingly 233
Ch-50.indd 233 11/19/2016 3:15:19 PM

• Nutrition: early feeding should be initiated SUGGESTED READINGs

• Psychological support to patient and family.
1. Guidelines: Clinical Management of Acute Encephalitis Syndrome including
Japanese Encephalitis. Government of India. Directorate of National Vector Borne
PREVENTION OF Disease Control Programme. Directorate General of Health Services, Ministry of
acute encephalitis syndrome Health & Family Welfare, 2009.
2. Japanese Encephalitis Clinical Care Guidelines. PATH, November, 2006.
Prevention and/or control of AES require a multipronged
[online] Available from: www.path.org/vaccineresources/filesJE_clinical_care_
strategy. It consists of: guidelines_PATH. pdf. [Accessed November, 2013].
• Surveillance for cases of AES 3. John TJ. Outbreak of killer brain disease in children: mystery or missed diagnosis?
• Vector control Indian Pediatr. 2003;40:863-9.
• Reduction in man-vector contact 4. Kneen R, Michael BD, Menson E, Mehta B, Easton A, Hemingway C, et al.
• Vaccination. Management of suspected viral encephalitis in children—Association of British
Neurologists and British Pediatric Allergy Immunology and Infection Group
National Guidelines. J Infect. 2012;64:449-77.
Key points
5. Kumar R, Tripathi P, Singh S, Bannerji G. Clinical features in children hospitalized
))
Acute encephalitis syndrome (AES) may be due to different during the 2005 epidemic of Japanese encephalitis in Uttar Pradesh, India. Clin
viruses including Japanese B encephalitis, bacteria, fungus, Infect Dis. 2006;43:123-31.
parasites, spirochetes, chemical/toxins, etc. 6. Ministry of Health and Family Welfare, Government of India. Facility-based IMNCI
(F-IMNCI) Participants Manual. Government of India, New Delhi, 2009. [online]
))
Clinically acute onset of fever (period of up to 14 days is
Available from: www.unicef.org/india/FBC_Participants_Manual.pdf. [Accessed
considered acute)and a change in mental status and/or new November, 2013].
onset of seizure
7. Sharma S, Mishra D, Aneja S, Kumar R, Jain A, Vashishtha VM. Consensus
))
Case fatality is high and survivors often have neurologic Guidelines on Evaluation and management of Suspected Acute Viral Encephalitis
sequelae in Children in India. Indian Pediatr. 2012;49:897-910.
))
Acute encephalitis syndrome is a medical emergency, requires 8. World Health Oraganization. Acute Encephalitis Syndrome. Japanese encephalitis
immediate consideration of vital functions, identification of surveillance standards. January 2006. From WHO-recommended standards for
cause, and institution of specific therapy, if available surveillance of selected vaccine-preventable diseases. WHO/V&B/03.01. [online]
))
All AES cases should be reported. Available from: http://www.who.int/vaccines-documents/DocsPDF06/843.pdf.
[Accessed November, 2013].
234
Ch-50.indd 234 11/19/2016 3:15:19 PM

Chapter 51
Acute Osteomyelitis
Baldev S Prajapati, Rajal B Prajapati
INTRODUCTION
Acute osteomyelitis in children is an important condition
because of its potential to cause permanent disability. It
is common in infants and toddlers than in older children.
Early recognition of acute osteomyelitis in young patients
before extensive infection develops and prompt institution of
appropriate medical and surgical therapy minimize permanent
damage. Acute osteomyelitis in neonates and infants is
commonly associated with septic arthritis due to peculiar
vascularity of the physis and epiphysis. The risk is greatest if the
physis (the growth plate of bone) is damaged. Once the growth
plate forms, it acts as a barrier and in toddlers and children the
infection is usually confined to the metaphysis.
Fig. 1: Anatomy and circulation of the ends of long bones—the hair-
PATHOGENESIS pin bend (sharp loop) of the blood vessels resulting in sluggish blood
flow and stasis of bacteria
The unique anatomy and circulation of the ends of long bones
result in the predilection for localization of blood borne
bacteria. In the metaphysis, nutrient arteries branch into
non-anastomosing capillaries under the physis, which make
a sharp loop before entering venous sinusoids draining into
the marrow (Fig. 1). Blood flow in this area is sluggish and
provides an ideal environment for bacteria seeding. Once a
bacterial focus is established, phagocytes migrate to the site
and produce inflammatory exudates (metaphyseal abscess).
The generation of proteolytic enzymes, toxic oxygen radicals,
and cytokines result in decreased oxygen tension, decreased
pH, osteolysis, and tissue destruction. As the inflammatory
exudate progresses, pressure increases spread through the
porous metaphyseal space via the Haversian system and
Volkmann canals into the subperiosteal space. Purulence
beneath the periosteum may lift the periosteal membrane of Fig. 2: In the new born and young infant, transphyseal blood vessels
the bony surface, further impairing blood supply to the cortex connect the metaphysic and epiphysis resulting in osteomyelitis with
septic arthritis.
and metaphysis.
In the newborns and young infants, transphyseal blood
vessels connect the metaphysis and epiphysis (Fig. 2). So it space. This extension through the physis (growth plate) has
is common for pus from the metaphysis to enter the joint the potential to result in abnormal growth and bone or joint
Ch-51.indd 235 11/19/2016 3:43:40 PM

deformity. During the later part of infancy, the physis forms, Table 1: Shows organisms causing acute osteomyelitis and
obliterating the transphyseal blood vessels. Joint involvement their association with different conditions
once the physis forms may occur in joint where the metaphysis
Common clinical association Microorganism
is intraarticular (hip, ankle, shoulder, and elbow) and
subperiosteal pus ruptures into the joint space. Frequent microorganism in Staphylococcus aureus (MSSA or
any type of osteomyelitis MRSA)
In the later childhood, the periosteum becomes more
adherent, favoring pus to decompress through the periosteum. Sickle cell disease Salmonella species, S. aureus and
Once the growth plate closes in the late adolescence, S. pneumoniae
hematogenous osteomyelitis more often begins in diaphysis Foreign body associated CONS (coagulase negative
and can spread to the entire intramedullary canal. With trivial infections (catheters) Staphylococcus)
trauma, the hematoma which forms in the metaphysis acts as a Nosocomial infections Enterobacteriaceae, Pseudomonas,
perfect soil for bacteria to seed. Canadida
HIV Bartonella
ETIOLOGY Immunocompromised Aspergillus species, Candida
albicans, Mycobacteria species
Bacteria are the most common pathogens in acute osteo
myelitis. Staphylococcus aureus is the most common infecting HIV, human immunodeficiency virus; MRSA, methicillin resistant staphylococcus
aureus; MSSA, methicillin sensitive staphylococcus aureus.
organism in all age groups, including new borns. Escherichia
coli, Klebsiella, and Group B streptococci are also prominent
pathogens in neonates. Group A streptococci constitutes less Box 1: Common clinical manifestations
than 10% of all cases. After the age of 6 years, most cases of • Abrupt onset of high grade fever. Fever only in 50% of neonates
acute osteomyelitis are caused by S. aureus, streptococcus or • Signs of toxemia, irritability more common in neonates
Pseudomonas aeruginosa. Salmonella species and S. aureus are
• Pain with movement of affected extremity
the two most common causes of osteomyelitis in children with
sickle cell anemia. Pneumococcus may also cause osteomyelitis • Restriction of movement—pseudoparalysis
in children with sickle cell anemia. • Limp or refusal to walk
Infection with atypical mycobacteria, S. aureus or • Limb held in flexion of adjacent joints
Pseudomonas can occur after penetrating injuries. Fungal • Local edema, erythema, tenderness, cellulitis
infection usually occurs as part of multisystem disseminated
disease. Candida osteomyelitis sometimes complicates • Limp or refusal to walk in older children with involvement
fungemia in neonates with indwelling vascular catheters. of lower extremities
Overcrowded neonatal nursery, poor aseptic precautions • Affected limb held in position of flexion of adjacent joints
while insertion of indwelling catheters and other procedures • Local edema, erythema and tenderness
and their poor maintenance are common factors responsible • Focal tenderness over a long bone
for hematogenous spread acute osteomyelitis in neonates and • Local swelling and redness indicate infection has spread
young infants. It is very common scenario at our set up that out of the metaphysis into the subperiosteal space. It
a neonate presents with acute osteomyelitis after few days of represents secondary soft tissue inflammatory response
discharge from nursery. Nosocomial infections are also very (cellulitis)
common in this group. • Long bones are commonly involved in acute osteomyelitis.
Community acquired Methicillin-resistant Staphylo Femur (27%), tibia (22%), and humerus (12%) are common
coccus aureus (MRSA) is also emerging as a potent cause of bones involved in osteomyelitis. The femur and tibia
acute osteomyelitis in children in many parts of the world, together constitute almost half of the cases. Flat bones are
including India. less commonly affected
Acute osteomyelitis following skin infection like pyoderma • Single site of bone or joint involvement is common. The
or pneumonia is also known in our patients (Table 1). exception is osteomyelitis in neonates, in whom two or
more bones are affected in almost half of the cases
• Subacute symptoms and focal findings in metaphyseal
CLINICAL MANIFESTATIONS
area over tibia may be due to a Brodie abscess.
The signs and symptoms of acute osteomyelitis are highly
dependent on the age of the patient (Box 1).
LABORATORY INVESTIGATIONS (box 2)
• Abrupt onset of high grade fever. Fever is present in only
50% of neonates • No specific laboratory tests for osteomyelitis
• Signs of toxemia and irritability, like generalized • Complete blood count (CBC), erythrocyte sedimentation
manifestations, are more common in neonates rate (ESR), and C-reactive protein (CRP) are sensitive for
• Pain with movement of the affected extremity. Pseudo bone infections but are non-specific and cannot distinguish
paralysis (restriction of movement) is very common in between skeletal infections and other inflammatory
236 neonates and young infants due to pain conditions. Leukocytosis with increased polymorphs is
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Chapter 51: Acute Osteomyelitis
Box 2: Laboratory investigations Computed Tomography Scan

• No specific laboratory tests • CT can demonstrate osseous and soft tissue abnormalities
• Leukocytosis with raised polymorphs and is ideal for detecting gas in soft tissues
• Significantly raised erythrocyte sedimentation rate and • Can depict abnormal calcification, ossification and intra-
C-reactive protein cortical abnormalities
• Blood culture • Most useful in the evaluation of spinal vertebral lesions,
• Aspiration for Gram stain and culture pelvis, sternum, etc.
very common. Acute phase reactants, like ESR, and CRP Magnetic Resonance Imaging
are significantly raised • Best radiographic imaging technique for identification of
• Blood culture should be routine in all cases of suspected abscess and differentiation between bone and soft tissue
osteomyelitis. It may be positive in 50% of cases with infection
hemaotgenous osteomyelitis • Effective in early detection and surgical localization of
• Aspiration for Gram stain and culture is the definitive osteomyelitis
diagnostic technique. • Sensitivity ranges from 90% to 100%.
RADIO IMAGING STUDIES (box 3) Radionuclide Bone Scanning

Radio imaging studies play a crucial role in evaluation of • Useful when osteomyelitis is suspected but difficult to
osteomyelitis. Conventional radiographs, ultrasonography, ascertain clinically
computed tomography, magnetic resonance imaging and • Can detect osteomyelitis within 24–48 hours after onset of
radionuclide studies may all contribute to establishing symptoms
the diagnosis. Plain radiographs are often used for initial • Three phase imaging with 99 m Tc has 85–100% sensitivity
evaluation to exclude other causes such as trauma and foreign and 75–95% specificity in hematogenous osteomyelitis
bodies. Magnetic resonance imaging has emerged as a very • Sensitivity in neonates is much lower due to poor bone
sensitive and specific test and is widely used for diagnosis. The mineralization.
sequence of radionuclide studies or MRI is often determined Radio nuclide bone scanning is useful when osteomyelitis
by age, site and clinical presentation. is suspected but difficult to ascertain clinically, can detect in
24–48 hours, less sensitive in neonates.
Plain Radiographs
• Overlying soft tissue edema after 3–5 days infection may be DIFFERENT DIAGNOSIS
suggesting osteomyelitis • Trauma
• Lytic bone changes are evident on radiographs after 7–14 • Leukemia
days of onset of infection in tubular long bones. Flat and
• Sickle cell disease
irregular bones can take longer time. Lytic bone changes
• Hemophilia
are not visible on radiographs until 30–50% of bony matrix
• Collagen disorders
is destroyed.
• Neuroblastoma
Ultrasonography
TREATMENT
• Simple and inexpensive
• Very sensitive, can diagnose subtle signs like subperiosteal The treatment of osteomyelitis comprised of:
edema soft tissue swelling within 2–3 days of infection • Antibiotic therapy
• USG guided aspiration can be attempted to determine • Surgical therapy
presence of infection. Aspiration has found positive results • Physiotherapy.
in 70–80% of cases.
Antibiotic Therapy (Box 4)
Box 3: Radio imaging studies The primary treatment for osteomyelitis is parenteral anti
• Plain radiograph shows lytic bone changes after 7–14 days of biotics that penetrate bone and joint covities and most effective
onset of infection. It is very late. Do not wait for radiographical to the likely organisms.
changes for diagnosis • Neonates:
• Ultrasonography (USG)—simple and inexpensive. Very sensitive. {{ Cefotaxime 200 mg/kg/day divided in three doses
USG guided aspiration has found positive in 70–80% of cases Intravenous (IV) + Injection cloxacillin 150–200 mg/
• Magnetic resonance imaging is best radiographic imaging, kg/day divided in four doses IV
effective in early detection and surgical localization, sensitivity {{ If MRSA is considered as likely organism → inj.
90–100%
vancomycin is substituted for cloxacillin 237
Ch-51.indd 237 11/19/2016 3:43:40 PM

Box 4: Antibiotic therapy

• Sequential antibiotics therapy:
{{ Intravenous antibiotics duration varies from 10 days
Neonates to 3 weeks. Appropriate antibiotic respond includes
• Inj. cefotaxime 200 mg/kg/day divided in three doses IV + inj. clinical and laboratory improvement. A decreasing
cloxacillin 150–200 mg/kg/day divided in four doses IV CRP and white blood cell count with absence of local
• If MRSA suspected → inj. vancomycin is substituted for inj. signs and symptoms should initiate to oral antibiotics.
cloxacillin • Duration of antibiotic therapy:
• If preterm or central vascular catheter → consider antibiotics to {{ For S. aureus or Gram-negative bacillary infections, the
cover CONS, pseudomonas and fungi minimal duration of antibiotics is 28 days, but 6 weeks
Older infants and children therapy is desirable.
• Injection cefazolin 100–150 mg/kg/day divided in three doses IV {{ For Group A streptococcus and S. pneumoniae or Hib,
or inj. cloxacillin 150–200 mg/kg/day in four divided doses IV the minimal duration is 14 days.
• If MRSA suspected → vancomycin is substituted by cloxacillin
• Injection cefotaxime or inj. ceftriaxone for Hib and other Surgical Therapy
organisms Indications for surgical therapy should be defined (Box 5).
Sickle cell • Interventions:
• Injection cefotaxime or inj. ceftriaxone or inj. clindamycin {{ Drainage of subperiosteal abscess
• Immunocompromised children: {{ Decompression of intra-medullary cavity
• Injection vanocmycin + inj. ceftizidime or Inj. piperacillin – • Complete removal of all necrotic tissues
tazobactam + Inj. amikacin • Splint application to prevent muscle spasm and patho
• Intravenous antibiotics 2–3 weeks → oral antibiotics. Total logical fractures.
duration 4–6 weeks
Inj., injection; MRSA, methicillin-resistant staphylococcus aureus; Hib, Physiotherapy for Prevention of
haemophilus influenzae type B; CONS, coagulase negative staphylococcus. Contractures and Early Mobility
{{ If neonate is a preterm baby or has a central vascular Prognosis
catheter → Possibility of nosocomial bacteria like • When the pus is drained and appropriate antibiotic therapy
pseudomonas or coagulase negative staphylococcus or is given, improvement in signs and symptoms is rapid
fungi should be considered • Failure to improve or worsening by 72 hours, requires
• In older infants and children: review of the appropriateness of antibiotic therapy, need
{{ Common organisms are S. aureus and streptococcus for surgical intervention or correctness or diagnosis
→ inj. cefazolin 100–150 mg/kg/day divided in three • Acute phase reactants (ESR and CRP) may be helpful for
doses or inj. cloxacillin 150–200 mg/kg/day in divided monitoring the response to therapy. Long-term follow-up
four doses is necessary for sequelae like contractures and bone length
{{ If MRSA is suspected → vancomycin is substituted for • Meticulous following to algorithm 1 is quite rewarding in
cloxacillin most cases.
{{ Injection cefotaxime 200 mg/kg/day in three divided
doses or inj. ceftrixone 100 mg/kg/day in two divided Complications

doses may be used to cover haemophilus influenzae • Septicemia
type B (Hib) and other organisms • Chronic osteomyelitis
• Patients of sickle cell disease with osteomyelitis, • Septic arthritis
Salmonella and S. aureus should be covered → inj. • Pathological fracture
cefotaxime 200 mg/kg/day divided in three doses IV or • Growth plate disturbances.
inj. ceftraixone 100 mg/kg/day divided in two doses IV →
inj. clindamycin 40 mg/kg/day divided in four doses IV CONCLUSION
is useful alternative for sensitive to beta lactam drugs. In
addition to good anti-staphylococcus activity, clindamycin Acute osteomyelitis in children is an important condition
has broad activity against anaerobes and is useful for the because of its potential to cause permanent disability.
treatment of infection secondary to penetrating injuries or
compound fractures Box 5: Indications for surgical therapy
• Injection vancomycin and injection clindamycin are • Soft tissue or periosteal abscess
alternatives for MRSA • Sinus tract formation
• Immunocompromised patients with osteomyelitis: • Presence of necrotic or non-viable bone
{{ Injection vancomycin + inj. ceftzidime or inj. • Prolonged fever, swelling, pain and erythema
piperacillin – tazobactam + inj. amikacin • Possibility of foreign body
• Changes of antibiotics should be considered, once
238 • Involvement of joint
pathogens are identified
Ch-51.indd 238 11/19/2016 3:43:41 PM

Chapter 51: Acute Osteomyelitis
Algorithm 1
Management of acute osteomyelitis
ESR, erythrocyte sedimentation rate; CRP, c-reactive protein; USG, ultrasonography; MRI, magnetic resonance imaging; IV, intravenous; CONS, coagulase negative
staphylococcus; MRSA, methicillin-resistant staphylococcus aureus.
Long bones are commonly involved in acute osteomyelitis in erythema, tenderness, and cellulitis are other manifestations.
children. The unique anatomy and circulation of the ends of There are no specific laboratory tests for osteomyelitis.
long bones (hair-pin bend of blood vessels) result in sluggish Leukocytosis with polymorphonuclear reactions, significantly
circulation and localization of blood borne bacteria. Acute raised ESR and CRP are very common. Blood culture should
osteomyelitis in neonates and infants is commonly associated be routine in all cases of suspected osteomyelitis. Aspiration
with septic arthritis due to peculiar vascularity of physis and for Gram stain and culture is the definite diagnostic technique.
epiphysis. Bacteria are the most common pathogens in acute Radio imaging studies play a crucial role in evaluation of
osteomyelitis in children. Staphylococcus aureus is the most osteomyelitis. Plain radiograph shows lytic bone changes after
common infecting organism in all age groups, including 7–14 days of onset infection. Do not wait for plain radiographical
newborns. Sickle cell anemia, penetrating injuries, nosocomial changes for diagnosis of acute osteomyelitis, it is very late.
infections, certain skin infections, and immunocompromised Soft tissue edema may be evident after 5 days of infection.
like conditions are known to have association with very specific Ultrasonography is simple, inexpensive and very sensitive for
organisms responsible for acute osteomyelitis. subtle signs like subperiosteal edema and soft tissue swelling.
The clinical manifestations of acute osteomyelitis in Ultrasonography guided aspiration is rewarding, positive in
children are highly dependent on the age of the patient. Fever, 70–80% of cases. Magnetic resonance imaging is considered
signs of toxemia, and irritability are more common in neonates. as best radio imaging technique for effective early detection
Pain, pseudoparalysis, limp, refusal to walk, local edema, and surgical localization of osteomyelitis. Sensitivity ranges 239
Ch-51.indd 239 11/19/2016 3:43:41 PM

from 90 to 100% Radionuclide bone scanning is useful when

osteomyelitis is suspected but difficult to ascertain clinically. It Key points
is less sensitive in neonates. ))
Acute osteomyelitis in children is an important condition
The treatment of acute osteomyelitis is comprised of proper because of its potential to cause permanent disability
antibiotics in optimum doses by specific route of administration, ))
Long bones are commonly involved in acute osteomyelitis
for defined duration, usually 4–6 weeks, surgical intervention in children
if required and physiotherapy. Early diagnosis and prompt, ))
Staphylococcus aureus is the most common infecting organism
efficient management favor good prognosis. in all age groups, including newborns
))
Fever, signs of toxemia, and irritability are more common
in neonates. Pain, pseudoparalysis, limp, refusal to walk,
Clinical Pearls local edema, erythema, tenderness, and cellulitis are other
manifestations
• Acute osteomyelitis is an important condition because of its
))
Blood culture should be routine in all cases of suspected
potential to cause permanent disability
osteomyelitis. Aspiration for Gram stain and culture is the
• Long bones are commonly involved in acute osteomyelitis in definite diagnostic technique
children. In neonates and infants, it is commonly associated
))
Plain radiograph shows lytic bone changes after 7–14 days of
with septic arthritis due to peculiar vascularity of physis and
onset infection. Magnetic resonance imaging is considered as
epiphysis
the best radio imaging technique
• Bacteria are the most common pathogens in acute
osteomyelitis in children. Staphylococcus aureus is the most ))
The drug of choice for treating osteomyelitis is cefazolin/
common organism. Association of different organisms with cloxacillin for 4–6 weeks. Intravenous antibiotics can be
very specific condition is known switched to oral once acute signs of inflammation have
subsided.
• Fever, toxemia, and irritability are common clinical
manifestations in neonates. Pain, pseudoparalysis, limp, refusal
to walk, local edema, erythema, tenderness, and cellulitis are
other manifestations SUGGESTED READINGs
• Leukocytosis with raised polymorphonuclear cells and raised
erythrocyte sedimentation rate and C-reactive protein are very 1. Bhaskar A. Acute osteomyelitis in children. In: Shah MA, Vekariya PM, Chowdhary J
common. Blood culture should be routinely done in all cases (Eds). Challenges in the Management of Pediatric Bone & Joint Infections. pp. 81-3.
• Radioimaging studies play a crucial role in evaluation of 2. Gutierrez KM. Osteomyelitis In: Long SS, Pickering LK, Prober C. (Eds). Principles
osteomyelitis. Plain radiograph shows lytic bone changes after & Practice of Pediatric Infectios Diseases, 3rd ed. 2008. pp. 474-82.
7–14 days of onset of infection. Do not wait for radiological 3. Kaplan S. Osteomyelitis. In: Kliegman RM, Stanton BF, Geme III JWS, et al. (Ed.).
changes for diagnosis, it is very late. Ultrasonography is Nelson Textbook of Pediatrics. 19th ed. India. Elsevier Saunders. 2012. pp.
simple, inexpensive, and very sensitive for subtle signs. 2394‑98.
Ultrasonography guided aspiration is rewarding, positive in 70– 4. Mitra M. Skeletal infections. In: Ghosh TK, Yewale V, Parathasarathy A, Shah NK
(Eds). IAP Speciality Series on Pediatric Infectious Diseases (Under IAP Action
80% of cases. Magnetic resonance imaging is considered as the
Plan, 2006), 1st ed. 2006. pp. 111-22.
best radioimaging technique. Radionuclide bone scanning is
useful when osteomyelitis is suspected but difficult to ascertain
• The treatment of acute osteomyelitis is comprised of
appropriate antibiotics in optimum doses by specific route of
administration, for 4–6 weeks duration, surgical intervention if
required, and physiotherapy
• Early diagnosis along with prompt and efficient management
favor the good prognosis.
240
Ch-51.indd 240 11/19/2016 3:43:41 PM

Chapter 52
Algorithmic Approach to Short Duration Fever
without Focus in Older Infants and Children
Suhas V Prabhu
INTRODUCTION • Color (cyanosis, pallor, decreased capillary fill time) and

Cry (weak or high pitched)
Fever in an older infant and child (>3 months of age) is one of • Dehydration (poor intake, oliguria).
the most common cases presenting to the pediatrician (up to Additional factors may exist that need to be considered
half of out-patient visits). The causes may vary from something such as an immune-compromised patient (human immuno
as innocuous as a non-specific viral infection needing only deficiency virus, asplenia, etc.), child with an indwelling foreign
symptomatic treatment to more dangerous ones like dengue, body (port, shunt, prosthesis, etc.), condition predisposing to
malaria, or bacteremic infections requiring correct diagnosis subacute bacterial endocarditis (bicuspid aortic valve, small
and prompt intervention. ventricular septal defect, etc.), compromised due to chronic
cardiovascular disease or severe protein energy malnutrition,
CAUSES latent cortisol deficiency congenital adrenal hyperplasia, and
so on. This sub-set of patients should be investigated and
Bacteremia will be seen in between 3 and 5% of children with
treated more aggressively than the general population.
fever without focus in this age group especially if the fever
is more than 39°C. While bacteremia due to organisms like The second step is to ensure that it is truly a fever without
Streptococcus pneumoniae, Staphylococcus and Haemophilus focus. Make an extra effort to look for a focus although in the
influenzae is more common in children younger than 2 years, history or on cursory examination there is no apparent one. In
in older children, typhoid and paratyphoid fevers account particular, look for otitis media, joint involvement, local skin
for the majority of bacterial causes. Parasitic infestations like infections, rash, urinary symptoms, etc., if found appropriate
malaria also account for a large percentage of fevers in this age investigation and treatment should be done.
group in certain parts of the country in certain seasons. If no focus is found after a thorough history and physical
examination, and the child is not toxic, there are no risk factors,
and the temperature is less than 39°C, it is safe to observe the
Approach child with antipyretics alone and reassess after 48–72 hours.
The clinician’s approaches to these patients need to be one Parents must be informed about danger signs (ABCD listed
of a cautious balance between over investigation and/or above) that should prompt them to return for medical re-
unnecessary usage of antibiotics versus the other extreme of evaluation earlier. However, if the child is already suffering
missing the child with serious infection who will suffer because with fever for the past 2–3 days and there is no focus found on
of delayed diagnosis and intervention. While the majority of the day of presentation, then the child should be investigated
cases will need only symptomatic treatment and observation straightaway.
for the first 2 or 3 days, the clinician needs to be alert to pick up If otherwise, initial investigation should consist of the
those who are more likely to have serious illnesses bacterial or following: complete blood count, acute phase reactant marker
otherwise that need to be investigated promptly. like C-reactive protein (CRP), urinalysis and, where feasible,
The first step therefore is to assess for toxicity (degree of blood and urine cultures. Tests for malaria (smear for malarial
severity of illness). Signs of severe infection/sepsis or danger parasite and/or rapid malarial antigen test) or dengue (NS1
signs requiring immediate workup and possible hospitalization antigen ± dengue immunoglobulin G and immunoglobulin M)
can be easily remembered by the mnemonic ABCD: should be added if the epidemiology warrants.
• Activity and Alertness (reduction of or Altered sensorium) However, additionally, if the child is severely toxic or
• Breathing (difficult or fast) dehydrated or has signs of early sepsis, hospitalization
Ch-52.indd 241 11/19/2016 3:45:20 PM

Algorithm 1
Approach to short duration fever without focus in older infants and children
WBC, white blood cell; CRP, C-reactive protein; CBC, complete blood count. *See text for details.
Table 1: Clues to the diagnosis from the humble complete blood count
Parameter Enteric fever Malaria Dengue fever Other viral fevers
hemoglobin/hematocrit Normal Low Normal/High Normal
Total white blood cell Normal/Low Normal/Low Low/Very low Normal/Low
Differential white blood cell Polys predominant, Eosinopenia Monocytosis Lymphocytosis Lymphocytosis, activated lymphocytes
Platelets Normal/Low Low Low Normal/Low
is mandatory for observation, stabilization, and prompt

empirical administration of antibiotics. Ceftriaxone at Clinical Pearls
100 mg/kg/day is usually an appropriate initial choice. On the • Examine thoroughly to rule out an occult focus
other hand, in situations where availability or affordability is • In all sick children or in those with no focus even after 2–3 days
a problem and the child is not too sick, the initial step may be of fever, perform investigations including complete blood
only a complete blood count with (where appropriate) smear count (CBC), smear for malarial parasite, C-reactive protein
for malarial parasite and a routine urinalysis. If the white (CRP), and urine routine
cell count is more than 15,000/mm3 or bandemia or toxic • Other investigations that may be asked for depending on
granulation is present, a blood culture would be advisable. findings on initial investigations or clinical setting include urine
Similarly, if the urinalysis shows pyuria, urine culture should and blood cultures and dengue serology
be asked for before the first dose of antibiotic is administered. • Careful interpretation of the CBC is important, often repeat
If there is leukopenia [White blood cell (WBC) count below testing is required
4,000] then possibilities of enteric fever, malaria, dengue, • Mildly elevated CRP can be seen in viral infections
and viral infection should be considered and appropriate • Widal test is of no value in the first 7 days. Blood culture is the
investigations asked for. If the WBC count is normal and most reliable method to diagnose enteric fever.
low with absolute eosinopenia and there is a very high CRP
enteric fever should be considered and blood cultures sent In certain circumstances, the first CBC may be un
before starting antibiotics. remarkable but repeat CBCs might yield the diagnosis, e.g.,
The CBC needs to be evaluated in detail rather than only in dengue, serial CBC shows decline in the WBC and platelet
looking for leukocytosis. Table 1 indicates possible clues to the count and rising hematocrit. The widal test is of no utility in
diagnosis from the humble CBC. evaluation of fever of less than 7 days duration.
The CRP (if done) can help to distinguish bacterial
from viral fevers even on the 2nd or 3rd day of illness. But a SUGGESTED READINGs
mildly elevated CRP can be seen in some viral infections
1. Baker MD. Evaluation and management of infants with fever. Pediatr Clinics North
like adenovirus or viral infections with secondary bacterial
Am. 1999;46:1061-72.
complications. However, a very high CRP (> 40 mg/L) is more 2. Lorin MI. Fever: Pathogenesis and treatment. In: Feigin RD, Cherry J, (eds).
242 likely to be due to a bacterial infection and a clue to further Textbook of Pediatric Infectious Diseases, 4th ed. Philadelphia, WB Saunders;
investigation or empirical antibiotic therapy. 1998. pp. 89-94.
Ch-52.indd 242 11/19/2016 3:45:21 PM

Chapter 53
Fever with Rash
Ritabrata Kundu
INTRODUCTION • Urticarial rash

• Nodular rash
Skin is the mirror of many internal ailments which may • Purpuric rash
manifest as rashes. At the outset one should determine the • Rashes with ulcer.
types of rashes which are as follows.
Macules are flat lesions of altered color in the skin. Centrally Distributed Maculopapular Rash
Papules are raised flat topped lesions with diameter of less
than 5 mm, whereas nodules are more than 5 mm in diameter They are most common type of rash which is mainly truncal.
with raised rounded configuration. Vesicles are fluid filled Most common viral infections seen in children belong to this
lesions less than 5 mm in diameter and are known as bullae group are discussed in table 1.
when they are more than 5 mm in diameter. Pustules are
Table 1: Centrally distributed maculopapular rash
raised pus filled lesions. Purpuras are bleeding into the skin
which are nonblanchable. When they are less than 5 mm in Diseases Common recognizing features
diameter they are known as petechiae and if more than 5 mm Measles Respiratory prodrome; Koplik’s spot in buccal
in diameter ecchymoses. mucosa which gradually wanes after onset of
A good history in all cases must include site of onset of rash, rash, maculopapular rash starting from hairline
rate and direction of its spread. Inquire about medications and behind the ears, spread down the trunk
taken in recent months, history of travel, exposure to insects and limbs. Rash fades in the order in which
and animals, immune status and immunization history. it appeared with brownish discoloration and
desquamation.
It should also include history of any cardiac abnormality
including prosthesis, exposure to ill individual, and sexually Rubella Prodrome of fever and malaise, followed by
transmitted diseases. posterior auricular, cervical and suboccipital
Next one should determine the type of rash, i.e., its lymphadenopathy; fever and rash. Rash,
maculopapular begins on face and spreads
morphology, distribution, and arrangement of the lesions. At
downward.
times, the morphology might change with passage of time for
instance in dengue the initial diffuse flushing may give away to Erythema Common in children between 3–12 years; bright
maculopapular rash. Also the spread of lesions should be taken infectiosum (fifth disease) red “slapped cheek” appearance
following a minor febrile prodrome.
into account as maculopapular rash of dengue which starts in
the trunk spreads centrifugally to extremities and face. Exanthem Common in children below 3 years; diffuse (ro
subitum seola) truncal maculopapular rash sparing face
following resolution of fever.
CLASSIFICATION OF RASH WITH FEVER Infectious • Common in older children and adolescents
It is broadly classified as follows: Fever, mononucleosis sore throat, and
• Centrally distributed maculopapular rash lymphadenopathy is most common
• Peripheral rash • Morbiliform or papular rash develops usually
• Confluent desquamative rash on trunk and arms
• Vesiculobullous rash Continued
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Continued Confluent Desquamative Rash (Table 3)

Diseases Common recognizing features They start with diffuse erythema often followed by
Drug rash • Usually maculopapular common in trunk and desquamation.
symmetrical
Table 3: Confluent desquamative rash
• Intensely pruritic, absence of respiratory
catarrh and enanthems helps to distinguish Disease Common recognizing features
from a viral eruption
Scarlet fever • Blanchable erythema over face and upper
Dengue • Initially diffuse red flushing with pruritus trunk to start
followed by maculopapular rash on trunk
• Minute papules which give the skin a sand
which spreads centrifugally to extremities and
paper feel
face
• Associated feature include strawberry tongue
• Petechiae may be seen in some cases on
extremities • Subsidence of rash is followed by
desquamation
Systemic lupus • Photosensitive butterfly rash on check and
erythematosus nose Streptococcal • Generalized erythematous macular rash which
• Discoid, urticarial, or bullous lesion may also toxic shock desquamate
be seen syndrome • May develop other features which usually
Juvenile Evanescent erythematous papules on trunk include hypotension, renal impairment,
rheumatoid appearing at the height of fever respiratory distress syndrome, coagulopathy, or
arthritis soft tissue infection
Staphyloccocal • Seen in infants and children below 5 years
scalded skin • Scarlatiniform erythema develops followed by
Peripheral Rash (Table 2) syndrome sterile flaccid blisters
These rashes start at the periphery (acral) and then spread • Nikolsky sign is positive with skin peeling off
centripetally. leaving moist, glistening denuded areas
Table 2: Peripheral rash • Patient may appear well despite marked skin
tenderness
Diseases Common recognizing features
Staphylococ- • Acute onset with high fever, erythematous
Erythema • Target lesions symmetrical on palms, soles, cal toxic shock macular rash which desquamates later and
multiforme knee, and elbow syndrome associated with hypotension
(infection, • The center of the lesion dusky violet color or • Multisystems involvement with
drugs) petechiae thrombocytopenia, renal failure, liver and
• In erythema multiforme major there is usually central nervous system abnormality are seen
involvement of ocular, nasal oral, or genital Kawasaki • Maculopapular, scarlatiniform or erythema
mucous membrane disease rashes multiforme with accentuation in the groin area
Hand-foot and • Tender maculopapular lesion on hand, fingers, • Associated feature includes fissuring of the lips,
mouth disease feet, buttocks associated and groin conjunctivitis, strawberry tongue, edema of
(Coxsackie • Vesicular lesions are also seen hands and feet with periungual desquamation
virus and • Involvement of buccal mucosa, pharynx, of finger and toes
enterovirus) gingiva, and palate • Illness predominantly in young children with
majority under 5 years
Secondary • Maculopapular rash frequently involving
syphilis palms and soles Steven • SJS start as erythematous macule which
Johnson syn- develops central necrosis to form vesicles,
• They are dark colored, nonpruritic, and discrete
drome (SJS), bullae, and skin denudation
• Constitutional symptoms other than fever toxic epidermal • Extend of involvement is less than 10% of body
include malaise, sore throat, weight loss, and necrolysis surface area
headache (TEN) • Skin lesions are accompanied by two or
• There is also involvement of mucous
more mucous membrane involvement like
membrane
conjunctivitis, oral ulceration, or anogenital
Bacterial • Erythematous or hemorrhagic macules on inflammation
endocarditis palms and soles are painless (Janeway lesions) • TEN has involvement more than 30% of body
• Petechiae on skin and mucosa; tender red surface area with more systemic symptoms like
nodules on finger and toe pads (Osler’s node) pulmonary or gastrointestinal involvement
• Associated heart murmur • In SJS/TEN involvement is between 10 and 30%
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Chapter 53: Fever with Rash
Vesiculobullous Rash (Table 4) Continued
They are mostly due to virus or bacterial infections. Disease Common recognizing feature
Table 4: Vesiculobullous rash • and purpura may spread to involve upper
extremities and face
Disease Common recognizing feature • Large ecchymoses with hemorrhagic bullae
Varicella • Macules appears on trunk and face that rapidly (purpura fulminans) indicate DIC
spreads to other areas of the body • Associated features of meningitis and shock
• Lesions have an erythematous base which quickly may be evident
evolves to vesicles, pustules and then crust
Dengue • After a relatively benign first stage with fever,
formation
hemorrhagic malaise and headache patient suddenly
• Lesions appear in crops with different stages of fever collapses with cold extremities and irritability
development
• Petechiae and purpura may be seen in
• In healthy children it is usually associated with mild extremities and face followed by ecchymoses
fever and malaise
Rickettsial • Indian spotted fever is associated with an
Herpes • Cutaneous lesions usually involve face, lips, gingiva,
infections initial maculopapular and then petechial/
simplex tongue and palate
purpuric rash with peripheral distribution
virus • Erythema followed by grouped vesicles, which and involvement of palms and soles
(HSV) progress to pustules and crust formation
infection • In scrub typhus a necrotic rash is seen at the
• There is regional lymphadenopathy but systemic bite site and a centrally distributed rash
symptoms are usually absent
DIC, disseminated intravascular coagulation.
Herpes • Clustered vesicular lesions confined to one or two
Zoster dermatomes
• Pain, hyperesthesia and fever are mild as compared
Nodular Rash
to adults The most common nodular rash with fever is erythema
• Lesions completely resolve within 1 or 2 weeks nodosum. They are violaceous, tender, and large subcutaneous
nodules seen particularly on lower legs above the shin bone.
Urticarial Rash It may be due to drugs (penicillin, sulfonamide) infection
(streptococcal, mycobacterial, fungal) or idiopathic. Common
Classic urticaria (hives) is not associated with fever. They do associated feature include arthralgias.
not last at a Particular location for more than 24 hours, does
not have purpuric or pigmented component and itch rather
than burn. Key points
Table 5: Urticarial rash ))
Fever with rash is a common and vexing problem
Disease Common recognizing feature
))
It may signify a serious disorder such as meningococcemia or
dengue hemorrhagic fever or may be associated with a minor
Urticarial • Raised erythematous lesions with flat top drug allergy
vasculitis • They are indurated, painful and sometimes ))
The most important factor that helps to determine the
lesions are purpuric etiology of an exanthematous febrile illness is the nature of
• May have burning sensation and individual rash
lesion lasts up to 5 days.
))
All efforts should be made to diagnose the serious entities
first and institute immediate treatment
Purpuric Rash (Table 6) ))
For stable children, a specific diagnosis may not be always
Nonpalpable purpura is flat lesion due to bleeding in the skin. be possible. In this situation symptomatic therapy, close
If less than 3 mm in diameter then it is known as petechiae observation, explanation of danger signs to parents,
whereas more than 3 mm in diameter then called ecchymoses. and staying away from school until the rash resolves are
Palpable purpura is due to inflammation of the vessel wall recommended.
(vasculitis) with subsequent hemorrhage causes raised lesions.
Table 6: Purpuric rash SUGGESTED READING

Disease Common recognizing feature
1. Cherry JD. Cutaneous manifestations of systemic infections. In: Feigen RD,
Acute meningo • Initial maculopapular lesion involving trunk Cherry JD (Eds). Textbook of Pediatric Infectious Diseases, 4th ed. Philadelphia:
coccemia and lower extremities WB Saunders; 1998. pp. 713-37.
• Lesions quickly evolving to petechiae
Continued
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Chapter 54
Approach to Managing
New Onset Fever in the Intensive Care Unit
Tanu Singhal
INTRODUCTION procedures/interventions at these sites. Occult sites of infection

include sinusitis, osteomyelitis, and septic arthritis. Eliciting
New onset fever defined as fever occurring after 48 hours of symptoms referable to a particular system is often difficult in
admission to the intensive care unit (ICU) in a patient who very sick children but should be done whenever possible. A
was previously afebrile is generally considered as a sign of head to toe assessment should be done with careful inspection
a hospital acquired/health care associated or nosocomial of the central line, exit site of central venous, respiratory
infection. However, an infection may occur without fever and system, nature of tracheal secretions, abdomen, bones, joints,
not all fever is due to infection. In certain circumstances, a examination of neck stiffness and surgical sites and the skin.
new onset fever may also be a continuum or a complication It is important to disrobe and examine the entire skin as these
of a community acquired infection. Approach to diagnosis and might show areas of cellulitis, eschars, and pustules which
management of this clinical entity is discussed in this chapter. often indicate bacteremia/fungemia.
GENERAL PRINCIPLES IN DIAGNOSIS Distinguishing Infection from Colonization

in the Nosocomial Setting
Distinguishing Infectious from An important issue in managing nosocomial infections is
Noninfectious Causes of Fever to differentiate infection from colonization. In several ICUs,
surveillance cultures are sent from nonsterile sites like
It must be remembered that fever can often be the result of
endotracheal tubes, central line ports, urinary catheters, and
noninfectious causes. Noninfectious causes of fever in the
EVD drains. These will always grow microbes as these sites are
hospitalized patient include postoperative atelectasis, drug
inevitably colonized. It is important that these colonizations
fever, thrombophlebitis, transfusions, deep venous thrombosis,
are not treated with antibiotics as treating colonization will
central fever, etc. Similarly, leukocytosis may not always be due
not prevent infection and only contributes to selection of
to an infection; noninfectious causes include stress, bleeding,
resistant organisms. Unless an infection is suspected, no
atelectasis, and steroids.
surveillance cultures should be sent. More difficult is to
differentiate infection from colonization, in the setting when
Determining the Site of Infection fever is associated with positive cultures from nonsterile sites.
Once, major noninfectious causes are excluded a thorough Here careful interpretation is needed to ascertain whether the
clinical assessment should be made for determining the site positive culture is colonization or true infection.
of infection. Common sites if infections in the ICU are blood
stream infections especially in patients who have central
INVESTIGATIVE APPROACH
lines, sinusitis/tracheobronchitis/pneumonia in patients on
invasive ventilation, urinary tract infections in those who have The initial investigations include a complete blood count and
indwelling catheters, surgical site infections in postsurgical peripheral smear evaluation with acute phase reactants such
patients and sometimes enteric infections. Clostridium difficile as C-reactive protein (CRP)/procalcitonin. Signs of sepsis
is less common in children as compared to adults. Central include neutrophilia/neutropenia, thrombocytopenia, shift
nervous system (CNS) infections and intra-abdominal sepsis to left/bandemia and toxic granules in the neutrophils. While
should be also considered in children with predisposing CRP has limited sensitivity/specificity for diagnosing sepsis,
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Chapter 54: Approach to Managing New Onset Fever in the Intensive Care Unit
a serum procalcitonin level of more than 2 ng/mL is highly • Local epidemiologic data: knowledge of common
specific for serious bacterial infection in a previously stable microbial pathogens and their resistance profile in a
patient. Procalcitonin can also be high due to previous surgery/ particular intensive care unit helps in making empirical
trauma/burns, etc. choice of antibiotics till cultures are available. The most
At least two aerobic/one aerobic and one anaerobic culture common etiologic agents for nosocomial infections in
should be sent. If there is a central catheter then one culture India are Gram-negative pathogens including Klebsiella,
should be sent from the catheter lumen and the other from E. coli, Pseudomonas, Acinetobacter, Enterobacter. These
peripheral venipuncture. Increasing the volume of blood are followed by Gram-positive including S. aureus, S.
cultured by sending two sets of culture (four bottles) increases epidermidis and enterococci There is an increase in
the sensitivity. Confirmation of the diagnosis of a catheter- infections due to fungi, mainly Candida albicans but
related bloodstream infections (CRBSI) involves isolation also non-albicans candida such as Candida tropicalis,
of the identical organism with the same antibiogram from Krusei, Glabrata, and Parapsilosis. Most of the nosocomial
simultaneous cultures; one obtained through peripheral pathogens are multidrug resistant. Foremost is drug
venipuncture and the other either catheter lumen blood resistance in Gram-negative pathogens with 80% of
culture or culture of the catheter tip. A positive lumen culture nosocomial E. coli and Klebsiella infections being resistant
alone has poor positive predictive value for CRBSI as it may just to third generation cephalosporins by virtue of production
indicate colonization; but high negative predictive value (90%). of extended spectrum beta lactamases (ESBL). The
In all children and especially those with suspected urinary emergence of Amp C mediated resistance, traditionally
tract infection, a routine urine analysis and culture should found in Pseudomonas, Enterobacter, Serratia, Citrobacter
be sent. Results of these investigations should be interpreted but now even in other Gram-negative bacilli has made
carefully as some degree of pyuria and significant bacteriuria third generation cephalosporins and beta lactam-beta
(colony count of more than 105/mL may be seen in any lactamase inhibitor (BL-BLI) combinations ineffectual.
catheterized patient with no urinary tract infection). The fall out of ESBL and Amp C mediated resistance
For suspected hospital acquired pneumonia, cultures of has been excessive use of carbapenems in ICU settings.
the respiratory secretions should be sent. Several methods Consequently, a significant proportion of Pseudomonas
like quantitative endotracheal aspirates, bronchoalveolar and Acinetobacter isolates in certain ICUs of tertiary care
lavage, protected specimen brush have been recommended hospitals are now resistant to even carbapenems. This
for diagnosis of pneumonia. Generally speaking, quantitative has led to colistin overuse and sporadic reports of colistin
cultures of endotracheal secretions are easily done and of resistance. S. aureus are generally methicillin resistant,
almost comparable yield as those of the bronchoscopic vancomycin resistant S. aureus/enterococci are not a
methods. Hence, in suspected ventilator associated pneumonia problem as yet. Also seen over time with increasing use of
(combination of fever/leukocytosis/purulent secretions/new fluconazole for therapy and prophylaxis, is rising incidence
infiltrates) quantitative endotracheal cultures should be sent of non-albicans Candida infections some of which are
and empirical antibiotic therapy initiated. fluconazole resistant
Cultures should also be sent from other suspected sites • Previous antibiotic usage: this again helps in predicting the
of infection such surgical sites, cerebrospinal fluid (CSF), likely resistance profile of the microbe till culture results are
abscesses, etc. Care should be taken to send deep samples; skin available. Additionally, it helps in guessing what pathogens
swabs and cultures from drains may just indicate colonization. have not been appropriately covered till now
Imaging also assists in diagnosing site of infections. Basic • Severity of infection: for a patient who is critically sick or
imaging includes chest X-ray and ultrasonography abdomen. in septic shock, a carbapenem may be needed as there is
Presence of a new infiltrate on chest imaging is also not specific high organism load and there is no leeway for making an
enough for a pneumonia as it may be due to atelectasis, error in choice of antibiotic nor is their time to upgrade.
progression of underlying lung disease, or due to thoracic On the other hand, if there is doubt about the presence of
surgery. In some patients, computerized scans of the thorax infection or there is mild infection a BL-BLI combination
and abdomen may be needed to detect site of infection. may be used
• Associated comorbidities: these are important consi
TREATMENT derations. For instance if there is associated renal
compromise, nephrotoxic drugs such as aminoglycosides,
The most important component of treatment of a nosocomial vancomycin, and colistin should be avoided or used with
infection is appropriate antimicrobial therapy administered as caution
soon as possible once sepsis is considered. However, source • Site of the infection: in the presence of a CNS infection a
control such as removal of an infected central line and drainage drug with good CSF penetration must be used. Hence, BL-
of pus and supportive therapy are also crucial. BLI combinations cannot be used as the BLI does not cross
the blood brain barrier.
Factors Determining Choice of
Antimicrobial Therapy Initial Empirical Antimicrobial Regimes
Various factors determine the empiric choice of antibiotics and Initial empirical therapy is necessary in seriously ill patients
include: before culture reports are available. The choice of such 247
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Algorithm 1
Algorithmic approach to new onset fever in intensive care unit
CBC, complete blood count; CRP, C-reactive protein; PCT, procalcitonin; BL-BLI, beta lactam-beta lactamase inhibitor; MRSA, methicillin-resistant
Staphylococcus aureus.
antimicrobial therapy should be carefully thought of since De-escalation

studies demonstrate that inappropriate initial therapy is
This is extremely important to prevent or mitigate antibiotic
associated with higher mortality. Since most nosocomial
resistance. Once culture reports are available and so indicate,
infections in Indian ICUs are due to resistant Gram-negative
the higher level antibiotic can be switched to a narrow
pathogens, the initial empirical regime should comprise of an
spectrum one. This may mean switching from a carbapenem
adequate Gram-negative cover such as BL-BLI combination
such as imipenem or meropenem to a cephalosporin/BL‑BLI/
or carbapenems. In units with high rates of carbapenem
quinolone or ertapenem. Even if cultures are negative, de-
resistance, colistin may be required upfront in very sick escalation may be practiced such as stopping the MRSA cover
patients. An anti methicillin-resistant Staphylococcus aureus if no Gram-positive pathogen has been isolated.
(MRSA) cover should be added to the regime if there is a high
incidence of MRSA in that unit, if there are Gram-positive cocci Duration of Therapy
in the Gram stain of secretions or if there are other features
suggesting a Gram-positive infection. If risk factors for fungal Newly emerging data supports the use of short-term antibiotic
infections are present such as prolonged ICU stay, renal therapy (usually 7 days) for most nosocomial infections
failure, prolonged antibiotic use, gut surgery, renal failure, use (exception S. aureus, fungal infections and necrotizing
of corticosteroids, use of intralipids, immunocompromised pneumonias). This helps in reducing the antibiotic pressure in
stay, extreme prematurity and isolation of candida from the unit and chances of selection of resistant pathogens apart
multiple nonsterile sites then an antifungal should be added from reducing costs.
either upfront or of there is failure to respond in 48 hours. The
choice of antifungal depends on previous azole exposure, CONCLUSION
the local patterns in the unit, the severity of infection and A new onset fever in the intensive care unit may be a harbinger
associated comorbidities but for most fluconazole suffices. of a serious possibly drug resistant infection. It is crucial to pay
due attention to infection control strategies so that such an
Dosing of Antibiotics event can be prevented.
Adequate attention is needed toward administration of
appropriate doses. Higher doses may be needed for serious Clinical Pearls
infections. Time dependent antibiotics such as beta lactams
and vancomycin should be dosed frequently to maintain • A robust infection control program is crucial in preventing
serum levels continuously above the minimum inhibitory health care associated infections
concentration. Recent data supports administration of • Appropriate antimicrobial therapy is essential for improving
beta lactams by continuous infusion. On the other hand, outcomes and reducing the burden of antimicrobial resistance
concentration dependent antibiotics, such as aminoglycosides, • Knowledge of local microbial flora and susceptibility helps in
designing empirical regimes.
may be effectively dosed once a day.
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Chapter 54: Approach to Managing New Onset Fever in the Intensive Care Unit
Key points
SUGGESTED READINGs
1. Alcon A, Fabregas N, Torres A. Hospital-acquired pneumonia: etiologic
))
All new onset fever in intensive care units may not be infectious
considerations. Infect Dis Clin N Am. 2003;17(4):679-95.
))
A careful examination is needed to identify the source of fever
2. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for
))
Relevant cultures should always be sent prior to starting nosocomial infections. Am J Infect Control. 1988;16:128-40.
antimicrobial therapy 3. Huskins WC, Goldmann DA. Nosocomial infections. In: Feigin RD, Cherry JD (Eds).
))
Results of investigations including cultures from nonsterile Textbook of Pediatric Infectious Diseases, 4th ed. Philadelphia: WB Saunders
sites should be carefully interpreted Company; 1998. pp. 2545-85.
))
The empirical antimicrobial therapy should be guided by local 4. Lodha R, Natchu UC, Nanda M, Kabra SK. Nosocomial infections in pediatric
susceptibility patterns, severity of illness, and prior antibiotic intensive care units. Indian J Pediatr. 2001;68:1063-70.
use. It should be broad enough especially in sick patients 5. Mermel LA, Farr BM, Sherertz RJ, Raad II, O’Grady N, Harris JS, et al. Guidelines
))
Efforts should be made to de-escalate antimicrobials at the for the management of intravascular catheter-related infections. Clin Infect Dis.
earliest 2001;32:1249-72.
))
Infection control strategies are paramount.
249
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Chapter 55
Infant Born to Human
Immunodeficiency Virus Infected Mother
Ira Shah
INTRODUCTION healthy mother and child at the end of intervention. The year
2009 was the turning point for the prevention of postnatal
Human immunodeficiency virus (HIV) in children is pre transmission of HIV where three randomized controlled trials
dominantly acquired as a vertically transmitted disease. found that antiretroviral prophylaxis in pregnant women
Without intervention the transmission rate from mother to and their infants coupled with breastfeeding could lead to a
child has varied from 20 to 40%. However, this risk can be significant decrease in the vertical transmission of HIV.
reduced to less than 2% with effective prevention of parent to
child transmission of HIV (PPTCT) programs.
Vertical transmission of HIV can occur in utero through Clinical Pearls
placental transmission, intrapartum through contact with
Prevention modalities include:
infected birth canal secretions or postpartum through breast
feeding. It is estimated that of the 30% of babies who get • Antiretroviral drugs to mother during pregnancy and while
infected vertically, 2% get infected in early gestation, 3% get feeding
infected in late gestation, 15% get infected intrapartum and • Antiretroviral prophylaxis to baby post delivery
10% get infected via breastfeeding. • Choice of feeding
• Mode of delivery
Clinical Pearls
• Mother to child transmission of Infant Born to human
immunodeficiency virus Infected Mother occurs in 20–40% ELECTIVE CAESAREAN SECTION
children without intervention
Elective caesarean section has been found to decrease
• 2% get infected in early gestation, 3% get infected in late
gestation, 15% get infected intrapartum, and 10% get infected transplacental hemorrhage during labor, reduce the length
via breast feeding of exposure of baby to vaginocervical secretions, and reduces
chances of ascending infection of HIV transmission. Studies
have found that among HIV-1 infected women not taking
Prevention Modalities ARV during pregnancy, ECS was efficacious for prevention of
Human immunodeficiency virus transmission from infected mother to child transmission (MTCT) of HIV-1, and decreased
mother to child is mainly prevented by antiretroviral drug transmission by approximately 50% as compared to other
(ARV) prophylaxis to mother and baby, replacement modes of delivery.
feeding and elective caesarean section (ECS). Antiretroviral However, ECS is associated with postpartum morbidity
prophylaxis acts by reducing viral load in the mother and as in the form of fever, urinary tract infection, endometritis
post-exposure prophylaxis to the fetus and baby. Caesarean and thromboembolism. Also, it is more expensive and not
section before onset of labor or rupture of membranes has universally available especially in resource limited settings.
been used as an intervention for PPTCT to decrease risk of When ARV prophylaxis to mother and child are available and
intrapartum transmission of HIV. replacement feeding can be issued, the added advantage of ECS
The goal of effective PPTCT is to ensure minimum risk is not seen and vaginal delivery may be a safe and inexpensive
of transmission of HIV from mother to child and ensuring a option in this setting.
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Chapter 55: Infant Born to Human Immunodeficiency Virus Infected Mother
ANTIRETROVIRAL PROPHYLAXIS Table 1: WHO Guidelines 2013 for Prevention of parent to child
transmission of human immunodeficiency virus
Many trials have demonstrated gradual reduction of the in
utero and intrapartum transmission rates with an increasing Option B+
length and potency of drug combinations used during For pregnant Triple ARV drugs starting from as early as
pregnancy and at delivery. In industrialized countries, highly women 14 weeks of gestation and continued lifelong
active antiretroviral therapy (Triple drug therapy) is used in Recommended Tenofovir + 3 lamivudine (or emtricitabine) +
pregnant women as prophylaxis. regimen efavirenz
For infants Daily administration of zidovudine or nevirapine
CHOICE OF FEEDING from birth until 4–6 weeks of age
Type of delivery Vaginal
Human immunodeficiency virus has been detected in breast
milk in cell-free and cell-associated compartments and there Feeding Breastfeeding
is now evidence that both compartments are involved in
transmission of HIV through breast milk. Even if intra-uterine These maternal antibodies may remain detectable in the
and intrapartum transmission are significantly reduced, infant’s serum for up to 12–15 months after birth. As a result,
postnatal transmission through breastfeeding still is an serological diagnosis of HIV infection is only reliable after 15–
additional risk for transmission of HIV (risk varies from 10 to 18 months of age. Infants infected with HIV must be diagnosed
15%). This risk increases with high viral load in the breast milk, as rapidly as possible to ensure the early institution of therapy
maternal nipple lesions, mastitis, and breastfeeding for longer to limit HIV related morbidity and to prevent opportunistic
than 15 months. infections. Tests that can be done for diagnosis of HIV infection
Replacement feeding clearly abolishes the risk of breast in children below 18 months of age are HIV culture, detection of
milk transmission. However, replacement feeding increases HIV proviral DNA by polymerase chain reaction (PCR). Human
the risk of diarrheal diseases and malnutrition. immunodeficiency virus culture is done from peripheral blood
Exclusive breastfeeding for up to 6 months, however, mononuclear cells (PBMCs) but is technically difficult and
is associated with a threefold to fourfold decreased risk of time consuming. It is expensive and done in research institutes.
transmission of HIV compared to non-exclusive breastfeeding; Positive results are available by 1–2 weeks but negative results
mixed feeding, therefore, appears to be a clear risk factor for are not reported till there is no evidence of HIV replication for
postnatal transmission. Various recent clinical trials have now 30 days. Thus, the test commonly used for diagnosis of HIV in
clearly shown that when antiretrovirals are taken through infants is PCR.
the pregnancy and breastfeeding stage, there is a greatly
reduced HIV infection rate of 2%. This approach offers new
hope for mothers with HIV infection who cannot safely feed TIMING OF TRANSMISSION OF
their babies with replacement. It will improve the chances of human immunodeficiency virus AND
infants remaining healthy and free of HIV infection as breast ROLE OF polymerase chain reaction
milk provides optimal nutrition and protects against other fatal
childhood diseases such as pneumonia and diarrhea. Human immunodeficiency virus PCRs are of two types: (1)
Qualitative and (2) Quantitative. The potential utility of DNA
PCR for the diagnosis of vertical HIV infection soon became
WORLD HEALTH ORGANIZATION (WHO) 2013 readily apparent in infants. Human immunodeficiency virus
GUIDELINES deoxyribonucleic acid (DNA) PCR has been found to be highly
sensitive and specific for early diagnosis of pediatric HIV
The new World Health Organization (WHO) 2013 Guidelines
infection. Sensitivity of HIV PCR is less at birth and sensitivity
have suggested a once-daily three drug fixed-dose combination
increases rapidly to 95% at 4 weeks and to 99% at 6 months
of tenofovir and lamivudine (or emtricitabine) and efavirenz as
of age. Thus, in non-breast fed infants, HIV PCR can be done
first-line antiretroviral therapy in HIV infected pregnant and
at 4–6 weeks after birth. In breastfeeding populations, HIV
breastfeeding women which should be continued lifelong.
PCR should be done after 1 or 2 months after cessation of
Infants of these mothers should receive 6 weeks of infant
breastfeeding. HIV PCR can be done on dried blood sample
prophylaxis with daily nevirapine (or twice-daily zidovudine).
transported to a laboratory on a filter paper or on whole blood.
Infant prophylaxis should begin at birth or when HIV exposure
False positive and false negative results with HIV DNA PCR
is recognized postpartum (Table 1).
may occur. The authors have reported a very high incidence of
false positive HIV DNA PCR (75%) especially in younger infants
DIAGNOSIS OF human immunodeficiency in their study. Repeating the PCR on independent samples
virus IN INFANTS BORN TO human immuno may be required to reduce the test errors. One of the reasons
stated for the false positive results is contamination. Optimal
deficiency virus INFECTED MOTHERS
PCR conditions, inclusion of control samples, strict rules on
All infants born to HIV-infected mothers carry maternal sample preparation, pre- and post-PCR handling, repetition
immunoglobulin G antibodies which cross the placenta freely. of results, confirmation of specificity by hybridization, choice 251
Ch-55.indd 251 11/19/2016 4:09:11 PM

of material from which HIV-1 is amplified, and the primers Children born to HIV-infected mothers should be adminis
used for amplification will all predict the reliability of HIV tered prophylaxis with trimethoprim sulfa methoxazole
DNA PCR. Thus, diagnosis of HIV should never be based on beginning at age 4–6 weeks. Prophylaxis should be dis
one result but should always be confirmed by a repeat test. continued for children who are subsequently determined not
Serological diagnosis at 18 months with HIV enzyme-linked to be infected with HIV. HIV-infected children and children
immunosorbent assay would also be useful. whose infection status remains unknown should continue to
receive prophylaxis for the first year of life.
DIAGNOSIS OF human immunodeficiency
virus IN CHILDREN ABOVE 18 MONTHS OF AGE Clinical Pearls
Enzyme-linked immunosorbent assay is the time-tested • Cotrimoxazole prophylaxis should be given to all children born
reliable method for detection of anti HIV antibodies with a to human immunodeficiency virus (HIV) infected mothers
sensitivity of more than 99.5% and specificity of 99%. starting from 4 to 6 weeks of age
• Prophylaxis should be discontinued for children who are
subsequently determined not to be infected with HIV
Clinical Pearls • Human immunodeficiency virus-infected children and children
• Diagnosis in children less than 18 months—human whose infection status remains unknown should continue to
immunodeficiency virus polymerase chain reaction receive prophylaxis for the first year of life.
• Diagnosis in children above 18 months—human immuno
deficiency virus enzyme-linked immunosorbent assay
CONCLUSION
While interventions to prevent MTCT of HIV can dramatically
COTRIMOXAZOLE PROPHYLAXIS reduce the risk of pediatric infections to less than 2% with
Cotrimoxazole prophylaxis is safe, inexpensive, and highly continuation of breastfeeding.
effective in reducing morbidity and mortality among HIV-
infected infants and children, as well as in adolescents and Key points
adults. Ideally, all infants exposed to HIV should be started
on cotrimoxazole prophylaxis during the first 4–6 weeks of ))
Human immunodeficiency virus (HIV) infected pregnant
life, as recommended by the WHO. This period is particularly women should be started on triple antiretroviral therapy lifelong
critical for HIV-infected infants. Providing cotrimoxazole ))
All babies should receive nevirapine or zidovudine after birth
prophylaxis protects against serious, often fatal, opportunistic for 6 weeks
infections (OIs). It has also been recognized that cotrimoxazole ))
Exclusive breast feeding recommended
prophylaxis provides benefits beyond the prevention of ))
Early diagnosis consists of HIV deoxyribonucleic acid
pneumocystis pneumonia. polymerase chain reaction in infants less than 18 months.
Algorithm 1 SUGGESTED READINGs

Strategy for prevention of parent to child transmission of 1. Mangano A, Pittis G, Galindoz C, Bologna R, Sen L. Reliability of laboratory
human immunodeficiency virus markers of HIV-1 infection in Argentinean infants at risk of perinatal infection.
AIDS Patient Care STDs. 1998;12:691-6.
2. Shah I. Efficacy of HIV PCR techniques to diagnose HIV in infants born to HIV
infected mothers—an Indian perspective. JAPI. 2006;54:197-9.
3. Shah I. Management of Pediatric HIV, 2nd edition. Pediatric on Call, Mumbai.
2011.
4. Shah Ira, Dhabe H, Lala M. Prevention of maternal to child transmission of HIV:
A profile in indian children. 42nd National Conference of IAP (PEDICON—2005),
Kolkata, January 2005; JF/08(P).
5. The International perinatal HIV Group. The mode of delivery and the risk of vertical
transmission of human immunodeficiency virus type 1—a meta-analysis of 15
prospective cohort studies. N Engl J Med. 1999;340:977-87.
6. World Health Organization (WHO). Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection. [online] Available
from: http://www.who.int/hiv/pub/guidelines/arv2013/download/en/index.html.
[Accessed November 2015].
7. World Health Organization (WHO). Rapid advice: use of antiretroviral drugs
for treating pregnant women and preventing HIV infection in infants. 2010.
HIV, human immunodeficiency virus; ART, antiretroviral therapy. WHO.
252
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Chapter 56
Fever of Unknown Origin
Raju C Shah, Tanu Singhal
DEFINITION APPROACH TO fever of unknown origin

The definition of fever of unknown origin (FUO) is fever more The first step is to identify sick patients who need stabilization
than 101°F lasting for 3 weeks or more for which no cause is and urgent referral to a tertiary care center. Subsequently, all
apparent after 1 week of outpatient investigation. A practical attempts should be made to reach an etiologic diagnosis. A
definition of FUO is simply fever more than 101°F measured on detailed history is of paramount importance. History should
several occasions over a 7-day period. include:
• Whether and how fever was documented (it is not
uncommon to find children with history of prolonged fever
CAUSES
not to have fever documented by a thermometer)
The principal causes of FUO are listed in box 1. Infections • Duration and pattern of fever (distinguish from recurrent
account for most of the cases of FUO in children (60–70%). fever)
Most common among infectious causes are enteric fever, • Symptoms referable to all organ systems, weight loss
malaria, pulmonary or extrapulmonary tuberculosis, and • History of recurrent infections, oral thrush [human
urinary tract infections. Malignancies especially leukemia immunodeficiency virus (HIV) infection]
and autoimmune diseases chiefly juvenile rheumatoid • History of joint pain, rash, photosensitivity (autoimmune
arthritis (JRA) account for the remaining cases. Relatively disease)
rare causes include drug fever, temperature dysregulation, • History of contact with tuberculosis and animals
diabetes insipidus, sarcoidosis, ectodermal dysplasia, (brucellosis)
sensory autonomic neuropathies, etc. Even with extensive • Travel to endemic zones (kala azar)
investigations the cause of FUO remains undiagnosed in 10– • Drug history particularly anticholinergics (drug fever).
20% of the cases. History is followed by a complete physical examination.
Documentation of fever is necessary, followed by assessment
of general activity, nutritional status, and vitals. A head to toe
examination, after removing all clothes, is vital. The physical
Box 1: Causes of fever of unknown origin examination should be repeated on daily basis as new findings
Infectious causes may emerge that provide a clue to the etiology. One must keep
• Enteric fever, Malaria, Urinary tract infections, Tuberculosis, Kawasaki disease (though a relatively uncommon illness) in
Chronic hepatitis, HIV, Hidden abscesses (liver, pelvic), Mastoiditis, mind as here diagnosis before the 10th day of fever is crucial to
Sinusitis, Osteomyelitis, Meningitis, Infectious mononucleosis, prevent coronary complications.
Infective endocarditis, Brucellosis, CMV, Toxoplasmosis, Kala azar
Autoimmune causes Investigations and Management
• Systemic onset Juvenile Rheumatoid Arthritis, Kawasaki disease,
Systemic lupus erythematosus, Inflammatory bowel disease, Preliminary investigations, which should be repeated in all
Polyarteritis nodosa patients with FUO (even if done earlier) include complete
blood counts (CBC), peripheral smear (PS), malarial parasite,
Malignant causes
ESR, blood cultures, Widal test, chest X-ray, tuberculin test,
• Leukemia, Lymphoma, Langer Han Cell histiocytosis
urinalysis and culture, hepatic transaminases, and abdominal
Ch-56.indd 253 11/19/2016 4:13:38 PM

ultrasound. The CBC and PS will help in the differential an initial investigation as it helps in detecting a liver abscess,
diagnosis. If the counts are low or normal, enteric fever, malaria gall bladder wall thickening and sludge (often seen in enteric
and viral infections are a possibility. A high white blood cell fever), pyelonephritis, and retroperitoneal adenopathy. Non-
(WBC) count with neutrophilia indicates a bacterial infection/ specific mesenteric lymphadenopathy is a common finding
pus collection, possible Kawasaki’s disease, systemic onset JRA and usually merits no consideration. The author does not
or even tuberculosis. A high WBC count with lymphocytosis recommend doing a tuberculin test at this point if there is no
suggests a mononucleosis syndrome or a hematologic clinical or radiologic suspicion of tuberculosis and unless more
malignancy. Absolute eosinopenia is indicative of an acute common causes such as enteric are ruled out. This is because
bacterial/viral infection particularly enteric fever. A low platelet a positive tuberculin test at this juncture may be indicative of
count points toward malaria, enteric fever or a malignancy latent tuberculosis infection and may not be causally associated
whereas a very high platelet count is present in Kawasaki’s with the fever.
disease or systemic onset JRA. The usefulness of an erythrocyte If a diagnosis is established on the basis of the above
sedimentation rate (ESR) as an investigative modality in approach, appropriate treatment should be instituted. If
prolonged fever is often debated. It is not a sensitive or specific no diagnosis is made, clinical reassessment and further
investigation. Studies show that one-third of pulmonary investigations are merited. While second line investigations
tuberculosis had a normal ESR. Exceptionally, a very high ESR is are being planned and executed, treatment with intravenous
indicative of an autoimmune process such as Kawasaki disease ceftriaxone may be considered as enteric fever is an important
or JRA. The C-reactive protein (CRP) parallels ESR and may not cause of FUO in our country, especially in those cases with
help to differentiate a viral from bacterial etiology. However, a negative clinical/preliminary investigations (Algorithm 1).
very high CRP points to a bacterial infection or autoimmune Second-line investigations include HIV enzyme-linked
disease. Evaluation for malarial parasite is a must. Repeated immunosorbent assay, contrast enhanced computed tomo
thick smears are gold standard for diagnosis and may be sent graphy of chest and abdomen, bone marrow histology and
irrespective of the fever spike. However, in a setting where cultures, 2D echocardiogram, complement level, antinuclear
reliable microscopy is not available, the malarial antigen tests and rheumatoid factors, tissue biopsies if indicated. Other
may be used; the parasite lactate dehydrogenase tests score serologic tests that may be done include brucella serology,
over the histidine rich protein 2 based tests. The blood culture hepatitis B surface antigen, Paul Bunnel/Monospot test/
is a crucial investigation in this setting as enteric fever is the immunoglobulin M viral capsid antigen (VCA) for infectious
most common differential. Though, it should be sent prior to mononucleosis. Tests which are of no clinical value include
starting antibiotics, the yield is fair for Salmonella even if the serology and polymerase chain reaction in blood for
patient is on antibiotics. If infective endocarditis is suspected Mycobacterium tuberculosis or other organisms.
then three blood cultures at 30 minutes interval should be sent
and if brucellosis is being considered as a differential then the
lab should be informed so that the cultures are incubated for Algorithm 1
longer and not discarded within 5 days. Widal may be sent Approach to a child with prolonged fever
as it is the 7th day of fever, but the results should be carefully
interpreted. It may be considered positive if both TO and
TH/TA titers are 1: 120/ 1: 160 or more. Either TO/TH being
positive or titers of 1: 40/80 should be considered as false
positive. Similarly a negative Widal does not rule out enteric
especially if the patient has been on antibiotics. Typhidot M
or Tubex tests do not offer any advantage over the Widal and
are not routinely recommended. Liver enzymes both aspartate
aminotransferase (SGOT) and alanine aminotransferase
(SGPT) should be assayed as these are often elevated in
malaria, enteric, infectious mononucleosis, and brucellosis;
SGOT being higher than SGPT. Urinary tract infection is a
diagnostic possibility and hence urine routine is mandatory.
Features of urinary tract infection include presence of one
or more of the following: more than 10 pus cells/hpf of
centrifuged urine, positive leukocyte esterase, positive nitrite
tests, and presence of bacteria on the Gram stain. If the urine
routine is suggestive of a urinary tract infection (UTI) then
urine culture should be sent before starting antibiotics. This
is to confirm the diagnosis and also to know the antibiotic
susceptibility of the isolate. A chest X-ray should also be done
to pick up pneumonia or features of pulmonary tuberculosis.
254 An ultrasonography abdomen with pelvis is recommended as AKT, empirical antitubercular therapy?
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Chapter 56: Fever of Unknown Origin
Clinical Pearls ))
Tuberculosis serology has no place in the diagnosis of FUO
• Infections particularly tuberculosis is the commonest cause for ))
With patience and application of methods, it should be possible
fever of unknown origin in India to make a diagnosis of the etiology of FUO in most cases
• A high index of suspicion should be kept for diagnosis of ))
In a small number of cases, it may not be possible to arrive at
Kawasaki disease the etiologic diagnosis. In such cases, periodic reassessments
should be done as the disease may finally surface (e.g.,
• Empirical therapy should be avoided as far as possible
lymphoma, systemic onset juvenile eheumatoid artheits).
• The diagnosis often evolves with time and patience is the key. Some cases of FUO may self-resolve over time
))
Empirical use of steroids should be avoided.
Key points
))
A practical definition of fever of unknown origin (FUO) is fever SUGGESTED READINGs
for which a cause cannot be established despite 1 week of
investigations 1. Campbell J. Fever of unknown origin in a previously healthy child. Semin Pediatr
))
A detailed history and physical examination is most crucial. Infect Dis. 2002;13:64-6.
This should include travel history, contact with tuberculosis 2. Edwards K. Fever: From FUO to PFAPA to recurrent or persistent. Program and
and animals abstracts from the American Academy of Pediatrics National Conference and
Exhibition; October 9-13, 2004; San Francisco, California. Session S375.
))
The primary objective is to identify sick children and prompt 3. Miller L, Sisson B, Tucker L, Schaller J. Prolonged fevers of unknown origin in
referral to an appropriate center children: patterns of presentation and outcome. J Pediatr. 1996;12:419-23.
))
Kawasaki disease should always be considered as a possibility 4. Miller ML, Szer I, Yogev R, Bernstein B. Fever of unknown origin. Pediatr Clin
in young children North Am. 1995;42:999-1015.
))
Investigative approach should be stepwise starting with basic 5. Steele R. Fever of unknown origin. A time for patience with your patients. Clin
Pediatr. 2000;39:719-20.
investigations and proceeding to more complex ones.
255
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Section 7: Hematology/Oncology
Chapter 57
A Mass in the Abdomen:
The Way to Diagnosis
Gauri Kapoor
INTRODUCTION Box 1: Presentation of abdominal mass

The identification of an abdominal mass in a neonate or child Asymptomatic
is a cause for concern because of the possibility of malignant • Incidentally detected
disease. In addition, even benign conditions can be serious • Prenatal ultrasound
and warrant prompt evaluation and treatment. Hence, the • Immunization visit—alert pediatrician
pediatrician needs to be wary of these masses and give them Symptomatic
urgent attention.
• Abdominal distension (right upper quadrant, epigastric mass)
Although abdominal masses could be any one of the
• Respiratory distress
following:
• Weight loss, fever, and anorexia
• Fluid
• Fat • Anemia, thrombocytosis, and leukocytosis
• Flatus • Congestive heart failure, hydramnios, fetal hydrops
• Solid mass. • Bowel obstruction, urinary retention
For the purpose of this chapter we will focus on solid
abdominal masses. on initial management and in making the most appropriate
referral. The evaluation of a child with an abdominal mass
involves a number of possibilities and depends to some extent
PRESENTATION
on the age and sex of the patient, the location of the mass, and
Children with abdominal masses may be asymptomatic or the presence or absence of other potentially related signs and
symptomatic at diagnosis as shown in box 1. The asymptomatic symptoms, as well as features of the physical examination.
cases may be incidentally picked up on a routine prenatal Determination of the organ or tissue of origin of the mass can
ultrasound or detected by a family member or alert pediatrician narrow down the diagnostic possibilities considerably. Thus,
during an immunization visit. The general presentation varies a completion of a careful history and physical examination,
depending on the underlying pathology of the abdominal baseline laboratory studies, and limited diagnostic imaging
mass. Patients can present with difficulty with urination or studies can provide sufficient information to determine the
defecation if the mass physically obstructs the gastrointestinal diagnosis or to choose the appropriate subspecialist and
(GI) or genitourinary (GU) tract. Patients presenting with counsel the family.
constitutional symptoms such as fever and weight loss with Clues to diagnosis based on:
an abdominal mass are more likely to be suffering from a • Age and sex
malignant condition. Neuroblastoma and Wilms’ tumor are • Location of the mass
two conditions pediatricians must be vigilant about as they are • Organ of origin
the two malignant tumors in children where abdominal mass • Signs and symptoms
is commonly the initial presentation. • Examination findings
Although it is imperative that a child be referred quickly to • Investigative workup (limited).
the appropriate specialist (e.g., pediatric oncologist, pediatric Some of the common conditions that might produce
surgeon, nephrologist, gastroenterologist, gynecologist), an abdominal mass in a child are listed in table 1 and are
evaluation by the pediatrician is of great value in deciding categorized by the organ of origin. Abdominal masses in the
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Chapter 57: A Mass in the Abdomen: The Way to Diagnosis
Table 1: Differential diagnosis based on organ of origin in the Table 2: Common abdominal masses in the newborn
non-neonatal age group
Masses Frequency
Organ Malignant disease Nonmalignant disease Retroperitoneal masses 65%
Adrenal • Adrenal carcinoma • Adrenal adenoma • Polycystic kidneys, hydronephrosis, dysplastic
• Neuroblastoma • Adrenal hemorrhage kidneys, neoplasms, other
• Pheochromocytoma Gastrointestinal masses 25%
Gallbladder • Leiomyosarcoma • Choledochal cyst • Things that cause obstruction, hepatic masses, other
• Gallbladder Genitosacral masses 10%
obstruction
• Teratomas, congenital genital anomalies, ovarian
• Hydrops cysts, other
(e.g., leptospirosis)
Gastrointes- • Leiomyosarcoma • Appendiceal abscess
tinal tract
the location and type of mass, and features of the history or
• Non-Hodgkin • Intestinal duplication
physical examination.
lymphoma • Fecal impaction
The differential for an abdominal mass can be extensive
• Meckel’s diverticulum and quite daunting, as it incorporates many systems including
Kidney • Lymphomatous • Hydronephrosis the GI, GU, and endocrine system. An organized approach
nephromegaly • Multicystic kidney to abdominal masses includes thinking about possible
• Renal cell carcinoma • Polycystic kidney etiologies based on the location of the mass with regards to the
• Renal • Mesoblastic nephroma underlining abdominal anatomy as well as discerning likely
neuroblastoma • Renal vein thrombosis pathologies based on the age of the patient and associated
• Wilms’ tumor • Hamartoma symptoms or signs.
Liver • Hepatoblastoma • Focal nodular
• Hepatocellular hyperplasia Clinical Pearl
carcinoma • Hepatitis • Most abdominal masses in neonates are benign unless they
• Embryonal sarcoma • Liver abscess are solid.
• Liver metastases • Storage disease
• Mesenchymoma
Lower geni- • Ovarian germ cell • Bladder obstruction HISTORY
tourinary tumor • Ovarian cyst
tract
When attempting to diagnose an abdominal mass, a proper
• Rhabdomyosarcoma • Hydrocolpos
history with a focused physical exam is necessary to direct you
of bladder
to the proper diagnostic tests to order, or the right specialist to
• Rhabdomyosarcoma
of prostate
refer too (i.e., pediatric oncologist, surgeon, gastroenterologist,
nephrologists, or gynecologist).
Spleen • Acute or chronic • Congestive
leukemia splenomegaly
• Histiocytosis • Histiocytosis
Age
• Hodgkin lymphoma • Mononucleosis The age of the patient is very important when approaching
• Non-Hodgkin • Portal hypertension abdominal masses in the pediatric population and should be
lymphoma • Storage disease the first question asked. Malignant tumors are uncommon
in the newborn period. These conditions are often related
Miscella- • Hodgkin lymphoma • Teratoma
to the kidney. Posterior urethral valves are manifested
neous • Non-Hodgkin • Abdominal hernia
during the newborn period by a very large urinary bladder.
lymphoma • Pyloric stenosis Hydronephrosis secondary to distal obstruction may result
• Pelvic • Omental or in a unilateral or bilateral flank mass. A multicystic kidney
neuroblastoma mesenteric cyst
also may be found at this time. Other considerations include
• Retroperitoneal
neuroblastoma
developmental abnormalities, such as duplications or cysts
of abdominal organs. Amongst the malignant conditions,
• Retroperitoneal
rhabdomyosarcoma neuroblastoma and extragonadal germ cell tumors are most
• Retroperitoneal common, followed by hepatoblastoma and Wilms’ tumor.
germ cell tumor Moreover, of the malignant conditions, children younger
than 2 years are more likely to suffer from neuroblastoma and
hepatoblastoma, whereas older children more frequently have
neonatal age group are often benign as shown in table 2, and Wilms’ tumor, hepatocellular carcinoma, GU tract tumors, and
will be further discussed in the section on age. Not all of these germ line tumors.
possibilities need be considered in every patient; many can Other important points to be noted in history are detailed 257
be eliminated on the basis of the age and sex of the patient, in table 3.
ch-57.indd 257 11/19/2016 4:15:32 PM

Table 3: History: special points Table 5: Laboratory investigations

History Clue Test Indication/clues
Age of the child Neonates (benign), children Complete blood count with • Anemia, neutropenia, or
(malignant) differential thrombocytopenia can indicate
How long has it been there Months to years (benign) bone marrow infiltration
How fast is it growing Faster growing (malignant) Bone marrow biopsy and/or • Indicated if one or more
aspiration bone marrow cell lines are
Pressure symptoms Constipation, urine retention compromised
Constitutional symptoms Fever, weight loss, pallor, bruising Chemistry panel • Electrolyte abnormality
(infection vs. marrow infiltrative) electrolytes uric acid, lactate indicates pathology with the
Watery diarrhea Neuroblastoma secreting vasoactive dehydrogenase kidney or tumor lysis syndrome
intestinal peptide • Elevated uric acid or lactate
Hematuria Renal pathology (Wilms’ tumor) dehydrogenase suggest a high
grade malignancy
Opsomyoclonus Neuroblastoma
Urinalysis • Hematuria or proteinuria
Periorbital ecchymosis, Neuroblastoma (Raccoon eye)
suggest renal involvement
ptosis
Acute abdomen Intussusception (benign or ileocecal Urinary homovanillic acid • Elevated levels indicate
lymphoma) and vanillylmandelic acid neuroblastoma or
pheochromocytoma
Cushing’s syndrome Adrenal adenoma, adrenocortical
carcinoma Tumor markers: serum • Elevated levels may occur in
B human chorionic teratomas, liver tumors, and
Genetic syndrome or Familial adenomatosis polyposis, gonadotropin, a-fetoprotein germ cell tumors
inherited predisposition Gardner’s, Beckwith-Weidemann
(Wilms’, hepatoblastoma,
adrenocortical carcinoma), aniridia look for in a child with abdominal mass. One must be patient
(Wilms’), hemihypertrophy (Wilms’) as physical examination in young children can be a difficult
proposition. Table 5 lists some of the important clinical findings
to look for during examination.
Clinical Pearl
• Abdominal masses in older children are usually malignant and INVESTIGATIONS
need prompt evaluation.
All children with abdominal masses should have a complete
blood count and peripheral smear examination as it may throw
EXAMINATION up important clues to diagnosis. Further investigations would
include baseline chemistries and specific tumor markers on
The importance of a thorough physical examination with
the basis of the clinical differential diagnoses (Table 5).
vitals (including temperature and blood pressure) cannot
be overemphasized. Table 4 highlights the salient features to
IMAGING
Table 4: Points to be considered during examination An abdominal mass in children is often first assessed by
System Clinical features a plain abdominal radiograph to rule out GI obstruction.
General appearance Well, ill, cachexic, anxious, in pain Next, an ultrasound study is helpful and can be done
without sedation. It is noninvasive, easily available and fairly
Weight and height Plot on growth chart
inexpensive and is sometimes the first investigation done
Vitals Include blood pressure, temperature for an abdominal mass. It can usually identify the organ of
Skin Jaundice, café au lait, nevi, freckles, skin origin of the mass, such as the kidney, adrenal gland or liver,
nodules, petechiae, purpura etc. and helps differentiate solid from cystic masses. Further
Head, neck, eyes, Pallor, aniridia, periorbital ecchymosis, information is provided in table 6.
nose throat ptosis, lymphadenopathy An algorithmic approach to evaluation of a child with
Abdomen Details of mass, quadrant, consistency, abdominal mass is depicted in algorithm 1. Once a malignancy
tenderness, mobility, bruit, veins over it, is suspected it is recommended that the child be referred to
possible organ of origin, bowel sounds a pediatric oncology unit, since early diagnosis of pediatric
Cardiovascular Murmurs cancers are associated with very good cure rates. Delayed
Respiratory Wheeze, superior vena cava syndrome
diagnosis not only reduces the chances of cure but is also
associated with higher complication rate. Parents should,
Genitalia Normal/abnormal
therefore, be appropriately counseled at this time and the
258 Others Stigmata of congenital syndrome pediatrician has a very important role to play in bridging the
(e.g., hemihypertrophy) gap between the family and the oncology center.
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Chapter 57: A Mass in the Abdomen: The Way to Diagnosis
Algorithm 1
Algorithmic approach to diagnosis of an abdominal mass in a child
GI, gastrointestinal; GU, genitourinary; US, ultrasound; CT, computed tomography; CBC, complete blood count; AFP, alpha-fetoprotein; b-HCG, b human chorionic
gonadotropin; VMA, vanillylmandelic acid; HVA, homovanillic acid; KFT, kidney function test; PNET, primitive neuroectodermal tumor.
Table 6: Imaging studies

))
Neuroblastoma and Wilms’ tumor are the two most common
Test Indication/clue malignant conditions that present as abdominal masses in
Plain • First imaging study to be ordered young children
abdominal • Helps determine the location and density of ))
The pediatrician plays an important role in early diagnosis,
X-ray the abdominal mass. prompt evaluation, and appropriate referral
• Multiple air fluid levels or absence of air in the ))
Most childhood cancers have good cure rates if diagnosed in
rectum—indicate obstruction time and treated properly.
• Calcification may indicate a neuroblastoma,
teratomas, kidney stones, or biliary stones
Ultrasound • Inexpensive and safe modality SUGGESTED READINGs
• Useful for discerning between solid versus
cystic mass 1. Broecker B. Non-Wilms’ renal tumors in children. Urol Clin North Am.
2000;27(3):463-9, ix.
Computed • Used to attain more specific anatomic
2. Castleberry RP. Biology and treatment of neuroblastoma. Pediatr Clin North Am.
tomography information about the abdominal mass
1997;44(4):919-37.
scan • CT scan can be used to determine invasion of 3. Golden CB, Feusner JH. Malignant abdominal masses in children: quick guide to
the malignant lesion to adjacent structures evaluation and diagnosis. Pediatr Clin North Am. 2002,49(6);1369-92.
Magnetic • Used for greater anatomic detai 4. Graf N, Tournade MF, deKraker J. The role of preoperative chemotherapy
resonance • Specially for imaging of brain and spine in in the management of Wilms tumor: The SIOP Studies. Urol Clin North Am.
imaging patients presenting with neurologic deficits 2000;27(3):443-54.
5. Groff DB. Pelvic neoplasms in children. J Surg Oncol. 2000;77(1):65-71.
6. Grossman H. Evaluating common intra-abdominal masses in children - a systematic
roentgenographic approach. CA Cancer J Clin. 1976;26(4);219-35.
Key points
7. Neville HL, Ritchey ML. Wilms’ tumor, overview of the National Wilms Tumor Study
))
Abdominal masses in children are a cause for concern Group results. Urol Clin North Am. 2000;27(3):435-42.
because of the possibility of malignant disease and need 8. Pappo AS, Shapiro DN, Crist WM. Rhabdomyosarcoma. Biology and treatment.
Pediatr Clin North Am. 1997;44(4):953-72.
prompt evaluation
9. Pfeifer SM, Gosman GG. Evaluation of adnexal masses in adolescents. Pediatr
))
Most abdominal masses in neonates are benign unless they Clin North Am. 1999;46(3):573-92.
are solid 10. Rahhal RM, Eddine AC, Bishop WP. A Child with an Abdominal Mass. Pediatric
))
Age of the patient, along with history and examination Rounds. 2006;37-42.
findings provide important clues to the possible organ of 11. Schteingart DE. Management approaches to adrenal incidentalomas. Endocrinol
origin and underlying pathology Metab Clin North Am. 2000;29(1):127-39. 259
12. Stringer MD. Liver tumors. Semin Pediatr Surg. 2000;9(4):196-208.
ch-57.indd 259 11/19/2016 4:15:32 PM

CHAPTER 58
Approach to a Child
with Persistent Anemia
Mamta V Manglani
INTRODUCTION Table 1 gives the normal values (normal mean, lower limit)
of various hematological parameters at different age groups.
Anemia in children is the most common cause of referral The initial diagnostic approach to the anemic patient
to a pediatric hematology-oncology clinic in our country. should include detailed history, physical examination, and
It reflects the disturbance of the dynamic balance between screening laboratory tests followed by specific laboratory tests
production and destruction of erythrocytes and hemoglobin. as indicated to confirm the diagnosis.
In normal subjects, the average life span of red cell, i.e., time
between the release of red cell from bone marrow and its
disappearance from circulation is between 100 and 120 days.
HISTORY IN THE DIAGNOSIS OF ANEMIA
Approximately 1% of the red cells are destroyed each day and
replaced by new cells released from marrow. Any disruption Age
of this balance, such as reduced production or increased Nutritional anemia is uncommon below the age of 6 months
destruction, leads to anemia. (especially in term breastfed infants), except in preterm infants.
Iron deficiency anemia (IDA) is most common in the age group
DEFINITION OF ANEMIA of 6 months to 3 years and 11–17 years (adolescent) age group.
Dietary habits and food fads may be responsible for anemia in
Anemia is defined as a reduction in the red cell mass and/ adolescent period. Development of anemia is almost always
or reduction in hemoglobin or hematocrit. A child is said to insidious in children and may go unnoticed till hemoglobin
be anemic when the hemoglobin and/or hematocrit is two concentration drops to as low as 3–4 g/dL, particularly in
standard deviations below mean for normal population. This nutritional anemia. Hemoglobinopathies (thalassemia major)
results in 2.5% of normal population being classified as anemic. commonly present during 6–18 months of age and rarely
On the other hand, some of the anemic individuals would be before that age.
classified as normal and these would only be recognized after Anemia manifesting in the neonatal period is generally
a response to treatment. as a result of blood loss, including fetomaternal hemorrhage,
TABLE 1: Normal blood values at different age groups

Age Hb g/dL RBC million/mL HCT % MCV (m3) MCH (pg) MCHC (%) Reticulocyte (%)
1 day 18.0 5.14 61 119 36.0 31.6 3.2
4 weeks 14.2 4.0 43 106 35.5 33.5 0.6
1 year 11.6 4.6 35 77 25.0 33.0 0.9
10–12 years 13.0 4.8 39 80 27.0 33.0 1.0
Adult men 16.0 5.4 47 87 29.0 34.0 1.0
Adult women 14.0 4.8 42 87 29.0 34.0 1.0
Hb, hemoglobin; RBC, red blood cell; Hct, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin
concentration.
CHAPTER 58: Approach to a Child with Persistent Anemia
fetofetal hemorrhage and occult hemorrhage, or due to anemia due to folate deficiency may be seen in children fed
hemolysis as a result of isoimmunization, uncommonly predominantly goat’s milk. Nutritional anemias are commonly
glucose-6-phosphate dehydrogenase (G6PD) deficiency, seen in adolescent females due to various food fads.
spherocytosis or due to congenital infections.
History of Drug Ingestion
Clinical Pearls Certain drugs cause hypoplasia of the bone marrow. Some of
• A neonate with hemoglobin of 11 g/dL is severely anemic, these are chloramphenicol, nonsteroidal anti-inflammatory
whereas a 1-year-old infant with same hemoglobin is normal drugs, anticonvulsants, antihistaminics, sulfonamides, heavy
• When interpreting presence or severity of anemia, age plays metals, etc. Oxidant-induced hemolytic anemia may occur in
an important role. people having G6PD deficiency (sulfonamides, antimalarials
such as primaquine, quinine and mefloquine, vitamin C
and K, furazolidone, nalidixic acid, etc.). Penicillins and
cephalosporins, a-methyldopa, stibophen, etc. are known to
Gender/Family History/Inheritance
precipitate autoimmune hemolytic anemias. Certain drugs
Though nutritional anemia is more common among females can cause megaloblastic anemias due to altered metabolism
during adulthood, the incidence is equal in both genders of folate and vitamin B12. These include phenytoin, folate
during childhood. Certain inherited anemias are transmitted antagonists, etc.
as X-linked recessive and hence are commonly seen in male
children. This includes G6PD deficiency; hence similar history Infections and Infestations
of anemia should be enquired in other male siblings, maternal
History of intrauterine infections (Toxoplasmosis, Rubella,
male cousins, maternal uncles, and maternal grandfather.
Cytomegalovirus, Herpes Simplex and Other Agents) should
Hereditary spherocytosis is an autosomal dominant disorder,
be elicited when dealing with neonatal anemia, especially
whereas hemoglobinopathies like thalassemia, sickle cell
when associated with hepatosplenomegaly, purpura, etc.
anemia, etc. are inherited as autosomal recessive conditions.
Hepatitis-induced aplasia and infection-induced pure red
It is important to enquire about family history of anemia,
cell aplasia or hemolytic anemia (malaria) need to be kept in
jaundice, gallstones, splenectomy, etc. in the other members
mind. Anemia also may be associated with chronic infections
of the family. A history of consanguineous marriage is also
like tuberculosis, tropical sprue, kala-azar, or with chronic
helpful in recessive conditions. Hence a detail pedigree chart
inflammations like collagen disorders, malignancies, etc.
including the family members, who have expired, should
Anemia due to worms, especially hookworms, is common in
be obtained.
developing countries.
Community Diarrhea
Certain types of anemias are known to occur in particular Malabsorption syndromes due to varied causes could be a
communities. G6PD deficiency is commonly seen in cause for nonresponding nutritional anemias.
Parsees, Punjabis, and Sindhis, whereas thalassemia is
common amongst Sindhis, Punjabis, Lohanas, Bhanushalis,
Kathiawadis, Mahars, Agris, Bauddhas, Kolis, Lingayat, Reddys, EXAMINATION FINDINGS AS
and Gaud communities. Sickle cell anemia is more commonly A CLUE TO THE DIAGNOSIS OF ANEMIA
seen in hilly and tribal communities especially around Nagpur,
Vidharbha, Andhra Pradesh, Orissa, etc. hemoglobin E is seen
more in Eastern India among Bengalis and hemoglobin D in
Skin
Punjabis and North Indians. Hyperpigmentation is common with Fanconi’s anemia,
dyskeratosis congenita, megaloblastic anemia, etc. (Fig. 1).
Dietary History Petechiae and purpura may be present in aplastic anemia,
leukemias, hemolytic uremic syndrome, etc. Leg ulcers are
Nutritional anemias are associated with poor dietary intake
seen in chronic congenital hemolytic anemias such as HbS
of iron, folic acid, proteins, and vitamin E in the diet. Breast
and HbC disease and occasionally in homozygous thalassemia
milk contains lesser quantities of iron; however, it has a very
(Fig. 2). Cavernous hemangiomas may be associated with
high bioavailability. Hence, IDA is uncommon in exclusively
micro angiopathic hemolytic anemia. Jaundice suggests
breastfed infants before 4–6 months of age. Inadequate iron
hemolytic anemias, hepatitis-induced aplasia.
containing weaning foods and/or predominantly milk-based
diet beyond 4–6 months of age contribute significantly to
occurrence of IDA in late infancy. History of pica may be
Facies
present as a cause or effect of IDA. Lead toxicity should be Presence of hemolytic facies is seen in congenital hemolytic
ruled out in such children if there is a history of exposure to anemias such as thalassemia major, sickle cell anemia and
lead directly or through parents’ occupation. Megaloblastic occasionally in severe chronic IDA (Fig. 3). 261
SECTION 7: Hematology/Oncology
Eyes
Fanconi’s anemia may have microphthalmia and micro
cornea, besides microcephaly (Fig. 4). Cataracts may suggest
galactosemia with hemolytic anemia in the neonatal period.
Vitreous hemorrhages are seen in sickle cell disease and retinal
hemorrhages may occur in severe chronic anemias. Edema of
the eyelids should make one suspect infectious mononucleosis,
or exudative enteropathy with iron deficiency. Visual loss may
be one of the features of osteopetrosis. Blue sclera is often a
feature of IDA (Fig. 5).
Hands and Nails

Thumb anomalies suggest constitutional hypoplastic anemias
(Diamond-Blackfan anemia, Fanconi’s anemia) (Figs 6 and 7).
If associated with radial anomalies, it is more likely to be
Fanconi’s anemia. Presence of platynychia and/or koilonychias
Fig. 1: Hyperpigmentation over distal phalanges in megaloblastic
(Fig. 8) are pathognomonic of IDA.
anemia
Fig. 2: Leg ulcer in an adolescent with thalassemia intermedia Fig. 4: Microcephaly in Fanconi’s anemia
262 Fig. 3: Hemolytic facies in a thalassemic child Fig. 5: Blue sclera in a child with iron deficiency anemia
Clinical Pearls
• Presence of blue sclera, platonychia or koilonychias, and/or
angular stomatitis suggests iron deficiency anaemia
• Iron deficiency anemia is a manifestation and not an etiological
diagnosis.
Mouth
Glossitis is seen in vitamin B12, folate, and iron deficiency;
angular stomatitis (Fig. 9) and bald tongue are seen in iron
deficiency. Occasionally, gum hypertrophy (Fig. 10) may
be seen in a patient with acute promyelocytic or acute
myelomonocytic leukemia.
Fig. 6: Ape thumbs in a case of Diamond-Blackfan anemia
Fig. 7: Thumb anomaly in Fanconi’s anemia Fig. 9: Angular stomatitis in a case of malnutrition and iron deficiency
anemia
Fig. 8: Koilonychia in a child with iron deficiency anemia Fig. 10: Gum hypertrophy in a child with acute promyelocytic leukemia 263
Clinical Pearl LABORATORY APPROACH TO ANEMIA

The investigations in children with anemia should be done
• Presence of lymphadenopathy, gum hypertrophy, and in a phased manner as expensive confirmatory tests may be
hepatosplenomegaly should prompt exclusion of malignancies useless and unnecessary in concluding the cause of anemia,
especially in presence of affection of other cell lines, i.e., white unless done judiciously. Therefore, it is imperative to follow
cells and platelets. a stepwise testing to get a better yield without spending the
patient’s money unnecessarily.
Investigations should be done as follows:
Lymphadenopathy • Screening tests
Lymphadenopathy would prompt one to consider various • Definitive diagnostic tests.
malignant disorders, such as leukemias, lymphomas, metastatic
malignancies such as neuroblastoma, infections such as Screening Tests
tuberculosis, infectious mononucleosis, human immuno Screening tests include:
deficiency virus, cytomegalovirus (CMV), etc. (Fig. 11). • Complete blood count including hematocrit and blood
indices
Hepatosplenomegaly • Reticulocyte count
Presence of hepatosplenomegaly almost always rules out • Examination of the peripheral smear.
hypoplastic anemia except the infiltrative causes of marrow
suppression. It suggests hemolytic anemias, the infiltrative Complete Blood Counts
causes such as leukemias, osteopetrosis, myelofibrosis, • Hemoglobin: the severity of anemia can be gauged with the
myelodysplasias, etc. (Fig. 12). value of hemoglobin
• Hematocrit: it is useful in neonates to diagnose poly
cythemia. In sickle cell disease, it is important to maintain
the hematocrit at 30–35%
• Red cell indices: these include mean corpuscular volume
(MCV), mean corpuscular hemoglobin (MCH), mean
corpuscular hemoglobin concentration (MCHC), and red
cell distribution width (RDW). This helps in typing the
anemia.
Based on MCV, MCH, and MCHC, anemias can be classified
into three categories to give a morphologic classification.
Besides, the RDW further elucidates the cause of anemia.
Along with the findings of the peripheral smear findings, most
anemias can be categorized completely with a few specific
confirmatory tests.
• Microcytic, hypochromic anemia—MCV <80 μ3, MCH <27
pg, and MCHC <32%
• Macrocytic anemia—MCV >95 μ3
• Normocytic, normochromic anemia—MCV 80–95 μ3,
Fig. 11: Lymphadenopathy in a case of lymphoma MCH 27–32 pg, and MCHC 32–36%.
Red cell distribution width: it is the measure of the degree
of anisocytosis. This is calculated from the histogram of MCV
and expressed as a coefficient of variation. The normal values
are 11.5–14.5%. Along with MCV, it can help categorize anemias
further. The relationship of MCV and RDW is given in table 2.
TABLE 2: Relationship of mean corpuscular volume and red cell

distribution width
RDW Low MCV Normal MCV High MCV
Normal Thalassemia trait Normal Aplastic anemia
Lead poisoning
High Iron deficiency Early IDA Newborns
HbH disease Liver disease Vitamin
HbS/thalassemia Mixed nutritional B12/folate
trait deficiency deficiency
264 MCV, mean corpuscular volume; RDW, red cell distribution width; IDA, iron
Fig. 12: Anemia and hepatosplenomegaly with malaria deficiency anemia
Hemoglobin distribution width (HDW): it is obtained

from the histogram of MCHC and depicts the hemoglobin
distribution. Combining MCV, RDW, and HDW can offer better
categorization of anemias. However, most automated cell
counters presently used in our country do not have the feature
of HDW.
Reticulocyte Count
As reticulocytes are the immediate precursors of mature red
blood cells (RBCs), their presence in the peripheral blood
reflects the marrow activity in response to anemia. Reticulocyte
count is expected to be high in children with anemia if they
have a responsive marrow. Therefore, one needs to consider
whether the reticulocytes have increased proportionate to the
degree of anemia. This is done by calculating the corrected
reticulocyte count as:
Reticulocyte count × Observed HCT Fig. 13: Microcytic, hypochromic smear in iron deficiency anemia
Desired HCT
Example: If the reticulocyte count of a child is 6% and
the HCT is 15%, the corrected reticulocyte count would be as
follows: 6 × 15/45 = 2%, which is not as high as it seems.
Polychromasia and basophilic stippling on peripheral
smear are indirect evidences of reticulocytosis.
Reticulocyte count is increased in hemolysis, hemorrhage,
or after starting therapy for nutritional deficiencies. However,
it is low or normal in nutritional anemias and it is below 1% in
bone marrow suppression.
Clinical Pearls
• Reticulocyte count is a window to the bone marrow and if
normal to increased suggests the pathology does not exist in
the marrow
• Red blood cell indices along with red cell distribution width
and reticulocyte count can help diagnose many of the causes
of anemia. Fig. 14: Macrocytes with macro-ovalocytes and hypersegmented
neutrophils in megaloblastic anemia
Peripheral Smear Examination seen in autoimmune hemolytic anemias, ABO

This is the single most important, cost-effective test for isoimmunization in the newborn, severe burns,
anemia. It not only suggests the type of anemia but also gives Clostridium welchii sepsis, etc. (Fig. 15)
the clue to the underlying cause and disease. The following –– Ovalocytes: oval-shaped cells are seen in
morphologic information can be obtained by reviewing a megaloblastic anemia (macro-ovalocytes), IDA,
peripheral blood smear: chronic hemolytic anemias like thalassemia, etc.
–– Elliptocytes: elliptical cells are seen in congenital
Red blood cell morphology elliptocytosis where more than 50% of cells will
{{ Size: be elliptical and also there will be elongated rod-
–– Microcytic: microcytic red cells are smaller than like cells in addition. Elliptocytes are also seen in
normal (Fig. 13) thalassemia, myelophthisic anemia, megaloblastic
–– Macrocytic: macrocytic red cells are larger than anemia, etc.
normal cells (Fig. 14) –– Helmet cells/schistocytes: broken cells like helmets
{{ Shape (poikilocytosis): or caps are seen in microangiopathic hemolytic
–– Spherocytes: these are cells without a central anemia, uremia, malignant hypertension, disse
pallor and are seen in hereditary spherocytosis minated intravascular coagulation (DIC), etc.
where virtually all red cells are spherocytic, (Fig. 16)
barring milder varieties, where about 30% of –– Acanthocytes (spur cell): RBCs with several
cells would be spherocytic. Spherocytes are also irregularly spaced large, coarse projections or 265
Fig. 15: Spherocytes in a peripheral smear of a child with hereditary Fig. 17: Shows irreversibly sickled cells in a sickle cell disease
spherocytosis
Fig. 16: Broken cells, helmet cells with thrombocytopenia in a case of Fig. 18: Target cells in hemoglobinopathies
hemolytic uremic syndrome
spicules of varying length and width are seen in producing concentric dark light zones which gives a
abetalipoproteinemia, liver cirrhosis or metastasis, Bull’s eye appearance. They are a kind of leptocytes
etc. or thin cells in which surface area to volume ratio
–– Echinocytes: RBCs with regularly spaced, uniform is high and is out of proportion to its meager Hb
in size, more numerous, and spicules are seen in content. They are seen in thalassemias, HbC, E, SS
uremia, PK or phosphoglycerate kinase deficiency, diseases, liver disorders, IDA, post-splenectomy,
cardiac bypass, burns, etc. sideroblastic anemia, etc. (Fig. 18)
–– Tear drop cells: RBCs with a tear drop shape are –– Stomatocytes: these are RBCs with a central
seen in thalassemia, myelofibrosis, myelophthisic slit or stoma in place of central pallor. It is seen
anemia, etc. in hereditary stomatocytosis, elliptocytosis,
–– Sickle cells are seen in sickle cell disease and alcoholism, etc.
double heterozygous states like HbSC, HbSD, HbS- –– Cabot’s ring: these are basophilic rings circular
thalassemia, etc. (Fig. 17) or twisted in figure of 8, staining reddish purple
–– Xerocytes: dense, dehydrated, contracted cell seen on Wright’s stain. They represent the remnants of
in congenital xerocytosis nuclear membrane or mitotic spindle apparatus
–– Leptocytes: normal or large cells with thin and are seen in severe megaloblastic anemia, lead
membrane poisoning, thalassemias, etc.
–– Target cells: in these cells, hemoglobin is –– Heinz body: seen on a reticulocyte smear (supravital
266 concentrated in the center and in the periphery staining), as a deep purple, irregularly shaped small
body in the RBCs in G6PD deficiency, unstable ALGORITHMS TO DIAGNOSE ANEMIA

hemoglobinopathy, thalassemia, chemical injury, BASED ON VARIOUS INVESTIGATIONS
etc.
–– Howell-Jolly bodies: they are small, rounded, Methods to diagnose anemia based on various investigation
densely staining nuclear remnants occurring are represented in algorithms 1–3.
single, doubly or rarely more frequently. They
are eccentrically placed and stain reddish blue ALGORITHM 1
or dark purple on Wright’s stain. They are seen
Microcytic, hypochromic anemia
in megaloblastic anemia, postsplenectomy,
functional asplenia, IDA, leukemia, congenital
dyserythropoietic anemia, etc.
–– Siderocytes: these are RBCs with non-Hb iron
particles visible when stained with Prussian blue/
safranin and are seen in sideroblastic anemia,
aplastic anemia, hemolytic anemia, chronic
infection and inflammation
–– Pappenheimer bodies: single or double blue staining
granules or dots on RBCs seen in hemolytic anemia,
postsplenectomy and represent the remnants of
ribosomes, mitochondria and ferric iron
–– Normoblasts: these are seen when there is a shift
of RBC maturation to the left as seen in cases of
congenital hemolytic anemias such as thalassemias, HPLC, high performance liquid chromatography..
sickle cell disease, congenital dyserythropoietic
anemias, hemorrhage, etc. (Fig. 19)
ALGORITHM 2
Confirmatory Tests Macrocytic anemia
These would be based on the screening test results. As per the
algorithms given below and the suspected diagnosis, these
confirmatory tests should be performed or ordered.
These include Coomb’s test, G6PD estimation, osmotic
fragility and flow cytometry for membrane defects, bone
marrow aspiration and biopsy, high-performance liquid
chromatography for hemoglobinopathies, serum iron studies,
ferritin, vitamin B12 and folate levels as well as blood lead
levels. Besides these, certain corroborative tests such as serum
bilirubin, LDH, haptoglobins, etc. also assist in diagnosing the
cause of anemia.
Occasionally, workup for a-thalassemia, unstable hemo
globins, rare hemoglobin variants, cytogenetics, and other
RBC enzyme levels may be required.
ALGORITHM 3
Normocytic, normochromic
267
Fig. 19: Smear showing a bizarre picture with normoblasts and target
cells in thalassemia major
CONCLUSION 3. Beuttler E. The red cell indices in the diagnosis of iron deficiency anemia. Ann
Intern Med. 1959;50:313-22.
With detailed history taking and relevant clinical examination, 4. Buch AC, Karve PP, Panicker NK, Singru SA, Gupta SC. Role of red cell distribution
basic screening tests, and minimum specific tests, it is possible width in classifying microcytic hypochromic anemia. J Indian Med Assoc.
2011;109:297-9.
to diagnose the type of anemia and institute appropriate
5. de Benoist B, McLean E, Egli I, Cogswell M (Eds). Worldwide prevalence of anaemia
treatment. This approach would definitely help in minimizing 1993–2005: WHO global database on anaemia.
the need for useless and expensive tests in children with anemia. 6. DeMaeyer EH, Adiels-Tegman M. The prevalence of anemia in the world. World
Health Stat Q. 1985;38:302-16.
KEY POINTS 7. Hermiston ML, Mentzer WC. A practical approach to the evaluation of anemic child.
Pediatr Clin North Am. 2002;49:877-91.
))
History and examination offers many important clues to the 8. Irwin JJ, Kirchner JT. Anemia in children. Am Fam Physician. 2001;64:1379-86.
diagnosis of anemia 9. Janus J, Moerschel SK. Evaluation of anemia in children. Am Fam Physician.
2010;81:1462-71.
))
A proper evaluation of the complete blood count especially
10. Lee GR. Iron deficiency and iron deficiency anemia. In: Lee GR, Bithel TC, Foester
red cell indices along with red cell distribution width, J, Athens JW, Lukens JN (Eds). Wintrobe’s Clinical Hematology. 9th ed. Philadelphia:
peripheral smear, and reticulocyte count would help in Lea & Febiger; 1993. pp. 808-39.
concluding the type of anemia in almost all patients 11. Lokeshwar MR, Manglani M. Antenatal supplementation--effect on iron status of
))
A stepwise approach helps in limiting the investigations infants. Indian Pediatr. 1990;27:677-80.
required to reach a diagnosis. 12. Manglani M, Lokeshwar MR, Vani VG, Bhatia N, Mhaskar V. ‘NESTROFT’-an effective
screening test for beta-thalassemia trait. Indian Pediatr. 1997;34:702‑7.
13. Mehta BC. Approach to a patient with anemia. Indian J Med Sci. 2004;
58:26-9.
SUGGESTED READINGS 14. Orkin SH, Fisher DE, Look AT, Lux SE, Ginsburg D, Nathan DG (Eds). Nathan and
Oski’s Hematology of Infancy and Childhood, 7th ed. Saunders, an imprint of Elsevier
1. Bessman JD, Feinstein DI. Quantitative anisocytosis as a discriminant between iron Inc.; 2009.
deficiency and thalassemia minor. Blood. 1979;53:288-93. 15. Vasanta G, Pawashi AR, Susie H, Sujatha T, Raman L. Iron nutritional status
2. Bessman JD, Gilmer PR, Gardner FH. Improved classification of anemia by MCV and of adolescent girls from rural area and urban slum. Indian Pediatr. 1994;31:
RDW. Am J Clin Pathol. 1983;80:322-6. 127-32.
268
Chapter 59
Algorithmic Approach to
Thrombocytopenia in Children
ATK Rau, K Shreedhara Avabratha
INTRODUCTION Decreased Platelet Production

Platelets are discoid, non-nucleated cells of 2–3 mm in • Pancytopenia: leukemia, bone marrow infiltration, hypo
diameter and 5–9 fL in volume, produced in the bone marrow plastic anemia, viral infections [e.g., human immuno
by fragmentation of megakaryocytes. Each megakaryocyte deficiency virus (HIV)], drugs, and radiation
produces about 4,000 platelets. These platelets circulate in the • Isolated thrombocytopenia: rare congenital defects—
blood for about 7–10 days and are subsequently culled by the thrombocytopenia-absent radius syndrome, Wiskott-
spleen and bone marrow. The main function of the platelet is Aldrich syndrome, congenital amegakaryocytic thrombo
the formation of a platelet plug at the site of vascular injury cytopenia, giant platelet disorder, e.g., Bernard-Soulier
(primary hemostasis). The normal range of platelet count is syndrome, viral infections like HIV, Epstein-Barr virus.
between 150,000/cumm and 450,000/cumm.
Thrombocytopenia is defined as platelet count of less Increased Destruction
than 150,000/cumm. However, clinically significant thrombo
cytopenia is defined as any count less than 100 × 109/L; • Immune: immune thrombocytopenic purpura (ITP)—
furthermore, it is considered severe if the platelet count is the most common cause of thrombocytopenia in
below 30 × 109/L, moderate if it is between 30 × 109/L and 50 × children, neonatal thrombocytopenia (alloimmune or
109/L, and mild (and usually asymptomatic) if above 50 × 109/L. autoimmune), and autoimmune disease—systemic lupus
erythematosus, drugs like heparin
CLINICAL FEATURES • Nonimmune: malaria, dengue, disseminated intravascular
coagulation (DIC), hemolytic uremic syndrome (HUS),
The clinical features of thrombocytopenia are due to the sepsis, thrombotic thrombocytopenic purpura (TTP), etc.
defect in primary hemostasis. It is clinically suspected when
there is history of easy bruising or bleeding. Petechiae, Platelet Sequestration
purpura, epistaxis, gum bleeding, gastrointestinal (GI) bleeds,
hematuria, and menorrhagia are some of the important Mainly in the spleen as in hypersplenism due to infections,
presenting features. Intracranial bleeding, though rare, is one storage disorders, and portal hypertension.
of the dreaded complications of low platelet counts. Deep and
intramuscular bleeds are uncommon with thrombocytopenia
CLINICAL APPROACH TO THE PATIENT WITH
and generally indicate a coagulation disorder, if encountered.
THROMBOCYTOPENIA
CAUSES
Detailed History
The causes of thrombocytopenia are many and broadly fall
under three categories. • Age at presentation
1. Decreased production of platelets—either congenital or • Associated respiratory infection, diarrhea, or drug intake
acquired • History suggestive of malaria and dengue
2. Increased destruction of normally synthesized platelets— • Family history of bleeding disorder or immune disease
which could be due to immune or nonimmune causes • History/risk for HIV or other immunodeficiency disorder
3. Sequestration of platelets in various organs. • History regarding the type and site of bleeding.
ch-59.indd 269 11/19/2016 4:50:54 PM

Physical Examination Algorithm 1

Fever and toxic appearance may suggest infection, malignancy, Approach to thrombocytopenia
DIC, TTP. The type and extent of bleeding is to be noted. An
absent radius or upper limb deformity, chronic eczema, and
recurrent infections are clues to various causes of congenital
thrombocytopenia. Lymphadenopathy or splenomegaly may
suggest malignancy, HIV, and infectious mononucleosis.
Immune thrombocytopenic purpura is conspicuous by the
nonoccurrence of splenomegaly. Arthritis, mouth ulcers, or
a characteristic rash may suggest autoimmune or collagen
vascular illness. Features of renal failure like edema,
hypernatremia, and hypertension may be noted in HUS.
Abnormal neurological examination should alert one to the
possibility of an intracranial bleed or TTP.
Investigations
Causes for mucocutaneous bleeding are many and specialized
testing for platelet disorders can be expensive and difficult to
perform. However, before resorting to any of these tests, it is HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency
important to eliminate spurious “pseudo” thrombocytopenia syndrome; PT, prothrombin time; aPTT, activated partial thromboplastin time;
by the direct finger prick peripheral smear examination. FDP, fibrin degradation product; ANA, antinuclear antibody; HUS, hemolytic
uremic syndrome; ITP, immune thrombocytopenic purpura; DIC, disseminated
Pseudo (or spurious) thrombocytopenia is an in vitro intravascular coagulation; ES, Evans syndrome; SLE, systemic lupus
artifact where platelets clump together due to poor quality erythematosus; IM, infectious mononucleosis.
ethylenediaminetetraacetic acid used as an anticoagulant. As
a result, the platelet counts appear to be decreased. A repeat
count with another anticoagulant will resolve the problem. Algorithm 2
Further investigations will include: Approach to isolated thrombocytopenia
• Complete blood count: will distinguish between
pancytopenia and isolated thrombocytopenia
• An increase in mean platelet volume (MPV, normal 5–9 fL)
will suggest increased turnover (e.g., in ITP where in the
bone marrow attempts to replace peripherally destroyed
platelets by younger larger platelets quickly) or hereditary
giant platelet syndromes while small platelets (low MPV)
suggest decreased platelet production and the Wiskott-
Aldrich syndrome
• Bone marrow aspirate and biopsy is essential to differentiate
ITP from leukemia and other infiltrative disorders when
doubts arise clinically. Normal or increased megakaryocytes
seen in the marrow in ITP will help resolve the issue
• Other clinically relevant investigations, e.g., specific
serological titers for various infections and cytogenetic
assessment for inherited disorders.
Algorithms 1 and 2 represent a simplified approach to
thrombocytopenia. BM, bone marrow; ANA, antinuclear antibody; HIV, human immunodeficiency
virus; TAR, thrombocytopenia-absent radius; WAS, Wiskott-Aldrich syndrome;
ITP, immune thrombocytopenic purpura; VWD, von Willebrand disease; IM,
TREATMENT infectious mononucleosis.
Treatment involves management of the underlying cause.

Platelet transfusions are often performed to tide over the CONCLUSION
crisis. Immune thrombocytopenic purpura is the most
common cause of acute thrombocytopenia in a well child and Thrombocytopenia is a common cause of bleeding in
the treatment involves observation, intravenous immuno children. A knowledge of its causes, detailed history, and
globulins, steroids, and others. In children without significant thorough clinical examination is necessary to narrow down
clinical bleeding, serial platelet counts will help decide the the diagnostic possibilities. Relevant investigations need to be
270 course of therapy to be adopted. done to reach a correct diagnosis.
ch-59.indd 270 11/19/2016 4:50:54 PM

Chapter 59: Algorithmic Approach to Thrombocytopenia in Children
Key points
SUGGESTED READINGs
1. Borkataky S, Jain R, Gupta R, Singh S, Krishan G, Gupta K, et al. Role of platelet
))
Thrombocytopenia is defined as platelet count less than volume indices in the differential diagnosis of thrombocytopenia: a simple and
150,000/cumm inexpensive method. Hematology. 2009;14:182-6.
))
Thrombocytopenia can have multiple etiologies: either due 2. Buchanan GR. Thrombocytopenia during childhood; what the paediatrician needs
to know. Pediatr Rev. 2005;26:401-9.
to decreased production, or increased destruction or due to 3. Israels SJ, Kahr WH, Blanchette VS, Luban NL, Rivard GE, Rand ML. Platelet disorders
splenic sequestration in children: a diagnostic approach. Pediatr Blood Cancer. 2011;56:975‑83.
))
Detailed history and thorough clinical examination and 4. Lombarts AJ, de Kieviet W. Recognition and prevention of pseudothrombocytopenia
and concomitant pseudoleukocytosis. Am J Clin Pathol. 1988;89:634-9.
relevant investigations need to be done to reach a correct
5. Panepinto JA. Thrombocytopenia. Berman’s Pediatric Decision Making.
diagnosis Philadelphia: Mosby; 2011. pp. 612-5.
))
Algorithmic approach to either isolated thrombocytopenia or 6. Scott JP, Montgomery RR. Platelet and blood vessel disorders. In: Kliegman RM,
with other cytopenias, along with a knowledge of causes will Stanton BM, St. Geme J, Schor NF, Behrman RE, editors. Nelson Textbook of
Pediatrics. 19th ed. Philadelphia: Saunders; 2011. pp. 1714-22.
help at arriving the diagnosis.
7. Veneri D, Franchini M, Randon F, Nichele I, Pizzolo G, Ambrosetti A.
Thrombocytopenias: a clinical point of view. Blood Transfus. 2009;7:75-85.
271
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Chapter 60
Algorithmic Laboratory
Approach to a Child with Anemia
Aarathi R Rau
INTRODUCTION concentration (MCHC)] and divided into microcytic

hypochromic, normocytic, normochromic, and macrocytic
Anemia is a condition in which there is a reduction in the total anemia. As children (other than neonates) have smaller
circulating red cell mass below normal limits and consequent erythrocytes than adults the determination of MCV and
decreased oxygen carrying capacity that is insufficient to meet subsequent classification of anemia must be determined by
the body’s physiologic needs. It is a common problem in India, age-related ranges. Morphological classification is useful as
and the National Family Health Survey III data showed the the differential diagnoses of microcytic hypochromic anemia
prevalence of anemia among children less than 5 years of age and macrocytic anemia are limited.
to be around 70% with nearly 73 million children below the age The functional classification is based on the number of
of 3 (79%) suffering from varying degrees of anemia. reticulocytes produced as a response to anemia. Reticulocyte
Anemia is measured by reduction in the volume of packed count can be corrected depending on the degree of anemia
red cells as measured by the hematocrit and reduction in the and the extent of stress/shift reticulocytosis to derive the
hemoglobin concentration below the normal for the age and reticulocyte production index (RPI), an index of bone marrow
gender of the individual. These values correlate with the red proliferation and its response to the degree of anemia. In
cell mass, except when there is change in the plasma volume hyperproliferative anemias seen in blood loss and hemolytic
caused by fluid retention or dehydration.
anemias, the RPI is greater than 2. In untreated thalassemia
major, however, the reticulocyte count may be low. In
DIAGNOSIS OF ANEMIA hypoproliferative anemias and maturation defects seen in
deficiency anemias, anemia of chronic disease, endocrine
Basic investigations are done to document the presence of
deficiencies, sideroblastic anemias, aplastic anemia, and
anemia and classify it according to morphology and function.
myelodysplasia, the RPI is less than 2. The morphological
Thereafter, based on the differential diagnosis and clinical
features, specific diagnostic tests are indicated that help classification combined with the functional classifications
establish the etiology and pathophysiology of anemia. The and the differential diagnoses thereof are applicable to the
initial laboratory studies should include a complete blood majority of anemias. Unusual patterns may occur while the
count with red cell indices, reticulocyte count, and study of a anemia is not fully developed, when there is a combination of
well-prepared peripheral blood smear. causes, the patient is under treatment or in an unusual cause
of anemia.
CLASSIFICATION OF ANEMIA
USE OF AUTOMATED BLOOD
Anemia is a manifestation of the underlying disease, which
COUNTING INSTRUMENTS IN ANEMIA
must then be determined and treated accordingly. The
common mechanisms of anemia are decreased production, Automated counters are widely available and have improved
decreased lifespan of red cells, blood loss, and splenic pooling. accuracy, precision, and reliability compared to manual
However, if the cause is not readily apparent from clinical methods. Most modern automated blood-counting instru
features, evaluation based on morphology and function is ments give the complete blood count which includes
a well-established approach. Morphological classification hemoglobin, hematocrit, RBC indices, white blood cell
of anemia is based on the red blood cell (RBC) indices that (WBC), and platelet counts which are useful in the initial
reflect the RBC volume [mean corpuscular volume (MCV)] morphological diagnosis of anemia. Red cell distribution
and hemoglobin content [mean corpuscular hemoglobin width (RDW) is a measure of anisocytosis and normally
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Chapter 60: Algorithmic Laboratory Approach to a Child with Anemia
Table 1: Hemoglobin and hematocrit cutoffs for a diagnosis of

Box 1: Red blood cell indices and their normal values
anemia in children
• MCV = hematocrit (%)/RBC count (×1012/L) × 10
• Normal value: 70–84 fL at 1 year. Mean 80 fL by 5 years Age (years)/gender Hemoglobin (g/dL) Hematocrit (%)
• MCH = hemoglobin (g/dL)/RBC count (×1012/L) × 10 Both sexes
• Normal value: 26–34 pg. Changes parallel to MCV in infancy and 1–1.9 11.0 33
childhood 2–4.9 11.2 34
• MCHC = hemoglobin (g/dL)/hematocrit (%) × 100
5–7.9 11.4 34.5
• Normal value: 32–36 g/dL
8–11.9 11.6 35
• Increased MCHC seen in hereditary spherocytosis, dehydrated
cells in sickle cell anemia, hereditary xerocytosis, and spuriously Females
in immune hemolytic anemias 12–14.9 11.8 35.5
RBC, red blood cell; MCV, mean corpuscular volume; MCH, mean corpuscular Males
hemoglobin; MCHC, mean corpuscular hemoglobin concentration.
12–14.9 12.3 37
Box 2: Data that are useful in anemia from automated

Box 3: Calculated indices which may be useful
blood-counting instruments
• Mentzer’s index = MCV/RBC count
• Complete blood counts hemoglobin, PCV, MCV, MCH, MCHC,
RDW, WBC, and platelet counts • <13 suggests thalassemia trait
• >13 suggests iron deficiency
• Volume histograms: help to diagnose dimorphic patterns which
can be present in combined nutritional anemias, sideroblastic • It is a sensitive but less specific test, therefore, confirmatory tests
anemia, MDS, post-transfusion, and during treatment must be carried out
• Automated counters give data on the leukocytes and platelets • Reticulocyte production index =
which can be correlated with the RBC parameters Patient hematocrit (%) Reticulotyte (%)
×
• Absolute reticulocyte count and immature reticulocyte fraction Normal hematocrit (%) Maturation days
is an indication of the proliferation of the bone marrow and • Maturation days depend on the hematocrit and are calculated as
response to treatment follows
{{ Hematocrit 0.25–0.35, maturation days: 1.5
PCV, packed cell volume; MCV, mean corpuscular volume; MCH, mean
corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin {{ Hematocrit 0.15–0.25, maturation days: 2
concentration; RDW, red cell distribution width; WBC, white blood cell; MDS, {{ Hematocrit <0.15, maturation days: 2.5
myelodysplastic syndrome; RBC, red blood cell. • <2 indicates hypoproliferative anemia
• >2 indicates hyperproliferative anemia
Algorithm 1 MCV, mean corpuscular volume; RBC, red blood cell.
Approach to anemia
reticulocyte count reflects the increased production of
reticulocytes as a response of the erythropoietic elements
of the bone marrow to anemia or treatment and is more
useful than the manually counted reticulocyte percentage.
In some automated counters, the immature reticulocyte
fraction, which reflects the early reticulocyte fraction and the
reticulocyte hemoglobin, which reflects the iron supply in the
bone marrow, are also available.
Certain indices either numerical or computational can
be calculated from data derived from automated counters,
e.g., Mentzer’s index, which is useful in the differentiation
of thalassemia minor from iron deficiency anemia can be
calculated.
EXAMINATION OF THE PERIPHERAL SMEAR

Examination of RBC morphology on a blood smear is
PCV, packed cell volume; RBC, red blood cell; MDS, myelodysplastic syndrome.
important in diagnosing the type of anemia, assessing
anisocytosis, and correlating it with the RDW. Smear
examination can assess poikilocytes, the most specific being
between 11.5 and 14.5%. A value of more than 14.5% indicates sickle erythrocytes. Erythrocyte inclusions when present
a heterogeneous population. Study of the volume histograms are at times useful in determining the cause of anemia like
give a guide to the RBC morphology as well as distribution, Howell-Jolly bodies seen in some hemolytic anemias and 273
which can be correlated with the peripheral smear. Absolute Pappenheimer bodies in sideroblastic anemia. Evaluating the
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morphology of the WBCs may be useful in diagnosing certain anemia from anemia of chronic disease; it is raised in patients
anemias like megaloblastic anemia and other hematological with iron deficiency anemia in comparison to anemia of
diseases where anemia is secondary to another cause, chronic disease, where levels are almost identical to normal
e.g., leukemia. Examination of a peripheral smear is also individuals.
invaluable in the diagnosis of malaria, a common cause of In α and β thalassemia trait, the peripheral smear will show
anemia. Data from automated counters may be correlated microcytic hypochromic RBCs with minimal anisocytosis
with peripheral smear findings. which is reflected as a decreased RDW. The RBCs are increased
in number and both these are reflected in the Mentzer’s index.
While investigating for β thalassemia trait, estimation of HbA 2
APPROACH TO MICROCYTIC
HYPOCHROMIC ANEMIA Table 2: Differential diagnosis of iron deficiency anemia
Microcytic RBCs are usually associated with decreased MCHC Iron Beta Anemia Sidero
and are, therefore, microcytic hypochromic. Iron deficiency is deficiency thalassemia of chronic blastic
the most common cause of microcytic hypochromic anemia minor disease anemia
but microcytic hypochromic anemia can also occur in Serum ferritin ↓* Normal/↑ Normal/↑ ↑
thalassemia minor (both α and β), in the late stages of anemia
Serum iron ↓ Normal/↑ Normal/↓ Normal/↑
of chronic disease, sideroblastic anemia, hemoglobin C and
hemoglobin E, and other rare causes. Beta-thalassemia Total iron ↑ Normal/↓ Normal/↓ Normal/↓
major and intermedia and hemoglobin H disease also binding
cause microcytic hypochromic RBCs; however, their clinical capacity
features and peripheral smear findings are usually significant RDW/ ↑ Normal Normal ↑/dimorphic
enough for them not to be included in the differential anisocytosis population
diagnosis of iron deficiency anemia. In iron deficiency Special Serum HbA 2 Serum Ringed
anemia, the RBCs are microcytic hypochromic with moderate tests for transferrin estimation transferrin sideroblasts
anisopoikilocytes. The platelet count is usually on the upper confirmation receptor >4% receptor in bone
level of normal and reticulocyte response is usually identified assay— assay— marrow
3 days after institution of iron therapy. Iron studies will show increased normal
decreased serum iron and ferritin and increased total iron RDW, red cell distribution width.
binding capacity. Serum transferrin receptor assay (sTFR) *Serum concentrations of ferritin are lower in children than in adults and ferritin
is useful in detecting and differentiating iron deficiency <12 µg/L is considered appropriate for detecting iron deficiency.
Algorithm 2
Approach to microcytic hypochromic anemia
274
TIBC, total iron binding capacity; LDH, lactate dehydrogenase; BMA, bone marrow aspiration.
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Chapter 60: Algorithmic Laboratory Approach to a Child with Anemia
is important as an increase (usually a value of between 4 and normal. Causes of nonmegaloblastic macrocytic anemia
7%) is considered diagnostic of β-thalassemia trait. If, after include hypothyroidism, liver disease, and rare conditions like
evaluation of the common causes, a diagnosis has not been pure red cell aplasia, and aplastic anemia. The smear shows
reached, unusual causes like lead toxicity may be considered. round macrocytes and may show features of the underlying
cause like target cells and stomatocytes in liver disease.
APPROACH TO MACROCYTIC ANEMIA Correlation with clinical and laboratory tests for the causative
disease must be done to confirm the cause.
Macrocytic anemias are those where the MCV is greater than Hemolytic anemias and blood loss may also have raised
100 fL. Macrocytic anemias may be megaloblastic or non- MCV due to reticulocytosis which can be excluded by
megaloblastic. reticulocyte count and peripheral smear examination.
In megaloblastic anemia, examination of the peripheral
smear will show macro-ovalocytes and hypersegmented
neutrophils. Increase in serum lactate dehydrogenase, NORMOCYTIC NORMOCHROMIC ANEMIA
unconjugated bilirubin, and decreased haptoglobin indicate
ineffective erythropoiesis and hemolysis. The MCV is usually The causes of normocytic anemia are many. Depending
greater than 120 fL and there is likely to be decrease in the RBC, on the RPI, they can be categorized into anemia with
WBC, and platelet counts. The bone marrow in megaloblastic hyperproliferative or hypoproliferative marrow. Normocytic
anemia shows nuclear: cytoplasmic asynchrony and giant anemia with hyperplastic marrow (>2 RPI) present from
metamyelocytes, however, bone marrow examination may birth are usually due to some nonthalassemic hemoglobin
not be essential for the diagnosis of megaloblastic anemia. opathies, RBC enzyme, or membrane defects. In addition to
Megaloblastic anemia may be due to folic acid, vitamin peripheral smear examination and tests for increased turnover
B12 deficiency which may be due to decreased absorption, of cells, further tests like hemoglobin electrophoresis can
inadequate nutrition, defects in metabolism, or increased characterize the disease. Rare causes of hemolysis including
requirements. Other causes include defects in purine and paroxysmal nocturnal hemoglobinuria and Wilson disease
pyrimidine synthesis either inherited or acquired as in must be confirmed by specific tests. Normocytic anemia with
myelodysplastic syndrome (MDS), drug induced or associated hypoplastic marrow (<2 RPI) can be seen early in the course
with human immunodeficiency virus infection. of iron deficiency, renal disease, liver disease, endocrine
In nonmegaloblastic anemia, the MCV is usually mild and disorders, chronic inflammatory disease, and anemia
between 100 and 110 fL and the WBC and platelets are usually secondary to medications. In these conditions, specific tests
Algorithm 3
Approach macrocytic anemia
MCV, mean corpuscular volume; DNA, deoxyribonucleic acid; MDS, myelodysplastic syndrome; PRCA, pure red cell aplasia; HIV, human immunodeficiency virus. 275
Note: Autoagglutination can cause spurious increase in mean corpuscular volume in automated counters. This can be ruled out by examination of the peripheral
smear and direct Coombs’ test.
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Algorithm 4
Approach to normocytic anemias
MCV, mean corpuscular volume; LDH, lactate dehydrogenase; AIHA, autoimmune hemolytic anemia; HDN, hemolytic disease of the newborn; HUS, hemolytic uremic
syndrome; DIC, disseminated intravascular coagulation; SLE, systemic lupus erythematosus; BMA, bone marrow aspiration; MDS, myelodysplastic syndrome;
PRCA, pure red cell aplasia; PNH, paroxysmal nocturnal hemoglobinuria.
following clinical evaluation will confirm the diagnosis.

Key points
Primary hematological conditions may also present with
hypochromic anemia and these include MDS, aplastic anemia, ))
The morphological classification of anemia is based on
pure red cell aplasia, and leukemia. Evaluation of the bone red cell indices and correlated with the red blood cell
marrow will be useful in confirming these diagnoses morphology on peripheral smear examination
))
The differential diagnosis of microcytic hypochromic anemia
ANEMIA IN THE NEWBORN and macrocytic anemias are limited
))
Based on the morphology and clinical features, further
Anemia in the newborn differs from those in children in that investigations can be done to help establish the etiology
the level of hemoglobin is higher (16–22 g/dL at birth), the
and pathophysiology of anemia; after which appropriate
MCV is higher (average 107 fL at birth) and the reticulocyte
treatment can be given.
count is higher (3–7%) in the newborn compared to children.
The etiologies that are uncommon in older children that need
to be considered in a newborn include congenital disorders, SUGGESTED READINGs
metabolic disorders, intrauterine infections, ABO/Rh
1. Bain BJ, Bates I, Laffan MA, Lewis SM. Dacie and Lewis practical hematology.
incompatibility, and internal hemorrhage. 11th ed. Churchill Livingstone: Elsevier; 2012.
2. Brugnara C, Platt OS. The neonatal erythrocyte and its disorders. In: Orkin SH, Nathan
Clinical Pearls DG, Ginsburg D, Look AT, Fisher DE, Lux SE, editors. Nathan and Oski’s hematology of
infancy and childhood. 7th ed. Philadelphia: Saunders Elsevier; 2009.
3. Centers for Disease Control (CDC). CDC criteria for anemia in children and
• The final diagnosis in anemia must be done after correlating childbearing aged women. MMWR Morb Mortal Wkly Rep. 1989;38(22):400-4.
the laboratory test results with patient history, symptoms, and 4. Dallman PR, Simes MA. Percentile curves for hemoglobin and red cell volume in
physical examination infancy and childhood. J Pediatr. 1979;94(1):26-31.
• Results of laboratory tests should be interpreted with an 5. Khoury MJ, Rhodes M. How to approach chronic anemia. Hematology Am Soc
Hematol Educ Program. 2012;2012:183-90.
understanding of the limitations of the test and the variations
6. Kotecha PV. Nutritional anemia in young children with focus on Asia and India.
with respect to age, gender, sample collection, etc. Indian J Community Med. 2011;36(1):8-16.
• All laboratory investigations should be interpreted in 7. McKenzie SB, Williams JL. Clinical laboratory hematology. 3rd ed. New Jersey:
276 relation to the reference range established in that individual Pearson Education Inc.; 2015.
laboratory using blood samples from the local population. 8. Tkachuk DC, Hirschmann JV, editors. Wintrobe’s atlas of clinical hematology.
Philadelphia: Lippincott Williams and Wilkins; 2007.
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Chapter 61
Recurrent Unusual Infections in
a Child: The Way Forward
Tulika Seth
INTRODUCTION medications should be checked as the child may be on steroids

or other immune-suppressants. Occasionally, the recurrent
Children are immunologically immature more prone to many infection can lead to the diagnosis of unsuspected condition
infections compared to adults. More than six infections per year like cystic fibrosis or a previously missed congenital heart
are suspicious of an immunodeficiency status, though some disease, etc. Most common infections in children are viral, of
studies report 4 to 8 may be normal. So when is it warranted to do short duration, and do not compromise growth. Children with
special and extra investigations in a child? Repeated infections inherited conditions like Down syndrome, DiGeorge syndrome,
with the same bacterial organism, serious infections of the etc. are also more susceptible to infections. Family history of
lower respiratory tract, repeated diarrhea, recurrent urinary other family members prone to infections (siblings, parents),
tract infection, and repeated pyogenic infections all warrant a history of human immunodeficiency virus (HIV) needs to be
detailed history and evaluation. Unusual organisms causing an taken. If none of the above then a primary immunodeficiency
infection should also get special attention. Before we discuss disorder may be the cause of the condition.
recurrent unusual infections, it is important to understand what In neutropenic patients, there are frequent bacterial and
are recurrent infections and unusual organisms. fungal infections. Though they present with fever, the classic
signs of infection are often less marked due to neutropenia,
DEFINITIONS hence a high index of suspicion is needed.
Unusual Infections: Causes

Recurrent or Repeated Infections:
Common Causes An unusual infection may be either an uncommon setting, or a
rare organism. These are warning flags to investigate a child for
The child referred for repeated or recurrent infection needs a immunodeficiency disorders or undiagnosed systemic disease
detailed history. Often a common mistake is to assume cases like malignancy. Certain signature infections can help pinpoint
of repeated infections, when in fact it is a case of inadequate, the type of immune defect (Box 1).
improper, or incomplete treatment of a previous infection. • If presented with an unusual organism, rule out conta
Compliance, dosage of antibiotics, and all culture reports mination and obtain a detailed history of travel, exposure
should be checked. Home environment, smoker at home, to pets, medication leading to immune-suppression, and
going to a crèche, etc. can predispose to recurrent infections previous courses of broad-spectrum antibiotics
in an otherwise normal child. The vaccination history and • If a usual setting, rule out underlying undiagnosed disease
documentation of vaccines is important. Malnutrition is the such as malignancy, metabolic or systemic disease, HIV,
most common cause of decreased immunity, hence nutritional malnutrition, or undisclosed use of steroids or other
parameters should be checked. Any anatomic malformation, immune-suppressive medicines.
gastroesophageal reflux, congenital masses, and foreign body As seen by the above discussion, all children with recurrent
aspiration may also be a cause of repeated infections. Atopic infections do not have a primary immune deficiency disorder. It
dermatitis may lead to skin infections due to scratching the is important to rule out secondary immunodeficiency as these
pruritic rash. Other systemic disease, e.g., sickle cell, nephrotic can be treated easily (Table 1) leaving the primary immuno
syndrome, etc., needs to be evaluated, if previous illness, then deficiency child who needs a more detailed investigation.
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Box 1: Clinical features of primary immunodeficiency Key Features of Unusual Recurrent Infections
disorders • Not all children with recurrent infections have a primary
Adaptive immunity immune deficiency disorder
• B cell defects • Immunodeficiency should be suspected if
{{ Six or more new infections within 1 year
{{ Recurrent bacterial sinopulmonary infections, with polys
{{ Two or more sinus infections or pneumonias in 1 year
accharide encapsulated organisms (Streptococcus pneumoniae,
{{ Two or more episodes of sepsis or meningitis
Haemophilus influenzae type b) or bronchiectasis
{{ Two or more months of oral antibiotics without
{{ Chronic or recurrent gastroenteritis (Giardia/enteroviruses)
{{ Chronic enteroviral meningoencephalitis

resolution of problem.
{{ Failure to thrive and/or autoimmune disease
• T cell defects WARNING SIGNS OF IMMUNE-DEFICIENCY

{{ Lymphopenia as a neonate or infant Presence of oral candidiasis, tissue or organ abscesses,
{{ Repeated severe, or unusual viral infections (varicella-zoster, and opportunistic infections all warrant investigation. A
CMV, HSV) complication from a live vaccine, in the child or elder siblings
{{ Chronic candidiasis and family history of siblings with history of early death or
{{ Chronic diarrhea similar presentation are important.
{{ Opportunistic infections like Pneumocystis pneumonia The immunodeficiency may be secondary or primary.
{{ Severe seborrheic rashes (skin rash, desquamating skin,
Secondary immune-deficiencies are due to contributing
abnormal liver function tests, and cytopenias) malnutrition, chronic disease, prematurity, cancer, HIV, etc.
{{ Associated features: failure to thrive
The type and pattern of recurring infections depend on which
components of the immune system are affected (Box 1). History
Innate immunity (Table 1) and examination (Box 2) give clues and signature
• Phagocytic defects infections help highlight disorders (Table 2). Initial steps with
{{ Delayed separation of the umbilical cord
workup of the child is represented in algorithm 1.
{{ Lymphadenitis or soft tissue abscesses
{{ Repeated infections due to catalase-positive bacteria and/or

GENERAL EXAMINATION
fungi
{{ Recurrent gastrointestinal or genitourinary tract obstruction Physical examination in children with recurrent infections
{{ Poor wound healing, oral ulcers provides information as to their general health and may suggest
• Complement defects the presence of allergy, chronic disease, or immunodeficiency.
{{ Angioedema of face, GI tract, etc.
A dysmorphic appearance may signify an underlying genetic
syndrome. Dark circles under the eyes, a transverse nasal
{{ Autoimmune disease
crease, and congested nasal turbinates suggest allergy. Mouth
{{ Pyogenic bacterial infections (e.g., Neisseria meningitidis),
ulcers, gingivitis, and mucosal candidiasis may be due to
Herpes simplex meningoencephalitis in infancy
an immunodeficiency state. Diminished or absent tonsils
{{ Papillomavirus infections of skin, including extensive warts
and cervical lymphadenopathy with a history of recurrent
{{ Autosomal dominant inheritance
respiratory infections suggest an antibody deficiency
CMV, cytomegalovirus; HSV, herpes simplex virus; GI, gastrointestinal. diagnosis. The presence of nasal polyps suggests cystic fibrosis,
and confirmatory testing should be performed.
Table 1: Historical details useful in differentiating between cases of suspected primary or secondary immunodeficiency
Primary immunodeficiency Secondary immunodeficiency
History
• Feeding history, history of food intolerance • Birth history: pregnancy history should be explored for
• Delayed detachment of the umbilical cord should be noted since maternal illness (e.g., HIV, CMV), birth history should include
persistent attachment beyond 30 days is suggestive of a leukocyte length of gestation, birth weight, and neonatal problems
adhesion defect such as jaundice, respiratory distress, or need for intensive
care. Transfusions in the neonatal period should be recorded
Growth
• Weight, height, and head circumference should be plotted and followed over time. Children with chronic disease or immunodeficiency
often have poor weight gain or even weight loss. Children with chronic lung, heart, or gastrointestinal disease are often small because of
anorexia, high energy expenditure, or malabsorption caused by infection or bacterial overgrowth
Development
• Children with ataxia-telangiectasia and DiGeorge syndrome can have • Children with HIV, and TORCH may have delays in
delayed developmental milestones milestones; children with other chronic disease may also lag
278 • Progressive neurologic dysfunction is seen in Chédiak-Higashi syndrome in development
Continued
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Chapter 61: Recurrent Unusual Infections in a Child: The Way Forward
Continued
Primary immunodeficiency Secondary immunodeficiency
Immunization history
• See for adverse effects from a vaccine, particularly live virus. The • The immunization record is valuable to see vaccine titers to
immunization record is valuable to see vaccine titers to evaluate evaluate antibody function
antibody function
Medications
• If immunoglobulin has been given, the route, dose, frequency, and • Current and past medications should be recorded, including
adverse effects should be noted duration, effectiveness, and adverse reactions. Use of any
immunosuppressive medications, such as glucocorticoids,
should be noted
Other illnesses
• Other immune problems such as allergies, anaphylaxis, arthritis, or • Severity of prior chicken pox, roseola, and other febrile
autoimmunity may give a clue to diagnosis illnesses should be noted
• Ask about surgery and hospitalizations
Family history
• Consanguinity, family members with similar diseases, recurrent • HIV, TB
infections, unexplained death, or autoimmune disease • Other similar problems in siblings, or other family members,
• Autosomal recessive pattern in ataxia-telangiectasia parental health, and occupation
• X-linked transmission (e.g., agammaglobulinemia, chronic
granulomatous disease)
Infection history
• The infection history should include the age of onset, duration, frequency, sites, organisms, treatment, and response to therapy
Age of onset
• Birth to 6 months: • Birth to 6 months:
{{ Several immune-deficiencies: congenital neutropenia, severe {{ Infections shortly after birth may be due to prolonged
combined immunodeficiencies, and complete DiGeorge syndrome rupture of membranes, congenital infection, or aspiration
{{ Persistent diarrhea, chronic cough, or failure to thrive suggests cystic {{ Premature infants are at high risk for sepsis
fibrosis or a primary immunodeficiency

{{ Inherited antibody deficiencies present at 7 -9 months, as the
maternal IgG decreases. Infants with TLR3 transduction may present

with herpes simplex encephalitis.
• 2–6 years: • 2–6 years:
{{ Less serious antibody deficiencies (e.g., immunoglobulin A deficiency {{ Secondary immune-deficiencies resulting from
and selective antibody deficiency) present at this age. Two or more malignancy, nephrotic syndrome, or gastrointestinal
episodes of bacterial meningitis or sepsis suggest a complement or problems, malabsorption often begin at this age
other innate immune defect {{ Daycare or school will result in frequent respiratory and
gastrointestinal infections
HIV, human immunodeficiency virus; CMV, cytomegalovirus; TORCH, Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes infections; TB, tuberculosis.
Box 2: Examination findings to look for in a child with recurrent infections

Skin
• See breach of skin barriers due to prematurity, atopy, chronic eczema, burns, wounds, fistula and sinuses. Several immunodeficiency
syndromes are also associated with eczema, including Wiskott-Aldrich, hyper immunoglobulin E, Omenn syndrome, and severe combined
immunodeficiency disease (SCID)
• Cutaneous granulomas, impetigo, or nonhealing ulcers suggest the diagnosis of an antibody or phagocytic disorder. Pyogenic abscesses are
common in chronic granulomatous disease, or leukocyte adhesion defects
• Oculocutaneous albinism is seen in Chédiak-Higashi disease
• Rashes: seborrheic dermatitis and alopecia can be seen in some forms of SCID, or may be found in other conditions like Langerhans cell
histiocytosis. Lupus-like rash in the children with early complement component defects. A dermatomyositis-like rash is found in X-linked
agammaglobulinemia (XLA)
• Extensive warts or molluscum contagiosum occurs in T cell disorders, innate immune defects, or a rare entity called Warts,
Hypogammaglobulinemia, Infections and Myelokathexis syndrome
Lymphadenopathy, hepatosplenomegaly
• Immune deficiency disorders can be characterized by paucity or even overabundance of lymphoid tissue (e.g., tonsils, lymph nodes,
adenoids, spleen). The absence of lymph tissue suggests XLA or SCID
• Lymphadenopathy and hepatosplenomegaly can be seen in B cell disorders (e.g., common variable immunodeficiency, IgA deficiency) and
also in children with human immunodeficiency virus infection 279
• Suppurative adenitis is common in chronic granulomatous disease
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Table 2: Signature infections in certain immunodeficiencies

Infection Immune defect
Recurrent sinopulmonary infections, pneumococcus, B cell abnormalities
Haemophilus influenzae type b
Enteroviral meningoencephalitis X-linked agammaglobulinemia
Severe oral candidiasis Abnormal T cell immunity
Staphylococcus aureus, coagulase-negative staphylococci, Chronic granulomatous disease
Serratia marcescens, Aspergillus
Neisseria species (Neisseria meningitidis, Neisseria gonorrhoeae) Deficiencies of the late components of complement (C5–C9)
Infection with vaccine strains following live vaccines, e.g., oral Primary immune deficiency
polio, measles, varicella, or BCG
Some infections can occur in both primary and secondary immunodeficiency states
Recurrent pneumococcal disease Primary immunodeficiency such as agammaglobulinemia or
complement defect or secondary immunodeficiency, due to sickle
cell disease, asplenia, HIV/AIDS, or nephrotic syndrome, also results in
recurrent pneumococcal disease
Pneumocystis jiroveci (carinii) pneumonia Severe combined immune deficiency, primary or secondary T cell
immunodeficiencies—HIV or immunosuppressive therapy
Pseudomonas infection Cystic fibrosis, skin burns, trauma, or neutropenia
BCG, Bacillus Calmette-Guérin; HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome.
Algorithm 1 of the immune system that is most likely to be involved based

Initial evaluation with workup of upon the screening tests.
a child with unusual recurrent infections
General Screening Tests
• The total absolute lymphocyte count is a useful test
(lymphopenia is defined as a count of <1,500 cells/µL
in patients over 5 years and <2,500 cells/µL in younger
children). The presence of anemia, thrombocytopenia,
or an abnormal differential count warrants further
investigation
• Neutropenia and absolute neutrophil count should be
checked:
WBC (cells/µL) × percent (PMNs + bands)
ANC =
100
Other important blood cells to be evaluated are
eosinophils; if increased, suggest an allergic state. Platelet
size and number should be seen as they are useful—small
platelets seen in Wiskott-Aldrich syndrome, etc. However,
thrombocytosis is less specific and only points to chronic
inflammation
• Chest X-ray, computed tomography scan: this will assist in
documenting serious infections like pneumonia, thymus
LABORATORY EVALUATION size, presence of mass in chest predisposing to infection,
bronchiectasis, etc. This may suggest a diagnosis of
Laboratory evaluation of children with recurrent infection previously unsuspected etiology
should be directed by history and physical examination • Immunoglobulin levels: immunoglobulin G (IgG), IgM,
findings (Table 1, Box 2, Algorithm 2), before evaluating for IgA, and IgE, must be compared with age-matched
primary immunodeficiency diseases exclude secondary controls for children. An antibody deficiency is suggested
immunodeficiency, which are more common. General by an IgG less than 200 mg/dL and a total Ig (IgG plus
screening tests should include the following to exclude IgM plus IgA) less than 400 mg/dL, or by the complete
systemic disease: complete blood count with differential absence of IgM or IgA (after infancy). A small increase of
electrolytes, glucose, renal and liver function tests, urinalysis, IgE (>100 IU/mL) can occur due to allergy, eczema, or with
280 autoimmune workup, and HIV testing. The evaluation for phagocytic dysfunction. In hyper IgE syndrome, the level of
primary immunodeficiency should focus on the component IgE are generally greater than 2,000 IU/mL
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Chapter 61: Recurrent Unusual Infections in a Child: The Way Forward
Algorithm 2
HIV, human immunodeficiency virus; PCR, polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay.
• Antibody titers, complement screening test: functional • Delayed cutaneous hypersensitivity is a good functional in
assessment of the antibody system can be done by vivo test of T cells; however, it is limited in utility as it can
checking antibody titers to vaccines that the child has been be performed only in older children
documented to have received. Titers to tetanus, diphtheria, • Lymphoproliferative assays are in vitro assays used to
and Haemophilus influenzae type b are available for evaluate the cellular immune system. This examines
reference. Response to polysaccharide antigens can be proliferative response of lymphocytes to mitogens
determined by measurement of pneumococcal titers (12– (phytohemagglutinin, pokeweed), stimulatory mono
14 serotypes) in children over the age of 2 years clonal antibodies (anti-CD3), etc. Defects in this assay
• Complement activity needs to be assessed in patients with suggest a T cell defect
recurrent sepsis due to neisserial infection. The screening • Phagocytic oxidative response is evaluated by a fluores
test is a total hemolytic complement determination cent dye (dihydrorhodamine) by flow cytometry. Chronic
(CH50). A normal CH50 level excludes nearly all hereditary granulomatous disease gives a negative test. This is more
complement deficiencies. accurate than the nitroblue tetrazolium dye reduction
assays
Diagnostic Tests • Leukocyte adhesion defect testing: cases presumed to
Specific testing is indicated when screening tests are abnormal suffer from leukocyte adhesion deficiency (LAD) can be
or if there is a convincing history or family history suggestive evaluated by flow cytometry evaluation of cell surface
of an immunodeficiency. The patient should be referred to a marker expression of CD11 and CD18. These are absent
special center for diagnostic tests and management. in LAD I and CD15a is absent in LAD II. However, patients
• Lymphocyte subset analysis: by flow cytometry for CD3 with LAD III have normal integrin expression and
(total T cells), CD4 (T helper), CD8 (T cytotoxic), CD19
demonstration of impaired integrin activation, is needed
(B cells), and CD16/56 (natural killer cells), compared with
• Complement component: if the screening test shows
age-matched controls (B or T cell defect)
very low or absent CH50 activity on repeat testing then
• An absolute CD4 count of less than 500 cells/µL in a child
complement component assays are indicated
over 5 or less than 1,000 cells/µL in younger children
• Confirmatory diagnostic studies: many immune defects
(suggests a cellular immunodeficiency)
have their molecular tests available; these tests are usually
• An absolute B cell (CD19) count of less than 100 cells/µL
can be seen in children with agammaglobulinemia performed in specialized labs. A definite diagnosis by
• Low levels of any lymphocyte subset should be repeated molecular testing helps in treatment, prognosis, and
and if still decreased, followed by functional analysis of the genetic counseling. Genetic diagnosis is available for the
respective subset majority of disorders commercially and confirmatory tests
• Immunoglobulin G subset levels can be tested if the should be done in conjunction with a specialist as these
patient has low total IgG levels and poor antibody response tests are expensive.
to vaccinations. A complete absence of IgG1, IgG2, or Confirm the neutropenia on a manual peripheral smear
IgG3 suggests immune dysregulation, and may indicate stained with Wright-Giemsa stain and perform a bone
the early onset of common variable immunodeficiency. marrow test. For cyclic neutropenia, there will be recurrent
However, a low level of only one or more IgG subclasses infections and a regular oscillation in the neutrophil count at
does not make a diagnosis if an antibody deficiency, for approximately 21 day intervals. Other causes of neutropenia
such a diagnosis functional antibody studies are needed are given in table 3. 281
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Table 3: Causes of isolated neutropenia

Key points
Acquired neutropenias Congenital neutropenias
Postinfectious: mechanisms are Kostmann’s syndrome
))
A single episode of unusual infection (rare organism or
sequestration, aggregation, or unusual severity of infection of common organism) should be
destruction of neutrophils by the taken seriously and investigated
circulating antibodies ))
Early diagnosis and referral is lifesaving.
Drug-induced: immune-mediated Shwachman-Diamond
destruction, drug-induced antibodies syndrome
or by direct toxic effects on bone SUGGESTED READINGs
marrow granulocyte precursors
Primary immune disorders: anti Chédiak-Higashi syndrome 1. Buckley RH, editor. Diagnostic and clinical care guidelines for primary
neutrophil antibodies in patients immunodeficiency diseases: Immune Deficiency Foundation 2006. [online]
of systemic lupus erythematosus, Available from: www.primaryimmune.org. [Accessed December, 2015].
rheumatoid arthritis 2. Grüber C, Keil T, Kulig M, Roll S, Wahn U, Wahn V, et al. History of respiratory
infections in the first 12 yr among children from a birth cohort. Pediatr Allergy
Isoimmune neonatal neutropenia: Cyclic neutropenia Immunol. 2008;19(6):505-12.
due to transplacental passage of 3. Skoda-Smith, S, Barrett, DJ. When earaches and sore throats become more than
immunoglobulin G antibodies a pain in the neck. Contemp Pediatr. 2000;17:156.
against specific paternal neutrophil 4. Stiehm ER, Ochs HD, Winkelstein JA. Immunodeficiency disorders: general
antigens in the infant considerations. In: Stiehm ER, Ochs HD, Winkelstein JA, editors. Immunologic
Chronic autoimmune neutropenia Rule out other diseases: disorders in infants and children. 5th ed. Philadelphia: Saunders/Elsevier; 2004.
occurs in infants and children and is a Fanconi anemia, reticular p. 289.
benign entity agenesis, myelodysplastic 5. Stiehm ER. Approach to the child with recurrent infections. 2015 [online]
syndrome (may precede Available from: http://www.uptodate.com/contents/approach-to-the-child-with-
pancytopenia), glycogen recurrent-infections. [Accessed December, 2015].
storage disease type 1 6. Wheeler JG. Evaluating the child with recurrent infections. Am Fam Physician.
1996;54(7):2276-82, 2285-6.
Clinical Pearls
• Opportunistic infections can be due to neutrophil defects,
T cell deficiency, or human immunodeficiency virus
• Recurrent sinopulmonary infections may be due to antibody
defects.
282
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Chapter 62
Approach to Persistent Fever with
Hepatosplenomegaly in a Child
Anupam Sachdeva, Vinod Gunasekaran
INTRODUCTION radiation, autoimmune disease, and Kupffer cell hyperplasia

also may cause hepatomegaly by this mechanism. Metastatic
Hepatosplenomegaly is a common clinical finding seen infiltration occurs in leukemia, lymphoma, neuroblastoma,
in infants and children presenting with fever. Hepato and histiocytosis. Extramedullary hematopoiesis and hemo
splenomegaly can be associated with a variety of clinical phagocytic syndrome cause hepatomegaly due to infiltration
conditions including infectious, hematological, malignant, by blood cells. Hepatomegaly due to other mechanisms may
congestive, storage disorders, connective tissue disorders, not be associated with fever usually.
and other miscellaneous conditions. Fever can be associated
in a majority of these conditions. Hence, a thorough history, Clinical Pearl
clinical examination, and relevant laboratory investigations
help the clinician in arriving at an early diagnosis and to • Liver can normally be palpable in young children. Enlarged
initiate appropriate treatment. This chapter discusses in liver span signifies hepatomegaly.
detail regarding a practical approach to a child with fever and
hepatosplenomegaly and a simplified algorithmic approach is
provided in algorithm 1. SPLENOMEGALY
Spleen becomes clinically palpable only after it enlarges two to
HEPATOMEGALY three times its normal size. Splenomegaly can be classified into
three grades based on the size enlarged below the left costal
A liver that is palpable clinically does not always indicate margin, i.e., mild, (1–3 cm), moderate (4–7 cm), and massive
hepatomegaly. Liver can normally be palpable in infants and (>7 cm).
young children. It can also be displaced inferiorly by pathology
involving diaphragm or thoracic organs, giving the impression Clinical Pearl
of hepatomegaly. Hence, the liver span measured by percussion
is more reliable and it should be more than the expected for the • A soft, thin spleen can be palpable in 15% of neonates, 10% of
corresponding age to consider as hepatomegaly. The normal normal children and 5% of adolescents.
range for liver span by percussion at 1 week of age is 4.5–5 cm.
At 12 years, the normal value for boys is 7–8 cm and for girls is Causes of persistent fever with hepatosplenomegaly in a
6–6.5 cm. The normal range of liver span in various age-groups child:
include: infants, 5–6.5 cm; 1–5 years, 6–7 cm; 5–10 years, 7–9 • Infectious:
cm; and 10–15 years, 8–10 cm. Hepatomegaly generally occurs {{ Viral
via five mechanisms: –– Infectious mononucleosis

1. Inflammation –– Congenital Toxoplasmosis, Other Agents, Rubella,
2. Excessive storage Cytomegalovirus, and Herpes Simplex (TORCH)
3. Infiltration infections
4. Congestion –– Human immunodeficiency virus (HIV)
5. Obstruction. –– Herpes simplex infections
Infections from viruses, bacteria, fungi, and parasites –– Dengue
promote inflammation-induced hepatomegaly. Toxins, –– Viral hepatitis
ch-62.indd 283 11/19/2016 5:03:45 PM

Algorithm 1
Approach to persistent fever with hepatosplenomegaly in a child
CBC, complete blood count; DLC, differential leukocyte count; PS, Peripheral Smear; RFT, renal function test; LFT, liver function test; PT, prothrombin time; aPTT,
activated partial thromboplastin time; RDT, rapid diagnostic test; ELISA, enzyme-linked immunosorbent assay; EBV, Epstein-Barr virus; TB, tuberculosis; USG,
ultrasound; TORCH, Toxoplasmosis, Other Agents, Rubella, Cytomegalovirus, and Herpes Simplex; LBW, low birth weight; HIV, human immunodeficiency virus.
{{Bacterial {{ Lymphomas
–– Salmonella typhi {{ Chronic myeloid leukemia
–– Rickettsial infections {{ Neuroblastoma
–– Leptospirosis • Miscellaneous:
–– Tuberculosis {{ Sarcoidosis
–– Borreliosis {{ Chronis granulomatous disease
–– Congenital syphilis {{ Hemolytic anemia with acute infections.
–– Brucellosis Among the various causes enumerated, infections like

–– Pyogenic liver abscesses malaria, dengue, tuberculosis, enteric fever, viral hepatitis,
–– Infective endocarditis septicemia, and rickettsial infections constitute a majority
–– Bacterial sepsis with disseminated intravascular of children presenting with fever and hepatosplenomegaly
coagulation (DIC) in tropical countries. Pallor, jaundice, anorexia, rashes, and
{{ Parasitic abdominal distension are the common associated complaints.
–– Malaria Lymphadenopathy is a common associated finding. These
–– Kala-azar signs and symptoms help in making a differential diagnosis
–– Toxoplasmosis and guide initial investigations.
–– Toxocariasis
{{ Fungal Clinical Pearl
–– Disseminated histoplasmosis
• In tropical regions, infections remain the common cause of
–– Systemic candidiasis (in immunosuppressed)
fever with hepatosplenomegaly.
• Connective tissue disorders:
{{ Systemic lupus erythematosus
{{ Systemic onset juvenile idiopathic arthritis

HISTORY
• Hemophagocytic syndromes:
{{ Postinfectious Evaluating a child with fever and hepatosplenomegaly starts
{{ Familial with a complete history. The etiology may differ depending
• Malignancies: on the patient’s age group. Acute leukemia usually presents in
284 {{ Acute leukemia the age group of 2–10 years. In an infant, a careful birth history
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Chapter 62: Approach to Persistent Fever with Hepatosplenomegaly in a Child
including birth weight may uncover risk factors for perinatally

acquired infections that include hepatitis B, toxoplasmosis, Clinical Pearl
syphilis, cytomegalovirus, rubella, herpes simplex, enterovirus, • Detailed history, complete physical examination, and having
rubella, and HIV. In older children, careful questioning about knowledge about infections prevalent in the locality and their
travel, insect exposure, ingestion of drugs, and environmental mode of presentations help in guiding initial investigations.
toxins may reveal risk factors for acute hepatitis or certain
infections. Epidemiology of the patient gives clue for certain
diseases like kala-azar, which is localized to certain parts of the INVESTIGATIONS
country (Bihar and eastern Uttar Pradesh). Investigations should be tailored for every patient based on the
A prodrome of upper respiratory infection is seen in Epstein- clinical clues attained from history and clinical examination.
Barr virus (EBV) infections. History of myalgia or arthralgia may Otherwise, investigations may be misleading, diagnosis may
be seen in viral infections and in leptospirosis. History of bony be delayed and the treatment cost would increase.
pain and tenderness is seen in acute leukemia. Acute onset of
hepatomegaly associated with hyperbilirubinemia in an older
child raises the suspicion of infection with hepatitis A. Previous
Initial Investigations
history of recurrent infections may give a clue to underlying Initial investigations in most patients would include:
immunodeficiency. History of raw milk consumption may • Complete blood count with differential count and a
be associated with Brucellosis infection. Systemic symptoms peripheral blood smear examination. It gives important
related to chronic inflammatory diseases should be sought in information about the cell lines involved and the degree
the older child. History of contact with tuberculosis or a person of cytopenia or elevated counts. A peripheral smear
with chronic cough is an important clue for a young child might show blasts, activated lymphocytes, evidence of
presenting with disseminated tuberculosis. Previous history hemolysis, or malarial parasites which may be of diagnostic
of repeated transfusions, jaundice, gallstones may be a clue importance
for an underlying hemolytic anemia, now presenting with an • Liver functions, renal function tests (if required), in a child
acute infection. Family history suggestive of a similar illness or with signs of liver or renal dysfunction or in any sick child
a recent infectious illness may be a clue for a communicable or • Workup for common infectious causes including blood and
a hereditarily predisposed illness. Other nonspecific signs and urine cultures, serology against infections like Salmonella,
symptoms include fatigue, anorexia, weight loss, blood in the Brucella, Rickettsia, leptospirosis, dengue, viral hepatitis
stool, and abdominal distension. markers, and EBV, as indicated by the clinical clues and the
current epidemiological pattern of infectious diseases in
the patient’s locality
PHYSICAL EXAMINATION
• Multiple smears especially during febrile episodes must
A careful physical examination often narrows the diagnostic be sent in a child with compatible clinical picture of
considerations. Neonatal history of intrauterine growth malaria. Although Plasmodium falciparum is most likely
retardation, microcephaly, chorioretinitis, and purpura to be identified from blood just after a febrile paroxysm,
accompanied by hepatomegaly strongly suggests congenital the timing of the smears is less important than their being
infection. Presence or absence of associated rash and the type obtained several times a day over a period of 3 successive
of rash give rise to a different set of differential diagnosis. Viral days. A single negative blood smear does not exclude
exanthems are by far the most common cause of fever with malaria; it may be necessary to repeat the smears as often
rash in children. Among them, dengue, dengue-like illnesses, as every 4–6 hours a day to confirm the diagnosis. Most
Herpes simplex infections, infectious mononucleosis, etc. symptomatic patients with malaria will have detectable
can have associated hepatosplenomegaly. Among bacterial parasites on thick blood smears within 48 hours. Rapid
infections, S. typhi, leptospirosis, rickettsial infections, diagnostic tests (RDT kits) are available for malaria, that
borreliosis, and brucellosis can have similar set of clinical can be done bedside without any equipments with good
findings. Connective tissue disorders like systemic lupus sensitivity and specificity. Presently, National Vector-Borne
erythematosus, juvenile idiopathic arthritis can also manifest Disease Control Programme supplies RDT kits for detection
skin rashes. Presence of lymphadenopathy is usually seen in of P. falciparum at locations where microscopy results are
the above clinical conditions. Lymphomas can present with not obtainable within 24 hours of sample collection.
fever, hepatosplenomegaly, and lymphadenopathy without
other manifestations.
Petechial rash may be seen in dengue hemorrhagic fever
Imaging of Abdomen
and meningococcal infections. Petechial, purpuric, and Abdominal ultrasound should be considered early in a child
ecchymotic rashes can be seen in fulminant sepsis with DIC who is toxic with tender hepatomegaly to rule out pyogenic
or in malignant conditions like acute leukemia. Bleeding liver abscess. Ultrasound may also give information
manifestations can be seen in dengue, severe malaria, DIC, and regarding mesenteric lymphadenopathy, minimal ascites,
acute leukemia. Other findings to be looked for include pallor, evidence of intestinal tuberculosis, etc. in selected cases.
jaundice, edema, and evidence of third spacing, evidence of Granulomatous lesions are detected as hypoechoic lesions
malnutrition, and involvement of other organ systems. in liver and spleen. 285
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Other Investigations like enteric fever and rickettsial infections should be

initiated after sending the initial etiological workup.
• Congenital Toxoplasmosis, Other Agents, Rubella,
Measures have to be taken to demonstrate malaria parasite
Cytomegalovirus, and Herpes Simplex screen may be sent
before starting empirical antimalarial therapy. However,
in neonate or an early infant with low birth weight
if clinical presentation indicates severe malaria and there
• Workup for tuberculosis including chest X-ray, Mantoux,
is no alternative explanation these patients should be
sputum, or gastric lavage for acid-fast bacilli must be
treated accordingly. Investigations should be continued
considered in a malnourished child or with a subacute
simultaneously till a definitive diagnosis is made and specific
or chronic presentation or a history of contact with an
therapy must be initiated.
open case
• Human immunodeficiency virus has to be ruled out in a
high-risk patient especially if the initial workup is negative Key points
• Recombinant K39 antigen test should be sent in a child from
))
Hepatosplenomegaly is a common clinical finding seen in
an endemic area for kala-azar. This test has a sensitivity and infants and children presenting with fever
specificity close to 100%
))
Fever with hepatosplenomegaly can be caused by infectious
• Autoimmune etiology should be considered in an older
(viral, bacterial, parasitic, and fungal), connective tissue
child with rashes, arthralgia, polyserositis, or characteristic
disorders, malignancies, hemophagocytic syndromes, and
rash. Antinuclear antibody and double stranded deoxy other rare conditions
ribonucleic acid should be sent in such cases
))
In tropical regions, infections remain the most common cause
• Fungal workup including fungal cultures from blood and
of fever with hepatosplenomegaly
urine, fungal serology, etc. may be considered in child
with underlying immunosuppression including those ))
Detailed history, complete physical examination and having
knowledge about infections prevalent in the locality and their
on chemotherapy, myelosuppressive agents, critically-
presentations help in guiding initial investigations
ill patients with multiple indwelling catheters, severely
malnourished children, HIV-infected children, etc ))
Complete blood count with a good peripheral smear
• Bone marrow aspiration and biopsy may be indicated in examination and workup for common infectious etiologies
give a clue to diagnosis in a majority of cases
children developing bicytopenia/pancytopenia or showing
abnormal cells on peripheral smear in order to rule out ))
Treatment of the underlying etiology remains the mainstay
hemophagocytosis or malignancy. Leishmania donovani of therapy. However, in a sick child, initial empirical therapy is
bodies in bone marrow confirm the diagnosis of kala-azar justified pending investigation reports.
• Fine needle aspiration cytology/biopsy of peripheral lymph
nodes or ultrasound-guided aspiration of mesenteric
lymph nodes may be of etiological value in case of tuber SUGGESTED READINGs
culosis or lymphoma 1. Anusha G, Somaiah G, Siddique AM, Srikanth B, Suresh Babu M, Vamsidhar
• Systemic-onset juvenile idiopathic arthritis is usually a NS. Study of etiological and clinical profile of hepatosplenomegaly in children
diagnosis of exclusion, which is made only after excluding between 1 month and 15 years of age. Sch J App Med Sci. 2014;2(2A):554-7.
common infectious etiology, autoimmune, and a malignant 2. Guidelines for Diagnosis and Treatment of Malaria in India. 2nd ed. New Delhi:
process. National Institute of Malaria Research; 2011.
3. Kliegman RM, Stanton BF, Geme JW, Schor NF, Behrman R, editors. Nelson
Textbook of Pediatrics. 19th ed. Elsevier Saunders; 2011.
TREATMENT 4. Lakshmanaswamy A. Clinical Paediatrics. History Taking and Case Discussion. 3rd
ed. Wolters Kluwer Health/Lippincott Williams and Wilkins (India); 2012.
Treatment of the underlying etiology remains the mainstay 5. Paul V, Bagga A. Ghai Essential Paediatrics. 8th ed. CBS Publishers; 2013.
of therapy. However, in a sick child presenting to emergency 6. Sarkar R, Mishra K, Garg VK. Fever with rash in a child in India. Indian J Dermatol
with fever and hepatosplenomegaly, initial stabilization, Venereol Leprol. 2012;78(3):251-62.
supportive care followed by intravenous (IV) antibiotics 7. Wolf AD, Lavine JE. Hepatomegaly in neonates and children. Pediatr Rev.
against the common infections prevailing in the community 2000;21(9):303-10.
286
ch-62.indd 286 11/19/2016 5:03:47 PM

Chapter 63
Approach to a Bleeding Child
Nitin K Shah
INTERPRETATION OF ALGORITHM CLINICAL HISTORY

Hemostasis is a delicate balance between fluidity of blood so
that it can circulate freely within blood vessels and coagulation Local versus Generalized Bleeding
so that any breach in continuity of blood vessels can be sealed Local cause should be suspected when bleeding is from a
efficiently and immediately so as not to exsanguinate the body. single site and recurs often from the same site, e.g. epistaxis
This delicate balance is maintained mainly by three factors, with bleeding from left nostril recurring every time from the
namely, vascular and extravascular tissues, platelets, and same nostril. Such bleeding should lead to a suspicion of local
plasma factors. Any disturbance in these three factors will lead causes such as a polyp or a foreign body. However, if bleeding is
to either bleeding or excessive clotting (thromboembolism). from both nostrils or from any of the nostrils and patient gives
Successful management of an acute bleeding episode in a history of hematuria or a past history of excessive bleeding after
child mainly depends on the ability to make a rapid diagnosis tooth extraction, then it is more likely to be due to a systemic
and prompt implementation of therapeutic measures. Proper defect. Common local causes of bleeding are shown in table 1.
detailed history and thorough clinical examination often In generalized bleeding disorders, bleeding is spontaneous
suggest the presence and type of bleeding disorder. However, or greater than expected for extent of injury or the site of bleeding
accurate diagnosis which is required for specific therapy and bleeding is from multiple sites like skin and mucous
depends on laboratory tests. A careful history also provides membrane, bleeding into interstitial tissue, muscles, joints, etc.
critical information in selecting subsequent tests thus avoiding
a battery of investigations. Further workup becomes necessary Platelet/Vascular Type versus
when there is:
• A recent bout of bleeding: spontaneous or after injury or Coagulation Type of Bleeding
surgery—usually prolonged and disproportionate to extent Bleeding following vascular disorder, thrombocytopenia, or
of injury functional platelet disorders is usually in the form of spon
• Family history of bleeding episodes
• Preparation for surgery or invasive procedures Table 1: Common local causes of bleeding based on site of
• Systemic diseases known to be associated with bleeding bleeding
disorders, e.g., liver disorder, renal disorder, disseminated
Site of bleeding Local cause of bleeding
intravascular coagulation (DIC), sepsis, etc.
Epistaxis Deviated septum, hypertrophic turbinate,
Whenever a child presents with bleeding episode it is
ectatic vessel
necessary to decide:
Oral Poor dental hygiene
• Whether bleeding is significant?
• Whether it is due to local causes, or whether it is a Upper Swallowed blood in newborn, varices,
gastrointestinal hemangioma
generalized hemostatic defect?
Lower Rectal polyp, Meckel’s diverticulum, anal fissure
• What is the nature of the bleeding episode? Is it due
gastrointestinal
to vascular, platelet, or a coagulation abnormality or a
Hematuria Cystitis, bladder stone, renal tumor
combination of two or more?
• Is it congenital or acquired? Umbilicus Slipped ligature, granuloma
ch-63.indd 287 11/19/2016 5:05:17 PM

taneous subcutaneous and mucous membrane bleeds like inherited bleeding disorders. Family history might be
petechiae, purpura, superficial, and few ecchymosis, epistaxis, negative, if the coagulation defect is mild or there is a
and menorrhagia. It is often controlled by pressure and once spontaneous mutation, as is seen in 20% of patients
controlled, it usually does not recur. However, in patients with with hemophilia A
coagulation factor deficiency, hematomas are usually deep (in • Site of bleeding: superficial bleeding is more common in
the muscles) and spreading, bleeding into cavities like joints platelet type of bleeding and most common platelet disorder
and retroperitoneal space is known. Post-traumatic bleeds are is ITP which is acquired cause of bleeding whereas deep
often delayed, sometimes hours after the injury. This may recur bleeding especially muscle hematoma or joint hematoma
and bleeding may not get controlled by pressure. are typically seen in coagulation factor deficiency like
hemophilia which are inherited causes of bleeding.
Inherited versus Acquired Causes
Acquired Causes
Inherited Causes Conversely, patients with acquired disorders usually present
• Age of presentation: inherited disorders usually present in later in life and have a negative family history. They may be
infancy and early childhood with history of bleeding from associated with underlying systemic disorders like kidney
the umbilical cord, without evidence of sepsis or slipped diseases and liver disorders, infections, etc. Previous history of
ligature; spontaneous large cephalhematoma during early operations like circumcision, dental extraction, tonsillectomy,
neonatal period, bleeding during the eruption or fall of or major operation practically rules out the possibility of a
deciduous tooth, etc.; exception being mild hemophilia moderate to severe inherited bleeding disorder. Absence of
though inherited cause of bleeding presenting late in life say bleeding from previous trauma, however, does exclude an
following a surgery. Whereas acquired bleeding disorders inherited bleeding disorder. Patients of mild hemophilia with
present at any age, usually later in life, like idiopathic factor level around 10–25% may bleed only after severe trauma.
thrombocytopenic purpura (ITP) presenting at 3–5 years Subject with normal hemostasis may also have bleeding from
of age, exception being hemorrhagic disorder of newborn nonhematological causes as seen in females with menorrhagia
due to vitamin K deficiency though being acquired cause of or of molar tooth extraction. History of ingestion of drugs like
bleeding presenting in first week of life aspirin, in the recent past should lead to the suspicion of a
• Family history: proper family history of bleeding disorders transient drug related hemostatic defect. Similarly, history of
of at least 2–3 generations on each side of parents (including oral contraceptives or pregnancy may temporarily increase
those who might have died) and noting the pedigree chart factor VIII and Von Willebrand factor levels and thus increasing
helps in realizing the mode of transmission of the disorder the hemostatic competency in women with Von Willebrand
such as sex-linked recessive, autosomal recessive or disease.
autosomal dominan
{{ X-linked recessive inheritance: females are carrier Associated Underlying Disorders
and males are affected. Only male siblings, males Certain characteristic hemostatic defects are associated with
on maternal side including maternal male cousins, specific clinical conditions, e.g., liver diseases with factor II,
maternal uncles, and maternal grandfather are VII, IX, and X deficiency and fibrinolysis due to decreased
affected. This is typically seen in hemophilia A and B or clearance of activators and hypercoagulable state because
Wiskott-Aldrich syndrome of antithrombin III and protein C deficiency. Malabsorption
{{ Autosomal recessive inheritance: both parents of states may be associated with vitamin K deficiency. Acute
affected person are heterozygotes and often there is promyelocytic leukemia is known to be associated with DIC due
a history of consanguinity. Siblings of either sex and to increased cellular procoagulant activities. Myeloproliferative
both maternal as well as paternal cousins of either sex disorder may have platelet defects, thrombocytopenia, and
are affected (horizontal transmission). This pattern is thrombocythemia. Amyloidosis may be associated with
typical of disorders of factor II, V, VII, X, XI, XII, and XIII factor X deficiency and capillary fragility. Systemic lupus
deficiency erythematosus (SLE) and antiphospholipid antibody (APLA)
{{ Autosomal dominant inheritance: there is vertical syndromes may be associated with thrombocytopenia,
transmission as the proband is affected, one of the acquired hemophilia or acquired Von Willebrand disease or
parents is affected and grandparents may be affected on the other hand with hypercoagulable states.
with variable penetrance and variable severity within
families. This is seen typically in Von Willebrand Clinical Pearls
disease, some types of qualitative platelet defects,
dysfibrinogenemia, and hereditary hemorrhagic Questions to be asked while history taking in a bleeding child:
telangiectasia. Some of the cases may be spontaneous • It the bleeding significant?
mutation with negative family history • Is the bleeding due to local cause or systemic cause?
{{ Although a positive family history is of great value
• Is the bleeding platelets/vascular type or coagulation type?
in the diagnosis of bleeding disorders, a negative • Is the bleeding due to congenital or acquired cause?
288 family history does not rule out the possibility of
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Chapter 63: Approach to a Bleeding Child
EXAMINATION Table 2: Syndromes associated with specific bleeding disorders

Associated condition Interpretation
Well versus Sick Child Oral or nasal telangiectasia, ataxia Hereditary telangiectasia
Well child with no fever, pain, organomegaly, bleeding, bone Partial albinism Hermansky-Pudlak
pains, or weight loss would suggest ITP, whereas sick child would syndrome
suggest other causes like bone marrow failure or infiltrates.
Syndactyly Factor V deficiency
Pallor and Organomegaly Skeletal malformation, short stature Fanconi’s anemia
Sick child with presence of pallor out of proportion of external Absent radius Thrombocytopenia-absent
bleeding would suggest bone marrow suppression like in radius syndrome
malignancies and aplastic anemia. Presence of organomegaly Injury marks, rib fractures, subdural Battered baby syndrome
like hepatomegaly, splenomegaly and significant lympha hemorrhage
denopathy, weight loss, and bony tenderness would suggest Linear purpura at accessible sites Fictitious purpura
malignancies whereas absence of organomegaly and bony
Keloids Afibrinogenemia
tenderness would suggest aplastic anemia.
Cigarette paper scar, hypermobile Ehlers-Danlos syndrome
Site of Bleeding joints
Presence of superficial bleeds like petechiae, purpura, and Thrombocytopenia, eczema, ear Wiskott-Aldrich syndrome
discharge
few superficial ecchymosis suggest ITP, vascular cause, or
platelet dysfunction. Deep bleeding like muscle hematoma, Giant hemangioma Kasabach-Merritt syndrome
exsanguinating hematomas, retroperitoneal bleeds, and
joint bleeds are pathognomonic of coagulation disorders like
hemophilia. INVESTIGATIONS
No single test is suitable for the laboratory evaluation or
Associated Syndromes the overall process of hemostasis and blood coagulation.
There are some specific systemic disorders which have Laboratory tests can be conveniently divided into screening
bleeding as a significant problem and have pathognomonic tests and special tests. Screening tests are applied only after
tell-tale signs as shown in table 2. This includes presence of evaluating the nature and clinical circumstances of bleeding
• Skeletal deformities, mental retardation, hypogonadism, and prior to surgery, so as to know the presence and nature of
short stature, hyperpigmentation, and renal anomalies in bleeding disorder so that special tests can be done to confirm
Fanconi’s anemia the diagnosis thus avoiding a battery of unnecessary tests.
• Absent radius in thrombocytopenia with absent radius
(TAR) syndrome Screening Tests
• Ataxia, mucosal telangiectasia, and mental subnormality
in ataxia telangiectasia Screening tests include:
• Partial albinism in Hermansky-Pudlak syndrome • Complete blood count (CBC) and peripheral smear (PS)
• Syndactyly or lobster hand in factor V deficiency examination
• Keloids in children with afibrinogenemia and factor XIII • Platelet count
deficiency • Prothrombin time (PT) and activated partial thromboplastin
• Cigarette paper scar, hyperextensible joints, cutis elastic in time (aPTT)
Ehlers- Danlos syndrome • Thrombin time
• Hematochezia, thrombocytopenia, recurrent infection, • Bleeding time (BT), clotting time, and clot retraction
otitis media, and eczema in a male child with Wiskott- (rarely).
Aldrich syndrome Interpretation of the screening tests is always done together
• Giant hemangioma associated with evidence of clinical and never in isolation as shown in the table 3.
and subclinical DIC and thrombocytopenia in Kasabach- Complete blood count and PS examination: CBC tells the
Merritt syndrome. involvement of red blood cell series (Hb and red cell indices),
white blood cell series (total leukocytes and absolute
Clinical Pearls neutrophil count), and platelet series. Peripheral smear
examination will confirm all these three cell series involvement
Questions to be asked while examining a bleeding child: and give clue to the probable diagnosis like leukemia, etc. For
• Is he a well or a sick child? platelets, PS is more reliable than machine reports. Presence
• Is there organomegaly? of 10–15 platelets per high power field and presence of platelet
• Are there other systemic disorder signs? clumps will suggest normal platelet counts. Large platelets
• Are there physical anomalies, especially skeletal deformities?
are seen in regenerative thrombocytopenia as seen in ITP,
normal size platelets are seen as in aregenerative cause of 289
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Table 3: Interpretation of screening tests for bleeding

Clinical aPTT PT TCT Bleeding Platelet count Possible defects
bleeding time
Absent Abnormal Normal Normal Normal Normal High-molecular-weight kininogen,
prekallikrein, factor XII, lupus inhibitor
Present Abnormal Normal Normal Normal Normal Factor XI, IX, VIII deficiency
Present Abnormal Abnormal Normal Normal Normal Factor V, X, II, coumarin, vitamin K
deficiency, mild hepatic disease
Present Normal Abnormal Normal Normal Normal Factor VII deficiency
Present Abnormal Normal Normal Abnormal Normal Von Willebrand disease
Present Abnormal Abnormal Abnormal Abnormal Normal Afibrinogenemia
Present Normal Normal Normal Abnormal Abnormal Thrombocytopenia
Present Normal Normal Normal Abnormal Normal Qualitative platelet disorder (aspirin,
thrombasthenia, Bernard-Soulier syndrome)
Present Normal Normal Normal Normal Normal Factor XIII deficiency
Present Abnormal Abnormal Abnormal Abnormal Abnormal Disseminated intravascular coagulation,
severe liver disease
Variable Normal Normal Abnormal Normal Normal Dysfibrinogenemia, myeloma, fibrinogen/
fibrin degradation products
Present Abnormal Normal Abnormal Normal Normal Heparin
TCT, thrombin clotting time; PT, prothrombin time; aPTT, activated partial thromboplastin time.
thrombocytopenia like aplastic anemia, giant platelets are Thrombin time measures thrombin induced conversion
seen as in Bernard-Soulier syndrome, microplatelets are seen of fibrinogen to fibrin and is abnormal in patients with
as in Wiskott-Aldrich syndrome, and presence of normal hypofibrinogenemia whether acquired or congenital or
platelets but not in clumps will indicate absence of aggregation, dysfibrinogenemia and in presence of inhibitors like heparin,
suggesting platelet functional disorder. myeloma proteins and fibrin degradation products which
block either thrombin cleavage of fibrinopeptide or fibrin
Platelet count: it is a simple first step in evaluating the cellular
monomer polymerization.
aspect of hemostasis. However, manual count is not reliable
A prolongation of PT with normal partial thromboplastin
and not reproducible and hence platelet count should be done
time (PTT) that is corrected by adding normal pooled plasma
on particle cell counter or using phase contrast microscope.
indicates factor VII deficiency that occurs with congenital
In platelet type of bleeding, if platelet count is normal or
deficiency, early during oral anticoagulant therapy, vitamin K
marginally low, vascular or platelet functional disorders should
deficiency, or liver diseases. This is further confirmed by factor
be kept in mind.
VII assay.
Prothrombin time, aPTT, and TT: aPTT is an excellent A prolonged aPTT with normal PT which is corrected
screening test for determining abnormality of intrinsic clotting by adding normal pooled plasma will suggest deficiency of
pathway and common pathways and is sensitive to activities factor VII, IX, XI, or XII, however, factor XII deficiency does
of approximately 20% or less of factor VIII and IX or XI. aPTT not manifest clinically with bleeding and in fact presents with
is prolonged during deficiency or abnormalities of extrinsic thromboembolism hence leaving deficiency of factor VIII,
pathway clotting factors like high molecular weight, kininogen, IX or XI as the cause. This can be confirmed further by doing
prekallikrein, factor XII, XI, IX, VIII; or of common pathway factor VIII, factor IX, and factor XI assay in that order based on
clotting factors like X, V, II, and fibrinogen; or by inhibitors their incidence.
of blood coagulation such as lupus inhibitors, heparin, and Prolongation of both PT and aPTT would suggest common
fibrin/fibrinogen degradation product. Activated partial pathway factor deficiency like factor X, V, II, or fibrinogen;
thromboplastin time of test more than 10 seconds over control or multiple factor deficiency of intrinsic as well as extrinsic
is considered abnormal. pathways as seen in chronic liver disease or vitamin K
Prothrombin time measures extrinsic clotting system deficiency.
and the common pathway. It is measured as International Prolonged TT would suggest fibrinogen deficiency or
Normalized Ratio (INR) and is considered abnormal when INR dysfunction. Prolonged TT with normal serum fibrinogen
is more than 1.2, however, if INR is not available it is considered would suggest dysfibrinogenemia, and with low or absent
abnormal when test Prothrombin time is more than 3 seconds fibrinogen levels would suggest hypo- or afibrinogenemia.
over control. PT is prolonged with deficiencies of intrinsic Prolonged aPTT should be screened for presence of
pathway clotting factor like VII; or common pathway factors inhibitor doing correction study where 1 mL of test plasma
290 like X, V, II, and fibrinogen and inhibitors of these factors. is mixed with 1 mL of pooled normal plasma and aPTT
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Algorithm 1
Approach to a bleeding child
ITP, idiopathic thrombocytopenic purpura; HSP, Henoch-Schönlein purpura; vWD, von Willebrand disease; LN, lymph node; DIC, disseminated intravascular
coagulation; FFP, fresh-frozen plasma; EACA, epsilon aminocaproic acid; TAR, thrombocytopenia and absent radius; SLE, systemic lupus erythematosus; CBC,
complete blood count; PT, prothrombin time; aPTT, activated partial thromboplastin time; FDP, fibrinogen/fibrin degradation products.
is repeated at zero and 4 hours. If aPTT corrects by more BT is usually prolonged and is often 15 minutes or longer and
than 50%, it suggests factor deficiency. If aPTT does not hence BT in severe thrombocytopenia is not required and can
correct and even worsens after 4 hours of incubation, it be hazardous as it can lead to scarring.
suggests of presence of inhibitor which is then confirmed by Qualitative platelet disorders have prolonged BT with
doing inhibitor assay. In such cases one must also rule out nearly normal platelet count as seen in Glanzmann’s
autoimmune disorders like APLA syndrome and SLE by doing thrombasthenia, Bernard-Soulier syndrome, storage pool
appropriate tests. disorder, Wiskott-Aldrich syndrome and with various drugs
like aspirin and nonsteroidal anti-inflammatory agents
Others like ibuprofen, etc. Even in Von Willebrand disease, BT is
Bleeding time: this test evaluates primary hemostatic stage usually prolonged as Von Willebrand factor is involved in
and is ideally done with the help of template. The normal BT is binding of platelets to matrix protein or to other cells. One
4–7 minutes and prolongation of BT usually occurs at platelet can do platelet aggregation study to prove platelet functional
count less than 50,000/cumm. At counts below 10,000/cumm, disorders as shown in table 4. This can be confirmed by doing
Table 4: Platelet aggregation study (for platelet dysfunction)

Disorder ADP Collegen Adrenalin Restocetin Arachidonic acid
Primary Secondry
Thrombasthenia ABN ABN ABN ABN N ABN
Bernard-Soulier syndrome N N N N ABN N
Von Willebrand disease N N N N ABN N
Cyclo-oxygenase deficiency N — ABN ABN N ABN
Thromboxane synthetase deficiency
Storage pool disorder N ABN decreased ABN ABN N N or decreased
Aspirin defect N ABN decreased ABN ABN N ABN
N, normal aggregation; ABN, impaired aggregation.
291
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Algorithm 2
Correction studies when activated partial thromboplastin time is prolonged
aPTT, activated partial thromboplastin time.
platelet surface receptor studies for gpIIB/IIIA or gpIX which MANAGEMENT OF BLEEDING CHILD
are now widely available.
Management of a bleeding child will include general
Clot retraction: retraction and exudation of the serum after 1 supportive care and specific supportive care and treatment of
hour is observed in the clotting tube. Normally, 50% exudation primary disease (the list is vast and beyond the scope of this
at the end of 1 hour of the original blood volume is taken chapter).
as normal retraction. However, with the advent of platelet
aggregation study and platelet receptor study, this test has General supportive care: this will include volume expansion
become obsolete. using crystalloids and colloids, inotropes for falling blood
pressure, oxygen to improve tissue oxygenation, and treatment
Factor XIII assay: factor XIII deficiency presents with delayed of primary disease if any.
umbilical cord falling, intracranial bleeds, or delayed bleeding
from wounds with poor healing. Screening tests for bleeding Specific supportive care: it includes packed red blood cells
are normal in such cases; one can do 5 molar urea solubility to maintain hemoglobin in physiological range, platelets to
test to prove factor XIII deficiency. arrest bleeding in a case of thrombocytopenia (mainly in cases
due to decreased production), DIC [along with fresh-frozen
Clinical Pearls plasma (FFP)] and platelet dysfunction; FFP in cases with
coagulopathy; specific factor replacement in a case of known
Never do bleeding time (BT) and clotting time (CT) as screening clotting factor deficiency; use of cryoprecipitate to increase
tests. fibrinogen levels; use of factor eight inhibitor bypassing
Always do following tests: activity or activated prothrombin complex concentrates
• CBC with platelets counts and a peripheral smear for platelet in hemophilia with inhibitor; plasma exchange in a case of
morphology any inhibitors; and activated factor VII for nonresponsive
• Prothrombin time (PT) bleeding due to any cause.
• Activated partial thromboplastin time (aPTT)
• Thrombin time (TT) with S. fibrinogen. Key points
))
Ascertain whether bleeding is significant, platelet/vascular/
Bleeding Disorders with Normal Screening Tests coagulation type
Bleeding disorders not associated with any abnormalities in ))
Ascertain whether the child is well or sick and whether it is
screening tests are: inherited or acquired in origin
• Vascular causes like Henoch-Schonlein purpura, here ))
Always to complete screening tests and not bleeding time/
ditary telangiectasia (Pender-Osler-Weber syndrome), clotting time
scurvy, Ehlers-Danlos syndrome, senile purpura, simple ))
Idiopathic thrombocytopenic purpura is the most common
purpura (seen in 10% of women) bleeding disorder in children
• Factor XIII deficiency
))
Presence of organomegaly, fever, and anemia out of
• Fibrinolytic pathway defects like a-2 antiplasmin deficiency
proportion to bleeding should arouse suspicion of systemic
• Amyloidosis (may or may not be associated with factor X
disease.
deficiency)
• Mild clotting factor deficiency.
292
ch-63.indd 292 11/19/2016 5:05:22 PM

SUGGESTED READINGs 6. Ingram GI. Investigation of a long-standing bleeding tendency. Br Med Bull.
1977;33:261-4.
1. Bachmann HF. Diagnostic approach to mild bleeding disorders. Semin Hematol. 7. Lowe GD, Forbes CD. Laboratory diagnosis of congenital coagulation defects. Clin
1980;17:292-305. Haematol. 1979;8:79-94.
2. Bithell TC, editor. Bleeding disorders caused by vascular abnormalities. Wintrobe’s 8. Miller CH, Graham JB, Goldin LR, Elston RC. Genetics of classic von Willebrand’s
Clinical Hematology. 9th ed. Philadelphia: Lea & Febiger; 1993. pp. 1374-89. disease. I. Phenotypic variation within families. Blood. 1979;54:117-36.
3. Bowie EJ, Owen CA. Significance of abnormal preoperative hemostatic test. Pros 9. Osler W. On a family form of recurring epistaxis, associated with multiple
Hemost Thromb. 1980;5:179-209. telangiectases of skin and mucous membranes. Bull John Hopkins Hosp.
4. Fisher S, Rikover M, Noor S. Factor XIII deficiency with severe hemorrhagic 1901;7:333-7.
diathesis. Blood. 1966;28:34. 10. Seeler RA. Parahemophilia. Factor V deficiency. Med Clin North Am. 1972;56:
5. Gilbert C, White II, Marder VJ, Colman RW, et al. Approach to bleeding patient. 119‑25.
In: Colman RW, Hirsh J, Marder VJ, Salzman EW, editors. Hemostasis and 11. Uden A. Collagen and bleeding diathesis in Ehlers-Danlos syndrome. Scand J
Thrombosis. Philadelphia: JB Lippincott Co; 1987. pp. 1048-960. Haematol. 1982;28:425-30.
293
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Chapter 64
Clinic Pathological
Approach to Coagulation Disorder
Sangeeta S Mudaliar, Bharat Agarwal
INTRODUCTION to conditions which present with large ecchymosis and/or

joint bleeding .
Bleeding in a child can be a diagnostic challenge because of the Algorithm 4 explains a comprehensive approach to a
wide range of possible causes. Evaluation of a child presenting child presenting with bleeding and/or abnormal coagulation
with bleeding should include a comprehensive medical and screening test.
bleeding history, a complete family history, a detailed physical
examination, and selected laboratory tests. Investigations and
lab tests should be requested based on history and clinical SCREENING TESTS
findings. Initial tests to screen for bleeding disorders should include a
This chapter will be focussed on the laboratory tests, their complete blood count (CBC) with platelet counts, blood film,
interpretation, and significance on arriving at a diagnosis of prothrombin time (PT), and activated partial thromboplastin
various bleeding disorders. Bleeding disorders can be inherited time (aPTT).
or acquired, and include coagulation factor deficiencies, Sample collection: improperly collected sample is the most
platelet deficiencies and/or dysfunctions, and von Willebrand common cause of falsely elevated clotting time. Also, samples
disease (vWD). collected from indwelling catheters give spuriously abnormal
Algorithm 1 represents the differential diagnosis of values due to contamination with heparin or intravenous fluids.
various clinical conditions which may present with purpura or Samples should be collected in tubes containing citrate
bleeding. The various disease conditions have been grouped as (3.2 or 3.8%) as anticoagulant. The ratio of citrate to whole
nice (benign course) or nasty (malignant or life threatening or blood should be 1:9. This needs to be adjusted if patient has
prolonged course). high hematocrit. For infants and children, small 3 mL tubes
Algorithm 2 gives an approach to causes of mucosal and (2.7 mL blood to 0.3 mL citrate) should be used.
superficial skin bleeding while algorithm 3 gives an approach Samples should be tested within 2 hours of collection if at
room temperature or within 4 hours if kept cold.
Algorithm 1
Clinical differential diagnosis of purpura/bleeding in a child Complete Blood Count
Complete blood count [blood collected into ethylene
diamine tetraacetic acid (EDTA)] is performed to exclude
thrombocytopenia. Complete blood count also provides
information about additional cytopenias and other white blood
cell (WBC) and red blood cell (RBC) abnormalities. Peripheral
blood film (blood collected into EDTA) provides additional
information regarding platelet number, size, clumping, and
granularity (the platelet count can be estimated by the number
of platelets per ×100 field multiplied by 20 × 109/L).
Pseudothrombocytopenia resulting from clumping of
platelets collected in EDTA anticoagulant can be identified by
HSP, Henoch-Schonlein purpura; ITP, immune thrombocytopenia; ALL, acute
lymphocytic leukemia; HUS, hemolytic uremic syndrome; DIC, disseminated examination of the blood film, and confirmed by recollecting
intravascular coagulation. a specimen in citrate anticoagulant in which clumping
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Chapter 64: Clinic Pathological Approach to Coagulation Disorder
Algorithm 2
Workup of a patient with a defect in primary hemostatic mechanism
DIC, disseminated intravascular coagulation; PNH, paroxysmal nocturnal hemoglobinuria; vWD, von Willebrand disease; HSP, Henoch-Schonlein purpura.
Algorithm 3
Approach to defects in plasma phase lab
PT, prothrombin time; PTT, partial thromboplastin time; vWD, von Willebrand disease; DIC, disseminated intravascular coagulation.
will not occur. If true thrombocytopenia is diagnosed, the FVII, FX, FV, FII, fibrinogen). Results should be compared with
next step is to differentiate between new onset acquired age-specific laboratory reference intervals, and are reported in
thrombocytopenia, chronic acquired thrombocytopenia, and seconds and/or as a percentage of a normal control sample.
congenital thrombocytopenia. The INR is the ratio of a patient’s PT to a normal control
Evaluation of WBC morphology allows identification sample, raised to the power of the ISI value for the analytical
of malignant blasts, granulocyte inclusions, such as Dohle- system used: INR = (observed PT/control PT) ISI, where ISI =
like bodies, or other WBC abnormities. Evaluation of RBC international sensitivity index (sensitivity of thromboplastin).
morphology is important to exclude a microangiopathic A prolonged PT/high INR (with normal aPTT) suggests
process as evidenced by presence of fragmented RBCs, FVII deficiency, or use of vitamin K analogs such as warfarin.
microcytosis, macrocytosis, and other RBC abnormalities. The PT is performed by adding a thromboplastin reagent that
contains calcium chloride to the citrated plasma sample of
Clinical Pearl patient. The time required for clot formation is recorded using
an automated instrument.
• Improperly collected samples are one of the most common
causes of spurious lab results. Activated Partial Thromboplastin Time
Activated partial thromboplastin time measures the intrinsic
and common pathways of coagulation (FXII, FXI, FIX, FVIII,
Prothrombin Time/International Normalized Ratio
FX, FV, FII, fibrinogen). The aPTT is less sensitive than the PT
Prothrombin time/International Normalized Ratio (INR) to deficiencies of the common pathway factors. Results should
(blood collected into citrate) measures the extrinsic and be compared with age-specific laboratory reference intervals,
common pathway in the coagulation cascade (tissue factor, and results are reported in seconds. 295
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Algorithm 4
Evaluation of a child with bleeding or abnormal coagulation screening tests
CBC, complete blood count; PT, prothrombin time; aPTT, activated partial thromboplastin time; ITP, immune thrombocytopenia; DIC, disseminated intravascular
coagulation; vWF, von Willebrand factor; vWD, von Willebrand disease; vWF:RCo, vWF:ristocetin ; vWF:Ag, vWF:antigen.
An abnormally prolonged aPTT (with normal PT/INR) weight kininogen). This mixture is then incubated for 2–5
suggests FVIII, FIX, FXI, or FXII deficiency. An aPTT within the minutes before adding calcium chloride and recording the
reference range does not reliably exclude mild FVIII, FIX, or time to clot formation by automated instrument.
FXI deficiency. Therefore, factor assays should be performed if A summary of clinical conditions presenting with
specific deficiencies are suspected. prolonged PT and aPTT are tabulated in table1.
Factor XII deficiency causes a prolonged aPTT, but is not
associated with clinical bleeding. A prolonged aPTT can occur Mixing Study
in severe vWD, as a result of the associated FVIII deficiency.
A mixing study (blood collected into citrate) is done when an
The aPTT is also prolonged in the presence of inhibitors
abnormal PT and/or an aPTT is identified. The patient’s plasma
including heparin. Heparin contamination occurs most often
in specimens drawn from arterial or central venous catheters. is mixed with normal plasma in a 1:1 ratio, and the screening
To avoid heparin contamination, an adequate volume of tests are repeated. This test differentiates between factor
blood should be removed prior to sampling. Where that is not deficiency (mixing corrects the PT or aPTT) and the presence
possible, heparin neutralization can be performed, usually by of an inhibitor (mixing does not correct the PT or aPTT). The
the addition of heparinase to the sample plasma. most common inhibitor that results in noncorrection of the
Combined prolongation of PT/INR and aPTT can result aPTT with mixing is a lupus anticoagulant. This is often an
from inherited deficiencies of individual factors in the incidental finding in children and is not associated with clinical
common pathway: FX, FV, FII, and fibrinogen, or from the rare bleeding. Specialized assays will confirm its presence. Specific
inherited deficiency of the vitamin K-dependent coagulation factor inhibitors also interfere with correction of screening
factors. More commonly, combined abnormalities of aPTT tests by mixing with normal plasma. Confirmation requires
and PT/INR are the result of acquired deficiencies of multiple specific inhibitor assays.
coagulation factors. The aPTT is performed by adding a partial Prothrombin time and aPTT reagents used for testing have
thromboplastin reagent to citrated plasma sample. The sample variable sensitivities to coagulation factors and insensitive
is preincubated with a surface activating reagent (like celite, reagents may result in false negative (i.e., normal) results for
kaolin, silica, or ellagic acid) to introduce controlled activation mild deficiencies. If there is a strong suspicion of a coagulation
296 of contact factor (FXI, FXII, prekallikrein, and high-molecular factor deficiency, specific factor assays should be performed.
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Chapter 64: Clinic Pathological Approach to Coagulation Disorder
Table 1: Causes of prolonged prothrombin time and activated partial thromboplastin time
Prolonged PT Prolonged aPTT Prolonged PT and aPTT
Inherited
Factor VII deficiency vWF, factor VIII, IX, XI, or XII deficiency Prothrombin, fibrinogen, factor V, X, or combined factor deficiency
Acquired
Vitamin K deficiency Heparin use Liver disease
Liver disease Inhibitor of vWF, factors VIII, IX, XI, or XII DIC
Warfarin use Antiphospholipid antibodies Supratherapeutic heparin or warfarin
• Combined heparin or warfarin use
Factor VII inhibitor — • Inhibitor of prothrombin, fibrinogen, factor V or X
• Direct thrombin inhibitor
PT, prolonged prothrombin time; aPTT, activated partial thromboplastin time; vWF, von Willebrand factor; DIC, disseminated intravascular coagulation.
Thrombin Time and Fibrinogen Measurement acute illness and stress. Fibrinogen levels can be measured
immunologically or by a chemical method. The level of function
Thrombin time measures the thrombin-induced conversion
of fibrinogen or fibrinogen activity can also be measured using
of fibrinogen to fibrin. A prolonged TT suggests a quantitative
von Clauss kinetic assay.
or qualitative abnormality of fibrinogen or the presence
of heparin in the sample. A quantitative measurement of
fibrinogen should also be performed. Fibrinogen Degradation Products or D-dimer
Prothrombin time, aPTT, and TT do not screen for factor Fibrin degradation products are fragments resulting from
XIII deficiency. the action of plasmin on fibrin or fibrinogen and reflect
Thrombin time is the time to clot formation after the high fibrinolysis states [such as disseminated intravascular
addition of thrombin to citrated blood. The TT is prolonged coagulation (DIC)], when their levels are elevated.
by heparin, direct thrombin inhibitors, fibrin degradation D-dimers are formed when cross-linked fibrin is degraded.
products, paraproteins, and fibrinogen deficiency (qualitative They can be measured specifically by enzyme-linked
and quantitative). Protamine is added to neutralize the heparin immunosorbent assay. Their level is usually higher in DIC and
so that the TT can be interpreted without heparin interference. in thrombotic conditions, such as deep venous thrombosis
This assay has been used to establish the presence of adequate and pulmonary embolism. Their elevation in the absence of
fibrinogen but is not being used as widely now. symptoms does not imply the presence of these disorders.
Reptilase Time Fibrinolysis Inhibitors

Reptilase time measures time to clot formation after the Abnormalities of fibrinolysis inhibitors (blood collected into
addition of reptilase, a thrombin-like snake enzyme, to citrate), such as α2-antiplasmin (α2-AP) and plasminogen
citrated blood. Unlike the TT, it is not affected by heparin. It activator inhibitor 1 (PAI-1), can cause rare bleeding disorders
can be useful to determine whether heparin is the cause of the because of increased fibrinolysis.
prolonged TT.
Genetic Testing
Urea Clot Lysis Test
The genetic mutations associated with inherited hemostatic
Urea clot lysis test (blood collected into citrate) measures the disorders are gradually being revealed. If available, mutational
solubility of the clot with the addition of urea. The urea clot analysis aids in accurate diagnosis and helps in genetic
solubility test relies on the ability of urea to dissolve unstable counseling and prenatal diagnosis.
clots, which are formed in the absence of factor XIII. Normal
clots are not dissolved by urea or monochloroacetic acid,
unlike clots in patients with factor XIII deficiency.
Specific Coagulation Factors
An abnormal test suggests severe FXIII deficiency or A specific factor assay measures the clotting time of a mixture
hypofibrinogenemia. Clot solubility is increased only at very of diluted test plasma and a specific factor deficient substrate
low levels of FXIII levels (<3%) and, therefore, does not detect plasma that supplies all the factors except the one being
mild/moderate deficiencies. A quantitative assay of FXIII measured.
should be used to confirm the result of this screening test.
Euglobulin Clot Lysis Test
Fibrinogen It is a screening test for excessive fibrinolysis. It is shortened in
Fibrinogen’s normal levels range from 200 to 400 mg/dL. conditions characterized by increased fibrinolysis like systemic
It is an acute phase reactant and higher levels are seen with fibrinolysis, PAI-1 deficiency, α2-AP deficiency. 297
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Bleeding Time (Using a Device patient’s vWF to agglutinate normal platelets in the presence of
Appropriate for Size of Child) ristocetin (vWF:RCo) or by its ability to bind collagen (vWF: CB).
Factor VIII:C activity is a functional assay for factor VIII that is
A lancet device is used to make a standardized cut on the measured by mixing normal plasma with factor VIII-deficient
volar surface of the forearm, and the time it takes for bleeding plasma. Levels of vWF:Ag and vWF:RCo may be elevated during
to stop is measured. The bleeding time assesses the function pregnancy, oral contraceptive use, and liver disease. They may
of platelets and their interaction with the vascular wall. The decrease with hypothyroidism and type O blood.
bleeding time test was widely used as a screening test for
primary hemostasis disorders, but is less often used now Platelet Aggregometry
because of difficulties in standardization.
The rapidity and extent of platelet agglutination are graphically
Platelet Function Analyzer recorded after adding a variety of agonists [ristocetin,
epinephrine, collagen, adenosine diphosphate (ADP), and
Platelet function analyzer, PFA-100 (blood collected into
arachidonic acid].
citrate) is an instrument in which primary, platelet-related
Platelet aggregation studies remain the most sensitive
hemostasis is simulated. A small sample of anticoagulated
method for detecting and distinguishing platelet function
whole blood (0.8 mL) is aspirated via a narrow-diameter
defects. In these tests, platelet aggregation is tested by
capillary through a microscopic aperture cut into a membrane
measuring changes in optical density as platelets respond to
coated with the platelet agonists collagen and epinephrine or
various agents such as ADP, epinephrine, collagen, arachidonic
collagen and adenosine 5’-diphosphate. The high shear rate
acid, and ristocetin. Different disorders will show different
generated under standardized flow conditions and presence
patterns. For example, platelets of patients with Glanzmann
of chemical stimuli result in platelet adhesion, activation, and
thrombasthenia (dysfunctional or deficient glycoprotein
aggregation at the aperture, building a stable platelet plug. The
IIb/IIIa complex in platelets) only aggregate with ristocetin,
time required to obtain full occlusion of the aperture is reported
whereas platelets of patients with Bernard-Soulier syndrome
as the closure time. The closure time is prolonged by low levels
(absent or decreased glycoprotein Ib complex on platelets)
of von Willebrand factor (vWF), thrombocytopenia, decreased
have no aggregation with ristocetin, reduced aggregation with
hematocrit, and by some platelet function abnormalities
(e.g., severe disorders such as Bernard-Soulier syndrome and collagen, and normal aggregation with ADP, arachidonic acid,
Glanzmann thrombasthenia). and epinephrine.
Due to issues of both sensitivity and specificity, use of the
PFA-100 as a routine screening test is still debated. However, Thromboelastography
the small blood volume needed for this test compared with Thromboelastography provides the whole dynamic process
the much larger volume required for platelet function testing of hemostasis from clot formation to its dissolution and also
by aggregometry (10 mL or more) is an advantage, especially provides information about platelet function.
for screening very young children for vWD or severe platelet
function disorders.
Key points
Testing for Defects in Primary Hemostasis ))
Evaluation of a child with bleeding should include a
von Willebrand Factor Antigen and Activity comprehensive medical and bleeding history, a complete
family history and a detailed physical examination
These tests help in making diagnosis of Von Willebrand disease
))
Based on history and clinical findings, investigations and lab
by measuring the level of von willebrand antigen and ristocetin
tests should be requested
cofactor activity.
))
Initial tests to screen for bleeding disorders should include
Platelet Function Testing a complete blood count with platelet counts, blood film,
prothrombin time, and activated partial thromboplastin time
The most common method of assessing platelet function is
light transmission aggregometry, in which the increase in ))
Faulty sample collection may lead to abnormal results, hence
light transmission through a rapidly stirred sample of citrated it is extremely important to ensure proper sampling.
platelet-rich plasma is recorded as platelets aggregate. As
a fresh blood sample is needed for aggregation testing, the
patient may have to be referred to a center with a specialized
SUGGESTED READINGs
laboratory. Specialized testing includes measurement of 1. Leung LK. Antithrombotic therapy: problems and issues. Hematology.
granule secretion, dense granule enumeration by whole 2006;457‑62.
mount electron microscopy, flow cytometric assessment of 2. Revel-Vilk S, Rand ML, Israels SJ. An approach to the bleeding child. In:
surface receptors, and evaluation of platelet ultrastructure by Blanchette VS, Breakey VR, Revel-Vilk S, editor. SickKids Handbook of Pediatric
Thrombosis and Hemostasis. Basel: Karger; 2013. pp. 14-22.
transmission electron microscopy.
3. Rajpurkar M, Lushar JM. Clinical and laboratory approach to the patient with
Screening platelet function for detecting vWD has a low bleeding. Nathan and Oski’s Hematology of Infancy and Childhood. 7th ed.
negative predictive value and may require repeat testing. One Philadelphia: Saunders Elsevier; 2009.
also may measure von Willebrand factor antigen (vWF:Ag) 4. Stasi R. How to approach thrombocytopenia. Hematology Am Soc Hematol Educ
298 by immunoassay and vWF activity by measuring the ability of Program. 2012;2012:191-7.
ch-64.indd 298 11/24/2016 1:42:46 PM

Chapter 65
Algorithmic Approach to
Eosinophilia in Children
ATK Rau, Sangeetha Shenoy
INTRODUCTION (IL)-3, granulocyte-macrophage colony-stimulating factor, and

IL-5, of which the IL-5 is the one which is primarily responsible
Eosinophilia is probably the second most common hematologic for the production. Hence, diseases like extrinsic asthma
abnormality in children in the tropics after anemia. The normal and helminthiasis which stimulate the T-helper 2 mediated
eosinophil count ranges from 0.04 × 109 to 0.4 × 109/L and the immune response have associated eosinophilia.
percentage in relation to the total leukocyte count ranges from
After transendothelial migration, eosinophils can invade
1 to 6%.
target organs, secreting their products into surrounding tissues
Eosinophilia is defined as eosinophil count more than 0.4 ×
causing local inflammation and tissue remodeling. Marked
109/L. The count has a diurnal variation, with the lowest value
changes in the microenvironment subsequently leading to
in the morning and the highest being at night.
chronic organ damage may be caused by the eosinophil derived
For standardization, the morning value at 8 am is taken as
substances. This may lead to fibrosis and/or thrombosis in
the baseline eosinophil count.
some of the patients. Certain organs like heart, lung, skin,
The count also varies with age (Table 1), exercise, and
environmental stimuli (allergen exposure). spleen, gastrointestinal tract (GIT), and central nervous system
Eosinophilia can further be classified as mild (<1.5 × are the ones predominantly affected.
109/L), moderate (1.5–5 × 109/L), and severe (>5 × 109/L). The
peripheral eosinophil count does not correlate with the level of ETIOLOGY
organ damage. The counts may be normal in conditions where
there is significant recruitment of eosinophils into organs as in Causes of eosinophilia can be divided into primary and
eosinophilic pneumonia. On the other hand, a high eosinophil secondary.
count may not have associated organ damage. But an eosinophil • Primary can further be divided into:
count of more than 1.5 × 109/L is considered the level above {{ Clonal: there can be neoplastic proliferation as part of
which organ damage is more likely to occur. Eosinophilia can an underlying myeloid malignancy. There is histologic,
also be masked because of pyogenic inflammation which cytogenetic, or molecular evidence of underlying
can lower the eosinophil counts, as well as by exogenous myeloid malignancy
administration of medications like corticosteroids, estrogen, {{ Idiopathic: this is considered once secondary and clonal
and epinephrine. eosinophilia is ruled out. It includes hypereosinophilic
The development and terminal differentiation of syndrome (HES)
eosinophils are controlled by several cytokines like interleukin • Secondary/reactive:
{{ Helminthiasis
Table 1: Eosinophil counts based on age
{{ Drugs
Age Eosinophil count × 109/L {{ Allergic vasculitis, eosinophilic pneumonia, allergic
Birth 0.1–1.0 bronchopulmonary eosinophilia, allergic angiitis,

Day 3 0.1–2.0 Churg-Strauss disease
{{ Neoplastic diseases as a paraneoplastic syndrome
1 month 0.2–1.0
{{ Immunologic disorders
2 months to 12 years 0.1–1.0 {{ Endocrine.
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Helminthiasis: worldwide, helminthiasis is the most common Hypereosinophilic syndrome: it is characterized by persistent
cause of eosinophilia. It can be associated with tissue eosinophilia more than 1.5 × 109/L for more than 6 months,
nematodes, cestodes, and trematodes. All parasitic infections, evidence of end organ damage but no explanation after
including hookworm, roundworm, tapeworm, filariasis, investigations. It has two variants: myeloproliferative variant
trichinella, strongyloides, and visceral larva migrans, have hypereosinophilic syndrome (M-HES) and lymphocytic variant
moderate to marked eosinophilia. Parasites elicit eosinophilia hypereosinophilic syndrome (L-HES). Myelo proliferative-
when they or their products come in contact with immune HES is associated with other features of myeloproliferative
effector cells in tissues which happen during migration. Hence, diseases like increased serum vitamin B12 levels, hepato
it is seen in infestation with worms that migrate through splenomegaly, anemia, thrombocytopenia, and increased
extraintestinal organs. Parasites that are wholly intramural like bone marrow cellularity. Lymphocytic-HES is associated with
adult tapeworm or contained in a cystic structure like hydatid cutaneous manifestations, increased serum IgE levels and
cyst do not cause eosinophilia unless the cyst wall ruptures hypergammaglobulinemia. There is overproduction of IL-5 by
and its contents leak. deregulated T cells leading to polyclonal eosinophil expansion.
Other infections like scabies, fungal diseases like dissemi
nated coccidioidomycosis, and aspergillosis [when presenting Clonal eosinophilia: there are two subcategories in
as allergic bronchopulmonary aspergillosis (ABPA)] can also World Health Organization classification of hematologic
be associated with marked eosinophilia. Tropical pulmonary malignancies: chronic eosinophilic leukemia, not otherwise
eosinophilia is the result of immunologic hyper-responsiveness specified and myeloid/lymphoid neoplasms with eosinophilia
to the filarial parasite. It should be considered in a child with and mutations involving platelet-derived growth factor
the following—residence in or has had a history of travel to a receptor, and -b or fibroblast growth factor receptor. It might
filarial endemic area, raised serum Immunoglobulin E (IgE) also be seen in other myeloid malignancies like myelodysplastic
(>1,000 U/L), raised antifilarial antibody titers, eosinophilia syndromes and systemic mastocytosis.
more than 3 × 109/L, absence of microfilaria in blood, and
significant clinical improvement after 3 weeks course of RARE SYNDROMES WITH EOSINOPHILIA
diethylcarbamazine. There is a dramatic fall in the eosinophil
count after 7–10 days of treatment. The importance of • Gleich’s syndrome
treatment lies in the fact that untreated tropical pulmonary • Churg-Strauss syndrome
eosinophilia can lead to progressive interstitial fibrosis and • Eosinophilia-myalgia syndrome
chronic bronchitis. • Omenn syndrome
• Hyper IgE syndrome.
Allergic diseases: in Western countries, allergic diseases are
the leading cause of eosinophilia. Asthma generally is not
associated with moderate or severe eosinophilia. If there PULMONARY INFILTRATES
is moderate to severe eosinophilia in asthma, possibility of WITH EOSINOPHILIA SYNDROME
Churg-Strauss disease or ABPA has to be considered.
• Loeffler’s syndrome
Drug-related eosinophilia: it is a common cause of persistent
• Allergic angiitis and granulomatosis
eosinophilia in parts of the world where helminthiasis is
• Hypersensitivity vasculitis
uncommon. It can be asymptomatic or associated with some
• Allergic bronchopulmonary aspergillosis: asthma, positive
symptoms as follows:
skin test to aspergillus and aspergillus precipitating anti
• Asymptomatic: quinine, penicillin, cephalosporins, and
bodies
quinolones
• In addition, drug reaction, HES, and parasitic infections
• Associated pulmonary infiltrates: nonsteroidal anti-
may be associated with pulmonary symptoms.
inflammatory drugs, sulfa drugs, and nitrofurantoin
• Hepatitis: tetracyclines, antipsychotics
• DRESS (Drug Reaction with Eosinophilia and Systemic APPROACH TO A PATIENT
Symptoms) syndrome: sulfasalazine, hydantoin, WITH EOSINOPHILIA (Algorithm 1)
carbamazepine, and D-penicillamine.
Firstly, an attempt should be made to rule out any underlying
Neoplastic diseases: lymphoid malignancy (Hodgkin’s treatable cause like parasitic infections or drug reaction.
lymphoma), B or T cell leukemia or lymphoma, Langerhans cell Secondly, any evidence of target organ damage should be
histiocytosis, solid tumors, and mastocytosis are associated with looked for.
eosinophilia. It could be a paraneoplastic feature of solid tumors History:
like adenocarcinoma of lung, cervix, and GIT because of ectopic • Travel history
production of IL-5 and other cytokines by malignant cells. • Occupational history
Immunologic disorders like Omenn syndrome, hyper-IgE • Drug history
syndrome, graft-versus host disease. • Family history
Endocrine: eosinophilia is seen in conditions with hypo • Allergy history.
adrenalism because of loss of endogenous glucocorticosteroids Physical examination of skin, liver, spleen, lungs, and soft
300 as in Addison’s disease, adrenal hemorrhage, hypopituitarism. tissues.
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Chapter 65: Algorithmic Approach to Eosinophilia in Children
Algorithm 1
Approach to a patient with eosinophilia
DEC, diethylcarbamazine
Laboratory investigations: serologic tests (filarial, stron • Complete blood count, chest X-ray, echocardiography,
gyloides, schistosomiasis, toxocara), stool ova, and parasite troponin levels
testing (hookworm, Schistosoma), chest X-ray. • Pulmonary function tests
Once secondary causes are ruled out, the following • Gastrointestinal endoscopy
investigations are performed (Table 2): • Skin biopsy
• Peripheral smear • X-ray paranasal sinuses
• Blood tryptase levels, serum vitamin B12 • Neuroimaging.
• Immunoglobulin E
• Bone marrow morphology
• Cytogenetic analysis
• Molecular studies. Clinical Pearls
The following investigations are done to look for evidence
• An eosinophil count of more than 0.4 × 109/L is considered as
of target organ damage:
eosinophilia and is further classified into mild (<1.5 × 109/L),
moderate (1.5–5 × 109/L) and severe (>5 × 109/L) eosinophilia.
Table 2: Laboratory investigations in a case of eosinophilia A count of more than 1.5 X 109/L is generally associated with
organ damage
Peripheral smear Circulating blasts, dysplastic cells,
monocytosis • Tropical pulmonary eosinophilia should be considered in a
child residing in or with a history of travel to a filarial endemic
Bone marrow — area with a raised serum immunoglobulin E (>1,000 U/L),
Cytogenetic analysis — raised antifilarial antibody titers, eosinophilia more than 3 ×
Molecular studies F1L1P1-PDGFRA using FISH or RT-PCR 109/L, absence of microfilaria in blood and significant clinical
improvement after 3 weeks course of diethylcarbamazine
Serum tryptase Systemic mastocytosis and other
vasculitides • Hypereosinophilic syndrome (HES) is defined by persistent
eosinophilia more than 1.5 × 109/L for more than 6 months,
ANCA Churg-Strauss disease evidence of end organ damage but no explanation after
PDGFRA, platelet-derived growth factor receptor-α; FISH, fluorescence in situ investigations. The two variants of HES are myeloproliferative
hybridization; RT-PCR, reverse transcriptase-polymerase chain reaction; ANCA, variant HES (M-HES) and lymphocytic variant HES (L-HES).
antineutrophil cytoplasmic antibodies. 301
ch-65.indd 301 11/19/2016 5:08:57 PM

8. Deshpande AD. Eosinophilia associated with scabies. Practitioner. 1987;231: 455.

Key points 9. Echols RM, Palmer DL, Long GW. Tissue eosinophilia in human coccidioi
domycosis. Rev Infect Dis. 1982;4:656-64.
))
The most common cause for eosinophilia worldwide is 10. Fulkerson PC, Rothenberg ME. Origin, regulation and physiological function of
helminthiasis whereas allergic diseases are the leading intestinal eosinophils. Best Pract Res Clin Gastroenterol. 2008;22:411-23.
causative factor in western countries 11. Gleich GJ. Mechanisms of eosinophil-associated inflammation. J Allergy Clin
))
Untreated eosinophilia can lead to chronic organ damage Immunol. 2000;105:651-63.
due to fibrosis and/or thrombosis and hence should be 12. Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, et al. Hyper-
IgE syndrome with recurrent infections-an autosomal dominant multisystem
treated
disorder. N Engl J Med. 1999;340:692-702.
))
A child living in the tropics with eosinophilia should be 13. Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev.
investigated to rule out tropical pulmonary eosinophilia 2005;203:244-50.
and treated with deworming and a 3-week course of 14. Harley WB, Blaser MJ. Disseminated coccidioidomycosis associated with extreme
diethylcarbamazine followed by repeat counts to see the eosinophilia. Clin Infect Dis. 1994;18:627-9.
15. Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, et al.
response
Eosinophils: biological properties and role in health and disease. Clin Exp Allergy.
))
Presence of moderate to severe eosinophilia in a child with 2008;38:709-50.
asthma points towards the possibility of Churg-Strauss 16. Hogan TF, Koss W, Murgo AJ, Amato RS, Fontana JA, VanScoy FL. Acute
disease or allergic bronchopulmonary aspergillosis lymphoblastic leukemia with chromosomal 5;14 translocation and hyper
eosinophilia: case report and literature review. J Clin Oncol. 1987;5:382-90.
))
Eosinophilia can also be associated with neoplastic diseases 17. Kita H. Eosinophils: multifaceted biological properties and roles in health and
like lymphomas, B or T cell leukemia, Langerhans cell disease. Immunol Rev. 2011;242:161-77.
histiocytosis, solid tumors, and mastocytosis which need to 18. Mahmoud AA. Eosinophilia. In: Warren KS, Mahmoud AA, editors. Tropical and
be excluded in persistent cases. Geographical Medicine. New York: McGraw Hill; 1989. pp. 65-70.
19. Moore TA, Nutman TB. Eosinophilia in the returning traveler. Infect Dis Clin North
Am. 1998;12:503-21.
SUGGESTED READINGs 20. Ogbogu PU, Rosing DR, Horne MK. Cardiovascular manifestations of
hypereosinophilic syndromes. Immunol Allergy Clin North Am. 2007;27:457-75.
1. Ackerman SJ, Bochner BS. Mechanisms of eosinophilia in the pathogenesis of 21. Ong R, Doyle R. Topical pulmonary eosinophilia. Chest. 1998;113:1673-9.
hypereosinophilic disorders. Immunol Allergy Clin North Am. 2007;27:357-75. 22. Ottesen EA, Nutman TB. Tropical pulmonary eosinophilia. Annu Rev Med.
2. Aleman K, Noordzij JG, de Groot R, van Dongen JJ, Hartwig NG. Reviewing 1992;43:417-24.
Omenn syndrome. Eur J Pediatr. 2001;160:718-25. 23. Parker RI. Hematologic aspects of systemic mastocytosis. Hematol Oncol Clin
3. Basara N, Kiehl MG, Fauser AA. Eosinophilia indicates the evolution to acute North Am. 2000;14:557-68.
graft-versus-host disease. Blood. 2002;100:3055. 24. Robyn J, Noel P, Wlodarska I, Choksi M, O’neal P, Arthur D, et al. Imatinib-
4. Bass DA. Behavior of eosinophil leukocytes in acute inflammation. I. Lack of responsive hypereosinophilia in a patient with B cell ALL. Leuk Lymphoma.
dependence on adrenal function. J Clin Invest. 1975;55:1229-36. 2004;45:2497-501.
5. Beeson PB, Bass DA. The eosinophil. Major Probl Intern Med. 1977;14:1-269. 25. Schermoly MJ, Hinthorn DR. Eosinophilia in coccidioidomycosis. Arch Intern Med
6. Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, et al. 1988; 148:895-6.
Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033-9. 26. Weller PF. Eosinophilia in travelers. Med Clin North Am. 1992;76:1413-32.
7. Dacie JV, Lewis SM. Practical Hematology. 6th ed. London: Churchill Livingstone. 27. Weller PF. Eosinophils: structure and functions. Curr Opin Immunol. 1994;6:85-90.
302
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Section 8: Pulmonology
Chapter 66
Respiratory Distress
Soumya Tiwari
INTRODUCTION DEFINITION
Respiratory distress is the most common presentation in Any unusual pattern of breathing, causing a subjective feeling
children visiting a hospital emergency. It initially, may manifest of discomfort, in a previously well child is termed as respiratory
only as fast breathing (rate more than the normal upper limit distress. It includes abnormally fast or slow breathing, shallow
for that age group; see Table 1), and signs of increased work or labored efforts, or noisy breathing.
of breathing in the form of nasal flaring and/or lower chest
indrawing, and/or head nodding can follow. It may also be ETIOLOGY OF RESPIRATORY DISTRESS
associated with stridor or wheeze suggestive of upper and
lower airway obstruction, respectively. There is a need of Respiratory distress may not always result from a lung disease.
urgent assessment of airway patency and breathing, when a Rapid breathing may be physiological, e.g., exercise induced, or
child with respiratory distress is first evaluated. Stabilization pathological due to pulmonary or nonpulmonary causes. The
of vital parameters may require proper positioning, oronasal respiratory rate cut offs given in Table 1 are seen in pathological
suctioning, and intubation if the airway patency cannot conditions and these could be seen in many different clinical
be maintained and use of oxygen by hood/nasal prongs. situations as detailed in Box 1.
Supportive therapy in the form of maintaining temperature
or correction of hyperthermia/hypothermia; intravenous Box 1: Causes of respiratory distress in children
fluid boluses; correction of hypoglycemia; nebulization with Upper respiratory tract involvement
bronchodilator; intercostal tube drainage of any air or fluid • Croup, acute epiglottitis, • Diphtheria
collection in the pleural cavity, etc. Such initial treatment Ludwig’s angina • Laryngospasm
coupled with a thorough history, physical examination and • Retropharyngeal abscess
relevant investigations, is followed by establishing a provisional • Foreign body aspiration
diagnosis and instituting appropriate empirical treatment in Lower respiratory tract involvement
the emergency ward itself. Uncommonly, a serious terminally • Pneumonia • Pneumothorax
sick child may show bradypnea (decreased heart rate) instead • Bronchiolitis • Atelectasis
of tachypnea. • Asthma • Hypersensitivity
• Pleural effusion or empyema pneumonitis
and hemothorax
Table 1: The cut offs for respiratory rate marking significant
Nonpulmonary causes
lower chest disease (World Health Organization)
• Congestive heart failure due to • Metabolic acidosis
Age group Respiratory rate cut-off heart disease or severe anemia {{ Renal failure
Young infant (<2 months) >60/min • CNS infections, cerebral {{ Renal tubular acidosis
edema, tumor (raised ICT, {{ Diabetic ketoacidosis
Infant (2 months–1 year) >50/min compression of the brainstem), {{ Psychogenic
spinal cord injury, Guillain hyperventilation, anxiety,

Children (1–5 years) >40/min Barre syndrome and panic attacks
School children (>5 years) >30/min ICT, intracranial tension; CNS, central nervous system.
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CLINICAL FEATURES Clinical Pearls

A child with respiratory distress may have tachypnea with Symptoms of impending respiratory failure
increased work of breathing (suggested by use of accessory • Cyanosis
muscles), cyanosis and lethargy or altered sensorium. • Silent chest
Alteration in sensorium (in the form of irritability, agitation,
• Poor respiratory efforts
lethargy, or coma) indicates brain hypoxia and is one of the
• Fatigue/exhaustion
earliest indicators of impending respiratory failure. While fast
breathing is commonly associated with respiratory diseases, • Agitation or reduced level of consciousness
it may also occur with fever, crying, or metabolic acidosis. Preterminal signs
However, normal or decreased respiratory rate may be more • Bradycardia, desaturation, and altered sensorium.
ominous if it is associated with severe retractions (paradoxical
breathing), cyanosis, grunting, or altered sensorium. Central INVESTIGATIONS
cyanosis is a late sign but may not be detected in presence of
Laboratory investigations help to confirm the diagnosis but
severe pallor (low hemoglobin) and dark skin color.
the immediate management of a patient should not be delayed
Stridor is a harsh inspiratory sound that indicates upper
pending the reports of the investigations. Use of noninvasive
airway obstruction. Grunt is a loud noise produced by a
devices, such as pulse oximeter and end-tidal carbon dioxide
forceful expiration against a closed glottis. Grunt and wheeze detector lessen the need for repeated invasive tests for monitoring
(a musical sound) are suggestive of lower airway obstruction. of the child. Table 3 shows the relevant investigations to ascertain
A complete history including the onset, duration, the cause of respiratory distress in a child.
progression of dyspnea, the aggravating and relieving factors as
well as the associated symptoms, like fever, cough, sore throat,
chest pain, choking episodes, accidental ingestion of poisons, TREATMENT
etc. can help in short listing the likely cause (Table 2). The management of a child with respiratory distress includes
supportive treatment in the form of stabilization of vital
parameters, i.e., airway, breathing, and circulation followed
Table 2: Clinical feature based diagnostic clues by definitive treatment by instituting appropriate respiratory
Clinical features Diagnosis support, antibiotics, chest tube drainage, decongestive
Fever, cough, and rapid breathing Lower respiratory tract measures, etc. The algorithmic approach to management of
infections, like pneumonia, such a child is shown in algorithm 1.
bronchiolitis and virus and
associated wheeze Table 3: Laboratory investigations
Exercise-induced dyspnea Asthma, congestive heart Investigation Suggested diagnosis
failure, severe anemia
Complete blood count Leucocytosis/leucopenia, toxic
Nocturnal cough, orthopnea and Congestive heart failure with peripheral smear granules, shift to left, anemia/
dyspnea polycythemia, eosinophilia-pneumonia,
sepsis, TPE
Fever, sore throat, stridor Acute epiglottitis
CRP, ESR Raised-pneumonia, bronchiolitis
Severe chest pain with rapid, shallow Pneumonia,
Blood culture Sepsis with pneumonia
breathing, decreased air entry pneumothorax, pulmonary
embolism Kidney function tests Acute/chronic kidney disease
Persistent wheezing, recurrent Gastroesophageal reflux Arterial blood gas Hypoxemia, hypercarbia, acidosis
vomiting, failure to thrive disease (metabolic/respiratory)—
pneumothorax, AKI
Acute respiratory distress after Foreign body inhalation Chest X-ray, Pneumonia, pneumothorax, effusion,
sudden choking, hyperinflated chest foreign body, acute epiglottitis, CHF
X-ray soft tissue neck
Fever with altered sensorium, Encephalitis involving Bronchoscopy Foreign body
convulsions, fast breathing brain stem
Echocardiography Cardiac disease
Chest-wall retractions, paraplegia Acute flaccid paralysis
24-hour pH monitoring GERD
Acute respiratory distress with Poisoning Pleural tap Pneumonia (bacterial, tubercular)
vomiting, altered sensorium
Lumbar puncture/ Pleocytosis, raised protein and
Fast breathing usually without other Acute kidney injury/ cranial CT scan decreased sugar meningoencephalitis/
signs of respiratory distress, may be chronic kidney disease raised ICT
associated with oliguria or anuria with metabolic acidosis TPE, therapeutic plasma exchange; CRP, C-reactive protein; ESR, erythrocyte
Fast breathing, altered sensorium, Diabetic ketoacidosis sedimentation rate; AKI, acute kidney injury; CHF, congestive heart failure;
GERD, gastroesophageal reflux disease; CT, computed tomography; ICT,
304 polyuria, dehydration
intracranial tension.
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Chapter 66: Approach to a Child with Respiratory Distress
Algorithm 1
Management of a child with respiratory distress
Continued
305
ch-66.indd 305 11/19/2016 5:11:48 PM

Continued
TABC, temperament assessment battery for children; NS, normal saline; DPT, diptheria-pertussis-tetanus; CXR, chest X-ray; AP, anteroposterior; ICD, implantable
cardioverter-defibrillator; LRTI, lower respiratory tract infection; URTI, upper respiratory tract infection; ICT, intracranial tension; VBG, venous blood gas; IV,
intravenous; JVP, jugular venous pressure; ECG, electrocardiogram; echo, echocardiogram; KFT, kidney function test; I&D, incision and drainage; B/L, bilateral; U/L,
unilateral; ATT, antitubercular treatment; RF, rheumatic fever; IE, infective endocarditis.
306
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Chapter 66: Approach to a Child with Respiratory Distress
CONCLUSION SUGGESTED READINGS

It is essential to promptly triage children with impending 1. Fallot A. Respiratory distress. Pediatr Ann. 2005;34(11):885-91.
respiratory failure and quickly institute supportive 2. Kilham H, Gillis J, Benjamin B. Severe upper airway obstruction. Pediatr Clin North
management, simultaneously searching for the etiology Am. 1987;34(1):1-14.
and planning a definitive treatment. The above mentioned 3. Mathew JL, Singhi SC. Approach to a child with breathing difficulty. Indian J
approach will improve the outcome of children, especially the Pediatr. 2011;78(9):1118-26.
under-five ones, in whom respiratory infections lead to the 4. Singh V, Tiwari S. Respiratory problems. In: Gupta P (Ed). Textbook of Pediatrics.
India: CBS publishers; 2013. pp. 335-68.
highest number of mortalities.
Key points
))
Respiratory distress may not always be due to respiratory
diseases, nonpulmonary causes should be carefully evaluated
))
Stabilization of vital signs is the first step in the management
of a child with respiratory distress
))
Signs of impending respiratory failure should prompt
immediate respiratory support
))
Clinical features guide further investigations and definitive
treatment.
307
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Chapter 67
Assessing and
Managing a Child with Stridor
Dhulika Dhingra, Varinder Singh
INTRODUCTION the forward vector and decreases the lateral pressure. When air
passes through a narrowed flexible airway in a child, the lateral
Stridor is a harsh, high-pitched vibratory sound caused pressure that holds the airway open can drop precipitously
by partial obstruction of respiratory passages that result (venturi principle) and cause the tube to collapse. A similar
in turbulent passage of air through the airways. It can process obstructs airflow and produces stridor in cases with
be almost always heard without stethoscope though not upper-airway obstruction.
uncommonly it may be audible directly to the ear. Stridor The most common causes of stridor are summarized in
is usually heard during inspiration, but sometimes may Table 1.
be biphasic. Inspiratory stridor may result if the child
breathes against a closed glottis, expiratory stridor results
due to semiapproximated vocal cords causing resistance to HISTORY AND CLINICAL EXAMINATION
exhalation and biphasic stridor may result due to subglottic or A good history and the clinical examination are the key to
glottic anomaly or a severe obstruction of the extra-thoracic localization of the cause of stridor. A child presenting with
airway. Loudness of the sound is poor marker of the degree of stridor should be inquired about the onset of stridor (onset
obstruction, while its presence even when the patient is quiet in first few months of life usually indicate a congenital cause),
or biphasic stridor is associated with significant compromise. postural variation, feeding difficulties, any change in voice
Stridor must be differentiated from stertor, which is produced quality, pattern of fever, history of foreign body inhalation in
by an obstruction in the nose or nasopharynx. form of sudden choking, any neurological symptoms, history
Stridor is the sound caused by abnormal air passage of trauma to head and neck (to look for neurogenic stridor),
during breathing. The cause of stridor can usually be located
somewhere in extra-thoracic airway (pharynx, larynx, and
trachea). Stridor may be acute (caused by inflammation/ Table 1: Causes of stridor
infection or foreign body inhalation) or chronic. It may be
congenital or acquired. Stridor is a sign and not a diagnosis Acute stridor Chronic stridor
and the cause for which must be ascertained. This chapter aims Laryngotracheobronchitis Laryngomalacia
to educate the pediatrician faced with a child or infant with Epiglottitis Congenital or acquired
stridor to determine the severity or respiratory compromise subglottic stenosis
and the need for immediate intervention, to decide based
Diphtheria Laryngeal webs
upon history and clinical examination whether a significant
lesion is suspected and to understand the consequences and Bacterial tracheitis Congenital laryngeal cysts
management strategies of the underlying lesion for follow-up Retropharyngeal abscess Tracheal stenosis or complete
and subsequent management of the child. tracheal rings
Allergic reactions Tracheomalacia
PATHOPHYSIOLOGY Vocal cord palsy Subglottic hemangioma
Gases produce pressure equally in all directions; however, Acquired subglottic stenosis Posterior laryngeal cleft
when a gas moves in a linear direction, it produces pressure in (following prolonged intubation)
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Chapter 67: Assessing and Managing a Child with Stridor
Table 2: Voice changes with localization of site of stridor INVESTIGATIONS

Change in Localization of Differential diagnosis Establishing a patent airway is of utmost importance. No
voice lesion laboratory investigation or imaging should take precedence
Hoarseness of Vocal cords • Laryngeal webs over establishing airway. If the patient has chronic stridor, has
voice • Abductor palsy no or minimal respiratory distress, he/she may be taken up for
• Croup flexible laryngoscopy or bronchoscopy to look for underlying
• Retropharyngeal abscess abnormalities. The procedure may also rule out secondary
• Diphtheria airway lesions.
If the child has an acute stridor in the absence of severe
Muffled voice Supraglottic • Tonsillitis
respiratory distress, one may go for a chest X-ray or soft-tissue
involvement • Parapharyngeal abscess lateral neck imaging depending upon the history. A clinician
• Peritonsillar abscess capable of establishing airway should accompany such a
Weak voice Subglottic • Subglottic stenosis patient to the X-ray department.
obstruction (congenital or acquired)
Clinical Pearl
immunization history, and history of similar illness in the
• Establishing a patent airway must take precedence over
neighborhood (diphtheria). It is, however, emphasized that
imaging and bronchoscopy in evaluating patients with stridor.
parents may not have noticed the choking episode hence, a
high index of suspicion is warranted if stridor has appeared all
of a sudden without any other attendant symptoms, like fever, Chest X-ray in a child with history of foreign body
coryza, etc. inhalation may reveal unilateral hyperinflation or collapse,
Detailed clinical examination may also help in identifying while radiograph of a child with laryngotracheobronchitis
the cause. Onset of stridor, presence/absence of fever, voice shows subglottic narrowing (steeple sign).
change and ability of patient to handle secretions will aid in
determining the site. A positional change in severity of stridor MANAGEMENT
may indicate laryngomalacia. A child with choanal atresia
may have increased distress as he closes his mouth and with
crying his distress may be relieved. Voice quality should also
Laryngotracheobronchitis/Croup
be observed during the examination; however, it must be Croup is a heterogeneous group of acute and infectious
remembered that a normal voice quality does not rule out processes in children (between 6 months to 6 years of age)
laryngeal or pharyngeal pathology though presence of changes that manifest most commonly with characteristic inspiratory
in voice quality does. Table 2 summarizes important voice stridor, barking cough, hoarse voice, and varying degrees of
changes associated with different pathologies. respiratory distress. Parainfluenza viruses type 1 (50%), 2 and
Clinical examination must also include a detailed 3; respiratory syncytial virus, influenza A and B, and rhinovirus
neurological examination and inspection of the spine to rule account for the majority of cases. The illness usually starts with
out neurogenic stridor. Neck should be examined for any a common cold, like illness with symptoms of rhinorrhea,
lymph node masses or for any evidence of trauma. Note should cough, sore throat, and fever. Features of upper airway
also be made of craniofacial anomalies including macrglossia, obstruction, i.e., inspiratory stridor, hoarseness, and barking
retrognathia and maxillary hypoplasia. Throat examination cough develop over next 2–3 days.
may reveal presence of a membrane, tonsillar enlargement, Treatment is dependent upon the severity of croup and
or presence of exudates. Throat examination should not be includes humidified oxygen, oral or parental steroids, and
attempted for a child who is drooling, has high grade fever, and inhaled adrenaline.
is agitated. • Humidified air: It has been widely advocated in the past
Apart from ascertaining the diagnosis, clinical examination without any scientific validation, but it still can be used as
should also aim at assessing the severity of respiratory distress. home remedy in children with mild croup.
Retractions/use of accessory muscles are better clinical signs • Oxygen therapy: Oxygen is the most important treatment for
than degree of stridor when assessing degree of respiratory a child with moderate or severe croup who has considerable
distress. Cyanosis is a late finding and is a sign of impending upper-airway obstruction or SpO2 less than 92%.
respiratory failure. • Oral or inhaled steroids: Steroids can improve the
symptoms of croup within 6–8 hours after starting the
treatment. They also result in shorter duration of hospital
Clinical Pearl stay, lesser need of endotracheal intubation, and decreased
• Onset of stridor, presence/absence of fever, voice change, and
need for adrenaline nebulization. Oral corticosteroids
ability of patient to handle secretions will aid in determining are preferred as they are inexpensive, easy to administer,
the diagnosis. readily available, as effective and produce measurable
improvements within hours. The recommended dose of 309
ch-67.indd 309 11/19/2016 5:15:58 PM

dexamethasone is 0.15–0.3 mg/kg body weight (oral or IM) Child may be administered oxygen. Emergency intubation is to
and prednisolone (suspension or tablets) is 1 mg/kg body be avoided and early tracheostomy to establish a patent airway
weight. Nebulized budesonide (2 mg) has been shown to should be done. Diphtheria antitoxin [80,000–1,20,000 IU,
be equally efficacious. This can be repeated 12 hourly for intravenous (IV)] should be administered and child should be
up to 48 hours. The choice of route is based upon the cost treated with crystalline penicillin (40,000 U/kg/dose 6 hourly
and the child condition. for 14 days).
• Nebulized adrenaline: It is indicated in children with
moderate to severe croup with stridor at rest and marked Retropharyngeal Abscess
intercostal or subcostal indrawing. One needs to administer Retropharyngeal abscess is a complication of bacterial
1:1000 dilution solution of nebulized adrenaline 0.5 mL/kg pharyngitis observed in children younger than 6 years. The
of body weight (maximum of 5 mL). It has a rapid onset child presents with abrupt onset of high fever, difficulty in
of action on bronchial and tracheal epithelial vascular swallowing, refusal to feed, sore throat, hyperextension of
permeability, thereby decreasing airway edema, which, the neck, stridor and respiratory distress. Most often they are
in turn, increases the airway radius and improves airflow,
polymicrobial; usual pathogens include group A streptococci,
with improvement in croup severity score within 30
oropharyngeal anaerobic bacteria and Staphylococcus
minutes. However, it has a temporary action on the airway
aureus. Treatment options include IV antibiotics, like co-
obstruction and only gives time for the underlying basic
amoxyclavulinic acid with or without surgical drainage.
pathology to resolve and may delay or decrease the need
Endotracheal intubation is indicated in any child with stridor
for intubation/tracheostomy. If the severity recurs, the
at presentation.
dose can be repeated after 2–4 hours.
• Antimicrobials: These have no role in treatment of viral
croup, even to prevent secondary bacterial infection.
Allergic Reactions/Angioneurotic Edema
• Airway management: A severely obstructed airway leading Allergic reaction (i.e., anaphylaxis) occurs within 30 minutes of
to signs of impending respiratory failure will need either an adverse exposure. Hoarseness and inspiratory stridor may
endotracheal intubation or tracheostomy. Intubation be accompanied by allergic symptoms (e.g., dysphagia, nasal
with a size smaller than the most appropriate size based congestion, itching eyes, sneezing, and wheezing). Oxygen
on the age of the child is preferred as there is significant should be administered and endotracheal intubation is
edema of the airway. Tracheostomy can often be avoided indicated in any child with stridor at presentation. Adrenaline
if an experienced pediatrician/anesthetist is available for a (0.01 mL/kg subcutaneous), hydrocortisone (10 mg/kg), and
rapid-sequence intubation. antihistaminics are administered.
• Discharge: Child can be sent home when there is no
stridor at rest. Parents need to be educated for monitoring Laryngomalacia
worsening of symptoms. It is the most common congenital laryngeal anomaly and
the most common cause of stridor in infants and children.
Epiglottitis Expectant observation is suitable for most infants because
Epiglottitis is a medical emergency occurring most commonly symptoms resolve spontaneously as the child and airways
in children aged 2–7 years, due to fulminant inflammation of grow. If significant obstruction or failure-to-thrive is present,
the supraglottic structures: epiglottis, arytenoids, aryepiglottic surgical correction (supraglottoplasty) may be considered
folds, and uvula, due to infection by Haemophilus influenzae which may be warranted in only 10% cases. It is usually a clinical
type B. It is not often reported from India. Clinically, the diagnosis however, cases presenting early (under 4 weeks of
child appears toxic. The disease is characterized by an abrupt age) or with severe obstruction should preferably have an early
onset of high-grade fever, sore throat, dysphagia, respiratory airway examination to rule-out alternative causes, requiring a
distress, and drooling of saliva. Establishing an airway by different treatment approach.
nasotracheal intubation or less often, by tracheostomy is
indicated. In general, children with acute epiglottitis are Subglottic Stenosis
intubated for 2–3 days, because the response to antibiotics is
It can be congenital or acquired. Congenital subglottic stenosis
usually rapid.
occurs due to incomplete canalization of the subglottis and cricoid
rings leading to narrowing of the subglottic lumen. Acquired
Diphtheria stenosis is most commonly caused by prolonged intubation
Diphtheria is commonly seen in partially or completely or due to a neglected foreign body. The symptomatology will
unimmunized children. Throat examination reveals a thick depend on degree of stenosis. Symptomatic children may be
pharyngeal membrane spreading to the adjacent larynx. This tracheotomized. Definitive surgical management includes
results in airway obstruction. It is important not to agitate the endoscopic methods, laser coagulation, or laryngotracheal
child as this may precipitate aspiration or airway obstruction. reconstruction.
310
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Chapter 67: Assessing and Managing a Child with Stridor
Algorithm 1
Algorithm for approach to a child with stridor
Vocal Cord Paralysis Key points

Vocal cord paralysis can be congenital or secondary to trauma ))
Stridor is a harsh, high-pitched vibratory sound caused by
at birth or during cardiac or intrathoracic surgery. The left partial obstruction of respiratory passages that result in
vocal cord is more commonly affected as the left recurrent turbulent passage of air through the airways
laryngeal nerve may get damaged, secondary to ligation of ))
Stridor is a sign and not diagnosis. Hence, every effort should
patent ductus arteriosus. Since vocal cord paralysis usually be made to identify the cause of this sign
resolves in 6–18 months in infants, those with bilateral vocal ))
Maintenance of airway should take precedence over making
cord paralysis can be managed either by lateralization of the a diagnosis
cords or by tracheostomy. In case of nonresolution in follow ))
A detailed history and clinical examination will help in
up, definitive surgical management, such as partial cordotomy determining the cause at the earliest
and arytenoidopexy may be required. ))
Neurogenic stridor is an important entity which is often
ignored. Hence, a detailed neurological examination should
not be ignored while examining a patient with stridor.
Conclusion
Stridor is a sign and not a diagnosis. Any child presenting Suggested readings
with stridor should be evaluated to determine the cause 1. Boudewyns A, Claes J, Van de Heyning P. Clinical practice: an approach to stridor
(Algorithm 1). Onset of stridor, presence/absence of fever, in infants and children. Eur J Pediatr. 2010;169:135-41.
2. D’ Agostino J. Pediatric airway nightmares. Emerg Med Clin North Am.
voice change and ability of patient to handle secretions will aid
2010;28:119-26.
in determining the diagnosis. Establishing a patent airway is of 3. Tibballs J, Watson T. Symptoms and signs differentiating croup and epiglottitis. J
utmost priority in such children. Paediatr Child Health. 2011;47:77-82.
4. Leung AK, Cho H. Diagnosis of stridor in children. Am Fam Physician.
1999;60:2289-96.
5. Sly PD, Collins RA. Physiological basis of respiratory signs and symptoms.
Paediatr Respir Rev. 2006;7:84-8.
311
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Chapter 68
Recurrent Wheezing in
Infants and Preschool Children
Ankit Parakh, Varinder Singh
INTRODUCTION factors with certain types of early child wheezing. The API has
a moderate positive predictive value and a very high negative
Recurrent wheezing in children less than five years of age is predictive value. Hence, an early childhood wheezer with a
a common childhood respiratory problem and possibly the negative API has very low chance of developing asthma later
most common indication for referral to pediatric respiratory in life.
physicians. Asthma in school-age child is due to cellular European Respiratory Society task force recommended
airway inflammation and inhaled corticosteroids (ICS) are classifying these children in a more pragmatic clinically
pivotal to management in school-age children with asthma. relevant syndrome based on their temporal pattern, named
However, much less is known about pathophysiology of pre- as episodic viral wheeze (EVW) and multiple-trigger wheeze
school wheeze and its management has been extrapolated (MTW) (Table 1). The task force agreed not to use term
from studies on older children. The present chapter deals with asthma to describe preschool wheezing illness since there
the phenotypes, causes, investigations, and management was insufficient evidence showing that pathophysiology
under-five childhood wheezing with a focus on practical of preschool wheezing is similar to childhood asthma.
aspects. Inflammation has been poorly studied in preschool children
and might be absent in very young children who wheeze.
PHENOTYPES OF PRESCHOOL WHEEZE However, easy as it seems, yet these divisions do not remain
as distinct compartmental entities and there is a shift of
The conventional teaching was to classify children into phenotypes in many cases. The temporal pattern of wheeze
wheeze associated lower respiratory tract infection and early during preschool years (EVW or MTW) is a relatively poor
onset asthma. This distinction was based on whether there predictor of long-term outcome (transient versus persistent
were afebrile episodes, personal/family history of atopy and wheeze). Frequency and severity of wheezing episodes are
response to bronchodilators. Although this distinction could stronger predictors of long-term outcome and should be
be useful in clinical practice; a significant overlap between taken into consideration when deciding treatment. As a
phenotypes made it less useful. These terms, however, are still result of which GINA guidelines 2015 suggests a probability
commonly used in clinical practice. based approach to assess which under-five children with viral
The largest epidemiological data comes from the work of induced wheezing are more likely to have asthma and hence
Fernado Martinez and colleagues from the Tucson children’s are more likely to respond to controller therapy.
cohort with a follow up into adulthood. Children were classified
as transient early wheezers, late onset wheezers and persistent
Causes
wheezers. Although this has been extremely important in
understanding of childhood wheezing, the classification The forgoing discussion of the under-five wheezers is
system is retrospectively based on the follow-up of the child. not for an atypical wheezer. Unlike a typical wheezer, the
What a clinician needs and the parents want is to know whether atypical wheezer is always marking an underlying disorder.
the index case shall develop asthma early in disease. They need A detailed description of various form of atypical wheezing
a prognostication as soon as possible and not a retrospective is out of scope of the present chapter but the common
epidemiological tool. An Asthma Predictive Index (API) has differential diagnosis, clinical pointers, and investigations are
been suggested based on the association between certain risk summarized in table 2.
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Chapter 68: Recurrent Wheezing in Infants and Preschool Children
Table 1: New classification of phenotypes of wheezing by the European Respiratory Society

Episodic viral wheeze Multiple-trigger wheeze
Definition Wheezing during discrete time periods, often in association Wheezing that shows discrete exacerbations
with clinical evidence of a viral cold but also symptoms between episodes
Triggers Viral infections Viral infections, tobacco smoke, allergen
exposure, mist-exposure, crying, exercise
Possible underlying factors Pre-existent impaired lung function, tobacco smoke Eosinophilic inflammation?
exposure, prematurity, atopy
Continues treatment with ICS Little or no benefit Significant fewer days with symptoms
Treatment with montelukast Moderate benefit Moderate reduction in exacerbations
Long-term outcome Declines over time (<6 years), can continue as episodic viral Can continue as asthma into adulthood
wheeze into school age, can change in multiple-trigger wheeze
ICS, inhaled corticosteroid
Table 2: Causes of atypical wheezing in preschool children

Differential diagnosis Clinical pointers Investigations
Infections
Protracted bacterial Wet cough for >4 weeks, no wheezing, complete response Clinical features usually suffice, cough swabs
bronchitis (PBB) to co-amoxiclav for 14 days or BAL might be considered
Chronic suppurative lung Recurrent episodes for wet cough, wet cough lasting for Usually clinical diagnosis, HRCT chest normal
disease >6 months, clubbing
Bronchiectasis Recurrent episodes for wet cough with or without wheezing, HRCT changes of bronchial wall thickening
wet cough lasting for >6 months and dilatation
Tuberculosis Prolonged fever, weight loss, anorexia, contact with TB case Mantoux, gastric aspirates, chest X-ay
Chronic rhino-sinusitis Chronic cough with upper airway signs (postnasal drip, Sinus X-ray, CT useful but required only in
chronic pharyngeal congestion) with no wheezing resistant cases for surgical intervention
Adenoid hypertrophy Chronic mouth breathing, adenoid facies X-ray lateral soft-tissue neck
Bronchiolitis obliterans Usually post infectious are viral bronchiolitis, persistent Pulmonary functions tests suggestive of non-
wheezing lasting for >60 days reversible severe obstruction, HRCT pattern of
mosaic perfusion, lung biopsy in atypical cases
Congenital problems
Tracheobronchomalacia Onset of symptoms since birth, usually symptoms persists Flexible bronchoscopy: dynamic airway
during interval periods, monophonic wheezing compression
Cystic fibrosis Features of CSLD/bronchiectasis, malabsorption, failure to Sweat chloride, mutation analysis
thrive
Bronchopulmonary Preterm birth, HMD, oxygen requirement during neonatal Chest X-rays, CT chest
dysplasia period, ventilation
Primary ciliary dyskinesia Features of CSLD/bronchiectasis, rhinitis since birth, chronic Ciliary motility and ultrastructural studies
otitis, situs inversus
H type tracheoesophageal Cough with feeding since birth, recurrent pneumonias Flexible bronchoscopy, contrast study
fistula
Vascular airway Onset of symptoms since birth, usually symptoms persist Flexible bronchoscopy: non dynamic airway
compression during interval periods, monophonic wheezing, feeding pulsatile compression
difficulties
Non-vascular airway Congenital cardiac disease, other suggestion of TB, Flexible bronchoscopy, Chest X-rays, CT chest
compression (lymph node, lymphoma, monophonic wheezing, feeding difficulties
cardiomegaly, tumors, cyst)
Mechanical problems
Gastroesophageal reflux Early onset symptoms (<6 months), severe wheezing 24 hours pH study, GER scan
disease (GERD) episodes, gastroesophageal symptoms, features of
aspiration on chest X-ray
Foreign body aspirations Choking while feeding, monophonic wheezing, lateralizing Flexible bronchoscopy
signs 313
TB, tuberculosis; CSLD, chronic suppurative lung disease; HMD, hyaline membrane disease; BAL, bronchoalveolar lavage; HRCT, high resolution computed
tomography; CT, computed tomography; GER, gastroesophageal reflux
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Children who are asymptomatic during intervals and have

Clinical Pearls a normal examination (normal respiratory rate, no noisy
• Preschool wheeze is a very common disorder and usually does breathing, no wheeze) are unlikely to have any atypical cause
not need to be investigated of wheeze.
• Clinicians should try and clinically differentiate these typical The role of investigations to differentiate the phenotype
wheezers form children having atypical wheezing of preschool wheeze and predict whether this child might
• Red flag signs need to be identified go on to develop asthma or remit is still a matter of research.
Preschool pulmonary function testing techniques (impulse
• Children with atypical wheezing would need a pediatric
oscillometry/interrupter technique), fractional exhaled nitric
pulmonology referral and will have to be investigated further
oxide and biomarkers on exhaled breath condensate have
• Further investigation can be decided on a case-to-case basis been used. Since there is no final conclusion on any of these
and might need (one or multiple) sweat chloride, studies
modalities their routine use in clinical practice needs to wait.
for gastroesophageal reflux disease, flexible bronchoscopy,
Gastroesophageal reflux disease (GERD) has been
immune studies and computed tomography chest.
evaluated as a cause of wheezing in children but still many
questions remain unanswered. Gastroesophageal reflux
disease is physiological and whether the “D: the disease” can
HISTORY AND EXAMINATION be attributed to reflux or is just a cotraveler, needs to be defined
A detailed history should be obtained including the age of for each case. Children with severe episodes, especially less
onset of the first episode, frequency of episodes, severity of than 6 months are more likely to have GERD as the sole or one
episodes [requiring out-patient department, and emergency of the reasons of persistent or recurrent wheezing.
visits, admissions, and intensive care unit (ICU) admissions], Investigations are required only in children suspected to
association with viral upper respiratory infection (URI), and have atypical causes of wheezing. The red flag signs in Box 1
nature of drugs used including response should be sought. should prompt referral for a detailed evaluation. Focused
Seasonal variation and severity trend should also be seen. investigations would be required and might include GER
It would be extremely important to elicit details regarding scan/24 h pH study, flexible bronchoscopy, sweat chloride test,
symptoms during interval period (any cough, wheezing, etc.), and computed tomography chest.
symptoms with activity, and any aeroallergen sensitization.
History of feeding difficulty, choking, and regurgitation of feeds TREATMENT
should be asked. History for allergic rhinitis and conjunctivitis
should be elicited. A detailed family history including grand
parents would also be useful. All details of the previous
Acute Episode
medicines taken should be recorded. Inhaled short-acting β2-agonists remain the cornerstone of
Examination should focus particularly on the growth therapy although nebulized and oral route are also acceptable
velocity of the baby, since children who have failure to thrive although inferior options. Inhaled or nebulized ipratropium
could have an underlying serious illness, like cystic fibrosis may be added in severe wheezy episodes. Systemic steroids
(CF). Presence of clubbing indicates an underlying suppurative short course (either patient initiated or doctor initiated) have
lung disease and should be carefully seen. not shown to reduce the symptom scores, hospital admission
Adenoid facies, Dennie-Morgan Folds, transverse rate or duration of hospital stay. It might be considered for a
nasal creases, nasal examination (nasal mucosa, turbinate, very severe episode as a counsel of despair but its routine use
deviated nasal septum) are also important features on is not recommended. Routine use of nebulized steroids has
physical examination. Respiratory examination should focus shown to be ineffective and is not recommended.
on shape of chest (any increased anteroposterior diameter), Recent studies have evaluated the role of pre-emptive
symmetry, and type of wheeze (monophonic or polyphonic). therapy, i.e., treatment started at the beginning of a URI to
Presence of monophonic wheeze would indicate a lesion/ prevent a wheezy episode. Both inhaled fluticasone and
compression of the intrathoracic airway and if persistent, oral montelukast have been shown to have an only modest
should be investigated further, e.g., endoscopic evaluation. The effect on reduction in number of wheezing episodes and the
examination should also cover the cardiovascular, abdominal, number needed to treat is high. Hence, their routine use is
and nervous systems. not justified and might be reserved for children with severe
EVW episodes.
INVESTIGATIONS: HOW AND HOW FAR?
Most children with recurring wheezing (EVW or MTW) do not Box 1: Red flag signs
require any investigations. A detailed history and complete
• Failure to thrive • Stridor/noisy breathing
physical examination usually is sufficient. As a rule, wheeze
• Clubbing • Age of onset <6 months
should be documented as clinical mimickers, like recurrent or
back to back URI (nursery school syndrome) and protracted • Presence of persistent wet cough • Severe wheeze episodes
314 bacterial bronchitis do not have a wheeze but have ruttles. • Persistent wheezing >4 weeks
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Chapter 68: Recurrent Wheezing in Infants and Preschool Children
Regular Prophylaxis 2. Consistently require symptomatic treatment more than 2

days per week for a period of more than 4 weeks
The key issues while considering long-term treatments are:
• Can we identify a child who is more prone to be an 3. Second asthma exacerbation requiring systemic cortico
asthmatic in the future? steroids within 6 months.
• Can we modify the natural history of the disease with any Although, these guidelines are also based on expert
intervention? opinion but appears to be useful.
• Can we modify lung function levels in adult life?
There is no clear consensus on the type of ICS, dose at
Three landmark trials (Peak, Ifwin, and PAC) over the last
which ICS to be started, maximum dose and when to label
10 years have shown that ICS only improves symptoms with
therapy as ineffective. Also there are no studies on the addition
no long-term benefit in the form of modification of the natural
course of disease or alteration in lung function. Interested of leukotriene receptor antagonist (LTRA) to ICS. Since long-
readers could refer to these very important studies mentioned acting b-agonist are Food and Drug Administration (FDA)
under Suggested Readings. approved for more than 6 years of age due to concerns on
safety, there are no studies on the use of LABA in preschool
What Does all this Mean in and What are the children with wheezing in addition to ICS.
Given the significant shift between the phenotypes,
Implications for Clinical Practice?
ICS/LTRA may be considered on a trial basis in preschool
Preschool children with recurrent wheeze, selected based on the child with recurrent wheeze (MTW or EVW with severe and
API do respond to ICSs as a group although the effect size is less
recurrent episodes), but should be discontinued if there is no
as compared to older children with asthma. There are no studies
clear clinical benefit. Children treated with a low-dose ICS
on non-atopic MTW, but recent data showed that the pathology
have an average of 5% fewer days with symptoms (or 18 days
of non-atopic and atopic MTW can be similar. Recent meta-
analysis suggests no difference in response between atopic per year) than children receiving placebo. Hence, it is arguable
versus nonatopic, although this awaits further studies. whether this increase in symptom-free days is clinically
The NHLBI-EPR 3 Guidelines has recommended using significant. The increase cost of therapy, negative impact on
prophylaxis in the following subset of children with recurrent height and other unrecognizable adverse effects should also
wheezing less than 5 years of age: be considered. Hence, the use of preventer regimen should be
1. Greater than 4 episodes of wheezing in past 1 year lasted reserved for only those with very troublesome symptoms and
more than 1 day and affected sleep and who have risk needing repeated oral steroids. The management algorithm is
factors for developing persistent asthma: positive API discussed in Algorithm 1.
Algorithm 1
Approach to management of wheezing in preschool children
ICS, inhaled corticosteroids; LTRA, leukotriene receptor antagonist.
315
ch-68.indd 315 11/19/2016 5:19:11 PM

Key points
SUGGESTED READINGS
1. Bacharier LB, Guilbert TW. Diagnosis and management of early asthma in
))
Most children wheeze only when they have upper respiratory preschool-aged children. J Allergy Clin Immunol. 2012;130(2):287-96.
infection, are usually nonatopic, and outgrow symptoms by 2. Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A,
6 years of age et al. Definition, assessment and treatment of wheezing disorders in preschool
))
A good history and physical examination would suffice in children: an evidence-based approach. Eur Respir J. 2008;32(4):1096-110.
most cases. Invasive investigations would be only required for 3. Brand PL, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, et al.
Classification and pharmacological treatment of preschool wheezing: changes
atypical cases
since 2008. Eur Respir J. 2014;43(4):1172-7.
))
Most children would require only symptomatic therapy 4. Castro-Rodriguez JA, Pedersen S. The role of inhaled corticosteroids in
))
Some with very frequent or severe symptoms require some management of asthma in infants and preschoolers. Curr Opin Pulm Med.
2013;19(1):54-9.
prophylaxis: either pre-emptive or regular
5. Castro-Rodriguez JA, Rodrigo GJ. Efficacy of inhaled corticosteroids in infants
))
Inhaled corticosteroids (ICS) do control symptoms but do not and preschoolers with recurrent wheezing and asthma: a systematic review with
seem to alter the natural history of wheezing (benefit not as meta-analysis. Pediatrics. 2009;123(3):e519-25.
much as children with school asthma) 6. Global Initiative for Asthma. (2015). Global Strategy for Asthma Management and
Prevention. [online] Available from: www.ginasthma.org [Accessed December
))
Efficacy of ICS with episodic viral wheeze remains contro
2015].
versial, while with multiple-trigger wheeze (MTW) appears
7. Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al.
to be at least somewhat effective. However, the effect size in Long-term inhaled corticosteroids in preschool children at high risk for asthma. N
preschool children with MTW is smaller than the effect size in Engl J Med. 2006;354(19):1985-97.
school-aged children with asthma 8. Rosenfeld M, Allen J, Arets BH, Aurora P, Beydon N, Calogero C, et al. An official
))
Treatment of children with recurrent wheezing in <5 years still American Thoracic Society workshop report: optimal lung function tests for
monitoring cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheezing
remains practice imperfect.
in children less than 6 years of age. Ann Am Thorac Soc. 2013;10(2):S1-S11.
316
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Chapter 69
Managing Acute Severe Asthma
Ankit Parakh, Shalu Gupta, Varinder Singh
INTRODUCTION CLINICAL FEATURES

Acute severe asthma or acute exacerbations are acute A rapid initial assessment is a must to determine degree of
episodes of progressive deteriorating shortness of breath, airway obstruction and hypoxia. Immediately identify severe
cough, wheezing, chest tightness, or a combination of these or life-threatening attack in children and institute immediate
symptoms. These acute episodes of asthma are an important measures to treat it (Box 1).
cause of morbidity, school absenteeism, and frequent hospital A detailed and rapid clinical assessment is done on the basis
admissions in children. The severity of these episodes varies of history, physical examination, and relevant investigations. A
from mild to severe and each episode has the potential to clinical history should include episodes/duration of respiratory
progress to respiratory failure. The term “critical asthma distress, fever, cough, noisy breathing, abnormal respiratory
syndrome” is now used to describe any child who is at high risk sounds, episodes of lethargy and cyanosis, records of past
of fatal asthma and includes acute severe asthma, refractory treatment and current treatment, any previous hospitalization
asthma, status asthmaticus, and near fatal asthma. Status or intensive care unit admission, use of steroids, and exposure
asthmaticus refers to an acute asthma exacerbation in which to any allergen or trigger which could have triggered this
bronchial obstruction is severe and continues to worsen or not attack. A child with asthma will present with bouts of cough,
improve despite the institution of adequate standard therapy, wheezing, dyspnea, and increases work of breathing. Because
leading to respiratory fatigue and finally to respiratory failure. early recognition is important for improving outcomes, various
A step-wise approach is required for the early recognition, risk factors are defined for early identification of fatal asthma
coordinated evaluation, and prompt treatment by an (Box 2).
experienced healthcare provider team. Detailed clinical examination should include level of
consciousness and degree of agitation, respiratory rate,
heart rate, temperature, peripheral pulses, blood pressure,
EPIDEMIOLOGY pulsus paradoxus, use of accessory muscles including chest
In USA more than 3.5 million children have greater than or retractions and nasal flaring, chest auscultation (wheeze), and
equal to 1 exacerbation/year, resulting in approximate 1.75 oxygen saturation. Categorization of the acute attack can be
million total emergency department (ED) visits, including 0.64 done into mild, moderate, or severe (Table 1).
million for children aged 0–17 years. Children younger than 4 Chest radiography is not routinely indicated in a child with
years old age have the highest rate of hospitalizations. Children previous history of asthma. Indications for chest radiography
aged 5–17 years missed 10.5 million school days owing to may include clinical suspicion for pneumothorax, atelectasis,
asthma, and activity limitations were reported in 5.5% as well. foreign body aspiration, after endotracheal intubation or
In the Indian subcontinent as per the phase 3 ISAAC study, failure to respond to standard therapy.
in children aged 13–14 and 6–7 years, the prevalence of asthma
increased per year by +0.02 and +0.06%, respectively. Although Box 1: Identification of life-threatening attack
there is little change in the overall prevalence of the current • Silent chest with increasing • Inability to speak
wheeze, the percentage of children reported to have had respiratory effort • Diaphoresis
asthma increased significantly, possibly reflecting a greater • Agitation with decreased level of • Inability to lie down
awareness of this condition and/or changes in diagnostic consciousness • Hypotension
practice. No country wide or large series data exist regarding • Central cyanosis • Bradycardia
burden of disease due to acute exacerbations.
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Box 2: Risk factors for potentially fatal asthma in children Clinical Pearls
• Previous near fatal asthma
• Previous admission to a PICU for asthma • Clinical signs correlate poorly with the severity of airways
• Admission for asthma in the last year obstruction. Some children may have very severe airways
• Excessive use of or overdependence on b2 agonists obstruction without appearing to be obviously distressed
• Current use or recent use of oral corticosteroids • In a tachypneic and hyperventilating child, a normal PaCO2
• Repeated attendances at emergency unit for asthma treatment, value should be interpreted as a sign of early muscle fatigue
especially if in the last year • The decision to intubate a child with severe acute asthma
• “Brittle” asthma (sudden onset of acute severe asthma attacks) should be based on the child’s clinical status and not simply
• Poor adherence to medication the arterial blood gas values.
• Psychosocial and/or family problems
PICU, pediatric intensive care unit.
Source: Adapted from Global Initiative for Asthma, British Thoracic Society/ TREATMENT
Scottish Intercollegiate Guidelines Network
There is good evidence supporting recommendations for the
initial treatment of acute asthma. Most children would respond
Arterial blood gas measurement provides objective to these measures although a small proportion of children
assessment of gas exchange. Early in the course of asthma, would need further therapy. There is less evidence to guide the
hypoxemia and hypocapnia are found due to ventilation/ use of second line therapies to treat the small number of severe
perfusion mismatch and hyperventilation. With the progression cases poorly responsive to first line measures.
of airflow obstruction, PaCO2 measurement returns to normal The details regarding assessment, first line treatment,
values, though in a tachypneic and hyperventilating child, a second line treatment, algorithm, further evaluation and drug
normal PaCO2 value should be interpreted as a sign of early doses should be present in all emergency and pediatric inten
muscle fatigue. With further progression of the disease mixed sive care unit as a ready to use tool. A suggested algorithm is
respiratory and metabolic acidosis occurs. Lactic acidosis shown in Algorithm 1 and drugs with doses, delivery methods,
indicates a combination of excess production from respiratory and adverse effects are summarized in Table 2. After each step in
muscles, tissue hypoxia (due to hypoxemia and decreased the algorithm the child should be reclassified. Children moving
cardiac output), and dehydration (due to decreased intake down a category (e.g., severe to moderate) suggest a good
and increased insensible losses). The decision to intubate a response; remaining in the same category (e.g., severe to severe)
child with severe acute asthma should be based on the child’s suggests a partial response; and children moving up a category
clinical status and not simply the arterial blood gas values. (e.g., severe to life threatening) suggest a poor response.
Table 1: Acute asthma severity assessment

Examination Mild Moderate Severe
Breathing frequency (awake) Increased Increased >30/min
Wheezing None or mild end expiratory Throughout expiration Both inspiratory and
expiratory
Work of breathing and use of Normal or minimal retractions Intercostals retractions Suprasternal retractions,
auxiliary muscles present
Expiration Normal or minimally prolonged Moderately prolonged Severely prolonged
Pulsus paradoxus Absent Can be present Often present
Pulse pressure fluctuation <10 mmHg 10–25 mmHg 20–40 mmHg
Air entry Normal Decreased at bases Wide-spread decrease
Breathlessness With activity or walking While at rest: While at rest
For infants: soft or shorter cry, difficulty For infants: stops feeding, sits
feeding, prefers sitting upright
Talks Sentences Phrases words
Alertness Alert/can be agitated May be agitated agitated
Investigations
Pulse oximetry (room air) >95% 91–95% <91%
PaCo2 (KPa) <5.6 <5.6 ≥5.6
PaO2 (KPa) Normal >8 <8, possible cyanosis
318 PEF (% of predicted for height) ≥70% 40–69% <40%

PEF, peak expiratory flow.
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Chapter 69: Managing Acute Severe Asthma
Table 2: Doses of common drug used in acute severe asthma

Dose Available formulations Adverse effects and comments
Short-acting b-agonists
Salbutamol • Nebulized: 0.15 mg/kg (minimum • Respules: 2.5 mg/2.5 mL; • Tachycardia, palpitations, headache,
dose 2.5 mg) every 20 min for • Respirator solution: 5 mg/mL; hypokalemia, hyperglycemia
3 doses then 0.15–0.3 mg/kg up to • MDI: 100 µg/puff
10 mg every 1–4 hour as needed,
or 0.5 mg/kg/hour by continuous
nebulization
• MDI: 2–4 puffs (up to 10 puffs) at
the same intervals as above
Levo salbutamol • 0.075 mg/kg usage similar to • Respules: Three • Same as above
salbutamol strengths available
0.31/0.63/1.25 mg/2.5 mL
Terbutaline • 0.01 mg/kg subcutaneous • Inj 0.5 mg/mL • IV terbutaline drip necessitates continuous
• Bolus 5–10 µg/kg over 10 minutes heart rate and ECG
followed by 2–10 µg/kg/hour IV • If heart rate i.e.,180/min or if ECG changes
(1 mL terbutaline + 50 mL 5% develop, halve the drip rate
dextrose, thus, • Discontinue nebulized β2 agonist if using
1 mL = 10 µg terbutaline) high infusion rates of IV terbutaline
• Dose of IV terbutaline to be halved if
concurrently used with theophylline drip
Anticholinergics
Ipratropium • 125 µg <1 year; 250 µg >1 year • Respules: 0.5 mg/2 mL • Dryness of mouth increased wheezing in
bromide every 20 min for 3 doses, then • Respirator solution: some
every 6–8 hours 0.25 mg/mL; • Slower onset of than β2 agonists but
• MDI: 20 µg/puff may provide additive effect in severe
exacerbations
Corticosteroids
Hydrocortisone • 10 mg/kg stat followed by 5 mg/kg • Injection 100 mg/vial • Oral steroids are equally effective
every 6 hourly IV • Shift to oral as soon as the child is able to
accept orally
• Tapering not required for short courses
Prednisolone • 1–2 mg/kg in 2 divided doses • Tablet 5, 10, 20, 30 mg, syrup
(maximum 60 mg/day) 5 mg/mL and 15 mg/mL
Others
Aminophylline • 6 mg/kg bolus over 30 min • Injection 250 mg/10 mL • Omit bolus in children already on oral
followed by 0.5–1 mg/kg/hour aminophylline
continuous infusion in 5% dextrose
Magnesium • 25–50 mg/kg IV bolus over 20 min • Injection 50% (500 mg/mL), • Tachycardia, hypotension, muscle
sulfate (maximum 2 g) 1 mL ampoule weakness
MDI, metered-dose inhaler; ECG, electrocardiogram; IV, intravenous.
First Line Treatment exacerbations of asthma across all severity. Children with
severe or life-threatening asthma should receive frequent doses
Oxygen of nebulized bronchodilators (2.5–5 mg salbutamol) driven by
All children with severe and life-threatening asthma or SpO2 oxygen, repeated every 20–30 minutes; although metered-dose
less than 92%, should receive supplemental oxygen via a inhaler with spacers can be used (10–12 puffs of salbutamol
face mask or nasal cannula at sufficient flow rates to achieve 100 µg repeated every 2–4 minutes titrated according to clinical
normal saturations. Partial rebreathing and non-rebreathing response). Continuous nebulized β2-agonists are of no greater
masks are useful in providing high concentration of fraction of benefit than the use of frequent intermittent doses in the same
inspired oxygen in children not maintaining on simple/venturi total hourly dosage.
face mask.
Anticholinergics
Short-acting β-2 Agonists Children with severe exacerbation or moderate exacerbation
Short-acting b-2 agonists (salbutamol, levosalbutamol, with poor response to the initial dose of β2-agonists, are usually
terbutaline) are the bronchodilators of choice for acute nebulized with combination with nebulized ipratropium 319
ch-69.indd 319 11/19/2016 5:21:45 PM

Algorithm 1
Algorithm for management of acute severe asthma
PICU, pediatric intensive care unit; ECG, electrocardiogram; IV, intravenous; NPO, nil per os; IV, intravenous; SC, subcutaneous; NiPPV, nasal intermittent positive
pressure inhibitors.
bromide. There is good evidence for the safety and efficacy of Second Line Treatment
frequent doses of ipratropium bromide (every 20–30 minutes)
Children with continuing severe asthma, despite frequent
used in addition to β2 agonists for the first two hours of a severe
nebulized β2 agonists and ipratropium bromide plus oral
asthma attack. Benefits are more apparent in the most severe
steroids, and those with life-threatening features, need transfer
patients.
to a high dependency unit or PICU to receive second line IV
therapies. There are three options to consider: (1) magnesium
Corticosteroids sulfate, (2) aminophylline and (3) continuous IV salbutamol/
Systemic corticosteroids are pivotal in the management terbutaline.
of acute severe asthma and reduce the need for hospital
admission and prevent a relapse in symptoms after initial Intravenous or Nebulized Magnesium Sulfate
presentation. Benefits can be apparent within 3–4 hours. Both Magnesium sulfate is a physiological calcium antagonist that
oral as well as intravenous (IV) steroids have similar efficacy. acts by inhibiting the contraction, mediated by the bronchial
Intravenous hydrocortisone (4 mg/kg repeated 4-hourly) smooth muscle. In addition, it interferes with the para-
should be reserved for severely affected children who are sympathetic stimulation and prevents acetylcholine release
320 unable to retain oral medication. to the axon terminal; therefore promoting a bronchodilating
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Chapter 69: Managing Acute Severe Asthma
effect. It has been usually recommended as an add-on therapy The use of a helium-oxygen gas mixture is another
after the first hour of treatment with salbutamol and steroids potentially attractive therapy for the treatment of status
(GINA 2015, Evidence level A). One large open-labeled trail asthmaticus in children. The use of helium-oxygen–driven
from Argentina has shown that magnesium sulfate when used aerosolized therapy increases drug delivery by improving gas
in the first hour itself can reduce significantly, the percentage exchange to the distal airways.
of children who required mechanical ventilation support.
There is now evidence to support use of nebulized isotonic
magnesium sulfate. Key points
Intravenous Aminophylline ))
Acute asthma management involves prompt recognition
of severity and treatment using short-acting β-agonists,
There is no evidence that aminophylline is of benefit for anticholinergics, and systemic corticosteroids
mild to moderate asthma and side effects are common and
troublesome. One well-conducted study has shown evidence of ))
Children with severe exacerbations should receive high-dose
short-acting β-agonists mixed with ipratropium bromide as
benefit in severe acute asthma unresponsive to multiple doses
well as systemic steroids
of β2 agonists and steroids, although the loading dose used
was double that currently recommended in UK and one-third ))
Children with less-severe exacerbations might benefit from
of patients were withdrawn from active medication because of systemic steroids
vomiting. Two studies have compared IV β2 agonists with IV ))
Patients not improving after multiple high-dose systemic
theophylline/aminophylline. One demonstrated equivalence. steroids should receive adjunctive therapy, such as intra
The other resulted in a shorter period of inpatient treatment venous magnesium
among the children receiving an aminophylline bolus followed ))
Prepare a written asthma action plan. Ensure proper follow-
by infusion but in the salbutamol arm of the study an infusion up after discharge with an aim to implement a long-term
was not given after the bolus dose. management plan.
Intravenous Terbutaline
A continuous IV infusion of terbutaline could be used in SUGGESTED READINGS
children not responding to the above mentioned drugs. This
should be given in a high dependency unit or PICU with 1. Camargo CA Jr, Rachelefsky G, Schatz M. Managing asthma exacerbations in
the emergency department: summary of the National Asthma Education And
continuous electrocardiogram (ECG) monitoring and twice Prevention Program Expert Panel Report 3 guidelines for the management of
daily electrolyte monitoring. Nebulized bronchodilators asthma exacerbations. Proc Am Thorac Soc. 2009;6(4):357-66.
should be continued while the patient is receiving IV 2. Carroll CA, Sala KA. Pediatric status asthmaticus. Crit Care Clin. 2013;29(2):
bronchodilators. Once the patient is improving the IV infusion 153-66.
should be reduced before reducing the frequency of nebulized 3. Kling S, Zar HJ, Levin ME, Green RJ, Jeena PM, Risenga SM, et al. Guideline
bronchodilators. Currently, the availability of this drug is poor for the management of acute asthma in children: 2013 update. S Afr Med J.
across our country. 2013;103(3 Pt 3):199-207.
4. Koninckx M, Buysee C, dee Hoog M. Management of status asthmaticus in
Other Modalities children. Paediatr Respir Rev. 2013;14(2):78-85.
5. Nelson KA, Zorc JJ. Asthma update. Pediatr Clin North Am. 2013;60(5):1035-48.
Children not responding to the above measures should be 6. Nievas IF, Anand KJ. Severe acute asthma exacerbation in children: a
considered for noninvasive ventilation, IV ketamine, and if stepwise approach for escalating therapy in a pediatric intensive care unit.
required, intubation and mechanical ventilation. J Pediatr Pharmacol Ther. 2013;18(2):88-104.
321
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Chapter 70
Management of Bronchiolitis
Preeti Singh, Varinder Singh
INTRODUCTION Table 1: Markers of an increased risk and severity of bronchiolitis
Bronchiolitis accounts for significant number of hospital Personal risk factors Environmental Clinical clues
admission worldwide especially less than 2 years of age. The risk factors
American Academy of Pediatrics Clinical Practice Guideline • Male gender • Having older • Toxic or ill
defines bronchiolitis as “a constellation of clinical symptoms • Prematurity <34 weeks siblings appearance
and signs including a viral upper respiratory prodrome • Age <6 months • Passive • Oxygen
followed by increased respiratory effort and wheezing in • Absence of breast- smoke saturation
children less than two years of age”. feeding • Household <95%
• Chronic pulmonary crowding • Respiratory rate
disease • Child-care ≥70 breaths per
EPIDEMIOLOGY • Hemodynamically attendance minute
significant congenital • Moderate/
Bronchiolitis is primarily a disease of infancy, with the first
heart disease severe chest
(and the most severe) episodes occuring between 2–6 months
• Immunodeficiency retractions
of age. Respiratory syncytial virus (RSV) is the most common • Family history of asthma • Atelectasis
etiological agent and accounts for 50–80% of cases. In Indian • Personal atopy on chest
studies, RSV infection was implicated in 30–70% of children • Congenitally small radiograph
with bronchiolitis. Other viruses responsible are rhino airways
virus, adenovirus, coronavirus, enterovirus, parainfluenza • Airway hyperactivity
virus type 3, influenza, and the recently identified human • RSV-specific IgE
metapneumovirus (HMPV). Molecular diagnostic techniques responses
have also revealed that young children with bronchiolitis have RSV, respiratory syncytial virus; IgE, immunoglobulin E
mixed viral infections (10–30%) most commonly with RSV and
either HMPV or rhinovirus. Bronchiolitis shows a seasonal with subsequent absorption, atelectasis, and a ventilation
pattern with highest rates occurring during winter in most perfusion mismatch leading to hypoxemia. The degree of
locations and in more tropical and subtropical latitudes during obstruction may vary as these areas are cleared, resulting in
rainy season. There has been no evidence for a role of bacteria rapidly changing clinical signs. Certain underlying conditions,
in etiology of bronchiolitis. Data on synergistic viral-bacterial such as prematurity, chronic lung disease, cardiac disease,
infections also are unconvincing. immunodeficiency, and neuromuscular disorders can
predispose a child to a more turbulent course while certain
PATHOGENESIS clinical clues suggest a more likely stormy course (Table 1).
Bronchiolitis is characterized by acute inflammation of the
bronchiolar epithelium, with peribronchial infiltration of Clinical Pearl
white blood cells, mostly mononuclear cells, edema of the
submucosa and adventitia, necrosis of small airway epithelial • Bronchiolitis is primarily a disease of infancy with respiratory
cells, increased mucus production, and bronchospasm. Plugs syncytial virus being responsible for more than 50% of cases.
of sloughed, necrotic epithelium and fibrin in the airways Host, anatomical immunologic, environmental and nature of
cause partial or total obstruction to airflow. A “ball-valve” the viral pathogen plays an important role in severity of clinical
mechanism results in air trapping distal to obstructed areas, syndrome.
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Chapter 70: Management of Bronchiolitis
CLINICAL FEATURES AND COURSE Box 1: Differential diagnoses for acute bronchiolitis
Bronchiolitis typically starts with fever and rhinorrhea. • Virus-induced wheeze of infancy
After 1–3 days, a prominent staccato-like cough and wheeze • Viral and bacterial pneumonias
develop. The clinical presentation of bronchiolitis can be • Other pulmonary infections (e.g., Mycoplasma, Chlamydia,
quite variable, both over time and between patients. It can tuberculosis)
range from mild respiratory distress with transient events, • Gastroesophageal reflux disease
such as mucous plugging, to apnea and respiratory failure. • Congestive heart failure
Excessive nasal secretions can cause upper airway obstruction, • Structural abnormalities, like congenital vascular ring, laryngo
with both inspiratory and expiratory noise on auscultation. tracheomalacia, mediastinal mass, bronchogenic cyst, etc.
Concurrent presence of respiratory symptoms in other family • Tracheoesophageal fistula
members is common. On examination child has tachypnea, • Foreign body aspiration
varying degree of hypoxemia due to ventilation perfusion • Cystic fibrosis
mismatch and increased work of breathing manifested as
nasal flaring, intercostal retractions, subcostal retractions, and
use of accessory muscles. Upon auscultation, diffuse bilateral Clinical Pearl
wheezes and crackles are often present; the expiratory phase
of respiration can also be prolonged. The liver and spleen can • The diagnosis of bronchiolitis is essentially clinical, particularly
in a previously healthy infant with first episode of wheezing.
be palpable due to hyperinflation of the lungs secondary to
air trapping. Other manifestations of upper respiratory tract
infection (URTI), like mild conjunctivitis, otitis media, and
pharyngitis may be present. MANAGEMENT
The mean duration of illness with bronchiolitis is 15 days, The treatment of bronchiolitis is often debated and no
and the majority of these infections resolve uneventfully consistently effective therapy has shown to alter the course of
within 3–4 weeks. The mortality rate is less than 1%, being the disease or its major outcomes. It is critical to remember
attributable to apnea or respiratory failure. The association that most infants with mild bronchiolitis improve and
of bronchiolitis with the subsequent wheezing is not clearly resolve spontaneously and hence can be successfully treated
established as causal. While RSV bronchiolitis actually leads at home. The cornerstone of therapy for bronchiolitis is
to long-term changes in the lungs in a proportion of patients supportive care. Infants with moderate to severe respiratory
while in others who continue to wheeze later, RSV infection distress need hospitalization for management of this life-
simply may serve as a marker for a genetic or physiologic/ threatening condition. The need for treatment is either
anatomic predisposition to wheezing. hypoxemia necessitating supplemental oxygen or the inability
to take adequate fluids by mouth. Monitoring the child with
bronchiolitis for disease progression and complications is
DIAGNOSIS a vital part of supportive care. Table 2 details the current
The diagnosis of bronchiolitis is essentially clinical and does evidence for the management of acute bronchiolitis.
not require diagnostic testing, but the differential diagnosis
is broad and multifactorial which warrants consideration Supportive Care
(Box 1). The use of complete blood counts has not proved
Fluid and Hydration Management
to be useful in either diagnosing bronchiolitis or guiding
its therapy. A blood gas (capillary, venous, or arterial) Children with bronchiolitis often have potential problem of
can aid with assessment of gas exchange in a child with dehydration because of decreased intake and increased needs
moderate to severe respiratory distress. If a child has poor (due to fever and tachypnea), so fluid and hydration status
oral intake, one can assess electrolyte abnormalities and should be properly maintained. Care should be taken not to
extent of dehydration by measuring the plasma blood urea overhydrate them because edema is an important part of the
nitrogen, creatine, and electrolytes. The typical findings pathology of bronchiolitis (excessive antidiuretic hormone
on chest radiograph are hyperinflation and peribronchial production), which can lead to pulmonary congestion. Breast
thickening. Areas of atelectasis are not uncommon. Indian feeding should be encouraged as it provides hydration and
Academy of Pediatrics and American Academy of Pediatrics confers immunological protection. Nasogastric feedings may
does not recommend the routine use of chest radiography be considered for a child who has decreased oral intake, with
for diagnosis and management of bronchiolitis. It may be mild to moderate respiratory distress. In infants with diificulty
useful when the hospitalized child does not improve at in feeding, persistent vomiting or with moderate to severe
the expected rate, if the severity of disease requires further respiratory distress intravenous fluids should be considered to
evaluation, or if another diagnosis is suspected. Laboratory maintain hydration. Usual maintainence fluids are needed.
testing of nasopharyngeal aspirates for identification of
viruses can support patient diagnosis, aid with syndromic Oxygen Supplementation
surveillance, but has limited utility and does not aid The keystone of therapy for bronchiolitis is the administration
individual case management. of oxygen because hypoxemia is seen in moderate to severe 323
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Table 2: Evidence-based recommendations for treatment of

bronchiolitis Clinical Pearl
Intervention Recommendation • The cornerstone of therapy for bronchiolitis is supportive
• Supportive-care fluid and • Strong recommendation care with maintenance of adequate hydration and nutrition,
hydration management ensuring adequate oxygenation, and nasal decongestion
• Use of supplemental oxygen using nasal saline washes.
if SpO2 <90%
• Nebulized bronchodilators • Consider trial under strict
(epinephrine/salbutamol) monitoring but use of either Bronchodilators
drug continued only if The evidence to support the routine use of bronchodilators in
proven benefit the management of bronchiolitis is not very strong, and the
• Nebulized hypertonic saline • May reduce length of practice remains controversial. The Cochrne review does not
inpatient hospitalization but show any benfit of short-acting β-2 agonists in the manage
no recommendation ment of bronchiolitis. Another meta-analysis demonstrated
• Corticosteroids • Not recommended for superiority of epinephrine compared to placebo for short-term
routine use outcomes for outpatients.
• Antibiotics • Specific indications in case of If the decision is made to use an inhaled bronchodilator,
coexisting bacterial infection it should be based on personal or family history of atopy
• Ribavarin • Not recommended for or asthma; if present, salbutamol inhalation may be given,
routine use otherwise a trial of epinephrine inhalation may be given.
• CPAP, mechanical • Possibly effective for most
Further doses of either medication may be continued only on
ventillation, surfactant, heliox severe cases and areas of documentation of improvement.
future research
• Leukotriene receptor • Possibly ineffective so no Corticosteroids
antagonists/montelukast recommendation The use of systemic corticosteroid in bronchiolitis is still
• Oral bronchodilators controversial. A recent Cochrane review conducted in
• Chest physiotherapy 2010 including 17 trials with a total of 2596 infants did not
• Inhaled furosemide/inhaled demonstrate a benefit in significantly reducing outpatient
interferon a-2a/inhaled visits, hospital admission rate, clinical score after 12 hours
recombinant human DNase and length of stay for inpatients. Combined dexamethasone
CPAP, continuous positive airway pressure; DNase, deoxyribonuclease. and epinephrine may reduce outpatient admissions, but result
from this single study at best be called exploratory and safety
data is limited. Currently, there is no definitive evidence to
cases due to ventilation perfusion mismatch. Humidified support the use of inhaled corticosteroids for acute or long-
oxygen should be administered using nasal cannula, face mask, term benefit in bronchiolitis.
or head box and the patient’s respiratory status monitored by
pulse oximetry. In an irritable child one may have to accept the Mucolytics
least threatning but most acceptable manner of oxygen therpy
(like nasal blow by) in which the baby tolerates it. The American Mucous plugging plays a significant role in the small airway
Academy of Pediatrics (AAP) recommends supplemental obstruction of bronchiolitis and interventions, like hypertonic
oxygen if the hemoglobin oxygen saturation is persistently saline and deoxyribonuclease (DNase) decrease epithelial
below 90%. Their suggested point of discontinuation of edema and elasticity and viscosity of mucus which could
oxygen therapy is when the child’s oxygen saturation can be improve clinical outcomes. Hypertonic saline inhalation may
maintained at or above 90% with room air and the child is be considered as potential treatment for bronchiolitis. Recent
feeding well, with minimal respiratory distress. Premature or randomized controlled trial reported that high volume normal
low birth weight infants, as well as those with chronic lung saline was as effective as 3% saline in children with mild
disease or congenital heart disease have lower tolerance for bronchiolitis.
hypoxemia and a higher likelihood of severe disease, so need
to be careful while discontinuing oxygen. Antibiotics
As bronchiolitis is a viral disease, antibiotics are not useful
Nasal Decongestion or necessary. Institution of antibiotics should be considered
Children with bronchiolitis suffer from nasal blockade due to only when a change in course of illness suggests the possibility
thick copious nasal secretions. Cleaning of nostrils by instilling of secondary bacterial infection. A recent review did not
saline drops and gentle suction may help to relieve nasal block find sufficient evidence to support the use of antibiotics for
and facilitate feeding. Parents should be taught this effective bronchiolitis, but concluded that research may be justified
self-clearing of the nasal passages before discharge from to identify a subgroup of patients who may benefit from
324 hospital. antibiotics. It also stressed that the future research should
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Chapter 70: Management of Bronchiolitis
Algorithm 1
Algorithmic approach and management of a child with bronchiolitis
IVF, in vitro fluid; ICU, intensive care unit; ABG, arterial blood gas.
focus on determining the reasons that clinicians use antibiotics significant cardiopulmonary disease) and in infants requiring
so readily for bronchiolitis, so that the antibiotic usage in mechanical ventilation.
bronchiolitis is reduced and also the clinician anxiety about
not using antibiotics is reduced. Others
Current evidence suggests that surfactant therapy may have
Mechanical Ventilation and potential use in acute severe bronchiolitis requiring mechanical
Continuous Positive Airway Pressure ventilation in decreasing duration of mechanical ventilation
Assisted ventilation is indicated in infants with moderate to and intensive care unit stay. There is a need for larger trials with
severe bronchiolitis with progressive clinical deterioration, adequate power and to establish beneficial role of administration
i.e. increasing respiratory distress, apnea and poor peripheral of surfactant in infants with severe bronchiolitis. Currently, there
perfusion. In severe bronchiolitis early intervention in form of is insufficient evidence to recommend leukotriene modifier and
continuous positive airway pressure (CPAP) did not produce heliox use for bronchiolitis.
any conclusive evidence to decrease the need for intubation.
Current evidence is inconclusive regarding routine use of PREVENTION
CPAP in children with acute bronchiolitis. The use of chest
physiotherapy is discouraged in children with bronchiolitis There is no effective therapy that can improve outcome,
as it did not reduce supplemental oxygen requirement, or if administered early in course of bronchiolitis. Hand
length of hospital stay rather it may increase the distress and decontamination is the most important step in preventing
irritability of ill infants. nosocomial spread of RSV. Clinicians should educate health
personnel and family members on hand sanitation.
Currently, no vaccine exists for the prevention of RSV
Antiviral infection. Passive immunoprophylaxis using palivizumab
Ribavarin is the only antiviral agent licensed for use with RSV [humanized mouse immunoglobulin G1 (IgG1) monoclonal
bronchiolitis. Routine use of ribavirin is not recommended antibody] to high-risk infants (Table 3) before RSV season has
for children with bronchiolitis. It may be considered in high documented marked reduction in the severity of illness and
risk infants (immunocompromised and/or hemodynamically rate of hospitalization after RSV infection. It is administered 325
ch-70.indd 325 11/19/2016 5:23:07 PM

Table 3: Recommendations for respiratory syncytial virus respiratory syncytial virus bronchiolitis in children. Am J Respir Crit Care Med.
immunoprophylaxis with palivizumab 2008;178(8):854-60.
6. Davison C, Ventre KM, Luchetti M, Randolph AG. Efficacy of interventions for
High-risk group Details bronchiolitis in critically ill infants: a systematic review and meta-analysis. Pediatr
Crit Care Med. 2004;5(5):482-9.
Prematurity • Infants born at 28 weeks of gestation or 7. Donlan M, Fontela PS, Puligandla PS. Use of continuous positive airway pressure
earlier who are younger than 12 months of (CPAP) in acute viral bronchiolitis: a systematic review. Pediatr Pulmonol.
age at the start of the RSV season 2011;46(8):736-46.
• Infants born at 29–32 weeks of gestation who 8. Farley R, Spurling GK, Eriksson L, Del Mar CB. Antibiotics for bronchiolitis in children
are younger than 6 months of age at the start under two years of age. Cochrane Database Syst Rev. 2014;10:CD005189.
9. Fernandes RM, Bialy LM, Vandermeer B, Tjosvold L, Plint AC, Patel H, et al.
of the RSV season
Glucocorticoids for acute viral bronchiolitis in infants and young children.
• Infants born between 32 and 35 weeks of Cochrane Database Syst Rev. 2010;(10):CD004878.
gestation, who have 2 or more of the following 10. Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database
risk factors (child care attendance, school- of Syst Rev. 2014;6:CD001266.
aged siblings, exposure to environmental air 11. Gupta S, Shamsundar R, Shet A, Chawan R, Srinivasa H. Prevalence of respiratory
pollutants, congenital abnormalities of the syncytial virus infection among hospitalized children presenting with acute lower
airways, or severe neuromuscular disease) and respiratory tract infections. Indian J Pediatr. 2011;78(12):1495-7.
are younger than 6 months of age at the start 12. Hartling L, Bialy LM, Vandermeer B, Tjosvold L, Johnson DW, Plint AC, et al.
of the RSV season Epinephrine for bronchiolitis. Cochrane Database Syst Rev. 2011;6:CD003123.
13. Jat KR, Chawla D. Surfactant therapy for bronchiolitis in critically ill infants.
Chronic lung • Required medical therapy for CLD within Cochrane Database Syst Rev. 2012;9:CD009194.
disease (CLD) 6 months before onset of RSV season 14. Jat KR, Mathew JL.Continuous positive airway pressure (CPAP) for acute
bronchiolitis in children. Cochrane Database Syst Rev. 2015;1:CD010473.
Congenital • Cyanotic heart disease 15. Liet JM, Ducruet T, Gupta V, Cambonie G. Heliox inhalation therapy for bronchiolitis
heart disease • Taking medications for congestive heart in infants. Cochrane Database Syst Rev. 2010;4:CD006915.
failure 16. Loda FA, Clyde WA Jr, Glezen WP, Senior RJ, Sheaffer CI, Denny FW Jr. Studies on
the role of viruses, bacteria, and M. pneumoniae as causes of lower respiratory
RSV, respiratory syncytial virus. tract infections in children. J. Pediatr. 1968;72(2):161-76.
17. Maitreyi RS, Broor S, Kabra SK, Ghosh M, Seth P, Dar L, et al. Rapid detection of
intramuscularly at a dose of 15 mg/kg monthly (every 30 days) respiratory viruses by centrifugation enhanced cultures from children with acute
during the RSV season with maximum of 5 doses being lower respiratory tract infections. J Clin Virol. 2000;16(1):41-7.
required for prophylaxis during one season. 18. Mansbach JM, Clark S, Christopher NC, LoVecchio F, Kunz S, Acholonu U, et al.
Prospective multicenter study of bronchiolitis: predicting safe discharges from the
emergency department. Pediatrics. 2008;121(4):680-8.
Key points 19. McConnochie KM, Roghmann KJ. Parental smoking, presence of older siblings,
and family history of asthma increase risk of bronchiolitis. Am J Dis Child.
))
Bronchiolitis is a disease of infancy with essentially clinical 1986;140(8):806-12.
diagnosis 20. Meissner HC. Selected populations at increased risk from respiratory syncytial
virus infection. Pediatr Infect Dis J. 2003;22(2 Suppl):S40-4.
))
The cornerstone of therapy for bronchiolitis is supportive 21. Mejías A, Ramilo O. Review of palivizumab in the prophylaxis of respiratory
care with maintenance of adequate hydration and nutrition, syncytial virus (RSV) in high-risk infants. Biologics. 2008;2(3):433-9.
ensuring adequate oxygenation, and nasal decongestion 22. Paranhos-Baccalà G, Komurian-Pradel F, Richard N, Vernet G, Lina B, Floret D.
Mixed respiratory virus infections. J Clin Virol. 2008;43(4):407-10.
))
Bronchodilators should not be routinely used in the 23. Pickering, Baker CJ, McMillanassociate JA (Eds). Red Book: 2006 Report of the
management of bronchiolitis. A carefully monitored trial of Committee on Infectious Diseases, 27th ed. Elk Grove, Illinois: American Academy
either α or β adrenergic inhalation is an option of Pediatrics; 2006.
))
Hand decontamination is the most important step in 24. Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R, et al. Epinephrine
preventing nosocomial spread of RSV and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):
2079-89.
))
Breastfeeding is recommended to decrease a child’s risk of 25. Shaw KN, Bell LM, Sherman NH. Outpatient assessment of infants with
having LRTI. bronchiolitis. Am J Dis Child. 1991;145(2):151–5.
26. Smyth RL, Openshaw PJ. Bronchiolitis. Lancet. 2006;368(9532):312-22.
27. van Steensel-Moll HA, Hazelzet JA, van der Voort E, Neijens HJ, Hackeng WH.
Excessive secretion of antidiuretic hormone in infections with respiratory syncytial
SUGGESTED READINGS virus. Arch Dis Child. 1990;65(11):1237-9.
1. American Academy of Pediatrics Subcommittee on Diagnosis and Management 28. Verma N, Lodha R, Kabra SK. Recent advances in management of bronchiolitis.
of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. Indian Pediatr. 2013;50(10):939-49.
2006;118(4):1774-93. 29. Voets S, van Berlaer G, Hachimi-Idrissi S. Clinical predictors of the severity of
2. Anil AB, Anil M, Saglam AB, Cetin N, Bal A, Aksu N. High volume normal saline bronchiolitis. Eur J Emerg Med. 2006;13(3):134-8.
alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal 30. Wang EE, Law BJ, Stephens D. Pediatric Investigators Collaborative Network on
saline, and 3% saline in mild bronchiolitis. Pediatr Pulmonol. 2010;45(1):41-7. Infections in Canada (PICNIC) prospective study of risk factors and outcomes
3. Beem M, Wright FH, Fasan DM, Egerer R, Oehme M. Observations on the etiology in patients hospitalized with respiratory syncytial viral lower respiratory tract
of acute bronchiolitis in infants. J Pediatr. 1962;61:864-9. infection. J Pediatr. 1995;126(2):212-9.
4. Bharaj P, Sullender WM, Kabra SK, Mani K, Cherian J, Tyagi V, et al. Respiratory 31. Wright AL, Taussig LM, Ray CG, Harrison HR, Holberg CJ. The Tucson Children’s
viral infections detected by multiplex PCR among pediatric patients with lower Respiratory Study. II. Lower respiratory tract illness in the first year of life. Am J
respiratory tract infections seen at an urban hospital in Delhi from 2005 to 2007. Epidemiol. 1989;129(6):1232-46.
Virol J. 2009;6:89. 32. Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic
326 5. Bisgaard H, Flores-Nunez A, Goh A, Azimi P, Halkas A, Malice MP, et al. saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev.
Study of montelukast for the treatment of respiratory symptoms of post- 2013;7:CD006458.
ch-70.indd 326 11/19/2016 5:23:07 PM

Chapter 71
Management of Bronchiectasis
Kana R Jat
INTRODUCTION CAUSES OF BRONCHIECTASIS

Bronchiectasis is a disease of conducting airways charac Bronchiectasis is secondary to many diseases or conditions
terized clinically by chronic moist or productive cough, that injure the conducting airways with recurrent respiratory
airway hyperreactivity, recurrent respiratory infections, infections (Table 1). Bronchiectasis may be grouped in two
and failure to thrive and radiologically by dilated airways. major categories: (1) associated with cystic fibrosis (CF); and
Chronic suppurative lung disease (CSLD), is a broad category (2) non-CF bronchiectasis. The both group may differ in age
with sign and symptoms similar to bronchiectasis with or of onset, airway colonization, disease severity and distribution,
without radiological evidence of dilated airways. There is lack extra pulmonary manifestations, treatment strategies, and
of consensus whether bronchiectasis and CSLD represent overall prognosis. Bronchiectasis is mainly secondary to CF
a spectrum of common disease or are different entities. in industrialized countries, whereas in developing countries
Empyema and lung abscess are considered different from both postinfectious bronchiectasis forms a major chunk. In a study
bronchiectasis and CSLD. from Korea, the underlying etiology was identified in 85.8%
(79/92) patients that included bronchiolitis obliterans (32.6%),
Clinical Pearl childhood respiratory infection (20.6%), interstitial lung
• Never ignore a child with chronic wet cough. disease (17.3%), immunodeficiency (8.6%), primary ciliary
dyskinesia (PCD) (4.3%), and CF (2%).
The prevalence of bronchiectasis had decreasing trend
in developed countries, but it is still an important chronic
PATHOPHYSIOLOGY OF BRONCHIECTASIS
respiratory disease in developing countries including India. In
early 90s, bronchiectasis was present in approximate 1% children Bronchiectasis is characterized by tortuous and dilated airways
at pediatric respiratory centers in developed countries. filled with infected secretions with airway obstruction. There
Table 1: Causes of bronchiectasis

Causes of bronchiectasis*
Postinfectious: after severe LRTI: tuberculosis, Airway obstruction (intraluminal or external compression): Yellow nail lymphedema
pertussis, measles, and severe viral pneumonia foreign body, granulation tissue, lymph node, tumor, syndrome
vascular ring
Primary ciliary dyskinesia Bronchiolitis obliterans (postviral, posttransplant) Marfan syndrome
Immune deficiencies: both primary and secondary Cystic fibrosis Usher syndrome
Congenital airway malformation: tracheomalacia, Recurrent aspiration: tracheoesophageal fistula, Alpha-1 trypsin
bronchomalacia, etc. gastroesophageal reflux deficiency
Allergic bronchopulmonary aspergillosis Neuromuscular weakness Eosinophilic lung disease
Interstitial lung disease Asthma Idiopathic
LRTI, lower respiratory tract infection.
Note: * Not in order of incidence or prevalence.
ch-71.indd 327 11/23/2016 10:30:11 AM

is neutrophilic inflammation, peribronchial fibrosis, and

accompanying pulmonary and bronchial vascular changes.
Pathologically, bronchiectasis may be classified as cylindrical (or
tubular), varicose (or fusiform), and cystic (or saccular). Cystic
bronchiectasis mostly reflects advanced irreversible disease.
CLINICAL FEATURES
Chronic wet sounding cough with or without sputum
expectoration is hallmark of bronchiectasis. Other clinical
features include failure to thrive, hemoptysis, exertional
dyspnea, wheezing, recurrent respiratory infections, clubbing
and/or chest hyperinflation. Auscultation of chest may reveal
coarse crackles, and/or rhonchi or it may be normal. Cyanosis
and pulmonary hypertension are late ominous signs of
bronchiectasis.
Clinical Pearl Fig. 1: Bronchiectasis in a child with allergic bronchopulmonary

aspergillosis (Arrow: dilated central bronchus)
• Every wheezing child does not have asthma and every
asthmatic child does not wheeze. Clinical examination is
a never ending weapon for a physician: Get alerted if you Clinical Pearl
find clubbing and coarse crackles in a child with respiratory
• High-resolution computed tomography chest (HRCT) is useful
symptoms.
to confirm and to define extent of bronchiectasis, but do not
delay treatment if facility for HRCT is not available. If treated at
Bronchiectasis may be generalized or localized to very early stage, much of the disease can be reversed.
one or more lobes. In localized form, left lower lobe is
most commonly affected followed by right upper lobe. Other HRCT chest findings in bronchiectasis may include
Airway hyperreactivity is not uncommon in children with mucus plugs, bronchial wall thickening, lack of normal
bronchiectasis ranging from 26–74%. Presence of cough airway tapering towards lung periphery, visualization of the
and wheezing may not always suggest asthma, rather it peripheral bronchi within 1 cm of the costal pleural surface,
may be due to airway obstruction and increased secretion air-fluid levels in dilated bronchi, a linear array or cluster of
in bronchiectasis. Gastroesophageal reflux disease (GERD) cysts, mosaic perfusion, string of pearls (ectatic bronchi with
may coexist with bronchiectasis and should be looked for beaded appearance), and air trapping.
and treated when clinically indicated. Complications of After diagnosing bronchiectasis, try to identify underlying
bronchiectasis may include pulmonary hypertension with/ etiology by performing sweat test, immunological workup,
without cor pulmonale, hypertrophic osteoarthropathy, sputum analysis, workup for tuberculosis and other
systemic amyloidosis, scoliosis, and social problems. infections, bronchoscopy, tests for primary ciliary dyskinesia,
gastroesophageal reflux (GER), or allergic bronchopulmonary
aspergillosis (ABPA), as suggested by associated clinical
DIAGNOSIS
features. There are many scoring systems to assess severity of
Once bronchiectasis is suspected clinically, child should be bronchiectasis based on chest X-ray and HRCT chest findings,
evaluated to confirm the diagnosis, to find extend and severity but later one are preferred (Bhalla HRCT score, Reiff scoring
of disease, and to identify underlying cause. Bronchiectasis system, etc.). Pulmonary function tests (PFTs) may also be
may be suspected on chest X-ray but high-resolution computed performed to assess the severity of bronchiectasis, but there
tomography (HRCT) scans of the chest is investigation of is lack of good correlation between PFTs and HRCT scores. A
choice to diagnose and to define extend of bronchiectasis. parent cough-specific quality of life questionnaire is available
Chest X-ray may reveal peribronchial thickening, bronchial to assess quality of life in children with bronchiectasis.
crowding, atelectasis, and persistent infiltrates in early stages; Isolation rate for micro-organism from sputum or broncho
and cystic spaces, air-fluid levels, dilated thick-walled bronchi, alveolar lavage (BAL) in children varies between 53–67%.
and mucus plugging in advanced stage. Common pathogens isolated in children with bronchiectasis
Diagnostic criteria for bronchiectasis are based on HRCT include Streptococcus pneumoniae, Staphylococcus aureus, and
chest findings. A dilated bronchus having size greater than Hemophilus influenzae non-type b, Pseudomonas aeruginosa,
nearby artery is considered diagnostic of bronchiectasis in and Moraxella catarrhalis. Exacerbation in bronchiectasis
HRCT chest (Fig. 1). This appears as signet rings or tramlines may be suggested by increased sputum production, purulent
depending on precise orientation of bronchi to the plane of sputum, increase in cough severity, and/or cough changing
328 section. from dry to weight.
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Chapter 71: Management of Bronchiectasis
TREATMENT bronchiectasis as it had worsening of symptoms in non-CF

bronchiectasis. Alternative to rhDNase is N-acetylcysteine,
Therapy for bronchiectasis may be needed for acute exacer but there is lack of evidence for its efficacy. Role of
bations and chronic therapy for persistent bronchiectasis. anticholinergics and bromhexine is not established either.
The chronic therapy is different for CF- and non-CF-related
bronchiectasis. Early diagnosis and aggressive treatment Chest Physiotherapy
of bronchiectasis and underlying etiology has paramount
importance in reducing morbidity and mortality associated
(Airway Clearance Methods)
with bronchiectasis. Airway clearance techniques (ACTs) with spontaneous
or directed cough help in improving mucus clearance. A
recent Cochrane review revealed that ACTs appear to be
Clinical Pearl safe and beneficial for both adults and children with stable
• If you diagnose bronchiectasis, do not look for higher center; it bronchiectasis. The role of these techniques in people with
may reasonably be managed at any center. an acute exacerbation of bronchiectasis is unknown. There
are many ACTs, but data is lacking to suggest superiority of
one over other and choices may be individualized. Regular
Management of bronchiectasis requires a team approach
physical activity is also encouraged for children with
comprising pediatrician, nurse, physiotherapist, social worker,
bronchiectasis.
nutritionist, etc. The general management for bronchiectasis
is discussed here. The therapeutic options for bronchiectasis
Anti-inflammatory Agents
include: (1) rational use of antibiotics (for maintenance and
exacerbation), (2) airway hydration and mucoactive drugs, There is lack of evidence for or against use of inhaled non-
(3) effective chest physiotherapy (airway clearance methods), steroidal anti-inflammatory agents in the management
(4) use for anti-inflammatory and antisecretagogues, (5) of bronchiectasis in adults or children; one small trial of
bronchodilators, (6) good nutritional support, (7) treatment inhaled indomethacin in adults reported a reduction in
of comorbid conditions and complications, (8) surgical sputum production and improved dyspnea. Use of high-dose
intervention if required, (9) education and social support, and ibuprofen for 4 years in children with CF showed a reduction
(10) prevention. in the rate of lung function decline and improved weight gain
but no change in the frequency of pulmonary exacerbations.
There are no randomized controlled trials regarding efficacy
Rational Use of Antibiotics
of oral nonsteroidal anti-inflammatory drugs (NSAIDs) in
Long-term antibiotics may be used as aerosol or orally patients with non-CF bronchiectasis. Inhaled corticosteroids
for bronchiectasis. Data regarding efficacy of antibiotics (ICS) failed to benefit in adults with stable bronchiectasis;
for chronic maintenance in children with non-CF- therefore routine use is not recommended. There is lack
bronchiectasis are limited. Till further evidence is available, of trials of ICS for children and for acute exacerbation of
chronic maintenance antibiotics should be used for a group bronchiectasis. Inhaled corticosteroids may be beneficial if
of selected children only, e.g., with frequent exacerbations, there is associated asthma. Long-term oral steroids in CF-
children having severe lung disease with documented bronchiectasis improved lung function, but with significant
pseudomonas endobronchial infection (inhaled tobramycin adverse effects; therefore not recommended to treat CF-
may be useful) and CF. Long term use of oral macrolide related bronchiectasis. There is lack of trials for use of oral
therapy is found to be beneficial for both CF and non-CF steroids in acute and stable non-CF bronchiectasis both
children with bronchiectasis; mainly because of its anti- in children and adults except for ABPA, where steroids are
inflammatory and antisecretagogue properties, rather than indicated whether bronchiectasis is present or absent. Thus,
due to antimicrobial properties. Acute exacerbations must be steroid therapy in children with bronchiectasis is related to
treated with antibiotics based on isolated pathogen and local etiology and it’s use should be individualized.
antibiotic sensitivity pattern.
Bronchodilators
Airway Hydration and Mucoactive Drugs There is insufficient evidence for or against use of short or
Mucus clearance is impaired more in children with CF long acting β-2 agonists, adrenergics, and leukotriene receptor
and PCD as compared to idiopathic bronchiectasis. Use anta-agonists for management of bronchiectasis and their
of inhaled hypertonic saline (6–7%) is associated with use should be individualized. Increased cough or wheezing in
decreased exacerbation and improved lung function in CF children with bronchiectasis should be treated as exacerbation
bronchiectasis, but data is limited for non-CF bronchiectasis. at first instance.
Risk of bronchospasm following hydrating agents can be Data regarding use of conventional sequence of broncho
minimized with pre-treatment with inhaled salbutamol. To dilator, hypertonic saline, DNase, ACT, and aerosol antibiotics,
further enhance mucus clearance, mucolytic agents may be frequently used in CF patients, are lacking for non-CF-related
used. Recombinant human deoxyribonuclease (rhDNase) is bronchiectasis in children and treatment in these patient must
efficacious in CF, but is contraindicated in non-CF-related be individualized. 329
ch-71.indd 329 11/23/2016 10:30:11 AM

SURGICAL TREATMENT An approach to a child with suspected bronchiectasis is

shown in algorithm 1.
There are no randomized trials comparing medical versus Prognosis of bronchiectasis depends on underlying
surgical treatment. Usual indication of surgery is failure etiology; extent and severity of disease at diagnosis, frequency
of medical therapy in localized disease. Other indications of exacerbations; base-line lung function; rate of decline in
for surgery may include severe persistent hemoptysis FEV1, bacterial density and neutrophils in sputum; and nature
uncontrolled by bronchial artery embolization, severe chronic of treatment. Delayed diagnosis, presence of asthma, bilateral
symptoms, and growth failure in localized disease. Surgery lung involvement, and saccular bronchiectasis are some of
should not be considered for generalized disease, children poor prognostic factors. Bronchiectasis may be reversible in
below 6 years of age and in bronchiectasis with mild to certain situations, e.g., after removal of chronic foreign body.
moderate symptoms. At present, perioperative morbidity and Although lack of mortality data for pediatric bronchiectasis;
mortality is minimum after lobectomy or pneumonectomy. nearly one-fourth children had respiratory failure in an about
Outcome after lung transplantation in children with non-CF 7 years follow-up. With availability of better and inhaled
bronchiectasis is not available. antibiotics, ACTs, and good nutrition support, the prognosis of
bronchiectasis has improved with time.
PREVENTION
Children with bronchiectasis should receive routine vacci
CONCLUSION
nation as per national schedule. Limited evidence suggests that Bronchiectasis is chronic disease of conducting airways
routine 23-valent pneumococcal vaccination in children with with a variety of underlying conditions. Data is lacking for
bronchiectasis may be useful, though robust trials are needed. effective treatment in children with non-CF bronchiectasis.
Role of new 13-valent pneumococcal vaccine requires further Early diagnosis and aggressive multidisciplinary therapy with
trials for young children. Although, there is neither evidence good nutritional and social support has improved prognosis
for, nor against, routine influenza vaccination for children of bronchiectasis in children. More robust clinical trials for
and adults with bronchiectasis, it may be used if affordability various treatment options are required especially for children
is not the problem. Children with bronchiectasis should have with non-CF bronchiectasis. In developing countries, control
no/minimal environmental tobacco-smoke exposure as it of infectious diseases is needed to curb the load of post-
increases susceptibility to respiratory infections. infectious bronchiectasis.
Algorithm 1
Approach to a child with suspected bronchiectasis
HRCT, high-resolution computed tomography; CF, cystic fibrosis.
330
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Chapter 71: Management of Bronchiectasis
3. Evans DJ, Bara Al, Greenstone M. Prolonged antibiotics for purulent

Key points bronchiectasis in children and adults. Cochrane Database of Syst Rev.
2007;(2):CD001392.
High index of suspicious is required to diagnose bronchiectasis
4. Flume PA, O’Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ Jr, Willey-Courand DB,
at early stage in children. et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of
))
Multidisciplinary comprehensive management is key for both lung health. Am J Respir Crit Care Med. 2007;176(10):957-69.
CF- and non-CF-related bronchiectasis 5. Kim HY, Kwon JW, Seo J, Song YH, Kim BJ, Yu J, et al. Bronchiectasis in
))
Pathogen-directed inhaled antibiotics, inhaled hypertonic children: 10-year experience at a single institution. Allergy Asthma Immunol Res.
saline, and oral macrolides are important component of 2011;3(1):39-45.
therapeutic regimen for children with CF-related bronchiectasis 6. Lee AL, Burge A, Holland AE. Airway clearance techniques for bronchiectasis.
Cochrane Database of Syst Rev. 2013;5:CD008351.
))
Data is lacking for use of inhaled antibiotics, airway hydrating
7. Newcombe PA, Sheffield JK, Chang AB. Parent cough-specific quality of
treatments, mucolytic agents, inhaled anti-inflammatory
life: development and validation of a short form. J Allergy Clin Immunol.
agents, and bronchodilators in children with non-CF-related
2013;131(4):1069-74.
bronchiectasis.
8. Redding GJ. Bronchiectasis in children. Pediatr Clin North Am. 2009;56(1):157-71.
9. Reiff DB, Wells AU, Carr DH, Cole PJ, Hansell DM. CT findings in bronchiectasis:
limited value in distinguishing between idiopathic and specific types. AJR Am J
SUGGESTED READINGS Roentgenol. 1995;165(2):261-7.
1. Chang CC, Morris PS, Chang AB. Influenza vaccine for children and adults with 10. Southern KW, Barker PM, Solis A. Macrolide antibiotics for cystic fibrosis.
bronchiectasis. Cochrane Database Syst Rev. 2007;(3):CD006218. Cochrane Database Syst Rev. 2004;(2):CD002203.
2. Chang CC, Singleton RJ, Morris PS, Chang AB. Pneumococcal vaccines 11. Wilson JF, Decker AM. The surgical management of childhood bronchiectasis. A
for children and adults with bronchiectasis. Cochrane Database Syst Rev. review of 96 consecutive pulmonary resections in children with nontuberculous
2007;(2):CD006316. bronchiectasis. Ann Surg. 1982;195(3):354-63.
331
ch-71.indd 331 11/23/2016 10:30:11 AM

Section 9: Cardiology
Chapter 72
Management of Congestive Heart Failure in
Infants and Children: An Algorithmic Approach
M Zulfikar Ahamed
INTRODUCTION Type I Congestive Heart Failure

Heart failure in infancy and childhood is “a clinical syndrome • Left to right shunt: VSD, PDA, aortopulmonary window
which reflects the inability of the heart to pump blood to meet (APW), atrioventricular septal defect (AVSD)
the metabolic requirements of the body, including those needs • Admixture CHD: total anomalous pulmonary venous
incurred by growth; or able to do so at a higher filling pressure”. connection (TAPVC), single ventricle, double outlet right
It is a complex syndrome that can result from any structural or ventricle (DORV), truncus arteriosus
functional disorder that can impair the ability of ventricle(s) to • Valvular regurgitation: MR, aortic regurgitation
fill with or eject blood. • Left ventricular outflow tract (LVOT) obstruction: AS,
While adult congestive heart failure (CHF) is often due coarctation of aorta
to coronary artery disease (CAD), hypertension, valvular • Rheumatic fever, carditis.
heart diseases, and cardiomyopathies, infants and children
have CHF primarily due to congenital heart disease (CHD), Type II Congestive Heart Failure
valvular heart diseases, and cardiomyopathies. Overall, • Dilated cardiomyopathy
75% of CHF in pediatric population is due to CHD and the • Myocarditis
rest due to acquired heart diseases. About 80% of CHF • Postoperative CHD
occurs in infants (<1 year). While in market economies, • Tachycardiomyopathy
cardiomyopathies, CHD, and postoperative CHD cause CHF • Chronic RHD with left ventricular dysfunction.
in that order, in India, the leading causes of pediatric CHF are Congestive heart failure can be caused mostly by structural
CHD, rheumatic fever/rheumatic heart disease (RF/RHD), lesions. Occasionally, functional heart diseases can also cause
and cardiomyopathies. CHF. They could be either remediable or nonremediable
Pathophysiologically, CHF can be divided into three types, (Algorithm 1).
which are as follows:
• Type I: CHF due to abnormal loading conditions. It can be
due to preload abnormality or afterload problem. This is Algorithm 1
the most common variety of CHF in infants Congestive heart failure broad classification
{{ Preload: ventricular septal defects (VSD), patent ductus
arteriosus (PDA), mitral regurgitation (MR)

{{ Afterload: aortic stenosis (AS), coarctation of aorta
• Type II: CHF due to abnormality of contractility (inotropy)—

dilated cardiomyopathy
• Type III: CHF due to abnormality of diastolic function
(lusitropy)—hypertrophic cardiomyopathy
In addition, heart rate abnormalities (very slow rate or
very fast rate), such as complete heart block (CHB), and
supraventricular tachycardia (SVT), can also cause CHF.
ch-72.indd 332 11/19/2016 5:55:20 PM

Chapter 72: Management of Congestive Heart Failure in Infants and Children: An Algorithmic Approach
Most congenital structural heart diseases are remediable Manifestations of CHF are also age and etiology dependent.
either surgically or by intervention. Many acquired heart It may present as:
diseases are also amenable to correction, e.g., mitral stenosis, • Shock: in new born, conditions presenting are duct
MR; some are not—dilated cardiomyopathy and hypertrophic dependent left sided critical lesions, sepsis, hypoxemic
cardiomyopathy. Tachycardiomyopathy is a functional heart ischemic problems, and arrhythmia
disease which is remediable, by conversion to sinus rhythm. • Acute/subacute CHF: occurs in post tricuspid left to
right shunts, obstructive lesions, admixture lesions, and
cardiomyopathies
CAUSES
• Chronic CHF: occurs due to cardiomyopathies, valvular
Causes of CHF in infancy and childhood have a chronological heart disease, and moderate left to right shunts.
order. This phenomenon is quite useful, looking for and
identifying a cause for CHF in childhood.
RECOGNITION OF
Fetal Causes CONGESTIVE HEART FAILURE IN INFANTS
• Congenital heart disease: Ebstein anomaly, systemic Clinical recognition of CHF in infancy (Box 1) is different
arteriovenous fistula from that of an older child. The classical quartet of findings
• Others: intrauterine myocarditis are tachycardia, tachypnea, tender hepatomegaly, and
• Arrhythmia: CHB, SVT. cardiomegaly. Others are S3 gallop, prolonged capillary refill
time, and bibasal crepitation. Elevated jugular venous pressure
Day One Causes (0–24 h) (JVP), pedal edema, and hypotension are less common
manifestations.
• Ebstein anomaly, systemic arteriovenous fistula, absent Functional assessment in an infant or child with CHF will
pulmonary valve syndrome, severe MR, myocarditis be based on New York Heart Association (older child) or Ross
• Complete heart block, SVT. (infants) classification.
Ross (2002) classification:
First Week Causes (1–7 Days) 1. No symptom, no feeding difficulty, normal growth
• Critical left heart obstruction: AS, hypoplastic left heart 2. Tachypnea on feed, sweating on feed, normal growth
syndrome, coarctation of aorta, interrupted aortic arch 3. Significant tachypnea/sweating on feed, retractions at rest,
• Obstructed TAPVC growth failure
• Extension of day one causes. 4. All the above on rest also.
1–4 Weeks Causes EVALUATION

• Large left to right shunts: VSD, PDA, AVSD Evaluation of CHF includes recognition and characterization
• Admixture lesions: TAPVC, DORV, single ventricle, truncus of CHF and investigations (Algorithm 2).
arteriosus
• Less critical CHD: coarctation, AS
Investigations
• Rare defects: Pompe, anomalous origin of the left coronary
artery arising from the pulmonary artery (ALCAPA), The investigations can be either definitive or nondefinitive.
endocardial fibroelastosis (EFE). One has to decide whether CHF is acute or chronic. Acute
CHF could be either primary or decompensated. Both chronic
1 Months–1 Year Causes and acute CHF can be either responsive or nonresponsive
(refractory) (Algorithm 3).
• Left to right shunts: PDA, APW, VSD, AVSD Investigations can be either definitive or nondefinitive
• Admixture lesions (Algorithm 4).
• Acquired: SVT, dilated cardiomyopathy, and myocarditis.
1–6 Years Causes Box 1: Recognition of congestive heart failure in infants

• Viral myocarditis, dilated cardiomyopathy Key items Less common items
• Left to right shunts with complications • Tachypnea • Edema
• Infective endocarditis. • Tachycardia • Elevated jugular venous
• Tender hepatomegaly pressure
6–12 Years Causes • Cardiomegaly • Hypotension
• Rheumatic fever/RHD Important items
• Infective endocarditis • S3 gallop
• Congenital heart disease: postoperative • Bibasal crepitations
• Viral myocarditis/dilated cardiomyopathy. • Prolonged capillary refill time 333
ch-72.indd 333 11/19/2016 5:55:20 PM

Algorithm 2 (e.g., figure of “8” in TAPVC). It can also sort out primary or
Evaluation and treatment of congestive heart failure additional lung issues.
Practically, all causes of CHF in infancy will cause cardio
megaly (cardiothoracic ratio >50% in a child, >55% in infants,
>60% in neonates). The exceptions could be obstructed TAPVC
or cor triatriatum.
Electrocardiography
A 14-lead electrocardiography (ECG) with or without a rhythm
strip (lead II) is quite useful. It is a must in all forms of CHF.
Electrocardiography can be a pointer to a specific CHD (e.g.,
biventricular hypertrophy in large VSD) or characteristic of a
CHD (e.g., left deviation of the QRS axis and right ventricular
hypertrophy in AVSD). It can diagnose tachyarrhythmia as
cause of CHF (e.g., SVT leading to “dilated cardiomyopathy”
like picture) and can pick up drug toxicity (e.g., digitoxicity).
Echocardiography
Algorithm 3 It is the most useful tool in evaluating CHF in infants and
Congestive heart failure types children. It can virtually diagnose all structural heart lesions,
both congenital and acquired. It can pick up diastolic
abnormalities and hemodynamic problems such as PAH
(Table 1).
Others
Brain natriuretic peptide is useful in assessing CHF in infants,
especially recent onset (acute). It will help in differentiating
between cardiac and respiratory causes of distress. The normal
value is less than 30 pg/mL. Abnormal value (>100 pg/mL)
will indicate cardiac cause of respiratory distress with high
sensitivity and specificity.
Troponins, either troponin T or troponin I can be useful in
Algorithm 4 conditions like myocarditis.
Evaluation of congestive heart failure
Radionuclide studies, cardiac magnetic resonance
imaging, and computed tomography are occasionally useful in
evaluating cause of CHF, especially in adult CHD. Postoperative
catheterization and endomyocardial biopsy could also be
utilized in evaluating cause of CHF.
TREATMENT
Treatment of CHF involves three facets, which are as follows:
1. Treating the cause
2. Treating the precipitating cause
3. Treating the congestive state.
Table 1: Echocardiography
CMR, cardiac magnetic resonance imaging; CT, computed tomography; TC, Looks for Conditions
total count; DC, differential count; ESR, erythrocyte sedimentation rate; CRP, Structural congenital Coarctation of aorta, ventricular septal
C-reactive protein; ABG, arterial blood gas; BNP, brain natriuretic peptide.
heart disease defect
Ventricular day function Dilated cardiomyopathy, myocarditis
Chest X-ray Pulmonary arterial Persistent pulmonary hypertension of
hypertension the newborn, idiopathic pulmonary
Chest X-ray is still useful in preliminary evaluation of CHF
arterial hypertension
at any age. It looks at heart size, lung blood flow, presence of
334 pulmonary arterial hypertension (PAH) and the ‘typical’ look Mechanical heart disease Acute aortic and mitral regurgitation
ch-72.indd 334 11/19/2016 5:55:21 PM

Mostly, causes of CHF in infancy are mechanical problems Algorithm 6

which need mechanical solutions—either surgical or Treating left to right shunts
interventional.
Monitoring is an important factor in treating CHF. We can
monitor:
• Heart rate, respiratory rate, blood pressure, capillary refill
time
• Cardiomegaly, S3, murmur, lungs
• Urine output, pulse oxymetry/arterial blood gas, renal
function.
Drug therapy in CHF in infants and children is a
temporizing measure which could be a short-term or long-
term bridge. It is also an initial lifesaver. In addition, some
drugs may eventually “correct” the abnormality, e.g., prosta
ACEI, angiotensin converting enzyme inhibitor; PO, per oral, IV, intravenous.
glandin E1 (PGE1) or adenosine (Algorithm 5).
Following examples of CHF treatment in specific satuation
algorithms 6 and 7, table 2. Algorithm 7
Treating dilated cardiomyopathy
Management of Chronic/Subacute
Congestive Heart Failure
It is the most common situation. It can be treated in the wards
or as outpatient department. Initial general measures include
rest, fowler position, oxygen when indicated, correction of
electrolytes and hemoglobin abnormalities, and volume
depletion. Drug therapy primarily uses four drugs: diuretics,
Algorithm 5
Congestive heart failure treatment protocol
PO, per oral; ACEI, angiotensin converting enzyme inhibitors.
Table 2: Dilated cardiomyopathy treatment protocol

Drug Functional class
I II III IV
Diuretic 0 + + +
Digoxin + + + +
ACEI + + + +
Carvedilol + + + +
Spironolactone 0 + + +
CHF, congestive heart failure; MFU, medical follow-up; ACEI, angiotensin
converting enzyme inhibitors, PO, per oral. ACEI, angiotensin converting enzyme inhibitors. 335
ch-72.indd 335 11/19/2016 5:55:21 PM

digoxin, angiotensin converting enzyme (ACE) inhibitors and Algorithm 10

β-blockers. Pharmacotherapy of acute CHF
Management of Acute Congestive Heart Failure

Acute CHF can be either primary or decompensated
(Algorithm 8).
Management of acute CHF will include admission into
pediatric intensive care unit. General measures include
temperature control, oxygen supply, alkali therapy, sepsis
management, and metabolic correction.
Specific measures will be by using intravenous (IV)
inotrope, IV diuretic, and IV vasodilators. Targeted therapy will
be using phosphodiesterase inhibitors, sildenafil, adenosine,
or ibuprofen, according to indications. Additional measures
will be IV access, multiorgan protection, and mechanical
ventilation (Algorithms 9 and 10).
CHF, congestive heart failure; IV, intravenous.; *Hypotension.

Newborn: <60 mmHg; infant: <70 mmHg; child: <80 mmHg;
Algorithm 8 adolescent: <90 mmHg.
Acute congestive heart failure types
Management of Refractory
Congestive Heart Failure
Refractory CHF is the one not responding to (favorably)
conventional medical management (diuretics, digoxin, ACE
inhibitors) (Algorithms 11 and 12).
Algorithm 11
APHF, acute primary heart failure; ADHF, acute decompensated heart failure; Treating refractory congestive heart failure
DCM, dilated cardiomyopathy; CHF, congestive heart failure; CoA, coarctation
of aorta; AS, aortic stenosis; RHD, rheumatic heart disease; MR, mitral
regurgitation; AR, aortic regurgitation; SVT, supraventricular tachycardia.
Algorithm 9
Principles of management
IV, intravenous; AR, aortic regurgitation; NSAID, nonsteroidal anti-inflammatory

CHF, congestive heart failure; DHF, decompensated heart failure; PHF, primary drug; ECMO, extracorporeal membrane oxygenation; LVAD, left ventricular
336 heart failure. assist device.
ch-72.indd 336 11/19/2016 5:55:21 PM

Algorithm 12 Continued
Refractory congestive heart failure of causes Drugs Doses
Digoxin • PO:
(maintenance) {{ Preterm newborn: 5 mg/kg OD
{{ Term newborn: 7.5 mg/kg OD
{{ Infant: 10 mg/kg BD
{{ 2–10 years: 7.5 mg/kg OD
{{ >10 years: ½–1 tab OD
Captopril • PO: 1–4 mg/kg/day TID

Enalapril • PO: 0.1–0.3 mg/kg/day as OD/BD
Carvedilol • PO: 0.1–0.5 mg/kg/day BD
Dobutamine • IV: 2–20 mg/kg/h for 72–96 h
Milrinone • IV: 50 mg/kg/bolus (10–15)
• Infusion: 0.375–0.75 mg/kg/min
Nesiritide • IV: 1–2 mg/kg/bolus
Specific Situations • Infusion: 0.01–0.03 mg/kg/min
• Newborn with CHF and persistent pulmonary hyper Levosimendan • IV: 6–12 mg/kg/bolus
tension of the newborn: IV milrinone, IV sildenafil • Infusion: 0.05–0.60 mg/kg/min
• Newborn with CHF and CHB: IV dobutamine
Dopamine • IV: 2–20 mg/kg/h for 72–96 h
• Newborn with CHF and sepsis: IV dobutamine
IV, intravenous; PO, per oral; OD, once a day; BD, twice a day; TID, thrice a day;
• Newborn with CHF and preterm PDA: indomethacin/
tab, tablet.
ibuprofen
• Postoperative CHD-CHF, PAH: IV milrinone, sildenafil,
nitric oxide SUGGESTED READINGS
• Hypertensive CHF: IV sodium nitroprusside (NTP), IV 1. Beggs A, Thompson R, Nash A, Tompson G, Petersen RE, Shaddy LY, et al. Chronic
diuretic heart failure in children. In: Allen HD, Driscoll DJ, Shaddy RE, Felters TF (Eds).
• Infective endocarditis, acute MR: IV NTP, IV antibiotics Moss and Adams’ Heart Disease in Infants, Children and Adolescents, 8th edition.
• Dilated cardiomyopathy on β-blockers, CHF: IV milrinone Philadelphia: Lippincott Williams Wilkins; 2013.
• Viral myocarditis CHF: IV immunoglobulin 2. Beggs S, Thompson A, Nash R, Tompson A, Peterson G. Cardiac failure in children.
• Postoperative ventricular dysfunction: ACE inhibitor. 17th Expert Committee on the Selection and Use of Essential Medicines. Geneva:
World Health Organization; 2009.
3. Burch M. Heart failure in the young. Heart. 2002;88(2):198-202.
DRUGS AND DOSES 4. Chaturvedi V, Saxena A. Heart failure in children: clinical aspects and management.
Indian J Pediatr. 2009;76(2):195-205.
Drugs employed in the management of CHF and the respective 5. Kantor PF, Lougheed J, Dancea A, McGillion M, Barbosa N, Chan C, et al ;
doses are provided in table 3. Children’s Heart Failure Study Group. Presentation, diagnosis and medical
management of heart failure in children: Canadian Cardiovascular Society
Guidelines. Can J Cardiol. 2013;29(12):1535-52.
6. Kay JD, Colan SD, Graham TP Jr. Congestive heart failure in pediatric patients.
Table 3: Drugs employed in the management of CHF and the Am Heart J. 2001;142(5):923-8.
respective doses 7. Opie LH, Gerst BJ. Drugs for the Heart, 7th edition. Philadelphia: Elsevier-
Saunders; 2009.
Drugs Doses 8. Ross RD. Medical management of chronic heart failure in children. Am J
Furosemide • PO: 1 mg/kg OD/BD/TID Cardiovasc Drugs. 2001;1(1):37-44.
9. Shaddy RE, Penny DJ. Chronic cardiac failure: physiology and treatment. In:
• IV: 1 mg/kg OD/BD/TID
Anderson RH, Baker EJ, Penny DJ, Redington AN, Rigby ML, Wernovsky G (Eds).
• Infusion: 0.1–1.0 mg/kg/h Paediatric cardiology, 3rd edition. Philadelphia: Churchill Livingston/Elsevier;
Torsemide • PO: 0.25–0.5 mg/kg 2010.
10. Working Group on Management of Congenital Heart Diseases in India, Saxena A,
• IV: 2.5–5 mg OD
Juneja R, Ramakrishnan S. Drug therapy of cardiac diseases in children. Indian
Bumetanide • PO: 0.45 – 0.1 mg/kg BD Pediatr. 2009;46(4):310-38.
Continued
337
ch-72.indd 337 11/19/2016 5:55:21 PM

Chapter 73
Approach to a Child
with Chest Pain
Vikas Kohli, Neeraj Agarwal
INTRODUCTION Breast tenderness can be physiologic during thelarche,

or caused by infectious or inflammatory conditions such as
Chest pain is not an uncommon complaint with which mastitis.
children present to the pediatric outpatient. It is not easy to Cutaneous chest wall pain may occur during an episode
differentiate the cardiac form non cardiac chest pain. Cardiac of herpes zoster, in a unilateral dermatome distribution and
origin of chest pain is not the most common cause, but, it is
may precede the development of characteristic skin findings
definitely one of the most serious causes, and potentially
by several days.
can result in mortality also rarely. Definitely chest pain with
Costochondritis is pain localized to costal cartilage and can
exertion indicates cardiac origin and postural chest pain may
be elicited by tenderness at costochondral junction. There is
indicate pericardial effusion.
no joint inflammation, involves two to four joints, is unilateral,
This chapter helps localise the cause of chest pain and
and exacerbated by deep breathing. Tietze syndrome is a
focuses of cardiac origin of chest pain.
specific form of costochondritis characterized by localized,
painful, nonsuppurative costochondral swelling involving
CAUSES OF CHEST PAIN single costochondral junction.
Chest pain in a child is often benign, but cardiac and serious Slipping rib syndrome is an unusual cause of lower chest
life-threatening causes do exist. The differential diagnosis pain that results when the medial fibrous attachments of the
is exhaustive and in most of the cases, etiology can be found 8th, 9th, or 10th ribs are inadequate or ruptured. Pain can be
out by thorough history and examination. Major causes of reproduced by hooking the fingers under the lowest costal
chest pain can be grouped as: musculoskeletal, pulmonary, cartilages and drawing them anteriorly and superiorly.
psychological, gastrointestinal, cardiac, and idiopathic (Box 1). Hypersensitive xiphoid syndrome is uncommon in
In general, the most frequent cause reported is children and can be diagnosed easily because digital pressure
musculoskeletal pain. Approach to pain lies in history and on the xiphoid process reproduces the pain.
examination leading to source of pain. Specific features which
pinpoint to an organ system should be remembered. Pulmonary
Chest Wall Most common pulmonary causes are reactive airway diseases;
auscultation, chest X-ray, or a pulmonary function test (PFT)
Chest wall trauma or a new strenuous physical activity are a can get the diagnosis. Pleurodynia (caused by coxsackie virus)
frequent cause for chest pain. New intense physical activity is characterized by fever, pleuritic chest pain, and pleural rub.
is an important source and such type of pain peaks in 48 Pleuritis can be seen in children with infections, collagen
hours of activity. This pain is reproducible by palpation or by vascular disease, and malignancy.
repeating the particular action. Chest wall deformities, like
pectus excavatum/carinatum, can also be associated with
musculoskeletal chest pain and thorough general examination Clinical Pearl
should pick up these findings.
• Chest pain only during exertion is a significant indicator of
Precordial catch syndrome is a clinical diagnosis described
heart disease, but exercise induced asthma will also present
as a sharp pain of sudden onset localized to the anterior chest
only during exertion. However, asthma mostly will be
wall that occurs mostly at rest. It tends to last from a few seconds associated with coughing followed by chest pain.
to 3 minutes and may be exacerbated by taking a deep breath.
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Chapter 73: Approach to a Child with Chest Pain
Box 1: Causes of chest pain in pediatrics Clinical Pearl

Chest wall and musculoskeletal
• Chest wall strain/trauma (exercise, overuse injury, forceful • Normal auscultation of lung fields and heart sounds
coughing, myositis, rib fracture) significantly rules out a life-threatening cause of chest pain.
• Skeletal anomaly (chest wall or thoracic spine, cervical ribs,
slipping rib, osteomyelitis, thoracic outlet obstruction) Pulmonary embolism is rare in healthy children, but may
• Costochondritis/Tietze syndrome be seen in the presence of risk factors, such as coagulopathy,
• Slipping rib syndrome a central venous catheter, malignancy, nephrotic syndrome,
• Precordial catch syndrome major surgery, trauma, or sepsis. Ventilation perfusion scan is
• Breast tenderness usually diagnostic. It should be suspected in cases who present
• Cutaneous (e.g., herpes zoster) with dyspnea, cyanosis, or hemoptysis.
Cardiovascular
• Arrhythmias Gastrointestinal
• Coronary artery disease (anomalous coronary arteries), acute Chest pain due to gastric causes is common in childhood
Kawasaki disease (coronary arteritis), premature atherosclerosis and a detailed history for dietary pattern, abdominal signs/
(e.g., dyslipidemia), congenital coronary artery aneurysm, symptoms like burning epigastric pain, constipation, high
coronary artery vasospasm (toxicologic ingestion as cocaine/ intake of fast food, irregular dietary behavior, relationship
marijuana) of pain with meals, and epigastric tenderness should point
• Structural [hypertrophic cardiomyopathy, valvular stenosis towards gastric etiology. Gastroesophageal reflux disease is the
(pulmonary, aortic), mitral valve prolapse, ruptured sinus of
most frequent gastric cause for chest pain in children.
Valsalva, coarctation of aorta], aortic aneurysm or dissection
(Marfan, Turner, and Noonan syndromes), congenital absence of
Eosinophilic esophagitis may cause chest pain because of
pericardium esophageal inflammation, dysmotility, and reflux.
• Myocarditis, pericarditis, endocarditis Coins and other objects lodged in the esophagus typically
• Pulmonary hypertension present with chest pain that is often accompanied by drooling
and dysphagia.
Respiratory
Pill esophagitis is chemical irritation of the esophageal
• Reactive airway disease, pneumonia, pneumothorax/
mucosa from certain medications, particularly iron pre
pneumomediastinum
parations, tetracyclines, and chronic usage of nonsteroidal
• Pulmonary embolism
anti-inflammatory agents. The pill esophagitis is common in
• Pleuritis/pleural effusion (e.g., systemic lupus erythematosus),
young adolescent patients who typically ingest a tetracycline
pleurodynia (coxsackievirus)
capsule with too little water and present with chest pain,
• Chronic cough, foreign body aspiration
dysphagia, and occasionally hemoptysis.
Abdominal and gastrointestinal
• Esophagitis (gastroesophageal reflux disease, eosinophilic Cardiac
esophagitis, bulimia, pill esophagitis)
• Gastritis, pancreatitis Cardiovascular disease is identified in only 2–5% of pediatric
• Esophageal spasm/dysmotility patients with chest pain. The presence of dyspnea on exertion,
• Foreign body
palpitations, or abnormal cardiac auscultation has been found
to be statistically significantly related to a cardiac etiology.
• Hiatus hernia
Acute myocardial infarction has been described in
• Referred pain from abdominal trauma (Kehr’s sign)
association with coronary artery anomalies, congenital heart
Neurologic disease, Kawasaki disease, familial hypercholesterolemia,
• Migraine, spinal nerve root compression sickle cell disease, cardiac myxoma, hypercoagulable states,
Psychiatric substance abuse, and certain metabolic conditions such as
• Anxiety, phobia, somatoform disorder (e.g., conversion), homocystinuria and mucopolysaccharidosis. It is diagnosed
depression, emotional stress by classical symptoms (persistent crushing chest pain may/
Hematologic and oncologic may not radiate to neck/arm, sweating, and dyspnea), serial
• Sickle cell disease (crisis) and tumor (chest wall, thoracic, or electrocardiography (ECG), and elevated cardiac enzymes
mediastinal) (troponin I/creatine phosphokinase-MB).
Congenital coronary artery abnormalities mainly
Pneumothorax or pneumomediastinum may occur after an involve anomalous origin of the left coronary artery from the
episode of bronchiolitis, choking/aspiration, or after inhalation pulmonary artery. It is often identified when the pulmonary
of cocaine/marijuana. Pneumothorax should be suspected in artery pressure declines, usually around 2–3 months of age.
a child with unexplained dyspnea, tachypnea, or decreased Patients may present with crying, poor feeding, and signs of
breath sounds. Pneumomediastinum should be suspected congestive heart failure. Anomalous origin of the left coronary
if subcutaneous emphysema or Hamman sign (precordial artery from the pulmonary artery may also present in later
crackles that correlate with the heartbeat) are present. childhood with angina pain. The typical ECG pattern is that 339
ch-73.indd 339 11/19/2016 5:58:05 PM

of an anterolateral infarction with large and wide Q waves, ST mitral valve prolapse could cause pain because of papillary
changes, and T wave inversion in leads I, aVL, V5, and V6. Other muscle ischemia. Children with severe pulmonary stenosis
coronary artery abnormalities, including anomalous origin of or pulmonary hypertension are also at risk for myocardial
the left main coronary artery or right coronary artery from the ischemia. Pain in such cases often occurs with exercise. Most
contralateral sinus of Valsalva and hypoplastic coronary arteries common associations are dyspnea on exertion and syncope.
may also present in childhood. Coronary artery abnormalities Aortic aneurysm and dissection have been described both
can be picked up or suspected by echocardiography and in healthy pediatric patients and in those with known risk
later confirmed by angiography. Kawasaki disease has been factors such as bicuspid aortic valve, coarctation of the aorta,
associated with myocardial infarction both in the acute and and valvular aortic stenosis. Other causes include Marfan
subacute phases and as a long-term consequence. Infarction syndrome, Ehler-Danlos syndrome, Turner syndrome, trauma,
can occur during the acute phase caused by coronary arteritis/ cocaine use, and weight lifting. Pectus excavatum may be
aneurysmal rupture or during resolution caused by obstruction associated with aortic root dilation, even when other stigmata
or stenosis. of Marfan syndrome are absent. The pain of aortic dissection is
Arrhythmias are one of the more common causes of often described as severe and tearing. It tends to be located in
cardiac-related chest pain in children. Tachyarrhythmias may the anterior or posterior chest, neck, jaw, or shoulder. Patient
cause chest pain because of a reduction in myocardial blood usually presents with hypotension. The chest radiograph
flow. Hyperthyroidism should be ruled out in all patients with is likely to show mediastinal widening, pleural effusion,
tachyarrhythmia. abnormal aortic contour, or cardiomegaly. Diagnosis can be
Structural heart disease in form of obstructive lesions confirmed by echocardiography.
mostly presents with a pathological heart murmur. Left
ventricular outflow obstruction caused by aortic stenosis or Psychiatric
hypertrophic cardiomyopathy causes pain that is typically Chest pain has been attributed to a psychiatric cause in
exertional and is caused by subendocardial ischemia. In approximately 5–9% of cases and incidence may be rising in
hypertrophic cardiomyopathy/obstruction, the physical recent years. A history of a preceding stressful event, such as
examination is characterized by a harsh systolic ejection death or hospitalization in the family, family separation, or
murmur. Myocardial ischemia has also been reported in school changes, has been reported. Other reported psychiatric
children with sickle cell disease. In a study of pediatric sickle causes include anxiety disorders, depression and social phobia,
cell patients with a history of chest pain, heart failure, abnormal and sleep disturbances. Features of depression may be visible
ECG, left ventricular dilation, or hypokinetic left ventricle, 64% and hyperventilation may be a presenting sign in such cases.
had perfusion defects on thallium-201 single-photon emission
computed tomography (CT). Three children who were started
on hydroxyurea therapy underwent repeat single-photon Clinical Pearl
emission CT, and all showed improvement. No occlusion of
• Young adolescent or children should be evaluated privately for
coronary arteries was found, suggesting that pathology of the
psychosomatic disorders and spending time alone with kids in
microcirculation is responsible for the defects. a friendly manner will mostly yield the results.
Myocarditis is a rare, but serious cause of chest pain in
children. Children present with symptoms of chest pain,
palpitations, dyspnea, sweating, giddiness, syncope, and signs APPROACH
of heart failure (congestive cardiac failure). Electrocardiography
and chest radiography is mostly suggestive of diagnosis. The primary goals in evaluation of a child with chest pain are to
Laboratory abnormalities include elevated troponin, elevated rule out cardiac and other serious life-threatening causes and
creatine kinase, and elevated erythrocyte sedimentation to classify the origin of the pain. In cases in which the cause
rate. Diagnosis can be confirmed with echocardiography. remains unclear or if concerning features are identified, further
Pericarditis is diagnosed by pericardial rub or distant heart evaluation and sometimes, referral are warranted (Box 2).
sounds and endocarditis is suspected with prolonged fever.
Partial or complete congenital absence of the pericardium
is rare, but may produce murmur that is heard best at the Box 2: Danger signs which need further diagnostic workup
apex and lower left sternal border. An increase in the intensity • Pain associated with exercise, palpitations, or syncope
of the murmur is seen when the patient assumes an upright • Dyspnea
posture from a squatting, sitting, or supine position, and with • Pain preventing daily activities/play of child
the Valsalva maneuver. A decrease in intensity is heard after • Pain awakens the child from sleep
going from a standing to a sitting or squatting position, or with • Substance abuse
passive elevation of the legs. The decrease in intensity occurs • Presence of prothrombotic conditions
when increased ventricular filling increases the size of the
• Features of Kawasaki disease
outflow tract and decreases the gradient across the obstruction.
• Family history of sudden death or early cardiac death
Mitral valve prolapse has been reported in pediatric
340 patients with chest pain. It has been hypothesized that severe • Abnormal vital signs or physical findings
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Chapter 73: Approach to a Child with Chest Pain
The history should begin with the onset of pain, with the The chest wall should be inspected for signs of trauma,
knowledge that acute pain is more likely to be caused by an asymmetry, pectus carinatum or excavatum, or costosternal
identifiable organic cause. The pain that makes child awaken swelling. Tenderness of the chest wall, costochondral or
from sleep has a higher likelihood of an organic cause. The costosternal junctions suggests a musculoskeletal etiology.
family should be asked about events that may have precipitated Auscultation of the lungs for crepts, wheezes, and decreased
the pain such as exercise, trauma, eating, potential foreign breath sounds may suggest pneumonia, asthma, or pneumo
body ingestion, or psychological stressors. thorax. Pneumomediastinum may cause sub cutaneous
Characteristic pain patterns have been described with emphysema, which can be detected by crepitus on palpation
certain conditions. Chest wall pain is often localized and of the supraclavicular area or neck.
sharp, and exacerbated by deep breath/palpation. Pleural The heart should be auscultated to identify the presence
or pulmonary pain may also be accentuated with inspiration of an irregular rhythm, murmur, rub, gallop, or muffled heart
or cough, although pain is less likely to be well-localized sounds. The rub of pericardial effusion is best appreciated
than musculoskeletal pain, and less likely to be reproduced when the patient is leaning forward. Patients with myocarditis
with palpation. Pleuritic pain is often sharp and superficial, may have tachycardia, gallop rhythm, displaced point of
whereas pulmonary pain, such as that associated with maximal impulse, or a murmur of mitral regurgitation. If
asthma, is more likely to be diffuse and deep. A description coarctation or aortic dissection is suspected, four-limb blood
of midsternal or precordial pain that worsens after eating or pressures should be obtained.
when lying down may be esophageal. The classic description Palpation of the abdomen may reveal epigastric tenderness
of cardiac pain is that of pressure, crushing, or a squeezing in patients with a gastrointestinal cause for their pain. The
sensation that may radiate to the neck or arm. There is little skin and extremities should be examined for evidence of
information on whether this classic description is typical trauma, chronic disease, or dysmorphology. Xanthomas on
in pediatric cases. Pain that is relieved by sitting up and the hands, elbows, knees, and buttocks are characteristic of
leaning forward may be caused by pericarditis. The presence familial dyslipidemia. Markers for Marfan syndrome or other
of blood or other irritants in the peritoneal cavity may cause connective tissue disorders should be searched.
referred chest or shoulder pain (Kehr’s sign). Psychogenic
pain is expected to be vague, poorly localized, varying in INVESTIGATIONS
location, and associated with other somatic complaints. Pain
A chest radiograph should be obtained if there is unexplained
associated with palpitations, dyspnea, or syncope should be
pain of acute onset, respiratory distress, abnormal pulmonary
considered a possible indicator of cardiac disease, and pain
or cardiac auscultation, fever, significant cough, history of
associated with exertion could be either cardiac or related to a
drooling or foreign body ingestion, or significant underlying
respiratory cause such as exercise induced asthma. A history
medical conditions.
of fever is likely to be reported with pneumonia, but may also
A 12-lead ECG should be obtained if there is pain or
be present with myocarditis, pericarditis, or pleural effusion.
syncope with exertion, abnormal cardiac auscultation, a
A history of drooling or reluctance to swallow may be present
clinical suspicion for myocarditis or pericarditis, or serious
in a child with an esophageal foreign body. The presence of
underlying medical conditions that carry an increased risk of
joint pain or rash may suggest collagen vascular disease. The
cardiac disease.
patient and family should be asked about emotional stressors Laboratory investigations are rarely necessary, but may
or presence of anxiety or depression. Adolescents should be be useful when certain conditions are suspected. A complete
asked about use of medications, especially oral contraceptives blood count may be obtained for suspected infectious causes
and pills that have been associated with esophagitis such or in a patient with an underlying condition such as sickle
as tetracycline. They should also be interviewed privately cell disease. In a patient with suspected cardiac ischemia or
and asked about use of illicit substances such as cocaine or myocarditis, cardiac enzymes may be useful; Holter monitor
marijuana. Past medical history, such as Kawasaki disease, if arrhythmia is suspected, exercise stress test or PFT for
asthma, sickle cell disease, diabetes, or connective tissue unexplained exertional pain, and endoscopy for possible
disorders (Marfan syndrome etc.), should be ruled out. The gastrointestinal sources of pain.
family history should focus on history of unexplained or
sudden death, serious underlying conditions, and whether
CONCLUSION
family members have a history of chest pain or heart disease.
The examination should include vital signs and an assessment As the differential diagnosis of chest pain is exhaustive
of the general appearance, noting level of alertness, color, and and many diagnoses are based on case reports rather than
presence of distress or anxiety. prospective studies, it is difficult to develop evidence-based
Fever may suggest the presence of infectious or inflamma guidelines for evaluation. The clinician should keep in mind the
tory condition, and tachycardia or tachypnea suggests the broad differential diagnosis and order further investigations
possibility of serious organic etiology. when the history and physical examination are not conclusive.
341
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Algorithm 1
Approach to chest pain
ECG, electrocardiography; ALCAPA, anomalous origin of the left coronary artery arising from the pulmonary artery; HOCM, hypertrophic obstructive cardiomyopathy;
MRI, magnetic resonance imaging; CT, computed tomography.
7. Lin CH, Lin WC, Ho YJ, Chang JS. Children with chest pain visiting the emergency
Key points department. Pediatr Neonatol. 2008;49(2):26-9.
8. Mahle WT, Campbell RM, Favaloro-Sabatier J. Myocardial infarction in
))
Chest pain in not usually cardiac in children adolescents. J Pediatr. 2007;151(2):150-4.
))
If present during exercise it may be cardiac 9. Pantell RH, Goodman BW Jr. Adolescent chest pain: a prospective study.
))
History of syncope or palpitation are red flags for cardiac Pediatrics. 1983;71(6):881-7.
chest pain 10. Rokicki W, Krzystolik-Ladzinska J, Goc B. Clinical characteristics of primary mitral
valve prolapse syndrome in children. Acta Cardiol. 1995;50(2):147-53.
))
Gastric etiology is most common
11. Rowe BH, Dulberg CS, Peterson RG, Vlad P, Li MM. Characteristics of children
))
History of traume or viral may help diagnose etiology presenting with chest pain to a pediatric emergency department. CMAJ.
))
R/o myocarditis with troponin I 1990;143(5):388-94.
12. Rowland TW, Richards MM. The natural history of idiopathic chest pain in
children. Clin Pediatr (Phila). 1986;25(12):612-4.
SUGGESTED READINGS 13. Said SA, el Gamal MI, van der Werf T. Coronary arteriovenous fistulas: collective
review and management of six new cases-changing etiology, presentation, and
1. Asnes RS, Santulli R, Bemporad JR. Psychogenic chest pain in children. Clin treatment strategy. Clin Cardiol. 1997;20(9):748-52.
Pediatr (Phila). 1981;20(12):788-91. 14. Selbst SM. Chest pain in children. Pediatrics. 1985;75(6):1068-70.
2. Brenner JI, Ringel RE, Berman MA. Cardiologic perspectives of chest pain in child 15. Selbst SM. Consultation with the specialist. Chest pain in children. Pediatr Rev.
hood: A referral problem? To whom? Pediatr Clin North Am. 1984;31(6):1241-58. 1997;18(5):169-73.
3. Brown RT. Costochondritis in adolescents. J Adolesc Health Care. 1981;1(3): 16. Selbst SM. Evaluation of chest pain in children. Pediatr Rev. 1986;8(2):56-62.
198‑201. 17. Tsuji A, Nagashima M, Hasegawa S, Nagai N, Nishibata K, Goto M, et al. Long-
4. Coleman W. Recurrent chest pain in children. Pediatr Clin North Am. term follow-up of idiopathic ventricular arrhythmias in otherwise normal children.
1984;31(5):1007-26. Jpn Circ J. 1995;59(10):654-62.
5. Driscoll DJ, Glicklich LB, Gallen WJ. Chest pain in children: a prospective study. 18. Tunaoglu FS, Olgunturk R, Akcabay S, Oguz D, Gücüyener K, Demirsoy S. Chest
Pediatrics. 1976;57(5):648-51. pain in children referred to a cardiology clinic. Pediatr Cardiol. 1995;16(2):69-72.
6. Lane JR, Ben-Shachar G. Myocardial infarction in healthy adolescents. Pediatrics. 19. Zav aras-Angelidou KA, Weinhouse E, Nelson DB. Review of 180 episodes of
2007;120(4):e938-43. chest pain in 134 children. Pediatr Emerg Care. 1992;8(4):189-93.
342
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Chapter 74
Systemic Hypertension
Nurul Islam
INTRODUCTION Secondary
Hypertension is defined as average systolic blood pressure Childhood hypertension is mainly secondary. The most
(SBP) and/or diastolic blood pressure (DBP) that is ≥95th common cause is renal etiology, contributing almost 90%.
percentile for gender, age, and height on more than or equal to Smaller group belongs to cardiac and endocrinal etiology.
three 3 occasions. • Renal:
As with adults, adolescent with blood pressure levels {{ Parenchymal lesions
≥120/80 mmHg should be considered prehypertensive. {{ Glomerulonephritis
{{ Pyelonephritis
{{ Reflux nephropathy
GRADATION {{ Hydronephrosis
• Normotensive: both SBP and DBP less than 90th percentile {{ Renal dysplasia
• Prehypertension: when SBP/DBP more than 90th percentile {{ Polycystic kidney disease
but less than 95th percentile {{ Chronic renal failure
• Stage I hypertension: SBP or DBP more than 95th percentile {{ Renal tumor
but not 5 mmHg above the 99th percentile {{ Postrenal trauma
• Stage II hypertension: SBP or DBP is more than 5 mmHg {{ Systemic lupus erythematosus
above the 99th percentile • Renovascular:

• White coat hypertension: when hypertension is noted {{ Renal artery stenosis
inside physicians office but not in normal surroundings {{ Fibromuscular dysplasia
• Marked hypertension: when present in surroundings. {{ Renal vein thrombosis
{{ Umbilical artery catheter-related thrombosis
{{ Takayasu’s arterirtis
CAUSES
{{ Moyamoya disease
• Cardiac: coarctation of the aorta

Primary • Endocrinal
• Genetic influence {{ Hyperthyroidism
• Dietary habits {{ Hyperparathyroidism
• Decreased physical activity {{ Congenital adrenal hyperplasia
• Obesity {{ Cushing syndrome
• Increased salt intake {{ Pheochromocytoma
• Stress {{ Catecholamine excess
• Low birth weight {{ Neuroblastoma
• Smoking. {{ Iatrogenic steroid
ch-74.indd 343 11/19/2016 5:59:37 PM

• Central nervous system • Creatinine

{{ Intracranial mass • Electrolytes
{{ Hemorrhage • Urine—routine examination, culture and sensitivity
{{ Quadriplegia. • Ultrasound—kidneys, ureters, bladder.
TRANSIENT HYPERTENSION Second Line

• Antineutrophil antibodies
• Renal
• C3, C4, antineutrophil cytoplasmic antibody
{{ Poststreptococcal glomerulonephritis
• Dimercaptosuccinic acid scan
{{ Henoch-Schönlein purpura
• Doppler scan
{{ Acute tubular necrosis
• Urinary—vanillylmandelic acid, catecholamine.
{{ Postrenal transplant
{{ Postblood transfusion
{{ Hypervolemia
Confirmatory Test
{{ Pyelonephritis • Renal biopsy
{{ Trauma • Micturating cystourethrogram
{{ Leukemic infiltration • Renal arteriography for renin angiotensin system
• Central nervous system • Magnetic resonance angiography
{{ Increased intracranial pressure • Computed tomography scan.
{{ Guillain-Barré syndrome
{{ Burn Special Tests for Endocrine Function

{{ Familial dysautonomia
• Hormonal profile
{{ Stevens-Johnson syndrome
• Serum cortisol
{{ Porphyria
• Catecholamine
{{ Poliomyelitis
• Renin activity
• Drugs • Aldosterone estimation.
{{ Cocaine
{{ Oral contraceptive pills
{{ Amphetamine
When Primary Hypertension Suspected
{{ Cyclosporine • Take proper history
{{ Tacrolimus • Dietary habits
{{ Vitamin D toxication. • Fasting blood sugar
• Lipid profile
• Uric acid.
CLINICAL PRESENTATION
The children are mostly asymptomatic. Document Target Organ Damage
Nonspecific symptoms are: • 12-lead electrocardiogram
• Irritability • Echocardiography evaluation
• Excessive sweating • Opthalmic evaluation
• Feeding problem in small baby • Urinary microalbuminuria.
• Failure to thrive.
Specific symptoms are:
• Features of cardiac failure PRIMARY HYPERTENSION EVALUATION
• Headache Primary hypertension in childhood is usually characterized
• Vomiting by mild or stage 1 hypertension and is often associated with
• Altered sensorium positive family history of hypertension or cardiovascular
• Convulsion disease.
• Facial hemiparesis. • Rule out overweight
Sometimes, clinical symptoms may be on the basis of • Body mass index calculation
system involved or main problem. • Assessment of other cardiovascular risk factors
{{ Low plasma high density lipoprotein cholesterol
{{ Increased triglycerides
INVESTIGATIONS
{{ Abnormal glucose tolerance
{{ Fasting plasma insulin concentration

First Line {{ Fasting lipid profile
• Complete blood count • Fasting glucose level

344 • Blood urea nitrogen • Rule out sleep disorder.
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Chapter 74: Systemic Hypertension
How Will You Approach • Do systemic examinations

{{ Cardiac
a Child with Hypertension?
{{ Respiratory
• Take good history {{ Abdomen
• Classify as {{ Central nervous system
{{ Transient (see table for causes) (Table 1)
• Plan for investigations on prority basis (as above).
{{ Chronic
–– Renal Indications for Measurement

–– Endocrine, etc.
{{ Other group of patients
of Blood Pressure in Children
–– With c/o urinary tract infection, hematuria, growth • Children >3 years old seen in medical settings
retardation, pain abdomen, swelling • Children <3 years old
• Take family history—rule out familial causes {{ History of prematurity, very low birth weight, neonatal
• Sleep history—rule sleep associated problem (sleep apnea) complications

• Birth history—umbilical artery catheterization done or not {{ Congenital heart disease
• Proper diet history {{ Recurrent urinary tract infection
• Drug history {{ Hematuria, proteinuria
• General survey {{ Known renal disease
{{ Facies {{ Family history of renal disease
{{ Built {{ Solid organ transplant
{{ Growth {{ Malignancy or bone marrow transplant
{{ Pallor {{ Drugs known to raise blood pressure.
{{ Edema
{{ Pulses
NONPHARMACOLOGICAL
{{ Four limb blood pressure
{{ Head neck examination

MANAGEMENT OF HYPERTENSION
{{ Ophthalmic findings
{{ Skin markers Hypertension

Table 1: Clinical features giving a clue to the etiology of Therapeutic Lifestyle Modification
hypertension • This is the first line of management of pediatric hyper
tension and can be the sole modality of therapy in patients
Moon facies Cushing syndrome
diagnosed with pre-hypertension and stage I hypertension
Elfin facies William syndrome
• It focuses on dietary management, increased physical
Webbing of neck Turner syndrome activity, stress reduction and avoidance of illicit drug and
Pallor, edema and growth Chronic renal failure tobacco use
retardation • Dietary management should include an age appropriate,
Webbing of neck, low Turner syndrome salt restricted diet with emphasis on weight loss in the
hairline, widely spaced nipple overweight or obese children
• To have a better chance of success, the entire family should
Moon facies, buffalo hump, Cushing syndrome
hirsutism, truncal obesity adopt these lifestyle modifications.
Thin built Hyperthyroidism, renal disease, Pharmacological Therapy

pheochromocytoma
Please put in the table of guidelines of the international task
Presence of virilization Congenital adrenal hyperplasia force on hypertension
Ophthalmic findings— Hyperthyroidism
proptosis Other Forms of Therapy
Café au lait spots, tubers, Neurofibroma • Bariatric surgery has a role in the treatment of hyper
rashes, striae tension in the morbidly obese adult and might become
Goiter Thyroid an option in the obese pediatric adolescent in the
future. A recent study (demonstrated an improvement in
Asymmetric limb pulses, Arteritis metabolic syndrome including hypertension with up to
bruits
30% reduction in weight.
Weak lower limb pulses Coarctation of aorta Renal nerve denervation is a therapeutic option in
Acute congestive heart failure Acute nephritis adults with resistant hypertension, which refers to un
controlled hypertension despite therapy with 3 or more anti
Adenotonsiller hypertrophy Suggestive of sleep apnea
hypertensives. 345
ch-74.indd 345 11/19/2016 5:59:37 PM

Indications for Antihypertensive Drug • Facial palsy

Therapy in Children • Hemiparesis
• Left ventricular failure
• Symptomatic hypertension • Renal failure
• Secondary hypertension • Retinopathy.
• Hypertensive target organ damage Aim of treatment:
• Diabetes (type 1 and type 2) • Urgent reduction of blood pressure
• Persistent hypertension despite nonpharmacologic • Reduction by 25% over the next 1 hour
measures. • Gradual reduction to 95th percentile over the next 24 hours
• Below 95th percentile achieved by 48 hours.
HYPERTENSIVE EMERGENCIES Drugs of choice:
• Intravenous labetalol—bolus 1 mg/kg/dose, infusion
Manifestations: 2 mg/kg/h, max 30 µg/kg/min
• Headache • Sodium nitroprusside—0.3–8 µg/kg/min
• Vomiting • Nifedipine—1–2 mg/kg/h
• Altered sensorium • Rapid acting diuretics
• Convulsion • Seizure control with intravenous diazepam—0.2 mg/kg.
Table 2: Classification of hypertension in children and adolescent and guidelines

Category Frequency of blood pressure measurement Therapeutic lifestyle changes Pharmacologic therapy
Normal Recheck at next schedule physical examination Encourage healthy diet, sleep, No
and physical activity
Prehypertension Recheck in 6 month Weight management, physical None unless compelling indications
activity, diet management such as chronic kidney disease,
diabetes mellitus, heart failure, or
left ventricular hypertrophy
Stage 1 Recheck in 1–2 week or early if symptomatic; if Weight management, physical Initiate treatment based on
hypertension persistently elevated on two occasions, evaluate activity, diet management indications or if compelling
or refer to source of care within 1 month indications
Stage 2 Evaluate or refer to source of care within 1 week Weight management, physical Initiate therapy
hypertension or immediately if the patient is symptomatic activity, diet management
Algorithm 1
Classification of hypertension, types, etiology, workup and treatment
346
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Chapter 74: Systemic Hypertension
Table 3: Drug treatment of hypertension

Drug Dose range Frequency
Angiotensin II receptor blockers
Losartan ≥6 years of age 0.7–1.4 mg/kg, up to 50–100 mg Once daily
Valsartan ≥6 years of age 1.3–2.7 mg/kg, up to 40–160 mg Once daily
Angiotensin-converting enzyme inhibitors
Benazepril ≥6 years of age 0.2–0.6 mg/kg, up to 10–40 mg Once daily
Enalapril 0.08–0.6 mg/kg, up to 5–40 mg Once or twice daily
Fosinopril ≥6 years of age and weighing >50 kg 5–10 mg up to 40 mg Once daily
Lisinopril ≥6 years of age 0.07–0.6 mg/kg, up to 5–40 mg Once daily
Beta blockers
Metoprolol, extended release, ≥6 years of age 1–2 mg/kg, up to 50–200 mg Once daily
Propranolol 1–4 mg/kg, up to 20–40 mg Two or three times daily
Vasodilator
Hydralazine 0.75–7.5 mg/kg, up to 200 mg Four times daily
Other
Calcium channel blocker: amlodipine ≥6 years of age 2.5–5 mg, up to 5 mg Once daily
Central a agonist: clonidine ≥12 years of age 0.2–2.4 mg, up to 2.4 mg Twice daily
Diuretic: hydrochlorothiazide 1–3 mg/kg, up to 50 mg Once daily
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Chapter 75
Pediatrician’s Perspective for
Postoperative Follow-up of a Child
Vikas Kohli, Mridul Agarwal
INTRODUCTION Mild cough with clear expectoration is common after

discharge for few days but cough with colored sputum, fever,
Once a child gets operated, the surgical issues dominate crepitation, or increase rate and/or work of breathing need
in the immediate post-operative. As the child recovers, the attention.
surgical issues decrease and the cardiology issues come to the
forefront. Finally, as the child gets out of the ICU, the child’s Feeding
cardiology issues also become less dominating, the pediatric
issues related to feeding and infection (prevention) become Feeding and eating advice are no different from routine care.
dominant.
Finally, on the long term, the pediatric issues like any WOUND CARE
normal child remain in the forefront. The pediatrician’s
though need to be sure that there is no special issue because
of the cardiac surgery. So this chapter is devoted to this one
Dressing
special aspect related to Pediatricians in long term follow up of Children discharged after 5–7 days of surgery, do not have
pediatric cardiac patients who have been operated. closed dressing over sternotomy or thoracotomy wound and
Children after cardiac intervention procedure and cardiac do not requires active dressing.
surgery are under care of their pediatrician. Common concerns
are discussed here. Discharge
Any signs of redness, swelling, discharge, or opening of the
GENERAL CARE wound need to be reported to the cardiac unit.
General Hygiene and Isolation Sutures

Parents are always counseled well regarding the hygienic The skin sutures used to close stenotomy and thoracotomy
handling of the child. The re-emphasis on hand washing wound are dissolvable and do not need removal. The sutures
and separation from other family members especially small used to close the drain sites need removal at first follow-up
children, ensures the adherence. visit.
Fever and Cough Scar

Persistent fever of more than 100°F always need evaluation. If The nature of skin scar after surgery depends on personal
cause of fever is obvious, like dehydration, upper respiratory propensity of scaring. The scar can be from thin white line
tract infections, gastroenteritis etc., it can be treated accordingly to large with keloid. Some children have lot of itching and
or else further investigation in the form of white blood cell warmth over scar tissue; they can be advised calamine lotion
count, C-reactive protein, chest X-ray, or urine examination or coconut oil along with cotton clothing to decrease friction
required localizing focus of infection. and avoid direct sun exposure.
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Chapter 75: Pediatrician’s Perspective for Postoperative Follow-up of a Child
PAIN RELIEF While aspirin is stopped after 3–6 months, in the latter case, it
is continued throughout the duration of BT shunt.
Most of the children at the time of discharge are on round-the- Patients with artificial conduit and prosthetic valve remain
clock or SOS nonsteroidal anti-inflammatory drug (NSAID; on anticoagulants (warfarin or nicoumalone) for lifetime. The
mostly paracetamol). If the child complains of persistent pain international normalized ratio should be only monitored and
or the infant cries excessively, the NSAID combination can be adjusted by the cardiac unit, although bleeding complication
given. may need immediate attention.
Parents of infant and toddler are always counseled
regarding handling for the first two weeks after surgery. They
should avoid picking up baby under the arms, so that the VACCINATIONS
stretching of the wound should not cause pain. Re-emphasis of
the same is sometimes required. Rearranging the Vaccination Schedule
Factors that should be considered prior to immunization
INITIAL FOLLOW-UP before surgery:
• Diphtheria pertussis tetanus (DPT or DTaP) vaccine can
Most of the children are called for follow-up by 5–7 days. At this cause fever within 2–3 days of administration
visit, the child assessed for any sign of infection, adequacy of • Rash and fever can be caused by measles or MMR (measles,
oral intake, and the status of the wound. Stiches are removed, mumps, and rubella) vaccine as late as 2 weeks and by
if any present, and analgesics are discontinued and cardiac varicella vaccine as late as 4 weeks
medicines are adjusted. • Blood product administration can interfere with the
antibody response to live attenuated vaccine such as
FOLLOW-UPS measles, rubella, and varicella vaccines; therefore, it
should not be given within 2 weeks of cardiac surgery, else
Corrective Surgeries repeat dose will be required later
• Oral polio vaccine should be avoided in hospital inpatients.
If no significant issues are noted during the initial follow-up,
further follow-up are planned after 3–6 months depending
on institutional policy. After that, usually annual follow-up Clinical Pearls
is required unless indicated. After adolescence, the follow-
Vaccination plan before surgery
up usually decreased to two yearly and then to five yearly
thereafter. • No vaccine in the last week before surgery
• No measles, rubella, or varicella vaccine in previous 2–4 weeks.
Palliative Surgeries
These include children who have undergone Blalock-Taussig Factors to be considered prior to immunization before
(BT) shunts or single ventricle palliation. These children surgery
require different plan and close follow-up along with oxygen • According to the Centers for Disease Control and
saturation monitoring. Prevention’s general recommendations on immunization,
blood products can interfere with antibody response to
measles, rubella, and varicella vaccine for 3–6 months;
MEDICATIONS therefore, these vaccinations should be delayed at least by
3 months. Typhoid (Ty21a), yellow fever, live attenuated
Antibiotics influenza vaccine, zoster, and rotavirus vaccines may be
Children are rarely discharged on antibiotics for non administered at any time before, concurrent with, or after
bloodstream infection. administration of any blood or immune product
• The chance of a vaccine associated fever complicating
Diuretics and Vasodilators postoperative management.
After cardiac surgeries, lots of time children have diuretics

in their discharge medication. In absence of residual lesion, Clinical Pearls
diuretics are usually stopped by 4–6 weeks. Angiotensin
Vaccination plan after surgery
converting enzyme inhibitors, angiotensin receptor blockers,
• No vaccine for the first 4–6 weeks
and β-blockers are given to some children for remodeling of
ventricles, usually stopped by 3–6 months. • No measles, rubella, or varicella vaccine for 3 months.
Aspirin and International Additional Vaccine

Normalized Ratio Drugs Children with corrected or uncorrected congenital heart
The patients of BT shunt and with the suture lines on side of disease are at higher risk for lower respiratory tract infection, 349
systemic circulation are on aspirin at the time of discharge. and should be considered for pneumococcal and influenza
ch-75.indd 349 11/19/2016 6:01:10 PM

Algorithm 1
General care of post of child
CBC, complete blood count;CRP,C-reactive protein;BT, Blalock-Taussig.
vaccine at appropriate time. Influenza vaccine is a must for all Algorithm 2

patients on aspirin. Long term follow up of post of child
DENTAL PROCEDURE
• No dental cleanings or scheduled surgeries for 3 months
after heart surgery
• Between 3 and 6 months after surgery, antibiotics should
be taken before any dental procedures.
ACTIVITY
Infants hypertension, saturations less than 80%, and significant

• Babies can sleep on back and sides from the beginning and ventricle dysfunction. Children with pacemaker and
also prone after skin healing (2–3 weeks) implantable cardioverter defibrillator have different
• Bath can be given without soiling wound during first week, security check guidelines which need to be followed.
and all over after, with soft soap
INFECTIVE ENDOCARDITIS PROPHYLAXIS
Children
• For palliative shunts and conduits
• Should not be send to day care or school for the first 2–3 • Completely repaired congenital heart defect with pros
weeks thetic material or device, whether placed by surgery or by
• Swimming can be allowed (if no other contraindication) to catheter intervention, during the first 6 months after the
private pool after 4 weeks and to public pool and sea after procedure
6 weeks • Repaired congenital heart disease with residual defects
• Gym, games, or bike riding can be allowed after 6 weeks, at the site or adjacent to the site of a prosthetic patch or
although contact sports should be avoided for up to 3–6 prosthetic device (which inhibit endothelialization).
months in most cases and forever when on anticoagulants
• Lifting weight, back pack, or items more than 10 pound
should be avoided for 6 weeks. CARE OF SPECIAL CHILD
Children with genetic issues need multidisciplinary approach
Young Adults involving different pediatric specialties.
• Similar to children, except they can be given more leverage
on weight up to 20 pounds. NEXT CHILD
• Counseling of genetic studies
AIR TRAVEL • Fetal echocardiography should be done in all mothers
350 • Air travel is usually safe after 2–3 weeks, except for if and when they conceive the next time, as there is an
few contraindications like severe pulmonary arterial increased risk of heart disease in the next child.
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Chapter 75: Pediatrician’s Perspective for Postoperative Follow-up of a Child
Key points
Suggested Readings
1. http://www.aboutkidshealth.ca/en/healthaz/testsandtreatments/procedures/
))
No vaccinations for 6 weeks
pages/after-heart-surgery-caring-for-your-child.aspx
))
If on aspirin, avoid chicken pox vaccination
2. JOAO, Paulo Ramos David and FARIA JUNIOR, Fernando. Immediate post-
))
Isolation at home from other children to avoid infection operative care following cardiac surgery. J. Pediatr. (Rio J.) [online]. 2003, vol.79,
especially respiratory suppl.2 [cited 2016-07-05], pp.S213-S222.
))
Infective endocarditis prophylaxis is provided for procedures 3. Pediatric home care for nurses: a family centred approach. By Wendy Votroubek,
is provided for 6 months unless it is a palliative surgery like Aaron Tabacco. Chapter 8: Care of the child with altered ccardiac function
BT shunt pp217-244.
))
Avoidance of school or day care for first 4–6 weeks
351
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Chapter 76
Chronic Diarrhea in Children
Less than 3 Years of Age
Moinak S Sarma, Surender K Yachha
INTRODUCTION DEFINITIONS
This topic will address only the relatively common causes of Before embarking upon the details of this topic, a few
chronic diarrhea in children less than 3 years of age that are of clarifications regarding the terminologies used in diarrhea
practical importance to the physician and also the emerging need to be understood.
entities that are often missed. Management of persistent While describing diarrhea of a fairly large duration, the
diarrhea is beyond the scope of this chapter. terms “chronic”, “persistent”, “protracted”, and “intractable” are
Chronic diarrheas may arise from intestinal diseases (small loosely interchanged in literature and creates confusion in the
or large bowel), pancreatic, hepatobiliary, or systemic causes. minds of the pediatricians.
Their differentiation is elaborated in the next chapter “Chronic
Diarrhea in Children More than 3 Years of Age”. Chronic Diarrhea
Gastrointestinal and systemic causes of chronic diarrhea in Chronic diarrhea is defined as an insidious onset diarrhea of
children less than 3 years of age are shown in boxes 1 and 2. >2 weeks duration in children rarely leading to dehydration with
Box 1: Gastrointestinal causes of chronic diarrhea in children less than 3 years of age
Common causes Uncommon causes
• Secondary lactose intolerance% • Intractable diarrhea of infancy (congenital diarrheas)
• Food protein allergy • Hirschsprung enterocolitis
{{ Bovine/cow’s milk intolerance (most common) • Infantile inflammatory bowel disease
{{ Concomitant soy allergy • Pancreatic insufficiencies
• Celiac disease {{ Cystic fibrosis
• Parasitic infections: giardiasis and others {{ Shwachman-Diamond syndrome
• Opportunistic infections in immunodeficiency states: • Abetalipoproteinemia

{{ Human immunodeficiency virus • Glycogen storage disease type 1b*
{{ Primary immunodeficiency • Congenital disorder of glycosylation type 1b#
• Intestinal lymphangiectasia • Progressive familial intrahepatic cholestasis type 1$
• Short bowel syndrome • Wolman disease (lysosomal acid lipase deficiency)
• Acrodermatitis enteropathica
• Anatomical defects
{{ Malrotation
{{ Fistula (duodenocolic, small bowel)* bacterial overgrowth syndrome
(secondary to blind loop syndrome)

• Nonspecific (Toddler’s) diarrhea (diagnosis of exclusion)
*Diarrhea in glycogen storage disease type 1b is due to opportunistic infections because of neutropenia and colitis due to inflammatory bowel disease
#Diarrhea in congenital disorder of glycosylation type 1b is due to protein-losing enteropathy
$Diarrhea in progressive familial intrahepatic cholestasis type 1 is due to bile acid malabsorption (deficiency of familial intrahepatic cholestasis 1 protein in small bowel)
%Secondary lactose intolerance in persistent diarrhea may often have a prolonged course and mimic chronic diarrhea.
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Chapter 76: Chronic Diarrhea in Children Less than 3 Years of Age
Box 2: Systemic causes of chronic diarrhea in children less BOVINE OR COW’S MILK PROTEIN ALLERGY
than 3 years of age Bovine or cow’s milk protein allergy (CMPA) affects 2–5% of all
Common causes children in the West, with the highest prevalence during the
• Urinary tract infection (most important) first year of life. In India, CMPA accounts for approximately
• Nephrotic syndrome 13% of all malabsorption cases in children less than 2 years
• Septicemia of age. Temporal association with introduction to animal or
• Drugs: laxatives, antacids, antineoplastic formula milk (± products) is often noted. Wheeze, eczema, and
atopy (20–30%) with similar history in family members (10%)
Uncommon causes
may be associated. Nearly 50% children outgrow the allergy by
• Endocrinal causes, e.g., Addison’s disease, hypoparathyroidism
(autoimmune polyendocrinopathies) 1 year and approximately 90% by 5 years of age. It is the most
common food allergy in small children who are top fed.
• Neuroblastoma and ganglioneuroblastoma
There are two kinds of reactions to cow’s milk:
• Constrictive pericarditis and restrictive cardiomyopathy
1. Immediate [immunoglobulin E (IgE) mediated]: it occurs
within minutes of milk intake and is characterized by
a wide range of underlying structural or chronic inflammatory anaphylaxis-like features: vomiting, pallor, shock-like state,
causes (acquired or congenital) causing malabsorptive or urticaria, and swelling of lips seen in 10–20% cases
maldigestive states. 2. Delayed (T-cell, non-IgE mediated): it has an indolent
course and presents mainly with gastrointestinal (GI)
Persistent Diarrhea symptoms. This is more common in India seen in 80–90%
cases.
Persistent diarrhea is an episode of diarrhea of presumed
infectious etiology, which starts acutely but lasts for >14 days
commonly seen in children <2 years age resulting dehydration
Symptoms
and dyselectrolytemia with or without gain in weight or loss in The most common presentation is diarrhea with blood and
weight and not responding to usual therapy. mucus. Depending upon the site and extent of involvement,
the child may have small bowel, large bowel, or mixed type
Protracted Diarrhea diarrhea. Diarrhea and colitis is seen in 80% cases. They
may have iron deficiency anemia and failure to thrive rarely
Usually the term describes a prolonged diarrhea that
as a clinical manifestation (especially those presenting as
resolves despite its initial severity. However, this term is
predominant small bowel diarrhea).
often interchangeably used by several authors to encompass
chronic and persistent diarrheas. Most authors, at present,
restrict this term to those with prolonged diarrheas in
Diagnosis
infancy of postinfectious origin, allergy-related, or due to Gold standard for diagnosis is double blind placebo controlled
immunodeficiency. food challenge, but it is cumbersome to execute. A simpler
yet conclusive way in India is to document the disease by the
Intractable Diarrhea following methods:
• Flexible proctosigmoidoscopy: aphthous ulcers (80%
Prolonged diarrhea of more than 2 weeks occurring in infants
cases)
less than 3 months of age. The term is used to describe a
• Rectal biopsy: more than 6 eosinophils per high power field
specific group of severe diarrheas of congenital nature that
+ eosinophilic cryptitis (97% cases)
persist despite bowel rest and often require total parenteral
• Symptom resolution after withdrawal of animal milk or
nutrition for survival. This is a distinct entity and has been
milk products (including formula feeds).
briefly discussed below.
The new European Society of Pediatric Gastroenterology,
Hepatology, and Nutrition, 2012 guidelines recommend the
Secretory Diarrhea
following:
Secretory diarrhea refers to a diarrhea with profound losses of 1. Non-IgE mediated CMPA: a response to a trial of elimination
water and electrolytes in stools that persists despite bowel rest. diet for 2–4 weeks, followed by relapse of symptoms in next
It occurs due to sodium pump failures at the enterocyte as a 2 weeks of oral challenge with cow’s milk protein diagnoses
result of toxins (e.g., Vibrio cholera). the condition without any biopsy. Thereafter a therapeutic
elimination diet is given
Osmotic Diarrhea 2. IgE mediated disease: CMP-specific IgE and skin prick
Osmotic diarrhea is caused by damage to epithelium and tests. However these tests are not reliable in India due to
loss of brush border enzymes resulting in poor tolerance and lack of standarised laboratories.
purging after an osmotic load and quiesence with bowel rest. The above recommendations reserve rectal biopsy and
(eg: secondary lactose intolerance due to lactase enzyme histopathology in scenarios of diagnostic dilemma, compli
deficiency). cated disease and non-response to elimination diet
353
Ch-76.indd 353 11/24/2016 1:47:53 PM

Treatment American Academy of Pediatrics). Concomitant soy allergy is

seen in 10–15% due to allergens (conglycinin and glycinin).
All animal milk/milk products have to be eliminated
Other problems with soy are high amounts of phytoestrogens
from the diet. Breast milk should be continued. Calcium
that may interfere with neuroendocrine functions, high
supplementation is mandatory as milk that has been withdrawn
phytates that limit zinc, iodine, and iron absorption, and,
is a rich source of calcium. Explaining the natural history of the
manufacturing related aluminum contamination. Hence,
disease to parents, counseling, vigilance, and compliance are
there is a dire need to urge the marketing of hypoallergenic
the cornerstones.
formulae in India.
Child less than 4 Months of Age
Child more than 4 Months of Age
In Western countries, an exclusive extensively hydrolyzed
formulation (EHF) is prescribed. In case of nonresponse to EHF, Formula feeds, animal milk, and milk products are stopped.
an elemental (amino acid formula) is used. Hypoallergenic Children more than 4 months of age are at an appropriate
formulae (EHF or elemental formulae) are not marketed in age for weaning and hence, dietary supplementation with
India. Hence, we are compelled to use soy formulae (not casein cereals and pulses (region specific) is started. Rice gruel which
based). Soy formulations in infants less than 6 months of age is relatively hypoallergenic may be tried. If the child is more
are not recommended in the West (the European Society of than 6 months of age, then, soy formulae can be permitted.
Pediatric Gastroenterology, Hepatology, and Nutrition and the Algorithm 1 outlines the for management of CMPA.
Algorithm 1
Approach and management of food protein allergy
#Inan academic setting, biopsy is repeated twice after initial milk withdrawal. First assessment is at 6–8 weeks as shown above to confirm normalization of histology.
Second assessment is at 48 hours of reintroduction of milk to decide wether it is safe to continue milk or not by (a) clinical symptoms and (b) histologic changes.
Milk-free diet is continued if symptoms or histological changes reappear. If histology is normal and symptoms do not reappear, then, child can be continued on milk.
However, in practical setting, both the repeat biopsies are not feasible due to the cumbersome process.
354 *Reintroduction of milk: child is given 10 mL/kg cow’s milk (0.3 g/kg milk protein) initially and watched for 1 h. If there are no adverse events, then, 20 mL/kg cow’s
milk is given again watched for another 1 h. If there are no symptoms, such as diarrhea, vomiting, etc., then, normal milk feeding is continued.
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SECONDARY LACTOSE INTOLERANCE NONSPECIFIC OR TODDLER’S DIARRHEA

This condition is commonly seen as a cause of persistent This is a diagnosis of exclusion and contributes to 16% of all
diarrhea (secondary to viral gastroenteritis). However, chronic diarrheas in preschool children. It is seen usually in
it may be associated with underlying chronic diarrhea thriving children of 6–20 months of age and spontaneously
(celiac disease, Crohn’s disease, giardiasis) due to villous resolves by 3 years of age in majority. The diarrhea worsens
atrophy and secondary deficiency of brush border enzymes with high osmolar feeds, e.g., juices, nectar fruits (grapes,
(including lactase). It manifests as explosive (gaseous melons, etc.). Occasionally, undigested food particles are seen
and noisy) stools and perianal excoriation that resolves in stool. No nocturnal symptoms or red flags are associated.
on lactose-free diet. Persistent diarrhea causes damage to Family history of irritable bowel syndrome may be present.
enterocyte and causes deficiency of the lactase enzyme Normal anthropometry and absence of anemia differentiate
located at the top of brush border epthelium. Hence lactose this condition from common conditions like celiac disease
is not broken down to glucose and galactose. Unabsorbed and CMPA. Treatment consists of reassurance, high fat
dietary lactose delivered to colon is converted to hydrogen (2 g/kg butter), and high fiber diet with reduced intake of
and lactic acid by colonic bacteria. Lactic acid results in juices. Antimotility agents should not be prescribed.
decreased stool pH, hydrogen gives explosive stool and Celiac disease, and intestinal lymphangiectasia are
unabsorbed lactose gives positive reducing substances if discussed in detail in next chapter.
tested. Lactose increased the osmolality (osmotic diarrhea). Box 3 shows brief clinical pointers and management of
Fungal infection of the perineum in fungal diarrhea may other pertinent causes of chronic diarrheas in children less
mimic secondary lactose intolerance. In fungal infections, than 3 years of age.
there are curdy white, satellite lesions and extension into the
genitalia and groin flexures. Box 3: Salient features and management of common causes
Confirmation is not required if stools are explosive and of chronic diarrhea in children less than 3 years of age
perianal area is excoriated. In doubtful cases, the diagnosis is • Short gut syndrome
confirmed by stool pH less than 6.0 and reducing substances {{ History of intestinal resection for small bowel obstruction or
more than 0.5%. Withdrawal of lactose containing milk for 3 necrotizing enterocolitis in infancy
weeks is the mainstay of treatment. Perianal area is managed {{ Functional definition: massive small bowel resection >75% or
by nursing on soft cloth, avoiding diapers, maintaining proper dependence on parenteral nutrition for >6 weeks
hygiene, and applying local emollients (coconut oil, liquid {{ Symptoms occur when >150 cm small bowel + no colon or
paraffin zinc oxide). <70 cm small bowel + intact colon (older children/adults)
{{ Long-term total parenteral nutrition requirement
{{ Treatment: small bowel lengthening surgeries or small bowel
IMMUNODEFICIENCY STATES transplant)

• Anatomical defects
Common presenting features and brief management of {{ Duodenocolic fistula or small bowel fistulas:
immunodeficiency has been discussed in detail in the next –– May be idiopathic or secondary to inflammatory
chapter. Additionally, there are few more immunodeficiency conditions, e.g., IBD, TB
states with GI manifestations that are seen in younger –– Passage of undigested food particles soon after intake
children. –– Fistulous tract delineated by barium studies
–– Duodenocolic fistulous openings seen on UGIE ± colonoscopy
{{ Malrotation: bacterial overgrowth, secondary lymphangiectasia
X-linked Agammaglobulinemia
• Acrodermatitis enteropathica
• Onset after 6 months of age {{ May be primary (symptoms after weaning) or secondary to
• Chronic rotavirus infection persistent diarrhea

• Absent tonsils {{ Eczematous exfoliative rash in perioral, and perianal areas and
• Panhypogammaglobulinemia + B cells less than 1%. extremities

{{ Associated alopecia and sinopulmonary infections
Normal T cells.
{{ Oral supplementation of 2–3 mg/kg or 50–150 mg zinc sulfate
or gluconate daily
Severe Combined Immunodeficiency • Infantile inflammatory bowel disease
• Onset in first few months {{ Less than 3% of all IBD in children
{{ Emerging entity associated with rare immunodeficiency states

• Cytomegalovirus colitis and mucocutaneous candidiasis
• Absent tonsils such as interleukin-10 receptor defect or deficiency
{{ Colitis in 100%, perianal disease in 80–90%, sepsis in >90%
• Leukopenia, hypogammaglobulinemia, absent T cells ±
{{ May be associated with glycogen storage disease type 1b
B cells
{{ Aggressive disease with poor prognosis and resistance to
In both the groups, the children die by 1–2 years of
biological therapeutics (infliximab)
age, if untreated. Treatment is specific; antimicrobials and {{ Hematopoietic stem cell transplant: promising therapeutic
intravenous immunoglobulin 400–600 mg/kg to tide over modality
crisis. Allogenic bone marrow transplantation is curative. 355
Continued
Ch-76.indd 355 11/24/2016 1:47:53 PM

Continued Setting to Suspect Intractable

• Shwachman-Diamond syndrome Diarrhea of Infancy
{{ Exocrine pancreatic insufficiency (steatorrhea) beginning in
• Dehydrating diarrhea in an infant beginning in neonatal
infancy
{{ Cyclical neutropenia with risk of recurrent bacterial infections
period or less than 3 months of age and
± thrombocytopenia • Prolongation of diarrhea beyond 2 weeks despite extensive
{{ Dental and skeletal abnormalities including short stature hospital therapy with one or more of the following:
{{ Transient hepatomegaly ± transaminitis till 5 years of age {{ At least 3 negative stool cultures for bacterial pathogen
{{ Diagnosis: abnormal pancreatic function tests, cyclical {{ Family history of consanguinity, sibling death, or
neutropenia, hypoplastic pancreas on computed tomography polyhydramnios
and genetic testing for abnormal Shwachman-Bodian- {{ Associated dysmorphism or systemic features
Diamond syndrome gene
{{ Common conditions like food protein allergy, intestinal
{{ Treatment: enzyme supplements, granulocyte colony
stimulating factor, and regular skeletal monitoring lymphangiectasia, antibiotic associated diarrhea ruled
• Hirschsprung enterocolitis out
{{ Explosive diarrhea or colitis in a background history of {{ No response to empirical elemental diet.
constipation from birth or after pull through surgery for Common causes of intractable diarrhea of infancy (IDI)
Hirschsprung disease with their salient features are shown in table 1. Brief approach
{{ History of delayed passage of meconium. Distension, to IDI is shown in algorithm 2.
tenderness, fever, and shock
{{ Erect X-ray abdomen: intestinal cutoff sign
Except congenital alactasia which has favorable prognosis
{{ In the setting of enterocolitis, barium enema is also
with absolute restriction of lactose in diet, the rest of the
contraindicated for the risk of perforation disorders have no definitive treatment; often require life-long
{{ Treatment: intravenous antibiotics, rectal irrigation (saline parenteral nutrition or small bowel transplant. Intractable
washes). Colonic decompression (diversion colostomy) in diarrhea of infancy patients patients have very high mortality.
severe cases
• Wolman disease
{{ Stormy neonatal course in first 2 weeks of life, rapid Table 1: Common causes of intractable diarrhea of infancy and
deterioration and death within 6 months their characteristic features
{{ Associated with hepatosplenomegaly, liver failure, and
intractable ascites Condition Characteristic features
{{ Consanguinity and sibling death Congenital sodium • Elevated levels of fecal Na+ and HCO3–
{{ Bilateral adrenal calcification on abdominal imaging and diarrhea • Antenatal polyhydramnios
foamy histiocytes on bone marrow studies
{{ Enzymatic studies: deficient lysosomal acid lipase in white
Congenital chloride • Elevated levels of fecal Cl–
diarrhea (>90 mmol/L)
blood cells and fibroblasts
{{ Corticosteroids for adrenal insufficiency • Antenatal polyhydramnios
{{ Bone marrow transplant may not be useful in all cases
Microvillus inclusion • Absent microvilli with inclusions in
• Abetalipoproteinemia disease enterocytes
{{ Diarrhea begins within first year of life, worsens with high fat
Tufting enteropathy • Epithelium of villi arranged in “tufts”
diet, and some improvement is noted when patient learns
dietary aversion • Associated with choanal, esophageal,
{{ Neurologic symptoms (ataxia, areflexia, loss of vibration and or anal atresia
position) appear after first decade Autoimmune entero • Eczema, type I diabetes mellitus, and
{{ Retinitis pigmentosa seen in adulthood
pathy polyendocrinopathy
{{ Absence of chylomicron, low density lipoprotein and very low
Part of IPEX syndrome • High serum immunoglobulin E and
density lipoprotein in plasma (fasting lipid profile) (Immune dysregulation- anti-enterocyte antibody positive
{{ Hemolytic anemia and acanthocytosis in peripheral smear
polyendocrinopathy-
{{ UGIE (fat loading): white duodenal mucosa
enteropathy-X linked
{{ Small bowel histology: lipid droplet filled enterocytes at villus
disease)
tips
{{ Treatment: restricted fat intake with supplementation of all fat Syndromic diarrhea • Facial dysmorphism, trichorrhexis
soluble vitamins. High dose vitamin E (1000–2000 mg/day) nodosa (wooly hair), immuno
deficiency, and cirrhosis of liver
UGIE, upper gastrointestinal endoscopy; TB, tuberculosis; IBD, inflammatory
Congenital alactasia • Improvement on lactose-free diet
bowel disease
(primary lactase • Deficient lactase activity in a
deficiency) duodenal or jejunal biopsy when the
other disaccharidases are normal
INTRACTABLE DIARRHEA OF INFANCY Glucose-galactose • Elimination of glucose and galactose
These are very rare causes of chronic diarrhea that are of malabsorption (and lactose) from the diet results in
congenital nature, severe in their course, often dependent on the complete resolution of diarrhea
parenteral nutrition and most requiring small bowel transplant. • Diagnosis of exclusion
356
Ch-76.indd 356 11/24/2016 1:47:53 PM

Algorithm 2
Approach to intractable diarrhea of infancy
2. Bhatia J, Greer F. American Academy of Pediatrics Committee on Nutrition. Use of

Clinical Pearls soy protein based formulas in infant feeding. Pediatrics. 2008;121(5):1062-8.
3. ESPGHAN Committee on Nutrition, Agostoni C, Axelsson I, Goulet O, Koletzko
• Relatively thriving child with colitis: think of bovine (cow’s) milk B, Michaelsen KF, et al. Soy protein infant formulae and follow-on formulae: a
protein allergy commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol
• Severe colitis with failure to thrive not responding to milk- Nutr. 2006;42(4):352-61.
free, soy-free, hydrolysed or elemental diet: think of infantile 4. Goldman AS, Anderson DW, Sellers WA, Saperstein S, Kniker WT, Halpern SR.
inflammatory bowel disease Oral challenge with milk and isolated milk proteins in allergic children. Pediatrics.
• Small bowel diarrhea + perianal erythema + explosive stool: 1963;32:425-43.
think of secondary lactose intolerance 5. Goulet O, Philips AD. Congenital enteropathy involving intestinal mucosa
development. In: Walker AW, Goulet O, Kleiman RE, Sherman PM, Shneider BL,
• Severe intractable diarrhea beginning just after neonatal Sanderson RI (Eds). Pediatric Gastointestinal Diseases, 4th edition. BC Decker;
period: think of congenital diarrheas 2004. pp. 922-31.
• Diarrhea + fever: think of urinary tract infections and sepsis 6. Guarino A, Spangnuolo MI, Russo S, Albano F, Guandalini S, Capano G, et al.
• Chronic diarrhea with recurrent systemic infections: think of Etiology and risk factors of severe and protracted diarrhea. J Pediatr Gastroenterol
immunodeficiency states. Nutr. 1995;20:173-8.
*Diarrhea in an underlying surgical setting are short gut syndrome, 7. Høst A, Halken S, Jacobsen SP, Christensen AE, Herskind AM, Plesner K. Clinical
hirschprung enterocolitis, duodenocolic fistula, bacterial overgrowth course of cow’s milk protein allergy/intolerance and atopic diseases in childhood.
syndrome (due to malrotation, blind-loop syndrome) Ped Allergy Immunol. 2002:13 (Suppl 15):23-8.
8. Høst A. Frequency of cow’s milk allergy in childhood. Ann Allergy Asthma
Immunol. 2002;89(6 Suppl. 1):33-7.
9. Kneepkens CM, Hoekstra JH. Chronic nonspecific diarrhea of childhood:
Key points pathophysiology and management. Pediatr Clin North Am. 1996;43:375-90.
10. Kotlarz D, Beier R, Murugan D, Diestelhorst J, Jensen O, Boztug K, et al. Loss of
))
Cow’s milk protein allergy (CMPA) is the most common cause interleukin-10 signaling and infantile inflammatory bowel disease: implications
of colitis in children less than 3 years of age for diagnosis and therapy. Gastroenterology. 2012;143:347-55.
))
Algorithm approach of management of CMPA is to be 11. Matthai J. Yachha SK. Pediatric Gastroenterology Chapter, Indian Academy of
followed Pediatrics. Chronic and Persistent Diarrhea in Infants and Young Children: Status
))
Secondary lactose intolerance, celiac disease, and intestinal Statement. Ind Pediatr. 2011;48:37-42.
lymphangiectasia are common causes of small bowel 12. Poddar U, Agarwal J, Yachha SK, Srivastava A. Toddler’s diarrhea: is it an under
diarrhea in children less than 3 years of age recognized entity in developing countries? J Trop Pediatr. 2013;59:470-5.
13. Poddar U, Yachha SK, Krishnani N, Srivastava A. Cow’s milk protein allergy (CMPA):
))
Urinary tract infections and sepsis are important systemic causes.
an entity for recognition in children in developing countries. J Gastroenterol
Hepatol. 2010;25:178-82.
SUGGESTED READINGs 14. Wales PW, Christison-Lagay ER. Short bowel syndrome: epidemiology and
etiology. Semin Pediatr Surg. 2010;19:3-9.
1. Avery GB, Villacivencio O, Lilly JR, Randolph JG. Intractable diarrhea in early 15. Yachha SK, Misra S, Malik A, Nagi B, Mehta S. Spectrum of malabsorption
infancy. Pediatrics. 1968;41:712-22. syndrome in North Indian children. Indian J Gastroenterol. 1993;12:120-5. 357
Ch-76.indd 357 11/24/2016 1:47:54 PM

Chapter 77
Chronic Diarrhea in
Children More than 3 Years of Age
Surender K Yachha, Moinak S Sarma
INTRODUCTION • Gastrointestinal (GI) versus systemic causes: commonly,

diarrhea is of intestinal origin and sometimes due to
Chronic diarrhea is defined as an insidious onset diarrhea of pancreatic etiology, and rarely, hepatobiliary causes.
more than 2–3 weeks duration in children. Causes of chronic Cholestasis due to biliary obstruction or intrahepatic
diarrhea in older children (>3 years) and adolescents are cause can cause diarrhea due to fat malabsorption as a
distinctly different from those in younger age. result of deficiency of bile. Diarrhea may be caused due to
liver diseases having genetic or metabolic defects mostly
prevalent among young children. Pruritus, fat soluble
APPROACH TO CHRONIC DIARRHEA vitamins (A, D, E, and K), and calcium malabsorption
is commonly associated with hepatobiliary diseases.
Approach to chronic diarrhea should be considered with the
Maldigestion due to deficiency of pancreatic enzymes
following points in mind: results in clinical steatorrhea in cystic fibrosis, Shwachman-
• Small or large bowel type of diarrhea: features in history Diamond syndrome (cyclical neutropenia and skeletal
and examination that help in differentiating small from dysplasia), or chronic pancreatitis. Diarrhea may also be a
large bowel diarrhea shown in table 1. To summarize, systemic manifestation of other conditions like nephrotic
large volume diarrhea without blood and mucus suggests syndrome, sepsis, or collagen vascular disorders. Box 1
“small bowel type” and small volume stools with blood and enumerates the common and uncommon causes of
mucus suggests “large bowel type” of diarrhea. diarrhea in children more than 3 years of age.
Table 1: Differentiating small versus large bowel diarrhea

Features Small bowel diarrhea Large bowel diarrhea*
Stool volume Large Small
Blood in stool No Usually present
Rectal symptoms (urgency, tenesmus) No Yes
Carbohydrate malabsorption Yes, explosive No
Protein malabsorption Yes No
Pain (if any) Periumbilical, no reduction after passage of stool Hypogastric, reduced after passage of stool
Color of stool Pale Normal
Smell of stool Unusually offensive Normal
Nutrient deficiency (iron, calcium, Frequent Can occur due to blood loss
mutivitamins)
*Large bowel diarrhea in exceptional cases may not necessarily have blood in stools or rectal symptoms.
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Chapter 77: Chronic Diarrhea in Children More than 3 Years of Age
Box 1: Causes according to age of onset (in order of priority)

• Common causes • Uncommon causes
{{ Celiac disease {{ Tropical sprue
{{ Parasites: giardiasis and others {{ Immune proliferative small intestinal disease (IPSID)
{{ Lymphangiectasia {{ Anatomical causes (malrotation of gut)
{{ Gastrointestinal tuberculosis {{ Intestinal fistulae (duodenocolic commonest)
{{ Inflammatory bowel disease (Crohn’s disease; ulcerative {{ Late-lactose intolerance (very rare)
colitis* unclassified IBD) {{ Autoimmune enteropathy
{{ Immunodeficiency syndromes {{ Systemic causes:
{{ Pancreatic insufficiency –– Nephrotic syndrome#

{{ Bacterial overgrowth syndrome (diagnosis of exclusion) in –– Constrictive pericarditis$
a non-surgical setting {{ Endocrine causes:
–– Hyperthyroidism
–– Addison’s disease
*Ulcerative colitis presents as bloody diarrhea. Crohn’s disease may present either as colitis or small bowel diarrhea or both.
#
Diarrhea in nephrotic syndrome is presumed to be due to bowel wall edema (hypoalbuminemia).
$
Secondary lymphangiectasia due to chronic back pressure is the cause of diarrhea in constrictive pericarditis, can also occur due to other causes.
WHAT SHOULD YOU LOOK FOR IN HISTORY? The common etiologies are elaborated below. Algorithm 1
shows an approach to chronic diarrhea more than 3 years of
• Details of duration of symptoms, nature, frequency and age (major etiologies).
consistency of stools, and presence of blood/mucus/clinical
steatorrhea (stool floating in water, greasy oily droplets)
• Age of onset, dietary details, i.e., introduction of wheat/ CELIAC DISEASE
wheat products and their relationship with onset of It is an enteropathy caused by permanent sensitivity to gluten
diarrhea. Relationship with milk intake and quantity in genetically susceptible subjects. It is the most common
• Family history of atopy (food allergy, asthma, or allergic cause of chronic diarrhea in children over 2 years of age in
rhinitis), celiac disease, inflammatory bowel disease (IBD) North India. Boxes 2 and 3 summarize the diagnosis and
or cystic fibrosis management of the same.
• History of abdominal surgery, systemic disease, features of
intestinal obstruction, pedal edema, anasarca, recurrent
infections at multiple sites, previous blood transfusion, Intestinal Lymphangiectasia
and coexisting medical problems which predispose the It is characterized by ectasia of the bowel lymphatic system,
child to diarrhea like congenital immuno deficiency, which on rupture causes leakage of lymph in the bowel. Box 4
diabetes mellitus, hyperthyroidism, cystic fibrosis, etc. summarizes the diagnosis and management of the same.
WHAT SHOULD YOU LOOK FOR Immunodeficiency

IN PHYSICAL EXAMINATION?
Both congenital and acquired immunodeficiency can cause
• Growth parameters chronic diarrhea. It should be suspected if there is history
• Volume status and rarely, presence of dehydration of recurrent infections at multiple sites (chest/GI/skin) and
• Signs of vitamin and mineral deficiencies anemia, tetany, wasting. The common immunodeficiency conditions in
(conjunctival xerosis, bitot’s spots, angular stomatitis, children more than 3 years of age presenting with diarrhea
glossitis, cheilitis, rickets, phrynoderma) are human immunodeficiency virus (HIV) infection, selective
• Edema: symmetric and pitting (hypoalbuminemia) or immunoglobulin A deficiency, common variable immuno
asymmetric and nonpitting (lymphedema) deficiency, and chronic granulo matous disease. Boxes 5
• Fever and other signs of toxicity and 6 summarize the diagnosis and management of the same.
• Extra-gastrointestinal manifestations in eye, skin, joints, Diarrhea is either due to opportunistic enteric infections or
oral cavity (particularly aphthous ulcers) in IBD due to bacterial overgrowth.
• Inspection of perianal area for fissures, anal tags, and
fistulae in IBD
Inflammatory Bowel Disease
• Oral thrush and scars of recurrent skin infections in
immunodeficiency Inflammatory bowel disease (IBD) is a chronic inflammatory
• Abdominal examination: abdominal distention, localized disease of the GI tract and is of two main types: (1) Crohn’s
or generalized tenderness, masses, hepatosplenomegaly, disease (CD) and (2) ulcerative colitis (UC). In approximately
and ascites. 10% cases, the findings are nonspecific and subjects cannot 359
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Algorithm 1
Approach to management of chronic diarrhea in children more than 3 years of age: major etiologies
CT, computed tomography; MRI, magnetic resonance imaging; AFB, acid fast bacilli; TB, tuberculosis; ATT, antitubercular therapy; MDR-TB, multidrug resistance
tuberculosis; anti-tTG, anti-tissue transglutaminase; IBD, inflammatory bowel disease; IgA, immunoglobulin A; IgM, immunoglobulin M; IgG, immunoglobulin G; CRP,
C-reactive protein; ESR, erythrocyte sedimentation rate; PCR, polymerase chain reaction.
Note:*
• Selective IgA deficiency: recurrent giardiasis
• IgA anti-tTG positive + villous atropy + other biopsy changes (Box 2): celiac disease
• IgA anti-tTG negative + low IgA level + villous atropy + other biopsy changes (Box 2): celiac disease
• Dilated lacteals on duodenal biopsies: intestinal lymphangiectasia (Box 4 for other supportive features)
• Low IgA, IgM, and IgG ± villous atropy ± paucity of plasma cells on duodenal biopsies: immunodeficieny workup as shown in Box 5.
be classified into one of the above two groups. These cases diarrhea, commonly without constitutional symptoms. Table 2
are labeled as IBD unclassified. Nearly 25% of all IBD patients summarizes the clinical, histologic, and endoscopic differences
present in the pediatric age group. Worldwide, the incidence of between UC and CD.
IBD is increasing in children with increase in recent reports of Extraintestinal manifestations are seen in 25–30% children
both UC and CD from India. The average age of presentation with IBD. They can precede, follow, or occur concurrently
in children is nearly 10–11 years. Genetics is a very important with the intestinal disease and may be related or unrelated to
risk factor for IBD and up to 30% patients may have an affected the activity of the intestinal disease. Arthralgia/arthritis is the
family member with IBD. Box 7 summarizes the disease most common manifestation seen in 15–17% cases. Uveitis,
distribution of UC and CD. erythema nodosum and sclerosing cholangitis are the other
manifestations.
Clinical Features
Children with CD present with abdominal pain, diarrhea
Diagnosis
(with or without blood), and constitutional symptoms The initial evaluation of a child with suspected IBD includes
360 (fever, anorexia, growth failure). In contrast, children with UC a detailed clinical, family, and treatment history. Also, a
present with only recurrent or prolonged episodes of bloody complete examination with growth charting, perianal and
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Box 2: Classical clinical features and workup of celiac disease Box 3: Diagnosis and treatment of celiac disease
• Presentation Diagnosis of celiac disease based on the modified ESPGHAN
{{ Onset after weaning when gluten is introduced 1990 criteria:
{{ Small bowel diarrhea, failure to thrive, short stature, and • Clinical picture consistent with celiac disease
gaseous abdominal distension • Changes in intestinal biopsy as described above (+ serology*)
{{ Anemia, rickets, and multivitamin deficiencies • Unequivocal response to GFD within 12 weeks of initiation of GFD
• Workup: mandatory in India New ESPGHAN 2012 guidelines for diagnosis:
{{ Positive serology: IgA anti-tTG (preferred) or IgA anti-EMA
• Small bowel biopsy may be omitted when all three following
{{ Upper gastrointestinal endoscopy: scalloping ± reduced
tests are fulfilled: anti-tTG ≥10 times upper limit, anti-EMA
number of duodenal folds, mosaic pattern, cobblestoning of positive and HLA DQ 2/8 positive (details in original article)
duodenal mucosa (not specific) • However, due to certain limitations in India (cost, unreliability
{{ Endoscopic duodenal biopsy:*
of laboratory reports, and overlap with other chronic diarrheal
–– Partial to total villous atrophy diseases), the above guideline is difficult to implement currently.
–– Hyperplastic crypts Hence, small bowel biopsy is still recommended for diagnosis
–– Increased intraepithelial lymphocytes (>30/100 (personal view).
enterocytes) Treatment:
–– Lymphoplasmacytic infiltrates • GFD (wheat and barley) should never be started without a
• Workup: supportive positive histology
{{ HLA-DQ2 or 8 positive (not done routinely). Only in exceptional
• Lifelong GFD, vigilance, and counseling. Region-specific dietary
cases where diagnosis is doubtful chart
{{ Serum IgA levels:
• Hematinics, folic acid, and multivitamin supplementation for
–– Suspect if serology is negative and clinical suspicion is high 3 months
–– Levels <5 mg/dL suggests IgA deficiency • Response to GFD should be assessed at 8–12 weeks to label the
{{ Serum IgG anti-DGP patient having celiac disease as per diagnostic criteria
–– Children <2 years of age if tTG or EMA is negative • At follow-up: compliance with repeated reinforcement of GFD,
–– Concomitant IgA deficiency symptomatic, anthropometric, and laboratory (hemoglobin,
IgA, immunoglobulin A; tTG, tissue transglutaminase antibody; EMA, albumin, and transaminases) normalization to be assessed
endomysial antibody; DGP, deamidated gliadin peptide; HLA, human ESPGHAN, European Society for Pediatric Gastroenterology, Hepatology,
leukocyte antigen. and Nutrition; GFD, gluten-free diet; EMA, endomysial antibody; tTG, tissue
*Between 4–6 biopsies should be obtained (at least 4 from second part of transglutaminase; HLA, human leukocyte antigen; IgA, immunoglobulin A.
duodenum and one from first part). Biopsies should be directly immersed in *In India positive serology (IgA-tTG) should be demonstrated as there are
formalin solution for best orientation under microscope. other conditions that may result in villous atrophy mimicking celiac disease
rectal examination for fistulae, tags, and fissures to be done.

Laboratory tests may reveal anemia and thrombocytosis Box 4: Features and management of intestinal lymphangiectasia
(67%), low albumin, high erythrocyte sedimentation rate Presentation:
(ESR) and C-reactive protein in 40–60% cases. Hence, IBD • Small bowel diarrhea with anasarca ± lymphedema of peripheries
must be suspected in any child presenting with constitutional • Abdominal or thoracic chylous effusions may be associated
symptoms, chronic large bowel diarrhea (± blood), and • Usually, absence of anemia and rickets (in contrast to celiac
thrombocytosis. Table 3 summarizes the diagnostic modalities disease)
available for IBD. • Hypocalcemic tetany
Diagnosis:
Treatment • Panhypoproteinemia, low immunoglobulins, hypocalcemia, and
lymphopenia
The goal of treatment is to control inflammation, mucosal • Upper gastrointestinal endoscopy: white patches in duodenum
healing, improve growth, and ensure a good quality of life with (snow-flake appearance), better appreciated after overnight fat
the least toxic therapeutic regimen. Ensuring proper nutrition (butter) loading 2 g/kg
with caloric supplementation (~120% of recommended dietary • Small bowel biopsy: dilated lacteals in the villi
allowances) is a necessity for children with IBD. Calcium and Treatment:
vitamin D supplementation should be given as these children • Diet: low fat, high medium chain triglyceride with high protein
are at an increased risk of osteoporosis. As IBD is a chronic (2–4 g/kg)
disease with remissions and exacerbations, proper counseling • Medium chain triglycerides should be 85% of total fat intake
of both, patient and family, at diagnosis is essential. The main • Calcium supplementation
drugs used for IBD are listed in the tables 4 and 5. Additionally, • Intravenous albumin (1 g/kg) during acute exacerbations
for perianal fistulizing CD, antibiotics (ciprofloxacin 20 mg/kg, • In refractory cases: subcutaneous octreotide 15–20 µg daily
twice or 10–20 µg depot preparation once in 4 weeks
metronidazole 10–20 mg/kg, azithromycin 10 mg/kg, or rifaximin
• Resection if localized segment of small bowel is involved by
10–30 mg/kg) for 4–6 weeks have shown good short-term
identifying the segment by 99Tc albumin scintigraphy 361
response.
Ch-77.indd 361 11/21/2016 9:53:06 AM

Box 5: Clinical features of common immunodeficiency states Box 7: Disease distribution

(above 3 years of age) • Ulcerative colitis
Common features {{ Distal colitis (proctitis/proctosigmoiditis): 5–20%
• Positive family history, affected sib, or sib death {{ Left side colitis (up to splenic flexure): 10–40%
• Associated systemic infections (sinopulmonary, skin, urinary, {{ Pancolitis: 50–90%
meningeal, etc.) • Crohn’s disease

• Small bowel, large bowel, or mixed diarrhea depending on the {{ Ileocolonic disease: 50–70%
opportunistic pathogen {{ Isolated colonic involvement: 10–20%
• Recurrent GI infections: Cryptosporidia, Isospora, Giardia, {{ Small bowel: 10–15%

Cytomegalovirus, fungal {{ Associated:
Human immunodeficiency virus infection –– Upper gastrointestinal involvement: 30–40%
• Hepatosplenomegaly, lymphadenopathy, thrombocytopenia, –– Perianal disease: 20–25%
hypergammaglobulinemia
• Enzyme-linked immunosorbent assay and Western blot tests Note: Crohn’s disease is also classified as predominantly inflammatory,
positive fistulizing, or stricturing disease based on the clinical features.
• Opportunistic infections depending upon the level of CD4 count
Selective IgA deficiency
• Recurrent giardiasis Table 2: Differentiation between Crohn’s disease and ulcerative
• Serum IgA <5 mg/dL colitis
Common variable immunodeficiency Parameters Crohn’s disease Ulcerative colitis
• Age of onset variable usually after 2 years of age Distribution Entire GI tract Colon only
• Low serum IgG ± low IgA or M with variable B-cell numbers
Chronic granulomatous disease Transmural Mucosal disease
inflammation
• Multifocal abscess (skin, liver), colitis
• Blood nitro-blue tetrazolium reduction test positive Discontinuous (skip) Continuous
lesions involvement
IgA, immunoglobulin A; IgG, immunoglobulin G.
Bloody diarrhea Less common Common
Abdominal pain Common Less common
Box 6: Common infections and management of immuno Growth failure Common Less common
deficiency states Perianal disease Present Absent
• Common infections include: (abscess/fistulae)
{{ Viral: Cytomegalovirus, Herpes simplex, Adenovirus
Histopathology Noncaseating Widespread crypt
{{ Bacterial: Salmonella, Shigella, Mycobacterium avium complex
granuloma (any part architectural
(MAC), Campylobacter jejuni, Clostridium difficile of GI tract) distortion
{{ Fungal: candidiasis, histoplasmosis, cryptococcosis
Transmural Diffuse inflammatory
{{ Protozoa: Microsporidium, Isospora belli, Cryptosporidium,
involvement infiltrate
Entamoeba histolytica, Giardia lamblia, Cyclospora, Blastocystis
Focal discontinuous Basal plasmacytosis
hominis
{{ Parasites: strongyloides
crypt architectural
distortion
• Diagnosis:
{{ Serum immunoglobulin, B-cell and T-cell assays
Focal discontinuous Goblet cell depletion
{{ Colonic biopsies, duodenal fluid examination and multiple
chronic inflammation
stool samples for opportunistic infections (special stains, Focally enhancing Crypt abscess
polymerase chain reaction and fungus gastritis (stomach)
• Treatment: Pyloric gland Paneth cell
{{ Specific antimicrobials for the isolated organisms metaplasia (terminal metaplasia
{{ Acquired immunodeficiency syndrome: highly active anti ileum)
retroviral therapy (HAART) Endoscopy Deep irregular Diffuse superficial
{{ Common variable immunodeficiency: intravenous immuno
serpiginous or ulceration
globulin therapy 400–600 mg/kg every 3–4 weeks to maintain aphthous ulcers
serum immunoglobulin G levels >500–700 mg/dL
Normal intervening Granularity, loss of
mucosa (skip lesion) vascular pattern,
Surgery is indicated in UC patients with severe acute colitis friability
refractory to medical disease. Uncontrolled hemorrhage, Ileal involvement, Rectal involvement
perforation, toxic megacolon, abscesses, and obstruction are rectal sparing (60%) and ileal sparing
the other indications for surgery. Nearly 40% pediatric patients (unless back-wash
362 with UC require total colectomy within 5–10 years of diagnosis. ileitis)
Ch-77.indd 362 11/21/2016 9:53:06 AM

Table 3: Diagnostic modalities available for inflammatory bowel disease

Diagnostic modality Importance
Colonoscopy with ileal intubation Most important to differentiate ulcerative colitis vs. Crohn’s disease
Multiple biopsies from disease sites
Upper gastrointestinal endoscopy with biopsies To look for granulomas (40%)
Small bowel imaging For small bowel strictures fistula

Barium enteroclysis, CT or magnetic resonance enteroclysis Extramural complications may be seen in CT/MRI
MRI pelvis Fistula, pelvic and genitourinary abscess
Capsule endoscopy Ideal to evaluate small bowel involvement after excluding intestinal stricture
that may result in retention of capsule. Disadvantage: biopsies cannot be taken
Enteroscopy Limitation of not able to pass bigger diameter enteroscopes in younger
children
CT, computed tomography; MRI, magnetic resonance imaging.
Table 4: Drugs used in inflammatory bowel disease (first line therapy)

Drug Dosage and route Indication Main side effects
• Sulfasalazine or • 40–60 mg/kg/day oral • Anti-inflammatory (local action) in mild • Folate deficiency
ulcerative colitis and maintenance • Pancreatitis
• 5-aminosalicylic acid • 50–100 mg/kg/day • Enema in mild-to-moderate left-sided • Steven-Johnson syndrome
or mesalamine (active oral colonic disease • Hepatotoxicity
moiety of sulfasalazine) • Enema • Oligospermia (with sulfasalazine)
• Prednisolone • 1–2 mg/kg oral • Induction therapy (first line) in all types of • Cushingoid facies
inflammatory bowel disease • Hypertension
• Glaucoma
• Cataract
• Fractures
• Hyperglycemia
• Growth impairment
Thiopurines:
• Azathioprine • 2–3 mg/kg/day oral • Frequent relapses* • Myelosuppression
• 6-Mercaptopurine • 1–2 mg/kg/day oral • Steroid dependence# • Hepatotoxicity
(active moiety of • Steroid resistance† • Pancreatitis
azathioprine) • Maintenance in moderate-to-severe
disease
*Frequent relapses: 2–3 relapses per year.
#Steroid dependency: initial remission but recurrence while tapering or inability to stop steroids in 14–16 weeks of initiation.
†Steroid resistance: nonresponse to optimal doses of oral steroids within 7–14 days of initiation and good compliance.
Risk of adenocarcinoma colon is 8% after 20 years of disease in Diagnosis

pediatric UC.
• Definitive: demonstration of acid fast bacilli (fine needle
aspiration cytology from lymph nodes, ascitic fluid,
ABDOMINAL TUBERCULOSIS endoscopic biopsies) on Ziehl‒Neelson (ZN) staining
High index of suspicion for abdominal tuberculosis is to be or culture (BACTEC or Lowenstein-Jensen media). If
considered in any child with: adequate tissue is sampled and processed, a definitive
• Constitutional symptoms (prolonged fever, anorexia, and diagnosis is achievable in up to 64% of pediatric cases
weight loss) + any of the features in table 6 • Supportive: tubercular granuloma with caseation in the
• Contact with open case of tuberculosis (adult) biopsies (endoscopic/peritoneal/liver)
• Mantoux test positivity (≥5 mm in HIV and ≥10 mm in • In the absence of above features, a probable diagnosis of
non-HIV patients irrespective of age at 48–72 hours of abdominal tuberculosis is made when suggestive clinical
tuberculin injection) features and response to antitubercular therapy (ATT)
• Contributory laboratory features: high ESR, lymphocytosis. without relapse after completion of therapy is observed 363
Ch-77.indd 363 11/21/2016 9:53:06 AM

Table 5: Drugs used in inflammatory bowel disease (second line therapy)

Drug Dosage and route Indications Main side effects
• Methotrexate • 15 mg/m2 IM weekly • Steroid sparing • Hepatotoxicity

• Refractory disease and/or • Myelosuppression
intolerant to thiopurines • Folate deficiency
• Cyclosporine • 2–4 mg/kg/day IV infusion • Rescue therapy for maximum • Nephrotoxicity

followed by 5–8 mg/kg/day oral 4 weeks in severe refractory • Hypertrichosis
ulcerative colitis • Gum hyperplasia
• Tacrolimus • 0.1 mg/kg oral
• Hypertension
• Paraesthesia
• Biological • 5 mg/kg IV at 0, 2, 6 weeks and • Fistuling CD • Autoimmunity

agents thereafter need based • Severe disease not responding to • Demyelination
(infliximab, immunomodulators • Psychiatric problems
adalumimab)
• Flare infections (espc. tuberculosis)
• Hepatosplenic T-cell lymphoma
(in combination with azathioprine)
• Thalidomide • 1.5–2.5 mg/kg oral • Refractory CD and intolerant to • Irreversible peripheral neuropathy
biological agents (very selective • Agitation
group) • Hallucination
CD, Crohn’s disease; IM, intramuscular; IV, intravenous.
Table 6: Presentation and specific workup in abdominal tuberculosis

Involvement Features Tissue sampling and specific workup (laboratory and
abdominal imaging)
Peritoneum • Dry: adhesive intestinal obstruction lump (cocoon abdomen) • Peritoneoscopy/laparoscopy: peritoneal tubercules
• Wet: exudative ± loculated ascites • Ascitic fluid: lymphocytosis with high adenosine
• “Doughy” feel of abdomen deaminase
Lymph nodes • Lump (lymph nodal mass) • Fine needle aspiration from necrotic, enlarged
(>10 mm) and/or calcified, conglomerate lymph nodes
Gastrointestinal • Ulcerative: abdominal pain, GI bleed, anemia • Features on colonoscopy*
tract (luminal) • Hypertrophic: Intestinal obstruction • Colonic and ileal biopsies by endoscopy#
• Ulcerohypertrophic: Combination of above 18–64% present • Laparotomy and surgical biopsy of small bowel
as chronic diarrhea or colitis
Hepatic • Systemic symptoms with hepatomegaly • Raised serum alkaline phosphatase
• Non-resolving liver abscess • Multiple hypodense ± calcified foci in liver
Combination • Nodal ± peritoneal ± GI • Tissue sampling and workup as above
Disseminated • Abdominal + other organs (lungs, peripheral LN, bone
marrow)
*Ab.TB is a close differential of Crohn’s disease. Some major endoscopic features (though not discriminatory) may favor Ab.TB:
• Segmental involvement (as compared to skip areas in CD)
• Deep circular transverse ulcers (as compared to deep linear serpiginous ulcers in CD)
• Short colonic strictures (as compared to multiple long strictures in CD).
#Due to significant overlap between the two diseases, all biopsy specimens should be simultaneously sent for histopathology, ZN staining, TB culture and TB-PCR
(polymerase chain reaction). Culture positivity may be seen despite initial ZN stain negativity. Tissue TB-PCR (nested or real time) has high specificity (98%) but lower
sensitivity (68–75%).
• Due to emergence of multidrug resistance tuberculosis

Treatment
(MDR-TB) and delay in obtaining culture sensitivity, World
Health Organization recommends “Line Probe Assay” Antitubercular drugs are the mainstay of treatment of
from all acid fast bacilli positive tissue samples (ZN stain or abdominal tuberculosis as per the current pediatric guidelines
culture). Line probe assay provides drug sensitivity within in India. Surgery is indicated if there is bowel perforation,
364 6 hours and differentiates Mycobacterium tuberculosis obstruction, or massive hemorrhage. It is important to
from nontubercular Mycobacteria. differentiate intestinal tuberculosis from Crohn’s disease
Ch-77.indd 364 11/21/2016 9:53:06 AM

as they mimic each other in clinical presentation but have SUGGESTED READINGs
different treatment. One should also suspect MDR-TB in
patients with a definite diagnosis of abdominal tuberculosis 1. Al Sinani S, Rawahi YA, Abdoon H. Octreotide in Hennekam syndrome-associated
intestinal lymphangiectasia. World J Gastroenterol. 2012;18:6333-7.
but a poor response to standard ATT. Multidrug resistance
2. Baldassano RN, Piccoli DA. Inflammatory bowel disease in pediatric and
tuberculosis presents mostly as refractory lymph nodal
adolescent patients. Gastroenterol Clin North Am. 1999;28:445-58.
masses in the abdomen with close differential diagnosis of 3. Husby S. For ESPGHAN Working Group on Coeliac Disease. European Society for
non-Hodgkin’s lymphoma. Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis
of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54:136-60.
Clinical Pearls 4. Kumar A, Gupta D, Nagaraja SB, Singh V, Sethi GR, Prasad J, et al. Updated
National Guidelines for Pediatric Tuberculosis in India, 2012. Indian Pediatr.
• Small bowel diarrhea 2013;50:301-6.
{{ Small bowel diarrhea + anemia and rickets: think of celiac 5. Lee HS, Park KU, Park JO, Chang HE, Song J, Choe G, et al. Rapid, sensitive,
disease and specific detection of M. tuberculosis complex by real-time PCR on paraffin-
{{ Small bowel diarrhea + predominant edema without embedded human tissues. J Mol Diagn. 2011;13:390-4.
anemia: think of intestinal lymphangiectasia 6. Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris GJ, et al.
{{ Small bowel diarrhea + recurrent infections: think of
European Consensus on the histopathology of inflammatory bowel disease.
J Crohns Colitis. 2013;7:827-51.
immunodeficiency
7. Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, et al. Consensus
{{ Abdominal tuberculosis rarely presents as small bowel
guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s
diarrhea disease. J Crohns Colitis. 2014;8(10):1179-207.
{{ In celiac disease, do not start gluten-free diet without
8. Sabery N, Bass D. Use of serologic markers as a screening tool in inflammatory
confirmation of diagnosis (serology + histopathology) bowel disease compared with elevated erythrocyte sedimentation rate and
• Large bowel diarrhea anemia. Pediatrics. 2007;119:e193-9.
{{ Large bowel diarrhea in an older child: think of inflammatory 9. Sandhu BK, Fell JM, Beattie RM, Mitton SG, Wilson DC, Jenkins H; on Behalf
bowel disease and tuberculosis of the IBD Working Group of the British Society of Paediatric Gastroenterology,
{{ Workup for both should be sent together as they may mimic
Hepatology, and Nutrition. Guidelines for the Management of Inflammatory
Bowel Disease in Children in the United Kingdom. J Pediatr Gastroenterol Nutr.
each other
2010;50:S1-13.
{{ Necrotic or calcified lymph node in chest or abdomen and
10. Sari S, Baris Z, Dalgic B. Primary intestinal lymphangiectasia in children: Is
exudative ascites is specific for tuberculosis octreotide an effective and safe option in the treatment? J Pediatr Gastroenterol
{{ Attempt to obtain tissue diagnosis in abdominal tuberculosis
Nutr. 2010;51:454-7.
before starting antitubercular therapy. 11. Sauer CG, Kugathasan S. Pediatric inflammatory bowel disease: highlighting
pediatric differences in IBD. Med Clin North Am. 2010;94:35-52.
12. Sawczenko A, Sandhu BK. Presenting features of inflammatory bowel disease in
Great Britain and Ireland. Arch Dis Child. 2003;88:995-1000.
Key points
13. Thapa BR, Yachha SK, Mehta S. Abdominal tuberculosis. Indian Pediatr.
))
Differentiating small from large bowel diarrhea, mal 1991;28:1093-100.
absorption from maldigestion clinically provides a clue to 14. Turner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dignass A, et al.
diagnosis Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-
based consensus guidelines. J Pediatr Gastroenterol Nutr. 2012;55:340-61.
))
Common causes of chronic small bowel diarrhea in children
15. Van Limbergen J, Russell RK, Drummond HE, Aldhous MC, Round NK, Nimmo ER,
above 3 years of age are celiac disease (in North India),
et al. Definition of phenotypic characteristics of childhood-onset inflammatory
giardiasis, intestinal lymphangiectasia, and immunodeficiency bowel disease. Gastroenterology. 2008;135:1114-22.
))
Celiac disease and lymphangiectasia require life-time 16. Walker Smith JA. For working group of European Society of Pediatric
therapy whereas giardiasis and opportunistic infections in Gastroenterology and Nutrition. Revised criteria for diagnosis of celiac disease.
immunodeficiency states require antimicrobials. Immuno Report of Working group of ESPGHAN. Arch Dis Child. 1990;65:909-11.
deficiency needs to be treated as per cause 17. Malik R, Srivastava A, Yachha SK, Poddar U, Lal R. Childhood abdominal
))
Common causes of small bowel diarrhea in children above tuberculosis: Disease patterns, diagnosis, and drug resistance. Indian J
3 years of age are abdominal tuberculosis and inflammatory Gastroenterol. 2015 Nov;34(6):418-25
bowel disease (IBD) 18. Yachha SK, Poddar U. Celiac disease in India. Indian J Gastroenterol. 2007;
))
Antitubercular therapy is the mainstay of therapy in 26:230-7.
abdominal tuberculosis. Multidrug resistance tuberculosis
(MDR-TB) should be considered if there is nonresponse and
acid fast bacilli is positive in tissue. Usually, abdominal MDR-TB
presents as large abdominal lymph nodal masses
))
Immunosuppression is the mainstay of treatment in IBD. Only
a small proportion requires surgeries in select situations.
365
Ch-77.indd 365 11/21/2016 9:53:06 AM

CHAPTER 78
Approach to Upper
Gastrointestinal Bleed in Children
Anshu Srivastava
INTRODUCTION etiology after a diagnostic esophagogastroduodenoscopy and

colonoscopy. It accounts for ~5% of all gastrointestinal bleeds
Upper gastrointestinal bleeding (UGIB) is a commonly and is classified into two types:
encountered problem in children that usually manifests 1. Occult OGIB: presents as stool occult blood positivity and
as hematemesis or melena. The incidence in pediatric iron deficiency anemia
intensive care unit (ICU) is reported to vary from 6 to 25% and 2. Overt OGIB: presents as visible blood in stool and/or
approximately 5% of UGI endoscopies in children are done vomitus.
for UGIB. Although less than 1% of UGIB is life threatening,
medical attention is sought early in majority due to its alarming Approach: a detailed history, followed by physical examination,
nature and this helps in prompt diagnosis and management. is helpful in determining the most probable cause of UGIB.
Children tolerate UGIB better than adults due to absence of Management includes simultaneous stabili zation of child
systemic comorbidities but are at greater risk of developing and determination of etiology of UGIB, followed by definitive
shock due to their smaller blood volumes. Approach to a child therapy (Algorithm 1).
with UGIB is discussed in this chapter. • The first question is if the hematemesis and/or melena is
due to blood or not, especially in an otherwise healthy child
{{ The food items looking like blood in vomitus are shown
DEFINITIONS
in box 1
Upper gastrointestinal bleeding: this denotes bleeding from {{ An Apt-Downey test is used to differentiate the
a site in the gastrointestinal tract above the ligament of Trietz swallowed maternal blood from hematemesis in a
(esophagus to duodenojejunal flexure). neonate
{{ Box 2 shows ingested items which may present as
The common terms used to describe UGIB are as follows:
melena. The differentiation is made by performing a
• Hematemesis is presence of bright red or altered coffee-
guaiac (detects “heme” component of hemoglobin)
ground blood in vomiting
or fecal immunochemical testing (detects “globin”
• Melena is passage of black, tarry, sticky stools with an
component of hemoglobin) in stool
offensive smell and suggests an UGI or small bowel site of
• The next step is to differentiate UGIB from epistaxis,
bleeding
oropharyngeal bleeding, and hemoptysis:
• Hematochezia is passage of bright red blood in stools and
{{ History of chronic cough and passage of bright red
is usually seen with bleeding in colon but very brisk UGIB
blood associated with sputum indicates toward
with fast gut transit may also present with hematochezia
hemoptysis
• Hemobilia refers to bleeding from the biliary tree and
{{ Nose and oropharynx should be examined to rule out
hemosuccus pancreaticus to bleeding from the pancreas.
other sites of bleed
In both these conditions, blood enters the duodenum
{{ It is important not to confuse onset of menarche with
from the common bile duct or pancreatic duct through the
melena
ampulla of vater.
{{ History of bleeding from multiple sites points
Obscure gastrointestinal bleeding (OGIB): bleeding from toward systemic causes like thrombocytopenia and
gastrointestinal tract that persists or recurs without any obvious coagulopathy.
CHAPTER 78: Approach to Upper Gastrointestinal Bleed in Children
ALGORITHM 1
Approach to a patient with acute upper gastrointestinal bleeding
*As per discussion in the text.

EVL, endoscopic variceal ligation; EST, endoscopic sclerotherapy; SB, Sangstaken Blakemore; TIPS, transjugular intrahepatic
portosystemic shunt; PPI, proton pump inhibitors.
Box 1: Causes of red colored vomitus (other than upper TABLE 1: Causes of upper gastrointestinal bleeding
gastrointestinal bleeding) Neonate/infant Child and adolescent
• Food items containing red food coloring (jelly, candies, Kool aid, Swallowed maternal blood Esophagitis—reflux, infections, pill
juices) Esophagitis Mallory–Weiss tear
• Tomatoes, strawberries, beetroot, cranberries
Gastritis, gastroduodenal Caustic ingestion
• Ingestion of maternal blood (in neonates) ulcer/erosion
Foreign body ingestion Foreign body
Box 2: Causes of melena like stools (other than upper Sepsis/coagulopathy/stress Portal hypertension—esophageal/
gastrointestinal bleeding) erosions gastric varices; congestive gastro
pathy; gastric antral vascular ectasia
• Food items: ingestion of spinach, licorice, grape juice
Cow’s milk protein allergy Gastritis, peptic ulcer (duodenal/
• Drugs: peptobismol (contain bismuth), Iron
gastric)
• Ingestion of maternal blood (in neonates)
Hemorrhagic disease of Arteriovenous malformation
newborn
The important causes of UGIB in children are given in Vascular malformation Henoch–Schönlein purpura,
table 1 and clues in history and physical examination toward Esophageal varices Crohn’s disease, stress/sepsis/
the likely cause are shown in table 2. coagulopathy related erosions
Upper gut duplication Tumors—leiomyoma, lymphoma
Clinical Pearl Uncommon: trauma Rare: gastrointestinal duplication,
(nasogastric tube), gastric hemobilia, radiation gastritis,
• Tests for occult blood are required to distinguish blood from cardia prolapse, heterotopic Munchausen’s syndrome by proxy
367
other similar appearing substances in vomitus and stool. pancreatic tissue
SECTION 10: Gastroenterology
TABLE 2: Clues in history and examination toward etiology of Upper gastrointestinal endoscopy is the investigation of
upper gastrointestinal bleeding choice both for diagnosing the cause and providing therapy.
It should preferably be done under general anesthesia or
Likely diagnosis Clinical signs/symptoms
conscious sedation with airway protection to avoid aspiration
Variceal • Painless significant bleed, similar episode in and only after the patient is hemodynamically stable. The
bleeding the past, splenomegaly, jaundice, ascites
yield of UGI endoscopy is best if it is done within 24 hours
Esophagitis • Presence of heart burn/regurgitation/ of onset of UGIB. A complete examination of esophagus,
dysphagia/odynophagia, placement of Ryle’s stomach, and duodenum with retroflexion to inspect the
tube, corrosive intake fundus and gastroesophageal junction is essential (Figs 1–3).
Mallory–Weiss • Repeated retching and vomiting followed by Biopsy should always be taken to look for helicobacter pylori
tear hematemesis in patients with gastric/duodenal ulcers.
Gastritis/ • History of drug ingestion like aspirin/non
erosions/ulcer steroidal anti-inflammatory drugs/steroids
• Epigastric pain
• Intensive care unit patient on mechanical
ventilation
• Family history of peptic ulcer disease
Vascular • Painless bleed, presence of hemangiomas at
malformation other sites
Cow’s milk • Introduction of animal milk, presence of
protein allergy diarrhea/eczema, family history of atopy
Munchausen’s • Complaints disproportionate to examination
syndrome by findings, absence of anemia, negative stool
proxy occult blood during active bleeding
MANAGEMENT
The management approach is as shown in algorithm 1.
Assessment of severity of bleed and hemodynamic status
should be done by measurement and monitoring of heart rate,
blood pressure, postural change in blood pressure and heart Fig. 1: Upper gastrointestinal endoscopy showing large esophageal
varices
rate, pulse volume, capillary refill time, oxygen saturation
(pulse oxymetry), and urine output.
Minor bleed has no effect on heart rate and blood pressure,
moderate bleed is associated with postural hypotension and
tachycardia whereas massive bleed is associated with shock
(defined in children as tachycardia with signs of decreased
organ or peripheral perfusion).
Presence of blood on nasogastric (NG) tube aspiration
confirms an UGI source of bleeding. However, absence of
blood on NG aspiration does not rule out an UGIB (duodenal
source or intermittent bleeding from stomach/esophagus). A
serum urea nitrogen to creatinine ratio above 30 also points
toward an upper gastrointestinal source of bleeding.
INVESTIGATIONS
Investigations are aimed at establishing the site, severity, and
cause of bleeding. Hematocrit (Hct) should be monitored
frequently to assess severity of blood loss as the hemoglobin
falls only after a few hours, after hemodilution. A complete
hemogram including platelet count, coagulation profile (PT/
APTT), liver function tests, urea, creatinine, electrolytes, and Fig. 2: Upper gastrointestinal endoscopy showing gastric varices
cross matching should be done in all patients at admission. with red color signs on retroversion
368
General supportive measures: a good venous access, intake

output monitoring, oxygen supplementation (if required), and
charting of vitals are mandatory. Blood transfusion should be
given to achieve hemoglobin of 7–8 g/dL. Coagulopathy and
thrombocytopenia are corrected by appropriate component
therapy (plasma, platelets, etc.) if required. Short-term
antibiotic prophylaxis (third generation cephalosporin for 7
days), should be given to children with cirrhosis and variceal
bleed as it reduces bacterial infection, variceal rebleeding
and death.
Specific treatment: the choice of treatment depends upon
the patient’s condition, available facilities, and expertise of
the personnel. Specific treatment can be broadly divided into
management of variceal and nonvariceal bleed.
Variceal Bleeding
In a child with portal hypertension, esophageal varices are
Fig. 3: Upper gastrointestinal endoscopy showing duodenal ulcer the most common cause of UGIB (Fig. 1). Gastric varices,
without signs of active bleeding congestive gastropathy and gastric antral vascular ectasia can
also present with hematemesis.
Somatostatin and octreotide: these drugs decrease the
The other investigations which help in reaching a diagnosis splanchnic and azygous blood flow, thus reducing the portal
are discussed below. pressure. Somatostatin and octreotide both are equally
Ultrasonography with Doppler provides information about effective. Limited studies in children have shown control
portal vein, hepatic veins, inferior vena cava, presence of of bleeding in 64–71% children. Overall, this therapy is well
collaterals, etc. and helps in diagnosis of portal hypertension tolerated with mild side effects like hyperglycemia, abdominal
[extra hepatic portal venous obstruction (EHPVO) and chronic discomfort, nausea, and diarrhea which often resolve
liver disease]. spontaneously. Infusion should be given for at least 24–48
hours after the bleeding has stopped to prevent recurrence and
Contrast enhanced computed tomography scan: this is
infusion should not be stopped abruptly. The doses are shown
useful in evaluation of patients with mass lesions, suspected
in table 3. Vasopressin, terlipressin, and nitroglycerine are
hemobilia or hemosuccus pancreaticus. Selective angiography
other drugs useful in management of variceal bleed but data
of celiac trunk is required in patients where a vascular lesion
are largely limited to adults.
like pseudoaneurysm is suspected. Therapy with coil/gel
embolization can be done at the time of angiography.
Nuclear scintigraphy (technetium 99m labeled Clinical Pearls
pertechnetate scan) is helpful in children suspected to have
• In patients with upper gastrointestinal endoscopy, transfusion
duplication cyst of proximal gastrointestinal tract.
should be given to achieve a hemoglobin of 7–8 g/dL
Enteroscopy (single/double balloon) is required in some
cases for evaluation of lesions in distal duodenum (third and • Antibiotic should be given to all patients with chronic liver
disease and variceal bleeding.
fourth part) if the etiology cannot be determined on standard
UGI endoscopy.
Endoscopic Therapy
Clinical Pearls
Esophageal varices: endoscopic variceal ligation (EVL) and
• Hematocrit should be monitored to assess severity of bleeding endoscopic sclerotherapy (EST) are the two main methods.
as hemoglobin falls later, after hemodilution. The varices are inspected and their location, size, and extent
• The yield of upper gastrointestinal endoscopy in patients with are documented with a fiber-optic endoscope. In EST, 2–3 mL
upper gastrointestinal endoscopy is maximum if done within of sclerosant (1% ethoxysclerol) is injected into each variceal
24 hours of onset of bleed. column. Endoscopic variceal ligation is done with a device
called multiple band ligator. The variceal column is sucked into
a cylinder attached at the tip of the endoscope and the band is
deployed by pulling the trip wire around the varix. Both EST
TREATMENT
and EVL have a 90–100% efficacy in controlling acute bleeding.
The treatment of a child with UGIB depends on the severity of The major complications include esophageal ulceration,
bleeding and has two main arms. stricture esophagus and rarely perforation. 369
TABLE 3: Drugs used to control upper gastrointestinal bleeding with 75–150 mL of air depending on the size of the patient
(stomach) and the tube is gently pulled outward so that it sits
Drugs for acid suppression
snugly against the fundus and gastroesophageal junction.
Antacids • 0.5–1.0 mL/kg q 4 h PO, titrate to keep gastric A plain X-ray of the abdomen is done to check the proper
pH >4
placement of gastric balloon in the stomach. If the bleeding
Ranitidine • PO 2–4 mg/kg/day q 8–12 h, max 10 mg/kg/d continues after inflation of gastric balloon then the esophageal
(300 mg) balloon is inflated. Esophageal necrosis and perforation,
• IV 2–4 mg/kg/day q 8–12 h pulmonary aspiration and rebleeding on deflation of balloon
Sucralfate • 0.5–1.0 g PO q 6 h are important complications. The esophageal balloon should
Proton pump • Omeprazole 0.7–3.3 mg/kg/day single or two be deflated after 12–24 hours, and in case of continued bleeding
inhibitors divided doses it can be reinflated. However, it should be remembered that
• Lansoprazole 15 mg/day if weight less than SBT is a temporary treatment and efforts should be done to
30 kg; 30 mg if weight more than 30 kg arrange for endoscopic therapy at the earliest.
• Esomeprazole 10 mg/day if weight <20 kg;
20 mg if weight >20 kg Transjugular intrahepatic portosystemic shunt (TIPS): it is
• Proton pump inhibitors infusion for ulcer indicated in patients where the variceal bleeding cannot be
bleed-intravenous pantoprazole 2 mg/kg controlled by medical and endoscopic measures. The TIPS can
(max 80 mg) loading followed by 0.2 mg/kg/h be done in cirrhotic patients with a patent splenoportal axis.
infusion (max 8 mg/h) It is not feasible in patients with EHPVO due to thrombosed
Drugs for variceal bleeding portal vein. It involves insertion of a multipurpose catheter
through the jugular vein and superior vena cava. The catheter
Vasopressin • Start at 0.002–0.005 U/kg/min, increase to a
max dose of 0.01/U/kg/min is thereafter passed via hepatic vein into a branch of portal vein
through the hepatic parenchyma. The passage is dilated by a
Octreotide • 1 μg/kg bolus and then 1 μg/kg/h infusion,
balloon and an expansile metallic mesh prosthesis is placed
max 5 μg/kg/h
to maintain the communication directly between the portal
Somatostatin* • 250 μg bolus and then 250 μg/h infusion in vein and hepatic vein. This procedure results in bypassing liver
adults
resistance and consequently decreases the portal pressure.
Terlipressin* • 2 mg every 4 h IV for 24–48 h, then 1 mg every Experience in children is limited with an overall success rate is
4 h in adults approximately 75–85%.
PO, per os; IV, intravenous.
Surgical Management
Endoscopic variceal ligation is preferred over EST due to
Emergency surgery is required when all the other therapeutic
lesser side effects and quicker eradication with less number of
measures have failed or when bleeding is from ectopic varices
sessions. However, EVL cannot be done in children less than
that cannot be effectively controlled by endoscopic procedures.
2–3 years due to technical reasons and in them EST is the only
Surgery can be done either in the form of portocaval
option.
shunt (selective or nonselective) or devascularization with
Gastric varices: endoscopic injection of tissue adhesive glue, esophageal staple transection.
i.e., N-butyl-2-cyanoacrylate or isobutyl-2-cyanoacrylate is Acute variceal bleeding (AVB) is a serious and life-
used for gastric varices (Fig. 2). These agents harden within threatening complication of patients with portal hypertension.
20 seconds of contact with blood, and lead to a more rapid Standard of care mandates early administration of vasoactive
control of active bleeding. Only a small volume (0.5–1 mL) of drugs followed by endoscopic therapy preferably within 12
glue is injected at a time and multiple injections can be done hours of bleed. Balloon tamponade followed by TIPS or surgery
in a single session. Appropriate care must be taken to avoid may be done in patients who fail endoscopic and drug therapy.
damage to the endoscope during glue injection. The role of All patients surviving an episode of AVB should undergo further
Balloon-occluded retrograde transvenous obliteration in the secondary prophylaxis with EST/EVL to prevent rebleeding.
management of acute gastric varices bleeding is promising but
merits further evaluation. Nonvariceal Bleeding
Tamponade of varices: this is required only when the The etiology of nonvariceal UGIB is diverse and management
endoscopic and pharmacologic measures have failed. largely depends on the cause.
Sangstaken‒Blakemore tube (SBT) is a triple lumen tube with
connection to an esophageal balloon, a gastric balloon and Pharmacological Therapy
one perforated distal end which helps in aspiration of the Proton pump inhibitors (PPI) promote clot stability and
stomach contents. The SBT is relatively cheap, requires little facilitate hemostasis by raising the intragastric pH. Proton
skill vis-à-vis EST and has efficacy of above 75% in controlling pump inhibitors infusion should be initiated in any patient
acute variceal bleeding. Both pediatric and adult size SBTs are suspected to have nonvariceal bleeding from the upper
available. The tube is passed through the nose and allowed to gastrointestinal tract as it reduces both the incidence of high-
370 reach the stomach. Thereafter, the gastric balloon is inflated risk stigmata of hemorrhage on endoscopy [37.2 vs. 46.5%;
odds ratio (OR) 0.67, 95% confidence interval (CI) 0.54–0.84) PREVENTION
and the need for endoscopic hemostasis (8.6 vs. 11.7%; OR
0.68, 0.50–0.93). • Stress ulcers, erosions of the stomach and duodenum are
Drugs like NSAID/aspirin/anticoagulants should be well-known complications of critical illness in children
stopped as far as possible in patients with UGIB. admitted to the pediatric intensive care unit (Fig. 3).
Nearly 10% of PICU subjects have UGIB but it is clinically
Specific therapy: antifungal (fluconazole) in esophageal significant only in less than 2% cases. Children with
candidiasis and specific antiviral therapy (acyclovir/gancylovir) coagulopathy, respiratory failure, and high pediatric risk
in esophagitis due to herpes/cytomegalovirus infection is of mortality score >10 are at an increased risk of bleeding.
essential. Although literature is limited, pooled data from two
Helicobacter pylori infection should be looked for and randomized controlled trials shows that prophylactic acid
treated in all patients with bleeding peptic ulcers. The high neutralizing treatment was significantly more effective in
false-negative rate for H. pylori testing in the setting of acute preventing UGIB compared with no treatment (two studies
UGIB should be remembered. Triple therapy [PPI plus two = 300 participants; relative risk, 0.41; 95% CI 0.19–0.91)
of the three antibiotics (amoxicillin, clarithromycin, and • Secondary prophylaxis for variceal bleeding by EST/EVL as
metronidazole)] for 7–10 days is the treatment of choice. discussed above
Dietary changes: stoppage of milk and milk products is • H. pylori eradication therapy to prevent recurrence of
required for infants with UGIB due to cow’s milk allergy. peptic ulcer. Eradication should be ensured by repeat
testing.
Endoscopic Therapy
An early (within 12–24 h) and meticulous UGI endoscopy done CONCLUSION
after resuscitation of the patient is essential both for finding the
cause of NVB and offering therapy. Blood coming from papilla Acute UGIB is a potentially serious problem in children and
at endoscopy suggests hemobilia or hemosuccus pancreaticus. presents with hematemesis or melena. As the causes of UGIB
Pre-endoscopy administration of prokinetic is beneficial vary with age, it is important to evaluate children for the age
in patients at risk of having blood obscuring endoscopic specific etiologies. Esophagitis, gastritis, and varices are the
visualization. most common causes of UGIB in Indian children with peptic
Endoscopic biopsies are taken to diagnose H. pylori ulcer disease being uncommon. The approach to diagnosis is
infection in patients with ulcer disease and in those with largely dictated by the child’s condition. Prompt hemodynamic
esophagitis/gastritis. Endoscopic treatment is effective in stabilization is of utmost importance and physical examination
patients with focal sites of bleeding and involves injection and blood investigations are done simultaneously. Upper
(adrenaline or hypertonic saline), electrocoagulation, heater gastrointestinal endoscopy is the most useful diagnostic
probes, and hemoclips application. and therapeutic tool for children presenting with UGIB.
Medications like octreotide and PPI are useful in variceal and
Peptic ulcer bleeding: endoscopic hemostasis using thermal or
ulcer bleed respectively with surgery being reserved for cases
mechanical therapies alone or in combination with injection
with continued bleed and failure of endoscopic therapy.
should be done in all patients with high-risk ulcers [Forrest
Ia (active spurting bleeding), Ib (active oozing bleeding), IIa
(nonbleeding visible vessel), and IIb (adherent clot)].
KEY POINTS
The intravenous PPI infusion should be continued for
72 hours as it has been shown to decrease rebleeding, need for ))
Upper gastrointestinal bleeding (UGIB) is a common emergency
surgery and also mortality. Patients who have hemodynamic in children and presents as hematemesis or melena
instability, active bleeding at endoscopy, ulcer size over 2 ))
Urgent upper gastrointestinal endoscopy should be done
cm, ulcer located in high lesser gastric curvature or posterior after hemodynamic resuscitation to evaluate the cause of
duodenum, hemoglobin level less than 10 g/dL, and need bleeding and provide endoscopic therapy
for transfusion are at a higher risk of having rebleeding after ))
In patients with variceal bleeding (esophageal or gastric):
endoscopic hemostasis. The therapeutic options for patients
––
Octreotide infusion should be started at admission
with postendotherapy rebleeding include repeat endoscopic
hemostasis, transcatheter arterial embolization of the bleeding
––
Blood transfusion should be given to target a hemoglobin of
~8 g/dL
vessel and surgery.
––
Antibiotic should be given in patients with chronic liver disease
and variceal bleeding
Clinical Pearls
))
Proton pump inhibitor infusion followed by oral therapy should
• Intravenous octreotide and proton pump inhibitors infusion be given in patients with UGIB due to peptic ulcer disease
should be given to all patients with upper gastrointestinal ))
Specific therapy according to the etiology of UGIB is essential
bleeding due to varices and peptic ulcer, respectively to improve patient outcome
• Endotherapy (endoscopic variceal ligation/endoscopic sclero ))
Surgery is recommended for children with UGIB and failed
therapy) is the main stay for management of variceal bleeding. medical and endoscopic therapy. 371
SUGGESTED READINGS 6. Jorge L. Herrera. Management of acute variceal bleeding. Clinics Liver Disease.
2014;18:347-57.
1. de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno 7. Khamaysi I, Gralnek IM. Acute upper gastrointestinal bleeding (UGIB)—initial evaluation
IV Consensus Workshop on methodology of diagnosis and therapy in portal and management. Best Pract Res Clin Gastroenterol. 2013;27:633-8.
hypertension. J Hepatology. 2005;43:167-76. 8. Kim SJ, Kim KM. Recent trends in the endoscopic management of variceal bleeding
2. Eroglu Y, Emerick KM, Whitingon PF, Alonso EM. Octreotide therapy for control of in children. Pediatr Gastroenterol Hepatol Nutr. 2013;16:1-9.
acute gastrointestinal bleeding in children. J Pediatr Gastroenterol Nutr. 2004;38:41- 9. Molleston JP. Variceal bleeding in children. J Pediatr Gastroenterol Nutr.
7. 2003;37:538-45.
3. Franciosi JP, Fiorino K, Ruchelli E. Changing indications for upper endoscopy in 10. Reveiz L, Guerrero-Lozano R, Camacho A, Yara L, Mosquera PA. Stress ulcer, gastritis,
children during a 20-year period. J Peadiatr Gastroenterol Nutr. 2010;51:443-7. and gastrointestinal bleeding prophylaxis in critically ill pediatric patients: a
4. Garcia–Pagán JC, Barrufet M, Cardenas A, Escorsell A. Management of gastric varices. systematic review. Pediatr Crit Care Med. 2010;11:124-32.
Clin Gastroenterol Hepatol. 2014;12:919-28. 11. The Harriet Lane Handbook, 6th edition. Mosby (An Imprint of Elsevier); 2002.
5. Hegade VS, Sood R, Mohammed N, Moreea S. Modern management of acute non- 12. Yachha SK, Khanduri A, Sharma BC, Kumar M. Gastrointestinal bleeding in children.
variceal upper gastrointestinal bleeding. Postgrad Med J. 2013;89:591-8. J Gastroenterol Hepatol. 1996;11:903-7.
372
CHAPTER 79
Management of
Lower Gastrointestinal Bleed
Malathi Sathiyasekaran
DEFINITION INCIDENCE
Lower gastrointestinal bleed (LGIB) indicates bleeding from Lower gastrointestinal bleeding in infants and children is
sites distal to the ligament of Trietz presenting as bleeding per common in clinical practice yet its epidemiology has not been
rectum (PR). well studied. In an emergency department in Boston, United
The introduction of capsule endoscopy and double balloon States, rectal bleeding was the prime complaint in 0.3% of more
enteroscopy in the diagnostic armamentarium of LGIB has than 40,000 patients with life-threatening bleed occurring in
given rise to a new term midgastrointestinal bleeding (MGIB) 4.2%, three of whom had ileocolic intussusception and one
for a bleed occurring anywhere distal to the ampulla of Vater Meckel’s diverticulum.
and up to the ileocecal valve. In this article, both small bowel
bleed (MGIB) and colonic bleed have been included in the
discussion.
ETIOLOGY
The common causes of LGIB in children depend on the age of
presentation. In this article, the neonatal causes of LGIB have
TYPES OF BLEED
not been included. The causes of LGIB are:
Lower gastrointestinal bleed may be overt or occult. Overt 1. Gastrointestinal (Table 1)
bleeding can be acute massive or chronic intermittent and can 2. Hematological: bleeding disorders, coagulation defects,
present as hematochezia (passage of frank blood per rectum), DIC, thrombocytopenia (dengue, idiopathic thrombo
melena or streaks of blood. Occult bleeding is not clinically cytopenia purpura)
apparent but becomes manifest by laboratory evidence of 3. Vasculitic disorders: Henoch‒Schönlein purpura
iron deficiency or chemical evidence of blood in the stool. 4. Connective tissue disorders: Ehlers-Danlos syndrome and
Obscure gastrointestinal bleeding refers to a bleed where the Cutis laxa
bleeding site is not obvious even after evaluation by upper 5. Factitious: various coloring agents, jelly, beetroot, and
gastrointestinal endoscopy, an ileocolonoscopy, or a contrast drugs such as phenolphthalein or rifampicin can color the
radiological study of the small intestine. stool.
TABLE 1: Gastrointestinal causes

1 month to 2 years 2 to 12 years 12–18 years
Anal fissure Anal fissure Anal fissure
Cow’s milk protein allergy Juvenile polyp Infection colitis
Infectious/Allergic colitis Infectious colitis Inflammatory bowel disease
Lymphonodular hyperplasia Inflammatory bowel disease Solitary rectal ulcer
Meckel’s diverticulum Solitary rectal ulcer Colonic polyp
Intussusception Intussusception Hemorrhoids
Volvulus Intestinal duplication Intestinal duplication
Segmental enteritis Segmental enteritis Segmental enteritis
Vascular malformations Vascular malformations Vascular malformations
MANAGEMENT OF LOWER • A family history of bleeding PR requiring surgical

GASTROINTESTINAL BLEED intervention polyposis coli may be a possibility
• Failure to thrive, recurrent infections with bleeding PR may
point to immune deficiencies either congenital or human
Clinical Evaluation immunodeficiency virus related
A focused yet detailed history and physical examination are • History of ingestion of beet or coloring agents suggests
essential in the evaluation of all children with LGIB. factitious bleed
• History of recurrent petechiae, ecchymosis, or epistaxis
History in addition to bleeding PR may suggest a hematological
A meticulous history including details such as whether disorder
bleed is major or minor, chronic recurrent or acute massive, • Abdominal pain, diarrhea, loss of weight, pedal edema,
treatment, and associated symptoms. Details of the bleed such and fever suggests inflammatory bowel disease (IBD)
as duration, number of episodes, frequency, volume, color, • History of abdominal pain, bleeding PR with rash on legs
presence of clots, mucus, frank bleed, or mixed with feces and gluteal region suggests Henoch‒Schönlein purpura
should be obtained. History will help in establishing the site • History of fever, rash, features of third spacing, and bleeding
and probable etiology. PR consider dengue fever
Site of bleed: 10% of UGIB may present with bleeding PR. • Cutaneous hemangioma and bleeding PR suspect blue
Hematemesis is suggestive of UGIB. Similarly, melena is more rubber bleb nevus syndrome (Fig. 1)
often seen in UGIB, whereas hematochezia is usually from • Family history of bleeding PR, buccal pigmentation
small bowel or colon. Specks or streaks of bright red blood consider Peutz Jegher’s syndrome (Fig. 2)
indicate bleed from anorectal region. • Telengiectasia on fingers and lips with bleeding PR
consider hereditary hemorrhagic telangiectasia
Etiology: acute massive bleed may be due to Meckel’s
diverticulum, intestinal duplication, or arteriovenous
malformation. Eliciting certain associated symptoms in the
history help in determining the etiology of LGIB:
• Crampy abdominal pain and frequent loose stools mixed
with mucus and blood suggest an infectious, inflammatory,
or ischemic pathology
• Painless bleeding is more typical of a colonic polyp,
Meckel’s diverticulum, ulcerated duplication, or vascular
malformation
• Painful defecation with streaks of blood suggests anal
fissure
• Colicky abdominal pain, vomiting, red currant jelly stool,
and mass abdomen are suggestive of intussusception
• Constipation, mucorrhea, small rectal bleed, with or
without digital evacuation, and rectal prolapse may suggest
Fig. 1: Bluish black hemangiomas on the sole and hemangiomas on
solitary rectal ulcer syndrome (SRUS) colonoscopy (blue rubber bleb nevus syndrome)
• Recent antibiotic administration followed by passage
of blood and mucus in stools would indicate antibiotic
associated colitis or pseudomembranous colitis
• An infant with stools mixed with blood following
introduction of bovine milk protein one should suspect
Cow’s milk protein allergy
• An infant of normal weight on breast milk with blood in the
stool may have benign allergic proctocolitis due to transfer
of allergen through breast milk
• Passage of large volume, maroon or bright red blood
requiring blood transfusions suspect Meckel’s diverticulum,
intestinal duplication, or arteriovenous malformation
• Mass prolapsing per rectum with bleeding could be due to
a prolapsing polyp, prolapse rectum, or an intussusceptum
vascular. A polyp is globular and prolapses soon after
defecation, a prolapse is circumferential with a central
lumen whereas in intussusception severe pain is a Fig. 2: Oral buccal mucosal pigmentation and colonic polyps (Peutz
characteristic feature Jegher’s syndrome)
374
CHAPTER 79: Management of Lower Gastrointestinal Bleed
Examination Stool examination: a simple macroscopic examination of the

General: in children with acute lower gastrointestinal bleed stool is essential before considering sophisticated investigations.
whether major or minor a complete examination including Microscopic examination: if the stools show more than 10 pus
vital signs is necessary. cells/HPF it may indicate an invasive form of colitis. Presence
Skin: examination of the skin for petechia, ecchymosis, palpable of numerous eosinophils would suggest an allergic colitis
purpura (Figs 3 and 4) and hemangiomas, buccal pigmentation, or cow’s milk protein allergy. The presence of trophozoites
and café au lait spots to exclude familial syndromes. with hemophagocytosis would be diagnostic of Entamoeba
histolytica infection. If the clinical setting is suggestive of
Abdomen: Splenomegaly may indicate portal hypertension. infectious colitis then stool culture for Shigella, Salmonella,
Right upper quadrant mass may indicate intussusception. and Campylobacter jejuni may be helpful. Occult bleeding is
Distended abdomen with dilated bowel loops suggests intestinal identified by testing stool for occult blood.
obstruction, volvulus, gangrene, or segmental enteritis.
Radiology: plain X-ray abdomen is done when there is
Perianal examination: the presence of skin tags, perianal fistula pain, bilious vomiting, or features of intermittent intestinal
or fissure may be markers of IBD. obstruction. Ultrasonography can detect bowel wall thickening
pseudokidney appearance or identify characteristic features
Investigations of intussusception such as target sign (Fig. 5). Air contrast or
Laboratory studies: basic investigations such as hemoglobin, saline contrast enema helps not only to confirm but also treat
total and differential white blood cell count, platelet, bleeding ileocolonic intussusception. Computerized tomography or
time, clotting time, and prothrombin time are included in the magnetic resonance angiography is generally reserved for
investigative panel. Refractory iron deficiency anemia is an evaluation of mass lesions or complex vascular anomalies.
important manifestation of occult gastrointestinal bleed and Endosonography helps in the visualization of submucosal
should be evaluated diligently. lesions and arteriovenous malformations.
Radionuclide studies: scintigraphy is useful in the evaluation
of children with obscure but active LGI bleed of at least 0.1 mL/
minute. In young children with acute massive bleed if Meckel’s
diverticulum or duplication cyst is suspected radionuclide
studies may be done even prior to endoscopy. Radionuclide
study using technetium-99m (Tc99m) pertechnetate helps to
identify ectopic gastric mucosa within a Meckel’s diverticulum
or a duplication cyst with a sensitivity of 85%, specificity 95%.
Technetium-labeled red blood cells identifies arteriovenous
malformations and bleeding ulcers.
Endoscopy: when the bleed is chronic and intermittent
ileocolonoscopy is preferred as the first line of investigation.
Upper gastrointestinal endoscopy should always be done along
with ileocolonoscopy since 10% of upper gastrointestinal bleed
can present as bleeding per rectum.
Fig. 3: Infant with dengue and thrombocytopenia with ecchymosis
both ankles
Fig. 4: Palpable Henoch-Schonlein purpura Fig. 5: Abdominal ultrasound showing target sign “intussusception” 375
Ileocolonoscopy: early colonoscopy helps both in diagnosis

and therapy of mucosal lesions of the colon. The overall yield
ranges from 69 to 80%. Bowel preparation is safely achieved in
children using a standard oral polyethylene-glycol electrolyte
solution. Ileocolonoscopy helps both in the diagnosis and
therapy of LGIB. The majority of mucosal lesions, such as
allergic colitis, polyps, solitary rectal ulcer, IBD, vascular
malformations, rectal varices, portal colopathy (Figs 6–12),
can be diagnosed. Biopsy of the mucosal lesions will help in
confirming the etiology.
Additional Procedures
The above investigations will suffice to identify the source of
bleeding in the majority of children with LGIB. However, in
a small percentage (3–5%), the source will remain obscure
necessitating small bowel examination, either with triple
vessel arteriography, small bowel enema, magnetic resonance Fig. 8: Colonic polyp
enteroclysis, enteroscopy, or intraoperative enteroscopy.
Fig. 6: Solitary rectal ulcer Fig. 9: Ano fissure
376 Fig. 7: Rectal varices Fig. 10: Irregular colonic ulcer: Crohn’s disease
Impaction of the capsule may occur if there is an underlying

stricture
Intraoperative Enteroscopy
In this procedure, both surgeon and endoscopist work as a team
in the evaluation of a child with LGIB. A pediatric colonoscope
or enteroscope can be negotiated through an operative
enterotomy and the small bowel visualized. It helps in detecting
the majority more than 85% of obscure small bowel bleeding
lesions. The surgeon guides the intestine over the scope and
examines the outer serosa by palpation and transillumination
while the endoscopist examines the inner mucosa.
Diagnostic Laparoscopy/Laparotomy
In children with recurrent gastrointestinal bleed, and if
investigations are futile, it may be worthwhile performing
Fig. 11: Severe ulcerative colitis a diagnostic laparoscopy to identify lesions such as enteric
duplication cyst.
Management
The management of lower GI bleed includes prompt resusci
tative measures and treatment of the specific condition by five
distinct modalities such as diet modification, medications,
endotherapy, radiological intervention, and surgery.
Diet
• Cow’s-milk protein allergy (CMPA): avoidance of bovine
milk protein and milk products till the age of 9 months to
1 year is recommended for all infants diagnosed as having
significant CMPA. Majority will be able to tolerate cow’s
milk protein by the age of 3–5 years
• Fissure in ano and solitary rectal ulcer syndrome (SRUS):
introduction of fruits and vegetables to increase bulk and
fiber will benefit children with LGIB due to fissure in ano
Fig. 12: Nodular lymphoid hyperplasia cow’s-milk protein allergy or SRUS.
Medications
Triple Arteriography • Bacillary dysentery: in India, the recommendation is to
consider infectious colitis as Shigella colitis and treat with
This is rarely necessary in children with LGIB. It is, however, oral cefixime 10 mg/kg/day for 7 days if child is ambulant
useful in obscure small bowel bleed if there is active bleeding and with intravenous ceftriaxone 100 mg/kg for those
of at least 0.5 mL/minute. The advantage of arteriography is hospitalized
that it helps both in localization and embolization of the lesion. • Amoebic colitis: routine antiamebic medication
should not be prescribed for children with acute colitis.
Double Balloon Enteroscopy Metronidazole 10 mg/kg/day thrice a day for 5 days
This procedure helps in visualizing the entire small bowel is given only if trophozoite with hemophagocytosis
up to the ileocecal valve. It is not regularly used in pediatrics suggestive of Entamoeba histolytica is identified or in
but may be warranted in older children and adolescents with spite of two antibiotics which are known to be sensitive
obscure LGIB. for Shigella in that region have been administered and the
child has persistence of symptoms
Capsule Endoscopy • Ulcer bleeds: proton pump inhibitors like omeprazole
Children more than 5 years of age can swallow the capsule at a dose of 0.7 to 1 mg/kg/day or H2 blockers, such as
but in younger children, it can be introduced endoscopically. ranitidine at a dose of 4–6 mg/kg/day, can be administered
Capsule endoscopy is an excellent modality for identifying or orally if the bleed is secondary to duodenal ulcer, gastric
obscure gastrointestinal bleed. The detection rate is higher ulcer, or nonsteroidal anti-inflammatory drugs induced
(87–92%) if the procedure is done during active bleed. gastrointestinal injury. Proton pump inhibitors score over 377
ranitidine in controlling ulcer bleeds and is recommended • Anal fissure can be managed with stool softeners and high
at a dose of 1 mg/kg and given slow intravenous followed fiber diet
by infusion • Solitary rectal ulcer syndrome is managed by encouraging
• Coagulopathy: injection of vitamin K (1 mg/year of age, the child to increase fiber in the diet and thus avoiding
maximum 10 mg) intravenous/intramuscular is given constipation and straining during defecation. The child
when the bleed occurs in individuals with colopathy and is trained to acquire a proper and regular bowel habit. In
hepatocellular dysfunction. Fresh frozen plasma (FFP) some situations, several sittings of biofeed back therapy
may be necessary in children with prolonged international may be required. Various modalities of topical therapy
normalized ratio not responding to injection of vitamin K have been tried such as 5 amino salicylic acid suppository
• Thrombocytopenia and coagulopathy: in children with and sucralfate enema. When the bleed is severe and
LGIB secondary to thrombocytopenia as in dengue fever not responding to dietary modifications Argon plasma
or dengue shock syndrome platelet transfusion, FFP and coagulation and surgery may be recommended.
rarely recombinant factor V may be required
• Variceal bleed: the role of octreotide and somatostatin is Endotherapy
well established in acute variceal bleed. When the bleed • If SRUS does not respond to medications, endoscopic
is nonvariceal, somatostatin and its analog octreotide laserization with argon plasma can be attempted
(1–2 μg/kg bolus followed by 1 μg/kg/hour continuous
• Colonic polyps are managed by endoscopic polypectomy
intravenous or 1 μg/kg every 8–12 hours subcutaneously
for 24–48 hours) may reduce the risk of continued or Interventional Radiology
recurrent bleeding. These vasoactives act by reducing the
splanchnic flow and may help in tiding over the crisis till • Intussusception in infants less than 2 years can be reduced
active intervention is available either with air or saline enema
• Inflammatory bowel disease: in IBD, the bleeding • When the bleed occurs due to an arteriovascular
stops once the activity of the disease is controlled. malformation or a bleeding, aneurysm embolization using
Inflammatory bowel disease is managed according to the coils is an excellent method to arrest the bleed.
severity of disease. Five amino salicylic acid 40–50 mg/
kg/day is initiated in children with mild ulcerative Surgery
colitis (UC) and mild Crohn’s disease (CD). Steroids at a • Children with familial polyposis coli are advised total
dose of 1 mg/kg/day is given for induction of remission colectomy to prevent malignancy
and tapered over a period of 12 weeks in moderate • Intussusception which has not been reduced by pneumatic
UC or CD. Immunomodulators such as azathioprine 6 reduction should be tackled surgically
mercaptopurine are excellent steroid sparing agents and • Meckel’s diverticulum, volvulus, and duplication are all
used in the phase of maintenance managed surgically.
ALGORITHM 1
Management of lower gastrointestinal bleeding after stabilization of child
*Radionuclide studies RBC tagged/pertechnetate.

378 LGIB, lower gastrointestinal bleeding; RNS, radio nuclide studies; UGIE, upper gastrointestinal endocospy.

Lower gastrointestinal bleed presenting as bleeding per 1. Abraldes JG, Bosch K. Somatostatin and analogues in portal hypertension. Hepatology.
rectum is a common problem in children and may be due to 2002;35:1305-12.
several causes. The bleed may be very insignificant or sinister. 2. Arguelles-Arias F, Caunedo A, Romero J, Sánchez A, Rodríguez-Téllez M, Pellicer FJ, et
A careful detailed history and clinical examination will help al. The value of capsule endoscopy in pediatric patients with a suspicion of Crohn’s
disease. Endoscopy. 2004;36:869-73.
in diagnosis. Since acute massive bleed in young children
3. Chaudhary V, Hyser MJ, Gracias VH, Gau FC. Colonoscopy: the initial test for acute
is usually due to Meckel’s diverticulum or duplication cysts, lower gastrointestinal bleeding. Am Surg. 1998;64:723-8.
radio nuclide scan using Tc99m pertechnetate may be done as 4. Ell C, May A. Mid-gastrointestinal bleeding: capsule endoscopy and push-and-pull
a precedent to ileocolonoscopy. The given algorithm 1 for LGIB enteroscopy give rise to a new medical term. Endoscopy. 2006;38(1):73-5.
should be modified according to the age of the child, clinical 5. Fox VL. Gastrointestinal bleeding in infancy and childhood. Gastroenterol. Clin N
presentation, and feasibility of investigation. Amer. 2000;29:36-64.
6. Khurana AK, Saraya A, Jain N, Chandra M, Kulshreshta R. Profile of lower gastrointestinal
bleeding in children from a tropical country. Tropical Gastroenterol. 1998;19:70-1.
Clinical Pearls 7. Lacroix J, Nadeau D, Laberge S, Gauthier M, Lapierre G, Farrell CA. Frequency of
upper gastrointestinal bleeding in a pediatric intensive care unit. Crit Care Med.
• Lower gastrointestinal bleed may be insignificant or sinister in
1992;20:35-42.
presentation
8. Leung Alexander KC, Wong AL. Lower gastrointestinal bleeding in children. Pediatr
• Detailed history and simple macroscopic examination of stool Emeg Care. 2002:18:319-23.
is the most important tool in evaluation 9. Pandey S, Srivastava A, Lal R, Yachha SK, Poddar U. Enteric duplication cysts in
• Meckel’s scan should be included in the initial diagnostic children: A target in algorithm for evaluation of lower gastrointestinal bleeding.
workup of infants with acute massive bleed Indian J Gastroenterol. 2014;33:285-8.
• Ileocolonoscopy is a safe procedure for both diagnosis and 10. Poddar U, Thapa BR, Vai phei K, Singh K. Colonic polyps: experience of 236 children.
therapy of lower gastrointestinal bleeding. Am J Gastroenterol. 1998;93:619-22.
11. Siafakas C, Fox VL, Nurko S. Use of octreotide for the treatment of severe
gastrointestinal bleeding in children. J Pediatr Gastroentrol Nutr. 1998;26:356-9.
12. Strate LL. Lower GI bleeding:epidemiology and diagnosis. Gastroenterol Clin N Am.
KEY POINTS 2005:34:643-64.
13. Vinton NE. Gastrointestinal bleeding in infancy and childhood. Gastroent Clin N
))
Lower gastrointestinal (GI) bleeding may be due to GI and Amer. 1994;93-188.
non-GI causes
))
Lower gastrointestinal bleeding (LGIB) may be chronic
intermittent or acute massive
))
Essential to evaluate and identify the etiology
))
In acute massive GI bleed, radio nuclide scan may be done
prior to endoscopy
))
Ileocolonoscopy should be included in the protocol
))
Surgery is indicated in some select conditions of LGIB.
379
Chapter 80
Acute Liver Failure
Vidyut Bhatia, Anupam Sibal, Akshay Kapoor
INTRODUCTION
Clinical Pearl
Acute liver failure (ALF) is a devastating illness associated
• Encephalopathy is not essential to make a diagnosis of acute
with high mortality mainly due to rapid death or injury
liver failure in children.
to a large proportion of hepatocytes, leaving insufficient
functional hepatocytes to sustain life. Acute liver failure is a
multisystem disorder wherein liver cell function dysfunction ETIOLOGY OF ACUTE LIVER FAILURE IN INDIA
and coagulopathy exist with or without the presence of
encephalopathy. Recently, the gastroenterology chapter of Acute viral hepatitis is the most common cause of ALF either
Indian Academy of Pediatrics (IAP) has published guidelines alone or in combination with other etiologies. The other
for the management of ALF. The management of ALF described underlying causes of ALF are given in table 1.
in this chapter is largely based on the IAP guidelines.
DIAGNOSTIC WORK-UP
DEFINITION AND DIAGNOSIS Table 2 summarizes the diagnostic work-up necessary to
Earlier classification of ALF was based on the time interval establish the etiology of ALF. An approach to a child presenting
between jaundice and onset of encephalopathy. However, this with features of acute liver diseases is presented in algorithm 1.
definition failed to capture the complexities associated with
ALF in infants and children. Since in most young children and TRANSPORT AND INITIAL MANAGEMENT
infants it is difficult to define and classify encephalopathy, the
The main objective of transporting a child with ALF is to ensure
current definition relies more on coagulopathy as an index of
safe and timely transfer to a tertiary center with liver transplant
liver function.
facilities. It is important to act early because the risks involved
The consensus report of the gastroenterology subspeciality
with patient transport may increase or even preclude transfer
chapter of IAP has defined ALF as “Severe hepatocellular
once deeper stages of encephalopathy are reached. Any child
injury presenting with biochemical evidence of liver injury
who develops grade III encephalopathy should be intubated and
and uncorrectable coagulopathy 6–8 hours after one dose of
the airway secured before transport. A continuous monitoring of
parenteral Vitamin K. Uncorrectable coagulopathy is defined
vital parameters should be available during transport.
as INR >1.5 in patients with HE or INR >2.0 in patients without
HE, with no previous evidence of CLD”.
As noted above, staging of hepatic encephalopathy in Table 1: Underlying etiology of acute liver failure in children
infants and young children is difficult as compared to adults.
Infections Acute viral hepatitis (A, E, B)
The grading as recommended by the guidelines is as follows.
Drugs Valproate, isoniazid, paracetamol
Grades I and II are indistinguishable with clinical features of
Toxins Iron, herbal medicines, mushroom
inconsolable cry and poor attention to tasks, inappropriate
behavior, and hyperreflexia. In grade III, somnolence, stupor, Metabolic Wilson’s disease, galactosemia, tyrosinemia type 1,
fructosemia
combativeness, and hyperreflexia are present. In grade IV,
the child is comatose, arousable with painful stimuli (IVa) Vascular Budd-Chiari, veno-occlusive disease
or no response (IVb). Reflexes are absent and neurological Autoimmune Autoimmune liver disease
manifestations like decerebration or decortication are seen. Idiopathic –
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Chapter 80: Acute Liver Failure
Table 2: Diagnostic workup for acute liver failure in children

Clinical Pearl
General workup Total and conjugated bilirubin, AST, ALT, GGTP,
alkaline phosphatase, prothrombin time (INR), • Sedation should be given to a child only when support for
PTTK, hemogram, serum electrolytes, blood intubation and ventilation is available.
urea, creatinine, blood and urine cultures, blood
group, chest X-ray, serum a-fetoprotein, lactate,
lactate dehydrogenase, blood ammonia, ABG, SUPPORTIVE MANAGEMENT
urine for reducing substances, G6PD levels
Specific workup Medications or devices that may support a failing liver is the
Infectious IgM anti-HAV, IgM anti-HEV, HBsAg, IgM anti- holy grail of current hepatology research on the management
hepatitis B core antigen, CMV PCR, IgM varicella of ALF. Most of the drugs currently being used have not
zoster virus, IgM Epstein-Barr virus, HIV 1,2 undergone vigorous clinical trials before being used in the
Wilson’s disease Serum ceruloplasmin, 24 urinary copper management of ALF. N-acetyl cysteine (NAC) has been used
estimation, KF ring in the management of ALF secondary to acetaminophen
Autoimmune Coombs test, antinuclear antibody (>1:40), liver poisoning. There is increasing evidence for its use in non-
kidney microsomal antibody, smooth muscle acetaminophen causes of ALF. NAC can be used in the dose
antibody (>1:20), IgG levels of 100 mg/kg/24 hours. Its role has been questioned by a
Hemophago Serum triglyceride, cholesterol, ferritin, and recent multicentric study, wherein it was seen as no better
cytosis bone marrow biopsy than placebo. However, most patients in this study were not
Drug overdose Acetaminophen, valproate drug levels infectious hepatitis related (only 10%), and a large proportion
of the (50%) patients were found to be ineligible for the study
AST, aspartate transaminase; ALT, alanine transaminase; GGTP, gamma-
glutamyl transpeptidase; INR, international normalized ratio; PTTK, partial (50% of these are recorded as “reasons unknown”). Moreover,
thromboplastin time activated with Kaolin; G6PD, glucose-6-phosphate the study was conducted over a period of 9 years leading
dehydrogenase deficiency; ABG, arterial blood gas; Ig, immunoglobulin; HAV, to heterogeneity in treatment received over the years as
hepatitis A virus; HEV, hepatitis E virus; HBsAg, hepatitis B surface antigen; CMV, treatment modalities do change with time.
cytomegalovirus; PCR, polymerase chain reaction KF, Kayser-Fleischer.
Ammonia is an accepted triggering factor in cerebral
edema; however, agents that decrease blood ammonia levels
Algorithm 1 (L-ornithine L-aspartate, lactulose and other non-absorbable
Approch to a child with acute liver disease antibiotics) have not been found to be beneficial. Protein
restriction in children with hepatic encephalopathy is no
longer recommended. Energy intakes should be increased
appropriately to counter catabolic stat. Prophylactic adminis
tration of proton pump inhibitors in ALF is found to be useful
as it is helpful in prevention of gastrointestinal hemorrhage.
Specific therapy should be administered if the underlying
cause of ALF has been determined (Box 1).
MANAGEMENT OF RAISED
INTRACRANIAL PRESSURE
Raised intracranial pressure more than 20 mmHg occurring as
a consequence of cerebral edema is one of the leading causes of
mortality in ALF. Sustained severe hypertension, bradycardia,
pupillary changes, reflexes (brisk—sluggish), muscle tone
changes, and decerebrate posturing are clinical indicators of
presence of cerebral edema.
INR, international normalized ratio; ALF, acute liver failure. Children with lower grade encephalopathy (I–II) should be
managed in a quiet environment and general measures such
The management of child with ALF should always be done as treating fever, infection, and seizures must be implemented.
in the intensive care unit of the hospital. Initial management However, if encephalopathy progresses to a higher grade,
includes placement of a central venous catheter line, volume endotracheal intubation must be done.
resuscitation as per protocol, glucose given at least 4–6 mg/ Prophylactic administration of 3% saline to maintain
kg/min, so as to keep the blood glucose level between sodium at 145–155 mmol/L in patients with severe encephalo
120–200 mg/dL, and use of vasoactive drugs if required. All pathy is recommended over mannitol. However, once
such medications that decrease the level of consciousness obvious neurological signs develop, a bolus of intravenous
should be avoided to prevent worsening of encephalopathy. mannitol (0.25–1 g/kg, 20% mannitol) over 15 minutes must
If sedation is mandatory (e.g., for intubation) a short acting be given. This can be repeated if serum osmolality is less than
agent like propofol can be given. 320 mOsmol/L. 381
Ch-80.indd 381 11/21/2016 10:41:25 AM

Box 1: Specific therapy of common causes of pediatric acute SEPSIS

liver failure Infection remains one of the major causes of death in patients
Neonatal hemochromatosis with ALF. The reasons for increased sepsis in these children are
• High-dose of intravenous immunoglobulin in combination with management in intensive care with invasive modalities, neutro
exchange transfusion penia (secondary to bone marrow suppression), deranged
• Liver transplantation if no improvement is seen neutrophil function (due to defective sodium pump) and
Herpes simplex defective opsonization (due to decreased plasma complement).
• High dose acyclovir 60 mg/kg/day for 21 days, continued till The most commonly isolated organisms are Gram-positive
polymerase chain reaction is negative cocci (Staphylococci, Streptococci), enteric Gram-negative
Type 1 tyrosinemia bacilli, and Candida albicans. Prophylactic antibiotics or
• Nitisinone 1 mg/kg/day per os divided bid antifungals have not been shown to improve outcome or
• Dietary restrictions of phenylalanine and tyrosine survival in patients with ALF. However, as suggested in the
• Liver transplantation if no improvement is seen
recommendations, “empirical administration of antibiotics is
Galactosemia recommended when
• Lactose-free diet, avoid galactose containing dietary items
• Infection or the likelihood of impending sepsis is high, e.g.,
Hereditary fructose intolerance surveillance cultures reveal significant isolates
• Fructose-free diets, avoid fructose and sorbitol infusions
• Progression of, or advanced stage (III/IV) HE
Acetaminophen poisoning • Refractory hypotension
• N-acetyl cysteine
• Renal failure
Mitochondrial cytopathies • Presence of systemic inflammatory response syndrome
• Electron acceptors and cofactors: coenzyme Q10: 3–5 mg/kg components (temperature >38 or <36°C, white blood count
• Antioxidants: vitamin E: 25 IU/kg
>12,000 or <4,000/mm3, tachycardia)
• Carnitine: 50–100 mg/kg
• Empirical antibiotics are also recommended for patients
Wilson’s disease (therapy based on scoring system)
listed for liver transplantation, since infection often results
• D-penicillamine/trientine (20 mg/kg/day) may be administered
• Liver transplantation in delisting or delay and immunosuppression postliver
transplantation is imminent.”
Broad-spectrum coverage with a third-generation cephalo
sporin and an antifungal have been recommended.
Clinical Pearl
• Three percent saline is preferred to 20% mannitol for decreasing LIVER ASSIST DEVICES
raised ICP in children with acute liver failure. The high cost of liver transplantation, lifetime immuno
suppression, limited availability of donors, and risk of death
while awaiting liver transplantation have stimulated the
COAGULOPATHY development of liver assist devices (LAD) and other modalities
Patients with ALF develop failure of synthesis of clotting like plasmapheresis, exchange transfusions, extracorporal blood
factors, altered platelet number and function, intravascular cleansing, devices containing cultured hepatocytes, cross-
coagulation, and altered blood vessel wall integrity. Routine circulation with animals, and molecular adsorbent recirculating
correction of coagulopathy or thrombocytopenia is not system. Experience on the use of LAD in children is limited and
recommended. Prophylactic fresh frozen plasma (FFP) is not restricted to case reports or small series.
recommended, as it does not reduce the risk of significant
bleeding nor transfusion requirements and obscures the HEPATOCYTE TRANSPLANTATION
trend of international normalized ratio (INR) as a prognostic Hepatocyte transplantation has been performed in patients
marker. However, replacement with FFP is recommended in with ALF as a potential alternative to liver transplantation.
patients with clinically significant bleeding, while performing Cryopreserved hepatocytes are usually infused into the
invasive procedures or in situations where INR >7. Single dose intrahepatic portal vein with many cells rapidly cleared by
of vitamin K1 (5–10 mg, slowly not more than 1 mg/min) is the innate immune system, which needs to be prevented.
recommended empirically in all patients with ALF. According Newer methods that utilize encapsulation of hepatocytes are
to the consensus statement, platelet transfusion is not being used through the intraperitoneal route in ALF with the
recommended unless a threshold platelet count of 10,000– advantage of avoiding immunosuppression.
20,000/mm3 is reached or there is significant bleeding and
thrombocytopenia less than 50,000 per cubic millimeter. CRITERIA FOR LIVER TRANSPLANTATION
A platelet count of 50–70,000/mm3 is usually considered
adequate when an invasive procedure is to be performed. Liver transplantation is the only definite treatment available
for ALF. Several prognostic scores have been used to identify
children who may benefit from an early liver transplantation.
Clinical Pearl These include King’s College Hospital criteria, pediatric end-
382 • Prophylactic fresh frozen plasma is only recommended when stage liver disease score, Acute Physiology and Chronic Health
any invasive procedure is attempted. Evaluation II, and Clichy criteria. However, an INR >4 or
factor V concentration of less than 25%, as recommended in
Ch-80.indd 382 11/21/2016 10:41:25 AM

Chapter 80: Acute Liver Failure
the consensus statement, are by far the best available criteria SUGGESTED READINGs
for listing for liver transplantation. Acute fulminant Wilson’s
disease has a high mortality necessitating liver transplantation 1. Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK. Efficacy of L-ornithine
in most cases. Special prognostic score is now available for L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled
study. Gastroenterology. 2009;136:2159-68.
these children and a score of 11 or more indicates mortality,
2. Alagille D, Habib EC, Thomassin N. L’atresie des voies biliaires extrahepatiques
with 93% sensitivity and 98% specificity.
permeables chez l’enfant. J Par Pediatr. 1969:26(1):51-71.
Recently, the authors performed a survey of seven major
3. Arora NK, Nanda SK, Gulati S, Ansari IH, Chawla MK, Gupta SD, et al. Acute
transplant centers across India. Out of approximately 355
viral hepatitis types E, A, and B singly and in combination in acute liver failure in
pediatric liver transplantation performed at these centers, ALF children in north India. J Med Virol. 1996;48:215-21.
constituted about 19% of all cases. In India, majority of liver 4. Bernal W, Auzinger G, Sizer E, Wendon J. Intensive care management of acute
transplants are living related, as cadaveric donation is a rarity. liver failure. Semin Liver Dis. 2008;28:188-200.
A welcome development has been the increasing numbers of 5. Bhatia V, Sibal A. Are fathers catching up with mothers in liver donation? Indian
fathers willing to come forward as donors. Another positive Pediatr. 2013;50:158.
aspect has been the involvement of community in arranging 6. Bucuvalas J, Yazigi N, Squires RH, Jr. Acute liver failure in children. Clin Liver Dis.
for funds for those who cannot afford liver transplantation. 2006;10:149-68.
The availability of generic immunosuppressant drugs and 7. Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G.
consumables has greatly aided in bringing doing costs. The Wilson’s disease in children: 37-Year experience and revised King’s score for liver
average cost of transplant in India is 12–15 lakhs. This is only transplantation. Liver Transplantation. 2005;11:441-8.
about 1/5th to 1/10th the cost in the West. 8. Kamath BM, Spinner NB, Piccoli DA. Alagille syndrome. In: Suchy F, Sokol RJ,
The paucity of facilities for liver transplantation in several Balistreri WF, editors. Liver disease in children. 3rd ed. New York: Cambridge
regions of the world has prompted many foreign nationals to University Press; 2007. pp. 326-45.
come to India for liver transplants. India has now become a 9. Kapoor A, Bhatia V, Jerath N, et al. Expanding indications for pediatric liver
major center for liver transplantation for international patients transplantation. Apollo Medicine. 2012;9:55-61.
because of the high quality—low cost value proposition. 10. Kaur S, Wadhwa N, Sibal A, Jerath N, Sasturkar S. Outcome of live donor
Children from over 20 countries have now received a liver liver transplantation in Indian children with bodyweight 7.5 kg. Indian Pediatr.
transplantation in India (personal communication). 2011;48:51-4.
11. Kortsalioudaki C, Taylor RM, Cheeseman P, Bansal S, Mieli-Vergani G, Dhawan
Clinical Pearl A. Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-
induced acute liver failure. Liver Transpl. 2008;14:25-30.
• International normalized ratio >4 is the best available 12. Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, et al.
parameter for listing for transplant. Intravenous N-acetylcysteine improves transplant-free survival in early stage
non-acetaminophen acute liver failure. Gastroenterology. 2009;137:856-64,
864.e1.
PROGNOSIS AND OUTCOME 13. Raghunathan A. An abdominal affair 2012 [19-07-2013]. Available from: http://
In more than 50% of children with ALF, there is poor survival week.manoramaonline.com/cgi-bin/MMOnline.dll/portal/ep/theWeekContent.do?p
unless liver transplantation is offered at the appropriate rogramId=1073755753&contentId=13007946&tabId=13.
time. Prognostic factors that have been found to predict poor 14. Sales I, Dzierba AL, Smithburger PL, Rowe D, Kane-Gill SL. Use of acetylcysteine
for non-acetaminophen-induced acute liver failure. Ann Hepatol. 2013;12:6-10.
outcome in ALF include unknown etiology, high grade (III/IV)
15. Schweizer P. Treatment of extrahepatic bile duct atresia: results and long-term
of encephalopathy, time to onset of encephalopathy more than
prognosis after hepatic portoenterostomy. Pediatric Surgery International. 1986;
7 days, higher bilirubin (>17.5 mg/dL), lower ALT (≤2384 IU/L), 1:30-6.
uncorrected prothrombin time more than 55s and clinical signs of
16. Sgroi A, Serre-Beinier V, Morel P, Bühler L. What clinical alternatives to whole
cerebral edema. Children with encephalopathy and coagulopathy liver transplantation? Current status of artificial devices and hepatocyte
have a poorer outcome than those with coagulopathy alone. transplantation. Transplantation. 2009;87:457-66.
17. Sibal A, Gupta S, Bhatia V, et al. Liver transplant for children: Indian scenario.
Key points Indian Journal of Transplantation. 2011;5:53-5.
18. Soin A, Kumaran V, Mohanka R, Mehta N, Mohan N, Nundy S. Bridge venoplasty:
))
Hepatitis A and E infections are responsible for the majority of a new technique to simplify venous outflow reconstruction in living donor domino
cases of acute liver failure, with death rates of more than 50% liver transplantation. Surgery. 2010;148:155-7.
reported from the developing world 19. Sperl J, Prochazkova J, Martasek P, Subhanová I, Franková S, Trunecka P, et al.
))
Early restoration of intravascular volume and maintenance of N-acetyl cysteine averted liver transplantation in a patient with liver failure caused
systemic perfusion mitigates the severity of organ failure by erythropoietic protoporphyria. Liver Transpl. 2009;15:352-4.
))
Acetylcysteine may benefit patients with non-acetaminophen- 20. Squires RH, Dhawan A, Alonso E, Narkewicz MR, Shneider BL, Rodriguez-
related acute liver failure Baez N, et al. Intravenous N-acetylcysteine in pediatric patients with
))
For children who progress to stage 3 encephalopathy endo- nonacetaminophen acute liver failure: a placebo-controlled clinical trial.
tracheal intubation and sedation for airway control is recom- Hepatology. 2013;57:1542‑9.
mended 21. Zhu JJ, Xia Q, Zhang JJ, Xue F, Chen XS, Li QG, et al. Living donor liver
))
Serial evaluation of laboratory coagulation variables transplantation in 43 children with biliary atresia: a single-center experience from
(prothrombin time) is central to prognostic evaluation the mainland of China. Hepatobiliary Pancreat Dis Int. 2012;11:250-5.
))
Administration of coagulation factors should be avoided,
except when needed to treat bleeding or before invasive 383
procedures.
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Chapter 81
Corrosive Injury in Children
Barath Jagadisan
INTRODUCTION PATHOGENESIS OF CORROSIVE INJURY

In a pediatric emergency room, ingestion of corrosive The nature and severity of corrosive injury is a function of
substances by children and adolescents is not an uncommon the type of corrosive (acid/alkali; table 1), amount ingested,
cause of visit. Children beyond 1 year of age and less than 6 concentration of the corrosive and the physical state of the
years, who are ambulant and inquisitive and who can drink corrosive (solid/liquid). Acids cause coagulative necrosis
from bottles are the ones who commonly come with accidental of the mucosa. This results in the formation of eschar on the
ingestion. The common practice of storing acid toilet cleaners surface of the esophagus. If the amount of acid consumed is
in bottles meant for beverages and water is one of the reasons less, the eschar might prevent further penetration of the acid
for accidental ingestion. Corrosive ingestion for self-harm, into deeper tissue. In contrast, alkalis produce liquefactive
similar to that seen in adults, is usually seen in adolescent necrosis, saponification and thrombosis of underlying vessels
age group. Based on the data available from the American and thereby have the potential to penetrate deep into the tissue
Association of Poison Control Centers, children under the causing transmural injury and perforation. This distinction is
age of 6 years account for 51% of individuals who ingest not absolute since acids cause deep injuries and perforation
corrosives. Such data are not available in developing countries when ingested in higher amounts. The volume of ingestion is
due to under-reporting of cases resulting from the absence of more in self-harm rather than in accidental ingestion. Hence,
effectively functioning poison control centers or systematic the proportion of severe injury is less in children compared
data collection. to that in adolescents. Also, because of their higher viscosity
and longer time for clearance from the esophagus, alkalis can
potentially cause predominant damage to the esophagus while
TYPES OF CORROSIVES acids are rapidly cleared into the stomach causing predominant
The corrosives ingested may be common household solutions
like toilet cleaners, household bleach, laundry detergents, Table 1: Difference between injury from alkalis and acids
drain cleaners and oven cleaners or they may be farm and Injury Acids Alkalis
industrial chemicals stored in the house. Thus, parental
Type of necrosis Coagulative Liquefactive
occupation also seems to have an influence on corrosive
injury in children. A popular herbicide, paraquat, which is Formation of Yes No
eschar/coagulum
widely stored in agrarian rural households is corrosive in
nature and is available in containers that are not child proof. Depth of injury Limited by coagulum Deep, transmural
Children from households of goldsmiths come with accidental formation
ingestion of aqua regia, a combination of hydrochloric Risk of perforation Lower Higher
and nitric acid. Broadly, these corrosives are classified as Location of injury Predominantly Predominantly
acids and alkalis. Unlike in the west, acid ingestion is more esophagus due to stomach due to
common in developing countries like India because of the viscous nature and slow rapid esophageal
free availability of acids. esophageal clearance clearance
Ch-81.indd 384 11/21/2016 10:43:35 AM

Chapter 81: Corrosive Injury in Children
Algorithm 1 • Drooling of saliva

Pathogenesis of corrosive ingestion • Dysphagia
• Odynophagia
• Retrosternal pain
• Abdominal pain
• Vomiting
• Hematemesis. Large volume hematemesis is seen with
extensive gastric injury
• Oral cavity may show erythema, edema, bleeding and
ulceration
• Systemic involvement in the form of acute lung injury,
renal and hepatic failure and disseminated intravascular
coagulation
• Perforation and mediastinitis leading to death.
The clinical presentation in a tertiary care center is not
necessarily an exact representation of the spectrum of injury
and clinical manifestations of CI, as children with extensive
injury and rapid deterioration are unlikely to reach the hospital.
In an attempt to find a noninvasive indicator of injury or its
severity, the presence of symptoms and oral cavity injury have
been compared with endoscopic findings in the esophagus
and stomach. Among 378 children with corrosive injury,
symptoms were shown to have no correlation with esophageal
injury. Eighty two percent of the symptomatic children had no
esophageal injury while 12% of asymptomatic children were
shown to have severe esophageal injury. Even though increasing
number of symptoms may correlate with a greater likelihood
of significant injury, deep mucosal injuries can occur without
gastric injury. Again, this distinction is more theoretical rather symptoms. The presence of airway injury in the form of stridor
than a reality as acid ingestion causing deep esophageal injury is is frequently associated with esophageal injury, but most
not uncommon. The concentration of the corrosive determines studies indicate that no single symptom or group of symptoms
the depth of injury and time taken for clinical deterioration. can reliably predict esophageal or gastric injury. Similarly,
Solid corrosives have a prolonged contact with the mouth and the absence of oral lesions does not rule out esophageal
esophagus while liquids are rapidly cleared into the stomach. injury. Esophageal injury can be found in up to 61% children
The antrum and pylorus are the areas that receive the corrosive in the absence of oral lesions. The reverse is also true where
first from the esophagus and thus perforation and strictures significant oral cavity lesions may not have any distal injury.
are seen more in these areas. Apart from the local effects, These observations are the basis of recommending endoscopic
corrosives like acids have significant systemic complications assessment in all children with corrosive injury irrespective of
including disseminated intravascular coagulation and organ their symptoms or their oral cavity manifestations.
(renal, hepatic) dysfunctions. A common cause of death in This does not undermine the importance of clinical
paraquat ingestion is acute lung injury. examination. The presence of respiratory symptoms points
The sequence of events following a corrosive ingestion is to the need for early management of airway or pulmonary
depicted in algorithm 1. Before 4 weeks, the tensile strength problems. Careful clinical examination together with computed
of the tissue is less and hence late endoscopies beyond 96 tomography (CT) is more relevant in diagnosing perforation
hours carry a risk of perforation. For the same reason, stricture rather than endoscopy alone. Since perforation can occur at
dilatation is usually not attempted before 3 weeks after any time in the first 2 weeks, any clinical worsening or new
corrosive injury. The process of fibrosis progresses even after symptoms should be carefully evaluated.
epithelialization and hence the stricture continues to worsen.
Therefore, a much delayed follow-up endoscopy will detect INVESTIGATIONS IN THE ACUTE PHASE
mature tight strictures where, even visualization of a lumen for
cannulation and dilatation becomes difficult.
Chest and Abdominal Radiographs
Radiographs of the chest and abdomen may show evidence
CLINICAL MANIFESTATIONS of mediastinal air or subdiaphragmatic air in the case of
The manifestations of corrosive injury include: esophageal or gastric perforation. In the case of esophageal
• Airway injury in the form of stridor and dyspnea perforation, there is evidence of mediastinitis and pleural
• Refusal of feeds effusion. 385
Ch-81.indd 385 11/21/2016 10:43:35 AM

Laboratory Investigations discharged early. The injury grading correlates well with
morbidity and mortality. Children with grades 1 and 2A injury
Investigations to look for acidosis, dyselectrolytemia, dis
do not usually develop strictures. Stricture frequency in grade 3
seminated intravascular coagulation and multiple organ
injury may approach up to 75%. Mortality is more in grade 3
dysfunctions are relevant in a sick child prior to surgery and as
injuries. Endoscopic grading can guide the need for feeding
part of monitoring during the course of management.
jejunostomy. Extensive grade 3b injuries may necessitate
emergency surgical procedures.
Early Endoscopic Evaluation A grade 3 injury may not always indicate a definite
Endoscopic evaluation provides an evaluation of the extent of transmural involvement. Emergency resective surgery guided
mucosal injury and an estimate of its severity in terms of the by endoscopic mucosal injury grading alone may result in
possible transmural extent of the injury and thereby, guides unnecessary gastrectomy and esophagectomy in 12–15% cases,
management and helps in prognostication. thus necessitating a better mode of identifying transmural injury.
The selection of time for endoscopic evaluation has varied Endoscopic ultrasound with miniprobes has been used in
in the past. Since ongoing mucosal necrosis and sloughing corrosive injury to predict the risk of stricture in follow-up. In
increases the friability of tissues, endoscopy is done before patients who have developed stricture, endoscopic ultrasound
96 hours. The practice of delaying endoscopy with the idea with a radial probe has been used to predict the response to
of visualizing a more mature state of necrosis is not preferred dilatation.
nowadays. Most endoscopists prefer early endoscopy within
72 hours because of the lower risk of perforation. Endoscopic Computed Tomography
assessment, in the hands of an expert, is a safe procedure when
Unlike endoscopy which assesses only the mucosal aspect of
done with care.
the injury, CT provides information on the extent of transmural
Endoscopic assessment is contraindicated in the case of
injury. In situations where clinical assessment suggests a
severe hypopharyngeal injury and in the case of perforation. It
high possibility of perforation even in the absence of obvious
is best done under sedation. Deep sedation without intubation
evidence of perforation in chest and abdominal radiographs, a
is required in children. Routine anesthesia and intubation is
CT rather than an endoscopy should be the first investigation to
not preferred unless there is stridor and respiratory problems.
be performed to look for perforation. Computed tomography
Caution is to be exercised in the case of epiglottic or laryngeal
grading of the injury has also been used as a modality to predict
inlet edema where respiratory problems are anticipated
the risk of stricture formation but is not routinely done for this
and intubation is advisable. The principles of endoscopy in
purpose alone.
corrosive ingestion include gentle scope maneuvering and
minimal air insufflation. It is recommended that the scope
is not negotiated beyond severe mucosal injuries of grade 3 MANAGEMENT (ALGORITHM 2)
especially if it is circumferential. Some endoscopists do not
follow this rule and consider it safe to negotiate beyond these Management in the Acute Phase
severe injuries also. Adherence to the basic tenets of emergency care is essential in
The purpose of endoscopy is to grade the mucosal injury. the management of patients with corrosive injury. The patient
Injury is graded as in table 2. Presence of perforation may is assessed for respiratory distress and airway intubation or
be referred to as grade 4 injury where endoscopy is contra tracheostomy may be required in cases with airway problems.
indicated. Epiglottic and supraglottic edema are harbingers for airway
Many cases of corrosive injury may not have any compromise even in the absence of symptoms at presentation.
gastrointestinal injury, more so in the cases of accidental The patient’s ventilation and hemodynamic status may require
ingestion. These patients identified by endoscopy can be support in cases with perforation.
There is no role for gastric lavage or inducing emesis to
Table 2: Endoscopic grading of mucosal injury during endoscopy remove the corrosive. Inducing emesis will only lead to repeat
exposure of proximal mucosa to the corrosive and lead to
Grade of injury Endoscopic findings
aspiration of the corrosive. Similarly, attempts at neutralization
0 Normal appearance of the corrosive by weak acids or weak bases will prove counter
1 Edematous and hyperemic mucosa productive. Milk and activated charcoal should be avoided.
2A Superficial injury—friability, hemorrhagic areas, Blind placement of nasogastric tube should be avoided.
erosions with whitish exudates and membranes, This might lead to perforation. Some centers prefer placing a
superficial ulceration endoscopically guided nasojejunal tube to assist feeding and
2B Grade 2A with deep discrete ulcers or to use it as a stent that might maintain at least a narrow lumen
circumferential involvement that can be used for cannulation during stricture dilatation.
This is controversial and is discouraged by others as the tube
3A Multiple scattered areas of ulceration and
necrosis seen as brown/black/gray areas
increases reflux and might lead to the development of long
strictures. The latter view is contested as one study shows
386 3B Extensive areas of necrosis equivalence of nasojejunal feeding with jejunostomy feeding
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Chapter 81: Corrosive Injury in Children
Algorithm 2 early surgery is essential in view of the high suspicion of

Management of corrosive ingestion in children perforation. Any clinical suspicion of perforation based on the
general condition of the patient and the quantity of corrosive
ingested, should lead to an early surgical exploration.
In patients in whom endoscopic assessment of mucosal
injury has been done, the grade of injury guides further
management. Children with normal mucosa can be
discharged immediately. Children with grades 1 and 2A injury
can be allowed to take orally and can be discharged after a
brief period of observation when oral intake is satisfactory.
Children with grades 2B and 3 injuries are restricted from
oral intake. In cases of grades 2B and 3A injuries, where oral
intake is restricted, the choice of nutrition delivery is between
total parenteral nutrition (TPN), jejunostomy feeding and
endoscopically placed nasoenteral tube feeding. Most
centers, at least in developing countries, avoid TPN due to
the high cost and high frequency of infections. Kochhar et al.,
in a retrospective study comparing nasoenteric feeding and
jejunostomy feeding, had shown that nasoenteric feeding
maintains a comparable nutrition status without increased
stricture rates. The tube also provides a lumen for guidewire
passage during future dilatation. This study also included
cases of 3B mucosal injury that did not require a laparotomy,
who were fed by nasoenteral feeding.
The role of emergency surgical procedure in the presence
of evidence of perforation or a massive hemorrhage is quite
obvious. These situations are dealt with by esophagectomy and
in maintaining nutrition in patients with corrosive injury
cervical esophagostomy when the esophagus is perforated.
without increasing the frequency of strictures.
The area of the stomach with transmural involvement may
Based on the data suggesting the presence of lower
need resection. The entire stomach may need resection. A
esophageal sphincter relaxation, high frequency of acid
gastrostomy during surgery provides an accurate assessment
reflux into the esophagus and the preliminary data showing
of the extent of involvement. There is no role for surgical
impressive healing of corrosive injury with infusion of proton
closure of perforations. Distal jejunostomy is required to
pump inhibitors (PPI), administration of PPI, at least as bolus
maintain nutrition. In case of extensive grade 3B injuries,
doses, is a regular practice.
laparotomy may be required to look for transmural extensive
Systemic steroid use with the purpose of preventing
necrosis that can be a harbinger of perforation. The surgery
strictures is to be avoided as meta-analysis analyzing steroid
may result in variable degree of resection and a jejunostomy
use in corrosive injury has shown that steroids do not provide
for feeding. The role of laparoscopy in such situations is
this benefit. Also, the risk of infections may be increased
controversial in view of long operating time involved in the
with steroid use. There is always the theoretical possibility of
procedure and the difficulty in thorough assessment of extent
steroids masking features of inflammation arising from bowel
of injury.
perforation. Systemic steroids are indicated only in cases with
airway edema.
Antibiotics are not routinely indicated. They are used
Management of Strictures
only in cases with perforation. In addition, broad spectrum Stricture frequency increases with increasing grades of
antibiotics may be relevant in cases receiving steroids for mucosal injury. Systemic steroids do not prevent strictures.
airway edema. Strictures in the esophagus present with dysphagia and
When there is overt clinical or radiological evidence of aspiration pneumonia while strictures in the antral and pyloric
perforation, emergency laparotomy is required. In case of high area present with features of gastric outlet obstruction. It is
index of suspicion of perforation, laparotomy may be indicated always preferable to have a contrast radiograph before an
even in the absence of radiological evidence. When there is endoscopic evaluation of the stricture as it gives an idea of the
ambiguity regarding perforation in a clinically stable patient, position, number and length of strictures and information on
CT may be useful to look for evidence of perforation. If there the presence of diverticulae. On radiography with oral contrast,
is no suspicion of perforation on clinical and radiological stricture is seen as an area of narrowing with hold-up of contrast
assessment, the patient is subjected to endoscopic assessment proximal to the stricture. Depending on the chronicity of the
of mucosal injury. The decision for early surgery is not entirely stricture, there can be variable degrees of proximal dilatation.
dependent on overt clinical or radiological signs of perforation. Diverticulae are common in corrosive strictures, especially
In case of acidosis, renal injury or hemodynamic instability, those presenting late. Barium would be the preferable contrast 387
Ch-81.indd 387 11/21/2016 10:43:35 AM

except in children with severe dysphagia where there is a

possibility of aspiration of the contrast. Key points
Stricture dilatation before 3 weeks after corrosive injury ))
Early recognition of airway compromise and perforation is
is not advisable due to the high risk of perforation. At the essential to ensure survival
same time, delayed dilatations lead to a nonvisualization of ))
Endoscopic assessment of severity of mucosal injury directs
lumen for dilatation, strictures refractory to dilatation and early management and prognosticates the likelihood of
poor nutrition of the child. Long strictures are common after strictures
corrosive injury, where Savary‒Gillard (bougie) dilator may be ))
Existing data is insufficient to support use of systemic corti
preferred to a balloon dilator. Refractory strictures may require costeroids for prevention of strictures
local triamcinolone injection or mitomycin application. In
))
Routine barium esophagogram at 3 weeks after corrosive
cases presenting months after corrosive injury, dilatation may ingestion is necessary for early diagnosis and management
not be possible and surgical correction may be the only option. of strictures.
Detailed discussion of surgical reconstructive procedures
to correct the late sequelae of corrosive injury is beyond the
scope of this review.
SUGGESTED READINGs
Long-term Complications of Corrosive Injury 1. Ananthakrishnan N, Parthasarathy G, Kate V. Acute corrosive injuries of
the stomach: a single unit experience of thirty years. ISRN Gastroenterol.
The long-term complications include dysmotility and possible 2011;2011:914013.
risk of dysplasia and malignancy in the affected tissue. 2. Betalli P, Falchetti D, Giuliani S, Pane A, Dall’Oglio L, de Angelis GL, et al. Caustic
ingestion in children: is endoscopy always indicated? The results of an Italian
multicenter observational study. Gastrointest Endosc. 2008;68:434-9.
CONCLUSION 3. Chirica M, Resche-Rigon M, Bongrand NM, Zohar S, Halimi B, Gornet JM, et
In summary, the optimal management of corrosive injury is al. Surgery for caustic injuries of the upper gastrointestinal tract. Ann Surg.
2012;256:994-1001.
dependent on adherence to the basic tenets of life support,
4. Doˇgan Y, Erkan T, Cokuˇgra¸s, Kutlu T. Caustic gastroesophageal lesions in
avoidance of lavage or emesis, early and optimal selection of childhood: an analysis of 473 cases. Clin Pediatr. 2006;45:435-8.
patients for emergency surgical resection, decision making 5. Gaudreault P, Parent M, McGuigan MA, Chicoine L, Lovejoy FH Jr. Predictability of
guided by endoscopic evaluation, close attention to nutrition, esophageal injury from signs and symptoms: a study of caustic ingestion in 378
and avoiding delay in stricture detection and management. children. Pediatrics. 1983;71:767-70.
The free availability of acids in the unregulated market is a 6. Kochhar R, Poornachandra KS, Puri P, Dutta U, Sinha SK, Sethy PK, et al.
problem in many developing countries where acids are used as Comparative evaluation of nasoenteral feeding and jejunostomy feeding
in acute corrosive injury: a retrospective analysis. Gastrointest Endosc.
toilet cleaners, leading to a high frequency of corrosive injury.
2009;70:874-80.
Rules governing concentration of household caustics and child
7. Kochhar R, Ray JD, Sriram PV, Kumar S, Singh K. Intralesional steroids augment
resistant packaging of toilet cleaners and other corrosives need the effects of endoscopic dilation in corrosive esophageal strictures. Gastrointest
to be strictly implemented. Endosc. 1999;49:509-13.
8. Lakshmi CP, Vijayahari R, Kate V, Ananthakrishnan N. A hospital based
Clinical Pearls epidemiological study of corrosive alimentary injuries with particular reference to
the Indian experience. Natl Med J India. 2013;26(1):31-6.
• Oral manifestations and symptoms do not predict the degree 9. Uhlen S, Fayoux P, Vachin F, Guimber D, Gottrand F, Turck D, et al. Mitomycin C: an
of esophageal and gastric mucosal injury alternative conservative treatment for refractory esophageal stricture in children?
Endoscopy. 2006;38:404-7.
• Blind nasogastric tube insertion, lavage, emesis, charcoal and
10. Watson WA, Litovitz TL, Rodgers GC Jr, Klein-Schwartz W, Reid N, Youniss J, et al.
milk are to be avoided after corrosive injury 2004 Annual report of the American Association of Poison Control Centers Toxic
• Steroids are indicated only in cases of airway edema Exposure Surveillance System. Am J Emerg Med. 2005;23:589-666.
• Esophagogastroduodenoscopy is indicated in all children with 11. Zargar SA, Kochhar R, Mehta S, Mehta SK. The role of fiberoptic endoscopy in
the management of corrosive ingestion and modified endoscopic classification of
CI who do not have perforation or severe hypopharyngeal injury.
burns. Gastrointest Endosc. 1991;37:165-9.
388
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Chapter 82
Chronic Abdominal Pain
Sarah Paul, John Matthai
Introduction Box 1: Red flag signs in chronic abdominal pain

Chronic (recurrent) abdominal pain is the commonest • Clearly localized/radiating pain • Perirectal disease
abdominal symptom that a pediatrician confronts in his • Pain that wakes the child from • Dysphagia
practice. Modifying the conventional definition by Apley, sleep • Persistent vomiting
the symptom duration has recently been reduced from 3 to • Gastrointestinal blood loss • Nocturnal diarrhea
2 months and the preferred term as chronic abdominal pain • Deceleration of linear growth • Unexplained fever
(CAP). Advances in investigative facilities over the years have • Family history of inflammatory • Arthralgia, rash
failed to yield a cause in a majority of children. This has led bowel disease • Delayed puberty
to the concept of functional abdominal pain, wherein the • Celiac disease or peptic ulcer • Weight loss
pain is real and not imaginary, and may be related to stress,
environmental and familial factors.
Functional Dyspepsia
CLASSIFICATION
Diagnostic Criteria
Rome III criteria laid down in 2006 categorized pain related
Diagnostic criteria must include all of the following (at least
functional gastrointestinal disorders (FGIDs) into five groups
once per week for at least 2 months):
(Table 1) and laid down diagnostic criteria for each.
• Persistent or recurrent pain or discomfort centered in the
upper abdomen (above the umbilicus)
Red Flag Signs
• Not relieved by defecation or associated with the onset of
Chronic abdominal pain may not always be functional. The red a change in stool frequency or stool form [i.e., not irritable
flag signs that suggest a possible organic basis are given in box 1. bowel syndrome (IBS)]
• No evidence of an inflammatory, anatomic, metabolic, or
Clinical Pearl neoplastic process that explains the subject’s symptoms.
• Do not ignore red flag signs in abdominal pain. Investigate Evaluation

children with any of them. The dyspeptic symptoms may follow a viral infection. Delayed
gastric emptying, disordered gastric myoelectrical activity, and
Table 1: Rome III criteria-H2: abdominal pain-related functional altered antroduodenal motility are implicated in pathogenesis.
gastrointestinal disorder An upper gastrointestinal (GI) endoscopy is not mandatory
for making a diagnosis, unless the patient has dysphagia or
H2a Functional dyspepsia symptoms improve with antacids and relapse on withdrawal
H2b Irritable bowel syndrome or Helicobacter pylori disease is suspected.
H2c Abdominal migraine
Treatment
H2d Childhood functional abdominal pain
Avoidance of drugs particularly analgesics, and specific foods
H2d1 Childhood functional abdominal pain syndrome that aggravate symptoms should be avoided. Antacids and
Ch-82.indd 389 11/21/2016 10:48:16 AM

prokinetics may offer symptom relief in some patients, but Evaluation

their routine use is not recommended without an upper GI Cyclic vomiting syndrome, migraine headache, and
endoscopy. A search for psychological factors may be made in abdominal migraine are believed to be the spectrum of the
appropriate settings. same disease with overlap. Family history of migraine and
motion sickness, are therefore, often present. In appropriate
Irritable Bowel Syndrome settings, subacute obstruction of the intestine, urinary and
biliary tract, as well as chronic pancreatitis and porphyria
Diagnostic Criteria should be ruled out. Response to migraine prophylactic drugs
Diagnostic criteria must include all of the following (at least is supportive evidence.
once per week for at least 2 months):
• Abdominal discomfort (an uncomfortable sensation not Treatment
described as pain) or pain associated with two or more of Avoidance of potential triggers, like caffeine, prolonged
the following, at least 25% of the time: fasting, sleep deprivation, and exposure to flickering
{{ Symptoms improved with defecation lights, may be suggested. In those with recurrent episodes,
{{ Onset associated with a change in frequency of stool (4 propranolol, cyproheptadine, and sumatriptan can be tried.
or more stools per day and 2 or less stools per week)
{{ Onset associated with a change in form of stool
Childhood Functional Abdominal Pain
• No evidence of an inflammatory, anatomic, metabolic, or
neoplastic process that explains the subject’s symptoms. Diagnostic Criteria
Diagnostic criteria must include all of the following (at least
Evaluation once per week for at least 2 months):
Visceral hypersensitivity related to genetic predisposition and • Episodic or continuous abdominal pain
early stressful events is a likely cause. Anxiety, depression, • Insufficient criteria for other FGIDs
and multiple somatic complaints are often reported not only • No evidence of an inflammatory, anatomic, metabolic, or
by the patient, but also by the parents. In the absence of red neoplastic process that explains the subject’s symptoms.
flag signs, a positive diagnosis of IBS can be made without any
investigations. Evaluation
These children are not troubled by their symptoms and
Treatment parental anxiety is the main compounding factor. No
A confident diagnosis, reasonable explanation of pain investigations are necessary in the absence of any red flag
experience, and reassurance are by themselves therapeutic. signs, provided the parents can be convinced of the diagnosis.
While peppermint oil is reported beneficial in children, anti-
depressants have not been proven useful. Treatment
Parents need to be reassured that there is no organic basis.
Placebo drugs should be discouraged. Psychological evaluation
Clinical Pearl is not necessary.
• Abdominal discomfort associated with a change in frequency
or form of the stool and improves on defecation suggests Childhood Functional Abdominal Pain Syndrome
irritable bowel syndrome.
Diagnostic Criteria
Diagnostic criteria must include childhood functional
Abdominal Migraine abdominal pain at least 25% of the time, and one or more of the
following (at least once per week for at least 2 months):
Diagnostic Criteria • Some loss of daily functioning
Diagnostic criteria must include all of the following (two or • Additional somatic symptoms, such as headache, limb
more times in the preceding 12 months): pain, or difficulty in sleeping.
• Paroxysmal episodes of intense acute periumbilical pain
that lasts for 1 hour or more Evaluation
• Intervening periods of usual health lasting weeks to months A limited screening which includes complete blood count,
• The pain interferes with normal activities erythrocyte sedimentation rate or C-reactive protein,
• The pain is associated with two or more of the following: urinalysis, and urine culture is indicated. Other investigations
anorexia, nausea, vomiting, headache, photophobia, and may be decided by the clinician depending on the predominant
pallor symptom and degree of functional impairment. Anxiety
• No evidence of an inflammatory, anatomic, metabolic, or depression and somatization may be seen in the patient and
neoplastic process that explains the subject’s symptoms. parents.
390
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Chapter 82: Chronic Abdominal Pain
Treatment should be minimized by preventing the child from using the

The contribution of psychosocial factors should be evaluated pain to avoid unpleasant but essential responsibilities. Diet
and behavioral therapy can give positive results. changes have little role in reducing pain, but a regular balanced
diet with adequate fibers must be insisted on. Though some
small studies have reported benefits, most do not show any
APPROACH TO A CASE OF statistically significant difference between amitriptyline and
CHRONIC ABDOMINAL PAIN placebo in functional GI diseases in children. Interaction with
the teachers may help identify children with special needs
Children presenting with CAP can broadly be classified into
(specific learning disability, attention deficit hyperactivity
three groups, based on the pattern of pain (Table 2).
disorders). They can be informed directly or through the
1. Isolated paroxysmal periumbilical CAP
parents that they need to be sympathetic to the child while
2. Chronic abdominal pain with dyspepsia
not creating panic. Consultation with a psychiatrist is not
3. Chronic abdominal pain with altered bowel habits.
recommended unless there are compelling reasons to do so,
since it can affect the morale and outlook of the parents and
Clinical Pearl the child.
• Isolated paroxysmal periumbilical pain in children is most
commonly functional pain.
Clinical Pearl
What to tell the parents?
MANAGEMENT OF FUNCTIONAL PAIN • The pain in functional abdominal pain is real, not imaginary.
Do not deny the presence of pain. The reassurance is only that
The first step in management is making a positive diagnosis. there is no organic basis.
Parental counseling should be well planned with an
unequivocal reassurance that there is no organic disease and
that the prognosis is good. They need to understand that the
pain is real and the child is not feigning, but there is no need for Key points
medication. Hospitalization is ideally avoided since it is likely
))
Functional gastrointestinal (GI) disorders are the most
to reinforce pain behavior. The treatment aims to normalize common cause of chronic abdominal pain in children
lifestyle (school attendance, extracurricular activities, sleep) ))
Functional dyspepsia, irritable bowel syndrome, and
by benign negligence or distraction techniques. It is also functional abdominal pain are the most common causes
important to identify and reduce stress/triggers at home, ))
Look for red flag signs before considering functional disorders
neighbourhood or with peers. Any form of secondary gain ))
Isolated paroxysmal periumbilical pain is most likely functional
))
Chronic abdominal pain with dyspepsia or altered bowel
habits warrant consideration of upper/lower GI disorders
Table 2: Classification of chronic abdominal pain based on the ))
Children with functional pain need reassurance and return to
pattern of pain normal lifestyle at the earliest, after an attempt to correct or
Isolated paroxysmal periumbilical abdominal pain reduce trigger/stress factors.
Functional • Organic abdominal pain <5%

pain 95% • In test: malrotation, Crohn’s disease, adhesions SUGGESTED READINGS
• Renal: stone colic, PUJ obstruction
• Infection: tuberculosis, Yersinia 1. Bhaskar R, Ghosh M, Pal S, Gupta SD. Recurrent (chronic) abdominal pain in
children. In: Bavdekar A, Matthai J, Sathiyasekaran M, Yachha SK (Eds). Pediatric
• Others: food allergy, dysmenorrhea
Gastroenterology, 2nd edition. New Delhi: Jaypee Brothers Medical Publishers (P)
CAP with dyspepsia Ltd.; 2013. pp. 22-36.
Functional • Organic abdominal pain 10% 2. Caplan A, Walker L, Rasquin A. Validation of the pediatric Rome II criteria for
functional gastrointestinal disorders using the questionnaire on pediatric
pain 90% • GERD, Helicobacter pylori, Giardia gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. 2005;41(3):305-16.
• Pancreatitis, biliary disease 3. Di Lorenzo C, Colletti RB, Lehman HP, Boyle JT, Gerson WT, Hyams JS, et al.
• Food intolerance, drugs Chronic abdominal pain in children: a clinical report of American Academy
of Pediatrics and the North American Society for Pediatric Gastroenterology,
CAP with altered bowel habits Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40(3):245-8.
Functional • Organic abdominal pain 25% 4. Milla PJ. Irritable bowel syndrome in childhood. Gastroenterology. 2001;
pain 75% • Constipation, IBD, TB, parasites 120(1):287-90.
• Lactose intolerance, food allergy 5. Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, et al.
Childhood functional gastrointestinal disorders: child/adolescent. Gastro
• Gynecological, drugs enterology. 2006;130(5):1527-37.
CAP, chronic abdominal pain; PUJ, pelvi-ureteric junction, GERD, gastro 6. Zeiter DK, Hyams JS. Recurrent abdominal pain in children. Pediatr Clin North
esophageal reflux disease; IBD, inflammatory bowel disease; TB, tuberculosis. Am. 2002;49(1):53-71.
391
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Section 11: Neurology
Chapter 83
Approach to Global
Developmental Delay
Pratibha D Singhi, Naveen Sankhyan
DEFINITION CLINICAL ASSESSMENT

Global developmental delay (GDD) is an umbrella term
used to describe young children with developmental delay.
History
Conventionally, the term developmental delay is reserved for The clinical assessment of a child with GDD/ID begins with a
children below 5 years of age. The term mental retardation thorough and directed history (Box 1).
or more appropriately, “intellectual disability (ID)” is A detailed history is essential to elicit antenatal and
usually applied to older children (>5 years), when intelligent perinatal risk factors for GDD/ID. The history should be
quotient testing is valid and reliable. Global developmental focused on maternal health during the first trimester of
delay implies a significant delay in two or more areas of pregnancy including fever, drug intake or toxin exposures,
developmental performance: defined as gross⁄fine motor, and clues to intrauterine difficulties (oligohydramnios, pre-
speech⁄language, cognition, social⁄personal, and activities of eclamptic toxemia, poor growth, antenatal bleeding, reduced
daily living. Significant delay is defined as a developmental fetal movements, etc.). The timing and mode of delivery, birth
level two standard deviations or more below the mean on age- weight, APGAR scores, head circumference at birth, time to
appropriate, standardized, norm-referenced tests. Contrary to independent feeding, and duration of postnatal hospital stay
popular use, GDD is not a diagnosis by itself and so it should are important objective markers of newborn health status.
be used only as a basis for reaching a diagnosis. The prevalence One needs to remember that a history of delayed cry, although
of intellectual disability is estimated to be around 1–3% of the an important clue is insufficient to conclude perinatal insult,
population. unless there is definite suggestion of neonatal encephalopathy
(e.g., excessive lethargy, seizures, and feeding difficulties
requiring orogastric/nasogastric feeding).
APPROACH TO DIAGNOSIs
A systematic approach to a child with GDD will help in the
proper and optimum evaluation. The essential components of Box 1: Questions to be answered after history in a child with
the diagnostic evaluation of a child with GDD or intellectual global developmental delay/intellectual disability
disability include the following:
• Is it a static or progressive disorder?
• History: including prenatal and birth history, family
• Is there an obvious etiologic cause?
history, and construction of a pedigree of three generations
• Physical examination (special emphasis on dysmorphism): • What is the timing of the possible underlying cause?
neurologic examination, organomegaly • What is the developmental and functional level of the child?
• Psychometric evaluation: to document and objectify the • What are the associated comorbid medical or behavioral
functional level in various domains conditions (e.g., epilepsy and attention deficit hyperactivity
disorder)?
• Laboratory tests: radiological evaluation (X-rays and
neuroimaging), genetic testing, metabolic tests, etc. as • In what socioeconomic and sociocultural milieu is the child
being raised?
indicated.
Ch-83.indd 392 11/21/2016 11:06:11 AM

Chapter 83: Approach to Global Developmental Delay
Clinical Pearl Developmental Assessment

The clinical history should be supplemented with
• Remember that a history of delayed cry, although an important
standardized testing of developmental level by a clinical
clue is insufficient to conclude perinatal insult, unless there
is definite suggestion of neonatal encephalopathy (e.g., psychologist. Standardized tools include screening tests
excessive lethargy, seizures, feeding difficulties requiring such as the Denver’s Development Screening Test, and the
orogastric/nasogastric feeding). Ages and Stages Questionnaire, and more detailed tests
such as the Gesell Development Schedules and the Bailey’s
Developmental Scales. When there is a concern about
Postnatal insults such as neuroinfections are common in developmental delay in a child, a developmental quotient
the resource-poor countries and account for a large number should be calculated for each developmental stream. It
of children with acquired GDD/ID. A detailed developmental is a means to simply express a developmental delay in
history and past history should be elicited for presence quantifiable terms. The “developmental quotient” is the ratio
of seizures, hospitalizations, and other acute or chronic of the child’s developmental age over the chronological age.
conditions. A family history of ID can point toward a genetic Typical development is a developmental quotient greater
cause of GDD/ID, for example fragile-X syndrome or other than 70%, and atypical development is a developmental
X-linked mental-retardation syndromes. Family history may quotient of less than 70%. The term GDD delay is used if a
also point toward an unrecognized metabolic disorder such as
child—younger than 5–6 years of age—has a developmental
phenylketonuria.
quotient less than 70% in two or more domains.
Clinical Pearl Investigations

• A three-generation family history should be carefully elicited The choice and the sequence of investigations should be
in all children with developmental delay to unearth possible guided by the clinical evaluation, cost of investigations, and
inherited causes. availability (Algorithm 1). Some investigations are a part of
complete evaluation (e.g., standardized vision, hearing testing,
To recognize patterns of inheritance, it is essential that a ultrasound, and skeletal X-rays) while others tests offer means
carefully elicited history is used to construct a three-generation to establish the diagnosis (genetic and metabolic testing).
pedigree and identify consanguinity. In the absence of a universal thyroid screening in India,
thyroid function tests should be done in all children with
Examination GDD/ID. Additionally, keeping in mind that large numbers
of children in resource-poor countries have acquired causes
A child with GDD/ID evaluation with special focus on
for GDD/ID, it is prudent to opt for imaging studies as the
dysmorphic features. Special attention is to be paid to the size
initial diagnostic testing. Magnetic resonance imaging is the
and shape of head, facies, eyes, stature, skin, hearing, hair, and
imaging modality of choice, given the higher resolution and
organomegaly. Any abnormalities in the head shape, sutures,
better resolution to pick up dysgenesis and white-matter
and fontanels should be noted. In children with abnormal
abnormalities.
head size, head circumferences of both parents should be
obtained. The head circumference has to be assessed over a
period of time to understand the trajectory of head growth.
Genetic Testing
When a child is noted to have an unusual appearance, It is preferable to involve experts in clinical genetics whenever
a diagnosis is significantly more likely. Neurological possible for the genetic evaluation of GDD/ID.
examination is important to identify cerebral palsy, muscle-
tone abnormalities, weakness, paresis, ataxia, and other Cytogenetic Studies
specific neurological signs. A good physical examination, Chromosome abnormalities are found in all categories of
particularly to look for organomegaly is also essential. intellectual disability, mild to profound and in both sexes.
Such abnormalities on neurologic examination assist in The reported frequency of chromosomal anomalies detected
determining the need for additional investigations such as by high-resolution karyotyping (i.e., 550 bands) in patients
electroencephalography, neuroimaging or molecular genetic evaluated for intellectual disability or developmental delays is
testing, or referral to other specialists such as psychologists, around 10%. This test is reported to be a valuable initial test for
or geneticists for further assessment. evaluation of GDD.
The history and examination provide essential clues to the
diagnosis, which can be later confirmed by additional studies, Fluorescent in situ Hybridization Testing (FISH)
for example, in patients with Pradder‒Willi syndrome, the About half of all structural chromosome abnormalities include
history and examination may be contributory to the diagnosis the telomere of the chromosome. Many of these abnormalities
and the molecular genetic analysis confirms it. may be missed by the standard karyotype. Fluorescent in situ
393
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Algorithm 1
Approach to diagnosis in a child with global developmental delay/intellectual disability
GDD, global developmental delay; ID, intellectual disability; FISH, fluroscent in situ hybridization; MRI, magnetic resonance imaging; MRS, magnetic resonance
spectroscopy; CDG, congenital disorders of glycosylation; aCGH, array comparative genomic hybridization.
hybridization techniques have been applied to examine the Metabolic Testing (Box 2)
subtelomeric regions of each chromosome for abnormalities
Both genetic testing and metabolic testing is expensive; hence its
that are known to cause intellectual disability. The yield is
judicious use is warranted. In such situations, it would be wise to
higher among familial cases as compared with sporadic cases. obtain an expert consultation before proceeding with these tests.
Array Comparative Genomic Box 2: Indications for screening for inborn errors of
Hybridization Techniques (aCGH) metabolism in children with global developmental delay/
intellectual disability
It is a better technique to evaluate chromosomal abnormalities.
It identifies deletions and/or duplications of chromosome • Pregnancy: a history of maternal acute fatty liver of pregnancy
material with a high degree of sensitivity in a more efficient or hemolysis, elevated liver enzymes, and low platelets are
associated with several fatty acid oxidation disorders
manner than FISH techniques. Furthermore, the FISH test is
• Family history: parental consanguinity, unexplained neonatal or
predominantly used to confirm a clinical diagnosis, whereas infant deaths, family history of suspected metabolic disorder
aCGH does not require an expert clinician to suspect a specific • Others: unexplained hypoglycemia, recurrent encephalopathy,
394 diagnosis. However, it is expensive and not available at most protein aversion, multisystem involvement, possible white
centers in India. matter involvement
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Chapter 83: Approach to Global Developmental Delay
3. Schroeder S, Gerry M, Gert G, Velazquez F. Final Project Report: Usage of the

Key points term “Intellectual disability:” Language, Image and Public Education, in American
Association of Intellectual Disability Resource Network International. Center on
))
Global developmental delay means a significant delay in two
Developmental Disabilities; Center for the Study of Family, Neighborhood and
or more areas of developmental performance Community Policy, University of Kansas; 2001. pp. 1-216.
))
The term mental retardation or more appropriately, “intellectual 4. Sherr EI, Shevell MI. Global developmental delay and mental retardation/
disability” is usually applied to older children (>5 years).The intellectual disability. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF (Eds).
essential components of the diagnostic evaluation include: Pediatric Neurology: Principles and Practice, 5th edition. Saunders, Elsevier;
history (including prenatal and birth history), family history, 2012. pp. 554-74.
physical and neurologic examinations, laboratory tests, 5. Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtiz D, et al: Practice
including metabolic, and genetic testing, and imaging. parameter: evaluation of the child with global developmental delay—Report of
the Quality Standards Subcommittee of the American Academy of Neurology
and the Practice Committee of the Child Neurology Society. Neurology.
2003;60:367‑80.
SUGGESTED READINGS
6. Van Karnebeek CDH, Janswiejer MCE, Leenders AGE, Offringa M. Diagnostic
1. Battaglia A, Carey JC. Diagnostic evaluation of developmental delay/mental investigations in individuals with mental retardation: a systematic literature
retardation: an overview. Am J Med Genet C Semin Med Genet. 2003:117C(1);3‑14. review of their usefulness. Eur J Human Genet. 2005;13:2-65.
2. Cleary MA, Green A. Developmental delay: when to suspect and how to investigate 7. Williams J. Global developmental delay—globally helpful? Dev Med Child Neurol.
for an inborn error of metabolism. Arch Dis Child. 2005;90:1128-32. 2010;52:227.
395
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Chapter 84
Approach to Psychomotor
Regression in Children
Anaita Udwadia Hegde, Omkar P Hajirnis
INTRODUCTION patterns are disease specific and a history of consanguinity is

especially important in autosomal recessive disorders.
Neurodevelopmental regression is often challenging to
clinicians in terms of diagnosis and management. The purpose Clinical Pearl
of this chapter is to outline a systematic approach to a child
presenting with suspected neurodevelopmental regression. • It is important to differentiate between developmental delay
Reaching a specific diagnosis is of pivotal importance for and developmental regression.
providing appropriate early therapy, prognosis, and genetic
counseling. Although the causes of psychomotor retardation The four-step approach described below provides a useful
are individually rare, the combined estimate can be as high as strategy for initial evaluation of patients with neurodegenerative
about 1 in 2,000 live births. diseases:
• Identify the form of inheritance: autosomal recessive, auto
DEFINITION somal dominant, X-linked, and mitochondrial inheritance
• Age at onset of regression: based on this, the disorders
Neuroregression is defined as loss of previously achieved can be divided into neonatal, infantile, late infantile, and
milestones in a previously healthy child with progressive childhood or juvenile onset
loss of speech, hearing, vision, locomotion, bulbar function, • Determine from the history the predominant neuro
and cognitive abilities. They are often associated with anatomical system involved: gray matter, white matter,
seizures. It is also extended to a decrease in the normal rate basal ganglia, cerebellar, spinal cord, etc.
of acquisition of developmental milestones, followed by a • Review other system involvements: involvement of skin,
developmental plateau. liver, spleen, dysmorphic features, ophthalmic changes,
presence of seizures, peripheral neuropathy, etc.
Clinical Approach
A history of loss of skills helps distinguish the neuro
Step 1: Inheritance
degenerative from static, nonprogressive conditions. The onset A detailed family tree or a pedigree chart helps to define
may be insidious but is sometimes acute and may hence cause different modes of inheritance. The most common modality
diagnostic confusion. The regression may thereafter progress of inheritance is autosomal recessive, seen commonly in
at varying speeds or also have an intermittent plateauing of our circumstances due to high degree of consanguineous
milestones prior to the next period of deterioration, which may marriages. It is important to note that mitochondrial disorders
be triggered by factors like viral infections. The presentations can be inherited by maternally-transmitted modalities or an
can be varied from behavioral changes to recurrent seizures autosomal pattern of inheritance. This is because mitochondria
mimicking epileptic encephalopathies. It is a dictum that contain two types of genetic material, namely mitochondrial
greater the genetic deficiency, earlier and more aggressive is deoxyribonucleic acid (DNA) which can only be passed on
the presentation. Knowing the age at which signs first appear from the mother and nuclear DNA which is passed on from
helps enormously in narrowing the diagnosis. The diagnostic both parents. A few examples of neurodegenerative disorders
process begins with a detailed family history as inheritance with their modes of inheritance are listed in the table 1.
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Chapter 84: Approach to Psychomotor Regression in Children
Table: 1 Neurodegenerative disorders and their inheritance initially representing a toxic or intoxication encephalopathy.
patterns Liver involvement may be evident in few disorders presenting
Inheritance Neurodegenerative disorders
with jaundice, liver failure, and failure to thrive.
Autosomal • Disorders involving white matter Infancy onset (1–12 months): onset at this age usually presents
recessive {{ Canavan’s disease with loss of interest in surroundings which can be either visual
{{ Krabbe’s disease or in nonverbal communication. The inability to roll over,
{{ Metachromatic leukodystrophy sit, use the hands in play, and vocalize suggests neurologic
• Disorders involving gray matter difficulties at this age.
{{ Progressive myoclonic epilepsies (Lafora
body disease, etc.)

Late infantile age group onset (1–5 years): the changes noted in
{{ Progressive infantile poliodystrophy
this age group are more commonly in the speech and behavior
{{ Sialidosis type 1
along with motor disabilities. They may exhibit clumsiness,
{{ Neuronal ceroid lipofuscinosis (variable)
tremors, and gait abnormalities. They can present primarily
• Disorders involving predominantly basal with seizures.
ganglia Juvenile age group onset (5–15 years): in disorders of
{{ Wilson’s disease
childhood and adolescence, the onset is more insidious and
{{ Pantothenate kinase-associated
the progression slower than in disorders appearing earlier.
neurodegeneration
Regression in this age group can present with seizures along
• Spinocerebellar degeneration/spinal cord and
with deterioration of school performance, lack of new learning
peripheral nerve conditions
{{ Friedreich’s ataxia
skills, handwriting changes, poor concentration, and memory.
{{ Spinal muscular atrophy
{{ Infantile neuroaxonal dystrophy

Step 3: Neuroanatomical Localization
{{ Refsum’s disease The next most important feature to assess from the history and
Autosomal • Juvenile Huntington’s disease examination is the onset of symptoms and progression to the
dominant • Dystonia musculorum deformans present state. The first sign or symptom of neuroregression
• Spinocerebellar ataxia usually but not always gives a clue to the neuroanatomical
• Familial spastic paraplegia localization. For example, gait or motor regression at the onset
• Charcot-marie-tooth disease is suggestive of white matter pathologies, whereas seizures,
X-linked • Pelizaeus-Merzbacher disease
dementia, and cognitive decline is more suggestive of gray-
recessive • Adrenoleukodystrophy
matter pathologies. Those who start with chorea, dystonia,
• Menke’s kinky hair syndrome and involuntary movements suggest that the primary area
of involvement is the basal ganglia. Over a period of time,
Mitochondrial • Alpers-Huttenlocher syndrome
symptoms evolve to involve multiple neuroanatomical sites;
• Leigh’s syndrome
for example, Krabbe’s disease starts with increase in tone or
• Kearns Sarne syndrome
loss of motor milestones suggestive of white matter pathology.
• Myoclonic epilepsy with ragged red fibers
There may also have some dystonia, indicative of basal ganglia
• Leber’s hereditary optic neuropathy
involvement and over time, the child will become loose with
• Mitochondrial encephalomyopathy with lactic
absent reflexes suggestive of additional peripheral neuronal
acidosis and stroke like episodes
involvement.
Hence by careful history taking and detailed general and
nervous system examination, it is easier to determine which
Step 2: Age of Onset pathways are involved and the range of diagnostic possibilities
The age of onset of neuroregression helps us classify the is more easily circumscribed (Algorithm 2).
disorders. It goes without saying that the earlier the onset,
the more severe and progressive is the disorder. Those who Clinical Pearl
manifest late in childhood or adolescence usually have milder
symptoms and the progress is slower as compared to those who • The first sign of neuroregression usually correlates best with
manifest early and progress faster. Age of onset is divided into neuroanatomical localization.
neonatal (0–1 month), infantile (1–12 months), late infantile
(1–5 years), childhood (5–10 years), and adolescent or juvenile
onset (5–15 years). Step 4: Identifying Associated
System/Organ Involvement
Age-related Presentations Multiple systems get involved with different degenerative
Neonatal onset (0–1 month): acute encephalopathy presents disorders. The physician needs to carefully screen other
early in life with recurrent vomiting, poor feeding, lethargy, associated systemic involvements beginning with a detailed
and dehydration. This suggests a gray matter involvement head-to-toe general examination. The examination should 397
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Algorithm 1
Approach to psychomotor regression in children
SSPE, subacute sclerosing panencephalitis.
begin with height, weight, and head-circumference measure Box 2: Neurodegenerative disorders with dysmorphic features
ments. Many disorders eventually lead to acquired microcephaly
due to brain atrophy; others are noted for megalencephaly. • Zellweger’s syndrome • Mucopolysaccharidoses
Dysmorphisms may be evident at birth or may be noted later as • Inclusion-cell disease • Oligosaccharidoses
the disorder manifests (Boxes 1 and 2). • Smith-Lemli-Opitz syndrome • Mucolipidosis
A careful observation of the skin and hair and a full • 18 q syndrome • Prader-Willi syndrome
assessment of the chest, abdomen, and extremities are part of • Pyruvate dehydrogenase • Cockayne’s syndrome
deficiency • GM1 Gangliosidosis
the examination (Tables 2 and 3).
A detailed ophthalmologic examination with fundoscopy
is pivotal and the various disorders associated with eye Table 2: Hair and skin changes in neurodegenerative disorders
abnormalities are listed in table 4.
Hair changes Skin changes
Seizures may be a presenting complaint or may present as
the disease progresses. The age of onset and also the seizure • Menkes syndrome (kinky, • Phakomatosis
type provides useful information to arrive at the diagnosis colorless or steel-colored and {{ Neurofibromatosis
easily broken—Pili torti) {{ Tuberous sclerosis

(Algorithm 3). The peripheral nervous system may be
• Biotinidase deficiency (alopecia {{ Sturge-Weber syndrome
involved in certain neurodegenerative disorders giving rise to and fine, brittle hair)
diminution or absence of deep-tendon reflexes and sensation • Angelman’s syndrome
• Homocystinuria • Hypomelanosis of Ito
(Box 3). (thin and fair hair) • Incontinentia pigmenti
Thus, all the features and clues mentioned above along with • Cockayne’s syndrome • Homocystinuria (pale, pink
a careful history and examination help to arrive at a diagnosis. (fine, thin, and dry hair) skin, malar rash, livedo
Each associated system needs to be examined in detail to be • Mucopolysaccharidosis reticularis)
able to put all the pieces of the puzzle together. (alopecia areata and pale- • Ataxia telangiectasia
colored hair) (vitiligo, warts,
• Arginosuucinic acidurias granulomas)
(sparse brittle hair) • Cockayne’s syndrome
Box 1: Neurodegenerative disorders with megalencephaly • Ataxia telangiectasia (photosensitivity)
(progeroid changes like • Multiple sulfatase
• Alexander disease • Sandhoff’s disease premature graying of hair) deficiency (ichthyosis)
• Tay-Sachs disease • Glutaric aciduria type I • Multiple sulfatase deficiency
398 • Canavan’s disease (hypertrichosis)
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Algorithm 2
Clinical features of neurodegenerative disorders with categorization according to age of onset
PMD, pelizaeus merzbacher disease; VWM, vanishing white matter disease, CDG, congenital defects of glycosylation, MLC, megalencephalic leukoencephalopathy
with subcortical cysts; MSUD, maple syrup urine disease; FAO, fatty acid oxidation, MCAD, medium chain acyl-coa dehydrogenase, NCL, neuronal ceroid
lipofuscinosis, ALD, adrenoleukodystrophy, PKAN, pantothenate kinase-associated neurodegeneration, H-ABC, hypomyelination with atrophy of the basal
ganglia and cerebellum, INAD, infantile neuroaxonal dystrophy; DRPLA, dentatorubral-pallidoluysian atrophy; SCA, spinocerebellar ataxia; HMSN, hereditary
motor sensory neuropathy; HSP, hereditary spastic paraplegia, LBSL, leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation,
MLD, metachromatic leukodystrophy.
INVESTIGATIONS and physical examination. The basic metabolic screen which

The investigations should cater to the common causes seen includes blood, urine, and sometimes the cerebrospinal fluid
in each age group and proceed from common to rarer causes. examination should be done initially along with neuroimaging
All disorders that are potentially treatable or have genetic [magnetic resonance imaging (MRI) brain] for suspected
implications should be screened in all cases. For example, metabolic disorders. More advanced tests should be prioritized
thyroid function tests should be done as hypothyroidism according to the condition suspected. Now genetic diagnosis is
can present with no obvious signs in infancy. Although the gold standard of diagnosis and wherever possible should
below mentioned is an exhaustive list of investigations, the be attempted as it is useful not only for diagnosis but also for
physician should prioritize from specific clues in the history future genetic counseling (Table 5). 399
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Table 3: Visceromegaly associated with neurodegenerative Algorithm 3

disorders Epilepsies associated with neurodegenerative disorders
Hepatosplenomegaly Hepatomegaly
• Lipid storage disorders • GSD Type 1
{{ Gangliosidosis • GSD Type II, VI, IX
{{ Mucolipidosis • Wolman’s disease
{{ Farber disease • Zellweger’s syndrome
• Mucopolysaccharidosis • Hunter’s syndrome
{{ Hurler’s syndrome • Glycogenosis Type II
{{ Hunter’s syndrome
• Glycogen storage disorders (GSD)

{{ GSD Type IV
Splenohepatomegaly Splenomegaly
• Gaucher’s disease • Alpha mannosidosis
• Niemann-Pick disease • Hurler’s syndrome and other
mucopolysaccharidosis
• Tangier disease
• Sandhoff’s disease
Table 4: Eye abnormalities associated with neurodegenerative

disorders
Eye abnormalities
Cornea Pigmentary retinopathy
• Wilson’s disease • Fetal cytomegalovirus infection
• Hurler’s disease • Fetal toxoplasmosis
• Maroteaux-Lamy syn- • Hallervorden-Spatz disease
drome • Kearns-Sayre syndrome
• Morquio’s disease • Neuronal ceroid lipofuscinosis
• Mucolipidosis type IV • Zellweger’s syndrome
• Mannosidosis • Cockayne’s syndrome
• Fucosidosis • Congenital disorder of glycosylation
• Aspartylglucosaminuria • Abetalipoproteinemia
Conjunctiva Cherry-red macula
• Ataxia telangiectasia • GM1 gangliosidosis
• Niemann-Pick disease, types A and B
• Tay-Sachs disease
• Sialidosis type I
Lens Optic atrophy
• Homocystinuria • Adrenoleukodystrophy NCL, neuronal ceroid lipofuscinosis; MERRF, myoclonic epilepsy with ragged
• Myotonic dystrophy • Metachromatic leukodystrophy red fibers, MELAS, mitochondrial encephalomyopathy lactic acidosis and
• Galactosemia • Globoid cell leukodystrophy stroke-like episodes, GLUT, glucose transporters.
• Lowe syndrome • Pelizaeus-Merzbacher disease
• Fabry’s disease • Mitochondrial–MELAS, LHON
• Cerebrotendinous • Canavan disease
xanthomatosis • Sulfite oxidase deficiency The workup involves neuroimaging in most cases. Magnetic
• 3-methylglutaconicaciduria III resonance imaging with or without contrast is preferred over
computed tomography. It is useful for visualizing cerebral
Cortical blindness Abnormal eye movements
malformations and for documenting the degree of cerebral
• MELAS syndrome • Opsoclonus myoclonus atrophy or white matter changes, such as those that occur
syndrome (with progressive in various leukodystrophies. Magnetic resonance imaging
ophthalmoplegia)
with contrast is ordered in suspected adrenoleukodystrophy,
• AD spinocerebellar ataxias
• Ataxia telangiectasia
Alexander’s disease, etc. Specific spectroscopy is useful in
• Gaucher’s disease, types 2 and 3 mitochondrial disorders, Canavan’s disease, and creatine
• Kearns-Sayre syndrome deficiency. Increased N-acetylaspartate peak is detected in
• Niemann-Pick disease type C Canavan’s disease, and in mitochondrial disorders a high
• Pelizaeus-Merzbacher disease lactate peak may be found. Magnetic resonance imaging
400
AD, autosomal dominant; MELAS, mitochondrial encephalomyopathy, lactic with angiography is done in suspected Menke’s disease to
acidosis, and stroke-like episodes; LHON, Leber’s hereditary optic neuropathy. demonstrate tortuous vessels.
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Continued
Box 3: Peripheral neuropathies associated with neuro-
degenerative disorders Test/Study Abnormalities of Interest
Episodic neuropathy • Free fatty acids
• Acute intermittent porphyrias • Plasma amino acids
• Tyrosinemia type I • Plasma organic acids
Progressive neuropathy • Acylcarnitine profile
• Metachromatic leukodystrophy Advanced workup • Very long-chain fatty acids
• Refsum’s disease • Immunoglobulin levels
• Mitochondrial neuropathy/myopathy (Leigh’s syndrome, neuro • Autoantibodies
pathy ataxia and retinitis pigmentosa syndrome, etc.) • White cell enzyme studies to look for
• Abetalipoproteinemia vacuolation of lymphocytes
• Pyruvate dehydrogenase deficiency • Isoelectric focusing of transferrin
• Friedreich’s ataxia Cerebrospinal fluid
• Juvenile GM2 gangliosidosis Neurotransmitters are • Opening and closing pressures
• Krabbe’s disease (late infantile form) collected in specific • Cell count, protein, glucose with
• Adrenomyeloneuropathy tubes and transported simultaneous blood glucose (For
• Cockayne’s syndrome in dry ice; collect suspected GLUT1 deficiency—4 h
• Methylenetetrahydrofolate reductase deficiency minimum 2 mL stat minimum fasting needed)
• Carbohydrate deficient glycoprotein syndrome (on ice) for chemistries • Lactate
• 3-hydroxy dicarboxylic aciduria and lactate • Pyruvate
• Familial dysautonomia • Neurotransmitters
Genetic analysis • DNA analysis of specific suspected
Table 5: Investigations for suspected metabolic/neurode disorders
generative disorders Bone marrow • For foam cells, sea blue histocytes, etc.
examination
Test/Study Abnormalities of Interest
Skin biopsy • Enzyme analysis in cultured fibroblasts
Urine (lysosomal disorders)
• Collect each fresh • Smell (special odor), look (special color) • Staining for lipids, glycogen,
sample separately • Acetone cholesterol, fatty acids
in clean container • Reducing substances • NP-C (cholesterol esterification, filipin
and store at 4°C • Ketoacids (DNPH) staining)
(short term). • pH • DNA analysis
• Freeze at –20°C for • Electrolytes • Electron microscopy for storage inclu-
long-term storage. sions (lysosomal, mitochondrial NCL)
• Sulfite oxidase
Compare samples
• Uric acid Muscle biopsy • Light and electron microscopy,
collected before
• Aminoacids immunohistochemistry, trichrome for
and after treatment.
• Organic acids (quantitative) ragged red fibers, lipid storage, etc.
• 24-h urine copper excretion Liver biopsy • Staining for accumulation of lipids,
glycogen, cholesterol, fatty acids,
• MPS screening and electrophoresis
immunohistochemistry
Blood EMG/SSEP • Lower motor neuron disease patterns
• 5 mL plasma • Complete blood count • Neuropathies
(heparinized or • Electrolytes (for anion gap, glucose, • Myopathies
plain tube) calcium) EEG • Associated seizures (clinical and sub
• 5–10 mL whole • Blood gas (pH, pCO2, HCO3–, pO2) clinical) and their pattern
blood in EDTA (for • Uric acid ERG • In suspected retinitis pigmentosa
molecular DNA • Prothrombin time BERA • In suspected hearing loss
studies) • Liver function tests USG abdomen • Organomegaly, nephrocalcinosis, renal
• Blood on filter • Thyroid function tests cysts
paper (Guthrie’s
• Plasma ammonia (on ice) 2D echocardiography • Cardiomyopathy in storage disorders,
test)
• Lactic acid (on ice; stat processing) rhabdomyosarcomas in tuberous
• Pyruvic acid (requires specialized sclerosis
deproteinization tube) X-ray screening • For dysostosis multiplex in MPS,
• Serum ketones assessment of bone age
• Serum homocysteine NCL, neuronal ceroid lipofuscinosis; NP-C, niemann-pick type c disease, NTBC,
• Serum vitamine B12 levels nitisinone, DNPH, 2 4-dinitrophenylhydrazine, GLUT, glucose transporter; MPS,
• Serum copper and ceruloplasmin mucopolysaccharidosis; EMG/SSEP, electromyography/somatosensory evoked
potentials; EEG, electroencephalogram; ERG, electroretinography; BERA,
Continued brainstem evoked response audiometry.
401
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Algorithm 4
Approach to neuroregression according to major neuroimaging pattern
MLD, metachromatic leukodystrophy; ALD, adrenoleukodystrophy; INAD, infantile neuroaxonal dystrophy, LBSL, leukoencephalopathy with brainstem and spinal
cord involvement and lactate elevation; NCL, neuronal ceroid lipofuscinosis; MLC, megalencephalic leukoencephalopathy with cysts; CACH/VWM, childhood ataxia
with central hypomyelination/vanishing white matter; CXT, cerebrotendinous xanthomatosis; PKAN, pantothenate kinase-associated neurodegeneration.
Thus, the MRI is an important ancillary test in approaching in supportive care. Careful attention to nutrition helps in
neuroregression and helps the clinician to delineate disorders maintaining general well-being. Symptomatic treatment of
based on the findings on it (Algorithm 4). disturbed sleep, behavior and mood disturbances should be
done. A small number of disorders have specific treatment and
maximum effort should be made to diagnose these conditions.
Clinical Pearl
They can be enumerated as in the box 4.
• Carefully planned investigations are needed rather than Bone marrow transplantation has been tried in various
ordering a battery of tests disorders and has shown promise when it has been done at
a stage where irreparable brain damage has not occurred.
This includes lysosomal storage disorders, metachromatic
MANAGEMENT leukodystrophy, Gaucher’s disease, mucopolysaccharidosis,
and adrenoleukodystrophy.
The specific cause of regression in childhood can be difficult to Every effort should be made to prevent the family from
elucidate and a large number of children remain undiagnosed. having another affected child with the help of antenatal
It is essential to maintain the child’s quality of life and help screening.
402
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Box 4: Treatable neurodegenerative/metabolic conditions Key points

• Wilson’s disease—D-Penicillamine and other chelating agents
))
Never ignore a parent’s concerns. A history of loss of
• Aminoacidopathies—specific diets. Nitisinone in tyrosinemia
milestones helps distinguish neuroregression from develop
• Pyridoxine and pyridoxal phosphate dependent seizures— mental delay
pyridoxine
))
A detailed pedigree chart helps to identify different modes
• Biotinidase deficiency and biotin responsive basal ganglia of inheritance. The most common modality in neuro
disease—biotin degenerative conditions is autosomal recessive type
• Glucose transporter-1 deficiency—ketogenic diet ))
The dictum is earlier the onset, more severe and aggressive
• Folinic acid responsive seizures—folinic acid is the disorder due to greater genetic deficiency. The
• Creatine deficiency syndromes—creatine regression may progress at varying speeds and some may
• Serine biosynthesis disorders—L-serine and glycine evolve with time
• Neurotransmitter disorders—dopamine in some cases ))
The presenting symptom is usually but not always a pivotal
• Inborn errors of folic acid and cobalamin synthesis—folic acid clue to the neuroanatomical localization. Magnetic resonance
and vitamin B12 imaging with or without contrast is preferred over computed
• Homocysteinemia, methylenetetrahydrofolate reductase—B12, tomography as the neuroimaging of choice and is an
folic acid, pyridoxine important ancillary test in approaching neuroregression
• Gaucher’s disease, Fabry’s disease, mucopolysaccharidosis, ))
The disorders that have specific treatment should always be
Pompe’s disease—enzyme replacement looked out and diagnosed promptly
))
Although most disorders do not have specific treatment,
maximum effort should be made to reach a genetic diagnosis
for genetic counseling and antenatal testing later. Every effort
ANTENATAL TESTING AND COUNSELING should be made to prevent the family from having another
Having an accurate genetic diagnosis helps immensely for affected child.
genetic counseling and antenatal testing. A clear explanation
of the inheritance pattern will clear up misunderstandings in
the family about who is “at fault”. Once a genetic diagnosis is SUGGESTED READINGS
made, this should be used to screen other family members.
1. Barkovich AJ. An approach to MRI of metabolic disorders in children. Journal of
This is especially important for younger, as yet asymptomatic, Neuroradiology. 2007;34:75-88.
siblings who might benefit greatly from specific therapies if 2. Cognitive and motor regression. In: Swaiman KF, Ashwal S, Ferriero DM,
these are instituted prior to the development of symptoms or Schor NF (Eds). Swaiman’s Pediatric Neurology: Principles and Practice,
in the early symptomatic period. 5th ed. Elsevier Saunders; 2012. pp. 575-603.
3. Metabolic and heredodegenerative disorders of central nervous system. In:
Aicardi J (Ed). Diseases of the Nervous System in Childhood, 3rd edition. Mac
Clinical Pearl Keith Press; 2009. pp. 243-371.
• Every effort should be taken to diagnose treatable causes of 4. Metabolic disorders and leukodystrophies. In: Sims KB, Peters JM, Musolini
psychomotor regression. PL, Elibol MZ (Eds). Handbook of Pediatric Neurology. Lippincots Williams and
Wilkins; 2014. pp. 155-91 and 206-20.
5. Neurology—degenerative brain disorders. In: Forfar & Arneil’s Textbook of
The following is an algorithmic flowchart to aid the Pediatrics, 7th ed. Churchill Livingstone; 2008. pp. 898-903.
physician in approaching a child with psychomotor regression. 6. Psychomotor retardation and regression In: Fenichel’s Clinical Pediatric
However, significant overlaps exist and also disorders with Neurology: A Signs and Symptoms Approach, 6th ed. Elsevier Saunders; 2009.
atypical presentations can confuse the physician. A systematic pp. 119-52.
clinical approach with a sound theoretical knowledge helps in 7. Schiffmann R, van der Knaap MS. An MRI-based approach to the diagnosis of
reducing the investigative burden on the patient. white matter disorder. Neurology. 2009;72(8):750-9.
403
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Chapter 85
Approach to a Child
with First Seizure
Anju Aggarwal, Anaita Udwadia Hegde
INTRODUCTION Box 1: Operational (practical) clinical definition of epilepsy

In 2005, a Task Force of the International League Against Epilepsy is a disease of the brain defined by any of the following
Epilepsy (ILAE) formulated conceptual definition of a “seizure” conditions:
where an epileptic seizure is defined as a transient occurrence • At least two unprovoked (or reflex) seizures occurring >24 hours
of signs and/or symptoms due to abnormal excessive or apart
synchronous neuronal activity in the brain. • One unprovoked (or reflex) seizure and a probability of further
Epilepsy was defined as a disorder of the brain characterized seizures similar to the general recurrence risk (at least 60%) after
by an enduring predisposition to generate epileptic seizures. two unprovoked seizures, occurring over the next 10 years
This definition is usually practically applied as having two • Diagnosis of an epilepsy syndrome
unprovoked seizures more than 24-hours apart. A seizure that • Epilepsy is considered to be resolved for individuals who had
is provoked by a transient factor acting on an otherwise normal an age-dependent epilepsy syndrome but are now past the
brain to temporarily lower the seizure threshold, does not applicable age or those who have remained seizure-free for the
last 10 years, with no seizure medicines for the last 5 years
count toward a diagnosis of epilepsy. However, conceptually,
epilepsy also exists after at least one unprovoked seizure, when
there is high risk for another, although the actual required risk Risk of Recurrence after First Status Epilepticus
is debatable. • The recurrence risk after a prolonged event or status
The term “provoked seizure” is considered being synonymous epilepticus is the same as that of a brief seizure.
with a “reactive seizure” or an “acute symptomatic seizure”. • However, if they do recur they have a higher chance of
getting a repeat status epilepticus.
NEWER DEFINITIONS
In the need to address circumstances with high risk for Clinical Pearls
future seizures after a first unprovoked seizure, the ILAE
• If an event is ambiguous, it is better to wait for a recurrence for
commissioned a Task Force in December 2013 to formulate an
clarification
operational definition of epilepsy for the purposes of clinical
• Misdiagnosis of an “epileptic” seizure may be more stigmatizing
diagnosis (Box 1).
than a delayed diagnosis of epilepsy.
STATISTICS
High Risk Factors Associated with
About 2–5% of children experience a seizure one time or the
other in their lifetime. This includes both febrile and afebrile Recurrence after First Unprovoked Seizure
seizures. After a single unprovoked seizure, risk for another is • Pre-existing static brain abnormalities
40–52%. With two unprovoked nonfebrile seizures, the chance • Focal neurological deficits
by 4 years of having another is 73%, with a 95% confidence • Focal seizure semiology (including Todd’s paresis)
interval (CI) of 59–87%, subsequently herein portrayed as • Focal/generalized epileptiform activity on electro
approximately 60–90%. encephalogram (EEG)
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Chapter 85: Approach to a Child with First Seizure
• Tumors or other progressive lesions History should include a detailed antenatal history of
• Status epilepticus mother, birth history, and developmental history to find out
• Family history of epilepsy any associated risk factors or etiology of seizures.
• Previous febrile seizures.
EXAMINATION
Fctors Known to Provocate Seizures and Epilepsy
In addition to the vitals including a blood pressure reading
Fctors known to provocate seizures and epilepsy are given in
and general physical examination, one should look for neuro
table 1.
cutaneous markers, microcephaly, dysmorphic features, and
signs of raised intracranial pressure. Detailed neurological
Table 1: Factors provoking seizures and epilepsy examination is required to detect neurological deficit, altered
Acute symptomatic seizures Susceptible to epilepsy sensorium and meningeal signs should be looked for.
• Fever • Sleep deprived
• Head injury • Severe psychological stress
Clinical Pearl
• Hypoglycemia • Extremes of emotion • Determination of type of seizure and distinction from
• Electrolyte disturbance • Fatigue nonepileptic events is best done by clinical history (preferably
• Brain infections • Infections from the person who has witnessed the seizure).
• Stroke • Family history
• Hemorrhage • Higher risk of epilepsy DIFFERENTIAL DIAGNOSIS
• Drugs (50–70%)
The differential diagnosis of seizures can range from a variety
• Minor risk of epilepsy (3–10%)
of clinical presentations. Understanding the occurrence and
nature of minor events is crucial to make an accurate diagnosis.
Clinical Evaluation after a First These are principally:
• Loss of awareness
Seizure in a Child • Generalized convulsive movements
Whenever a child comes with first episode of seizure, what we • Drop attacks
need to know is: • Transient focal motor attacks
• Is it a seizure or other events which mimic seizures? • Transient focal sensory attacks
• What is the type of seizure? • Facial muscle and eye movements
• What is the possible etiology? • Psychic experiences
• What investigations are required? • Aggressive or vocal outbursts
• Does he or she require therapy? • Episodic phenomena in sleep
• Prognosis in terms of recurrence of seizure or remission of • Prolonged confusional or fugue states.
epilepsy? Some of the common differential diagnoses are described
below:
HISTORY
Syncope with Secondary Jerking Movements
A good clinical history is what is going to help us decide the
People who faint often have small, brief myoclonic twitches
type of seizure and distinguish it from nonepileptic events.
of the extremities which can be prominent with prolonged
Best is to elicit history from the care taker or parent who has
cerebral hypoperfusion.
witnessed the seizure. If not possible, history should be elicited
again after the initial control of seizure activity.
Questions that need to be addressed are: Nonepileptic Attack Disorder
• What was the child doing when he had a seizure? Nonepileptic attack disorder (NEAD), previously known as
• What happened in intricate detail? pseudoseizures typically gives rise to episodes of two broad types:
• Did the eyes turn to one side? 1. Attacks involving motor phenomena
• Did the child become stiff? 2. Attacks of lying motionless.
• Did the child have clonic movements or jerks or just brief A child with NEAD will have a seizure-like-episode only
flickering of eyes? during the awake state, may remember the sequence of events
• How long the seizure did last? well, will not have any injury during seizure, may have family
• Was the child unconscious after that and for how long? history of seizure and may not have seizure-like-movements of
• Did the child experience any weakness of any limb after the any particular seizure type. They may talk during the seizure
seizure? like activity, usually will not have cyanosis or incontinence.
• Did the child pass urine and stool during the episode? They usually do not have any postictal changes. Seizure can be
• Did the child suffer any injury during the seizure? precipitated or mimicked on suggestion.
405
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Breath Holding Spells • Neuroimaging

{{ Emergency imaging:
Children of breath-holding-spells will have seizure like activity
–– Computed tomography (CT) Scan is equally
only during awake period when the child is not attended ,
effective as magnetic resonance imaging
usually not followed by neurological deficit; may be associated
–– Child of any age who experiences postictal focal
with anemia, usually seem to occur in children less than 2 years.
deficit not resolving/not returned to baseline after
many hours
Sleep Disorders –– Suspicion of structural lesion
At times sleep disorders as night terrors mimic seizures {{ Nonemergency imaging:
usually seen in children 4–8 years of age. Child wakes up with –– Magnetic resonance imaging is routinely much
sweating, tachycardia, tachypnea, fear, and anxiety. They better for all epilepsies
do not remember the event. These are usually self-limiting. –– Some indications for CT scan especially in our
Nightmares occur in children 5–12 years, who suddenly get up country where cost is a major issue.
during rapid eye movement sleep with an unpleasant dream;
they have autonomic activity and are able to describe the event.
Clinical Pearl
Primary Cardiac or Respiratory Abnormalities • A normal electroencephalogram does not rule out and an
Presenting with Secondary Anoxic Seizures abnormal electroencephalogram does not prove epilepsy; it is
only a supportive investigation.
Episodes of complete heart block may have syncopal features
followed by collapse and secondary anoxic seizures. Usually
the attacks last for less than 1 minute.
TREATMENT RECOMMENDATIONS
Involuntary Movement Disorders and Other • Treatment with antiepileptic drugs is not indicated for the
Neurological Conditions prevention of epilepsy after the first unprovoked seizure
There is no alteration in consciousness. Some of the common • Treatment is considered in circumstances where the
examples include paroxysmal kinesigenic choreoathetosis, benefit of reducing risk of second seizure outweighs the
idiopathic torsion dystonia, etc. risk of pharmacologic and psychosocial side effects.
Hyperekplexia Clinical Pearl

Attacks are characterized by excessive startle, may cause
stiffening, and collapse with a sudden jerk of all four limbs. • Treatment decision is made depending on the risk of
Attacks are provoked by sudden unexpected stimuli, usually recurrence of seizure in a particular situatio.
auditory. Hyperekplexia needs to be distinguished from
seizures induced by startle.
COUNSELING AND
ROLE OF INVESTIGATIONS EMERGENCY HOME MANAGEMENT
Investigations after first unprovoked seizure: Education of the child and parents about seizures, epilepsy
• Routine labs: complete blood counts, serum electrolytes, and, medication plays an important part in reducing the
blood urea nitrogen, serum creatinine, glucose, calcium, emotional stress on the family. Providing the child and
and magnesium based on individual clinical circum family with written material on epilepsy and antiepileptic
stances—based on suggestive history, clinical findings or medications can be very helpful.
failure to return to baseline alertness It is important to review appropriate seizure precautions
• Lumbar puncture: nonfebrile seizure does not warrant a with the family, including proper positioning of a child during
lumbar puncture a seizure and issues regarding water safety and driving. The
{{ In less than 6-months-old or with persistent alteration parents and other care givers can be taught the emergency
of alertness and meningeal signs, lumbar puncture management of a seizure when prolonged beyond 3–4 minutes
should be performed with usage of intranasal or buccal midazolam or rectal
• Electroencephalogram is recommended as part of the diazepam as per the age and weight of the child.
diagnostic evaluation of a child with a first unprovoked The following is an algorithmic approach (Algorithm 1) to
seizure, preferably 5–7 days after the seizure management of a first unprovoked seizure in a child.
406
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Chapter 85: Approach to a Child with First Seizure
Algorithm 1
Management of first unprovoked seizure
CBC, complete blood count; Alk PO4, alkaline phosphatase; BUN, blood urea nitrogen; EEG, electroencephalogram; N, normal; Abn, abnormal; AED, antiepileptic
drugs; MRI, magnetic resonance imaging; CT, computed tomography.

))
Simple febrile seizures do not require any investigates as 1. Arzimanoglou A, Guerrini R, Aicardi J. In: Arzimanoglou A, Guerrini R, Aicardi J
magnetic resonance imaging or electroencephalogram (EEG). (Eds). Aicardi’s Epilepsy in Children, 3rd ed. Lippincott Williams & Wilkins; 2004,
pp. 11-114.
Investigations as to the cause of fever should be carried out
2. Freeman JH. Practice parameter: evaluating a first nonfebrile seizure in children:
))
First nonfebrile seizure requires a detailed clinical evaluation,
Report of the Quality Standards Subcommittee of the American Academy of
electroencephalogram, and neuroimaging whenever possible Neurology, the Child Neurology Society, and the American Epilepsy Society.
))
There is no long-term difference if treated after the first or Neurology. 2001;27:56:574.
second seizure 3. Michoulas A, Farrell K, Connolly M. Approach to a child with a first afebrile
))
Antiepileptic drug treatment is not usually started after a first seizure. BCMJ. 2011:53:274-7.
unprovoked seizure, unless the clinical or EEG features suggest 4. Waite Sehelly R, Chu-shore CJ, Neumeyer AM. Pediatric First Seizure. [online].
a high risk of recurrence Available from: emedicine.medscape.com/article/1179097 [Accessed December,
))
Patient education is perhaps the most important and often 2015].
neglected aspect of management of seizures and hence needs
to be stressed on when explaining to the care givers.
407
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Chapter 86
Medical Management of Epilepsy
Veena Kalra, Omkar P Hajirnis
INTRODUCTIOn • Third antiepileptic drug: an additional 1–3% will become

seizure free.
The aim is restoration of normal life through complete seizure Thus, after three first-line-antiepileptic drugs, a maximum
control with minimal or no drug side effects. It is imperative of 66% will be seizure free.
to develop a management algorithm based on knowledge • With two antiepileptic drugs together: 3% more will be
of the epilepsy disease, likely outcome, and rational use of seizure free
antiepileptic drugs. • With three antiepileptic drugs together: no additional
The basic steps in management of epilepsy are as follows: benefit seen.
• Differentiate a seizure from nonseizure event Thus, about 30% of patients by definition will fall under
• Identify cause of seizures and distinguish provoked seizure “intractable epilepsy”.
• Diagnose epilepsy and epilepsy syndrome
• Distinguish benign and severe epilepsy syndromes.
Clinical Pearl
Clinical Pearls • Children with treatment-resistant epilepsy are defined as “failure
of adequate trials of two tolerated, appropriately chosen and
• The first step in approaching a child with seizure disorder is to used antiepileptic-drug schedules (whether as monotherapies
determine whether the event in the patient is truly a seizure or in combination) to achieve sustained seizure freedom”.
or not
• It is surprising to note that many other paroxysmal events are
misdiagnosed as seizures and the consequences of this can be MANAGEMENT OF THE FIRST SEIZURE
disastrous.
• The first seizure is not designated epilepsy and manage
ment approach is to treat the seizure and identify its cause
DEFINITIONS • The first generalized seizure may not recur in 50–60% cases.
Anticonvulsant therapy, is therefore, not indicated for the
First-line-antiepileptic drug: it is a drug internationally
first generalized seizure
recognized as appropriate treatment for pediatric epilepsy as
• Predicts high recurrence risk (80%) in symptomatic
monotherapy.
seizures and in patients with abnormal electro
Add-on-antiepileptic drug: it is a drug recognized inter encephalogram (EEG) versus a 40% risk with a normal
nationally as appropriate for treatment of pediatric epilepsy EEG.
not as monotherapy but in addition to another already existing Anticonvulsant therapy is started after the first episode in the
antiepileptic drug. following situations:
• If first seizure is a partial seizure—it merits anticonvulsant
therapy as the recurrence risk is high (60–80%) and it may
STATISTICS be symptomatic
• First antiepileptic drug: will make 50% of children seizure • Examples of first seizures which merit treatment are
free myoclonic seizures and absence attacks
• Second antiepileptic drug: an additional 15% will become • Acute symptomatic seizures, e.g., ring-enhancing lesions,
seizure free etc.
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Chapter 86: Medical Management of Epilepsy
Indications of Electroencephalogram • Identifiable unilateral structural lesions on MRI

• Hemiatrophy due to congenital, perinatal, or acquired causes
Electroencephalogram is recommended as part of the
• Tumors
diagnostic evaluation of a child with a first unprovoked seizure,
• Suspected Rasmussen’s encephalitis
preferably 5–7 days after the seizure.
• Conditions listed for ketogenic diet.
Table 1 highlights the clinical usefulness of an EEG in
The above conditions require early referral to specialized
epilepsy management.
centers.
Neuroimaging
DRUG TREATMENT OF EPILEPSY
Conventional radiography has no place in epilepsy
management. Magnetic resonance imaging scan with epilepsy
How to Start Treatment
protocol is the preferred modality. It is far superior to computed
tomography scan for epileptogenic lesion identification, • Start low, go slow
focal cortical dysplasias, etc. and thus helps to distinguish • Reach maximum dose/side effects before you discard the
symptomatic epilepsies of partial/generalized nature from drug
idiopathic epilepsy. In intractable epilepsy, advanced MRI • Dosage to ideally once-a-day or twice-a-day
techniques, volumetric evaluation of hippocampi, etc. are • Adjust to the child’s daily activity
useful. However, a large number of epilepsies do not require • Add a second (first-line-drug); achieve control; then try
neuroimaging, e.g., absence attacks. and taper off the first antiepileptic drug
Functional scans like positron emission tomography/single- • If seizure frequency is decreased but not stopped after the
photon emission computed tomography scans are useful in first antiepileptic drug, add a second drug; use rational
presurgical evaluation of patients in addition to MRI scans. polytherapy.
The following logistic approach provides a simple clinical
approach to drug for the treatment of epilepsy:
WHEN TO LOOK BEYOND ANTIEPILEPTICs
• If patient has a clear-cut, well-defined focal cortical How to Choose the First Drug?
dysplasia—surgery is best option Start with the correct “first line” antiepileptic drug. “Correct”—
good efficacy (effectiveness) and low on side-effects
Table 1: Indications of electroencephalogram (tolerability).
Efficacy is the time to “repeat seizure” after starting the
Usefulness Remarks drug while tolerability is the time to “withdrawal” due to
• Differentiate seizures from • Interictal electro ineffectiveness or side-effects.
nonseizures encephalogram (EEG) may be
normal in epilepsy (30%) and Clinical Pearls
abnormal in normal children
(7–10%). Ictal record must • Effectiveness = Efficacy + Tolerability
show epileptiform activity • When two drugs are equally effective, tolerability is the
• Classify seizures and • Interpreter fallacies are deciding factor.
epilepsy type common
Table 2 provides a useful guide to choose and start the
• To identity background • Background rhythm data
rhythm and origin of important: appropriate first-line antiepileptic drug. However, the decision
epileptic focus {{ Hyperventilation, photic
regarding specific drug depends upon the age, seizure type,
stimulation, and sleep/sleep side effects, cost, and life style of the patient.
deprived record essential
{{ Helps to locate epilepsy- Clinical Pearl
related-lesion
• Whenever in doubt as to seizure type or syndrome, sodium
• Classify epileptic syndromes • Ictal recording is necessary Valproate is the best first choice for first-line therapy
and to distinguish:
{{ Complex-partial-seizures
{{ Absence seizures
Table 3 enumerates the dosing guidelines for the various
{{ Epileptic syndromes
commonly used antiepileptic drugs.
• In intractable epilepsy, to • Helps to take therapy decision, Do I Use an Established Antiepileptic Drug or
localize epileptogenic focus identify nonconvulsive status
Try a Newer Antiepileptic Drug?
• Monitoring of status • EEGs essential for diagnosis of
Evidence-based medicine proves that the efficacy is similar
epilepticus and epilepsy syndromes
in most first-line antiepileptic drugs, new or old. Thus, it is
nonconvulsive status
important to choose your drug by identifying the seizure
• Underlying disease state • May point to metabolic/ type and knowing the common side effects of the drug in 409
identification genetic basis of epilepsy relation to your patient.
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Table 2: Choosing the appropriate antiepileptic drug

Partial seizures Generalized seizures Absence Myoclonics
First line Add on First line Add on
• Carbamazepine • Clobazam • Valproate • Clobazam • Valproate • Valproate
• Oxcarbazepine • Clonazepam • Topiramate • Clonazepam • Ethosuximide* • Lamotrigine
• Sodium valproate • Levetiracetam • Levetiracetam • Levetiracetam • Lamotrigine • Topiramate
• Topiramate • Zonisamide • Lamotrigine • Pyridoxine • Zonisamide
• Lamotrigine • Tiagabine* • Phenobarbitone • Levetiracetam
• Levetiracetam • Pyridoxine • Vigabatrin (IS)
• Phenytoin • Gabapentin
• Gabapentin
*Not available in India
Table 3: Dosing guidelines for established and new anti • Lamotrigine: rash with danger of Stevens-Johnsons
epileptic drugs in children syndrome, or hair loss
• Topiramate: weight loss, cognition issues, or incontinence,
Established AED Starting dose Maintenance Dosing
(mg/kg/day) dose (mg/kg/day) interval hypohidrosis leading to pyrexia
• Vigabatrin: visual field cuts
Phenobarbital 3–5 3–5 OD or BD • Levetiracetam: mood swings, or drowsiness
Phenytoin 5–8 5–8 OD or BD • Benzodiazepine: drowsiness, low tone, or tolerance.
Carbamazepine 5–10 20–30 BD or TDS
What do I do if there is no Response to
Valproate 10–15 20–60 OD or BD
First-line Antiepileptic Drug?
Clonazepam 0.025 0.025–0.1 BD or TDS
• Firstly use all tests available to confirm the seizure type
Clobazam 0.25 0.5–1 OD or BD • Choose a drug with a different mechanism of action to your
Ethosuximide 10 15–30 OD or BD first-line antiepileptic drug.
The following drug combinations are effective and
New antiepileptic drugs
recommended:
Oxcarbazepine 5–10 10–50 BD or TDS • Valproate + Lamotrigine
Lamotrigine • Topiramate + Carbamazepine
• Monotherapy 0.4 2–8 BD • Topiramate + Valproate
• With valproate 0.15 1–5 BD • Valproate + Carbamazepine
• Carbamazepine + Phenytoin
Topiramate 1–3 3–8 BD
Identify an epileptic syndrome and choose a drug known
Levetiracetam 10 20–60 BD or TDS to work on the identified syndrome.
Vigabatrin 40 50–150 OD or BD Table 4 and 5 lists the various epileptic syndromes and the
Zonisamide 2–4 5–6 BD
preferred drugs for the same.
It is prudent to remember some antiepileptic drugs are
Gabapentin 10 20–50 TDS known to worsen certain epilepsies. Table 6 depicts the drugs
OD, once-a-day; BD, twice-a-day; TDS, thrice-a-day. to avoid in certain epilepsies.
What are the Common Side Effects of

DISCONTINUATION OF
Each Drug I Should Know? ANTIEPILEPTIC THERAPY
The usual dose-related side-effects of most antiepileptic drugs Epilepsy therapy need not be life-long in most subjects. In
include drowsiness, dizziness, nystagmus, cognitive decline, most epilepsies, the antiepileptic drug is withdrawn after
gastrointestinal dysfunction, etc. 2 years of seizure-free period. However, about 20–29%
subjects relapse after antiepileptic drugs withdrawal. Drug
Specific side effects withdrawal is over 3–6 months and is one drug at a time in
• Carbamazepine: diplopia, dizziness, cognition, or counts cases of polytherapy. When withdrawing on abnormal EEGs,
• Sodium valproate: weight gain, hair loss, or liver dysfunction adolescent epilepsies or remote symptomatic epilepsies
• Phenytoin: hirsutism, coarse facies, gingival hyperplasia, adequate counseling is required to parents and patient with
drowsy, ataxia, cognition, or nausea—toxic range regards to chances of relapse.
• Phenobarbitone: drowsiness, cognitive decline, ataxia, Algorithm 1 depicts the approach to withdrawing anti
withdrawal seizures epileptic drugs.
410
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Table 4: Preferred drugs for different epileptic syndromes

Severe myoclonic epilepsy of Benign rolandic epilepsy with Juvenile myoclonic Myoclonic astatic Childhood absence
infancy (Dravet syndrome) centrotemporal spikes epilepsy epilepsy epilepsy
• Clobazam • Carbamazepine • Valproate • Clonazepam • Valproate
• Valproate • Oxcarbazepine • Lamotrigine • Clobazam • Clobazam
• Topiramate • Valproate • Levetiracetam • Valproate
• Stiripentol • Topiramate • Clonazepam • Lamotrigine
• Levetiracetam • Levetiracetam • Topiramate
• Lamotrigine • Levetiracetam
Table 5: Preferred drugs for different malignant epileptic syndromes

Lennox-Gastaut Infantile spasms Landau-Kleffner syndrome Rasmussen’s Progressive myoclonic epilepsies
syndrome syndrome (metabolic epilepsies)
Combination of:
• Valproate (VPA) + • ACTH • Intravenous • Steroids • Zonisamide
• Lamotrigine (LMT) + • Oral steroids immunoglobulin • Antiepileptic • Levetiracetam
• Topiramate (TPM)) • Vigabatrin • Steroids drugs • Valproate
• Zonisamide (ZNS) • Nitrazepam • Antiepileptic drugs • Surgery
• Levetiracetam (LVT) • Valproate
• Clobazam (CLBZ) • Topiramate
• Clonazepam (CLNZ) • Clonazepam
ACTH, adrenocorticotropic hormone.
Table 6: Drugs worsening certain epilepsies

Drug Syndrome Worsening
Carbamazepine Absence seizures, juvenile myoclonic epilepsy, progressive Absence seizures, myoclonic seizures, or
myoclonic epilepsies, benign rolandic epilepsy continuous slow wave in sleep
Phenytoin Absence, progressive myoclonic epilepsies Absences, cerebellar syndrome
Phenobarbitone Absence seizures At high doses, absences
Benzodiazepines Lennox-Gastaut syndrome Tonic seizures
Vigabatrin Absence, myoclonic seizures Absences, myoclonic seizures
Lamotrigine Severe myoclonic epilepsy of infancy, juvenile myoclonic epilepsy At high doses, myoclonic seizures
Algorithm 1
Algorithmic approach to antiepileptic drug withdrawal
411
EEG, electroencephalogram; GTC, generalized tonic clonic seizure; JME, juvenile myoclonic epilepsy; RR, relative risk; v/o, view of.
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Algorithm 2
Algorithm for a Newly Diagnosed Epilepsy
AED, antiepileptic drug.
DRUG MONITORING Clinical Pearls

Therapeutic range is the optimum level of a drug in the body
• Treat the patient, not the drug level
which is effective, but not toxic. However, there are wide
variations in blood levels are observed at the same dosage in • If a value does not make sense—ignore it or repeat it.
different patients. Also, there is no correlation between efficacy
and toxicity of the antiepileptic drug in the blood for a given
patient. There is also a difference between total drug and free PARENTAL COUNSELLING
drug in the system—total is what is being tested, free is what is
Explain the Disease
effective.
Timing of collection is most important as the trough levels • Explain the nature of the disease and alleviate fears of
are determined for efficacy and peak levels for toxicity (Table 7). supernatural involvement
• In vast majority of cases (80%), epilepsy would improve
with first-line drug therapy
Table 7: Drugs for which therapeutic drug monitoring is • Most children are normal and their mental development
available would not be affected by drugs or disease
Drug Effective plasma concentration (mg/mL) • Remind about seizure precipitants:
{{ Sleep deprivation
Carbamazepine 6–12 {{ Exhaustion
{{ Excessive emotion: stress/anxiety/anger/tear/excite

Lamotrigine 2–16
ment
Phenobarbital 15–40 {{ Illness/infection
Phenytoin 10–20 {{ Usually a combination of two or more factors
{{ Days to be careful: birthday, exam, festivals, holiday,

412 Valproate 50–120
travelling, or illness
Ch-86.indd 412 11/24/2016 1:58:12 PM

• Must explain how to abort an event at home. Draw, write,

whatever is easier for the parent to understand ))
After a second unprovoked seizure, the chances of a third
unprovoked seizure are 80–90% within 2 years if treatment
• The use of intranasal midazolam spray or buccal midazolam
is not initiated. Therefore, treatment after the second (rather
or rectal diazepam should be explained to the parents and
than the first) unprovoked seizure is recommended
caretakers in detail
• Explain the need to keep medication near the patient and ))
The choice of antiepileptic drug in treating the childhood
not at a different venue so that when he/she seizures, the epilepsies will be determined by the epilepsy syndrome (and
drug is readily available hence the specific seizures help to define the syndrome), side
effects profile and, to an extent, its ease of use (formulation
• Answer all their queries and alley their anxiety regards
and dosing regimen)
academics, medicines, social stigmas, marriage, and
children. ))
Sodium valproate appears to remain the most effective
antiepileptic drug in treating most seizure types
Drug Therapy ))
It is important to be aware of drugs that may exacerbate some
• Compliance: regular drug treatment is the corner stone of seizure types
therapy ))
The temptation should be strongly resisted to indulge in
• Safety: the drugs should be kept out-of-reach of children to polytherapy, as it is always easier to add another drug than to
avoid inadvertent ingestion withdraw one
• Empowerment: parents should be explained the ))
There are no convincing data that the simultaneous use of
domiciliary management of acute breakthrough seizures three antiepileptic drugs results in better seizure control than
• Follow-up: appropriate timely drug withdrawal. two drugs
))
In order to assess response to treatment, information on
Lifestyle baseline seizure frequency and intervals between initial
• Maintain a normal healthy lifestyle seizures is crucial. Tracking response to seizures is important,
• No food restrictions needed either with paper diaries or with online seizure-tracking tools
• School teachers should be informed ))
A trial of epilepsy medication discontinuation is usually
• Children should carry a card displaying their diagnosis recommended after 2 seizure-free years. Medications should
• Caution is advocated in dangerous activities such as cycling, be discontinued over at least a 6-week period, and if the
swimming. and fire particularly during early therapy. patient is on polytherapy, only one medication should be
weaned at a given time
))
Children with pharmacologically-resistant epilepsy and
Clinical Pearl seizures due to focal abnormalities are potential candidates
• Domiciliary management of seizures is extremely important for epilepsy surgery.
and should be taught to every family
• Facility of intranasal midazolam should be available in all schools
SUGGESTED READINGS
FOLLOW-UP
1. Arhan E, Serdaroglu A, Kurt AN, Aslanyavrusu M. Drug treatment failures and
Initially after 6 weeks and then 3 monthly if seizures are effectivity in children with newly diagnosed epilepsy. Seizure. 2010;19(9):
controlled. Refer to a higher center if: 553Y557.
2. Commission on Classification and Terminology of the International League
• Uncontrolled seizures/side effects against Epilepsy. [online] Available from: http://www.ilae.org/
• Suspected syndromes 3. Epilepsy. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF. Swaiman’s Pediatric
• Suspected inborn errors of metabolism Neurology: Principles and Practice, 5th ed. Elsevier Saunders; 2012. pp. 811-35.
• Deteriorating cognition 4. Jerome Engel Jr. Seizures and Epilepsy, 2nd ed. Oxford; 2012.
• Fresh neurological deficits. 5. Kossoff EH. Intractable childhood epilepsy: choosing between the treatments.
Semin Pediatr Neurol. 2011;18(3):145Y149.
6. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;
Key points 342(5):314Y319.
7. Pestian J, Matykiewicz P, Holland-Bouley K, Standridge S, Spencer M, Glauser T.
))
The first step in approaching a child with suspected epilepsy Selecting anti-epileptic drugs: a pediatric epileptologist’s view. Acta Neurol
is to confirm that the reported spells are actually seizures Scand. 2013;127(3):208-15.
rather than another condition such as syncope, migraines, 8. Vendrame M, Loddenkemper T. Approach to seizures, epilepsies, and epilepsy
tics, or behavioral events syndromes. Sleep Med Clin. 2012:7(1):59Y73.
9. Wallace S, Farrell K. Epilepsy in Children, 2nd ed. London: Arnold; 2004.
413
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Chapter 87
Approach to Refractory Epilepsies
Neelu A Desai, Vrajesh Udani

Drug refractory epilepsy (DRE) or intractable or pharmaco
• Appropriately chosen first antiepileptic drug will control half
resistant epilepsy is epilepsy which does not successfully
the cases of new-onset epilepsy while only one-third of these
respond to antiepileptic drug (AED) therapy. About one-
will be drug resistant.
third of children with newly diagnosed epilepsy are likely
to subsequently develop drug resistant epilepsy which has
tremendous implications not only on the child but also on the
patient’s family members and care givers. Aggressiveness in WHAT ARE THE CONSEQUENCES OF
the diagnosis and treatment of medically refractory epilepsy Drug-refractory epilepsy?
in children is imperative given the adverse effect of recurrent
Recurrent seizures are associated with a range of deleterious
seizures on early brain development, learning, and memory.
consequences including death. Uncontrolled epilepsy in
infants and children has deleterious effect on early brain
DEFINITION development, learning, and memory. Refractory seizures
Conventionally, therapeutic failure of three AEDs defined restrict patients’ social activities, academic achievements
intractability. Frequency, duration, and severity of seizures are and in adults reduce the ability to hold a driving license or
less commonly included in definition of DRE. The International keep a job. It is a great economic burden for society through
League against Epilepsy defines DRE as failure of adequate expenditures in health-care and unemployment. Patients
trials of two well-tolerated and appropriately chosen and used with epilepsy have a mortality rate significantly higher than
AED schedules (monotherapies or in combination) to achieve that of the general population. Sudden unexpected death in
sustained seizure freedom. epilepsy (SUDEP) accounts for 8–17% of deaths in people
with epilepsy.
International League against Epilepsy
Definition of Drug Refractory Epilepsy COMPLICATIONS OF Drug-
Failure of adequate trials of two well-tolerated and refractory epilepsy
appropriately chosen and used AED schedules (monotherapies
• Mortality: underlying neurological disorder, status
or in combination), to achieve sustained seizure freedom.
epilepticus, seizure-related accidents; treatment-related
deaths, SUDEP
EPIDEMIOLOGY • Morbidity: increased cognitive, behavioral, and psychiatric
Incidence and prevalence of DRE is uncertain due to problems
unstandardized definitions as well as misdiagnoses. Almost 20– • Nonfatal injuries: head injury, burns, drowning, and
40% of epilepsy cases become medically resistant. Data from fractures
various studies on DRE reveal that with the first drug-trial, 50% • Diminished quality of life: developmental delay, poor-
patients would become seizure-free. A second medication- academic performance, unemployment, and other lifestyle
trial produced remission in an additional 13%, while with the restrictions
third drug, only a further 4% would become seizure-free. • Social stigma.
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Chapter 87: Approach to Refractory Epilepsies
RISK FACTORS OF Drug- • Others: early age of onset, abnormal development/

refractory epilepsy neurological examination, EEG abnormality, presence of
status epilepticus, and comorbidities.
A number of prospective studies have attempted to identify
factors that predict the risk of true DRE. Some of these factors
are as follows:
DIfFERENTIAL DIAGNOSIS
• The response to the first AED trial has been found as the
most consistent and vital predictive factor for DRE. As
Pseudorefractory Epilepsy
mentioned before, half of patients with new-onset epilepsy Very often in practice, medical intractability is not true. This
respond to the first appropriate AED prescribed. With apparent treatment failure which is not true intractability
subsequent AED trial, less than 20% are likely to respond. could be due to:
High seizure frequency prior to treatment is consistently • Wrong diagnosis: some paroxysmal events appear like
identified risk factor for DRE seizures but are not due to abnormal electrical discharges.
• Etiology of epilepsy and syndrome classification is also a They could be physiological or psychogenic in nature
relevant factor deciding prognosis. Idiopathic syndromes and do not respond to AEDs. Video EEG is a golden tool
have a better prognosis than symptomatic/cryptogenic to prove or disprove them. In one study almost 20% of
epilepsy syndromes. Certain pediatric epilepsy syndromes patients seen at epilepsy referral centers were nonepileptic
that are usually medically intractable include early attack disorder (NEAD). Some common seizure mimics
(neonatal) myoclonic encephalopathy, early infantile are mentioned in the table 1.
epileptic encephalopathy, Lennox-Gastaut syndrome, etc. • Wrong choice of drug: inappropriate drug selection
• Other variables such as electroencephalographic (EEG) is often responsible for intractability. For example, a
findings and the presence or absence of psychiatric narrow-spectrum AED like carbamazepine can worsen
comorbidities have been correlated with outcomes in seizure frequency in generalized epilepsy, e.g., absence or
some analyses myoclonic jerks
• Some findings such as status epilepticus, a long duration • Wrong dosage: inappropriate dosages and frequency can
of epilepsy, a family history of epilepsy, and febrile also lead to pseudo refractoriness. For example, giving
convulsions are variable determinants of prognosis. Some short half-life AEDs, e.g., syrup carbamazepine in once or
studies have also identified an abnormal neurologic twice daily-doses.
examination and/or developmental delay/intellectual • Wrong lifestyle: recreational drug or alcohol abuse, sleep
disability as risk factors for DRE deprivation or noncompliance and self-adjustment of drug
• Some studies, but not all, suggest that age at presentation doses can also lead to improper seizure control.
may be a factor in the development of DRE. Some pediatric
studies have found that seizure onset in later childhood MANAGEMENT OF
or adolescence appears more likely to be associated with
DRE than seizures with onset between the ages of 5 and
Drug-refractory epilepsy
10 years. One series found onset in the neonatal time- The treatment of children with medically intractable epilepsy
period associated with DRE. is both challenging and rewarding. True refractory epilepsy
needs referral to a Comprehensive Epilepsy Care Center for
Predictors of True optimal evaluation and management. This comprises of a
pediatric neurologist/epileptologist, electrophysiologist,
Drug-Refractory Epilepsy epilepsy surgeon, neuropsychologist, and counselor.
• Lack of efficacy with first appropriate AED If initial history, examination, and videos suggest pseudo-
• High number of seizures prior to treatment refractoriness, appropriate steps should be taken to resolve
• Underlying etiology: symptomatic/cryptogenic rather than them. This would include discontinuing AEDs in NEAD and
idiopathic epilepsy syndrome counseling.
Table 1: Common seizure mimics in childhood

Neonates Infants Children Adolescents
• Jitteriness • Breath-holding spells • Stereotypies • Pseudoseizures
• Benign sleep myoclonus • Colic • Self-gratification • Syncope
• Hyperekplexia • Self-gratification • Sleep disorders • Migraine
• Benign paroxysmal vertigo • Tics • Tics
• Benign paroxysmal torticollis
• Sandifer syndrome (gastroesophageal reflux disease)
• Shuddering attacks 415
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Antiepileptic Drugs improved by an epilepsy protocol with spoiled gradient

sequences to delineate subtle malformations of cortical
Medical management with AEDs remains the first-line
development like focal cortical dysplasias which often
treatment in patients with epilepsy. A good number of patients
underlie refractory epilepsy. Functional neuroimaging like
respond to small changes in treatment like switching to
ictal single photon emission computed tomography (SPECT)
appropriate monotherapy according to seizure/syndrome,
can help delineate the ictal onset zone and often complements
increasing dose, frequency, and assuring strict compliance.
MRI in the search of the epileptogenic zone (EZ), critical
Rational polytherapy is recommended in nonresponders to
for planning any surgical intervention. Similarly, positron
monotherapy, e.g., synergistic combinations like valproate
emission tomography (PET) is very useful as a tool to map
and lamotrigine; AEDs with different mechanisms of action
out glucose metabolism in the interictal state as many EZs are
like a sodium channel blocker carbamazepine with a gamma-
hypometabolic. Post-processing techniques coregistering MRI
aminobutyric acid ergic drug like clobazam. Tapering drugs like
and functional images enhance the information. Another very
carbamazepine in generalized epilepsies is rewarding. Drug
important consideration in presurgical evaluation is defining
levels may sometimes help in adjustment of drug dosages.
the eloquent cortex for sensorimotor, language, and visual
functions. If this overlaps with the EZ, postoperative deficits
Seizure Diary may be unacceptable (Algorithm 1).
A seizure diary is a very helpful tool in all patients with DRE Neuropsychological evaluations help understand the
to document seizure frequency and intensity with specific specific cognitive defects a patient has, e.g., verbal or visual
interventions, e.g., a new AED. This improves drug compliance memory deficits in hippocampal sclerosis when planning
and helps to identify triggers like menstrual cycle, etc. It often surgery in older children and teenagers.
would help to avoid unnecessary polytherapy with ineffective Surgical options in DRE are either resective or palliative
AEDs and identify scenarios where the AED itself leads to epilepsy surgery.
paradoxical increase in seizures. Resective epilepsy surgery has the best-established efficacy
for individuals with lesional epilepsy. Patients with concordant
Clinical Pearl abnormalities on MRI, EEG, SPECT, and PET have a rate of
seizure remission as high as 90%.
• Seizure diary is an essential tool kept by patient or caregivers of Disconnective surgery is sometimes employed for palliative
drug-refractory epilepsy, recording frequency and intensity of treatment in children with catastrophic epilepsy syndromes
seizures along with antiepileptic drugs and precipitants. with no resectable lesion (Table 2).
As mentioned before, of the 30–40% of individuals Ketogenic Diet

with DRE about half will continue their seizures despite Ketogenic diet (high-fat, low protein) in children with DRE is
three appropriate drugs being tried to their full therapeutic an effective therapy with more than one-third experiencing a
potential. Though new AEDs have undoubtedly reduced drug 50% or greater reduction in seizures. Behavioral improvement
interactions and adverse effects the number of DRE patients is often an additional bonus. It is tried for about 3 months
who become seizure free after the first 2–3 drugs is not more and if effective, is continued for 2–3 years. Less restrictive
than 5%. These patients should be evaluated for possibility of modifications like the modified Atkins diet can be used in older
epilepsy surgery, ketogenic diet, or vagal nerve stimulation. children, though with less success (Table 3).
Clinical Pearl Vagus Nerve Stimulation

• Drug-refractory epilepsy represents a significant portion Vagus nerve stimulation (VNS) has been approved for
of all pediatric epilepsies and should be referred early to a adjunctive treatment of DRE in adults and children over
Comprehensive Epilepsy Center where all treatment options
including epilepsy surgery and the ketogenic diet are available Table 2: Resective surgery (curative) and disconnective surgery
for optimal management. (palliative)
Resective surgery (curative) Disconnective surgery
Epilepsy Surgery (palliative)
• Children with recognized • Severe uncontrolled
Surgery has the potential of altering the natural history of
resectable lesions (FCD, MTS) and epilepsy with no
epilepsy by improving or eliminating seizures in carefully failed appropriate AED trial resectable lesion
selected patients. Epilepsy surgery should be considered early
• Improvement of seizure control • Prevents falls/injuries,
in appropriate patients with DRE when seizures are sufficiently with developmental, cognitive e.g., corpus callosotomy
frequent or severe as to significantly disrupt the patient’s and, behavioral improvement, e.g., in Lennox-Gastaut
quality of life. lesionectomy or hemispherotomy syndrome
Presurgical evaluation would need video-EEG monitoring for hemispheric epilepsies
and high-resolution magnetic resonance imaging (MRI) of FCD, focal cortical gradient; MTS, mesial temporal sclerosis; AED, antiepileptic
416 brain in all cases. The sensitivity of MRI can be substantially drug.
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Chapter 87: Approach to Refractory Epilepsies
Algorithm 1
Surgical approach in drug refractory epilpsy
CC, corpus callsostomy; VNS, vagus nerve stimulation; KD, ketogenic diet; FMRI, functional magnetic resonance imaging; MRI, magnetic
resonance imaging; PET, positron emission tomography; SPECT, single photon emission computed tomography; EEG, electroencephalogram.
Table 3: Ketogenic diet

Indication Any DRE, West syndrome, epilepsy associated with tuberous sclerosis complex, Dravet syndrome, Doose syndrome, Lennox-
Gastaut syndrome, and glucose transporter 1 deficiency
Response One-third experiencing 50% or greater reduction in seizures, one-sixth achieve seizure freedom; behavioral improvements
Side effects Gastrointestinal or metabolic side effects, drowsiness, and increased susceptibility to infections
Duration 3-months trial; if effective continued for 2–3 years
DRF, drug-refractory epilepsy.
Algorithm 2
Approach to drug refractory epilepsy
417
CC, corpus callsostomy; VNS, vagus nerve stimulation; KD, ketogenic diet; EEG, electroencephalogram; MRI, magnetic resonance imaging; AEDs, antiepileptic
drugs; NEAD, non epileptic attack disorder; PET, positron emission tomography; SPECT, single photon emission computed tomography.
Ch-87.indd 417 11/24/2016 1:59:00 PM

12 years of age. Approximately 30–40% of patients achieve SUGGESTED READINGs

a greater than 50% reduction in seizure frequency. Serious
adverse events are rare. 1. Berg AT, Kelly MM. Defining intractability: comparisons among published
definitions. Epilepsia. 2006;47:431-6.
Vagus nerve stimulation is efficacious in patients with
2. Berg AT, Langfitt J, Shinnar S, Vickrey BG, Sperling MR, Walczak T, et al.
well-documented DRE, who are not candidates for intracranial
How long does it take for partial epilepsy to become intractable? Neurology.
surgery, or whose seizures were not benefitted by prior epilepsy 2003;60:186‑90.
surgery. In resectable lesions, resective surgery is preferred 3. Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B. Early
over VNS because of the greater potential for complete seizure development of intractable epilepsy in children: a prospective study. Neurology.
remission (Algorithm 2). 2001;56:1445-52.
4. Devinsky O. Patients with refractory seizures. N Engl J Med. 1999;340:
1565-70.
Key points 5. Dlugos DJ, Sammel MD, Strom BL, Farrar JT. Response to first drug trial predicts
))
Around 20–40% of patients with epilepsy have incomplete outcome in childhood temporal lobe epilepsy. Neurology. 2001;57:2259-64.
seizure control with antiepileptic drug (AED) therapy alone 6. Dlugos DJ. The early identification of candidates for epilepsy surgery. Arch
))
Most patients with drug resistant epilepsy (DRE) can be Neurol. 2001;58:1543-6.
identified early in their presentation, after a failure of two 7. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, et al.
appropriate AED trials Definition of drug resistant epilepsy. Consensus proposal by the ad hoc Task
))
As many as 20% of patients with apparent DRE will have a Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):
nonepileptic paroxysmal disorder. Video EEG monitoring is 1069‑77.
the gold standard to confirm 8. Kwan P, Brodie M. Issues of medical intractability for surgical candidacy. In: Wyllie
))
Predictors of true DRE—lack of efficacy of a first appropriate E, Gupta A, Lachhwani D (Eds). The Treatment of Epilepsy and Practice, 4th ed.
AED trial, a high number of seizures prior to treatment, and a Philadelphia: Lippincott, Williams & Wilkins; 2006. p. 983.
symptomatic/cryptogenic epilepsy syndrome 9. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med.
))
Individuals with DRE have an increased risk of mortality as well 2000;342:314-9.
10. Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med.
as morbidity. Hence, aggressive treatment is imperative
2011;365:919-26.
))
Patients with true DRE should have a high resolution magnetic
resonance imaging study to identify a potential surgical lesion.
Other neuroimaging studies (e.g., single photon emission
computed tomography, positron emission tomography) can
be helpful for maximum localization
))
For patients in whom epilepsy surgery is not an option or
whose seizures persist after surgery, treatment trials with other
AEDs appropriate for their epilepsy syndrome, ketogenic diet
or vagus nerve stimulation is suggested.
418
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Chapter 88
Acute Flaccid Paralysis
V Viswanathan, Padma Balaji
INTRODUCTIOn Acute Myelopathies

Acute flaccid paralysis (AFP) is something that most pediatric • Transverse myelitis
neurologists see on a regular basis particularly during certain • Acute disseminated encephalomyelitis
seasons (mostly during the winter seasons) although they • Spinal cord ischemia
seem to occur most of the year round. These children, who are • Spinal cord injury
previously healthy, develop weakness in both legs to start with • Perioperative complication.
and then progressing to involve the breathing muscles quickly
over a few hours to days. They then develop difficulties in
Systemic Disease
swallowing and invariably end up getting admitted to hospital. • Critical illness neuropathy/myopathy
In some cases, they may follow mild upper respiratory illnesses • Conversion disorder.
or fever.
World health organization defines AFP syndrome as Metabolic Neuropathy
“characterized by rapid onset of weakness of an individual’s • Acute porphyria
extremities, often including weakness of the muscles of • Hypokalemia, hypokalemic periodic paralysis, hypo
respiration and swallowing, progressing to maximum severity phosphatemia.
within 1–10 days. The term ‘flaccid’ indicates the absence of
spasticity or other signs of disordered central nervous system Muscle Disorders
(CNS) motor tracts such as hyper-reflexia, clonus, or extensor
• Polymyositis, dermatomyositis
plantar responses”.
• Trichinosis
• Periodic paralysis
CAUSES OF ACUTE FLACCID PARALYSIS • Corticosteroids and blocking agents
• Mitochondrial diseases (infantile type)
When one looks at various causes of such paralysis in children, • Benign acute childhood myositis and others.
they are many and sometimes very difficult for one to identify
the clear cause. Some of these are listed below. Disorders of Neuromuscular Transmission
• Immune myasthenia gravis presenting in crisis
Peripheral Neuropathy • Botulism
Guillain-Barre syndrome (GBS) and other variants • Insecticide (organophosphate poisoning
• Tick-bite paralysis
Anterior Horn Cell Disease • Snake bite.
• Acute poliomyelitis presently eradicated in India
• Vaccine-associated poliomyelitis Others
• Other neurotropic viruses like Japanese B, rabies, non • Traumatic neuritis
polio enteroviruses • Japanese B encephalitis
• Acute myelopathy. • Conversion reaction.
Ch-88.indd 419 11/21/2016 11:18:26 AM

CLUES IN HISTORY AND EXAMINATION • Descending weakness: diphtheria, botulism.
• Fever at onset: polio or enteroviral myelitis, transverse Prominent and Early Ptosis
myelitis, myositis, epidural abscess, and Koch spine
(prolonged history) • Myasthenia Gravis, botulism
• Trauma: head/neck trivial trauma may lead to spinal • Facial weakness: Guillain-Barre syndrome, myasthenia
compression in patients with cervical vertebral instability gravis, botulism
(patients with Down’s syndrome, congenital cervico- • Fluctuating symptoms, fatigability: myasthenia gravis
vertebral anomalies or juvenile idiopathic arthritis) • Muscle tenderness: myositis, inflammatory myopathy
• Exposure toxins: lead, Arsenic, or snake envenomation (myalgias may be severe in GBS).
• Dog bite: rabies and postrabies-vaccine encephalomyelitis.
Muscle Stretch Reflexes
Preceding Infectious Prodrome/Vaccination • Absent: Guillain-Barre syndrome, poliomyelitis, diphtheria,
spinal shock, at level of spinal-cord damage
• Guillain-Barre syndrome or transverse myelitis
• Preserved: myasthenia Gravis, periodic paralysis, botulism
• Sore throat, neck swelling: diphtheritic polyneuropathy
• Exaggerated: below level of spinal lesion/upper motor
(non/partly immunized).
neuron lesion.
Precipitating Factors
Spinal Tenderness, Painful Spine Movement
• Diarrhea: hypokalemia, enteroviral myelitis
• Exertion or postprandial: hypokalemic periodic paralysis • Spinal trauma, epidural abscess, or other extra-dural
• Intramuscular injection: polio, traumatic sciatic neuritis compression
• Sensory loss: compressive myelopathy, transverse myelitis • Neck stiffness: poliomyelitis, enteroviral myelitis, GBS,
• Early bowel/bladder involvement: compressive myelo transverse myelitis.
pathy, transverse myelitis
• Constipation in less than 1 year: botulism (history of honey Clinical Approach
exposure). Clinical approach to a child with acute paraplegia or
paraparesis is given algorithm 1.
Prominent Autonomic Signs/Symptom
• Guillain-Barre syndrome, rabies, acute myelopathy Clinical Pearl
• Ascending weakness: Guillain-Barre syndrome, rabies,
• Investigations only help to reconfirm our clinical findings.
Varicella zoster virus, ascending myelitis
Algorithm 1
Approach to child with acute paraplegia or paraparesis
DTR, deep tendon reflexes; CPK, creatine phosphokinase; GBS, Gullain-Barre syndrome; NCV, nerve conduction velocity; CSF, cerebrospinal fluid; ATT, anti-TB
treatment; IVIG, intravenous immunoglobins.
*Bony tenderness/deformity, root pains, girdle sensation/early bladder or bowel involvement.
420
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Chapter 88: Acute Flaccid Paralysis
Acute Inflammatory Polyradiculo initial progressive phase of the illness and so needs close
neuropathy (Guillain-Barre Syndrome) monitoring and appropriate intervention.
Recovery usually begins about 2–3 weeks after the progres
This is one of the most common causes of AFP in children. sion stops and is usually complete in most children but takes
Peripheral nerves are the target of an abnormal immune even as much as 2–3 months in some cases. The prognosis is
response. In most cases, there is a history of an antecedent best when recovery begins early and also in children with the
viral infection. Commonest viral infection that precipitates demyelinating variety rather than the axonal type.
this is usually respiratory infection, although in some Diagnosis is best with the help of nerve-conduction studies
gastrointestinal infections may be the cause. Enteritis caused which will help to distinguish the axonal variety from the
by specific strains of Campylobacter jejuni is more often demyelinating type. Cerebrospinal fluid (CSF) examination
the cause of the acute axonal form of GBS, rather than the during the second week may show mild elevation in CSF
demyelinating variety. protein and a few mononuclear leukocytes (usually <10).
The clinical presentation is usually with progressive motor Management is primarily supportive with careful
weakness involving more than one limb—usually the legs. monitoring for respiratory function and adequate support
Mild sensory symptoms are usually present characterized including ventilation in some during the initial phase. Plasma
by dysesthesia and muscle tenderness in the limbs. The exchange and intravenous immunoglobulin hastens the
weakness progresses to reach a nadir by about 2–3 weeks. recovery of GBS. Although, we have discussed so much about
Deep tendon reflexes are absent in all the weak muscles. differential diagnosis in most cases once we have a good
Bilateral facial weakness occurs in about half of the children. reliable history and clinical examination findings, diagnosis is
Autonomic dysfunction like arrhythmia, labile blood pressure clear, cut and management is straight forward.
and gastrointestinal dysfunction may be seen. Respiratory All cases of AFP should be notified in the appropriate form
involvement is not uncommon in this condition during the to the corporation health officials as it is mandatory that we
Table 1: Features to differentiate poliomyelitis, transverse myelitis, Guillain-Barre syndrome, and traumatic neuritis
Signs and Poliomyelitis/polio-like Guillain-Barre syndrome Transverse myelitis Traumatic neuritis
symptoms enteroviral myelitis
Development 24–48 h from onset From hours to 10 days From hours to 4 days From hours to 4 days
of paralysis to full paralysis
Fever onset High, always present at onset Not common rarely present Commonly present before,
of flaccid paralysis, gone the during and after flaccid
following day paralysis
Flaccidity Acute, asymmetrical, Acute, symmetrical, distal Acute, lower limbs, Acute, asymmetric limb
proximal symmetrical
Deep-tendon Decreased or absent absent Absent early, hyperreflexia Decreased or absent
reflexes late
Sensation Severe myalgia and backache, Cramps, tingling, hypo Anesthesia of lower limbs Pain in gluteal region
no sensory changes esthesia of palms and with sensory level
soles
Cranial nerve Only when bulbar and Often present, affecting Absent Absent
bulbospinal nerves VII, IX, X, XI, XII
Respiratory Only when bulbar and In severe cases sometimes Absent
insufficiency bulbospinal
WBC in CSF High WBCs <10 WBCs Normal/mild pleocytosis Normal
CSF protein Normal or slightly increased High Normal or slightly elevated Normal
Bladder dysfunction Absent Transient Present Never
Nerve conduction Abnormal, anterior horn cell Abnormal demyelination/ Normal or abnormal, no Abnormal in sciatic nerve
velocity: third week disease (normal during the axonal diagnostic value
first 2 weeks)
EMG 3 weeks Abnormal Normal Normal Normal/may be abnormal
in that muscle subserved
by that nerve
Sequelae at 3 Severe, asymmetrical Normal/symmetrical Flaccid/spastic paraplegia Moderate atrophy only in
months and up to atrophy, skeletal deformities atrophy of distal muscles in some affected lower limb
a year developing later in some
EMG, electromyography; CSF, cerebrospinal fluid; WBC, white blood cells.
421
Source: Modified from Global Program for Vaccines and Immunization: Field Guide for Supplementary Activities Aimed at Achieving Polio Eradication. Geneva, World
Health Organization, 1996
Ch-88.indd 421 11/21/2016 11:18:26 AM

take samples for polioviruses from the stool specimen, soon SUGGESTED READINGs
after the diagnosis and then they will follow-up the cases and
do the needful. 1. Fenichel GM. Clinical Paediatric Neurology, 5th ed. Saunders, 2005.
2. Field Guide Surveillance Of Acute Flaccid Paralysis, 3rd ed. 2005
Acknowledgments 3. Hughes RAC, Wijdicks EFM, Barohn R, Benson E, Cornblath DR, Hahn AF, et al.
Practice parameter. Immunotherapy for Guillain-Barre syndrome. Report of
We thank with gratitude to Dr Pratibha Singhi and her team to the quality standards subcommittee of the American Academy of Neurology.
have permitted me to reproduce her work in this section. We Neurology. 2003;61:736-40.
thank Indian Journal of Paediatrics for allowing us to reproduce 4. Paediatric active enhanced disease surveillance (Paeds) study protocol—acute
charts from their publication. flaccid paralysis (AFP) Australia.
5. Paradiso G, Tripoli J, Galicchio S, Fejerman N. Epidemiological, clinical and
Key points electrodiganostic findings in childhood Guillain-Barre syndrome. A reappraisal.
Ann Neurol. 1999;46:701-7.
))
A good clear history is important 6. Singhi SC, Sankhyan N, Shah R, Singhi P. Approach to a child with acute flaccid
))
Good clinical examination with the history will give us the paralysis. Indian J Pediatr. 2012;79(10):1351-7.
diagnosis. 7. World Health Organization 1993 WHO/MNH/EPI/93.3. Geneva.
422
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Chapter 89
Approach to Floppy Infant
Vrajesh Udani, Sarbani S Raha
INTRODUCTION Box 1: Salient points in history-taking

Floppiness or hypotonia is a common neurologic symptom • Consanguineous marriage • Family history of sibling death/
in infancy. Hypotonia may be secondary to diseases • Reduced fetal movements similar illness
involving brain, spinal cord, nerve, or muscle. Hence, a • Feeding difficulty in • Static versus progressive
systematic approach is must while evaluating a floppy infant neonatal period • Choking episodes
to avoid ordering many investigations and to reach a proper • Increased respiratory efforts
diagnosis.
Weak infants always have hypotonia but it may exist
without weakness.
EXAMINATION OF A HYPOTONIC INFANT
• Posture: lack of/reduced spontaneous movements; full
abduction of legs; arms either extended at the sides of the
DEFINITION
body or flexed at elbow with hands beside the head (Fig 1A)
Hypotonia is an impairment of the ability to sustain postural • Skeletal: fixed deformities like clubfoot, arthrogryposis,
control and movement against gravity. Floppy infants exhibit pectus excavatum, hyperlaxity of skin and joints
poor control of movements, delayed motor skills, and • Dysmorphic features
hypotonic motor movement patterns. • Evidence of hypotonia:
{{ Horizontal suspension: the infant is suspended in
Phasic tone is a rapid contraction in response to a high-
intensity stretch. Postural tone is the prolonged contraction of prone position with the examiner’s palm underneath
antigravity muscles in response to the low-intensity stretch of the chest. The hands and legs of a hypotonic infant lies
gravity. The maintenance of normal tone requires intact central limply forming an inverted “U” posture
{{ Vertical suspension: an infant who has hypotonia “slips
and peripheral nervous system.
through” at the shoulders when the examiner grasps
A hypotonic infant needs to be evaluated adequately. A
him/her under the arms in an upright position
detailed history and neurological examination would help
{{ Traction response: head lag or hyperextension is
us to differentiate between central hypotonia of upper motor
evident when the infant is pulled by the arms from a
neuron origin and motor unit disorders. supine to sitting position (Fig 1B)
Infants who show delay in all aspects of development and {{ Scarf sign: in a hypotonic infant, on grasping the
have other evidence of brain dysfunction like abnormal eye infant’s hand and pulling it across the chest, the elbow
movements or seizures, dysmorphic features or exaggerated can easily be brought well beyond the midline
deep-tendon reflexes probably have a central cause of {{ Wheel barrow: in prone position when the child is
hypotonia. On the other hand, an alert and active infant who raised holding his legs in the air, whether he/she can
has significant motor weakness and absent deep-tendon support his weight on hands is tested
reflexes is most likely to have a peripheral cause of hypotonia • A complete neurological examination should be performed.
involving anterior horn cells, nerve, neuromuscular junction, Of particular importance are the following:
or muscle (Box 1). {{ Measurement of head circumference
Ch-89.indd 423 11/21/2016 11:21:04 AM

A B
Fig 1: A, Posture of a hypotonic infant; B, Traction response
Algorithm 1
Suggested approach to a floppy infant and stepwise investigations that would help reach a diagnosis
MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; CPK, creatine phosphokinase; NCV, nerve conduction velocity;
EMG, electromyography; RNS, repetitive nerve stimulation; SMN, survival motor neuron; FISH, fluorescence in situ hybridization.
Facies: myopathic/hypotonic
{{ SYNDROMIC HYPOTONIA
Hypophonia
{{
{{ Power: presence of antigravity movements An infant with dysmorphism and hypotonia may require
{{ Tongue fasciculations, polyminimyoclonus chromosomal analysis and fluorescence in situ hybridization
{{ Paradoxical respiration (FISH) studies to diagnose the appropriate syndrome.
{{ Examination of mother for myotonia.
A systemic approach and stepwise investigations will go Prader-Willi Syndrome (PWS)

a long way in diagnosing the underlying disorder in a floppy
This is caused by deletion of paternally-contributed proximal
infant (Algorithm 1).
long arm of chromosome 15 or maternal disomy (both
chromosomes 15 received from mother). Hypotonia at birth
CEREBRAL HYPOTONIA along with severe feeding problems requiring nasogastric tube
Neonatal and infantile hypotonia is common in most cerebral feeding is a significant neonatal history in patients of PWS.
disorders. But in some of them, hypotonia is one of the most Delayed milestone is the usual presenting feature. Hyperphagia
prominent features, making it difficult to differentiate between and obesity develops later in childhood.
a central versus peripheral cause (Box 2).
Joubert Syndrome
Box 2: Points favoring central hypotonia
Classic Joubert syndrome is characterized by distinct cerebellar
• Global developmental delay • Normal or brisk tendon and brainstem malformations, hypotonia, and developmental
• Dysmorphic features reflexes
delays. Often there is presence of oculomotor apraxia and
• Increased tone of neck extensor • Other organ involvement
424 episodic tachypnea. Cognitive disabilities are variable.
Ch-89.indd 424 11/21/2016 11:21:05 AM

Chapter 89: Approach to Floppy Infant
Many other syndromes have central hypotonia. Among Box 3: Evaluation of motor unit disorders
them, Down syndrome is usually diagnosed early due to
presence of typical facies. • Creatine phosphokinase, • Genetic test: survival motor
aldolase neuron and congenital
• Neostigmine test muscular dystrophy screening
NONSYNDROMIC CENTRAL HYPOTONIA • Electrodiagnosis: nerve • Enzyme analysis—alpha
conduction study, glucosidase (acid maltase)
There are patients who have anomalies or abnormalities of
electromyography, • Muscle biopsy
central nervous system in absence of any particular syndrome.
repetitive nerve • Nerve biopsy
The neurological examination may reveal global or motor delay stimulation
in presence of signs suggestive of central hypotonia. These
patients may have presence of minor anomalies of the brain
broadly classified as cerebral dysgenesis, some of them may have
delayed myelination or even normal neuroimaging findings.
Differential Diagnosis (Table 1)
Spinal Muscular Atrophy
Systemic Disease These are progressive group of disorders associated with
In a newborn and sometimes in infants, systemic disease can deletions or mutations in exons 7 and 8 of the telomeric copy
cause hypotonia. Presence of congenital heart disease and in of the survival motor neuron gene (SMN1). The centromeric
an acute setting, sepsis may be responsible for hypotonia. copy (SMN2) is the disease-modifying gene with milder cases
having more copies.
Craniocervical Junction Lesions In type 1, onset of weakness is before 6 months of age; most
Obstetric injuries to the cord result in neonatal hypotonia. patients do not achieve sitting. In type 2, onset is between 6–18
Later patients may have flexion of arms with flaccid paraplegia. months; most patients can sit but never walk. In type 3, onset is
A distended bladder with overflow incontinence is highly after 18 months and such patients may be difficult to diagnose
suggestive of cord injury in such cases. and confused with limb-girdle muscular dystrophy.
In spinal muscular atrophy (SMA), there is presence of
proximal more than distal weakness and despite of intrauterine
BENIGN CONGENITAL HYPOTONIA hypotonia, arthrogryposis is not present. Electromyography
This is a nonprogressive neurological disorder characterized study reveals fibrillations and fasciculations.
by generalized flaccidity of muscles and hypermobile joints. Once the genetic testing confirms SMA, the same should
Deep-tendon reflexes are normal or mildly exaggerated. be performed in chorionic villi biopsy sample for prenatal
An increased incidence of intellectual disability, learning diagnosis.
disability and likewise is evident later in life. A high family
incidence is reported. This is a diagnosis of exclusion, and all
Congenital Muscular Dystrophy
routine investigations are normal. This group is classified into syndromic and, nonsyndromic
forms. The nonsyndromic form may have merosin deficient
Clinical Pearl congenital muscular dystrophy (CMD) or merosin positive
CMD.
• Hypotonia without weakness may suggest a syndromic Delayed motor milestones, hypotonia, contractures,
diagnosis (Down’s, Prader-Willi). and high creatine phosphokinase (CPK) values help to
diagnose this condition. In merosin deficient CMD, MRI brain
shows abnormal T2 hyperintensity giving an impression of
MOTOR UNIT DISORDERS leucodystrophy (Fig. 2).
There may be many clues in history and neurological Syndromic congenital muscular dystrophy is characterized
examination that suggest a peripheral cause of hypotonia. by anomalies of cortical migration, ocular abnormalities like
A maternal account of reduced fetal movements and cataract, and muscle disease with high CPK.
polyhydroamnios; “myopathic” facies; tongue fasciculations
or polyminimyoclonus; low-pitched cry; and lack of antigravity Congenital Myotonic Dystrophy
movements are all markers of a lower motor neuron cause of a Prominent clinical feature of this autosomal dominant
floppy infant (Box 3). disorder include facial diplegia; significant neonatal feeding
Table 1: Differential diagnosis of peripheral hypotonia depending on the component of motor unit involved
Motor neuron Nerve Neuromuscular junction Muscle
• Spinal muscular • Congenital hypomyelinating neuropathy • congenital and transient • congenital myotonic dystrophy
atrophy • hereditary motor sensory neuropathy- myasthenia • congenital muscular dystrophy
familial dysautonomia • Pompe’s disease 425
• congenital myopathy
Ch-89.indd 425 11/21/2016 11:21:05 AM

Clinical Pearl
• A very high creatine phosphokinase value usually points
toward a muscular dystrophy.
NEONATAL HYPOTONIA
Hypotonia is a manifestation of many acute neonatal injuries.
The profile of disorders presenting with neonatal hypotonia
to the neonatal intensive care unit was studied in an 11-year
retrospective cohort of neonates admitted to the Neonatal
Intensive Care Unit at the Montreal Children’s Hospital
(Montreal, Québec). Of the 50 neonates, who met the inclusion
criteria, hypotonia was classified as central in 33 patients (66%)
and peripheral in 17 (34%). Hypoxic-ischemic encephalopathy
(n = 13), Prader-Willi syndrome (n = 6), myotonic dystrophy
Fig. 2: T2 weighted axial sections of magnetic resonance imaging of (n = 6), other muscle disorders (n = 6), chromosomal disorders
brain in a patient with merosin deficient congenital muscular dystrophy
(n = 4), and peripheral nerve disorders (n = 3) were the most
common diagnoses. The genetic tests of highest yield were
difficulty; and mental retardation. The mother is usually the FISH and DNA methylation studies for PWS, trinucleotide
affected parent when a child has the disease. There is unstable repeat testing for myotonic dystrophy, and karyotype analysis
trinucleotide expansion with 300–1000 CTG repeats and hence (Richer et al. 2001).
genetic anticipation is common in myotonic dystrophy type 1.
Cardiac dysrhythmias and cataract may also be present.
Key points
Pompe’s Disease ))
Differentiating between central and peripheral hypotonia is
Hypotonia in Pompe’s disease is the result of glycogen storage the first step
in brain, spinal cord, and skeletal muscles. The presence of ))
Targeted investigations will yield better results
cardiomegaly with abnormal electrocardiogram is highly ))
Many of the diseases are inherited, hence genetic counseling
suggestive of alpha glucosidase deficiency. is important
After establishing the diagnosis with the help of enzyme ))
Neonatal hypotonia can be specially challenging to
analysis, patient should be offered enzyme-replacement investigate.
therapy which is available at certain centers in India.
Myasthenic Syndromes SUGGESTED READINGs

Transitory neonatal myasthenia usually presents as hypotonia
1. Bodensteiner JB. The evaluation of the hypotonic infant. Semin in Pediatr Neurol.
and feeding difficulty; the cry of such an infant is weak and there 2008;15:10-20.
is lack of facial expression. Antiacetylcholine receptor (AChR) 2. Fenichel Gerald. Clinical Pediatric Neurology: A Signs and Symptoms Approach,
antibody is high and such newborns respond to neostigmine. 5th ed. Philadelphia: Elsevier; 2005. pp. 149-69.
Familial infantile myasthenia with prominent respiratory 3. Prasad AN, Prasad C. Genetic evaluation of the floppy infant. Semin Fetal
and feeding difficulty at birth and congenital myasthenia Neonatal Med. 2011;16:99-108.
with predominant ocular findings are genetic myasthenic 4. Peredo DE, Hannibal MC. The floppy infant: evaluation of hypotonia. Pedaitr in
syndromes with negative anti AChR antibodies. These patients Review. 2009;30(9):66-76.
may have episodic apneas which could be life threatening.
426
Ch-89.indd 426 11/21/2016 11:21:05 AM

CHAPTER 90
Approach to Ataxia
Jayakumar Vaikundam
INTRODUCTION SENSORY ATAXIA

Ataxia is a common symptom manifesting as unsteady gait, The most common cause of sensory ataxia in children
frequent falls, and clumsiness in walking or in using the hands is vitamin B12 deficiency. It is more commonly seen in
due to derangement in posture control, movement, and co- vegetarians. Apart from the dietary insufficiency and
ordination. malabsorptive state, lack of intrinsic factor can also lead to
Ataxia can occur as a result of: vitamin B12 deficiency state.
• Cerebellar dysfunction It is clinically characterized by anemia, lethargy, poor
• Posterior column dysfunction cognitive performance, hypotonia, sensory ataxia, and
• Vestibular dysfunction involuntary movements especially in infants. Neurological
Hence, as a first step one should be able to identify which examination will reveal hyporeflexia, posterior column
is the main structure that is affected to result in ataxia. Table 1 involvement, and bilateral extensor plantar response due to
will help in the differentiation. additional pyramidal tract involvement.
TABLE 1: Differentiating features of different structures involved in the causation of ataxia

Features Posterior column Vestibular Cerebellar
Headache/vomiting – +/– +/–
Tinnitus/vertigo – Often present +/–
Speech Normal Normal Slurring/Scanning/Staccato
Titubation – – +/–
Nystagmus – • Seen in primary position • Usually not seen in primary position
often with rotary Gaze evoked (fast component to the
component with direction of direction of gaze)
the fast phase away from the • Rebound nystagmus is also a sign of
side of lesion intrinsic cerebellar lesion
• Positional nystagmus is • Positional nystagmus is not
common common
Clumsiness and in – – Common
coordination of upper limb
Hypotonia +/– – Often seen in acute lesions
Romberg sign + – –
Gait Sensory ataxia more prominent Tendency to lurch to one side Wide based, staggering, lurching, and
on eye closure or in darkness drunken ataxia
Other signs Other signs of peripheral nerve Positional vertigo and blocking Dysdiadochokinesia, dyssynergia, and
or cord involvement feeling in the ear dysmetria
SECTION 11: Neurology
One important clinical clue for vitamin B12 deficiency TABLE 2: Cerebellar ataxia: localizing features
state is the presence of hyperpigmentation over the dorsum of
Site of involvement Clinical features
interphalangeal joints, knuckles, palmar creases, intertriginous
areas, and recent scars. The mechanism for hyperpigmentation • Midline: • Abnormal stance, truncal ataxia,
titubation abnormal head-posture
is not known and it is reversible disappearing with treatment.
and eye-movement abnormalities
Peripheral smear studies will show macrocytic anemia,
hypersegmented polymorphs, bone marrow showing mega {{ Upper vermis lesion {{ Abasia, gait ataxia are prominent
loblastic reaction. Serum vitamin B12 level is low. Magnetic {{ Lower vermis lesion {{ Nystagmus is prominent
{{ Fastigial nuclear {{ Abasia (difficulty in maintaining
resonance imaging studies usually show the picture of subacute
lesion the stance)
combined degeneration causing increased signal intensity in
T2W images in the posterior columns of cervical and thoracic • Intermediate (lesions • Rebound response, titubation,
spinal cord. Treatment may reverse these changes. affecting interposed dysdiadochokinesia, finger nose,
nuclei) heel-knee shin incoordination,
kinetic tremor, proximal limb
Clinical Pearl oscillation of outstretched arms
• Lateral hemispherical • Cerebellar dysarthria (especially
• Hyperpigmentation over the knuckles, interphalangeal joints (lesions affecting in left-sided lesions), limb ataxia,
in an ataxic child should suggest the possibility of vitamin B12 dentate nuclei) hypotonia, kinetic tremor and eye-
deficiency which is eminently treatable. movement abnormalities
VESTIBULAR ATAXIA Clinical Pearls

Recurrent attacks of vertigo with unsteadiness, nystagmus, • Nystagmus is a sign of flocculonodular lobe lesion
and vomiting sometimes can occur in infants and preschool • Truncal ataxia is a sign of vermis lesion
children as a part of benign paroxysmal vertigo. The episode • Limb incoordination is a sign of cerebellar hemispherical lesion
lasts for few minutes and may recur irregularly. • Gait ataxia is a sign of involvement of anterior lobe of
It is often considered as a variant of migraine and nearly cerebellum.
one-fourth of them subsequently develop migraine. There is
often a family history of migraine.
Clinical Approach to Cerebellar Ataxia
Cerebellar ataxia can be acute, intermittent/episodic or
CEREBELLAR ATAXIA chronic. Algorithm 1 describes the different causes.
Cerebellar dysfunction appears to be the most common cause
for ataxia and is characterized by the following clinical features Acute Cerebellar Ataxias
which will help to some extent to identify which portion Acute cerebellar ataxias due to
of the cerebellum is the most affected, although there is a infective/parainfective causes
considerable overlap.
• Often occur following infections with varicella, mumps,
• Ataxia:
and other viral infections
{{ Vermis lesions produce truncal ataxia and titubation
{{ Hemispherical lesions produce limb ataxia with a
tendency to lurch to the side of lesion ALGORITHM 1

{{ Anterior lobe lesions produce gait ataxia Approach to an ataxic child (acute/episodic intermittent
• Kinetic tremor and incoordination: seen in hemispherical cerebellar ataxia)
lesions involving dentate nucleus
• Hypotonia: seen mostly in acute lesions than in chronic
• Nystagmus and eye movement abnormalities: seen
commonly in flocculonodular lobe and vermis lesions
• Dysarthria: slurring, scanning, and staccato speech are
commonly in left cerebellar hemispherical lesions.
Clinical Pearls
• Nystagmus, dysarthria, incoordination suggest cerebellar ataxia
• Hypotonia is usually seen in acute lesions than in chronic.
SOL, space occupying lesion; GBS, Guillain-Barré syndrome; ADEM, acute
428 Table 2 describes the localizing features of different signs. disseminated encephalomyelitis, MS, multiple sclerosis.
CHAPTER 90: Approach to Ataxia
• Occur either immediately following fever or within 6 Acute disseminated encephalomyelitis

weeks, characterized by headache, vomiting, a severe gait • Acute disseminated encephalomyelitis is usually a
disturbance, nystagmus, and behavioral changes with monophasic illness following a viral infection, immuni
increased cerebrospinal fluid (CSF) cell count in viral zation or vaccination usually after an afebrile period
cerebellitis and normal cell count in postinfectious ataxia following the initial febrile illness
along with mild increase in proteins • Usually characterized by altered mental status, irritability
• Although there is no specific therapy, most of them respond and lethargy, seizures, and focal neurological deficits
well to antiviral (acyclovir) drugs, steroids, and intravenous • Some children may present with brainstem signs, limb
immunoglobulin therapy. ataxia, nystagmus, and bilateral optic neuritis (in multiple
sclerosis the optic neuritis is unilateral)
Ataxia due to drugs • In MRI, T2W/FLAIR images will show multiple subcortical
• Overdose of phenytoin, phenobarbitone, carbamazepine, lesions (usually at the junction of deep cortical gray
phenothiazines, benzodiazepines, and sometimes and subcortical white matter) with smudging of edges
anthelmintic drugs like piperazine; antihistamine are well- (in contrast the multiple sclerosis lesions will have sharp
known to produce acute ataxias clear margins)
• Some helpful clues are drowsiness, vomiting, or nystagmus • Treatment involves mainly intravenous methyl predni
which is less prominent on downward gaze and absence solone and in some cases intravenous immunoglobulin.
of fever Childhood multiple sclerosis
• Electroencephalogram in some of these patients may show
diffuse fast activity, indicative of sedative drug overdose • Around 4–5% of them can occur in children (mostly around
10–15 years of age)
• The treatment depends on the identification of the specific
• Visual disturbances are common apart from brainstem,
causative drug. In certain life-threatening situations,
cerebellar, and long tract disturbances
dialysis and vital support function may be required.
• In contrast to adult type of multiple sclerosis, seizures and
Kinsbourne syndrome mental status changes are common in children
(opsoclonus myoclonus syndrome) • Magnetic resonance imaging typically shows hyperintense
T2W lesions in cerebellum, brainstem, periventricular, and
It is characterized by: pericallosal white matter
• Acute or subacute onset of peculiar dancing eye movements • Evoked potentials studies and CSF immunoglobulin G
in different directions and planes (opsoclonus) due to index and CSF analysis for oligoclonal bands are useful
unwanted spontaneous saccades. Opsoclonus may persist • Treatment involves intravenous methyl prednisolone.
during sleep
• Myoclonic jerking of the trunk and limbs which may be Psychogenic
stimulus sensitive and may increase with action The following clues help in the diagnosis of acute psychogenic
• Child is often irritable and ataxic and may require support ataxia:
with hands and may be even afraid of standing or sitting • Ataxia occurs immediately on standing
without support • Bizarre and gross
• Nearly about 50% of the children with opsoclonus- • Absence of wide based stance
myoclonus may have occult neuroblastoma and these • Tendency to move from one object to another in a room to
symptoms can precede the diagnosis of the tumor get a support
• May need abdominal ultrasonogram; urinary vanillyl • Absence of other neurological signs.
mandelic acid and homovanillic acid estimation; and Other causes
in some cases computed tomography chest, abdomen;
• Space-occupying-lesions—cerebellar abscess
metaiodobenzylguanidine; or Dotatoc scan may be
• Traumatic
required
• Vascular—cerebellar hemorrhage, infarct, or arterial
• Injection adrenocorticotropic hormone is useful in some
dissection
patients.
• Basilar migraine.
Guillain-Barre syndrome/Miller Fisher syndrome
Clinical Pearls
• Early stages of Guillain-Barre syndrome (GBS) can
present with ataxia and subsequently patient may develop • Drug-induced ataxia should always be considered first in acute
weakness ataxia
• A variant of GBS—viz. Miller Fisher syndrome characterized • Past history of chicken pox should always be asked
by acute ataxia, ophthalmoplegia, and areflexia can present • Guillain-Barré syndrome should be considered when there is
with acute ataxia ataxia with absent deep tendon reflexes
• Ophthalmoplegia in Miller Fisher syndrome starts initially • In a febrile ataxic child with history of chronic suppurative otitis
media, always rule out cerebellar abscess
with upward gaze restriction followed by lateral gaze and
• Past history of similar episode could suggest the possibility of
finally down gaze restriction 429
episodic ataxias.
• Intravenous immunoglobulin therapy is useful.
TABLE 3: Hereditary episodic ataxias

Features Type I Type II
Age 5–7 years School going/adolescents
Precipitating factors Exercise, fever, sudden movement, carbohydrate meal –
Duration Few seconds to minutes Few minutes to few days
Frequency Several times per day 1 to 3 times per month
Attacks Mainly ataxia Ataxia, dysarthria, diplopia, vertigo
Useful clinical clue in Myokymia (seen in periorbital, facial, and hand muscles) Nystagmus
between the attacks
Ion channel involved Potassium channel gene KCNA1 linked to chromosome 12p13 Calcium channel CACNA1A in Chromosome 19p
Treatment Acetazolamide, phenytoin Acetazolamide, flunarazine, 4-aminopyridine
Episodic/Recurrent/Intermittent Ataxias ALGORITHM 2

Recurrent attacks of ataxia can occur either as a form of
hereditary episodic ataxia or due to some metabolic disorders.
Hereditary episodic ataxia

Although there are four types of hereditary ataxias Type I and
Type II are more common and their differentiating features are
outlined in the table 3.
Metabolic disorders producing intermittent ataxia

The usual clues are—lethargy, vomiting and occasional ICT. The
following metabolic disorders can present with intermittent
ataxia.
• Hartnup disease
• Pyruvate dehydrogenase deficiency
• Biotidinase deficiency
• Maple syrup urine disease
• Certain urea cycle—ornithine transcarbamylase deficiency
Other causes of intermittent ataxia

Children with Down syndrome can present with ataxia,
transient weakness of the limbs, especially after sudden flexion
of the neck usually after vigorous towelling of the head after
head bath due to recurrent atlanto-axial subluxation.
Clinical Pearls
• Pellagra like pigmentation suggest the possibility of Hartnup
Disease
Chronic nonprogressive cerebellar ataxias
• Increased blood pyruvate and lactate suggest pyruvate
dehydrogenase deficiency There are two major conditions which can cause nonprogressive
• Alopecia, dermatitis, and deafness suggest biotinidase deficiency cerebellar ataxias, viz.
• Acetazolamide is useful for Type I and Type II hereditary episodic 1. Congenital malformations of the brain
ataxias 2. Ataxic form of cerebral palsy.
• Always rule-out atlanto-axial subluxation in an ataxic Down
Congenital malformations of the brain
syndrome child.
The following malformations often cause nonprogressive
cerebellar ataxia:
• Cerebellar hypoplasia
Chronic Ataxias • Vermian hypoplasia:
Chronic ataxia can be nonprogressive or progressive and the {{ Joubert’s syndrome
430 various causes are outlined in the algorithm 2. {{ Dandy-Walker syndrome
{{ Chiari malformation Chronic Progressive Cerebellar Ataxias

{{ Rhombencephalosynapsis Chronic progressive cerebellar ataxias could be due to:
• Congenital cerebellar hypoplasia: • Hereditary ataxias which could be autosomal dominant or
{{ Autosomal recessive disorder
autosomal recessively inherited
{{ Characterized by hypotonia, ataxia, nystagmus
• Metabolic disorders
{{ Magnetic resonance imaging (MRI) of brain will show
• Cerebellar tumors
mainly cerebellar hemispherical atrophy • Chronic hydrocephalus.
{{ It should be differentiated from other progressive
• Hereditary ataxias:
conditions by serial MRI and involvement of brainstem {{ Autosomal dominant variety is mostly seen in adults
and other neurological findings. {{ Autosomal recessive disorders include:
• Cerebellar vermian hypoplasia: The vermis of the cerebellum –– Friedreich’s ataxia
is maximally involved in the following conditions: –– Ataxia telangiectasia
{{ Joubert’s syndrome:
–– Ataxia with oculomotor apraxia
–– Autosomal recessive disorder with partial or total –– Abetalipoproteinemia
agenesis or hypoplasia of the vermis –– Vitamin E deficiency
–– Characteristic facies, squint, ataxia, oculomotor –– Congenital disorder of glycosylation
apraxia, and breathing abnormalities are typical –– Refsum disease
–– MRI brain will show the following characteristic –– Marinesco-Sjogren syndrome.
findings: {{ Autosomal Recessive hereditary ataxias:
■■ Molar tooth appearance of the brainstem –– Friedreich’s ataxia:
■■ Bullet-shaped upper-fourth ventricle ■■ Autosomal recessive disorder due to defective
■■ Horizontal superior cerebellar peduncle expression of “frataxin” encoded by X25 gene at
■■ Bat-wing appearance of the lower fourth ventricle. chromosome 9
{{ Dandy-Walker malformation:
■■ Onset around puberty
–– Clinically patients present with hydrocephalus and ■■ Pes cavus, loss of deep tendon reflexes; extensor
large posterior fossa plantar and posterior column sensory loss, apart
–– Vermian hypoplasia (mainly caudal vermis) from cerebellar signs are the cardinal features
and cystic dilatation of the fourth ventricle are ■■ In 25% of them deep-tendon reflexes may be
characteristic imaging findings normal
{{ Chiari malformation:
■■ Magnetic resonance imaging brain will show
–– Clinically patients present with vague pain in the atrophy of cerebellum, cervical cord and
neck, suboccipital headache, and ataxia abnormal signals in the posterior and lateral
–– The characteristic clinical clues are presence of columns
down beat nystagmus, oscillopsia ■■ Nerve conduction and somatosensory evoked
–– May be associated with syrinx, lower cranial nerves potentials studies may show abnormality
palsy and skeletal abnormalities ■■ Cardiomyopathy is seen in 50% and diabetes in
–– Magnetic resonance imaging of craniovertebral 10%
junction will show downward displacement of the ■■ Idebenone has been found to be useful for
cerebellar tonsil which is peg shaped. Coexistent cardiac dysfunction
syrinx may be seen ■■ Diagnosis is confirmed by genetic testing
–– Treatment involves surgical decompression. showing GAA trinucleotide repeats in the range
of 600–900 repeats
Ataxic form of cerebral palsy
• Accounts for 5–10% of all forms of cerebral palsy
• 50% of them are autosomal recessively inherited Clinical Pearl
• History of birth asphyxia, mild spasticity, brisk reflexes,
• Deep tendon reflexes can be normal in 25% of patients with
and ataxia
Friedreich’s ataxia.
• Lack of correlation between imaging and clinical findings
• Recent gene mapping to chromosome 9p12-q12 is useful –– Ataxia telangiectasia:
to differentiate this from other conditions. ■■ Autosomal recessive disorder affecting nervous
and immune system due to deficiency of ataxia-
Clinical Pearls telangiectasia mutated (ATM) protein
■■ Mutation in the large ATM gene linked to
• Most of the congenital cerebellar malformations cause non-
chromosome 11q22-23
progressive ataxias
■■ Choreoathetosis followed by ataxia and
• Brisk deep tendon reflexes in a child with nonprogressive
dysarthria occur early
ataxia suggest the possibility of ataxic form of cerebral palsy
■■ Oculomotor apraxia is seen in 90% of patients.
• Imaging findings do not correlate with clinical picture in ataxic
cerebral palsy.
■■ Telangiectasia: 431
ǅǅ Develops after 2–10 years of age
■■ Two types are described.

–– Others:
■■ GM2 Gangliosidosis—low α and β hexo
saminidase A in fibroblasts
■■ Ramsay-Hunt syndrome is characterized by
progressive myoclonus and ataxia
■■ Marinesco-Sjogren syndrome is characterized
by congenital cataract, skeletal abnormalities,
mental retardation, and ataxia
■■ Dentato rubro-pallidoluysian atrophy seen
mostly among Japanese.
• Metabolic Disorders causing progressive ataxias:
{{ Abetalipoproteinemia (Bassen-Kornzweig Disease):
–– Autosomal recessive disorder

–– Due to absence of microsomal triglycerides
transfer protein, linked to chromosome 4q22-q24
causing absence of apolipoprotein B which results
Fig. 1: Bulbar conjunctival telangiectasia in deficiency of vitamins A, D, E, and K
–– Failure to thrive, steatorrhea, vomiting, ataxia,
ǅǅ Seen in bulbar conjunctiva, upper ears, areflexia, and proprioceptive disturbance are the
forearm, and face (Fig. 1) common clinical features
ǅǅ Exacerbated by exposure to sunlight –– Retinitis pigmentosa is a constant feature usually
ǅǅ Tends to grow with advancing age seen before 10 years of age
■■ Recurrent sinopulmonary infection and prone –– Peripheral smear will reveal acanthocytosis
for lymphoma and leukemia (38%) –– Plasma cholesterol and triglycerides are low (due
■■ Serum α-fetoprotein and carcinoembryonic to low apolipoprotein B)
antigen are elevated –– Nerve conduction studies may show abnormalities
–– Treatment includes restriction of fat, and large
■■ Serum IgG, IgA are reduced and IgM elevated
doses of vitamin E (100 mg/kg/day).
■■ Betamethasone 0.1 mg/kg/day divided every
{{ Vitamin E deficiency:
12 hours for 4 weeks has been found to be
–– Autosomal recessive disorder linked to chromosome
useful in some patients.
8q13
–– No malabsorption only isolated deficiency of
Clinical Pearls vitamin E
–– Ataxia and peripheral neuropathy
• Conjunctival telangiectasia develops later usually after 2 years –– Resembles Friedreich’s ataxia
of age –– Diagnosed by low vitamin E level and normal
• Telangiectasia tends to grow with age vitamin E absorption
• Telangiectasia becomes more prominent after exposure to –– Treatment includes 800–900 IU of vitamin E.
sunlight for some time
• Oculomotor apraxia is seen in Joubert’s syndrome, ataxia Clinical Pearl
telangiectasia, ataxia with oculomotor apraxia without
telangiectasia, and in Gaucher’s disease • Isolated vitamin E deficiency can resemble Friedreich’s ataxia.
Hence, when in doubt, it is always better to give a therapeutic
• Serum albumin testing is important.
trial with vitamin E
–– Ataxia with oculomotor apraxia (Table 4):
{{ Refsum disease:
■■ Autosomal recessive disorder often mistaken
–– Autosomal recessive disorder due to deficiency of
for ataxia telangiectasia
phytanic acid oxidase
■■ No conjunctival telangiectasia and linked to
–– Clinical features include:
chromosome 9p14
■■ Cerebellar ataxia
■■ Deafness
TABLE 4: Types of ataxia with oculomotor apraxia
■■ Retinitis pigmentosa
Features Type I Type II ■■ Thickened nerves
Age of onset Early age Adolescence ■■ Chronic demyelinating sensory motor neuro
Gait ataxia + + pathy
■■ Increased CSF proteins
Oculomotor apraxia Common and Less common
■■ Serum phytanic acid level increased
432 prominent
ǅǅ Plasma exchange is useful apart from
Serum albumin Reduced Normal
restriction of dietary phytanic acid.
{{ Congenital disorder of glycosylation (carbohydrate • Cerebellar tumors:

deficient glycoprotein syndrome): {{ Medulloblastoma
–– Autosomal recessive disorder linked to chromo {{ Cerebellar astrocytoma
some 16p13 affecting glycoprotein synthesis as a {{ Ependymoma
result of abnormal glycosylation {{ Cerebellar hemangioblastoma (von Hippel-Lindau
–– Clinically characterized by multisystem involve disease)

ment: {{ Brainstem glioma.
■■ Neurological: psychomotor retardation, hypo
tonia ataxia, cerebellar hypoplasia, squint, Clinical Pearls
stroke-like-episodes, sometimes seizures, and
peripheral nerve involvement • Vomiting, nystagmus, truncal ataxia and torticollis in a
■■ Dysmorphism: almond shaped eyes, large preschool child suggest the possibility of medulloblastoma
forehead, and inverted nipples • Unilateral cerebellar signs with features of increased intracranial
■■ Lipocutaneous anomalies: peau d’ orange skin, pressure (ICP) in a 5–10 years old child think of the possibility of
and infiltration with fat over the thighs and cerebellar astrocytoma which has a good prognosis
buttocks producing pads of fat • Ependymoma of the floor of the fourth ventricle can present
■■ Hepatodigestive: hepatic cytolysis, and hepatic with only intractable vomiting
fibrosis
• Presence of retinal angioma in an ataxic child suggests the
■■ Cardiac: pericarditis and cardiomyopathy
possibility of von Hippel-Lindau disease
–– Diagnosis: isoelectrofocusing of serum transferrin
–– Treatment consists of use of ketogenic diet, • Ataxia with multiple lower cranial nerve palsies (6th and 7th)
mannose, aspirin, and bisphosphonates. suggest the possibility of brainstem glioma where symptoms
of ICP manifest late.
Clinical Pearl
• Hydrocephalus: Hydrocephalus due to any cause can
• Suspect congenital disorder of glycosylation in a child with present with gait ataxia and symptoms of raised ICT.
ataxia with inverted nipples, supragluteal pads of fat and peau
Algorithm 3 gives the summary of approach to ataxias in
d’ orange skin.
children.
ALGORITHM 3
Summary of approach to ataxias in children
433
GBS; Guillain-Barre syndrome; MS, multiple sclerosis.

KEY POINTS
SUGGESTED READINGS
1. Brazis PW, Masdeu JC, Biller, J. Localization in clinical Neurology, 5th ed. (Indian reprint).
))
First evaluate whether ataxia is due to cerebellar, vestibular or Philadelphia: Li ppincott Williams & Wilkins; 2007. pp. 374.
sensory involvement
2. Facchini SA, Jami MM, Neuberg RW, Sorrell AD. A treatable cause of ataxia in children.,
))
Vitamin B12 deficiency should be suspected when there is Pediatr Neurol. 2001;24(2):135-8.
predominant sensory ataxia with hyperpigmentation over the 3. Ghezzi A, Deplano V, Faroni J, Grasso MG, Liguori M, Marrosu G, et al. Multiple sclerosis
knuckles, interphalangeal joints in childhood: clinical features of 149 cases. Mult Scler. 1997;3(1):43‑6.
))
In cerebellar ataxias ascertain which part of cerebellum is 4. Jayaram S, Soman A, Tarvade S, Londhe V. Cerebellar Ataxia due to isolated vitamin E
maximally involved by looking at the appropriate clinical signs deficiency., Indian J Med Sci. 2005;59(1):20-3.
))
Acute ataxias are commonly due to drugs, infectious and post- 5. McHale DP, Jackson AP, Campbell, -Levene MI, Corry P, Woods CG, et al. A gene for
infectious causes, acute disseminated encephalomyelitis, ataxic cerebral palsy maps to chromosome 9p12–q12. Eur J Hum Genet. 2000;8(4):267-
cerebellar abscess and early stages of Guillain-Barre syndrome 72.
6. Neeraj Srivastava N, Chand S, Bansal M, Srivastava K, Singh Set al., Reversible
))
Episodic ataxias often respond to acetazolamide
hyperpigmentation as the first manifestation of dietary vitamin B12 deficiency. Indian
))
Down syndrome with atlantoaxial subluxation can also J Dermatol Venereol Leprol. 2006;72(5):389-90.
present with intermittent ataxia in addition to some inborn 7. Pandolfo M. Friedreich’s ataxia: clinical aspects and pathogenesis. Semin Neurol.
errors of metabolism 1999;19:311-21.
))
Nonprogressive cerebellar ataxias are often due to congenital 8. Peter H. Berman PH., Ataxia in children., International Pediatrics. 1999;14(1): 44-7.
cerebellar malformations and ataxic form of cerebral palsy 9. Sabrina Buoni, S, Zannolli R, Sorrentino L, Fois A. Betamethasone and improvement of
))
Chronic hereditary cerebellar ataxias in children are often due neurological symptoms in ataxia-telangiectasia., Arch Neurol. 2006;63:1479-1482.
to autosomal recessively inherited conditions 10. Schols, L, Bauer P, Schmidt T, et al. Autosomal dominant cerebellar ataxias;
))
Eye signs like oculomotor apraxia, bulbar conjunctival clinical features, genetics and pathogeneses. The Lancet Neurology. 2004;3:
telangiectasia are important to look for (ataxia telangiectasia) 291-304.
11. Singhvi JP, Prbhakar S, Singh P. Episodic ataxia: a case report and review of
))
Vitamin E deficiency induced ataxia may resemble Friedreich’s
literature. Neurol India. 2000;48;78-80.
ataxia. Hence a therapeutic trial of vitamin E is worth
12. Stephanie Grunewald S, Gert Mathuus G, and Jaak Jaeken J., Congenital disorders of
))
Cerebellar tumors and hydrocephalus can present as chronic glycosylation. Pediatric Research. 2002;52: 618-624.
progressive cerebellar ataxia 13. Jayakumar V. Childhood ataxias. Reviews in Neurology. 2008;14:339-372.
))
Always look for treatable causes of cerebellar ataxia before
making the diagnosis of cerebellar degeneration.
434
Chapter 91
Acute Hemiplegia in Children:
An Algorithm for Diagnosis and Treatment
Viraj V Sanghi

Hemiplegia is defined as complete paralysis of one-half of the
• Focal clonic seizure in the newborn period is the most common
body with or without facial involvement. The term hemiparesis
clinical presentation of perinatal arterial ischemic stroke.
refers to partial weakness of one-half of the body. The etiology
of hemiplegia is vast and varied. The age of onset plays a vital
The majority of newborns do not go onto develop epilepsy.
role in determining the etiology.
About 40% of patients do not have specific symptoms in the
neonatal period and may be asymptomatic until months later
HEMIPLEGIA IN INFANTS when the infant is first noted to have pathological handedness.
Infantile hemiplegia is most commonly seen as a result Hemiparesis is then noticed on clinical examination in later
of perinatal hypoxic or vascular events, infantile acquired stages of infancy. Neuroimaging in these infants then leads to
cerebral infections, and the hemiconvulsion-hemiplegia- a retrospective diagnosis of perinatal arterial ischemic stroke
epilepsy syndrome. (AIS). The recurrence rate after perinatal stroke is very low
(Fig. 1) .
Perinatal Stroke
Hemiconvulsion-hemiplegia-epilepsy Syndrome
The rate of arterial infarction in neonates is as high as the
annual incidence of large-vessel ischemic stroke in adults. Hemiconvulsion-hemiplegia-epilepsy syndrome is an un
The incidence of perinatal stroke has been estimated at 1 in common outcome of prolonged focal status epilepticus in
1,600–5,000 births. Neonatal cerebral infarction accounts childhood. The prolonged focal motor seizure usually occurs
for 10–15% of the total number of neonates with seizures during the course of a febrile illness and is followed by
and is the main identified cause of congenital hemiplegia. hemiplegia, ipsilateral to the side of convulsions. A prolonged
Most perinatal strokes involve the middle cerebral artery febrile seizure results in inflammation which may worsen the
and are caused by thromboembolism from an intracranial level of cell injury. Inflammation and prolonged ictal activity
or extracranial vessel, the heart, or the placenta. Various risk act on blood-brain-barrier permeability. There may also be
factors have been associated with perinatal stroke. Maternal predisposing factors facilitating prolonged seizure such as
risk factors associated with fetal stroke include prothrombotic genetic factors or focal epileptogenic lesion (Fig. 2).
disorders, cocaine abuse, and placental complications such as
chorioamnionitis and placental vasculopathy. During delivery, HEMIPLEGIA IN OLDER CHILDREN
cervical arterial dissection may occur which leads to stroke.
In older children, the etiology differs from that of infantile
In the neonatal period, prothrombotic disorders, congenital
hemiplegia. The causes of acute hemiplegia are varied (Box 2).
heart disease, meningitis, and systemic infection can all lead to
Extensive clinical, radiological, and laboratory workup is
perinatal stroke (Box 1).
essential to arrive at a diagnosis before commencing treatment.
Box 1: Maternal risk factors associated with stroke Childhood Stroke

• Prothrombotic disorders • Placental vasculopathy Childhood stroke has been considered to be a rare disorder.
• Chorioamnionitis • Substance abuse The reported incidence for ischemic stroke has increased
Ch-91.indd 435 11/21/2016 11:31:35 AM

Fig. 2: T2 weighted magnetic resonance imaging of brain: left

hemispheric atrophy in chronic stage of hemiconvulsion-hemiplegia-
epilepsy syndrome
Box 2: Causes of acute hemiplegia in children

• Stroke (ischemic and hemorrhagic)
• Infections (bacterial abscess, tuberculosis, viral encephalitis, parasitic)
• Demyelination (acute disseminated encephalomyelitis, multiple
sclerosis, neuromyelitis optica); autoimmune encephalitis (anti
N-methyl-D-aspartate receptor/anti voltage gated potassium
channel receptor encephalitis)
• Metabolic (hypoglycemia, diabetic ketoacidosis, hyponatremia,
mitochondrial)
Fig. 1: T2 weighted coronal and axial magnetic resonance imaging: • Migraine and familial hemiplegic migraine; alternating hemiplegia
large cystic encephalo malacic lesion in left hemisphere due to of childhood
perinatal stroke • Postseizure hemiparesis (Todd’s paralysis)
• Tumors
during the past two decades. The recent reported incidence • Trauma
rates are between three and eight per 100,000 children per
year. The major syndromes comprising ischemic stroke in Box 3: Clinical presentation of arterial ischemic stroke
childhood consist of AIS and sinovenous thrombosis (SVT).
• Toddlers: • Older children:
Arterial ischemic strokes constitute 80% of cases.
{{ Facial droop {{ Hemiparesis
Toddlers with AIS more frequently present with abrupt
{{ Difficulty using one hand {{ Speech disturbances
onset of a hemiparesis, with facial droop, difficulty using
{{ Dragging of one leg {{ Visual disturbances
one hand, or dragging of one leg. In school age or teenage {{ Headache
child, other symptoms such as speech or visual disturbance; {{ Focal sensory deficits
headache, or focal sensory deficits may be seen in addition to {{ Seizures
hemiparesis. Seizures accompany the stroke in approximately
50% of children (Box 3) .
In SVT, a clinical picture indistinguishable from an increased central scotoma or diplopia are present in 18%
“pseudotumor cerebri” is the most frequent presentation, of children with SVT. Hemiparesis and other focal signs are
characterized by prominent headache, papilledema and present in 35–45%. Seizures occur at presentation in 48% of
436 occasionally sixth nerve palsy. Visual disturbances including older infants and children (Box 4).
Ch-91.indd 436 11/21/2016 11:31:35 AM

Chapter 91: Acute Hemiplegia in Children: An Algorithm for Diagnosis and Treatment
Algorithm 1
Box 4: Clinical presentation of sinus venous thrombosis
Causes of stroke in children
• Headache, papilledema, and • Visual disturbances
6th nerve palsy • Seizures
• Hemiparesis
A wide range of risk factors/causes associated with

childhood AIS (Box 3). These include cardiac disorders,
sickle-cell disease, prothrombotic disorders, trauma, and
major infections such as meningitis, sepsis, and encephalitis.
However, in the majority of the children, no underlying
systemic disease is found. With advances in neuroimaging,
cerebral arteriopathies are increasingly recognized as one of
the major causes of childhood stroke, in otherwise healthy
children. Some arteriopathies are due to well-recognized
causes such as arterial dissection, moyamoya syndrome or
disease, connective tissue disorders, and sickle-cell disease.
Late effects of radiation to the head and neck in childhood
cancer survivors have also been associated with stroke due to
cerebrovascular disease, and children with neurofibromatosis
can have complications of a cerebral arteriopathy. However, in
up to 30% of children presenting with a first AIS, a focal arterial
stenosis is identified but none of the classic underlying causes
are discovered.
Transient Cerebral Arteriopathy (TCA), the most common
type of arteriopathy identified in pediatric stroke, is a monophasic
arterial disease characterized by a unilateral focal or segmental
stenosis involving the distal part of the internal carotid and the
initial segments and branches of the anterior and/or middle
cerebral artery followed by complete or partial resolution. The
pathophysiology of TCA is uncertain. 44% of TCA cases are
associated with varicella zoster infection in the 12 months prior
to AIS causing postvaricella arteriopathy. Varicella virus invades
the arterial wall causing an acute vasculitis. Other frequent
infectious agents such as parvovirus B19, cytomegalovirus,
Mycoplasma pneumoniae, Borrelia burgdorferi, enterovirus,
human immunodeficiency virus and Helicobacter pylori might TB, tuberculosis; HIV, human immunodeficiency virus; AV, arteriovenous.
be responsible for TCA (Algorithm 1).
Treatment
Demyelination in Children
Acute treatment of children with stroke includes:
• Maintenance of respiratory and cardiovascular status Acute disseminated encephalomyelitis (ADEM) is an immune-
• Aggressive treatment of infection, seizures, and fever mediated inflammatory and demyelinating disorder of the
• Maintenance of normoglycemia and normovolemia central nervous system, commonly preceded by an infection.
• Adequate blood pressure should be maintained It principally involves the white matter tracts of the cerebral
• Intracranial hypertension may require mannitol and hemispheres, brainstem, optic nerves, and spinal cord. Acute
hyperventilation to prevent cerebral herniation. disseminated encephalomyelitis mainly affects children.
Anticoagulation with heparin can be considered in some Clinically, patients present with multifocal neurologic
children with AIS, particularly those with arterial dissection abnormalities that reflects the widespread involvement in
or progressive neurologic deficits believed to be a result of central nervous system. Cerebrospinal fluid may be normal
recurrent emboli or thrombosis. Anticoagulation in cardiac or may show a mild pleocytosis with or without elevated
embolism is controversial. Aspirin is the most commonly used protein levels. Magnetic resonance image shows multiple
antiplatelet agent. The recommended dosage is 3–5 mg/kg/ demyelinating lesions. The diagnosis of ADEM requires both
day. Treatment of children with AIS using tissue plasminogen multifocal involvement and encephalopathy by consensus
activator (t-PA) is limited due to delayed diagnosis and lack of criteria. Acute disseminated encephalomyelitis typically has a
safety and efficacy studies and is not currently recommended monophasic course with a favorable prognosis.
as standard treatment protocol. Moyamoya disease can be Multiple sclerosis (MS) is a chronic, inflammatory
treated surgically with revascularization. demyelinating syndrome of the central nervous system. 437
Ch-91.indd 437 11/21/2016 11:31:36 AM

Algorithm 2
Management of acute hemiplegia in children
ICU, intensive care unit; MRI, magnetic resonance imaging; MRA, magnetic resonance angiography; CT, computed tomography; TIA, transient ischemic attack; AHC,
alternating hemiplegia of childhood; ICP, intracranial pressure; TCA, transient cerebral arteriopathy.
Consensus criteria have been proposed by the International

Paediatric Multiple Sclerosis Study Group. Acute attacks are Key points
managed with intravenous methylprednisolone (10–30 mg/ ))
Detailed clinical history and examination are essential in
kg/dose) for 3–5 days. This may be followed by a tapering establishing a diagnosis
course of oral prednisone (starting dose of 1–2 mg/kg/ ))
Focal clonic seizure in the newborn period is the most common
day). Immunomodulatory therapies are introduced early clinical presentation of perinatal arterial ischemic stroke
in the course of disease with the aim of reducing disability ))
The most common cause of infantile hemiplegia is perinatal
stroke; risk of recurrence is extremely low
and cerebral atrophy. First line agents include interferon-β
))
Pediatric stroke is not uncommon. The diagnosis is often
and glatiramer acetate. Disease modifying therapy should delayed and early recognition is vital
be offered to any patient with MS after a second attack of ))
In previously healthy children, the most common cause of
demyelination. stroke is an arteriopathy. Imaging with computed tomography
angiography or conventional 4-vessel angiography is essential
Recurrent Hemiplegia in Children ))
Transient (Focal) cerebral arteriopathy is an important cause
• Demyelination: relapsing ADEM, MS, and neuromyelitis of stroke in children. Preceding history of varicella infection
optica (up to 12 months prior) must be sought as it is a major cause of
• Ischemic stroke: cardioembolic, vasculitis, and moyamoya transient cerebral arteriopathy
vasculopathy ))
Acute episodes of demyelination must be treated with
• Metabolic: mitochondrial intravenous steroids (3–5 days). Differentiating acute dis
seminated encephalomyelitis from multiple sclerosis in
• Migraine and familial hemiplegic migraine
children using current criteria is essential for long-term therapy
• Alternating hemiplegia of childhood and prognosis.
438 • Todd’s paralysis.
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Chapter 91: Acute Hemiplegia in Children: An Algorithm for Diagnosis and Treatment
SUGGESTED READINGs 10. Fullerton HJ, Wu YW, Sidney S, Johnston SC. Risk of recurrent childhood arterial
ischemic stroke in a population-based cohort: the importance of cerebrovascular
1. Alper G. Acute disseminated encephalomyelitis. J Child Neurol. 2012;27(11): imaging. Pediatrics. 2007;119:495-501.
1408-25. 11. Hirano K, Aiba H, Yano M, Watanabe S, Okumura Y, Takahashi Y. Effect of tacrolimus
2. Amlie-Lefond C, Bernard TJ, Sebire G, Friedman NR, Heyer GL, Lerner NB, et in a case of autoimmune encephalitis. No To Hattatsu. 2007;39(6):436-9.
al. Predictors of cerebral arteriopathy in children with arterial ischemic stroke: 12. Johnston J, So TY. First-line disease-modifying therapies in paediatric multiple
results of the International Pediatric Stroke Study. Circulation. 2009;119: sclerosis: a comprehensive overview. Drugs. 2012;72(9):1195-211.
1417‑23. 13. Kirkham F, Sebire G, Steinlin M, Sträter R. Arterial ischemic stroke in children.
3. Armstrong-Wells J, Ferriero DM. Diagnosis and acute management of perinatal Thromb Haemost. 2004;92:697-706.
arterial ischemic stroke. Neurol Clin Pract. 2014;4(5):378-85. 14. Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al. International
4. Auvin S, Bellavoine V, Merdariu D, Delanoë C, Elmaleh-Bergés M, Gressens P, Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis
et al. Hemiconvulsion-hemiplegia-epilepsy syndrome: current understandings. and immune-mediated central nervous system demyelinating disorders: revisions
Eur J Paediatr Neurol. 2012;16(5):413-21. to the 2007 definitions. Mult Scler. 2013;19(10):1261-7.
5. Chabrier S, Husson B, Dinomais M, Landrieu P, Nguyen The Tich S. New insights 15. Lynch JK, Nelson KB. Epidemiology of perinatal stroke. Curr Opin Pediatr.
(and new interrogations) in perinatal arterial ischemic stroke. Thrombosis 2001;13(6):499-505.
Research. 2011;127:13-22. 16. Lynch JK. Epidemiology and classification of perinatal stroke. Semin Fetal
6. deVeber G, Andrew M, the Canadian Pediatric Ischemic Stroke Study Group. Neonatal Med. 2009;14(5):245-9.
Cerebral sinovenous thrombosis in children. N Engl J Med. 2001;345: 17. Pediatric Stroke Working Group. Stroke in childhood: clinical guidelines for
417-23. diagnosis, management and rehabilitation. 2004.
7. deVeber G, The Canadian Pediatric Ischemic Stroke Study Group. Canadian 18. Sebire G, Meyer L, Chabrier S. Varicella as a risk factor  for cerebral infarction in
paediatric ischemic stroke registry: analysis of children with arterial ischemic childhood: a case-control study. Ann Neurol. 1999;45:679-80.
stroke. Ann Neurol. 2000;48:526. 19. Sebire G. Transient cerebral arteriopathy in childhood.  Lancet. 2006;368:8-10.
8. deVeber G. Stroke and the child’s brain: an overview of epidemiology, syndromes 20. Tenney JR, Schapiro MB. Child neurology: hemiconvulsion-hemiplegia-epilepsy
and risk factors. Current Opinion in Neurology. 2002;15:133-8. syndrome. Neurology. 2012;79(1):e1-4.
9. Fox CK, Fullerton HJ. Recent advances in childhood arterial ischemic stroke. Curr 21. Wu YW, Lynch JK, Nelson KB. Perinatal arterial stroke: understanding mechanisms
Atheroscler Rep. 2010;12:217-24. and outcomes. Semin Neurol. 2005;25(4):424-34.
439
Ch-91.indd 439 11/21/2016 11:31:36 AM

Chapter 92
Approach to a Child
with Spastic Paraplegia
Arun G Roy, Vinayan KP
INTRODUCTION spasticity is most marked in extensors of lower limbs which is

best elicited on flexion movements of leg. Deep tendon reflexes
Paraplegia is defined as partial or complete weakness of both (DTR) are exaggerated with extensor plantars in UMN lesion.
legs sparing the upper limbs. This can be due to upper motor
neuron (UMN) or lower motor neuron (LMN) pathology. Clinical Pearl
The UMN lesion should be above L1 segment involving
the pyramidal tract (thoracic or cervical) of spinal cord or • By rule, upper motor neuron (UMN) lesions cause spastic
rarely in cerebral cortex involving the leg area (parasagittal) paraplegia and lower motor neuron lesions result in flaccid
or subcortical regions affecting the fibers to legs to cause paraplegia with exemption of acute spinal shock where lesion
spastic paraplegia. Lower motor neuron lesion of paraplegia is UMN but paraplegia is flaccid
is secondary to intramedullary lesion affecting the lumbar
and sacral spinal segments of legs (L1–5 and S1–3), multiple In LMN lesion, the weakness is in distribution of spinal
root involvement (L1–5 and S1–3), multiple peripheral nerve segment, root, nerve, anterior horn cell, or muscle depending
involvement, and rarely anterior horn cell disease. In this on site of involvement with hypotonia in weak muscles. Wasting
chapter we are describing paraplegia secondary to spinal of muscles is another feature noted. The DTRs are hyporeflexic
lesions. The most common cause of cerebral paraplegia in with flexor plantars (Table 1).
children is cerebral palsy, which is not discussed in this chapter. Primary sensations, pain, and temperature are carried
by lateral spinothalamic tract while vibration, joint-position
Clinical Pearl sensations, and fine touch are by posterior column and
crude touch by anterior spinothalamic tract. An older child
• The first step of diagnosis is to localize whether it is primarily
can complain of burning pain, tingling, numbness of legs, or
upper motor neuron or lower motor neuron lesion as it helps
loss of sensations which can indicate a sensory involvement.
to narrow down the localization and avoid over investigating
The distribution of sensory level depends on site of lesion. In
the patient. Hence, a detailed history and examination is vital.
spinal cord, there can be differential involvement of tracts and
sensation will be lost below the level of lesion. Since posterior
column crosses at level of medulla, spinal cord lesion causes
Clinical features of upper motor
and lower motor neuron lesions
Table 1: Clinical features to differentiate upper motor neuron
A child refusing to stand or walk or bear weight is the most and lower motor neuron
common complaint in acute causes, while dragging of legs,
Features Upper motor neuron Lower motor neuron
tripping of toes while walking may favor spasticity of legs in
chronic disorders. Parents may describe the limb as flaccid Weakness Pyramidal pattern Depending on site of lesion
or stiff on handling. In an acute UMN lesion, muscle tone is Atrophy Late disuse atrophy Prominent, early feature
flaccid with hyporeflexia before the appearance of spasticity. Tone Spasticity Flaccid
The pyramidal distribution of weakness has specific pattern
DTR Exaggerated Sluggish/Absent
in limbs which is seen when weakness is not severe. In lower
limbs, weakness is most marked in flexors and internal rotators Plantar reflex Extensor Flexor
of hip, knee flexors, and toe and ankle dorsiflexors. The DTR, deep tendon seflexes.
Ch-92.indd 440 11/21/2016 11:33:57 AM

Chapter 92: Approach to a Child with Spastic Paraplegia
Types of spinal cord disorders

Spinal cord disorders can be extramedullary or intramedullary
(Fig. 2 and 3). The clinical features can vary in extramedullary
and intramedullary spinal disease (Table 3). This is because of
the lamination of tracts in the cord and type of compression
of these tracts. Extramedullary means the lesion is outside
the cord and can be intradural or extradural. Intradural
lesions involve predominantly dura and root (examples:
neurofibroma, meningioma), while extradural lesions are in
vertebrae and surrounding structures (example: Pott’s spine).
Fig. 1: Transection of spinal cord Radicular pain, giibbus, vertebral pain, and spine tenderness
are features of extramedullary disorders.
Table 2: Major tracts of the spinal cord-location and functions
Spinal Cord Syndromes (Table 4)
Tracts Location in spinal segment Function
These depend on the extent of lesion. (1) hemisection of the
Posterior Posterior cord Vibration, joint cord (Brown Sequard syndrome), (2) complete spinal cord
column position, Fine touch
syndrome, (3) central cord syndrome (Box 1), (4) Combined
Lateral spino Lateral cord Pain and
thalamic tract temperature
Anterior spino Anterior cord Crude touch
thalamic ract
loss of sensation ipsilaterally, while spinothalamic tract

crossing occurs at spinal level, hence, the loss of sensation
will be contralateral to site of lesion while transection of cord
will cause sensation loss of all tracts bilaterally (Fig 1). In
cortex and subcortical region, sensory loss is contralateral to
site of lesion (Table 2).
Normal bladder and bowel control depends on segmental
Fig. 2: Extramedullary compression
reflexes involving both autonomic and somatic motor neurons,
as well as descending and ascending tracts of the spinal cord.
Hence, bladder and bowel function may be impaired after
an injury to any segmental level of the spinal cord. Bladder
involvement can be retention of urine or incontinence of urine
(urge or over flow). Urge incontinence is seen in UMN bladder,
where lesion is above S2–S4 segments, while retention and
overflow incontinence favors LMN bladder (S2–S4 segments or
roots). A palpable bladder indicates retention of urine. Injuries
to the spinal cord that result in paraplegia from a lesion above
T6 may also impair autonomic control and result in episodes
of severe hypertension or hypotension. This is due to excessive
and uncontrolled sympathetic output from the spinal cord. Fig. 3: Intramedullary compression
Common triggers include bladder distension, constipation,
rectal fissures, joint injury and urinary tract infection. Table 3: Clinical features of extramedullary and intramedullary
spinal cord disorders
Clinical Pearls Clinical features Extramedullary Intramedullary

• Cortical lesions: spastic paraparesis is usually accompanied by Radicular pain Common Rare
upper motor neuron (UMN) cranial nerve palsies, UMN bladder Funicular or tract pain Rare Common
• Brainstem lesions: spastic paraparesis is accompanied by Sensory loss Ascending type Descending type
cranial nerve palsies—UMN or lower motor neuron depending
on the site of lesion (mid brain, pons, medulla), UMN bladder Band of hyperesthesia At the site of lesion Rare
± sensory tracts Lower motor neuron At the site of Depends on extent
• Spinal cord lesions: spastic paraparesis with sensory tract signs compression of lesion
involvement, sensory level and UMN bladder, there is no Upper motor neuron Below the level of Late and less severe
cranial nerve involvement. signs lesion and early 441
Ch-92.indd 441 11/21/2016 11:33:57 AM

Table 4: Clinical features of various spinal cord syndromes

Spinal cord syndrome Motor deficit Spinothalamic tract involvement Posterior columns involvement
Brown Sequard syndrome Ipsilateral UMN weakness Contralateral loss of pain and Ipsilateral loss of touch, position, and
(hemisection of cord) below the lesion temperature sensation vibratory sensation
Complete transection of Bilateral UMN weakness Bilateral loss of pain and temperature Bilateral loss of touch, position, and
cord below lesion vibratory sensation
Anterior cord syndrome Bilateral UMN weakness Bilateral loss of pain and temperature Sparing of touch, position, and
vibration sensation
Posterior lateral column UMN weakness Sparing of pain and temperature Loss of touch, position, and vibratory
syndrome sensation sensation
UMN, upper motor neuron; LMN, lower motor neuron.
Box 1: Central cord syndrome Table 6: Causes of chronic myelopathy

• This is not a classical cause for paraplegia. Lesion in cervical Compressive myelopathy
cord resulting in upper limb weakness more than leg weakness. Neoplasm Neurofibroma, meningioma
Another classical feature is suspended sensory loss for pain and
Infective Pott’s spine
temperature due to involvement of decussating fibers carrying
these sensations. Congenital disorders Dermoid cyst, arachnoid cyst
Noncompressive myelopathy
posterior and lateral column disease, (5) anterior spinal Demyelinating disorders MS, NMO
artery disease. Infections HIV, neurosyphilis, TB
At the site of lesion, there can be LMN weakness, band Vascular Ischemia due to AVM
of hyperesthesia, and loss of all sensations due to radicular
Nutritional Vitamin B12 deficiency
involvement.
Toxic Radiation and chemotherapeutic agents
Congenital disorders Tethered cord syndrome
CAUSES OF SPASTIC PARAPLEGIA
MS, multiple sclerosis; NMO, neuromyelitis optica; HIV, human immuno
Depending on presentation and duration it can be acute or deficiency virus; AVM, arteriovenous malformation; TB, tuberculosis.
chronic. Etiology varies depending on presentation, hence
onset is important. Family history should be asked regarding
Algorithm 1
similar illness, which helps in diagnosing inherited causes of
spastic paraplegia like hereditary spastic paraplegia and leuko Approach to paraplegia
dystrophy. Etiology can be broadly classified into compressive
and noncompressive myelopathy (Table 5 and 6). In compressive
myelopathy, there is definite sensory level, radicular symptoms
at site of compression with asymmetric involvement of tracts
while in non compressive myelopathies, radicular symptoms
and definite sensory level are not seen and there is selective
sparing of tracts and findings are usually symmetric.
Table 5: Causes of acute myelopathy

Compressive myelopathy
Traumatic Vertebral body fracture, or direct injury Pott's Spine
Hemorrhage Epidural or subdural hematoma One of the leading causes of compressive myelopathy in
Infective Epidural or subdural abscess, Pott’s spine children. This can have an acute or a chronic presentation and
is due to cord compression secondary to vertebral destruction
Noncompressive myelopathy
and wedging. Local spine tenderness and Gibbus are features
Vascular Embolism, dural arteriovenous fistula, of Pott’s spine. Gentle tapping over vertebra with finger is best
APLA syndrome
and safe way to elicit tenderness. Direct spinal cord involvement
Inflammatory Demyelinating disorders (MS, ADEM, NMO) due to tuberculosis infection is seen but less compared to Pott’s
Infective Viral, bacterial, tuberculosis spine. Magnetic resonance imaging (MRI) is the investigation
APLA, antiphospholipid antibody; MS, multiple sclerosis; ADEM, acute of choice as it shows involvement of disk, vertebra, and
442 disseminated encephalomyelitis; NMO, neuromyelitis optica. the extension of disease into soft tissues. Treatment is with
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Chapter 92: Approach to a Child with Spastic Paraplegia
antitubercular drugs and surgical intervention is indicated in Deficiency of Vitamin B12

acute and severe paraparesis secondary to compression and
Deficiency of vitamin B12 leads to degeneration of the dorsal
unstable spine.
and lateral white matter of the spinal cord, producing a slowly
progressive weakness, sensory ataxia, and paresthesias, and
Acute Transverse Myelitis ultimately spasticity, paraplegia, and incontinence.
Transverse myelitis is a segmental spinal cord injury caused
by acute inflammation. The inflammation of TM is generally Tethered Cord Syndrome
restricted to one or two segments, usually in the thoracic
Classically tethered cord syndrome has been defined as a
cord. The deficits are usually bilateral, producing weakness
spectrum of congenital anomalies resulting in an abnormally
and multimodality sensory disturbance below the level of the
low position of the conus medullaris. Motor deficits are due
lesion. Majority of cases are idiopathic but other causes are
to UMN and LMN features, since there is involvement of
infections, autoimmune disorders, demyelinating disorders
pyramidal tracts and lumbosacral roots. Children can present
like multiple sclerosis (MS) and neuromyelitis optica.
with delayed gait development, spasticity, hyperreflexia,
Cerebrospinal fluid can be normal or may show a moderate
hyporeflexia, and muscular atrophy. Sensory deficits, when
lymphocytosis (typically <100/mm3) and an elevated
present, are due to tract or root involvement and children
protein level (usually 100–120 mg/dL). Glucose levels are
can present with painless ulcers in leg. Neurogenic bladder
normal. Magnetic resonance imaging is the investigation of
dysfunction can be incontinence, urgency, or with recurrent
choice and can show local enlargement of the spinal cord
urinary tract infections. Magnetic resonance imaging is
and increased signal intensity on T2 weighted images which
the modality of choice in visualizing the level of the conus
can extend few segments of cord. In MS, the extent is two or
medullaris and for identifying terminal filum.
less than two segments. Contrast enhancement may or may
not be there.
Key points
Intramedullary Spinal ))
Paraplegia is weakness of lower limb sparing upper limbs; it
Arteriovenous Malformations can be flaccid or spastic
Twenty percent of the lesions are diagnosed in children under ))
Involvement of sensory tracts and bladder with sparing of the
16 years of age. Myelopathy is produced by the mass effect of cranial nerves and cognition localizes the lesion to spinal cord
the lesion or by ischemia or hemorrhage into the cord. ))
The causes can be compressive and noncompressive, extra
medullary and intramedullary which can be differentiated by
history and clinical findings
Adrenomyeloneuropathy
))
History of systemic illness, family history, trauma, onset and
A variant of adrenoleukodystrophy, an X-linked recessive progression of disease can give clue to etiology.
disorder, is characterized by a slowly progressive spastic
paraparesis and mild polyneuropathy. Sensory and sphincter
disturbances are typically absent. There may be mild adrenal SUGGESTED READINGs
insufficiency. 1. Blackmer J. Rehabilitation medicine: 1. autonomic dysreflexia. CMAJ. 2003;
169(9):931-5.
Hereditary Spastic Paraplegia 2. Brinar VV, Habek M, Brinar M, Malojcić B, Boban M. The differential diagnosis of
acute transverse myelitis. Clin Neurol Neurosurg. 2006;108:278-83.
Inherited disorders, in which the prominent feature is a 3. Bui CJ, Tubbs RS, Oakes WJ. Tethered cord syndrome in children: a review.
progressive spastic paraparesis. Hereditary spastic paraplegia Neurosurg Focus. 2007;23(2):E2.
is classified according to the mode of inheritance, and the 4. Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev
spastic paraplegia syndrome occurs alone or is accompanied Neurosci. 2008;9(6)453-66.
by additional neurologic or systemic abnormalities (“pure” 5. Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, et al.
Neuropsychiatric disorders caused by cobalamin deficiency in the absence of
versus “complicated”). Hereditary spastic paraplegia is a
anemia or macrocytosis. N Engl J Med. 1988;318:1720-8.
clinical diagnosis, based in large part on the family history. 6. Moser HW, Mahmood A, Raymond GV. X-linked adrenoleukodystrophy. Nat Clin
Magnetic resonance imaging spine may be normal or show Pract Neurol. 2007;3:140-51.
cord atrophy. 7. Pidcock FS, Krishnan C, Crawford TO, Salorio CF, Trovato M, Kerr DA. Acute
transverse myelitis in childhood: center-based analysis of 47 cases. Neurology.
Spinal Cord Tumors 2007;68:1474-80.
8. Raghavan N, Barkovich AJ, Edwards M, Norman D. MR imaging in the tethered
This is a rare diagnosis in the pediatric population. The spinal cord syndrome. AJR Am J Roentgenol. 1989;152(4):843-52.
types of tumors seen in children tend to be different than 9. Salinas S, Proukakis C, Crosby A, Warner TT. Hereditary spastic paraplegia: clinical
the adult types. Intramedullary tumors are most common features and pathogenetic mechanisms. Lancet Neurol. 2008;7:1127-38.
10. Schick U, Marquardt G. Pediatric spinal tumors. Pediatr Neurosurg. 2001;35:
type in children. In children with intramedullary tumors,
120‑7.
astrocytomas represent around 60% of tumors, ependymomas 11. Yasargil MG, Symon L, Teddy PG. Arteriovenous malformations of the spinal cord.
30%, developmental tumors 4%, and then a group of other In: Symon L (Ed). Advances and Technical Standards in Neurosurgery. Wien:
less frequently identified types. Springer; 1984. p. 61. 443
Ch-92.indd 443 11/21/2016 11:33:58 AM

Chapter 93
Acute Febrile Encephalopathy
Rashmi Kumar
INTRODUCTIOn Workup
The term acute febrile encephalopathy (AFE) literally A pragmatic investigative workup can be planned according to
means acute onset of fever with encephalopathy (or altered common etiology of the region (Box 4).
consciousness). This presentation is a very important cause
of hospital admissions in children in India. In 2006, World Clinical Pearl
Health Organization coined the term acute encephalitis
• Acute febrile encephalopathy/acute encephalopathy syndrome
syndrome (AES) to include “a person of any age at any
can be divided into illnesses which are purely neurological as in
time of year with the acute onset of fever and a change in
japanese encephalitis, herpes simplex virus and rabies; or into
mental status (including symptoms such as confusion,
neurological plus systemic type as in dengue, malaria, enteric
disorientation, coma, or inability to talk) and/or new onset of
and other non-viral agents like leptospirosis and rickettsioses.
seizures (excluding simple febrile seizures)”. Basically these
two terms mean the same thing and for the sake of uniformity
the term “acute encephalitis syndrome” is used. Encephalopathies versus Meningoencephalitis
The term encephalopathy, besides meaning altered sensorium
Causes also refers to a diffuse disturbance of cerebral function due to
Causes of AFE/AES are varied. Most commonly this presen a noninflammatory cause. Metabolic or toxic encephalopathy
tation is caused by actual invasion of the brain by an infectious can produce a picture of AFE. Examples of such metabolic/
agent. The important causes of AFE are given in box 1. toxic causes include Reye’s syndrome, dyselectrolytemia,
Examination should be focused and should be looked for diabetic, uremic or hepatic coma, poisoning, and heat stroke.
(Box 2). Clues must be sought to differentiate encephalopathy from
Although the etiology is varied, common causes may encephalitis, but the distinction is not always possible on
predominate depending on the region. For example, Japanese clinical grounds. General features of encephalopathies are
encephalitis (JE) is very common in large parts of east and shown in box 5.
south India. Cerebral malaria is important in areas endemic for
Plasmodium falciparum. Dengue encephalopathy, rickettsiae, TREATMENT (BOX 6)
leptospirosis, etc. are also reported from different parts of
India. The age, seasonal and rural-urban distribution, and Supportive treatment is the mainstay of therapy. A severe case
other epidemiologic clues may be helpful in suspecting specific should be managed in an intensive care unit. Measures include
infections. Box 3 gives some epidemiological and clinical clues maintenance of airways, breathing, and circulation; hydration;
to etiology. electrolyte status; and control of pyrexia and convulsions. It is
In practice, the diagnosis of encephalitis is presumptive, prudent to use appropriate parenteral antibiotics to cover for
based on clinical assessment and exclusion of other meningitis. Raised intracranial tension should be controlled
possibilities. Specific virological investigations are complex, with mannitol infusion (0.25–1.0 g/kg every 4–6 hours),
time consuming, and expensive. Even in advanced centers, hypertonic saline infusion, intravenous furosemide or inter
etiological diagnosis is possible in only a small proportion of mittent positive pressure ventilation to keep arterial CO2
clinically suspected cases (Algorithm 1). tension between 25–30 mmHg. Proper nursing care must
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Chapter 93: Acute Febrile Encephalopathy
Box 1: Causes of acute febrile encephalopathy/acute encephalopathy syndrome (AFE/AES)

Neuroinfections Noninfectious inflammation
• Viruses • Acute disseminated encephalomyelitis
{{ Arbo or “arthropod borne” viruses: examples, Western equine, Eastern • Autoimmune encephalitis
equine, Venezuelan equine, Japanese, St Louis, West Nile, Dengue, Infectious encephalopathy
Murray valley encephalitis viruses. These viruses are naturally • Cerebral malaria
transmitted between insects and vertebrate animals that decide the • Dengue encephalopathy
geographical habitat and seasonal occurrence of the infection • Virus associated encephalopathy, e.g., influenza
{{ Herpesviruses: Herpes simplex 1 and 2, Varicella zoster, Epstein-Barr,
• Enteric encephalopathy
Cytomegalovirus, Human Herpesvirus-6, B virus • Sepsis
{{ Enteroviruses: Polioviruses, Coxsackie, Echo, Enteroviruses 70 and 71
• Shigella encephalopathy
{{ Orthomyxoviruses: Influenza viruses
Structural coma with fever due to another cause
{{ Paramyxoviruses: Measles, Mumps, parainfluenza, Nipah virus
• Structural causes of coma like tumors, vascular events, etc. if
{{ Adenoviruses
associated with fever due to any other cause may present as
{{ Rhabdoviruses: Rabies, chandipura
AFE/AES
{{ Parvoviruses
Functional coma with fever due to another cause
• Nonviral agents • Many causes of coma such as toxic and metabolic
{{ Bacteria: disorders, poisoning, inborn errors, etc. if associated with
–– Pyogenic and tuberculous meningitis fever due to another cause may present as AFE/AES
–– Mycoplasma pneumoniae
–– Listeria monocytogenes
–– Spirochetes: syphilis, Leptospirosis, Lyme disease
–– Brucellosis
–– Legionella
–– Salmonella typhi
–– Cat scratch disease (Bartonellosis)
{{ Rickettsia
{{ Fungi: Cryptococcus, histoplasma, Aspergillus, mucormycosis, Candida,
coccidioidomycosis
{{ Protozoa: Plasmodium, Trypanosoma, Naegleria, Acanthamoeba,
Toxoplasma gondii, schistosomiasis, Echinococcus granulosus

{{ Metazoa: Trichinosis, Echinococcus, cysticercus, Schistosoma.
Box 2: Clinical assessment Box 3: Epidemiological and clinical clues

Epidemiology Examination • Monsoon and postmonsoon season, rural, older child, endemic
• Age • Depth of coma area—Japanese encephalitis
• Location • Bleeding manifestations • Plasmodium falciparum endemic area—cerebral malaria
• Rural/urban • Features of shock • Prominent extrapyramidal features—Japanese encephalitis
• Season of year • Hepatosplenomegaly • Sudden onset high fever with chills and rigors, multisystem
History • Rash involvement with anemia, acidosis, blackwater fever, and
• Fever • Signs of raised bilateral upper motor neuron signs—cerebral malaria
• Headache intracranial tension • Rash, bleeding, hepatic involvement, nonpitting edema—
• Meningeal signs dengue encephalopathy
• Vomiting
• Focal neurological • History of exposure to animal urine, and liver and kidney
• Seizures
deficits involvement—leptospirosis
• Altered sensorium
• Prominent meningeal signs—bacterial meningitis
• Altered behavior • Muscle tone
• Focal neurological deficits, personality change, fulminant
• Personality changes • Extrapyramidal features
course—herpes encephalitis
• Prodromal flu-like symptoms • If in deep coma, signs of
• History of animal bite, fatal course—rabies
• Rash, bleeding from any site brainstem death
• Rash, eschar
• Animal contact or dog bite
• Drug or toxin exposure
• Recent travel or immunization be given. The role of steroids in acute viral encephalitis is
• Trauma debatable. Theoretic arguments exist for and against their use.
• Recurrent episodes of A study that evaluated high-dose dexamethasone in JE found
encephalopathy no benefit of steroid therapy.
• Jaundice Specific therapy is recommended in encephalitis caused
• Premorbid medical condition such by herpes group of viruses. Acyclovir in a dose of 10 mg/kg
as diabetes or renal impairment administered as an intravenous infusion over 1 hour every 445
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Algorithm 1
Approach to diagnosis in acute febrile encephalopathy
CSF, cerebrospinal fluid; PCR, polymerase chain reaction; MP, malarial parasite; TBM, tuberculous meningitis; ANE, acute necrotizing encephalopathy
Box 4: Suggested workup for acute febrile encephalopathy/ Box 5: Features of encephalopathies (diffuse cerebral
acute encephalopathy syndrome disturbance without inflammation)
Workup Features of encephalopathies
• Blood counts including platelets and packed cell volume • Absence of fever or meningeal signs
• Rapid malaria test and smear for malarial parasite/dengue • Absence of focal neurologic signs or focal seizures
• Cerebrospinal fluid (CSF) examination: this is an essential • No peripheral leukocytosis
investigation but should be done only when considered safe. • Normal cerebrospinal fluid
CSF should be examined for total and differential cell count, • Diffuse slowing on electroencephalography
protein and sugar, bacterial culture and Gram stain; viral PCRs • Normal imaging studies
and serology
• Virology: samples for viral culture from respiratory secretions,
throat swab, CSF, blood, urine, and stool taken as early as possible
in the illness should be collected in appropriate transport media Box 6: Treatment of AFE/AES
and sent to the reference laboratory Initial rapid assessment and stabilization
• Serological investigations in acute serum for specific • Establish and maintain airway: Intubate if GCS ≤8, impaired airway
immunoglobulin M (IgM) antibody level. JE is commonly reflexes, abnormal respiratory pattern, signs of raised ICP, oxygen
diagnosed by the antibody capture ELISA for IgM antibody in saturation <92% despite high flow oxygen, fluid refractory shock
acute phase serum and CSF • Ventilation, oxygenation
• Polymerase chain reaction is being developed to provide a rapid, • Circulation:
and accurate diagnostic tool for a host of pathogens and is the {{ Establish IV access, take samples (CBC, Blood sugar, KFT, LFT,
mainstay of diagnosis. This is widely used for diagnosis of HSE electrolytes, blood gas, lactate, PS and RDT for malarial parasite,
with high sensitivity (>90%) and specificity (100%) serology for viruses),
• Neuroimaging should be done whenever possible. As far as {{ Fluid bolus if in circulatory failure (20 mL/kg NS), inotropes if
possible, magnetic resonance imaging should be insisted on. required
It can show nonspecific features of encephalitis or specific
• Identify signs of cerebral herniation or raised intracranial pressure
features suggestive of JE, Herpes simplex encephalitis or acute
disseminated encephalomyelitis. Imaging may also occasionally • Temperature: treat fever and hypothermia
reveal structural cause of coma (Figs 1 and 2) • Treat ongoing Seizures: Benzodiazepine, followed by phenytoin
• Blood chemistry: a routine blood chemistry may reveal a loading
metabolic cause of encephalopathy. Blood glucose, urea, Empirical treatment must be started if CSF examination cannot be
creatinine, electrolytes and liver function tests should be done. done or report will take time and patient is sick:
• Blood culture: should be done in every case • Ceftriaxone
• Other investigations may be done according to clinical clues • Acyclovir (treat in all suspected sporadic viral encephalitis)
446 JE, Japanese encephalitis; HSE, herpes simplex encephalitis; ELISA, enzyme- • Artesunate (stop if peripheral smear and rapid malaria test are
linked immunosorbent assay; PCR, polymerase chain reaction. negative)
Continued
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Chapter 93: Acute Febrile Encephalopathy
Continued 8 hours for 14 days (21 days in immunocompromised) is

indicated in herpes simplex encephalitis. Success of antiviral
Supportive care and treatment
therapy depends on early institution of therapy. Acyclovir is also
• Maintain euglycemia, control fever, maintain hydration recommended for varicella-zoster encephalitis. Oseltamivir
• Treat raised intracranial pressure, mild head end elevation—15–30° can be considered for influenza encephalitis. Trials with
• Treat seizures. Give anticonvulsant if history of seizures or if GCS α-interferon and nasogastric ribavirin in JE in children have
<8, or child has features of raised ICT revealed no benefit. Specific antimalarial therapy may also be
• Steroids—Pulse steroids (methylprednisolone or dexamethasone) indicated if suspicion of cerebral malaria exists.
must be given in children with suspected ADEM Minocycline is a semisynthetic penicillin which has
Prevention/treatment of complications and rehabilitation neuroprotective properties. It has excellent penetration in
• Physiotherapy, posture change, prevent bed sores and exposure the cerebrospinal fluid. Besides its direct effects on non-viral
keratitis pathogens, it has been shown to have antiviral, anti-apoptotic
• Complications—aspiration pneumonia, nosocomial infections, and anti-inflammatory actions with significant benefit in
coagulation disturbances animal models of viral encephalitis. There may be a role of
• Nutrition—early feeding minocycline in AES even of undetermined etiology and human
• Psychological support to patient and family trials with this agent are underway.
GCS, glasgow coma scale; ICP, intracranial pressure; IV, intravenous; CBC,
complete blood count; KFT, kidney function test; LFT, liver function test; Clinical Pearl
PS, peripheral smear; CSF, cerebrospinal fluid; ADEM, acute disseminated
encephalomyelitis; RDT, rapid diagnostic test; ICT, intracranial tension. • Tuberculous meningitis (TMB) usually has a subacute onset.
Here the prodromal stage with nonspecific symptoms will be
longer than a week. If the child is comatose and computed
tomography scan does not show hydrocephalus it is unlikely
to be TBM; presence of basal exudates and/or granulomas is
suggestive of TBM while subdural collections are suggestive
of bacterial meningitis. Cerebral malaria is a multisystem illness
with acute onset of high fever, chills and rigors, bilateral upper
motor neurone signs, anemia, hemoglobinuria and normal
cerebrospinal fluid.
Key points
))
Acute febrile encephalopathy is a common cause of intensive
care admissions in pediatrics
))
Etiology is varied with both infectious and non infectious
causes
))
A good history along with targetted investigations like Magnetic
resonance imaging brain, infection screen and Cerebrospinal
Fig. 1: Magnetic resonance imaging brain showing temporal fluid analysis help in reaching diagnosis in majority
lobe changes in herpes encephalitis ))
Pending investigations, empirical ceftriaxone, acyclovir and
artesunate could be started in Indian scenario
))
A subset of patients may be undiagnosed despite extensive
investigations. Autoimmune or inflammatory causes should
be suspected in these.
SUGGESTED READINGs
1. Bale JF. Viral encephalitis. Med Clin North America. 1993;77(1):25-41.
2. Cherry JD. Encephalitis. In: Behrman RE, Kleigman RM (Eds). Nelson Textbook of
Pediatrics, 14th edition. Pennsylvania: WB Saunders Co; 1993. pp. 666-9.
3. Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B, Cossen CK, et
al. Beyond viruses: clinical profiles and etiologies associated with encephalitis.
Clinical Infect Dis. 2006;43:1565-77.
4. Kalra V. Acute febrile encephalopathy. In: Gupta V, Gupta D (Eds). Practical
Paediatric Neurology, 2nd edition. Avichal Publishing Co. (Arya Publication).
2008. p. 112.
5. Kumar R. Viral encephalitis and encephalopathies in Medical Emergencies in
Children Ed M Singh. 447
6. Sharma S, Mishra D, Aneja S, Kumar R, Jain A, Vashishth VM. Evaluation and
Fig. 2: Magnetic resonance imaging brain showing changes of Management of Suspected Acute Viral Encephalitis in Children in India. Indian
acute disseminated encephalomyelitis Pediatrics. 2012;49:897-903.
Ch-93.indd 447 11/21/2016 11:35:52 AM

Chapter 94
Approach to Pediatric
Movement Disorders
PA M Kunju, Anoop K Verma
INTRODUCTIOn • Benign neonatal sleep myoclonus

• Benign myoclonus of infancy
Movement disorders are characterized by abnormal or excessive • Jitteriness
involuntary movements that may result in abnormalities in • Shuddering attacks
posture, tone, balance, or fine motor control. It is often used • Paroxysmal tonic upgaze of infancy
synonymously with basal ganglia or extrapyramidal disease but • Spasmus nutans
it does not adequately describe all the movement disorders. • Benign paroxysmal torticollis
Basically movement disorders are characterized as akinetic • Benign idiopathic dystonia of infancy.
rigid syndrome and hyperkinetic or dyskinetic syndrome. In
akinetic syndrome there, is slowness or paucity of movement,
for example, parkinsonism, (this particular disorder is rare in CATEGORIZATION OF MOVEMENT DISORDER
pediatric age group). In dyskinetic syndrome, there is excessive If we categorize the movement disorder according to the level
movement, e.g., chorea, athetosis, ballismus, tremor, dystonia, of involvement at the brain, it can be summarized as per the
tics, and other stereotypic behavior. following algorithm 1.
The structures responsible for motor control are upper
How They Differ in Children motor neuron (UMN), lower motor neuron (LMN), cerebellar
Movement disorders in childhood are a heterogeneous circuitry, basal ganglia circuitry, motor activation cortex, and
group of diseases with presentations that vary according to sensory cortex. Virtually the entire nervous system is engaged
etiopathogenesis and age of onset. Involuntary movements can in motor control.
represent the sole disease manifestation, or they may be one of The basal ganglia consist of five large subcortical nuclei that
many symptoms and signs of other systemic disorder. While are the caudate nucleus, putamen, globus pallidus, substantia
sharing certain characteristics with the conditions that affect nigra, and subthalamic nuclei. Bradykinesia is related to insult
adults, they also have unique features that are determined at substantia nigra, ballismus to subthalamic nucleus, dystonia
by the metabolic, physiological, and environmental to putamen, and chorea to caudate nucleus, but overlaps are
distinctiveness of the developing brain. So they show some also seen.
particular characteristics:
• An increased occurrence of hyperkinetic movements,
Clinical Pearls
rather than bradykinesia or rigidity • Movement disorder and seizures can be differentiated by the
• A higher frequency of transient motor phenomena in the preservation of consciousness
first year of life • Except ballism movement disorders stop during sleep
• A higher prevalence of paroxysmal movement disorders • Video recording using mobile phones will help in identifying
• A major primary etiology for chronic motor dysfunction the type of abnormal movements.
being residue of static encephalopathy
• A greater likelihood that symptoms are secondary to
hereditary metabolic disorders PHENOMENOLOGY OF
• An evolving pattern of movements associated with MOVEMENT DISORDERS
metabolic disorders.
Some of the common benign movement disorders that have to Phenomenology refers to the clinically observable aspects
be ruled out in infancy are: of movement disorder, and one must be able to identify, the
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Chapter 94: Approach to Pediatric Movement Disorders
Algorithm 1
Categorization of movement disorders
characteristic of each movement disorder as each of them has GENERAL APPROACH TO

a different character (Table 1).
MOVEMENT DISORDERS
Clinical Pearl Evaluation of movement disorders, like all neurologic
symptoms, begins with a comprehensive history:
• Movement disorders can be grouped according to the speed • Patient’s gestation, detailed birth history, early develop
of movement
ment, previous illnesses, drug history, exposure to potential
• Fastest being myoclonus, slightly slower will be ballism, then toxins, and social and family history, are often essential for
chorea, then athetosis, and slowest dystonia. proper classification
• The key questions to be asked are as follows:
{{ What is the distribution? (e.g., orofacial—chorea)
Table 1: Charecteristics of movement disorders
{{ Is it unilateral or generalized? (e.g., Hemidystonia
Movement Brief description associated with structural lesion)

disorder {{ What is the speed of movement—fast (excessive
Chorea Chorea is rapid jerky, large amplitude involuntary movement, hyperkinetic) or slow (paucity of move
movements of proximal more than distal muscles ment, hypokinetic)?
{{ Is it rhythmic or is it jerky? (e.g., rhythmic—tremor;
Athetosis Slower writhing irregular movements predomi
nantly in the hands and wrist palatal myoclonus)
{{ Is it present at rest? With action? Is there any relation
Dyskinesia General term for abnormal movement; however,
commonly denotes movements of mouth and face, to certain postures or positions? (e.g., rest tremor-
usually drug induced (orofacial dyskinesia) parkinsonism; action tremor—familial essential tremor)
{{ Is there any task specificity? (e.g., kinesigenic
Dystonia Cocontraction of agonist and antagonist, which
lead to an intermittent or persistent maintenance
choreoathetosis)
{{ Is patient able to suppress it? (e.g., tics)
of abnormal posture
{{ Is it stereotyped? (e.g., Tics/Stereotypy)
Hemiballis Violent flinging movements, which are irregular
{{ Is movement disorder continuous or intermittent
mus affecting one side
or occurring in discrete episodes? (e.g., paroxysmal
Myoclonus Sudden shock-like contraction of a muscle or a dyskinesia)
group of muscle leading to involuntary purposeless {{ Is there an association with an urge? (e.g., tics)
jerk of affected limb
{{ Is it related to sleep? (e.g., hemiballism/restless leg
Ataxia Ataxia is inability to control movements and syndrome; seizure)
typically is caused by cerebellar dysfunction {{ Is it associated with functional motor impairment?
Tics Tics are rapid, complex, nonvoluntary, repetitive {{ Are there any aggravating/alleviating factors?
segmental movements. Simple tics last less than 6
months. Chronic tics last longer than 6 months Clinical Pearl
Tourette There are motor tics and vocalizations lasting longer
syndrome than 12 months, start between 2 and 10 years of age, • Video of abnormal movement is important which can
and may fluctuate in severity over time supplement witnessing the real-time abnormal movement
of the patient.
Tremor Rhythmic oscillation about a certain point or
position involving one or more body part
A critical feature is determining whether the presenting
Stereotypies Stereotypies are repetitive, patterned involuntary signs/symptoms are an isolated disorder, associated with
movements that have no apparent function other neurologic findings, part of a static condition, or 449
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appearing in conjunction with a loss of other previously Table 2: Features of movement disorders
acquired skills.
Features Category Examples
A comprehensive general examination is further required
Speed • Hyperkinetic • Tremor, chorea, myoclonus, tics,
for properly defining the movement and identifying clues
• Hypokinetic restless legs syndrome, dystonia
indicating a systemic problem. The category of movement • Apraxia, Parkinson bradykinesia
assists in localizing the pathologic process, whereas the onset,
Region • Whole body • Generalized dystonia
age and degree of abnormal motor activity and associated • Hemibody • Hemidystonia, hemichorea
neurologic findings help organize the investigation. Correct • Segmental • Segmental myoclonus
classification of the type of movement disorder forms the basis • Multifocal • Polyminimyoclonus
for the subsequent diagnostic process. • Focal • Writer’s cramp
The features of movement disorders are discussed in • Proximal • Rubral tremor
table 2. • Distal • Athetosis
Thus, compiling the important pieces of information from • Oral • Tardive dyskinesia
history and examination, the strategy is to reach the diagnosis Character Rhythm
from recognizing the patterns based on phenomenology • Rhythmic • Tremor, dystonic tremor,
and then focus on the causes as possible etiologies for acute, periodic movements in sleep
subacute onset and acquired causes. • Arrhythmic • Akathitic movements,
athetosis, ballism, chorea,
dystonia, hemifacial spasm,
CAUSES OF MOVEMENT DISORDERS hyperekplexia, arrhythmic
myoclonus, stereotypy, tics
The causes of movement disorders can be summarized as in
algorithm 2. Frequency
• Fast • Chorea, tics, minipolymyoclonus
Clinical Pearl • Slow • Ballism
• Hemidystonia may indicate a structural abnormality and Amplitude

generalized dystonia may indicate a possible idiopathic disorder. • Large • Ballism
• Fine • Tremor, minipolymyoclonus
At Rest
Drug-induced Movement Disorders • At rest and • Ballism, chorea, dystonia,
There are various movement disorders which are caused due to continues postural tremor
adverse effects of medications or drugs. They are summarized with action • Action tremor, ataxia
• With action
in table 3.
Before discussing the individual movement disorders, Force
it would be prudent to take a look at the inherited disorders • Powerful • Stiff-man syndrome
causing movement disorders (Table 4). Trigger • Action • Writer’s cramp
• Position • Orthostatic tremor
Clinical Pearl Intention • Voluntary • Tics
ality • Involuntary • Tardive dyskinesia
• Three generations pedigree, including cousins and siblings Relieving • Sleep • Dystonia, tremor
of parents and grandparents can give a clue to the hereditary factor
causes of movement disorders. Psychiatric Huntington disease
Algorithm 2
450
SLE, systemic lupus erythematosus; MERRF, myoclonic epilepsy with ragged red fibers; SSPE, subacute sclerosing panencephalitis; DOPA, dopamine.
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Table 3: Drug-induced movement disorders

Type of movement disorder Drugs Presence in sleep
Bradykinesia Typical neuroleptics and atypical antipsychotic No
Chorea/athetosis Phenytoin, carbamazepin, valproic acid, dopamine receptor blocking agent, tricyclic No
antidepressant, theophylline, oral contraceptives, steroids, and stimulants
Dystonia Typical neuroleptics, antipsychotics, metoclopramide No
Myoclonus Epileptic myoclonus can be aggravated by some antiepileptics Yes
Tremor Tricyclic antidepressant, valproic acid, phenytoin, carbamazepine, theophylline No
Tics Lamotrigine, stimulants, levodopa, neuroleptics Yes
Table 4: Inherited condition causing movement disorders

Etiology Age at onset Clinical signs EEG and Imaging Lab finding and
genetic testing
Glutaric aciduria 5–10 months Acute encephalopathy followed by dystonia, CT/MRI: Frontotemporal Organic acid in urine,
Type 1 motor impairment, macrocephaly atrophy enzyme assay
Glucose transporter 1 Infancy Seizures, developmental delay, complex EEG improves Low-glucose
deficiency syndrome movement disorder postprandially concentration in CSF
Lesch-Nyhan 3–13 months Self-mutilation, facial grimacing, involuntary Development of kidney Hyperuricemia
syndrome writhing repetitive movement of arm stone
Leigh’s disease Birth to first year Diffuse encephalopathy, dysphagia, MRI: PVL, hyperintense High serum/CSF
dystonia, myoclonus, hypotonia central T2 signal in the basal lactate
respiratory insufficiency ganglia and thalami
PKAN 1st decade Delayed motor and language, later MRI: Eye of the tiger Noncontributing
choreoathetosis, dystonia, dysarthria, sign
dysphasia, spasticity retinopathy
Wilson’s disease 1st and 2nd decade Dysarthria, gait disturbances, risus MRI: High signal in KF ring, low-serum
sardonicus, dystonia, rigidity, tremor, basal ganglia, dentate ceruloplasmin
dysphagia nuclei and cerebellum
on T2
Huntingtons disease 2nd decade Neurological and psychiatric symptoms, MRI: Nonspecific Noncontributing
chorea, rigidity, hypokinesia generalized or striatal
atrophy
Early onset torsion Between 3 and Ashkenazi Jews, dystonia affecting first one Noncontributing Noncontributing
dystonia 26 years arm or leg progressing to generalized or
multifocal
PKAN, pantothenate kinase-associated neurodegeneration; CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging; EEG,
electroencephalography; KF ring, Kayser–Fleischer ring; PVL, periventricular leukomalacia.
The category of movement assists in localizing the immunological, or other investigations as applicable. Magnetic
pathologic process, whereas the onset, age and degree of resonance imaging (MRI) brain is the neuroimaging modality
abnormal motor activity and associated neurologic findings of choice in pediatric movement disorders and the following
help to organize the investigation. Correct classification of the algorithm 3 proves a good guide to diagnosis.
type of movement disorder forms the basis for the subsequent
diagnostic process. Clinical Pearl
No specific biological marker is available:
• Many diagnostic tests are available but these are often • Magnetic resonance imaging will help in identifying various
expensive, time-consuming or invasive disorders. Basal ganglia calcification can be due to Fahr
• The diagnostic value of these tests is often limited, syndrome or pseudohypoparathyroidism and basal ganglia
especially in early stages of the disease. hyperintensity can be commonly due to Wilson disease
The investigational workup can be greatly simplified once (caudate) and kernicterus (globus pallidus)
the type of movement disorder has been defined properly.
INVESTIGATIONS TREATMENT
The investigations in movement disorders can be divided Although the treatment of movement disorders is varied 451
logical,
under different headings of neuroimaging, hemato and multidisciplinary according to the type, the common
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Algorithm 3
Brain MRI changes in movement disorders
MRI, magnetic resonance imaging; CNS, central nervous system; AIDS, acquired immunodeficiency syndrome; CO, carbon monoxide; MELAS, mitochondrial
encephalomyopathy, lactic acidosis, and stroke-like episodes.
Table 5: Drugs used in movement disorders

Drugs Doses Precautions Indications in movement disorders
Pimozide 1–2 mg/day (2–6 mg, if required) Prolong QT interval Gilles de tourette syndrome
Cardiac arrhythmias
Haloperidol 20–50 mg/kg initially; maximum to 10 mg/day Liver, kidney disease epilepsy, Choreiform movement, rheumatic
thyrotoxicosis chorea, hemiballismus
Gilles de tourette syndrome
Tetrabenazine 12.5 mg bid; increment of 12.5 mg every Pregnancy, lactation Chorea, hemiballismus, myoclonus,
3–4 day to a maximum of 3 mg/kg/day depression, patient on buccolingual dyskinesia, in certain
levodopa, reserpine dystonia
Trihexyphenidyl 1 mg first day, 2 mg second day, then increase Glaucoma, sick sinus syndrome, Dystonia, myoclonus, drug induced
to 2 mg every 3–5 day; maintenance usually cardiac failure, tachycardia movement disorders, torticollis
6–16 mg/day
Levodopa- Up to 5 mg/kg/day – Dopa responsive dystonia, dystonia
carbidopa and Parkinson state
Carbamazepine <6 years: 5 mg/kg/24 hours orally; may Porphyria, hepatic failure, MAO Chorea, Athetosis, Ballismus,
increase every 5–7 day by 5 mg/kg/day inhibitors Paroxysmal kinesigenic dyskinesia
6–12 years: initially 10 mg/kg/day; increase by
5/mg/day at weekly intervals
Usual dose—800–1200 mg/24 h
Sodium valproate Below 20 kg: 20 mg/kg/day Liver disease, SLE, porphyria Chorea
Above 20 kg: 400 mg/day
Clonazepam Initial 0.01–0.03 mg/kg/24 h in 2–3 divided Hypersensitivity to Dystonia, torticollis, myoclonus,
doses; increase 0.25–0.5 mg/24 h every benzodiazepine startle syndrome
3–5 days; maximum dose 0.3 mg/kg/24 h
SLE, systemic lupus erythematosus; MAO, monoamine oxidase; BID twice a day.
drugs used to treat and their dosages are given in table 5. The INDIVIDUAL MOVEMENT DISORDERS
drugs are thereafter mentioned briefly when describing the
452 individual movement disorders. Following is a short discussion of movement disorders.
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Dystonia –– Axial: Neck and trunk

–– Brachial: Arm and trunk
Though dystonia is a common symptom in neurology, it is
–– Crural: One leg and trunk; both legs with or without
being recognized less frequently by pediatricians.
trunk
• Generalized—Crural
Definition
{{ With any other segmental involvement.
Dystonia is a hyperkinetic movement disorder characterized {{ Focal or segmental dystonia may progress and become
by sustained or intermittent muscle contractions causing generalized if:
abnormal (often repetitive) movements, postures, or both. The –– Childhood or adolescent onset
factor which distinguishes myoclonus, chorea, athetosis, and –– Beginning in the lower limbs
dystonia would be the variable speed of movement; fastest • Hemidystonia: when one side of the body is involved.
being myoclonus, 50–100 ms and slowest one being dystonia,
which may last at least a second. Type of Onset
Dystonia evolves in a focal manner and during voluntary
It is broadly divided in to four groups:
activity—“action dystonia”.
1 Acute dystonia
Pathophysiology 2 Tardive dystonia
3 Paroxysmal dystonia
Dystonia is a circuit disorder, historically thought to arise
4 Chronic nonprogressive/progressive dystonia.
from basal ganglia but now recognized to result from injury or
malfunction in any of the several nodes within the motor cortex. Acute dystonia
Acute dystonia arise from neuroleptic drugs, exposure to toxins,
Classification
infections, and certain familial disorders. Acute reactions can
The dystonias are classified according to their distribution, age appear soon after starting treatment with phenothiazine, or
of onset, type of onset, and etiology. even promethazine. Manifestations include bizarre postures
of face (sustained grimacing), eyes (oculogyric crisis), jaw
Distribution (trismus, mandibular dystonia), tongue (lingual dystonia),
• Focal neck (torticollis), trunk (scoliosis, lordosis, kyphosis, and
{{ When dystonia is confined to anyone single region: opisthotonos) and limbs (torsion spasm). These may be
–– Ocular muscles: Blepharospasm confused with seizure, tetany or encephalitis if a proper history
–– Tongue: Lingual dystonia of drug ingestion is not obtained.
–– Vocal cord: Dystonic dysphonia The acute dystonic reactions may be the result of excess
–– Mouth: Oromandibular dystonia dopaminergic activity. Response to treatment of acute dystonia
–– Neck: Torticollis is often dramatic. Anticholinergic drugs like diphenhydramine
–– Hand: Writer’s cramp (Fig. 1) or promethazine will reverse the acute dystonia within
• Segmental minutes. We have seen transient dyskinesia in asthmatic
{{ When focal dystonia spreads to contiguous area: patients receiving theophylline. Interaction of theophylline
–– Cranial: Face and neck and hypoxemia with other factors may induce this.
Fig. 1: Writers cramps—before and after Botox injection 453
Ch-94.indd 453 11/24/2016 2:17:07 PM

1. Primary dystonia
Clinical Pearl 2. Secondary dystonia.
Acute dystonias can be remembered by VITS:
Primary dystonia
• V—Vascular (infarct; hemorrhage, etc.) In the past 20 years, monogenic defects have been found to
• I—Infection and post-infectious, e.g., Japanese encephalitis; underlie many forms of dystonia. Monogenic forms of isolated
autoimmune encephalitis dystonia are referred to as DYTs.
• T—Toxin (drugs like phenothiazine toxicity) • Idiopathic torsion dystonia (ITD)/Dystonia musculorum
• S—Space occupying lesion (subacute) deformans (DMD): Autosomal dominant dystonia gene is
found to be located on chromosome 9q34. The usual age of
onset is 5–15 years with dystonia of legs and within 5–10
Tardive dystonia
years disease reach to maximum level of disability. At that
It is a separate entity from acute dystonic reactions in that time they are twisted axially with contorted oromandibular,
it is persistent, does not show response to intravenous neck, trunk, and limb musculature.
diphenhydramine or anticholinergics. Another striking feature • Dopa-responsive dystonia: This group of patients with
is the distribution of dystonic movement. Generalized dystonia
dystonia respond dramatically to a very low dosage of
is more in younger individuals whereas in older subjects it has
levodopa. Features include onset of dystonia before the age
a more restricted distribution.
of 16, onset in the legs or with gait, and often having features
Paroxysmal dystonia of parkinsonism. Inheritance is autosomal dominant.
A group of interesting disorders which may be confused with Since the demonstration of dopa-sensitive dystonic states,
seizures: levodopa has been tried in some of the cases of the congenital
• Familial paroxysmal dystonic choreoathetosis: This rare cerebral palsy where choreoathetotic rigidity is seen.
bizarre paroxysmal movements occurring in an autosomal • Diurnal dystonia (Segawa syndrome): Relatively free of
dominant manner. Each attack is characterized by (a) dystonic movements and postures in the morning and
painful spasm of affected musculature, (b) choreoathetosis be afflicted severely in the late afternoon. Segawa had
and (c) return to normality described this type of dystonia and we have seen many
• Paroxysmal kinesigenic dystonia: Sudden movement or with similar involvement and who showed dramatic
startle and stress will precipitate an attack. These patients response to levodopa. . The disease is caused by a GTP
can avert an attack by avoiding abrupt movement and cyclohydrolase 1 (GCH) deficiency. Genetic mutations in
sensory stimuli the tetrahydrobiopterin synthetic pathway, specifically the
• Exercise induced paroxysmal dystonia: A paroxysmal GCH1 gene (DYT 5) in the autosomal-dominant variant,
dystonic choreoathetosis, which is seen after continued and the TH gene in the autosomal recessive form, are
exercise or by sensory stimuli but not after a sudden responsible for the condition.
movement
• Paroxysmal hypnogenic dystonia: Certain varieties of Clinical Pearls
dystonia may be brought on by sleep. In addition to the
idiopathic variety, we have seen paroxysmal dystonias • Common cause of nonprogressive dystonia is dyskinetic
due to intracranial tumor, hyperthyroidism and transient cerebral palsy due to kernicterus or birth asphyxia (Fig. 2)
ischemic attacks. • However, in such cases a dose of levodopamine must be tried
Recently following genetic associations are found with to rule-out diurnal dystonia (Segawa syndrome), which is an
paroxysmal movement disorders. Paroxysmal kinesigenic eminently treatable condition.
dyskinesia due to PRRT2 mutations (DYT10); paroxysmal
nonkinesigenic dyskinesias (DYT8) with mutations in the
PNKD (also known as MR-1) gene; and exertion-induced Secondary dystonias
dyskinesia (DYT18) with SLC2A1 mutations. Secondary dystonia can be due to congenital, hereditary,
metabolic, vascular, infection, degeneration, demyelination,
Clinical Pearl tumor, drugs, toxins, etc.
Useful clinical pointers to suggest a secondary dystonia:
• Paroxysmal movement disorders (PD) may resemble
• History to suggest involvement of other organ systems, e.g.,
seizures but will respond to antiepileptic drugs like
phenytoin, carbamazepine (kinesgenic PD), or clonazepam liver (Wilson’s disease), multiple system (systemic lupus
(nonkinesegenic PD) erythematosus)
• Coexistent neurological signs indicating involvement of
higher mental, retinal, pyramidal, or LMN function
Treatment: Paroxysmal kinesigenic choreoathetosis responds
• History of exposure to antipsychotic drugs, toxins, injury,
to phenytoin. Other varieties may respond to clonazepam,
L-tryptophan and carbamazepine. or cerebrovascular disorders.
Chronic nonprogressive/progressive dystonias Treatment

454 Etiology: Dystonias are divided into two types on the basis of Treatable dystonic conditions like Wilson’s disease, tardive
etiology as follows: dystonias, etc. have to be considered first.
Ch-94.indd 454 11/24/2016 2:17:07 PM

{{ Hyperparathryoidism/hypoparathryoidism, pseudo
hypoparathyroidism—Basal ganglia calcification.
• Autoimmune:
{{ Autoimmune encephalitis—underlying ovarian tera
toma/positive N-methyl-D-aspartate receptor antibody

{{ Systemic lupus erythematosus—signs of systemic
erythematosus
{{ Sydenham’s chorea—preceding streptoccal infection
{{ Antiphospholipid antibody syndrome—focal signs
stroke; hypercoagulable state.

• Genetic
{{ Chorea-acanthocytosis syndrome—obsessive compul
sive behaviors, orolingual dystonia, peripheral neurop

athy, seizures
{{ Wilson’s disease—tremor, dystonia typical, psychiatric
features
{{ Huntington’s disease—in children more of rigid
dystonia
{{ Ataxia-telangiectasia—ataxia, oculomotor apraxia,
increased sinopulmonary infection
Fig. 2: A child with dystonic choreoathetosis {{ Spinocerebellar ataxia 1, 2, 3, 17—ataxia, peripheral
neuropathy, abnormal movements

• Drugs: Trihexyphenidyl, dopamine agonists, baclofen,
{{ Lesch–Nyhan syndrome—self mutilation
clonazepam, carbamazepine and clonidine)
{{ Leigh’s syndrome—dystonia, spasticity, myoclonus,
• Local administration of botulinum toxin for focal dystonias
lactic acidosis
(Fig. 2)
{{ Pantothenate Kinase-Associated Neurodegeneration—
• Surgical methods
progressive dystonia, dysarthria, rigidity, ballism,
• Psychological methods.
choreoathetosis, spasticity, dementia and pigmentary
retinal degeneration; MRI shows the characteristic “eye
Clinical Pearl
of the tiger” sign within globus pallidus interna (Figs 3
• Dopa-responsive dystonia (DYT5, Segawa disease) is the most and 4)
important cause of primary dystonia with childhood onset, {{ Fahr’s disease—second decade of life, microcephaly,
responds dramatically to low doses of levodopa hypertonia, and choreoathetosis

{{ Basal ganglia and cerebellar nuclei calcification and
also punctate calcifications in thalamus (Fig. 5).

Chorea
Involuntary, purposeless/quasi purposive, jerky, dance-like Tremor
movements.
Athetosis: Now described as a slow, writhing form of chorea. Definition
Ballism: Forceful, flinging form of chorea; proximal more than Regular rhythmic repetitive to and fro oscillatory movements.
distal, typically unilateral, and often coexistent with chorea.
Pathophysiology of Chorea
Injury to basal ganglia, especially the striatal indirect pathway,
is a common anatomic precipitant for many forms. The
neurophysiology underlying chorea is still poorly understood.
Causes of Chorea
• Structural:
{{ Ischemic stroke—acute/subacute—unilateral chorea;
localizing neurologic signs

{{ Tumor—subacute—symptoms of raised intracranial
pressure
{{ Moyamoya disease—Subacute, multifocal seizures.
• Metabolic/Endocrine:
{{ Hypernatremia/hyponatremia; hypomagnesemia— Fig. 3: Pantothenate kinase-associated neurodegeneration—severe
altered biochemical status dystonia 455
Ch-94.indd 455 11/24/2016 2:17:07 PM

Rigidity
A form of hypertonia in which resistance to passive movement
is present at low speeds, does not depend on the speed and
does not exhibit a speed or threshold angle.
Hallmarks of Rigidity
Associated with diseases with a primary failure of dopamine
production:
• Juvenile Parkinson’s disease—rigidity, bradykinesia (no
tremor in children)
• Dopa-responsive dystonia
• Dystonic cerebral palsy.
Tics
Fig. 4: Eye of the tiger sign in coronal magnetic resonance imaging Definition
Rapid, arrthymic, repetitive movements or sounds that wax
and wane over weeks/months to involve other body parts
and actions.
Types
• Simple—e.g., blinking or sniffing.
• Complex—e.g., gesticulating or uttering
• Transient tics—less than 12 months
• Chronic motor or vocal tics—last at least 1 year.
Tourette syndrome
Criteria requires the (a) combination of motor and vocal
tics, (b) duration of at least 1 year, (c) onset before the age
of 18; exclusion of other causes [direct physiologic effects
of a substance (e.g., stimulant drugs) or a general medical
condition (e.g., Huntington disease or postviral encephalitis)].
Associated with other comorbid disorders like obsessive
compulsive disorders, attention deficit hyperactivity disorder
Fig. 5: Computer tomography scan-basal ganglia calcification— or behavioral problems.
Pseudohypoparathyroidism
Pediatric autoimmune neuropsychiatric disorders
associated with streptococcal infections (PANDAS)
Pathophysiology Now regarded as a controversial diagnosis. Abrupt onset of tics
or obsessive compulsive disorders after infection with group
Can arise from cortex, basal ganglia, brainstem, cerebellum,
A β-hemolytic streptococcus in prepubertal children, with
or periphery—each location associated with distinct tremor
motoric hyperactivity and adventitious movements but not
characteristics.
frank chorea.
Types Treatment of Tics
• Resting tremor—decreases or resolves with movement. • 1st tier drugs: a2-agonists (clonidine, guanfacine)
Worsens with agitation or inattention • 2nd tier drugs: Atypical antipsychotics (risperidone,
• Action tremor—elicited by initiating movement or olanzapine, etc.)
increasing force generated. Four subtypes can be postural • 3rd tier drugs: Typical antipsychotics (haloperidol,
tremor, intention tremor kinetic, or isometric tremor pimozide, fluphenazine)
• Physiologic tremor—seen with particular situational • Others: Tetrabenazine, botulinum toxin (for single site
challenges, e.g., stress, caffeine, fatigue bothersome tics).
• Rubral tremor—coarse, jerky, irregular, large amplitude
and low frequency (Holmes tremor or midbrain tumor)
• Psychogenic tremor—variability in tremor frequency,
Clinical Pearl
Tics “rule of three”,
amplitude, distribution, and direction. Usually acute in
• One-third disappears
onset but non progressive
456 • One-third are better
• Drug-induced tremors—seen with medications (broncho
• One-third continue.
dilators, thyroid hormone, stimulants, steroids, etc.).
Ch-94.indd 456 11/24/2016 2:17:07 PM

Stereotypy Excessive irritability, sleep disturbances, and mutism are

common.
Described as repeated, purposeless movements
Divided into two groups: Diagnosis
1. Primary, indicating a physiologic basis, and It is essentially a clinical diagnosis but neuroblastoma
2. Secondary, for those associated with other neuro screening is mandatory.
developmental problems like:
{{ Pervasive developmental disability—Autism spectrum Prognosis and treatment
disorders, Rett syndrome Neurologic outcome is unfavorable and a significant affected
{{ Intellectual retardation
are left with motor and cognitive sequelae. Treatment includes
{{ Sensory deprivation—congenital blindness/deafness
immunosuppression and supportive medication for sleep and
{{ Inborn errors of metabolism—Lesch-Nyhan syndrome
behavior disruption.
{{ Genetic—Neuroacanthocytosis.
Tics are different from stereotypies which can be

reproduced voluntarily and the patient has partial control. Key points
They do not interfere with voluntary activity. ))
Establishing phenomenology is key to diagnosis to movement
disorder
Myoclonus ))
Every type of MD has its own characteristic, and combinations
of them are also not rare, try to find the dominant one and
Definition existence of others also
It is an involuntary muscle jerk which cannot be suppressed ))
Presence of neurological and non-neurological causes of
and generally with no premonitory features. It can be isolated abnormal movements, epilepsy and epilepsy mimics should
though uncommon in children or a symptom of other disorders. be also considered
In children it should be evaluated for epileptic myoclonus. ))
After having reached to clinical based movement disorder
type, proceed for diagnostic workup to locate the cause
Types behind and accordingly plan for treatment
Myoclonus can be subdivided according to the anatomic ))
Keep your camcorder ready; patient never gives you second
origin: chance.
• Cortical: Originates from the sensorimotor cortex. Seen as
focal, distal and arrthymic movement usually seen in the
arms or trunk. It can be spontaneous or induced by action. SUGGESTED READINGs
Examples: progressive myoclonic epilepsies, Angelman’s
1. Albanese A, Bhatia K, Bressman S, Delong MR, Fahn S, Fung VS, et al.
syndrome, Huntington’s disease, Rett’s syndrome, etc.
Phenomenology and classification of dystonia: a consensus update. Mov Disord.
• Subcortical: Seen with injury to thalamus or brainstem.
2013;28(7):863-73.
Examples: palatal myoclonus, hyperekplexia, etc.
2. Butler IJ. Movement disorders of children. Pediatr Clin North Am. 1992;39:727‑42.
• Spinal: Duration is longer and more variable than cortical 3. Emilio Fernandez-Alvarez. Movement disorders in children: recent advances in
or subcortical myoclonus. Examples: post-trauma, management. Indian Journal of Pediatrics. 2009;76:531-6.
ischemic myelopathy, etc. 4. Fenichel GM. Movement disorders. Clinical Pediatric Neurology, 4th edition.
• Peripheral: Peripheral nerves lesions where sensory input 2001. p. 281.
is affected. They are typically arrthymic and non-stimulus 5. Fuchs T, Ozelius LJ. Genetics of dystonia. Semin Neurol. 2011;31:(5):441-8.
sensitive. Example: hemifacial spasm. 6. Grosset KA, Grosset DG. Prescribed drugs and neurological complication. Journal
Physiological myoclonus is much more common and of Neurology, Neurosurgery, and Psychiatry. 2004;75(Suppl 3):iii2-8.
should be differentiated from pathological causes. The 7. Jarman PR, Wood NW. Genetics of movement disorders and ataxia. Journal of
common types of physiological myoclonus include benign Neurology Neurosurgery and Psychiatry. 2002;73:ii22.
neonatal sleep myoclonus and benign myoclonus of infancy. 8. Kennards C (Ed). Recent Advance in Clinical Neurology. Edinburgh: Churchill
Livingstone; 1988. pp. 175-200.
Opsoclonus-myoclonus-ataxia Syndrome 9. Korn-Lubetzki I, Stelner I. Common movement disorders in children: diagnosis,
(“Dancing Eyes, Dancing Feet”) pathogenesis and management. Neuroscience & Medicine. 2012;3:90-100.
10. Kunju PAM. Extrapyramidal disorders. In: Gupte S (Ed). Recent Advances in
It is a rare but a dramatic, autoimmune disorder most commonly Pediatrics. New Delhi: Jaypee Brothers Medical Publishers; 1994. pp. 140‑66.
seen between 1 and 5 years. 11. Lees AJ. Odd and unusual movement disorders. Journal of Neurology
Neurosurgery and Psychiatry. 2002;72:i17-21.
Etiology
12. Nygaad TG, Wooten GF. Dopa-responsive dystonia: some pieces of puzzle are still
In children, 50% are associated with neuroblastoma and missing. Neurology. 1998;50:853-5.
majority of nonneoplastic remain idiopathic but presumed 13. Rojahn J. Self-injurious and stereotypic behavior of non institutionalized mentally
postinfectious. retarded people: prevalence and classification [published erratum appears in Am
J Ment Defic. 1987;91(6):619]. Am J Ment Defic 1986;91(3):268-76 [Medline].
Clinical presentation 14. Singer HS, Mink JW, Gilbert DL, Jankovik J. Movement disorders in Childhood, 1st
Presents with robust myoclonus and opsoclonus seen as edition. Saunders Elsevier, 2010. 457
multidirectional, darting, chaotic, conjugate eye movements. 15. Thyagarajan D. Recent advances. J Clin Neuroscience. 1999;6:1-8.
Ch-94.indd 457 11/24/2016 2:17:07 PM

Chapter 95
Afebrile Encephalopathy: Bedside Approach to
Diagnosis and Management
Lokesh Lingappa, Sirisharani Siddaiahgari
INTRODUCTION Table 1: List of disorders known to present with afebrile

encephalopathy
Encephalopathy sets in with diffuse cerebral involvement,
Categories Disorders
bilateral thalamic or ascending reticular activating system
pathology. In children, diffuse cerebral involvement is the Autoimmune • NMDA receptor encephalitis, voltage
most common pathology leading to altered sensorium. A gated potassium channel antibody
encephalitis
study by the California Encephalitis Project on epidemiology
• Hashimoto encephalitis
and etiology of encephalitis found that 63% of the patients
remained without an etiology after a battery of tests for 16 Epilepsy • Nonconvulsive status epilepticus,
prolonged postictal state
potential infectious agents. The situation is much more
difficult in the developing world in view of limited viral Metabolic • Mitochondrial disorders, urea cycle
testing facilities. disorders—Inherited disorders, organic acidemias and fatty
acid oxidation disorders
Any child with encephalopathy needs to be evaluated for
presence of an infectious etiology. This can be because of direct Metabolic • Hepatic failure, uremia, hypoglycemia,
disorders—Acquired hyponatremia/hypernatremia
infection by the organism or part of systemic inflammatory
response syndrome. Once these possibilities are ruled out one Parainfectious/ • Acute disseminated encephalomyelitis,
systemic vasculitis SLE, antiphospholipid antibody
needs to consider other etiologies. Absence of fever during
syndrome, hemolytic uremic syndrome
an infection may be due to immunocompromised states
Structural • Acute hydrocephalus, intracranial space
(including acquired and inherited immunodeficiency state,
occupying lesion
drug induced immunosuppression), chronic kidney disease,
chronic liver disease, etc. Trauma • Accidental, nonaccidental
Toxins • Drugs of abuse, antiepileptic drugs,
organophosporous/organochloride
Clinical Pearl compounds
• Absence of fever does not negate the presence of infection, Vascular • Posterior circulation stroke, cerebral
10% of Herpes simplex encephalitis children may not have sinovenous thrombosis, intracranial
fever as presenting manifestation. bleed, hypertensive encephalopathy
NMDA, N-methyl-D-aspartate; SLE, systemic lupus erythematosus.
Approximately 30–70% of acute encephalopathies do

not receive etiologic diagnoses. Many of them might have an
autoimmune basis some easily diagnosable and some still Clinical Pearl
challenging. Most of them present acutely in pediatric practice.
• History from parents or adult person present at onset of altered
They can be broadly classified as infective pathology; the
sensorium is very important to generate appropriate differential
noninfective pathology consists of a wide range of etiologies diagnoses (80% of diagnoses are suspected based on history).
(Table 1).
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Chapter 95: Afebrile Encephalopathy: Bedside Approach to Diagnosis and Management
VARIED ETIOLOGIES AND Urea cycle disorder will have variable presentations
THEIR BRIEF PRESENTATION Algorithm 1 including encephalopathy, recurrent vomiting in association
with hyperammonemia. Newborn presentation with progres
sive encephalopathy and abnormalities on magnetic resonance
Metabolic
imaging (MRI) brain with restricted diffusion on brainstem is
Inborn errors of metabolism: in infants and young children suggestive of maple syrup urine disease.
presenting with encephalopathy one of the important etiology
would be inborn errors of metabolism. Most present before age
of two years, except few organic acidurias which may present
Clinical Pearl
later on. • Ammonia levels need to be processed immediately and to
Small molecule diseases (amino acid disorders, fatty be transported on ice to the laboratory for accurate results.
acid oxidation disorders, organic acidurias, and urea cycle Borderline elevation of ammonia is usually due to delayed
disorders) present with encephalopathy, symmetric motor processing of samples
signs. They have presence of increased anion gap metabolic
acidosis along with variable hypoglycemia, hyperammonemia,
Stepwise decompensation in infancy with presence of
lactic acidemia, and ketones.
breathing difficulty and lactic acidosis needs consideration
Presence of metabolic acidosis with variable lactic
acidosis and hypoglycemia and ketosis would point toward of mitochondrial disorder. Neuroimaging demonstrating
organic acidurias. Evidence of bone marrow suppression with bilateral basal ganglia hypodensities on computed
bicytopenia also is manifestation of org anic aciduria. tomography of brain along with involvement of peri
Child presenting with nonketotic hypoglycemia especially aqueductal gray matter suggests Leigh’s disease. Magnetic
in early morning hours with or without hepatomegaly and resonance imaging with MRI spectroscopy with elevated
anicteric hepatitis would strongly point toward the presence lactate and elevated cerebrospinal fluid (CSF) lactate further
of underlying fatty acid oxidation disorder. Medium chain Acyl confirm the diagnoses.
Co A dehydrogenase deficiency is the most common followed
by carnitine palmitoyl 1A deficiency. Clinical Pearl
• It is imperative that in an infant or young child less than 3 years
Clinical Pearl with unexplained encephalopathy with or without acidosis
• In fatty acid oxidation disorder hepatomegaly and elevation and hypoglycemia, samples (tandem mass spectroscopy,
of liver enzymes may evolve over initial days and may not be lactate and ammonia, urine for organic acids,) should be taken
seen at presentation. before starting vitamin cocktails
Algorithm 1
Diagnosis and investigations of acute encephalopathy based on presentation
*Children less then two years are at risk of presenting with encephalopathy due to inborn errors of metabolism.
ЄAutoimmune antibody associated encephalitis can be suspected within first one or two weeks of onset.
¥Mitochondrial disorders can have varied presentation and needs to be differential diagnoses in unexplained encephalopathies.
MRI, magnetic resonance imaging; MRA, magnetic resonance angiogram; CT, computed tomography; HI, head injury; CNS, central nervous system; HIE, hypoxic 459
ischemic encephalopathy; IEM, inborn errors of metabolism; NCSE, nonconvulsive status epilepticus; SIRS, systemic inflammatory response syndrome; HLH,
hemophagocytic lymphohistiocytosis EEG, electroencephalogram; TMS, tandem mass spectrometry; CSF, cerebrospinal fluid; PCR, polymerase chain reaction;
ICSOL, intracranial space occupying lesion; ESR, erythrocyte sedimentation rate; ANA, antinuclear antibody.
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An EDTA sample should be stored in case of sudden differential diagnoses. Magnetic resonance imaging brain
death and further pregnancy counseling can be possible after performed early on may be normal; most will demonstrate
performing appropriate genetic analysis. changes by 5–7 days in subcortical white matter along with
deep gray nuclei especially in poststreptococcal ADEM.
Acquired: Hepatic/Uremic/Others N-methyl-D-aspartate receptor (NMDAR) encephalitis can
also have similar presentation with minimal MRI changes.
Hepatic Encephalopathy
Spectrum of neuropsychiatric abnormalities in patients with Vasculitis/Hypertensive Encephalopathy/
liver dysfunction are characterized by personality changes, Vascular Etiologies
intellectual impairment, and depressed level of consciousness. Adolescent age group especially in girls presenting with multi
The diagnosis is usually given away by presence of icterus, system involvement and focal neurological presentation or
significant elevation of liver enzymes, and in few children with diffuse encephalopathy consider systemic vasculitis disorder.
history of pre-existing liver disease. Neuroimaging might provide the directions for vasculitic
Uremic encephalopathy may be more challenging to pathology or elevated ESR might suggest the underlying
diagnose. Hypertension would be an independent risk factor etiologic process.
for encephalopathy. Short stature, anemia, hypertension,
and features of rickets would be the systemic clues to chronic Autoimmune Pathologies
kidney disorders. Children present with neurological syndromes associated with
serum and/or CSF antibodies directed against ion channels,
Clinical Pearl receptors and associated proteins are diagnosed as antibody-
mediated encephalopathies. The clinical features of these
• Early central visual impairment before losing consciousness disorders overlap and, in many cases, the etiology may not be
would be a pointer toward hypertensive emergency causing apparent at presentation. Investigation and treatment needs to
posterior reversible leukoencephalopathy syndrome be ongoing in this clinical situation. Many patients present with
fever, seizures, amnesia, confusion, and psychiatric features,
and some develop encephalopathy with a movement disorder.
Electrolyte Disturbances/
Hyperglycemia/Hypoglycemia Clinical Pearl
Children with acute gastroenteritis and endocrine disorders
• Presence of characteristic movement disorder with perioral
can present with altered sensorium. Severe gastroenteritis
dyskinesia and dystonia is the usual key to diagnoses of
leads to sinovenous thrombosis with raised intracranial
N-methyl-D-aspartate encephalitis with no diagnostic cerebro
pressure. Slow correction of hyponatremia is essential. spinal fluid or magnetic resonance imaging brain findings.
Hyperglycemia as first presentation or poor control of
insulin dependent diabetes mellitus is associated with
encephalopathic presentation. In some the encephalopathy can be part of a para
Insulin dependent diabetes mellitus is associated with neoplastic syndrome. Majority of children do not have
detectable tumors except in adolescent girls who harbor
encephalopathic presentation.
ovarian teratoma.
Autoimmune encephalopathies are increasingly being
Clinical Pearl diagnosed in children with antibodies to NMDAR, and rarely
• Normal magnetic resonance imaging brain with symmetrical with antibodies to voltage-gated potassium channel (VGKC)-
encephalopathy (encephalopathy with preserved eye complex proteins or other central nervous system antigens
movement without lateralizing neurological findings) points such as glutamic acid decarboxylase. The clinical phenotypes
toward metabolic encephalopathy, systemic inflammatory associated with these conditions are increasingly recognized
response syndrome and toxins. Magnetic resonance imaging but some patients are negative for the available antibody tests.
can be normal in early phases of acute disseminated
encephalomyelitis. Acquired Brain Injury
Accidental/nonaccidental injury
Inflammatory/Vasculitis In onset of altered sensorium is immediate in significant head
injury except in cases of epidural hematoma where symptoms
Parainfectious/Postinfectious Demyelination can evolve over 24 hours. An inconsistent history from different
In children presenting with biphasic illness, neurological family members and varied stages of injuries on neuroimaging
worsening with polyfocal symptoms and encephalopathy, or unexplained fractures would suggest nonaccidental injury
acute disseminated encephalomyelitis (ADEM) is a relevant (Tables 2 to 5).
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Chapter 95: Afebrile Encephalopathy: Bedside Approach to Diagnosis and Management
Table 2: Course of illness as clue to diagnoses Continued

Abrupt onset • Intracranial bleed Neuroimaging • CT brain—done in acute situation—is good for
(onset within minutes • Posterior circulation stroke acute bleeding, head injuries, rule out a space
to hours) • Trauma—accidental/nonaccidental occupying lesion
• Poisoning • MRI brain—undiagnosed encephalopathy,
Acute onset • Central nervous system infection stroke, demyelination, etc.
(hours to less than • Demyelinating disorder • Caveat—normal MRI brain is seen in significant
week) • Hypoxia ischemic event proportion of NMDAR encephalitis/ADEM in
• Hydrocephalus first week of illness
• Hypertensive emergencies • MR angiogram and venogram in appropriate
• Inborn errors of metabolism clinical setting
• Nonconvulsive status epilepticus EEG • Continuous EEG monitoring will help to
• Septicemia with systemic inflammatory diagnose nonconvulsive status epilepticus
response syndrome Cerebrospinal • Opening pressure, cell count, protein, paired
• Hemophagocytic lymphohistiocytosis fluid sugar and lactate, cultures
Subacute progression • Intracranial space occupying lesion Always • PCR for Herpes simplex infection and other
(More than 1 week of • Hydrocephalus preserve extra viruses as appropriate
symptoms) • Tubercular meningitis (20% can present samples for • Anti-N-methyl-D-aspartate receptor antibodies
acutely in children) later testing and antivoltage gated potassium channel
• Central nervous system vasculitis— antibodies
primary/secondary (variable course) Ophthalmo • Retinal haemorrhages—consider
logical nonaccidental injury
opinion • Papilledema—Sinovenous thrombosis
Table 3: Clinical clues to diagnoses • Hypertensive changes
• Whitening of vessels, papilledema and cotton
General • Short stature—Chronic renal failure wool spots in malaria
physical • Icterus—Hepatic encephalopathy, rarely in FAOD
Urine • Cultures, toxicology screen
examination • Hypertension—Hypertensive encephalopathy,
raised ICP CBC, complete blood count; CRP, C-reactive protein; PS, peripheral smear;
ESR, erythrocyte sedimentation rate; MP, malarial parasite; ANA, antinuclear
• Skin-rash—Vasculitis, HSP
antibodies; APLA, antiphospholipid antibodies; ANCA, anti-neutrophil
• Joint swelling—HSP, Rachitic features in chronic cytoplasmic antibody; IEM, inborn error of metabolism; CT, computed
renal failure tomography; MRI, magnetic resonance imaging; NMDAR, N-methyl-D-aspartate
Abdomen • Hepatosplenomegaly—Hemophagocytic receptor; ADEM, acute disseminated encephalomyelitis.
lymphohistiocytosis
Large head • Hydrocephalus, glutaric aciduria type I Table 5: Bilateral basal ganglia lesions in context of acute
(6 to 18 months) encephalopathy
Neurocu- • Multiple cafe au lait spots—Moyamoya Metabolic Toxins Vascular
taneous syndrome with stroke
markers • Hypopigmented macules—TSC complex with • Organic acidurias • Carbon • Deep venous
nonconvulsive status epilepticus • Mitochondrial disorders monoxide thrombosis
• Facial angioma—Stroke like episodes, status • Thiamine deficiency • Methanol • Hypertensive
epilepticus in Sturge-Weber syndrome • Hypoxic insult • Cyanide encephalopathy
FAOD, fatty acid oxidation disorder; ICP, intracranial pressure; HSP, Henoch- • Hypoglycemia • Basal meningitis
Schonlein purpura; TSC, tuberous sclerosis alliance.
• Hemolytic uremic syndrome
• Osmotic myelinolysis
Table 4: Investigations
Blood • Markers of infection—CBC, CRP, procalcitonin,
blood and urine cultures
• PS for MP, Mycoplasma antibodies, Weil Felix test
Clinical Pearls
• ESR—elevation more than 100 mm/1st hour • An inconsistent history from different family members and
usually indicates either active systemic varied stage of injuries or unexplained fractures—suspect
vasculitis/chronic infection or a malignancy nonaccidental injury
• ANA, APLA, ANCA antibody studies
• Documentation of anthropometry, blood pressure, heart rate,
• Thyroid function, antithyroid antibodies
breathing pattern are important clues to etiologic diagnoses
• IEM workup—blood lactate, ammonia, tandem
mass spectroscopy • Detailed eye examination-pupils—eye movements, and
fundus has great localizing and diagnostic value.
Continued
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MANAGEMENT Key points

Management of acute encephalopathy involves stabili
))
Afebrile encephalopathy is a common clinical problem of
zation of airway, breathing, and circulation. Start treatment
varied etiologies and presentations
for infection with antibiotics and antiviral medications
))
Accurate history and comprehensive examination will provide
as appropriate. Symptomatic treatment of seizures and
clue to the etiologic diagnoses in many children
management of raised intracranial pressure is essential.
Ongoing monitoring on vital parameters and end-
))
Investigations are to be performed as per individual patient
including appropriate neuroimaging
organ functions are essential part of treating a child with
encephalopathy. Once accurate etiology is established the ))
Early identification of etiologic diagnoses helps in appropriate
management and improved outcome.
management will have to focus and unwarranted medications
can be withdrawn.
N-methyl-D-aspartate receptor encephalitis responds
to immunomodulation and even the severe motor disability
SUGGESTED READINGS
improves significantly. First-line immunotherapy includes 1. Armangue T, Petit-Pedrol M, Dalmau J. Autoimmune encephalitis in children.
steroids and intravenous immunoglobulin. If there is no J Child Neurol. 2012;27:1460-9.
response, rituximab once a week for 4 weeks improves the 2. Hegde AN, Mohan S, Lath N, Lim CC. Differential diagnosis for bilateral
abnormalities of the basal ganglia and thalamus. Radiographics. 2011;31:
condition. It is imperative to monitor CD20 levels during
5-30.
therapy. Acute disseminated encephalopathy usually responds 3. Maguire S, Pickerd N, Farewell D, Mann M, Tempest V, Kemp AM. Which clinical
to methylprednisolone followed by oral steroids in most. features distinguish inflicted from non-inflicted brain injury? A systematic review.
Outcomes are dependent on etiology and severity of Arch Dis Child. 2009;94:860-7.
pathology. Ongoing counseling of family and involving them 4. Plum and Posner’s Diagnosis of Stupor and Coma, 4th edition. Oxford University
in important decision-making will help to reduce the stress on Press, 2007.
the treating team and the family. 5. Wong CP, Forsyth RJ, Kelly TP, Eyre JA. Incidence, aetiology, and outcome of non-
traumatic coma: a population based study. Arch Dis Child. 2001;84:193-9.
462
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Section 12: Nephrology
Chapter 96
Approach to Rickets in Children
S Thangavelu, M Vijayakumar
Introduction Thorax
Rickets is caused by defective mineralization of growing bones Palpable and visible knobby enlargement of costochondral
resulting in bony deformities. Vitamin D deficiency is the junctions are called rachitic rosary (Fig. 1A). Harrison’s sulcus
most common cause of rickets. Rickets, like illness can occur (Fig. 1B) is the horizontal depression along the lower part of
in wide variety of other disorders like renal tubular disorders, chest corresponding to the costal attachment of diaphragm
chronic liver disease, and some metabolic disorders. Clinical due to traction on the rib cage. This may also be associated with
appearance is similar, but after biochemical evaluation, one pectus carinatum or violin-shaped chest. In severe forms and
can differentiate one from the other. untreated cases, spinal and pelvic deformities can occur.
Nutritional rickets being common in the past, the
traditional practice consisted and still consists of treating every Extremities
child having rickets with vitamin D, particularly stoss therapy Palpable and visible knobby enlargement of long bones around
using high dose of intramuscular D3. Then child is reevaluated wrists and ankles (double malleoli) are present. Weight bearing
clinically and radiologically after 6 weeks and 12 weeks. In a can lead to bow legs, knock knees, and anterior curving of
fair number of cases, the decision of non-nutritional rickets is legs, coxa vera, and greenstick fractures. Deformities of spine,
made only after 12 weeks. Gradually this scenario has changed pelvis, and leg results in short stature called ”rachitic dwarfism”
to complete evaluation to a specific diagnosis so as to decide on (Fig. 1C). Lower extremities are almost always more extensively
need for vitamin D. This is possible because of the availability involved than upper extremities in familial hypophosphatemic
of sophisticated investigations and subspecialty consults rickets (FHR), whereas upper limb involvement is more
like pediatric nephrology, gastroenterology, and metabolic pronounced in hypocalcemic rickets.
specialists. Here, the process is completed in a short time of 5–7
days. But in peripheral areas and in the absence of adequate General
laboratory and subspecialty facilities, the traditional method is
Pot belly abdomen can be pressent (Fig. 1D). Motor symptoms
still an ideal one. Specific management differs according to the
are more common with hypocalcemic rickets whereas
underlying illness. Most of them present with symptomatology
motor symptoms are usualy absent in predominantly hypo
of delayed walking or bony deformities. Head to foot clinical
phosphatemic rickets. One can approach rickets in children
examination may reveal following findings.
through the following algorithm (Algorithm 1).
clinical examination
METAPHYSEAL DYSPLASIA
Head Though there are many clinical findings, bony changes
Features include craniotabes, delayed closure of anterior such as enlarged bony ends are the striking clinical
fontanel, and frontal and parietal bossing leading to box-like features and they form the center point of clinical differen
appearance of head known as caput quadratum. Delayed tiation. Few conditions closely mimic rickets clinically as
eruption of primary teeth, enamel defects, and caries teeth are well as radiologically. They are (i) metaphyseal dysplasia,
the dental abnormalities. (ii) hypophosphatasia, and (iii) mucopolysaccharidosis.
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C D
Fig 1: Clinical features of rickets. A, Rachitic rosary; B, Harrison’s sulcus; C, Rachitic dwarfism; D, Pot belly
Algorithm 1 Do preliminary investigations like serum calcium, phos

Algorithmic approach to rickets in children phorous, serum alkaline phosphatase (SAP), and have a
close look at the X-rays. Though rickets like states such as
hypophosphatasia (caution: not hypophosphatemia) and
metaphyseal dysplasia are far rarer than rickets, it is wise to
confirm the diagnosis of rickets before proceeding further.
This will avoid unnecessary therapy with vitamin D.
Clinical Features and Radiological Signs

Suggestive of Metaphyseal Dysplasia
Clinical and radiological signs are similar to rickets but
with subtle difference. Here, growth plate is not wide with
differential involvement of bones in a joint, e.g., femur
shows radiological changes, but tibia is normal. Biochemical
investigations, such as serum levels of calcium, phosphate and
alkaline phosphatase, are normal.
Clinical Features and Radiological Signs

464
Suggestive of Hypophosphatasia
Clinical signs of rickets are present but X-ray of long bones
GI, gastrointestinal; VDDR, vitamin D dependent rickets. show tongue-like radiolucency projecting from growth plate
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Chapter 96: Approach to Rickets in Children
into metaphysis whereas in rickets growth plate is uniformly appears between the age group of 6 months to 2 years. Any
wide. Biochemical changes will be different from rickets as child presenting beyond this age group, involvement of
SAP levels are low and serum calcium and phosphate levels more than one family member, and associated failure to
are normal. thrive or failure of adequate vitamin D therapy to correct
rickets indicates the diagnosis of non-nutritional rickets.
Clinical Pearl Differentiation is important because non-nutritional rickets
• Metaphyseal dysplasia and hypophosphatasia can needs extensive biochemical evaluation and specialist’s
be confused with rickets in children. In metaphyseal opinion. Diagnosis and management of nutritional rickets
dysplasia, serum levels of calcium, phosphate, and alkaline is straightforward, but in non-nutritional rickets, it is
phosphatase are normal and there will be differential
complicated and needs prolonged therapy. In nutritional
involvement of bones in a joint. In hypophosphatasia,
biochemical changes will be different from rickets as serum rickets, 25-hydroxy vitamin D level will be low and other
alkaline phosphate levels are low and serum calcium and associated features include low serum calcium, phosphate,
phosphate levels are normal. and high alkaline phosphatase with elevated serum levels
of parathyroid hormone (PTH). Radiological changes are
observed in ends of long bones such as knees or wrist.
Classical radiological changes of rickets are absence of zone
NUTRITIONAL RICKETS
of provisional cartilaginous calcifications and widening,
Nutritional rickets is reappearing in large numbers all over fraying and cupping (concavity) of the distal ends of shaft.
the world. Inadequate exposure to sunlight, lack of dietary But some studies indicate the lack of correlation between
or vitamin supplements, and deficiency of vitamin D in low serum levels of vitamin D and presence of radiological
breastfeeding mothers are important reasons. This being changes. Despite very low levels, no radiological changes are
a disease of growing children, nutritional rickets usually observed in some (Figs 2A to C).
A B
Figs 2: A, Active rickets (before vitamin D); B, Healing rickets (after
C vitamin D); C, Nonhealing rickets 465
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Clinical Pearl RENAL CAUSES
• Vitamin D deficiency rickets previously called as nutritional Clinical and Laboratory Features
rickets will show healing after adequate vitamin D therapy. Indicating Renal Etiology Leading to Rickets
Rickets without obvious clues definitely needs serum vitamin D Clinical features: recurrent vomiting, failure to thrive, lethargy,
level assessment at whatever age they are presenting to us. acidotic breathing, and presence of underlying renal disorders
One should note that even before healing rickets is seen in the are indicative of renal etiology.
X-rays, the elevation of serum phosphate level from its original When renal cause is suspected, investigations play a major
low level will give us clue that we are dealing with vitamin D role in confirming or excluding them. Four renal diseases
deficiency rickets only. constitute the following causes: (i) RTA, (ii) hypophosphatemic
rickets, (iii) Fanconi syndrome, and (iv) renal failure.
Among these four causes, chronic renal failure leading to
NON-NUTRITIONAL RICKETS renal osteodystrophy will have the following features.
Among the non-nutritional causes, three common causes are Clinical and laboratory features: vomiting, lethargy, growth
seen. Most commonly renal, next gastrointestinal, and third retardation, hypertension, anemia, with or without edema,
are miscellaneous causes. Sometimes obvious clues may be features of obstructive uropathy, raised blood urea, and
identified which will lead to the diagnosis of the underlying serum creatinine. Serum potassium may be normal or high.
cause. Abnormalities in abdominal ultrasonography (USG) showing
renal anomalies, obstruction, and renomegaly or contracted
Etiology with Clues kidney can be seen. Dimercaptosuccinic acid scan showing
scars and micturiting cystourethrogram showing vesicoureteric
History of prematurity and lack of vitamin D supplementation,
reflux should be noted in specific situations.
neonatal cholestasis, chronic renal failure, or child taking
If there is no renal failure, one of the other three renal
anticonvulsant therapy are obvious clues. One should look
problems are considered: RTA, Fanconi syndrome, or FHR.
for leading points in the history and examination in a child
with rickets like positive family history which is common in History, examination, and laboratory features suggestive of
metabolic diseases and in renal tubular acidosis (RTA). RTA: recurrent vomiting and diarrhea with acidotic breathing
• Jaundice may be a clue toward hepatobiliary disease, associated with positive family history is common. Metabolic
metabolic disorders, and tyrosinemia acidosis with low serum bicarbonate, low serum pH, normal
• Cataract and rickets are seen in galactosemia, Wilson’s serum anion gap, hypokalemia, and raised serum chloride are
disease, and Lowe syndrome usually seen. Normal blood urea and serum creatinine with no
• Mental retardation and seizures are seen in Lowe proteinuria or glycosuria is noted.
syndrome, galactosemia, and in primary central nervous
system problem with drug-induced rickets. History, examination, and laboratory features suggestive
At this stage, one should differentiate between two causes: of Fanconi syndrome: clinically severe form of rickets with
(i) gastrointestinal including hepatobiliary and (ii) renal stunting and deformity and features mentioned in RTA are
causes. seen. Aminoaciduria, glycosuria, and phosphaturia are
present. Usually normal blood urea and serum creatinine or
minimally increased blood urea and serum creatinine can be
GastrointestinaL Causes seen. Features of underlying causes such as cystinosis and
Features Indicating Gastrointestinal Wilson’s disease may be present.
Etiology (Particularly Malabsorption History, examination, and laboratory features suggestive of
Disorders Leading to Rickets) familial hypophosphatemic rickets: prominent lower limb
deformity with stunted growth and often with family history is
History: recurrent diarrhoea, oily stools, abdominal pain, and noted. Frequent dental abscess and early decay are common.
distention Low serum phosphate and low tubular reabsorption of
Examination: anemia, hypoproteinemia, multiple vitamin and phosphate are documented.
mineral deficiencies, and failure to thrive. If clinical, laboratory features are not suggestive of any one
Laboratory features: vitamin D deficiency, low phosphate, of the above-mentioned conditions leading to rickets, then one
calcium may be normal or low with raised PTH. of the following diagnoses discussed in the next section is likely.
Features Indicating Hepatobiliary Clinical Pearl

Disorder Leading to Rickets • Renal osteodystrophy (ROD) is different from other forms
Clinical features: jaundice, pale stools, oily stools, high colored of renal rickets though included in them, as it designates
urine and hepatomegaly, alteration in skeletal growth and remodeling that occurs in
466 children with chronic renal disease, because of alteration in
Laboratory features: raised serum total and direct bilirubin,
bone and mineral metabolism. Even treatment for ROD is not
raised hepatic enzymes, low serum albumin, and prolonged
straight forward therapy for vitamin D defects alone.
prothrombin time.
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Chapter 96: Approach to Rickets in Children
Vitamin D-dependent rickets Type 1 of metabolism” are done as per the clinical diagnosis suspected
at this level. Parathyroid hormone level is elevated in rickets
History, examination, and laboratory features suggestive of and is useful in determining certain forms of rickets.
VDDR type 1: often presents in early infancy with afebrile
seizures and hypocalcemic tetany with or without radiological Tertiary Level Investigations
changes. The differentiating feature from vitamin D deficiency
Estimation of vitamin D metabolites (to differentiate VDDR
is improvement with vitamin D therapy and recurrence
type 1 from type 2), in vitro studies to assess receptor-vitamin D
of symptoms after stopping the therapy. In this situation,
interaction (VDDR-type 2) and bone mineral content by bone
estimating vitamin D metabolites will be very useful. Here,
densitometry are investigations done at this stage.
serum 25-hydroxy vitamin D [25(OH) D] levels will be normal,
unlike in vitamin D deficiency. But 1,25-dihydroxy vitamin D
level is low despite normal or high 25(OH) D indicating that Clinical Pearl
there is defective conversion. In vitamin D-dependent rickets • In modern era, vitamin D level estimation in the serum is
type 1, the pathology is defect in 1 a-hydroxylation. readily available. 25-hydroxy vitamin D level should be tested
to confirm vitamin D deficiency rickets and to rule out vitamin
D deficiency itself. Even in renal osteodystrophy, estimation
Vitamin D-dependent rickets Type 2 of 25-hydroxy vitamin D levels should not be ignored as
History, examination, and laboratory features suggestive of treatment involves therapy with 25 hydroxy vitamin D as well.
VDDR type 2: these children may present with or without 1,25-dihydroxy vitamin D levels are essential to differentiate
alopecia, in addition to features of florid rickets. Very often vitamin D-dependent rickets type 1 from type 2.
they would have received one or multiple doses of vitamin
D3 as injection or in oral form, without any clinical or
radiological response. In this receptor defect, 1, 25-dihydroxy MANAGEMENT
vitamin D level is high in contrast to vitamin D-dependent Management of rickets becomes straight forward once the
rickets type 1 and this investigation is absolutely essential for cause is found out. Table 1 outlines the management strategy
differentiation. for treatment of various types of rickets in children. While
a large dose of vitamin D has been classically used to treat
Oncogenic Rickets rickets/vitamin D deficiency, whether slow correction over
6–10 weeks is equally or more beneficial with lesser adverse
History, examination, and laboratory features suggestive of effects is a matter of research and debate at present. The
oncogenous rickets: it is a rare disease, where phosphate present recommendations are given in table 1.
loss in the urine associated with mesenchymal tumors like
hemangioendothelioma or neurofibroma. They are commonly
seen in hands, feet, and abdominal sheath. Sometimes they
Table 1: Guidelines in the treatment of rickets
may be small and undetectable and rickets develops years
before tumor is apparent. Phosphate loss is due to secretion Types of Treatment
of fibroblast growth factor. Phosphate replacement along with rickets
1,25-dihydroxy vitamin D and tumor removal are the steps in Vitamin D • Traditional therapy: vitamin D 10,000 IU/kg IM is
the management. deficiency given and then X-ray repeated after 4–6 weeks. If
rickets radiological healing is seen, then switched to daily
maintenance. If no improvement second stat dose
INVESTIGATIONS DONE IN may be needed
ANY CHILD WITH RICKETS • Recent guidelines for therapy: *Oral preparations
preferred over IM. Though daily dose is preferred,
Investigations are done stepwise or at one stretch if clinical for practical reasons, stoss therapy can be used
{{< 3 months – large oral dose not recommended
features warrant.
{{3–12 months – one single oral dose 50,000 units
{{12 months to 12 years – 150,000 IU (50,000

Basic Investigations to Confirm Rickets
weekly three doses)
Serum calcium, phosphorous, alkaline phosphatase, X-rays {{12 years – 3,00,000 IU (50,000 weekly six doses)
of ends of long bones such as knee or wrist are the basic VDDR type 1 • 1,25-dihydroxy vitamin D3 (0.25–1.0 mg/day orally)
investigations in any child with rickets. VDDR type 2 • 1,25-dihydroxy vitamin D3 or 1 a-hydroxy vitamin
D3 (6 mg/day or a total of 30–60 mg orally per day)
Second Level Investigations with supplemental calcium
Blood urea, creatinine, electrolytes, arterial blood gas analysis, Renal tubular • Alkali therapy: 3–5 mEq/kg/day in distal RTA and
and tubular reabsorption of phosphate are second level acidosis (RTA) 5–15 mEq/kg/day in proximal RTA
investigations. Urine analysis for glucose, protein, specific • Supplements of potassium as per serum
potassium levels
gravity, and anion gap are needed. Liver function test, USG
abdomen, investigation for malabsorption, and ”inborn errors Continued 467
ch-96.indd 467 11/24/2016 2:18:40 PM

Continued
))
In rickets, mimicking conditions like metaphyseal dysplasia,
Types of Treatment
biochemical investigations like serum calcium, phosphate,
rickets
and alkaline phosphatase are normal, though radiological
Fanconi • Phosphate replacement (40 mg of elemental changes may be similar
syndrome phosphorous/kg per day to start with, later
increased to 250–500 mg and to maximum of ))
Estimating serum electrolytes, urea, creatinine, and
3,500 mg/day) either as sodium or potassium arterial blood gas analysis will identify renal disorders like
phosphate or as Joulie’s solution renal osteodystrophy, renal tubular acidosis, and hypo
• 1-a-hydroxy vitamin D3 or 1,25-dihydroxy phosphatemic rickets. Because in addition to radiological
vitamin D3 changes, each disorder will have its own biochemical features.
• Alkali therapy as for proximal RTA In addition to this, abdominal ultrasonography and other
Renal osteo- • 1-a-hydroxy vitamin D3 or 1,25-dihydroxy renal imaging modalities like dimercaptosuccinin acid and
dystrophy vitamin D3 voiding cystourethrography are necessary to confirm them
• Phosphate binders ))
In disorders of vitamin D metabolism, estimating the serum
• Alkali therapy 25-hydroxy vitamin D and 1,25-dihydroxy vitamin levels
• Renal replacement therapy
are absolutely necessary. A low 25-hydroxy vitamin D level
• Cholecalciferol as per 25-hydroxy D3 levels
confirms vitamin D deficiency, but a low 1,25-dihydroxy
Familial hypo • Phosphate replacement every 4–6 hour vitamin D in the background of a raised 25-hydroxy vitamin
phosphatemic • 1-a-hydroxyvitamin D3 or 1,25-dihydroxy-
D level confirms the diagnosis of vitamin D-dependent type 1
rickets vitamin D3
rickets. But in a child with clinical features of rickets and
Rickets of • Calcium 100 mg/kg/day alopecia, raised 1,25-dihydroxy vitamin D level is diagnostic
prematurity • Phosphate 50 mg/kg/day for 3 month
of vitamin D-dependent type 2 or end organ receptor defect
• Vitamin D in normal requirements
Note: Reassess the response to treatment to decide need for further therapy.
))
Low alkaline phosphatase level is seen only in rare condition
Maintenance calcium 50 mg/kg/day in 3 divided doses. like hypophosphatasia.
IM, intramuscularly; VDDR, vitamin D-dependent rickets.
*Modified from Global Consensus Recommendations on Prevention and
Management of Nutritional Rickets. J Clin Endocrinol Metab. 2016;101(2):394-415.
SUGGESTED READINGs
1. Graham R William. Bone structure and metabolism. Medicine Group (Journals)
Ltd. Medicine. 1997;60-98.
Key points 2. Pitt MJ. Rickets and osteomalacia. In: Resnick D (Ed). Diagnosis of Bone and Joint
Disorders, 4th edition. Philadelphia: PA: Saunders; 2002. pp. 1901-935.
))
Vitamin D deficiency rickets is clinically suspected first and 3. Specker BL, Tsang RC. Bone mineralization. Ann Nestle. 1987;45:18-25
then confirmed by laboratory investigations such as X-ray 4. Mehls O, Klans G. Childhood renal osteodystrophy. Ann Nestle. 1989;47:144-57.
of long bones, serum calcium, phosphate, and alkaline 5. Thangavelu S, Vijayakumar M. Approach to Rickets in children. In: Vijayakumar M,
phosphatase Nammalwar BR (Eds). Principle and Practice of Pediatric Nephrology, 2nd edition.
New Delhi: Jaypee Brothers Medical Publishers (P) Ltd; 2013. pp. 795-803.
468
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Chapter 97
Disorders of
Sodium and Potassium
Sushmita Banerjee
INTRODUCTION Box 2: Etiology of potassium imbalances

Sodium (Na+) is the major extracellular cation in the body, Causes of hyperkalemia
whereas potassium (K+) is the main intracellular cation. Their • Increased total body potassium
location across the cell membrane is maintained by the Na+/ {{ Reduced excretion: renal failure, mineralcorticoid deficiency,
K+-adenosine triphosphatase pump, which by an active type 4 renal tubular acidosis, and K+ sparing diuretics
process extrudes Na+ from the cell and pushes K+ into the cell. {{ Increased intake: iatrogenic potassium administration
Sodium balance occurs in close conjunction with water • Increased cell breakdown: hemolysis and tumor lysis (also
balance, with the same homeostatic pathways causing parallel increased total body potassium)
changes in Na+ and water. The mechanisms of Na+ and K+ • Increased catabolism: sepsis and burns
balance are also closely interlinked and both are dependent on • Redistribution from ICF to ECF: acidosis, insulin deficiency
renal function. Boxes 1 and 2 list the common causes of Na+ Causes of hypokalemia
and K+ balance in children. • Reduced total body potassium:
{{ Inadequate intake, iatrogenic
Box 1: Etiology of sodium imbalances {{ Renal loss: renal artery stenosis, tubular diseases,
Causes of hyponatremia mineralcorticoid excess, diuretics, and other drugs

{{ GIT loss: diarrhea, vomiting, fistulae, stomas
• Associated with reduced or normal total body water:
{{ Excess Na+ loss compared to water loss, from: • Redistribution from ECF to ICF:
{{ Alkalosis
–– GIT (diarrhea, vomiting, fistulae, ileostomies)
–– Skin (burns, cystic fibrosis) {{ Beta-2 agonists
–– Kidney (tubular diseases: Bartters syndrome, Fanconi’s {{ Insulin
syndrome, hypoaldosteronism, cerebral salt wasting) {{ Periodic paralysis

{{ Administration of hyponatremic fluids in sick patients or
hyponatremic feeds in infants ICF, intracellular fluid; ECF, extracellular fluid.

• Associated with increased total body water:
{{ Increased levels of antidiuretic hormone (SIADH, iatrogenic)
{{ Fluid overload (oliguric renal failure, excessive fluid

CLINICAL FEATURES
administration, nephrotic syndrome, hepatic cirrhosis
congenital heart failure) Electrolyte abnormalities are commonly seen in children
Causes of hypernatremia with vomiting, diarrhea, and dehydration. They also occur
• Associated with normal or increased total body water: when patients are otherwise ill and dependent on extraneous
{{ Administration of hypernatremic fluids to sick patients or
fluid therapy to maintain balances. This is particularly
hypernatremic feeds to infants seen in pediatric intensive care unit patients who may also
{{ Hyperaldosteronism
have disorders of different organs and altered homeostatic
• Associated with decreased total body water:
{{ Inadequate fluid administration to sick patients
mechanisms. More rarely, electrolyte abnormalities occur due
{{ Fluid losses (excess water loss compared to Na+ loss): GI/renal
to chronic diseases which may be genetically acquired.
(diabetes insipidus, osmotic diuresis in diabetes mellitus)/skin The symptoms of Na+ imbalance are often nonspecific
diseases and can include lethargy, irritability, drowsiness, confusion,
GIT, gastrointestinal tract; SIADH, syndrome of inappropriate antidiuretic convulsions, and coma. There are often associated
hormone secretion; GI, gastrointestinal; Na+, sodium. abnormalities in water balance, with history of vomiting
ch-97.indd 469 11/21/2016 12:05:06 PM

or diarrhea and clinical features of dehydration, hypo- or extracellular fluid (ECF) volume contraction. In acute
hypervolemia. tubular necrosis, there is tubular damage with lack of
Abnormalities in K+ balance may present as an emergency tubular Na+ reabsorbtion causing high urinary sodium
and significant hyperkalemia can cause ventricular excretion (>20 mg/dL in a spot sample or FeNa >2.5%)
arrhythmias and death. Acute severe hypokalemia can {{ In the investigation of hyponatremia, low urinary
cause acute profound weakness, cardiac arrhythmias, ileus, sodium (<5–10 mg/dL in a spot sample or FeNa <1%)
myopathy, and respiratory failure. Characteristic electro indicates extrarenal sodium losses, whereas high
cardiogram changes are used in monitoring of severity and urinary sodium (>20 mg/dL in a spot sample or FeNa
treatment. Hypokalemia is associated with appearance of U >2.5%) indicates renal sodium loss or syndrome of
wave, flattening of T wave, and ST depression. In hyperkalemia, inappropriate antidiuretic hormone.
there is appearance of tall T waves, widening of QRS complex, • Plasma (P) and urine (U) osmolality: the normal threshold
and disappearance of P waves. for AVP release ranges from 275 to 290 mOsm/kg H2O.
Chronic disorders, most commonly the renal tubular Patients who are in a antidiuretic mode due to volume
diseases, present with chronic weakness, recurrent dehydration depletion or increased plasma osmolality, will normally
and fever, failure to thrive, short stature, rickets, and polyuria. concentrate their urine and will have U:P osmolality ratio
Hypertension may be associated with conditions like Liddle’s greater than 1. Conversely, in the diuretic mode, due to
syndrome and hyperaldosteronism. Ultimately, the diagnosis the presence of hypervolemia or hyponatremia, dilute
of the specific etiology is necessary for directing specific urine will be produced and U:P osmolality will be less than
treatment, and for predicting long-term outcome. 1. If the serum Na is below 130 mmol/L, or if the serum
osmolality is less than 270 mosm/kg H2O the urine should
be maximally dilute. These parameters are useful in the
DIAGNOSTIC TESTS
investigation of:
Patients who are at risk of having electrolyte abnormalities, {{ Syndrome of inappropriate antidiuretic hormone,
as discussed above, should have biochemical tests including where there is inappropriate arginine vasopressin
serum Na+, K+, chloride as well as urea and creatinine levels secretion causing intravascular free water excess
checked at presentation, and regularly thereafter until and dilutional hyponatremia, with inappropriately
resolution. Further investigations are directed according to the concentrated urine. U:P osmolality is greater than 1
specific etiology suspected. The definitions are given in table 1. {{ Diabetes insipidus, where the lack of action of arginine
vasopressin causes dilute urine to persist even in the

Useful Biochemical Indices in Investigation of presence of hypernatremia and dehydration. U:P ratio
Sodium and Potassium Abnormalities is less than 1.
• Urinary potassium levels of >20 mg/dL in the presence of
• Renal sodium excretion can be measured as a spot urinary low serum K+ is an indication of renal K+ loss. Similarly, a
sodium or the fractional excretion of sodium. high urine potassium/creatinine ratio >15 mEq/g indicates
Urinary sodium × serum creatinine renal K+ loss.
FeNa = × 100 • Transtubular potassium gradient (TTKG): in the presence
Urinary creatinine × serum sodium
of normal renal function, this assesses the response of the
The spot urinary sodium concentration may be distal tubule and collecting duct to aldosterone which is
unreliable and variable as it would depend on the influenced by serum potassium.
volume and concentration of the urine sample. The FeNa
measurement is more reliable, fairly easy to perform, and Urinary potassium × Serum osmolarity
TTKG =
requires a random spot urine sample with a simultaneous Serum potassium × Urinary osmolarity
blood sample. These indices are useful in: Normal value being 8–9. A high TTKG in the presence
{{ The investigation of oliguric acute renal failure, to
of hypokalemia and indicates renal potassium loss. A low
detect whether the etiology is prerenal or renal. In TTKG in the presence of hyperkalemia indicates inability
prerenal acute renal failure due to volume depletion of the kidneys to excrete K+, due to mineralcorticoid
and avid salt and water reabsorbtion, urinary Na+ is deficiency or inacivity.
low (<5–10 mg/dL in a spot sample or FeNa <1%). • Renin and aldosterone levels: raised levels of both
A urine Na+ >40 mmol/L is strong evidence against renin and aldosterone levels occur in diseases with
primary renal Na+ and water loss, and contribute to the
Table 1: Standard definitions development of hypokalemia (e.g., Bartter’s syndrome,
RTAs, and pseudohypoaldosteronism). Both these levels
Hyponatremia Na+ <135 mEq/L are suppressed in Liddle’s syndrome. Primary diseases of
Hypernatremia Na+ >145 mEq/L the adrenals associated with reduced or increased levels of
aldosterone will be associated with conversely increased or
Hyperkalemia K+ >5.5 mEq/L
decreased renin, respectively. The titers of these hormones
470 Hypokalemia K+ <3.5 mEq/L are affected by body position and stress, therefore, standard
ch-97.indd 470 11/21/2016 12:05:06 PM

Chapter 97: Disorders of Sodium and Potassium
levels are described according to body position in which Acute hypernatremia causes brain cell shrinkage due to
sample is taken (e.g., on 2-hour supine samples). fluid shifts from ICF to ECF compartments, and in severe cases,
can cause intracerebral hemorrhage.
Note: Spurious hyponatremia (due to high serum lipids or proteins) is Hypernatremia may be associated with severe dehydration
unusual nowadays due to technical improvements in sodium assay. and volume depletion which needs emergency correction.
However, again further Na+ correction should be slow to
prevent rapid fall in ECF osmolarity which may cause reverse
MANAGEMENT fluid shift into brain cells and cerebral edema.
Sodium abnormalities in particular are often associated
Hyponatremic symptoms are more marked, if the disorder with abnormalities in water balance, and the correction of
develops acutely, and occur due to fluid shift from ECF to overt hypo- or hypervolemia takes precedence.
intracellular fluid (ICF) causing brain edema. The rate of
correction should equal assessed rate of development. Acute Clinical Pearls
symptomatic hyponatremia is corrected on an emergency basis
with hypertonic saline. However, generally, abnormal sodium • Sodium abnormalities are often associated with anomalies of
levels are corrected slowly over 48–72 hours, particularly in water balance
conditions of chronic hyponatremia, to prevent rapid reversal • In such cases, restoration of intravascular volume to normal
of fluid shifts from the brain cells to the ECF which can cause takes precedence.
a central nervous system demyelinating disorder known as
central pontine myelinosis (Algorithm 1). Abnormalities in K+ balance may need to be treated on an
emergency basis, since significant hyperkalemia can cause
Algorithm 1 cardiac arrhythmias and death and severe hypokalemia can
cause weakness, muscular paralysis, and respiratory failure.
Management of sodium imbalances.
A, Hyponatremia; B, Hypernatremia Once the acute stage is corrected, determination of etiology
allows planning of a long-term corrective therapy. Details of
A
treatment are given in algorithm 2.
Clinical Pearls
• In hyperkalemia, methods to shift K+ to intracellular spaces are
quick acting and should be instituted first for rapid effect
• Methods to remove K+ from the body take time but are
effective in the long term.
Algorithm 2
Management of potassium imbalances
The total sodium correction is calculated as: Deficit + assessed ongoing losses,
where Deficit (mmol) = (desired Na – present Na) × 0.6 × wt (kg). The change in
serum Na should not exceed 0.5 mmol/L/h.
*To calculate decrease in serum Na with 1 liter of infusate: Change in serum Na

= (infusate Na+ – serum Na+)/total body water (0.6 × wt) + 1.
Note: The change in serum Na+ should not exceed 0.5 mmol/L/h.
Correction should be limited to 8 mmol/L in the first 24 h and 18 mmol/L in
the first 48 h.
471
ch-97.indd 471 11/21/2016 12:05:06 PM

CONCLUSION while chronic imbalances of Na+ require slow correction to

Sodium and potassium abnormalities occur in a large number prevent complications
of acute and chronic conditions. The imbalances may be acute ))
Potassium imbalances can present as major emergencies, and
and severe and need emergency treatment. Occasionally, need rapid recognition and correction
the etiology is chronic and requires prolonged specific and ))
Once the emergency electrolyte imbalances are corrected, a
supportive treatment with long-term monitoring and follow- diagnostic work up and specific management of the cause is
up. A systematic clinical and biochemical work-up will usually instituted.
indicate the cause and guide directed therapy once the acute
situation is controlled.
SUGGESTED READINGs
Key points
1. Alfonzo AV, Isles C, Geddes C, Deighan C. Potassium disorders—clinical
))
Sodium and potassium imbalances are common in acutely ill spectrum and emergency management. Resuscitation. 2006;70(1):10-25.
children, and in some renal and endocrine diseases 2. Bagga A, Sinha A, Gulati A. Protocols in Pediatric Nephrology. New Delhi: CBS
Abnormalities of intravascular volume often coexist with Na+
)) Publishers; 2012. pp. 41-54.
imbalances and take precedence in management 3. Khilnani P. Electrolyte abnormalities in critically ill children. Crit Care Med.
1992;20(2):241-50.
After emergency management, further correction of Na+ levels
))
4. Moritz ML, Ayus JC. Disorders of water metabolism in children: hyponatremia and
should match the duration of evolution of the abnormality: hypernatremia. Pediatr Rev. 2002;23(11):371-80.
acutely occurring Na+ imbalances can be treated rapidly,
472
ch-97.indd 472 11/21/2016 12:05:06 PM

CHAPTER 98
Acute Glomerulonephritis
Noopur Singhal, Abhijeet Saha
INTRODUCTION systemic lupus erythematosus, shunt nephritis, endocarditis-

associated GN, and Wegener’s granulomatosis. Diagnostic
The term acute glomerulonephritis (AGN) defines a patho approach has been mentioned in algorithm 1.
logical process that may manifest clinically as acute nephritic In the clinical scenario of a child with edema, hyper
syndrome, nephrotic syndrome, or rapidly progressive tension, and oliguria, the initial evaluation must be targeted
glomerulo nephritis (GN). Nephritic syndrome is a clinical to differentiate acute nephritis from nephrosis. Table 1 lists
syndrome defined by the association of hematuria, proteinuria, important clinical and laboratory criteria to differentiate
and often arterial hypertension and renal failure. between these two entities.
Acute postinfectious glomerulonephritis (APIGN) includes
a large proportion of GN resulting from a variety of infectious
agents, most common being streptococci. The common ACUTE POSTSTREPTOCOCCAL
infectious agents implicated in the causation of APIGN GLOMERULONEPHRITIS
have been enumerated in box 1. Acute poststreptococcal
glomerulonephritis (APSGN) is the prototype of APIGN Acute poststreptococcal glomerulonephritis is a non
occurring due to immune complex deposition. Less common suppurative, immunologically mediated complication of group
diseases include immunoglobulin A (IgA) nephropathy, A β-hemolytic streptococcal infection. It continues to remain
Box 1: Etiology of postinfectious glomerulonephritis

Bacteriae Viruses Fungi
• Gram-positive bacteria (streptococci, staphylococci, DNA viruses • Candida albicans
pneumococci, enterococci, Listeria monocytogenes) • Hepatitis B • Histoplasma capsulatum
• Gram-negative cocci (meningococcus, Neisseria • Varicella zoster • Coccidioides immitis
gonorrhoeae)
• Epstein-Barr Parasitic infestations
• Gram-negative coccobacilli (hemophilus)
• Cytomegalovirus • Plasmodium falciparum, P. malariae
• Gram-negative bacilli (Salmonella, Klebsiella, Serratia,
• Parvovirus B19 • Schistosoma haematobium, S. mansoni
Yersinia, Proteus, Pseudomonas)
• Adenovirus
• Other infections (Legionellosis, brucellosis, • Toxoplasma gondii
bartonellosis) RNA viruses • Filariasis, trichinosis, hydatid disease
Mycobacteria, Rickettsia, Mycoplasma, Chlamydia and • HIV • Amebiasis (Entamoeba histolytica)
Spirochetes • Coxsackie, Enteric cytopathic
• Tuberculosis and nontuberculous mycobacteria human orphan (ECHO) virus
• Syphilis (Treponema pallidum) • Hepatitis A, hepatitis C
• Leptospirosis (Leptospira interrogans) • Dengue virus
• Rickettsial diseases (Coxiella burnetii) • Mumps and measles
• Mycoplasma pneumoniae • Hantavirus and rotavirus
• Chlamydia pneumoniae
SECTION 12: Nephrology
ALGORITHM 1
Algorithm of approach to the patient with acute glomerulonephritis
RBCs, red blood cells; ANA, antinuclear antibody; ANCA, anti neutrophil cytoplasmic antibody; ASO, antistreptolysin-O; c-ANCA, cytoplasmic antineutrophil
cytoplasmic antibody; GBM, glomerular basement memberane; HSP, Henoch-Schonlein purpura; MPGN, membranoproliferative glomerulonephritis; PAN,
periarteritis nodosa; p-ANCA, perinuclear antineutrophil cytoplasmic antibody; SLE, systemic lupus erythematosus.
TABLE 1: Differences between nephrotic syndrome and nephritic Group A streptococci are most commonly typed by their
syndrome surface M proteins, which are virulence factors. They can also
Nephrotic syndrome Nephritic syndrome be divided into two groups based on the presence or absence
of a lipoproteinase that causes serum to become opaque
Edema Gross Mild to moderate
(serum opacity factor). Each of these two groups contains a
Hematuria Absent/minimal Marked/gross characteristic group of M proteins. The opacity factor-positive
Hypertension Absent/minimal Common group contains the “nephritogenic” strains. Nephritogenic
Urine output Normal/decreased Decreased
strains are further subdivided into those primarily associated
with pyoderma (M47, M49, M55, M56, M57, and M 60), and
Serum cholesterol Elevated Mildly elevated/normal those that most often cause pharyngitis.(M1, M4, M25, and
Proteinuria Gross Moderate some M12 strains).
Glomerular Normal Decreased Acute poststreptococcal glomerulonephritis is one of
filtration rate the most common causes of acute kidney injury in children
of developing countries. Poor hygiene and lack of access to
an important cause of acute renal failure and hospitalization medical care increases the risk in these countries.
for children in developed and developing nations despite
having an excellent spontaneous cure rate. PATHOGENESIS
EPIDEMIOLOGY The fundamental pathogenic mechanism of postinfectious GN
is believed to be the deposition of immune complexes within
Out of the estimated worldwide yearly burden of APSGN of the glomerular tufts. Other proposed mechanisms include
472,000 cases; approximately 404,000 occur in children (9.3 elicitation of an autoimmune response between streptococcal
cases per 100,000 population). The male and female ratio is components and renal components (molecular mimicry);
2–3:1. The risk of nephritis in epidemics varies from 5% with and alteration of a normal renal antigen eliciting autoimmune
474 throat infections to as high as 25% with pyoderma. reactivity.
CHAPTER 98: Acute Glomerulonephritis
Much of the early work on the pathogenesis of APSGN Immune Complex Deposition and
focused on the group A-specific streptococcal M proteins Complement Activation
but it has now been discounted as the nephritogenic antigen
because, in addition to the increasing number of M-serotype The critical role played by an in situ immune reaction
strains that are nephritogenic (M serotypes 1, 2, 4, 12, 18, 42, resulting from the antibody meeting free antigen deposited
49, 56, 57, and 60), some M-type strains are non-nephritogenic. in the glomeruli was suspected by Rodriguez-Iturbe. This
possibility was emphasized by the difficulty of inducing GN
Nephritogenic Streptococcal Antigens and the near impossibility of inducing subepithelial immune
deposits (humps), the prototype lesion in the APSGN, with
Two possible antigens being currently investigated as the preformed immune complexes. Large amounts of preformed
potential cause of PSGN include the nephritis-associated complexes may produce GN, but this is leukocyte-mediated
plasmin receptor, identified as glyceraldehyde-3-phosphate and the localization of the immune deposits is largely
dehydrogenase, and a cationic cysteine proteinase known subendothelial.
as streptococcal pyrogenic exotoxin B that is generated by Complement activation is a central feature in APSGN. The
proteolysis of a zymogen precursor. Both of these fractions alternate pathway is preferably activated as substantiated
are capable of activating the alternate pathway of the by the serum complement profiles (low C3 and normal
complement system. C4) and immunofluorescence pattern typically comprising
Glomerular binding and plasmin activation are considered of immunoglobulin G (IgG), C3, and C5. These deposits
key pathogenic properties of these proteins. When deposited virtually never contain the classical pathway components
in glomeruli, glyceraldehyde 3-phosphate dehydrogenase, C1q and C4.
streptococcal cationic proteinase exotoxin B (speB), or
zymogen (whether bound by specific antibody or not), can
Cellular Immune Mechanisms
interact with plasmin or plasminogen to cause glomerular
damage by degrading the glomerular basement membrane Immunocompetent cells like macrophages and T helper cells
(GBM) through the activation of latent metalloproteinases infiltrate the glomeruli. There is increased circulatory levels of
or collagenases (Fig. 1). The circulating or in situ immune IL-6, IL-8, tumor necrosis factor-α, and monocytic chemotactic
complexes can then move across the altered GBM and protein-1. The infiltrating immune cells play an important role
accumulate as “humps” in the subepithelial space. in the development and severity of inflammation.
GBM, glomerular basement membrane; MMP, matrixmetalloproteinase; speB, streptococcal cationic proteinase exotoxin B.
Fig. 1: Possible pathogenic mechanism of post-streptococcal glomerulonephritis. (a) The putative nephritogenic antigens streptococcal
cationic proteinase exotoxin B (speB) or zymogen and glyceraldehyde 3-phosphate dehydrogenase are normally repelled in both their free
and antibody-bound forms by the negatively charged glomerular basement membrane (GBM); (b) However, these antigens can interact with
plasmin or plasminogen to activate procollagenase and latent matrixmetalloproteinase; (c) The active enzymes (and the nephritogenic antigen
itself, in the case of speB or zymogen) degrade the GBM, and abolish its negative charge; (d) The nephritogenic antigen and immune complexes
can then pass through the damaged GBM and form the characteristic “hump”-like deposits under the podocyte processes; (e) Damage to the
GBM also causes effacement of podocyte foot processes, which leads to loss of protein in the urine 475
Autoimmune Reactivity
Though a number of autoimmune findings have been reported
in APSGN, they represent epiphenomena and do not define
a specific clinical course of the disease. Anti-IgG antibodies
are frequently seen in serum and in glomerular deposits. This
autoimmune reactivity may modulate the course of APSGN.
PATHOPHYSIOLOGY
The primary physiological abnormality in children with
APSGN is reduction in glomerular filtration rate (GFR) due to
infiltration of the GBM by inflammatory cells and reduction
in permeability of the basement membrane. The endothelial
or mesangial factors released by glomerular injury, over
expression of epithelial sodium channel and interstitial
inflammatory cells also contribute to sodium and fluid
retention by the distal tubule. Intravascular and subsequent
interstitial fluid retention leads to hypertension and edema.
Fig. 2: Summary of the typical clinical course of post-streptococcal
Significant reductions in GFR cause azotemia, acidosis, acute glomerulonephritis
hyperkalemia, and hyperphosphatemia. Anemia occurs as a
consequence of volume expansion and is usually normocytic
normochromic.
Clinical Pearls
Indications for hospitalization
The classical presentation of APSGN is a triad of abrupt • Severe edema • Hypertension
onset of gross hematuria, edema, and hypertension, and is • Severe azotemia • Respiratory distress
usually, but not always preceded by an episode of group A
β-hemolytic streptococcal pharyngitis or pyoderma. The
latency between the streptococcal infection and the onset of Clinical evaluation should include a detailed description
the clinical syndrome is 7–14 days in sore throat, while it is of hematuria which is an almost universal finding in APSGN.
2–4 weeks in pyoderma. In some cases, mild pharyngitis may Hematuria is typically described as “coke, “tea”, or “smoky”
go unnoticed whereas preceding pyoderma can be detected colored in 25–60% of these children. Urine color is uniform
by healed scars. throughout the stream and the gross hematuria of AGN is
The median age at presentation is between 6–8 years. The virtually always painless. It is also important to detect any
rarity of APSGN in children younger than 2 years is attributed symptoms suggestive of complications especially dyspnea
to the low rate of streptococcal pharyngitis in this group and an due to fluid overload or headaches, visual disturbances, or
immature immune (antibody) response. alteration in mental status due to hypertension. Any history
Three phases of the disease can be identified as the of rash, arthritis, hepatosplenomegaly, recent weight change,
latent, acute, and the recovery phases (Fig. 2). The recovery or recent medication exposure should lead to search for
phase occurs after resolution of fluid overload with diuresis, alternative causes.
normalization of blood pressure and resolution of proteinuria
and gross hematuria. Urine volume usually increases 4–7 days Clinical Pearls
after hospital admission, and this increase is rapidly followed When to suspect rapidly progressive glomerulonephritis?
by resolution of edema and normalization of blood pressure.
• Persistent oliguria
Microscopic hematuria takes several months to resolve and
can persist for 1 year after the acute attack. • Severe azotemia
Acute poststreptococcal glomerulonephritis can have • Nephrotic range proteinuria
varying severity, mild cases may just present with microscopic
hematuria with mild proteinuria, while those at the other end Hypertension due to sodium and water retention and
of the spectrum may have anuria and severe hypertension. consequent expansion of extracellular space occurs in up
Edema is turgid, unlike in nephrotic syndrome where it is to 80% of children with APSGN. Cerebral complications
flaccid and may increase to the entire body in unrestricted fluid of hypertension including headache, drowsiness, seizure,
intake. Proteinuria is usually mild and not in the nephrotic mental status, and visual changes occur in 30–35% of the
range. Massive proteinuria may be found in about 2–4% of children. Patients may present with clinical and radiologic
cases and its persistence is a risk factor for progression to signs of pulmonary edema. Evidence for congestive heart
476 chronic renal disease. failure may be found in almost half of these children. Initially,
blood pressure is high, buthypotension occurs in later stages TABLE 2: Indication for renal biopsy
when heart failure and shock supervenes. Other atypical
Early stage Recovery phase
presentations of poststreptococcal GN have been listed in the
clinical pearl below. • Short latent period • Depressed GFR >4weeks
Rapidly rising azotemia and persistent oliguria should • Severe anuria • Hypocomplementemia
raise a suspicion of rapidly progressive GN. • Rapid progressive course >12 weeks
• Hypertension >2 weeks • Persistent proteinuria
Clinical Pearls • Depressed GFR >2 weeks
>6 months
• Persistent microhematuria
• Normal complement levels
Atypical presentations of acute poststreptococcal >18 months
glomerulonephritis • Nonsignificant titers of
• Subclinical disease antistreptococcal antibodies
• Seizures • Extrarenal manifestation
• Acute hypertensive crisis GFR, glomerular filtration rate.
• Acute pulmonary edema

• Acute kidney injury Light Microscopy
• Reversible posterior leukoencephalopathy syndrome
On light microscopy, there is diffuse hypercellularity
• Autoimmune hemolytic anemia of endothelial and mesangial cells and infiltration of
• Rash similar to Henoch-Schönleinpurpura the glomerular tuft with polymorphonuclear cells with
obliteration of the capillary lumina. GBM is normal and there
is little or no evidence of tubular or vascular injury (Fig. 3).
INVESTIGATIONS Rarely, patients with APSGN may have crescent formation
Urine examination shows acidic pH, dysmorphic red blood in over 50% of glomeruli, leading to the clinical picture of
cells, red cell casts, granular casts, and neutrophils suggestive of rapidly progressive GN.
glomerular inflammation. Mild to moderate (1‑2+) proteinuria
is commonly seen. Blood urea is increased in 60–65% of cases Immunofluorescence
and estimated creatinine clearance is decreased to less than Immunofluorescence pattern typically seen during the acute
90 mL/min/1.73 m2 in 20%. The GFR is often decreased during phase of APSGN shows discrete granular deposits of IgG
the acute phase of the disease. A mild degree of normocytic and C3 in the capillary loops and mesangium (Figs 4 and 5).
normochromic anemia is also seen due to volume overload. Three patterns of the deposits are described in box 2. The
Hypoalbuminemia may be present in those with nephrotic garland pattern is associated with heavy proteinuria and
range proteinuria. worse long-term prognosis. Absence of immunofluorescence
Serologic evidence of a recent streptococcal infection (IF) deposits should prompt search for c-ANCA and p-ANCA
should be sought in suspected cases of APSGN because antibodies.
positive streptococcal serology is more sensitive (94.6%)
for diagnosis than history of recent infection (75.7%) or
positive cultures (24.3%). The most important serological
marker is antistreptolysin O (ASO) titer. ASO titers are
higher in pharyngitis-associated APSGN whereas cases
following pyoderma are more likely to demonstrate elevated
anti-deoxyribonuclease (DNase) B titer. Streptozyme test,
which includes four antigens (DNase B, streptolysin O,
hyaluronidase, and streptokinase) is reported to be positive
in 80% cases. Acute reduction in serum C3 level in APSGN
with a typical return to normal levels within 6 weeks of onset
is of foremost diagnostic importance. A minimal decrease in
C4 can occur transiently.
Renal Biopsy Findings

A renal biopsy is not indicated for diagnosis of APSGN but is
usually performed when atypical clinical manifestations are
present or the resolution is delayed. Conditions which require Fig. 3: Acute postinfectious glomerulonephritis. Glomerulus showing
a renal biopsy in the course of poststreptococcal GN are listed cellular proliferation obstructing capillaries and there are abundant
in table 2. polymorphs (hematoxylin and eosin)
477
complex deposition. Immunoelectronmicroscopy has facili

tated the demonstration of IgG, C3, and SPEB within the
subepithelial humps.
Acute poststreptococcal glomerulonephritis in majority
of the cases is a straightforward diagnosis. The differential
diagnosis includes several glomerulonephritides related to
chronic infection, infectious glomerulonephritides without an
immune-mediated etiology, and other primary and secondary
glomerular diseases. It should be differentiated from IgA
nephropathy (short latent period), membranoproliferative
GN (persistent hypocomplementemia, unresolving nephritic
syndrome), lupus nephritis (persistent hypocomplementemia,
systemic manifestation), vasculitides (polyarteritis nodosa),
Henoch-Schonlein purpura (normal C3), hemolytic uremic
Fig. 4: Acute postinfectious glomerulonephritis. Immunofluores
syndrome (hemolysis, thrombocytopenia), endocarditis-
cence for immunoglobulin G showing smaller and spaced parietal
granular deposits giving a “starry sky” appearance associated nephritis, and shunt nephritis.
MANAGEMENT
Treatment of APSGN is largely supportive and should be
targeted toward the problem of hypertension and fluid
overload. Restriction of fluid and sodium intake with
adequate caloric intake is recommended. Hypertension
is managed with fluid restriction and administration of
loop diuretics (furosemide). Two or more antihypertensive
drugs may be needed including calcium-channel blockers.
Although captopril has been shown to reduce blood pressure
and improve GFR in APSGN patients, angiotensin converting
enzyme inhibitors should be used with caution due to
possible renal failure and hyperkalemia. Severe hypertension
may mandate the use of sodium nitroprusside infusion or
vasodilators (hydralazine).
Pulmonary edema is uncommon and should be treated
with oxygen and loop diuretics. Digitalis is not indicated,
because it is ineffective and may result in intoxication. Rarely,
Fig. 5: Acute postinfectious glomerulonephritis. Immunofluorescence
overt heart failure and pulmonary edema may complicate
for C3 showing extensive granular deposits in the capillary walls
giving it a garland appearance the clinical course. Occasionally, acute kidney injury, severe
fluid retention unresponsive to diuretics, pulmonary edema,
and intractable hyperkalemia necessitate hemodialysis
or continuous venovenous hemofiltration. Management
Box 2: Immunofluorescence patterns in acute poststrepto of hypertensive emergencies, acute kidney injury, acute
coccal glomerulonephritis
pulmonary edema, and severe hyperkalemia must be done as
• Starry sky appearance (discrete mesangial and basement per standard guidelines.
membrane deposits, usually of complement) Acute poststreptococcal glomerulonephritis is pre
• Mesangial pattern (thick deposits in the mesangium) vented by early antibiotic treatment, and the spread of
• Garland pattern (heavy garland-like deposits in the basement nephritis associated streptococcal infection is contained
membrane) by prophylactic antibiotic treatment to individuals at risk.
Early administration of penicillin is reported to prevent or
ameliorate the severity of AGN. Single dose of intramuscular
Electron Microscopy benzathine penicillin G or alternatively oral penicillin V for
The hallmark pathologic finding in electronmicroscopy is 10 days is recommended. Erythromycin or azithromycin are
subepithelial “hump” that represents subepithelial immune used in patients allergic to penicillin.
478
Clinical Pearls Henoch-schönlein Purpura and

Immunoglobulin A Nephropathy
Antibiotic therapy in acute poststreptococcal glomerulo
Although clinically different, these two entities are histo
nephritis
logically identical. A typical case of Henoch-Schonlein purpura
• Children <27 kg: benzathine penicillin G single dose 600,000 presents with gross hematuria, edema, purpura, arthritis, and
units intramuscularly abdominal pain. IgA nephropathy manifests with recurrent
• Children >27 kg: benzathinepenicillin G single dose 1.2 million gross hematuria. Renal histology varies from mild mesangial
units intramuscularly proliferation to crescentic GN. Prominent IgA deposition in the
• Oral penicillin V 250 mg 2–3 times per day for 10 days mesangium is characteristically seen.
Allergic to penicillin
• Erythromycin 40 mg/kg/day for 10 days Hepatitis B and
• Azithromycin for 5 days. C Virus-related Glomerulonephritis
Renal involvement with hepatitis B is particularly common
in East Asian countries and South Africa. The lesions
PROGNOSIS seen commonly with this infection are membranous GN,
membranoproliferative GN, and occasionally vasculitis.
Acute poststreptococcal glomerulonephritis is typically
Hepatitis C virus infections are more commonly associated
characterized by rapid resolution and an excellent prognosis.
with proliferative GN.
Clinical improvement begins by 4–6 days with decrease in
edema and hypertension and increase in urine output. Gross
hematuria clears in first week, but microscopic hematuria may KEY POINTS
persist for up to 6–12 months. Intermittent mild proteinuria may
persist, which is of no significance. Mortality is extremely rare ))
Acute poststreptococcal glomerulonephritis is a non
but may result due to severe hyperkalemia or pulmonary edema. suppurative complication of group A β-hemolytic streptococci
Recurrence of disease is rare since immunity to ))
Clinical triad of abrupt onset of gross hematuria, edema, and
streptococcal M protein is type-specific and long-lasting and hypertension
nephritogenic serotypes are limited. Long-term antibiotic ))
Acute reduction in serum C3 levels with return to normal
prophylaxis is thus not recommended. Certain histologic levels within 6 weeks is characteristic
findings may predict a poor prognosis. Garland pattern on IF ))
Treatment is largely supportive
has been associated with heavy proteinuria and poor outcome.
))
Prevention of glomerulonephritis is by early administration of
Extracapillary crescent formation is the most ominous
penicillin after streptococcal infection.
histological finding in PSAGN. Patients with APSGN should
be followed up for several years for proteinuria and blood
pressure, and if there is persistent proteinuria or a decline in
renal functions, a renal biopsy is indicated. SUGGESTED RAEDINGS
1. Ahn SY, Ingulli E. Acute poststreptococcal glomerulonephritis: an update. Curr Opin
Endocarditis Associated Renal Disease Pediatr. 2008;20(2):157-62.
2. American Academy of Pediatrics, Committee on infectious diseases. Group A
Microscopic hematuria and proteinuria are indicative of renal
streptococcal infections. In: Redbook, CBS Paediatric series, American Academy of
lesion in a child with infective endocarditis. Azotemia may Pediatrics; 2006. pp. 610-20.
develop, but is mild except in cases that develop crescentic 3. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A
GN. Serological findings include reduced C3 and C4. Antibiotic streptococcal diseases. Lancet Infect Dis. 2005;5(11):685-94.
treatment needs to be given for 4–6 weeks. 4. Eison TM, Ault BH, Jones DP, Chesney RW, Wyatt RJ. Poststreptococcal acute
glomerulonephritis in children: Clinical features and pathogenesis. PediatrNephrol.
Shunt Nephritis 2011;26(2):165-80.
5. Kanjanabuch T, Kittikowit W, Eiam-Oug S. An update on acute postinfectious
Infected ventriculoatrial shunts and rarely ventri culo
glomerulonephritis worldwide. Nat Rev Nephrol. 2009;5(5):259-64.
peritoneal shunts may be complicated by development of
6. Kasahara T, Hayakawa H, Okubo S, Okugawa T, Kabuki N, Tomizawa S, et al. Prognosis
postinfectious GN. Common microorganisms causing shunt acute of poststreptococcal glomerulonephritis (APSGN) is excellent in children, when
infections are S. epidermidis in about 75% of cases and less adequately diagnosed. Pediatr Int. 2001;43(4):364-67.
frequently S. aureus. Renal involvement is indicated by 7. Rodríguez-Iturbe B, Batsford S. Pathogenesis of poststreptococcal glomerulo
nephritis a
proteinuria (nephrotic range), hematuria, and hypertension. century after Clemens von Pirquet. Kidney Int. 2007;71(11):1094-104.
Laboratory findings include reduced C3 and C4 levels with 8. Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal
isolation of the organism from blood or shunt fluid cultures. glomerulonephritis. J Am Soc Nephrol. 2008;19(10):1855-864.
Renal biopsy mostly shows membranoproliferative GN. 9. Srivastava RN. Acute glomerulonephritis. Indian J Pediatr. 1999;66:199-205.
Treatment of shunt nephritis includes intravenous antibiotics 10. Vijayakumar M. Acute and crescentic glomerulonephritis. Indian J Pediatr.
and removal of infected shunt. 2002;69:1071-74.
479
CHAPTER 99
Approach to
Hematuria in Children
INTRODUCTION tract (extraglomerular). Cola-colored urine, presence of RBC

casts, and deformed (dysmorphic) RBCs suggest glomerular
Hematuria is an uncommon condition in childhood. Yet it is bleeding. Phase contrast microscope or staining with special
frightening to the parents and results in an almost immediate stains (Wright stain) is required for detection of dysmorphic
referral to a pediatrician. An approach to this entity will be RBCs (Fig. 2). Presence of more than 20% dysmorphic RBCs
discussed in this chapter. The incidence of gross hematuria suggests glomerular hematuria (Table 1). The causes of
in children is estimated to be around 0.13%. Asymptomatic hematuria are listed in table 2.
microscopic hematuria is common in unselected populations
of children, with a prevalence that ranges from 0.4 to 4.1%.
Box 1: Causes of red colored urine
However, on repeated evaluations, the prevalence of persistent
microscopic hematuria is about 0.5% based on the surveys of • Food items
school going children. {{ Ingestion of beetroot, blackberries, food coloring agents
• Drugs
{{ Nitrofurantoin, phenophthalein, pyridium, rifampicin,
DEFINITION
phenothiazines, sulfasalazine
Hematuria is defined as the presence of five or more red blood • Metabolites
cells (RBCs) per high-power field in multiple centrifuged urine {{ Homogentisic acid, melanain, methemoglobin, porphyrins,
examinations (at least 3; 1 week apart). Children are referred for urates, tyrosinosis
presence of gross hematuria, persistent isolated microscopic
hematuria, and microscopic hematuria with clinical symptoms
or with proteinuria.
GROSS HEMATURIA
Gross hematuria must be confirmed by microscopic
demonstration of RBC. If no RBCs are seen on microscopy, a
dipstick test is done to look for other causes of red colored urine.
If the dipstick is positive, it is indicative of hemoglobinuria
(usually caused by severe intravascular hemolysis) or
myoglobinuria from rhabdomyolysis (due to muscle trauma or
strenuous exercise). A negative dipstick test would point toward
the discoloration due to porphyria, drugs such as rifampicin,
pigments in foods, ingestion of beetroot and urates (Box 1).
Glomerular and Extraglomerular Hematuria

bright-red urine, visible clots or crystals with normal-looking Fig. 1: Urine microscopy showing normal red blood cell
eumorphic RBCs (Fig. 1) suggest bleeding from the urinary
CHAPTER 99: Approach to Hematuria in Children
TABLE 3: Clinical pointers in history to identify the causes of

hematuria
Clinical signs/symptoms Likely diagnosis
Edema, hypertension Glomerulonephritis
Dysuria, loin pain, colic Calculi, hypercalciuria
Joint pains, rash, edema SLE, HSP, vasculitis
Positive family history, Alport syndrome, thin basement
deafness membrane disease
Renal lump Polycystic kidney disease, Wilm’s
tumor, hydronephrosis
Bleeding tendency Coagulation and bleeding disorders
SLE, systemic lupus erythematosus; HSP, Henoch-Schonlein purpura
History and Physical Examination

Fig. 2: Urine examination with phase contrast microscopy showing
Some clinical pointers in history and examinations may
dysmorphic red blood cell
indicate the cause for hematuria (Table 3).
TABLE 1: Differentiation of glomerular and extraglomerular Investigations

hematuria An episode of gross hematuria needs evaluation. After
confirming hematuria, algorithm 1 can be followed. If the
Glomerular hematuria Extraglomerular hematuria
onset is acute and proteinuria is present, the likelihood of an
Color red or brown Bright red usually episode of postinfective glomerulonephritis (PIGN) is high.
Clots absent Clots present The relevant investigations like anti-streptolysin (ASLO) titers,
Proteinuria (2 + or more) No proteinuria; 1+ complement C3 levels and kidney function tests (KFT) should
be done. An elevated ASLO (>200 IU/L), low C3 levels with
Red cell casts Absent cellular casts normal or deranged KFT are confirmative of poststreptococcal
Dysmorphic RBC >20% Dysmorphic RBC <20% glomerulonephritis (PSGN). If the history is of prolonged
RBC, red blood cells. (3–4 weeks) duration, other causes like immunoglobulin A
(IgA) nephropathy, membranous or membranoproliferative
disease are more likely. Patients with IgA nephropathy are
TABLE 2: Causes of hematuria likely to have recurrent episodes of gross hematuria, especially
with episodes of upper respiratory tract infections. Presence
Glomerular Extraglomerular
of fever, joint pains, photosensitive rash points toward a
Acute onset diagnosis of systemic lupus erythematosus. Most of these
• Acute glomerulonephritis • Urinary tract infections conditions can be identified on a renal biopsy specimen which
(PSGN, others*) • Urolithiasis; should include light microscopy, immunofluorescence, and
• Rapidly progressive hypercalciuria electron microscopy (if available). Serological tests that help
glomerulonephritis • Cystic kidney disease in identification of the underlying cause are hepatitis B surface
• Hemolytic uremic syndrome • Vascular malformations antigen (HBsAg) and antihepatitis C virus (HCV) for related
Chronic glomerulonephritis (kidney or bladder) nephropathy [membranous and membranoproliferative
• Membranous, • Wilm’s tumor glomerulonephritis (MPGN)]. Anti nuclear antibodies
membranoproliferative GN, IgA • Renal vein thrombosis (ANA) and anti-dsDNA for lupus nephritis; antineutrophilic
nephropathy • Trauma cytoplasmic antibodies (P-ANCA and C-ANCA; both these
• Thin basement membrane disease are immuno fluorescence based tests) for identification of
• Bleeding and clotting
• Alport syndrome disorders
vasculitis (microscopic polyangiitis, Wegener’s and Churg
Strauss disease). Identification of ANCA can also be done by
• Focal segmental glomerulosclerosis • Drugs (NSAIDS)
enzyme-linked immunosorbent assay (ELISA) based tests
• Goodpasture’s syndrome
(antimyeloperoxidase-anti-MPO corresponding to P-ANCA;
Multisystem disease antiproteinase-3-antiPR3 corresponding to C-ANCA) which
• SLE, HSP, vasculitis are simpler and yield faster results.
*Typhoid, Pneumococcal pneumonia, meningococcemia, shunt nephritis,
bacterial endocarditis, varicella, mumps associated
Presence of extraglomerular hematuria points towards local
PSGN, poststreptococcal glomerulonephritis; GN, glomerulonephritis; IgA,
causes, polycystic kidneys, hydronephrosis, urolithiasis, and
immunoglobulin A; SLE, systemic lupus erythematosis; HSP, Henoch–Schönlein hypercalciuria. Vascular abnormalities of urinary bladder can
purpura; NSAIDS, nonsteroidal anti-inflammatory drugs also cause hematuria rarely. An ultrasound kidney, ureter, 481
ALGORITHM 1
Approach to gross hematuria
ANA, antinuclear antibodies; ANCA, antineutrophilic cytoplasmic antibodies; ASLO, antistreptolysin; HBsAg, hepatitis B surface antigen; IgA, immunoglobulin A;
KUB, kidney ureter bladder; KFT, kidney function tests; MPGN, membranoproliferative glomerulonephritis; PSGN, poststreptococcal glomerulonephritis; RBC, red
blood cell; UTI, urinary tract infection; C/S, culture sensitivity; USG, ultrasonography; CT, computed tomography; D/D, differential diagnosis; HCV, Hepatitis-C virus;
SLE, systemic lupus erythematosus.
bladder (KUB) would identify any structural abnormalities and/ evaluation is given in algorithm 2. If the hematuria is associated
or, stones in kidney. Ureteric stones are usually not identified with proteinuria, chronic glomerulonephritis is the chief
with ultrasound and require a radiograph of KUB region. If suspect, hence investigations as suggested for gross hematuria
calculi are identified, a complete urinary biochemistry needs should be performed (C3, ANA, ANCA, renal biopsy). Other
to be done (24-h urinary excretion of calcium, oxalates and causes of asymptomatic isolated microscopic hematuria are
urates). If there is a difficulty in collecting 24 hours sample spot, benign familial hematuria, IgA nephropathy, MPGN, Alport
urine sample can be used for determining urinary calcium/ syndrome. If the hematuria is nonglomerular, investigations
creatinine ratio and oxalate/creatinine ratio. Hypercalciuria should be done to identify hypercalciuria and urolithiasis.
is defined as urine calcium to creatinine ratio greater than 0.2 Invasive investigations, like cystoscopy and angiography,
(under 6 months of age: >0.8; 6–12 months: >0.6) or a 24-hour would be required if no cause is found on other investigations.
calcium excretion exceeding 4 mg/kg/day. Referral to a pediatric
surgeon/urologist will be required when clinical evaluation
and work up indicates a structural urogenital abnormality, an ALGORITHM 2
obstructing calculus or a tumor. The most common malignant Approach to microscopic hematuria
renal tumor in childhood is Wilm’s tumor and is associated with
a palpable abdominal mass and hematuria in most patients.
Other primary urinary tract tumors, e.g., hemangiomas,
rhabdomyosarcomas, lymphomas resulting in hematuria
are rare. Cystoscopy to identify the source of bleeding is best
performed during active bleeding.
Clinical Pearl
• Neither visual description nor the dipstick alone is sufficient to
diagnose gross hematuria; urine microscopy is required.
MICROSCOPIC HEMATURIA
Isolated microscopic hematuria is benign on most occasions.
However, it needs to be evaluated if it is symptomatic, i.e., ANA, antinuclear antibodies; ANCA, antineutrophilic cytoplasmic antibodies; KFT,
kidney function tests; KUB, kidney ureter bladder; UTI, urinary tract infection;
associated with edema, hypertension, rash, fever, joint pains or USG, ultrasonography; CT, computed tomography; D/D, differential diagnosis;
deranged KFT. Also, persistent microscopic hematuria (more C/S, culture sensitivity.
482 than 1–2 years duration) needs an evaluation. The approach for *Urine spot calcium/creatinine ratio (>0.2 mg/mg abnormal)
CHAPTER 99: Approach to Hematuria in Children
Indications for Renal Biopsy Persistence of hypocomplementenemia (beyond 12 weeks) or

absence of is another indication.
Glomerular hematuria persisting for more than 4 weeks and
without features of PSGN merits a renal biopsy. Also, decreased
complement levels beyond 3 months indicate a need for
Immunoglobulin A Nephropathy
renal biopsy to rule out other causes like IgA nephropathy, The condition is typically associated with gross hematuria but
membranous or MPGN nephropathy. Patients with deranged at times, may present with microscopic hematuria.
renal functions (urea and creatinine) and/or presence of The diagnosis of IgA nephropathy is confirmed on renal
proteinuria also need a renal biopsy to detect the presence biopsy that shows predominantly immunoglobulin IgA
of chronic glomerulonephritis. Patients with rapid worsening deposits in the mesangium on immunofluorescence. While
of renal functions presenting like RPGN should have an early ACE inhibitors are given to all patients with IgA nephropathy,
biopsy to detect crescentic glomerulonephritis. Presence of immunosuppressants like steroids, azathioprine, or
ANA, HBsAg, anti-HCV or ANCA positivity is also an indication mycophenolate mofetil may be required in patients having
for renal biopsy. nephrotic range proteinuria.
Alport Syndrome
MANAGEMENT
Alport syndrome should be suspected in patients (especially
The definitive management of hematuria is based on the males) with persistent glomerular microscopic hematuria
underlying etiology. Briefly the management of the two most once structural abnormalities of the kidney and urinary tract
common causes of hematuria, i.e., postinfective glomerulo have been ruled out. A positive family history of hematuria
nephritis and idiopathic hypercalciuria are discussed below. or renal failure may be a pointer towards the diagnosis. Light
microscopy may show variable thickening of the glomerular
Postinfective Glomerulonephritis basement membrane. Initially the changes are thinning of the
membrane that later change to basket weaving and lamellation
The investigations useful in confirming the diagnosis are a of the glomerular basement membrane. These changes are
urinalysis, complete blood count, antistreptolysin O (ASLO) most marked on electron microscopy and may not be well
titers, blood urea, serum creatinine, complement C3 levels. marked in pediatric patients as compared to adults. Early
Most patients with PSGN would have elevated ASLO titers treatment with ACE inhibitors has been shown to slow down
(>200 IU/L); low complement levels (<60 mg/dL) and mildly the progression to end stage renal disease in children.
deranged KFT. Urinalysis always shows glomerular hematuria,
presence of RBC casts, and leukocyturia. Proteinuria is usually Idiopathic Hypercalciuria
less than 2+. If these tests are negative and there is resolution
of symptoms, a presumptive diagnosis of postinfectious It is found to be a common cause of gross as well as microscopic
glomerulonephritis can be made. Most patients with an acute hematuria. A family history of renal calculi may be present. A
PIGN would resolve of their hematuria and edema within spot urinary calcium to creatinine ratio of more than 0.2 or a
24-hour urinary calcium excretion of over 4 mg/kg is abnormal.
10–14 days. The kidney functions also normalize by this time.
The condition is managed with a high fluid intake, low salt and
Persistence of gross hematuria or proteinuria beyond 4 weeks
protein intake, and use of hydrochlorthiazide. This will reduce
is unusual and often becomes an indication for kidney biopsy
urinary calcium excretion, stop hematuria, and prevent stone
in these patients. Hypertension and fluid overload can be
formation. Do not restrict dietary calcium intake.
managed by use of diuretics like furosemide in doses of 2–4 mg/
kg/day in two or three divided doses. If hypertension persists,
it can be controlled with calcium channel blockers or use of Benign Familial Hematuria
b-blockers. Amlodipine in doses of 0.2–0.5 mg/kg/day; atenolol It is characterized by persistent, isolated microscopic hematuria.
in doses of 0.5–2 mg/kg/day are often sufficient in controlling Other family members may also have microscopic hematuria.
elevated blood pressure. Use of angiotensin converting enzyme Glomerular capillary basement membrane thinning is seen on
inhibitors and angiotensin receptor blockers postinfective electron microscopy. Though the condition is usually benign
glomerulonephritis is not recommended as most patients but these children need a long-term follow-up.
with acute glomerulonephritis have a transient reduction
in their glomerular filtration rate. The duration for use of
diuretics and antihypertensives is usually less than 2 weeks.
CONCLUSION
Patients with severe fluid overload and acute renal failure may Hematuria is an uncommon condition in childhood. An
require renal replacement therapy in the form of peritoneal or episode of gross hematuria and symptomatic microscopic
hemodialysis. This occurs in less than 10% patients of acute hematuria should always be evaluated. Asymptomatic
glomerulonephritis. microscopic hematuria needs evaluation only if it persists on
Patients having persistence of gross hematuria or heavy repeated microscopic examination of urine (beyond 1 year).
proteinuria beyond 4 weeks duration need a renal biopsy An effort should be made to identify the underlying cause
to determine the underlying cause. Presence of rapidly of hematuria. Treatment of the cause results in resolution of
progressive renal failure is an urgent indication for biopsy. hematuria on most occasions. 483

1. Crompton CH, Ward PB, Hewitt IK. The use of urinary red cell morphology to detect
the source of hematuria in children. Clinical Nephrology. 1993;39:44-47.
Hematuria and proteinuria 2. Diven SC, Travis LB. A practical primary care approach to hematuria in children.
• The presence of both hematuria and proteinuria is sinister Pediatr Nephrol. 2000;14:65-72.
3. Feld LG, Waz WR, Perez LM, Joseph DB. Hematuria: An integrated medical and
• Renal biopsy should be considered whenever glomerular or surgical approach. Pediatr Clin North Am. 1997;44:1191-1210.
tubulointerstitial lesions are suspected. 4. Kashton CE. Familial hematuria. Pediatr Nephrol. 2009;24:1951-8.
What to tell the parents? 5. Kashton CE. Familial hematuria: What we know and what we don’t. Pediatr Nephrol.
2005;20:1027-35.
• For children with only microscopic hematuria, reassurance is 6. Stapleton FB. Hematuria associated with hypercalciuria and hyperuricosuria: a
sufficient. They should, however, be instructed to notify as and practical approach. Pediatr Nephrol. 1994;8:756-61.
when gross hematuria occurs. These children should have an 7. Vehaskari VM. Asymptomatic hematuria-A cause for concern? Pediatr Nephrol.
annual urine examination to detect any proteinuria, a much 1989;3:240-41.
more sinister marker of glomerular disease. 8. Wood EG. Asymptomatic hematuria in childhood: A practical approach to evaluation.
Indian J Pediatr. 1999;66:207-14.
484
Chapter 100
Approach to
Urinary Tract Infection
Pankaj V Deshpande
INTRODUCTION to be aware of! Let us be clear that this means that on clinical
examination, you cannot identify a source of the fever. All of
Urinary tract infections (UTIs) in children generate the us are pretty good clinicians and hence, let us use our clinical
strongest emotions across the pediatric field! It has evoked a skills well! There is no point in sending tests in a child with
lot of fear in parents as well as health carers to the extent that fever and a severe cough or cold! You have identified a cause of
each episode is viewed as a disaster for the kidneys! There has fever and doing tests at this stage will only serve to confuse you!
been literature ad nauseum about UTIs in children and if you Apart from this, if the infant is obviously crying persistently
consider this to be another of those articles, (I wouldn’t blame (not an occasional episode in 2 days) while voiding, has
you!) I am hoping that you will be slightly wrong as I take you turbid/discolored urine or has a poor stream of urine (in
along to look at the practical aspect of approaching a child with a boy), UTI should be thought of. Persistent jaundice in a
UTI and look at it with the same care as with other illnesses neonate beyond 2 weeks of age is an examination question
rather than dread! more than a practical reality!
In the first year of life, both boys and girls have the same rate In older children, the symptoms are more likely to be
of developing a UTI (certainly in the first 6 months). Thereafter, related to the urinary tract as they will be able to communicate
the incidence in girls is higher than boys. their ailment better. Presence of frequency of voiding, dysuria
(pain while voiding), urgency with daytime wetting may be
DEFINITION seen more commonly here. They may also have fever, loin
pain, vomiting and in some cases, may actually have diarrhea
Urinary tract infection in children is based on the presence of a as the presenting symptom. Fever without focus should also
positive urine culture in a symptomatic child. There are several prompt a thought about UTI though it will be less common
parts to this statement. Firstly, the child has to be symptomatic, than in infants.
either in the form of urinary symptoms or have a fever without
an identifiable source. Secondly, urine culture being positive
would vary according to the method of collection of urine Clinical Pearl
(clean catch, catheter, suprapubic, etc.). Urine test for urinary tract infection should be done only in
As you will realize, the common test used for diagnosing symptomatic children
UTI is not included in the pure definition of UTI. Pyuria
• Fever without focus
(presence of leukocytes in the urine) is only an indicator of
• Urinary symptoms, especially in older child.
inflammation and not always the sign of UTI in children.
CLINICAL FEATURES: (WHEN TO SUSPECT) DIAGNOSIS

The first major task is to be aware of UTIs in children but also This aspect of UTIs always raises a hornet’s nest and strong
that only appropriate tests done at the appropriate times will emotions! I am not going to quote all literature about this
help you in diagnosing but not over or underdiagnosing UTIs! aspect but let us get our basic concepts right before embarking
Unfortunately, both are common! on other thought provoking aspects of diagnosis (Algorithm 1).
In infants and children up to 2 years of age, the symptoms As explained above, once a UTI is suspected, urine tests will
may be subtle. Fever without a focus is an important feature be required to diagnose or rule out a UTI. Those who have sat
ch-100.indd 485 11/24/2016 2:22:15 PM

Algorithm 1
Algorithm for diagnosis and management of UTI
UTI,urinary tract infection; US, ultrasound; DMSA, dimercaptosuccinic acid; MCUG, micturating cystourethrogram.
patiently beside their child (boy or girl) waiting for him/her to For a clean catch/mid-stream urine sample, the genital
pee (void) will realize the eureka moment when the child pees area is cleaned with normal soap and water and dried. In an
(voids)! The two tests that are used commonly are a routine older child, a mid stream sample can be attempted but in an
examination of urine with microscopy and a urine culture. infant, a clean catch sample is good enough. This implies that
Unfortunately, there is no advice given to the parents in the urine is collected straight into the container and not on a
most places which causes a lot of heartburn amongst doctors plastic sheet, ”dabba” or cotton! Once collected it needs to be
regarding results as they cause a lot of confusion! Sample transported to the microbiology lab immediately and plated
486 collection is crucial to the diagnosis of UTI. within 30–60 minutes. If a delay is anticipated, the sample
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Chapter 100: Approach to Urinary Tract Infection
should be stored in the refrigerator at 4°C (to a maximum of Though, leukocyturia is considered to have less than an ideal
24 h). This implies that the urine sample will not be left on the role in predicting UTI, we should realize that more than only
table for 2 hours before being given in the lab. This is because it a positive urine culture may not indicate a UTI. Here, the
will allow the growth of contaminant organisms. symptoms of a child play an important role. Positive cultures
If the urine is collected appropriately as described above, a may be due to many reasons, the chief being improper
pure growth of more than 100,000 organisms/mL is considered collection and contamination and no test is 100% accurate!
as significant and positive. Recent literature would even suggest
that a count of 50,000 may also be significant. However, lower Clinical Pearl
counts are more likely to represent contamination and efforts
should be made to collect the urine appropriately, unless the • Presence of significant number of leukocytes in urine can be
due to many reasons, urinary tract infection (UTI) being one of
child is completely asymptomatic.
them. Unless associated with symptoms and a positive urine
culture, it does not represent a UTI.
Clinical Pearl
• Advice regarding collection of urine (cleaning, clean catch, and Urine dipstick can be used as a better way to screen for
appropriate transport). UTI. Presence of leukocytes is detected by the presence of
leukocyte esterase and the conversion of nitrate to nitrite
is detected by the nitrite test. When both are positive, the
If the urine is collected by using a urinary catheter, the
predictive value for a UTI is very high (UTI very likely).
cleaning should be adhered to and strict asepsis maintained
It should be remembered that false positives for both
or you may be the cause of the child’s subsequent UTI! If this
leukocytes and nitrites can occur (especially in exposed
is done, a colony count of more than 10,000 organisms/mL will sticks, medications, etc.).
be considered significant and positive. Dipslide has been used to plate the urine immediately after
Suprapubic aspiration of urine (using a syringe and it is collected with good results.
needle to aspirate urine directly from the bladder) is possible
in young children as the bladder is an abdominal organ till
5 years of age. In this case, the trick lies in knowing when to DIFFERENTIAL DIAGNOSIS
do the aspiration. If one waits till about half to one hour after
I think it is extremely important to realize that every ”positive”
the last void, the chances of obtaining urine increase. In this urine test is not a UTI. As explained above, urine routine
case, any growth of organisms is considered significant and showing ”significant” number of leukocytes when the child is
implies a UTI. asymptomatic, carries no meaning in the general population
It is important to note that bag urine samples have a of children! Similarly, one of the biggest problems with a
high contamination rate and are not recommended for urine positive urine culture is contamination as the collection is
collection in children. In any case, bag urine is often collected not ideal in children and several authors have addressed
in an inappropriate manner (as the child needs to be upright this issue suggesting that a fair number of children/adults
before collection and the bag removed soon after voiding) and receive antibiotic therapy when they do not have a UTI. The
hence, should not be used in children. most important message is that in the absence of symptoms
suggesting UTIs, urine tests are not required and do not
Clinical Pearl indicate a UTI!
• Method of urine collection important to determine significant Similarly, there are several conditions in children that
colony count. Bag urine not recommended. mimic a UTI and unfortunately all these children keep on
receiving antibiotics for suspected UTIs. I will mention a couple
of them. One of the common causes of dysuria, frequency, and
Microscopy of the urine may reveal the presence of urgency in girls is vulval erythema. Remember, this is not a
leukocytes. There is ample literature about what constitutes bacterial or fungal infection. They will present with exactly the
significant pyuria, but it is very important to note that same symptoms as a UTI and unless local examination is done
leukocytes may be present in the urine for varied other reasons properly, they will all have urine tests done. Often the urine
and do not always imply a UTI. They may be seen in any tests are abnormal as they reflect local inflammation rather
fever, dehydration, hypercalciuria, urolithiasis, inflammatory than a UTI and they get treated with antibiotics and have many
conditions like interstitial nephritis, glomerulonephritis and unnecessary tests done! It is an extremely common condition
in fact, in any inflammatory condition in the body (even a in outpatient department (OPD) practice, more so in the
severe respiratory infection). For the purpose of diagnosing tropical countries and the common causes of worsening this
UTI, presence of more than 5 leukocytes/hpf in fresh condition are repeated washing of the genital area and use of
centrifuged sample or more than 10 leukocytes/mm3 in an antifungal creams. These children do not have a UTI and do not
uncentrifuged sample is considered significant. Presence need antibiotics. A similar condition would be vulvovaginitis
of a positive urine culture in the absence of leukocytes in secondary to an infective etiology.
the urine, especially in an older child, should be a cue for Another condition that gets treated with multiple courses of
a thoughtful consideration about whether it is really a UTI. antibiotics is detrusor instability in children that presents with 487
ch-100.indd 487 11/24/2016 2:22:16 PM

frequency, urgency, and dysuria. They also will have daytime • Sick looking/“toxic” child
wetting, the information usually not being volunteered. Again, • Very young infants (less than 3 months of age) with high
stimulant drinks worsen this condition and no amount of grade fever.
antibiotic therapy will alleviate the symptoms. In case of an “office” UTI (OPD treatment), antibiotic
Another ”mimic” of a different category is a positive course of 7–10 days is sufficient. In children needing parenteral
tests for urine routine and/or urine culture when the child antibiotics, a total duration of 14 days would be required.
is asymptomatic. Assuming the urine is collected in an ideal However, once the fever and symptoms settle in 48–72 hours,
manner, this indicates asymptomatic bacteruria and needs no the antibiotic can be changed to an appropriate oral antibiotic.
treatment! There is no need to repeat the urine culture after the
When interpreting a urine test, all the above factors need to treatment is complete. Urine culture may need to be done
be borne in mind. again only if there is no symptomatic improvement suggesting
that UTI persists.
Clinical Pearl One of the common queries that crop up is regarding the
antibiotic sensitivity pattern. It usually becomes available after
• Remember urinary tract infection mimics like vulval redness, about 48–72 hours of starting therapy. Unless the child has not
detrusor instability, and asymptomatic bacteruria. responded in terms of symptoms, there is usually no need to
change antibiotics. In vitro and in vivo sensitivities are quite
different and an antibiotic that is perceived as resistant often
COMMON ORGANISMS works well in eliminating a UTI.
Briefly, gram-negative organisms usually cause UTIs.
They include E. coli, Klebsiella, Proteus and in some cases,
Other/Nonpharmacologic Therapy
Pseudomonas. Enterococci may be seen in infants and Often the most forgotten part! One needs to make an effort to try
some older children. UTIs due to gram-positive cocci, and decipher the reason for developing the UTI. This not mean
like Staphylococcus, should raise suspicion of obstructive jumping to radiological investigations, but talking to the child
pathology in the urinary tract. Atypical infections with fungi- and parents! Local factors, especially bladder bowel dysfunction
like Candida are also seen especially in children exposed to is a major risk factor for UTI. Addressing constipation, voiding
many antibiotics. regularly, ensuring an adequate fluid intake, and keeping the
postvoid residue to a minimum are some factors that go a long
way in preventing UTIs. Using a cotton underwear and clean
TREATMENT hygienic practice should also be advised.
Once a suspicion of UTI has been confirmed on the urine
tests, an antibiotic course has to be started. Remember, urine Clinical Pearl
culture reports become available after 24–48 hours and hence,
antibiotics have to be started based on local practice. The table • Do not forget to talk to the child/parent regarding constipation,
below suggests the antibiotics that can be used (Algorithm 1). regular voiding, and adequate fluid intake.
A single antibiotic is adequate to clear a UTI. Table 1
provides the options available . Following are the indications for
parenteral antibiotics, options of which are described in table 2: FOLLOW UP AND SUBSEQUENT CARE
• Inability to tolerate oral antibiotics
• Persistent vomiting Once the antibiotic course is completed, one of the dilemmas
is about prophylaxis, especially in view of recent literature.
The recommendation here is that prophylaxis is advocated for
Table 1: Oral antibiotics
all infants who have a UTI till all radiological investigations
Drugs Dose are complete or till 1 year of age. For older children, the role
Cefixime 10 mg/kg/day in 2 doses of prophylaxis looks less clear and if used, should be till all
investigations are complete or factors that are believed to be a
Co-amoxiclav 35 mg of amoxicillin, in 2 doses
risk factor for recurrent UTIs are addressed (e.g., constipation).
Ciprofloxacin 10–20 mg/kg/day in 2 doses There certainly seems no role for long-term prophylaxis for
Ofloxacin 15–20 mg/kg/day in 2 doses years together. The commonly used prophylactic agents are:
Cephalexin 50 mg/kg/day in 3 doses • Co-trimoxazole (to give trimethoprim in the dose of
1–2 mg/kg) once a day
Table 2: Intravenous antibiotics • Nitrofurantoin 1 mg/kg once a day
• Cephalexin 15 mg/kg once a day.
Drugs Dose The ideal prophylactic agent should not change the normal
Ceftriaxone 75–100 mg/kg/day in 1–2 doses periurethral flora. Hence, co-trimoxazole and nitrofurantoin
Amikacin 10–15 mg/kg single dose are better agents than cephalexin. There is no need to rotate
prophylactic agents. If the urine culture shows resistance to the
488 Gentamicin 5–6 mg/kg/day single dose
preventive agent, there is usually no need to change the agent
Co-amoxiclav 35 mg/kg/day of amoxicillin in 2 doses after the treatment of the UTI.
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Chapter 100: Approach to Urinary Tract Infection
There is no role for checking urine regularly (once a week/ Table 3: Recommended guideline for investigating urinary
fortnight/month) for reasons made very clear above. If the tract infections in children
child has symptoms, he/she should have urine tests done.
Age Investigations recommended
Clinical Pearl Less than 1 year US scan, DMSA, and MCUG
1–6 years US scan, DMSA
• Regular urine test to detect urinary tract infections has no role.
Do urine test only in symptomatic children as explained. More than 6 years US scan
US, ultrasound; DMSA, dimercaptosuccinic acid; MCUG, micturating cysto
urethrogram.
Radiological Investigations
There are recommended guidelines about the investigations
required after a child develops a UTI. They are listed in Table 3. Finally, an micturating cystourethrogram (MCUG) is not
These are the minimum investigations suggested for the indicated in all children with UTIs. Far too many MCUGs are
particular age group. Additional investigations are recom done for weak indications. In children less than 1 year of age
mended in the presence of recurrent UTIs, pyelonephritis or with a UTI or when bladder outlet obstruction is suspected,
abnormal investigations like an ultrasound scan. it is definitely indicated. Symptoms suggesting bladder outlet
Unfortunately, the recommended tests get done at the obstruction are as follows:
wrong time and are liable to wrong interpretation. • Poor urine stream
An ultrasound scan of the kidneys and bladder should be • Dribbling of urine
done as soon as possible in a child with UTI. For an inpatient, • Abdominal swelling (bladder)
it should be when the child is admitted and for an outpatient, it • Voiding by pressing the abdomen
should be soon and certainly within a week. Please be careful • Bilateral hydronephrosis and hydroureter on ultrasound
about interpreting the evidence of cystitis on the ultrasound scan
scan as a mildly thickened bladder wall. Unless the bladder • Large thick walled trabeculated bladder on ultrasound
is full, thickness cannot be interpreted with accuracy and • Antenatal scans with bilateral hydronephrosis/hydroureter
will look ”thickened”! One needs to look at the scan and not or large bladder.
the report. Please remember to give antibiotics to the child when the
The dimercaptosuccinic acid (DMSA) scan is useful in MCUG is being done. A 7-day course of antibiotics (2 days
showing up nonfunctioning areas of the kidneys. Acute changes before and 5 days after MCUG) is a fair practice. One could also
secondary to a UTI can last for as long as 4–6 months. The DMSA use intravenous antibiotics before MCUG or follow any other
scan is used to determine changes that may need to long-term local practice guideline for the purpose. I have seen several
monitoring. Hence, it is pointless to do a DMSA scan soon after a children who have developed a UTI after an MCUG when
UTI. Please remember that a DMSA scan should be done at least antibiotics have not been used and that is not acceptable.
4–6 months after an episode of UTI (the later, the better). It would be impossible to start commenting on actions
One should also realize that all changes seen on a DMSA required for various abnormalities seen on various scans as
scan do not indicate scarring secondary to a UTI (though the that would take up too much space. It should be remembered
report may say so!). One presumes that the DMSA scan would that an intravenous pyelogram is an extremely poor test for
have shown normal kidneys before the episode of UTI to be able renal scarring and is not recommended.
to confidently report scarring. That is a very big presumption.
There are many children who are born with abnormal kidneys/
imperfect embryogenesis/dysplasia and changes seen on a CONCLUSION
DMSA scan are similar to those reported as scarring. Note Last but not the least, do not forget to check the renal function
that the ultrasound scan may actually show normal kidneys of the child. As explained above, the only way to detect children
in these children. Hence, abnormalities on a DMSA scan have with abnormal DMSA scans (abnormality existing before
to be interpreted with caution. Clinical interpretation is more the UTI) is looking at the renal parameters. Ensure a serum
important rather than what is printed on the report (e.g., a single creatinine is done at least 2 weeks after the episode of UTI and
UTI is unlikely to cause a small kidney with very poor function). interpret appropriately to calculate the estimated glomerular
filtration rate. Also ensure a urine protein/creatinine ratio is
Clinical Pearls done to look for proteinuria at the same time.
• Dimercaptosuccinic acid scan for detecting long-term Urinary tract infection is a fairly common condition in
changes should be done at least 4–6 months after a urinary children and instead of alarming everyone including ourselves,
tract infection (UTI) let us analyze the situation correctly and take appropriate steps
• Ultrasound scan soon after a UTI so that management of a child with UTI is kept simple. Let us
also realize that recent literature is suggesting that long-term
• Micturating cystourethrogram, if required, after the UTI is
outcome for the kidneys is good in the face of an occasional
adequately treated.
UTI also! So it’s not all doom and gloom! 489
ch-100.indd 489 11/24/2016 2:22:16 PM

Key points
SUGGESTED READINGs
1. Indian Society of Pediatric Nephrology, Vijayakumar M, Kanitkar M, Nammalwar
))
Urine test for urinary tract infection (UTI) should be done only BR, Bagga A. Revised Statement on management of Urinary tract Infection. Indian
in symptomatic children. This includes children having fever Pediatrics. 2011 (48):709-17
without focus and or exhibiting urinary symptoms 2. Subcommittee on Urinary Tract Infection, Steering Committee on Quality
))
Appropriate advice regarding cleaning, collection of urine Improvement and Management, Roberts KB. Urinary tract infection: clinical
practice guideline for the diagnosis and management of the initial UTI in febrile
as a clean catch, and transport absolutely vital in making a
infants and children 2 to 24 months. Pediatrics. 2011; 128(3):595-610.
diagnosis of UTI 3. Tosif S, Baker A, Oakley E, Donath S, Babl FE. Contamination rates of different
))
Presence of significant number of leukocytes in the urine does urine collection methods for the diagnosis of urinary tract infections in young
not always indicate UTI. In the absence of symptoms and/or a children: observational cohort study. 2012;48(8):659-64.
positive urine culture, be careful of misdiagnosing UTI 4. Bachur R, Harper MB. Reliability of urinalysis for predicting UTI in young febrile
children. Arch Pediatr Adolesc med. 2001;155(1):60-5.
))
Do not forget to consider UTI mimics like vulval redness and 5. Luco M, Lizama M, Reichhard C, Hirsch T. Urine microscopy as a screen for
detrusor instability in the differential diagnosis of UTI urinary tract infection in a pediatric emergency unit in Chile. Pediatr Emerg Care.
2006;22(10):705-9.
))
In most cases, oral antibiotics suffice as treatment. In special
6. Silver SA, Baillie L, Simor AE. Positive urine cultures: A major cause of inappropriate
circumstances, intravenous antibiotics are needed to treat UTI antimicrobial use in hospitals? Can J Inf Dis Med Microbiol. 2009;20(4):107-11.
))
Apart from pharmacologic treatment, please ensure that 7. Fischer GD. Vulval disease in prepubertal girls. Australian J Dermat. 2001;
appropriate advice regarding prevention of further UTIs like 42:225-36.
treating constipation, fluid intake, etc. are also provided 8. Fischer G, Rogers M. Vulval diseases in children: a clinical audit of 130 cases.
Pediatr Dermatol. 2000;17:1-6.
))
Appropriate radiologic investigations need to be done after 9. Hannula A, Perhomaa M, Venhola M, Pokka T, Renko M, Uhari M. Long-
UTI, but ensure they are done at the appropriate times. term follow-up of patients after childhood UTI. Arch Pediatr Adolesc Med.
2012;166(12): 1117-22.
490
ch-100.indd 490 11/24/2016 2:22:16 PM

Chapter 101
Antenatal Renal Anomalies:
Outcome and Postnatal Management
Mehul A Shah
INTRODUCTION ureteric junction obstruction (PUJO), vesicoureteral reflux

(VUR), vesicoureteric junction obstruction (VUJO), and
Antenatal ultrasonographic-detected renal anomalies were multicystic dysplastic kidneys needs further evaluation in the
first reported by Garrett et al. in 1970. Since then, with routine neonatal period.
screening during pregnancy and availability of sophisticated
equipment, the incidence of antenatal renal anomalies has Clinical Pearl
increased. Initial reports showed 1% incidence of major
structural fetal anomaly with approximately 50% of those 1% • Most antenatal renal anomalies are BENIGN and only ~25% have
affecting central nervous system (CNS), 30% genitourinary, significant nephrouropathy that require further evaluation.
15% gastrointestinal (GI), and 5% cardiopulmonary systems.
Data from the past decade and half indicate a higher incidence
of renal anomalies, especially fetal hydronephrosis (HN) in up NORMAL FETAL URINARY TRACT
to 4.5% of pregnant women.
The fetal kidneys can be identified in utero by the 15th gestational
It is well recognized that delay in the maturation of renal
week, but visualization of internal renal architectures is usually
system can lead to transient dilatation of the urinary tract. Also,
the fetal upper urinary tract dilatation can be a dynamic process not possible until after the 20th week. The pelvicalyceal system
related to the effect of bladder (full bladder can cause back- and capsule are highly echogenic while the medulla is almost
pressure changes on upper tract). The early diagnosis of renal anechoic. The urine-filled pelvis may appear prominent
anomalies allows the obstetrician to plan delivery, especially in without obstruction. The fetal bladder can also be identified
those women with associated oligohydramnios, early neonatal in the early second trimester. Hourly fetal urine production
management, and prevention of long-term complications increases from 12 mL/h at 32 weeks to 26 mL/h at term. The
such as recurrent urinary tract infections (UTIs), hypertension, ureters are not imaged sonographically unless they are dilated.
and renal failure. On the other side, the disadvantages of early The amniotic fluid volume reflects renal function and
detection of renal anomalies include over work up and also patency of the genitourinary tract. The total volume of amniotic
excessive parental anxiety since approximately 70% of these fluid, which ranges from 500 to 2,000 mL, is also an important
anomalies are benign and known to resolve spontaneously. factor in a fetus with HN. In early gestation, the source of
Two risks should be avoided when managing antenatal amniotic fluid is a transudate of maternal plasma. By 20 weeks,
detected renal anomalies: (1) delayed therapy and (2) most amniotic fluid is fetal urine. The volume increases until
excessive treatment. Hence, knowledge about the correlation the end of the second trimester at a relative constant rate, then
of fetal renal ultrasonography (USG) abnormalities and it remains steady, and then decreases shortly before term. The
the final outcome is important for proper counseling. The normal amniotic fluid index (AFI) is between 8 and 20 cm.
challenge, within the babies with antenatal detected renal Decreased amniotic fluid volume, called oligohydramnios
anomalies, is to identify the small (<25%) number of babies (<8 cm), often indicates decreased fetal kidney function
who have significant renal disease requiring later surgery or (dysplasia). The other cause of oligohydramnios is placental
long-term follow up of renal function without subjecting the insufficiency. On the contrary, polyhydramnios (AFI >20 cm)
majority (~75% of those detected antenatally) to unnecessary is often associated with renal tubulopathy (such as Bartter’s
investigations and antibiotics. Certainly, baby boys with syndrome) indicating fetal polyuria, GI tract obstruction, CNS
posterior urethral valves (PUVs), and other babies with pelvi- malformation, and maternal diabetes mellitus.
ch-101.indd 491 11/21/2016 12:53:39 PM

Table 1: Hydronephrosis grading systems

Society for Fetal Urology Grading System (qualitative) Blachar’s Grading System (quantitative)
Grade 0: Normal No hydronephrosis, intact central renal complex Pelvis APD <4 mm
Grade 1: Mild Dilated renal pelvis Pelvis APD 5–9 mm
Grade 2: Moderate Dilated renal pelvis (more than grade 1) Pelvis APD 10–15 mm
Grade 3: Severe Dilated renal pelvis + dilated calyces Pelvis APD >15 mm + cortical thinning
Grade 4: Severe Dilated renal pelvis + dilated calyces + cortical thinning –
APD, anteroposterior diameter
Renal malformations detected antenatally, now referred to as Antenatal Hydronephrosis: Postnatal Outcome
congenital anomalies of the kidney and urinary tract can be
Based on several published reports, the following observations
broadly classified into three groups:
can be made:
1. Upper tract dilatation, without bladder abnormalities
(most common), and includes ureteric dilatation [antenatal • ~70% with AH are transient or isolated or benign (resolve
hydronephrosis (AH)] spontaneously)
2. Cystic kidney diseases (including multicystic dysplastic • 10–15% have VUR
kidneys, polycystic kidney disease, and cystic dysplasia) • 8–10% have PUJO
3. Bladder outlet obstruction (posterior urethral valves). • 5–10% have other urinary tract anomalies (PUV, VUJO,
duplex, etc.)
Grading System for Hydronephrosis
Antenatal Renal Anomalies: When to Worry?
There are different grading systems in the literature to assess
severity of HN (Table 1). Some are based on qualitative (only ~ 5–10% of all antenatal renal anomalies)
change in the pelvicalyceal system that are subjective and not • Oligohydramnios (indicates renal dysplasia/decreased
reproducible (such as Society for Fetal Urology system) and renal function)
some are based on quantitative changes (such as Blachar’s • Bilateral hydroureteronephrosis (boys/girls)–PUV, high
grading system for HN). Blachar’s grading system is based grade VUR
on anteroposterior renal pelvis diameter (APRPD), and is a • Bilateral severe HN (boys–PUVs, although not always)
quantitative system, thus more likely to be reproducible. • Bilateral enlarged and echogenic kidneys (ARPKD)
• Other organ anomalies (CNS, syndromic).
Clinical Pearl
Clinical Pearl
• Anteroposterior diameter of renal pelvis is the preferred
method for assessing severity of hydronephrosis and should • Only ~5–10% of all antenatal renal anomalies cause major
be insisted in the report. problems.
ANTENATAL HYDRONEPHROSIS Postnatal Evaluation

As with the grading system for postnatal HN, there is no The goal of evaluation is to identify all infants with significant
uniformly accepted definition of AH. In general, most authors nephrouropathy (~25% of all antenatal renal anomalies)
would define AH when the APRPD is greater than 5 mm at without subjecting the majority (~75%) to unnecessary
20 weeks of gestation and greater than 7 mm at 34 weeks. The radiological investigations and thereby, minimizing parental
APRPD greater than or equal to gestational age in months is anxiety, costs, and radiation exposure.
considered significant (for e.g., at 6 months, 6 mm or greater The possibility of significant nephrouropathy increases
dilatation of pelvis is significant). Of importance to note is that with the severity of HN, persistence of HN into the third
presence of calyceal dilatation or hydroureter at any stage is trimester, and bilateral involvement. Certainly, presence of
significant. Prenatal USG examination is important not only in oligohydramnios (AF <8 cm) and bilateral severe HN indicates
mid pregnancy (~20–22 weeks) but also in the third trimester to high possibility of PUV in a male baby.
detect upper tract anomalies that can be missed in early scans. According to the study by Bernardica Valent-Moric, the
In the study by Bernanrdica Valent-Moric et al., almost 47% of incidence of significant nephrouropathy was 95% (19 of 20) in
AH was detected between 30 and 38 weeks of gestation. Hence, infants with severe HN, 53% (23 of 43) in infants with moderate
a third trimester USG between 30 and 38 weeks’ gestation is HN, and 29% (23 of 82) in infants with mild HN.
necessary in addition to targeted imaging for fetal anomalies The management of infants with AH is based upon two
scan at 20 weeks to detect renal anomalies. factors: severity of HN and presence of unilateral or bilateral
HN. With severe or bilateral HN, the first postnatal USG is done
Clinical Pearl within 2 days of birth, and in others, the first USG is postponed
492 • Third trimester scan is necessary to detect at least 40% of renal
until 7–10 days of life when diuresis is established.
anomalies.
Table 2 shows the timing of various radiological imaging
in relation to severity of HN. There is practically no role of
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Chapter 101: Antenatal Renal Anomalies: Outcome and Postnatal Management
Table 2: Postnatal evaluation of antenatal hydronephrosis— timing of imaging studies

USG MCUG DTPA/EC/MAG3 renal scan
Unilateral or bilateral mild hydronephrosis 1st: 7–14 days 3–6 months age* 2–3 months age (Algorithm 1) may not
2nd: 1–2 months† (Algorithm 1) be required in most cases
Bilateral moderate-to-severe‡ hydronephrosis or 1st: 1–3 days Boys: 2–4 days (before 2–3 months age
unilateral/bilateral hydroureteronephrosis 2nd: 1–2 months discharge) to r/o PUV
Girls: 2–3 months
Severe hydronephrosis in a solitary kidney 1st: 1–3 days Boys: 2–4 days 2–3 months or may be earlier if serum
2nd: 1–2 months Girls: 2–4 days creatinine is increasing, or urosepsis
*Perform MCUG in first week of life if there is any suspicion of PUV (in boys)
†Always perform second USG at 1–2 months even if first USG was normal
‡Hydronephrosis: mild, pelvis APD 5–9 mm; moderate, pelvis APD 10–15 mm; severe, pelvis APD >15 mm.
USG, ultrasonography; DTPA, diethylene triamine pentaacitic acid; MCUG, micturating cystourethrogram; EC, ethylcysteine; MAG3, mercaptoacetyltriglycine; APD,
anteroposterior diameter.
intravenous pyelogram (IVP) in neonates or infants. Rarely, UNILATERAL OR BILATERAL MILD-

IVP or magnetic resonance urogram may be required to TO-MODERATE HYDRONEPHROSIS
evaluate ectopic/single/malrotated kidney with either HN
or hydroureteronephrosis (where there is a doubt regarding (anteroposterior renal pelvis
presence of only PUJO, only VUJO or both). diameter 5–14 mm)
Clinical Pearl Ultrasonography at 7–10 days and 1–2 months (second USG
is always done even if first USG is normal—since first USG
• Possibility of significant nephrouropathy in infants with may be normal due to the effect of physiological oliguria
severe hydronephrosis (anteroposterior renal pelvis diameter in first few weeks of life where HN may not be apparent)
>15 mm) is 95%. (Algorithm 1).
Algorithm 1
Approach to a newborn with antenatal hydronephrosis
IAHN, isolated antenatal hydronephrosis; VUR, vesicoureteral reflux; PUJO, pelviureteric junction obstruction; APRPD, anteroposterior
renal pelvis diameter; USG, ultrasonography; DTPA, diethylene triamine pentaacitic acid; MCUG, micturating cystourethrogram.
493
ch-101.indd 493 11/21/2016 12:53:40 PM

If HN is persisting on the second USG, then a micturating

cystourethrogram (MCUG) is performed to rule out VUR. Clinical Pearl
Infants with normal MCUG and increasing HN will require • If renal ultrasonography (USG) is performed on day 1–3 of
diethylene triamine pentaacitic acid (DTPA) or ethylcysteine life, repeat renal USG is mandatory between 2 and 4 weeks of
(EC) renal scan at 3–6 months to rule out PUJO. If the HN is age (since in first few days, because of physiological oliguria,
stable or improving, a DTPA renal scan may not be necessary. hydronephrosis may not be evident)
If the suspicion of PUV is high (poor urinary stream,
palpable bladder, oligohydramnios), USG and MCUG should
be performed before baby is discharged from nursery. ISOLATED ANTENATAL HYDRONEPHROSIS
The majority of cases with mild or moderate HN appear to
resolve by 18 months of age, In one study of 282 infants with It is defined as isolated renal pelvic dilatation without
mild-to-moderate HN, majority resolved by 18 months age (i.e., associated urinary tract abnormalities (i.e., absence of calyceal
APRPD less than 5 mm on two consecutive USG) and only 6% dilatation, cortical thinning, hydroureter, VUR, PUJO, and
had significant nephrouropathy (14 had PUJO and 4 had VUR). bladder anomalies) i.e., these infants have a normal MCUG
and a normal DTPA renal scan.
In a paper published by Sidhu et al. from the Hospital for
Unilateral severe hydronephrosis Sick Children, Canada, following observations were made:
Here, USG is performed in first week of life followed by another • APRPD <12 mm, Society of Fetal Ultrasound grade 1–2:
at 1–2 months age. Since the possibility of PUJO is higher, DTPA benign condition, most improve (95%)
or EC renal scan is next performed at 2–3 months of age. If the • Presence of cortical thinning: marker of deterioration
DTPA scan is negative for obstruction, then a MCUG is done to • Severe grades: variable rates of stabilization (60%).
rule out VUR. The authors concluded that there is sufficient evidence
to suggest that mild HN (APRPD <12 mm) is a self-limited
condition and that clarification is required for moderate-to-
Severe hydronephrosis
severe HN.
(bilateral or solitary kidney) Rarely, HN may worsen after initial improvement (<2%).
Infants with severe bilateral AH and/or bladder distension As a result, if there is persistent dilation at 3 months of age (in
should have serial renal function tests done in first few days of absence of VUR or PUJO), we suggest to monitor the degree
life. USG and MCUG [under intravenous (IV) cefotaxime cover] of HN with an ultrasound performed at 1 and 2 years of age,
are performed in first 2 days of life to exclude PUV in boys and and if needed, between 3 and 5 years of age. Most often the
VUR in boys and girls. If there is no evidence of bladder outlet resolution of mild-to-moderate HN occurs by 18 months of age
obstruction (PUV or neurogenic bladder), then a DTPA or EC in majority of patients.
renal scan is performed between 2 and 3 months of age to rule
out PUJO or VUJO.
Obtaining DTPA renal scan in first month of life does not
Vesicoureteral REFLUX
provide accurate results due to renal function immaturity After isolated (benign) HN, VUR is the next common urinary
[i.e., low glomerular filtration rate (GFR) physiologically and tract abnormality detected though antenatal screening in
DTPA molecule is excreted mainly by glomerular filtration]. approximately 10–15% babies.
Hence, a dynamic scan is delayed until 2–3 months age Vesicoureteral reflux is associated with long-term
when the GFR is roughly 50–60 mL/min/1.73 m2 [except complications related to recurrent UTIs as well as dysplasia
mercaptoacetyltriglycine (MAG3) renal scan that can be associated with high-grade reflux. These complications
performed in first month since MAG3 is excreted mainly by include hypertension, proteinuria, chronic kidney disease, and
tubular secretion and this function matures faster than the pregnancy-related complications in women.
GFR in newborns]. Through antenatal screening, VUR is suggested by
• APRPD <15 mm (15% incidence)
ROLE OF PROPHYLACTIC ANTIBIOTICS • APRPD >15 mm and PUJO is ruled out on DTPA scan
• Fluctuating renal pelvis anteroposterior diameter on serial
Based on the low risk of UTI in most babies with PUJO and USGs
isolated HN as well as the current evidence suggesting an • Hydroureteronephrosis.
early diagnosis followed by prompt treatment of febrile UTI in
children with VUR, most babies do not need chemoprophylaxis.
This is also suggested from our observation of only 4 out of 115
Diagnosis
babies with antenatal renal anomalies developing febrile UTI The diagnosis is made using MCUG done under antibiotic
(2 had PUV, 1 VUJO, and 1 had isolated HN). cover (1 day before and 2 days after MCUG). Treatment of VUR
In babies with documented VUR or PUV or those with depends upon several factors especially severity of reflux and
severe HN pending further imaging (MCUG and DTPA renal includes chemoprophylaxis, surgical therapy in elect cases,
scan), cephalexin should be used for UTI prophylaxis at 5 mg/ circumcision in boys, and only observation in infants with
494 kg/dose two times a day. grades 1–2 VUR.
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Chapter 101: Antenatal Renal Anomalies: Outcome and Postnatal Management
PELVIURETERIC JUNCTION OBSTRUCTION Management of MCDK is conservative. Until mid-1980s,

infants were subjected to surgery (nephrectomy) that is now
Pelviureteric junction obstruction is often due to lack of or reserved for infants with huge renal mass. Most children are
decreased ganglion cells with resultant decreased peristalsis. followed conservatively with:
It is suggested by APRPD greater than 15 mm and diagnosis is • Renal USG once in a year for 5 years and then every
confirmed by DTPA (or EC) renal scan at 2–3 months of age. 2–3 years
This renal scan is delayed until 2 months of age since there is • Asessment of growth and blood pressure (BP) once a year
a natural maturation of renal function and GFR usually triples (routine)
that of newborn period at 2 months (~60 mL/min/1.73 m2) • Moderate salt and nonvegetarian (meat) protein reduction
that permits better visualization of the kidneys. Occasionally, in family’s diet to decrease the risk of hypertension and
EC or MAG3 renal scan may be performed in the first few proteinuria in later life
weeks of life especially if there is bilateral severe HN or HN • Avoidance of contact sports to prevent trauma to contra-
in a solitary kidney. IVP essentially does not have a role in lateral hypertrophied kidney.
diagnosis of PUJO.
Since the natural history of PUJO is that of spontaneous
resolution in a significant number of cases, majority of children POSTERIOR URETHRAL VALVES
with PUJO can be managed conservatively. Conservative Posterior urethral valves are the most serious and fortunately
management includes 3–4 monthly USG and DTPA renal scan less common of the antenatal renal anomalies. During
until 1 year of age and then 6 monthly for another 1 year. Early the antenatal period, PUV can be suggested by bilateral
detection and prompt treatment of UTI is very important. hydroureteronephrosis/bilateral HN, echogenic renal cortex,
Since the risk of UTI is low, chemoprophylaxis is usually not distended bladder, and decreased amniotic fluid. Adequate
indicated. AFI is one of the most important predictors of long-term renal
Surgery for PUJO is indicated in following conditions: outcome in PUVs. Oligohydramnios is associated with more
• Palpable renal mass than 75% incidence of renal failure and pulmonary hypoplasia.
• Presence of cortical thinning Postnatal evaluation includes observation of urinary
• APRPD >25 mm stream, presence of renal and bladder mass, and respiratory
• Split renal function <40% on DTPA renal scan status (distress, oxygen requirement, lung expansion on
• Recurrent UTI’s. X-ray). Renal USG is to be performed on day 1–2 followed
by MCUG under antibiotic cover. Serial monitoring of renal
MULTICYSTIC DYSPLASTIC KIDNEY parameters and serum electrolytes including bicarbonate
is very important. In most cases, cystoscopy and primary
Multicystic dysplastic kidney (MCDK) is the most common
fulguration of valves can be performed in the neonatal period.
cystic renal anomaly and occurs in approximately1 in 2,000
Postfulguration, infants need to be maintained on cephalexin
births. The MCDK is a nonfunctioning kidney characterized
prophylaxis (until at least 6 months or longer duration in
by multiple noncommunicating cysts and absence of
presence of VUR). Long-term follow-up for growth, blood
identifiable renal parenchyma. It results from disturbance
pressure, metabolic acidosis (Type IV renal tubular acidosis),
in ureteric bud development during early pregnancy.
and renal and bladder function is mandatory.
The differential diagnosis of MCDK includes severe PUJO
Approximately 25–30% of children with PUVs can progress
(dilated pelvi-calyceal system appears as “cysts”), autosomal
to end-stage renal disease (chronic renal failure). Poor
dominant polycystic kidney disease, and simple cysts (usually
prognostic markers include oligohydramnios, bilateral high
single). There is a 25–30% incidence of renal anomalies on the
grade VUR, and echogenic kidneys. Appropriate and timely
contra lateral side (i.e., the normal kidney). Of these, VUR
intervention can decrease the morbidity associated with PUVs.
(reflux) is the most common followed by PUJO, VUJO, and
duplex system.
The natural history of MCDK includes spontaneous Prenatal Counseling
involution/regression in 75% cases and decrease in size to
smaller than 5th percentile after 6 years of age in majority. The Obviously, presence of fetal kidney dilatation causes parental
outcome of children with MCDK is benign. The incidence of anxiety and raises a number of doubts regarding the immediate
hypertension and malignancy/Wilm’s tumors is essentially and long-term outcome of the baby specifically regarding the
zero percent. kidney function. Since most studies report lower incidence of
Evaluation of a neonate with antenatal suspicion of MCDK significant uropathies (PUV, PUJO, and VUR), first thing to do
includes is to reassure the family regarding the common nature and
• Renal USG between 7 and 21 days of life usually benign course of most conditions. Most unilateral HN
• DTPA/dimercaptosuccinic acid renal scan at 3 months of or cystic kidneys have a good long-term outcome as long as
age the other kidney is normal. When dealing with unilateral HN,
• MCUG at 3–6 months of age to rule out VUR on the normal the family can be counseled regarding the step-wise work up
side. of the baby between birth and 3 months of age. Unilateral 495
ch-101.indd 495 11/21/2016 12:53:40 PM

fetal HN of any severity does not need any intervention or

early delivery. Key points
With bilateral severe HN, possibilities of PUV, VUR, PUJO ))
Approximately 75% of antenatal renal anomalies are benign
and other uropathies is discussed. Of all the uropathies, and ~25% have significant nephrouropathies. Balance between
PUV is the only one that is associated with chronic kidney overinvestigation and underinvestigation is important
disease chronic renal failure in approximately 30% children. ))
First postnatal ultrasonography (USG) should be obtained
Adequacy of amniotic fluid in the second and third trimester between 7 and 14 days in babies with unilateral hydro
is an important prognostic marker for future/long-term renal nephrosis (HN) or bilateral mild HN.
function. If amniotic fluid is decreased (especially if AFI is <5 ))
Based on second USG at ~ 1–2 months, further investigations
cm] in presence of bilateral HN, the risk of postnatal kidney [micturating cystourethrogram (MCUG) or diethylene triamine
failure requiring dialysis and kidney transplantation is very pentaacitic acid renal scan] can be planned
high (~90%). In case of VUR or PUJO, even if surgery is required, ))
We do not want to miss posterior urethral valves in baby boys
the timing of surgery is usually between 2 and 24 months of age before discharge. Obtain serial renal function test, USG, and
and not immediately after birth. MCUG in first few days of life if there is bilateral moderate-to-
The indication for early delivery is usually based on severe HN, hydroureteronephrosis, or distended bladder in
obstetric factors. The only fetal factor that may necessitate early baby boy.
delivery is when there is worsening oligohydramnios (usually
seen in boys with PUV or neurogenic bladder associated renal
dysplasia) After inducing lung maturation with steroids, early SUGGESTED READINGs
delivery can then be planned. 1. Alconcher LF, Tombesi MM. Natural history of bilateral mild isolated antenatal
hydronephrosis conservatively managed. Pediatr Nephrol. 2012;27:1119‑23.
2. Blachar A, Blachar Y, Livne PM, Zurkowski L, Pelet D, Mogilner B. Clinical outcome
CONCLUSION and follow-up of prenatal hydronephrosis. Pediatr Nephrol. 1994;8:30-5.
3. Brunisholz Y, Vial Y, Maillard-Brignon C, Meyrat BJ, Frey P, Hohlfeld P. Prenatal
Antenatal renal anomalies are being identified more diagnosis of urinary malformations: results in a series of 93 consecutive cases.
frequently. Postnatally, balance between overinvestigation Swiss Med Weekly. 2001;131:95-8.
and underevaluation is required. The goal is to identify 4. Duncan KA. Antenatal renal pelvis dilatation: the long-term outlook. Clin Radiol.
significant nephrouropathy (such as PUV, VUR, PUJO, VUJO, 2007;62:134-9.
and MCDK) before long-term complications set in and 5. Gupta DK, Bajpai M, Chandrasekharam VVSS, et al. Antenatally detected
prevent complications such as recurrent UTI’s, renal stones, pelviureteric junction obstruction: safety of conservative management by our
protocol. Indian Journal of Urology 2000;17:24-7.
hypertension, proteinuria, and kidney failure. Transient
6. Hadlock FP, Deter RL, Carpenter R, Gonzalez ET, Park SK. Sonography of fetal
(isolated or benign) HN is the most common cause of AH. urinary tract anomalies. Am J Radiology. 1981;137:261-7.
Unilateral HN can be completely evaluated by 3 months of 7. Ismaili K, Avni FE, Alexando M. Routine VCUG is of no value in neonates with
age starting with a renal USG between 7 and 14 days of life unilateral MCDK. J Pediatr. 2005;146:759-63.
followed by second USG at 2 months of age and then MCUG 8. Khalid I, Avni FE, Wissing M, Hall M. Long-term clinical outcome of infants with mild
(if APRPD is between 5 and 15 mm) or DTPA renal scan (if and moderate fetal pyelectasis: validation of neonatal ultrasound as a screening tool
APRPD > 15 mm). If renal USG is done in the first week of to detect significant nephro-uropathies. J Pediatr. 2004;144:759-65.
9. Kitagawa H, Pringle KC, Stone P, Flower J, Murakami N, Robinson R. Postnatal
life, a repeat renal USG should be performed between 2 and
follow-up of hydronephrosis detected by prenatal ultrasound: the natural history.
4 weeks of age, once the urine output is established. Two Fetal Diagn Ther. 1998;13:19-25.
normal renal USGs (APRPD <5 mm) in first 2 –3 months of life 10. Narchi H. Risk of hypertension with multicystic kidney disease: a systematic
can rule out approximately 95% of urinary tract abnormalities. review. Arch Dis Child. 2005;90:921-4.
Calyceal dilatation and cortical thinning always indicate a 11. Sidhu G, Beyene J, Rosenblum ND. Outcome of isolated antenatal hydronephrosis:
serious pathology. Bilateral hydroureteronephrosis or severe a systematic review and meta-analysis. Pediatr Nephrol. 2006;21:218-24.
bilateral hydronephrosis should be evaluated with serial 12. Valent-Morić B, Zigman T, Cuk M, Zaja-Franulović O, Malenica M. Postnatal
evaluation and Outcome of infants with antenatal hydronephrosis. Acta Clin
creatinine, USG, and MCUG in first week of life (mainly to Croat. 2011;50:451-55.
detect PUV). The only major anomaly that should not be 13. Zaccara A, Giorlandino C, Mobili L, Brizzi C, Bilancioni E, Capolupo I, et al.
missed before discharge of a new born baby boy is posterior Amniotic fluid index and fetal bladder outlet obstruction. Do we really need more?
urethral valves. J Urol. 2005;174:1657-60.
496
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Chapter 102
Acute Kidney Injury
VK Sairam
INTRODUCTION CLASSIFICATION
Acute kidney injury (AKI) is a sudden loss of renal function The classification of AKI is based on the anatomic location of
that occurs due to multiple causes leading to a decline in initial injury. It is classified as prerenal, renal, and postrenal
glomerular filtration rate (GFR) and accumulation of urea and locations for AKI.
nitrogenous waste products. It also results in fluid imbalance Prerenal AKI in children is due to hypovolemia [bleeding or
and electrolyte dysregulation. The presence of AKI results in gastrointestinal (GI) loss, or urinary loss or cutaneous, loss], or
increase in mortality and morbidity of children. Hence, it is reduction of effective circulatory volume (nephrotic syndrome,
very essential that pediatricians are aware of this entity and be cirrhosis, or septic shock)
competent to prevent and treat it. Renal AKI is due to structural damage to the kidney due
The new terminology AKI has replaced acute renal failure. to glomerular disease or prolonged hypoperfusion, sepsis, or
It is now widely used by Nephrologists to indicate acute loss nephrotoxins.
of renal function. AKI presents with wide range of clinical Postrenal AKI is due to congenital or rarely acquired causes
manifestation from a slight rise of serum creatinine to an of obstruction of lower urinary tract.
anuric renal failure. The rise in serum creatinine is considered
to be the marker of an acute event of the kidney. It has to be Clinical Pearl
remembered that serum creatinine rise is often delayed and • The clinician should evaluate and understand the site of renal
imprecise. It is a value that reflects GFR in a steady state and injury.
does not reflect GFR in a patient with changing renal function.
Despite these limitations, serum creatinine continues to be the
most widely used laboratory parameter to indicate AKI. CLINICAL features
The recognition for a definition for AKI, the pediatric
Risk, Injury, Failure, loss of kidney function, and End-stage The signs and symptoms are directly related to the alteration of
kidney disease (RIFLE) classification was proposed. This will renal function. These include edema, reduced urine output or
enable us to recognize children with AKI early and intervene anuria, hematuria (microscopic or gross), hypertension, and in
appropriately. It has graded levels of injury (risk, injury, failure, some children, breathing difficulties. There may be features of
loss of kidney function and ESRD) based on the elevation of shock or heart failure or features of acute PIGN. There may be
serum creatinine or urine output. in few children features of joint pain, rash, and associated renal
The etiology of AKI in developed countries in the last two injury due to disorders such as systemic lupus erythematosus
decades has been changing from primary glomerular diseases (SLE) or Henoch-Schonlein purpura (HSP). Rarely, patients
to hospital-acquired renal diseases. The causes that lead to with interstitial nephritis can present with rash, malaise,
hospital-acquired AKI are sepsis, nephrotoxic drugs, and renal vomiting, and rise in serum creatinine.
ischemia. In developing countries, the etiology is due to dehy On physical examination, edema, rise in blood pressure,
dration, sepsis, and primary renal diseases such as postinfective respiratory distress, weight gain, and signs of underlying
glomerulonephritis (PIGN) and hemolytic uremic syndrome disease (PIGN, SLE, or HSP) can be detected. Also signs of
(HUS). The incidence of AKI is increasing in developed countries volume depletion (dry mucous membrane, decreased turgor,
due to increased number of complicated patients taken care in orthostatic fall of blood pressure, or decreased blood pressure)
the neonatal and pediatric intensive care units. are all indicative of a prerenal AKI.
ch-102.indd 497 11/21/2016 12:55:37 PM

Diagnosis prognostic utility in setting of AKI and may allow clinicians to

diagnose early and intervene.
Elevated blood urea nitrogen or urea and serum creatinine is a
hallmark of AKI. Abnormal urine analysis is feature of nephritis.
Renal Imaging
Other features such as hyperkalemia, hypo- or hypernatremia,
high anion gap acidosis, hypocalcemia, or hyperphosphatemia Renal ultrasound is useful in patients whose etiology of AKI is
are noted in AKI. not clear. The presence of a normal architecture of the kidneys
is reassuring to the nephrologist. The presence of small-sized
Urinalysis kidney means the etiology is of long-standing chronic disease.
An acute injury to the kidney results in increased size of the
Urine analysis is very helpful to detect the cause of AKI. The kidney. The echogenicity is increased in patients with AKI or
presence of red blood cell casts, dysmorphic red blood cells, in patients with a chronic kidney disease. Renal ultrasound is
and proteinuria are all indicative of nephritic urinary sediment. diagnostic in patients with obstructive etiology such as posterior
Muddy-brown granular casts is suggestive of acute tubular urethral valves, neurogenic bladder, or high grade reflux.
necrosis. Pyuria with white cell casts is indicative of urinary Renal biopsy is rarely required in patients with AKI. It is
tract infections. White cell casts can also be seen in acute done in patients with rapidly progressive glomerulonephritis
glomerulonephritis. The positive response to heme on dipstick (RPGN) to enable guide therapy. Similarly, in patients with
with absence of RBC in the sediment is seen in patients with lupus nephritis associated AKI, renal biopsy is indicated.
hemolysis or rhabdomyolysis. Patients with prerenal AKI have Once diagnosis of AKI is made, then further evaluation is
a normal urine analysis. focussed on determining the cause. The evaluation consists
Urine specific gravity is less than 1.010 in acute tubular of history, physical examination, and laboratory evaluation.
necrosis (ATN). Patients with prerenal disease have a specific Renal imaging is performed in most patients. Renal biopsy is
gravity greater than 1.020. very rarely required.
Urine osmolality is more accurate measure of the
concentrating ability. Patients with ATN have an osmolality of Clinical Pearl
less than 350 mosmol/kg and patients with prerenal disease
have osmolality greater than 500 mosmol/kg. • Urinalysis is an essential initial investigation in evaluation of a
Fractional excretion of sodium (FENa) is used to child with acute kidney injury and often forgotten.
differentiate prerenal AKI and intrinsic AKI.
Urine sodium × Serum creatinine TREATMENT

FENa = × 100
Serum sodium × Urine creatinine The management of a child with AKI should be initiated
Less than 1% prerenal, greater than 2% intrinsic renal AKI immediately under the guidance of a pediatric nephrologist.
FENa in neonates is higher. Less than 2% prerenal, greater It is very essential to first assess the fluid status of the child
than 2.5% intrinsic renal AKI. and identify the etiology of AKI. The treating physician has to
deal with the volume issues of the child and decide to treat
Other Investigations accordingly (Algorithm 1). Any treatable underlying causes
of AKI should be considered, such as RPGN and septic AKI,
Blood urea nitrogen/creatinine greater than 20 suggestive of should be treated accordingly.
prerenal AKI and 10–20 suggestive of ATN. The principles of treatment of a child with AKI are:
Complete blood count with a peripheral smear is suggestive (Algorithm 2)
of thrombocytopenia and hemolytic anemia in patients with • Hypovolemic children require normal saline bolus of
HUS. The presence of blasts cells are seen in patients with 10–20 mL/kg over 30 minutes repeated twice as needed.
leukemia with tumor lysis-associated AKI. The presence of This is given to restore the renal function to prevent the
eosinophils in the urine is suggestive of interstitial nephritis. progression of prerenal AKI to intrinsic renal AKI.
Complement levels C3 is low in PIGN, membrano • In euvolemic children, fluid should be administered to a
proliferative glomerulonephritis (MPGN), and SLE. total of urine output in addition to insensible water loss
Serological testing for streptococcal infection is required (400–500 mL/m2/day).
in patients with PIGN. In patients with drug-induced • Hypervolemic children with fluid overload require fluid
nephrotoxicity, the drug levels are measured such as levels removal and restriction of fluid intake. Furosemide is
of aminoglycosides or acetaminophen. The rise in the levels attempted to convert oliguric to nonoliguric AKI, thereby
of uric acid is seen in patients with leukemia, and lymphoma making it easy for the treating physician to give fluids and
associated with tumor lysis syndrome. Lactate dehydrogenase nutrition without altering the overall course of the disease.
is increased in patients with HUS, hemolytic disorders, or If the bolus of lasix (2–5 mg/kg/dose) provide a response
malignancies. immediately and the AKI is less than 24-hour duration,
then a continuous lasix infusion (0.1–0.3 mg/kg/h) can be
Biomarkers provided.
Novel biomarkers such as neutrophil gelatinase-associated • In critically sick children, percent fluid overload correlates
498 lipocalin, kidney injury molecule, or interleukin-18 have with overall survival rate. Fluid overload more than 10%
ch-102.indd 498 11/21/2016 12:55:37 PM

Chapter 102: Acute Kidney Injury
Algorithm 1
Clinical Pearl
Assessment of initial fluid status and management
• Assessment of fluid status of the child is the most important
step in the management of acute kidney injury.
Key points
))
There is a new terminology of acute kidney injury (AKI) for
acute renal failure with a classification system of pediatric
Risk, Injury, Failure, loss of kidney function, and End-stage
kidney disease to enable treating physicians to recognize the
condition early and intervene appropriately
Algorithm 2 ))
The incidence of AKI in developed countries is increasing due
to increased number of complicated patients that are now
Management of acute kidney injury
taken care in intensive care units
))
It is important to pinpoint the location of the renal injury
(prerenal, renal, or postrenal). This is an essential step in
understanding of AKI
))
The detailed history of the presenting illness is an essential
requirement and there may be clues on the physical
examination and etiology of AKI
))
The signs and symptoms are directly related to the alteration
of renal functions
))
Urine analysis is a very important initial investigation
))
The most essential step in the management of AKI is for the
clinician to learn to assess the fluid status of the child and
treat accordingly
))
Electrolyte dysregulation is common in AKI and needs
treatment accordingly
))
Underlying causes of AKI, if detected, should be treated
correlates with higher morbidity and consideration of
renal replacement therapy. It is highly recommended to
))
Assessment of fluid overload and early initiation of appropriate
renal replacement therapy
initiate renal replacement therapy if the fluid overload is
greater than 15%. ))
It is also very essential to avoid nephrotoxic drugs and all
renally excreted drugs should be adjusted to a GFR of less
Percent fluid overload than 10 mL/min irrespective of the present serum creatinine.
Total fluid in litres – Total fluid out in litres Other investigations to be done are based on the clinical
= × 100 presentation and initial course.
Admission weight
Electrolyte dysregulation, such as hyperkalemia, hyper
phosphatemia, hypocalcemia, and elevated anion gap SUGGESTED READINGs
metabolic acidosis is common in AKI and needs treatment 1. Goldstein SL. Advances in Pediatric renal replacement therapy for acute kidney
accordingly. Children with AKI develop hypertension due to injury. Semin Dial 2011;24:187-91.
fluid overload or renin mediated and requires monitoring and 2. Goldstein SL, Currier H, Graf Cd, Cosio CC, Brewer ED, Sachdeva R. Outcome
treatment accordingly. in children receiving continuous venovenous hemofiltration. Pediatrics.
Acute kidney injury is associated with increased catabolic 2001:107;1309-12.
rate and therefore, good nutritional support is needed 3. Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epidemiology at a tertiary
to enable good recovery. It is also very essential to avoid care center from 1999 to 2001. Am J Kidney disease. 2005;45;96-101.
nephrotoxic drugs and all renally excreted drugs should be 4. Modem V, Thompson M, Gollhofer D, Dhar AV, Quigley R. Timing of continuous
adjusted to a GFR of less than 10 mL/min irrespective of the renal replacement therapy and mortality in critically ill children. Crit care med.
2014;42(4):943-53.
present serum creatinine.
5. Krishnamurthy S, Narayanan P, Prabha S, Mondal N, Mahadevan S, Biswal N,
The renal replacement therapies are hemodialysis,
et al. Clinical profile of acute kidney injury in a Pediatric intensive care unit
peritoneal dialysis, and continuous renal replacement therapy. form southern India. A prospective observational study. Indian J Crit care med.
The choice of therapy depends on clinical situation and the 2013;17:207-13.
expertise of the treating physician. The indications of renal 6. Imani PD, Odiit A, Hingorani SR, Weiss NS, Eddy AA. Acute kidney injury and its
replacement therapy are fluid overload, hyperkalemia, uremia, association with in-hospital mortality among children with acute infections. Pediat
and life-threatening pulmonary edema or hypertension. Neph. 2013;11;2199-206. 499
ch-102.indd 499 11/21/2016 12:55:37 PM

Chapter 103
Enuresis
Jyoti Sharma
INTRODUCTION Table 1: Conditions that may precipitate secondary enuresis
Enuresis refers to intermittent incontinence in discrete episodes Condition Possible mechanism

while asleep; sometimes called nocturnal enuresis (NE) to Cystitis Reduced bladder capacity
add extra clarity. It is essential to subgroup these children as
Constipation Reduced bladder capacity
having monosymptomatic (MNE) and nonmonosymptomatic
enuresis (NMNE). The latter refers to children who have Sleep-disordered breathing Impaired arousal
concomitant symptoms of lower urinary tract (LUT) Diabetes mellitus Nocturnal polyuria
malfunction, i.e., increased (>eight times) or decreased (<three
times) voiding frequency, daytime incontinence, urgency, Diabetes insipidus Nocturnal polyuria
hesitancy, straining, a weak stream, intermittency, holding Chronic kidney disease Nocturnal polyuria
maneuvers, a feeling of incomplete emptying, postmicturition Urethral obstruction Reduced bladder capacity
dribble, and genital or LUT pain.
Neurogenic bladder Reduced bladder capacity
Clinical Pearl Psychological stress —
• Nonmonosymptomatic enuresis is more common; when a voiding, incontinence, urinary retention, renal scarring, and
detailed history is obtained, the majority of children have at hypertension. It is important to identify this disorder based on
least subtle daytime symptoms history and abnormal uroflowmetry since it requires specific
• Children and adult perceptions of daytime voiding symptoms management.
differ. Hence, careful questioning of the child is recommended. The focus of this chapter is MNE and NMNE with symptoms
of an overactive bladder and does not address conditions
Genetic influences on primary NE are heterogenous and requiring special investigations and management, including
complex. When one or both parents have a history of enuresis, dysfunctional voiding.
the incidence in children is 44 and 77% respectively, compared
with a 15% incidence in children whose parents do not have a
history of enuresis.
PATHOGENESIS
The term secondary enuresis is used to describe children The three factors presumed to play a role in the pathogenesis
who have had a previous dry period of at least 6 months; and hence, also targeted for management are:
otherwise the term primary enuresis should be used. A 1. A disorder of sleep arousal: children do not wake up to the
cause for secondary enuresis can usually be identified and sensation of a full or contracting bladder
management is directed toward this (Table 1). 2. Nocturnal polyuria
Dysfunctional voiding, which may also be associated with 3. A reduced nocturnal bladder capacity.
enuresis is characterized by an intermittent and/or fluctuating Nocturnal polyuria may be due to a combination of factors
uroflow rate due to urethral sphincter overactivity during that include a low fluid intake during the school hours and large
voiding in children with normal neurological function. This intakes in the evening, a high solute intake (dinner) close to the
leads to very high filling and voiding pressures, prolonged bedtime, and a low nocturnal secretion of antidiuretic hormone.
ch-103.indd 500 11/21/2016 12:57:03 PM

Chapter 103: Enuresis
Reduced functional nocturnal bladder capacity increases bladder capacity; these children often do not drink appreciably
with age, so younger children have a small normal functional during the day, and urinary frequency is evident only after a
bladder capacity. Presence of constipation further reduces fluid load. Other details required are a sleep history that
bladder capacity and enhances the prevalence of bedwetting. should include the times the child goes to bed, falls asleep,
The bladder is located in the narrowest dependant portion of and awakens in the morning, and the presence of snoring.
the funnel formed by the pelvic bones and it cannot escape the Presence of an overactive bladder or dysfunctional voiding
impact of stool in the small pelvis of a child. Also, nocturnal e.g., Vincent’s curtsy, that usually present with frequency,
colonic movement may stimulate detrusor contractions. urgency, maneuvers to suppress the urge to void (squatting
Other comorbid conditions associated with NE that need behavior), and daytime and nighttime wetting should be noted.
to be addressed for successful therapy are neuropsychiatric Constipation and cystitis are common associated problems
disorders, such as attention deficit hyperactivity disorder in patients with overactive bladder or dysfunctional voiding.
(ADHD) and sleep disordered breathing due to adenotonsillar Differential diagnoses, such as neurogenic bladder and
hypertrophy. ectopic ureter, can be excluded on history. Neuropsychiatric
abnormalities, if any, need to be identified.
EVALUATION (See Algorithm 1)
Clinical Pearls
History Usefulness of a voiding diary
The most important aspect of the investigation is a meticulous • Provides objective data that may support the history
history, which can establish the diagnosis, lead to more precise • Helps detect children with nonmonosymptomatic enuresis
treatment recommendations, and minimize the need for • Detects children who require extra evaluation
invasive and expensive investigations. • Detects families with low adherence to instructions
Parents are requested to maintain a record over 2–3 days
in a frequency-volume chart and record of bowel movements
during a week. Points to be noted are details of fluid intake, Physical Examination
daytime voiding pattern, and number and time of episodes
of bedwetting. Some children void with a normal frequency The examination should be carried out to exclude pathological
or even a reduced frequency and yet have a low functional causes of incontinence, i.e., measurement of blood pressure,
inspection of external genitalia and of the lumbosacral spine,
Algorithm 1 palpation in the renal and suprapubic areas to look for enlarged
Evaluation and management of a child kidneys or bladder, and a thorough neurologic examination of
with primary nocturnal enuresis the lower extremities. Abnormal physical findings are absent in
children when enuresis is the sole symptom.
Laboratory Testing and Imaging Studies

A urinalysis is warranted in all children to rule out urinary
tract infection and glycosuria. A high specific gravity in a urine
specimen obtained in the afternoon suggests low fluid intake
during the day. Ultrasonography (USG) of the pelvis is helpful
in children with day time symptoms. USG performed when
the child feels the bladder is “full,” can be used to estimate
functional bladder capacity, which can be compared with
norms for bladder capacity according to age (Box 1). USG
should also be performed after voiding to assess the patient for
bladder wall thickness and residual urinary volume; abnormal
parameters suggest NMNE.
Box 1: Expected bladder capacity

• >2 years of age: {Age (years) + 2} × 30 mL
• Maximum bladder capacity is too small if <65% or too large if
>130% of expected bladder capacity.
Clinical Pearls
Red flags on ultrasonography
• Thick bladder wall (>5 mm after voiding)
501
• Elevated residual urinary volume (>20 mL)
NE, nocturnal enuresis
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MANAGEMENT Clinical Pearl

Enuresis that occurs as infrequently as once a month is
• Training programs that involve either “holding on” and waiting
associated with reduced self-esteem, and treatment has been
before voiding or stopping the flow of urine have not been
reported to improve self-esteem, regardless of the type or
shown to be effective, hence have no role.
the success of therapy. Management should be instituted
as soon as the child is motivated to be dry and the parents
are supportive. An explanation of the probable cause of the If the above preliminary management program does not
enuresis is important. Motivation of the child needs to be result in dryness in 3 months, then the use of an alarm should
sustained by providing emotional support and an attempt to be considered.
remove any feelings of guilt. Efforts of the child to remain dry
need to be rewarded with praise. Alarm Therapy
Alarm therapy is presumed to cure NE by the conditioning effects
Behavioral Therapy on arousal and by increasing nocturnal bladder capacity. The
Behavioral modification directed at good bladder and bowel device consists of a sensor, attached to the child’s underwear
health offers the potential to cure NE without the need for or to a mat placed below the child, which is activated when
medication (Box 2). It also increases the success rate of the child begins to wet the bed. It works on the principle that
the alarm or pharmacological therapy. Clinical experience sustained use causes conditioned wakening to a full bladder.
suggests that the ability to establish a rapport with the child and Success with alarm therapy is related to the motivation of the
to induce and sustain motivation is important for successful child and that of the parent who must participate in the therapy.
behavioral therapy. It requires a minimum 3-month trial. Its use results in dryness in
about two-thirds of children and the relapse can be minimized
with behavioral therapy prior to alarm therapy, by close follow-
up during therapy, and by ‘overlearning’, which involves slowly
Box 2: Behavioral therapy: good bladder and bowel habits increasing the evening fluid intake in successfully treated patients
• Advice regarding timed voiding, i.e., every 3–4 hours, frequent while continuing to wear the alarm.
enough to avoid urgency/incontinence, including during school
hours; and before going to bed Pharmacological Treatment
• Voiding should be unhurried and complete
• Instructions to drink liberal amounts during the day (50 mL/kg/ Pharmacological options are resorted when behavioral therapy
day), not to drink excess with the evening meal, and to minimize and alarm fail (Table 2).
fluid intake afterward Desmopressin acetate (DDAVP) reduces nocturnal polyuria
• Encouragement toward good bowel health, characterized by but relapse rates are high and offers only a control rather than
a soft bowel movement, with a diameter less than 2 or 3 cm, a cure of the NE. It is recommended when fast-acting, short-
passed without discomfort every morning before the child term improvement is the priority, if alarm treatment is not
leaves for school successful, or the parents or child no longer want to use an
• Strategies to improve bowel emptying include the intake of alarm. It is most effective in children 8 years and older who
foods that soften stool, use of a stool softener, and patient and have MNE with nocturnal polyuria, normal bladder capacity,
parent education about optimal posture to relax the pelvic floor and infrequent bed wetting. The immediate onset of action
muscles. Children should be counseled not to rush or push
of DDAVP allows the flexibility of intermittent administration
Table 2: Drugs used in the management of enuresis

Drug Dosage Adverse Effects
• Anticholinergics • Nighttime wetting: 0.1 mg/kg HS; nighttime • Include dry mouth, blurred vision, headache,
{{ Oxybutynin wetting with daytime symptoms: 0.1 mg/kg/ nausea, dizziness, gastrointestinal upset, and
{{ Tolteridine (has selectivity dose PO up to tid; not to exceed 5 mg/dose tachycardia
for urinary bladder over • 0.5–1 mg PO qd/bid
salivary glands)
• Desmopressin (DDAVP) • 0.2 mg, may be titrated upward to a maximum • The adverse event of water intoxication and
of 0.6 mg hyponatremic seizures can be avoided by
• Melt tablet 120 mg OD, maximum dose is 360 mg withholding oral fluids 2 h prior to bedtime
• Should be administered 1 h before bedtime
• Imipramine • 25 HS, may be titrated upward • Drowsiness, lethargy, agitation, depression, sleep
• 6–12 years: maximum dose 50 mg/dose disturbance, and gastrointestinal upset may occur
• >12 years: maximum dose 75 mg/dose • Rare adverse effects include seizures, cardiac
arrhythmias, and death from accidental overdose.
Pretreatment electrocardiography to identify
502 underlying rhythm disorders is recommended
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Chapter 103: Enuresis
for special occasions or long-term use to maintain dryness. habits and alarm therapy is the mainstay of management of
For long-term use, DDAVP may be used for 3 months then NE. Pharmacological therapy is indicated when there are
3-month quantities; a slow stepwise dose reduction over 6–7 additional symptoms and when behavioral and alarm therapy
months decrease relapse rates after discontinuation of therapy. fail. Treatment for comorbid conditions, like constipation
The International Children’s Continence Society reco and ADHD, must be offered simultaneously.
mmends that imipramine should be used only when all other
therapies have failed, only after assessment by a healthcare
professional who specializes in the management of bedwetting Key points
that has not responded to treatment. It should not to be used in ))
A detailed history including a voiding diary are essential for
combination with an anticholinergic. the diagnosis of primary nocturnal enuresis
Imipramine facilitates urine storage by decreasing bladder ))
Urinalysis and ultrasonography with a full bladder help rule
contractility and increasing outlet resistance. It inhibits reuptake out pathological conditions with which enuresis may be
of norepinephrine or serotonin (5-hydro xytryptamine) at associated
presynaptic neuron. Parents should be warned about the ))
The mainstay of management of primary monosymptomatic
potentially serious, dose-related adverse effects of cardiac nocturnal enuresis is behavioral modification directed at
arrhythmias. Reboxetine, a noradrenaline reuptake inhibitor, good bowel and bladder habits. Success depends on the
is pharmacologically related to imipramine but is without motivation of the child and parents
apparent cardiovascular toxicity. Further study is needed to ))
An alarm may be used when good bladder and bowel habits
define the role of this agent in clinical practice. alone is not enough
Anticholinergics are indicated when bladder capacity is
))
Medications are resorted when behavioral therapy and alarm fail.
found to be small or when there are symptoms of detrusor
instability (urge syndrome).
Nocturnal enuresis is more common in children with
ADHD, behavioral problems and adenotonsillar hypertrophy. SUGGESTED READINGs
Treatment of these conditions is important for success of
management. Complete success of therapy is said to have 1. Humphreys MR, Reinberg YE. Contemporary and emerging drug Treatments for
urinary incontinence in children. Pediatr Drugs. 2005;7(3):151-62.
occurred when there is no relapse even after 2 years of
2. Neveus T, Eggert P, Evans J, Macedo A, Rittig S, Tekgül S, et al. Evaluation
discontinuing therapy.
of and treatment for monosymptomatic enuresis: a standardization document
from the international children’s continence society. J Urol. 2010;183:441-7.
CONCLUSION 3. Nunes DV, O’Flynn N, Evans J, Evans, Sawyer L, Guideline Development Group.
Guidelines: Management of bedwetting in children and young people: summary
Nocturnal enuresis is very common and has the potential of NICE guidance. BMJ. 2010;341:c5399.
for an appreciable negative emotional impact on affected 4. Ramakrishnan K. Evaluation and treatment of enuresis. Am Fam Physician.
children. It is important to differentiate MNE from NMNE 2008;78(4):489-96.
and pathological conditions associated with enuresis. 5. Robson WL. Evaluation and Management of Enuresis. N Engl J Med. 2009;360:
Behavioral modification promoting good bladder and bowel 1429-36.
503
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Chapter 104
Approach to Renal
Tubular Disorders in Children
Manoj G Matnani
INTRODUCTION Table 1: Clinico-physiologic correlation of renal tubular

disorders
Renal tubules are the real brains of the kidney. They reabsorb
most of the glomerular ultrafiltrate and fine tune the Segment Function Disorder
remainder of urine by the processes of concentration, dilution, Proximal Phosphate transport Hypophosphatemic
acidification, and secretion in order to maintain an intact tubule rickets
homeostatic milieu on a continuous basis. Glucose transport Renal glucosuria
Hence, it is obvious that disorders of the renal tubules will Amino-acid transport Isolated, generalized
lead to serious fluid-electrolyte and acid base disturbances, amino aciduria
affecting the growth and development of the child and Bicarbonate transport Proximal renal tubular
sometimes even pose a serious threat to survival. acidosis
Ascending Sodium-potassium Bartter’s syndrome
PATHOPHYSIOLOGY (Table 1) limb of loop of chloride transport and variants
Henle (NKCC-2 and others)
Functionally, various diseases affecting a particular segment of
Distal tubule Proton secretion Distal RTA
the kidney lead to the following pathophysiological features:
• Disorders affecting the proximal tubule, which is the main Sodium chloride Gitelman’s syndrome
site of reabsorption of multiple solutes, e.g., Fanconi’s transport (sodium
chloride cotransporter)
syndrome
• Disorders affecting the loop of Henle and the early parts Collecting duct Sodium-potassium Pseudohypoaldoste-
of the distal tubule, which fine tune the sodium chloride transport ronism
reabsorption and potassium secretion, e.g., Bartter’s Sodium transport Liddle’s syndrome
syndrome and its variants (epithelial sodium
• Disorders affecting the a-intercalated cells of the cortical channel)
collecting ducts, which is the main site for hydrogen ion Water transport Nephrogenic diabetes
secretion (aldosterone sensitive segment), e.g., distal insipidus
renal tubular acidosis (RTA), type 4 RTA, and pseudo
hypoaldosteronism
• Disorders affecting the medullary collecting ducts, which
CLINICAL FEATURES (Fig. 1)
is the anti diuretic hormone (ADH) sensitive segment
(responsible for water reabsorption through aquaporin Clinical
channels), e.g., nephrogenic diabetes insipidus (DI). • Recurrent episodes of dehydration, vomiting, fever causing
• Disorders affecting primarily the phosphate (PO43–) growth retardation, and failure to thrive
reabsorption by the proximal tubule, e.g., X-linked • Polyuria, polydipsia causing constipation and preference
hereditary hypophosphatemic rickets (XLHHR) for savory foods, and salt craving
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Chapter 104: Approach to Renal Tubular Disorders in Children
4. Rickets with phosphate wasting: Fanconi’s syndrome,

XLHHR.
Clinical Pearls
Suspect renal tubular disorder in a child with
gastroenteritis if:
• The amount of dehydration is out of proportion to the number
of loose stools
• Fairly preserved urine output despite severe dehydration.
EVALUATION OF RENAL
TUBULAR DISORDERS (Algorithms 1 and 2)
• Estimate acid-base status—metabolic acidosis or meta
bolic alkalosis
{{ If metabolic acidosis, determine
Fig. 1: Features suggestive of renal tubular disorders
Plasma anion gap = Na+ – (Cl– + HCO–3)
• Refractory rickets, bone pains, and muscle weakness Normal plasma anion gap is 8–12 mEq/L. Normal
causing delayed gross motor milestones anion gap is seen in RTA (renal loss of HCO–3) and diarrhea
• Renal calculi, and nephrocalcinosis if untreated for (gastrointestinal loss of HCO–3)
prolonged periods • Estimate urine anion gap (UAG)– The UAG (urine net
• Hypertension seen in monogenic disorders, e.g., Liddle’s charge) is useful for estimating NH4+ excretion in patients
syndrome/pseudohypoaldosteronism. with hyperchloremic metabolic acidosis.
Laboratory Na+ + K+ + Unmeasured cations = Cl– + Unmeasured anions

• Hyperchloremic metabolic acidosis • Since the sum of charges on cations and anions is equal,
• Metabolic alkalosis with or without hypokalemia the difference between unmeasured anions (sulfates,
• Hyponatremia with hyperkalemia phosphates, organic anions) and cations (calcium,
• Hypercalciuria with normal serum calcium. magnesium) is relatively constant (about 80 mEq/L),
The clinical phenotypes can be classified into following
hence,
four groups:
+
1. Hyperchloremic normal anion gap metabolic acidosis: Na+ + K+ + NH4 = Cl– + 80
renal tubular acidosis, Fanconi’s syndrome The UAG is the difference between the sum of urinary
2. Hypokalemic metabolic alkalosis: Bartter’s syndrome and Na+, K+ and Cl–, hence UAG gives an approximate estimate
its variants +
of urinary NH4 excretion
3. Polyuria with/without hypernatremic dehydration with +
normal acid-base status–nephrogenic DI UAG = 80 – NH 4
Algorithm 1
Approach to metabolic acidosis
GFR, glomerular filtration rate. 505
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Algorithm 2
Evaluation of a patient with renal tubular acidosis
RTA, renal tubular acidosis; U-B Co2, urine to blood CO2 gradiam; FEHCO3, fractional excretion of bicarbonate.
+
A positive UAG indicates inappropriately low renal NH4 {{ In hyperkalemic (type 4 RTA), levels vary from 5 to 10%
excretion, as seen in RTA. • Fludrocortisone furosemide test: This is a sensitive test to

• Determine the urine pH: It is useful for assessing the assess distal urinary acidification, used in patients with
integrity of distal urinary acidification. type 4 RTA.
Presence of urine pH greater than 5.5 during metabolic
acidosis suggests defective distal secretion of H+ (distal Additional Tests for
RTA); urine pH smaller than 5.5 is seen in proximal RTA Renal Tubular Acidosis (Table 2)
or in patients with selective aldosterone deficiency (type 4
RTA) Proximal RTA (type 2) needs evaluation of other proximal
• If systemic acidosis is absent, an oral ammonium chloride tubular functions.
(0.1 mg/kg) load (acid load test) is given to induce acidosis • Evaluation of aminoaciduria, glucosuria, and low
and the capacity of the distal tubule to secrete H+ is molecular weight proteinuria (if available)
assessed by serial monitoring of the blood and urine pH • Assessment of phosphate excretion to assess phosphaturia
(done at higher centers as an inpatient procedure)
• To characterize the type of RTA, bicarbonate loading test Table 2: Investigations to differentiate types of RTA
is done Proximal RTA Distal RTA Type 4 RTA
{{ Measurement of fractional excretion of bicarbonate
Plasma K+ Normal/low Normal/low High
(FEHCO3) and urine to blood CO2 gradient (U-B CO2) Urine pH <5.5 >5.5 <5.5
allows characterization of RTA
Urine anion gap Positive Positive Positive
{{ The urine PCO is above 70 mmHg and the U-B CO
2 2
gradient is above 20 mmHg in normal individuals Urine NH4+ Low Low Low
{{ Urine PCO below 50 mmHg and U-B CO gradient
2 2
Fractional HCO3– >10–15% <5% >5–10%
below 10 mmHg suggests distal RTA U-B PCO2 mmHg >20 <20 >20
• FEHCO3 (%) = Urine calcium Normal High Normal/low
Urine bicarbonate × plasma creatinine Other tubular Often present Absent Absent
× 100 defects
Plasma bicarbonate × urine creatinine
Nephrocalcinosis Absent Present Absent
{{ A value greater than 15% indicates bicarbonaturia,
suggestive of proximal RTA Bone diseases Common Often present Absent
506 {{ Levels in the normal range (<5%) indicate distal RTA U-B PCO2, urine to blood PCO2 gradient.
ch-104.indd 506 11/21/2016 12:59:00 PM

TRP, tubular reabsorption of phosphate; GFR, glomerular filtration rate; TmP/GFR, tubular maximum for phosphate, corrected GFR.
Fig. 2: Bijvoet’s nomogram for estimation of renal threshold phosphate concentration(TmP/GFR)
Fractional excretion of phosphate (FEPO4) =
Urine phosphate × plasma creatinine

× 100
Plasma phosphate × urine creatinine
3–
Tubular reabsorption of PO 4 (TRP) = 100 – FEPO4.
3–
Normally 5–15% of the filtered PO 4 is excreted and the
tubular reabsorption is 85–95%
3–
Limitation: TRP depends on plasma PO 4 levels and
glomerular filtration rate (GFR) and is therefore, is not an
3–
optimal index of tubular PO 4 handling, especially in patients
with hypophosphatemia.
3–
Tubular maximum for PO 4, corrected for GFR (TmP/GFR)
3–
is independent of plasma PO 4 and renal function. TmP/
GFR (Bijvoet index) (Fig. 2) represents the concentration
Fig. 3: Medullary nephrocalcinosis in a child with distal RTA
above which most PO4 is excreted and below which most is
reabsorbed. The normal value is 2.8–4.4 mg/dL with lower {{ Hypercalciuria (see appendix 1 for normal values) and
values for older children and can be calculated from the hyperphosphaturia occur due to:
following nomogram. –– The release of calcium phosphate from bone in
Distal RTA (type 1): All patients should undergo: order to buffer excess H+ during acidosis
• Hearing evaluation to diagnose proton adenosine –– The direct effects of acidosis on tubular reabsorption
triphosphatase channel defects causing distal RTA of these ions
• Renal ultrasound for medullary nephrocalcinosis (Fig. 3) {{ Hypocitraturia results from:
and renal calculi –– Citrate utilization in proximal tubular cells
• Measurement of urinary calcium and citrate excretion to –– Due to high luminal pH favoring conversion of
assess hypercalciuria and hypocitraturia citrate3– to the readily absorbable citrate2– 507
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Algorithm 3
Evaluation of a patient with metabolic alkalosis and hypokalemia
11 b-HSD, 11b-hydroxysteroid dehydrogenase deficiency.
Hyperkalemic RTA (type 4): In children, aldosterone unres be evaluated through the algorithmic approach mentioned
ponsiveness is more common than aldosterone deficiency, in algorithm 3.
and is commonly associated with obstructive uropathy.
Transtubular potassium gradient (TTKG): This provides an TREATMENT GUIDELINES
accurate estimate of aldosterone effect on late distal and • Alkali supplements: bicarbonate solutions (Table 3) and
cortical collecting tubules. tablets to correct acidosis. The requirement in distal RTA
TTKG = Urine K+ × Plasma osmolality is around 2–5 mEq/kg/day, and higher, around 5–20 mEq/
kg/day in proximal RTA/Fanconi’s syndrome
It is an index of K+ gradient in the distal tubular lumen
(Plasma K+ × Urine osmolality) and interstitial blood capillaries.
Normal range is 6–12. Table 3: Commonly available alkali and phosphate supplements
• Hypokalemia from extrarenal causes results in renal K+
conservation and TTKG smaller than 2 Preparation Composition Remarks
(per 1000 mL)
• Higher TTKG suggests renal losses, as seen in hyper
aldosteronism Bicitra • 100 g sodium citrate 1 mL = 1 mEq base
• During hyperkalemia, the expected TTKG should be • 60 g citric acid
greater than 10, an inappropriately low level suggests Polycitra • 110 g potassium citrate 1 mL = 2 mEq base
hypoaldosteronism or tubular resistance to aldosterone. • 100 g sodium citrate = 1 mEq Na+
• 66.8 g citric acid = 1 mEq K+
EVALUATION OF Polycitra K • 220 g potassium citrate 1 mL = 2 mEq base
METABOLIC ALKALOSIS (Algorithm 3) • 66.8 g citrric acid
• Rule out common causes first, viz. vomiting, nasogastric Shohl • 140 g citric acid 1 mL = 1 mEq base
suction, diuretic usage, or drugs like bicarbonate and solution • 90 g sodium citrate
steroids Joulie • 136 g dibasic sodium 1 mL = 30 mg
• Examine for presence of dehydration/hypovolemia and solution phosphate inorganic phosphorous
hypertension • 58.8 g phosphoric acid
• Clinical features like failure to thrive and triangular facies Neutral • 18.2 g sodium 60 mL = 1000 mg
suggest Bartter’s syndrome phosphate dihydrogen phosphate inorganic phosphate
• Laboratory investigations needed serum electrolytes • 145 g dibasic sodium
(Na+, K+, Cl–), urine electrolytes (Na+, K+, Cl–), and plasma phosphate
renin activity and aldosterone levels in patients with
Sodium • Solution (7.5%) 1 mL = 0.9 mEq base
hypertension
bicarbonate • 325, 650 mg tab 325 mg = 4 mEq base
• Rare monogenic disorders (Liddles, syndrome, 11b-hydroxy
508 steroid dehydrogenase deficiency) present with hyper Calcium • 250, 500 mg tab 1000 mg = 22.3 mEq
tension, mild metabolic alkalosis, and hypokalemia and can carbonate base
ch-104.indd 508 11/21/2016 12:59:00 PM

• Phosphate supplements with vitamin D are needed in

Fanconi’s syndrome and hypophosphatemic rickets
))
Early treatment of distal renal tubular acidosis (RTA) prevents
grave consequences like medullary nephrocalcinosis and
• Electrolyte solutions to correct hypokalemia and
end-stage renal disease (ESRD), hence it is a preventable
hyponatremia are needed in salt losing tubulopathies like
cause of ESRD
Fanconi’s syndrome, Bartter’s syndrome, etc.
• Thiazides and sometimes prostaglandin inhibitors like ))
Early treatment of distal RTA leads to good catch up growth
indomethacin are used to decrease polyuria (to augment in children
growth) in Bartter’s syndrome and nephrogenic DI. ))
It is important to rule out renal tubular disorder in patients
presenting with recurrent dehydration as the blood gas
and electrolyte abnormalities frequently overlap in both
APPENDIX 1 the conditions (e.g., metabolic acidosis and hypokalemia in
Hypercalciuria is defined as gastroenteritis and RTA, metabolic alkalosis and hypokalemia
• Twenty four-hour urine calcium greater than 4 mg/kg/day in vomiting and Bartter’s syndrome)
• Spot urine calcium: creatinine ratio greater than 0.8 ))
Children with obstructive uropathy should undergo a detailed
(0–6 months) renal tubular evaluation to categorize the tubulopathy.
{{ Greater than 0.6 (6 months–2 years)
{{ Greater than 0.2 (>2 years).

SUGGESTED READINGs
1. Ali U. Renal tubular disorders, Indian Academy of Pediatrics: Specialty series on
Key points Pediatric Nephrology. 212-23.
2. Bagga A, Bajpai A, Menon S. Approach to renal tubular disorders. Indian J
))
Early diagnosis of renal tubular disorders is of paramount Pediatric 2005;72:771-6.
importance as most of them present with recurrent life- 3. Bagga A, Sinha A, Gulati A. Metabolic alkalosis, Textbook on Protocols in Pediatric
threatening episodes of vomiting and dehydration Nephrology. 2012.pp. 66-72.
))
Early treatment is essential as it prevents growth failure, 4. Bagga A, Sinha A, Gulati A. Renal Tubular Acidosis, Textbook on Protocols in
Pediatric Nephrology. 2012. pp. 55-65.
stunting, and wasting along with metabolic bone compli
5. Sobh M. Renal Tubular Disorders, Textbook on Essentials of Clinical Nephrology.
cations like recurrent pathological fractures, osteopenia etc. 2000. pp. 197-211.
509
ch-104.indd 509 11/21/2016 12:59:00 PM

Chapter 105
Nephrotic Syndrome in Children
INTRODUCTION etiologies causing nephrotic syndrome are focal segmental

glomerular sclerosis, mesangioproliferative glomerulonephritis,
Nephrotic syndrome is a common chronic disorder in children, membranoproliferative glomerulonephritis, and membranous
characterized by heavy proteinuria (>40 mg/m²/h in timed nephropathy.
urine sample), hypoalbuminemia, and edema. The proteinuria
in nephrotic syndrome is relatively selective and constitutes
primarily of albumin. The peak incidence of the disease is in EVALUATION
between 2 and 6 years of age. Ninety percent of the children with The primary evaluation of a child with suspected nephrotic
minimal change disease respond to treatment with steroids. syndrome includes estimation of serum total proteins, albumin,
Majority of these relapse and about 50–60% become steroid- globulin, cholesterol, urea, and creatinine concentrations.
dependent or frequent relapsers. Frequency of relapses is higher Urinary proteins can be estimated with dipsticks. Values
in first 10 years after the diagnosis. By puberty the relapse rate of more than +3 proteins are indicative of nephrotic range
decreases and most children show sustained remission. proteinuria. Urinary spot samples can be used for determining
Some common definitions to define the course of nephrotic the urinary protein or creatinine ratio. Values beyond 2 are
syndrome are tabulated in table 1. suggestive of nephrotic range proteinuria. Hepatitis B status
The most common etiology of childhood nephrotic status should be determined if the child is unimmunized.
syndrome is minimal change disease. The other glomerular Serum complement (C3) levels are recommended if persistent
hematuria or hypertension occurs.
Table 1: Definitions
Terms Definitions INDICATIONS FOR RENAL BIOPSY
Nephrotic Presence of edema, serum albumin <2.5 g/dL and
syndrome proteinuria >40 mg/m²/h in timed urine sample or Renal biopsy is indicated for children with steroid-resistant
urine spot (mg/mg) Up/Uc >2 nephrotic syndrome, age at onset below 1 year or more than
Relapse Urinary protein excretion >40 mg/m²/h or >+3 by 12 years, gross or persistent microscopic hematuria, or persistent
dipstick on spot sample for 3 consecutive days hypertension. Children with features suggestive of systemic
Remission Urinary protein excretion <4 mg/m²/h in timed lupuserythematosus, other secondary causes of nephrotic
sample, nil or trace by dipstick on spot sample for syndrome, or before starting calcineurin inhibitors should also
3 consecutive days be biopsied.
Frequent Two or more relapses in 6 months of initial
relapses response or four or more in any 12-month period
MANAGEMENT OF NEPHROTIC
Steroid Occurrence of 2 consecutive relapses during
dependence steroid therapy or within 2 weeks of its cessation in SYNDROME INCLUDES SPECIFIC
absence of infections AND SUPPORTIVE MANAGEMENT
Steroid Failure to achieve remission after 4 weeks of daily
resistance therapy of steroids (prednisolone oral) 2 mg/kg/day Specific Management
Initial Nonresponse to initial steroid therapy
resistance (2 mg/kg/day daily for 4 weeks) Treatment of the Initial Episode
Late Failure to respond in subsequent relapses after Indian Society of Pediatric Nephrology currently recommends
resistance initial response to steroids that initial episode of nephrotic syndrome be treated with
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Chapter 105: Nephrotic Syndrome in Children
prednisolone at 2 mg/kg (max 60 mg) or 60 mg/m2 in single or Steroid-resistant Disease

divided dose for 6 weeks followed by 1.5 mg/kg (max 40 mg) All patients with minimal change disease, focal segmental
or 40 mg/m2 single morning dose on alternate days for next
glomerulosclerosis, or mesangioproliferative changes on renal
6 weeks.
biopsy are treated with calcineurin inhibitors like cyclosporine
and tacrolimus. The duration of treatment is at least 2–3 years
Management of Relapse for steroid-resistant disease. The response rate to these agents
Identify and treat any infections present. Prednisolone is is about 70–80%. Intravenous steroids like methylprednisolone
administered at a dose of 2 mg/kg/day until protein is nil or and dexamethasone have been used for prolonged periods in
trace for 3 consecutive days followed by 1.5 mg/kg/day on the past, but due to their poor response rates and high toxicity,
alternate days for 4 weeks and then discontinued abruptly. their use is discouraged. Intravenous cyclophosphamide
monthly pulses in doses of 500 mg/m² for 6 doses along with
Frequent Relapser and Steroid-dependent low dose alternate day steroids have a response rate of about
Long-term alternate day oral prednisolone is the initial 50%. This drug can be used if the cost of calcineurin inhibitors
strategy. Slow tapering of prednisolone is done to reach to is a constraint.
a maintenance dose of 0.25–0.5 mg/kg on alternate days.
These doses are given for prolonged periods of 9–18 months.
Requirement of steroids at doses more than 0.5 mg/kg/day is
Supportive Management
an indication for use of alternative agents. The commonly used
steroid sparing drugs are levamisole, mycophenolate mofetil, Diet
and alkylating agents (cyclophosphamide and chlorambucil). A balanced diet adequate in protein (1.5–2 g/kg) and calories
Calcineurin inhibitors like cyclosporine and tacrolimus are is recommended. Fats should provide less than 30% calories
used sparingly for steroid-sensitive disease (Algorithm 1). and saturated fats should be avoided. Salt restriction is advised
Specific drug usage is given in table 2. only for patients with persistent edema or hypertension.
Algorithm 1
Management protocol of childhood nephrotic syndrome
511
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Table 2: Drugs used for treatment of steroid-sensitive nephrotic syndrome

Drugs Dosage and side effects
Levamisole Immunomodulatory drug. Doses of 2–2.5 mg/kg/day on alternate days for 12–24 months. Low dose alternate day
prednisolone is coadministered. Side effects include neutropenia, rashes, cutaneous vasculitis, and gastrointestinal
symptoms. Monitoring of total leukocyte counts recommended every 3–4 months. Available 50 mg/150 mg tablets
Cylcophosphamide It is administered at a dose of 2–2.5 mg/kg/day for 12 weeks. Prednisolone is coadministered at a dose of
1.5 mg/kg on alternate days for 4 weeks, followed by 1 mg/kg the following 8 weeks; steroid therapy tapered and
stopped in 2–3 months. The drug should be started preferably in remission. Side effects include bone marrow
suppression with leukopenia, hemorrhagic cystitis, alopecia, vomiting, and gonadal toxicity. Monitoring of total
leukocyte counts recommended every 2 weeks. Available as a 50 mg tablet
Mycophenolate Is a purine antagonist; is a prodrug that is rapidly hydrolyzed to its active metabolite mycophenolic acid in the liver.
mofetil It is given in doses of 25–35 mg/kg/day in 2 doses (12 hourly) for prolonged periods (1–2 years). Side effects include
gastrointestinal intolerance. The drug can also cause lymphopenia. Monitoring of counts and LFT. Available as
250 mg/500 mg tablets.
Cyclosporine Inhibits interleukin-2-driven T-cell activation. In SSNS used in doses of 3–5 mg/kg (100–150 mg/m2) in 2 divided doses
for 1–2 years. For SRNS duration of therapy 2–3 years. Co-administration of low dose corticosteroids is often required.
Side effects includes nephrotoxicity, hypertension, and hypertrichosis. Monitor LFTs every 2–3 months. Kidney biopsy
is recommended after 2–3 years of use to identify nephrotoxicity. While drug levels are recommended to monitor
toxicity, finances often becomes a limitation. It is available as as syrup (100 mg/mL) and capsules (25, 50, and 100 mg)
Tacrolimus Doses of 0.15–0.20 mg/kg/day. Available as 0.5 mg/1.0 mg/ 2.0 mg tablets. Side effects are nephrotoxicity, and
hyperglycemia, neurotoxicity. Cosmetic side effects are less with tacrolimus compared to cyclosporine. Available as
0.5, 1.0 mg capsules/tablets
Rituximab Is a chimeric monoclonal antibody that inhibits CD20 mediated B lymphocyte proliferation and differentiation. Used
in severe steroid dependency. It is given at doses of 375 mg/m² as weekly infusion for 2–4 doses. It is an expensive
drug and should be used as a salvage drug after using all the above drugs. Available in 100 mg/500 mg vials
SSNS, steroid-sensitive nephrotic syndrome; SRNS, steroid-resistant nephrotic syndrome; LFT, liver function test.
Table 3: Management of edema in nephrotic syndrome Table 4: Complications of nephrotic syndrome and their
management
Step 1 Assess volume status*
Step 2a If hypovolemia give 5 or 20% albumin infusion** Complication Management
Step 2b If normovolemia or hypervolemia, furosemide Infections Most common being peritonitis, cellulitis,
2–8 mg/kg/day. Add spironolactone 2–3 mg/kg/day and pneumonias. Penicillin most effective.
at high doses of furosemide. Restrict sodium intake. If Injectable third-generation cephalosporins and
inadequate response, add metalozone (0.1–0.3 mg/kg/ aminoglycosides used in serious cases. Duration
day) or hydrochlorothiazide 2–3 mg/kg/day. of therapy 10–14 days
Ill sustained response to above measures Thrombo Ultrasound Doppler for diagnosis of deep vein
Step 3 Administer intravenous furosemide 2–3 mg/kg/day embolism thrombosis is useful. Ventilation perfusion scan
every 12 h helps in identification of pulmonary embolism.
Step 4 Consider intravenous furosemide infusion 0.1–1.0 mg/ Low molecular weight heparin+ oral warfarin for
kg/h if the intravenous bolus effect not sustained 3 months duration or till relapse persists. Aim INR
between 2.5–3.0 when on warfarin therapy
Step 5 If significant edema persists, give 20% albumin infusion
with intravenous furosemide over 4 h Hyperlipidemia Dietary management with fat restriction. No
*Assess volume status clinically-monitor pulse, blood pressure. In patients with
clear guidelines for use of statins in children.
hypovolemia, blood urea may be elevated, fractional excretion of sodium <0.2% Simvastatin and atorvastatin can be used in
**20% albumin may be diluted in normal saline or 5% dextrose to prepare 5% children with persistent hypercholesterolemia in
albumin if preparation unavailable. steroid-resistant disease
Source: Vasudevan A, Mantan M, Bagga A. Management of edema in nephrotic Hypertension ACE inhibitors and ARB’s preferred drugs. Beta-
syndrome. Indian Pediatr. 2004;41:787-95.
blockers and calcium channel blockers can be
used additionally if not controlled. Use diuretics
Edema if edema present
Judicious use of diuretics helps in controling edema. A protocol
Steroid toxicity Short stature, cataract, glaucoma, and
of edema management is given in table 3. Rapid diuresis can hypertension features of toxicity. Use
occur with synergistic therapy, resulting in hypovolemia and alkylating and steroid sparing agents like
hypokalemia. Monitoring of electrolytes is recommended cyclophosphamide, levamisole, cyclosporine,
512 during diuretic therapy. and mycophenolate mofetil
The complications of nephrotic syndrome and their INR, international normalized ratio; ACE, angiotensin-converting enzyme; ARB,
management is given in table 4. angiotensin receptor blockers.
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Chapter 105: Nephrotic Syndrome in Children
Key points SUGGESTED READINGS

1. Bagga A, Ali U, Banerjee S, Kanitkar M, Phadke KD, Senguttuvan P, et al.
))
Treatment with daily steroids for 4 weeks distinguishes
Management of steroid sensitive nephrotic syndrome: Revised guideline. Indian
steroid-sensitive from steroid-resistant nephrotic syndrome
pediatric nephrology group. Indian Pediatric. 2008;45:203-14.
))
Edema needs to be treated only if there is significant ascites, 2. Bagga A, Mantan M. Nephrotic syndrome in children. Indian J Med Res.
respiratory distress due to ascites or effusions, excoriation, 2005;122:13-28.
and extrusion of fluid from the skin 3. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003;362:
))
Intravenous albumin is indicated for treatment of hypovolemia 629‑39.
in nephrotic syndrome 4. Gulati A, Bagga A, Gulati S, Mehta KP, Vijayakumar M, Indian Society of Pediatric
))
Alternative agents like cyclophosphamide, levamisole, Nephrology. Management of steroid resistant nephrotic syndrome. Indian Pediatr.
and mycophenolate mofetil are used in patients having a 2009;46:35-47.
frequently relapsing or dependent course 5. Lombel RM, Gipson DS, Hodson EM. Treatment of steroid-sensitive nephrotic
syndrome: new guidelines from KDIGO Kidney Disease: Improving Global
))
Calcineurin inhibitors along with low dose alternate day
Outcomes. Pediatr Nephrol. 2013:28:415-26.
steroids are the first-line drugs for treatment of steroid
6. Vasudevan A, Mantan M, Bagga A. Management of edema in nephrotic syndrome.
resistant disease.
Indian Pediatr. 2004;41:787-95.
513
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Section 13: Endocrinology
Chapter 106
Approach to Short Stature
Vaman V Khadilkar, Supriya Phanse Gupte
INTRODUCTION a developing country like India. A small number have an

endocrinopathy, a syndrome, or a skeletal dysplasia.
Short stature although common can be a challenging problem A wide variety of conditions both physiological and
to deal with. Growth monitoring of children from birth till pathological can lead to short stature in children. In many
adulthood provides invaluable information toward diagnosis cases, short stature may be the only presentation of the
and management of a whole range of pediatric disorders. disease and therefore, investigating the cause of short stature
Growth monitoring can prevent loss in the adult height, which is important.
may occur if diagnosis is delayed. Therefore, it is very important
to monitor growth of the child on a regular basis. Parents often Familial Short Stature
bring their child with complaint of short stature because they
compare the height of the child with his/her peers at school. These are usually normal short children born to short parents.
This can be misleading and needs to be confirmed by use of Their height falls below the 3rd percentile of population
appropriate growth charts. standards but is within the midparental height range. However,
When a short child is referred, following important points they need monitoring of growth velocity to ensure normal
need to be considered: growth. Rarely, short stature in both the parents is caused by
• Define whether the child is actually short or not using a heterozygous condition manifesting in a mild form and the
appropriate growth charts child may be a homozygote with severe short stature such as
• Differentiate a short normal child from a child with an in familial cases of growth hormone deficiency. In dominantly
organic cause inherited conditions such as hypochondroplasia, the affected
• Decide whether a child can be monitored or needs parent is short and transmits the mutated gene to the offspring
immediate referral. resulting in short stature in the child. Treatment of these
children is warranted.
DEFINITION Constitutional Delay in Growth and Puberty

A child is short if the height is less than 2 standard deviations This is usually seen in boys. These children grow well in infancy
(SDs) below the mean for age and gender for country specific and early childhood. Thereafter, their height begins to falter
updated population standards. However, a child falling much on growth charts and usually lies just below the 3rd percentile
below his midparental (target) range percentile and a child below mid-parental height (MPH). It cruises parallel to the
having a poor growth velocity (<25th percentile) also needs to 3rd percentile from thereon. They also have delayed puberty
be investigated. further worsening the growth pattern at puberty. Family history
of short stature in childhood and adolescence, late pubertal
spurt, and achievement of final height as per genetic potential
ETIOLOGY
usually exists, mostly in the father. These children usually
Most of the children presenting with short stature have follow the same trend and will achieve their final height as per
physiological causes, namely familial short stature and their genetic potential. If the puberty is delayed beyond the age
constitutional delay in growth and puberty (CDGP). Chronic of 15 years, it may require treatment in the form of small dose
illness and malnutrition also form major contributors in of sex steroids.
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Chapter 106: Approach to Short Stature
Box 1: Causes of short stature

are preserved. Obesity is uncommon in Indian children
unlike their counterparts in Western countries. They have
• Physiological short stature: low stimulated growth hormone levels, insulin-like growth
{{ Idiopathic short stature
factor 1 and insulin-like growth factor binding protein 3. They
–– Familial respond well to growth hormone therapy. Rare exceptions
–– Nonfamilial are conditions with growth hormone antibodies and growth
{{ Constitutional delay in growth and puberty hormone insensitivity syndromes.
• Pathological short stature:
{{ Malnutrition Hypothyroidism
{{ Chronic illness: Short stature can be the presenting complaint of children
–– Chronic anemia with acquired hypothyroidism. They are short and puffy with
–– Chronic renal disease, renal tubular acidosis coarse facies. Occasionally, a child with less severe congenital
–– Chronic liver disease hypothyroidism (e.g., dyshormonogenesis) may present in
–– Chronic pulmonary disease including asthma childhood for the first time.
–– Celiac disease, giardiasis
–– Hematological disorders, e.g., thalassemia
Cushing Syndrome
{{ Endocrinopathies: In childhood, it is usually the result of exogenous steroid
–– Growth hormone deficiency administration or adrenal tumors. Rarely, in older children,
–– Hypothyroidism a pituitary lesion or a carcinoid tumor may be the cause.
These children are short and obese. Other stigmata, such as
–– Cushing syndrome
purplish striae, muscular weakness, and buffalo hump, are
–– Pseudohypoparathyroidism
not commonly seen in children. Hypertension is an important
{{ Syndromes:
indicator of this disorder in children.
–– Turner syndrome
–– Down syndrome Turner Syndrome
–– Noonan syndrome
Short stature is a consistent feature of Turner syndrome
–– Other syndromes, e.g., Edward syndrome, Patau syndrome
especially as the child grows older. The other stigmata include
{{ Small for gestational age:
webbing of neck, low posterior hair line, antimongoloid
–– Nonsyndromic slant, widely spaced nipples, wide carrying angle, Madelung
–– Syndromic with primordial short stature: Russell-Silver, deformity, and short 4th/5th metacarpals or metatarsals. They
Seckel syndrome develop ovarian failure early in life and so have no/delayed
{{ Nutritional rickets, hypophosphatemic rickets
puberty and infertility. They are predisposed to autoimmune
{{ Skeletal dysplasia, osteogenesis imperfecta disorders such as autoimmune thyroid disease and celiac
{{ Intracranial tumors, trauma, surgery, and irradiation disease. Higher incidence of coarctation of aorta, left sided
{{ Psychosocial short stature heart disease, renal disorders, and pigmented nevi have been
{{ Medications: prolonged steroid intake, methylphenidate noted in these children. All features may not be present in
most children and short stature may be the only indicator of
the disorder. Growth hormone is a licensed indication for
Malnutrition and Chronic Illness treatment of short stature in Turner syndrome.
Chronic malnutrition leads to stunting of growth due to lack
of nutrient supply, associated illnesses leading to a state of Psychosocial Short Stature
catabolism, anemia, and micronutrient deficiency. Chronic Emotionally deprived children do not grow well. They do not
illnesses, such as chronic anemia, chronic kidney disease, respond to nutritional supplementation or any other form
liver disease, heart and respiratory disease including asthma, of treatment. However, it is a reversible condition and these
are catabolic states. In addition, poor appetite, electrolyte children grow well once placed in a loving environment as
imbalance and congestive heart failure further worsen the their pituitary hypothalamic function reverts to normal when
condition. Malabsorption syndromes including celiac disease they live in a stress free environment.
also cause stunting.
Small for Gestational Age Sequelae
Growth Hormone Deficiency Most small for gestational age (SGA) children catch up by
These children usually have normal weight and height at birth. 2–4 years of age. However, up to 30% do not catch up. Those
They grow normally in the first year of life as growth in this who fail to catch up and remain below -2.5 SD score for the
phase is influenced by nutrition and is mediated by insulin population are candidates for growth hormone therapy.
and related growth factors. Growth falters in early childhood Skeletal dysplasias, hypophosphatemic rickets, and
leading to severe stunting. They have immature facies, pseudohypoparathyroidism form rare causes of short stature
childlike voice, and small hands and feet. Body proportions and should be looked for. 515
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MANAGEMENT Clinical Pearl

Measurement of Height/Length • A child with height plot above the 3rd percentile may still be
It is important to accurately measure height with a stadiometer, abnormal if he falls below the target range or has a growth
to avoid errors in measurement. For children less than 2 years velocity less than 25th percentile.
of age, the length is measured with the child in supine position
with the help of an infantometer.
Preliminary Workup
Calculate the Midparental Height (Target Height) History
and the Target Range A detailed history of duration of apparent short stature,
Midparental height (MPH) = (father’s height + mother’s history of pubertal delay in adolescent boys and girls should
height + 13)/2 for boys and be noted. Evidence of chronic illnesses, such as renal, liver,
= (father’s height + mother’s malabsorption, respiratory illness including asthma, and
height - 13)/2 for girls. tuberculosis, should be looked for.
Target range = MPH ± 6 cm History of severe headache, vomiting suggestive of
Plot the child’s height, and target height (with target range) intracranial space occupying lesions, intracranial surgeries,
on country specific contemporary growth charts: for children craniospinal irradiation, head trauma, history of other
under the age of 5 years, use of WHO 2006 growth standards is malignancies, bone disorders, and prolonged steroid intake
recommended. would add valuable information.
If previous height records are available, plot previous Birth history including birth weight (SGA), birth length,
height readings to observe the pattern of the growth. history of breech delivery, birth trauma, neonatal hypo
Calculate the annual growth velocity as change in height glycemia, and neonatal jaundice should be asked for. Family
divided by change in time. For example, if a child grows 3 cm history of consanguinity, short stature, delayed puberty, sterile
in 6 months, the annualized growth velocity is 3 divided by half uncle/aunts, and tuberculosis should be reviewed.
year which is 6 cm. Developmental history suggestive of delayed milestones,
and visual disturbances (r/o anatomical causes like corpus
Normal Growth Velocity callosum agenesis, septo-optic dystrophy associated with
multiple pituitary hormone deficiency) could be pointers
• In 1st year: 25 cm/year toward an anatomical brain abnormality and congenital
• In 2nd year: 12 cm/year hypothyroidism.
• In 3rd year: 6 cm/year A proper assessment of dietary intake helps to ensure
• From 4th year till pubertal spurt: 5 cm/year adequate calorie intake and assess for malnutrition. Social
• During puberty: 6–8 cm/year in girls and 10–12 cm/year in history to assess for signs of child abuse and neglect should be
boys. looked for.
Growth velocity can be plotted on growth velocity curves.
Growth velocity less than 25th percentile is abnormal and Anthropometry
needs investigations.
Interpreting the severity of height and weight deficit can be
If previous height records are not available: assess the height of very useful to reach the diagnosis. This can be assessed by
the child in relation to the midparental height. calculating child’s height age and weight age.
If the height of the child is more than 3rd percentile and Height age is assessed by drawing a horizontal line from
within target range, it is a normal child. No investigations are the present height plot to the 50th percentile and drawing a
needed. Serial height measurements need to be plotted on perpendicular on the X-axis (age in years) on the growth chart.
growth charts at 6 monthly-yearly intervals. Monitor growth The point on the X-axis where the perpendicular meets, gives
velocity annually. the height age. Weight age is calculated in a similar way. If the
If height of the child is less than 3rd percentile but within weight age is more retarded than the height age, it is a case of
target range, it is a short normal child with familial short malnutrition, chronic disease, or syndrome. The height age
stature. Continue annual plotting on growth chart and monitor is more retarded than the weight age in endocrinopathies as
growth velocity. A high index of suspicion is needed to suspect weight is usually preserved.
and diagnose a subtle growth disorder in parents, such as In addition to height and weight, the upper segment/lower
hypochondroplasia, which may be inherited by the child. segment ratio (US/LS ratio) provides useful information and
helps in establishing a definite etiology. The lower segment is
Indications for Further Workup measured from the superior border of pubic rami till the feet
• Height less than -2.5 SD of population standard for age and with the child standing upright. The upper segment (vertex-
gender pubic symphysis) is calculated by subtracting the lower
• Height less than -1.5 SD below the MPH segment from the total height. Another method of assessing
• Growth velocity has deteriorated and dropped below 25th US/LS ratio is by measuring the sitting height and subtracting
516 percentile. it from the standing height to get the subischial limb length.
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Table 1: Pointers toward diagnosis from history Clinical Examination

Small for gestational age SGA sequelae, Russell-Silver It includes a thorough examination to look for any pointers of
(SGA) syndrome, Seckel syndrome a specific etiology of short stature. Facial dysmorphism adds
Breech delivery Growth hormone deficiency important information. Few of these are listed below.
(GHD), multiple pituitary hormone Evidence of anemia, cyanosis, jaundice, signs of chronic
deficiency (MPHD) illness such as renal, liver, pulmonary disorders including
Neonatal hypoglycemia, GHD, MPHD asthma and nutritional deficiency, including features of
jaundice malabsorption syndrome. Bony deformities including bow
legs, knock knees, kyphosis, and scoliosis would indicate
Family history of Genetic causes
involvement of the skeletal system. A detailed systemic
consanguinity
examination would add to the information.
Family history of delayed Constitutional delay in growth and
puberty with short stature puberty
with normal final height Clinical Pearl
Family history of short Familial short stature, parents
stature with heterozygote state for • Short stature with anemia should raise suspicion of celiac
conditions such as achondroplasia, disease.
hypochondroplasia
Short stature in infancy Syndromic short stature, skeletal
1st tier investigations
dysplasia
• Hemogram
Short stature in childhood GHD, hypothyroidism, MPHD,
chronic illness, Turner syndrome • Biochemical investigations:
{{ Serum creatinine (renal function)
Intracranial tumors, MPHD {{ Serum glutamic pyruvic transaminase (liver function)
irradiation, trauma, surgery
{{ Venous blood gas (if evidence of rickets to rule out
Headache, vomiting, visual Intracranial tumor renal tubular acidosis in case of rickets)
disturbances {{ Thyroid function test
Persistent diarrhea, Celiac disease {{ Anti-tissue transglutaminase (TTG) immunoglobulin A

abdominal distension (IgA) (anti-TTG antibody, if low, reconfirm with total
History of asthma, liver, Pointers of chronic disease IgA levels and immunoglobulin G antibody)
renal disease {{ Karyotype in a girl with unexplained short stature
• Radiological investigations: bone age [using Gruelich

This can be plotted on sitting height and subischial leg length and Pyle, Tanner Whitehouse 3 (TW 3), Gilsanz and Ratib
combined charts. methods].
The US/LS ratio is 1.7:1 at birth. It gradually decreases Bone age is a useful, cheap, and invaluable investigation
reaching to a ratio of 1:2 at around 7 years and 1.1:1 at 10 years. in the assessment of short children. In Gruelich and Pyle
It remains so till puberty when it further dips to 0.98:1 due to an atlas, comparison of a radiograph of the left hand is done
earlier spurt in limb height as compared to the spine growth. with that of standard age and gender specific radiographs.
Toward the end of puberty with an increase in spine height The age at which the radiograph in the atlas matches
with a nearly stabilized limb length, the ratio again rises to 1:1, closest to the actual one of the patient in terms of maturity
which persists thereafter. of ossification centers of bones, is the bone age of the
Disproportionate short stature is seen in conditions
wherein the growth of either the limbs or spine is more
affected. In skeletal dysplasias, the limbs are more affected Box 2: Causes of proportionate and disproportionate short
and the spine is spared. An exception is spondyloepiphyseal stature
dysplasia wherein both the spine and limbs are affected. Proportionate short stature Disproportionate short stature
Spinal shortening is seen in storage disease such as
• Growth hormone deficiency Short upper segment
mucopolysaccharidosis.
• Malnutrition • Mucopolysaccharidosis
• Rickets • Spondyloepimetaphyseal
Clinical Pearl • Chronic illness dysplasia
• Syndromic short stature Short lower segment
• A short and thin child with weight most severely affected: think • Small for gestational age • Achondroplasia, hypo
of chronic illness, syndromic short stature, and malnutrition sequelae chondroplasia
• A short and overweight child: think of endocrinopathy—growth • Osteogenesis imperfecta
hormone deficiency, hypothyroidism, and Cushing syndrome. • Hypophosphatemic rickets
517
ch-106.indd 517 11/25/2016 9:41:46 AM

patient. This is a fairly reliable method that can be used in Table 2: Clinical signs indicating etiology
day-to-day practice.
Clinical signs Etiology
The TW 3 atlas is more exhaustive method, wherein
13 or 20 ossification centers in the hand are scored. The Immature facies with frontal bossing, Growth hormone deficiency
summation of these is then looked up in a table to give the depressed nasal bridge, midfacial
hypoplasia, high pitched voice
final bone age. This is more of a research tool.
Gilsanz and Ratib have recently released their own atlas Mental slowing, coarse facies, puffy Hypothyroidism
of bone age assessment which is very similar to Gruelich appearance, goiter
and Pyle method with an added advantage of digital Antimongoloid slant, low posterior Turner syndrome
processing. hair line, webbed neck, short 4th/5th
metacarpals, metatarsals, wide
carrying angle, pigmented nevi,
Clinical Pearl difference in upper limb lower limb
blood pressure
• Karyotype to rule out Turner syndrome is needed in all short
Beak headed dwarfism, height less Seckel syndrome
girls even in the absence of stigmata. than -7 SD, developmental delay
Small triangular facies with Russell-Silver syndrome
Interpretation of Growth Velocity hemiatrophy
Child has normal growth velocity with growth curve Almond shaped eyes, hypo Prader-Willi syndrome
gonadism, obesity, behavioral
cruising below the 3rd percentile is a short normal child and
problems, hyperphagia
needs continued monitoring. He/she may need 2nd level
of investigations to rule out all causes before diagnosing as Coarse facies, macrocephaly, short Skeletal dysplasia
idiopathic short stature. Growth hormone has been used to stubby fingers, rhizomelia
treat short normal children who are below –2.5 SD and who are Short 4th/5th metacarpal or SHOX gene defect,
not likely to achieve normal adult stature. metatarsal pseudopseudo
hypoparathyroidism, Turner
Low Growth Velocity (Faltering Growth Curve) syndrome
Consider 2nd tier investigations:
• Anti-TTG IgA Table 3: Growth hormone dose
• Growth hormone stimulation test: two provocation tests
using clonidine, glucagon, insulin, dopamine, arginine, Underlying condition Dose
and growth hormone–releasing hormone (in India, Growth hormone deficiency 25–40 µg/kg/day
clonidine, glucagon, arginine, and insulin are available) Turner syndrome 50–60 µg/kg/day
• Magnetic resonance imaging brain: pituitary size, and Small for gestational age sequelae 35–70 µg/kg/day
congenital malformations of the brain Prader-Willi syndrome 25–50 µg/kg/day
• Molecular testing for syndromes.
Idiopathic short stature 50 µg/kg/day
Idiopathic short stature if all tests are negative.
Algorithm 1
Short stature
518 SD, standard deviation; GV, growth velocity; BA, bone age; CDGP, constitutional delay in growth and puberty; SS, short stature.
ch-106.indd 518 11/25/2016 9:41:46 AM

Management Strategies CONCLUSION

Treatment of the underlying condition usually leads to It is necessary to differentiate a short normal child from a
improvement in the growth velocity and catch up growth. short child with pathology. Treatment of only pathological
short stature is warranted. Growth hormone therapy is
Growth Hormone indicated for special conditions, is usually for long term. The
Growth hormone therapy is used in the following conditions: therapy aims at achieving genetic potential and depends
Licensed indications: on many factors, such as age at onset of therapy, etiology,
• Growth hormone deficiency degree of short stature, and duration of therapy, contrary to
• Small for gestational age sequelae unrealistic expectations of most parents.
• Turner syndrome
• Prader-Willi syndrome Key points
• Idiopathic short stature
• Chronic renal failure prior to renal transplant ))
Anthropometry and plotting of growth chart remains the
• Glucocorticoid induced short stature most powerful tool for the diagnosis of short stature
Conditions with doubtful benefit (under research at ))
Longitudinal assessment of growth and growth velocity is
present): much more important than a single time evaluation as it gives
• Hypochondroplasia idea of growth pattern
• Chronic inflammatory disorders like rheumatoid arthritis ))
Bone age beyond 2 years of actual age on either side is
• Noonan syndrome considered abnormal and points toward an endocrine disease
• Other skeletal dysplasia. ))
Adjusting height for midparental target height often reduces
Recombinant human growth hormone is given in the form unnecessary investigations in short child
of subcutaneous injections daily at bedtime for a period of at ))
A short and fat child has an endocrine disease, skeletal
least 2 years, ideally till the final height is achieved. Growth dysplasia, or syndrome whereas tall and fat child has
hormone therapy is not useful once there is complete bony nutritional obesity.
fusion. Response depends on indication for which it is used,
age of starting therapy, duration of therapy, dose used, MPH,
and bone age at onset. suggested readings
Although adverse effects are rare, they may include:
1. Bull RK, Edwards PD, Kemp PM, Fry S, Hughes IA. Bone age assessment: a large
benign intracranial hypertension, hyperglycemia, worsening
scale comparison of the Greulich and Pyle, and Tanner and Whitehouse (TW2)
of scoliosis, slipped capital femoral epiphyses, gynecomastia, methods. Arch Dis Child. 1999;81:172-3.
rash, and hives. Increased predisposition for neoplasia in 2. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, et al. Consensus
those with increased chromosomal breakage syndromes statement on the diagnosis and treatment of children with idiopathic short
has also been reported and is a contraindication to growth stature: a summary of the Growth Hormone Research Society, the Lawson
hormone therapy. Wilkins Pediatric Endocrine Society, and the European Society for Paediatric
Endocrinology Workshop. J Clin Endocrinol Metab. 2008;93(11):4210-7.
3. Gilsanz V, Ratib O. Hand Bone Age: A Digital Atlas of Skeletal Maturity. Berlin,
Androgens
Heidelberg: Springer-Verlag; 2005.
Depot testosterone in small doses of 50 mg monthly for 4. Khadilkar V, et al. 2007 Indian growth references. [online] Available from http://
3–6 months has been used in boys with CDGP. It is used to trigger www.indiachildgrowth.com/growth-charts.html.
the onset of pubertal spurt and usually results in attainment 5. Khadilkar V, Khadilkar A. Growth charts: a diagnostic tool. Indian J Endocr Metab.
of satisfactory final height. In some conditions wherein the 2011;15(Suppl 3):S166-71.
predicted adult height is less, it may be combined with growth 6. Khadilkar V, Phanse S. Growth charts from controversy to consensus. Indian J
hormone. The disadvantage of testosterone is that it aromatizes Endocrinol Metab. 2012;(16):S185-7.
to estrogen and thus results in rapid bone maturation and 7. WHO Multicentre Growth Reference Study standards. [online] Available from
http://www.who.int/childgrowth/standards/en/[Accessed February, 2016].
fusion. Oxandrolone, a nonaromatizable androgen is a better
8. Wilson TA, Rose SR, Cohen P, Rogol AD, Backeljauw P, Brown R, et al. Update
alternative as it does not lead to early bony fusion. of guidelines for the use of growth hormone in children: the Lawson Wilkins
Limb lengthening using Ilizarov may be offered for children Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr.
with achondroplasia. 2003;143(4):415-21.
519
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Chapter 107
Childhood Obesity
Anurag Bajpai
INTRODUCTION charts should be used. Body mass index between 85th and
95th percentile for age indicates overweight, above the 95th
Childhood obesity has emerged as a global epidemic with percentile suggests obesity, and greater than 99th percentile
doubling of prevalence over the last two decades. Studies (120% of 95th percentile) severe obesity.
from different parts of India have shown a rise in prevalence of For the same BMI, Indians have a greater risk of metabolic
overweight and obesity from 15 to 28%. The risk of numerous syndrome compared to their Western counterparts. As the aim
complications of early onset obesity imposes significant burden of assessing BMI is to identify individuals at risk for metabolic
on the individual and society. Moreover, most obese children complications, lower BMI cutoffs have been recommended
become obese adults. Timely evaluation and management of for Indian adults (23 kg/m2 for overweight and 28 kg/m2 for
childhood obesity is, therefore, crucial. obesity). The applicability of lower cutoffs in Indian children
needs study.
WHAT IS OBESITY?
Weight for Height
The term implies excessive body fat, not merely excess body
weight. Thus, body weight alone is not a reliable marker of Weight for height should be used in children younger than
obesity. The gold standard for diagnosis is increased body 2 years of age. Weight for height more than 120% suggests
fat measured by bioimpedance or dual energy enhanced obesity.
X-ray absorptiometry. These methods are cumbersome, used
mainly for research purposes. In practice, surrogate markers of Waist Circumference
adiposity using a combination of height and weight are used. Waist circumference is a marker of abdominal obesity, a
predictor of metabolic syndrome. Levels higher than 95th
Body Mass Index percentile for age and gender are abnormal.
Body mass index (BMI) should be used for diagnosing obesity
after 2 years of age. It takes into account the weight and height WHAT CAUSES OBESITY?
of the individual.
In most children, obesity is not due to a disease, but related
BMI = Weight (kg) ÷ height (m)2 to lifestyle factors (constitutional obesity), while pathological
causes account for less than 1% cases (Table 1). It is important to
Body mass index correlates well with body fat and
identify pointers to pathological obesity to avoid unnecessary
complications in children; however it may incorrectly diagnose
workup in children with constitutional obesity.
obesity in muscular individuals, while under estimating
adiposity in sedentary children with reduced muscle mass.
Body mass index cutoffs for diagnosing obesity have been Clinical Pearl
developed using statistical distribution (Centers for Disease
Control and Prevention charts) or extrapolating from adult • Obesity implies increased body fat and not weight; body mass
index may erroneously diagnose obesity in short, muscular
cutoffs (International Obesity Task Force). It varies with age,
individuals.
ethnicity, and gender. Thus, age and gender specific local
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Chapter 107: Childhood Obesity
Table 1: Causes of obesity Monogenic Obesity

Class Etiology Single gene defects are a very rare cause of obesity, and
Constitutional Lifestyle issues should be suspected with early onset obesity, rapid weight
gain and strong family history. Inefficient leptin action
Endocrine Cushing syndrome, hypothyroidism, growth (deficiency or resistance) results in uncontrolled appetite
hormone deficiency, Turner syndrome,
and obesity. Abnormalities in mineralocorticoid receptor
pseudohypoparathyroidism
and proconvertase have also been associated with obesity.
Dysmorphic Prader-Willi, Lawrence-Moon- melanocortin 4 (MC4) receptor defects are the commonest
syndromes Biedl-Bardet, Cohen, Alstrom, Carpenter monogenic form of obesity and are associated with growth
Monogenic Leptin deficiency, leptin resistance, melanocortin acceleration.
4 receptor, proconvertase II
Drugs Corticosteroids, olanzapine, risperidone, valproate
Drugs
Commonly used drugs associated with obesity include
cortico
steroids, antipsychotics (olanzapine, risperidone),
Constitutional Obesity anti
depressants (paroxetine), and antiepileptics (valproate,
lamotrigine).
Constitutional obesity results from an imbalance between
energy intake and expenditure. It is caused by a combination Clinical Pearl
of genetic and environmental factors. Family history is
common. Both low birth weight and high birth weight are • Think of pathological obesity in children with growth failure
associated with increased risk of obesity later in life. Dietary and/or developmental delay. Constitutional obesity is more
habits associated with childhood obesity include missing likely if the child is tall and fat.
meals (especially breakfast), higher portion size, snacking,
frequent eating out, and watching television while eating.
Breastfeeding in infancy has a protective effect. Lack of WHY BOTHER ABOUT OBESITY?
activity and increased screen time are associated with obesity.
Childhood obesity is a predictor of a number of short- and
Clinical Pearl long-term complications (Table 2).
• Childhood obesity is most commonly due to lifestyle factors. Endocrine

Endocrine complications are the most important adverse
effects of childhood obesity. Central to this is the development
Endocrine Causes of insulin resistance (IR), caused by overspill of fat and its
Endocrine diseases are rare but treatable causes of childhood deposition in liver and skeletal muscle. Insulin resistance
obesity. They should be considered in the presence of clinical predisposes to the development of type 2 diabetes mellitus
pointers, mainly growth failure and delayed puberty. Cushing (T2DM), polycystic ovarian syndrome (PCOS) and non
syndrome presents with central obesity, high blood pressure, alcoholic fatty liver disease (NAFLD). Hyperandrogenism
growth failure, and violaceous striae. Hypothyroidism is a rare is common in obese girls, as is accelerated growth, skeletal
cause of isolated obesity, usually associated with growth failure maturation, and early puberty.
and developmental delay. In growth hormone (GH) deficiency
and pseudohypoparathyroidism, growth retardation and
hypocalcemia are dominant clinical features. Table 2: Complications of obesity
Dysmorphic Syndromes Category Complications

Obesity is often a manifestation of dysmorphic syndromes. Metabolic Insulin resistance, type 2 diabetes mellitus,
Many of these syndromes are associated with hypogonadism metabolic syndrome, hyperandrogenism
or hypotonia (Prader-Willi, Carpenter, Lawrence-Moon-Biedl- Cardiovascular Hypertension, dyslipidemia, atherosclerosis
Bardet syndromes). Gastrointestinal Nonalcoholic fatty liver disease, gall stones,
gastroesophageal reflux
Hypothalamic Obesity
Skeletal Blount’s disease, slipped capital femoral
Hypothalamic obesity is caused by increased appetite due to epiphysis, fractures
a central nervous system (CNS) insult by surgery, radiation,
Respiratory Obstructive sleep apnea, hypoventilation
tumors and trauma. These disorders are associated with syndrome
excessive appetite, signs and symptoms of CNS involvement,
and other hypothalamic-pituitary defects. Neurological Benign intracranial hypertension
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Cardiovascular What Is the Cause of Obesity?

Obese children have a higher prevalence of dyslipidemia, Most obese children do not require investigations for the
hypertension, atherosclerosis, and increased risk of adult cause. It is important to identify the children who need workup
coronary disease. Importantly, hypertension may be masked, by clinical examination (Table 3 and Algorithm 1).
warranting repeated blood pressure measurements.
Clinical Evaluation
Central Nervous System The clinical evaluation should include detailed history and
Benign intracranial hypertension is common in children with examination. Pathological obesity should be considered
obesity and presents with headache and vomiting. with early onset of obesity, rapid weight gain, growth failure,
dysmorphism, developmental delay, and pubertal delay.
Orthopedic Pointers to specific disorders should be evaluated (Tables 4
and 5). Detailed dietary history, including duration of
These children have a higher risk of flat foot, Blount’s breastfeeding, age at weaning, meal pattern, calorie intake,
disease, fractures, genu valgum, and osteoarthritis. The most snacking, consumption of junk food, and features of feeding
debilitating complication is slipped capital femoral epiphysis, disorders should be taken. Duration of activity and inactivity
which presents with dull aching pain in the knee, hip or groin,
with abnormal gait. Blount’s disease (tibia vara) presents with Table 3: Differentiating features of constitutional and
progressive bowing of legs and knee pain. X-ray of knee and pathological obesity
hip should be done in obese children with pain in hip or knee,
or abnormal gait. Feature Constitutional Pathological
Pattern Generalized Central
Respiratory Growth rate Accelerated Retarded
Obese children are at increased risk of respiratory distress and Skeletal maturation Advanced Retarded
bronchial asthma. Obesity predisposes to the development of Dysmorphic features Absent May be present
obstructive sleep apnea and hypoventilation syndrome. Endocrine features Absent May be present
Gastrointestinal
Algorithm 1
Obesity is associated with gastroesophageal reflux and
NAFLD. Fatty liver is present in 40%, elevated transaminases Approach to a child with obesity
in 25%, and gall stones in 2%. Rapid weight fluctuations are
associated with gall stone disease, which should be suspected
in an obese child with abdominal pain, jaundice, nausea, and
intolerance to fatty foods.
Psychological
Obesity is associated with increased prevalence of mood
disorders. This represents intrinsic effects of obesity on one
hand and psychological effects of bullying on the other. It is
important to assess the effect of an obese child, as depression MPH, midparental height.
increases the risk of obesity.
Clinical Pearl Table 4: Clues to diagnose obesity

Disorder Features
• Obesity causes several short- and long-term complications,
Delayed puberty Lawrence-Moon-Biedl-Bardet, Prader-Willi
including insulin resistance, type 2 diabetes mellitus,
syndrome
polycystic ovarian syndrome, nonalcoholic fatty liver disease,
dyslipidemia, hyper tension, atherosclerosis, orthopedic Retinitis pigmentosa, Alstrom, Lawrence-Moon-Biedl-Bardet
problems, obstructive sleep apnea, and mood disorders. polydactyly syndrome
Small hands and feet Prader-Willi syndrome
Buffalo hump, striae Cushing syndrome
HOW TO EVALUATE A CHILD WITH OBESITY? th
Short 4 metacarpal Pseudohypoparathyroidism, Turner
Evaluation involves careful clinical assessment followed by syndrome
focused investigations. The key questions are the cause of Developmental delay Prader-Willi, hypothyroidism,
obesity and its effects. pseudohypoparathyroidism
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Table 5: Features of common causes of obesity diagnosed as Cushing syndrome. Genetic testing for Prader-
Willi syndrome should be done in the presence of facial
Disorder Features
features, history of infantile hypotonia, and growth failure.
Prader-Willi syndrome Infantile hypotonia, hyperphagia, Monogenic causes of obesity should be considered only in
almond like eyes, acromicria,
the presence of clinical features or pointers to diagnosis.
hypogonadism, behavioral abnormalities
Lawrence-Moon-Biedl- Hypogonadism, retinitis pigmentosa,
Bardet syndrome polydactyly, renal abnormalities, mental
What are the Complications of Obesity?
retardation When to Evaluate?
Beckwith-Wiedemann Organomegaly, ear lobe creases, Assessment of complications of obesity should be done in
hemihypertrophy
children with BMI above 95th percentile and those with BMI of
Cushing syndrome Hirsutism, central obesity, growth 85th–95th percentile and family history of T2DM, hypertension,
retardation, striae, buffalo hump, PCOS, or acanthosis nigricans.
hypertension, myopathy
Hypothyroidism Growth retardation, coarse facies, Clinical Evaluation
developmental delay
History should inquire about symptoms of complications
Pseudohypopara Tetany, round facies, short 4th of obesity like headache, vomiting (benign intracranial
thyroidism metacarpal, cutaneous calcifications
hypertension), day time somnolence, respiratory distress,
snoring (obstructive sleep apnea), abdominal pain (fatty liver,
gall stone disease), acne, hirsutism, menstrual irregularity
should be looked into. Family history of consanguinity,
(PCOS), pain in hip and knee (slipped capital femoral
T2DM, ischemic heart disease, and dyslipidemia should
epiphysis) or abnormal gait (Blount’s disease). Examination
be inquired. Drug history should assess intake of steroids,
should include measurement of blood pressure, acanthosis
valproate, antipsychotic, and any other drugs. History of
nigricans, hepatomegaly, cardiac examination and pedal edema
CNS infection, trauma, radiation, tumor or surgery indicates
(obstructive sleep apnea and cor pulmonale), and range of
hypothalamic obesity.
movement of knee and hip (slipped capital femoral epiphysis).
Examination should include assessment of growth
parameters, pubertal status, and clues to diagnosis. Pubertal Investigations
assessment may be challenging. Parents of obese girls are often
concerned about premature thelarche. While this may reflect Investigations should include an oral glucose tolerance
true precocious puberty caused by obesity, it is most likely test: blood sugars fasting and 2 hours after 1.75 g/kg glucose
due to increased fat and not true thelarche. To distinguish (maximum of 75 g), lipid profile, and liver function tests. Age
these conditions, approximate the thumb and index finger appropriate cutoffs should be used for interpretation (Table 6).
around the nipple: lack of resistance indicates lipomastia; These tests should be repeated every 3 years if normal. Fasting
breast nodule can be felt as an area of resistance. Obese boys insulin has limited role and is not routinely required; serum
frequently present with concerns of small penile size, which insulin 2 hours post glucose load may be raised, though
is usually due to penis being buried in the suprapubic pad. there are no definite cutoffs in the pediatric age group. Mildly
Stretched penile length should be measured after pressing the elevated liver transaminases are common in obesity; persistent
suprapubic pad of fat, to ascertain the actual size of penis. elevation beyond twice the upper limit indicates nonalcoholic
steatohepatitis. Children with elevated transaminases should
Clinical Pearl undergo ultrasound abdomen and workup for other causes of
hepatic dysfunction (hepatitis B and C, Wilson disease, and
• Lipomastia may look like thelarche. Buried penis in suprapubic
fat may give false impression of micropenis in obese boys. Table 6: Pediatric cutoffs for investigations for assessment of
obesity complications
Investigation Normal Borderline Abnormal
Investigations
Blood sugar <100 mg/dL 100–125 mg/dL >126 mg/dL
No workup for cause is required in children with normal
fasting
growth, facies, development, and pubertal development.
Thyroid profile and evaluation for Cushing (serum cortisol Blood sugar 2 h <140 mg/dL 140–199 mg/dL >200 mg/dL
after glucose load
at 8 am after dexamethasone at 11 pm) should be done in
the presence of growth failure and/or characteristic clinical Total cholesterol <170 mg/dL 170–199 mg/dL >200 mg/dL
features. The effect of obesity on endocrine function should LDL cholesterol <110 mg/dL 110–129 mg/dL >130 mg/dL
be considered while assessing endocrine functions. Mildly
Triglyceride <90 mg/dL 90–129 mg/dL >139 mg/dL
elevated thyroid-stimulating hormone (TSH) levels with
normal free thyroxine are common in obesity, and should HDL cholesterol >45 mg/dL 40–45 mg/dL <40 mg/dL
not be treated unless TSH is persistently and significantly AST <40 IU/L 40–80 IU/L >80 IU/L
(>10 IU/mL) elevated. Similarly, cortisol levels may be mildly LDL, low density lipoprotein; HDL, high density lipoprotein; AST, aspartate
523
elevated and easily suppressed, and should not be mistakenly aminotransferase.
ch-107.indd 523 11/21/2016 2:12:33 PM

autoimmune hepatitis). Sleep studies may be required in the Treatment of Complications

presence of snoring, day time somnolence, or lethargy.
Complications should be treated early to avoid long-term
adverse effects. Metformin is indicated for IR, T2DM, NAFLD
How to Manage a Child with Obesity? and PCOS; statins for persistent dyslipidemia. Treatment of
NAFLD includes metformin, vitamin E, and pioglitazone. Girls
Management is a big challenge, requiring a multidisciplinary
with PCOS benefit from lifestyle modification, metformin, oral
approach involving physician, nutritionists, and physical
contraceptives, and antiandrogens. Medroxy progesterone
trainers, with changes made by the entire family. The goal is to
acetate is beneficial in children with obesity hypoventilation
bring BMI as close to the normal range for age and gender as
syndrome. Continuous positive airway pressure is needed in
possible. Normalization may be difficult; excessive and rapid
obstructive sleep apnea.
weight loss adversely affects the growth of the child and should
be avoided. In most cases, weight stabilization is the initial
aim. Weight loss should not exceed 1 kg every month in most Medical Treatment for Obesity
children. The child and parents should be counseled that there Drugs used in the past have faced problems due to adverse
is no quick fix solution, and the family would need to adhere effects. Orlistat is the only drug approved for use in children with
to the modified lifestyle throughout life. The key focus is on obesity. It inhibits gastric lipase, resulting in reduced absorption
changing the lifestyle of the child and family, with use of drugs of fat, with modest weight loss. Major side effects include
and surgery in the rarest of rare cases. abdominal pain, bloating, steatorrhea, and anal leakage of oil.
It has to be combined with fat soluble vitamins. Newer agents
Clinical Pearl in the pipeline include MC4 receptor modulators, glucagon-like
peptide 1 analogs, and endocannabinoid agonists.
• Lifestyle measures should be adopted by the entire family, not
just the child. Surgical Management
Bariatric surgery should be considered only in severe obesity
Lifestyle Measures when other measures have failed, only after achievement of
This is the cornerstone to management. The whole family is final height, due to potential adverse growth effects. It is a major
encouraged to follow a healthy lifestyle: focusing on the child surgical undertaking, to be viewed as potentially life-saving,
alone is counterproductive. not just a cosmetic procedure. Patients need to adhere to strict
dietary restriction for life. In children, laparoscopic adjustable
Nutritional Therapy banding is the recommended procedure; malabsorptive
The child should be advised to eat regular meals. Skipping procedures and gastric sleeve should not be done.
meals and snacking between meals should be discouraged.
The caloric intake should be reduced by 20%. Overzealous Clinical Pearl
restriction and fad diets are not recommended. Food pyramid
• Medical and surgical treatment of childhood obesity should be
and traffic light approach for diet may be used to highlight considered only in severe cases associated with complications.
healthy eating patterns, with special emphasis on fixed portion
size, decreased junk food consumption, avoiding television
viewing while eating, and increased fruit consumption. HOW TO PREVENT CHILDHOOD OBESITY?
Physical Activity Given the difficulties in management, prevention is the desirable
goal. Though this is very challenging, the recent plateauing of
Periods of inactivity should be reduced and increased physical
childhood obesity rates in several states in the United States
activity should be planned. Screen time (television, computer,
and some European countries is encouraging. This is proof
and mobile devices) should be restricted to less than 1 hour
that awareness and societal changes can reduce this important
a day. Increased routine activities (e.g., household chores,
public health problem. Key measures include prevention and
walking to school) should be encouraged. A minimum of 30
treatment of adult obesity (due to intergenerational effects
minutes daily of enjoyable activity like dancing, sports, and
of obesity), early identification and treatment of gestational
running should be ensured, avoiding weight bearing exercises
diabetes mellitus, and increased consumption of healthy
and over regimented schedules.
food. Exclusive breastfeeding should be done till 6 months, on
a demand basis, not according to a schedule. Infants should
Specific Management be given the freedom to decide the frequency and amount of
Specific treatment is needed for hypothyroidism, GH feeds. Saturated fats (e.g., full fat milk) should be restricted after
deficiency, and Cushing syndrome. Mild elevations of TSH age 2 years. Changes in dietary habits—eating food with family
do not need treatment. Obese children with Prader-Willi at regular times, avoiding snacking, avoiding television while
Syndrome and growth failure may benefit from GH therapy. eating, and fixed portion size, should be advised. The child is
Octreotide is effective in hypothalamic obesity, leptin in leptin encouraged to play (moderate physical activity) for at least 60
524 deficiency. minutes daily. The overall screen time should be limited to
ch-107.indd 524 11/21/2016 2:12:33 PM

less than 2 hours a day. Television should be removed from SUGGESTED READINGs
children’s bedrooms, and avoided in children under 2 years.
1. Alemzadeh R, Rising R, Cedillo M, Lifshitz F. Obesity in children. In: Lifshitz F (Ed).
Pediatric Endocrinology, 4th ed. New York: Marcel Dekker; 2003. pp. 823-58.
Key points 2. Barlow SE, Expert Committee. Expert committee recommendations regarding the
))
Childhood obesity is now a global epidemic, mainly due to prevention, assessment, and treatment of child and adolescent overweight and
lifestyle changes, pathologic causes are rare obesity: summary report. Pediatrics. 2007;120 Suppl 4:S164.
))
Body mass index after the age of 2 years, and weight for 3. CDC. (2013). Progress in Childhood Obesity. CDC vital signs. [online] Available
height in infants, and waist circumference, are used for from http://www.cdc.gov/vitalsigns/pdf/2013-08-vitalsigns.pdf. [Accessed May,
routine diagnosis 2015].
4. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk
))
In constitutional obesity, the child is usually tall for age.
Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute.
Pathologic causes should be suspected in a child with growth
Expert panel on integrated guidelines for cardiovascular health and risk reduction
retardation (i.e., short and fat) and/or delayed puberty
in children and adolescents: summary report. Pediatrics. 2011;128 Suppl
))
Obesity leads to several health problems, so it should be 5:S213.
taken seriously
5. Freemark F. Metabolic consequences of obesity and their management. In:
))
Most obese children require investigations not for the cause, Brook CGD, Clayton PE, Brown RS (Eds). Clinical Pediatric Endocrinology, 5th ed.
but for the consequences of obesity London: Blackwell publishing; 2005. pp. 419-35.
))
Management involves lifestyle changes for the entire family, 6. Gillman MW, Ludwig DS. How early should obesity prevention start? N Engl J
and treatment of consequences Med. 2013;369(23):2173-5.
))
Management is difficult. Prevention is critical, at all levels, from 7. Muglia LJ, Majzoub JA. Nutritional disorders. In: Sperling MA (Ed). Pediatric
individual to societal Endocrinology, 2nd ed. Philadelphia: WB Saunders; 2002. pp. 671-88.
))
Lipomastia and buried penis require weight loss, and no other 8. Speiser PW, Rudolf MC, Anhalt H, Camacho-Hubner C, Chiarelli F, Eliakim A, et al.
treatment. Childhood obesity. J Clin Endocrinol Metab. 2005;90(3):1871-87.
525
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Chapter 108
An Approach to Hyperglycemia
Aspi J Irani
INTRODUCTION • In the NICU, an increased risk of severe retinopathy of

prematurity, necrotizing enterocolitis (NEC) broncho
Normoglycemia is defined as fasting venous plasma glucose pulmonary dysplasia, septicemia, with longer duration of
between 70 and 100 mg/dL and a 2-hour postprandial or post NICU stay, and a higher mortality
glucose value less than 140 mg/dL. Corresponding values • In the long-term, persistent hyperglycemia can affect many
more than 126 and 200 mg/dL are used to define diabetes organs by glycosylation of proteins/collagen.
mellitus (DM).
Hyperglycemia is encountered by the pediatrician/
neonatologist in five different settings: CHILD OR ADOLESCENT WITH TYPICAL
1. Child or adolescent with typical symptoms of DM SYMPTOMS OF DIABETES MELLITUS
2. Hyperglycemia as an incidental pick up (or during
screening) in an obese (but asymptomatic) adolescent Polyuria, polydipsia, polyphagia, weight loss, and weakness
3. Neonate or infant (below 6 months) with symptoms of (with or without a history of ants around the urine and of vaginal
hyperglycemia candidiasis) are typical symptoms due to hyperglycemia.
4. Hyperglycemia during an acute illness in a child/ If ketosis has set in, there would be anorexia, abdominal
adolescent [stress hyperglycemia (SH)] pain, vomiting, abdominal distension, dehydration, acidotic
5. Hyperglycemia in a sick neonate in the neonatal intensive breathing with a peculiar “acetone” odor to the breath, and
care unit (NICU). drowsiness. Shock and coma may occur but are uncommon.
Hyperglycemia is due to a disturbed balance between In the presence of typical symptoms of hyperglycemia
insulin on one hand and the counter-regulatory hormones with ketosis, single random blood glucose over 200 mg/dL is
(adrenaline, glucagon, cortisol, and growth hormone) on the sufficient to clinch the diagnosis of DM. In this situation, an
other. While insulin promotes utilization or storage of glucose oral glucose tolerance test (OGTT) is not only unnecessary but
entering the body, and promotes protein and fat anabolism, can also be dangerous.
the counter-regulatory hormones promote catabolism of In an asymptomatic or mildly symptomatic child, a fasting
protein and fat and favor movement of glucose into the blood blood glucose (done after 8 h of no calorie intake) of 126 mg/
stream from storage sites (chiefly liver, muscle, and kidneys) by dL or above with 2-hour postprandial value 200 mg/dL or more
promoting gluconeogenesis and glycogenolysis. on two occasions is diagnostic of DM. The OGTT should never
Adverse effects of hyperglycemia include: be done if DM can be diagnosed from the fasting, random, or
• Osmotic diuresis with dehydration and electrolyte postprandial blood glucose values. A fasting blood glucose
derangements once the renal threshold has been exceeded between 100 and 125 mg/dL is referred to as “impaired fasting
• Hyperosmolarity (An 18 mg/dL rise in blood glucose raises glucose” while a post glucose reading between 140 and 199
osmolarity by 1 mOsm/L) and osmotic shifts with brain cell mg/dL is labeled as “impaired glucose tolerance”; both these
dehydration and risk of intracranial bleeds are considered as prediabetic states.
• Glucose overload in insulin independent endothelial Having made the diagnosis of DM, the next step is to
cells (hepatic, immune, and nerve cells) with generation ascertain the type of DM. Type 1, is, by far, the commonest
of oxygen free radicals and resultant mitochondrial variety encountered in childhood. Presence of detectable
dysfunction and enhanced apoptosis pancreatic autoantibodies (common antibodies tested are to
• Impaired leukocyte phagocytic function predisposing to glutamic acid decarboxylase (GAD) 65, insulin, islet cell, and
infections and leading to delayed clearing of infections tyrosine phosphatase) with low C-peptide values in a child
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Chapter 108: An Approach to Hyperglycemia
with acute onset of symptoms of DM confirms the diagnosis Algorithm 1

of T1DM. One should look for associated autoimmune Approach to a pediatric patient with typical symptoms of hyper
disorders, both endocrine (thyroid dysfunction, adrenal glycemia with or without ketonuria
disease, and hypoparathyroidism) and nonendocrine (celiac
disease, alopecia areata, vitiligo, autoimmune hepatitis,
mucocutaneous candidiasis, and pernicious anemia).
Type 2 DM (T2DM) is becoming commoner because of
the increasing incidence of adolescent obesity. It must be
suspected in any obese adolescent with a family history of
T2DM, especially if there are associated features indicating
insulin resistance [acanthosis nigricans, hypertension,
hyperlipidemia, evidence of polycystic ovarian syndrome
(PCOS)]. In such cases, absence of antibodies typical of T1DM
with high C-peptide levels would confirm T2DM. It must be
emphasized that diabetic ketoacidosis (DKA) at presentation
does not exclude T2DM; 6–33% of T2DM present in DKA.
A nonobese adolescent with mild diabetes and a family
history of DM in three generations, possibly has one of the
varieties of maturity onset diabetes of the young. If there is
optic atrophy or associated deafness or persistent polyuria
despite good control of DM (pointing to an associated diabetes
insipidus), the diagnosis would be “Wolfram syndrome”. In a
child with recurrent abdominal pain, the development of DM
should initiate a search for pancreatic calculi (fibrocalculus
pancreatic diabetes). Diabetes associated with sensorineural
deafness and thiamine responsive megaloblastic anemia is
referred to as “Roger syndrome”. The clinician needs to look
for any syndromic features in a child with DM as Mongolism,
Turner syndrome, Prader-Willi, and Klinefelter syndromes
(besides many others) can be associated with DM with a higher
frequency than in the general population. Adolescents with
thalassemia major tend to develop DM in the second decade
of life due to iron loading in the pancreas (causing insulin
deficiency) and in the liver (leading to insulin resistance).
Algorithm 1 outlines the approach to a pediatric patient with
typical symptoms of hyperglycemia with or without ketonuria.
Insulin is the mainstay of treatment for T1DM and also for F/H, family history; T1DM, type 1 diabetes mellitus; PCOS, polycystic ovarian
initial treatment in T2DM with acute presentation. Metformin syndrome; T2DM, type 2 diabetes mellitus; FCPD, fibrocalculous pancreatic
is the only approved oral drug for pediatric T2DM. All varieties diabetes; MODY, maturity onset diabetes of the young; H/O, history of.
of DM also require lifestyle change, meal planning, regular
planned physical activity, counseling, and attention to the diagnostic approach and classification of deranged glucose
comorbidities. All patients with DM must receive intensive and metabolism in these cases.
ongoing education in diabetes self-management.
Clinical Pearl
HYPERGLYCEMIA DETECTED ON SCREENING • Obese adolescents with evidence of insulin resistance or
IN AN OBESE ASYMPTOMATIC ADOLESCENT a family history of diabetes mellitus (DM) or with in-utero
exposure to DM must have a fasting blood glucose test every
Children above the age of 10 years who have attained puberty 2 years to screen for DM.
must be screened for DM if they have any two of the following
risk factors Early detection and treatment (lifestyle change and
• Obesity metformin) is very important as microvascular and
• Family history of DM in a 1st or 2nd degree relative macrovascular complications occur earlier and are more
• Evidences of insulin resistance(hypertension, acanthosis severe in adolescents than in adults with T2DM. Screening
nigricans, dyslipidemia, fatty liver, and PCOS) is very important as T2DM may remain asymptomatic and
• In utero exposure to DM. escape detection for a prolonged period of time. Some patients
In these patients, a fasting and preferably also a 2-hour with T2DM may test positive for autoantibodies characteristic
post glucose (1.75 g/kg to a maximum of 75 g) blood glucose of T1DM; they are classified as having “latent autoimmune
should be checked once in every 2 years or whenever there are diabetes” and are likely to need insulin in the near future 527
symptoms suggestive of hyperglycemia. Algorithm 2 outlines (usually in next 3 years).
ch-108.indd 527 11/21/2016 2:14:05 PM

Algorithm 2 inherited chromosome. Three novel heterozygous mutations

Approach to a patient with mild symptoms suggestive of in the KCNJ11 gene (G53S, G53R, and I182V) have been
hyperglycemia and a patient with clinical picture/setting shown to result in TNDM in some patients who do not have
suggestive of type 2 diabetes mellitus abnormalities of chromosome 6q24. Some mutations in the
ABCC8 gene and the HNF1b gene are also associated with
this transient variety of DM.
Although these patients grow out of their insulin
dependence by 18 months of age (usually earlier), 50–60%
will have a recurrence of DM later in life (average age 14 years
with a range of 4–25 years). On recurrence, most would require
insulin though the dose is small or the requirement may be
intermittent; some may be controlled with sulfonylureas. A few
may display hyperglycemia only during intercurrent illnesses.
Thus, what is referred to as TNDM may actually be a
permanent defect in b-cell insulin release with variable
expression at different stages of development.
Permanent Neonatal Diabetes Mellitus

Permanent neonatal diabetes mellitus is a genetically
heterogeneous disorder with at least nine different genetic
etiologies reported till date. These genetic defects may be
associated with either deranged b-cell function or reduced
DM, diabetes mellitus; T2DM, type 2 diabetes mellitus.
pancreatic mass with or without syndromic features. Thyroid,
pancreas, liver, heart, brain, kidney, and skeletal abnormalities
may be associated.
Approximately 95% of patients with monogenic causes
NEONATE/INFANT (BELOW 6 MONTHS) WITH of neonatal DM present within the first 6 months of life, with
SYMPTOMS OF HYPERGLYCEMIA around 3% diagnosed between 6 and 12 months of age.
The neonate/infant with diabetic hyperglycemia would
present with irritability, polyuria, weight loss, failure to thrive, Clinical Pearl
and dehydration with or without acidotic breathing and
• All patients diagnosed with diabetes mellitus before 6 months
occasionally with candidiasis in the genital region. Important of age, as well as those patients diagnosed between 6 and12
differentials include diabetes insipidus, renal tubular acidosis, months of age, who have no detectable pancreatic auto
diluted feeds, and hyperthyroidism. In patients presenting antibodies, should undergo molecular genetic testing.
with hyperglycemia and metabolic acidosis, if there is lack
of improvement with appropriate treatment of DKA, the
There are five genes known to be associated with
possibility of certain inborn errors of metabolism must be kept
nonsyndromic PNDM. The first two listed below have
in mind: these include methylmalonic acidemia, propionic
important therapeutic significance as they can be managed on
acidemia, isovaleric acidemia, biotinidase deficiency, and
sulfonylurea group of drugs and are not insulin requiring:
cobolamine metabolism defects. If the diagnosis of DM
1. Heterogeneous activating mutations of the KCNJ11 gene
is confirmed (as above), the two broad possibilities are:
which encodes one of the two protein subunits (Kir6.2) of
(1) transient neonatal diabetes mellitus (TNDM) and (2)
the adenosine triphosphate sensitive K+ (KATP) channel in
permanent neonatal diabetes mellitus (PNDM).
the b-cells account for 30% of cases of PNDM. Low birth
weight (LBW) is a consistent phenotypic marker but after
Transient Neonatal Diabetes Mellitus insulin treatment, there is marked catch up growth followed
The presentation is soon after birth (median age 3 days). Most by normal growth. Twenty percent have developmental
cases are below the 3rd percentile in weight (average weight delay and muscle weakness and 5% have epilepsy in
2 kg). Associated congenital anomalies reported include association with neonatal diabetes (the so called DEND
macroglossia in 20% and umbilical hernia in 10%. They show syndrome)
remarkable improvement with insulin therapy. This is a self- 2. Mutation in the ABCC8 gene which encodes the other
limited condition and resolves by 18 months (median age protein subunit (the SUR1 subunit) of the KATP channel
12 weeks). constitutes another genetic etiology and is the cause in 19%
Abnormalities of chromosome 6q24 with overexpression of all PNDM
of paternally expressed genes are seen in 65% of cases. 3. Mutations of the gene encoding insulin (INS gene) accounts
The defect may be paternal uniparental isodisomy of for a further 20% of cases of PNDM: these babies are born
chromosome 6, paternally inherited duplications within the at full term, have a better average birth weight (2.86 kg) and
528 long arm of chromosome 6, or loss of methylation within the are diagnosed later (13 weeks as against 5–7 weeks) than
TNDM critical region of chromosome 6 on the paternally those with defects in ABCC8 or KCJN11
ch-108.indd 528 11/21/2016 2:14:05 PM

4. Homozygous inactivating mutations of the gene encoding Management of

glucokinase must be suspected in PNDM with history Neonatal Diabetes Mellitus
of consanguinity especially if both parents have mild
hyperglycemia. These cases present at birth with severe Molecular genetic studies must be done in all infants
LBW. As a first test in any LBW baby born with neonatal presenting below 6–12 months of age with diabetes. A search
diabetes, the parents blood glucose should be checked for the KCNJ11 and ABCC8 mutations should be urgently
5. Rarely, neonatal diabetes may be due to inactivating undertaken as it has important therapeutic implications. An
mutations of the PDX1 (IPF1) gene. This is associated with ultrasound or preferably computed tomography or magnetic
pancreatic agenesis or hypoplasia and hence with exocrine resonance imaging scan of the abdomen should be obtained
pancreatic insufficiency. These patients have the severest to look for hypoplastic/absent pancreas. Appropriate tests
insulin deficiency and present early with significant LBW. to detect associated hypothyroidism, cerebellar hypoplasia,
Carrier parents would have mild adult onset diabetes. renal cysts, skeletal defects, agenesis of the gall bladder, or
deranged liver function should be undertaken in selected
cases. Screening of the parents for undiagnosed diabetes and
Clinical Pearl
gene mutations is essential.
• Neonatal diabetes mellitus due to mutations of the KCNJ11 At presentation, if the infant is dehydrated with or without
and ABCC8 genes do not require insulin therapy; these can be ketoacidosis, intravenous fluids and insulin infusion would be
controlled with sulfonylurea group of drugs. required as per the DKA protocol.
For long-term management, insulin injections (coupled
with a high calorie intake) are crucial to achieve normal
There are at least four syndromes associated with neonatal catch up growth and sustained weight gain. Rapid and short
DM which can be suspected in a given case from their acting insulin preparations should be avoided as the risk of
associated features: hypoglycemia is high (these are used only in babies started on
1. GLIS3 gene mutation has PNDM due to pancreatic the “insulin pump”). It is best to prescribe two or three injections
hypoplasia with severe congenital hypothyroidism, of neutral protamine Hagedorn insulin subcutaneously each
glaucoma, hepatic fibrosis, and cystic renal disease day. The average dose would be 0.5–1.0 units/kg/day but this
2. PTF1α gene mutation of severe PNDM due to pancreatic must be periodically adjusted on basis of home blood glucose
agenesis or hypoplasia has associated exocrine pancreatic monitoring results. Glargine insulin with its flat pharmacokinetic
insufficiency, dysmorphic facies, micro cephaly, and profile might prove useful but is not licensed for use in this age
impaired cerebellar development with severe develop group. Continuous subcutaneous insulin infusion (the “insulin
mental delay and occasionally, gall bladder agenesis pump”) has been successfully tried in neonates with 30% of
3. FOXP3 gene mutation (the “IPEX syndrome”) is a X-linked the total dose given as a continuous basal infusion and 70% as
disorder of autoimmunity that occurs in males who boluses divided equally between the total daily feeds.
present with neonatal diabetes, immune dysregulation, In the first 6 months, the infant needs to be exclusively
autoimmune thyroid disease, intractable diarrhea, breastfed at frequent intervals. If the mother is not in a position
exfoliative dermatitis, eczematous skin rash, and very to breastfeed, a milk formula may be offered. Frequent small
high serum immunoglobulin E. Most die of overwhelming feeds are preferred in order to prevent swings in blood glucose.
sepsis in the first months or years of life When weaning foods are introduced, one should prefer foods
4. Mutations of the EIF2AK3 gene lead to persistent with a low glycemic index.
neonatal diabetes and either multiple epiphyseal Regular home monitoring of blood glucose (checked 2–3
or spondyloepiphyseal dysplasia (Wolcott-Rallison hours after a feed and immediately before a feed) should be
syndrome). Transmission is autosomal recessive. Some done and the recommended target blood glucose is between
may have progressive renal failure from glomerulo 100 mg and 200 mg/dL. It should be remembered that
nephritis. One-fourth patients have exocrine pancreatic prevention of hypoglycemia is an important priority in the first
insufficiency. They may also have recurrent hepatitis and 3 years of life as it can have a permanent detrimental effect on
mental retardation. brain development.
There is a case report of maternal enteroviral infection at Patients with NDM owing to KCNJ11 and ABCC8 mutations
the end of the first trimester leading to pancreatic hypoplasia can be successfully shifted to oral treatment with sulfonylureas
with presence of GAD and anti-insulin antibodies and neonatal after initial stabilization with insulin. Glibenclamide appears
diabetes mellitus (NDM) presenting at or soon after birth. to be more effective than other sulfonylureas. Doses required
It is often difficult to clinically distinguish TNDM from are usually higher than those used in adult patients with T2DM
PNDM, however, patients with PNDM are usually born (0.33 mg/kg/day for a 60 kg adult). The median dose in NDM is
closer to term, have a higher birth weight, length and head 0.45 mg/kg/day (range 0.1–1.5 mg/kg/day). Glycemic control
circumference, a later age of presentation, and a higher tends to improve with time, and the dose of sulfonylurea can
insulin requirement. Presence of associated anomalies or subsequently be decreased. Transient diarrhea and yellow
syndromic features may be helpful in differential diagnosis. or grayish staining of deciduous teeth may occur, but other
On follow-up, declining insulin requirement over weeks/ adverse effects are rare.
months with return to normoglycemia off therapy clinches Pancreatic enzyme replacement therapy is required for
the diagnosis of TNDM. those with exocrine deficiency. 529
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STRESS HYPERGLYCEMIA Are children with SH more likely to develop DM in

future? Studies have reported an incidence of later diabetes
Stress hyperglycemia refers to transiently elevated blood ranging from 0–33% in patients with a history of SH. In one
glucose during an illness. The American Diabetic Association detailed study only 2.1% developed DM during 42 months of
has defined SH as any blood glucose more than 140 mg/dL follow-up; all of these had human leukocyte antigen types or
in a hospitalized nondiabetic patient. About 3.8% of children autoimmune markers known to be associated with T1DM, or
presenting to the emergency department would have SH. Fever an abnormal OGTT on recovery from the acute illness. Those
more than 39.5°C, febrile seizures, traumatic brain injuries, with hyperglycemia during relatively minor illnesses have a
burns, sepsis, pancreatitis, and dehydration are the most higher risk than those who develop SH during major illnesses.
common acute situations associated with SH. The more severe
the illness, the greater is the likelihood of SH. A glycosylated
hemoglobin test would help in excluding the possibility of HYPERGLYCEMIA IN
hitherto undetected DM as the cause for hyperglycemia. NEONATAL INTENSIVE CARE UNIT
Stress hyperglycemia is caused by changes in glucose
metabolism, due to increase in counter-regulatory hormones, Hyperglycemia in neonates, defined historically as a whole
leading to increased glycogenolysis, neoglucogenesis, blood glucose more than 125 mg/dL or serum glucose more
and development of insulin resistance both central (in the than 150 mg/dL, is common in critically ill neonates and in the
liver) and peripheral (in muscle and fat). Proinflammatory very low birth weight (VLBW) premature babies. Its occurrence
cytokines tumor necrosis factor-α [increased free fatty acid is inversely related to gestational age and birth weight and
(FFA) causing insulin resistance], interleukin (IL)‑1 (increased directly related to the severity of any accompanying illnesses.
gluconeogenesis), and IL-6 (increased glycogenolysis) also
contribute. Interleukin-10 and transforming growth factor-β Pathophysiology and Causes
may also be involved. Intensive care unit (ICU) procedures Lower and delayed insulin production in response to glucose
(particularly, mechanical ventilation), use of vasoactive agents, load is reported in the VLBW neonates, due to smaller beta
prolonged immobilization, and nutritional practices in the ICU cell mass, preferential release of inactive proinsulin instead
further add to SH. of insulin, and lack of enteral feeding which eliminates the
Modest hyperglycemia (<180 mg/dL) may be beneficial boosting effect of gut incretins on insulin release. Glucose
(an adaptive response) by providing additional energy to utilization is further limited because of their small mass
meet the increased metabolic demand of the brain, red of insulin dependent tissues: fat and muscle. Sick preterm
blood cells, and other cells; but if prolonged or severe, it has babies have increased insulin resistance due to increased
been associated with higher morbidity and mortality. Both inflammatory markers, cytokines, and catecholamines.
the peak and the duration of hyperglycemia affect prognosis. Hyperglycemia could result from:
Stress hyperglycemia is more dangerous than hyperglycemia • Excess/rapid exogenous glucose delivery (iatrogenic)
without stress. In the former, the glucose transporters are over- • Stress (serious illness especially septicemia, respiratory
expressed. Hence, more glucose enters the cells. This leads to distress, or NEC; pain; surgical procedures)
altered cell metabolism with increased reactive oxygen species • Therapy with certain drugs (corticosteroids, theophylline,
generation which causes altered mitochondrial function and caffeine, phenytoin, or use of diazoxide in mother)
apoptosis. Stress hyperglycemia also impairs macrophage and • Cerebral pathology with large damaged areas having
neutrophil function and complement activity.
reduced metabolism and thus, decreased glucose utilization
Does stress hyperglycemia need to be treated and if so,
(trauma, hypoxemic-ischemic lesions, hemorrhage,
what is the best approach? There is no conclusive answer to
meningitis, and encephalitis)
this question in adult and in pediatric studies conducted till
• Total parenteral nutrition can also affect blood glucose
date. Two major trials addressing this issue are underway.
status.
Trials concluded so far in the pediatric population using
Intralipid infusion raises blood glucose as it stimulates
insulin infusion to achieve tight blood glucose control have
gluconeogenesis by supplying FFA and glycerol. Intralipid
given conflicting results. The duration of hospital stay may be
supplies nearly three times more energy than glucose, hence
reduced with tight blood glucose control but the incidence
when a neonate is started on intralipid, there is no need to
of hypoglycemia also goes up significantly. Thus, it may be
give glucose at higher than physiological rate of 6–8 mg/
reasonable to try and maintain the blood glucose at levels of
kg/min. Aminoacids also support gluconeogenesis but to
140–180 mg/dL rather than aggressively controlling blood
a lesser extent than intralipid. High amounts of aminoacid
glucose to lower levels. When insulin is used, it should be given
infusion, however, may help by increasing insulin secretion
as a continuous infusion of regular human insulin with close
and glucose utilization.
monitoring of blood glucose.
Clinical Pearl Management

• Anticipate and monitor for hyperglycemia: all susceptible
• Stress hyperglycemia needs treatment with insulin infusion, neonates must have blood glucose screening. Heel prick or
only if blood glucose is more than 180 mg/dL with glycosuria; fingers prick blood glucose at bedside though inaccurate
530 the target blood glucose should be 140–180 mg/dL, with all is very useful in screening for hyperglycemia. The results
efforts to prevent hypoglycemia.
must be confirmed with laboratory estimation of plasma
ch-108.indd 530 11/21/2016 2:14:06 PM

glucose. The continuous glucose monitoring system The infusion should be changed every 24 hours. Large
measures interstitial tissue glucose level every 5 minutes; inter-subject variation in response is common, thus blood
it has been successfully used in the NICU. Urine should be glucose must be checked every 30–60 minutes initially till
checked for glycosuria as this is likely to be accompanied it has stabilized and thereafter every 4 hours for titration
with changes in serum osmolarity of insulin dose. Some studies have shown insulin to be
• Any underlying cause of hyperglycemia must be sought safe and beneficial and others report risks and problems.
out and addressed first (such as sepsis, TNDM and PNDM, A threefold increased lactate concentration and significant
specific illnesses, or hyperglycemia inducing drugs) acidosis is reported when insulin is given with high glucose
• Consider limited reduction of glucose infusion rate: When infusion rate. Careful monitoring is required to minimize
hyperglycemia is detected, the first intervention is to risks of hypokalemia and hypoglycemia which are known
reduce the glucose infusion rate to 6–12 mg/kg/min; stable complications of insulin therapy. Algorithm 3 outlines the
preterms need a glucose supply of 6 mg/kg/min, an ill approach to a neonate with symptoms of hyperglycemia or
preterm would require more glucose. A lower rate would who is susceptible to hyperglycemia.
not meet the basic glucose requirement. A higher rate
than 12 mg/kg/min would be detrimental as the maximal
Key points
glucose oxidative capacity is exceeded and beyond this
level, conversion to fat occurs. Further, high glucose rates ))
Diabetes mellitus (DM) must be considered in any child
increase carbon dioxide production which is undesirable presenting with polyuria, polydipsia, polyphagia, weight loss,
in respiratory compromised infants. Dextrose solutions and weakness or with secondary enuresis, ants around the
with concentration less than 5% should never be used as urine, or recurrent vaginal candidiasis
these would be hypo-osmolar and can cause hemolysis and ))
All pubertal adolescents with obesity and a family history of
hyperkalemia. Total parenteral nutrition should be started type 2 diabetes mellitus or evidence of insulin resistance or
as soon as possible in LBW babies; certain aminoacids can with history of in utero exposure to DM must be screened for
stimulate insulin release DM every 2 years
• Insulin therapy: it should be started when the blood ))
Neonates/infants with irritability, polyuria, weight loss, failure
glucose exceeds 250 mg/dL or when there is glycosuria to thrive, and dehydration with or without acidotic breathing
despite above measures. Blood glucose should be or genital candidiasis must have a blood glucose test; if
brought down slowly to avoid rapid fluid shifts. Insulin diagnosed to have diabetes, they should undergo genetic
is given as an infusion at a rate of 0.02–0.1 units/kg/h. At molecular testing for monogenic diabetes
the outset, it is important to run off about 50 mL of the ))
Preterm babies, very low birth weight babies, and critically ill
insulin infusion to saturate binding sites on the tubing. neonates must be screened for hyperglycemia and measures
Algorithm 3 should be instituted to keep the blood glucose below a level
at which there is significant glycosuria.
Approach to a neonate with suspected hyperglycemia or
susceptible to hyperglycemia
SUGGESTED READINGs
1. Aguilar-Bryan L, Bryan J. Neonatal diabetes mellitus. Endocr Rev. 2008;29(3):
265-91.
2. Guven A, Cebeci N, Dursun A, Aktekin E, Baumgartner M, Fowler B. Methylmalonic
acidemia mimicking diabetic ketoacidosis in an infant. Pediatr Diabetes.
2012;13(6):e22-5.
3. ISPAD Clinical Practice Consensus Guidelines 2009 Compendium. [online]
Available from: www.ispad.org.
4. Khadilkar VV, Khadilkar AV, Kapoor RR, Hussain K, Hattersley AT, Ellard S. KCNJ11
activating mutation in an Indian family with remitting and relapsing diabetes.
Indian J Pediatr. 2010;77(5):551-4.
5. Pati NK, Maheshwari R, Chellani H, Salhan RN. Transient neonatal hyperglycemia.
Indian Pediatr. 2001;38(8):898-901.
6. Pearson ER, Flechtner I, Njølstad PR. Switching from insulin to oral sulfonylureas in
patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006;355:467‑77.
7. Preissig CM, Hansen I, Roerig P, Rigby MR. A protocolized approach to identify
and manage hyperglycemia in a pediatric critical care unit. Pediatr Crit Care Med.
2008;9:581-8.
8. Preissig CM, Rigby MR. Pediatric critical illness hyperglycemia: risk factors
associated with development and severity of hyperglycemia in critically ill
children. J Pediatr. 2009;155(5):734-9.
9. Rafiq M, Flanagan SE, Patch AM, Shields BM, Ellard S, Hattersley AT. Effective
treatment with oral sulfonylurea in patients with diabetes due to sulfonylurea
receptor 1 (SUR1) mutations. Diabetes Care. 2008;31(2):204-9.
10. Sellers EAC, Moore K, Dean HJ. Clinical management of type 2 diabetes in
indigenous youth. Pediatr Clin North Am. 2009;56(6):1441-59. 531
11. Srinivasan V. Stress hyperglycemia in pediatric critical illness: the intensive care
NEC, necrotizing enterocolitis; RDS, respiratory distress syndrome. unit adds to the stress! J Diabetes Sci Technol. 2012;6(1):37-47.
ch-108.indd 531 11/21/2016 2:14:06 PM

Chapter 109
Gynecomastia in Children
Raghupathy Palany
INTRODUCTION liver disease, malnutrition, hyperthyroidism, adrenal

tumors, and familial gynecomastia
Gynecomastia is a benign enlargement of the male breast due • From the testes: this can be due to testicular tumors or to
to proliferation of the glandular component. The condition ectopic production of human chorionic gonadotropin, as
may occur in one or both breasts and begins as a small firm is reported with carcinoma of lung, kidney, gastrointestinal
lump beneath the nipple, which may be tender and later tract, and extragonadal germ cell tumors.
extend concentrically. If the breast enlargement is soft in Pathologic gynecomastia can be caused by:
consistency, then it indicates fat deposition which is termed as • Increase in the production and/or action of estrogen
pseudogynecomastia (lipomastia), and there is no glandular {{ Increased aromatization of androgens to estrogens
proliferation. {{ Increased androgenic precursors [dehydroepiandro
Physiologic gynecomastia is seen in newborns and in
sterone (DHEA) and androstenedione]
pubescent males. In newborns, breast development in both
{{ Increased sex hormone-binding globulin (SHBG)—
sexes may be associated with milk flow (galactorrhea). This
binds testosterone with higher affinity than estrogen
condition usually lasts for a couple of weeks, but in rare cases
favoring greater peripheral estrogen action
may last until the child is 2 years old.
{{ Estrogen receptor agonism.
Pubertal gynecomastia is quite common and occurs in
• Decrease in the production and/or action of testosterone
nearly two-thirds of pubertal boys. It appears around 12 years,
{{ Decreased production
and regresses in around 18–24 months. Obese boys appear to be
–– Primary hypogonadism—Klinefelter syndrome
more affected and may improve when adipose tissue becomes
less on weight reduction. Gynecomastia is stated to be caused by ■■ Congenital anorchia
relatively increased aromatization or higher than normal adult ■■ Enzymatic defect in testosterone biosynthesis
values of estrogen- testosterone ratio in this period, or through ■■ Infection (viral orchitis)
episodic elevations of estrogen, although many studies failed to ■■ Infiltrative disorders
document these changes conclusively. Increased sensitivity of ■■ Testicular trauma
the breast tissue to estrogens may be operative. –– Secondary hypogonadism—hypothalamic or
Pathologic causes of gynecomastia should be sought pituitary disorder
carefully as they require to be treated appropriately. ■■ Low testicular production of testosterone/
The histology of the male and female breast tissue being estriol—adrenal androgens are aromatized—
similar, exposure to estrogen in both sexes induces ductal estrogen/androgen imbalance
epithelial hyperplasia, ductal elongation and branching, ■■ Kallmann syndrome with anosmia
{{ Androgen insensitivity syndrome
proliferation of the periductal fibroblasts, and an increase in
vascularity. {{ Increased SHBG—binds testosterone with greater
Increased estrogen production and/or action can occur at affinity than estrogen favoring greater peripheral
the testicular level or at the periphery and is characterized as estrogen action
follows: • Androgen receptor antagonism
• From peripheral conversion: this can be due to increased • Idiopathic
substrate or increased activity of aromatase, as in chronic • Drug use (Box 2).
ch-109.indd 532 11/21/2016 2:15:55 PM

Chapter 109: Raghupathy Palany
Box 1: Clinical approach for evaluation of gynecomastia • Examination of the testes, with attention to size and
History Physical examination
consistency, as well as nodules or asymmetry
• Dimpling of the skin, nipple retraction and discharge,
• Duration of symptoms, • Height, weight
undescended testis, mumps
and axillary lymphadenopathy are suggestive of breast
• Feminizing signs, Tanner
carcinoma.
• Intake of medications staging
• Symptoms of psychological • Breast and overlying skin
stress • Regional lymph nodes DIAGNOSIS
• Local symptoms, palpable • Undescended testes, Patients with physiologic, asymptomatic, and pubertal
mass, tenderness and testicular mass gynecomastia do not require further evaluation and should be
enlargement of breasts, nipple • Chronic renal or hepatic re-evaluated in 6 months. Further evaluation is necessary in
discharge disease the following situations:
• Breast size greater than 5 cm (macromastia)
• A lump that is tender, of recent onset, progressive, or of
Box 2: Drugs known to cause gynecomastia unknown duration
Antiandrogens/inhibitors of Psychoactive drugs • Signs of malignancy (e.g., hard or fixed lymph nodes or
androgen synthesis • Haloperidol positive lymph node findings).
• Cyproterone acetate • Diazepam
• Flutamide, bicalutamide, • Tricyclic antidepressants Laboratory Tests
nilutamide • Phenothiazines • Serum chemistry panel
• Finasteride, dutasteride
Anti-infective agents • Free or total testosterone, luteinizing hormone, estradiol,
• Ketoconazole and DHEA levels
• Antiretroviral therapy for
• Spironolactone HIV/AIDS (e.g., indinavir) • Thyroid stimulating hormone and free thyroxine levels.
Chemotherapeutic drugs • Isoniazid
• Alkylating agents • Ethionamide Imaging Studies
• Methotrexate • Griseofulvin • Mammography, if one or more features of breast cancer
• Vinca alkaloids • Minocycline are apparent upon clinical examination, followed by fine
• Imatinib • Metronidazole needle aspiration or breast biopsy as appropriate
Cardiac drugs and • Ketoconazole • Testicular ultrasonography: indicated if the serum estradiol
antihypertensives Drugs of abuse level is elevated and the clinical examination findings
• Calcium channel blockers suggest the possibility of a testicular neoplasm
• Amphetamines
(verapamil, nifedipine, • Breast ultrasonography (though the positive predictive
diltiazem) • Heroin
value of imaging in males is low).
• ACE Inhibitors (captopril, • Methadone
enalapril) • Alcohol Clinical Pearl
• Digoxin • Marijuana
• The diagnosis of pathologic gynecomastia must be made
• Alpha-blockers Miscellaneous
only after ruling out lipomastia and physiological breast
• Amiodarone • Theophylline
enlargement.
• Methyldopa • Omeprazole
• Reserpine • Auranofin
• Nitrates • Diethylpropion MANAGEMENT
Hormones • Heparin • No treatment is required for physiologic gynecomastia
• Anabolic steroids • Domperidone • Pubertal gynecomastia resolves spontaneously within
• Androgens • Penicillamine several weeks to 2 years in most patients; therapy must be
• Estrogens • Sulindac considered if remission has not occurred in 2 years
• Chorionic gonadotropin • Breasts larger than 4 cm in diameter may not regress
completely
HIV/AIDS, human immunodeficiency virus/acquired immunodeficiency
syndrome; ACE, angiotensin converting enzyme.
• Identifying and managing an underlying primary disorder
often alleviates breast enlargement
• For patients with idiopathic gynecomastia or with residual
gynecomastia after treatment of the primary cause, medical
SIGNS AND SYMPTOMS or surgical treatment may be considered
• History of mumps, testicular trauma, or drug use should be • In pathologic causes of gynecomastia, medical therapies
obtained should be tried early after onset.
• Thorough examination of the size and consistency of the Medical therapy involves the following drugs, but
breasts and to differentiate from lipomastia is essential controlled studies are lacking: 533
ch-109.indd 533 11/21/2016 2:15:55 PM

Algorithm 1
Approach to gynecomastia estrogen excess, androgen deficiency, or androgen/estrogen imbalance
US, ultrasound; hCG, human chorionic gonadotropin; BP, blood pressure; 11β-OH, 11β-hydroxylase; FSH, follicle-stimulating hormone; AIS,
androgen insensitivity syndrome.
• Clomiphene
• Tamoxifen or Clinical Pearls
• Danazol (less frequently used).
• Dimpling of the skin, nipple retraction and discharge, and
Aromatase inhibitors are also currently being tried. axillary lymphadenopathy are suggestive of breast carcinoma
Surgical excision of glandular and adipose tissues by
• Enlarged lymph nodes, hard or fixed lymph nodes are
circumareolar approach leaving minimal scarring is the
suggestive of malignant changes.
best form of treatment for those requiring treatment, in
macromastia, long-standing gynecomastia, or failed medical
therapy, as well as for cosmetic reasons. Liposuction may not
be as safe and successful. Key points
))
Lipomastia needs to be distinguished from gynecomastia
PATIENT EDUCATION ))
Accurate diagnosis is essential for planning appropriate
therapy
Patients with physiologic gynecomastia should be reassured
regarding the benign nature of their condition, and informed ))
Medical therapy must be tried first, prior to advising surgical
that most cases spontaneously resolve. excision.
PROGNOSIS SUGGESTED READINGs

In approximately 90% of cases, pubertal gynecomastia 1. Carlson HE. Approach to the patient with gynecomastia. J Clin Endocrinol Metab.
resolves within a period of months to several years. However, 2011:96:15-21.
macromastia seldom resolves completely and often requires 2. Hormone Foundation. Patient information page. Gynecomastia. J Clin Endocrinol
Metab. 2011;96:0.
surgery.
3. Laituri CA, Garey CL, Ostlie DJ, St Peter SD, Gittes GK, Snyder CL. Treatment of
Gynecomastia that occurs secondary to an underlying, adolescent gynecomastia. J Pediatr Surg. 2010;45:650-4.
treatable cause (e.g., drug-induced gynecomastia) usually 4. Mahoney CP. Adolescent gynecomastia. Differential diagnosis and management.
responds to treatment or removal of the primary cause. Men Pediatr Clin North Am. 1990;37:1389-404.
with Klinefelter syndrome have a 10–20-fold increased risk for 5. Nordt CA, DiVasta AD. Gynecomastia in adolescents. Curr Opin Pediatr.
534 breast cancer. 2008;20:375-82.
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CHAPTER 110
Precocious Puberty
Puthezhath SN Menon, Madhava Vijayakumar
INTRODUCTION (DHEAS), associated with the development of the zona

reticularis of the adrenal cortex and is independent of gonadal
Precocious puberty (PP) is characterized by the appearance maturation.
of markers of pubertal development at an age earlier than the
usual pattern. Tremendous advances in the understanding
of the pathophysiology have resulted in paradigm shifts in NORMAL PUBERTY
the current management. Precocious puberty represents a Testicular enlargement from 3 to 4 mL is the first sign of puberty
significant diagnostic, psychosocial, and therapeutic challenge in boys, followed by enlargement of penis, pigmentation of
for the pediatrician. Most cases in girls are an exaggeration scrotum, and growth of pubic and axillary hair. The various
of the normal physiological process, whereas in boys half the stages of puberty are graded as Tanner stages 1–5 (sexual
cases are pathological. In general, younger the age, more is the maturity rating; Table 1). Peak growth velocity occurs in the
chance of detecting an organic pathology. Early diagnosis and later stages of puberty (Table 2). Onset of puberty is closely
treatment is pivotal since, if left untreated, PP leads to eventual related to skeletal maturation.
short stature and also causes psychological stress in the Breast development is the first sign of puberty in girls,
affected children. Some of the underlying causes (e.g., tumors) followed by growth acceleration, pubic hair development,
may even be fatal. and menarche (Tables 3 and 4). Onset of breast development
usually occurs at a bone age of 10 years and menarche at
PHYSIOLOGY OF PUBERTY 12.5 years, irrespective of the chronological age. Peak growth
velocity occurs in the initial 2 years, before menarche.
The pulsatile release of gonadotropin-releasing hormone
(GnRH) from the hypothalamus stimulates the pituitary
gland to secrete the gonadotropins—luteinizing hormone
DEFINITION OF PRECOCIOUS PUBERTY
(LH) and follicle-stimulating hormone (FSH). Luteinizing Puberty is considered precocious when signs of puberty appear
hormone stimulates the Leydig cells of testes which secrete before the age of 9 years in boys and 8 years in girls. The onset of
testosterone, initiating the pubertal changes in boys. menarche before 9.5 years is also termed as precocious.
Follicle-stimulating hormone stimulates spermatogenesis
by the seminiferous tubules. Luteinizing hormone and FSH
TYPES OF PRECOCIOUS PUBERTY
stimulate the ovaries to secrete estrogen which initiates the
onset of puberty in girls and leads to the development of • Central precocious puberty (CPP) or gonadotropin-
secondary sexual characters as well. dependent precocious puberty is caused by early release of
The secretion of GnRH is regulated by the “hypothalamic gonadotropins (FSH and LH) from the pituitary, which in
pulse generator” constituted by the neurons in the arcuate turn stimulate the testes to produce testosterone, or ovaries to
nucleus of the hypothalamus, which expresses several produce estrogen. In CPP, the sequence of pubertal changes
neurotransmitters, including kisspeptin and neurokinin B. The mimics normal puberty, but begins at an earlier age
gonadal sex steroids exert a negative feedback regulation of • Peripheral precocious puberty (PPP) or gonadotropin-
gonadotropin secretion through the hypothalamic neurons. independent precocious puberty is caused by secretion
Adrenarche is the increased production of the adrenal of sex steroids from any organ which is outside the
androgens—dehydroepiandrosterone (DHEA) and its sulfate hypothalamic-pituitary-gonadal axis and independent of
SECTION 13: Endocrinology
TABLE 1: Classification of sexual maturity rating (Tanner’s staging) in boys

Pubertal Genital development Pubic hair development Axillary hair
stage development
1 Prepubertal: testes size 1–3 mL Nil Nil
2 Testes size ≥4 mL in volume or ≥2.5 cm in length Minimally pigmented hair at base of Few axillary hair
Early penile growth penis
Scrotal skin thin and pink
3 Testes enlarge to 10–15 mL in volume or ≥3.3–4 cm in length Darker, coarser, and curled hair Adult pattern
Penis grows in length extending to mons pubis
Scrotal thickening and pigmentation
4 Testes enlarge to 15–20 mL in volume or ≥4–4.5 cm in length Thicker adult pattern of hair not yet
Penis grows in breadth; glans increases in size extending to medial surface of thighs
5 Adult genitalia; testes 25 mL in volume or >4.5 cm in length Adult distribution spreading to medial
side of thighs
TABLE 2: Normal pubertal development in boys TABLE 4: Normal pubertal development in girls
Onset of pubertal changes Mean age (years) Range (years) Onset of pubertal changes Mean age (years) Range (years)
Testicular enlargement begins 11–12 9–14 Breast development (thelarche) 10–11 8–15
Penile enlargement begins 12 9–14 Acceleration of growth 10–11 8–15
Pigmentation of scrotum 12 9–14 Pubic hair appears (pubarche) 11–12 9–15
Pubic hair appears 12–13 11–14 Menarche 12–13 10–16
Acceleration of growth 13–14 12–16
Axillary hair appears 14 12–16
pubic hair development. Premature adrenarche is the early
development of pubic hair without other pubertal changes.
TABLE 3: Classification of sexual maturity rating (Tanner’s Both are normal physiologic variants.
staging) in girls
Pubertal Breast Pubic hair Axillary hair CAUSES OF PRECOCIOUS PUBERTY
stage development development development
1 Prepubertal Nil Nil Box 1 lists the common causes of precocious puberty.
Idiopathic precocity is rare in boys. Organic causes account for
2 Appearance of Minimally Few axillary hair
breast buds and pigmented hair a majority of cases in younger girls, whereas idiopathic causes
slight areolar on labia are more common after the age of 6 years.
enlargement
3 Further Darker, coarser, Adult pattern APPROACH TO DIAGNOSIS
enlargement of and curled hair
breast and areola extending to
mons pubis
History
4 Areola and nipple Thicker but not Note the age at onset of the first signs of puberty and its progress
(papilla) form yet adult pattern over time. The growth spurt or peak growth velocity is important,
a secondary as the acceleration of linear growth results in tall stature initially,
mound above the but eventually the affected children become short adults since
level of the breast fusion of bones occur early. Onset of puberty in early childhood
5 Areola part of Adult distri (below age 6 years) is highly suggestive of organic central nervous
breast contour, bution extending system (CNS) pathology, particularly hypothalamic hamartoma,
projection of to medial surface or McCune-Albright syndrome (MAS). Inquire about details
nipple only of thighs of childbirth, perinatal insults, head trauma, CNS infections,
tumors, and craniospinal radiation. History of headache,
vomiting, and visual disturbances suggests an intracranial tumor.
the hypothalamic pulse generator. Here, the sequence of Gelastic epilepsy is a characteristic feature of hypothalamic
puberty does not follow the normal pubertal pattern. hamartoma. Prematurity, intrauterine growth retardation, and
Premature thelarche is the early development of breasts, adoption may be associated with PP. Developmental delay and
536 without other signs of puberty such as rapid linear growth or behavioral disturbances are associated with CNS involvement as
CHAPTER 110: Precocious Puberty
Box 1: Etiology of precocious puberty

Central isosexual precocious puberty in girls and boys
• Idiopathic (common in girls): sporadic, familial
• Genetic: KISS1, GPR54, and MKRN3 mutations
• Neurogenic:
{{ Hypothalamic hamartoma (common)
{{ Central nervous system tumors: glioma, astrocytoma,
ependymoma, pineal tumors, craniopharyngioma
{{ Central nervous system infections: neurotuberculosis, post-
meningitis/encephalitis
{{ Central nervous system insults: trauma, neurosurgery, cranial
irradiation, perinatal asphyxiation

{{ Central nervous system malformations: arachnoid cyst,
hydrocephalus, septo-optic dysplasia, neurofibromatosis,
neural tube defects, cerebral dysgenesis
Fig. 1: Premature thelarche due to gonadotropin-dependent
• Miscellaneous: adoption, intrauterine growth retardation,
precocious puberty in a 4-year-old girl with spastic quadriplegia with
Russell-Silver syndrome, endocrine disruptor syndrome
seizures on anticonvulsant therapy
Peripheral precocious puberty in girls
• Hypothyroidism
in cerebral palsy, hamartoma, and CNS malformations (Fig. 1).
• Ovarian causes A detailed family history of early puberty and consanguinity is
{{ McCune-Albright syndrome (more common in girls) helpful to diagnose constitutional forms, familial male-limited
{{ Benign follicular cysts precocious puberty (FMPP or testotoxicosis) and congenital
{{ Tumors: granulosa-theca cell tumors, arrhenoblastoma, adrenal hyperplasia (CAH). Carefully elicit the history of drugs
teratoma or creams consumed/applied by the child or parents/other
• Adrenal causes: feminizing adrenal neoplasia family members, including illicit drug use (anabolic steroids,
• Exogenous estrogen exposure: medications, phytoestrogens estrogen creams, androgen, and phytoestrogens). Possibility of
sexual abuse, foreign body or vaginal infection must be probed
Peripheral precocious puberty in boys
in girls with isolated vaginal bleeding. Ask for any previous height
• Adrenal causes
measurements (pediatrician/school).
{{ Congenital adrenal hyperplasia (CAH): 21-hydroxylase and
11β-hydroxylase deficiency
Physical Examination
{{ Adrenal tumors: virilizing adenoma, carcinoma
• Testicular causes The height, weight, span, and body proportions should be
measured carefully and plotted on growth charts. It is important
{{ Tumors: Leydig cell tumor, adrenal rest tumor
to measure the height of father and mother to calculate the
{{ Apparent luteinizing hormone excess: familial male-limited
midparental height, which is plotted on the right side of the
precocious puberty (FMPP or testotoxicosis)
growth chart. Compare with previous height measurements to
• Human chorionic gonadotropin-secreting tumors: intracranial
assess growth velocity. Note the development of acne, pubic,
(germinoma or teratoma), ectopic (hepatoblastoma, teratoma,
choriocarcinoma)
axillary and facial hair, as well as appearance of hair in unusual
areas. Look for voice change and muscle development. Skin
• Exogenous androgen/testosterone exposure: testosterone
should be checked for texture (hypothyroidism), macules
creams and medications
(neurocutaneous syndromes), neurofibromas, and café-
Combined peripheral and central precocious puberty au-lait spots (neurocutaneous disorders and MAS; Fig. 2).
• Prolonged undertreated precocious puberty (CAH, McCune- It is important to look for skeletal deformities (e.g., MAS).
Albright syndrome, FMPP) Hyperpigmentation of mucosa and skin is a common feature
Heterosexual precocity of CAH. Check for other clinical stigmata of hypothyroidism,
• Virilization in girls: CAH, virilizing ovarian/adrenal neoplasia, e.g., weight gain with decreased linear growth, puffiness,
polycystic ovarian syndrome lethargy, constipation, or coarse skin. Precocious puberty
• Feminization in boys: estrogen secreting adrenal tumor, is characterized by rapid growth rate, deepening of voice
exogenous estrogens/drugs (in boys), and enlargement of genitalia. However, PP associated
with hypothyroidism is characterized by growth faltering and
Variations in pubertal development
absence of pubarche.
• Premature thelarche
Pubertal development should be assessed according
• Premature pubarche/adrenarche to Tanner’s stages. In boys, assess testicular volume using
• Premature menarche an orchidometer and measure the stretched penile length
(from the base of the shaft of the penis to the tip, excluding 537
may be high in children with 11β-hydroxylase deficiency or

adrenal tumor. Abdominal examination may reveal adrenal or
ovarian mass as well as enlarged uterus. Firm hepatomegaly
may be a manifestation of hCG-secreting tumors such as
hepatoblastoma.
If breast development is the only clinical feature, without
growth acceleration and pubic hair development, the condition
is labeled as premature thelarche. Premature adrenarche is
the likely diagnosis if signs of virilization (pubic hair, axillary
hair, facial hair, or acne) appear without breast development,
growth acceleration, or advanced bone age. These children
should be followed up regularly, to look for later development
of growth spurt and other pubertal changes. A fluctuating
course is suggestive of intermittent estrogen production by
ovarian cysts. Discordant puberty (e.g., vaginal bleeding within
short duration of thelarche) indicates withdrawal bleeding
following removal of the source of estrogen production as with
ovarian cyst, hypothyroidism, or MAS.
Fig. 2: McCune-Albright syndrome in a 4-year-old girl. Note the

Investigations
premature thelarche and the large café-au-lait pigmented macule in Investigations should be directed to confirm PP and find out
the axilla the etiology. Bone age should be assessed accurately, using
a Greulich-Pyle or Tanner-Whitehouse atlas, and pelvic
the foreskin). In children with CPP (e.g., hypothalamic ultrasound done in girls by an ultrasonologist experienced in
hamartoma), penile enlargement is associated with increase pediatrics. Precocious puberty is associated with advanced
in testicular volume (>4 mL, or diameter >2.5 cm). In PPP bone age except in hypothyroidism. If the bone age
(e.g., CAH), testicular volume remains prepubertal (<4 mL). advancement is appropriate for the height age, it is likely that
In testotoxicosis and human chorionic gonadotropin (hCG)- the precocity is benign, probably a normal variant that needs
secreting tumors, testes are modestly and symmetrically only careful follow-up and no treatment. An advanced bone
enlarged (3–4 mL). Asymmetrical or unilateral enlargement of age, coupled with pubertal changes on pelvic ultrasound,
testis is seen in Leydig cell tumors or adrenal rests. suggests the need for an endocrine evaluation.
Hormonal investigations are recommended in very young
Clinical Pearl children with advancing puberty—if more than one sign of
puberty is present; if a new sign of puberty appears during
• Measuring testicular volume carefully narrows down follow-up; if the growth rate is accelerated; or if bone age is
the possibilities, thus reducing the cost and number of advancing rapidly. Serum estradiol in girls, and testosterone in
investigations and the time taken for establishing the etiology. boys in early morning samples confirm the diagnosis. Serum
levels of estradiol less than 10 pg/mL and testosterone less
In girls, evaluation of the breast as well as genital than 25 ng/dL rule out CPP. However interpretation of the
examination in an appropriate position is important. Vaginal results, especially for serum estradiol, might be difficult as the
mucosa should be examined in good light for signs of estrogen sensitivity of most available assays is much above these levels.
effect (e.g., pale pink color instead of glistening red prepubertal Basal level of serum LH in a pooled or midnight sample
mucosa). Presence of vaginal secretions and menstruation (since the secretion of LH is pulsatile) is the best screening
should be noted. Clitoral size should be evaluated. Vaginal test to diagnose CPP. Luteinizing hormone is more useful than
bleeding without breast development may indicate sexual FSH: levels less than 0.1 IU/L by a very sensitive assay indicate
abuse: marks of injury should be looked for. Virilization prepubertal state, while those above 0.6 IU/L suggest pubertal
without signs of estrogen effect indicates androgens from the levels. In premature adrenarche, gonadotropin levels are
adrenal or rarely, the ovary or an androgen-secreting tumor. prepubertal, while in PPP, they are suppressed.
Rapid virilization may suggest androgen-secreting tumors of Gonadotropin-releasing hormone stimulation test or
adrenal gland or ovary. Breasts should be carefully examined GnRH agonist analog stimulation test is required if baseline
for nodules and galactorrhea. gonadotropin levels are inconclusive.
In a boy with true precocious puberty, an organic cause is The GnRH stimulation test is performed by collecting
far more likely, unlike in girls older than 6 years, where most 3–7 blood samples at 30-minute intervals after injection of
investigations are likely to be normal. All young children with intravenous or subcutaneous GnRH (2.5 µg/kg; maximum
precocious puberty should be evaluated for an underlying CNS 100 µg). Normal prepubertal children show a peak increment
disorder. This should include the signs of raised intracranial of 3–4 IU/L of LH and 2–3 IU/L of FSH. Pubertal LH levels
538 pressure and examination of optic fundi. Blood pressure
(>6 IU/L) and LH to FSH ratio greater than 0.9 are diagnostic volume is usually above 3 mL. Large ovarian cysts are often
of CPP. A predominant FSH response is seen in premature seen in girls with hypothyroidism: these regress with thyroxine
thelarche. However, this test is difficult to do, due to the limited replacement, and do not require surgery. In the uterus, the
availability of GnRH and the higher number of samples, which earliest feature of estrogenization is a change in the shape from
makes it more invasive and expensive. prepubertal tubular shape (diameters of fundus and cervix are
equal) to pubertal pear shape (diameter of the fundus is more
Gonadotropin-releasing Hormone than that of cervix). Endometrial thickness of 6–8 mm indicates
Agonist Analog Test menarche is imminent.
Gonadotropin-releasing hormone agonist analog test is,
therefore, the preferred test now. A single sample is taken Abdominal Ultrasound
60 minutes after a subcutaneous injection of leuprolide acetate It is useful in diagnosing adrenal tumors and ultrasound
10–20 µg/kg (maximum of 500 µg) or of triptorelin 0.1 mg. A of testes is used to diagnose testicular tumors. Computed
stimulated LH level of 6 IU/L or more is consistent with CPP. tomography (CT) or magnetic resonance imaging (MRI) of
abdomen may be confirmatory in adrenal tumors.
Clinical Pearl
Neuroimaging
• Luteinizing hormone level in a pooled serum sample is the best High resolution MRI of hypothalamus and pituitary helps
screening test for central precocious puberty; gonadotropin- to detect lesions such as hypothalamic hamartoma, glioma,
releasing hormone stimulation test is confirmatory. astrocytoma, and structural malformations like septo-optic
dysplasia. Magnetic resonance imaging should be done in all
Other Hormones boys, and in girls below 6 years, since the chance of finding
an organic cause is high. In girls above 6 years, since most will
Estimation of serum total testosterone is useful in girls to be idiopathic, MRI should be individualized, e.g., it should be
differentiate between premature adrenarche and virilization, done if the pubertal progression is very rapid or there is other
and in polycystic ovarian syndrome. Serum free testosterone evidence of a CNS pathology. Further hormonal evaluation
is not a useful test. Pubertal levels of DHEAS characterize of the hypothalamic-pituitary axis may be indicated if an
premature adrenarche, while greatly elevated level of DHEAS abnormality is detected.
is seen in virilizing adrenal tumors.
Elevated unstimulated plasma 17-hydroxyprogesterone Clinical Pearl
levels are seen in CAH. If the levels are inconclusive, an
adrenocorticotropic hormone stimulation test is performed. • An organic etiology is more likely in a young boy with
Testosterone levels are very high in tumors. Pubertal central precocious puberty, unlike an older girl where most
testosterone levels with suppressed gonadotropins are seen investigations are likely to be normal.
in FMPP (testotoxicosis). Human chorionic gonadotropin
and often a-fetoprotein are elevated in patients with hCG- Algorithm 1 summarizes the approach to the diagnosis of
secreting tumors. In girls, increased estrogen with suppressed PP in girls where as algorithm 2 details the approach to the
gonadotropins is seen in conditions causing autonomous diagnosis of PP in boys.
secretion of estrogen such as functional ovarian cysts, ovarian
tumor, or MAS.
Serum thyroid stimulating hormone and thyroxine levels MANAGEMENT
should be checked if the bone age is delayed, especially Untreated PP leads to early pubertal maturation with
with slow height velocity. Serum prolactin levels should be advancement of bone age and early epiphyseal fusion, leading
estimated in the presence of galactorrhea. to tall stature in childhood, but short stature in adulthood,
and psychological problems. Treatment is aimed at arresting
Imaging the progression of puberty, identifying and managing the
underlying cause, increasing the prospects for better adult
Plain X-rays of the Skull height, and providing psychosocial support to affected children
They may show sellar enlargement, calcification, and evidence and their families.
of raised intracranial pressure, but are almost always of little Tumors of the brain, gonads, adrenals, or ectopic sites
utility. A skeletal survey should be done if clinical features may require surgery, radiotherapy, or chemotherapy. Ovarian
suggest fibrous dysplasia (MAS). cysts more than 3 cm in diameter, which are persistent or
have a solid component, may need exploration and excision.
Pelvic Ultrasound Smaller cysts are monitored by frequent estrogen estimations
It helps in girls to arrive at a diagnosis by visualizing the uterus, and ultrasounds. Congenital adrenal hyperplasia is managed
adrenals, and ovaries. Ovarian volume more than 1–2 mL, with hydrocortisone (15–20 mg/m2) and fludrocortisone.
with multiple cysts (>6 cysts and greater than 4 mm diameter) Hypothyroidism is managed with thyroxine replacement.
is characteristic of a peripubertal state. The pubertal ovarian 539
ALGORITHM 1
Approach to the diagnosis in a girl with precocious puberty
T4, thyroxine; TSH, thyroid-stimulating hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; GDPP,
gonadotropin-dependent precocious puberty; CPP, central precocious puberty; GIPP, gonadotropin-independent precocious puberty; PPP, peripheral precocious
puberty; 17-OHP, 17-hydroxyprogesterone; CNS, central nervous system; DHEA, dehydroepiandrosterone.
ALGORITHM 2
Approach to the diagnosis of precocious puberty in boys
540 T4, thyroxine; TSH, thyroid-stimulating hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; GDPP,
gonadotropin-dependent precocious puberty; CPP, central precocious puberty; GIPP, gonadotropin-independent precocious puberty; PPP, peripheral precocious
puberty; CAH, congenital adrenal hyperplasia; MRI, magnetic resonance imaging; CNS, central nervous system; hCG, human chorionic gonadotropin.
In CPP, long-acting GnRH analogs are the mainstay of

treatment. They decrease the episodic release of GnRH due ))
Serum luteinizing hormone level (pooled sample) is the best
screening test for CPP; gonadotropin-releasing hormone
to their continued high levels, causing desensitization of
stimulation test is confirmatory
gonadotropin-producing cells of the pituitary. They slow down
rapid skeletal maturation and linear growth, which remain ))
Untreated precocious puberty is associated with short final
height
unaffected by other forms of therapy. Depot preparations
are preferred. These include leuprolide (3.75 and 11.25 mg), ))
Gonadotropin-releasing hormone analog is the treatment of
triptorelin (3.75 and 11.25 mg), and goserelin (3.6 mg). choice for CPP
Treatment should be continued till the child reaches the ))
Hypothyroidism is the only condition which causes precocious
normal pubertal age (10–11 years). The effectiveness of therapy puberty associated with growth delay and retarded bone age.
is monitored by clinical evaluation of puberty, growth, and
hormone evaluation. The sex steroids should revert to normal
prepubertal levels for age. An effective dose is one where the
gonadotropin response to exogenous GnRH is obliterated. This has not been generally successful, in contrast to the success of
can be done by testing serum LH 60 minutes after the depot GnRH analogs for CPP.
injection. Gonadotropin-releasing hormone analog treatment
in girls with CPP has no long-term deleterious effects on SUGGESTED READINGS
reproductive function or bone mineralization. 1. Bajpai A, Sharma J, Kabra M, Gupta A, Menon PS. Precocious puberty:
In patients with autonomous gonadal steroid production clinical and endocrine profile and factors indicating neurogenic
such as MAS and FMPP, therapy is aimed at reducing sex precocity in Indian children. J Pediatr Endocrinol Metab. 2002;15:1173-
steroid production or its effects, thereby arresting acceleration 81.
of growth and progression of puberty. Medroxyprogesterone 2. Bajpai A, Menon PS. Contemporary issues in precocious puberty.
Indian J Endocrinol Metab. 2011;15:S172-9.
acetate and cyproterone acetate interfere with sex steroid
3. Bajpai A, Sharma J, Kabra M, Gupta AK, Menon PS. Long-acting GnRH
synthesis, but have no beneficial effect on final height outcome. analogue therapy in central isosexual precocious puberty. Indian Pediatr.
Aromatase inhibitors prevent testosterone conversion to 2002;39:633-9.
estrogens or block the receptors for testosterone and dihydro 4. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR. Consensus
testosterone. Medical management of peripheral precocity statement on the use of gonadotropin-releasing hormone analogs in
children. Pediatrics. 2009;123:e752-62.
5. Chalumean M, Hadjiathanasiou CG, Ng SM, Cassio A, Mul D,
Cisternino M, et al. Selecting girls with precocious puberty for brain
KEY POINTS imaging: validation of European evidence-based diagnosis rule. J
Pediatr. 2003;143:445-50.
))
Central precocious puberty (CPP) is idiopathic in 90% girls,
6. Dattani MT, Tziaferi V, Hindmarsh PC. Normal and abnormal
but only 10% boys. Hence careful search for a cause, including
puberty. In: Brook CG, Clayton PE, Brown RS (Eds). Clinical Pediatric
neurological imaging, is warranted in boys and girls less than Endocrinology, 6th ed. Chichester: Wiley-Blackwell; 2009. pp. 183-210.
6 years of age 7. Lee PA, Houk CP. Puberty and its disorders. In: Lifshitz F (Ed). Pediatric
))
Genital maturation without testicular enlargement rules out Endocrinology, 5th ed. New York: Informa Healthcare; 2007. pp. 207-324.
CPP in boys 8. Rosenfield RL, Cooke DW, Radovick S. Puberty and its disorders
in female. In: Sperling MA (Ed). Pediatric Endocrinology, 3rd ed.
Philadelphia: Saunders Elsevier; 2008. pp. 530-600.
9. Sathasivam A, Rosenberg HK, Shapiro S, Wang H, Rapaport R. Pelvic
Ultrasonography in the Evaluation of Central Precocious Puberty:
Comparison with Leuprolide Stimulation Test. J Pediatr. 2011;159:490-
5.
10. Vijayakumar M, Menon PS. Precocious puberty—Perspectives in
diagnosis and management. Indian J Pediatr. 2014;81:76-83.
541
Chapter 111
Persistent Hypoglycemia in
Newborns and Infants
Ganesh S Jevalikar
INTRODUCTION and the nonspecific nature of the symptoms. , Recognition of

hypoglycemia may therefore require confirmation by repeated
The neonatal period marks the transition of continuous measurements of plasma glucose.
supply of glucose from maternal circulation in intrauterine Due to possible risks of hypoglycemia to the developing
life to interrupted availability of glucose in extrauterine life. brain evaluation and management is recommended in infants
Hypoglycemia is a significant threat to the developing brain and whose plasma glucose concentrations are documented by
if inadequately treated, can lead to permanent brain damage. laboratory quality assays to be below the normal threshold
This chapter discusses causes and approach to treatment of for neurogenic responses (<60 mg/dL). This is especially
persistent hypoglycemia in infants. Transient hypoglycemia is applicable beyond first 2-3 hours of life. Plasma glucose values
more common, particularly in preterm, low birth weight, and are 10–15% higher than whole blood values and appropriate
sick newborns and is discussed in the later section. corrections should be made before interpreting the values.
Low values obtained on capillary testing should be
DEFINITION OF HYPOGLYCEMIA confirmed by laboratory assessment, since capillary assess
A single cut-off to define normal plasma glucose is not ments are not accurate enough (particularly in the low range)
possible as specific brain responses to low glucose depend to diagnose hypoglycemia. Samples for blood glucose must be
on several factors like the duration of low glucose and the analyzed immediately as delayed processing decreases values.
availability of alternative fuels. The Whipple’s triad used to
define hypoglycemia in older children and adults cannot be Clinical Pearls
used in infants, due to the inability to communicate symptoms
and the nonspecific nature of the symptoms. Recognition of • Diagnosis of hypoglycemia should be based on a level in a
hypoglycemia may therefore require confirmation by repeated venous sample, not capillary glucose by finger stick
measurements of plasma glucose. • Plasma glucose values are 10–15% higher than whole blood
Due to the possible risks of hypoglycemia to the developing • Delay in processing of sample causes drop in measured glucose.
brain, evaluation and management is recommended in infants
whose plasma glucose concentrations are documented by
laboratory quality assays to be below the normal threshold GLUCOSE HOMEOSTASIS IN
for neurogenic responses (<60 mg/dL). This is especially FETUS AND NEWBORN
applicable beyond the first 2-3 hours of life. Plasma glucose
values are 10–15% higher than whole blood values and Fetal blood glucose remains around 54 mg/dL over most
appropriate corrections should be made before interpreting of gestation, especially after 20 weeks of pregnancy. In the
the values. first 1–2 hours after birth, blood glucose drops to as low as
A single cut-off to define normal plasma glucose is not 30 mg/dL. This stimulates glycogenolysis, gluconeogenesis,
possible as specific brain responses to low glucose depend and ketogenesis, mediated by hormonal changes [suppression
on several factors like duration of low glucose and the of insulin and release of counter-regulatory hormones:
availability of alternative fuels. The Whipple’s triad used to catecholamines, glucagon, and growth hormone (GH)],
define hypoglycemia in older children and adults cannot be changes in hormone receptors, and expression of key enzymes
used in infants due to the inability to communicate symptoms of glucose production, which increase the blood glucose to
ch-111.indd 542 11/21/2016 2:27:52 PM

Chapter 111: Persistent Hypoglycemia in Newborns and Infants
greater than 45 mg/dL by 12 hours of birth. Initiation of feeding

after birth maintains ongoing supply of energy substrates.
Breastfed newborns have lower blood glucose and higher
ketone concentrations (principal alternative fuel for brain)
compared to formula-fed newborns.
GLUCOSE HOMEOSTASIS
IN OLDER CHILDREN
Understanding glucose homeostasis in the fed and fasting
states is important to understand the causes of hypoglycemia.
Although the mechanisms of control are analogous to adults,
children have lesser tolerance to fasting due to lesser glycogen GLUT2, glucose transporter 2; GK, glucokinase; GDH, glutamate dehydro
stores and lesser muscle mass. In the fed state, insulin promotes genase; SUR, sulfonylurea receptor α-KG , α-ketoglutarate; ATP, adenosine
glucose utilization by insulin-dependent tissues (utilization by triphosphate; ADP,adenosine diphosphate; GTP, guanosine triphosphate.
brain is insulin independent) and promotes glycogenesis and Fig. 2: Physiology of insulin secretion. Diagram of b-cell of pancreas
lipogenesis, the storage forms of energy. In the fasting state, a showing major steps in insulin secretion
drop in blood glucose is prevented by suppression of insulin
and release of counter-regulatory hormones (catecholamines, adenosine diphosphate ratio closes ATP sensitive potassium
glucagon, GH, and corticosteroids) which mediate glyco (KATP) channels [which consist of inward rectifying K+ channel
genolysis, gluconeogenesis, and lipolysis. Lipolysis generates Kir 6.2, surrounded by sulfonylurea receptor (SUR)]. This
alternative fuels through fatty acid oxidation and formation causes depolarization and opening of voltage-gated calcium
of ketone bodies. These mechanisms come into play at channels. Increased intracellular calcium causes exocytosis of
different intervals of fasting, with glycogenolysis being the insulin vesicles. Glutamate dehydrogenase (GDH) catalyzes
immediate mechanism and gluconeogenesis the principal glutamate oxidation leading to formation of ATP and further
mechanism after depletion of glycogen stores. Insulin has an cascade of reactions leading to insulin release. Leucine is an
inhibitory effect on fatty acid breakdown and ketogenesis. allosteric activator of GDH action.
Figure 1 illustrates glucose homeostasis in the fasting state in
a simplified way.
Interruption of normal homeostatic mechanisms TRANSIENT HYPOGLYCEMIA OF NEWBORN
maintaining blood glucose levels causes hypoglycemia. As noted above, blood glucose less than 45 mg/dL may be
Glucose entry into β-cells through glucose transporter 2 observed in 5–15% healthy term newborns. Some newborns
initiates the process of insulin secretion (Fig. 2). Upon entry, are at risk for transient hypoglycemia (Box 1). In some of these
glucose is metabolized to glucose-6-phosphate by glucokinase conditions, hypoglycemia may be recurrent or persistent
which is further metabolized, leading to generation of over first few weeks (e.g., in small for gestational age babies),
adenosine triphosphate (ATP). Increase in intracellular ATP/ therefore needing evaluation as persistent hypoglycemia.
PERSISTENT HYPOGLYCEMIA IN
NEWBORNS, INFANTS, AND CHILDREN
Persistent hypoglycemia can result from conditions (Box 2)
which interfere in normal glucose homeostasis (Fig. 1)
Box 1: Causes of transient hypoglycemia in neonatal period

• Preterm appropriate for • Transient hyperinsulinism
gestational age {{ Infant of diabetic mother
• Small for gestational age {{ Small for gestational age
(term or preterm) {{ Birth asphyxia

Dashed arrows indicate actions mediated by insulin which are inhibited in a • Birth asphyxia {{ Rh incompatibility
fasting state, whereas weighted arrows indicate actions which maintain plasma
glucose level or provide alternate fuel in fasting state. These are mediated by • Neonatal sepsis {{ Exchange transfusion
counter-regulatory hormones. Insulin is inhibitory to fatty acid breakdown and • Systemic diseases: liver {{ Syndromic causes:
ketogenesis. disease, cardiac failure/
*Important reactions involved in glucose homeostasis Beckwith-Wiedemann,
cyanotic heart disease Turner, Kabuki, and
FFAs, free fatty acids; FAO, fatty acid oxidation. • Polycythemia trisomy 13 syndromes
Fig. 1: Glucose homeostasis in fasting state
• Cold injury 543
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Box 2: Etiology of persistent hypoglycemia in newborns,

excessive) at the time of hypoglycemia (normally with low
infants, and children blood glucose, insulin gets totally suppressed). It poses more
risk to the brain than other causes, as unsuppressed insulin
Hyperinsulinism also prevents ketogenesis (alternative fuel for the brain). In
• Congenital hyperinsulinism spite of significant recent advances in molecular genetics, in
{{ ABCC8, KCNJ11, GDH, glucokinase, HADH, HNF4a, HNF1a,
nearly 40–50% of cases of CHI, precise genetic mechanisms
SLC16A1, UCP2, PGM1, HK1 remain unknown. Mutations causing CHI generally increase
{{ Syndromic: Beckwith-Wiedemann, trisomy 13, Kabuki, and
intracellular ATP, leading to persistent closure of KATP
Costello syndromes channels and uninhibited insulin release. Most commonly,
• Insulinoma (sporadic or MEN1 associated) these are mutations in subunits of KATP channels (SUR1
• Dumping syndrome receptor coded by ABCC8 gene and Kir6.2 channel coded by
• Exogenous insulin administration KCNJ gene). Autosomal recessive (AR) mutations present
• Sulfonylurea ingestion earlier, are associated with macrosomia, and are more
Hormone deficiencies commonly unresponsive to diazoxide. Autosomal dominant
• Adrenocorticotropic hormone/cortisol deficiency (AD) mutations are generally milder and diazoxide responsive.
• Growth hormone deficiency
Other types include activating mutations of glucokinase, GDH
(characterized by hyperammonemia and leucine sensitivity,
• Catecholamine deficiency (rare as isolated entity)
macrosomia is unusual), short chain hydroxylacyl-coenzyme
Carbohydrate disorders A (CoA) dehydrogenase, SLC16A1 (characterized by exercise-
• Glycogen storage diseases induced hyperinsulinism), and recently described mutations
• Galactosemia in several newer genes (Box 2)
• Hereditary fructose intolerance Histologically, focal and diffuse types are seen. Focal
• Other disorders of gluconeogenesis forms are due to paternally inherited recessive mutations of
Fatty acid disorders KATP channel and somatic loss of heterozygosity in maternal
• Carnitine transporter deficiency
chromosome 11, and can be completely cured by selective
pancreatectomy.
• Carnitine palmitoyltransferase-1/2 deficiency
Clinically, CHI can be divided into diazoxide responsive
• Carnitine translocase deficiency
and unresponsive. Genetic studies can be helpful in predicting
Very long/long/medium/short chain acyl-coenzyme A dehydro response to treatment and need for surgical management, and
genase deficiency
must be attempted in all cases presenting with CHI.
Amino acid disorders
• Methylmalonic acidemia Clinical Pearls
• 3-hydroxy-3-methylglutaric aciduria
• Maple syrup urine disease • Congenital hyperinsulinism is the most common cause of
• Tyrosinemia type 1 persistent neonatal hypoglycemia
• Insulin secretion is inappropriate rather than excessive
Increased utilization
• Sepsis • Genetic analysis may be helpful in deciding the line of
treatment and must be attempted in all cases.
• Systemic disease: liver disease, heart failure, falciparum malaria
Miscellaneous
• Ketotic hypoglycemia Hormone Deficiencies
• Congenital disorders of glycosylation
Growth hormone (GH) and/or adrenocorticotropic hormone
• Insulin antibodies (ACTH) deficiency can present as neonatal hypoglycemia. It is
• Drugs∗: quinine, pentamidine, salicylates, alcohol more common with multiple pituitary hormone deficiencies
*Except insulin and sulfonylurea.
than with isolated hormone deficiencies. Microphallus,
conjugated hyperbilirubinemia, and midline defects are
clinical clues to these deficiencies. Low serum free thyroxine
including alterations in hormones, or deficiencies of enzymes can be suggestive. The diagnosis is suspected if GH and/
of glycogenolysis, gluconeogenesis, and fatty acid oxidation. or cortisol levels are low in a hypoglycemic blood sample,
keeping in mind that persistent or recurrent hypoglycemia
Congenital Hyperinsulinism per se can impair GH and cortisol responses. Primary adrenal
Congenital hyperinsulinism (CHI) [previously called insufficiency can cause hypoglycemia, e.g., neonates with
nesidioblastosis, persistent hyperinsulinemic hypoglycemia congenital adrenal hyperplasia, but usually other clinical
of infancy (PHHI), or leucine sensitive hypoglycemia] is the features dominate (genital ambiguity, salt wasting crisis).
most common cause of persistent hypoglycemia in neonates Hypoglycemia due to hormone deficiencies responds to
and infants. Insulin secretion is inappropriate (rather than appropriate hormone replacement.
544
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Disorders of Carbohydrate Metabolism or functional scanning of pancreas. If present, it should prompt

evaluation for features of MEN1 in the child.
Glycogen storage disorders (GSDs) are AR enzyme deficiencies
of glycogen metabolism. Ketotic hypoglycemia is commonly
seen in types I, III, VI, and IX GSD. Although they can present
Accelerated Hypoglycemia
in the newborn period, more often they manifest when the (Ketotic Hypoglycemia)
interval between feeding and the duration of fasting increases. This condition usually presents at 1.5–5 years of age, typically
Failure to thrive, short stature, hepatomegaly, and doll-like as early morning lethargy and difficulty in getting up in
facies are clinical clues. In some, skeletal or cardiac muscle the morning, associated with ketonemia/ketonuria. These
involvement may be present but is usually asymptomatic in children have relatively lesser concentrations of alanine and
childhood. Renal tubular dysfunction can be seen in type less tolerance to fasting. Spontaneous improvement is seen
1 GSD, and hypophosphatemic rickets in Fanconi-Bickel after 8–9 years of age.
syndrome. Biochemical evaluation shows elevated lactate,
uric acid, triglycerides, and hepatic transaminases (serum
glutamic oxaloacetic transaminase, serum glutamic pyruvic Symptoms of Hypoglycemia
transaminase). Lactate and uric acid are usually elevated in Symptoms of hypoglycemia in neonates (Box 3) can be non-
type 1 GSD. Glycemic response to glucagon tends to be absent specific and caused by other etiologies like sepsis, asphyxia,
or poor. Definitive diagnosis can be established by genetic and electrolyte disturbances.
analysis or enzyme studies in liver biopsy specimen. Treatment Symptoms are usually divided into those resulting
of hypoglycemia usually consists of frequent carbohydrate from autonomic system activation and those resulting
feeding and supplementation with uncooked cornstarch. from neuroglucopenia (Table 1). However, in newborns, in
Defects in gluconeogenesis (phosphoenolpyruvate carboxy poorly controlled type 1 diabetes mellitus, and in those with
kinase deficiency, fructose-1,6-biphosphatase deficiency) autonomic dysfunction, autonomic symptoms may be absent.
present with fasting hypoglycemia, high lactate and alanine The threshold blood glucose value at which symptoms appear
levels, and fatty infiltration of liver and other organs. Hereditary can be variable.
fructose intolerance presents on exposure to fructose containing
food (sucrose, fruits, and juices), with hypoglycemia, vomiting,
failure to thrive, hepatomegaly and renal tubular dysfunction. CLINICAL EVALUATION
Classic galactosemia [galactose-1-phosphate uridyl Careful history and examination is the first step in diagnosis.
transferase (GALT) deficiency] presents in neonates and Clues to diagnosis on history and examination are listed in
infants with hypoglycemia, cholestatic jaundice, vomiting, and Tables 2 and 3, respectively.
Escherichia coli sepsis. Urine tests positive for non‑glucose
reducing substances and diagnosis is confirmed by GALT assay.
Box 3: Symptoms of hypoglycemia in newborns
Fatty Acid Oxidation Disorders • Seizures • Limpness
• Jitteriness • Lethargy
Hereditary or acquired defects of fatty acid oxidation
• Apathy • Poor suck/feeding
impair ketogenesis and produce nonketotic hypoglycemia,
liver dysfunction, cardiomyopathy, and encephalopathy. • Cyanosis • Eye rolling
Manifestations can be of variable severity, including risk • Apnea or tachypnea • Sudden pallor, mottling
of sudden death. Episodes of decompensation are usually • Hypothermia • Cardiac arrest
triggered by fasting or intercurrent illnesses. Treatment
includes avoidance of fasting, frequent feeding, high Table 1: Symptoms of hypoglycemia in children
carbohydrate (up to 70% of energy intake)-low fat diet, use of
cornstarch, and carnitine supplementation (not useful in long Autonomic symptoms Neuroglucopenic symptoms
chain hydroxyacyl CoA dehydrogenase). Tremors Headache
Palpitations, tachycardia Lightheadedness
Aminoacidopathies Anxiety Sensation of warmth
Aminoacidopathies (Box 2) present with ketotic hypo Restlessness Fatigue, weakness
glycemia, repeated vomiting, and developmental delay. Sweating Inability to think, inappropriate behavior
Seizures, encephalopathy, and hepatomegaly can be present.
Hunger Emotional lability
Hyperammonemia is seen in organic acid disorders. Diagnosis
depends on finding of specific organic acids in urine and Paresthesias Blurring of vision
analysis of liver biopsy or cultured fibroblasts. Pallor Seizures
Increased systolic blood Transient focal neurological deficits
Insulinoma pressure (diplopia, hemiparesis, etc.) ,
Islet cell adenoma (insulinoma) is a rare cause of hypoglycemia unconsciousness, brain damage and
in children. Diagnosis is based on magnetic resonance imaging death if prolonged untreated episode 545
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Table 2: Clues to diagnosis of persistent hypoglycemia in Table 3: Clues to diagnosis of persistent hypoglycemia on
children physical examination
Points in history Diagnostic clues Clinical feature Possible diagnosis
Age of onset • Early onset in hyperinsulinism (severe forms) Short stature GSDs, hypopituitarism
• Onset after gaps between feeds increase (GSD)
Macrosomia Infant of diabetic mother,
Gestational age • Transient hyperinsulinism in SGA hyperinsulinism
and birth weight • Macrosomia (infant of diabetic mother, Hepatomegaly GSDs, FAO disorders*,
hyperinsulinism) galactosemia, other metabolic
• Prematurity diseases
Relation of • In fed and fasting state—hyperinsulinism Midline defects (midline cleft Hypopituitarism
hypoglycemia to • In early hours of fasting—defects in lip, single central incisor),
feeding glycogen metabolism micropenis, nystagmus
• In later hours of fasting—defects in Hyperpigmentation Adrenal insufficiency
gluconeogenesis, FAO disorders
Hyperventilation Metabolic acidosis (inborn errors
Relation of • Protein (leucine) exposure—hyperinsulinism of metabolism)
specific feeds • Fruits—hereditary fructose intolerance
Gallop rhythm Cardiomyopathy in FAO disorders
• Milk—galactosemia
Dysmorphism Beckwith-Wiedemann and other
Antenatal • Gestational diabetes (infant of diabetic syndromes
history mother, HNF4a mutations)
*Hepatomegaly may be present only in decompensated stage
• Medications (tocolytics in mother)
GSD, glycogen storage disorder; FAO, fatty acid oxidation.
• Blood group (Rh incompatibility)
Perinatal history • Prolonged labor in macrosomia
Table 4: Tests to be done on critical sample collected during
• Birth asphyxia
hypoglycemia
Family history • Consanguinity (autosomal recessive
disorders) Blood Urine
• Affected siblings • Glucose (fluoride vial) • Ketones
• Neonatal/sudden deaths (hyperinsulinism, • Insulin • Urinary organic
FAO disorders) • Cortisol acids
Associated • Jaundice (hypopituitarism, galactosemia, • Growth hormone • Urine acylglycines
symptoms other inborn errors of metabolism) • β-hydroxybutyrate
• Features of sepsis/cardiac failure or other • Plasma acylcarnitine profile
systemic disease
• Ammonia (heparinized sample on ice)
• Recurrent vomiting (metabolic disease,
• Lactate (fluoride vial)
adrenal insufficiency)
A serum and urine sample is preserved for subsequent analysis.
• Abnormal odors (aminoacidopathies)
• Genital ambiguity (congenital adrenal
hyperplasia) episode) needs to be analyzed for tests mentioned in Table 4.
Drug history Potential exposure to insulin/sulfonylurea In any sick neonate/child, a sample of blood should be taken
GSD, glycogen storage disorder; SGA, small for gestational age; FAO, fatty acid and stored, so further tests can be decided depending on
oxidation. further clues and detecting the cause of the seizure/coma
(e.g., hypoglycemia/hypocalcemia/hyponatremia/other).
Alongside diagnosis, hypoglycemia has to be managed,
especially if neuroglucopenic symptoms (like seizures) are
Diagnostic Algorithm present. High IV glucose requirement (>8 mg/kg/min) is
Evaluation of the hypoglycemic infant starts with an accurate a strong pointer in favor of CHI. Criteria for diagnosis of
blood glucose, obtained by laboratory analysis. Plasma blood hyperinsulinism are mentioned in Box 4.
glucose less than 50 mg/dL during infancy, and less than Growth hormone levels greater than 20 ng/mL in neonates
60 mg/dL beyond infancy is consistent with the diagnosis, (>10 ng/mL in children) and cortisol greater than 20 µg/dL
especially when associated with symptoms. At all ages, cases in the critical sample rule out GH and cortisol deficiency,
with persistent hypoglycemia must be referred urgently to respectively. Lower values in the hypoglycemic sample need
centers having expertise in managing CHI. Prolonged fruitless confirmation by definitive testing unless hypopituitarism/
attempts at making diagnosis can lead to irreversible brain adrenal insufficiency is obvious clinically. High insulin with
damage. Diagnostic sampling at the time of hypoglycemia is low C-peptide indicates exogenous insulin administration.
most important; this critical sample taken before administering A commonly used algorithm (Algorithm 1) for diagnosis of
546 medication, of blood and urine (passed after the hypoglycemic persistent hypoglycemia is given below.
ch-111.indd 546 11/21/2016 2:27:53 PM

Box 4: Criteria for diagnosis of hyperinsulinism

orally, and increased up to 20 mg/kg/day. A trial of at least
5–7 days is needed before labeling a patient diazoxide
Glucose infusion rate >8 mg/kg/min laboratory plasma blood unresponsive. Common side effects include fluid retention,
glucose <50 mg/dL with
tachycardia, and hypertrichosis (reversible on stopping).
• Detectable insulin concentration (>2 mIU/L)* Diazoxide is not freely available and costs up to Rs 50–60
• Suppressed/low ketones (serum/urine) per tablet. Diazoxide unresponsive hypoglycemia can be
• Suppressed/low serum fatty acids† medically managed with injection octreotide or glucagon.
• Supportive criteria (when diagnosis is in doubt) Nifedipine and chlorothiazide may help as add-on oral agents
• Positive glycemic response to IM/IV glucagon but should not be used alone (Table 5).
• Positive glycemic response to SC/IV octreotide Diazoxide unresponsive patients need mutation analysis
• Low IGFBP-1 and 18F-fluorodihydroxyphenylalanine positron emission
tomography/positron emission tomography-computed tomo
*Depends on sensitivity of the assay used. graphy (18F DOPA PET/PET-CT) to differentiate focal and
†Not commonly available at many centers in India. diffuse forms of disease. Selective pancreatectomy can be
IGFBP-1, insulin-like growth factor binding protein-1; IM, intramuscular; IV, curative in cases with the focal form. The diffuse form can be
intravenous; SC, subcutaneous.
managed with long-term octreotide if response to treatment
is present and resources permit. Use of long acting octreotide
A fasting challenge may be occasionally required for preparations and sirolimus has been recently described
diagnosis, but should be done only at experienced centers in some cases. Other cases are managed with near-total
under careful supervision of pediatric endocrinologists. It pancreatectomy which is associated with development of
may be particularly risky for infants with fatty acid oxidation diabetes mellitus in the postoperative period.
disorders.
Specific Treatment of
MANAGEMENT Other Causes of Persistent Hypoglycemia
Acute symptomatic hypoglycemia should be treated with General principles of management of persistent hypoglycemia
a 2 mL/kg IV 10% dextrose bolus, followed by continuous are described in box 5.
infusion of 10% dextrose at the rate of 6–8 mg/kg/min. Frequent Growth hormone/cortisol deficiencies are treated with
monitoring of capillary glucose is required initially to judge specific hormone replacement. Galactosemia and fructose
the required concentration to maintain blood glucose greater intolerance require avoidance of milk or lactose-containing
than 60 mg/dL. Real-time continuous glucose monitoring can substances/fruits, honey, and sucrose-containing foods,
be a useful tool. Efforts to start and maintain enteral feeds can respectively. Frequent feeds, nocturnal cornstarch, and
then be done, and if successful, IV glucose tapered gradually. avoidance of fasting are the treatment for many of the
Breastfeeding should be encouraged, as it favors ketogenesis. metabolic diseases. Carnitine supplementation can be useful
Frequent feeding, including at night, is important, and may in some fatty acid oxidation (FAO) disorders.
require tube feeding. Raw cornstarch (1–2 g/kg/day) can be
added to feeds for children older than 1 year of age. It can be PROGNOSIS
given at bedtime to prevent morning hypoglycemia. Glucose
polymers (polyjoule, maxijoule, etc.) can be useful for infants Persistent hypoglycemia and hyperinsulinism are a major risk
as a source of complex carbohydrates, but are not easily for neurologic damage, resulting in sequelae like psychomotor
available in India. Higher concentrations should be avoided as retardation and epilepsy. All children should have periodic
they increase the risk of necrotizing enterocolitis. neurodevelopmental evaluation. Early referral to experienced
Inability to start or maintain enteral feeds/persistent centers, aggressive treatment of hypoglycemia, and timely
hypoglycemia is managed with increasing the concentration of decision of surgery in diazoxide unresponsive cases can help
IV glucose. Glucose infusion rates greater than 8 mg/kg/min prevent brain damage in hyperinsulinism. Surgical treatment
should prompt consultation with a pediatric endocrinologist for diffuse hyperinsulinism results in diabetes mellitus.
to rule out CHI (such infants often require rates
>10–15 mg/kg/min). Glucose boluses reflexly stimulate insulin
secretion and should be avoided after the initial bolus. A patent Box 5: Principles of management of persistent hypoglycemia
IV access must always be ensured and higher concentrations of • Early recognition and aggressive treatment of hypoglycemia
glucose (>10–12%) given through central vascular access. • Frequent/continuous glucose monitoring
• Early referral to pediatric endocrinologist
Specific Treatment for • Intravenous glucose treatment through patent central/
Congenital Hyperinsulinism peripheral line
• Regular enteral feeds, addition of glucose polymer/cornstarch if
After documenting high glucose requirement, a trial of
necessary.
diazoxide is given for infants with proven or suspected CHI,
usually started at 7–10 mg/kg/day in three divided doses • Specific treatment of underlying cause 547
ch-111.indd 547 11/21/2016 2:27:53 PM

Algorithm 1
Diagnostic algorithm for persistent hypoglycemia
FAO, fatty acid oxidation; GH, growth hormone.
Table 5: Medications used in management of hyperinsulinism

Medication Route Dose Mechanism Side effects
Diazoxide Oral 5–20 mg/kg/day ATP sensitive K+ channel agonist Fluid retention
3 doses/day Hypertrichosis
Chlorothiazide Oral 7–10 mg/kg/day ATP sensitive K+ channel agonist Hyponatremia
(used with diazoxide) 2 doses/day Hypokalemia
Nifedipine Oral 0.25–0.5 mg/kg/day Calcium channel blockade Hypotension (uncommon)
Glucagon SC/IV infusion 1–20 µg/kg/h Gluconeogenesis and glycogenolysis Vomiting, rebound hypoglycemia
Octreotide SC/IV infusion or 5–25 µg/kg/day Multiple actions GI side effects, cholelithiasis
6–8 hourly divided
GI, gastrointestinal; SC,subcutaneous; IV, intravenous.

1. Committee on Fetus and Newborn. Adamkin DH. Postnatal glucose homeostasis
))
Persistent hypoglycemia, especially in the newborn/infant, in late-preterm and term infants. Pediatrics. 2011;127:575-9.
can permanently damage the developing brain 2. Hay WW, Raju TN, Higgins RD, Kalhan SC, Devaskar SU. Knowledge gaps and
))
Early diagnosis and aggressive management is important to research needs for understanding and treating neonatal hypoglycemia: workshop
prevent brain damage report from Eunice Kennedy Shriver National Institute of Child Health and Human
Development. J Pediatr. 2009;155:612-7.
))
Neonatal hypoglycemia is usually defined as <47 to <50 mg/dL 3. Kapoor RR, Flanagan SE, James C, Shield J, Ellard S, Hussain K. Hyperinsulinaemic
beyond the first 2–3 hours of life. Low values obtained on capillary hypoglycaemia. Arch Dis Child. 2009;94:450-7.
testing should be confirmed by laboratory assessment 4. Desai MP, Khatri JV. Persistent hyperinsulinemic hypoglycaemia of infancy. Indian
))
A critical sample of blood and urine must be collected in any Pediatr. 1998;35:317-28.
sick baby before starting medication 5. Aynsley-Green A, Hussain K, Hall J, Saudubray JM, Nihoul-Fékété C, De Lonlay-
Debeney P, et al. Practical management of hyperinsulinism in infancy. Arch Dis
))
Congenital hyperinsulinism (CHI) is the most common cause Child Fetal Neonatal Ed. 2000;82:F98-F107.
of persistent nonketotic hypoglycemia in neonates and 6. Wolfsdorf JI, Weinstein DA. Hypoglycemia in children. In: Lifshitz F (Ed). Pediatric
infants. Genetic analysis must be done to look for mutations Endocrinology (Volume 1), 5th edition. USA: Informa Healthcare; 2007.
))
In CHI due to focal nesidioblastosis, selective pancreatectomy 7. Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K,
is curative Levitsky LL, Murad MH, Rozance PJ, Simmons RA, Sperling MA, Weinstein DA,
White NH, Wolfsdorf JI; Pediatric Endocrine Society. Recommendations from
))
Diazoxide and other drugs may give long-term control the Pediatric Endocrine Society for Evaluation and Management of Persistent
of hypoglycemia. In diazoxide unresponsive babies, total Hypoglycemia in Neonates, Infants, and Children. J Pediatr. 2015;167:238-45.
pancreatectomy may be needed, and results in diabetes 8. Stanley CA. Perspective on the Genetics and Diagnosis of Congenital
))
Hormone deficiencies (growth hormone and/or adreno Hyperinsulinism Disorders. J Clin Endocrinol Metab. 2016;101:815-26.
corticotropic hormone deficiency) and inborn errors of 9. Vora S, Chandran S, Rajadurai VS, Hussain K. HYPERLINK “https://www.ncbi.nlm.
nih.gov/pubmed/26713990” Hyperinsulinemic Hypoglycemia in Infancy: Current
metabolism need specific treatment.
Concepts in Diagnosis and Management. Indian Pediatr. 2015;52:1051‑9.
548
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Chapter 112
Disorder of Sex Development
Vijaya Sarathi
INTRODUCTION virilisation in an apparent female, breast development or gross

hematuria in an apparent male.
Disorders of sex development (DSDs) are defined as
congenital conditions in which development of chromosomal, Clinical Pearl
gonadal, or anatomic sex is atypical. A 2006 Consensus
Conference suggested that the potentially pejorative terms • Isolated penile hypospadias or isolated micropenis does not
“pseudohermaphroditism” and “intersex” be replaced by the merit evaluation for disorders of sex development.
diagnostic category “disorders of sex development”. The most
common presentation of DSDs is with abnormalities of the
CAUSES AND CLASSIFICATION
external genitalia (ambiguous genitalia), usually detected at
birth. Abnormalities of external genitalia sufficient to prompt Ambiguous genitalia usually results due to virilization of a
evaluation (Box 1) occur in approximately 1 in 4,500 live births. female fetus (XX DSD), undervirilization of a male fetus (XY
Early evaluation of a child with ambiguous genitalia is of DSD), or mixed sex chromosome disorders. An example of
utmost importance due to the association with life-threatening classification of DSDs is shown in table 1.
disorders like congenital adrenal hyperplasia (CAH) and early Virilization of a female fetus occurs due to androgen
assignment of appropriate sex. Some DSDs are not characterized exposure during some critical periods of development. Fetal
by genital ambiguity (Turner syndrome, Klinefelter syndrome). androgen exposure between 8 weeks and 12 weeks of fetal
Some others will have apparently normal genitalia at birth, and life leads to urogenital sinus (single opening at introitus)
get diagnosed at an older age. Presentation in older individuals and labioscrotal fusion. Androgen exposure after 12 weeks
may include genital ambiguity unrecognized at birth, inguinal of gestation will lead to isolated clitoromegaly. Significant
hernia, delayed/incomplete puberty, primary amenorrhea, undervirilization of a male fetus occurs due to low or absent fetal
androgen exposure during the critical developmental period.
Box 1: Problems in newborns that merit evaluation for Low or absent androgen after this critical developmental
disorders of sex development period will cause isolated micropenis.
• Ambiguous genitalia
• Apparent female genitalia with EVALUATION OF A CHILD
{{ Enlarged clitoris WITH AMBIGUOUS GENITALIA
{{ Posterior labial fusion
Evaluation of an infant or a child with ambiguous genitalia is
{{ Inguinal/labial mass
challenging. Most virilized 46XX infants have CAH; however,
• Apparent male genitalia with only 50% of undervirilized 46XY patients receive a definitive
{{ Nonpalpable testes
diagnosis.
{{ Isolated perineoscrotal hypospadias
{{ Severe hypospadias, undescended testi(e)s, micropenis

History
• Family history of DSD, such as complete AIS
A detailed history and thorough physical examination have
• Discordance between genital appearance and prenatal karyotype
a pivotal role in the evaluation of a child with ambiguous
DSD, disorder of sex development; AIS, androgen insensitivity syndrome. genitalia. History should include family history of DSDs,
ch-112.indd 549 11/21/2016 2:39:10 PM

Table 1: An example of classification of disorder of sex development

Sex chromosome DSD 46, XY DSD 46, XX DSD
• 45,X (Turner • Disorders of gonadal development • Disorders of gonadal (ovarian) development
syndrome and {{ Gonadal dysgenesis {{ Ovotesticular DSD
variants) {{ Ovotesticular DSD {{ Testicular DSD (e.g. SRY, duplicate SOX9)
• 47,XXY (Klinefelter • Disorders of androgen synthesis or action: {{ Gonadal dysgenesis
syndrome and {{ Androgen biosynthesis defect • Androgen excess

variants) (e.g., 17α hydroxylase deficiency, {{ Fetal (e.g., 21-hydroxylase deficiency, 11-hydroxylase
• 45,XO/46,XY (Mixed 3β hydroxysteroid dehydrogenase deficiency)
gonadal dysgenesis) deficiency, 5αRD2 deficiency and star {{ Fetoplacental (aromatase deficiency, P450 oxidoreductase
• 46,XX/46,XY mutations) deficiency); and
(Chimeric {{ Defect in androgen action (e.g., CAIS, {{ Maternal (luteoma, exogenous, etc.)
ovotesticular DSD) PAIS) • Others
{{ Luteinizing hormone receptor defects
{{ Cloacal exstrophy
(e.g., Leydig cell hypoplasia, aplasia) {{ Vaginal atresia
• Disorders of anti-Mullerian hormone {{ MURCS (Mullerian, renal, cervico-thoracic somite
and anti-Mullerian hormone receptors abnormalities)
(persistent Mullerian duct syndrome) {{ Other syndromes
DSD, disorder of sex development; CAIS, complete androgen insensitivity syndrome; PAIS, partial androgen insensitivity syndrome; StAR, steroidogenic acute
regulatory protein; 5αRD2, 5-alpha-reductase type 2.
Table 2: Clinical pointers towards etiology of disorder of sex development

Maternal virilization during Placental aromatase deficiency, luteoma of pregnancy, maternal androgen secreting tumors,
pregnancy maternal androgen intake
Early sibling death CAH with salt wasting
Failure to thrive, hypotension, CAH with salt wasting, SF-1 mutation
hyperkalemia
Hypertension, hypokalemia 11β-hydroxylase deficiency, 17α-hydroxylase deficiency
Hyperpigmentation CAH, SF-1 mutation
Peripheral precocity 21-hydroxylase deficiency, 11β-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency,
gonadal dysgenesis with gonadoblastoma
Inguinal hernia in a baby girl Complete androgen insensitivity, testosterone synthetic defects, Leydig cell aplasia
Bilateral well palpable gonads with Androgen insensitivity syndrome, 5α-reductase deficiency, testosterone synthetic defects, Leydig cell
ambiguous genitalia hypoplasia
Asymmetric genitalia Mixed gonadal dysgenesis, ovotesticular DSD
Apparent male external genitalia Severely virilized CAH female, hypogonadotrophic hypogonadism, testicular regression syndrome
with no palpable gonads
Cyclical hematuria Ovotesticular DSD
Virilization at puberty Partial androgen insensitivity syndrome, 5α-reductase deficiency, 17β-hydroxysteroid dehydrogenase
deficiency, partial gonadal dysgenesis
Gynecomastia Partial androgen insensitivity syndrome, partial gonadal dysgenesis, 17β-hydroxysteroid
dehydrogenase deficiency
Progressive postnatal virilization CAH, aromatase deficiency (at puberty)
Primary amenorrhea, severe Complete androgen insensitivity, pure gonadal dysgenesis, 17α-hydroxylase deficiency, aromatase
oligohypomenorrhea deficiency
CAH, congenital adrenal hyperplasia; DSD, disorder of sex development.
previous perinatal or neonatal deaths in siblings or other family should also focus on postnatal progression of virilization
members, consanguinity, maternal drug (androgen, alcohol (increasing clitoral size, premature pubarche, or precocious
or progesterone) intake during pregnancy, and maternal puberty), pubertal events (virilization of an apparent girl at
history of virilization during pregnancy. In an infant, history puberty, gynecomastia, delayed or absent puberty), gross or
of vomiting, dehydration, inadequate weight gain, and dark cyclical hematuria in a boy, and response to hormonal therapy,
pigmentation of oral mucosa and/or genital mucosa should be especially to testosterone in boys. Certain key pointers in
asked for. In a newborn boy with marked pigmentation of the history and physical examination provide useful clues towards
550 scrotum, CAH should be ruled out. In an older child, history the etiological diagnosis and are listed in table 2.
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Chapter 112: Approach to a Child with Disorder of Sex Development
Physical Examination Urethral Opening

Physical examination should include measurement of blood It may be present anywhere from the tip of the phallus to the
pressure with appropriate sized cuff, an accurate and objective perineum and should be assessed by careful examination of
assessment of genitalia, and evaluation for any dysmorphic the ventral aspect of the phallus for grooves. A single opening
features. While 21-hydroxylase deficiency is characterized by at the base of the phallus may be either an incompletely fused
hypotension with dyselectrolytemia and hypoglycemia due penile urethra (hypospadias) or a virilized urogenital sinus
to adrenal insufficiency, presence of hypertension raises the (e.g., internal connection between the vagina and urethra).
possibility of 11β-hydroxylase deficiency. Accordingly, these findings must be confirmed either by
cystoscopy/vaginoscopy or radiographically, because the
Dysmorphic Features physical examination can be misleading.
A thorough evaluation should be done in all children with
Prader Stages
ambiguous genitalia, so that if it is part of a syndrome, the
diagnosis can be made. Degree of genital ambiguity does not differentiate between
46XX DSD and 46XY DSD. It merely provides information
Clinical Pearl about the extent of abnormality once the karyotype is known.
Prader staging is commonly used to describe the degree of
• All infants with ambiguous genitalia and nonpalpable gonads virilization in 46 XX DSDs. Different Prader stages are depicted
should be considered to have congenital adrenal hyperplasia in figure 1. Stage 1 is otherwise normal looking female genitalia
and closely monitored until proven otherwise. with isolated phallic enlargement, stage 2 is further phallic
enlargement and posterior labial fusion without urogenital
sinus, stage 3 is significant phallic enlargement with almost
Gonads
complete fusion of labioscrotal folds and urogenital sinus
The scrotum, labia majora, and inguinal area should be with single perineal opening, stage 4 is phallus with penile
carefully palpated to identify the presence, position, size, and appearance with complete labioscrotal fusion and urogenital
consistency of the gonads. Palpable gonads in the scrotum sinus opening at the base or ventral surface of the phallus, and
or inguinal canal are almost always testes or rarely ovotestes; stage 5 is phallus with the appearance of well-developed penis
hence, suggest 46XY DSD or ovotesticular DSD. Pigmentation with completely fused labioscrotal folds and urogenital sinus
and rugae of the labioscrotal folds and presence of epididymis opening at the body or glans of the phallus.
should also be evaluated. Non-palpable gonads suggest either
XX DSD (most likely CAH) or XY DSD with gonadal dysgenesis Laboratory Evaluation
or cryptorchidism.
First line laboratory testing, especially in newborns, includes
Phallic Length karyotyping with SRY detection (even when prenatal karyotype
is available), imaging (abdomino-pelvic ultrasound), and
Penile/clitoral length is measured from the pubic ramus to the measurement of 17-hydroxyprogesterone, testosterone,
tip of the glans (excluding any excess foreskin) after stretching gonadotropins, anti-Mullerian hormone, and electrolytes. The
the penis to the point of increased resistance. The ruler should results of these investigations are generally available within 48
be pressed down against the ramus to completely depress the hours and will be sufficient for making a working diagnosis.
suprapubic fat pad. Normal values for stretched penile length To minimize psychological distress during evaluation, the
and clitoris are available and vary among different ethnic patient/family should be informed exactly what will be done
populations. In general, a penile length of less than 2.5 cm and why. Congenital adrenal hyperplasia is always a possibility
suggests micropenis whereas a clitoral length of greater than or in an infant with ambiguous genitalia. Hence, throughout the
equal to 1 cm suggests clitoromegaly in term infants. evaluation period, careful monitoring of the infant for weight,
vitals, and blood chemistry (blood glucose, sodium and
Clinical Pearl potassium) should be carried out to start early treatment if the
• Normal preterm female infants may appear to have clitoro findings suggest CAH.
megaly since they have larger clitoral breadth compared to
body size. Karyotype
Karyotype is performed, usually using peripheral leukocytes.
Because of the possibility of mosaicism, it is suggested that at
Anogenital Ratio
In apparently female external genitalia, mild degree of
virilization in the form of posterior labial fusion can be
evaluated with measurement of anogenital ratio. This is the
ratio of the distance from the anus to the posterior fourchette,
and the distance from the anus to the base of the clitoris. A ratio
of greater than 0.5 suggests virilization with some posterior Fig. 1: Prader’s staging to describe the degree of virilization in female
labial fusion. infant 551
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least 200 cells should be examined. The results of the karyotype hypoplasia, or testosterone biosynthetic defect. The most
permit classification of the infant into one of three diagnostic common testosterone biosynthetic defect, 17β-hydroxysteroid
categories (XX DSD, XY DSD, and mixed sex chromosome dehydrogenase (17β-HSD) deficiency, is diagnosed by
DSD) that guide further evaluation. decreased testosterone to androstenedione ratio.
Fluorescence In Situ Hybridization Imaging

Fluorescence in situ hybridization using Y specific (SRY) and Ultrasonography of the abdomen and pelvis by an
X specific probes will provide results within hours compared ultrasonologist experienced in neonatal work is important to
to conventional karyotype which takes days to provide results. determine the presence of gonads, a uterus, and/or a vagina.
Retrograde urethrogram may be necessary, although most
Adrenal Steroids surgeons find direct visualization by cystoscopy/vaginoscopy
Measurement of 17-hydroxyprogesterone should be done under general anesthesia to be the single best method
promptly in all infants presenting with genital ambiguity of assessing the urethral and vaginal anatomy. In some
or marked genital pigmentation, to exclude CAH due to complicated cases (particularly those infants with elements
21-hydroxylase deficiency. It should be measured on or of male and female gonads/internal reproductive structures),
after day 3–4 of life since maternal steroid may result in laparoscopic visualization may ultimately be required to
spuriously high values if determined during day 1–2. Levels completely delineate reproductive anatomy and this allows for
of 17-hydroxyprogesterone (17-OHP) should be interpreted simultaneous gonadal biopsy for histologic/genetic evaluation.
using gestational age matched reference ranges to avoid Urinary steroid profile by gas chromatography/mass
spurious diagnosis of CAH. It should also be noted that stress spectrometry is useful when rarer forms of CAH are suspected.
responses like sepsis may falsely elevate 17-OHP levels. Specific genetic analyses may be helpful in reaching the exact
Other tests for adrenal evaluation include serum cortisol, diagnosis.
plasma adrenocorticotrophic hormone, plasma renin activity, Given the spectrum of findings and diagnoses, no specific
17-hydroxypregnenolone, 11-desoxycortisol, and dehydro single evaluation protocol can be used. Evaluation of each
epiandrosterone. case must be individualized. In this chapter, author provides
a practical decision-making algorithm based on karyotype
Clinical Pearls of the child (Algorithm 1). A simplified practical algorithm
to approach a child with apparently male genitalia and
• Measurement of 17-hydroxyprogesterone (17-OHP) should be
avoided during first 2 days of life undescended testes is depicted in algorithm 2. A detailed
algorithmic approach to a child with XX DSD and XY DSD are
• Levels of 17-OHP may be falsely elevated in infants with sepsis
depicted in algorithm 3 and algorithm 4 respectively.
and prematurity and should be interpreted with caution.
MANAGEMENT
Gonadal Steroids
Gonadal steroid assessment during the prepubertal period The primary aim in managing an infant with DSD should be to
requires a human chorionic gonadotropin (hCG) stimulation achieve a diagnosis, sex assignment, and management plan as
test. However, in infants between 1 month and 6 months, quickly as possible. This requires involvement of an experienced
transient activation of hypothalamic-pituitary-adrenal axis multidisciplinary team. Ideally, the team includes pediatric
may provide an opportunity for gonadal steroid assessment endocrinologist, pediatric surgeon, child psychologist/
without hCG stimulation. psychiatrist, gynecologist, geneticist, neonatologist, medical
social worker, and medical ethics specialist.
Human Chorionic Gonadotropin Stimulation Test
There are many protocols for hCG stimulation test. The most Newborn Gender Assignment
widely used one is the short hCG stimulation test. Human Infants with 46XY complete androgen insensitivity syndrome
chorionic gonadotropin (500–1,500 IU/day) is administered (CAIS) and 46XX CAH should be reared as females, whereas for
intramuscularly on 3 consecutive days; 24 hours after the last those with 5α-reductase deficiency or 17β-HSD3 deficiency, a
dose, blood sample is collected and analyzed for testosterone, male assignment should be strongly considered. In other cases,
dihydrotestosterone, and androstenedione. factors that influence gender assignment include diagnosis,
Normal or high testosterone levels suggest androgen genital appearance, surgical options, need for lifelong
insensitivity or 5α-reductase deficiency. An elevated replacement therapy, potential for fertility, views of the family,
testosterone to dihydrotestosterone ratio (T/DHT) suggests and, sometimes, circumstances relating to cultural practices.
5α-reductase deficiency. However, a recent study has suggested Feminizing genital surgery involves external genitalia
that the use of T/DHT ratio has poor sensitivity for the diagnosis reconstruction and vaginal exteriorization, with early separation
of 5α-reductase deficiency. Hence, molecular studies are of the vagina and urethra. Clitoral reduction is considered with
essential for appropriate diagnosis of these conditions. Low severe virilization (Prader III–V) and preferably, performed in
552 testosterone values suggest gonadal dysgenesis, Leydig cell conjunction with common urogenital sinus repair. Procedures
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Algorithm 1
A simplified practical algorithmic approach to a child with ambiguous genitalia
17-OHP, 17-hydroxyprogesterone; AMH, anti-Mullerian hormone; CAH, congenital adrenal hyperplasia; DHT, dihydrotestosterone; DSD, disorder of sex development;
T, testosterone.
Algorithm 2 should be inserted after sufficient pubertal scrotal development.

For XY DSD individuals (except for CAIS) who have been
Algorithm to approach a child with apparently male genitalia and
assigned female gender, gonadectomy should be performed
undescended testes
before puberty. Patients with GBY-positive gonadal dysgenesis
and partial androgen insensitivity syndrome (PAIS) with intra-
abdominal testis, and Turner syndrome with Y chromosome
have high risk of germ cell malignancy and should undergo
gonadectomy before puberty.
Hypogonadism is common in patients with dysgenetic
gonads, defects in sex-steroid biosynthesis, and resistance to
androgens. Intramuscular depot injections of testosterone
esters are commonly used in males. Other options include
oral testosterone undecanoate, and transdermal preparations.
Patients with PAIS may require supraphysiologic doses of
testosterone for optimal effect. Females with hypogonadism
require estrogen supplementation to induce pubertal changes
and menses. For women with a uterus, a progestin is usually
added after breakthrough bleeding develops or within 1–2
years of continuous estrogen.
Amongst all causes of DSD, CAH is the most important
condition that needs to be promptly diagnosed and treated.
AMH, anti-Mullerian hormone; CAH, congenital adrenal hyperplasia; hCG, Most commonly it manifests with a salt wasting crisis
human chorionic gonadotropin; T, testosterone. during the 2nd week of life and if untreated may cause death.
During infancy, initial reduction of markedly elevated
should emphasize functional cosmetic appearance and adrenal sex hormones may require hydrocortisone up to
be designed to preserve erectile function and enervation. 25 mg/m2 per day, but typical dosing is 10–15 mg/m2 per
Vaginoplasty should be performed in the teenage years. day divided three times daily. Mineralocorticoid should be
Masculinizing genital surgery involves more surgical procedures replaced in the form of fludrocortisone (100–200 µg/day).
and urologic difficulties than feminizing genitoplasty. Standard Sodium chloride supplements are often needed in infancy
surgical repair involving hypospadias includes chordee (1–3 g/day) distributed in several feedings. During period of
correction, urethral reconstruction, and judicious testosterone sickness or surgery, stress doses of hydrocortisone should be
supplementation. If needed, adult-sized testicular prostheses supplemented.
553
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Algorithm 3
Approach to a child with XX disorder of sex development
DSD, disorder of sex development; 17-OHP, 17-hydroxyprogesterone; FSH, follicle-stimulating hormone; PRA, plasma renin activity; DHEA, dehydroepiandrosterone;
3β-HSD, 3β-hydroxysteroid dehydrogenase; LDDST, low-dose dexamethasone suppression test; AB, Antley-Bixler; POR, P450 oxidoreductase.
Algorithm 4
Approach to a child with XY disorder of sex development
LH, luteinizing hormone; FSH, follicle-stimulating hormone; T, testosterone; hCG, human chorionic gonadotropin; DHT, dihydrotestosterone; AMH, anti-Mullerian
hormone; PMDS, persistent Mullerian duct syndrome; DSD, disorder of sex development; DHEA, dehydroepiandrosterone; 17-OHP, 17-hydroxyprogesterone; HSD,
hydroxysteroid dehydrogenase; SCC, side-chain cleavage enzyme; SLO syndrome, Smith-Lemli-Opitz syndrome; A4, androstenedione; AIS, androgen insensitivity
syndrome; POR, P450 oxidoreductase; StAR, steroidogenic acute regulatory protein.
554
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Key points
))
The most common presentation of disorders of sex development (DSD) is with abnormalities of the external genitalia (ambiguous
genitalia), usually detected at birth (1 in 4500 live births)
))
Most virilized 46XX infants have congenital adrenal hyperplasia (CAH) which may lead to death if untreated
))
Only 50% of undervirilized 46XY patients receive a definitive diagnosis. The common diagnoses include androgen insensitivity
syndrome, 5α-reductase deficiency, gonadal dysgenesis, and testosterone biosynthetic defects
))
Degree of genital ambiguity (Prader staging) does not differentiate between 46XX DSD and 46XY DSD. It merely provides information
about the extent of abnormality once the karyotype is known
))
First line investigations of an infant with ambiguous genitalia should include karyotyping with SRY detection, pelvic ultrasound, and
measurement of 17-hydroxyprogesterone (day 3 onwards)
))
All infants with suspected CAH should be closely monitored for weight, serum electrolytes, and blood glucose
))
Management of an infant with ambiguous genitalia requires involvement of an experienced multidisciplinary team. Ideally, the team
includes pediatric endocrinologist, pediatric surgeon/urologist, child psychologist/psychiatrist, gynecologist, geneticist, neonatologist,
medical social worker, and medical ethics specialist
))
Infants with 46XY complete androgen insensitivity syndrome and 46XX CAH should be reared as females, whereas for those with
5α-reductase deficiency or 17β-HSD3 deficiency, a male assignment should be strongly considered
))
Patients with GBY-positive gonadal dysgenesis and partial androgen insensitivity syndrome with intra-abdominal testis, Turner with Y
chromosome have high risk of germ cell malignancy and should undergo gonadectomy before puberty.
SUGGESTED READINGs on intersex disorders and their management. International Intersex Consensus
1. Carillo AA, Damian M, Bercovitz G. Disorders of sexual differentiation. In: Lifshitz Conference. Pediatrics. 2006;118(2):753‑7.
F editor. Pediatric Endocrinology. Vol 2. 5th ed. London: Informa Healthcare; 2007. 3. Lambert SM, Vilain EJ, Kolon TF. A practical approach to ambiguous genitalia in
pp. 365-413. the newborn period. Urol Clin North Am. 2010;37(2):195-205.
2. Houk CP, Hughes IA, Ahmed SF, Lee PA; Writing Committee for the International
Intersex Consensus Conference Participants. Summary of consensus statement
555
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Chapter 113
Approach to
Thyroid Disorders in Children
Anju Virmani
INTRODUCTION papers on day 3–5 of age (or at time of discharge). This timing is
meant to reduce the impact of the neonatal thyroid-stimulating
Thyroid disorders are common in childhood, and can cause hormone (TSH) surge, and allow for screening of other
significant morbidity. Symptoms may be confusing or disorders like phenylketonuria which cannot be done in cord
misleading, but diagnosis and treatment are becoming easier
blood. If only CH screening is planned, to avoid problems due
with increasing availability of reliable hormone and other
to early discharge of mothers, cord blood can be collected, as
tests, and wide availability of inexpensive medication. Yet this
was done in early studies in the 1970s. This has several logistic
increases the responsibility of the pediatrician to take timely
advantages: it is easily done in 100% deliveries, no needle
and correct decisions. This chapter will discuss the approach
prick is needed, the report is available by the time the baby is
to the following:
• Universal thyroid screening discharged, hence in those newborns in whom confirmation
• Hypothyroidism by repeat testing and start of replacement is required, it is
• Hyperthyroidism. easily done well in time.
The primary TSH method is most widely used, with a
sensitivity of 97.5% and specificity of 99%; the best method
CONGENITAL HYPOTHYROIDISM is combined TSH and thyroxine (T4) screening, which is
Of the various thyroid disorders, congenital hypothyroidism somewhat more expensive (higher cost of testing, lesser cost
(CH) is the most important as it needs early diagnosis based of recall and confirmation). Most programs use a cutoff for
on lab screening and early treatment, if permanent brain TSH of greater than 20–25 mU/mL. The American Academy
damage is to be prevented. Congenital hypothyroidism is of Pediatrics suggests a cutoff of greater than 40 mU/mL.
the most common cause of preventable mental retardation. Any level above this should be confirmed by an urgent
Because 90% of affected newborns look normal, the cost- repeat venous sample for T4 and TSH, so that replacement
effectiveness of screening each and every newborn is can be started within 1–2 weeks of life. Once the diagnosis is
undoubted. Worldwide incidence is reported as 1 in 3,000– confirmed (usually TSH is >50 mU/mL), if it is conveniently
4,000 newborns, but in India, it may be much higher. Several possible, a Tc-99m thyroid scan should be done: this would
hospitals now screen all newborns, and some states have also help in diagnosing dysgenesis (agenesis, hypoplasia, and
begun programs for universal screening. ectopia, i.e., lingual thyroid). Treatment should not be delayed
just to obtain a scan.
Clinical Pearl Initial doses of thyroxine are 10–15 µg/kg, i.e., usually
• All newborns must get thyroid function tested, not just those 25–50 µg given orally as a once-daily dose, to allow for rapid
whose mothers have thyroid disorders. If not done at birth, normalization of serum T4. Doses should be titrated on the
it should be done whenever the baby is first seen (e.g., for basis of serum T4 (keep in the upper half of normal range) and
vaccination). TSH, done after 2 weeks of starting, then every 1–2 months for
the first 6 months, then every 3–4 months till age 3 years. It
International recommendations for mass newborn must be remembered that up to age 3–4 months, normal TSH
screening advise taking a heel prick sample on special filter levels are up to 9 mU/mL.
ch-113.indd 556 11/21/2016 2:40:38 PM

Chapter 113: Approach to Thyroid Disorders in Children
morning, as TSH levels decrease in the evening. Serum

Clinical Pearl triiodothyronine (T3) rarely contributes to the diagnosis.
• Congenital hypothyroidism confirmation should be done Thyroid antibodies are expensive, and do not alter the
urgently, so that thyroxine can be started as soon as possible. management. In addition, they may be present in 5–10% of
This should preferably begin by age 2 weeks, to ensure normal the normal population, and raised antibodies in themselves
brain development. do not justify any medication. Increased TSH with low T4 is
diagnostic of primary hypothyroidism. Low T4 with normal,
low, or even mildly increased TSH is diagnostic of secondary/
If a cause of permanent CH is found, e.g., dysgenesis, tertiary hypothyroidism, which is much rarer. Secondary
parents are explained that treatment is needed lifelong. hypothyroidism should be thought of if there is any reason to
Otherwise, to confirm if CH is permanent or transient, thyroxine suspect pituitary or hypothalamic disorders. Indian normative
is discontinued at the age of 2.5–3 years for 4–5 weeks, and data for thyroid hormones is comparable with that elsewhere.
T4, TSH (and if necessary, thyroid scan) repeated. If the TSH
rises, thyroxine replacement is reinstituted (monitored by T4 Clinical Pearl
and TSH every 6–12 months), and the family explained that
replacement would be needed lifelong. • Hypothyroidism must be confirmed by lab testing. Treatment
Periodic training of staff and validation of correctness of started on clinical suspicion alone is not justified.
sample collection and lab performance is essential, especially
with filter paper samples. Replacement is also quite straightforward: with oral
thyroxine. Even if iodine deficiency is suspected or proven,
iodine should not be given for treatment. Thyroxine is started as
HYPOTHYROIDISM IN THE OLDER CHILD
a once daily oral dose of 2–10 µg/kg. Higher doses are needed
Symptoms and signs of hypothyroidism are variable and often in young children; with age, the dose/kg reduces, such that the
subtle, so a high index of suspicion is needed. These may be total daily dose is not very different across different ages. Iron,
slow height gain, unexplained weight gain, decreased academic soya, and calcium can interfere with absorption of thyroxine,
performance, dullness, fatigue, lethargy and increased sleep, and should not be given within a few hours of medication.
cold intolerance, constipation, puffy pale face, dry skin and Doses are titrated on the basis of serum TSH (which takes
hair, irregular and/ or heavy periods, bradycardia, hoarse voice, 4–5 weeks to normalize) and T4. Thus, testing should be done
and thinning of sides of eyebrows. The most common causes after 6 weeks of a dose change, and every 3–6 months if no dose
are chronic lymphocytic thyroiditis and iodine deficiency; change is needed. Testing TSH too soon after a dose change
rarer causes include CH (diagnosed late), pituitary disorders, can be misleading. Growth and puberty should be monitored,
surgery, or radioiodine ablation. Children with Turner and should proceed normally if replacement is adequate. Once
syndrome, Down syndrome, and autoimmune disorders like growth is complete, a trial of stopping thyroxine can be offered:
type 1 diabetes mellitus or celiac disease, are more prone to thyroxine is stopped for 4–5 weeks and then TSH tested. If the
primary hypothyroidism, and should be screened periodically. TSH rises, thyroxine is reinstituted (monitored by T4 and TSH
Diagnosis is relatively straightforward: serum levels of every 6–12 months), and the family explained that replacement
T4 and TSH. Sampling should preferably be done in the would be needed lifelong.
Algorithm 1
Approach to thyroid function at birth
*Possibilities:
delayed maturation, thyroid hormone resistance, Down syndrome.
†Possibilities:
transient intrauterine exposure to drugs or maternal antibodies, iodine deficiency, pre- or postnatal exposure to iodides.
TSH, thyroid-stimulating hormone.
557
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Clinical Pearl Box 1: Thyroid function in hypothyroidism

• High TSH, low T4
• Thyroid stimulating hormone takes 4–6 weeks to change. {{ Primary hypothyroidism
Testing too soon after a dose change may be misleading.
• High TSH, high T4
{{ Primary hypothyroidism with poor compliance with treatment
Thyroid stimulating hormone levels of less than • Normal/borderline high/low TSH, low T4
10 mU/mL with normal T4 levels are considered compensated {{ Central (secondary/tertiary) hypothyroidism
or bio chemical hypothyroidism, and ordinarily may not
• Borderline TSH, normal T4
merit replacement with thyroxine. Obese children often have
{{ Biochemical hypothyroidism
mildly raised TSH, and should not be labeled hypothyroid
unless they are short (cf. midparental height) or growing TSH, thyroid stimulating hormone.
slowly. In most obese children, the cause is related to excess
calories in diet and inadequate exercise: such children tend
to be tall, which is not compatible with hypothyroidism. Box 2: Treatment of hyperthyroidism
However, replacement may be considered if symptoms are • Graves’ disease
significant or if growth velocity is subnormal. In a child with {{ Medical: neomercazole + b-blockers (i.e., delete rarely)
slow height gain, evaluation of growth hormone status should {{ Definitive treatment: lifelong thyroxine replacement needed
only be done after normalizing thyroid status. In this situation –– Radioiodine ablation: no anesthesia/scar. Not if nodular or
also, treatment of compensated hypothyroidism may be large goiter; ophthalmopathy
considered. –– Surgical: thyroidectomy—immediate relief, no worsening
of ophthalmopathy. But, risk of hypoparathyroidism/injury
Clinical Pearl to recurrent laryngeal nerve
• Thyroiditis
• All obese children are not hypothyroid. Start treatment if the {{ Symptomatic relief with b-blockers
TSH is >10, and/or the T4 is low, and the child is short for age
• Thyroid nodule
and midparental height, or growing slowly.
{{ Surgical excision
HYPERTHYROIDISM TSH and T4. Beta-blockers are needed for symptomatic relief.
Remissions can be seen in up to two-thirds of patients, but over
Hyperthyroidism is uncommon in children, and symptoms half of them later relapse. In those with allergy to antithyroid
and signs are even more variable and confusing, so a high drugs, or prolonged therapy (no remission, or relapse), ablation
index of suspicion is needed. These may be unexplained weight with RAI or surgery may be needed.
loss often in spite of increased appetite, decreased academic In general, RAI ablation is preferred as there is no
performance, irritability, palpitations, sweating, nervousness, risk of anesthesia or scarring. However, RAI ablation is
fatigue, poor sleep, and heat intolerance. Goiter is almost always contraindicated if the patient is pregnant, and does not work
present. Signs include nervousness, fine tremors, warm sweaty well if the gland is nodular or very large, when surgery is
palms, tachycardia, and exophthalmos. The most common needed. If ophthalmopathy is present, it may get aggravated,
causes are Graves’ disease (GD), initial stages of thyroiditis, so surgery is preferable. Thyroidectomy gives immediate relief,
or an autonomous thyroid nodule. Serum T4 and T3 are high, but common complications include transient or permanent
and TSH is suppressed; antibodies may be positive. Rarely, T3 hypoparathyroidism and injury to the recurrent laryngeal
may be raised with normal T4 (T3 toxicosis). A thyroid scan is nerve. Risks are lower in experienced hands, so it should be
useful to distinguish GD, which shows increased uptake, from done in centers with considerable experience.
thyroiditis, (put comma) which will show decreased, patchy
uptake, or from a nodule, which shows up as a discrete lesion.
THYROID NODULE
Clinical Pearl The biggest concern with a thyroid nodule is whether it is
malignant or benign. Thyroid cancer, uncommon in general, is
• Thyroid scan is useful in distinguishing the cause of hyper even rarer in children. Most nodules are picked up incidentally
thyroidism, and in guiding which treatment is appropriate. by family or physician, or on radiologic examination. A
history of previous thyroid disease or radiation to the head/
Treatment of GD can be with drugs, radioactive iodine neck region, or family history of thyroid disease is important.
(RAI) ablation, or surgery. Thyroiditis merely needs sympto A multinodular goiter is usually due to thyroiditis and/or
matic relief with b-blockers till hypothyroidism sets in. An iodine deficiency, and almost always benign. A single nodule
autonomous nodule needs surgical excision. or palpable lymph nodes are more worrying. During work-
Usually, GD is initially treated with antithyroid drugs, up, apart from TSH and T4, a careful ultrasound should look
558 usually neomercazole. Doses are titrated on the basis of serum at the size of the gland, the number, size, and appearance of
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Chapter 113: Approach to Thyroid Disorders in Children
nodules and cervical lymph nodes. A fine needle aspiration

cytology (FNAC) to look for malignancy should be done from ))
Treatment is with oral thyroxine, doses to be titrated with TSH
and if needed, T4 levels every 3–12 months
a nodule which is single, suspicious looking, or increasing in
size. If the cells are follicular, since adenoma and carcinoma ))
Compensated or biochemical hypothyroidism (TSH <10 mU/
mL, normal T4) may not need treatment, just follow-up
cannot be distinguished on FNAC, the entire nodule would
have to be surgically removed (lobectomy). If a papillary ))
Hyperthyroidism is characterized by suppressed TSH, and
raised triiodothyronine (T3) and T4 (rarely only T3). A thyroid
carcinoma is detected, or FNAC is suspicious for malignancy, a
scan helps decide treatment
total thyroidectomy should be done. If the TSH is suppressed, a
))
Treatment of Graves’ disease is with drugs, or radioactive
Tc-99m thyroid scan would be useful as a “hot” autonomously
iodine ablation, or surgery. Thyroiditis needs only symptomatic
functioning nodule is less likely to be malignant.
treatment
))
Malignancy should be ruled out in solitary thyroid nodules.
Key points
))
Screening for congenital hypothyroidism (CH) must be
offered to every single newborn, since it is the most common SUGGESTED READINGs
cause of preventable mental retardation
))
Screening for CH can be done in cord blood, or in a filter 1. American Academy of Pediatrics, Rose SR; Section on Endocrinology and
paper heel prick sample on day 3–5 of age Committee on Genetics, American Thyroid Association, Brown RS; Public Health
))
Primary thyroid stimulating hormone (TSH) method is most Committee, et al. Update of newborn screening and therapy for congenital
hypothyroidism. Pediatrics. 2006;117(6):2290-303.
widely used worldwide for screening
2. Manglik AK, Chatterjee N, Ghosh G. Umbilical cord blood TSH levels in term
))
High levels should be urgently confirmed, and replacement neonates: a screening tool for congenital hypothyroidism. Indian Pediatr.
started within 7–14 days of birth 2005;42(10):1029-32.
))
Initial treatment is with high doses of oral thyroxine 3. Marwaha RK, Tandon N, Karak AK, Gupta N, Verma K, Kochupillai N. Hashimoto’s
(10–15 µg/kg/day), titrated with serum thyroxine (T4) and TSH thyroiditis: countrywide screening of goitrous healthy young girls in postiodization
))
In older children, a high index of suspicion is needed. High phase in India. J Clin Endocrinol Metab. 2000;85(10):3798-802.
TSH and low T4 confirm hypothyroidism 5. Sanghvi U, Diwakar KK. Universal Newborn Screening for Congenital
Hypothyroidism. Indian Pediatr 2008; 45:331-332.
))
Children at risk of primary hypothyroidism should be screened
4. Virmani A. Neonatal Thyroid Screening, IAP Recommendations & Guidelines.
every 1–2 years
[online] Available from www.iapindia.org. [Accessed November, 2015].
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Chapter 114
Endocrine Hypertension in Children
Sudha R Chandrashekhar
INTRODUCTION Box 1: Endocrine causes of hypertension

Systemic hypertension is a leading cause of morbidity and • Hyperthyroidism • Apparent mineralocorticoid
mortality in adults and is an emerging public health concern. • Hyperparathyroidism excess
Hypertension in childhood and adolescence tracks into • Congenital adrenal • Dexamethasone suppressible
adulthood. The prevalence of hypertension increases with age hyperplasia hyperaldosteronism
from 15% in young adults to 60% in persons older than 65 years {{ 11β-hydroxylase defect • Liddle syndrome
of age. The reported prevalence of hypertension in children {{ 17α-hydroxylase defect • Gordon syndrome
is around 5% and hence, routine measurement of blood • Cushing syndrome • Mineralocorticoid receptor
pressure (BP) in children is recommended to pick up this • Pheochromocytoma mutation
silent killer disease. In infants and younger children, systemic • Neuroblastoma and other • Diabetic nephropathy
hypertension is almost always secondary to an underlying neural crest tumors
disease process and hence, careful and thorough evaluation is • Primary aldosteronism
essential. Endocrine hypertension in children is less common
than renovascular or cardiovascular causes.
Diagnosis of hypertension depends on accurate measure insulin and insulin receptors, endogenous ouabain and
ment of BP which is a difficult and time-consuming part of cardiotonic steroids, nitric oxide, etc. (Box 1).
clinical examination. Blood pressure is measured in a calm and
quite child, may be in parent’s lap, with a cuff size completely
CLINICAL APPROACH TO
encircling upper part of the arm and an inflatable bladder
covering two-thirds of upper arm length and encircling at ENDOCRINE HYPERTENSION
least three-fourths of the circumference. Although Doppler Primary hypertension in children and adolescents is incidentally
or oscillometric methods are useful, sphygmomanometry detected as they are silent and chronic. Secondary hypertension
happens to be the gold standard and the time of appearance that is sustained or is rising rapidly is always symptomatic and
of the first sound and complete disappearance of Korotkoff mode of presentation depends on age of the child.
sound is taken as systolic and diastolic BP, respectively. Mean Symptoms in infants could vary from irritability, poor
of at least three BP readings is taken as the representative feeding, lethargy, vomiting to convulsions, altered sensorium,
value. Interpretation of BP is dependent on age, gender, height, paresis/paralysis, or congestive cardiac failure. Older children
and population-specific reference standards. may complain of headache, behavioral changes, epistaxis,
Hypertension, defined as either systolic or diastolic BP dizziness, and visual disturbances. Intense headache,
more than 95th percentile of the reference standard, can be vomiting, ataxia, hyperthermia, altered consciousness, and
primary or essential where cause is not known or secondary to seizures suggest hypertensive encephalopathy and is a medical
cardiac, renal, or endocrine disturbances. emergency.
Multiple endocrine systems can lead to hypertension— To rule out cardiac causes, palpation of all peripheral
the renin-angiotensin-aldosterone system (RAAS), mineralo pulses, four limb BP measurements, and auscultation of
corticoid and mineralocorticoid receptors, catecholamine and abdominal bruit is essential. Renal cause of hypertension is
sympathetic nervous system, the kinin system, vasopressin, either renovascular or glomerular and hence, presence of
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Chapter 114: Endocrine Hypertension in Children
Table 1: Clinical clues to underlying cause

Endocrine hypertension Features Causes
Hyperthyroidism • Weight loss, goiter, tremors, excessive sweating • Increased sympathetic activity mediated
by high thyroid hormone levels
Hyperparathyroidism • Muscle weakness, seizures, failure to thrive, polyuria, fever • Hypercalcemia
Congenital adrenal hyperplasia • Hypokalemic metabolic alkalosis
11β-hydroxylase defect • In females—virilization, atypical genitalia • Excess androgens, low cortisol,
• In males—precocious puberty • Low aldosterone, high
• May present in metabolic crisis of salt waste, shock, deoxycorticosterone
hypoglycemia
17α-hydroxylase defect • In females—sexual infantilism • Low gonadal steroids,
• In males—undervirilization • High 17-deoxy-steroids
Cushing syndrome • Obesity, poor linear growth, striae, • Hypercortisolism with/without
• hyperglycemia, hypertrichosis, abdominal mass mineralocorticoid excess
Primary aldosteronism • Edema, muscle weakness, failure to thrive, polyuria, • Hyperaldosteronism
familial hypokalemic metabolic alkalosis
Dexamethasone suppressible • Autosomal dominant trait • 11β-hydroxylase gene, aldosterone
hyperaldosteronism synthase gene defect
Liddle syndrome • Autosomal dominant • Gain of function mutation in epithelial
• Low renin, low aldosterone sodium channel
Apparent mineralocorticoid • Low birth weight, failure to thrive, polyuria, nephrogenic • 11β-hydroxysteroid dehydrogenase type
excess diabetes insipidus, nephrocalcinosis, severe hypertension, 2 mutation
end-organ damage, renal failure
Mineralocorticoid receptor • Rare autosomal dominant • Mineralocorticoid receptor activating
activating mutation • Hypokalemic metabolic alkalosis mutation
• Low renin, low aldosterone
Pheochromocytoma • Features of catecholamine excess, tachycardia, flushing, • Increased adrenergic hormones
abdominal mass, excessive sweating, weight loss
Neuroblastoma and other • Similar to pheochromocytoma • Increased sympathetic activity mediated
neural crest tumors • Abdominal mass by adrenergic hormones
Diabetic nephropathy • Poorly controlled diabetes • Persistent hyperglycemia, glomerular
injury due to ultrafiltration
urinary symptoms like oliguria, dysuria, gross hematuria, In comparison to essential hypertension where the typical
anasarca, pallor, failure to thrive, rickets must be looked for. presentation is an adolescent, who is obese with positive family
Signs of systemic diseases like vasculitis syndrome, collagen history and has mildly elevated BP without signs and symptoms
vascular disorder, neurocutaneous syndrome should be of underlying disease, secondary hypertension is seen in
examined. younger children, with moderate-to-severe elevation of BP with
Features of stigmata of endocrine disturbances like symptoms and signs pertaining to organ system affection.
Cushing syndrome (centripetal fat distribution, pink striae, Transient hypertension is seen in children with acute
buffalo hump, etc.), hyperthyroidism (tachycardia, palpitation, illnesses like glomerulonephritis, rapid colloid infusion, drugs
flushes, loss of weight, etc.), pheochromocytoma (episodes of (catecholamines), and autonomic disturbances. Although
palpitation, sweating, flushes, etc.), palpable abdominal mass hypertension is transient, these children need to be monitored
(Wilms’ tumor, pheochromocytoma, adrenal tumor, etc.), and treated as other causes.
features of atypical genitalia [congenital adrenal hyperplasia
(CAH) 11β-hydroxylase and 17α-hydroxylase deficiency] are
INVESTIGATIVE APPROACH
clues to underlying diagnosis (Table 1).
High body mass index, presence of acanthosis nigricans, Investigations are guided by the underlying diagnosis
and normal stature suggest metabolic syndrome and the suspected and are not only for ascertaining the etiology but
hypertension is often essential or primary where a cause is not also to find out the degree of end organ damage.
known. A family history for hypertension, stroke, myocardial Initial test would include screening for renal and cardiac
infarction, and dyslipidemia needs to be elicited in the first- disorders. Thus, serum creatinine, blood urea nitrogen, serum
degree relatives. electrolytes, routine urine analysis, testing for presence of
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Algorithm 1
Approach to endocrine hypertension
BP, blood pressure; PAC, plasma aldosterone concentration; PRA, plasma renin activity; CAH, congenital adrenal hyperplasia.
hematuria, proteinuria, and calciuria would be required in 94%), plasma epinephrine/metane phrine (sensitivity 85%,
all cases. Renal sonography for sizes of the kidneys, collecting specificity 80%), urinary total metanephrine (sensitivity 76%,
system defects besides renal Doppler and renal scan should be specificity 94%), plasma-free metanephrine (sensitivity 99%,
done to rule out renal/renovascular cause of hypertension. specificity 92%) levels are useful in children suspected to have
Echocardiography to rule out coarctation of aorta and end- pheochromocytoma.
organ changes like hypertrophic cardiomyopathy, diastolic Urinary and plasma steroid profile in CAH, hyper
dysfunction, and carotid intimal thickness are advised. cortisolism; thyroid profile in suspected hyperthyroidism;
Hypokalemia with metabolic alkalosis is seen in primary or serum calcium, parathyroid hormone, and serum 25-hydroxy
secondary hyperaldosteronism. vitamin D levels in hypercalcemia; are some of the other tests
Plasma renin activity helps in differentiating the high renin which provide diagnostic clue.
(renal/renovascular hypertension) from low renin (hyper Radiographic imaging of the adrenals, 123I-metaiodobenzyl
aldosteronism, Gordon syndrome, hypercortisolism) or guanidine (MIBG) scan in suspected pheochromo cytoma,
normal renin (often seen in essential hypertension) forms of positron emission tomography radiotracers like fluorine-18
hypertension. L-3,4-dihydroxyphenylalanine (18F-DOPA), 18-fluoro-2-deoxy
Plasma aldosterone concentration (PAC) to plasma glucose (18F-FDG), etc. help localizing tumors as cause of
renin activity (PRA) ratio helps in differentiating primary hypertension.
hyperaldosteronism wherein the PAC/PRA ratio is greater Detailed ophthalmological evaluation for hypertensive
than 20 from secondary hyperaldosteronism (renovascular retinopathy and urine for microalbuminuria for hypertensive
disease, renin producing tumors, coarctation of aorta) where nephropathy should also be checked to rule out end-organ
it is less than 10. These ratios are very high in aldosterone effects.
producing adrenal adenoma. Both PAC and PRA are low in
hypercortisolism and thus the ratio is less than 10. Saline loading
TREATMENT
test, fludrocortisone suppression, or captopril challenge tests
are other confirmatory tests for primary hyperaldosteronism. Therapy is provided to children with persistent hypertension
Urinary vanillylmandelic acid (sensitivity 63%, specificity and the goal is to decrease BP to less than 95th percentile of the
562 94%), urinary catecholamine (sensitivity 73%, specificity target for age, gender, and height.
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Chapter 114: Endocrine Hypertension in Children
In mild cases as also in adolescents with primary

hypertension, this could be achieved by nonpharmacological Clinical Pearls
means like dietary modifications, weight reduction, regular • Hypertension in children is often due to an organic cause
exercise, and stress reduction. Sodium intake restricted to less • Measurement of blood pressure should always be done
than 1.2 g per day by avoiding added salt in the diet, pickles, annually in children as a screening parameter
baked, canned, and processed foods help decrease BP. Fruits • Blood pressure measurement should be done with appropriate
and nuts beneficial in lowering BP should be included in the cuff size and interpreted in relation to age gender and height
diet. Regular exercise schedule helps and outdoor activities • Both systolic and diastolic blood pressure should be recorded
like swimming, running, sports should be promoted. Weight
• Investigations depend on clinical clues to underlying etiology
reduction is an important therapeutic aspect of BP control in
• Therapy is tailored to the underlying pathophysiology.
obese children.
Children with persistent hypertension require long-term
therapy and the drug of choice depends on the underlying
pathophysiology. Key points
Angiotensin converting enzyme inhibitors are used in ))
Endocrine causes of hypertension are rare in children and are
high renin hypertension (renovascular, essential). Angiotensin often chronic, persistent, and symptomatic
receptor blockers (ARBs) like losartan are useful in high renin ))
Etiological investigations are based on clinical clues.
hypertension wherein they block angiotensin II receptors.
Aldosterone antagonist (spironolactone) or ARB (eplerenone)
is used in hyperaldosterone states. Adrenergic blockers Suggested readings
(labetalol, phenoxybenzamine, propranolol) are indicated in 1. Ali US. Systemic hypertension in children. In: Kumar K, Prabhu S, et al. (Eds). IAP
increased catecholamine states (pheochromocytoma, neural Textbook of Pediatric Cardiology, 1st edition. Jaypee Brothers Medical Publishers;
crest tumors). Diuretics are indicated in high volume output 2009. pp. 143-62.
states. 2. Bernstein D. Systemic hypertension. In: Behrman RE, Kliegman RM, Jenson HB
Calcium channel blockers are often used as first line (Eds). Nelson Textbook of Pediatrics, 17th edition. Elsevier Saunders; 2004. pp.
1592-8.
antihypertensives.
3. Carey RM. Overview of endocrine systems in primary hypertension. Endocrinol
In hypertensive crisis, gradual drop in BP over 24–48 hours Metab Clin North Am. 2011;40(2):265-77.
should be aimed with a drop of not more than 25% every 4. National High Blood Pressure Education Program Working Group on High Blood
hour as acute drop in BP leads to ischemic damage to brain, Pressure in Children and Adolescents. The fourth report on the diagnosis,
myocardium, retina, and kidneys. Controlled drop in BP is evaluation and treatment of high blood pressure in children and adolescents.
Pediatrics. 2004;114 (2 Suppl):555-76.
best achieved with nitroprusside infusion drip. Sublingual
5. Sahay M, Sahay R. Low renin hypertension. IJEM. 2012;16(5):733-9.
nifedipine can be used where facilities for infusion or
6. Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ. Overweight, ethnicity
monitoring for cyanide toxicity are not available. Labetalol and and the prevalence of hypertension in school aged children. Pediatrics.
nicardipine infusions can also be used. 2004;113(3):475-82.
563
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Chapter 115
Approach to Oligoarthritis
Vijay Viswanathan
Introduction SOME COMMON SCENARIOS OF

Arthritis in childhood is not that uncommon as it may sound. ACUTE ARTHRITIS
Depending on the number of joints involved, it could either be
oligoarticular (≤4 joints) or polyarticular (≥5 joints). Formerly Scenario 1: Reactive/Postinfectious Arthritis
known as pauciarticular, the oligoarticular variant can be a Many viral illnesses may be followed by onset of inflammation
single joint (monoarthritis) or more than a single but less than at the joints after an incubation period. Most of them are self-
4 joints. It could be acute or chronic. A detailed history with limiting and do not leave any long-term deformities. A few
regards to the onset, pattern of involvement, presentation, and specific types of the same with some salient features are shown
duration of arthritis help differentiate between the various in box 2.
possible diagnoses. This, coupled with a meticulous clinical
examination and supported by relevant investigations, help
in nailing the diagnosis. In this chapter a clinical approach to
decipher oligoarticular presentation in a child is discussed. Box 2: Specific causes of postinfectious/reactive arthritis
Postinfectious/viral Reactive (Reiter syndrome)
Definition • Immediately/weeks to arthritis
months • Arthritis, conjunctivitis, and
Acute monoarthritis: it is inflammation of one joint only,
• Pauci/polyarticular urethritis
characterized by pain, swelling, redness, and/or restriction of
• Lower limb joints knees/ • Time to evolve 2–4 weeks
movement with duration of less than 3 weeks.
ankles • Lower limb joints knees/ankles
Chronic monoarthritis: arthritis in the single joint lasting for at
least 6 weeks is said to be chronic (Box 1). • Flu virus, parvovirus B19, C • Occasionally dactylitis
• Coxsackie, chikungunya, • Shigella, Salmonella, Yersinia,
arbovirus, HIV, hepatitis A, Campylobacter, Chlamydia, and
Mycoplasma
Box 1: Causes of monoarthritis in children and HBsAg
• HLA B27
Acute Chronic Poststreptococcal RA
Transient synovitis of hip
• Septic arthritis • Juvenile arthritis (systemic • Short incubation period
onset, oligoarticular, and the • Up to 8 years
• Reactive • Large and small joints
enthesitis-related arthritis • Differentiate from septic
• Hemarthrosis subcategories • Additive involvement arthritis
• Traumatic joint effusion/ (nonfleeting)
• Chronic hemarthrosis • Nonweight bearing,
mechanical causes • Poor response to NSAIDs leukocytosis, ESR, and CRP
• Malignancies/bone tumors
• Bone tumors and acute • Echocardiography/penicillin • Always aspirate when in doubt
leukemia • Infections such as prophylaxis
tuberculosis
• Juvenile arthritis (systemic HIV, human immunodeficiency virus; HbsAG, hepatitis B surface
onset or enthesitis)/collagen • Miscellaneous disorders, antigen; NSAIDs, nonsteroidal anti-inflammatory drugs; ESR, erythrocyte
vascular disease e.g., sarcoidosis, pigmented sedimentation rate; CRP, C-reactive protein; HLA, human leukocyte antigen;
villonodular synovitis RA, reactive arthritis.
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Chapter 115: Approach to Oligoarthritis
It is an apophysitis of the immature skeleton subjected to too

Clinical Pearls much physical strain causing pull on the tibial tubercle that sits
• Most cases of postinfectious/reactive arthritis (RA) are self- adjacent to a growth plate. Slipped upper femoral epiphyses
limiting occurring in adolescent/preadolescent boys can present with
• Anti-inflammatory agents/intra-articular steroids form the hip pain/knee pain (due to radiation from hip). Perthes disease
main line of therapy or avascular necrosis of head of femur is classically seen in
• Poststreptococcal RA necessitates a two dimensional echo toddlers and early childhood. It affects boys more than girls,
cardiography and occasionally penicillin prophylaxis and presents as a painful limp. In addition, children who have
• Transient synovitis can recur in 4–17% (first 6 months); excess ligament laxity (hypermobile) do complain aches and
differentiation from infection is mandatory. pains and also benign joint effusions.
A detailed history and clinical examination reveal that
the problem is mechanical and there is no/mild arthritis on
Scenario 2: Septic Arthritis examination.
Septic arthritis in infancy and childhood is a true clinical CHRONIC OLIGOARTICULAR PRESENTATION
emergency. Delay in the diagnosis and treatment of septic
arthritis can result in disastrous complications including
History
complete destruction of the articular cartilage and epiphysis,
loss of the growth plate, and joint dislocation. Inquire about systemic symptoms such as fever, weight loss,
and night sweats.
Clinical Pearls Detailed history of morning stiffness, night pains, and
restriction of activities are important. History of a recent sore
• Fever, malaise, along with erythema, local warmth, and throat, gastroenteritis, red and painful eyes, and chronic skin
significant pain. disease such as psoriasis or significant trauma should be asked
• Pain on passive motion (many times position of pseudoparalysis) for. A past history of tuberculosis (TB) or contact with an open
highly suggestive of septic arthritis case of TB is important in India, where monoarticular disease
• Joint aspiration is a must in all doubtful scenarios (occasionally in a child is often considered to be TB unless proved otherwise.
fluid may be sterile) It is also important to check for the history of recent travel to
• Imaging is not the primary means of diagnosing septic arthritis an area endemic for Lyme disease, brucellosis, or a history of
• Ensure complete therapy for 4–6 weeks. tick bite.
Examination
Scenario 3: Malignancies Detailed general, systemic, and local examination as
Hematological malignancies (leukemia and lymphoma) as previously outlined above including skin examination,
well as localized osseous, malignancy (osteosarcoma/ Ewing’s formal ophthalmology evaluation by slit lamp for uveitis, and
sarcoma) can present with musculoskeletal complaints. musculoskeletal examination are a must in all children who
Symptoms of arthritis, sometimes with a migratory pattern can present with a single swollen joint.
precede hematological feature of malignancy by months.
Chronic Oligoarticular
Clinical Pearls Juvenile Idiopathic Arthritis
• Sick child with nocturnal pains (bone pains) Oligoarticular juvenile idiopathic arthritis (JIA) can present
• Periarticular pain with less than 4 joints (oligo persistent) or can involve more
• Pallor than 4 joints after 6 months (oligo extended).
• Lymphadenopathy
Clinical Pearls
• Organomegaly
• High lymphocytes, elevated erythrocyte sedimentation rate • Systemically well
with low platelets • Present with a painless limp with swollen joint
• Whenever in doubt, order a marrow prior to starting steroids. • Blood tests are usually normal with magnetic resonance
imaging revealing effusion and synovitis
• Antinuclear antibody positivity associated with uveitis
Scenario 4: Mechanical Causes
• Intra-articular steroids form first line therapy
Acute pain and limitation of movement may be due to
• Good prognosis except in extended oligovariant
mechanical causes such as Osgood-Schlatter syndrome
• Rule out mimics like tuberculosis, pigmented villonodular
(osteochondritis), which is a painful condition caused by
synovitis and associated collagen disorder.
irritation and sometimes fragmentation at the tibial tuberosity.
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APPROACH TO ACUTE Algorithm 1

ONSET OLIGOARTICULAR ARTHRITIS Algorithmic approach to acute arthritis
The following approach may assist in finding out the etiology

behind the articular involvement. These are generalized
guidelines and there may be the odd exception to the rule,
however this could serve as a starting approach.
History
• Number of joints
{{ Monoarthritis—reactive, septic/osteomyelitis, malig-
nancies, trauma/mechanical, and other collagen dis-

eases
{{ More than one joint-reactive, leukemia, sickle cell
disease, systemic (metastatic) infections, e.g., infective

endocarditis and meningococcemia
• Nature of onset
{{ Acute/in minutes to hours—reactive, septic arthritis,
trauma, and coagulopathy/sickle cell disease

{{ Hours to days—reactive, systemic infections, hemar
throsis, and leukemia

• Diurnal variation *Appearance, constitutional.
{{ Morning stiffness/pain—inflammatory arthritis
HSP, Henoch- Schönlein purpura; IE, infective endocarditis; JIA, juvenile
idiopathic arthritis; SLE, systemic lupus erythematosus; JDM, juvenile dermato
{{ Nocturnal pains—malignancies and mechanical myositis.
(growing pains)
• Trauma—important only when considering coagulo-
pathies
• Pattern of involvement • Pattern of pain
{{ Pain throughout range of movement—septic arthritis
{{ Migratory—acute rheumatic fever and leukemia
{{ Additive or simultaneous—reactive/poststreptococcal and reactive arthritis

{{ Pain experienced as the joint is gently forced (i.e.,
reactive arthritis (PSRA), collagen vascular disease,
systemic infections, and evolving JIA. stressed) towards its limitation of range—synovitis
• Associated features (Transient synovitis, evolving JIA)
{{ Pain not present throughout the entire range of
{{ Fever—infection. Inflammation [other collagen dis
orders, e.g., systemic lupus erythematosus (SLE)], motion—mechanical and tendinitis.

malignancy, systemic disease and infective endo- • Skin—petechiae, purpura, Gottron’s papules (JDM), rashes
carditis/meningococcemia (e.g., Butterfly rash in SLE < vasculitis rashes, etc.).
{{ Bleeding tendency/fly—hemophilias
{{ Septic focus—septic arthritis and osteomyelitis Laboratory Investigations

{{ Systemic features—systemic-onset JIA, SLE, juvenile (As Guided by History and Examination)
dermatomyositis (JDM), reactive, and infection • Complete blood count, erythrocyte sedimentation rate,
{{ Eye—conjunctivitis—reactive (Reiters syndrome)
C-reactive protein, viral titers, and blood culture
{{ Uveitis—evolving JIA
• Antistreptolysin O titer
{{ Episcleritis/scleritis—collagen vascular disease, e.g.,
• Throat swab
vasculitis.
• Coagulation studies
• Tuberculin test
Physical Examination • Joint aspiration (always whenever in doubt to rule out
• Appearance septic arthritis specially hip joint)
{{ Sick—malignancy, infection, and systemic disease • Imaging:
{{ Well—reactive arthritis and mechanical {{ X-rays—trauma and malignancy
• Gait/posture: Antalgic/pain on passive motion/pseudo- {{ Bone scan—infections
paralysis—septic arthritis {{ Magnetic resonance imaging—synovitis, tumors, and
• Nature of joint swelling infections

{{ Articular—septic arthritis (erythematous and warm {{ Two dimensional echocardiography—PSRA and
joint), acute rheumatic fever, and other arthritis Kawasaki disease
{{ Periarticular/focal tenderness—leukemia and osteo {{ Antinuclear antibody (suspected juvenile oligo
566 myelitis arthritis), HLA B27 (suspected enthesitis).
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Chapter 115: Approach to Oligoarthritis
Key points
SUGGESTED READINGS
1. Cabral DA, Tucker LB. Malignancies in children who initially present with
))
More than one joint involvement almost always rules out an rheumatic complaints. J Pediatr. 1999;134:53-7.
infective arthritis (more likely to be reactive) 2. Cassidy JT, Petty RE. Textbook of pediatric rheumatology. 4th ed. Philadelphia: WB
))
Morning stiffness suggests inflammatory etiology, while Saunders; 2001. pp. 726-79.
3. Kocher MS, Zurakowski D, Kasser JR. Differentiating between septic arthritis and
nocturnal limb pains are always suggestive of a malignancy transient synovitis of the hip in children: an evidence based clinical prediction
))
Always aspirate a joint when in doubt algorithm. J Bone Joint Surg Am. 1999;811662-70.
))
Recognizing patterns through a good history, clinical 4. Prabhu AS, Balan S. Approach to a child with monoarthritis. Indian J Pediatr.
2010;77(9):997-1004.
examination, and less reliance on costly investigations is
5. Roberton DM, South MJ. Arthritis and connective tissue disorders. In: Roberton
paramount. DM, Robinson MJ. editors. Practical Pediatrics. 5th ed. London: Churchill
Livingstone; 1994. p. 457.
567
ch-115.indd 567 11/21/2016 2:52:29 PM

Chapter 116
Approach to Polyarthritis
Rashna D Hazarika
INTRODUCTION Etiology
Joint diseases in children are not so uncommon and can The etiology of polyarthritis is varied and outlined in table 1.
range from infections to injuries to hematological conditions
like hemophilia, leukemia, and to the more serious forms of
arthritis of varying etiology and prognosis. It often becomes
IMPORTANT POINTS IN HISTORY
a cause of concern for parents and caretakers especially if the Looking at the diverse etiologies of polyarthritis, it may seem
etiology is of a chronic nature. An approach to polyarthritis in difficult to know where to start looking for a diagnostic label.
children has been discussed in this chapter. However, attention to a number of important clinical clues
Arthritis is inflammation of the joints and can be a single or both in the history and examination can help to narrow down
a multiple joint involvement. Usually, single joint involvement, the possibilities. We look at each of these issues in detail.
like septic arthritis, prompts the parents to seek urgent medical
care. Similarly, patients with polyarthritis require detailed Age
evaluation and investigation as the causes are varied and
some, like leukemia and lupus, have serious consequences Juvenile idiopathic arthritis (JIA), juvenile psoriatic arthritis,
if not treated at the appropriate time. The other important Kawasaki disease (KD), and septic arthritis are most frequent
aspect of approaching a child with polyarthritis is “pattern in early childhood (1–4 years of age). Polyarticular JIA,
recognition”. Polyarticular joint disease has multifactorial Juvenile dermatomyositis, Henoch–Schönlein purpura, and
etiology. It may present as an acute self-limiting viral illnesses Polyarteritis nodosa have their peak frequencies by mid-
or it can be the beginning of a chronic sinister disease. The childhood (7–11 years). Juvenile ankylosing spondylitis (JAS)
underlying etiological process can be anything from infectious and systemic lupus erythematosus (SLE) show a marked
or postinfectious, rheumatological, or a manifestation of increase in late childhood. Rheumatoid factor positive arthritis
systemic diseases. It may take days or sometimes weeks for mimicking adult rheumatoid arthritis usually occurs after the
the disease to evolve and thus make it difficult to make a age of 10 years. Diseases like gout, calcium pyrophosphate
diagnosis at the time of presentation. Some viral infections deposition disease, polymyalgia rheumatica, and primary
like parvovirus causes a transient self-limited polyarthritis osteoarthritis almost never occur in childhood.
whereas organisms like Chlamydia, Gonococci, Salmonella,
and Shigella cause a postinfectious reactive (sterile) arthritis. Sex
Arthritis lasting for more than 6 weeks rules out an infective Polyarticular JIA and SLE have a predilection for girls whereas
etiology. With these issues in mind, this article will try to give JAS and KD for boys. However, many of these diseases can
an algorithmic approach to polyarthritis (Algorithm 1).
occur in both the sexes and one should keep an open mind
when evaluating a patient with polyarthritis.
Some Definitions
• Polyarthritis: involvement of more than one joint is known
Onset and Duration
as polyarthritis Usually, septic arthritis, trauma, and coagulopathies present
• Acute polyarthritis: joint involvement of less than 6 weeks within hours. Viral arthritis, acute rheumatic fever, vasculitides,
• Chronic polyarthritis: joint involvement for more than leukemia, reactive arthritis, and beginning of JIA can evolve over
6 weeks. days to weeks. Polyarticular JIA, tubercular arthritis, sarcoidosis,
ch-116.indd 568 11/21/2016 2:54:12 PM

Chapter 116: Approach to Polyarthritis
Algorithm 1
Algorithmic approach to polyarthritis
KD, Kawasaki disease; ARF, acute rheumatic fever; JIA, juvenile idiopathic arthritis; SLE, systemic lupus erythematosus; IBD, inflammatory bowel disease; JDMS,
juvenile dermatomyositis; SOJIA, systemic onset juvenile idiopathic arthritis; JAS, juvenile ankylosing spondylitis; PSRA, poststreptococcal reactive arthritis; TM,
temporomandibular; IP, interphalangeal.
Table 1: Etiology of polyarthritis and fungal arthritis go through an indolent process and present
Viral Parvovirus B 19, mumps, rubella, varicella, in weeks to months. However, many of these conditions may
hepatitis B, coxsackie virus, cytomegalovirus, be in the evolution phase in the initial weeks and it may not be
EBV, HIV, enteroviruses, and adenoviruses appropriate to give a diagnostic label at this stage.
Bacterial Neisseria meningitidis, gonococci, bacterial
endocarditis, staphylococci, streptococci, and
Pattern
Haemophilus Usually, in inflammatory arthritis, there will be complaints
Other infectious Mycobacteria, fungal infections, leptospirosis of early morning stiffness, stiffness after a period of activity
agents (gelling).
Reactive arthritis Chlamydia, Yersinia, Mycoplasma,
Campylobacter, Salmonella, Shigella, Past History
tuberculosis (Poncet’s arthritis), HIV History of recent diarrhea, acute conjunctivitis, urethritis, and
Rheumatological Juvenile idiopathic arthritis, systemic lupus fever with or without rash may give a clue to reactive arthritis.
erythematosus, juvenile dermatomyositis, A past history of heel pain, back pain, or transient redness of
Behcet’s disease eyes can indicate the beginning of JAS. Past history of repeated
Vasculitides Kawasaki disease, Henoch–Schönlein purpura, swelling in the same joint after a trivial trauma may indicate a
Polyarteritis nodosa previously undiagnosed bleeding disorder.
Spondyloar Juvenile ankylosing spondylitis, psoriatic
thropathy arthritis, enteropathic arthritis Family History
Miscellaneous Drug reactions, leukemia, sickle cell crisis, Diseases such as JIA, inflammatory bowel disease (IBD), and
neuroblastoma, metabolic conditions psoriasis may have a familial predilection.
(Fabry’s, Gaucher’s), mechanical problems
(Ehlers Danlos syndrome and benign joint
hypermobility syndrome), skeletal dysplasias,
Examination
inflammatory bowel disease The examination of the affected joints as well as picking up the
EBV, Epstein-Barr virus; HIV, human immunodeficiency virus. extra-articular manifestations form an important step toward 569
ch-116.indd 569 11/21/2016 2:54:12 PM

arriving at a diagnosis. A systemic approach in examination Extra-articular Manifestations

has to focus on identifying the following.
Diseases like SLE, IBD, malignancies, and systemic onset JIA
Articular Involvement have dominant extra-articular manifestations (Table 2).
Synovium, synovial fluid, articular cartilage, intra-articular Table 2: Extra-articular features in a patient with polyarthritis
ligaments, joint capsule, and juxta-articular bone form
a part of the articular structures. Presence of pain, joint Site Manifestations Diseases
line tenderness and limitation of both active and passive Eye • Nonpurulent • KD
movements, instability, locking of the joint, crepitus, and joint conjunctivitis • JIA
deformity signify articular involvement. In addition, swelling • Anterior uveitis • Psoriasis
may be there due to synovial thickening, joint effusion, or joint • Posterior uveitis
enlargement. In nonarticular involvement, findings are away Mouth • Fissures in lips, • KD
from the joint and pain may occur only on active movement. strawberry tongue • SLE, Behcet’s disease
• Oral ulcers • JDMS
Inflammatory Versus Noninflammatory • Red gums at tooth line
Head and • Alopecia/hair loss • SLE
Signs of local inflammation are erythema, tenderness, and
neck • Malar rash • SLE
redness of the joint. Systemic inflammatory signs include
• Heliotrope rash • JDMS
fever, weight loss, and fatigue. An effusion and pain at the end
• Psoriasis • Psoriatic arthritis
of range of movement indicates active arthritis.
Hands • Raynaud’s • SLE, JDMS,
phenomenon scleroderma
Pattern of Joint Involvement
• Nail pitting, • Psoriasis
Important clues to the diagnosis can be picked up if one tries onycholysis • Connective tissue
to identify some of the patterns known with specific diseases • Nail fold infarct disease
such as: • Periungual • KD
• Evolution of the joint pain: desquamation • PAN
{{ Migratory joint involvement is seen in acute rheumatic • Digital infarct • JDMS
fever as well as gonococcal arthritis. In acute rheumatic • Gottron’s papules • JDMS
fever, the joint can swell up in hours whereas in • Subcutaneous
gonococcal arthritis this happens over days calcinosis
{{ Additive joint involvement where new joints are Trunk and • Erythema marginatum • ARF
involved when the previously affected ones are still arms • Subcutaneous nodules • ARF, RF+ve JIA
painful occur in poststreptococcal reactive arthritis, • Urticaria • CTD
SLE, JIA, and psoriasis
{{ Intermittent arthritis where the symptoms can appear Muscles • Wasted muscles • JIA
and disappear is typical of reactive arthritis • Tender muscles, • JDMS
• Topography: involvement of the axial or peripheral skeleton proximal muscles
is an important clue to diagnosis. Axial skeleton includes weakness
the spine, sacroiliac joints, sternoclavicular joints, and the Hemato • Lymphadenopathy • TB, SLE, malignancy,
manubriosternal joints. Juvenile ankylosing spondylitis has logical • Petechiae KD
involvement of the sacroiliac and the lower spine. Others, • Pallor • Malignancy, SLE
like JIA and SLE, have peripheral skeletal involvement • Malignancy, SLE,
though rarely they can have a combined involvement SOJIA
• Symmetry: usually symmetrical joint involvement is seen
Gastro • Dysphagia • JDMS, sclerodema
in JIA and SLE and asymmetric joint involvement is seen in
intestinal • Abdominal pain • SLE, PAN
reactive arthritis
• Specific joint involvement: some diseases involve • Diarrhea • IBD, reactive arthritis
specific joints like dactylitis and distal interphalangeal • Malabsorption • Scleroderma
joint involvement indicates psoriatic arthritis. Similarly, • Hepatic involvement • SLE
temporomandibular joint involvement indicates JIA. Most • Organomegaly • SLE, malignancy
reactive arthritis would have a lower limb joint involvement Respiratory • Upper airway • Wegener’s
• Presence of joint deformity: joint deformity usually follows symptoms granulomatosis
long standing undiagnosed or untreated arthritis and is • Pleuritis, pleural • SLE, SOJIA
usually seen with JIA or hemophilia. Arthritis associated effusion
with SLE and IBD are usually nondeforming.
Continued
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Chapter 116: Approach to Polyarthritis
Continued Laboratory tests

Site Manifestations Diseases More than 95% of the cases of polyarthritis can be diagnosed
Cardiovas • Pericarditis • SLE, SOJIA, ARF based on a good history and examination. However, specific
cular • Myocarditis • ARF, SOJIA, tests like cell count and morphology can give clues to a
• Valvular disease polymyositis malignant process like leukemia, thrombocytopenia in
• ARF, SLE, JAS, SLE, thrombocytosis in KD, raised acute phase reactants,
hypermobility like ESR and CRP, indicate an active inflammatory process,
Genitouri • Urethritis • Reactive arthritis,
antineutrophil antibodies in SLE, rheumatoid factor
nary Reiter’s syndrome positivity in polyarticular JIA, human leukocyte antigen B
• Genital ulcers
• Behcet’s syndrome
27 in JAS and Antineutrophil cytoplasmic antibody for
• Proteinuria
systemic vasculitides. Other investigations, like ASO and
• Renal failure, • SLE, amylodosis,
NSAIDS echocardiography, are useful in acute rheumatic fever and
hematuria
synovial fluid analysis to differentiate between an infective
• SLE, NSAIDS,
amyloidosis, and an inflammatory process.
systemic vasculitides
Central • Chorea • ARF, SLE Treatment
nervous • Convulsions, coma, • SLE Treatment of polyarthritis depends on the specific diagnosis.
system psychosis, headache • PAN Pending the diagnosis, one must focus on providing
• Neuropathies symptomatic relief by using nonsteroidal anti-inflammatory
KD, Kawasaki disease; TB, tuberculosis; ARF, acute rheumatic fever; JIA, Juvenile agents, rest to the affected part as well as physiotherapy
idiopathic arthritis; SLE, systemic lupus erythematosus; IBD, inflammatory if possible. A brief outline of the management is shown
bowel disease; JDMS, juvenile dermatomyositis; SOJIA, systemic onset JIA; JAS, in table 3. However, many diseases may require extensive
juvenile ankylosing spondylosis; PAN, polyarteritis nodosa; CTD,Connective
tissue disease; NSAIDS, nonsteroidal anti-inflammatory drugs. and long-term management for achieving remission and
prevention of morbidity.
Pattern Recognition Prognosis

A good history and clinical examination can help the astute Prognosis depends on the diagnostic label, time to diagnosis,
and observant clinician recognize some typical patterns of presence of complications, and how aggressive the
joint disease. Some examples are: management has been. For example, reactive arthritis would
• Polyarthritis in a young girl may suggest SLE or poly have an excellent prognosis with supportive management,
articular JIA intravenous immunoglobulin in Kawasaki disease would
• Scattered small distal interphalangeal joint involvement lead to a possible cure and prevention of complications if
indicates psoriatic arthritis treated at the appropriate time. Early diagnosis and aggressive
• Hip and lower back involvement may point toward JAS management of arthritis prevent joint damage and other
• Inflammatory tarsal and enthesopathy may be a complications. Acute rheumatic fever responds well to
distinguishing feature between JAS and JIA in the absence treatment and initiation of penicillin prophylaxis prevents
of axial disease. future recurrences and the development of rheumatic
An algorithmic approach to polyarthritis is shown in valvular damage. Steroids in lupus is life saving and drugs like
algorithm 1. mycophenolate mofetil are offering good outcome in renal
Table 3: Outline of treatment of polyarthritis

Etiology Specific treatment Supportive treatment
Viral arthritis NSAIDS Self-limiting illness—counseling and reassurance
Bacterial arthritis Specific antibiotics. NSAIDS/steroids if needed Long-term penicillin prophylaxis for patients with rheumatic
fever
Reactive arthritis NSAIDS Specific treatment for bacterial etiology if any such as
gonococcal infection
Rheumatological arthritis NSAIDS/steroids depending on specific etiology Physiotherapy, counseling, and occupational therapy
Systemic vasculitides Intravenous immunoglobulin for Kawasaki Appropriate and prompt treatment in Kawasaki disease
disease, NSAIDS or steroids in Henoch– with intravenous immunoglobulin prevents long-term
Schönlein purpura and other vasculitides cardiac morbidity and steroids in lupus may be life saving
NSAIDS, nonsteroidal anti-inflammatory drugs. 571
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lupus. However, the main factor influencing the prognosis is

how early one has been able to identify the possible etiology of ))
Though polyarthritis can occur in both the sexes, it is
polyarthritis and initiate the treatment. important to remember that juvenile idiopathic arthritis and
systemic lupus erythematosus are more common in girls
whereas juvenile ankylosing spondylitis and Kawasaki disease
Clinical Pearls are more common in boys
• Pattern recognition helps to arrive at a diagnostic label ))
Inflammatory arthritis is characterized by early morning
stiffness
• Extra-articular manifestations form an important clue to
diagnosis ))
Prominent extra-articular manifestations must be looked for
and aid in arriving at a diagnosis
• Early morning stiffness characteristic of inflammatory arthritis
))
Diagnosis is mostly clinical. Tests help to rule out a malignancy
• Diagnosis mostly clinical. Laboratory tests only helps to rule
or idiopathic thrombocytopenic purpura
out sinister conditions such as leukemia, and also useful for
follow-up. ))
Treatment depends on the etiology, number of joint involved,
and other associated manifestations.
Suggested readings
Key points
1. Hull RG. Management guidelines for arthritis in children. Rheumatology.
))
Polyarthritis has multifactorial etiology 2001;40:1308.
))
Pattern recognition is very important 2. Khubchnadani RP, D’Souza S. Initial evaluation of a child with arthritis—an
algorithmic approach. Indian J Pediatr. 2002;69(10):875-80.
))
Rheumatoid factor positive arthritis mimicking adult onset
3. Singh S, Mehra S. Appriach to polyarthritis. Indian J Pediatr. 2010;77:1005-10.
rheumatoid arthritis usually occurs after 10 years of age
4. Sawhney S, Dass R. editors. Approach to Arthritis in Childhood. 2009.
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Chapter 117
Fever with Arthritis:
An Algorithmic Approach
Sathish Kumar
INTRODUCTION important step is to determine whether or not there is

associated fever (Algorithm 1). For practical purposes, this
Musculoskeletal and joint diseases appear to have increased initial screening should lead to the following four possible
in the last decade. Confusion over terminology and a lack of groups of diagnoses:
awareness of these conditions have probably contributed 1. Single joint involvement with associated fever
to their under recognition. In pediatric practice, physicians 2. Single joint involvement without fever
are often faced with a child presenting with musculoskeletal 3. Multiple joint involvement with associated fever
complaints. The differential diagnosis of fever with arthritis is 4. Multiple joint involvement without fever.
broad and includes a variety of causes. This chapter, is focused
on algorithmic approach to a child who presents with fever and
arthritis. ALGORITHMIC APPROACH TO
All joint pains are not arthritis. Arthritis is defined as MONOARTHRITIS (SINGLE JOINT)
a swollen joint or a joint having at least two of the following
conditions: tenderness, limited range of motion, pain on A carefully conducted history taking and physical examination
movement, or warmth overlying the joint. are the initial and most important steps in narrowing the
The first step in initial screening is to establish whether differential diagnosis and guiding the diagnostic evaluation
a single joint or multiple joints are involved. The second (Algorithm 2).
Algorithm 1
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Algorithm 2 Physical Examination

Approach to fever with monoarhritis The presence of fever should alert the clinician to the potential
for more severe conditions requiring urgent treatment (e.g.,
septic arthritis). On general examination, clues to underlying
diagnosis include rash (psoriasis, viral exanthems), iritis (IBD
or enthesitis-related arthritis), and hepatosplenomegaly/
lymphadenopathy suggestive of malignancy.
The focused examination of the affected joint should
include inspection of the skin for warmth, redness, swelling,
and soft tissue involvement, using the contralateral side for
comparison. Palpation of the surrounding bone is important
because the presence of pinpoint bony tenderness is suggestive
of fracture, osteomyelitis, or malignancy. An exquisite pain
in the joint on range of motion or a joint that is severely
restricted in its range of motion suggests an etiology other than
inflammatory arthritis (e.g., septic joint).
The differential diagnosis of monoarthritis includes
entities in the broad categories of infection, postinfection,
inflammation, and malignancy and trauma related to a
systemic illness (Box 1).
Preliminary investigations that are to be considered for the
evaluation of monoarthritis are presented in box 2. Laboratory
investigations of acute or chronic monoarthritis are performed
to confirm the clinician’s impression regarding the suspected
diagnosis or to exclude conditions.
Laboratory Investigations
WBC, white blood cell; JIA, juvenile idiopathic arthritis; SLE, systemic lupus Complete blood count (CBC) and differential white blood cell
erythematosus; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein;
count, inflammatory markers, and liver and renal functions
RF, rheumatoid factor; ANA, antinuclear antibody.
should be considered in any child with monoarthritis.
If the presentation is acute (<72 hours), a joint aspiration
must be performed if the clinician is concerned about a septic
History Taking joint, with the fluid sent for blood cell count, Gram stain, and
Important aspects to be considered in the history taking are as culture. In addition, culture of the throat, blood, stool, and/or
follows: urine should be considered to identify a potential organism
• Characteristics of the pain and/or stiffness (site, number in the case of reactive arthritis. An acute presentation is also
of joints, severity, frequency, duration, pattern, and observed with hematologic and malignant diseases (e.g.,
association of warmth or discoloration). Morning stiffness hemophilia and leukemia), highlighting the importance of
is a characteristic feature of inflammatory arthritis. Night CBC and coagulation studies. Antistreptolysin O (ASO) and
pain should alert the clinician to a malignancy or an
osteoid osteoma Box 1: Differential diagnosis of monoarthritis
• Review of systems focused on the presence of fever or other
constitutional symptoms (e.g., weight loss, anorexia, night Infection-related Malignancy
sweats, or nocturnal pain) • Septic arthritis • Leukemia
• Precipitating factors: traumas, infections (streptococcal, • Osteomyelitis • Neuroblastoma
enteric), travel to Lyme disease or tuberculosis (TB) • Transient synovitis Inflammation
endemic areas or other risk factors for TB (exposure to a • Reactive arthritis • Juvenile idiopathic arthritis
person with TB; close contact with a person with a positive • Lyme disease • Inflammatory bowel disease
TB skin test result) • Tuberculosis • Familial Mediterranean fever
• Presence of extra-articular features (diarrhea, urethral Trauma Hemarthrosis
discharge, ocular symptoms, and rash) • Fracture: accidental and • Hemophilia
• Personal or family history of a bleeding diathesis or human nonaccidental • Pigmented villonodular
leukocyte antigen (HLA) B27-associated diseases like • internal derangement: synovitis
inflammatory bowel disease (IBD), acute anterior uveitis, ligament rupture • Synovial hemangioma
psoriasis, ankylosing spondylitis. • Foreign body: synovitis
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Chapter 117: Fever with Arthritis: An Algorithmic Approach
Box 2: Preliminary investigations to be considered for the

and examination of the synovial fluid, and cell count. In the
evaluation of monoarthritis absence of Gram stain or culture, a cell count of 40,000/mm3 is
regarded as evidence of bacterial infection.
Basic screening Further investigations
• Complete blood count • Cultures of throat, blood, joint Osteomyelitis: with reactive arthritis or sympathetic arthritis,
and differential white fluid, stool, and/or urine this is arthritis with effusion in a nearby joint as a reaction to
blood cell count • Partial thromboplastin time osteomyelitis. A technetium or gallium joint bone scan often
• Erythrocyte • Antinuclear antibody titer reveals an osteomyelitis in the adjacent bone.
sedimentation rate • Serologic testing for Lyme disease Presence of foreign body in the joint: a thorn, shard of glass, or
• C-reactive protein • Antistreptolysin O titer other foreign body may cause a secondary infection or sterile
• Renal function and liver • Urinalysis synovitis. Computerized tomographic scan is superior to a
enzyme • Tuberculin skin test radiograph in demonstrating a nonopaque foreign body.
• Serum lactate • Further imaging (ultrasonography,
dehydrogenase magnetic resonance imaging) Traumatic arthritis: traumatic serosanguineous effusion can
• Radiographs • Bone marrow aspiration
cause fever secondary to blood within the joint. There is almost
always a history of trauma. Aspiration usually reveals sterile
• Slit lamp examination of the eyes
surgery will reveal the nature of this condition. In addition,
clotting abnormalities must be ruled out.
antideoxyribonuclease B (anti-DNaseB) titers are useful to
identify a recent streptococcal infection. Rheumatic diseases: oligoarticular onset of juvenile idiopathic
In chronic monoarthritis, Lyme serology (when history is arthritis may present with single joint disease. Usually, one of
suggestive of an exposure) and antinuclear antibody (ANA) the large joints is affected, and the patient is either afebrile or has
and rheumatoid factor (RF) titers should be considered. a low grade fever. Very rarely, children with systemic onset JIA
Human leukocyte antigen B27 testing is most relevant in may also present initially with monoarticular disease, usually
chronic arthritis when the child is suspected of having a specific in the knee or hip. In that case, look for other manifestations
category of juvenile idiopathic arthritis (JIA) (enthesitis-related of the disease such as rheumatoid rash, hepatosplenomegaly,
arthritis), which is generally seen in boys older than 8 years lymphadenopathy, pericarditis and, in rare instances, iritis. A
and often associated with enthesitis, lumbosacral back pain, diagnosis of JIA is made based on history taking and physical
and a family history of HLA-B27-associated diseases (e.g., IBD, examination and after exclusion of other causes.
ankylosing spondylitis). It is unusual for children with systemic lupus erythematosus
The presence of ANA or RF is neither necessary nor to present with single joint involvement. Occasionally,
sufficient to make a diagnosis of JIA. Antinuclear antibody rheumatic fever, Kawasaki disease, juvenile dermatomyositis,
should not be used as a screening test for rheumatic illness in a and certain viral infections may begin with arthritis affecting
primary care setting, because it may be positive in up to 5–10% one joint.
of healthy children. Postinfectious reactive arthritis: this includes postviral or
Antinuclear antibody is used as a diagnostic test for postbacterial diseases such as post-streptococcal reactive
children with probable systemic lupus erythematosus arthritis and post-salmonella, Shigella, and Yersinia reactive
or mixed connective tissue disease and other overlap- arthritis. These postviral or postbacterial conditions have a
like illnesses. In the context of JIA, a positive ANA titer is benign, self-limited course that may require symptomatic and
associated with a significantly increased risk of developing supportive therapy.
chronic anterior uveitis.
Rheumatoid factor has been associated with aging Toxic synovitis: if the hip joint is affected, toxic synovitis must
(>60 years), infections (bacterial endocarditis, hepatitis B be taken into account. It is also called transient synovitis and,
or C, parasitic disease, viral infection), pulmonary disease occurs in children aged 8 ± 10. Most of the patients are boys,
(sarcoidosis, interstitial pulmonary fibrosis), malignancy, and and there is often a history of respiratory infection. Within a
primary biliary cirrhosis and thus is not a specific test for the few weeks, a limp and pain referred to the knee develop along
diagnosis of rheumatic disease. with a low grade fever. The erythrocyte sedimentation rate
Only 5–10% of patients with JIA have a positive RF, may be mildly elevated. The disease usually subsides after 1 ±
highlighting the lack of sensitivity for the diagnosis of JIA. 2 weeks and does not commonly recur. However, Legg-Calve-
A joint aspiration must be performed when a septic Perthes disease is occasionally a sequelae.
joint (bacterial) is suspected but is also recommended for Hemoglobinopathy: in a child, sickle cell anemia must be
the diagnosis of TB arthritis. The presence of hemarthrosis ruled out by hemoglobin electrophoresis. In the very young
suggests coagulation disorder, trauma, or rare causes, child, it causes a dactylitis that may mimic true arthritis;
including synovial hemangioma or pigmented villonodular in older children it causes microinfarcts that give rise to
synovitis. The more common and/or serious causes of periostitis and periarthritis which are responsible for the pain
monoarthritis are addressed here. crises in this disease.
Septic arthritis: this condition classically presents with a Malignancies: leukemia is the most common malignancy
severely painful, swollen, warm, and red joint in a febrile in childhood. However, it rarely presents with single joint
child. The join must be aspirated for Gram stain, cultures involvement. Tumors, such as synovial cell sarcoma or
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bone tumors like osteosarcoma and Ewing’s sarcoma, can infection as indicated, ASO and anti-DNAase B titers, cardiac
rarely present as single joint involvement with fever. In any evaluation (electrocardiography and echocardiography),
malignancy, bone pain is usually prominent, and other features, chest radiography, ANA titer, other autoantibodies (anti-Ro,
such as weight loss and fatigue, are commonly present.
Table 1: Review of systems in the differential diagnosis of
ALGORITHMIC APPROACH TO polyarthritis
POLYARTHRITIS (MULTIPLE JOINTS) System Review of system or Diagnosis
involved physical finding
Differential diagnosis of polyarthritis essentially includes
infectious, inflammatory, and malignant causes (Box 3). Ophthalmo- Uveitis JIA
The review of systems and physical examination logic Conjunctival injection KD
(Algorithm 3) is critical to establishing a diagnosis because without exudate
Dermatologic Malar rash, alopecia SLE
Heliotrope rash, Gottron JDM
Box 3: Differential diagnosis of polyarthritis
papules
Infection-related Malignancy Polymorphous rash, perianal KD
• Neisseria gonorrhea infection • Leukemia desquamation, edema, and
• Viral infections (e.g., parvovirus B19, • Neuroblastoma erythema of hands
rubella virus/vaccine) Mechanical Evanescent salmon-colored SOJIA
• Infective endocarditis rash
• Hypermobility
• Acute rheumatic fever Palpable purpura HSP, SLE
• Skeletal dysplasia
• Post-streptococcal reactive arthritis Nail pitting or onycholysis JIA (psoriatic)
Other systemic illness
• Reactive arthritis Oral ulcers SLE
• Immunodeficiency-
Inflammatory associated arthritis Cardio New heart murmur ARF, IE
• Juvenile idiopathic arthritis vascular Pericarditis SOJIA, SLE, ARF
• Serum sickness
• Systemic lupus erythematosus Raynaud phenomenon SLE, MCTD,
• Juvenile dermatomyositis scleroderma
• Systemic vasculitides (Henoch- Respiratory Pleuritis SOJIA, SLE
Schonlein purpura, Kawasaki disease) tract Acute or chronic sinusitis, GPA
• Hereditary autoinflammatory pulmonary nodules, or
syndromes hemorrhage
• Sarcoidosis Interstitial lung disease SLE or scleroderma
• IBD-related arthritis Gastro Weight loss or poor growth IBD, malignancy,
intestinal/ SLE
Algorithm 3 genitourinary Diarrhea/hematochezia, IBD, HSP
tract colicky abdominal pain
Approach to fever with polyarthritis
History of gastroenteritis Reactive arthritis
History of urethritis or Reactive arthritis,
cervicitis gonococcal arthritis
Neurologic Seizures, psychosis, mood SLE
disorder, decline in school
performance
Stroke SLE, vasculitis
Proximal muscle weakness JDM, MCTD
JIA, Juvenile idiopathic arthritis; KD, Kawasaki disease; SLE, systemic lupus
erythematosus; JDM, juvenile dermatomyositis; SOJIA, Systemic onset Juvenile
idiopathic arthritis; HSP, Henoch–Schonlein purpura; ARF,acute rheumatic
fever; IE, Infective endocarditis; MCTD, mixed connective tissue disease; GPA,
granulomatosis with polyangiitis; IBD, Inflammatory bowel disease.
there are clues in the characteristics of the arthritis, fever, rash,

and other system involvements that often provide the correct
diagnosis (Table 1).
When polyarthritis is the presenting complaint, in addition
to the investigations outlined in box 2, additional investiga
tions may include serum C3 and C4 complement levels,
576 ESR, erythrocyte sedimentation rate; RF, rheumatoid factor; ANA, antinuclear
serum levels of quantitative immunoglobulins, urinalysis,
antibody. serologic testing for viral pathogens, swabs for gonococcal
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Chapter 117: Fever with Arthritis: An Algorithmic Approach
anti-La, anti-Smith, anti-ribonucleoprotein, anti-Scl 70), and

stiffness, systemic symptoms (fever, rash, weight loss, fatigue),
antineutrophil cytoplasmic antibody.
history of past medical illnesses, travel or positive family history
(arthritis, bleeding disorders, sickle cell anemia, inflammatory
Conclusion bowel disease, psoriasis)
Differential diagnosis for monoarthritis and polyarthritis ))
The important aspects of physical examination include
is broad. An organized approach within the framework assessing the joints (swelling, erythema, warmth, tenderness,
presented, including carefully attending to clues in the history deformity, range of motion), adjacent structures (bones,
tendons, muscles, skin), and gait and leg length discrepancy
taking and physical examination allows for correct diagnosis
in most cases. Laboratory evaluation is performed to support ))
The extent of investigations is determined from the infor
the clinician’s impression. Serious and/or potentially life- mation gained through the history and physical examination
threatening infections, malignant or orthopedic causes need to ))
Basic screening laboratory tests and radiographs of the
be identified, and the patient is referred for surgical or medical affected site should be obtained. Additional investigations
management. can be performed to arrive at a clinical diagnosis
))
Fever, redness, moderate-to-severe pain, pinpoint pain
Clinical Pearls or tenderness, and weight loss are clues to more serious
causes of limb pain that require additional investigations and
• Presence of antinuclear antibody or rheumatoid factor is
referrals to specialists (rheumatologists, orthopedic surgeons,
neither necessary nor sufficient to make a diagnosis of juvenile
neurologists, hematologist/oncologists).
idiopathic arthritis
• Antinuclear antibody should not be used as a screening test
for rheumatic illness in a primary care setting, because it may
be positive in 5–10% of healthy children
Suggested readings
• High antistreptolysin O titer with arthralgia does not warrant
Penicillin prophylaxis. 1. Abbassian A. The limping child: a clinical approach to diagnosis. Br J Hosp Med
(Lond). 2007;68(5):246-50.
2. Berard R. Approach to the child with joint inflammation. Pediatr Clin North Am.
2012;59(2):245-62.
Key points 3. Gedalia A. Joint pain in children: an algorithmic approach. Isr Med Assoc J.
2002;4(10):837-42.
))
A detailed history and physical examination are critical in 4. Leung AK, Lemay JF. The limping child. J Pediatr Health Care. 2004;18(5):
the initial assessment, with attention paid to the nature of 219‑23.
the pain, presence of limp, weight-bearing status, morning 5. Tse SM, Laxer RM. Approach to acute limb pain in childhood. Pediatr Rev.
2006;27(5):170-9.
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Chapter 118
Childhood Vasculitis
Indira Banerjee, Rakesh Mondal
INTRODUCTION CLASSIFICATION
Vasculitis is characterized by inflammation of blood vessel International Consensus Conference in Vienna (June 2005)
walls with resultant tissue ischemia and necrosis. The first case under the Pediatric Rheumatology European Society resulted
was described by Adolf Kussmaul and Rudolf Maier more than in a new proposal for childhood vasculitis classification
150 years ago, when they described a patient with what is today summarized in box 1. These were validated and given the final
known as polyarteritis nodosa (PAN). Since then, many more in form at the 2008 Ankara Consensus Conference with support
these categories have been described. Most pediatric vasculitis from the European League Against Rheumatism (EULAR) and
disorders need individual specific classification criterias for
their identification. Box 1: Classification of childhood vasculitis
• Predominantly large vessel vasculitis:
EPIDEMIOLOGY {{ Takayasu’s arteritis
Estimated overall annual incidence of new cases of pediatric • Predominantly medium-sized vessel vasculitis:
{{ Childhood PAN
vasculitis is 53.3 per 100,000 children under 17 years of age.
{{ Cutaneous polyarteritis
The two most common vasculitides were Henoch-Schönlein
{{ Kawasaki disease
purpura (HSP) and Kawasaki disease, with estimated annual
incidences of 20.4 and 5.5 per 100,000 in children less than • Predominantly medium-sized vessel vasculitis:
{{ Granulomatous:
17 years of age, respectively. Reported geographical variations
–– Granulomatous polyangiitis (previous nomenclature
in vasculitis may reflect an environmental influence, like
Wegner’s granulomatosis)
infections, drugs, allergy, vaccination, and desensitization
–– Churg-Strauss syndrome (eosinophilic polyangiitis)
procedures. {{ Nongranulomatous
–– Microscopic polyangiitis
PATHOGENESIS –– Henoch-Schönlein purpura (immunoglobulin A vasculitis)
–– Isolated cutaneous leukocytoclastic vasculitis
The exact pathogenesis of pediatric vasculitis is not known.
–– Hypocomplementemic urticarial vasculitis
The proposed mechanisms are vascular injury caused by
• Other vasculitides:
inflammation of vascular wall (vasculitis). The triggers for {{ Behçet’s syndrome
injury are genetic, environmental, infective, and immune {{ Vasculitis secondary to infection (including hepatitis
factors. B-associated PAN), malignancies and drugs (including hyper
Irrespective of the initial insult, inflicted injury to the sensitivity vasculitis)
vessel wall resulted in healing of vascular wall by fibrosis. It {{ Vasculitis associated with connective tissue diseases
causes narrowing of vascular lumen and ischemic injury to {{ Isolated vasculitis of the central nervous system
target organ. Abnormal healing of the vascular wall leads to {{ Cogan’s syndrome
aneurysm formation with disorganized blood flow which {{ Unclassified
can lead to ischemic target organ damage with or without

PAN, polyarteritis nodosa.
thrombus formation (Fig. 1).
ch-118.indd 578 11/21/2016 2:58:15 PM

Chapter 118: Childhood Vasculitis
Fig. 1: Schematic diagram showing vascular injury causing different changes including aneurysm formation
the Pediatric Rheumatology International Trials Organization. Suspect Childhood Vasculitis

There has been trend for use of vasculitic disorders names that
Common symptoms suggestive of childhood vasculitis include:
reflect increased pathophysiologic understanding of these
• Appearance: miserable look, more in pain or irritable, and
conditions. Revision in the commonly used terms has been
no toxic look
proposed by the 2012 International Chapel Hill Consensus
• Systemic features: fever, weight loss, fatigue, and arthralgias
Conference (CHCC) on nomenclature of vasculitides. Among
• Skin manifestation: range from palpable purpura to
the notable changes suggested by the 2012 CHCC were use
urticaria, livedo reticularis, nodules, and ulcers, even
of the term eosinophilic granulomatosis with polyangiitis
gangrenes
(EGPA), in place of Churg-Strauss syndrome, and adoption
• Hypertension
of the term antineutrophil cytoplasmic antibody (ANCA)
Organ specific involvement: this depends on the size of
associated vasculitis for the three disorders likely microscopic
the vessel involved, degree of collateral circulation, and the
polyangiitis, granulomatosis with polyangiitis (Wegener’s),
organ involved:
and EGPA.
{{ Nephrology: hematuria and proteinuria
{{ Joints: arthritis and joint effusions
Algorithmic Approach {{ Muscles: myalgia and myositis
{{ Serous cavities: serositis

to Childhood Vasculitis
{{ Cardiac: hypertension, myocarditis, and cardiomyopathy
Diagnosis and treatment of childhood vasculitis is explained in {{ Pulmonary: infiltrates, infract and or hemorrhage
detail below (Algorithm 1). {{ Neurologic: mono- or polyneuritis.
579
ch-118.indd 579 11/21/2016 2:58:15 PM

Algorithm 1
Approach to childhood vasculitis
Table 1: Clinical findings according to vessel involvement

Clinical Pearl
Large vessel Medium vessel Small vessel
• Severe constitutional symptoms, skin rash, and hypertension • Limb claudica- • Cutaneous • Purpura
are important clues for suspicion of vasculitides in children. tion nodules • Vesiculobullous
• Asymmetric • Ulcers nodules
blood pressure • Livedo reticularis • Urticaria
Support from Common Laboratory Findings
• Absent pulses • Digital gangrene • Glomerulonephritis
• Raised inflammatory markers such as raised erythrocyte • Bruits • Mononeuritis • Alveolar hemorrhage
sedimentation rates, C-reactive protein, polymorpho • Aortic dilation multiplex • Cutaneous granu-
neuclear leukocytosis, thrombocytosis, etc.
• Microaneurysms lomas
• Presence of hematuria, red blood cell cast, azotemia, etc.
• Splinter hemor-
rhages
Clinical Pearl
• Uveitis/Episcleritis/
• Raised inflammatory parameters, e.g., raised C-reactive Scleritis
protein, erythrocyte sedimentation rate, polymorphoneuclear
leukocytosis, and thrombocytosis adds as diagnostic clues.
Predominantly Large Vessel Vasculitis
Categorize the Involved Vessel Type Takayasu disease
Typical clinical findings according to vessel involvement are Angiographic abnormalities [conventional, computed tomo
580 given in table 1.5 graphy (CT), and magnetic resonance imaging] of the aorta or
ch-118.indd 580 11/21/2016 2:58:16 PM

its main branches (mandatory criterion), plus at least one of • Naso-sinus inflammation
the following four features: • Subglottic, tracheal, or endobronchial stenosis
• Decreased peripheral artery pulse(s) and/or claudication • Abnormal chest X-ray or CT and
of extremities • Proteinase 3 ANCA or cytoplasmic ANCA staining.
• Bruits over aorta and/or its major branches Churg-Strauss syndrome
• Hypertension (related to childhood normative data) The proposed classification criteria for presence of Churg-
• Blood pressure difference >10 mmHg Strauss syndrome is any four or more of the six criteria:
• Asthma
Predominantly Medium-sized Vessel Vasculitis • Eosinophilia >10%
• Neuropathy: mono- or polyneuropathy
Kawasaki disease
• Pulmonary infiltrates, non-fixed
Fever for 5 days or longer and least four of the following five • Paranasal sinus abnormality
signs: • Extravascular eosinophils.
• Nonpurulent conjunctivitis
• Rash (polymorphous erythematous) Nongranulomatous type
• Hyperemic lips and/or mucous membranes Henoch-Schönlein purpura
• Changes to the extremities (peripheral edema, peripheral Purpura with lower limb predominance and the presence of at
erythema, and periungual desquamation) least one of the following four features:
• Cervical adenopathy (usually unilateral) • Arthralgia or arthritis
Complication: coronary artery aneurysm • Diffuse abdominal pain
• Any biopsy showing predominant immunoglobulin A
Childhood polyarteritis nodosa
deposition
Histological evidence of necrotizing vasculitis in medium or • Renal involvement (any proteinuria and/or hematuria).
small-sized arteries or angiographic abnormalities (aneurysm Complication: Mainly HSP nephritis.
or occlusion) as a mandatory criterion, plus two of the following Microscopic polyangiitis
seven: Microscopic polyangiitis (MPA) is characterized by necrotizing
• Muscle tenderness or myalgia vasculitis with few or no immune deposits affecting small
• Skin involvement (livedo reticularis, tender subcutaneous vessels.
nodules, and other vasculitic lesions) Clinical features of MPA include disease involving
• Systemic hypertension the kidneys, lungs, joints, skin, gastrointestinal tract, and
• Mononeuropathy or polyneuropathy peripheral nerves. The cardinal features of MPA include
• Abnormal urine analysis and/or impaired renal function glomerulonephritis, pulmonary hemorrhage, fever, and
• Testicular pain or tenderness mono neuritis multiplex. Necrotizing glomerulonephritis is
• Signs or symptoms suggesting vasculitis of any other major very common. Pulmonary capillaritis often occurs, but no
organ system (gastrointestinal, cardiac, pulmonary, or granulomatous lesions of the respiratory tract is seen.
central nervous system)
Cutaneous polyarteritis nodosa Rule Out Mimickers
Cutaneous PAN is limited to skin with possible manifestations Mimickers for vasculitis include following:
in the musculoskeletal system. It is characterized by the: • Infections such as pneumococcal, mycobacterial, rickettsial
• Presence of painful subcutaneous nodules • Connective tissue disorders
• Nonpurpuric lesions with or without livedo reticularis • Bacterial endocarditis
• With no systemic involvement (except for myalgia, • Atrial myxoma
arthralgia, and nonerosive arthritis). • Vasoconstrictive drugs such as ergot
• Malignancy such as lymphomas
Predominantly Small Vessel Vasculitis • Disorders associated with antiphospholipid antibody
Granulomatous type syndrome.
Granulomatous polyangiitis
In January 2011, the Board of Directors of the American
Confirm the Diagnosis
College of Rheumatology, the American Society of Nephrology, The clinical diagnosis is confirmed by some specific tests in
and the EULAR recommended that the name Wegener’s association with supportive indicators and specific pattern of
granulomatosis be changed to granulomatosis with polyangiitis clinical involvement such as:
(Wegener’s), abbreviated as GPA. • Tissue biopsy (PAN)
The proposed classification criteria for GPA were that three • X-rays of the sinuses and chest
of the following six criteria should be presented: • Angiographic studies of the vessels (PAN, Takayasu
• Abnormal urinalysis arteritis)
• Granulomatous inflammation on biopsy • Nerve conduction studies 581
ch-118.indd 581 11/21/2016 2:58:16 PM

• Assessment of autoantibodies such as antinuclear antibody (n = 1544). HSP (56.9%) and Kawasaki disease (24%) were
(ANA), ANCA. major groups. The study revealed that primary vasculitides
• ANA would be positive in lupus associated vasculitis were diagnosed in 135 patients (male:female ratio was 1.9:1
• Cytoplasmic ANCA (c-ANCA) in Wegener’s granulomatosis and the mean age of onset was 5.5 years). Among the 38 cases
• Perinuclear ANCA in microscopic polyangiitis of Kawasaki disease, 20 had coronary artery involvement,
• Rheumatoid factor positivity is seen in hepatitis B 5 had persistent aneurysms, 29 received IVIG, non required
associated cryoglobulinemia. angioplasty. Other vasculitides included PAN (n = 4),
Wegener’s granulomatosis (n = 2), and Takayasu disease
Therapeutic Measures (n = 1). Secondary vasculitis accounted for 23 cases.
Supportive care along with definite treatment:
• Antipyretics and analgesics CONCLUSION
• Immunosuppressive: steroids, immunoglobulins, and
Pediatric vasculitis is a challenging disease for diagnosis as
others as indicated as per standard guidelines and stage of
well as treatment. It should be considered whenever there is
involvement
unexplained multisystem disease with evidence of vascular
• Surgery: repair of coronary aneurysm, amputation of
involvement. Fever, extreme irritability, hypertension,
gangrenous parts in selective cases.
hematuria, and skin lesions are some of the important clues
Medical for diagnosis. Other organs, such as the eye, peripheral
nervous system and the kidneys, must be examined to pick up
• Anti-inflammatory and analgesics: naproxen, sulfasalazine asymptomatic involvement. Prompt and aggressive treatment
• Steroids: reduce pain and inflammation of severe joint can prevent complications and decrease the morbidity and
disease, skin lesions, eye disease, and central nervous mortality in pediatric populations.
system. Routine follow-up is needed to detect features of
steroid toxicity
• Other immune suppressants: methotrexate (main stay Key points
of disease-modifying antirheumatic drug in the
treatment of juvenile idiopathic arthritis), azathioprine, Common childhood vasculitis
cyclophosphamides ))
Henoch-Schönlein purpura (HSP) is the most common
• Biologics: vasculitis in children
{{ Monoclonal tumor necrosis factor-α antibody ))
The main clinical features of HSP include purpura, arthritis,
(Infliximab: a chimeric monoclonal antibody) abdominal pain, gastrointestinal bleeding, and nephritis.
{{ Adalimumab (A humanized monoclonal antibody) Palpable purpura is the presenting sign in 100% of the patients
{{ Anakinra (anti-interleukin (IL)-1) ))
Glucocorticoids can lessen tissue edema, arthritis, and
{{ Toclizumab (humanized monoclonal antibody, abdominal pain. It decreases the rate of intussusception.
targeting both membrane bound and soluble IL-6 However, glucocorticoid therapy does not prevent recurrence
receptors) of abdominal symptoms, skin involvement, or renal disease
{{ Abatacept: (fusion protein that blocks the CD80 or and does not shorten the duration or lessen the likelihood
CD86 interaction with CD28 with inhibition of T cell) of relapse. Glucocorticoids combined with a cytotoxic agent
{{ Rituximab (chimeric monoclonal antibody against
might be beneficial in patients with active glomerulonephritis
CD20, targeting B cells) and progressive renal insufficiency
• Other: aspirin, clopidogrel and intravenous immuno ))
Nonpurulent conjunctivitis and hyperemic lips and/or
globulin (IVIG) (Kawasaki disease). mucous membranes with antibiotic-unresponsive fever for
more than 5 days—suspect Kawasaki disease
Surgical ))
Coronary artery lesions are responsible for most of the
disease-related morbidity and mortality in Kawasaki disease.
• Amputation of nonsalvageable gangrenous part
Aneurysms appear 1–4 weeks after the onset of fever and
• Repair of aneurysm. develop in 15–25% of untreated children
))
Standard treatment of Kawasaki disease in the acute phase
Indian Scenario is with intravenous gamma globulin (2 g/kg single dose in a
10–12 h infusion) and aspirin (50–80 mg/kg daily divided into
Large studies with uniform comprehensive data are not
four doses)
available from Asia. Indian data that included adult population
is not a true representation of pediatric vasculitides from all
))
Polyarteritis nodosa (PAN) is characterized by necrotizing
inflammatory changes in medium and/or small-sized arteries
over the country.
A pediatric study was done from Eastern India over a
))
Unlike clinical diagnosis of HSP and Kawasaki disease,
diagnosis of PAN needs histologic evidence of necrotizing
period of 7 years (2004 to 2010), on prospectively followed
vasculitis in medium or small-sized arteries or angiographic
up children (under 12 years) with vasculitis from a tertiary
abnormalities (aneurysm or occlusion) as a mandatory
care hospital from Kolkata. The study revealed 10.2% children
582 criterion. So, difficult to diagnose in resource poor country
(n = 158) had vasculitis among all rheumatological cases
ch-118.indd 582 11/21/2016 2:58:16 PM

))
The mainstay of therapy for PAN includes steroids and various
Suggested readings
immunosuppressive medications, depending on disease 1. Bosch X, Guilabert A, Font J. Antineutrophil cytoplasmic antibodies. Lancet.
severity 2006;368:404-18.
))
Cutaneous PAN is usually limited to skin with possible 2. Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR. Incidence of
manifestations in the musculoskeletal system Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children
))
ANCA-associated vasculitis (AAV) includes microscopic of different ethnic origins. Lancet. 2002;360:1197-202.
polyangiitis, granulomatosis with polyangiitis (Wegener’s), 3. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 Revised
and eosinophilic granulomatosis with polyangiitis International Chapel Hill Consensus Conference Nomenclature of Vasculitides.
Arthritis Rheum. 2013;65:1-11.
))
Two types of ANCA have been identified in patients with
4. Joshi VR, Mittal G. Vasculitis—Indian perspective. JAPI. 2006;54:12-4.
vasculitis 5. Kelley’s TB of Rheumatology, 8th edition. WB Saunders & Co. 2008.
1. ANCA directed against the neutrophil serine protease 6. Khasnis A, Langford CA. Update on vasculitis. J Allergy Clin Immunol.
proteinase 3 (PR3), which cause a cytoplasmic immuno 2009;123:1226-36.
fluorescence pattern (cytoplasmic ANCA) on ethanol fixed 7. Kussmaul A, Maier R. Ueber eine bisher nicht beschriebene eigenthumliche
neutrophils and Arterienerkrankung (Periarteritis nodosa). Deutsches Arch F Klin Med.1865;
2. ANCA directed against the neutrophil enzyme myelo 66:484-518.
peroxidase (MPO), which result in a perinuclear immuno 8. Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of therapy and a
fluorescence pattern (perinuclear ANCA) guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis
Rheum. 2007;56:1000-9.
))
Granulomatous polyangiitis is primarily associated with PR3-
9. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/
ANCA, while microscopic polyangiitis is primarily associated PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa,
with MPO-ANCA childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008.
))
Takayasu arteritis is a disease that affects the aorta, its main Part II: Final classification criteria. Ann Rheum Dis. 2010;69:798-806.
branches, and the pulmonary arteries in which granulomatous 10. Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, et al. EULAR/PRES
vasculitis results in stenosis, occlusion, or aneurysms of endorsed consensus criteria for the classification of childhood vasculitides. Ann
affected vessels Rheum Dis. 2006;65:936-41.
))
Takayasu arteritis can present as pulseless disease, asymmetric 11. Peru H, Soylemezoglu O, Bakkaloglu SA, Elmas S, Bozkaya D, Elmaci AM, et al.
hypertension with encephalopathy Henoch-Schonlein purpura in childhood: clinical analysis of 254 cases over a
3-year period. Clin Rheumatol. 2008;27:1087-92.
))
Asthma, atopy, and eosinophilia with vasculitis syndrome—
12. Sarkar S, Mondal R, Nandi M, Ghosh A. Trends of childhood vasculitides in
suspect Churg-Strauss syndrome
eastern India. Indian Pediatr. 2011;48:814.
))
Recurrent apthous oral ulcer with painful genital ulcers with 13. Saulsbury FT. Henoch-Schonlein purpura in children. Report of 100 patients and
ocular features—suspect Bechet’s syndrome review of the literature. Medicine (Baltimore). 1999;78:395-409.
))
Infection induced vasculitis is a common mimicker of 14. Tse SM, Silverman ED, McCrindle BW, Yeung RS. Early treatment with intravenous
vasculitis for pediatric population. immunoglobulin in patients with Kawasaki disease. J Pediatr. 2002;140:450-5.
583
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CHAPTER 119
Kawasaki Disease
Anju Gupta
INTRODUCTION PATHOGENESIS
Kawasaki disease (KD) is an acute systemic medium vessel Kawasaki disease is characterized by intensive T cell
vasculitis with strong predilection to childhood. Since its stimulation with activation of inflammatory cytokines and
first description in early 1960s by Dr Tomisaku Kawasaki, leukocyte recruitment. Activation of T cell may be responsible
this disease continues to remain enigmatic. What makes this for Bacillus Calmette–Guerin (BCG) site activation seen
disease so are factors like our inability to identify an etiologic so frequently in this disease. This leads to upregulation of
agent, absence of a specific diagnostic test in acute phase, proteolytic activity causing elastin degradation and vessel
and our inability to predict cardiac complications. Moreover, wall damage, which is responsible for characteristic coronary
clinical features often appear transiently and the examining lesions seen in this disease.
physician may not be able to see all the characteristic clinical
features at a time. Now, this disease has been described
CLINICAL FEATURES
worldwide with a distinct predilection for Japanese descent.
Characteristic clinical features of KD include fever, poly
morphous exanthem, bilateral conjunctival congestion,
EPIDEMIOLOGY
changes in extremities, changes in lips and oral cavity, and
Japan has a maximum incidence of KD with rates of cervical adenopathy. Fever is typically high grade (>39°C)
240/100,000 children less than 5 years. Korea and Taiwan have with an abrupt onset and responds transiently to antipyretics.
reported the next high incidences. Whereas, the incidence in Usually, fever persists for more than 5 days (median 11 days)
the United States (20 per 100,000 children of less than 5 years) and can persist for more than 3 weeks, if not treated. There
is static over the years, Japan has been reporting increasing is usually a diffuse erythematous maculopapular rash which
incidence rates over the years. A distinct seasonal predilection usually appears within first 5 days of illness. Conjunctivitis is
is seen in extratropical Northern hemisphere with maximum typically bilateral, nonexudative, and spares limbus (Fig. 1).
cases seen in January to March with a nadir from August to Changes in extremities include diffuse nonpitting edema on
October. However, a similar seasonal predilection is not the dorsum of hands and feet and characteristic periungual
consistently described in tropics. desquamation starting in late second or third week of illness
(Figs 2 and 3). Perianal desquamation is also characteristic
and usually precedes periungual desquamation (Fig. 4).
ETIOLOGY
Changes in lips and oral cavity include strawberry tongue
Etiology of KD remains elusive and likely involves an (Fig. 5) and cracking of lips. Cervical adenopathy is usually
environmental agent in presence of certain genetic factors. A single, unilateral, and nontender and involves anterior
ubiquitous environmental agent has been implicated because cervical chain.
of distinct seasonality, occurrence of epidemics, occurrence Besides these clinical features described in American
of rash-like in toxin mediated diseases, and efficacy of Heart Association criteria (Box 1), lots of other clinical
intravenous immunoglobulins (IVIg). Genetic factors also have features may be present and may help or confuse treating
been implicated because of strong racial predilection seen in physician further. Irritability is usually extreme in infants to
Japanese descent. the extent that clinician may think of pyogenic meningitis.
CHAPTER 119: Kawasaki Disease
Fig. 1: Nonexudative conjunctivitis sparing limbus Fig. 4: Perianal desquamation
Fig. 2: Periungual desquamation in upper limb Fig. 5: Strawberry tongue
Box 1: Diagnostic criteria for Kawasaki disease

Fever (>39°C) for at least 5 days plus at least four of the following
five diagnostic features
• Polymorphous exanthem
• Bilateral bulbar conjunctival injection without exudate
• Changes in lips and oral cavity: erythema, fissured cracked lips,
strawberry tongue, or diffuse injection of oral and pharyngeal
mucosae
• Cervical lymphadenopathy (>1.5 cm diameter), usually unilateral
• Changes in extremities:
{{ Acute: erythema of palms and soles, edema of hands and feet
{{ Subacute: periungual peeling of fingers and toes (in the
second and third week) plus exclusion of other diseases with
similar clinical features
Fig. 3: Periungual desquamation in lower limb, which usually follows
similar findings in upper limbs
585
SECTION 14: Rheumatology
Fig. 6: Prominent Beau’s lines Fig. 7: Coronary aneurysms on echocardiography
Aseptic meningitis is common in KD and responds briskly usually not seen in first week of illness. There could be other
to intravenous immunoglobulins (IVIG). We have seen suggestive findings in echocardiography like perivascular
significant joint manifestations in children with KD. These may brightness, lack of tapering of vessels, low ejection fraction,
include arthralgia and arthritis which could involve both large mitral regurgitation, and pericardial effusion. These findings
and small joints. Significant right hypochondriac pain can may be useful in diagnosis especially in those infants where all
occur due to hydrops of gallbladder. Hepatic dysfunction with the clinical features are not present (incomplete KD). A repeat
conjugated jaundice and transaminitis can lead to a diagnosis echocardiography at 6–8 weeks of illness is useful in picking up
of viral hepatitis. Reactivation of BCG site with erythema coronary abnormalities and guiding further treatment.
and induration can be a helpful sign. Rarely, respiratory
complications in the form of pulmonary nodules, interstitial
infiltrates, pleural effusions, and pneumothorax can occur.
Cranial nerve palsies, anterior uveitis, myocarditis, valvular Since the clinical features are relatively nonspecific, there are
regurgitation, and peripheral gangrene are other rarely many differential diagnoses of KD (Box 2). These include viral
described manifestations. Beau’s lines are frequently seen in infections (measles, adenovirus, enterovirus, Epstein-Barr
convalescent phase (Fig. 6). virus), Stevens-Johnson syndrome, toxin mediated syndromes,
scarlet fever, leptospirosis, and hypersensitivity reactions
INVESTIGATIONS to drugs. Exudative pharyngitis, exudative conjunctivitis,
discrete intraoral lesions, bullous or vesicular rash, and diffuse
None of the investigations are diagnostic in acute phase of lymphadenopathy suggest another diagnosis. Scarlet fever
KD. Thrombocytosis which is described as characteristic usually is not associated with conjunctivitis and shows a brisk
feature of KD is not seen before the end of second week response to antibiotics. Visceral involvement and hypotension
and hence, is not useful in making a decision regarding are frequent in toxin mediated syndromes.
treatment. Acute phase is associated with various markers
of inflammation which include neutrophilia, high erythro Box 2: Differential diagnosis
cyte sedimentation rate (ESR), high C-reactive protein (CRP), • Viral infections (measles, • Toxin mediated syndromes
anemia, hypoalbuminemia, sterile pyuria (due to uretheritis), adenovirus, enterovirus, • Scarlet fever
and transaminitis. Cerebrospinal fluid analysis may reveal Epstein-Barr virus) • Leptospirosis
pleocytosis. In children with arthritis, there may be synovial • Stevens-Johnson syndrome
fluid pleocytosis. Thrombocytopenia has been described in a
small minority of patients at onset and has been attributed to
increased adherence of platelets to activated endothelium or Clinical Pearls
to disseminated intravascular coagulation.
Echocardiography is an important tool and is usually Think of another diagnosis in presence of:
done at baseline and then after 6–8 weeks of illness (Fig. 7). • Exudative pharyngitis
Another echocardiography may be needed in second week of • Exudative conjunctivitis
illness in children who do not show response to IVIG. Coronary • Discrete intraoral lesions
dilatation is described as Z scores of more than or equal to • Bullous or vesicular rash
2.5 for internal diameters for both left anterior descending
586 • Diffuse lymphadenopathy.
and right coronary arteries. However, coronary dilatation is
CHAPTER 119: Kawasaki Disease
TREATMENT ALGORITHM 1
Management of Kawasaki disease
Standard treatment of KD involves administration of IVIg
and aspirin. It is better to wait for a day or two if one is seeing
the child for the first time on day 4 or 5 of illness and clinical
features are not clear-cut. This duration helps in evolution of
disease signs as well as in evaluation of response to empirical
antibiotics.
Intravenous immunoglobulins: IVIg is usually given at a dose
of 2 g/kg as a single dose infusion. Single dose infusion has
been found to be more effective than divided dose infusions.
Most patients show a brisk response to IVIg with defervescence
and general well-being. Inflammatory parameters also show
gradual improvement. Erythrocyte sedimentation rate is not
useful in evaluating response as high ESR continues to be seen
after administration of IVIg. IVIG, intravenous immunoglobulins; TNF-α, tumor necrosis factor-α.
However, 10–15% patients show IVIg resistance which *Means reappearance or continuation of fever after 36 h of completion of IVIg
is described as persistence or recrudescence of fever after infusion.
36 hours of completion of IVIg infusion. This is important to
identify as this is the most important clinical feature associated echocardiography at 6–8 weeks is normal. In all other children,
with high risk of coronary abnormalities (Box 3). One or two aspirin may be needed for longer duration.
fever spikes during or immediately after IVIg infusion are About 85% children show response to IVIg and aspirin
common and should not be labeled as IVIg resistance. (Algorithm 1). Rest of the children may need additional
Intravenous immunoglobulin therapy has been shown to therapy. There is no consensus on the second line treatment
reduce the risk of coronary abnormalities from 25 to 3–5%, if in KD; some centers use an additional dose of IVIg whereas
given within first 10 days of illness. Beyond the first 10 days, others use tumor necrosis factor-α inhibitors. Of late, there has
the benefit is not so great; however, most clinicians would give been resurgence in usage of corticosteroids in IVIg resistant
IVIg even beyond 10 days if the child is febrile and continues KD despite initial reports showing contradictory results.
to have high inflammatory parameters. It has also been seen
that the children who receive IVIg within first 5 days of illness
are more likely to need additional therapy. Whether this is due PROGNOSIS
to more inflammation per se and hence, more severe disease In the pre-IVIg era, about 25% children would go on to develop
is not very clear. coronary abnormalities. Use of IVIg has reduced this risk
Aspirin: aspirin is routinely used as first line therapy along to 3–5%. Coronary abnormalities can persist as ectasia or
with IVIG. Use of aspirin has not been shown either to reduce aneurysms which can be saccular, fusiform, or segmental.
the coronary risk or the time to defervescence. Usually anti- These aneurysms carry a significant risk of rupture, thrombosis
inflammatory doses in the range of 80–100 mg/kg/day are and stenosis, and predispose the individual to ischemic events.
used till subsidence of inflammation. However, because of Hence, all patients who develop coronary abnormalities
significant gastrointestinal toxicity, lower doses in the range of should continue to be on lifelong follow-up programs. These
30–50 mg/kg/day are being used frequently nowadays. Once children also need long-term aspirin in antiplatelet doses.
the child is afebrile and inflammatory parameters (CRP) show Those with giant aneurysms (>8 mm or Z scores >4) have
declining trend, dose of aspirin can be reduced to antiplatelet higher risk of complications. Addition of warfarin or heparin
doses (1–5 mg/kg/day). Aspirin is discontinued if the follow-up to aspirin in such patients has been shown to reduce risk of
thrombosis and lead to better event-free survival. Peripheral
artery involvement can occur in KD, however, is uncommon in
the absence of coronary artery involvement.
Box 3: Risk factors for coronary abnormalities
• Young age of less than 6 months
CONCLUSION
• Age more than 9 years
• Male sex Kawasaki disease is an acute systemic vasculitis which can
• Asian or Pacific Islander race mimic a myriad of childhood illnesses. Importance of timely
• Hispanic ethnicity recognition and management is important as it reduces the
risk of coronary complications to a significant extent. No
• Markers of severe inflammation (high neutrophils, low platelets,
low sodium, high C-reactive protein, and transaminitis) single diagnostic test is useful in the acute phase. Intravenous
immunoglobulins along with aspirin are the standard of care,
• Intravenous immunoglobulin resistance
and most patients respond briskly to this treatment.
587
KEY POINTS
SUGGESTED READINGS
1. Cheung M, Burgner D. Kawasaki disease: the importance of prompt recognition and
))
Diagnosis of Kawasaki disease in acute phase is based on early referral. Aus Fam Physician. 2013;42:473-6.
clinical findings and supportive investigations. No single 2. Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PA. Management of
investigation helps in clinching the diagnosis in this phase Kawasaki disease. Arch Dis Child. 2014;99(1):74-83.
))
Coronary involvement is the most sinister long-term 3. Dajani AS, Bisno AL, Chung KJ, Durack DT, Gerber MA, Kaplan EL, et al. Committee on
complication and seen more frequently in infancy rheumatic fever, endocarditis, and Kawasaki disease of the American Heart Association’s
Council on Cardiovascular Disease in the Young Diagnostic Guidelines for Kawasaki
))
Intravenous immunoglobulin therapy is the standard of disease. Am J Dis Child. 1990;144:1218-9.
care and has been shown to significantly reduce the risk of 4. Rowley AH, Shulman ST. Kawasaki syndrome. Pediatr Clin North Am. 1999;46:313-29.
coronary complications 5. Son MBF, Newburger JW. Kawasaki disease. Pediatrics in Review. 2013;34; 151‑62.
))
Despite timely intravenous immunoglobulin therapy within 6. Yim D, Curtis N, Cheung M, Burgner D. An update on Kawasaki disease II:
clinical features, diagnosis, treatment and outcomes. J Paediatrics and Child Health.
10 days, 3–5% children would develop coronary involvement.
2013;49:614-23.
Whereas, diffuse coronary dilatation and ectasia is more likely 7. Zhang T, Yanagawa H, Oki I, Nakamura Y, Yashiro M, Ojima T, et al. Factors related
to show regression by remodeling, the same is not frequently to cardiac sequelae of Kawasaki disease. Eur J Pediatr. 1999;158:694-7.
seen in giant aneurysms. These aneurysms carry a high
likelihood of thrombosis, stenosis, calcification, and rupture.
588
CHAPTER 120
Henoch-Schönlein Purpura
Anand P Rao
INTRODUCTION
Henoch-Schönlein purpura (HSP) is the most common
childhood vasculitis with an annual incidence of 20.4 per
100,000 population less than 17 years. It is characterized by
leukocytoclastic vasculitis histopathologically. It commonly
affects children between 5 and 15 years of age. About 50%
cases are reported in less than 5 years and 75% cases in less
than 10 years of age. It occurs most frequently between the
ages of 3 and 15 years and is slightly more common in boys
than in girls (1.5:1).
It commonly affects the small vessels of the skin, joints,
gastrointestinal tract, and kidneys. It is generally a self-limited
condition, but rarely can be associated with complicated
chronic course.
ETIOPATHOGENESIS
Henoch-Schönlein purpura is thought to be an immuno
Fig. 1: Predominant lower purpura in an adolescent girl
globulin A (IgA) mediated dysregulated immune process
with probable involvement of alternate complement pathway
caused by as yet unknown etiological agent.
disease. Vasculitis of the bowel wall can lead to intussusception,
CLINICAL MANIFESTATIONS gangrene, and perforation of the bowel wall.
Constitutional: it may be associated with low grade fever and Clinical Pearl
malaise.
• Please keep in mind Henoch-Schönlein purpura in any child
Cutaneous: predominant lower limb purpura with involve
who presents with acute abdominal pain and look for rashes
ment of buttocks, upper limbs, face, and very rarely, the trunk over the lower limbs before involving the surgeon.
is the classical feature of this condition. The rashes can range
from petechiae to ecchymosis to hemorrhagic bullae. Edema
Genitourinary involvement: it more often than not determines
of the dorsal surfaces of feet, hands, scrotum, scalp, and face
the outcome of the disease. The manifestations can range from
may sometimes be seen. Presence of palpable purpura is a sine
microscopic hematuria and mild proteinuria to nephrotic
qua non for the diagnosis of HSP (Fig. 1).
syndrome, acute nephritic syndrome, hypertension, or renal
Gastrointestinal manifestations: it is seen in about 70% of failure. The renal manifestations have been reported to be
patients. It can precede the purpura in about 14–46% of the seen in about 40% of patients and about 1–3% of the patient’s
patients but mostly happens in the first week of the onset of the progress to an end-stage renal disease (ESRD). Acute pain in
the scrotum can sometimes bring the child to medical attention • Skin biopsy is indicated in incomplete or atypical HSP.
and might indicate testicular ischemia. It reveals leukocytoclastic vasculitis involving dermal
capillaries and postcapillary venules with IgA deposition
Clinical Pearl • Imaging like ultrasonography might be required in patients
with severe abdominal pain to rule out intussusception.
• The nephritis in Henoch-Schönlein purpura can be silent.
It is important to look for it by checking the blood pressure,
urine routine, and microscopy weekly for at least 3 months
Clinical Pearl
from onset of disease. Serum creatinine should be checked at • Serum immunoglobulin A levels are not useful for the diagnosis
baseline. of Henoch-Schönlein purpura (HSP) as they are elevated only
in 50% of patients with HSP.
Arthritis: large joints like knee, ankle, wrist, and elbow seem
to be involved in this condition. It may precede the rashes TREATMENT
occasionally. It tends to be transient and may last from a few
days to a few weeks. Arthritis rarely goes on for months. • Rest
The diagnosis of HSP is based on the classification criteria • Hydration
proposed by EULAR/PRINTO/PRES. • Paracetamol/nonsteroidal anti-inflammatory drugs for
analgesia
Purpura (mandatory criterion): purpura (commonly palpable • Steroids indicated in the following conditions:
and in crops) or petechiae, with lower limb predominance. At {{ Orchitis
least one of the following criteria is required for the diagnosis {{ Severe gastrointestinal disease and hemorrhage
of HSP: {{ Henoch-Schönlein purpura nephritis (prophylactic
• Abdominal pain: diffuse abdominal colicky pain with acute steroid therapy has no role in preventing onset of
onset assessed by history and physical examination. It may nephritis).
include intussusception and gastrointestinal bleeding The steroid regimen recommended for severe extrarenal
• Histopathology: typically leukocytoclastic vasculitis with manifestations and renal manifestations of HSP is 1 mg/kg for
predominant IgA deposits or proliferative glomerulo 2 weeks followed by gradual taper over the subsequent 2 weeks
nephritis with predominant IgA deposits time. The diagnosis and management of HSP has been outlined
• Arthritis or arthralgia: arthritis of acute onset defined in algorithm 1.
as joint swelling or joint pain with limitation of motion.
Arthralgia of acute onset defined as joint pain without joint ALGORITHM 1
swelling or limitation of motion Diagnosis and management of Henoch-Schönlein purpura
• Renal involvement: proteinuria more than 0.3 g/24 hours
or more than 20 mg/mmol of urine albumin/creatinine
ratio on a spot morning sample. Hematuria or red blood
cell casts: more than 5 red blood cells/high power field or
red blood cells.
The following factors that are thought to be associated with
severe renal disease:
• Age more than 7 years of age
• Severe gastrointestinal disease as manifested by severe
abdominal pain or bloody stools
• Persistent or recurrent skin disease.
The cumulative proportion of patients with HSP developing
HSP nephritis by 1 month is 85%, by 2 months is 90%, and by
6 months is 97%, respectively. It has been suggested that all
patients should have urine routine microscopy examination
once a week for 3 months and for 6 months in those with
evidence of nephritis or recurrent purpura.
INVESTIGATIONS
• Complete blood count might reveal mild leukocytosis and
thrombocytosis
• Mild elevation of erythrocyte sedimentation rate is expected
• Urine routine microscopy might reveal hematuria/
proteinuria
590 • Serum creatinine might be increased in cases of nephritis IgA, immunoglobulin A; USG, ultrasonography; BP, blood pressure.
CHAPTER 120: Henoch-Schönlein Purpura
COURSE SUGGESTED READINGS

Two-thirds of patients get better by 4 weeks. But, one-third of 1. Jauhola O, Ronkainen J, Koskimies O, Ala-Houhala M, Arikoski P, Hölttä T, et al. Clinical
patients can have recurrences, commonly manifesting as rash course of extrarenal symptoms in Henoch–Schönlein purpura: a 6-month prospective
and abdominal pain and tends to be milder than the previous study. Arch Dis Child. 2010;95:871-6.
one. Prognostic features which portend poor outcome are: 2. Jauhola O, Ronkainen J, Koskimies O, Ala-Houhala M, Arikoski P, Hölttä T, et al. Renal
manifestations of Henoch-Schönlein purpura in a 6-month prospective study of 223
• Severe gastrointestinal manifestations
children. Arch Dis Child. 2010;95:877-82.
• Frequent skin rashes 3. Narchi H. Risk of long term renal impairment and duration of follow up recommended
• Severe renal manifestation at onset. for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic
Less than 5% of patients progress to ESRD. Those with review. Arch Dis Child. 2005;90:916-20.
clinical nephritis should be closely followed up for at least 4. Ozen S, Pistorio A, Iusan SM, et al. EULAR/PRINTO/PRES criteria for Henoch–
5 years. Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis
and childhood Takayasu arteritis: Ankara; 2008. Part II: Final classification criteria.
5. Saulsbury FT. Henoch-Schonlein purpura in children. Report of 100 patients and
KEY POINTS review of the literature. Medicine (Baltimore). 1999;78:395-409.
))
Henoch-Schönlein purpura is a usually benign small vessel
vasculitis involving skin, joint, and kidneys
))
The presence of severe gastrointestinal and renal involvement
would indicate worse prognosis
))
Skin biopsy is indicated when the diagnosis is in doubt
))
Steroids are recommended when there is evidence of
gastrointestinal or genitourinary involvement
))
Weekly urine dipstick for the first 3 months useful to pick up
patients with indolent nephritis.
591
CHAPTER 121
Systemic Lupus Erythematosus
Suma Balan
INTRODUCTION especially in the absence of the classic malar rash can be very
confusing. A series of clinical and laboratory criteria have
Acquired connective tissue disorders in children are a group been set out with mainly toward standardization for research
of conditions among which the most common is systemic purposes, but generally the presence in four criteria even over
lupus erythematosus (SLE). This is a disease of immune a longitudinal manner contribute toward making a diagnosis.
dysregulation where the immune system appears to be They have greater than 95% sensitivity and specificity toward
activated with the formation of autoantibodies to a wide the diagnosis; however, it is equally essential that obsessive
variety of antinuclear antigens and the formation of immune use of the criteria alone is not essential toward making the
complexes which can affect any organ, thus, creating a diagnosis (Table 1).
multisystem illness which can damage any organ in the body
if left untreated long term.
TABLE 1: Updated Revised criteria for classification of SLE
EPIDEMIOLOGY Criterion Definition
Worldwide SLE has an incidence between 20–150/100,000. Malar rash Flat or raised erythema over the malar eminences,
spares the nasolabial folds
Most prevalence studies come from developed world literature
where comparing the incidence between various ethnic Discoid Erythematosus raised patches with adherent
minorities shows a significantly higher incidence in Asian/ rash keratotic scaling and follicular plugging; atrophic
Afro-Caribbean and Oriental population compared to the scarring may occur
white/Caucasian population. The incidence in children has Photo Skin rash following sunlight exposure, by history or
been quoted between 4–250/100,000 depending upon race sensitivity physician observation
and location. Oral ulcers Oral or nasopharyngeal ulceration, usually painless
Approximately 20% of SLE commences in childhood, Arthritis Nonerosive arthritis involving two or more
before 18 years of age. The most common age of onset is peripheral joints, characterized by tenderness,
during teenage coinciding with puberty; however, it can occur swelling, or effusion
at any age. It is very uncommon to present below 5 years of
Serositis Pleuritis—convincing history of pleuritic pain or rub
age. In prepubertal children, the boy:girl ratio is almost equal on auscultation or evidence of pleural effusion or
(4:3), but postpubertal children show a significant girl to boy Pericarditis—documented by electrocardiogram,
dominance of 4:1. echocardiogram, or rub
There are no clear described prevalence figures for SLE in
Renal Persistent proteinuria greater than 0.5 g/day or
the Indian population.
disorder Cellular casts—may be red cell, hemoglobin,
granular, tubular, or mixed
DIAGNOSIS OF SYSTEMIC Neuro Seizures in the absence of offending drugs or
LUPUS ERYTHEMATOSUS logical metabolic derangements or
disorder Psychosis in the absence of offending drugs or
Like tuberculosis (TB) and syphilis, SLE is considered as one
metabolic derangements
of the great mimics in medicine owing to its widely variable
presentation, multisystem involvement, and the diagnosis, Continued
CHAPTER 121: Systemic Lupus Erythematosus
Continued • Skin: a biopsy can often be confirmatory especially if a

Criterion Definition
second sample is also sent for immunofluorescence
• Eyes: retinopathy and vasculitis of the retina can be
Hemato Hemolytic anemia with reticulocytosis or frequently associated and a professional ophthalmological
logical Leukopenia <4,000/mm3 on two or more occasions, examination must be undertaken in all children
disorder or • Blood: check for hematological manifestations. Baseline
Lymphopenia <1,500/mm3 on two or more clotting tests with prolongation of activated partial
occasions, or
thromboplastin time (APTT) are strongly suggestive of the
Thrombocytopenia <100,000/mm3 presence of antiphospholipid antibodies. A differential
Immuno Antibody to native deoxyribonucleic acid, or diagnosis for a child presenting with constitutional
logical Antibody to Sm protein, or symptoms and pancytopenia/bicytopenia is SLE and the
disorder Antiphospholipid antibodies—either anticardiolipin presence of lymphopenia on the white blood cell count is a
antibodies, presence of the lupus anticoagulant, or clue as opposed to neutropenia in childhood hematological
false positive serological test for syphilis malignancies
Antinuclear Presence of antinuclear antibody by • Renal: check serum albumin and a routine urine
antibody immunofluorescence or an equivalent assay examination in all children—the presence of active urinary
sediment is indicative of nephritis. If edema, hypertension,
oliguria, etc. are present, be alert to a proliferative nephritis
CLINICAL PRESENTATION and work-up has to be prioritized toward a biopsy to aid
Systemic lupus erythematosus can present as a chronic slowly early treatment
progressing low grade illness with troublesome skin, joint and • Musculoskeletal system: often more symptoms and signs
constitutional symptoms, as a subacute illness with internal and rarely erosive arthritis. Muscle enzymes may be
organ involvement or even as an acute florid illness with elevated
catastrophic presentations like renal failure, strokes, major • Central nervous system: observe mood and sleep patterns
thrombosis, etc. and be alert to cognitive changes or seizures. Baseline
As it is capable of involving every organ, the clinical features scans, electroencephalogram are not warranted unless
are myriad and difficult to outline all possible presentations. clinical concern exists
There are several children who are initially diagnosed as • Pulmonary: observe clinical changes
Henoch-Schonlein purpura or idiopathic thrombocytopenic • A chest X-ray will reveal the presence of pleural effusion/
purpura who turn out to have SLE. Again, children with existing pneumonitis, etc. One needs to be cautious to distinguish
autoimmune disease as in autoimmune hypothyroidism or between active disease and secondary infection that can
autoimmune hemolytic anemia might over the course of time present with similar signs. A serum C-reactive protein
develop a second autoimmune illness like SLE. is rarely elevated in active SLE and is often a good
marker to distinguish active disease and intercurrent
sepsis. Tuberculosis can present with similar features
WORKUP and prior to commencement of immunosuppressive
Once SLE is suspected, the following multisystem assessment therapy, it is recommended to check a Mantoux and
should be carried out. other tests as required—lymph node biopsy if significant
Fig. 1: Oral ulcer on hard palate in systemic lupus erythematosus Fig. 2: Extensive rash malar and on extremities in a child with 593
systemic lupus erythematosus
TABLE 2: The varied clinical manifestations of SLE ALGORITHM 1

System Clinical feature How to interpret ANA positivity
Constitutional • Fever—low grade/high grade
• Weight loss
• Malaise
Cutaneous • Rashes—malar/discoid/vasculitis
• Photosensitivity
• Oral ulcers (oral, nasal)
• Alopecia
Musculoskeletal • Polyarthralgia/arthritis (nonerosive)
• Tenosynovitis
• Myopathy
• Avascular necrosis
Vascular • Lupus crisis
• Raynaud’s
• Livedo reticularis
Cardiac • Pericarditis
• Myocarditis
• Endocarditis
• Coronary arteritis
Pulmonary • Pleuritis/effusion
• Pneumonitis
• Pulmonary hemorrhage
GI manifestations • Esophagus—dysphagia/reflux
• Stomach—gastritis, pernicious anemia (rare)
• Small bowel—mesenteric vasculitis
• Intestinal pseudo—obstruction (enteric
nervous system dysfunction)
• Malabsorption—antigliadin antibodies
• Peritonitis/ascites
• Large bowel—enteritis SLE, systemic lupus erythematosus; ANA, antinuclear antibody; ACR, American
• Vasculitic ulcers of rectum College of Radiology; dsDNA, double stranded deoxyribonucleic acid.
• Liver—deranged LFTs
• Autoimmune hepatitis
• Hepatic vein thrombosis
• Biliary tract—sclerosing cholangitis lymphadenopathy, etc. to rule out the presence of latent or
• Acalculous cholecystitis active TB
• Autoimmune cholangiopathy • In the presence of significant pneumonitis or pulmonary
• Pancreatitis—rare, but can be fulminant vasculitis, a high resolution computed tomography scan of
Immunological— • Functional asplenia the chest may be required to delineate the detailed changes
increased • Multiple defects—macrophage/
susceptibility to neutrophil/T cell/B cell/complement
present. Children can present with acute respiratory
infection deterioration, hypoxia, and diffuse alveolar hemorrhage
Renal • Nephritis classified as per WHO/ISKDC must be suspected if ground glass picture of lungs noted.
classification Hemoptysis may not be present externally and the child can
• Renal vein thrombosis develop acute pallor in this setting. Equally, a pulmonary
Neuropsychiatric • Aseptic meningitis embolism can also cause acute respiratory deterioration
• Headache and hypoxia
• Seizures
• Cerebrovascular disease
• Central nervous system: pericardial effusion at
• Movement disorder presentation is not uncommon. Myocarditis due to SLE
• Acute confusional state carries a grave prognosis if not recognized early and treated
• Anxiety disorder with aggressive immunosuppression. Endocarditis with
• Mood disorder large valve deposits (traditionally known as Libman-Sacks
• Psychosis
• Guillain—Barre syndrome
endocarditis) is rare. The author has seen two children with
• Acute transverse myelitis coronary arterial dilatations and aneurysms akin to the
• Mono/poly/cranial neuropathy picture in Kawasaki who presented with cardiac failure at
• Plexopathy presentation
Hematological • Anemia—hemolytic/macrocytic • Abdomen: SLE can present with a picture of hepatitis, hep-
• Leukopenia—often lymphopenia atosplenomegaly and ascites, abdominal lymphadenopa-
• Occasionally neutropenia
• Thrombocytopenia thy, etc. Acute abdominal pain in SLE needs attention as
• Antiphospholipid antibodies can be rarely due to pancreatitis, mesenteric vasculitis, or
LFTs, liver function tests; WHO, World Health Organization; ISKDC, International mesenteric thrombosis or even renal vein thrombosis and
594 Study of Kidney Disease of Children. these conditions need to be addressed very urgently.
of lupus in the vast majority of patients. No single titer is

Clinical Pearl diagnostic though titers of 1:1,280 or greater are less associated
with false positives.
• Along with making the diagnosis, describing the extent of
involvement is also important
Clinical Pearls
• All that is antinuclear antibody positive is not systemic lupus
erythematosus
INVESTIGATIONS
• The pretest probability (clinical suspicion) increases the
• Complete blood count: anemia—usually direct Coombs diagnostic yield of the immunological testing
test/cold agglutinin positive • Antinuclear antibody screen is for diagnosis and does not need
• White blood cell: leukopenia with lymphopenia repeating.
• A child with SLE presenting with fever and a neutrophilic
count must be assessed for the presence of secondary If ANA is positive, the serum complements have to be
infection estimated as hypocomplementemia is a feature of disease
• Platelet counts (often reduced) rarely below 50,000/mm3 activity. The anti-double stranded deoxyribonucleic acid
• When significant pancytopenia is present with high fever, (anti-dsDNA) is the most common antibody associated with
always consider the possibility of macrophage activation SLE and can be estimated qualitatively by immunofluorescence
syndrome due to uncontrolled inflammation from and quantitatively by ELISA. A quantitative estimation
active disease and look for the necessary parameters in is recommended since these levels and those of serum
biochemical testing and bone marrow examination may be complements are used for disease monitoring. The ANA
helpful profile estimates the presence of other extractable antinuclear
• Inflammatory markers: erythrocyte sedimentation rate antibodies like the ribo nucleoproteins (anti-RNP), the Sm
often elevated significantly in disease activity. C-reactive and the Ro (anti-SSA), and La (anti-SSB) and antihistone
protein is rarely elevated in active lupus disease—unless levels. Many of these antibodies remain positive and are
in presence of active pleural and pericardial effusions used more for diagnosis rather than monitoring, so they need
or synovitis with effusions. C-reactive protein can be not be repeated. Various antibodies are related to system
considered a good marker for detecting secondary bacterial manifestations in SLE e.g., anti-dSDNA and Sm for nephritis
infection in a child with SLE, a condition that needs to be and anti-RNP for neuropsychiatric disease.
addressed urgently All patients suspected/diagnosed to have SLE should
• Baseline renal function tests: liver function tests must be have their antiphospholipid antibody testing done. The
done in every patient. A low serum albumin can be part presence of a prolonged APTT/Prothrombin time gives a
of active inflammation as well as indicate proliferative clue to the presence of these antibodies. The serum levels of
nephritis or hepatic disease anticardiolipin-immunoglobulin (Ig) G and IgM, the lupus
• A detailed urine routine examination with examination of anticoagulant and the anti-b-lipoprotein 1 (IgG and IgM) are
the urinary sediment has to be done for every patient. The the ones tested.
presence of proteinuria/active sediment should lead to
quantification of proteinuria by 24 hours urinary protein Tissue Diagnosis
estimation or a random spot urinary protein/creatinine
ratio. Skin biopsy can be done to make the diagnosis—the histo
pathological appearances are characteristic as well as
immunofluorescence showing “full-house” deposition of IgG/
Immunological Testing
IgM/IgA/C3/C1q.
Antinuclear Antibody Test Lymph node biopsy may pick up Kikuchi-like changes
The antinuclear antibody (ANA) screening is advised by or a paracortical hyperplasia. Depending on the clinical
immuno fluorescence rather than the more commonly or presentation, the presentation of a significant lymph
cheaper mode of enzyme-linked immunosorbent assay adenopathy in the background of a pyrexia of unknown origin
(ELISA) testing. Immunofluorescence yields a titer and has presentation may necessitate a lymph node biopsy to rule out
both qualitative and quantitative enumeration with less differentials like TB or lymphoma.
false positivity and greater reliability than the ELISA test. It
is important to know that presence of ANA positivity does Renal Biopsy
not imply SLE—the ANA can be falsely positive in normal A renal biopsy with histologic, immunofluorescent, and
individuals, common infective, and other inflammatory electron micrographic analysis (where available) is necessary
conditions as well as other autoimmune diseases. The clinical to classify the histologic type of renal disease. In our country,
strength of a suspicion of SLE or the pretest probability of a electron microscopy is very expensive with very limited
patient to have lupus makes the positive ANA more diagnostic. availability, hence, not routinely requested.
However, a negative ANA (by immunofluorescence) with Renal biopsy is rarely done to make a diagnosis of SLE or
today’s techniques is more than enough to rule out a diagnosis lupus nephritis which is often already decided by this time; 595
however, it is to ascertain the class of nephritis which can then Mild lupus: largely characterized by musculoskeletal
guide the level of treatment. symptoms, and signs, mild systemic symptoms and mild
The International Society of Nephrology and the Renal hematological manifestations. A combination of low dose
Pathology Society have revised the original World Health steroids and hydroxychloroquine (up to 6 mg/kg/day) may be
Organization classification of renal biopsy findings in SLE into all that is required.
six different classes.
• Class 1 is generally considered minimal change and needs Moderate lupus: some systemic symptoms, moderate degree of
no treatment hematological, and some internal organ affectation. Moderate
• Class 2 is mesangioproliferative and needs no additional dose of steroids 0.5–1 g/kg/day weaned slowly over 3–6 months
treatment to steroids for a few months as would likely be with hydroxychloroquine and often second line agents like
used for background systemic disease methotrexate/azathioprine may be needed.
• Class 3 (focal proliferative) and 4 (diffuse proliferative) Severe lupus: with severe internal organ involvement, lupus
are proliferative and the most common presentations. nephritis, neuropsychiatric manifestations, macrophage
This class of patients commonly present with proteinuria/ activation syndrome, etc. are seen. High dose pulsed
nephritis, hematuria, hypertension, and some azotemia. intravenous steroids (30 mg/kg methylprednisolone to a
Patients may change from one class to another either maximum dose of 1 g/day for 3 days) followed by high dose
before or during treatment. These classes of patients are oral steroids—1–2 mg/kg/day initially in divided doses
meant to be treated aggressively to recruit back as many moving to single dose over 2 weeks and then a very slow
nephrons to normal activity and degree of reversibility wean is essential in the management of these patients. After
makes timely and appropriately aggressive therapy very appropriate assessment, there is a need for early consideration
important in these patients of a secondary agent in the form of mycofenolate mofetil or
• Class 5 is called membranous nephropathy and often
intravenous cyclophosphamide (intravenous pulse/month
presents as a nephrotic syndrome with the ongoing issues
for 6 months). In nonrenal systemic severe lupus like neuro
of anasarca. It can also be associated with proliferation
psychiatric/lung etc., cyclophosphamide has better results
which indicates aggressive management compared to pure
than mycophenolate mofetil.
membranous change which is controlled by antiedma
Catastrophic lupus; e.g., pancreatitis, diffuse alveolar
measures and lower levels of immunosuppression
hemorrhage, severe neuropsychiatric manifestation, gangrene,
• Class 6 or advanced glomerular sclerosis when >90% of
etc.—high dose steroids intravenous cyclophosphamide have
glomeruli are sclerosed, dictates poor renal prognosis and
to be commenced early. Intravenous immunoglobulin 2 g/kg
need for renal replacement therapy and a transplant.
over 1 day, 2 days in divided doses or divided over 5 days has
also been very helpful in serious emergencies with SLE.
TREATMENT OF Overall, the management is targeted toward seriousness
SYSTEMIC LUPUS ERYTHEMATOSUS of disease manifestations and balanced between controling
active disease, preventing organ damage due to disease
The treatment of SLE can be divided into: and damage, and morbidity due to treatment itself. All
1. General measures medications used in SLE have significant potential toxicity
2. Specific measures. and administration and care should be under the supervision
of a rheumatologist. Currently, the management of SLE solely
General Measures with long duration of systemic steroids alone is discouraged
• Use of sunscreen of sun protection factor 30+ to exposed due to problems with long-term steroid usage. Rituximab,
body areas when going out in sun an anti-CD20, monoclonal antibody is gaining preference
• Ensuring activity and exercise and preventative measures in the management of refractory or resistant manifestations
toward good cardiovascular health of SLE and may become part of the primary protocol for the
• Maintenance of weight and body mass index in healthy management of proliferative lupus nephritis in the future.
zone
• Intake of nutritious healthy varied diet unless specific Counseling
restriction advised
Counseling the family and the patient about the diagnosis
• Medication compliance
of SLE is very important. The family and patient need to
• Regular follow-up as advised
understand that it is a chronic lifelong disease. However, there
• Hydroxychloroquine is now recommended to be
can be periods of activity and inactivity and inactive periods
continued indefinitely for all children with SLE to improve
can often last very long durations. Hydroxychloroquine is
cardiovascular health and stabilization of antiphospholipid
now recommended for indefinite use (and 6–12 monthly eye
antibodies.
assessments with Humphrey Field Analyzer assessments
are very important). Along with the medication, the need for
Specific Measures regular follow-up and disease monitoring is very important.
The pharmacological management depends on level of disease Pregnancy and fertility are specific areas that need very careful
596 activity and severity of internal organ involvement. counseling and a rheumatologist has to remain part of the loop
from the advice of planning pregnancy through the pregnancy SUGGESTED READINGS
and delivery. Medications have to be explained with awareness
1. Habibi S, Saleem MA, Ramanan AV. Juvenile systemic lupus erythematosus: review
of potential side effects. The relationship between the
of clinical features and management. Indian Pediatrics. 2011;48(11): 879-87.
rheumatologist and the patient and family is very important to 2. Morgan TA, Watson L, McCann LJ, Beresford MW. Children and adolescents with SLE:
the patients overall improvement and well-being. not just little adults. Lupus. 2013;22(12):1309-19.
3. Pediatric lupus nephritis: more options, more chances? Lupus. 2013;22(6): 545‑53.
KEY POINTS 4. Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody
Weiss. Pediatrics in Review. 2012;33:62-74.
))
Between 15–20% of systemic lupus erythematosus commences
in childhood
))
High clinical suspicion in a child with a multisystem illness
))
Investigations only when there are clinical pointers because
false positive antinuclear antibody screen can cause much
concern
))
A detailed multisystem assessment at diagnosis needs to
be done
))
Treatment is tailored according to disease manifestations
))
Appropriate disease related counseling is essential
))
Long-term follow-up and management is necessary for these
patients
597
CHAPTER 122
Approach to
Juvenile Dermatomyositis
Deepti Suri, Sagar Bhattad
INTRODUCTION CLINICAL MANIFESTATIONS

Juvenile dermatomyositis (JDM) is an uncommon inflam Classical JDM, as the name suggests, involves skin along
matory myositis, characterized by a proximal muscle weakness, with proximal muscle weakness. Characteristic cutaneous
a heliotrope rash, and Gottron papules over the knuckles and abnormalities are seen in 75% of patients. These include
elbows. It can involve several other organ systems like the erythematous violaceous heliotrope rash seen over the upper
gastrointestinal tract, lungs, and heart. Lipodystrophy with eyelids, Gottron papules symmetrical shiny, erythematous,
insulin resistant diabetes is also a well-known association with scaly papules noted over extensor surfaces of small joints,
this condition. and wrist and elbows (Fig. 1). Nailfold capillaroscopy reveals
The primary lesion in JDM is a small vessel vasculopathy periungual erythema and capillary loop abnormalities which
of varying severity. Unlike adults, in whom polymyositis (PM), are pathognomonic and correlates with the disease severity.
inclusion body myositis, and cancer associated myositis are Classical JDM presents with insidious progression of
common causes of inflammatory myopathy; JDM is the most malaise, easy fatigue, muscle weakness, fever, and rash that may
common inflammatory myopathy in children. In the pre- predate diagnosis by 3–6 months. Muscle weakness at onset is
steroid era, one-third children died, one-third recovered, predominantly proximal and children most commonly present
and one-third of those who survived had significant residual with involvement of musculature of hip girdle. Involvement
problems of contractures and muscle atrophy. Over the last of anterior neck flexors leads to inability to hold head upright
few decades, survival and outcome has improved considerably and is an important finding pointing toward the diagnosis of
with aggressive immunosuppressive therapies. Mortality rate JDM. Pharyngeal, hypopharyngeal and palatal muscles are
in children in the West is reported to be less than 3%. However, frequently affected, resulting in difficulty in swallowing, nasal
JDM is still associated with significant morbidity and mortality regurgitation of feeds, and nasal twang to the voice. Weak gag
in our setting. reflex increases the risks of aspiration pneumonias. Although,
DEFINITION
Traditionally, the diagnosis of JDM is based on Bohan and
Peters criteria or Rider Taggoff criteria. The diagnosis is
essentially clinical and with the advent of muscle magnetic
resonance imaging (MRI), very few rheumatologist obtain
electromyographs, or muscle biopsies unless the diagnosis is
in doubt.
EPIDEMOLOGY
Incidence of JDM is reported to be 3.2 children/million/year
and girls are more commonly affected than the boys. Onset is Fig. 1: Juvenile dermatomyositis. Erythematous, scaly papules noted
between 4–10 years, with average age at onset being 7 years. over extensor surfaces of small joints, and wrist and elbows
However, 25% of children have onset before 4 years of age.
CHAPTER 122: Approach to Juvenile Dermatomyositis
muscle weakness may be impressive, the deep tendon reflexes Pulmonary involvement can occur in the form of interstitial
are usually preserved. lung disease, bronchiolitis obliterans organizing pneumonias,
and rarely pneumothorax and other air leak syndromes.
During the convalescence phase late complications
Clinical Pearl
like calcinosis and lipodystrophy are recognized. They have
• Weakness of anterior flexor muscles of the neck is important been linked to poor management of the disease at the initial
early indicator of inflammatory myositis. presentation and also corroborate well with the severity of
the first presentation. Calcinosis occurs in 10–40% of JDM
Diagnosis is rather clinical and certain in presence of patients and are extremely disfiguring. Calcinosis affecting
pathognomonic dermatological findings and proximal muscle subcutaneous tissues may result in cellulitis and painful
weakness. However, some children present with atypical superficial ulceration of overlying skin. Flexion contractures
features like subcutaneous tissue edema and can be confused may occur when these occur across joints.
with nephritic syndrome and other causes of anasarca. Some Lipodystrophy is usually associated with series of meta
children demonstrate exquisite muscle tenderness and refusal bolic derangements like insulin resistance, glucose intolerance
to walk or bear weight. Close looks for the dermatological and hypertriglyceridemia, and lipid abnormalities. Hirsutism
features help differentiate it from viral myositis. Transient and prominent dilated peripheral veins are also seen in some
nondeforming arthritis may also occasionally occur. However, patients.
presence of significant and persistent arthritis in a child with
JDM should suggest the possibility of an overlap syndrome Clinical Pearl
such as mixed connective tissue disorder.
Juvenile dermatomyositis sine myositis or amyopathic • Calcinosis is a late complication seen in patient with poor
dermatomyositis: it is characterized by only the skin initial immunosuppressive therapy.
manifestations and paucity of muscle involvement and is
relatively rare in childhood. Whether these children develop
INVESTIGATIONS
clinical overt myositis at follow-up is unclear, although
some studies report up to 26% of children do, when followed Indicators of inflammation (thrombocytosis, elevated erythro
for about 4 or more years. In contrast to adult amyopathic cyte sedimentation rate, and C-reactive protein) correlate
dermatomyositis, interstitial lung disease or internal with the degree of inflammation and help to differentiate
malignancy has not been reported from pediatric cases, inflammatory myopathies from noninflammatory disorders
and thus this subgroup carries good prognosis in children. like muscular dystrophy.
Magnetic resonance imaging is said to be a sensitive modality
for detection of muscle abnormalities in patients with Muscle Enzymes
amyopathic dermatomyositis. Serum levels of muscle enzymes are important for
Juvenile dermatomyositis with associated rheumatic diagnosis and for monitoring patients of JDM on therapy.
diseases: a subset of children with JDM may have features Aspartate aminotransferase, creatinine kinase (CK), lactate
of other rheumatic diseases as well. If children present dehydrogenase (LDH), and aldolase should be measures
with features of any two of the following diseases—juvenile at baseline. Aspartate aminotransferase or CK may be
rheumatoid arthritis, systemic lupus erythematosus (SLE), elevated 20–40 times normal. However, it is to be noted that
systemic scleroderma, and JDM—one should consider occasionally, CK levels may be normal, particularly with a
mixed connective tissue disease. Manifestations develop longer duration of untreated disease. Lactate dehydrogenase
sequentially, but not in any predictable order, although appears to correlate best with measures of disease activity.
majority would have the rash of SLE or JDM at the onset. Anti Serum levels of all muscle enzymes usually decrease 3–4 weeks
U1Anti-U1 small nuclear ribonucleoproteins antibodies are before improvement in muscle strength and rise 5–6 weeks
characteristically elevated. before clinical relapse. As a general rule, CK levels return to
normal first (usually several weeks after instituting therapy);
COMPLICATIONS and aldolase and LDH levels return to normal the last.
Vasculopathy results in many systemic complications in JDM.

Gastrointestinal vasculitis and mesenteric ischemia can lead
to acute gastrointestinal hemorrhages, intestinal perforation,
and even mortality. Abdominal pain, therefore, must never be
neglected in patients with JDM as this could be the earliest clue
to gastrointestinal vasculitis.
Clinical Pearl
• Abdominal pain in patients with juvenile dermatomyositis
may be the earliest clue to intestinal vasculopathy. Fig. 2: Erythematous violaceous heliotrope rash seen over the upper
eyelids 599
Autoantibodies ALGORITHM 1
Antinuclear antibodies may be positive in 10–85%. Myositis Basic diagnostic algorithm for diagnosis of juvenile
specific antibodies like anti-Jo-1 are uncommon in pediatric dermatomyositis
population and occur only in about 10% of children with JDM.
Anti-PM/Scl is associated with overlap syndrome.
Magnetic Resonance Imaging

Magnetic resonance imaging has dramatically replaced the
need for muscle biopsy for the diagnosis of JDM. The T2-
weighted magnetic resonance image with fat suppression
demonstrates muscle edema and inflammatory changes by a
hyperintense signal. magnetic resonance also helps in guiding
the extent of disease and also helps in selecting a site for
muscle biopsy.
Electromyography
Electromyography findings that suggest inflammatory myopathy
include a combination of changes of myopathy and denervation.
Muscle Biopsy
Muscle biopsy is largely performed when the diagnosis is
in doubt, if there are no skin findings and sometimes to
evaluate the disease activity. It may occasionally help in CK, creatinine kinase; LDH, lactate dehydrogenase; MRI, magnetic resonance
imaging.
making alternative diagnosis in children who fail trial of
immunosuppression.
Biopsy usually is performed from quadriceps or deltoid,
although the best specimen may be chosen based on KEY POINTS
electomyography or MRI. Muscle biopsy reveals perifascicular
atrophy and variations in fiber size, as an outcome to ongoing ))
Juvenile dermatomyositis (JDM) is the most common
degeneration and regeneration. Areas of focal necrosis would inflammatory myopathy of childhood
be noted and inflammatory exudates are often presented. ))
Serum muscle enzymes correlate with disease activity,
although normal creatinine kinase level does not exclude JDM
))
Magnetic resonance imaging is a good modality to demonstrate
TREATMENT muscle inflammation and is investigation of choice
Morbidity and mortality have greatly reduced over the decades ))
Muscle biopsy/electromyography is less commonly used and
as a result of effective immunosuppressive therapies. Use has a role in cases with diagnostic difficulties
of high dose corticosteroids early in the disease course has ))
Corticosteroids and methotrexate form the cornerstone of
dramatically improved prognosis. Treatment regimen consists therapy for the majority of patients with JDM.
of high dose oral corticosteroids (up to 2 mg/kg/day prednisone)
with a slow tapering regimen, often over a minimum of 2 years.
Intravenous pulse methyl prednisolone (30 mg/kg/dose) for SUGGESTED READINGS
3–5 doses are administered at the onset of therapy in some
children with severe inflammation and marked weakness. 1. Ravelli A, Trail L, Ferrari C, Ruperto N, Pistorio A, Pilkington C, et al. Long-
term outcome and prognostic factors of juvenile dermatomyositis: a multinational,
Majority of the children are also initiated on alternative
multicenter study of 490 patients. Arthritis Care Res. 2010;62:63-72.
immunosuppressive drugs, like methotrexate (15 mg/m2
2. Stringer E, Bohnsack J, Bowyer SL, Griffin TA, Huber AM, Lang B, et al. Treatment
subcutaneous weekly) along with folic acid as steroid sparing approaches to juvenile dermatomyositis (JDM) across North America: The Childhood
agents. Children who fail to respond to these, second line agents Arthritis and Rheumatology Research Alliance (CARRA) JDM Treatment Survey. J
including intravenous immunoglobulins, cyclophosphamide, Rheumatol. 2010;37;1953-61.
mycophenolate mofetil, tacrolimus, and rituximab can be
tried. Supportive care with graded physiotherapy and skin care
are of utmost importance.
600
Chapter 123
Acute Osteoarticular Infections
Jasodhara Chaudhuri, Tapas K Sabui
INTRODUCTION Acute hematogenous osteomyelitis is most common in

childhood with a peak incidence in neonates. The reported
Acute osteoarticular infections (AOI) are prominent areas incidence has been falling around the world but remains high
of bacterial infection in infancy and childhood with variable in developing nations.
clinical features that are often nonspecific. They may cause Osteomyelitis often is categorized into three different types:
significant mortality and morbidity. Major clinical entities • Acute hematogenous osteomyelitis
that are seen in children are septic arthritis, classic long bone • Osteomyelitis secondary to contiguous spread of infection
osteomyelitis, skeletal tuberculosis, disitis, and osteochondritis after trauma, puncture wounds, surgery, or joint replacement
complicating puncture wounds to the foot. Early diagnosis and • Osteomyelitis secondary to vascular insufficiency.
treatment of musculoskeletal infection are critical to prevent Acute hematogenous osteomyelitis is seen most often
sequelae. In children, these mean impaired growth with in children. Osteomyelitis caused by contiguous spread of
restricting lifelong deformity. However, children show a high infection is less common in children, and infection secondary
potential for healing and remodeling and less comorbidity to vascular insufficiency is rare in children.
than adults. Childhood bone infection generally has good
outcome provided appropriate treatment with antibiotics and Clinical Pearls
surgical intervention are offered in timely manner.
• Osteomyelitis is most common in neonates
The patterns of bone infection in children are changing in
terms of both clinical syndrome (fewer acute presentation) • Osteomyelitis is most common at metaphysis of long bones
and of microbiology (e.g., increased bacterial resistance • The history of trauma is common.
among community acquired Staphylococcus aureus). A greater
understanding of pathogenesis and the varied manifestations of
osteomyelitis and septic arthritis is thus required. There is also PATHOGENESIS
a need of clear guidelines with respect to treatment strategy, Pyogenic arthritis usually occurs as a result of infection of the
particularly the role of surgery and choice of antibiotic agents. vascular synovium by means of hematogenous dissemination
of bacteria followed by an acute inflammatory response,
Clinical Pearls resulting in migration of polymorphonuclear white blood
• Acute osteoarticular infections are prominent areas of bacterial cells (WBCs), production of proteolytic enzymes, and cytokine
infection in infancy and childhood secretion by chondrocytes. Degradation of articular cartilage
• Joint space infection in children usually arises as a complication begins 8 hours after onset of infection. In children younger than
of bacteremia 18 months of age, pyogenic arthritis can result from extension
• Virus, fungal, and tuberculous infections are rare. of a metaphyseal bone infection through transphyseal blood
vessels. The growth plate, the epiphysis, and eventually the
joint space may be infected.
On the other hand, osteomyelitis occurs mostly by
SEPTIC ARTHRITIS AND OSTEOMYELITIS hematogenous colonization of the bones by bacteria. The
Joint space infection in children usually arises as a compli metaphysis of long bones is the most common site. Theories
cation of bacteremia. Virus, fungal, and tuberculous infections supporting this fact include decreased blood flow in sinusoidal
are rare. Bacterial infection elsewhere in the body may also vessels in this area along with relative lack of phagocytic cells.
give rise to reactive arthritis. Although many children give a history of minor trauma, it is
ch-123.indd 601 11/22/2016 10:12:05 AM

very rare to see osteomyelitis complicating a closed fracture DIFFERENTIAL DIAGNOSIS

treated by nonoperative means. Other notable features
of epidemiology including the male preponderance and The most common cause of hip pain in childhood is transient
peak incidence remain to be explained. The pathological synovitis. Transient synovitis is predominantly seen in
response to osteomyelitis is one of acute inflammation in children 5–10 years old. Pain is usually unilateral. Pain ranges
the intramedullary cavity of the metaphysis of the long bone. from mild to severe enough to wake the child up. Physical
After 48 hours, pus accumulates subperiosteally and then examination generally reveals a nonill appearing child with
portions of the cortex may die as a result of the loss of blood decreased range of motion of the hip joint. Other common
supply forming a sequestrum and the abscess may rupture. causes of joint pain and swelling include reactive arthritis,
Occasionally, osteomyelitis can involve the epiphysis of a long rheumatic fever, juvenile rheumatoid arthritis, trauma,
bone and then is usually subacute although acute epiphyseal and malignancy. Malignancy often turns out to be the most
osteomyelitis has been reported. important differential diagnosis for osteomyelitis. Legg-
Calve-Perthes disease is an idiopathic avascular necrosis of
EPIDEMIOLOGY the capital femoral epiphysis and may cause mild pain and
limp in boys.
Most cases of AOI occur in children 3 years old or younger.
Boys are more frequently affected. The lower extremities (hips,
knees) are most commonly affected. DIAGNOSIS
A sample for bacteriology may be obtained by needle aspiration
Clinical Pearls of soft tissue in neonates, subperiosteal aspiration in infants,
• Acute osteoarticular infections is most common under 3 years or drilling of bone in older children. (Blood and joint fluid)
of life should be obtained for aerobic and anaerobic cultures.
• The most common agent is Staphylococcus aureus Blood tests, namely hemogram and acute phase reactants,
are used to assess the extent of inflammation. Blood leukocyte
count (WBC) is nonspecific and elevated only in 20% of
MICROBIOLOGY cases. Out of all acute phase reactants, C-reactive protein
The most common agent is Staphylococcus aureus, followed by (CRP) here is extremely helpful in diagnosis and monitoring
respiratory pathogens Streptococcus pyogenes, Streptococcus of AOI. Traditional radiographs have minimum or no value
pneumoniae (pneumococcus), and Haemophilus influenza in diagnosis of it as the changes appear late. Ultrasound is
type b (Hib). Kingella kingae is a common cause of osteomyelitis extremely helpful for detection of joint effusion. However,
and septic arthritis in some areas and requires special culture magnetic resonance imaging and computed tomography are
techniques or real-time polymerase chain reaction for diagnosis. the investigations of choice for early diagnosis. Bone scans
in acute hematogenous osteomyelitis have a sensitivity of
CLINICAL MANIFESTATIONS 84–100% and a specificity of 40–96%. The sensitivity of bone
scans is least in the first 48 hours due to the transitional period
The classical presentation of AOI is a locally swollen, warm between decreased and increased activity. Scintigraphy is
limb, or joint combined with high fever with no or minor prior most helpful in detecting multiple foci of disease and in the
history of trauma. Pyrexia of unknown origin may be initial assessment of the young child, where localization is difficult.
mode of presentation. Although cultures frequently fail to disclose the causative
Generally, children with septic arthritis are clinically more agent, every attempt should be made for isolation of
ill than those with osteomyelitis, which has a more insidious causative agent from the site of infection. The only indication
onset. Plenty of useful information may be obtained from the of joint aspiration in pediatric age group nowadays is septic
disease history and mere observation of the patient. Limping,
arthritis, even though the chance of getting positive culture
pseudoparalysis, refusal to use particular limb, and focal
is only 30%. Aspirated fluid should be inoculated directly into
tenderness are the common mode of presentation. Whenever
blood culture bottles. Gram stain and cell count should also
a previously well child presents with monoarthritis of acute
be performed on joint fluid. A WBC count of 50,000/mm3 or
origin, the possibility of septic arthritis should be considered.
greater with a predominance of polymorphonuclear cells is
Pelvic osteomyelitis is well known to mimic a number of other
consistent with bacterial infection.
diseases including appendicitis, lumbar disk prolapse, and
septic arthritis of the hip.
Clinical Pearls
Clinical Pearls • Every attempt should be made to find out the etiological
• The classical presentation of acute osteoarticular infections (AOI) agent from infected tissue
is a locally swollen, warm limb, or joint combined with high fever • C-reactive protein here is extremely helpful in diagnosis and
• Children with septic arthritis are clinically more ill than those monitoring of acute osteoarticular infections
with osteomyelitis • Traditional radiographs have minimum or no value in diagnosis
602 • Whenever a previously well child presents with monoarthritis • Magnetic resonance imaging and computed tomography is
of acute origin, think of AOI. the investigation of choice for the early diagnosis.
ch-123.indd 602 11/22/2016 10:12:05 AM

Chapter 123: Acute Osteoarticular Infections
TREATMENT were given in recent trials intravenously for first 2–4 days
except in newborns and thereafter it was given orally, provided
A local antibiogram would be of paramount importance in
the first signs of recovery including disappearance of fever,
these situations. As Staphylococcus aureus is a major player
taking oral fluids were observed, and the level of CRP began
in AOIs, its local sensitivity pattern influences the choice of
to descend. However, this protocol is not applicable in the case
the initial antibiotic. The empiric antibiotic treatment of AOI
for the management of complex infections including those
in primary methicillin sensitive and methicillin resistant
with multifocal disease, significant bone destruction, resistant
Staphylococcus aureus (MRSA) is first or second generation
cephalosporins (150 mg/kg/day four times a day)/cloxacillin or unusual pathogens, sepsis or in immunosuppressed
(200 mg/kg/day four times a day) and vancomycin (40 mg/kg/ children, and in neonates. The intravenous therapy to be
day four times a day)/trimethoprim/sulfamethoxazole (TMP- continued for 14–21 days in complex situations and switched
SMX) (TMP16 mg/kg/day twice a day), respectively. Linezolid over to oral medication provided the baby is afebrile, pain-
(30 mg/kg/day three times a day) is the drug of choice in areas free for at least 24 hours, and CRP descended by two-thirds of
where the organism is resistant to vancomycin/TMP-SMX. A highest value. The total antibiotic therapy here will be 6 weeks
Hib unvaccinated child from Hib endemic area should receive both in septic arthritis and osteomyelitis. The role of surgery
concomitant ampicillin or amoxicillin (200 mg/kg/day divided in the treatment of septic arthritis is in fact poorly defined
in four equal doses) until the agent is identified. Currently, except in relation to the hip, where prompt surgical drainage
there is no consensus about the route or duration for antibiotic is absolutely necessary. Aspiration, irrigation, and intravenous
treatment of acute osteomyelitis in children. Until recently, the antibiotic therapy is the preferred first line of treatment of
standard therapy was a long intravenous therapy and a long septic arthritis except in hip joint. No consensus prevails in the
duration of 4–6 weeks. However, the short antibiotic courses timing, procedures, extent, or even the overall need for surgical
tested in recent trials on osteomyelitis and septic arthritis. intervention in osteomyelitis. Surgical drainage is mandatory
The entire course of antibiotic was approximately 3 weeks in osteomyelitis if pus is obtained from the subperiosteal space
for uncomplicated osteomyelitis and 10–14 days for septic or metaphysic in nature. The abscess should be decompressed,
arthritis. A high dose of well absorbed first/second generation evacuated, and washed-out under general anesthesia. A
cephalosporins or clindamycin in equal doses four times a day suction drain should be left in place for 48 hours.
was used. These antibiotics penetrate bone and soft tissue well Though further studies are needed in this field, a placebo
in intravenous and oral administration. In absence of definite controlled randomized controlled trial examined the use
laboratory or clinical parameters that would determine the of 4 days of intravenous dexamethasone (0.2 mg/kg/dose
decision to switch to oral therapy, there is no clear guideline intravenously 8 hourly) and it significantly reduced the
of when to switch from intravenous to oral therapy. The drugs duration of acute phase and morbidity.
Algorithm 1
Algorithmic approach to monoarticular joint pain and arthritis
603
AOI, acute osteoarticular infections; JIA, juvenile idiopathic arthritis; CT, computed tomography; MRI, magnetic resonance imaging; USG, ultrasound.
ch-123.indd 603 11/22/2016 10:12:05 AM

Conclusion
The number of bone and joint infections resulting from vaccine
preventable pathogens like Haemophilus influenza and
Streptococcus pneumoniae are on the decline. Staphylococcus
aureus is the most common pathogen causing septic arthritis
and osteomyelitis in children all over the world. The incidence
of community acquired MRSA is increasing and is a cause
of concern for pediatricians. Early diagnosis and prompt
and appropriate treatment consisting of antibiotic therapy
and surgical intervention when required is the mainstay
of treatment and is extremely rewarding in majority of the
occasions.
Key points
))
Acute osteoarticular infections (AOI) are common in infancy
Fig. 1: X-ray of hip joint in a case of septic arthritis. The arrow sign and childhood under 3 years of age
shows the affected hip joint showing decreased and eroded joint
))
Joint space infection in children usually arises as a
space. Periosteal reaction in adjoining femur
complication of bacteremia and the most common agent is
Staphylococcus aureus
))
High fever, painful warm swollen limb or joint are the most
common mode of presentation
))
Children with septic arthritis are clinically more ill than those
with osteomyelitis
))
Whenever a previously well child presents with monoarthritis
of acute origin, think of AOI
))
Magnetic resonance imaging and computed tomography is
the investigation of choice for the early diagnosis
))
Identification of etiological agent and local antibiogram are
of paramount help
))
There is no consensus about the route or duration for
antibiotic treatment of acute osteomyelitis in children
))
Treatment is rewarding.
Fig. 2: X-ray showing osteomyelitis. The arrow sybmol shows the SUGGESTED READINGs
visible osteolytic changes of osteomyelitis and sequestrum
1. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in
children. Arch Dis Child. 2012;97:545-53.
PROGNOSIS 2. Grammatico-Guillon L. Paediatric bone and joint infections are more common
in boys and toddlers: a national epidemiology study. Acta Paediatrica. 2012;
Complications of AOI include abnormal bone growth, limp,
11:1-6.
unstable articulation of the affected joint, and decreased range
3. Grimprel E, Lorrot M, Haas H, Pinquier D, Parez N, Ferroni A, et al. Bone
of motion. Complications are reported in approximately 10– and joint infections: treatment proposals from the Group of Pediatricians
25% of all cases. Risk factors for squeal include delay in time to Specialised in Infectious Diseases (GPIP) French Pediatrics Society. Arch Pediatr.
diagnosis of more than 4 or 5 days, onset of disease in infancy, 2008;15:S74‑80.
infection with Staphylococcus aureus or Gram-negative 4. Gutierrez K. Bone and joint infections in children. Pediatr Clin North Am.
bacteria, and infection of adjacent bone. 2005;52:779-94.
5. Peltola H, Pääkkönen M, Kallio P, Kallio MJ; Osteomyelitis-Septic Arthritis
Clinical Pearls Study Group. Short-versus long-term antimicrobial treatment for acute
hematogenous osteomyelitis of childhood: prospective, randomized trial on
• A local antibiogram would be of paramount help 131 culture-positive cases. Pediatr Infect Dis J. 2010;29:1123-8.
• The Empiric antibiotic treatment depends on nature of 6. Susan S. Review article: paediatric bone and joint infection. J Orthop Surg.
etiological agent 2001;9:83-90.
• No consensus about the route or duration for antibiotic
treatment of acute osteomyelitis in children
604
• Complications are reported in approximately 10–25% of all cases.
ch-123.indd 604 11/22/2016 10:12:06 AM

Chapter 124
Eye Involvement: Beyond Infections
Manjari Agarwal
INTRODUCTION not be present in Kawasaki disease. Presence of purulent

conjunctivitis usually rules out Kawasaki disease.
Eyes are a window to systemic disease and can help a clinician
reach an elusive diagnosis, by simply doing a proper detailed
ophthalmological examination. Eyes are involved in a SCLERITIS
multitude of rheumatological illnesses and every incidence
Sclera is the outer protective layer of the eye, begins at the
of eye problem is not due to infection. For the sake of this
review, infectious etiologies would not be discussed. This limbus and is continuous with the cornea and ends at the optic
review aims at stressing upon the eye involvement in various canal in continuity with the dura.
rheumatological/immunoinflammatory diseases. For ease of Episcleritis is usually more painful and is often self-limiting.
explanation, involvement of each layer of the eye is discussed Scleritis usually affects the adult population between 30
separately (Fig. 1). and 50 years of age. The most commen association of scleritis
in this age group is with Granulomatous polyangiitis and
rheumatoid arthritis (Table 1).
CONJUNCTIVITIS
Redness of eyes with photophobia is seen in about 85% Diagnosis
children with Kawasaki disease. Bilateral, nonexudative, and
bulbar conjunctivitis is the hallmark of the disease. Perilimbal Detailed history, and physical examination is a must. Investi
sparing of the conjunctiva is usually seen. Uveitis may or may gations pertaining to the system involved must be carried
Table 1: Etiology of scleritis

Infections Autoimmune diseases Others
Viruses (varicella Rheumatoid arthritis Trauma
zoster, herpes
simplex, hepatitis C)
Bacteria Granulomatous polyangiitis Drug induced
pamidronate
Mycobacteria Inflammatory bowel disease 35–45
Fungi Systemic lupus –
erythematosus
Amebae Sarcoidosis –
Parasites • Takayasu’s arteritis
• Cogan’s syndrome
• Spondyloarthropathies
• Polyarteritis nodosa
Fig. 1: Schematic representation of eye • Vasculitis
ch-124.indd 605 11/22/2016 10:13:36 AM

out. Specific serologic testing should include antinuclear as arteries can be involved in Behçet’s disease and may lead to
antibodies (ANA), antineutrophil cytoplasmic antibodies arterial occlusion.
(ANCA), rheumatoid factor, and anticyclic citrullinated Systemic vasculitides can also cause retinal vasculitis
peptide antibodies. although these are uncommon.
Other investigations like Mantoux test can be done after Systemic lupus erythematosus can also cause retinal
history and physical examination. vasculitis even in the absence of antiphospholipid antibodies.
The retinal vessels can be involved causing cotton-wool spots
or microinfarcts of the nerve fiber layer of retina.
Treatment
Treatment of scleritis can be divided on the type of scleritis and Therapy
has been detailed in table 2.
Systemic glucocorticoids usually pulse methylprednisolone
(10–30 mg/kg/day) for 3–5 days followed by oral gluco
INTERSTITIAL KERATITIS corticoids are needed. Steroid sparing agents like
methotrexate and mycophenolate mofetil might be required
Interstitial keratitis is characterized by a nonsuppurative
for maintenance therapy.
inflammation, with vascularization of the cornea. It is
commonly seen with Cogan syndrome. It usually presents with
pain, lacrimation, photophobia, and conjunctival injection. Orbital Disease
This usually responds to topical corticosteroid therapy. Primary inflammation of the orbital tissue, e.g., orbital
pseudotumor or orbital myositis due to inflammation of the
Clinical Pearls extraocular muscles is usually seen. Secondary involvement
• Eyes can be involved in a myriad of immunoinflammatory occurs most commonly due to contiguous spread of
conditions inflammation from the sinuses seen typically in ANCA
• Redness of eyes with photophobia, with or without diminution associated vasculitis.
of vision might be a red flag and should be appropriately
evaluated. Therapy
Control of underlying disease with systemic corticosteroids
or immunosuppressive drug therapy, decreases associated
RETINAL VASCULITIS symptoms, as well as improves visual acuity.
Retinal vascular inflammatory diseases are termed retinal
vasculitis even in the absence of true vasculitis. It can be UVEITIS
defined as inflammation of the retinal vessels accompanied by
intraocular inflammation and retinal vessel occlusion. Retinal It is the most common ocular involvement of immuno
vasculitis may involve retinal arteries, veins, or capillaries. inflammatory diseases in childhood. Usually uveitis in
A common cause of retinal vasculitis leading to significant children is asymptomatic and hence can lead to significant
ocular morbidity is Behçet’s disease. Both retinal veins as well ocular morbidity.
Standardization of Uveitis Nomenclature working group
Table 2: Therapy of scleritis has defined the types of uveitis along with descriptors for each
type of uveitis (Tables 3–5).
Type of scleritis Systemic therapy
Nodular anterior scleritis NSAIDs Table 3: Standardization of Uveitis Nomenclature Working
Necrotizing anterior scleritis • Systemic glucocorticoids Group classification of uveitis
• Systemic immnuosuppression: Type Primary site of Lesions
{{ First line agents:
inflammation
–– Cyclophosphamide Anterior uveitis Anterior chamber • Iritis
–– Methotrexate • Iridocyclitis
–– Azathioprine • Anterior cyclitis
–– Mycophenolate mofetil
Intermediate Vitreous • Pars planitis
{{ Second line agents:
uveitis • Posterior cyclitis
–– Cyclosporine • Hyalitis
–– Tacrolimus
{{ Third line/experimental
Posterior uveitis Retina/choroid • Chorioretinitis
• Neuroretinitis
–– Infliximab
• Retinochoroiditis
–– Rituximab
• Focal, multifocal, diffuse
Posterior scleritis • Systemic glucocorticoids choroiditis
606 • Systemic immunosuppression • Retinitis
ch-124.indd 606 11/22/2016 10:13:36 AM

Chapter 124: Eye Involvement: Beyond Infections
Table 4: Standardization of Uveitis Nomenclature working Few children, especially older than 7–8 years of age can
goup descriptors of uveitis complain of pain, redness, headache, photophobia, or blurring
of vision.
Category Description Comment
Slit lamp examination is mandatory to diagnose uveitis.
Onset Sudden – Presence of inflammatory cells and increased protein
insidious
concentration (flare) in the aqueous humor of the anterior
Duration Limited ≤3 months chamber are the classic hallmark.
persistent >3 months Keratic precipitates (deposition of inflammatory cells on
Course Acute Episodes of sudden onset and limited the inner surface of the cornea) may be detected at onset or
duration may develop later.
Recurrent Repeated episodes separated by
Band keratopathy occurs due to deposition of calcium in
periods of inactivity without treatment the corneal epithelium and is also a late feature.
>3 months in duration Presence of posterior synechiae is also a feature of late
disease. Untreated synechiae might occasionally cause
Chronic Persistent uveitis with relapses in
<3 months after discontinuing therapy
obstruction to aqueous outflow and cause increased intra
ocular pressure.
Since chronic uveitis might lead to significant visual
Table 5: Guidelines for the ophthalmological screening of morbidity, it is prudent to electively screen children with JIA.
children with juvenile idiopathic arthritis Table 5 gives a guideline for screening of children depending
upon the risk involved. Uveitis may also be associated with
JIA onset ANA Onset <7 years Onset >7 years other inflammatory disorders in children like inflammatory
type of age of age
bowel disease and reactive arthritis. Uveitis can also in
Oligoarticular Positive Every 3–4 months Every 4–6 months occur in chronic infantile neurological cutaneous and
articular syndrome, sarcoidosis, Blau syndrome, Bechet’s
Oligoarticular Negative Every 4–6 months Every 4–6 months
disease and Kawasaki disease. Algorithm 1 gives provides an
Polyarthritis Positive Every 3–4 months Every 4–6 months outline of the diagnostic possibilities for children presenting
Polyarthritis Negative Every 4–6 months Every 4–6 months
with uveitis.
Systemic Negative/ Every 12 months Every 12 months Management

onset positive
Uveitis associated without arthritis needs to be evaluated
JIA, juvenile idiopathic arthritis; ANA, antinuclear antibodies.
and infections like tuberculosis need to be ruled out.
Angiotensin converting enzyme levels for sarcoidosis, HLA
Acute anterior uveitis is characteristic of human leukocyte B51 for Behçet’s disease, ANA need to be done if child does
antigen B27 (HLA-B27)–associated diseases such as enthesitis- not have arthritis. Human leukocyte antigen B27 associated
related arthritis. Patient presents with a red, painful, and uveitis is usually acute symptomatic but rarely may be
photophobic eye. The anterior chamber is best visualized by
the help of a slit lamp. The presence of cells in the anterior
chamber indicates disease activity. At times, the cells might Algorithm 1
aggregate in the lower part of the anterior chamber due to Approach to a child with uveitis
gravity and produce a hypopyon. If left untreated, there is a
tendency to form adhesions between the posterior part of iris
and lens; these are termed as posterior synechiae.
Clinical Pearl
• Acute anterior uveitis might often be the first presentation of
disorders like juvenile spondyloarthropathy and inflammatory
bowel disease.
Similar adhesions between peripheral iris and posterior

cornea are called anterior synechiae. Chronic uveitis is the
most common ocular complication of oligoarticular juvenile
idiopathic arthritis (JIA). It is initially asymptomatic and is
picked up on routine screening. It is predominantly insidious
in onset, anterior, nongranulomatous inflammation affecting JIA, juvenile idiopathic arthritis; ANA, antinuclear antibodies; IBD, inflammatory
the iris and ciliary body. bowel disease.
607
ch-124.indd 607 11/22/2016 10:13:36 AM

chronic persistent. Rheumatoid factor positivity generally

has a protective role for uveitis. Key points
))
Acute anterior uveitis might often be the first presentation of
Treatment disorders like juvenile spondyloarthropathy and inflammatory
The management of uveitis is done by ophthalmology and bowel disease (IBD)
rheumatology teams jointly. ))
Detailed ophthalmic examination is necessary in every child
Topical glucocorticoid drops with or without mydriatics with juvenile idiopathic arthritis (JIA)
are the first line agents. Topical therapy for prolonged period is ))
Chronic anterior uveitis is asymptomatic and a young child
associated with severe ocular complications like cataract and might not be able to complain of blurring of vision
glaucoma. ))
In a child with uveitis, diseases like tuberculosis, sarcoidosis,
Second line agent for uveitis unresponsive to topical Behçet’s, IBD, and JIA must be ruled out
therapy is methotrexate. It can also be used as a steroid sparing ))
Disease-modifying antirheumatic drugs are essential early
agent with excellent results. in the disease course to prevent side effects of topical/oral
Mycophenolate mofetil, cyclosporine, and tacrolimus are steroids.
the next line of management.
Severe, unresponsive disease can be managed by tumor
Suggested readings
necrosis factor alpha blocker, infliximab.
There is also some role of costimulatory blockade, abatacept 1. Galor A, Thorne JE. Scleritis and periplheral ulcerative keratitis. Rheum Dis Clin N
for resistant uveitis though large trials are still required. Am. 2007;33:835-54.
2. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature
for reporting clinical data: results of the First International Workshop. Amer J
Clinical Pearls Ophthalmol. 2005;140:509-16.
3. Nguyen QD, Foster CS. Systemic lupus erythematosus and the eye. Int Ophthalmol
• In children with diagnosed juvenile idiopathic arthritis, routine Clin. 1998;38:33-60.
screening for chronic anterior uveitis is a mandate 4. Okhravi N, Mc Cluskey P. Scleritis. Surv Ophthalmol. 2005;50(4):351-63.
• Topical therapy for prolonged period of time can cause 5. Yancey C, White P, Magilavy D, Gewanter H, Lowe B, Passo M, et al. The Guidelines
significant morbidity and must be avoided. of the Rheumatology and Ophthalmology sections of the American Academy of
Pediatrics. Pediatrics. 1993;92:295-6.
608
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Section 15: Pediatric Surgery
Chapter 125
Empyema Thoracis:
Management Algorithm
Rasik S Shah, Suyodhan A Reddy
INTRODUCTION is rare and occurs only in 2% of the cases of tubercular pleural

infections. Anaerobes are common in older children who often
Empyema thoracis (ET) is collection of purulent fluid in the have predisposing factors like aspiration pneumonia, lung
pleural cavity, which is either free or localized. Pneumonic abscess, and poor dental hygiene. Aspergillus and Candida
infection and the associated inflammation of the pleural albicans also have been isolated. Rarely, Entamoeba histolytica
lining lead to an exudative parapneumonic pleural effusion, abscess in the liver may rupture in the pleural cavity and
which upon invasion by bacteria becomes empyema. The term produce ET with Entamoeba histolytica.
“empyema” is derived from the Greek words pyon, meaning pus
and empyein, meaning pus producing. The optimal time and
the manner of drainage of empyema was a matter of concern PATHOPHYSIOLOGY
since the times of Hippocrates and Fabricus. In the last two
The smooth and synchronized expansion of the lung in
decades, many pediatric surgical centers are increasingly using
consonance with the expansion of the chest wall is facilitated
minimal access techniques in management of ET patients.
by a small amount of intrapleural fluid (0.3 mL/kg). This is
maintained in a dynamic equilibrium in visceral and parietal
EPIDEMIOLOGY pleura by unidirectional flow created by lymphatics. These
lymphatics generate a negative pressure of about 7 mmHg
Childhood empyema occurs in 0.7–3.3 per 100,000 worldwide.
and are capable of absorbing large volumes of clear low solute
There is gradual increase in the incidence. The pattern of use
fluids in the pleural space. However, a secondary infection
of antibiotics and incorporation of polyvalent pneumococcal
in the pleural space triggers an inflammatory process, which
vaccine (7vPVC) into immunization programs has led to an
makes the pleural vasculature to become more permeable
increase in invasive pneumococcal empyema by nonvaccine
serotypes. to inflammatory cells and bacteria. The pleural fluid now
transforms into exudates of frank pus, resulting in the classical
empyema. This influx is mediated by proinflammatory
ETIOPATHOGENESIS cytokines, such as tumor necrosis factor, interleukin (IL)-
Empyema thoracis most often occurs as a sequel of bacterial 1b, and IL-6, secreted from mesothelial cells. The activation
pneumonia; however, it can also occur following pulmonary of the coagulation cascade and disruption of enzymes of the
tuberculosis, trauma, perforation of intrathoracic esophageal, fibrinolytic system, such as tissue type plasminogen activator
or operations on chest. Lower respiratory tract infection and plasminogen activator inhibitor type 1, results in fibrin
in children may get complicated by parapneumonic fluid deposition and blockage of lymphatic pores leading to further
collections in 50% of patients. Progression to an established ET accumulation of fluid. This imbalance of the fibrin produces
occurs in 1 of every 155 cases of pneumonia according to one multiple loculations and formations of fibrinopurulent peel as
large pediatric series. seen in the later stages of empyema.
In India, Staphylococcus aureus is still the most common Empyema thoracis is classified in to three stages, i.e.,
isolate from the children of ET. This is followed by Strepto exudative, fibrinopurulent, and organizing stage by the
coccus pneumoniae and Streptococcus pyogenes. Although American Thoracic Society. The pathological response is
S. pneumoniae produces large effusion in 40% of the cases, divided in three phases that are not sharply distinct but
only 5% eventually progress to frank ET. Tubercular empyema gradually one phase merges into another (Table 1).
ch-125.indd 609 11/24/2016 2:28:04 PM

Table 1: Stages of empyema

Stage Duration Cellular content Glucose ratio fluid/plasma pH LDH Pleural space
Exudative 1–3 days Low >60 mg (>0.5) >7.30 <1,000 Thin sterile, low sediment fluid
Fibrino 4–14 days Neutrophilia <60 mg (<0.5) <7.10 >1,000 Purulent, viscous fluid, loculations, and limiting
purulent and fibrin membranes
Organisms isolated
Organized >14 days Fibroblasts proliferation leads to thick peel, which encases the lung. The pleural space contains very thick exudates
LDH, lactate dehydrogenase.
Hamm and light described a stage that proceeds to the Ultrasonography of Chest
stage of exudation, which they termed “pleuritis sicca stage”,
The ultrasonography of chest is the most useful investigation;
this is characterized by the presence of pleuritic chest pain and
it is noninvasive, does not use ionizing radiation, provides a
pleural rub. This does not proceed to exudative stage.
dynamic assessment of the chest, and can be done repeatedly
without fear of any adverse effect. It can differentiate between
CLINICAL FEATURES consolidated lungs from fluid in pleural space. It also detects
presence of loculations and fibrin strands, and volume of the
Empyema is more common in the poor socioeconomic group.
fluid in the pleural space. The sonologist can mark the spot
The incidence peaks between 6 months and 3 years of age.
for the aspiration of fluid and/or chest-tube insertion. The
Clinical signs vary depending on the type of organism isolated,
aspiration of fluid differentiates between sympneumonic
age of the patient, stage of the effusion, and type of prior
effusion and ET. Though ultrasound is useful to stage the ET in
antibiotic therapy.
children, it is not helpful in predicting its outcome.9
The bacterial pneumonia in children usually presents
with cough and fever; development of pleuritic chest pain and
dyspnea heralds complication of ET. Children may lie on the Computed Tomography Scan
affected side in attempt to splint the chest. The breath sounds The role of routine computed tomography (CT) is controversial.
and respiratory movements’ decreases on the side of empyema. The CT scan often requires general anesthesia or sedation,
There may be shift of the mediastinum. Often scoliosis is seen which may be a limiting factor in some very small and sick
toward the affected side on both clinical examination and chest child. CT scan also gives lot of radiation. Its role is limited in
X-ray. This occurs initially in an attempt to reduce the pleural patients, who are not responding to the treatment. The CT scan
pain and later on due to the result of fibrosis of the parietal precisely shows site of fluid collection, thickness of fibrotic
pleura. In late stages of ET, the ipsilateral chest is collapsed with peel, its location, and whether it is on visceral surface of lung
crowding of ribs leading to obliteration of intercostal space, or on diaphragm or chest-wall. This information is useful to
pulling of mediastinum, and diaphragm on the side of ET and endoscopic surgeons for the port placement to avoid trauma
scoliosis. The patients can develop pyopneumothorax due to air to the lung and subsequent PPF or BPF. Though the CT scan
leak either from lung parenchyma [parenchymo-pleural fistula can demonstrate the lung parenchyma and it pathologies
(PPF)] or by erosion of bronchus [bronchopleural fistula (BPF)]. accurately, it is unable to identify the presence of thin fibrinous
strands in pleural fluid. Coren et al. reviewed the use of CT
scanning in preoperative assessment and found that CT scans
INVESTIGATIONS
were least useful in the preoperative assessment of empyema
Investigations are performed to determine quantity and complicating community-acquired pneumonia.
quality of fluid present in the pleural space and its effect on the
cardiorespiratory system. Clinical Pearls
• X-ray chest posteroanterior view should be done in all children
Chest Radiograph in whom an empyema is suspected
All children with symptoms suggestive of febrile respiratory • Ultrasound is the most informative investigation
illness should have a chest X-ray posteroanterior view. Blunting • Computed tomography scan is reserved for patients who are
of costophrenic angle and pleural shadowing suggests presence not responding to treatment or as a preoperative investigation.
of free fluid in the pleural space. Massive fluid accumulation
in the chest may show opacified hemithorax with or without
mediastinal shift. Presence of air fluid level suggests either Hematological Investigations
anaerobic infection, or BPF or PPF. Advanced stage of the The total blood count may reveal anemia, leukocytosis with
disease may show fibrosis where the mediastinum is pulled polymorphonuclear predominance, and thrombocytosis and
toward the fibrosed pleura. The chest X-ray is not helpful raised C-reactive protein. The falling levels of white blood
in monitoring the progress of the disease and radiological cell count and C-reactive protein are indicative of clinical
610 features lag behind the physiological changes. improvement. Thrombocytosis is common in many chronic
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Chapter 125: Empyema Thoracis: Management Algorithm
inflammatory conditions including empyema. However, low ensure adequate cover for S. pneumonia, and consideration
platelet count with low hemoglobin in a child with empyema should be given to antistaphylococcal cover, particularly if
should alert the physician about possibility of the hemolytic pneumatoceles are present. Adequate anaerobic cover should
uremic syndrome, which often develops secondary to be given when there is a clinical suspicion for aspiration
neuraminidase release by Streptococcus pneumonia. pneumonia. Once the child is afebrile then child can be shifted
The coagulation studies are usually normal in healthy to oral therapy, which can extend up to 6 weeks.
children with normal liver. However, children with impaired
liver and chronic malnutrition may have abnormal blood Pleural Cavity Drainage
coagulation. Single screening of coagulation should suffice at
the time of initial venous cannulation. Clinical Pearls
Clinical Pearl Modalities for Drainage
• Resolution of fever, falling levels of total leucocyte counts and • Multiple needle thoracocentesis
C-reactive protein are favorable indicators. • Tube drainage of chest with or without fibrinolytics
• Video-assisted thoracic surgery
• Open thoracotomy.
Pleural Fluid Analysis
Pleural fluid tapping is highly informative, however, the
procedure is challenging as it might require sedation in a Timing of Drainage
sick child. Small collections are best left alone. The fluid is The timing of pleural cavity drainage should be individualized
examined for Gram staining, aerobic and anaerobic culture, depending upon the local expertise and the balance of
pH, specific gravity, protein content, glucose estimation, and noninvasive monitoring and expectant management. The
LDH levels. The specimen should be sent for microscopy and decision to intervene and drain the fluid is taken when the fluid
culture. The reported rate of isolating a pathogen varies and analysis is suggestive of empyema and/or if child develops
depends on the prior antibiotic usage. If facilities permit 16s respiratory distress (Algorithm 1).
ribosomal RNA ploymerase chain reactions (PCR) should be
done and suitable antibiotics should be instituted. The fluid
Options for Drainage
should also be cultured for Mycobacterium tuberculosis..
Aspiration is done under local anesthesia with sedation at
Clinical Pearls the most dependent site or in the fifth intercostal space in
midaxillary line. In the exudative stage, it may be possible to
• Pleural fluid is sent for microscopy, cytology and culture aspirate ET completely; however, as the pus becomes thicker
• Polymerase chain reaction if available should be used and flakes of fibrinopurulent material starts forming, it is not
• There is no role of biochemical markers in children. possible to aspirate the ET completely. Some studies have
compared the efficacy of repeated thoracocentesis to that of
chest tube drainage and found both comparable. These studies
MANAGEMENT concluded that repeated needle aspirations are more traumatic;
require multiple anesthesia and ultrasonography assistance.
The broad principles in management of empyema include These studies recommend early chest tube insertion.
treatment to stop ongoing sepsis, restoring the normal lung Chest tube drainage along with parenteral antibiotic
volume, and reestablish the physiological pleural fluid is the standard management in the exudative stage and in
circulation. The child’s hemodynamic status should be fibrinopurulent stage. Addition of fibrinolytics shortens the
stabilized with oxygen therapy, parenteral fluids, antipyretics, duration of the chest drainage and improves the clinical
and analgesia. outcome. Adequate chest drainage and good broad-
spectrum antibiotics resolve the fever and leukocytosis, with
Clinical Pearl almost complete lung reexpansion as seen on X-ray and/
• Sterilize and evacuate the thorax at the earliest or sonography. The chest drainage should be continued till
drainage decrease to less than 10–15 mL/day, which usually
takes 7–14 days. The successful resolution with conservative
Antibiotics management has been reported in 65–82% of the patients, and
Antibiotics alone have a role in small effusions in which the rest will require surgical therapy.
child has no respiratory compromise. The choice of antibiotic
should be based on local policy on pneumonia guidelines Clinical Pearl
and knowledge of both community and hospital acquired
• More than two-thirds of early empyema can resolve with
pathogens. The antibiotics are selected empirically and standard management of antibiotics and chest tube drainage.
changed according to the Gram staining and culture sensitivity Remaining needs surgical intervention.
of the aspirated pus. Broad-spectrum antibiotics are used to 611
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Algorithm 1
Management algorithm for empyema in children
USG, ultrasonography; ICD, intercostal drainage; VATS, video-assisted thoracoscopic surgery.
Pepperpoint et al. compared and reviewed the outcomes lymphatics, and liquefy the pus. The literature is replete with
in terms of length of hospital stay and the need for further case series describing the management using streptokinase,
intervention in children with empyema treated either with urokinase, aleptase, or tissue plasminogen activator in various
a stiff large bore tube or with small bore pig tail catheter. The different protocols.
outcomes were significantly better in children who received In fibrinopurulent stage with loculations and in organizing
small bored catheter. It has been observed that the most of the stage, the simple chest drain or cyclical irrigation is unlikely to
patients in India presents late and they do better with large work and they would need either formal decortication or video-
bore chest drain then pigtail catheter. assisted thoracoscopic surgery (VATS). In fibrinopurulent
Satish et al. in their study conducted in the secondary referral stage, it is more of pleural debridement and breaking up of
center on 14 children concluded that chest drainage along with the loculations, which ensures adequate drainage. This can be
antibiotics is sufficient to treat empyema. They also suggested safely accomplished by VATS. Open decortication is required in
there is no need for surgical decortications in children. However, a miniscule number of advanced cases of empyema. The term
in this study, the physiological and radiological resolution was decortication refers to the removal of the thick fibrotic parietal
obtained up to 16 months. The prolonged hospital stay, coupled and visceral pleural peel found in the late chronic disease is
with the extraordinarily long recovery of lung has significant accomplished with open thoracotomy either with or without
economic, social, and academic implications of a growing rib resection.
child. Spencer in his editorial comment observed, “it is not time
to put the knife down”. Clinical Pearl
As the duration of the empyema advances, there is increased
• Early surgical intervention allows faster recovery and rapid
fibrin formation and this result in loculated pus pockets. Use lung expansion.
612 of fibrinolytics in pleura is to lyse the fibrin strands, clear the
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Chapter 125: Empyema Thoracis: Management Algorithm
The term primary and secondary VATS is used for the that children who underwent primary VATS significantly
procedures performed before or after the trial of standard reduced hospital stay compared to those who had secondary
management, respectively. VATS offsets many disadvantages VATS or open decortications for failed medical treatment.
of open thoracotomy and provides excellent vision of the Cohen et al. compared results of primary VATS with
entire hemithorax. The primary VATS allows determination chest drainage alone and found significant reduction in
of the stage of the disease, breaking of all loculi with complete the hospital stay (7.4 vs. 15.4 days) and removal of chest
evacuation of thick pus, and fibrinopurulent material. In drain (4.0 vs. 10.2 days) in VATS group. In addition, 39% of
early stage, it may reduce the bacterial load and chest drain children with chest drainage alone required some other form
is inserted in the proper dependent position. In addition, of surgical intervention. This study clearly demonstrates the
VATS gives visual impression of condition of underlying lung, superiority of VATS over chest drain alone. This observation
its capacity to expand, and presence, site, and size of PPF or has been confirmed from different centers. There are no
BPF. However, it may be difficult to perform formal resection studies comparing primary VATS with open decortication in
of lung parenchyma to control the air leak using VATS in children. Subramanium et al. demonstrated reduced hospital
small children. The almost complete removal of thick pus and stay in VATS group of children in comparison to the open
fibrinopurulent material results in early resolution of fever, thoracotomy group in children who were referred for the
chest drain is required for short duration and postprocedure failure of medical treatment.
hospitalization is reduced to 6–7 days. VATS causes minimal Gates et al. carried out a systematic review of 44 retrospective
disturbance in the anatomy of nerves, muscles, and ribs. The studies to assess the superiority of VATS over chest drainage
integrity of the chest wall and the dynamics of the respiration alone, fibrinolysis, or thoracotomy. They concluded VATS and
are not disturbed. Kyphoscoliosis is avoided in children who open decortication led to early recovery in children. The study
undergo VATS. The less invasive nature of VATS produces less also identifies the lack of properly designed study to answer
pain and better postoperative lung movements. This finally the question of superiority of VATS over the other available
translates into early recovery and excellent cosmesis. The modalities of treatment.
aesthetic appearance and the normal anatomy of the spine
and the rib cage improve the child’s posture and self esteem.
The above-mentioned benefits make VATS as an attractive Clinical Pearl
option in treatment for empyema in children. Moreover, the
• Multiple studies throughout the world have confirmed the
VATS reduce the cytokine response of the body in comparison safety, efficacy, and cost effectiveness of video-assisted thoraco
to open thoracotomy. scopic surgery in the treatment of empyema in children.
However, VATS needs general anesthesia, operating room,
endoscopic equipment, and team of experienced anesthetist
and endoscopic surgeon. Some of the very sick patients
undergoing VATS may need postprocedure careful monitoring, Key points
preferably in pediatric intensive care unit. The primary VATS in
))
Empyema thoracis is a complex pediatric surgical disease and
ET have been reported to have the best outcome. The author
the best standard of care involve pediatric surgeon as soon as
recommends primary VATS if patient presents late (>7 days it is suspected
history) or if there are loculations on imaging studies as the ))
Management needs to be individualized depending upon
standard management is likely to fail. If thick fibrotic peel does the presentation and stage of disease
not allow dissection to proceed to create enough space then ))
For patient presents early (<7 days of symptoms), standard
the open decortication by minithoracotomy with or without rib management can be offered in the form of intravenous
resection should be performed. antibiotics and intercostal drainage
Open thoracotomy and decortication involves opening ))
Patients presenting late (>7 days of symptoms), or having
of the thorax posterolaterally and excision of the thickened loculations on imaging studies (X-ray or ultrasonography of
pleural encasing the lung. Lung pathologies like lung chest) should be offered primary video-assisted thoracoscopic
abscesses, necrotic lung, and BPF, if any, can be addressed surgery
simultaneously. It is an excellent modality of treatment useful ))
Patients who fails to respond to standard management
in the treatment of advanced stage of empyema. Long-term clinically and radiologically in 48–72 hours should be offered
aftereffects of open thoracotomy are often crippling. secondary video-assisted thoracoscopic surgery
Alexiou et al. reviewed their data of 44 children and ))
Patients having chronic disease with crowding of ribs should
concluded that open decortications are an excellent option for be offered an open surgery
treating of advanced empyema. Fibrinolysis and VATS should ))
Video-assisted thoracoscopic surgery in treatment of empyema
be considered on their own merits, and should not be based on has decreased morbidity and mortality of the disease
the adverse outcomes of open thoracotomy. ))
In India, due to limited availability of resources and the
endoscopic surgical expertise, many patient who fails to
In the past, VATS was used after the failure of medical
received standard care may need either referral to higher
therapy, now it is increasingly used as primary therapy. In an center or an open surgery at appropriate time.
study from Dallas on 139 children, Doski et al. demonstrated
613
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SUGGESTED READINGs 15. Jaffé A, Cohen G. Thoracic empyema. Arch Dis Child. 2003;88:839-41.
16. McAvin JC, Reilly PA, Roudabush RM, et al. Sensitive and specific method for
1. Alexiou C, Goyal A, Firmin RK, Hickey MS. Is open thoracotomy still a good rapid identification of Streptococcus pneumoniae using real-time fluorescence
treatment option for the management of empyema in children? Ann Thorac Surg. PCR. J Clin Microbiol. 2001;39(10):3446-51.
2003;76:1854-8. 17. Merry CM, Bufo AJ, Shah RS, Schropp KP, Lobe TE. Early definitive Intervention by
2. Balfour-Lynn IM, Abrahamson E, Cohen G, Hartley J, King S, Parikh D, et al. thoracoscopy in pediatric empyema. JPS. 1999;34:178-80.
BTS guidelines for the management of pleural infection in children. Thorax. 18. Mitri RK, Brown SD, Zurakowski D, Chung KY, Konez O, Burrows PE, et al.
2005;60(1):1-21. Outcomes of primary image-guided drainage of parapneumonic effusions in
3. Chan W, Keyser-Gauvin E, Davis GM, Nguyen LT, Laberge JM. Empyema thoracic children. Pediatrics. 2002;110:e37.
in children: a 26-year review of the Montreal Children’s Hospital experience. JPS. 19. Nyman AG, Pitchumani S, Jaffe A, Sonnappa S. Pneumococcal empyema
1997;32(6):870-2. and haemolytic uraemic syndrome in children: experience from a UK tertiary
4. Chiu CY, Wong KS, Huang JL Tasi MH, Lin TY, Hsieh SY. Proinflammatory cytokines, respiratory centre. Arch Dis Child. 2009;94(8):645-6.
fibrinolytic system enzymes, and biochemical indices in children with infectious 20. Peters RM. Empyema thoracis: historical perspective. Annals Thorac Surg.
para-pneumonic effusions. Pediatr Infect Dis J. 2008;27(8):699-703. 1989:48:306-8.
5. Chonmaitree T, Bwell KR. Parapneumonic pleural effusion and empyema. Review 21. Pierrepoint MJ, Evans A, Morris SJ, Harrison SK, Doull IJ. Pigtail catheter drain in
of a 19 year experience, 1962-1980. Clin Pediatr. 1983;72:414-9. the treatment of empyema thoracis. Arch Dis Child. 2002;87:331-2.
6. Cohen G, Hjortdal V, Ricci M, Jaffe´ A, Wallis C, Dinwiddie R, et al. Primary 22. Satish B, Bunker M, Seddon P. Management of thoracic empyema in childhood:
thoracoscopic treatment of empyema in children. J Thorac Cardiovasc Surg. does the pleural thickening matter? Arch Dis Child. 2003;88:918-21.
2003;125:79-84. 23. Shoseyov D, Bibi H, Shatzberg G, Klar A, Akerman J, Hurvitz H, Maayan Cl. Short-
7. Coren ME, Ng M, Rubens M, Rosenthal M, Bush A. The value of ultrafast
term course and outcome of treatments of pleural empyema in pediatric patients:
computed tomography in the investigation of pediatric chest disease. Pediatr
repeated ultrasound guided needle thoracocentesis vs. chest tube drainage.
Pulmonol. 1998;26:389-95.
Chest. 2002;121:836-40.
8. Doski JJ, Lou D, Hicks BA, Megison SM, Sanchez P, Contidor M, et al.
24. Singh M, Singh SK, Chowdhary SK. Management of empyema thoracic in
Management of parapneumonic collections in infants and children. J Pediatr
children. Indian Pediatrics. 2002;39:145-57.
Surg. 2000;35:265-8.
25. Sonnappa S, Cohen G, Owens CM, van Doorn C, Cairns J, Stanojevic S,
9. Gates RL, Hogan M, Weinstein S, Arca MJ. Drainage, fibrinolytics, or surgery:
et al. Comparison of urokinase and video-assisted thoracoscopic surgery for
a comparison of treatment options in pediatric empyema. J Pediatr Surg.
2004;39:1638-42. treatment of childhood empyema. Am J Respir Crit Care Med. 2006;174(2):
10. Hamm H, Light RW. Parapneumonic effusion and empyema. Eur Respir J. 221-7.
1997;10(5):1150-6. 26. Sonnappa S, Jaffe A. Treatment approaches for empyema in children. Paediatr
11. Hoff SJ, Noblett WW, Heller RM, Pietsch JB, Holcomb GW Jr, Sheller JR, et al. Post Respir Rev. 2007;8:164-70.
pneumonic empyema in childhood: selecting appropriate therapy. J Pediatr Surg. 27. Spencer D. Empyema thoracis: not time to put down the knife. Arch Dis Child.
1989;24:659-64. 2003;88:842-3.
12. Hull J, Thomson A. Empyema thoracis: a role for open thoracotomy and 28. Subramaniam R, Joseph VT, Tan GM, Goh A, Chay OM. Experience with video-
decortication. Arch Dis Child. 1999;80:581. assisted thoracoscopic surgery in the management of complicated pneumonia in
13. Jaffe A, Balfour-Lynn IM. Management of empyema in children. Pediatr Pulmonol. children. J Pediatr Surg. 2001;36:316-9.
2005;40(2):148-56. 29. Telunder RL, Moir CR. American Thoracic Society. Management of nontuberculous
14. Jaffe A, Calder AD, Owens CM, Stanojevic S, Sonnappa S. Role of routine empyema. Am Rev Respir Dis. 1962;85:935-6.
computed tomography in paediatric pleural empyema. Thorax. 2008;63(10): 30. Yim AP, Wan S, Lee TW, Arifi AA. VATS lobectomy reduces cytokine responses
897‑902. compared with conventional surgery. Ann Thorac Surg. 2000;70:243-7.
614
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CHAPTER 126
Evaluation of Acute
Abdominal Pain in Children
Ketan P Parikh
INTRODUCTION The fact that abdominal pain is so elusive is often a cause

for it being labeled as functional or psychogenic in some
The abdomen has often been labeled as a Pandora’s box. cases. However, it needs to be emphasized that the labeling of
This analogy is rooted in the fact that in many situations, the this pain as psychogenic should be an opinion of exhaustive
clinical presentation and investigative conclusions are rivaled exclusion rather than a default assumption.
by the finally ascertained diagnosis. Thus, every patient of an In spite of the multitude of investigative armamentarium
acute abdominal pain needs to be evaluated systematically to available, evaluation of a child with an acute abdomen relies
ascertain the most likely etiology to avoid long-term morbidity significantly on the clinical assessment and its correlation with
or an occasional mortality. the investigations. In doubtful situations, repeated physical
The term acute abdominal pain refers to a sudden, examination by the same physician is often useful.
severe pain in the abdomen of short duration—usually of
24–48 hours. In contrast the term acute abdomen refers to ))
Visceral pain: usually dull, poorly localized and in the midline
a clinical condition with other manifestations which may ))
Parietal pain: sharp, localized.
include (besides the acute abdominal pain) a variety of other
symptoms more particularly: vomiting, abdominal distension,
fever, constipation, or diarrhea besides other symptoms. There PAIN HISTORY
may be an element of general toxicity due to dehydration or
septicemia necessitating a more detailed assessment. The chronology of the clinical presentation and the age of the
child are important in the evaluation. In the acute surgical
abdomen, pain generally precedes vomiting, while the reverse
PATHOPHYSIOLOGY is true in medical conditions.
Clinically, three categories of pain may arise from the abdomen: Most preadolescents have a poor sense of onset or location
• Visceral (splanchnic) pain: it results from stimulation of a of pain. In children who cannot verbalize, the initial symptoms
viscous with a noxious stimulus like stretching or ischemia. of nausea or periumbilical (visceral) pain may go unnoticed,
It is usually dull, poorly localized, and is experienced in the and thus they often present at the second stage of visceral pain.
midline. Pain arising from foregut structures (e.g., lower A neonate or an infant with abdominal pain may express in
esophagus, stomach) is generally felt in the epigastrium, the form of excessive crying, transient apneic spells or even
from midgut structures (small intestine) to the umbilical grunting. These subtle symptoms require astute supervision to
area and from hindgut structures to the hypogastrium raise an early alarm to avoid missing life-threatening surgical
• Parietal pain: it follows a noxious stimulation of the emergencies.
parietal peritoneum. It is experienced with inflammation
of the parietal peritoneum. It is usually sharp, discrete, and ))
Pain preceding vomiting: possibly surgical abdomen
localized, and aggravates on coughing or movement ))
Vomiting preceding pain: more likely medical abdomen.
• Referred pain: it has characteristics of parietal pain but is
felt in remote areas supplied by the same dermatome as Associated symptoms which have a significant bearing are:
the diseased organ. A classic example: abdominal pain • Vomiting (Table 1):
experienced due to the supradiaphragmatic irritation of {{ Nonbilious vomiting:
pleura due to a lobar pneumonia. –– Common with a routine gastroenteritis

SECTION 15: Pediatric Surgery
TABLE 1: Associated clinical features in a patient with acute abdominal pain

Vomiting Before onset of pain Possibly medical cause
After onset of pain More likely to be surgical cause—e.g., appendicitis/intestinal
obstruction
Bilious More likely to be surgical cause—e.g., intestinal obstruction
Nonbilious May be either medical condition (gastritis/hepatitis, etc.) or
early surgical cause
Abdominal distension After excessive crying especially in a small child Aerophagia
With acute constipation Possibly surgical, e.g., intestinal obstruction
Upper abdominal distension Possibly an upper abdominal obstruction
With diarrhea Severe watery → ?enterocolitis
Persistent but small quantity → ?peritonitis
Constipation Absolute (feces + flatus) Intestinal obstruction
Passing more flatus Aerophagia (possibly supradiaphragmatic cause)
Fever If after 1 or 2 days of abdominal pain Surgical cause like appendicitis/peritonitis, etc.
If precedes abdominal pain More likely to be inflammatory like enterocolitis
Loose motions If feculent Enterocolitis
Mainly mucus/blood Intussusception/peritonitis/high intestinal obstruction
Dysuria Abnormal ultrasonography Maybe renal colic
Normal ultrasonography Maybe appendicitis, especially if pain is right sided
Gait Walking with stoop on one side Appendicitis/psoas irritation
Abdominal movements Restricted ?Peritonitis
Cough/shortness of breath — Pleural pathology
Joint pains/skin purpura — ?Henoch–Schönlein purpura
–– It is also an early feature of a surgical abdomen

(an intussusception) or an inflammatory cause
(like an acute appendicitis)
–– Persistent nonbilious vomiting along with abdo
minal pain at any age may also be seen in peritonitis.
These patients may have fever/abdominal distension
and constipation. A child with meconium peritonitis
with secondary bacterial peritonitis may also have a
periumbilical mottling besides radiological features
of calcification in a case of intestinal obstruction/
peritonitis (Fig. 1)
–– Some of the urogenital causes of acute abdomen
may also have nonbilious vomiting:
■■ Pyelonephritis—hypertension, urine exami
nation, abdominal USG
■■ Testicular torsion—clinical examination
■■ Ovarian torsion—USG or other imaging
Fig. 1: Mottling of the abdominal wall in an infected meconium
■■ Renal colics—dysuria/USG
peritonitis
■■ Bilious vomiting at almost any age signifies an
intestinal obstruction unless proved otherwise
• Abdominal distension: it is usually a late sign in most cases {{ Fluid in the peritoneal cavity—in an acute abdomen
of acute abdomen. It may result from: this may suggest peritonitis
{{ Gas (aerophagia)—predominant gaseous distension is {{ If accompanied by acute constipation or obstipation—
more a feature of hypoperistalsis surgical cause
{{ Intestinal obstruction—usually distension is a late {{ A neonate with a scaphoid abdomen or distension
symptom and may present as visible/palpable loops of restricted to upper half could possibly either be:
616 bowel –– A high bowel atresia (duodenal/high jejunal)
CHAPTER 126: Evaluation of Acute Abdominal Pain in Children
–– A midgut volvulus due to an intestinal malrotation • Loose motions: note the content of loose motions:
especially if there is a delayed onset of intestinal {{ If feculent—more chances of enteritis/colitis
obstruction {{ If mucoid—need to consider surgical causes
■■ In either case, a surgical exploration would be • Bleeding per rectum:

needed; a delay in surgically exploring a case of {{ In infants—typical currant jelly stools (mucoid mixed
midgut volvulus could lead to extensive gangrene with blood): high chances of intussusception
of the entire midgut which is incompatible to {{ If content is predominantly altered blood with mild
normal life without life-long total parenteral colics, consider bleeding due to a Meckel’s diverticulum
nutrition/intestinal transplantation {{ After 2 years of age—mild bleeding with feces with
■■ In those cases where the abdominal distension abdominal pain (not severe)—there is possibility
is more generalized, a lower intestinal obstruc of rectal juvenile polyps leading to localized intus
tion may be considered susception
{{ If accompanied with diarrhea:
• Dysuria:
–– Either severe enterocolitis (there would also be {{ In case with lateralized colics—renal colics
frequent passage of flatus) or peritonitis (there is {{ If right-sided pain with dysuria, the possibility of acute
usually infrequent passage of flatus and minimal appendicitis with ipsilateral ureteric/vesical irritation
fecal content) is a strong indication for a surgical can be a possibility and needs to be ruled out
opinion. Bogginess in the prerectal space on a per- • A history of recent trauma may indicate the cause of pain
rectal examination would almost be diagnostic of a {{ Additional history:
pelvic peritonitis –– Cough or shortness of breath, and chest pain point
–– An acute appendicitis in a pre-school child may to a thoracic source
present directly as peritonitis because of the –– Polyuria and polydipsia suggest diabetes mellitus
subtlety of the early symptoms and the rapid –– Joint pain, rash, and smoke-colored urine suggest
progression of the pathology at this age Henoch-Schönlein purpura
• Constipation: unlike chronic constipation, acute consti
–– High fever with toxicity acute hemolytic syndromes
pation usually has an organic cause:
like malaria/dengue which may mimic an acute
{{ Absolute constipation (obstipation—failure to pass
abdomen
feces/flatus)—strongly suggests a surgical cause of
–– Medication: a detailed drug history especially
acute abdomen
salicylates/nonsteroidal anti-inflammatory drugs/
{{ Frequent passage of flatus in a patient with abdominal
steroids
distension—possibly medical cause/pneumonia
{{ Chronic constipation preceding abdominal pain—
–– Gynecologic history: relevant especially in adoles
cent girls
more likely primary constipation
{{ Constipation following vomiting and abdominal pain— Past history: all previous hospitalizations or significant illnesses,
more likely surgical. Child may pass 1 or 2 normal e.g., sickle cell anemia/porphyria. A history of previous surgery
stools and constipation may set in later once the bowel or peritonitis may suggest adhesive obstruction.
distal to the obstruction is completely evacuated. In
neonates with congenital bowel obstruction, there may Family history: family history of sickle cell/or cystic fibrosis
be a history of passage of some meconium, but in most may indicate the diagnosis.
cases, direct questioning of the neonate’s attendant
may reveal that this meconium was pale colored. In CLINICAL EXAMINATION
those cases where the neonates acute abdomen has set
in a few days after the passage of normal meconium,
General Examination
the possibility of volvulus with malrotation becomes
higher A throat examination to identify enlarged tonsils leading to
{{ In the occasional patient with high obstruction and a swallowed gastrointestinal infection, a chest examination
peritonitis, the baby may pass loose motions due to rule out a pleural/pulmonary pathology is important
to peritoneal irritation of the distal bowel; however, complimentary clinical guide.
this would be predominantly mucoid and not bile
containing Gait
• Fever:
While a child with colics writhes with pain, children with
{{ If the acute abdominal pain follows a febrile illness, it
peritonitis remain quite still and resist movement. A patient
is likely to be secondary to gastroenteritis or gastritis
with acute appendicitis typically walks with a stoop to the right.
resulting from the medications
{{ However, if fever follows, an acute abdominal pain
episode for 1–3 days—possibility of localized or Vital Signs

generalized peritonitis/liver abscess or some other Dehydration (severity needs to be assesed), fever if any.
inflammatory pathology of the abdomen or even chest Kussmaul’s respiration indicates diabetic ketoacidosis. 617
Abdominal Examination
The abdominal movements should be observed, and the
patient should be asked to distend the abdomen and then
flatten it. Restricted abdominal movements indicate a
peritoneal irritation in that area:
• Visible contusions would suggest a traumatic etiology
• A definite examination of the hernial orifices is mandatory
in any case of acute abdominal pain since a strangulated
hernia may present as an acute abdomen (Fig. 2)
• Mottling of the abdomen may indicate an inflammatory
etiology especially in a neonate (Fig. 1)
• Tenderness of abdomen needs to be evaluated with the
palmar (flat) surface of the fingers rather than the tips
of the fingers (Figs 3 and 4). In a crying child, it is best Fig. 4: Avoidance of palpating the abdomen with the tips of the
evaluated between breaths whereas other children may fingers
be asked to take deep breaths with an open mouth to relax
the abdominal muscles. Since smaller children are not • A per rectal examination may reveal a loaded rectum
able to localize parietal pain well, guarding/rigidity is more leading to constipation and abdominal pain/a bogginess
relevant than tenderness in the pelvis indicative of a peritonitis/blood in the rectum
• Deeper palpation is necessary to discover masses and or a palpable rectal polyp.
organomegaly
INVESTIGATIONS (TABLE 2)
These should be tailored to the patient’s symptoms and clinical
findings.
TABLE 2: Investigative algorithm in a case of acute abdominal

pain
White blood Marginally high Appendicitis/intestinal
cell count obstruction
Very high Perforated appendicitis/
peritonitis/liver abscess
Normal/low Hepatitis/mesenteric
adenitis/viral infections
Urinalysis Pyuria/hematuria Renal etiology/appendicitis
Erect Gas under Major G.I. perforation
abdominal/ diaphragm
chest film Fluid levels Bowel obstruction/paralytic
Fig. 2: Neonatal peritonitis presenting as acute scrotum due to the ileus
patent processus vaginalis
Ground glass Peritonitis
appearance
Raised diaphragm ? Liver abscess
(rt )
Pleural/pulmonary Consolidation/diaphragmatic
shadow hernia/pleural effusion
Abdominal Highly sensitive Ovarian pathology/
ultra renal pathology/
sonography hepatic inflammation/
(operator pancreatic inflammation/
dependent) intussusception
Poor sensitivity Maybe negative in many
bowel pathologies including
appendicitis
Diagnostic — Possible only if bowel
Fig. 3: Demonstrating the correct method of palpation of abdomen
618 (with the flat of the hand)
laparoscopy distension is not severe
• Hemogram: leukocytosis, especially in the presence of

a shift to the left and toxic granulations in the peripheral
smear, indicates an infection
• Urinalysis: pyuria, hematuria—may suggest a renal cause
or a gastrointestinal cause irritating the urinary tract,
e.g., appendicitis
• Erect/lateral decubitus—plain abdominal films:
{{ Gas under diaphragm—major gastrointestinal per
foration
{{ Fluid levels—bowel obstruction (Figs 5 and 6)
{{ Ground glass appearance with or without fluid levels—
peritonitis (Fig. 7)
• Chest radiographs: gas under diaphragm/pneumonia/
raised diaphragm due to a liver abscess.
• Abdominal ultrasonography (results are operator
dependent): most useful in diagnosing gynecologic
pathology such as ovarian cysts, ovarian torsion, or Fig. 7: Central fluid levels surrounded by groundglass appearance of
advanced periappendiceal inflammation (Fig. 8) peritonitis
• Abdominal computed tomography: involves radiation
exposure and may require the use of contrast agents.
Fig. 8: Ultrasonographic picture of an acutely inflamed appendix
Fig. 5: Multiple fluid levels (mid-intestinal obstruction)
computed tomography may be necessary if excessive

bowel gas precludes ultrasonographic examination
• Diagnostic laparoscopy: it is increasingly being used
prior to a surgical intervention and thus avoids a formal
laparotomy in selected cases. Some of these may include
acute appendicitis, Henoch-Schonlein pupura, Meckels’
diverticulitis, idiopathic omental necrosis, diagnosing a
nonviable bowel, loop, etc. (Figs 9–11).
Specific Conditions Causing Acute Abdomen Pain

The specific conditions causing acute abdomen pain are given
in table 3.
Infantile Colic
Infantile colic affects about 20% of infants during the first few
months of life. Typically, the affected children scream, draw
Fig. 6: Double-bubble shadow of duodenal obstruction their knees up against their abdomen, and appear to be in 619
severe pain. There may be associated symptoms like vomiting;

however, this is rarely persistent. Most infantile colics subside
within a few hours. The closest differential which one needs to
be aware of and needs to be eliminated is intussusception and
volvulus with malrotation. In case of persistence of symptoms
beyond 1–2 hours or in case of bilious vomiting, bleeding per
rectum, an abdominal ultrasonography should be asked for as
a screening test.
Gastroenteritis
Gastroenteritis is one of the most common causes of
abdominal pain in children. Vomiting and/or diarrhea
are usually associated and there may also be fever.
Differentiation from an intussusception is done by the fact
that in intussusception, the stools usually does not contain
fecal matter after one or two motions and there is only blood
Fig. 9: Laparoscopic view of gangrenous bowel and/or mucus.
Appendicitis
Appendicitis is the most common surgical condition in
children with acute abdomen.
Western literature places the incidence as approximately
1 in 15 persons. While older children may show the classical
pain—vomiting-fever chronology, younger children may
present directly as peritonitis. Most children have the pain
mainly in the periumbilical area with a few vomits and the
pain then shifts to the right side only after localized peritonitis
sets in. In spite of the various investigative modalities, acute
appendicitis still remains a clinical diagnosis and investigations
only have a supportive role.
Mesenteric lymphadenitis often mimics appendicitis.
Being primarily an adenoviral infection, fever is a more
prominent symptom. Generalized lymphadenopathy on
abdominal ultrasonography may be a feature with high fever
may suggest the same.
Fig. 10: Laparoscopic view of an acutely inflamed appendix (covered
with surrounding omentum
TABLE 3: Causes of abdominal pain according to age

Infants Almost any age Older children
• Infantile • Gastroenteritis • Ovarian/testicular
colic • Appendicitis torsion
• Volvulus • Urinary tract infection • Pelvic
• Incarcerated hernia inflammatory
• Peritonitis disease
• Cholecystitis • Mittelschmerz
• Hepatitis • Diabetic
• Pancreatitis ketoacidosis
• Inflammatory bowel • Porphyria
disease
• Trauma
• Mesenteric lymphadenitis
• Henoch-Schönlein
purpura
• Intestinal obstruction
• Sickle cell crisis
Fig. 11: Idopathic omental torsion with necrosis of the omentum
620 • Meckel’s diverticulum
Abdominal Trauma • Marked abdominal distension with diffuse tympany

• Signs of acute fluid or blood loss into the abdomen
Abdominal trauma can be accidental or intentional. There
• Significant abdominal trauma
may be a bowel perforation, intramural hematoma, laceration,
• Suspected surgical cause for the pain
or hematoma of the liver or spleen, and avulsion of intra-
• Abdominal pain without an obvious etiology.
abdominal organs or vascular pedicles. These patients may
benefit from an abdominal computed tomography scan
in addition to an abdominal ultrasonography. Diagnostic Clinical Pearls
laparoscopy has a definite role in selected patients. • In the acute surgical abdomen, pain generally precedes
Intussusception is common around 8–10 months of age vomiting, while the reverse is true in medical conditions
and occurs due to a hypertrophied Peyer’s patch (acting as a • While a child with colics writhes with pain, children with
lead point). Such a hypertrophy may occur due to a change in peritonitis remain quite still and resist movement
the bacterial flora during weaning or gastrointestinal infection • Bilious vomiting at almost any age signifies an intestinal
or due to ingestion of infected respiratory secretions. obstruction unless proved otherwise.
Clinically: • Constipation following vomiting and abdominal pain—more
• There may be a prior history of an upper respiratory tract likely surgical
infection • If fever follows an acute abdominal pain episode for 1–3 days—
• Colics: pain occurs in short bursts with intermittent periods possibility of localized or generalized peritonitis or some other
of remission inflammatory pathology
• Vomiting: bilious only in late cases • Restricted abdominal movements indicate a peritoneal
• Red currant jelly stools: usually with no fecal matter after irritation in that area
1–2 times (a differentiating feature from dysentery) • A definite examination of the hernial orifices is mandatory in
• On abdominal palpation: intussusception may be felt any case of acute abdomen
as banana-shaped mass with the concavity toward the • A patient with acute appendicitis typically walks with a stoop
umbilicus. Occasionally the mass can be felt per rectally to the right.
• In late cases: features of septicemia and peritonitis.
Investigations:
• Ultrasound of the abdomen can be diagnostic KEY POINTS
• Alternatively, a barium enema: the coiled spring sign or the
claw sign. ))
While, the term “acute abdominal pain” refers to a sudden,
severe pain in the abdomen of short duration, the term
Intestinal Obstruction “acute abdomen” refers to a clinical condition with other
manifestations which may include (besides the acute
Intestinal obstruction is uncommon in older children unless
abdominal pain) vomiting, abdominal distension, fever,
there is a previous history of abdominal surgery. Additional constipation, or diarrhea
causes include volvulus, intussusception, incarcerated hernia,
))
Labeling of abdominal pain as psychogenic should be
congenital, or postinflammatory bands including intestinal
an opinion of exhaustive exclusion rather than a default
tuberculosis. An erect abdominal X-ray would be diagnostic in
assumption
most cases. A trial of conservative management under surgical
supervision may be indicated in case there is no suspicion ))
Tenderness of abdomen needs to be evaluated with the
of bowel ischemia. Pain not responding to antispasmodics, palmar (flat) surface of the fingers rather than the tips of the
fingers
tender/palpable loop of bowel, evidence of perforation/
ischemia on imaging, and failure of conservative treatment ))
Plain vertical abdominal X-ray is as important as abdominal
for more than a few days will be indications for surgical ultrasonography in the evaluation of acute abdominal pain
intervention. ))
An acute appendicitis in a preschool child may present directly
Pelvic inflammatory disease or primary peritonitis is as peritonitis because of the subtlety of the early symptoms
typically seen in females and the diagnosis is more on laparo and the rapid progression of the pathology at this age.
scopic/surgical exclusion of known causes of peritonitis.
Indications for surgical consultations in children with
acute abdominal pain: SUGGESTED READINGS
• Severe or increasing abdominal pain with progressive signs 1. Cope Z Early diagnosis of the acute abdomen. Oxford University Press; 2005.
of deterioration 2. Fleisher GR, Ludwig S, editors. Textbook of pediatric emergency medicine. Li ppincott
• Bile-stained or feculent vomitus Williams and Wilkins; 6th revised edition.
• Involuntary abdominal guarding/rigidity 3. Paterson-Grown S, Ellis BW, Paterson-Brown S. Hamilton bailey’s emergency surgery.
• Rebound abdominal tenderness 13th ed. Boca Raton: CRC Press; 2015.
621
CHAPTER 127
Management of Undescended
Testis: Cryptorchidism
Rasik S Shah, Suyodhan A Reddy, Nachiket M Joshi
reflex pulls the testis into suprascrotal position. This testis

INTRODUCTION can be manipulated into a dependent scrotal position, by
Undescended testis (UDT) or cryptorchidism is the most making the patient relax his cremasteric muscle. The testis
common congenital abnormality of the genitourinary tract. It will remain there as long as the cremasteric muscles are
comprises of true cryptorchid or UDT, ectopic testis, absent relaxed.
testis, atrophic testis, retractile testis, and ascended testis. It is • Ascended testis: the testis, which has been documented
important to differentiate the aforementioned conditions, as to be in the scrotum in neonatal period, is found to be at
their individual management is different. higher position in later childhood is known as the ascended
testicle.
TERMINOLOGY
• Cryptorchidism: cryptorchidism, by definition, means PATHOGENESIS
absence of one or both testis in the scrotum The factors responsible for normal testicular descent are not
• True UDT: the testis, which has failed to descend along its well understood. The intra-abdominal phase of descent is
normal pathway from the retroperitoneum to the scrotum, thought to be androgen-independent and is mediated by a
is known as true UDT. If the testis remains in abdominal polypetide “descendin”. The testis passes through the inguinal
cavity then it is known as abdominal UDT; if it comes out canal in 28th week of gestation; it is believed to be the combined
of internal ring and goes back to the abdomen, then it is result of interactions between mechanical, hormonal, and
known as emergent UDT; if it is in inguinal canal, then it neurotransmitters. Changes in abdominal pressure, patency of
is known as intracanalicular UDT; if it is just outside the the processus vaginalis, gubernacular regression, androgens,
external ring, then it is known as suprascrotal UDT. gonadotropins, Müllerian inhibiting substance (MIS), and
• Ectopic testis: the testis, which has normally descended calcitonin gene-related peptide are all thought to play a role.
from retroperitoneum up to the external ring subsequently The pathogenesis of UDT is less understood than that of
gets deviated to an aberrant position, is known as ectopic normal testicular descent. Alterations in any of the factors
testis. It may be palpable in the superficial inguinal pouch
that contribute to normal testicular descent may theoretically
(most common), suprapubic region, femoral triangle,
result in UDT. Gonadotropin deficiencies in utero, decreased
or perineum. Rarely, testis travels via opposite internal
MIS, and increased expression of estradiol in the placenta have
ring into contralateral scrotal compartment and then it is
been proposed as contributing factors.
known as transverse testicular ectopia.
• Absent testis: testis which embryologically has failed to
develop is known as absent testis. EPIDEMIOLOGY AND RISK FACTORS
• Atrophic testis: the testis was developed normally and
at some stage, it has undergone atrophy secondary to At birth, 2–5% of full-term and 25–30% of premature male
vascular compromise. If it occurs in the prenatal period, infants are born with an UDT. Of these, in approximately 70%,
then it is also known as the vanishing testis syndrome or the testis descends spontaneously within first 2–3 months of
testicular regression syndrome. life and is unlikely to descend after 3 months. At 1 year of age,
• Retractile testis: the testis normally descends to the the prevalence of UDT is around 0.8–1%, which is similar to
scrotum at birth; however, the hyperactive cremasteric that in adults.
CHAPTER 127: Management of Undescended Testis: Cryptorchidism
The prevalence of UDT varies geographically, which may COMPLICATIONS AND SEQUELS
be due to genetics or environmental factors. Prematurity, being
small for gestational age at birth, and birth weight less than Complications and sequels of UDT include inguinal hernia,
2.5 kg are common risk factor. Prenatal exposure to endocrine testicular torsion, testicular trauma, subfertility, and testicular
disruptors (e.g., diethylstilbestrol, pesticides) also has been cancer. The potential seriousness of these complications and
associated with cryptorchidism in some studies. sequels demands early referral for definitive treatment (Box 2).
Associated Conditions Inguinal Hernia

Cryptorchidism usually is an isolated finding. However, it The UDT have an associated patent processus vaginalis in
may occur in association with endocrine disorders, genetic about 60% cases. Inguinal hernia in UDT can present at any
syndromes, and morphologic abnormalities, especially if it is age with the typical symptoms or complications, including
bilateral. Associated conditions are shown in box 1. incarceration.
Clinical Pearl Testicular Torsion

• Patients having undescended testis and hypospadias have Testicular torsion is approximately ten times more common in
high incidence of underlying disorders of sexual development. UDT than in normal scrotal testis, but the true relative risk is
not known. The rate of salvage of torsion in cryptorchid testis
is decreased compared to that in normally descended testis,
CLINICAL FEATURES perhaps related to delay in diagnosis.
If patient with inguinal testis develops the torsion, then he
Clinical features of cryptorchidism include an empty, will present with local swelling and tenderness with an empty
hypoplastic, hypopigmented, and poorly developed rugae of ipsilateral hemiscrotum. If patient with intra-abdominal testis
scrotum or hemiscrotum. Inguinal fullness may be present. develops torsion, then he will present as an acute abdomen
In approximately 10%, it is a bilateral condition. Bilateral with empty one side of scrotum and usually diagnosis of
UDT are more commonly associated with other conditions. torsion is made only at the time of abdominal exploration.
Unilateral UDT is more common on left side.
The most common location for an UDT is just outside the Testicular Trauma
external ring (superficial inguinal pouch), followed by the
inguinal canal (intracanalicular), and finally intra-abdominal. Testis located in the inguinal canal is at increased risk of blunt
The testis is not palpable in 20% of patients with UDT. traumatic injury from compression against the pubic bone.
The growth of unilateral UDT is impaired compared
with the normally descended contralateral testis, whether it Subfertility
descends spontaneously or it is surgically brought in scrotum. Men with a history of UDT have lower sperm counts, sperms
Treatment before 1 year of age is associated with partial catch- of poorer quality, and lower fertility rates than men with
up of growth. normally descended testis. Impaired spermatogenesis is
probably related to underlying genetic, hormonal, and
Box 1: Associated conditions developmental abnormalities, some of which may be partially
• Prune belly syndrome reversible through early surgical intervention. Sperm counts in
• Myelomeningocele adulthood are directly related to prepubertal germ cell counts
• Cerebral palsy and type of cell (gonocyte versus adult dark spermatogonia) at
• Disorders of sexual development the time of orchidopexy. The local milieu reduces the number
• Genetic disorders with diminished testosterone production of Leydig cells, which produce testosterone. Testosterone plays
{{ Kallamann syndrome an important role in maturation of gonocyte to dark adult
{{ Klinefelter syndrome spermatogonia. This affects both quality and quantity of the
{{ Prader-Willi syndrome mature germ cells in the testis.
{{ Androgen insensitivity syndrome The degree of germ cell dysfunction increases with bilateral
• Genetic disorders involvement and with increasing duration of suprascrotal
{{ Noonan’s syndrome location. Intra-abdominal and intracanalicular UDT are
• Primary hypogonadism with increased gonadotropin levels affected similarly, probably related to the damaging effect of
{{ Laurence-Moon syndrome higher temperatures outside the scrotum on spermatogenesis.
• Other genetic disorders Elevated serum gonadotropin [follicle stimulating hormone
{{ Trisomy 18 (FSH) and luteinizing hormone (LH)] concen tration and
• With no effect on testosterone and gonadotropin levels
{{ Trisomy 13
Box 2: Complications and sequels of undescended testes
{{ 22q11.2 deletion syndrome
{{ 1p36 deletion syndrome

• Hernia • Subfertility
{{ Beckwith-Wiedemann syndrome Smith-Lemli-Opitz syndrome • Torsion • Testicular cancer with late 623
Cornelia de Lange syndrome, etc. • Trauma detection
decreased serum inhibin B concentration are endocrinologic these investigations induce confusion in minds of parents. On
markers of testicular dysfunction. imaging, if the testis is not visualized and surgeon recommends
surgery, then they start thinking although that testis is not seen
Testicular Cancer and even then the surgeon still wishes to operate. If the surgeon
explains why surgery is essential, then the parents might raise
Men with a history of UDT have an increased risk of developing
the query that if the surgeon has already decided to operate
testicular cancer compared with men in the general population
upon then what was the need to doing imaging studies. In
in whom the age adjusted incidence is approximately 5.4 per
order to avoid confusion, it is safer not to order investigations
100,000. The epidemiological data points toward a definite
for locating testis.
relationship between the intrauterine, perinatal development
The goal is to bring the apparently normal looking testis
and UDT.
into the scrotum from its abnormal position and to prevent
The risk of developing testicular cancer is further increased
the complications. It is essential to pex testes into scrotum to
in men with bilateral cryptorchidism (which may be associated
prevent postoperative ascent. Small atrophic testes should be
with endocrinologic abnormalities or abnormal karyotype)
removed.
and intra-abdominal UDT.
The testis in scrotal position is less likely to undergo torsion
A history of cryptorchidism is also a risk factor for
or blunt traumatic injury. In addition, it also permits easier self-
developing intratubular germ cell neoplasia of unclassified
examination for early detection of malignancy. If orchidopexy
type, a premalignant condition, which is also called carcinoma
is performed early, it may reduce the risk of infertility and
in situ, or testicular intraepithelial neoplasia.
testicular cancer. The testis in normal scrotal position is
Surgical repositioning of the testis (orchidopexy) before
likely to provide improved body satisfaction, although the
puberty appears to decrease the risk of testicular cancer, but
psychological impact of abnormal testicular position has not
does not completely eliminate it. Testicular malposition is not
been studied.
the only factor in the development of testicular cancer in men
Hormonal therapy has been tried in past, but it has not
with a history of cryptorchidism because surgical repositioning
proven to be efficacious in inducing testicular descent.
does not completely eliminate the risk.
Clinical Pearl Bilateral Undescended Testis

• Children who has been operated for orchidopexy should
If the patients have bilateral palpable UDT without hypo
be taught self-examination for early detection of testicular spadias, then they should be operated after the age of 6
carcinoma. months. If the patients have bilateral nonpalpable UDT or
if UDT is associated with hypospadias, then they should
be investigated for disorders of sex differentiation (DSD).
If investigations are in line of a normal boy, then the
MANAGEMENT
orchidopexy should be performed after the age of 6 months.
The patients of UDT should be worked up for anesthesia fitness Authors operate on both sides in the same sitting even when
preoperatively. Other hormonal investigations are optional they are nonpalpable, though some institutes have protocol
and may be performed depending upon local institutional of operating on one side first and then on other side. If
policy. Imaging studies for locating testis are not required, investigations are suggestive of DSD, then one should follow
as they have limited specificity and sensitivity. In addition, DSD protocol (Algorithm 1).
ALGORITHM 1
Management algorithm for bilateral undescended testis
624
DSD, disorders of sex differentiation.

Surgical Treatment Nonpalpable Testis

Timing of surgery: The spontaneous descent is less likely to The nonpalpable testis can be abdominal, atrophic, or
occur after 3 months of age and it has recommended that absent. It is difficult to differentiate between these conditions
children with UDT should be operated as soon as possible preoperatively and parents of these patients should be
after 6 months of age to prevent the complications. In children explained about possible outcome of surgery, i.e., single stage
with ascended testicle, surgery should be performed as soon as orchidopexy, two stage orchidopexy, or orchiectomy depending
possible after diagnosis is established. upon the operative findings. Even patients with nonpalpable
Early orchidopexy before 2 years (ideally before 1 year) of UDT can be operated as a day care surgery, but they need to be
age is associated with improved testicular growth and fertility preferably scheduled as first case in the morning.
potential. The first step is to perform examination under anesthesia
If a patient with UDT presents with inguinal hernia, and if testis is palpable, then to proceed with standard open
then orchidopexy with repair of inguinal hernia should be orchidopexy. If the testis is confirmed to be not palpable, then
performed at the time of presentation (Algorithm 2). proceed with the next step, i.e., laparoscopic surgery.
Following are the advantages of laparoscopic surgery over
Clinical Pearl open procedure in nonpalpable UDT:
• Orchidopexy should be performed any time after the age of • Probability of missing the high testis and testis in abnormal
6 months, the earlier the better to prevent its complications. position (retrovesical) is almost nil
Undescended testes presenting with inguinal hernia should • Laparoscopic mobilization of testicular vessels is far
be operated at the time of diagnosis. superior as compared to open mobilization. The incidence
of postoperative ascent and atrophy is less common
compare to open surgery.
Palpable Testis In a place, where option of laparoscopic pediatric surgery
Patients with palpable UDT should undergo open orchi is not available, surgeon may proceed with open surgery by
dopexy. The surgery is usually carried out as a day care lower inguinal crease incision. If the testis is not found in the
procedure under laryngeal mask and caudal anesthesia. groin, then the peritoneal exploration may be performed by
An incision is taken in the lower skin crease in the groin. extending the groin incision laterally or to reverse the patient
The testis along with the cord structures are mobilized, from anesthesia and refer the patient to the higher center.
herniotomy (if hernial sac is present) is performed and testis If cord structures or testicular remnants are found, they are
is manipulated into the scrotum and sutured in place. Usually removed and the procedure is terminated.
palpable testis can be brought down to the scrotum as the cord The diagnostic laparoscopy is a safe procedure in
structures have adequate length. Sometimes, even palpable experienced hands. The laparoscope is placed via the
(especially emergent) UDT has short cord and they may umbilicus and following observations are carried out, patency
not come down to scrotum without tension and can ascend of the processus vaginalis, location of testis, testicular vessels,
postoperatively into higher position needing second surgery. vas deferens, gubernaculum, and presence of Müllerian
The exact incidence of such a scenario has not been reported, structures. The findings on laparoscopy decide the further plan
but it is likely to be in range of 2–3% (personal experience). of action (Algorithm 3).
The presence of blind ending vas and vessels in the
Clinical Pearl retroperitoneum (usually 2–3 cm proximal to the internal ring)
is suggestive of vanishing testis syndrome. In this situation,
• Palpable undescended testes (UDT) should undergo open
nothing further needs to be done for the UDT, though fixation of
surgery and nonpalpable UDT should undergo laparoscopic
contralateral testis to prevent torsion and loss of only testicular
surgery
tissue remains controversial at present. Authors routinely
ALGORITHM 2
Timeline for surgery in undescended testis
625
ALGORITHM 3
Treatment algorithm for undescended testis
fix the contralateral testis in such a scenario. In addition, if

facilities are available, then surgeon can insert the testicular
prosthesis on the ipsilateral side at the time of surgery or later
on at puberty. If the prosthesis is inserted in a young child,
then it may need to be revised at the time of puberty to match
the normal contralateral testicular size. The psychological
assessment of these young adults with or without prosthesis
has not been performed, but logically the person with normal
feel of scrotum is likely to have better self-esteem.
On laparoscopy, if vas and vessels are entering internal ring,
then patient is likely to have atrophic testis either in the inguinal
canal or in the scrotum. This patient should undergo excision of
atrophic testicle either laparoscopically (if hernial sac is open
and atrophic testis is visualized) or by an open inguinal incision
along with fixation of contralateral testis by scrotal incision to
prevent torsion and loss of only testicular tissue.
On laparoscopy, if apparently normal looking testis is seen,
then surgeon needs to decide whether to bring the testis to Fig. 1: Laparoscopic findings in the low abdominal testis near the
scrotum in one or two operations. This decision is based on internal ring
following factors:
• Age of patient
• Distance of testis from the internal ring
• Mobility of testicular vessels.
In infants, length of the inguinal canal is much shorter than
the older children and it is easy to bring the testis in scrotum.
The term low abdominal testis is used when the distance of
testis from the internal ring is less than 2.5 cm (Fig. 1). The
term high abdominal testis is used when the distance of testis
from internal ring is more than 2.5 cm. In children who are less
than 5 years old with low abdominal testis and mobile vessels,
usually the testis can be brought down in single operation. The
success rate of single stage orchidopexy is more than 95%.
The children with high abdominal testis, age more
than 5 years, and short testicular vessels usually needs two
stage Stephen-Fowler (SF) orchidopexy. In the first stage,
the testicular vessels are controlled either using bipolar
diathermy, clipped or with an ultrasonic scalpel and then
transected. This is performed approximately 2.5 cm away Fig. 2: Laparoscopic findings during second stage of Stephen-Fowler
from the testis. This allows the development of collaterals orchidopexy showing collaterals between artery to vas deferens and
626 between artery to vas deferens and testicular vessels (Fig. 2). testicular artery
The second stage SF orchidopexy is usually performed after 6 of age and in up to 26% of cases who underwent orchidopexy in
months, wherein the testis is brought down to scrotum on the the age group 4–14 years of age. The timing of the surgery does
pedicle of vas. The two stage orchidopexy has success rate of not influence fertility in unilateral cryptorchidism. Though
more than 80%. the fertility is not impaired, there are distinct benefits of early
In past for high abdominal testis, microvascular surgery surgical orchidopexy.
was performed by anastomosis of testicular artery with inferior
epigastric artery but has limited success and is not popular. Malignancy
Adult men with history of UDT have higher probability
Retractile Testis
of developing a testicular malignancy. The risk increases
A retractile testes should be under careful surveillance. The to 32 fold in comparison to the general population. The
probability of spontaneous descent is 58 % in boys older intra-abdominal testis has the highest risk of developing
than 7 years and 21% in boys younger than 7 years. It has 32% malignancy, which is five times higher than that of inguinal
risk of becoming an ascending UDT. Surgical repositioning UDT. The risk of malignancy is higher in bilateral UDT. The
of the testis should be done if the testes become ascended children who undergo orchidopexy after puberty are twice
testes (acquired cryptorchidism) or there is significant loss of at the risk of developing the malignancy than those who
testicular volume in comparison to contralateral testes. undergo orchidopexy before puberty. The incidence of
malignant degeneration in contralateral descended testis is
Clinical Pearl about 8–15%.
• Retractile testis needs a close supervision and 32% becomes

ascended testicle needing surgery. KEY POINTS
))
One percent of male child suffers from undescended testes
(UDT) at the age of 1 year
Ascended Testicle
))
Imaging studies are not reliable and are not advocated to
Ascended testicle should be surgically positioned at the time locate UDT
of presentation. Ascended testes are seen in mid-childhood,
))
Surgery is performed to prevent the complications, e.g., hernia,
are usually unilateral, and are present in distal inguinal canal.
torsion, trauma, subfertility, and malignancy
Ascended testis is prone to the same germ cell maldevelopment
seen in congenital cryptorchidism. ))
Clinically, UDT should be classified as palpable and non
palpable variety
))
Surgery should be performed after the age of 6 months
LONG-TERM OUTCOME OF ))
UDT presenting with hernia should be operated at the time
THE ORCHIDOPEXY of diagnosis
))
Retractile testis needs a close supervision
Testicular Atrophy ))
In 32% of patients diagnosed to have retractile testis, becomes
Testicular atrophy is a serious negative outcome of the ascended testicle and needs surgery
orchidopexy. It is reported in 1% in ectopic testis, up to 5% of the ))
Palpable UDT should undergo an open surgery
distal testis, and in up to 9% of cases in intra-abdominal testis. ))
Nonpalpable UDT should undergo laparoscopic surgery
The preoperative location of testes, torsion, and anomalies of ))
There is no role of hormonal treatment
vas deferens determines the occurrence of postorchidopexy ))
Insertion of testicular prosthesis should be considered in
testicular atrophy. Inadvertent trauma to the testicular vessels, patients with absent or atrophic type of UDT to prevent
postoperative edema, and local infections may also play a role psychological issues and to improve the self-body image
in testicular atrophy. The resultant postoperative ischemia ))
All children undergoing orchidopexy should be taught self-
leads to complete or partial atrophy of the testis. examination for early detection of malignancy.
Fertility
Adults with bilateral UDT have azoospermia in almost 100% SUGGESTED READINGS
of cases, while more than 20% adults will have normal sperm 1. Abaci A, Catli G, Anik A, Bober G. Epidemiology, classification and management of
counts when their orchidopexy was done in early childhood. undescended testes: does medication have any value in its treatment? J Clin Res
Adults who underwent orchidopexy generally have low sperm Pediatr Endocrinology. 2013;5(2):65-72.
count and have poor semen quality. This subfertility is not 2. Agarwal PK, Diaz M, Elder JS. Retractile testis—is it a normal variant? J Urol.
completely compensated by the contralateral descended 2006:175(4):1496-9.
3. Al-Zahem A, Shun A. Routine contralateral orchidopexy for children with a vanished
testis. The fertility is further compromised if both testes are
testis. Eur J Pediatr Surg. 2006;16(5):334-6.
undescended and if the treatment is delayed. In bilateral UDT, 4. Alagaratnam S, Nathaniel C, Cuckow P, Duffy P, Mushtaq I, Cherian A, et al. Testicular
the studies quotes normal sperm counts in up to 76% of cases outcome following laparoscopic second stage Fowler-Stephens orchidopexy. J Pediatr
when the orchidopexy was done between 10 months and 4 years Urol. 2014;10(1):186-92. 627
5. Baker LA, Docimo SG, Surer I, Peters C, Cicek L, Diamond DA, et al. A multi- 17. Li p SZ, Murchison LE, Cullis PS, Govan L, Carachi R. A meta-analysis of the risk
institutional analysis of laparoscopic orchidopexy. BJU Int. 2001;87:484-9. of boys with isolated cryptorchidism developing testicular cancer in later life. Arch
6. Barthold JS, González R. The epidemiology of congenital cryptorchidism, testicular Dis Children. 2013;98(1):20-6.
ascent and orchidopexy. J Urol. 2003;170:2396-401. 18. Ludwikowski B, GonzálezR. The controversy regarding the need for hormonal
7. Belkar AM. Urologic microsurgery—current perspectives: II. Orchiopexy and testicular treatment in boys with unilateral cryptorchidism goes on: a review of the literature.
homotransplantation. Urology. 1980;15(2):103-7. Eur J Pediatr. 2013;172(1):5-8.
8. Biers SM, Malone PS. A critical appraisal of the evidence for improved fertility 19. Mano R, Livne PM, Nevo A, Sivan B, Ben-Meir D. Testicular torsion in the first year
indices in undescended testes after gonadotrophin-releasing hormone therapy and of life—characteristics and treatment outcome. Urology. 2013;82(5):1132-7.
orchidopexy. J Pediatr Urol. 2010;6(3):239-46. 20. Mathers MJ, Sperling H, Rubben H, Roth S. The undescended testis: diagnosis,
9. Ein SH, Nasr A, Wales PW, Ein H. Testicular atrophy after attempted pediatric treatment and long-term consequences. Dtsch Artzbel Int. 2009;106(33):527‑32.
orchidopexy for true undescended testis. J Pediatr Surg. 2014;49(2):317-22. 21. McAleer IM, Packer MG, Kaplan GW, Scherz HC, Krous HF, Billman GF. Fertility index
analysis in cryptorchidism. J Urol. 1995;153:1255-8.
10. Favorito LA, Costa WS, Sampaio FJ. Relationshi p between the persistence of the
processus vaginalis and age in patients with cryptorchidism; International. Braz J 22. Miller KD, Coughlin MT, Lee PA. Fertility after unilateral cryptorchidism. Paternity,
Urol. 2005; 31(1):57-61. time to conception, pretreatment testicular location and size, hormone and sperm
parameters. Horm Res. 2001;55:249-53.
11. Fedder J. History of cryptorchidism and ejaculate volume as simple predictors
23. Osifo DO, Osaigbovo EO. The prevalence, postnatal descent, and complications of
for the presence of testicular sperm. Syst Biol Reprod Med. 2011;57(3):
undescended testes among children who underwent neonatal circumcision in Benin
154-61.
City, Nigeria. J Pediatr Surg. 2009;44(4):791-6.
12. Giwercman A, Bruun E, Frimodt-Møller C, Skakkebaek NE. Prevalence of carcinoma in
24. Osime O, Momoh M, Elusoji S. Torsed intraabdominal testis: a rarely considered
situ and other histopathological abnormalities in testes of men with a history of
diagnosis. Cal J Emerg Med. 2006;7(2):31-3.
cryptorchidism. J Urol. 1989;142:998-1001.
25. Pettersson A, Richiardi L, Nordenskjoid A, Kaijser M, Akre O. Age at surgery for
13. Giwercman A, Grindsted J, Hansen B, Jensen OM, Skakkebæk NE. Testicular cancer risk undescended testis and risk of testicular cancer. N Engl J Med. 2007;356(18):1835-
in boys with maldescended testis: a cohort study. J Urol. 1987;138:1214-6. 41.
14. Lee PA, Coughlin MT, Bellinger MF. Inhibin B: comparison with indexes of 26. Virtanen HE, Bjerknes R, Cortes D, Jørgensen N, Rajpert-De Meyts E, Thorsson AV, et al.
fertility among formerly cryptorchid and control men. J Clin Endocrinol Metab. Cryptorchidism: classification, prevalence and long-term consequences. Acta Paediatr.
2001;86(6):2576-84. 2007;96(5):611-6.
15. Lee PA, Coughlin MT. Fertility after bilateral cryptorchidism. Evaluation by paternity, 27. Weir HK, Marrett LD, Kreiger N, Darlington GA, Sugar L. Pre-natal and peri-natal
hormone, and semen data. Horm Res. 2001;55:28-32. exposures and risk of testicular germ-cell cancer. Int J Cancer. 2000;87:438-43.
16. Lee PA. Fertility in cryptorchidism. Does treatment make a difference. Endocrinol 28. Zilberman D, Inbar Y, Heyman Z, Shinhar D, Bilik R, Avigad I, et al. Torsion of the
Metab Clin North Am. 1993;22(3):479-90. cryptorchid testis—can it be salvaged? J Urol. 2006;175(6):2287-9; discussion 2289.
628
CHAPTER 128
Acute Scrotum
Mohan K Abraham
INTRODUCTION CLINICAL FEATURES

Acute scrotum is an alarming condition both for the parents
and the child. Since the most common cause in children is History
torsion of the testis, emergency management is indicated. History gives a clue in most of the conditions. Pain of sudden
Epididymo-orchitis and trauma can also present as acute onset may indicate torsion. Torsion is commonly seen in
scrotum. However, these conditions are rarer and torsion postpubertal or new born age. Torsion of appendages of the
should be ruled out first. testis occurs in the prepubertal age. History of trauma does
not rule out torsion. If pain from trauma lasts more than 1
DEFINITION hour, torsion should be considered. History of urinary tract
infection, surgery for hypospadias, or sexual activity may be
Any sudden swelling of the scrotum, unilateral or bilateral with obtained in epididymo-orchitis. Fever also may be present
redness and edema, should be considered as acute scrotum. in case of epididymo-orchitis. Pain of epididymo-orchitis is
gradual in onset. Henoch–Schönlein purpura can also present
ETIOLOGY with acute scrotum, but the lesions in other parts of the body
will point to the diagnosis. Obstructed hernia can also mimic
Etiology can be divided into infective causes like epididymo- acute scrotum. History of a reducible swelling existing before
orchitis, allergic causes like idiopathic scrotal edema or the onset of acute scrotum will point to the diagnosis.
ischemic causes like torsion testis and torsion of the appendages
of the testis. Epididymo-orchitis is usually due to ascending Clinical Examination
infection through the vas because of a urinary tract infection.
It is important to gain the confidence of the child or mildly
There are two peaks when torsion of the testis occurs; one is in
sedate the child before starting the examination. This will
the new born period and another at puberty. Lack of fixation in
facilitate proper examination. Abdominal examination
the new born period and over activity of the cremaster muscle
including the inguinal area should be done first. Incarcerated
has been attributed to the increased incidence during these
hernia will have a swelling extending into the inguinal canal. A
periods. Torsion is mostly extravaginal in the new born period
thickened and tender spermatic cord in the inguinal canal will
where the twist occurs in the cord. Torsion is intravaginal in
indicate epididymo-orchitis.
the rest of life. Intravaginal torsion is due to high investment
of tunica vaginalis which gives rise to a bell clapper deformity.
Here, the mesentery of the testis is narrow and testis hangs Examination of the Scrotum
like a bell-clapper in a church bell predisposing it to torsion. In idiopathic scrotal edema, both the sides are involved but
The appendages of the testis can also undergo torsion when tenderness is absent. In torsion and epididymo-orchitis, the
signs and symptoms are minimal. Idiopathic scrotal edema involvement is unilateral to start with and becomes bilateral
is another condition that mimics acute scrotum. Absence of as time passes. A testis felt in the root of the scrotum or a
tenderness and normal testis felt on palpation or a normal testis with a transverse lie should warn about the possibility of
testis without edema and good blood flow seen by ultrasound torsion. Absence of cremasteric reflex indicates torsion. This
distinguishes this from other conditions. is elicited by stroking the medial side of the thigh which gives
demonstrate any difference in tissue saturation between

testis that had undergone torsion and normal testis.
Clinical Pearl
• There is no investigation that is completely reliable to rule out
torsion in a reasonable time frame.
MANAGEMENT
Epididymo-orchitis
Empirical antibiotics are given till urine culture and sensitivity
is obtained. Bed rest and scrotal elevation will lessen the pain.
If urine culture is positive, then child will need further work up
to look for any underlying anatomical abnormality.
Fig. 1: Showing red edematous scrotum on left side due to torsion
Idiopathic Scrotal Edema
rise to ipsilateral elevation of testis because of the contraction Bed rest and scrotal elevation will be enough. Edema will
of cremaster muscle. Pain duration less than 24 hours, nausea subside in 48–72 hours.
or vomiting, a high position of the testis, and an abnormal
cremasteric reflex has a positive predictive value for torsion. Torsion of Testis
Testis should be examined carefully. Testis should be held
Points to consider in the management of torsion are:
between thumb and two fingers. Epididymis should be felt
• Duration of torsion. Some studies have shown that
as a soft linear structure on the posterior lateral aspect of the
testicular atrophy occurred in all cases where the symptom
testis. If this is tender and swollen, then epididymitis should be
duration was more than 24 hours
thought of. Tenderness limited to the upper pole of the testis
• Triggering of immune mechanism because of loss of
suggests torsion of the appendage of the testis. A small area
blood testicular barrier due to ischemia is a matter of
of bluish discoloration at the upper pole, also known as blue
dot sign, also represents torsion of an appendage of the testis. concern. This can result in damage to the normal testis
Testis is swollen and tender in early torsion and epididymo- and infertility.
orchitis. Tenderness may disappear once complete gangrene Testicular torsion is a surgical emergency and no time
of the testis has set in. As time passes, the erythema and edema should be wasted between diagnosis and exploration. Scrotal
involves both sides of the scrotum (Fig. 1). Palpation of the exploration is done and the testis is fixed to the dartos with
testis will reveal a hard enlarged testis on the affected side. nonabsorbable sutures. Alternatively, it can be put in a dartos
Elevation of testis may give relief of pain in case of pouch to prevent torsion. However, suture fixation has the
epididymo-orchitis, but not in torsion. potential danger of violating testicular barrier and triggering
an immune response damaging the contralateral testis.
Contralateral side also needs to be fixed to prevent torsion
INVESTIGATIONS because the bell clapper deformity can be bilateral. There is
• Urine analysis: if pyuria is present, it may suggest some controversy regarding the fixation of the contralateral
epididymo-orchitis testis in newborn torsion. Neonatal torsions are usuallyextra
• Ultrasound: conventional ultrasound has not been vaginal and bilateral involvements are not usually seen in these
found useful. Color Doppler has improved the diagnostic cases. However, most surgeons favor fixing the contralateral
accuracy in expert hands. However, Doppler may miss a side since bilateral torsions are known to occur. If testis is
partial torsion which will eventually lead to testicular loss. found to be ischemic as evidenced by dark discoloration, testis
A hypervascular enlarged epididymis can occur in 5% of should be detorsed and warm sponges applied to see if there is
torsion cases. Color Doppler can avoid surgery in cases regaining of color (Fig. 2). If there is no improvement in color,
of increased or normal blood flow; in rest of the cases, testis can be incised to see the state of testicular tissue inside. If
exploration may be needed the testis is found to be gangrenous, orchiectomy is indicated.
• Nuclear scanning: nuclear scanning is highly accurate in Contralateral side testis should be fixed in the dartos pouch to
demonstrating torsion as a photopenic area. However, this prevent torsion.
is not widely available and consumes time which may lead Drugs have been studied in experimental animal models
to testicular gangrene. Moreover, it gives a small dose of to reduce the ischemia reperfusion injury. These include
radiation also allopurinol, calcium channel blockers, oxypurinol, and super
• Near infrared spectroscopy: though some usefulness oxide dismutase. But, none of these studies have produced
630 was seen in animal studies, in human studies it failed to enough evidence to allow its usage in human beings.
CHAPTER 128: Acute Scrotum
ALGORITHM 1
Fig. 2: Testis with torsion and gangrene
Testicular Trauma
Perinatal Torsion
Testicular trauma occurs as a result of direct blow to the
Management of perinatal torsion is controversial. One school
testis or straddle injury. Post-traumatic epididymo-orchitis
of thought considers that salvage of a perinatally torted testis is
occurs within a few days after trauma. This has noninfectious
very poor so that there is no need for emergency exploration.
cause and can be managed with scrotal elevation and rest.
Other school of thought wants to give the benefit of the doubt
Intratesticular hematoma can also be managed conservatively.
and explore the testis since there is a possibility that torsion has
However, rupture of the testis will require emergency surgery.
occurred during or immediately after delivery and potential for
salvage of the testis is higher. Clinical Pearl
Torsion of the Appendages of Testis • Epididymo-orchitis in childen should be a postoperative
diagnosis.
Torsion of the appendages of testis as evidenced by blue
dot sign is conservatively managed with bed rest and anti-
inflammatory drugs are justifiable. But, this is usually possible KEY POINTS
only in fair skinned children and that too if they present
before scrotal edema develops. If doubt exists, exploration ))
Torsion testis should be suspected in every case of acute
is the safer option. Exploration of contralateral side is not scrotum
indicated (Fig. 3). ))
It is better to explore the scrotum than wait when you are in
doubt
))
In the absence of predisposing causes for epidydimo-orchitis
like urinary tract infections or genital abnormality, torsion
testis should be the working diagnosis.
SUGGESTED READINGS
1. Boettcher M, Bergholz R, Krebs TF, Wenke K, Aronson DC. Clinical predictors of
testicular torsion in children. Urology. 2012;79(3):670-4.
2. D’Andrea A, Coppolino F, Cesarano E, Russo A, Cappabianca S, Genovese EA, et al. LUS
in the assessment of acute scrotum. Crit Ultrasound J. 2013;5(Suppl 1):S8.
3. Kravchick S, Cytron S, Leibovici O, Linov L, London D, Altshuler A, et al. Color
Doppler sonography: its real role in the evaluation of children with highly suspected
testicular torsion. Eur Radiol. 2001;11(6):1000-5.
4. Nussbaum Blask AR, Rushton HG. Sonographic appearance of the epididymis in
pediatric testicular torsion. AJR Am J Roentgenol. 2006; 187(6):1627-35.
5. Schoenfeld EM, Capraro GA, Blank FS, Coute RA, Visintainer PF. Near-infrared
spectroscopy assessment of tissue saturation of oxygen in torsed and healthy testes.
Acad Emerg Med. 2013;20(10):1080-3.
6. Tryfonas G, Violaki A, Tsikopoulos G, Avtzoglou P, Zioutis J, Limas C, et al. Late
postoperative results in males treated for testicular torsion during childhood.
Fig. 3: Torsion of appendix of epididymis J Pediatr Surg. 1994;29(4):553-6. 631
Chapter 129
Per-rectal Bleeding
Dasmit S Khokar
INTRODUCTION Etiology
Lower gastrointestinal (GI) bleeding is an alarming symptom The most common causes of bleeding vary with the age at
of presentation. Among children of all ages, lower GI bleeding presentation, although almost all causes may be encountered
is the main symptom in 0.3% of patients presenting to the at any age.
casualty; 50% are less than 1 year of age. Per-rectal bleeding Neonates:
accounts for 10–15% of referrals to a gastrointestinal service. • Healthy baby: hemolytic disease of the newborn, fissure in
In most children, bleeding stops spontaneously but since ano, local trauma (as happens with an attempted forced
the blood volume is small, resuscitation must begin early. catheter insertion into the rectum)
Children can tolerate even massive blood loss surprisingly well, • Sick baby: necrotizing enterocolitis, bowel gangrene, sepsis,
but sudden deterioration occurs when a critical point is reached. disseminated intravascular coagulation, Hirschsprung’s
At the outset, it is imperative to remember the thumb disease with enterocolitis, complicated malrotation, milk
rule that age-appropriate tachycardia is the most sensitive or soya milk enterocolitis, or allergic colitis.
indicator of critical blood loss in children. Any patient with an • Drugs causing GI bleeds include nonsteroidal anti-
estimated blood loss more than 10% of the blood volume must inflammatory drugs (NSAIDs), indomethacin, tolazoline,
be monitored in an intensive care unit. heparin, etc.
Twenty percent patients in the neonatal intensive care unit • Some maternal medications like cephalothin, aspirin, and
are likely to experience stress gastritis with resultant coffee phenobarbital can cross the placenta and cause per-rectal
grounds in the nasogastric aspirate followed thereafter by bleeding in the neonate after delivery
malena. • Preemies and ventilated babies are prone to stress gastritis
with resultant malena
• Idiopathic.
Clinical Classification
Up to 2 years of age:
• Hematochezia: fresh bleeding per rectum in large • Milk protein allergy
quantities. Clots plus fresh blood may be seen, hardly any • Intussusception
stool matter • Fissure in ano
• Malena: usually a sign of bleeding that comes from a source • Rectal polyps
proximal to the ligament of Treitz. However, massive upper • Malrotation
GI bleeding can produce bright red blood per rectum if GI • Hemangioma and other vascular lesions of the gut
transit time is rapid • Intestinal duplication
• Red currant jelly stools: blood mixed with mucus • Trauma due to foreign body or sexual assault
• Maroon colored stool: occurs with distal small bowel • Lymphonodular hyperplasia
bleeding, such as with Meckel’s diverticulum. • Eosinophilic gastroenteropathy
• Blood mixed with loose stools: infective diarrhea, dysentery. • Acquired thrombocytopenia
Painless bleeding in an otherwise healthy child will be • Infectious diarrhea.
construed differently from per-rectal bleeding in a sick child, Elder than 2 years age:
irrespective of the quantity of bleeding. • Infectious diarrhea
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Chapter 129: Per-rectal Bleeding
Algorithm 1
Basic algorithm of per-rectal bleeding
• Amoebic colitis • Colicky pain followed by red-currant jelly stools: intus

• Ulcerative colitis susception
• Crohn’s disease • Copious bleeding, usually painless or lower abdominal
• Meckel’s diverticulum pain followed by hematochezia: meckel’s diverticulum
• Inflammatory bowel disease and duplication of the gut
• Bleeding dyscrasias • Abdominal pain, diarrhea, fever, prostration: infective
• Antibiotic-associated bleeding ulceration
• Food allergies • Bleeding associated with abdominal distention in a septic
• Trauma child: intestinal gangrene, necrotizing enterocolitis.
• Rectal polyp In spite of extensive investigations, the cause may not be
• Juvenile polyposis coli found in which case it is labeled as idiopathic. Munchausen
• Familial polyposis and colonic carcinoma or small bowel syndrome by proxy should also be ruled out.
malignancy with/without intussusception
• Villous adenoma of the rectum Investigations
• Rectal prolapse
• Solitary ulcer of the rectum • Digital rectal examination: it is the most essential primary
investigation that is needed when a child presents with
• Henoch-Schonlein purpura
such a history. Hard fecalomas, anal stenosis, fissure in
• Hemolytic uremic syndrome
ano, rectal polyps, mass lesion prolapsed from above, etc.
• Lymphonodular hyperplasia
can be judged quite accurately. It is possible to differentiate
• Eosinophilic gastroenteropathy
between advanced colonic intussusception and rectal
• Vascular lesions of the gut.
prolapse, judging by the depth to which the palpating
finger can be inserted. In addition, rectal tone should
Algorithm of Clinical always be assessed
Approach to the Diagnosis • Ultrasonography abdomen: mass lesions can be detected
as long as the bowel gas does not interfere with the medium
• Bleeding related to defecation: anal or rectal lesion is likely of passage of the ultrasonic waves
• Bleeding associated with pain: lesion is below the dentate • Barium enema: larger polyps and multiple polyps can be
line diagnosed quite easily with this investigation. However,
• Blood mixed with stool matter: lesion is higher than the smaller polyps are easier to see on endoscopy besides
rectum being amenable to biopsy also.
• Something coming out of the anus: rectal prolapse or rectal • Contrast enhanced computed tomography (CECT)
polyp, intussusception abdomen: this is used judiciously so as to avoid radiation
• Bleeding associated with epigastric pain and heartburn: to the child. This is a highly sensitive and specific imaging
dyspepsia/gastritis technique for the abdomen. However, a trained pediatric
• Bleeding associated with high fever: enteric fever with radiologist is essential for interpreting the images accurately
terminal ileitis • Magnetic resonance imaging abdomen: this is being tried
• Bleeding associated with loss of weight, anorexia, night as an alternative to CECT abdomen, but the resolution is
sweats, and fatigue: abdominal tuberculosis often insufficient to accurately make a diagnosis 633
ch-129.indd 633 11/22/2016 10:48:37 AM

• Meckel’s radionuclide scan with technetium 99 m coupled with short cut alternatives to preparing wholesome
pertechnetate: it can be used to detect the presence of a food at home. Thus, children consume more fast foods, street
Meckel’s diverticulum with ectopic gastric mucosa foods, single-pot meals, and high calorie foods with low
• Red blood cell (RBC) labeled radionuclide scan: any roughage value leading to constipation.
bleeding which is more than 0.1 mL/min can be detected Another phenomenon seemingly on the rise is early,
by this scan and the approximate location can be enforced toilet-training. The child is made to pass stools like an
established. Newer RBC scans have an accuracy of nearly adult even before the sensation of passing stools or defecation
90% in localizing the bleeding site reflexes are fully developed. This leads to acquired constipation
• Colonoscopy, gastroscopy, and capsule endoscopy: these with its ensuing complications one of which is fissure in ano.
are now being used with increasing frequency to try and
establish a diagnosis and avoid a surgical exploration. Pathogenesis
The overall yield of colonoscopy is 64–80%. When rectal
bleeding is associated with diarrhea, the yield is 97%. In The child strains and passes a hard stool. This hard bolus
children in the 0–12 years age group, colitis is the most causes a laceration at the mucocutaneous junction which is
common cause (36%), followed by polyps in (27%), whereas extremely sensitive to pain. Any attempt by the child at passing
rectal ulcers, chronic anal fissures, and hemorrhoids stools would now be very painful, so the child holds back the
account for 5% each stools. This leads to further water absorption from the stool
• Splanchnic angiography (superior mesenteric arterio matter causing it to harden further. This vicious cycle causes
graphy): it is sometimes resorted to for locating the the fissure to become chronic. The aim of treatment is to break
bleeding vessel when the bleeding is massive. Even super- this vicious cycle so that the fissure can heal on its own.
selective embolization has been successful in select cases It is important to differentiate between acute and chronic
although it can lead to bowel gangrene sometimes constipation when treating such children. Oral laxatives
• Laparoscopy: being minimally invasive, it is the last should be used for acute constipation only, along with advice
resort short of a laparotomy, in a case where all other on correction of diet. Oral laxatives are preferred for only acute
investigations have been unable to come to a diagnosis constipation and should never be used for prolonged periods.
• Laparotomy: It is the last desperate attempt when a life- Any patient, who needs an oral laxative for more than 7 days,
threatening bleeding event happens. It has the advantage needs to be investigated further for the cause of constipation
of allowing palpation of the bowel wall, but one still cannot and should be referred to a pediatric surgeon.
view the mucosal aspect unless opened. The limitation is Patients with chronic constipation need prolonged bowel
that it is not possible to open and view the entire bowel. training and should be managed by a suppository bowel
The yield is therefore increased further when laparotomy management program along with strict dietary correction.
is coupled with transluminal endoscopy (enteroscopy). An Suppositories having a local action are less habit-forming and
endoscope is inserted either through a natural orifice or are preferred over oral laxatives. Occasionally, soapy water
through an opening made in the bowel and guided by the enemas and mineral oil or olive oil instillation are needed for
operating surgeon. hard fecalomas. Phosphatic enemas can be used occasionally,
In most of the cases, if the GI endoscopies are negative, then but daily usage should be avoided to prevent electrolyte
a period of observation is desirable. In case the patient bleeds disturbances.
significantly or repeatedly, then more invasive investigations
become easier to justify. Many cases of idiopathic bleeding will Clinical Presentation
not last beyond a few months. The most common presentation is a painful passage of hard
Many of the causes of lower GI bleeding are medical causes stool accompanied by straining. This is followed by a few drops
and readers are directed to read appropriate source material of fresh blood. Passage of clots is unusual. Subsequent stools
for the same. are painful, streaked with blood on one side and few drops of
Some of the more common surgical causes have been blood at the end of defecation.
discussed here in this chapter. The child might be habituated to passing stools in a
standing position, pressing the buttocks together in an attempt
FISSURE IN ANO to prevent the stools from exiting the painful anus. The face
turns red as the child strains excessively and looks quite
This occurs due to trauma caused by passage of hard stools. frightening to the parents. Finally, the child painfully passes a
This is the most common cause of per-rectal bleeding in hard mass of stool with a streak of blood on it.
India. Faulty diet is the usual cause of hard stools. Excessive The fissure can be seen on careful examination of the
milk and bakery products like biscuits and bread are the usual perineum. The most common location is at the 6 o’clock
offenders. With increasing urbanization and break-down of the position but can occur in any position. A recurrent fissure at 12
joint family system, it is not unusual to obtain a history where o’clock position or in an older child should alert the physician
both parents are working, with lesser time at their disposal for to the possibility of an inflammatory bowel disease.
spending with their children. This fact directs them to resort Sometimes, a portion of the delicate anal valve can get
634 to appeasement methods to placate their demanding children, avulsed and protrude from the anus. This is called an external
ch-129.indd 634 11/22/2016 10:48:37 AM

Chapter 129: Per-rectal Bleeding
pile (although it is quite distinct from the usual piles). This normal saline enema under ultrasonography control or even
can get infected leading to further worsening of the pain and gas reduction with air/oxygen depending on the facilities and
tenderness. expertise available. Although many centers prefer the safety-
net of doing the procedure without any sedation, midazolam
Treatment sedation (both intranasal as well as intravenous, 0.1 mg/kg)
can be used in centers equipped with the requisite facilities
• The most important step is to treat the underlying cause
and experience.
of constipation as outlined above. Treating functional
It must be remembered that intussusception recurs in
or habitual constipation (acquired megacolon) is quite
5–10% of children when reduced by nonoperative reduction
difficult and the treatment may take anything from a few
and 1–4% after operative reduction.
months to a few years
Hydrostatic reduction treatment of intussusception is
• Treatment of chronic constipation causing acquired
contraindicated in cases where peritonitis/gangrene has
megacolon starts only after a mechanical cause like an
already developed as evidenced by severe rebound tenderness
anorectal malformation has been ruled out. A bowel
or rigidity of the abdomen.
training program is started which includes a suppository or
Thus, early referral is crucial to a center equipped to handle
a nonelectrolytic enema regime with progressively reducing
such cases and most cases referred within 24 hours of the
frequency, coupled with a strict high-roughage dietary
onset of symptoms will be successfully reduced by hydrostatic
program. This needs a very high degree of motivation of the
reduction.
parents to implement it appropriately
It is imperative to remember that hydrostatic reduction is
• Warm sitz bath twice a day
done on the threshold of the operation theatre and complete
• Local anesthetic ointment: (lignocaine jelly/proctosedyl)
readiness for an emergency laparotomy is essential. This may
application thrice a day
be needed if the bowel ruptures during attempted reduction
• NSAIDS when needed
leading to fecal peritonitis and delay can be fatal.
• Antibiotics if an external pile shows evidence of infection
In cases where reduction fails or gets complicated or the
• Almost all fissures will heal with this treatment. Very rarely,
intussusception is already advanced, then the surgical options
if the fissure has become chronic and the conservative
available are:
regime fails, a surgical option may need to be considered.
• Laparoscopic reduction or laparoscopic-assisted bowel
Lord’s dilatation or a lateral anal sphincterotomy may then
resection and anastomosis
be required under general anesthesia (GA).
• Laparotomy with reduction or bowel resection.
INTUSSUSCEPTION
RECTAL AND COLONIC POLYPS
The most common age group of presentation of intussus
Juvenile inflammatory polyps are the most common cause of
ception is 6–8 months, mean being around 10 months of age.
bleeding in children older than 2 years of age. Most polyps
The characteristic severe pain in abdomen accompanied
are solitary juvenile polyps located in the rectum, hence are
by facial pallor soon followed by red currant jelly stools
palpable during a digital rectal examination by an experienced
is pathognomonic of intussusception. The most common
pediatric surgeon. They present as painless, dropwise per-
location is ileocecocolic with a hypertrophied Peyer’s patch
rectal bleeding after defecation. They may be pedunculated
being the lead point. Sometimes, this episode may be preceded
and can protrude from the anus. Occasionally, the connecting
by an attack of acute gastroenteritis, so the clinician has to be
stalk may get broken leading to incessant bleeding, so even a
very vigilant in treating such cases.
per-rectal examination has to be done with great care.
Diagnosis is quite easily possible by a typical target sign
If polyps are multiple, then a more sinister disease has to be
on an ultrasound examination of the abdomen in 97–100% of
explained to the relatives. The final diagnosis will of course be
patients. Alternatively, barium enema can also be used with
made after a histopathological confirmation of the type of polyp.
the additional advantage of being both diagnostic as well as
Juvenile polyps are the most common intestinal polyps
therapeutic.
in children, accounting for almost 90% of colonic polyps in
In patients more than 2 years of age or a small bowel
children. Around 20–25% of patients with juvenile polyps
intussusception, we have to bear in mind the possibility of a
present with occult blood loss and anemia rather than visible
leading point being a bowel lesion, such as polyp, leiomyoma
bleeding.
or a lymphoma, which may necessitate a bowel resection
The majority of colonic polyps are sporadic and not
with anastomosis and the specimen being subjected to
associated with malignancy, but familial adenomatous
histopathological examination.
polyposis and Peutz-Jeghers syndrome carry a risk of malignant
transformation. When there are more than five polyps in the
Treatment colon, multiple polyps throughout the GI tract or any number
Almost 95% of intussusceptions can be treated by hydrostatic of juvenile polyps with a family history of juvenile polyps, it is
reduction and surgery is not needed. This can be done by either known as juvenile polyposis syndrome, which carries a high
using barium enema under an image intensifier fluoroscopy or malignant potential. 635
ch-129.indd 635 11/22/2016 10:48:37 AM

If the clinical history is strongly suggestive of the diagnosis of

an intestinal polyp, but it is not felt on a per-rectal examination, Key points
then a colonoscopy under GA is essential. ))
Age-appropriate tachycardia is the most sensitive indicator of
critical blood loss in children
Treatment ))
Clinical classification of bleeding is based on the gross stool
• Solitary rectal polyps are treated surgically by under- characteristics
running the base and excising the polyp under GA, ))
Etiology varies with age
transrectally ))
A detailed history and careful clinical examination can usually
• Proximally situated polyps or multiple polyps will need a elicit the cause in a majority of the cases
pediatric colonoscopy with excision by electrocautery or ))
The most common cause of per-rectal bleeding in India is
argon plasma coagulation fissure in ano caused by a faulty diet
• If multiple polyposis coli with adenomatous villous ))
Oral laxatives are preferred only for acute constipation and
polyps are detected, then a laparoscopic or open total should never be used for prolonged periods. Any patient,
proctocolectomy with an endorectal ileoanal anastomosis who needs an oral laxative for more than 7 days, needs to
procedure will be required. In addition, the patient will be investigated further and should be referred for a pediatric
have to be kept on a strict follow-up colonoscopy regime to surgical consult
look for early malignancies. ))
Treating functional or habitual constipation (acquired
megacolon) is quite difficult and the treatment may take
RECTAL PROLAPSE anything from a few months to a few years
))
Severe colicky pain in abdomen accompanied by facial pallor,
Diagnosis of rectal prolapse is quite easy with a good history soon followed by red currant jelly stools is pathognomonic of
taking and per-rectal digital examination. If there are hard intussusception
fecal masses present on per-rectal examination, then the ))
Almost 95% of intussusceptions can be treated by hydrostatic
management shifts to management of chronic constipation as reduction and surgery is rarely needed
outlined above. If the anal sphincter tone is good, then again ))
Almost all cases of intussusception referred within 24 hours
just softening of stools for a few months will cause the prolapse of the onset of symptoms will be successfully reduced by
to disappear. hydrostatic reduction
If conservative treatment fails, then a surgical intervention
))
Around 20–25% of patients with juvenile polyps present with
may need to be considered. occult blood loss and anemia rather than visible bleeding.
The various options available today are:
• Injection sclerotherapy for mild prolapse
• Laparoscopic mesh fixation of the rectum (may be done by
SUGGESTED READINGs
laparotomy, if facilities for laparoscopy are not available)
• Posterior sagittal rectopexy 1. Arain Z, Rossi TM. Gastrointestinal bleeding in children: an overview of conditions
• Excision of a persistent rectal prolapse (stage IV, procedentia). requiring nonoperative management. Semin Pediatr Surg. 1999;8:172-80.
2. Bisset GS III, Kirks DR. Intussusception in infants and children: diagnosis and
therapy. Radilogy. 1988;168:141-5.
Clinical Pearls 3. Clarke G. et al. Investigating painless rectal bleeding—Is there scope for
improvement? J Pediatr Surg. 2005;40:1920-2.
Counseling points for parents 4. Cynamon H A, Milov DE, Andres JM. Diagnosis and management of colonic
• Per-rectal bleeding has a wide variety of causes and needs a polyps in children. J Pediatr. 1989;114:593-5.
reliable history for the diagnosis 5. de Ridder L, van Lingen AV, Taminiau JA, Benninga MA. Rectal bleeding in children:
endoscopic evaluation revisited. Eur J Gastroenterol Hepatol. 2007;19:317-20.
• It may need a battery of investigations to determine the
6. Durno CA. Colonic polyps in children and adolescents. Can J Gastroenterol.
cause and in spite of that a small percentage of cases may be
2007;21(4):233-9.
idiopathic
7. El-Mouzan MI, Abdullah AM. Yield of colonoscopy in children with rectal bleeding:
• The commonest cause of per-rectal bleeding in India is caused Saudi Medical Journal. 2004;8:998-1001.
by an anal fissure due to a faulty diet 8. Friedman CJ, Fechner RE. A solitary juvenile polyp with hyperplastic and
• Avoid long-term oral laxatives adenomatous glands. Dig Dis Sci. 1982;27:946-8.
• Intussusception very rarely needs surgery 9. Rozen P, Baratz M. Familial juvenile colonic polyposis with associated colon
cancer. Cancer. 1982;49:1500-3.
• Estimated blood loss more than 10% of the blood volume
10. Teach SJ, Fleicher GR. Rectal bleeding in pediatric emergency department. Ann
must be treated in the intensive care unit.
Emerg Med. 1994;23:1252-8.
636
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CHAPTER 130
Inguinal Hernia
Satish K Aggarwal, Nitin Pant
INTRODUCTION sac is incomplete, lying proximal to an obliterated segment

that intervenes between the sac and the tunica vaginalis
Inguinoscrotal swellings in children are a common reason (bubonocele). This accounts for the vast majority of inguinal
for pediatric consultation. Some of them may resolve hernia in children. If the processus is narrow allowing only
spontaneously (e.g., hydroceles) while others (e.g., hernia) peritoneal fluid to pass through, a hydrocele results. If the
almost always require surgery. Obstructed hernia may require hydrocele extends up to the base of scrotum, it is called
emergency operation to prevent bowel strangulation. The aim a vaginal hydrocele. If the peritoneal fluid collects in a
of this chapter is to enable a pediatrician to understand the
loculus of the processus at some point along its course in the
anatomy and pathology of processus vaginalis, its association
spermatic cord, it is called encysted hydrocele. This loculus
with testicular decent, and its role in manifestations of
usually communicates with the peritoneal cavity proximally,
hydrocele and hernia. The reader should be able to make a
but the distal part remains obliterated.
correct diagnosis and counsel parents about need for surgery,
or watchful waiting in hydroceles, and make timely surgical
referral to avoid complications of obstruction and strangulation Types
in hernia. A brief description of available surgical techniques is Nearly all inguinal hernias in children are indirect, with
also given. patent processus vaginalis being the underlying abnormality.
The testis descends into the scrotum during the seventh It travels from the deep inguinal ring across the inguinal
month of gestation pushing a diverticulum of peritoneum canal, comes out of the superficial ring and travels along the
(processus vaginalis) ahead of it. This processus begins to spermatic cord to the scrotum. Incidence is 0.8–4.4% with
obliterate in a caudal-cranial fashion once the testis descends male to female ratio between 3–10:1. The incidence is higher
to the scrotal base. The closure starts shortly before birth and in infants—keeping with higher rates of patent processus
normally completed during the first year of life, leaving only vaginalis in infancy. Preterm babies accordingly have highest
the tunica vaginalis surrounding the testis. The obliterated incidence varying from 16–25%. Right-sided hernias are more
processus vaginalis lies alongside the vas and vessels within
common (60%), attributable to the late descent of the right
the spermatic cord. Failure of obliteration results in patent
testis as compared to the left, hence a higher probability of
processus vaginalis—the underlying abnormality in all hernias,
patent processus vaginalis on the right. In girls, the canal
hydroceles, and encysted hydrocele of the cord.
of Nuck undergoes the same obliteration as the processus
vaginalis in boys. The obliteration is more likely to be
INGUINAL HERNIA complete, hence a lower overall incidence of hernias, but
there is a higher incidence of bilateral hernias. The incidence
Definition of bilateral hernia is higher if the first presentation is on the
left side.
By definition, a hernia is the protrusion of the contents of Direct inguinal hernia results from a weakness in the
a cavity along with its membrane through any normal or
posterior wall of the inguinal canal. They are rare in children.
abnormal opening. If the processus is wide enough, it allows
intestinal contents (bowel, omentum) to herniate through
it. This processus vaginalis forms the hernia sac which Clinical Presentation and Examination
can extend from the internal inguinal ring to the tunica The typical presentation of inguinal hernia in boys is a smooth
vaginalis (the inguinoscrotal hernia). More commonly, the painless swelling in the groin, which bulges on crying or
typical hernia swelling is not elicitable during examination,

the index finger should be rolled transversely across the
spermatic cord over the pubic bone; if there is a hernial sac,
the “rustle” of contiguous layers of peritoneum represents the
empty hernial sac—referred to as a “silken sleeve” or “silk glove
sign”. Even if it is not present, it may be appropriate to assume
the diagnosis of hernia on the basis of intelligent history.
Another source of confusion arises when the parents mistake
a testis in the superficial inguinal pouch for a hernia. In these
cases, the site of the swelling should be precisely indicated
and the presence of a testis in the scrotum documented. If
doubt still exists, the parents can be advised to photograph
the swelling as it appears and examination can be repeated
later. The opposite side should always be examined, and both
testes confirmed to be in the scrotum. Certain conditions are
associated with an increased incidence of inguinal hernia
including prematurity, cryptorchidism, connective tissue
Fig. 1: Left-sided hernia in a boy. Note the left inguinoscrotal
disorders, mucopolysaccharidoses, congenital hip dislocation,
swelling. The right testis has been pushed due to the large hernia
cystic fibrosis, ascites, ventriculoperitoneal shunt, peritoneal
dialysis, abdominal wall defects, meningomyelocele, and
exstrophy bladder.
straining. The swelling may extend to the scrotum as seen
in figure 1. It disappears either spontaneously when the Management
child is quiet and relaxed, or by gentle manual pressure—a Algorithm 1 shows a suggested approach to the management
maneuver to elicit “reducibility” of a hernia. Older children of hernia and hydrocele.
often complain of groin or inguinal pain during exercise. An inguinal hernia will not resolve spontaneously, so
To elicit hernia in the clinic, a young child can be made to surgery is always indicated. Most full-term infants and older
strain or cry while older children can be asked to stand and children undergo an elective herniotomy soon after diagnosis.
perform valsalva maneuver or blow a balloon. Clinically, one It is a day care operation performed under general anesthesia
can elicit the characteristic cough/strain impulse over the through a small skin crease incision in the groin. The hernia sac
swelling. The swelling extends in the inguinal canal deep to the is gently dissected from the cord structures (vas and vessels)
external oblique aponeurosis and emerges from the superficial and transected and ligated at the deep inguinal ring. The distal
inguinal ring. Therefore, the upper margin is not well defined sac is left in situ but opened widely. The testis is confirmed
(one cannot get above the swelling), hence it is called an in the scrotum before closing. No repair of the inguinal floor
inguinoscrotal swelling. When the history is suggestive but the (herniorrhaphy) is needed unless special situations exist.
ALGORITHM 1
Algorithm for management of hernia/hydrocele in an infant
638
CHAPTER 130: Inguinal Hernia
Timing of Surgery HYDROCELE

Infants When the processus vaginalis is patent with a small lumen
Elective surgery within days to few weeks from diagnosis. it allows some peritoneal fluid to seep down along the cord
It is not a dire emergency but waiting longer may invite producing a soft, fluid-filled swelling (Fig. 2). This collection
complications like obstruction—requiring emergency surgery of fluid between the layers of the tunica vaginalis is referred
with possibility of bowel resection. Obstructed hernia is a to as hydrocele. Unilateral or bilateral congenital hydroceles
common complication during infancy. are common in the first few months of life. The swelling
usually is very mild in the morning when the child wakes up;
Older children it gradually fills up during the day as the child remains active.
Elective operation within few weeks. When sleeping, some fluid recedes back gradually making the
swelling smaller. But this swelling is not reducible manually
Preterm babies because of very small size of patent processus (ink well effect).
Table 1 shows how to differentiate between a hernia and
Low birth weight babies, who are admitted to neonatal units
a hydrocele. The child is unaffected by the presence of the
with prematurity related issues, often develop a hernias. The
swelling. Clinically, there is no impulse on crying or straining as
author’s practice is to operate on them once the medical
in hernia. The swelling is painless; it is situated around the testis,
issues are over and the child is otherwise ready to be sent
is brightly translucent and cannot be emptied by pressure. The
home. However, there is an increased risk of anesthesia and
underlying testis may be palpable when the hydrocele is lax,
postoperative apnea risk. They may require postoperative
and when it is tense, the testis shadow can be demonstrated
monitoring and ventilation for about 24 hours.
by transillumination. The upper limit of the hydrocele is
clearly defined—the palpating finger “can get above it”, except
INCARCERATED HERNIA
An incarcerated hernia is one which does not reduce
spontaneously and is not reducible by gentle pressure. If left
untreated, it soon becomes obstructed, causing symptoms
of intestinal obstruction which may progress quite rapidly
to strangulation. Strangulation may cause intestinal and
testicular ischemia—the swelling becomes tense and tender
and there are features of intestinal obstruction. Strangulated
hernia requires emergency surgery to relieve intestinal
obstruction and save the gut and the testis. If the hernia is
incarcerated but not strangulated, the child may be mildly
irritable with groin pain but there is no abdominal distension
and no features of intestinal obstruction or hemodynamic
instability. Such a child should be admitted for monitoring
and sedated. Often the hernia will reduce spontaneously
within about 30 minutes of the child becoming quiet. If not,
“taxis” is applied—the surgeon stands on the side of hernia
Fig. 2: Right hydrocele. It was a lax hydrocele. The testis could be felt
and pushes the contents toward the inguinal canal across the
easily through the hydrocele
superficial ring with fingers of the right hand, simultaneously
aligning the sac to the superficial ring by the fingers of the left
hand on the top of the sac. Simply pushing the contents are
TABLE 1: Differentiating between hernia and hydrocele
not successful because the sac turns on itself as it comes out
of the superficial ring. If taxis is successful, the hernia should Hernia Hydrocele
be repaired in 24–48 hours after the tissue edema subsides. If Inguinoscrotal swelling. One Scrotal swelling. One can get
taxis is unsuccessful, another attempt may be made about an cannot get above the swelling above*
hour later (provided the patient is stable). If it still fails, urgent Not transilluminant** Transilluminant
operation should be carried out.
Can feel testis separately below Cannot feel testis separately
Risk of incarceration is highest in infancy reaching an the sac except in very lax hydroceles,
incidence of up to 30%. Therefore, surgery should be performed when one can palpate testis
soon after the diagnosis in this subset of patients so as to avoid within the hydrocele sac
the risk of incarceration and strangulation. *Large abdominoscrotal communicating hydroceles can be inguinoscrotal, but
An obstructed or strangulated hernia needs urgent they are rare. Also, they are brilliantly transilluminant.
exploration after adequate resuscitation. **In an infant, a bowel loops in a hernia sac may become transilluminant.
639
in unusual varieties (abdominoscrotal hydroceles). Most The author favors laparoscopic approach in all female hernias.
hydroceles resolve spontaneously as the processus obliterates Routine use of karyotype to pick up a rare case of AIS is not
by the age of 1 year and surgery is only required if the hydrocele warranted. AIS requires removal of both testes and life-long
persists beyond 2 years. Unusual situation that may warrant replacement of estrogens.
an early surgery are: very tense hydrocele causing discomfort
to the child and possible compression of testicular vessels, Bilateral Hernia
abdominoscrotal hydroceles, hydroceles associated with
Twenty percent hernias are bilateral. Contralateral hernia may
ventriculoperitoneal (VP) shunts, and when a hernia cannot
also develop later after repair of ipsilateral hernia. It is more
be excluded with certainty. An encysted hydrocele of the cord
common in infancy and girls, and when the presenting hernia
is a loculus of fluid located above and separate from the tunica
is on the left. Bilateral repair should be performed for clinically
vaginalis. Clinically, the swelling is separate from the testis
present bilateral hernias. But, routine contralateral exploration
and one can get both above and below the swelling. As it is
for a unilaterally presenting hernia is controversial. Some
in line with the processus, it moves when the testis is pulled
surgeons follow the practice of bilateral exploration in selected
down. Uncommonly, an acute hydrocele develops secondary
situations like preterm babies, presenting hernia on left side,
to epididymo-orchitis, torsion, trauma or tumor—these
and infants and female hernia. With advent of laparoscopic
hydroceles resolve spontaneously. The operation for hydrocele
hernia repair, this issue is largely resolved as both the deep
is the same as that for hernia.
rings are clearly visible and without any additional ports,
bilateral repair can be performed laparoscopically.
SPECIAL CONSIDERATIONS
LAPAROSCOPIC VERSUS
Preterm Babies OPEN REPAIR OF HERNIA
They have high incidence of hernia but, owing to a wider neck,
Open repair of hernia through a skin crease incision is a
the rate of incarceration is comparatively lower than in term
standard time tested operation with universally good results.
babies. When diagnosed in the neonatal unit they should be
However, laparoscopic repair has also made inroads during
repaired just before sending them home from medical point of
the last decade with improved techniques largely resembling
view. Bilateral operation is often necessary.
open hernia repair. The advantages of laparoscopic repair are:
clear magnified view of vas and vessels (Fig. 3), therefore, less
Hernia with Undescended Testis chances of damaging them, no stretching of cord structures,
Undescended testis is always accompanied by a hernial sac, no disturbance to the testis, hence, less complication of
but is at low risk of incarceration. They can be safely repaired testicular fixation in the wound, and ability to do simultaneous
at the time of orchidopexy (generally at 6 months). However, bilateral repair, if necessary. The disadvantages are: need to
the parents are warned about the danger signs of obstruction. go transperitoneally, more cost, and a higher incidence of
If symptomatic hernia develops, an early repair of hernia and postoperative hydrocele. Most surgeons agree on its use for
undescended testis is performed. female hernia. For males, the debate continues (Table 1).
Hernia with Ventriculoperitoneal Shunts

These hernias tend to be bilateral and have about 20% risk of
incarceration. Bilateral early repair is in order.
Hernia in a Female Child

The incidence of bilaterality is high in females. The ovary
may be a content and it is difficult to reduce. Often, there
is a fallopian tube also herniating out. If there is no pain or
tenderness in the ovary, an elective operation may be done
within a few days to weeks, but if there is pain or tenderness,
it may indicate torsion and requires urgent operation. Rarely,
androgen insensitivity syndrome (AIS) in a phenotypic female
may present with a hernia with a testis in the sac. The authors
advocate a preoperative ultrasound in females with hernia to
confirm presence of uterus and tubes. If a suspicious gonad is
found in the sac on the table, gonad is not removed; parents are
counseled, hernia repaired, and the child investigated further Fig. 3: Laparoscopic view of left hernia in a boy. The vas and vessels
with karyotype. Laparoscopy is a good tool to confirm internal are clearly visible in the magnified view, hence less likely to be injured
genital anatomy and repair hernia, which are often bilateral. during repair
640
CHAPTER 130: Inguinal Hernia

1. Barthold JS. Abnormalities of the testis and scrotum and their surgical management.
Indications of surgery in hydrocele In: Wein AJ, Kavoussi LR, Partin AW (Eds). Campbell Walsh Urology. 10th ed.
• Persistent hydrocele beyond 2 years Elsevier-Saunders; 2012. pp. 3556-96.
• Tense hydrocele threatening testicular vessels at any age 2. Borkar NB, Pant N, Ratan SK, Aggarwal SK. Laparoscopic repair of indirect inguinal
hernia in children: does partial resection of sac make any impact on outcome? J
• Hydrocele developing de novo after 2 years Laparoendosc Adv Surg Tech. 2012;22(3):290-4.
• Hydrocele with ventriculoperitoneal shunt 3. Chan KL, Tam PK. Technical refinements in laparoscopic repair of childhood inguinal
• Abdominoscrotal hydrocele. hernias. Surg Endosc. 2004;18:957-60.
4. Glick PL, Boulanger SC. Inguinal hernias and hydroceles. In: Coran G, Adzick NS,
Krummel TM (Eds). Pediatric Surgery, 7th ed. Elsevier-Saunders; 2012. pp. 985-1001.
5. Inguinal Region and Acute Scrotum in Hutson JM, Brien MO, Woodward AA (Eds).
KEY POINTS Jones’ Clinical Paediatric Surgery Diagnosis and Management, 6th ed. Blackwell
Publishing; 2008. pp. 168-71.
))
Congenital hernia and hydroceles develop from patent
6. Lloyd DA. Inguinal and femoral hernia. In: Zeigler MM, Azizkhan RG, Weber Thomas
processus vaginalis R (Eds). Operative Pediatric Surgery, International edition. Mc Graw Hill Professional;
))
Hydrocele contains fluid and hernia contains bowel or 2003. pp. 543-54.
omentum 7. Saranga BR, Arora M, Baskaran V. Minimal access surgery of pediatric inguinal
))
Hernia is inguinoscrotal while hydrocele is scrotal hernias: a review. Surg Endosc. 2008;22:1751-62.
))
Incidence of hernia is high in infants. Probability of compli
cations—obstruction and strangulation, is also higher in them
))
Surgery should be performed soon after diagnosis to prevent
complications
))
Obstructed or strangulated hernia requires emergency
operation
))
Hydroceles usually resolve spontaneously in the first year of life
))
Tense hydroceles may cause compression of testicular vessels,
hence require surgery.
641
Chapter 131
Antenatal Hydronephrosis
Anurag Krishna
Introduction A renal pelvis anteroposterior diameter of more than 10

mm after 24–26 weeks of gestation is generally accepted as
Routine antenatal ultrasonography has focused our attention a reasonable criterion to denote significant dilatation. The
to urological abnormalities that occur in babies. Ultra presence of caliectasis or calyceal dilatation is considered
sonologists routinely use terms such as pelvicaliectasis, an additional factor indicative of significant hydronephrosis.
caliectasis, and hydronephrosis, leading to confusion in More recently, there is evidence to suggest that milder degrees
the minds of the obstetrician, the neonatologist, and the of dilatation may also be significant in such babies, who may
pediatric surgeon as to the precise significance of this finding.
have VUR rather than obstruction. Currently, a renal pelvis
This review aims to outline a logical approach to this problem
diameter of at least 4 mm before 33 weeks and 7 mm after 33
through the gestational period into the neonatal period
weeks is considered significant. ANH can be classified as mild,
emphasizing what needs to be done and when, and more
moderate, or severe for prognostic purposes (Table 2). A large
importantly, what need not be done.
systematic review suggests that the risk of significant postnatal
pathology is 11.9% for mild, 45.1% for moderate, and 88.3% for
MAGNITUDE OF THE PROBLEM severe hydronephrosis.
It is estimated that some degree of dilatation of the fetal renal
collecting system is identified in 1–5% of all pregnancies, Table 1: Grading of hydronephrosis
but in only one-fifth of these, dilatation is significant. The Grade Pattern of renal sinus splitting
term hydronephrosis simply denotes dilatation of the upper
urinary tract and does not necessarily imply the presence of 0 No splitting
an obstruction or a significant functional abnormality of any 1 Urine in pelvis barely splits sinus
kind. In fact, only 3% of babies with a renal pelvis diameter less
than 10 mm had a significant abnormality needing surgery. 2 Urine fills intrarenal pelvis
Antenatal hydronephrosis (ANH) could occur because of: 2 Urine fills extrarenal pelvis, major calyces dilated
• Functional dilatation: minor degree of dilatation that
usually spontaneously resolves or stabilizes later in 3 SFU grade 2 and minor calyces dilated and parenchyma
gestation or early infancy preserved
• Obstruction: usually at the pelvi-ureteric junction, at the 4 SFU grade 3 and parenchyma thin
ureterovesical junction, or in the urethra [as in posterior SFU, Socity of Fetal Urology.
urethral valves (PUV)]
• Vesicoureteral reflux (VUR)
Table 2: Definition of antenatal hydronephrosis by antero
• Renal dysplasia including multicystic dysplastic kidneys
posterior diameter
• Uncommon conditions like duplex collecting system or
prune belly syndrome, etc. Degree of ANH Second trimester Third trimester
Mild 4 to <7 mm 7 to <9 mm
What Is Significant Dilatation?
Moderate 7 to ≤10 mm 9 to ≤15 mm
The Society of Fetal Urology (SFU) has recommended a grading
system for hydronephrosis (Table 1). An alternate method is to Severe >10 mm >15 mm
measure the renal pelvis anteroposterior diameter. ANH, antenatal hydronephrosis
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Chapter 131: Antenatal Hydronephrosis
Information from a Natural History of Antenatal Hydronephrosis

Good Antenatal Ultrasound Scan Spontaneous resolution of prenatally detected hydronephrosis
While assessing the significance of the antenatal renal occurs in 50–70% of all fetuses. This regression may be noted
dilatation, particularly with a view to identify a possible cause on serial antenatal ultrasound scans or in the postnatal life
and whether it is worth continuing pregnancy, the ultrasound up to 3 years. Furthermore, in a substantial number, even if
must be done carefully and must give the following information: the hydronephrosis does not resolve completely, the renal
• Estimated fetal size and weight, and its comparison with function does not deteriorate despite persistence of pelvic
normal for that gestational age dilatation. On the other hand, 15–33% of patients show
• Amniotic fluid volume (AFV) progressive renal deterioration during observation. It has been
• Whether dilatation is unilateral or bilateral, and whether noted that increasing degrees of hydronephrosis correlated
ureters are dilated or not with increased risk of urological pathologies that may need
• Degree of dilatation (SFU grading) and dilatation of calyces surgical intervention.
• Bladder fullness, thickness, and emptying
• Appearance of external genitalia
POSTNATAL EVALUATION OF
• Any other associated malformation.
The initial study is usually done at 16–20 weeks of gestation ANTENATAL HYDRONEPHROSIS
using an appropriate transducer. There are no specific Immediately after birth, the following must be recorded:
guidelines on how frequently to image the fetus. It would be • Sex of the baby: in males, PUV is an important diagnosis to
reasonable to do the ultrasound every 4 weeks till 32 weeks and be ruled out as it requires early surgical intervention
two weekly thereafter, mainly to assess the AFV. • Palpable kidney: common causes are PUJO (more
commonly unilateral), multicystic dysplastic kidney
Current Status of Fetal Intervention (unilateral), and PUV (unilateral or bilateral)
The rationale for fetal urinary decompression is that those • Palpable bladder: indicative of PUV in boys.
with severe obstruction early in gestation have significant If the diagnosis of PUV is suspected, all further
impairment of both renal and pulmonary development. It has investigations need to be done urgently as the baby requires
been recognized that if the AFV is adequate up to 27 weeks early surgical intervention. These babies need renal function
of gestation, then severe pulmonary hypoplasia is unlikely to tests, ultrasound scan, voiding cystourethrogram (VCUG)
occur. Percutaneous shunting of the bladder into the amniotic within a day or two after birth so that surgical ablation of the
space is technically feasible with some morbidity. However, its valves may be done at the earliest.
role is extremely limited. In all other situations, there is no great haste to perform
There is no place for any fetal intervention in unilateral investigations (Algortihm 1). The initial study to be done is the
hydronephrosis. Even with bilateral pelviureteric junction ultrasound scan that must preferably not be done in the first
obstruction (PUJO), if the AFV is normal, percutaneous 2–3 days. However, if the mother is being discharged earlier, it
drainage of the fetal kidneys or early delivery are not warranted. is practical to send the baby with the ultrasound scan results.
Algorithm 1
Scheme for postnatal evaluation in patients with antenatal hydronephrosis
643
SFU, Society of Fetal Urology; APD, anteroposterior dianeter.
ch-131.indd 643 11/22/2016 10:55:43 AM

Following the ultrasound scan, a VCUG is done. There is and objective and quantitative assessment of relative
no doubt that the conventional VCUG is preferred to a direct function of each kidney is possible. The ideal radionuclide
radionuclide cystogram (DRCG) because the latter does not is mercaptoacetyltriglycine, but a cheaper, though less
give a good delineation of the bladder and urethral anatomy accurate option is the diethylenetriamine pentaacetate
and that reflux, if present, cannot be accurately graded. acid (not dimercaptosuccinic acid) scan. In lower grades
Controversy surrounds two aspects of VCUG: of hydronephrosis, if VUR has been excluded, no further
• Should VCUG be done in all babies? workup with renal scans may be necessary. These babies need
• When should it be done? observation with 3-monthly ultrasound to ensure that the
Should VCUG be done in all babies? degree of hydronephrosis is static and not worsening.
Voiding cystourethrogram is an invasive procedure, and
some studies have quoted a 6% rate of urinary tract infection Follow-up Evaluation
(UTI) following VCUG. This has made most clinicians reluctant
to ask for a VCUG in newborn babies. However, if properly Currently, no single test can reliably predict whether a
performed under antibiotic cover, the procedure is safe with hydronephrotic kidney will improve or deteriorate. Most people
no risk of UTI (personal experience). There are some recent agree that nearly all infants with unilateral PUJO are initially
reports that claim that routine VCUGs may not be indicated managed conservatively if the diuretic renogram shows at least
in all babies with antenatally detected hydronephrosis. These 35–40% differential renal function. Exception are infants with
studies recommend VCUG for those babies with: renal infection, tense renal lump or pelvis anteroposterior
• bilateral hydronephrosis diameter more than 50 mm. Follow-up ultrasound scan and
• dilated ureters diuretic renography is repeated at 3–6 months and if there
• presence of UTI. is a deterioration in differential renal function, pyeloplasty
This literature against routine use of VCUG is far from is indicated. Nearly 20% infants will show deterioration on
convincing. Most large centers recommend that this test follow-up requiring pyeloplasty. This usually happens in the
must be done in all babies with ANH even if the postnatal first year of life.
ultrasound scan is normal. VUR has been recorded in 15–30% Children with lesser degree of hydronephrosis (up to pelvis
babies born with an antenatal diagnosis of hydronephrosis. anteroposterior diameter of <20 mm) need to be followed up
Tibballs reported that among 255 renal units with reflux, the with a ultrasound scan at 3 months, 1 year, then 2, 5, and 10 years.
postnatal ultrasound was normal in 177 (70%). Furthermore, Radionuclide study is done at 3 months, 1 year, and if required
some studies have shown that the postnatal ultrasound may be at 2, 5, and 10 years. If the renal function or degree of dilatation
normal even with the higher grades of VUR (12% of grade V and improves, there is no further need for the isotope study.
31% with grade IV). The Indian Society of Pediatric Nephrology
has recommended a middle path for performing VCUG if
there is moderate-to-severe hydronephrosis, dilated ureters, or Clinical Pearls
bladder or urethral abnormalities. • Hydronephrosis >7 mm after 33 weeks is significant
When should it be done? • Look for bladder emptying in fetuses with hydronephrosis,
Some authors recommend that a VCUG should be done particularly bilateral
at 4–6 weeks postnatal age. Though, again, it would be more
• First postnatal ultrasound may be done 48–72 hours after birth
practical to do it before the baby leaves hospital. Either way, till
the VCUG has been done and VUR excluded the baby needs to • In male babies, always exclude possibility of posterior urethral
be on low dose antibiotics using amoxicillin (15 mg/kg/day) or valves by looking for bladder emptying
cephalexin (50 mg/kg/day). Trimethoprim (2 mg/kg/day) may • Till a voiding cystourethrogram is done, it may be safer to give
be used safely in babies after 4–6 weeks of age. Neonates who do low dose antibiotic prophylaxis
not have VUR do not need further antibiotic chemoprophylaxis. • Diethylenetriamine pentaacetate acid renogram should be
done if obstruction is suspected. Dimercaptosuccinic acid
Role of Radionuclide Imaging Studies renal scan is to be done in cases with vesicoureteral reflux.
In most babies, the ultrasound scan is repeated at 4–6 weeks of
age. In most situations, a diuretic renogram is done at about 4
weeks of age to evaluate renal functional status and presence Key points
of obstruction. Renograms performed immediately after birth
may be difficult to interpret due to the immature function of ))
Antenatal hydronephrosis does not necessarily mean
the kidneys and their handling of the radioisotope. Diuretic obstruction
renogram is indicated in all kidneys with grade 3 or 4, and ))
Most such pregnancies can be carried to term
occasionally grade 2 hydronephrosis; there is bilateral PUJO or ))
Fetal intervention is not required in majority of cases
ureterovesical junction obstruction; if there is a solitary kidney; ))
Postnatal evaluation must be done in all such babies and
or, the kidney is palpable and tense. must include a surgical opinion
The renal scan is superior to the introvenous pyelogram ))
A majority do not need surgical intervention, but those that
for many reasons. It is safer (contrast reactions and radiation do need, requires an early surgical evaluation.
644 are less), there is better visualization of the collecting system,
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Chapter 131: Antenatal Hydronephrosis
SUGGESTED READINGS 25. Mandell J, Blyth BR, Peters CA, Retik AB, Estroff JA, Benacerraf BR. Structural
genitourinary defects detected in utero. Radiology. 1991;178:193-6.
1. Ansari MS, Ayyildiz HS, Jayanthi VR. Is voiding cystourethrogram necessary in all 26. Mandell J, Lebowitz RL, Peters CA, Estroff JA, Retik AB, Benacerraf BR. Prenatal
cases of antenatal hydronephrosis? Indian J Urol. 2009;25(4):545-6. diagnosis of the megacystis-megaureter association. J Urol. 1992;148:1487-9.
2. Becker AM. Postnatal evaluation of infants with an abnormal antenatal renal 27. Mandell J, Peters CA, Estroff JA, Benacerraf BR. Late onset severe oligohydramnios
sonogram. Curr Opin Pediatr. 2009;21(2):207-13. associated with genitourinary abnormalities. J Urol. 1992;148:515.
3. Blane CE, DiPietro MA, Zerin JM, et al. Renal sonography is not a reliable 28. Marra G, Barbieri G, Moioli C, Assael BM, Grumieri G, Caccamo ML. Mild
screening examination for vesicoureteral reflux. J Urol. 1993;150:752. fetal hydronephrosis indicating vesicoureteric reflux. Arch Dis Child. 1994;70:
4. Coret A, Morag B, Katz M, Lotan D, Heyman Z, Hertz M. The impact of fetal F147-9.
screening on indications for cystourethrography in infants. Pediatr Radiol.
29. Mears AL, Raza SA, Sinha AK, Misra D. Micturating cystourethrograms are not
1994;24:516-8.
necessary for all cases of antenatally diagnosed hydronephrosis. J Pediatr Urol.
5. Corteville JE, Gray DL, Crane JP. Congenital hydronephrosis: correlation of 2007;3(4):264-7.
fetal ultrasonographic findings with infant outcome. Am J Obstet Gynecol.
30. Moorthy I, Joshi N, Cook JV, Warren M. Antenatal hydronephrosis: negative
1991;165:384.
predictive value of normal postnatal ultrasound—a 5-year study. Clin Radiol.
6. De Kort EHM, Bambang Oetomo S, Zegers SH. The long term outcome of 2003;58:964-70.
antenatal hydronephrosis up to 15 millimeters justifies a noninvasive postnatal
31. Nguyen HT, Herndon CD, Cooper C, Gatti J, Kirsch A, Kokorowski P, et al. The
follow-up. Acta Paediatrica. 2008;97;708-13.
Society of Fetal Urology consensus statement on the evaluation and management
7. Dhillon HK. Prenatally diagnosed hydronephrosis: the Great Ormond Street
of antenatal hydronephrosis. J Pediatr Urol. 2010;6(3):212-31.
experience. Br J Urol. 1998;81(Suppl 2):39-44.
32. Ouzounian JG, Castro MA, Fresquez M, al-Sulyman OM, Kovacs BW. Prognostic
8. DiSandro MJ, Kogan BA. Neonatal management. Role for early intervention. Urol
significance of antenatally detected fetal pyelectasis. Ultrasound Obstet Gynecol.
Clin North Am. 1998;25(2):187-97.
1996;7(6):424-8.
9. Dudley JA, Haworth JM, McGraw ME, Frank JD, Tizard EJ. Clinical relevance and
33. Palmer LS, Maizels M, Cartwright PC, Fernbach SK, Conway JJ. Surgery versus
implications of antenatal hydronephrosis. Arch Dis Child. 1997;76:F31.
observation for managing obstructive grade 3 to 4 unilateral hydronephrosis: a
10. Elder JS. Antenatal hydronephrosis. Fetal and neonatal management. Pediatr Clin
report from the Society for Fetal Urology. J Urol. 1998;159:222.
North Am. 1997;44(5):1299-321.
34. Passerotti CC, Kalish LA, Chow J, Passerotti AM, Recabal P, Cendron M, et al.
11. Freedman ER, Rickwood AMK. Prenatally diagnosed pelviureteric junction
The predictive value of the first postnatal ultrasound in children with antenatal
obstruction: a benign condition? J Pediatr Surg. 1994;29:769-72.
hydronephrosis. J Pediatr Urol. 2011;7:128-36.
12. Gloor JM, Ramsey PS, Ogburn Jr PL, Danilenko-Dixon DR, DiMarco CS, Ramin KD.
35. Persutte WH, Koyle M, Lenke RR, Klas J, Ryan C, Hobbins JC. Mild pyelectasis
The association of isolated mild fetal hydronephrosis with postnatal vesicoureteral
ascertained with prenatal ultrasonography is pediatrically significant. Ultrasound
reflux. J Matern Fetal Neonatal Med. 2002;12:196-200.
Obstet Gynecol. 1997;10(1):12-8.
13. Grignon A, Filion R, Filiatrault D. Urinary dilatation in utero: classification and
clinical applications. Radiology. 1986;160:645. 36. Phan VR, Traubici J, Hershenfield B, Stephens D, Rosenblum ND, Geary DF.
Vesicoureteral reflux in infants with isolated antenatal hydronephrosis. Pediatr
14. Herndon C, McKenna P, Kolon T, Gonzales ET, Baker LA, Docimo SG. A multicenter
Nephrol. 2003;18:1224-8.
outcomes analysis of patients with neonatal reflux presenting with prenatal
hydronephrosis. J Urol. 1999;162(3 Pt 2):1203-8. 37. Ransley PG, Dhillon HK, Gordon I, Duffy PG, Dillon MJ, Barratt TM. The postnatal
management of hydronephrosis diagnosed by prenatal ultrasound. J Urol.
15. Herndon CD. Antenatal hydronephrosis: differential diagnosis, evaluation, and
1990;144:584-7.
treatment options. Scientific World Journal. 2006;6:2345-65.
16. Homsy YL, Williot P, Danais S. Transitional neonatal hydronephrosis: fact or 38. Reddy PP, Mandell J. Ureteropelvic junction obstruction: prenatal diagnosis,
fantasy? J Urol. 1986;136:339. therapeutic implications. Urol Clin N Am. 1998;25(2):171-80.
17. Kitagawa H, Pringle KC, Stone P, Flower J, Murakami N, Robinson R. Postnatal 39. Sairam S, Al-Habib A, Sasson S, Thilaganathan B. Natural history of fetal
follow-up of hydronephrosis detected by prenatal ultrasound: the natural history. hydronephrosis diagnosed on mid-trimester ultrasound. Ultrasound Obstet.
Fetal Diagn Ther. 1998;13(1):19-25. Gynecol. 2001;17(3):191-6.
18. Kleiner B, Callen PW, Filly RA. Sonographic analysis of the fetus with ureteropelvic 40. Sinha A, Bagga A, Krishna A, Bajpai M, Srinivas M, Uppal R, et al. Revised
junction obstruction. AJR. 1987;148:359-63. guidelines on management of antenatl hydronephrosis. Indian Pediatr. 2013;
19. Koff SA, Campbell KD. The nonoperative management of unilateral neonatal 50(2):215-31.
hydronephrosis: natural history of poorly functioning kidneys. J Urol. 41. Thomas DFM, Madden NP, Irving HC, Arthur RJ, Smith SE. Mild dilatation of the
1994;152:593. fetal kidney: a follow-up study. Br J Urol. 1994;74:236-9.
20. Koff SA, McDowell GC, Byard M. Diuretic radionuclide assessment of obstruction 42. Tibballs JM, De Bruyn R. Primary vesicoureteral reflux—how useful is postnatal
in infant: guidelines for successful interpretation. J Urol. 1988;140:1167-8. ultrasound? Arch Dis Child. 1996;75:444.
21. Koff SA. Postnatal management of antenatal hydronephrosis using an 43. Vates TS, Shull MJ, Underberg-Davis SJ, Fleisher MH. Complications of
observational approach. Urology. 2000;55:609-11. voiding cystourethrography in the evaluation of infants with prenatally detected
22. Lee RS, Cendron M, Kinnamon DD, Nguyen HT. Antenatal hydronephrosis as a hydronephrosis. J Urol. 1999;162(3 Pt 2):1221-3.
predictor of postnatal outcome: a meta-analysis. Pediatrics. 2006;118:586. 44. Yerkes E, Adams M, Pope JC 4th, Brock JW 3rd. Does every patient with
23. Lee RS, Cendron M, Kinnamon DD, Nguyen HT. Antenatal hydronephrosis as a prenatal hydronephrosis need voiding cystourethrography? J Urol. 1999;162:
predictor of postnatal outcome: a metaanalysis. Pediatrics. 2006;118: 586-93. 1218-23.
24. Longpre M, Nguan A, Macneily AE, Afshar K. Prediction of the outcome of 45. Zerin JM, Ritchey ML, Chang AC. Incidental vesicoureteral reflux in neonates with
antenatally diagnosed hydronephrosis: a multivariate analysis. J Pediatr Urol. antenatally detected hydronephrosis and other renal abnormalities. Radiology.
2012;8(2):135-9. 1993;187:157-60.
645
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CHAPTER 132
Management of
Vesicoureteric Reflux
Minu Bajpai, Aparajita Mitra, Manisha Jana, Rakesh Kumar, Chandra S Bal
Primary vesicoureteric reflux (VUR) is seen in 1% of the [by ultrasonography and micturating cystourethrogram
general population. It is seen in 37% of children and up to 50% (MCU)] may offer the benefit of preventing hypertension
of neonates who present with urinary tract infection (UTI). and renal failure
The association of the triad of UTI-VUR-nephropathy forms • It has been recognized that, the diagnosis of UTI in young
the basis of treatment of VUR. However, lack of application of children is often delayed as the clinical presentation is
appropriate tools in the studies has led to inconsistencies in often with vague general symptoms
management protocols. In VUR, some urine flows back into • Any antenatally diagnosed and postnatally confirmed
the ureters during the act of micturation depending upon the dilated ureter or hydronephrosis or diagnosis of conditions
grade of reflux. VUR may resolve spontaneously with increasing like duplication anomalies or pelvic kidneys have a risk of
age, albeit slowly. At the end of 5 years, grades I and II reflux ipsilateral VUR, whereas, multicystic dysplastic kidney and
persist in 37% of children and at 10 years in 25%. During the renal agenesis has an increased incidence of contralateral
corresponding periods, grades III–V reflux persist in 48 and VUR. Therefore, MCU/voiding cystourethrogram (VCUG)
23%, respectively. Negative prognostic factors for resolution should be carried out after confirmed, UTI even in presence
are recurrent UTIs and bladder dysfunction. Bilateral reflux of mild hydronephrosis. Once VUR is confirmed, a full
resolved more slowly than unilateral reflux and it resolved more workup is carried out, which includes dimercaptosuccinic
rapidly in boys than in girls. Antibiotic prophylaxis has been acid (DMSA) scans and glomerular filtration rate (GFR)
widely employed in the hope of prevention of pyelonephritis. estimation
However, pyelonephritis occurs despite antibiotics. • Long-term antibiotic use may increase the severity of otitis
media in children. In some studies, including the National
MAINSTAY OF MODERN MANAGEMENT Institute for Clinical Excellence (NICE) guidelines,
prophylactic antibiotics have been found neither to be
OF VESICOURETERIC REFLUX effective in reducing the risk of recurrent pyelonephritis
• Continuing VUR has the potential to cause long-term nor incidence of renal scarring in children less than 30
renal damage, therefore, early diagnosis and prevention of months of age who have grade II–IV VUR
pyelonephritis are very important • It should be recognized that infants often have non-specific
• UTI may occur even in nondilating VUR (grades I and symptoms of UTI which may remain unnoticed
II). In a follow-up study in children with VUR, who • Renin angiotensin system has been shown to be activated
were evaluated using criteria specified in the American even in the presence of sterile reflux. The upper tracts are,
Academy of Pediatrics (AAP) guidelines, 17.2% of children therefore, at risk in presence of VUR even between the
with normal ultrasound had renal injury identified on renal episodes of UTI
scanning, and 62.1% had grade III or higher VUR • Endoscopic treatment is viewed as preferable to open
• The Subcommittee on UTI of the AAP acknowledges that surgery by 60% of parents even for grades I–II reflux and
it is important to detect urinary tract anomalies, such as 80% of those with grade III reflux over long-term antibiotic
VUR, at the outset, once UTI is confirmed. Children with prophylaxis (Figs 1A and B)
VUR are believed to be at risk for ongoing renal damage • Presently, the endoscopic treatment of VUR by
with subsequent infections, resulting in hypertension and dextranomer/hyaluronic acid (DXHA) is increasingly
renal failure. Therefore, identifying urinary abnormalities viewed as first line therapy for reflux (Figs 2A and B)
CHAPTER 132: Management of Vesicoureteric Reflux
A B
Fig. 1: Micturating cystourethrogram showing high grade reflux: A, before and B, after endoscopic injuction
A B
Fig. 2: Cystoscopic view of the ureteric orifice: A, before and B, after injection of dextranomer/hyaluronic acid
copolymer (deflux)
• Parental preference for choice of therapy is honored and Option B (Endoscopic Injection)
they should be offered information on the three options of
therapy: Endoscopic injection recreates the antireflux mechanism by
injecting an inert material into the bladder wall at the ureteric
Option A (Antibiotic Prophylaxis) orifice. While general anesthesia is required, it is generally a
day care procedure. Its success rates range from 70 to 83%.
Continuous antibiotic prophylaxis (CAP) does not require any Success for even grades IV and V reflux reaches above 90% after
procedure, as compared to the other two options. However, it two or more injections.
does not cure reflux and only reduces the incidence of UTI.
Pyelonephritis may continue to occur. It also requires long-
term treatment, with a low success rate after 1 year (33% Option C (Open Surgery)
in grades II–IV reflux) is a major disadvantage. It has been The aim of open surgery is to prevent reflux by reimplantation
recognized that after 2 years of age, chances of spontaneous of ureter and restoring the antireflux mechanism. Success rates
resolution of VUR are low, while prolonged antibiotic use leads for open surgery are 98%, with few complications. However,
to side effects. CAP is still being recommended until more the higher success rates for open surgery necessitate greater
definitive studies suggest otherwise. expense and the need for in-patient hospitalization. 647
• Grade V VUR should be offered open/laparoscopic MANAGEMENT OF

surgery. Depending upon the availability and affordability, VESICOURETERIC REFLUX
endoscopic injection may be offered as an option while
explaining the need for two or more injections. When Following considerations should be given while outlining
treated by surgery, ureteric reimplantation should be choice of therapy:
performed after 18 months of age. Till this age, CAP should • Reflux diagnosed in infancy resolves in about 50% within
be given. If recurrent infections continue to occur before 24 months
this period, either endoscopic injection or surgery may be • According to NICE guidelines, as well as other studies,
offered even earlier by creating a pop-off mechanism prophylactic antibiotics are not effective in reducing
• Grades III and IV VUR as well as associated cortical the risk of recurrent pyelonephritis or renal scarring in
abnormalities delay reflux resolution. Considerations children less than 30 months of age who have grade II–IV
should be given to treat these by intention to cure, such as VUR. However, antibiotics seem to be better than placebo
endoscopic injection (option 2) or open surgery (option 3) in preventing infection if given for short periods, but, have
• If CAP is used, reassessment of VUR by cystogram side effects with prolonged use
between 12 and 24 months after the prior cystogram is • Infants often have nonspecific symptoms of UTI which
recommended to determine when therapy can be stopped may remain unnoticed. They also have a greater risk of
• Open or endoscopic surgery shall be offered in the morbidity related to infection
presence of UTI, new scars in DMSA scanning, and • Continuing VUR has the potential to cause long-term
parental preference. If decision to intervene is postponed renal damage; therefore, early diagnosis and prevention of
even after frequent UTIs, there is a higher risk of continuing pyelonephritis are very important
postoperative UTIs • Renal injury/scars are mediated through the activation of
• After open surgery, ultrasonography should be performed renin angiotensin system:
to rule out obstruction. Follow-up monitoring should {{ Microalbuminuria indicates that renal tubular injury
be carried out for infections, new scarring, and somatic has already begun as this is an early marker of inception
growth through adolescence. of renal damage
ALGORITHM 1
Management of vesicoureteric reflux
VUR, vesicoureteric reflux; UTI, urinary tract infections; DMSA, dimercaptosuccinic acid; PRA, plasma renin activity.
648 *If recurrent UTIs develop during the waiting period, then some other temporizing surgery, such as lower ureteric pop-off mechanism, should be offered to the patient.
CHAPTER 132: Management of Vesicoureteric Reflux
{{ Raised plasma renin activity (PRA) indicates that Additional Information

activation of renin angiotensin system has already
• Endoscopic treatment can be offered concomitant with
begun
management of bladder and bowel dysfunction. It has been
• Renin angiotensin system has been shown to be activated
found to be safe and effective in resolving VUR in children
even in the presence of sterile reflux. Therefore, the upper
with associated lower urinary tract (LUT) dysfunction, even
tracts are at risk in presence of VUR even between the
before their LUT condition has fully resolved. However,
episodes of UTI
bladder bowel dysfunction should definitely be under
• It has been recognized that after 2 years of age, chances of
control before surgical intervention
spontaneous resolution of VUR are low
• Reflux in solitary kidney and bilateral reflux:
• Ureteric reimplantation should be avoided before 18
{{ Any grade of reflux with either UTI, cortical defects/
months of age.
scarring, raised PRA, or microalbuminuria should be
offered endoscopic injection/surgery
Management of Vesicoureteric Reflux in {{ Grades I and II reflux without UTI, cortical defects/
the Child under 2 Years of Age scarring, raised PRA, or microalbuminuria: antibiotics
Children under 2 years of age should be assessed for renal for a period of 12 months. If there is persistence of
abnormalities and bladder bowel dysfunction. When present, reflux or any of the above features develop they should
treatment for the latter is initiated. be offered option 2 or 3.
• Children with grades I, II, and III VUR who do not have either
UTI, cortical scarring, raised PRA, or microalbuminuria Clinical Pearls
form a special group: they should be offered option 1 (CAP)
• Antibiotics seem to be better than placebo in preventing
for a period of 12 months or till the time any of the above
infection if given for short periods, but have side effects with
features develop, whichever is earlier. In the absence of prolonged use
UTIs, MCU should be done between 12 and 24 months. If
• Infants often have nonspecific symptoms of urinary tract
there is persistence of reflux or any of the above features infection (UTI) which may remain unnoticed. They also have a
develop, they should be offered option 2 or 3, as follows greater risk of morbidity related to infection
• Children with any grade of reflux who have either UTI, • Continuing vesicoureteric reflux (VUR) has the potential to
cortical defects/scarring, raised PRA, or microalbuminuria: cause long-term renal damage. Therefore, early diagnosis and
they should be offered option 2 (endoscopic treatment). prevention of pyelonephritis are very important
In the event of nonavailability or, nonaffordability due to • Renin angiotensin system has been shown to be activated even
cost of injection, option 3 should be offered. In the case of in the presence of sterile reflux. Therefore, the upper tracts are at
decision on the latter case (option 3), antibiotics should risk in presence of VUR even between the episodes of UTI
be continued till 18 months of age (“waiting period” • It has been recognized that after 2 years of age, chances of
during which open surgery by ureteric reimplantation spontaneous resolution of VUR are low
is best avoided). During this “waiting period” if adverse • Ureteric reimplantation should be avoided before 18 months
circumstances appear, such as recurrent UTI, cortical of age.
defects, rise in PRA or microalbuminuria, surgical options
other than ureteric reimplantation may be considered.
These are temporizing procedures such as creating a pop- CONCLUSION
off mechanism.
• While managing VUR, it is important to take into account
Management of Vesicoureteric Reflux in the individual risk factors in each child. These are: age, sex,
grade of reflux, bilaterality, bladder dysfunction, and bowel
Child Over 2 Years of Age
function
Children over 2 years of age should be assessed for renal • It has been recognized that, while antibiotics have some
abnormalities and bladder bowel dysfunction. When present, role for short periods of time, endoscopic injection and
treatment for the latter is initiated. surgery are offered with intention to “cure” to stop reflux
• Children with grades I, II and III VUR over 24 months of and are more effective in long-term renal outcomes
age and who do not have either UTI, cortical scarring, • Parental preference should be honored and details of the
raised PRA, or microalbuminuria form a special group: three options of management of VUR should be explained
they should be offered option 1 for a period of 12 months to them.
or till the time any of the above features develop, whichever
is earlier. If there is persistence of reflux or any of the above
features develop, they should be offered option 2 or 3 KEY POINTS
• Children with any grade of reflux who have either UTI, ))
Children with vesicoureteric reflux (VUR) are believed to be at
cortical defects/scarring, raised PRA, or microalbuminuria: risk for ongoing renal damage
they should be offered option 2 (endoscopic treatment). In ))
Urinary tract infection (UTI) may occur even in nondilating
the event of nonavailability or, nonaffordability due to cost VUR (grades I and II)
649
of injection, option 3 should be offered.
R. Guy Hudson, MD; Antoine E. Khoury, MD; Armando J. Lorenzo, MD; Hans G. Pohl,
))
Therefore, identifying urinary abnormalities [by ultra
sono MD; Ellen Shapiro, MD; Warren T. Snodgrass, MD.
graphy and micturating cystourethrogram (MCU)], at the 12. Margolis DJ, Bowe WP, Hoffstad O, Berlin JA. Antibiotic treatment of acne may be
outset—once UTI is confirmed—may offer the benefit of associated with upper respiratory tract infection. Arch Dermatol. 2005;141:1132‑6.
preventing hypertension and renal failure 13. Matouschek E. Die behandlung des vesikorenalen refluxes durch transurethrale
))
Micturating cystourethrogram/voiding cystourethrogram einspritzung von Teflon paste. Urologe A. 1981;20:263-4.
should be carried out after confirmed UTI even in presence of 14. Mentzel HJ, Vogt S, Patzer L, Schubert R, John U, Misselwitz J, et al. Contrast-enhanced
sonography of vesicoureterorenal reflux in children: preliminary results. AJR Am J
mild hydronephrosis
Roentgenol. 1999;173:737-40.
))
Pyelonephritis occurs despite antibiotics 15. Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D, et al. Prophylaxis
))
Long-term antibiotic use may increase the severity of otitis after first febrile urinary tract infection in children? A Multicenter, Randomized,
media in children. In some studies, including the National Controlled, Noninferiority Trial. Pediatrics. 2008;122:1064-71.
Institute for Clinical Excellence guidelines, prophylactic 16. Mori R, Lakhanpaul M, Verrier-Jones K. Diagnosis and management of urinary tract
antibiotics have been found neither to be effective in infection in children: summary of NICE guidance. BMJ. 2007;335:395-7.
reducing the risk of recurrent pyelonephritis nor incidence of 17. Nelson CP, Copp HL, Lai J, Saigal CS; the Urologic Diseases in America Project. Is
renal scarring in children less than 30 months of age who have Availability of Endoscopy Changing Initial Management of Vesicoureteral Reflux? J
grade II–IV VUR Urol. 2009;182:1152-7.
18. Noe HN, Wyatt RJ, Peeden JN Jr, Rivas ML. The transmission of vesicoureteral reflux
))
Endoscopic treatment is viewed as preferable to open surgery
from parent to child. J Urol. 1992;148:1869-71.
by 60% of parents even for grades I–II reflux and 80% of those
19. Ogan K, Pohl HG, Carlson D, Belman AB, Rushton HG. Parental preferences in the
with grade III reflux over long-term antibiotic prophylaxis management of vesicoureteral reflux. J Urol. 2001;166:240-3.
))
Presently, the endoscopic treatment of VUR by dextranomer/ 20. Pennesi M, Travan L, Peratoner L, et al. North East Italy Prophylaxis in VUR study
hyaluronic acid is increasingly viewed as first line therapy for group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in
reflux preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatr.
))
Parental preference for choice of therapy is honored and 2008;121:e1489-94.
they should be offered information on all the three options 21. Riccabona M. Management of recurrent urinary tract infection and vesicoureteral
of therapy: CAP, endoscopic injection treatment, and open/ reflux in children. Curr Opin Urol. 2000;10:25-8.
laparoscopic surgery. 22. RIVUR Trial Investigators, Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews
R, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J
Med. 2014;370(25):2367-76.
SUGGESTED READINGS 23. Roussey-Kesler G, Gadjos V, Idres N, Horen B, Ichay L, Leclair MD, et al. Antibiotic
prophylaxis for the prevention of recurrent urinary tract infection in children with
1. American Academy of Pediatrics. Practice parameter: the diagnosis, treatment & low grade vesicoureteral reflux: results from a prospective randomized study. J Urol.
evaluation of the initial urinary tract infection in febrile infants & young child. 2008;179:674.
Committee on Quality Improvement Subcommittee on Urinary Tract Infection. 24. Savage DC, Howie G, Adler K, Wilson MI. Controlled trial of therapy in covert
Pediatrics. 1999;103:843-52. bacteriuria of childhood. Lancet. 1975;1:358-61.
2. Bajpai M, Bal CS, Kalaivani M, Gupta AK. Plasma renin activity for monitoring 25. Schwab CW Jr, Wu HY, Selman H, Smith GH, Snyder HM 3rd, Canning DA.
vesicoureteric reflux therapy: mid-term observations. J Pediatr Urol. 2008;4(1):60-4. Spontaneous resolution of vesicoureteral reflux: a 15-year perspective. J Urol.
3. Bajpai M, Bal CS, Kumar R, Chaturvedi PK, Kalaivani M, Gupta AK. Persistent renin- 2002;168(6):2594-9.
angiotensin system activation after anti-reflux surgery and its management. J Pediatr 26. Sencan A, Carvas F, Hekimoglu IC, Caf N, Sencan A, Chow J, et al. Urinary tract
Urol. 2011;7(6):616-22. doi: 10.1016/j.jpurol.2011.06.012. Epub 2011 Jul 31. infection and vesicoureteral reflux in children with mild antenatal hydronephrosis. J
4. Bajpai M, Mitra A, Bal CS, Kumar R, Jana M. Journal of Progress in Paediatric Pediatr Urol. 2014;10(6):1008-13.
Urology. July-September, 2014 (in press). 27. Sjöström S1, Sillén U, Bachelard M, Hansson S, Stokland E. Spontaneous resolution
5. Bajpai M, Pal K, Bal CS, Gupta AK, Pandey RM. Role of plasma renin activity in of high grade infantile vesicoureteral reflux. J Urol. 2004;172(2):694-8; discussion
the management of primary vesicoureteric reflux: a preliminary report. Kidney Int. 699.
2003;64(5):1643-7. 28. Smellie JM, Prescod NP, Shaw PJ, Risdon RA, Bryant TN. Childhood reflux and urinary
6. Bajpai M, Verma A, Panda SS. Endoscopic treatment of vesico-ureteral reflux: infection: a follow-up of 10–41 years in 226 adults. Pediatr Nephrol. 1998;12:727-36.
experience of 99 ureteric moieties. J Indian Assoc Pediatr Surg. 2013;18(4):133-5. 29. Suson KD, Mathews R. Evaluation of children with urinary tract infection—impact of
doi: 10.4103/0971-9261.121112. the 2011 AAP guidelines on the diagnosis of vesicoureteral reflux using a historical
7. Capozza N, Lais A, Matarazzo E, Nappo S, Patricolo M, Caione P. Treatment of series. J Pediatr Urol. 2014;10(1):182-5. doi: 10.1016/j.jpurol.2013.07.025. Epub
vesico-ureteric reflux: a new algorithm based on parental preference. BJU Int. 2013 Sep 8.
2003;92(3):285-8. 30. Tanagho EA, Hutch JA, Meyers FH, Rambo ON Jr. Primary vesicoureteral reflux:
8. Elder JS, Peters CA, Arant BSJ, Ewalt DH, Hawtrey CE, Hurwitz RS, et al. Pediatric experimental studies of its etiology. J Urol. 1965;93:165-76.
vesicoureteral reflux guidelines panel summary report on the management of primary 31. Van Batavia JP, Nees SN, Fast AM, Combs AJ, Glassberg KI. Outcomes of vesicoureteral
vesicoureteral reflux in children. J Urol. 1997;157:1846-51. reflux in children with non-neurogenic lower urinary tract dysfunction treated with
9. Froom J, Culpepper L, Green LA, de Melker RA, Grob P, Heeren T, et al. A cross- dextranomer/hyaluronic acid copolymer (Deflux). J Pediatr Urol. 2014;10(3):482-7.
national study of acute otitis media: risk factors, severity and treatment at initial doi: 10.1016/j.jpurol.2013.10.017. Epub 2013 Nov 12.
visit: Report from the International Primary Care Network (IPCN) and the Ambulatory 32. Verma A, Panda SS, Bajpai M. Role of endoscopic treatment of vesicoureteric reflux in
Sentinel Practice Network (ASPN). J Am Board Fam Pract. 2001;14:406-17. downgrading renin angiotensin system activation. J Pediatr Urol. 2014;10(2):386-90.
10. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical doi: 10.1016/j.jpurol.2013.10.015. Epub 2013 Nov 8.
significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis
after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics.
2006;117:626-32.
11. Management and screening of primary vesicoureteral reflux in children: AUA
guideline (2010). Panel Members: Craig A. Peters, MD, Chair; Steven J. Skoog, MD,
650 Vice-Chair; Billy S. Arant, Jr., MD; Hillary L. Copp, MD; Jack S. Elder, MD, Facilitator;
CHAPTER 133
Intussusception
Gautam S Agarwal, Anurag Krishna
INTRODUCTION DIAGNOSIS
Intussusception is an acquired invagination of the bowel into Radiographs typically are ordered by the clinician to exclude
itself, usually involving both small and large bowel (Figs 1 other diagnoses (Fig. 3). Even in experienced hands, abdominal
and 2). Ileocolic intussusception is the most common cause radiographs have poor sensitivity (45%) for the detection of
of small bowel obstruction in children. Intussusception is intussusception but may serve to screen for other diagnoses
an emergent condition where delay in diagnosis is not rare, in the differential diagnosis, such as constipation, and for free
and may result in bowel obstruction, venous congestion, peritoneal air.
subsequent bowel necrosis, and perforation.
INCIDENCE AND CLINCAL FEATURES

The peak age for idiopathic intussusception is 5–10 months
and typically ranges up to 3 years. The most common clinical
presentation is of an infant with crampy abdominal pain
and irritability, vomiting, and bloody stools, although signs
and symptoms vary considerably and overlap with other
abdominal conditions. The clinical features of intussusception
are given in table 1.
Fig. 2: Operative photograph showing the intussusception
TABLE 1: Clinical features of intussusception

Abdominal colic 65%
Lump 35–70%
Rectal bleeding 50–80%
Triad 7.5–50%
Vomiting 75–85%
Fig. 1: Diagramatic representation of intussusception Preceding respiratory/gastrointestinal symptoms <25%

A B C
Fig. 3: X-rays of abdomen: A, right iliac fossa empty; B, signs of intestinal obstruction; C, soft tissue mass (arrow). Normal
X-ray does not rule out intussusception
A B C
Fig. 4: Ultrasound showing whorled appearance of intussusception
The presence of a curvilinear mass within the course of the accuracy, approaching 100% in experienced hands, with a
colon (the crescent sign), particularly in the transverse colon sensitivity of 98–100% and specificity of 88–100% (Fig. 4).
just beyond the hepatic flexure, is a nearly pathognomonic sign
of intussusception.
TREATMENT
The absence of bowel gas in the ascending colon is one
of the most specific signs of intussusception on radiographs. For the treatment of intussuception, follow the following steps:
However, small-bowel gas located in the right abdomen on • Resuscitate first
radiographs may mimic ascending colon or cecal gas. • Nonoperative reduction contraindicated if
Sonography increasingly is used to diagnose either {{ Long-standing—usually v>36–48 h
intussusception or alternative causes for a child’s abdominal {{ Gross abdominal distension
symptoms. {{ Hemodynamic instabillity. Intussuception
Sonography also plays a role in the evaluation of reducibility Treatment options:

of intussusception, the presence of a lead point mass, the • Nonsurgical perferred, except in few cases
potential incomplete reduction after enema (vs. edema of the • Surgery is absolutely indicated in
ileocecal valve), and of intussusception limited to small bowel. {{ Shock, sepsis
At this point in time, there are no reliable clinical {{ Perforation peritonitis
prediction models that accurately can identify all patients with {{ Failed reduction
intussusception. The clinical triad of colicky abdominal pain, • Nonsurgical

palpable abdominal mass, and current jelly stools is present in {{ “Pushing” agent
less than 50% of cases. –– Air

There is no doubt that a computed tomography scan –– Fluid—water, saline, barium
of the abdomen may diagnose intussusception. However, {{ Imaging modality
the cost, radiation dose, and risk of sedation in these young –– Ultrasound
children make it far less practical than sonography. Published ■■ Pros: avoids radiation
652 sonography studies from single institutions suggest high ■■ Cons: operator dependent
CHAPTER 133: Intussusception
–– Fluoroscopy Air is rapidly insufflated into the colon under fluoroscopic

■■ Pros: Confidence observation.
■■ Cons: Radiation. Once the intussusception is encountered, its reduction is
Barium is no longer the liquid contrast medium of choice for followed fluoroscopically until it is completely reduced. Air
reduction of intussusception due to risk of barium peritonitis, should flow freely from the cecum into the distal small bowel
infection, and adhesions if perforation occurs during the loops to signify complete reduction. One critical safety issue is
enema. While iodinated contrast is considered a safer agent to keep air pressure below a maximum limit of 120 mmHg to
than barium, one should be aware that it may produce fluid avoid the risk of perforation.
and electrolyte shifts if perforation occurs because contrast is There is no direct evidence supporting the commonly
absorbed from the peritoneum. taught “rule of threes” regarding the liquid enema technique,
An intussusception encountered in the rectum has only particularly the appropriate height of the enema bag.
a 25% reduction rate, but intussusceptions encountered The superior air enema reduction rate may be due to the
elsewhere in the colon, including the hepatic flexure, can be presence of higher intraluminal pressure for air compared with
expected to have a successful reduction rate of approximately standard hydrostatic reduction.
80%. The most common location to encounter idiopathic In case of failure of reduction and above mentioned absolute
intussusception is at the hepatic flexure. indications, sometimes an operative reduction is required. At
Before enema reduction, dehydration should be treated laparotomy, the mass is delivered and gentle manual reduction
with intravenous fluid resuscitation. If the child is clinically is done. The key to reduction is slow, constant milking and
unstable, he or she should not undergo enema. Children with squeezing in a retrograde manner.The intussusceptum is
evidence of peritonitis, shock, sepsis, or free air on abdominal pushed rather than pulled. Infrequently when the maneuver
radiographs are not candidates for enema. These children fails, or if the bowel is gangrenous, resection of the intestine
should be stabilized and treated surgically. with end-to-end anastomosis may be required.
The presence of small-bowel obstruction reduces the
probability of successful enema reduction but it is not a
RECURRENCE
contraindication to performing the enema.
The most important factor that decreases the reduction rate Fifty percent of children who develop recurrent intussusception
of enema is the duration of symptoms. The longer the duration will present within 48 hours, although recurrences have been
of symptoms beyond 24 hours, the lower the likelihood of reported up to 18 months later. If the clinical concern is for
successful contrast enema reduction. Most literature suggests recurrent intussusception, there is little added information
a significant delay is typically 48 hours of symptoms but some gained by abdominal radiography. Radiographs may show
reports suggest 24 or 72 hours. alternative diagnoses or obstruction but if the clinical concern
Age less than 3 months is associated with both a higher is for recurrent intussusception, sonography is the most
perforation rate and a lower rate of successful reduction, as reliable test.
is dehydration and small-bowel obstruction. These situations There is no question that sonography to screen for
are less common. The lethargy, as seen in this child, is not rare intussusception is a valid imaging test. However, in this
when they become dehydrated. It is important to correct the situation, the pretest probability is high for the diagnosis of
child’s dehydration to improve the enema intussusception intussusception and, therefore, enema would be the reasonable
reduction rate. next step. Repeat enema is both safe and effective in recurrent
The most important potential complication of enema is intussusception, as long as the child remains clinically stable.
bowel perforation. The most common site is at or just proximal If the patient is not clinically stable, or has signs of peritonitis,
to the intussusception in the transverse colon. Perforations then the patient should undergo surgical reduction.
with air tend to be smaller than those with liquid enema Intussusception recurrence rates average 10% in large
although the overall perforation rates are similar. series, with a range of 5.4–15.4%, regardless of air versus liquid
The air enema is considered superior at reduction, enema technique. The recurrence rates are less than or equal
cleaner (based on appearance of peritoneal cavity at surgery to 5% when surgical reduction is performed, presumably due
when perforation occurs), safer, and faster with less radiation to the development of adhesions.
when compared with liquid enema. In a summary of the The risk of a pathologic lead point (Fig. 5) in children
literature, there were 32 studies using air reduction and 39 with recurrent intussusception is low. No predictive clinical
using liquid (barium, iodinated contrast, saline, or water) factors have been identified for pathologic lead point in these
reduction techniques. Air enema studies had significantly children with recurrent intussusception. No clear risk factors
higher mean reduction rates compared with liquid enema are known for why some children have recurrences although
studies (82% vs. 68%). some do have a focal pathologic lead point. Those with diffuse
The air enema technique is well described in the literature. bowel abnormalities (diffuse pathologic lead points) and
Briefly, the enema tip should be placed within the child’s ileocolic intussusception, such as children with cystic fibrosis,
rectum and taped in place with abundant tape. The child is Henoch-Schönlein purpura, or celiac disease, may be treated
placed in a prone position to allow the radiologist or assistant with enema reduction more aggressively than those with focal
to squeeze the buttocks closed and prevent air from leaking. pathologic lead points to avoid surgery. Repeat enema is both 653
Problems:
• Delayed presentation (meain 48 h)
{{ Rectal bleeding, vomiting, dehydration
• Abdominal distension
{{ Difficulty in feeling lump
{{ Difficulty in using ultrasound for dx/dt
• Will a radiologist come at night?
KEY POINTS
))
High index of suspicion
))
Rapid initial resuscitation
))
Attempt “safe” and “sure” reduction
))
Operate if doubtful.
SUGGESTED READINGS
Fig. 5: Operative photograph showing a small Meckel’s diverticulum
as the lead point 1. Beasley SW, Glover J. Intussusception: prediction of outcome of gas enema. J Pediatr
Surgery. 1992;27:474-5.
2. Bratton SL, Haberkern CM, Waldhausen JH, Sawin RS, Allison JW. Intussusception:
ALGORITHM 1 hospital size and risk of surgery. Pediatrics. 2001;107:299-303.
3. Daneman A, Alton DJ, Ein S, Wesson D, Superina R, Thorner P. Perforation during
Algorithm for management of intussusception attempted intussusception reduction in children: a comparison of perforation with
barium and air. Pediatr Radiol. 1995;25:81-8.
4. Daneman A, Navarro O. Intussusception part 1: a review of diagnostic approaches.
Pediatr Radiol. 2003;33:79-85.
5. Daneman A, Navarro O. Intussusception part 2: an update on the evolution of
management. Pediatr Radiol. 2004;34:97-108.
6. Del-Pozo G, Gonzalez-Spinola J, Gomez-Anson B, Serrano C, Miralles M, González-
deOrbe G, et al. Intussusception: trapped peritoneal fluid detected with US:
relationshi p to reducibility and ischemia. Radiology. 1996;201:379-83.
7. Ein SH. Leading points in childhood intussusception. J Pediatr Surgery. 1976;11:209-
11.
8. Ein SH. Recurrent intussusception in children. J Pediatr Surgery. 1975;10:751‑5.
9. Gu L, Alton D, Daneman A, Stringer DA, Liu P, Wilmot DM, et al. John Caffey
award. Intussusception reduction in children by rectal insufflation of air. AJR.
1988;150:1345-8.
10. Guo JZ, Ma XY, Zhou QH. Results of air pressure enema reduction of intussusception:
6396 cases in 13 years. J Pediatr Surgery. 1986;21:1201-3.
11. Hernanz-Schulman M, Foster C, Maxa R, Battles G, Dutt P, Stratton C, et al. Experimental
study of mortality and morbidity of contrast media and standardized fecal dose in
the peritoneal cavity. Pediatr Radiol. 2000; 30:369-78.
12. Katz M, Phelan E, Carlin JB, Beasley SW. Gas enema for the reduction of
intussusception: relationshi p between clinical signs and symptoms and outcome.
AJR. 1993;160:363-6.
13. Kirks DR. Diagnosis and treatment of pediatric intussusception: how far should we
push our radiologic techniques? Radiology. 1994;191:622-3.
14. Mercer S, Carpenter B. Mechanism of perforation occurring in the intussusci piens
during hydrostatic reduction of intussusception. Can J Surgery. 1982;25:481-3.
15. Navarro O, Daneman A. Intussusception part 3: diagnosis and management of those
with an identifiable or predisposing cause and those that reduce spontaneously.
Pediatr Radiol. 2004;34:305-12.
safe and effective in recurrent intussusception as long as the 16. Parashar UD, Holman RC, Cummings KC, Staggs NW, Curns AT, Zimmerman CM, et al.
child remains clinically stable. Trends in intussusception-associated hospitalizations and deaths among US infants.
Pediatrics. 2000;106:1413-21.
Some articles have reported associations between 17. Shiels WE II, Kirks DR, Keller GL, Ryckman FR, Daugherty CC, Specker BL, et al. John
intussusception and viral infection, particularly adenovirus, Caffey award. Colonic perforation by air and liquid enemas: comparison study in
although the lack of seasonality suggests more than one young pigs. AJR. 1993;160:931-5.
pathogen. Approximately 5–6% of intussusceptions in children 18. Shiels WE II, Maves CK, Hedlund GL, Kirks DR. Air enema for diagnosis and
are caused by pathologic lead points that are due to either reduction of intussusception: clinical experience and pressure correlates. Radiology.
1991;181:169-72.
focal masses or diffuse bowel wall abnormality. The most
19. Stringer MD, Pablot SM, Brereton RJ. Paediatric intussusception. BR J Surg.
common focal pathologic lead points are (in decreasing order 1992;79:867-76.
654 of incidence) Meckel’s diverticulum, duplication cyst, polyp, 20. West KW, Stephens B, Vane DW, Grosfeld JL. Intussusception: current management in
and lymphoma. infants and children. Surgery. 1987;102:704-10.
Chapter 134
Neonatal Jaundice:
Surgical Perspective
Nidhi Sugandhi, Veereshwar Bhatnagar
INTRODUCTION PHYSIOLOGICAL VERSUS

Jaundice in a neonate can have varied connotations. Its PATHOLOGICAL JAUNDICE
spectrum ranges from physiological jaundice on one hand to Confusion with the physiological jaundice normally present
obstructive jaundice requiring urgent surgical correction on in the early neonatal period can lead to delay in identification
the other hand. of neonates requiring further investigations and treatment.
Structural anomalies in the biliary tract causing direct Specific parameters indicate pathological jaundice. These are
hyperbilirubinemia due to obstruction to bile outflow are enumerated in table 1.
amenable to surgical correction. Box 1 lists the structural A noteworthy point is that even minimal rise of direct
anomalies presenting with neonatal hyperbilirubinemia. or conjugated bilirubin is pathological and needs to
These anomalies may be intrahepatic or extrahepatic; of these, be investigated. Thus the most important initial test is
extrahepatic biliary atresia (EHBA) is the most common. While measurement of the serum conjugated bilirubin concentration
extrahepatic obstructions have high likelihood to be surgically to establish the presence of cholestasis.
correctable, others with diffuse intrahepatic structural Cholestatic jaundice or direct hyperbilirubinemia is the
anomalies, such as Caroli’s disease and Alagille syndrome may hallmark of surgically correctable biliary tract anomalies.
be cured only with radical surgery like segmental hepatectomy However, it is also a component of mixed hyperbilirubinemia
or liver transplantation. in another group of disorders with intrahepatic cholestasis
Though they constitute only 0.2–0.4% of total cases of including idiopathic neonatal hepatitis (INH). Box 2 lists the
neonatal hyperbilirubinemia, the urgency to diagnose and causes of direct hyperbilirubinemia including the structural
treat the surgical causes of neonatal jaundice stems from two anomalies and causes of neonatal cholestasis. Thus, once
facts: (i) most of the surgical causes of neonatal jaundice are cholestatic liver disease has been established, the next
correctable if operated upon early and (ii) if left untreated they challenge is to differentiate the structural anomalies from
progress rapidly to cause irreversible liver damage, cirrhosis, INH which can be treated medically in most cases. The clinical
portal hypertension, liver failure, and eventually death. Thus it features and investigations needed to differentiate between
is important to diagnose the group of jaundiced neonates likely the two groups of disorders are discussed in subsequent
to have surgically correctable causes of jaundice and initiate sections.
appropriate treatment.
Table 1: Indicators of pathological jaundice
Box 1: Causes of neonatal surgical jaundice
• Extrahepatic biliary atresia Onset <24 h
• Choledochal cyst: Rate of progression >0.5 mg/dL/h or >5 mg/dL/24 h

{{ Caroli’s disease Total bilirubin >15 mg/dL
• Inspissated bile syndrome Direct bilirubin >2 mg/dL or >20% total bilirubin
• Gallstones or biliary sludge Duration Any jaundice lasting beyond 3 weeks
• Biliary hypoplasia and Alagille syndrome Associated symptoms Clay colored stools/dark colored urine/
• Neonatal sclerosing cholangitis sepsis/poor feeding
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Box 2: Causes of conjugated hyperbilirubinemia cholestasis

Physical examination reveals firm to hard hepatomegaly. Late
stages may reveal cirrhotic liver and splenomegaly indicating
Obstructive cholestasis development of portal hypertension. Signs of liver failure appear
• Biliary atresia • Gallstones/biliary sludge later and include ascites, spider nevi and coagulopathy.
• Choledochal cysts • Caroli disease However, no details in the history or physical examination
• Bile duct paucity • Neonatal sclerosing are capable of differentiating all infants with neonatal hepatitis
• Inspissated bile syndrome cholangitis from those who have biliary atresia. Many infants who have
intrahepatic cholestasis (10–15%) have cholestasis so severe
Intrahepatic cholestasis and neonatal hepatitis
that they mimic biliary obstruction.
• Viral infection: • Endocrine disorders:
{{ Herpes simplex {{ Hypothyroidism
{{ Cytomegalovirus {{ Hypopituitarism EVALUATION OF

{{ Human immunodeficiency • Toxic: THE CHOLESTATIC NEONATE
virus {{ Drugs
{{ Parvovirus B19 {{ Parenteral nutrition Pathological jaundice with conjugated bilirubin fraction
{{ Other • Systemic: above 20% establishes the diagnosis of cholestasis. Further
• Bacterial infection: {{ Shock
investigations are aimed at differentiating between neonatal
{{ Sepsis {{ Heart failure
hepatitis and extrahepatic obstruction and assessing the
{{ Urinary tract infection {{ Neonatal lupus
severity of liver derangement.
{{ Syphilis • Neonatal cholestasis
• Genetic/metabolic disorders: • Obstructive cholestasis
{{ Alpha1-antitrypsin Initial Investigations
deficiency Conventional serologic liver function tests are often non
{{ Tyrosinemia
specific but discrimination between extrahepatic ductal
{{ Galactosemia
disease and neonatal hepatitis is sometimes possible.
{{ Progressive familial
Hyperbilirubinemia secondary to neonatal hepatitis is
intrahepatic cholestasis
{{ Alagille syndrome
characterized by elevation of both the direct and indirect
{{ Other component whereas rise in indirect bilirubin in extrahepatic
obstruction is a late event after the onset of liver failure.
Similarly, synthetic function of the liver as assessed by
CLINICAL FEATURES coagulation profile and serum proteins is impaired only in
later stages in extrahepatic obstruction. Gamma-glutamyl
Surgical jaundice is not evident immediately after birth transferase may be elevated in both the conditions but is
and appears after 5–7 days. Usually, it merges with the usually higher in extrahepatic obstruction. Box 3 enumerates
physiological jaundice and is suspected due to unusual the basic serologic tests for patients suspected with jaundice
prolongation of the physiological jaundice. Sometimes, it due to a surgical cause.
may also appear 2–3 weeks after birth, subsequent to clearing
of the physiological jaundice. Typically, the first stools of
Specific Investigations
the neonate are normal and cholic. Differentiating features
need to be looked for. Characteristically, history of clay A battery of tests is required to establish the presence and
colored stools and dark colored urine indicates direct hyper cause of extrahepatic obstruction. Despite these the definitive
bilirubinemia. It should be noted that intermittent passage
of cholic stools, though more frequent in intrahepatic
Box 3: Initial investigations in neonatal direct
cholestasis, does not rule out extrahepatic obstruction.
hyperbilirubinemia
Children are initially active with normal growth during
the first few weeks. Neonatal choledochal cyst can closely • Fractionated serum bilirubin concentration
resemble EHBA clinically with a fulminant course including • Liver enzymes:
{{ Alanine aminotransferase
pancreatitis and cholangitis in contrast to intermittent
{{ Aspartate aminotransferase
symptoms as seen in older children. The classic triad of pain,
{{ Alkaline phosphatase
mass, and jaundice is typically not seen.
{{ Gamma-glutamyl transferase
Infants whose cholestasis is caused by bacterial sepsis,
hypopituitarism, or metabolic disorders such as galactosemia • Tests of liver function:
{{ Blood glucose
may be acutely ill. Infants who have metabolic liver disease
{{ Serum albumin
may have poor feeding, inadequate weight gain, hypoglycemia,
{{ Coagulation studies (prothrombin time, partial thromboplastin
and hypotonia. Hepatitis due to TORCH (Toxoplasmosis,
time, coagulation factor levels)
Other Agents, Rubella, Cytomegalovirus, HErpes simplex, and
• Complete blood count
Syphilis) agents may be associated with dysmorphic facies,
• Urinary bilirubin and urobilinogen levels
microcephaly, and low birth weight, prematurity, and other
656 • Bacterial cultures of blood, urine, others as indicated
congenital anomalies.
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Chapter 134: Neonatal Jaundice: Surgical Perspective
diagnosis may be established only on the operating table with

the help of intraoperative cholangiogram (IOC).
Ultrasonography
A quick, noninvasive, and cheap initial investigation, an
ultrasonography is very useful to indicate extrahepatic
obstructive lesions. It can definitively diagnose or rule out
choledochal cyst which is visible as a cystic subhepatic mass.
Gall bladder stone and biliary sludge are also easily visible.
Certain features, viz., absence of gall bladder or a gall bladder
less than 1.5 cm in size with no contractility in response
to feeding, triangular cord sign due to hyperechoic portal
plate, and fibrous cord remnant raise suspicion of EHBA. In
particular, the triangular cord sign has 100% specificity but
only 73% sensitivity to diagnose EHBA. Preduodenal portal
vein, asplenia, or polysplenia are further supportive of a
diagnosis of EHBA. Dilated proximal biliary radicles rule out Fig. 1: Magnetic resonance cholangiopancreatography in a patient
EHBA and favor inspissated bile duct syndrome. However, this with extrahepatic biliary atresia demonstrating absence of gall
is an operator dependent investigation and can, therefore, only bladder and intrahepatic ducts
guide further investigations rather than definitively diagnose
all extrahepatic obstructions.
Tc99m-hepatobiliary Iminodiacetic Acid Scintigraphy

Failure to excrete this technetium labeled isotope into
the duodenum even after 24 hours is diagnostic of EHBA.
Infants who have biliary atresia do not excrete isotope into
the gut, making the test 100% sensitive for this disorder.
Unfortunately, specificity is not satisfactory as severe neonatal
hepatitis cases may also not excrete the isotope. Pretreatment
with phenobarbitone (5 mg/kg/day) for 3–5 days preceding
imaging enhances excretion and increases discrimination
between EHBA and neonatal hepatitis, and therefore, should
always be followed.
Magnetic Resonance Cholangiopancreatography

Magnetic resonance cholangiopancreatography (MRCP) is
being increasingly used to evaluate extrahepatic obstruction Fig. 2: Magnetic resonance cholangiopancreatography showing a
and in one small series has shown 100% diagnostic accuracy in cystic dilatation of the common bile duct suggestive of choledochal cyst
the evaluation of biliary atresia (Figs 1 and 2). However, further
evaluation is required in larger series before establishing its guaranteed adequacy of size of specimen) and operative
role in diagnostic evaluation. The usefulness is also limited due cholangiography is recommended as the ideal approach to
to high cost and difficulty in performing this investigation in the obstructed child.
neonates.
Intraoperative Cholangiogram
Liver Biopsy The gold standard for the diagnosis of EHBA with highest
Liver biopsy was earlier considered a definitive investigation sensitivity and specificity and widely employed as an
for differentiating neonatal hepatitis and biliary obstruction. effective practical tool is operative cholangiography. The
However, characteristics thought to suggest EHBA (including liver and extrahepatic biliary atresia ducts are inspected by
bile ductular proliferation, bile plugs in small bile ducts, a minilaparotomy incision and, if present, gall bladder is
portal tract fibrosis and edema, swelling, vacuolization, cannulated and injected with radiopaque dye (Fig. 3). Failure
sloughing of biliary epithelium, inflammatory cell infiltration, of the dye to reach the duodenum and/or nonopacification
and giant cell transformation) may also be present in of the proximal biliary ducts, confirm the diagnosis of EHBA
advanced stages of severe neonatal hepatitis. Moreover it (Fig. 4). Additionally, flushing of bile ducts may prove to be
is an invasive investigation and may require some time for therapeutic in cases of inspissated bile ducts and some cases of
analysis. In approximately one-third of the specimens, the neonatal hepatitis with secondary bile duct obstruction. Liver
histological findings are not clear-cut, so further evaluation biopsy can be taken at the same time. Details of intrahepatic
becomes necessary. A combination of open biopsy (with a ductal anatomy are also clearly seen with an IOC (Fig. 5). 657
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Box 4: Additional tests for neonatal hepatitis/cholestasis

• Serum a1-antitrypsin level and phenotype
• Serologies and cultures for viruses (TORCH agents, parvovirus
B19, human herpes virus type 6, human immunodeficiency virus,
others)
• Sweat chloride analysis for cystic fibrosis
• Metabolic screen (urine and serum, amino and organic acids)
• Endocrine studies (thyroxine, thyroid-stimulating hormone,
evaluation for hypopituitarism as indicated)
• Specific enzyme assays on liver tissue, fibroblasts, others
such as red blood cells (e.g., red cell galactose-1-phosphate
uridylyltransferase activity)
• Genetic testing as indicated:
{{ Cystic fibrosis
{{ Alagille syndrome
{{ Three forms of progressive familial intrahepatic cholestasis
Fig. 3: Intraoperative cholangiogram demonstrating normal opacifi

cation of proximal and distal bile ducts and dye entering the duodenum Additional Tests
Additional serological tests may be done simultaneously with
above investigations to negate the possibility of neonatal
hepatitis. It is important to perform the above mentioned
investigations like ultrasound and cholangiography
simultaneously along with the following serological tests
rather than wait for the results of serological tests as timing of
intervention in cases of extrahepatic obstruction is of utmost
importance in determining the long-term prognosis. The
serological tests for neonatal hepatitis are listed in box 4.
MANAGEMENT (Algorithm 1)
Direct hyperbilirubinemia with non-excretion of radio
nuclide in Tc99m-hepatobiliary iminodiacetic acid (HIDA)
scans even after 24 hours mandate a minilaparotomy with
cholangiography and liver biopsy. It cannot be emphasized
enough that the surgery should never be delayed to wait for
results of the serological tests. The timing of the surgery to
Fig. 4: No opacification of the proximal bile ducts on intraoperative
cholangiogram suggestive of extrahepatic biliary atresia
restore the bile flow is crucial. Best immediate and long-term
results are obtained when surgery is performed at less than 60
days of age. Delay leads to proportionally more liver damage
and poorer outcome. Studies have demonstrated 10-year
survival rate of patients undergoing surgery before 60 days
to be 68–80% compared to 15% survival in those undergoing
surgery after 90 days.
The infant should be stabilized preoperatively with special
attention to correction of any coagulopathy and antibiotics to
prevent or treat cholangitis.
Infants with preoperative diagnosis of choledochal cyst
undergo a straightforward excision of cyst with Roux-en-Y
hepaticojejunostomy. For others, findings on IOC determine
the further procedure.
Nonexcretion or minimal excretion of dye with proximal
dilatation of biliary radicles indicate inspissated bile syndrome
which responds to thorough flushing of the ducts. Clearing of
the ducts may be confirmed by repeating the IOC at the end of
Fig. 5: Intraoperative cholangiogram showing a fusiform dilatation the procedure.
along the course of common bile duct and common hepatic duct Absence of gall bladder with atretic common bile duct,
658 nonexcretion of dye with no proximal visible biliary radicles
suggesting a choledochal cyst. The intrahepatic ductal anatomy and
the pancreatico-choledocal junction are also visualized along with a firm or hard, cirrhotic enlarged liver confirms
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Chapter 134: Neonatal Jaundice: Surgical Perspective
Algorithm 1
Management of neonate with jaundice
CBD, common bile duct; HIDA, Tc99m-hepatobiliary iminodiacetic acid; UDCA, ursodeoxycholic acid.
the diagnosis of EHBA and the surgeon proceeds with Kasai few years after surgery and contributes to progressive liver
portoenterostomy (KPE). This entails resecting the fibrous dysfunction and cirrhosis, thus being responsible for delayed
tissue at the area of porta hepatis, with subsequent apposition failure of KPE. The incidence can be reduced with a longer
of a Roux-en-Y loop of intestine to act as a conduit for biliary Roux loop (>50–70 cm), construction of an intussuscepted
drainage. The resection at the area of the porta hepatis is valve at the jejunojejunostomy site, postoperative prophylactic
believed to expose small but patent bile ducts that can directly antibiotics [recommended trimethoprim (4 mg/kg/day)—
drain into the jejunal loop and restore the bile flow. sulfamethoxazole (20 mg/kg/day or neomycin 25 mg/kg/day)]
and use of oral steroids [prednisone (2 mg/kg/day)] for at least
3 months postsurgery.
COMPLICATIONS
Poor weight gain and malnutrition with poor absorption
Cholangitis is the most common and serious complication of fat soluble vitamins may persist even after surgery. Portal
with an incidence of 33–60%. It is more common in the first hypertension may progressively worsen due to initial liver 659
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damage and can cause life threatening variceal bleeding and instead of KPE has been suggested as an alternative but not
hypersplenism. recommended. Apart from shortage of donor organs, KPE
restores bile flow in at least one-third of the patients and delays
the onset of end stage liver disease in another third. Thus liver
POSTOPERATIVE MANAGEMENT
transplantation is an important but only a salvage procedure in
Prophylactic antibiotics and steroids are continued for 3 the management of EHBA.
months after surgery to prevent cholangitis. Steroids are known
to have additional anti-inflammatory and immunosuppressive
CONCLUSION
effects, thus decreasing edema, collagen deposition, and
scarring. They are also thought to have choleretic effect by Conjugated hyperbilirubinemia in a neonate presents a
stimulation of Na+/K+-ATPase. surgical challenge and indicates intrahepatic or extrahepatic
Ursodeoxycholic acid is administered for its choleretic bile flow obstruction. EHBA, choledochal cysts, biliary
effect and is specially indicated after flushing in inspissated bile sludge/gall stones, and inspissated bile are the common
syndrome. Additionally, Vitamin A, D, E, and K supplements causes of surgically correctable neonatal jaundice, of which
are recommended to prevent malnutrition. Box 5 surmises EHBA is the most common. USG, HIDA, and IOC should be
post-KPE treatment. undertaken early in the workup of direct hyperbilirubinemia
to differentiate surgically correctable lesions from neonatal
hepatitis. Surgical correction should be done by the age of
OUTCOME
2 months for best outcomes. The pediatrician has an important
If the Kasai operation succeeds in restoring bile flow, the role in identification and early referral of infants with surgically
evolution of biliary cirrhosis is prevented or at least delayed; correctable causes of neonatal jaundice.
10-year survival rate for patients who have their native livers
is approximately 30% in reports from multiple centers. Key points
As a general observation, out of all the infants diagnosed
with EHBA undergoing KPE, in one-third bile flow is never ))
Direct hyperbilirubinemia is always pathological
restored despite anatomically patent hepaticojejunostomy, ))
Intrahepatic or extrahepatic cholestasis causes direct hyper
possibly due to irreversibly fibrosed biliary ductules at the bilirubinemia
porta hepatis. Two-thirds achieve bile flow after KPE; half ))
Extrahepatic cholestasis is amenable to surgical correction
of these (30–35% of total) will have sustained bile flow and ))
Jaundice due to extrahepatic obstruction appears 5–7 days
remain free of long-term sequelae. However, in the other postnatally and may be waxing and waning
half of those achieving initial bile drainage (35% of total), ))
Infants with extrahepatic obstruction are better preserved
progressive liver insufficiency insidiously develops with than those with neonatal hepatitis
return of jaundice, cirrhosis, and portal hypertension. Thus, ))
Intraoperative cholangiogram is the gold standard for
despite initial palliation, these children eventually require liver diagnosing extrahepatic biliary obstruction
transplantation. Factors influencing prognosis are the patient’s ))
A non-excretory Tc99m-hepatobiliary iminodiacetic acid scan
age at the time of surgery, extension of liver fibrosis at surgery, with suggestive ultrasonography mandate an intraoperative
degree of intrahepatic bile duct injury, number of episodes of cholangiogram.
ascending cholangitis, the surgeon’s expertise, and the site of
bile duct obstruction.
SUGGESTED READINGs
LIVER TRANSPLANTATION 1. Davenport M, Betalli P, D’Antiga L, Cheeseman P, Mieli-Vergani G, Howard ER.
The spectrum of surgical jaundice in infancy. Pediatr Surg. 2003;38(10):1471-9.
Extrahepatic biliary atresia accounts for nearly half of all
2. Grosfeld JL, O’Neill JA, Coran AG, Fonkalsrud EW. Pediatric surgery. 6th ed.
pediatric liver transplants. It is considered for patients in whom Mosby Elsevier; 2006.
there is delayed presentation with established liver failure, 3. Edward R Howard ER, Mark D Stringer MD, Paul M Colombani PM. Surgery of the
bile outflow cannot be established even after KPE, or there is liver, bile ducts and pancreas in children. 2nd ed. Arnold Publishers;2002.
progressive decrease in biliary outflow and worsening of the 4. Kliegman RM, Stanton BMD, St. Geme J, Schor N, Behrman RE. Nelson’s textbook
liver damage with uncontrollable sequelae. Primary transplant of pediatrics. 19th ed. Elsevier; 2011.
5. Moyer V, Freese DK, Whitington PF, Olson AD, Brewer F, Colletti RB, et al.; North
American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
Box 5: Postoperative medical treatment in extrahepatic Guideline for the evaluation of cholestatic jaundice in infants: recommendations
biliary atresia of the North American Society for Pediatric Gastroenterology, Hepatology and
• Ursodeoxycholic acid: 10–15 mg/kg/day Nutrition. J Pediatr Gastroenterol Nutr. 2004;39(2):115-28.
• Trimethoprim (4 mg/kg/day): sulfamethoxazole (20 mg/kg/day) 6. Sherlock S, Dooley J. Diseases of the liver and biliary system. 11th ed. Blackwell
or neomycin (25 mg/kg/day) Publishing; 2008..
• Vitamin A, D, E, and K drops 7. Suchy JF. Neonatal cholestasis. Pediatr Rev. 2004;25:388-95.
8. Wani BN, Jajoo SN. Obstructive jaundice in neonates. Trop Gastroenterol.
• Prednisone (2 mg/kg/day)
660 2009;30(4):195-200.
ch-134.indd 660 11/22/2016 11:08:08 AM

Section 16: Dermatology
Chapter 135
Atopic Dermatitis
INTRODUCTION In infants, an erythematous oozy rash may develop by 2 or

3 months of age. It develops suddenly, predominantly affecting
Atopic eczema is a chronic relapsing pruritic, non-contagious the scalp and face, especially on the cheeks. The extensors of
endogenous eczema. It begins in infancy and continues up to the limbs like elbows, knees, and ankles are more commonly
adulthood. It occurs in individuals who have atopic tendency. involved. It is intensely itchy and interferes with the sleep of
These individuals may develop any or all of the three closely the child. The skin of the child in general is dry and xerotic.
linked conditions: atopic eczema, asthma, or allergic rhinitis. The diaper area being constantly moist is never involved in
The hallmark of the disease is pruritic dermatitis that localizes AD. Atopic dermatitis has to be differentiated from seborrheic
in different areas depending on age. It is a familial and chronic dermatitis (SD) where in there are greasy scales over scalp
disease and its symptoms can increase or disappear over time. (cradle cap), and face mostly over eyebrows, nasolabial folds,
retroauricular grooves and neck. Diaper area is classically
EPIDEMIOLOGY involved unlike in AD. The rash in SD is nonpruritic, and the
infants are totally undisturbed by it. Hair loss is rare in SD, but
Atopic dermatitis (AD) most often begins in childhood before common in AD probably due to itching and rubbing.
age 5 and may persist into adulthood. For some, it flares
periodically and then subsides for a time, even up to several Clinical Pearls
years. Atopic dermatitis can affect almost 20% of children.
It affects between 1 and 3% of adults. It is estimated that • Pruritic exudative plaques over face and scalp: suspect atopic
75% of the cases of AD improve by the time children reach dermatitis
adolescence, whereas 25% continue to have difficulties with the • Diaper area is never involved in atopic dermatitis.
condition through adulthood. The prevalence of AD is however
quite difficult to establish since the diagnostic criteria are not Psoriasis in infants is not uncommon and is often
applied universally and are not standard, but it is thought to mistaken with AD. It often affects the scalp, folds and diaper
vary roughly between 10 and 30%. area. Lesions over trunk (if present) are well demarcated
erythematous plaques surmounted by a thin white scale.
ETIOLOGY Atopic dermatitis in children beyond 2 years of age
involves the flexures like the cubital fossa, popliteal fossa, neck,
Four main factors interact closely in the etiology and groins, wrists, and ankles. The involved skin is erythematous
pathogenesis of this condition: and oozy, at places lichenification develops due to constant
• Genetic predisposition itching. Scabietic eczema should be ruled out where in lesions
• Impaired immunity of varied morphology like papules, pustules and nodules along
• Epidermal barrier dysfunction with burrows can be seen especially over hands and feet with
• Environmental factors. relative sparing of face. History of nocturnal itching can be
elicited in family members.
Flexural erythematous rash along with dry xerotic skin
APPROACH TO THE PATIENT (Algorithm 1)
elsewhere is seen in Netherton syndrome, which makes
Atopic dermatitis looks different in infants, children, and adults. it essential to differentiate it from AD. Here, examination
ch-135.indd 661 11/22/2016 11:10:02 AM

Algorithm 1
Approach to a patient with eczematous dermatitis
of the hair will reveal trichorrhexis invaginata, with raised persistent localized eczema, possibly confined to the hands,
immunoglobulin E. eyelids, flexures, nipples, or all of these areas. The skin is prone
Zinc and biotin deficiency can present as an eczematous to secondary bacterial infections.
eruption or an erythroderma, and are often misdiagnosed as
AD before other symptoms and signs become evident. The skin Clinical Pearl
eruption consists of dermatitis on the face that has a typical
horseshoe appearance on the cheeks and around the chin, with • Always look for hyperlinerity of palms, Dennie morgan fold and
perianal involvement. However, there is no xerosis or pruritus. other features of atopy when suspecting atopic dermatitis.
In older children the lesions are seen on the elbows and knees,
whereas in AD the flexures are usually involved. Individuals with AD may show other associated features
Other dermatitis like nummular dermatitis, allergic or of atopy like generalized xerosis, Dennie morgan fold,
irritant dermatitis can resemble AD and should be ruled out. hyperlinearity of palms, pityriasis alba, keratosis pilaris,
It is rare for adults to get AD. About half (50%) of people allergic shiners, and ichthyosis vulgaris.
who get AD during childhood continue to have milder signs
and symptoms of AD as an adult. When an adult has AD, it often
MANAGEMENT
looks different from the AD of childhood. They may continue
to have a diffuse pattern of eczema but the skin is often more Treatment of atopic eczema may be required for many months
662 dry and lichenified than in children. Commonly, adults have and possibly years. It nearly always requires:
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Chapter 135: Atopic Dermatitis
• Reduction of exposure to trigger factors (where possible)

• Antihistamines: both first and second generation can be Key points
used to control pruritus. Regular application of emollients, ))
Atopic dermatitis is always itchy
multiple times per day is very important ))
It remits and relapses
• Topical steroids (current mainstay of treatment; commonly
))
It effects extensors and face in less than 2 years children, and
used in conjunction with moisturizers): Hydrocortisone,
flexures in children elder than 2 years and adults
triamcinolone, or betamethasone; ointment bases are
generally preferred, particularly in dry environments
))
Seborrheic dermatitis, flexural psoriasis, and zinc deficiency
are great mimickers and should be excluded.
• Immunomodulators: tacrolimus and pimecrolimus
(calcineurin inhibitors) are considered second-line therapy.
Other treatments options available include the following:
• Systemic therapy: systemic corticosteroids, methotrexate, SUGGESTED READINGs
azathioprine, cyclosporine, and mycophenolate mofetil 1. Arnacho-Saucedo G, et al. Actualización en dermatitis atópica. Propuesta de
• Phototherapy: ultraviolet A for acute exacerbations, algoritmo de actuación. Actas Dermosifiliogr. 2013;104:4-16.
narrowband ultraviolet B for chronic disease 2. Bhavani MN, Vandergriff T, Rasmussen H, Jacobe H. Phototherapy in the
• Biological: omalizumab management of atopic dermatitis: a systematic review. Photodermatology,
• Others: probiotics, antibiotics for clinical infections. Photoimmunology & Photomedicine. 2007;23(4):106-12.
3. De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA. Atopic dermatitis:
Clinical Pearl a disease caused by innate immune defects? The Journal of Investigative
Dermatology. 2009;129(1):14-30.
What to tell parents? 4. McCollum AD, Paik A, Eichenfield LF. The safety and efficacy of tacrolimus ointment
• Keep child in humid environment in pediatric patients with atopic dermatitis. Pediatr Dermatol. 2010;27:425-36.
• Avoid pets, dust 5. Morris A, Rogers M, Fischer G, Williams K. Childhood psoriasis: a clinical review
of 1262 cases. Pediatr Dermatol. 2001;18:188-98.
• Use lukewarm water for bathing
6. Torrelo A. Tacrolimus tópico en el tratamiento de la dermatitis atópica en niños.
• Apply adequate emollients immediately after bath. Actas Dermosifiliogr. 2008;99(Suppl 2):1428-9.
663
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Chapter 136
Hypopigmented Macules
Vibhu Mendiratta, Pravesh Yadav
Introduction Generalized hypopigmentation with hair and eye

involvement occurs in albinism. It results either from
Hypopigmented macules in a child can be a cause of worry enzymatic defects in the biosynthesis of melanin, from
for the parents and physician alike. Hypopigmented macules
melanosomal defects that interfere with melanin formation,
may be present since birth or may appear later in childhood.
or from problems in the intracellular transport and
This chapter briefly outlines the approach to such presentation
localization of proteins essential for melanin biosynthesis.
(Algorithm 1).
In oculocutaneous albinism (OCA) type 1A, or the classic
Various genetic, autoimmune, and infective diseases
tyrosinase negative OCA, there is a complete inability to
may manifest as hypopigmented lesions in children.
synthesize melanin in skin, hair, and eyes, which results in
Hypopigmented macules may present at birth or later in
the characteristic “albino phenotype”. Affected individuals
childhood. Localized hypopigmented lesions with forelocks
are born with white hair and skin. The phenotype OCA type
may present at birth in patients with piebaldism or Waardenburg
1B can range from minimal hair pigment to near normal skin
syndrome. Piebaldism presents as depigmented patches on
the ventral or lateral trunk and/or the mid-extremities with the and hair pigment. They have very little or no pigment at birth
sparing of hand and feet. Poliosis is a common feature. It is not and develop varying amounts of melanin in the hair and skin
associated with systemic features. Waardenburg syndrome is in the first or second decade of life.
associated with dystopia canthorum, broadening of the nasal Localized well defined, slightly, scaly, hypopigmented
root, presence of hypoplastic alae nasi, synophrys, poliosis, macules involving the trunk, chest, back, and shoulders
heterochromia iridis, congenital sensorineural hearing loss, occurs in pityriasis versicolor. It is caused by Malassezia
musculoskeletal abnormalities like limb contractures and species, which on potassium hydroxide microscopy show
hypoplasia of the limb musculature, and Hirschsprung disease. hyphae and blastospores in the typical “spaghetti and
Nevus depigmentosus presents as ill-defined hypo meatballs” appearance. A yellow-green fluorescence is visible
pigmented macules with feathery margins. Similar cutaneous using Wood’s lamp examination. Pityriasis alba typically
lesions along lines of blaschko with or without extracutaneous presents as ill defined localized powdery white scaly lesions
manifestations occur in hypomelanosis of Ito. Localized involving the head and neck region, which may progress to
hypopigmented lesions without forelock may occur in vitiligo. non-scaly hypopigmented macules. It is commonly seen in
Nevus anemicus presents as pale, ill defined hypopigmented atopic individuals. Leprosy presents as well to ill defined
macules, which merges with surrounding skin on diascopy. hypopigmented macules with loss of sweating, hair loss, and
Tuberous sclerosis may present as off white macules, which loss of sensation. Lesions in tuberculoid pole presents as
are oval at one end and taper to the other end, resembling single to a few xerotic hypopigmented macules with hair loss.
ash leaf called as ash-leaf macules. They are often present Lesions in lepromatous pole present as multiple ill defined,
at birth or appear within the first few years of life commonly infiltrated hypopigmented macules and hair loss may occur
over trunk and buttocks. Wood’s lamp may be used to improve later on. Diagnosis of leprosy may be confirmed by slit skin
detection especially in light pigmented individuals. Three smear or histopathological examination. Inflammatory
or more hypopigmented macules constitute a major feature lesions may lead to post-inflammatory hypopigmentation
for the diagnosis of tuberous sclerosis. A less common type which presents as well to ill defined hypopigmented
of hypopigmentation is the “confetti” skin lesions involving macules. Lichen sclerosus et atrophicus presents as a pruritic
the legs or forearms which are considered a minor feature for erythematous patch in the early stage, evolving into a well
tuberous sclerosis. defined porcelain hypopigmented plaques with epidermal
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Chapter 136: Approach to a Child with Hypopigmented Macules
Approach to a child with hypopigmented macules

Algorithm 1
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atrophy and follicular atrophy. Vitiligo is a common disorder of

depigmentation occurring in approximately 1% of the world’s Key points
population. Various hypotheses have been proposed including ))
Localized hypopigmentation without scaling at birth may
autoimmune, neurogenic, etc. Vitiligo may be associated be seen in nevus depigmentosus, nevus anemicus, vitiligo,
with diabetes mellitus, thyroid diseases, etc. Histopathology piebaldism or Waardenburg syndrome
shows absence of melanocytes and melanin in epidermis. ))
Generalized hypopigmentation may be seen in albinism or
Hypomelanotic macules present in a localized form or vitiligo
generalized form. Various morphological forms have been
))
Localized scaly acquired hypopigmentation may be seen in
described like acrofacial, segmental, etc. Hairs over the lesion
pityriasis versicolor, and pityriasis alba
may also turn gray. Spontaneous repigmentation may occur
in some lesions. Exposure to chemicals may lead to ill defined
))
Vitiligo presents as acquired depigmented, and non-scaly
macules
hypopigmented macules of chemical leukoderma.
Diffuse acquired hypopigmentation may occur in patients ))
Leprosy may present with hypopigmented lesions with loss
with hypothyroidism and hypopituitarism. of sensation.
Clinical Pearls
• Localized hypopigmented lesions with forelocks may present
SUGGESTED READINGs
at birth in patients with piebaldism (without systemic features) 1. Anstey AV. Disorders of skin colour. In: Burns T, Breathnach S, Griffiths C, Cox N
or Waardenburg syndrome (with systemic features) (Eds). Rook’s Textbook of Dermatology, 8th edition. India: Wiley-Blackwell; 2010.
• Generalized congenital hypopigmentation with hair and eye pp. 58.1-58.59.
involvement occurs in albinisim 2. Lapeere H, Boone B, Schepper SD, Verhaeghe E, Ongenae K, Geel NV, et al.
Hypomelanoses and hypermelanoses. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest
• Vitiligo may present in a localized form or generalized form at
BA, Pallar AS, Leffell DJ (Eds). Fitzpatrick’s Dermatology in General Medicine, 7th
birth or later in life. edition. New Delhi: McGraw Hill; 2008. p. 622.
666
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Chapter 137
Pediatric Acne
Vibhu Mendiratta, Niti Gaur, Aashim Singh
INTRODUCTION postulated to be transient rise in dehydroepiandrosterone

sulfate and luteinizing hormone levels. Most infantile acne
Acne vulgaris is a common inflammatory condition of the is self-limited and not associated with underlying endocrine
pilosebaceous unit with a peak incidence during adolescence. pathology. There is some evidence that infantile acne
However, it may be found in all age groups including neonates predisposes to more severe adolescent acne. Infantile acne
and infants (Algorithm 1). may be treated with topical antimicrobial agents; topical
retinoids; non-cycline antibiotics, such as erythromycin; and,
NEONATAL ACNE occasionally, isotretinoin.
The onset of neonatal acne is usually before the first 6 weeks of Clinical Pearl
life. It affects about 20% of the newborns. The papules typically
occur across nasal bridge and cheeks. There are no comedones. • Acne not responding to treatment or with unusual presentation
This benign condition is hormonally mediated. Neonatal acne should be further evaluated to look for underlying endocrine
may be hard to distinguish from heterogeneous papulopustular pathology.
acneiform conditions typically without comedones, such as
neonatal cephalic pustulosis or transient neonatal pustular
melanosis. Neonatal cephalic pustulosis pustules are usually MID-CHILDHOOD ACNE
confined to the cheeks, chin, eyelids, and forehead, but the Mid-childhood acne presents primarily on the face with a
scalp, neck, upper chest, and back may be involved. It has been mixture of comedones and inflammatory lesions. Children
attributed to overgrowth of Malassezia species. Newborns may between the ages of 1 and 7 years, however, do not normally
present with or develop transient neonatal pustular melanosis, produce significant levels of adrenal or gonadal androgens;
with pustules on the chin, neck or trunk. Within 24 hours, these hence, acne in this age group is rare. When it does occur, an
pustules rupture, leaving hyperpigmented macules with a rim endocrine abnormality should be suspected. In addition to
of faint white scale. Most cases of neonatal acne resolve by 3 treatments to address androgen-secreting tumors or congenital
months of age but severe cases can be treated topically with 2% adrenal hyperplasia, the treatment of mid-childhood acne is
ketoconazole cream, benzoyl peroxide or erythromycin. similar to that of adolescent acne except that oral tetracyclines
are usually not an option in children younger than 8 years of
INFANTILE ACNE age because of the risk of damage to developing bones and
tooth enamel. Hormonal therapy could be used if warranted
Infantile acne may begin approximately at 6 weeks of age and by endocrinologic pathology.
last for 6–12 months. It is more common in boys and presents
with comedones as well as inflammatory lesions, which can
include papules, pustules, or occasionally nodular lesions. Clinical Pearl
Physical examination should include assessment of growth
• Tetracyclines are contraindicated in children <8 years and
including height, weight, and growth curve; testicular growth
oral isotretinoin is not recommended in children <12 years
and breast development; presence of hirsutism or pubic hair; according to the food and Drug Administration.
clitoromegaly; and increased muscle mass. The etiology is
ch-137.indd 667 11/22/2016 11:14:05 AM

Algorithm 1
Approach to pediatric acne depending on age of onset
PREADOLESCENT ACNE Propionibacterium acnes, and consequent immune response

and inflammation.
Preadolescent (7–12 years) acne is common and may precede
other signs of pubertal maturation. It is characterized by a
predominance of comedones on the forehead and central TREATMENT OF MILD ACNE
face (the so-called “T-zone”) with relatively few inflammatory Topical therapy alone or in combination is recommended
lesions. Further workup is generally unnecessary unless there as initial treatment of mild acne. Benzoyl peroxide (BPO) as
are signs of excess androgens. Treatment of uncomplicated a single agent, topical retinoids, or combinations of topical
preadolescent acne is comparable to that of acne in older age retinoids, antibiotics and BPO as individual agents or fixed-
groups, as discussed later. dose combinations may be used. If the response is inadequate
then a topical retinoid or BPO may be added to monotherapy
ADOLESCENT ACNE with either agent.
Adolescent acne (12–19 years) is common and characterized

by comedones and inflammatory lesions over face, back,
TREATMENT OF MODERATE ACNE
arms. Acne can be categorized as predominately comedonal, Moderate acne may be initially treated with topical
inflammatory and/or mixed. Presence or absence of scarring, combinations including a retinoid and BPO and/or antibiotics,
post-inflammatory hyperpigmentation or erythema should or with oral antibiotics in addition to a topical retinoid and
be assessed. Severity may be broadly categorized as mild, BP and/or topical antibiotics. Optimally, the topical regimen
moderate or severe. The pathogenesis of acne involves the would include a retinoid and a benzyl peroxide-containing
interplay of four factors: sebaceous hyperplasia under the formulation, either separately or as a combination product. In
influence of increased androgen levels, alterations in follicular addition, use of an oral antibiotic may be especially prudent if
668 growth and differentiation, colonization of the follicle by there is evidence of acne scarring, even if the current severity
ch-137.indd 668 11/22/2016 11:14:05 AM

Chapter 137: Pediatric Acne
of inflammatory acne is more modest. Typically, 4–8 weeks of SUGGESTED READINGS

compliant oral antibiotic use are needed before the clinical
effects of an oral antibiotic are visible, whereas maximal 1. Cantatore-Francis JL, Glick SA. Childhood acne: evaluation and management.
Dermatol Ther. 2006;19(4):202-9.
response may require 3–6 months of administration.
2. Cunliffe WJ, Baron SE, Coulson IH. A clinical and therapeutic study of 29 patients
with infantile acne. Br J Dermatol. 2001;145(3):463-6.
TREATMENT OF SEVERE ACNE 3. Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol
Clin. 2009;27(1):33-42.
Patients with severe acne are at significant risk for scarring. 4. Niamba P, Weill FX, Sarlangue J, Labrèze C, Couprie B, Taïeh A. Is common
Severe acne should be treated with oral antibiotics and topical neonatal cephalic pustulosis (neonatal acne) triggered by Malassezia
retinoids with BPO, with or without topical antibiotics, with sympodialis? Arch Dermatol. 1998;134(8):995-8.
consideration of hormonal therapy in pubertal females or oral 5. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Global
alliance to improve outcomes in acne. Management of acne: a report from a
isotretinoin. Patients unresponsive to these topical and oral
global alliance to improve outcomes in acne. J Am Acad Dermatol. 2003;49(Suppl
therapies will benefit with oral isotretinoin. 1):S1-37.
6. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Global
alliance to improve outcomes in acne. Management of acne: a report from a
Clinical Pearl global alliance to improve outcomes in acne. J Am Acad Dermatol. 2003;49(Suppl
• Childhood acne may persist and raises the risk of development 1):S1-37.
7. Herane MI, Ando I. Acne in infancy and acne genetics. Dermatology.
of severe scarring acne in adulthood.
2003;206(1):24-8.
8. Jansen T, Burgdorf WH, Plewig G. Pathogenesis and treatment of acne in
childhood. Pediatr Dermatol. 1997;14(1):17-21.
Key points 9. Krakowski AC, Eichenfield LF. Pediatric acne: clinical presentations, evaluation,
and management. J Drugs Dermatol. 2007;6(6):589-93.
))
Acne may present in all age groups. It may be physiological or 10. Poli F. Acne on pigmented skin. Int J Dermatol. 2007;46(Suppl 1):39-41.
pathological in pediatric age groups
))
Mild to moderate forms are usually self-limited but severe
forms of acne require topical or oral treatment to prevent
scarring
))
Pediatric acne may be a pointer toward virilization, especially
if unresponsive to conventional treatment.
669
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Chapter 138
Approach to Congenital
Melanocytic Nevus
Vibhu Mendiratta, Pravesh Yadav
INTRODUCTION anomaly and may be symptomatic in sites such as over the

sacrum. Neurocutaneous melanosis may rarely produce raised
Congenital melanocytic nevus (CMN) represent a develop intracranial pressure, hydrocephalus or space-occupying
mental abnormality of normal melanocytic development. spinal lesions. A variety of proliferative neoplasms may
This is probably due to mutation that occurs in a progenitor develop in CMN. Superficial spreading melanoma is the
cell that results in the abnormal extensive accumulation of most significant complication of CMN but the level of risk is
melanocytic cells along migration pathways during normal reasonably low. In giant nevi, there is a definite risk, with the
development. The events leading to the nevomelanocyte age of onset of the melanoma being earlier than in the general
accumulation may also have effects on the surrounding tissue population. A magnetic resonance imaging scan should be
probably due to a change in the local cytokine environment of considered in babies with nevi over the cranium or spine to
the nevomelanocytic cells. According to American National exclude significant leptomeningeal melanocytosis. Regular
Institutes of Health consensus definition, CMN have been neurological examination, however, is clearly important.
categorized according to size into small, under 1.5 cm in Histopathology shows presence of nevomelanocytes in the
diameter, large as having a diameter between 1.5 and 20 cm and epidermis as well ordered theques and/or nevomelanocytes
giant nevi as having a diameter of 20 cm or more (Algorithm 1). in the dermis in the form of sheets, nests, cords and/or single
Congenital melanocytic nevi are usually obvious and deeply cells. Presence of nevomelanocytes in the lower two-thirds of
pigmented at birth. Majority of these nevi are macular at birth the reticular dermis and association with appendageal and
with smooth, regular and sharply demarcated contour and neurovascular structures is more commonly seen with CMN
distortion of the skin markings. As the child grows, the nevus than acquired nevi. Nevomelanocytes may be prominent
usually grows in proportion. At some sites, such as the scalp, within and around the blood vessels showing an inflammatory
there is commonly a considerable increase in terminal hair. In appearance. Hair follicles are often quite large and associated
other sites, an increase in terminal hair tends to occur more with abundant melanin in the hair bulb.
subtly over time and may be accompanied by the development Differentials of CMN include CALM (café au lait macules),
of rugosity. As the infant grows, the surface of the nevus may nevus spilus, Becker’s nevus, lentigo simplex, nevus sebaceous,
become rugose or warty and nodules can develop within a smooth muscle hamartoma, epidermal nevi, dermal melano
large nevus. Congenital melanocytic nevi may develop a halo of cytosis, and solitary mastocytoma.
depigmentation, heralding a potential spontaneous resolution. Congenital melanocytic nevi are essentially considered to
Loss of pigmentation has been associated with regression of be developmental abnormalities of the skin, with a very low risk
underlying melanocytes. Dermatoscopy can sometime prove of recurrence in subsequent pregnancies, which is particularly
to be helpful in the diagnosis showing a characteristic reticular important when reassuring parents who have a child with a
or globular pattern. A significant proportion of nevi may giant melanocytic nevus. The aims of treatment are to improve
become paler in the first 1–2 years of life, and at sites such as the cosmetic effect of nevi and to reduce the risk of malignant
the scalp may fade to cosmetic insignificance. transformation. The most common treatment is surgical,
There may be associated abnormalities such as meningeal using a variety of plastic surgical techniques such as multistep
involvement, spina bifida, or meningocele when the nevus surgery, the use of tissue expanders and grafting. Tissue
is located over the vertebral column, or club-foot and expansion is usually used for the head and neck, but in other
hypertrophy or atrophy of the deeper structures of a limb. sites excision and grafting are more usual, with consequently
Absence of subcutaneous fat is the most common associated poorer cosmetic results. Other ablative techniques have been
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Chapter 138: Approach to Congenital Melanocytic Nevus
tried such as cryotherapy and, more recently, the Q-switched

ruby laser. Clinical Pearls
Parents of children with CMN left in situ should be advised • Nevus located over the vertebral column: rule out abnormalities
to keep the nevus under review and to seek advice if it changes such as meningeal involvement, spina bifida, or meningocele
in shape, size, or color. Photographs of the child’s nevus and • Giant nevi (diameter of 20 cm or more): higher risk.
images of melanomas may be useful tools. Even small nevi that
are difficult to keep under review, such as those in the scalp
or in the middle of the back may be prophylactically excised,
particularly if they have any atypical features such as intense or Key points
irregular pigmentation which persists beyond infancy.
))
Congenital melanocytic nevus (CMN) is a developmental
abnormality of normal melanocytic development leading
Algorithm 1 to an abnormal accumulation of melanocytic cells along
migration pathways during normal development
Approach to congenital melanocytic nevus
))
Congenital melanocytic nevus are usually obvious and deeply
pigmented macules at birth and grow in proportion to the
body with age
))
Increase in terminal hair and rugosity are normal progression
changes with age
))
Congenital melanocytic nevus may be associated with
abnormalities such as meningeal involvement, spina bifida,
or meningocele when the nevus is located over the vertebral
column
))
A variety of proliferative neoplasms may develop in CMN,
superficial spreading melanoma being the most significant
))
Treatment indications are mainly cosmetic.
SUGGESTED READINGS
1. Anon. Consensus conference: precursors to malignant melanoma. JAMA.
1984;251:1864-6.
2. Bishop JAN. Lentigos, melanocytic naevi and melanoma. In: Burns T, Breathnach
S, Griffiths C, Cox N (Eds). Rook’s Textbook of Dermatology, 8th edition. India:
Wiley-Blackwell; 2010. pp. 54.1-54.57.
3. Goodman RM, Caren J, Ziprkowski M, Padeh B, Ziprkowski L, Cohen BE,
et al. Genetic considerations in giant pigmented hairy naevus. Br J Dermatol.
1971;85:150-7.
4. Grichnile JM, Rhodes AR, Sober AJ. Benign neoplasias and hyperplasias of
melanocytes. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Pallar AS, Leffell
DJ (Eds). Fitzpatrick’s Dermatology in General Medicine, 7th edition. New Delhi:
McGraw Hill; 2008. p. 1099.
5. Strauss RM, Bishop JAN. Spontaneous involution of congenital melanocytic nevi
of the scalp. J Am Acad Dermatol. 2008;58:508-11.
CALM, café au lait macules; MRI, magnetic resonance imaging
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Chapter 139
Seborrheic Dermatitis
INTRODUCTION be aggravated by illness, psychological stress, fatigue, sleep

deprivation, and reduced general health.
Seborrheic dermatitis (SD) is a chronic papulosquamous In children, excessive vitamin A intake can cause
inflammatory disorder affecting the sebaceous gland rich areas seborrhoeic dermatitis. Lack of biotin, pyridoxine (vitamin B6)
of the skin. It is a benign self-limiting condition characterized and riboflavin (vitamin B2) may also be a cause.
by remissions and exacerbations. It occurs due to seborrhea, Those with immunodeficiency (especially infection with
a pathologic overproduction of sebum, with subsequent HIV) and with neurological disorders such as Parkinson’s
infection and inflammation. It typically presents with scaly, disease and stroke are particularly prone to it.
flaky, greasy, and red skin. The severity ranges from mild
dandruff to exfoliative erythroderma. It can occur in any age Malassezia species: the most implicated species are Malassezia
group; however, two age peaks are noted; in infants—during globosa, others being Malassezia furfur and Malassezia restricta.
first 3 months of life and in adults—during 4th to 7th decade Infantile SD is more commonly associated with Malassezia
of life. These age peaks correlate with the high activity of furfur. Patients with seborrhoeic dermatitis appear to have a
sebaceous glands. reduced resistance to the yeast. Malassezia hydrolyze human
sebum releasing a mixture of saturated and unsaturated fatty
acids (FAs). They take up the required saturated FAs, leaving
EPIDEMIOLOGY behind unsaturated FAs. The unsaturated FAs penetrate the
Seborrheic dermatitis affects healthy individuals of any ethnicity, stratum corneum and because of their non-uniform structure
with no sex predilection. Estimates of SD prevalence and breach the skin’s barrier function. This barrier breach induces
incidence are hindered by many cases being mild and poor case an irritation response, leading to seborrhea and dermatitis.
definition, so probably underestimate the true figure. Estimates Environmental factors: worsening of SD occurs in winters and
are also limited due to absence of validated criteria for diagnosis. early spring. Remission can be seen in summers.
As per literature, SD affects 3–5% of the general population. Up
to 70% of newborns are affected by SD in their first 3 months CLINICAL PRESENTATION AND
of life. Dandruff, the mildest form of SD effects 15–20% of the
APPROACH (Algorithm 1)
population. SD is especially prevalent in those with human
immunodeficiency virus (HIV)/acquired immunodeficiency
syndrome and chronic neurodegenerative disorders. Infants
Cradle cap is the most common presentation in infants and
usually appears in the first few weeks of life. There are greasy,
ETIOLOGY
yellow scales and crusts that may eventually coalesce to a thick,
The exact etiology remains uncertain. It involves a complex scaly plaque with underlying mild to moderate erythema.
interaction between: Overall, scalp is the most commonly affected site, followed by
• Host factors face. Areas of face commonly affected are forehead, eyebrows,
• Malassezia species nasolabial folds and retroauricular areas.Seborrheic dermatitis
• Environmental factors. can also involve the thorax, upper back, external genitalia and
Host factors: overactivity of sebaceous glands leads to flexures such as the axillae, inguinal folds. Involvement of
excess production of sebum. Seborrhoeic dermatitis may perianal area in the form of diaper rash is also common.
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Chapter 139: Seborrheic Dermatitis
Algorithm 1
Seborrheic dermatitis and its differentials: Diagnostic approach
features along with seborrhic dermatitis like lesions, he should

Clinical Pearl be worked up for Langerhan’s cell histiocytosis. Scabies with
Seborrheic areas eczematisaton is also a close mimicker of the disease where
• Scalp, retroauricular areas, medial eyebrows, nasolabial fold, presence of nocturnal exacerbation itching and lesions in
anterior chest, interscapular area, axillae, groins, and diaper area. contacts help differentiate the conditions.
The condition is not itchy unlike in adolescents. The Adolescents

condition usually resolves without treatment in weeks to Seborrhea of scalp in the form of dandruff is the most common
months, although treatment may be used if needed. presentation in adolescents and adults. Greasy white to yellow,
On the other hand, patient with atopic dermatitis have fine scales with underlying erythema can be seen. This should
scalp and facial involvement in the form of oozy plaques be differentiated from well-defined plaques with micacious
which are extremely pruritic. Extensors may also be involved. scales seen in scalp psoriasis. The sites of predilection are the
Diaper area is characteristically spared unlike infantile SD and same as in infants. However, in adolescents SD is usually worse
673
psoriasis. If the infant exhibits systemic and constitutional in hair bearing areas of the face and involvement of flexures
ch-139.indd 673 11/22/2016 11:17:24 AM

and perianal area is less common. Centrofacial erythema is for additional benefits. For best results, the shampoo should
prominent with greasy scales over eyebrows, nasolabial folds be left in place for 5–10 minutes before rinsing. The shampoo
and retroauricular region. Absence of flushing, telangiectasias should be rinsed out of the hair completely.
help us differentiate it from rosacea where papulopustules are The shampoo may be used every day initially, and then
present on baseline facial erythema over convexities. Trunk every other day as symptoms improve. These shampoos can be
may also be involved with perifollicular papules (petaloid used for as long as needed.
pattern) and papulosquamous lesions (pityriasiform pattern)
with greasy scales. Truncal lesions resemble pityriasis rosea Nonscalp Seborrheic Dermatitis
and pityriasis versicolor. Candidal intertrigo and tinea cruris Seborrheic dermatitis of the face, trunk, and skin folds generally
can mimic flexural SD which can be diagnosed with simple is treated with topical corticosteroids or antifungal agents.
bedside testing with potassium hydroxide mount. Low potency topical corticosteroids (e.g., hydrocortisone
1% cream) may be tried initially. The cream is applied once
TREATMENT or twice a day until symptoms improve with gradual tapering.
Topical antifungal agents (ketoconazole 2%, miconazole)
The symptoms of SD can be effectively controlled with a either alone or in combination with topical steroids can also
combination of self-care measures and drug therapy. be used. Long-term application of steroids should be avoided
Topical antifungal agents and topical corticosteroids in view of side effects like atrophy, striae and telangiectasias.
are the principal forms of management for SD. Of these two The topical calcineurin inhibitors tacrolimus and pimecro
treatment modalities, antifungals are the mainstay. However, limus are effective in treating SD. Both can be used twice daily
during acute exacerbations, topical corticosteroids are often initially and weaned down as the SD improves. Proactive
used as first line therapy. treatment of adult facial SD to maintain remission with 0.1%
tacrolimus ointment once or twice per week is also effective.
Infant Seborrheic Dermatitis For refractory or widespread SD where topical therapy is
Cradle cap usually resolves without treatment. However, it impractical, oral itraconazole 200 mg daily for 2–4 weeks is
may require treatment in some cases. Regular emollients and effective.
mild non-medicated baby shampoos can be tried initially for
infantile SD, especially if asymptomatic. For more widespread, Clinical Pearls
symptomatic or persistent SD, topical ketoconazole 2% Cradle cap: What to tell parents
cream, mild corticosteroid ointments (hydrocortisone
• Regular scalp wash with mild baby shampoo
1%, desowen lotion 0.05%, clobetasone butyrate 0.05%) or
• Remove scales with a brush
combination preparations containing hydrocortisone and
• Emollients can be used to loosen the scales.
miconazole can also be used—initially twice daily on affected
areas, weaning down on improvement. The scales should be
gently removed with a soft brush after shampooing. A small
amount of emollient can be applied to the scalp overnight to
Key points
loosen the scaly plaques. There is no role of oral antifungals ))
Seborrheic dermatitis (SD) is physiological in infants below
in infantile SD. 3 months of age
))
Cradle cap is the most common presentation
Clinical Pearl ))
It is a non-itchy condition characterized by greasy yellow
• Infantile seborrheic dermatitis is a physiological condition and scales in seborrheic areas
usually does not require treatment. ))
Self-limiting course
))
Psoriasis, intertrigo, pityriasisrosea, and rosacea are close
mimickers for adolescent SD
Adolescent/Adult Seborrheic Dermatitis ))
Antifungals and topical steroids form the main stay of
Seborrheic dermatitis in adults is a chronic condition. Long- treatment.
term maintenance treatment is often necessary.
Scalp Seborrheic Dermatitis SUGGESTED READINGS

Dandruff (mild SD of the scalp) can be treated with anti- 1. Bikowski J. Facial seborrheic dermatitis: a report on current status and
therapeutic horizons. J Drugs Dermatol. 2009;8(2):125-33.
dandruff shampoos. Several types of anti-dandruff shampoos 2. Gaitanis G, Velegraki A, Alexopoulos EC, Chasapi V, Tsigonia A, Katsambas A.
are available, with the main difference between them being the Distribution of malassezia species in pityriasis versicolor and seborrhoeic
active ingredient. All of these treatments are equally effective dermatitis in Greece. Typing of the major pityriasis versicolor isolate M. globosa.
after 4 weeks of use. The main active ingredients are: Br J Dermatol. 2006;154:854-9.
• Selenium sulfide 3. Gupta AK, Bluhm R. Seborrheic dermatitis. J Eur Acad Dermatol Venereol.
• Tar 2004;18(1):13-26.
4. Hay RJ, Graham-Brown RAC. Dandruff and seborrhoeic dermatitis: causes and
• Zinc pyrithione
management. Clinical and Experimental Dermatology. 1997;22(1):3-6.
• Ketoconazole.
674 Shampoos containing corticosteroids, propylene glycol
5. Sheffield RC, Crawford P, Wright ST, King VJ. Clinical inquiries. What’s the best
treatment for cradle cap? J Fam Pract. 2007;56(3):232-3.
and keratolytics like coal tar and salicylic acid can also be used 6. Smoker AL. On top of cradle cap. J Fam Health Care. 2007;17(4):134-6.
ch-139.indd 674 11/22/2016 11:17:24 AM

Section 17: Ophthalmology
Chapter 140
Approach to Red Eye in Children
Suma Ganesh, Priyanka Arora
INTRODUCTION Table 1: Causes of red eye in children
Red eye is one of the most common reasons for acute eye- Most common Relatively common Uncommon
related visits to the pediatricians, while some causes are • Conjunctivitis • Trauma • Iridocyclitis or
uncomplicated and resolve within a few days, many cases {{ Infectious • Subconjunctival uveitis
require prompt treatment to prevent the disease from –– Bacterial hemorrhage • Episcleritis
worsening or spreading. The condition can be managed –– Viral due to vigorous • Scleritis
by pediatricians, but knowing when to refer the patient –– Chlamydial coughing • Contact lens
to ophthalmologist is crucial. In this chapter, we will be {{ Noninfectious: • Stye/hordeolum related
discussing the common causes of red eye in children and the –– Allergic • Keratitis/corneal • Severe dry eye
approach to management of these causes. conjunctivitis ulcer • Endophthalmitis
–– Chemical • Ocular fatigue • Glaucoma
irritants
CAUSES OF RED EYE • Foreign body
Conjunctivitis is the most common cause of red eye. It may • Blepharitis
be infectious (bacterial or viral) or noninfectious (allergic, • Corneal abrasions
chemical). At a leading cornea service (Will’s Eye Hospital),
blepharoconjunctivitis was the most common diagnosis in
children, accounting for 15% of all pediatric referrals. Most Tips for an Effective Patient History and
cases of infectious conjunctivitis are self-limiting. Other
common causes of red eye in children include blepharitis,
Examination
corneal abrasion, foreign body, subconjunctival hemorrhage, When a child presents with red eye, one must be able to identify
keratitis, iritis, chemical burns, trauma, endophthalmitis, and potentially serious ocular conditions that require immediate
severe dry eye. Some uncommon causes of red eye in children referral. Includes these questions in a through histroy to aid in
are iridocyclitis, episcleritis, contact lens related, due to differential diagnosis:
chemical irritants like chlorine in swimming pools, head • When did the symptoms start?
lice if they spread to ocular area, and congenital glaucoma • Are they in one eye or both?
(Table 1). • Is there any discharge in the eye? If yes, what kind and how
much?
• Is there any swelling or pain in eyes?
HISTORY AND EXAMINATION • Is there a history of similar complaints in any of the family
A thorough patient history and eye examination may provide member?
clues towards etiology of red eye (Table 2). Salient points in this • Any recent history of:
history includes whether the condition is unilateral or bilateral, {{ Explosure to chemicals
duration and type of symptoms, presence of discharge and its {{ Contact with another person with red eye
nature, visual changes, pain, photophobia, itching, and any {{ Injury to the eye
previous treatments. {{ Upper respiratory tract infection (URI)
ch-140.indd 675 11/24/2016 2:36:06 PM

Table 2: Clinical pointers in history and examination to identify Table 3: Comparison of bacterial and viral conjunctivitis
the causes of red eye
Parameters Bacterial Viral
Signs Symptoms Likely diagnosis • Common • Haemophilus • Adenovirus type 8
• Purulent • Matting of eyelashes • Bacterial organisms influenzae and 19
discharge on waking up in conjunctivitis • Streptococcus • Herpes simplex
morning (best pneumoniae virus
predictor) • Moraxella
• Preauricular • Watery or serous • Viral Catarrhalis
lymph discharge conjunctivitis • Neisseria
adenopathy • Recent history of gonorrhoeae
upper respiratory • Chlamydia
tract infection trachomatis
• Larger • Bilateral eye • Allergic Incubation period 24–72 h 1–14 days
cobblestone involvement conjunctivitis Prevalent age group Neonates to School age to adults
papillae under • Intense itching toddlers
upper eyelid • Ropy discharge Symptoms
• Eye lid swelling
Photophobia Mild Moderate-to-severe
• Lid vesicles • Painful red eye • Herpes
• Decreased vision • Photophobia simplex virus
keratitis Blurred vision Common due to Only if keratitis
discharge present
• Dandruff- • Red, irritated eye • Blepharitis
like flakes on • Worse in morning Foreign body Unusual Yes
eyelashes • Itchy crusted eyelids sensation
• Missing eyelashes Signs
• Swollen lids Discharge Purulent Watery
• Corneal edema or • Unilateral foreign • Corneal Palpebral reaction Papillary response Follicular response
haze body sensation abrasions
Preauricular Unusual Common
• Blepharospasm • Inability to open eyes
• Profuse watering • Profuse watering Chemosis Moderate Mild
• Recent history of Subconjunctival Only with Frequent
trauma (fingernail, hemorrhage Haemophilus
paper) • Associated • Otitis media • Pharyngitis
disorders • Upper respiratory
• Is there a personal or family history of atopy, asthma, or tract infection
eczema? • End of contagious • 24 h after start • 7 days after onset
• Does the child were any contact lens? period of treatment of symptoms
• Is there any history of ocular surgery?
During examination, do not forget:
• To evert eyelids • Examination reveals diffuse conjunctival congestion,
• To examine periorbital skin for any lesions matted eyelashes, and normal visual acuity
• To palpate preauricular lymph nodes. • Treatment includes topical antibiotics 2 hourly for 2 days
and four times a day for a week
• Refer if:
CONJUNCTIVITIS {{ Decreased vision, photophobia, or pain at any stage
It is a nonspecific term that means inflammation of the {{ Does not improve in 2 weeks.
conjunctiva causing hyperemia, general discomfort, and other

symptoms. A diverse range of etiologies present in a similar Clinical Pearl
manner that can be challenging to differentiate. Salient points • Otitis media associated with conjunctivitis is most frequently
of each variety of conjunctivitis has been provided in table 3. caused by nontypeable Haemophilus influenzae and occasionally
by Streptococcus pneumoniae and by other bacteria.
Bacterial Conjunctivitis
• Might be briefly unilateral, but usually becomes bilateral
• Red, sticky, gritty eyes with purulent discharge, but no Viral Conjunctivitis
pain/photophobia • Involvement can be unilateral or bilateral
• Family members are often affected (very contagious) • Often history of recent URI
676
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Chapter 140: Approach to Red Eye in Children
• Examination reveals diffuse conjunctival congestion with {{ Acute febrile systemic infections like malaria, typhoid,
watering, follicular reactor on lid eversion, normal visual diphtheria, meningococcal septicemia, measles, and
acuity, and preauricular lymphadenopathy scarlet fever
• Usually a self-limiting condition, but topical antibiotics an • Condition is often noticed incidentally and is asymptomatic
rarely necessary because secondary infection is uncommon • Reassure the parents about the benign return of the disease
• Give conservative treatment, like cold compression and and that it could take 2 or more weeks for the redness to
lubricating eye drops resolve
• The disease is highly contagious and usually resolves • Refer if recurrent, persistent or severe.
spontaneously in 2 weeks.
CORNEAL ABRASION
Allergic Conjunctivitis
• Any break in the corneal surface is known as corneal
• Often associated with atopic diseases, like allergic rhinitis, abrasion
eczema, and asthma • The patient present with painful red eye with swollen
• Itching of the eyes is the most predominant symptom This eyelids, excessive watering, and blepharospasm
can be seasonal, i.e., worse in spring season or chronic • It can be associated with a corneal foreign body
(associated with asthma, eczema, etc.) • The other eye is usually normal
• Watery or mucoid discharge which is usually not copious • Treatment includes topical antibiotics and frequent
• Examination of eyes reveals diffuse redness in the eyes instillation of artificial tears eye drops
with severe papillary reaction, especially under the upper • Referral to ophthalmologist is indicated if symptoms
eyelids worsen or do not resolve within 48 hours
• Treatment includes avoiding exposure to possible • Studies show that eye patches do not improve patient
allergens, topical mast-cell stabilizes like cromoglycate eye comfort or healing of corneal abrasions.
drops and lubricating eye drops
• Steroid eye drops should only be commenced under Clinical Pearl
ophthalmic supervision if distressing symptoms persist.
• In patients with corneal abrasion, it is good practice to check
for retained foreign body under the upper eyelid.
BLEPHARITIS
• Chronic inflammatory condition of eyelid margins RED EYE IN A NEWBORN
• Usually associated with seborrhea of scalp (dandruff ) or
can be due to chronic staphylococcal infection of the lid • Red eye in a newborn can be an alarming sign to the
margin by coagulase positive strains pediatricians as well as parents
• Children present with complaints of deposition of whitish • The common causes could be:
{{ Ophthalmia neonatorum (neonatal conjunctivitis)
material at lid margins associated with irritation, redness,
{{ Birth trauma: corneal injury during forceps delivery
and occasionally watering. There is a history of falling of
{{ Subconjunctival hemorrhage
eye eyelashes
{{ Nasolacrimal duct obstruction/dacryocystitis
• Treatment involves eyelid hygiene (cleansing with diluted
baby shampoo), gentle lid massage, and water compresses.
Associated seborrhea of the scalp should be adequately Ophthalmia Neonatorum
treated. (Neonatal Conjunctivitis)
It is an extremely common form of conjunctivitis in the first
SUBCONJUNCTIVAL HEMORRHAGE month of life and is the most common infection in the neonatal
period. The cause of neonatal conjunctivitis is difficult to
• Spontaneous appearance of bright red blood between the determine because the signs and symptoms do not vary by
sclera and conjunctiva cause. The timing and presentation of neonatal conjunctivitis is
• Often looks very dramatic and is worrisome to the patients, very useful in identifying the cause. In order of occurrence, the
but is most of the times trivial common causes of neonatal conjunctivitis include: chemical,
• It can occur spontaneously (without any evident cause) or bacterial, and viral.
may be associated with: • Chemical conjunctivitis: It occurs within first 24 hours of
{{ Severe coughing or straining life:
{{ Enteroviral conjunctivitis {{ Watery discharge with mild redness of the eye
{{ Trauma {{ Minimal swelling of eyelids
{{ Bleeding disorders like purpura, hemophilia, and {{ Symptoms last for only 24–36 hours
scurvy • Gonococcal conjunctivitis:

{{ Bleeding dyscrasias like anemia and leukemia, etc. {{ Caused by Neisseria gonorrhoeae
677
ch-140.indd 677 11/24/2016 2:36:06 PM

Algorithm 1
Approach to red eye in children
HSV, herpes simplex virus.
{{Newborn can be infected from the mother during {{ Can be associated with photophobia, in case cornea is
passage through birth canal involved
{{ Presents typically 1–7 days after birth with sudden {{ Intravenous antivirals are indicated as it can be
onset, severe, grossly purulent conjunctivitis associated with severe systemic infection.
{{ This can be very serious and can cause:
–– Bilateral severe infectious corneal ulcers resulting

CONCLUSION
in perforation of cornea and bilateral blindness
–– Bloodstream spread with fatal meningitis or With careful questioning and thorough examination,
encephalitis pediatricians can accurately differentiate among the various
{{ Needs intravenous antibiotics causes of red eye in children and address the common benign
• Chlamydial conjunctivitis conditions. All newborns with conjunctivitis in first week of
{{ Less common than gonococcal, but can be serious life should be evaluated with Gram staining and culture
{{ Presents at 2 weeks of age and if Gram-negative diplococci are seen, should be treated
{{ Discharge can be variable: watery/purulent with systemic antibiotics. Older infants and toddlers usually
{{ Associated with chlamydial lung infection have bacterial conjunctivitis associated with otitis media.
{{ Needs systemic antibiotics So, their ears need to be evaluated for otitis and if present,
• Herpes simplex viral conjunctivitis: should be treated with oral antibiotics. Viral conjunctivitis
{{ Accounts for less than 1% cases with neonatal mostly affects older children or adolescents and is associated
conjunctivitis with pharyngitis and preauricular lymphadenopathy. It
{{ Usually clear discharge with lid swelling is a self-limiting disease and requires only conservative
{{ Mostly due to herpes simplex virus 2 treatment. Allergic conjunctivitis is marked by presence of
678
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Chapter 140: Approach to Red Eye in Children
intense itching with associated rhinitis, asthma, or eczema. SUGGESTED READINGS

It is treated with antihistamines, decongestants, and mast-
1. Bielory L, Friedlaender MH. Allergic conjunctivitis. Immunol Allergy Clin North Am.
cell stabilizers. Referral to an ophthalmologist is necessary
2008;28(1):43-58.
if child has visual loss, pain, copious purulent discharge, or
2. Hammersmith KM, Cohen EJ, Blake TD, Laibson PR, Rapuano CJ.
corneal involvement. Blepharoconjunctivitis in children. Arch Ophthalmol. 2005;123(12):1667-70.
3. Kleigman RM, Mar KJ, Jenson HB, Behrman RE. Nelson Essentials of Pediatrics,
5th ed. Philadelphia, PA, USA: Elsevier-Saunders; 2006.
Key points
4. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician. 1998;57(4):735-46.
))
All cases of red eye with decreased vision, pain or photophobia 5. Teoh DL, Reynolds S. (2003). Diagnosis and management of pediatric
require urgent referral conjunctivitis. [online] Available from www.fmed.ulaval.ca/pediatrie/fileadmin/
docs/serveur_pediatrie/Acces_reserve/Medecins/Articles_scientifiques/recueil/
))
Not every red eye is due to conjunctivitis. Look for other
Conjunctivitis.pdf. [Accessed November, 2015].
causes
6. Turner A, Rabiu M. Patching for corneal abrasion. Cochrane Database Syst Rev.
))
Never prescribe steroid eye drops unless asked by an 2006;(2):CD004764.
ophthalmologist 7. Wirbelauer C. Management of red eye for the primary care physician. Am J Med.
))
A newborn baby with red eyes and eye discharge has sight 2006;119(4):302-6.
and life-threatening infections and require urgent referral.
679
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Chapter 141
Compensatory Head Posture
Manav D Singh
INTRODUCTION Box 2: Components of abnormal head posture

Compensatory or abnormal head posture (AHP) is not an • Chin: elevation or depression (vertical component)
uncommon condition in childhood with estimated incidence • Face turn: to right or left (horizontal component)
of 1.3%. Mostly congenital, it may be an acquired finding. • Head tilt: to right or left shoulder (torsional component)
Although it may be also of orthopedic or neurologic in origin,
our focus will be the one of ocular origin (Box 1).
the patient enters the examination room before he becomes
conscious of being examined. Compensatory head posture
Box 1: Origin of abnormal head posture
may be partially or totally lost by voluntary effort and lots of
• Orthopedic • Ocular information may, thus, be lost. The abnormal head posture has
• Neurologic three components (Box 2).
Each of them is compensation at different joints of head
In the process of evolution, humans have acquired and neck to correct respective ocular motility disorders in
binocular vision with the aim to provide stereopsis or depth an effort to achieve fusion by minimizing deviation. If the
perception or simply accurate assessment of distance. There deviation is too large to develop any level of fusion, no effort
are three levels of binocular vision; viz. may be made for the purpose and no AHP may develop. If
1. Simultaneous perception (SP) unable to fuse, head posture may also develop to provide
2. Fusion maximal deviation in an effort to suppress or ignore the
3. Stereopsis. peripheral image to avoid diplopia. It is also possible to
In general, SP is essential for fusion and fusion is essential develop AHP to permit fusion based on anomalous retinal
for stereopsis. The neuromuscular system of head and neck correspondence (ARC). Occasionally, a patient with very poor
tries to compensate for certain abnormalities of the ocular vision in one eye may develop face turn in the direction of
motor system (which may be primary or secondary to sensory non-seeing eye in order to improve field of vision (Fig. 1) or to
visual problems) in an effort to achieve single binocular vision, bring null point in straight gaze if he suffers from nystagmus
to avoid diplopia, or sometimes to achieve clear vision. This (Fig. 2).
results in AHP.
Clinical Pearl INTERPRETATION OF HEAD POSTURE

• Face turn:
• Head posture is an adaptation of head and neck musculature
{{ To right: keeps eyes in levoversion to avoid mani
to avoid diplopia and attain fusion and is mostly seen in
congenital disorders. festation of weakness of right superior rectus, right
inferior rectus, left inferior oblique, and left superior
oblique
{{ To left: keeps eyes in dextroversion to avoid mani
COMPONENTS OF HEAD POSTURE
festation of weakness of right interior oblique, right
Observation of head posture is the first step in the examination superior oblique (RSO), left inferior rectus, and left
of ophthalmic motor system. This should be done as soon as superior rectus
ch-141.indd 680 11/22/2016 11:37:12 AM

Chapter 141: Compensatory Head Posture
• Head tilt:
{{ To right: is a compensation for weakness of extorsion of
right eye or/and intorsion of left eye

{{ To left: is a compensation for weakness of intorsion of
right eye or/and extorsion of left eye

• Chin: Elevation/depression:
{{ Up: to compensate elevator weakness
{{ Down: to compensate depressor weakness.
SENSORY AND MOTOR FUSION

It is instinctual to have clear view of any object lying in the field
of vision. Therefore, once an object enters field of vision, eyes
turn in a way so that its image lies on to fovea. Farther is the
stimulated retinal element located from the fovea, higher is
the incentive for the eye to move or higher is the retinomotor
value of that retinal element. Not to mention, retinomotor
value of fovea is zero. Two eyes of the same person have retinal
elements that share common subjective visual directions.
These are called corresponding retinal points. This sensory
correspondence explains sensory fusion and is the essence
Fig. 1: Patient with phthisis bulbi of right eye showing face turn of binocular vision. Alignment of eyes in a way that sensory
to right fusion can be maintained is called motor fusion. The stimulus
A B
C D
Fig. 2: Congenital pendular nystagmus with null point in levoversion showing: A, Face turn to right; B, Preoperative
electronystagmogragh (ENG); C, Postoperative head posture and D, Postoperative ENG in primary gaze
Courtesy: Rohit Saxena.
681
ch-141.indd 681 11/22/2016 11:37:12 AM

for sensory fusion is the excitation of corresponding retinal CAUSES OF ABNORMAL HEAD POSTURE
elements and that of motor fusion is retinal disparity. However,
the ultimate goal of all this is to achieve stereopsis. At retinal The cause of the AHP can be ocular, orthopedic, and
element level, it can be said that stereoscopic vision is the neurologic. The orthopedic causes of AHP include congenital
result of simultaneous stimulation of horizontally disparate tightness of the sternocleidomastoid (SCM) muscle, Klippel-
retinal elements. The fusion of these (only horizontally not Feil anomaly, and brachial-plexus injury. Neurologic causes
vertically) disparate images gives rise to a visual impression of AHP are mainly related to brain tumors, postinflammatory
perceived in depth. central nervous system conditions, psychomotor delay, and
focal dystonia. However, only ocular causes will be discussed
The Association of Sensory and in detail.
Motor Visual System Incomitant Squint
The sensory visual system which consists of retinocerebral
Paralytic or restrictive musculofascial anomalies can lead
apparatus assisted by optico-refractory system of eye has
to abnormal head posture. Most patients with paralytic
the primary function of collection of information about the
strabismus habitually hold their head in a position so as to
outside world. However, the visual motor system is entirely
avoid the field of action of paretic muscle. Diplopia is, thus,
in the service of visual sensory system. Since motor system
eliminated and binocular single vision attained. A classical
has no independent existence, it adapts itself to assist a
malfunctioning sensory system in a way to get the best example is congenital superior oblique (SO) palsy (ocular
results in the form of binocular single and distinct vision at torticollis) in which patient maintains binocular vision with
all points of time. The musculature of head and neck region the help of compensatory head posture. In case of RSO palsy
may further assist the oculomotor system to achieve the same (Fig. 3), the child will have chin depression, face turn to
goal. Abnormal head posture is only one of such adaptations left, and head tilt to left shoulder. The head posture ensures
to regain this remarkable feature of binocular single vision that the paretic muscle is always in the state of relaxation.
inherent in human visual system which helps us to achieve the Position of head is then so adjusted that the visual axes are
function of stereopsis. directed straightforwards. Thus, in case of RSO palsy, with
its main action as depression, chin depression develops and
Clinical Pearl its secondary action as intorsion, head tilt towards opposite
shoulder develops. Face turn towards left brings the eye
• Ocular motor system has no independent existence and in abduction, so that vertical movements can be executed
adapts itself exclusively in the service of sensory visual system. exclusively by vertical rectii. Causes of ocular head posture
are given in table 1.
CONFUSION, DIPLOPIA, AND SUPPRESSION It is important to distinguish, especially from pediatrician’s
point of view, between congenital and ocular torticollis
In the presence of manifest deviation of eyes, images of
all objects in binocular field of vision are shifted from
corresponding retinal elements. Thus, images of different
objects are formed on foveae of two eyes leading to a
phenomenon called “confusion”. At the same time, image
of identical object is formed on noncorresponding retinal
elements of two eyes leading to diplopia. To avoid them,
the growing visual system in children has two mechanisms
to develop, viz., “suppression” (more common) in which
poor quality image is ignored by the retinocerebral system
and ARC in which disparate retinal elements acquire the
function of corresponding retinal elements. Diplopia is the
most repugnant sensation and the oculomotor system makes
every effort to avoid this. In congenital and early childhood
extraocular muscle paralysis, suppression will generally ensue
if head posture fails to develop fusion.
Clinical Pearls
• Diplopia is the most repugnant sensation
• In childhood abnormalities, if head posture fails to develop
fusion, diplopia will invariably be eradicated by suppression or
anomalous retinal correspondence (ARC)
• Suppression, amblyopia, and ARC are general features of
concomitant squint. However, they can develop in congenital Fig. 3: A child with right superior oblique palsy showing marked
682 head tilt to left, mild face turn to left, and minimal chin depression.
or early childhood paralytic squint as well.
Courtesy: Dr Zia Chaudhury
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Table 1: Differential diagnosis of ocular head posture

Face turn • Sixth nerve palsy [the face is turned to the side
of the paralyzed eye to maintain binocular single
vision (Fig. 4)]
• Duane syndrome
• Congenital nystagmus (face turn may put the
eyes in a particular position which reduces the
nystagmus and increases the visual acuity)
Head tilt • Fourth nerve palsy or superior oblique muscle
weakness of whatever cause
• Inferior oblique palsy (the face is turned to the
uninvolved side with the head tilting to the
affected side and the chin is elevated. Uncommon
clinical case)
• Superior rectus palsy (uncommon case; the tilt can
be to either side)
• Inferior rectus palsy (uncommon case; the tilt can
be to either side)
• Brown’s syndrome (head tilt to the involved side,
face turn to the normal side and chin elevation)
• Dissociated vertical deviation (can be to either side)
Chin • A-pattern esotropia Fig. 4: Adult showing acquired left lateral palsy with face turn to left
elevation • V-pattern exotropia Courtesy: Dr Zia Chaudhury.
• Ptosis
• Blow-out fracture with entrapment of inferior rectus
• Brown’s syndrome (bilateral case) Ocular torticollis, caused by SO palsy, on the other hand
develops later; the head can be moved easily passively or by
Chin • V-pattern esotropia
depression • A-pattern exotropia voluntary effort of the patient and SCM muscle if soft like in
• Bilateral fourth nerve palsy any normal human being. However, if an effort is made to
correct the head posture, diplopia generally ensues. If eye
with paretic muscle is occluded, head will straighten by itself
Table 2: Differences between congenital and ocular torticollis unless some secondary skeletal changes have developed over
Feature Congenital torticollis Ocular torticollis
a period of time.
Age at onset <6 months >18 months

Incomitance in Concomitant Squint
Restriction of passive Present Absent
movements (A or V Phenomenon)
Hardening of Present Absent Vertical incomitance is not uncommon in horizontal
sternocleidomastoid concomitant deviations (eso- or exotropias). Here, strabismus
muscle is comitant in primary gaze, but becomes incomitant in up
Visual disturbances None Diplopia on or down gaze or both. They are called A or V patterns. The
straightening or characters of common errors are given in table 3.
tilting of head to In these cases, dysfunction of oblique muscles is the most
opposite side common clinical finding and treatment is based on clinical
Influence of No effect of occlusion None if normal findings.
occlusion eye occluded.
Head straightens
if eye with paretic Nystagmus
muscle occluded Nystagmus is a regular, rhythmic, to and fro movement of
unless secondary eyes. Two common types of nystagmus are pendular and
skeletal changes jerk nystagmus. Pendular is smooth sinusoidal oscillations
developed
Table 3: Characters of common errors
(Table 2). Former is caused by malformation of cervical
Pattern Deviation
vertebrae or fibrosis of SCM muscle, usually secondary to birth
trauma and later by congenital SO palsy. In case of congenital A - Exotropia Exodeviation more in downgaze, less in upgaze
torticollis, torticollis sets in within 6 months of age, passive V - Exotropia Exodeviation more in upgaze, less in downgaze
straightening of head is difficult, palpation may suggest A - Esotropia Esodeviation less in downgaze, more in upgaze
hardening of SCM muscle, no visual disturbances are present
and torticollis is not influenced by occlusion of either eye. V - Esotropia Esodeviation less in upgaze, more in downgaze 683
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(commonly due to sensory deprivation) whereas jerk abduction (Fig. 6A). Patient may adopt a head posture to
nystagmus has a slow and a fast component. Although fast center his/her gaze through the better seeing eye (Fig. 6B)
component is conventionally labeled as the direction of • Undercorrected glasses may result in head posture in
nystagmus, the fact is that the primary abnormality causes an effort to take advantage of higher effective power in
slow drift and fast component is the corrective movement. In peripheral part of the lens
case of jerk nystagmus, there may be a gaze, where it cannot • Ocular/systemic syndromes like Brown’s (SO tendon
be elicited. This is called the null zone. Cases of nystagmus that sheath) syndrome or Duane syndrome, Mobius syndrome,
have a null point may have a head posture which can have any progressive external ophthalmoplegia (alone or as part of
of the three component(s) of head posture (Fig. 2). Kearns-Sayre syndrome) may also lead to AHP
• Orthopedic and neurologic causes more than what has
Clinical Pearls already been mentioned are beyond the scope of this
• Head posture is present only in jerk nystagmus with null point chapter.
• The purpose of head posture is to bring null point in straight
gaze for clear vision HISTORY AND EXAMINATION
• It is the congenital motor nystagmus that responds best to
surgery. History starts with age of patient at time onset of head posture,
whether congenital or acquired. Sometimes, parents may
have noticed it much later than its actual appearance. This
The surgical correction mainly involves shifting of
can be confirmed by a careful scrutiny of family photographs.
null point to primary gaze with the hope that it will lead to
Associated visual disturbances, refractive errors, ocular
correction of head posture. Workup of a case of abnormal
motility disturbances, presence of diplopia at present or in
head posture is given in algorithm 1.
past, abnormal movements of eyeballs, problems of movement
of head and neck region are all very important to find out
Other Causes the cause and plan management. History of neurological
Some uncommon/atypical causes of AHP may also be seen in symptoms like headache, vomiting, convulsions, or of
clinical situations: infections like meningitis and encephalitis are also important
• Ptosis, especially if bilateral, may lead to chin elevation to in relevant cases.
minimize restriction of superior field of vision Assessment of head posture is the first step in any
• One eyed persons (Fig. 1) or those with homonymous ophthalmic examination and especially so in a squint clinic. It
hemianopia (Fig. 5) may assume a head posture to center is prudent to start this examination as soon as patient enters
their gaze to the available field examiners room and certainly before the child becomes
• Strabismus fixus is an extremely large esotropic deviation conscious of the fact that he is being examined. Examiner
of both eyes seen in patients with maximum contracture should not only look for components of head posture, but also
of medial rectus (MR) muscles secondary to replacement do a comprehensive eye examination. Visual acuity, refractive
by fibrous tissue. A rarer variety may have fibrous band status, presence of any amblyopia, squint, restriction of ocular
replacing lateral rectii leading to anchorage of both eyes in motility in any of the nine directions of gaze, difference in
Algorithm 1
Workup of a case with abnormal head posture
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A B
Fig. 5: A, 34-year-old male with sellar tumor and right lateral rectus (RLR) palsy and face turn to left. Cause of face turn is not RLR palsy as this
eye is blind but is hemianopic visual field defect of left eye; B, visual field of left eye showing temporal hemianopia.
A B
Fig. 6: A, A rare variety of strabismus fixus with both eyes anchored in abduction in a young lady; B, showing face turn
towards left to get best possible vision in the central field.
ocular deviation in different directions of gaze and while shoulders and observing on which side the vertical deviation
separately fixing each eye, presence of nystagmus, effect of increases. Patient maintains a head posture of head tilt with
occlusion of individual eye on the head posture need to be least disparity, the disparity increases if head is forced towards
assessed. Diagnosing horizontal muscle palsy is, generally, the shoulder on the side of the paretic SO (Bielschowsky sign).
not difficult. However, diagnosis of isolated cyclovertical Assessment for restriction of passive movements of neck and
muscle paresis, e.g., trochlear nerve paresis requires three- hardness in SCM muscle is very essential to exclude nonocular
step evaluation, viz., side of hyperopia, side of gaze in which causes of head posture (Algorithm 1). Forced duction test is 685
vertical deviation increases, and then tilting the head towards invaluable in cases of suspected restrictive problem. One may
ch-141.indd 685 11/22/2016 11:37:14 AM

refer to any standard book on squint for details of methods of disease and waiting for spontaneous recovery, recession of
examination. Examination of nervous system, especially of antagonist muscle or weakening of yoke muscle of paralyzed
cranial nerves, may be very informative in relevant cases. muscle may be done depending on presence or absence of
contraction of antagonist. In congenital third nerve palsy,
surgery is required for exotropia, hypotropia, and ptosis. Bell’s
INVESTIGATIONS
phenomenon should be evaluated as there is significant risk
Apart from specific ophthalmic investigations like Hess’s (or of exposure keratitis following surgery. Acquired third nerve
Lee’s) charting, imaging of brain using computed tomography palsy is in children, is generally because of trauma, infections,
(CT) or magnetic resonance imaging (MRI) scan may be tumors, aneurysm, or migraine. Treatment is of underlying
required, especially in acquired cases to find out the cause or to cause. Residual diplopia and/or ptosis may require surgical
plan the treatment. Certain electrophysiological investigations correction depending on individual situation as the palsy is
like electromyography and electronystagmography (Fig. 2) generally incomplete.
may be invaluable in the management of certain case, and also
from academic point of view. A and V Phenomenon
In cases with oblique over action, oblique muscles should be
MANAGEMENT weakened (inferior oblique for V patterns and SO for A patterns)
in addition to recession resection of horizontal rectii. However,
Management depends on age at presentation and cause. in the absence of this feature, 5–8 mm of vertical transposition
Among congenital conditions, although no treatment is of horizontal rectii combined with their recession-resection
warranted in certain cases, early treatment may be indicated may suffice. For the correction of A patterns, MR is shifted up
in others before permanent secondary skeletal changes get and LR is shifted down. The opposite is done for patients with
established. However, in acquired cases, generally, a 6-month V patterns.
waiting period is given for the system to heal by itself (Algorithm
1). However, nonsurgical treatment like prisms or occlusion Nystagmus
may be temporarily prescribed to give relief to the patient from Surgery for nystagmus is based on three principles, viz.,:
intractable diplopia. Indications of therapy are diplopia in 1. To shift null point to primary position (Fig. 2)
the practical field of fixation and inability to maintain fusion 2. To induce extra convergence innervations by weakening
without cosmetically acceptable head posture. medial recti
3. To reduce muscle force by weakening all rectii to dampen
Nonsurgical Treatment amplitude of nystagmus.
Correction of refractive error and amblyopia should be done
in all cases. Prisms (in small ocular deviations) and occlusion Other Causes
may be indicated to avoid diplopia during acute phase or Ptosis is generally corrected by resection of levator palpebrae
while waiting for surgery. Prisms are usually effective in superioris (LPS) muscle or by sling surgery. The choice of
correcting diplopia up to a deviation of 10 prism diopter. operation is generally dependent on amount of ptosis, LPS
Chemodenervation with botulinum toxin may be helpful action present, Bell’s phenomenon, and associated features.
in cases of acute horizontal muscle paralysis, in dissociated Causes of head posture other than these are treated by surgical/
vertical deviations, and as postsurgical adjunct. nonsurgical methods from case-to-case basis.
Surgical Treatment acknowledgement

The aim of treatment is to develop single binocular vision
or provide clear vision without the presence of AHP. Type The author would like to thank Dr Rohit Saxena, additional
of preferred surgical technique depends on the cause and professor at AIIMS and Dr Zia Chaudhury, professor at Lady
duration of problem. Hardinge Medical College, for providing me some photographs
and Dr Shashi Vashisht for her constant encouragement.
Paralytic Squint
In paralytic squint, general principle is to wait for 6 months Suggested readings
for natural recovery and then to weaken the antagonist and to 1. Bagolini B, Campos EC, Chiesi C. Plagiocephaly causing superior oblique deficiency
minimize innervations to the paretic muscle. Strengthening and ocular torticollis. A new clinical entity. Arch Ophthalmol.1982;100(7):1093-6.
operations for paretic muscle are less effective. In case of 2. Pavan-Lagston D. Manual of ocular diagnosis and therapy. 6th ed. Philadelphia:
paralysis of sixth nerve, surgery will generally consist of MR Lippincott Williams & Wilkins; 2008.
recession and lateral rectus (LR) resection or transposition of 3. Nucci P, Curiel B. Abnormal head posture due to ocular problems: a review. Curr
vertical rectii lateral along with weakening of MR. Congenital Pediatr Rev. 2009;5(2):105.
4. Nucci P, Kushner BJ, Serafino M, Orzalezi N. A multi-disciplinary study of the
superior rectus palsy with significant head posture should
ocular, orthopedic, and neurologic causes of abnormal head postures in children.
undergo surgery, as soon as diagnosis is confirmed, to prevent Am J Ophthalmol. 2005;140(1):65-8.
686 permanent torticollis, facial asymmetry, and scoliosis. For 5. Von Noorden GK. Binocular vision and ocular motility. 5th ed. St Louis: Mosby;
acquired fourth nerve paresis, after ruling out underlying 1996.
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Chapter 142
Pediatric Epiphora
Shashi Vashisht
INTRODUCTION
Ocular surface is covered by a thin tear film which provides
a smooth optical surface, keeps the ocular surface moist and
plays an important role in the nutrition and protection of
cornea. Overflow of tears leads to watering from the eyes.
Tear film consists of three layers:
1. Superficial lipid layer: derived from secretions of
Meibomian, Zeiss, and Moll glands
2. Middle aqueous layer: secreted by lacrimal and accessory
lacrimal glands
3. Deep mucus layer: secretions principally from conjunctival
goblet cells.
THE OUTFLOW PATHWAY FOR TEARS

Fig. 1: Tear production and outflow pathway (lacrimal pathway)
• Lacrimal puncta: a small oval opening near the inner
canthus on upper and lower lids
• Lacrimal canaliculi: two superior and inferior lacrimal
structure from the primitive nasal cord. This solid cord starts
canaliculi extending from superior and inferior lacrimal
canalizing around 3 months of intrauterine life to form the
puncta, respectively, to lacrimal sac. They are directed 2
mm vertically and 8 mm horizontally. Before entering into NLD. It is generally canalized by birth or few weeks before.
the lacrimal sac, they join and form a common canaliculus However, in some cases, ectodermal debris or a membrane
in majority of cases may remain at the nasal end of the NLD resulting in congenital
• Lacrimal sac: it is located in lacrimal fossa in anterior part NLD block. Tear formation generally starts after second week
of medial orbital wall of birth (Fig. 1).
• Nasolacrimal duct (NLD): it is a continuation of the
lacrimal sac. It is about 18 mm long, directed downwards, Causes of Watering of Eyes in
backwards, and laterally and opens in the inferior meatus Relation to Lacrimal System
of nose.
Hyperlacrimation
DEVELOPMENT OF
There is increased secretion of tears due to any of the following
LACRIMAL DRAINAGE SYSTEM
causes:
The lacrimal drainage system is ectodermal in origin. The • Primary: overproduction from lacrimal gland, which is rare
lacrimal sac develops as a solid cord of ectoderm which sends • Reflex: secondary to ocular inflammation or ocular surface
two columns to the lids which form the canaliculi. The solid disease (cornea and conjunctiva) due to stimulation of
cord descends down to form the NLD. This is met by a similar sensory branches of fifth nerve.
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Epiphora Ophthalmia Neonatorum

This is a condition that constitutes inadequate drainage of Ophthalmia neonatorum (ON) is generally seen in the first
tears due to any of the following reasons: week of birth. Any infection in the first month of a baby’s life
• Physiological: lacrimal pump failure secondarily to lower can be classified as ON. There is copious discharge, swollen
lid laxity or weakness of orbicularis muscle lids, and watering without regurgitation. Conjunctival swab
• Mechanical: obstruction in outflow pathway involving any should be sent for Gram’s stain and culture (Table 2).
of its components, i.e., punctum, canaliculus, lacrimal
sac, or NLD. Treatment is discussed later. Causes and Clinical Pearl
management of epiphora in infants and children are
enlisted in table 1. • Watering and discharge from eyes in first week after birth,
diagnosis should be ophthalmia neonatorum.
Infective Causes
Depending on the causative organism suspected anti
microbial/antiviral eye drops/ointment started under Allergic Conjunctivitis
ophthalmic supervision.
Vernal Keratoconjunctivitis
Vernal keratoconjunctivitis (VKC) or spring catarrh is seen in
children of 4–20 years of age. This condition is more common
Table 1: Causes and management of epiphora in infants and
in boys than girls. It is an immunoglobulin E-mediated
children
hypersensitivity reaction to exogenous allergens. Recurrent
Causes Management bilateral redness, itching, photophobia, and watering occur
Lacrimal drainage related with onset of summer season. The term “spring catarrh” is a
• Agenesis or stenosis of • Surgical intervention
punctum • Conjunctivodacryo Table 2: Ophthalmia neonatorum
• Canalicular obstruction cystorhinostomy
Etiology Causative factor Incubation Treatment
• Mucocele • Dacryocystorhinostomy period
• Encysted mucocele (DCR)
Gonococcal Neisseria 2–4 days • Erythromycin
• Nasolacrimal duct obstruction • Dacryocystectomy
gonorrhoeae eye ointment
• Discussed later QID
Lid related • Bacitracin eye
• Entropion, ectropion, coloboma • Surgical intervention ointment QID
Infections • Penicillin
• Conjunctivitis (bacterial, viral, • Treat with appropriate 10,000 IU/mL
chlamydial), ophthalmia antibiotics or antivirals eye drops
neonatorum • Systemic
Allergic therapy
• Vernal keratoconjunctivitis • Medical management Bacterial • Staphylococcus 2–5 days • Antibiotic
Refractive errors • Good cycloplegic (other than aureus eye drops
refraction gonococci) • Streptococcus (depending
haemolyticus on
Corneal problems
• Streptococcus susceptibility)
• Abrasions, keratitis • Medical/surgical
pneumoniae
management
• Pseudomonas
Foreign body • Removal and medical
aeruginosa
management
Congenital or juvenile glaucoma Neonatal • Chlamydia 5–14 days • Tetracycline
inclusion trachomatis 1% eye
• Child presents with • Ophthalmic referral
conjunctivitis serotype D ointment QID
watering, photophobia, and
to K • Erythromycin
blepharospasm
eye ointment
Other causes
0.5% QID
• Uveitis, episcleritis, scleritis, • Ophthalmic referral; treat • Systemic
injuries. Some eye drops, like the cause treatment
pilocarpine, echothiophate,
and epinephrine, can cause Herpes Herpes simplex 5–7 days Topical antiviral
watering simplex II virus
688
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Chapter 142: Pediatric Epiphora
misnomer. Condition subsides in cooler months. About 95% • It may be constant or intermittent. Severity of signs and
of cases undergo remission in late teens. Pharmacological symptoms can vary with upper respiratory tract infection
treatment constitutes following: (URI), exposure to cold and wind. Pressure over the sac
• Mast cell stabilizers, e.g., sodium cromoglycate 2% eye may result in positive regurgitation from the puncta.
drops Gradually, secretions start stagnating in the sac and can
• Topical antihistaminics, e.g., olopatadine 0.1% eye drops give rise to recurrent infection. Chronic infection can lead
• Topical steroids eye drops give a quick relief, but their use to dacryocystitis and fistula formation
should be minimized and monitored as indiscriminate use • Congenital block can involve any other part of the drainage
of steroids can lead to steroid-induced glaucoma system.
• Topical cyclosporine 1% eye drop.
Clinical Pearl
Clinical Pearl • Blocked nasolacrimal duct is the most common cause of
• In a child complaining of recurrent redness, itching, and watering in infants.
watering in both the eyes with onset of summer season, most
common cause is vernal keratoconjunctivitis.
Tests to Check for Nasolacrimal Duct Block
Sac Syringing
WORKUP
It is done to know patency of lacrimal drainage system. Under
local/limited general anesthesia lower punctum is dilated with
History a punctum dilator. A blunt tipped lacrimal cannula on a 2 mL
Complete history should be taken including time of onset and syringe filled with saline is inserted into lower punctum and
duration of watering, unilateral/bilateral, any contributory canaliculus and the plunger is pushed slowly. Management is
cause, associated symptoms, seasonal variation, and previous done as per observations after syringing.
treatment taken.
Jones Dye Test
Clinical Examination with Torch light • Primary test: it is a test for lacrimal outflow function
• Secondary test: it is done in cases of negative primary test.
• Examine the lacrimal sac area for fullness, redness, or
fistula Fluorescein Dye Disappearance Test
• Regurgitation test: reflux of mucoid or mucopurulent
material from the punctum on pressure over the lacrimal Fluorescein 2% drops are instilled in both conjunctival fornices.
sac area suggests blocked NLD or mucocele Normally, no dye remains after 3 minutes. Prolonged retention
• Inspect lacrimal puncta for eversion or stenosis is inferred as inadequate lacrimal drainage.
• Examine eyelids for any skin lesions, entropion, ectropion, There are multiple other tests, like contrast dacryo
trichiasis, stye, blepharitis cystography, nuclear lacrimal scintigraphy, Schirmer’s test,
• Examination of the conjunctiva for congestion, discharge, tests to check tear film and ocular surface but they are done at
foreign body, tear, cyst, discoloration, chemosis, follicles, an ophthalmic set-up.
papillae (VKC), concretions, pterygium, pinguecula,
tumors, or any other abnormality Clinical Pearl
• Further examination should be done by an ophthalmologist. • When cause of watering is in doubt, ophthalmology reference
is mandatory.
Features of Congenital Obstruction of
Nasolacrimal Duct
• The lacrimal gland starts secreting around 2–3 weeks after Management of Congenital Blockage
birth. Therefore, effect of NLD block is not seen at birth. This
is seen in around 4–8% of newborns. It is more common in
of Nasolacrimal Duct
premature children. It may be uni- or bilateral and has no Sac massage is the mainstay, as spontaneous resolution
sex predilection. A membranous block at the lower end of occurs in 90% of cases within first year. Management of
NLD (valve of Hasner) is common, as this portion of NLD congenital blockage of nasolacrimal duct has been outlined
is last to canalize. Spontaneous resolution usually occurs in in algorithm 1.
90% of cases in first year. Other causes could be stenosis of • Sac massage: the child’s head should be held firmly. Mother
opening of NLD or a hypertrophied inferior nasal turbinate is instructed to compress the sac area by applying firm,
• Watering with or without mucoid/mucopurulent discharge gentle pressure with the pulp of index finger such that finger
and/or matting of lashes is seen blocks the common canalicular opening. This finger is then
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Algorithm 1 surgically creating anastomosis between the sac and

Management of congenital nasolacrimal duct block nasal mucosa. This procedure can be performed by
external approach or nasal approach.
CONCLUSION
Watering from eyes in childhood is a fairly common complaint.
The cause needs to be diagnosed before starting treatment.
Key points
))
Proper history taking and examination is important to come
to a diagnosis. It nasolacrimal duct obstruction is the most
common cause of epiphora in infants. In most of the cases, it
can be treated conservatively. It is imperative that the proper
procedure of sac massage be explained to the attendant and
reassurance given. When in doubt, ophthalmic referral must
be done.
SUGGESTED READINGS
1. Abdu L, Salisu AD. Pattern and outcome of surgical management of nasolacrimal
duct obstruction in children: A five-year review. Ann Afr Med. 2014;13(3):130-3.
2. Balasubramaniam SM, Kumar DS, Kumaran SE, Ramani KK. Factors affecting
eye care-seeking behavior of parents for their children. Optom Vis Sci.
firmly moved down the side of nose. Procedure is repeated 2013;90(10):1138-42.
3–4 times a day (4–5 times every sitting) and it is followed 3. Bremond-Gignac D, Chiambaretta F, Milazzo S. A European perspective on
by instillation of antibiotic (tobramycin or ciprofloxacin topical ophthalmic antibiotics: current and evolving options. Ophthalmol Eye Dis.
eye drops). By doing this massage, hydrostatic pressure in 2011;3:29-43.
the lacrimal sac increases and it may rupture membranous 4. Bremond-Gignac D, Nezzar H, Bianchi PE, Messaoud R, Lazreg S, Voinea L, et al.
Efficacy and safety of azithromycin 1.5% eye drops in paediatric population with
obstructions and/or displace the debris
purulent bacterial conjunctivitis. Br J Ophthalmol. 2014;98(6):739-45.
• Probing: if sac massage fails, probing and syringing is done
5. Chirinos-Saldaña P, Bautista de Lucio VM, Hernandez-Camarena JC, Navas A,
under general anesthesia. Age at which massage should Ramirez-Miranda A, Vizuet-Garcia L, et al. Clinical and microbiological profile of
be discontinued and probing done is controversial. Early infectious keratitis in children. BMC Ophthalmol. 2013;13:54.
intervention at 6–8 months of age has advantage of high 6. Davey J, Billson FA. Watering eyes: an important sign of congenital glaucoma.
success rate and prevents long-standing infections. Late Med J Aust. 1974;2(14):531-2.
intervention at about 12 months has an advantage as 7. Kumar R, Mehra M, Dabas P, Kamlesh, Raha R. A study of ocular infections
many cases show spontaneous resolution by a year. This amongst primary school children in Delhi. J Commun Dis. 2004;36(2):121-6.
8. Nemet AY, Fung A, Martin PA, Benger R, Kourt G, Danks JJ, et al. Lacrimal
obviates the need of surgical intervention. Probing should
drainage obstruction and dacryocystorhinostomy in children. Eye (Lond).
be avoided if the child has URI. Sac massage should be 2008;22(7):918‑24.
continued after probing. 9. Saboo US, Jain M, Reddy JC, Sangwan VS. Demographic and clinical profile
In case of failure, probing can be repeated after 3–4 weeks. of vernal keratoconjunctivitis at a tertiary eye care center in India. Indian J
If need be, inferior turbinate infracture can be done at the same Ophthalmol. 2013;61(9):486-9.
time. 10. Sielicka D, Mrugacz M, Bakunowicz-Lazarczyka A. [Nasolacrimal duct disorders
• In case of failed probing: in children. Part I. Anatomy, physiology and clinical signs]. Klin Oczna.
{{ Intubation with silicone tube can be done
2010;112(10-12):342-5.
11. Stepankova J, Odehnal M, Malec J, Dotrelova D. [Corneal foreign bodies in
{{ Balloon dacryoplasty can be done
children]. Cesk Slov Oftalmol. 2012;68(4):142-5.
{{ Dacryocystorhinostomy (DCR): if child presents late,
12. Vichyanond P, Pacharn P, Pleyer U, Leonardi A. Vernal keratoconjunctivitis: a
after 3 years of age or if repeated probing fails, then severe allergic eye disease with remodeling changes. Pediatr Allergy Immunol.
DCR is done. In this procedure, NLD is bypassed by 2014;25(4):314-22.
690
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Chapter 143
Deviation of Eyes
Taru Dewan, Harshika Chawla
INTRODUCTION {{ Hypo—the term for an eye whose gaze is directed lower
• Torsional strabismus: occurs when the eyes rotate around

Early and accurate detection of ocular motility disorders in the anterior-posterior axis to become misaligned, viz.,
children can present a challenge for family physicians. Children incyclotorsion and excyclotorsion.
may not be willing to participate in the screening process, • Combined: can be horizontal, vertical, torsional, or any
and interesting fixation devices are often not available in the combination thereof.
office. In addition, some of the diagnoses are complex. The
involvement of pediatric ophthalmologists with specialized Based on Latency
training, expertise, and examination equipment is, therefore,
often required. Despite these difficulties, most significant eye • Latent squint (heterophoria): it is present only when
problems in children can be identified with effective screening binocularity is disrupted, e.g., when covering an eye.
techniques. Such a patient has normal fusion mechanisms. Latent
strabismus is precipitated in conditions of ocular fatigue,
general debility, etc.
STRABISMUS
Strabismus may result from a variety of ocular or systemic
conditions. On the other hand, it can lead to severe visually
disabling consequences (amblyopia, abnormal head posture,
loss of binocularity, etc.).
The term “strabismus” is derived from the Greek word
strabismos, to squint/to look obliquely/askance. Strabismus
means ocular misalignment. The image is therefore not in
corresponding areas of both eyes, which may result in eventual
amblyopia in childhood or diplopia in adulthood.
A
CLASSIFICATION
There are several classifications that are used for strabismus.
Based on Direction
• Horizontal deviations are classified into two varieties:
{{ Eso—describes inward (Fig. 1A)
{{ Exo—describes outward misalignment (Fig. 1B)
• Vertical deviations can be: B

{{ Hyper—the term for an eye whose gaze is directed Fig. 1: Horizontal deviations in strabismus. A, Esodeviation.
higher than the fellow eye B, exodeviation
ch-143.indd 691 11/22/2016 11:40:58 AM

• Manifest squint (heterotropia): it is present even when

patient views binocularly, i.e., even without occluding an Clinical Pearl
eye. Such patients cannot align gaze to achieve fusion and • The type of squint and the response to treatment in other
children with manifest squint usually develop amblyopia family members may be similar.
and adults present with diplopia.
Based on Onset
CLINICAL FEATURES
• Infantile: deviation documented at birth or before 6 months
of age, presumably related to a defect present at birth • Patient may present with any of the following features:
{{ Parental concern due to the presence of a manifest
• Acquired: a deviation with later onset, after a period of
apparently normal visual development. squint
{{ Asthenopia
{{ Detection at a preschool screening clinic

Based on Constancy
{{ Compensatory abnormal head posture
• Constant: when one eye consistently deviates • Special points in history:
• Intermittent: when the deviation is not present all the time {{ Age of onset of deviation
and may be noticeable for limited time during the day. {{ Whether it was preceded by trauma or illness?
{{ Constant or intermittent?
Based on Comitance {{ Unilateral or alternating?
{{ Does the child close one eye?

• Comitant strabismus: the size of deviation does not vary
{{ History of double vision or abnormal tilting of head?
significantly with the gaze or eye used for fixating
{{ Family history of strabismus or amblyopia, the type of
• Noncomitant (incomitant) strabismus: the deviation varies
in size significantly with the gaze or eye used for fixating. squint and the response to treatment
{{ Prematurity, birth weight; neonatal history
{{ Development milestones
Based on Etiology
{{ Treatment history such as amblyopia treatment, squint
• Paretic strabismus: due to paralysis of one or several surgery, spectacle corrections.
extraocular muscles
• Non-paretic strabismus: due to causes other than paralysis Clinical Pearl
of extraocular muscles.
• Increased prevalence of strabismus has been reported in
Clinical Pearl association with assisted delivery (forceps or cesarean section),
low-birth-weight (including premature infants) and maternal
• Pseudostrabismus is the false appearance of strabismus. It
drug abuse.
generally occurs in infants and toddlers whose bridge of the
nose is wide and flat, causing the appearance of esotropia. With
age, the bridge of the child’s nose narrows and the folds in the
corner of the eyes become less prominent. Pseudoexotropia EXAMINATION
occurs with a wide interpupillary distance or a positive angle
• Visual acuity: special tests can be used depending on the
kappa.
age of the child to determine visual acuity for near and
distance (Table 1)
• Inspection: make a note of:
ETIOLOGY {{ Large angle squint
{{ Facial asymmetry/presence of epicanthal folds/ptosis

Etiology of strabismus is generally presumptive, especially
in congenital and nonparalytic cases. Development of or proptosis to rule out pseudostrabismus
{{ Abnormal head posture
nonparalytic squint is a result of factors which affect
development of normal binocularity. Binocular vision and Table 1: Visual acuity
coordination of ocular movements is an acquired process
which completely develops by the age of 5–6 years. Infants Preschool children School-aged children
Factors, which hinder normal binocular development, Fixation behavior Marble game test Snellen’s test chart
can be: tests
• Sensory: uncorrected refractive error, corneal opacity or Preferential Hand figure test Landolt’s broken C chart
cataract, optic atrophy, macular disorder, etc. looking test
• Motor: abnormal extraocular muscles or fascia, abnormal
Optokinetic Sheridan-Gardiner E chart
accommodation or convergence
nystagmus HOTV test
• Central: abnormal cortical control of ocular movements.
Heredity does play a major role but a distinct genetic Visually evoked Pictorial vision tests –
692 pattern for strabismus has not been identified. potential
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Chapter 143: Deviation of Eyes
• Pupillary reactions: light reflex may be abnormal in the other eye. Alternate cover test is done till there is
diseases of optic nerve or retina no recovery movement of the deviating eye under the
• Hirschberg’s reflex test: it gives a rough estimate on the prism bar
degree of manifest squint. Shine a pen torch into the {{ Krimsky prism bar reflex test (PBRT): in cases with
patient’s eyes at an arm’s length away and ask them to look poor vision in one eye, when patient cannot focus on
at the light (babies will tend to look towards it). Observe fixation target, use of PBRT comes into play.
where the reflection of the pen torch lies with respect to
the cornea. Normally, it should be central bilaterally. One
MANAGEMENT
millimeter of decentration of reflex corresponds to about
7° of deviation. When the reflection is at the margin of the • Referral: a neonate with a constant squint or with a squint
pupil, there is approximately 15° deviation, and, if it lies at that is worsening should be referred to an ophthalmologist.
the edge of the cornea, there is approximately 45° deviation The earlier the referral, the better chance the child has of
• Perform the cover/uncover test; if this appears to be avoiding the possibility of amblyopia
normal, try the alternate cover test: • Assessment: there will be both an orthoptic assessment
{{ Cover/uncover test: it confirms the presence of (to assess the visual acuity and ascertain the presence and
heterophoria. Patient is asked to focus on a target nature of the squint) as well as a medical review to ensure
held in front of him (at 33 cm). One eye is completely that the eye is otherwise healthy
occluded for several seconds and the uncovered eye is • Detailed neurological assessment may be required only in
observed for movement as it focuses on the object. This cases of paretic squints
eye is then covered and the other eye is observed for • General approaches (Algorithms 2 and 3):
movement. Movement of the eye outwards confirms {{ Treatment is guided by the exact nature of the squint
that there is an esodeviation (i.e., the eye was turned and by the patient’s age
inwards initially) and vice versa for exodeviation. The {{ Correction of refractive errors will be the first step. In
test is repeated for objects at 6 m the subset of accommodative esotropia, appropriate

{{ Alternate cover test: it differentiates comitant from refractive correction might be the only thing required.
noncomitant variety and it also tells us about the The true amount of surgically correctable deviation is
fixation behavior. The occluder is rapidly switched assessed only after refractive correction
from one eye to the other. Observing the eye movement {{ Any concurrent amblyopia will need treating too
as the occluder is removed, depending on whether it {{ Practical considerations include using plastic instead
moves inwards (i.e., there is an exophoria and the eye of glass lenses for spectacles made for children and
has to move in to see again) or outwards (revealing an ensuring that the lenses are large enough to prevent the
esophoria) confirms the type of strabismus child from looking over them
{{ Prism bar cover test (Algorithm 1): it is the most popular {{ Frequent refractions under full cycloplegia may be
and informative method to estimate the amount of required at short time intervals
squint objectively. Prisms of increasing strength with {{ Some patients are treated with prisms (placed
apex towards the direction of deviation are placed on spectacle lenses), miotics or other methods of
over one eye and patient is asked to fixate a target with nonsurgical management
{{ Most patients may require surgical alignment which
may be done using muscle recession (it is moved

backwards on the globe and so its action is weakened)
Algorithm 1
and/or antagonistic muscle resection (a segment
Prism bar cover test of muscle is removed, so strengthening its action).
Sometimes, it takes more than one procedure to get the
satisfactory result.
Clinical Pearl
• Infantile esotropia is best managed with early surgical
intervention to optimize outcome. There is evidence that early
surgery is associated with better binocular outcome.
PROGNOSIS
This depends on the nature and degree of the squint and level
of sensory development. Generally, early intervention should
produce good alignment and limit any amblyopia but perfect
stereopsis is rarely achieved. 693
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Algorithm 2
Algorithmic approach to esodeviation
Algorithm 3
Algorithmic approach to exodeviations
694
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Chapter 143: Deviation of Eyes
Key points SUGGESTED READINGS

1. American Academy of Ophthalmology. 2013-2014 Basic and Clinical Science
))
A small degree of heterophoria occurs in most normal subjects Course, Section 6: Pediatric Ophthalmology and Strabismus. 2013.
and must be considered physiologic 2. Khurana AK. Theory and Practice of Squint and Orthoptics, 2nd ed. New Delhi,
))
Approximately 50% of all childhood esotropias are either India: CBS Publishers and Distributors; 2013.
fully or partially accommodative. Cycloplegic refraction is 3. Maguire JI, Murchison AP, Jaeger EA (Eds). Wills Eye Institute 5-Minute
indispensable for the same Ophthalmology Consult. Philadelphia, PA, USA: Wolters Kluwer (India); 2012.
))
Unlike exodeviations, which are frequently intermittent or 4. von Noorden GK, Helveston EM. Strabismus: A Decision Making Approach. St.
latent, most esodeviations are manifest Luis, MO, USA: Mosby-Year Book; 1994.
))
A constant exotropia is clinically significant regardless of the 5. von Noorden GK. Binocular Vision and Ocular Motility: Theory and Management
of Strabismus, 6th ed. St. Luis, MO, USA: Mosby-Year Book; 2002.
angle of deviation or the cause
))
An anomalous head posture should raise concern because it
may cause neck strain; if left untreated, secondary scoliosis,
contracture of the neck muscles and facial asymmetry may
occur.
695
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Chapter 144
Decreased Vision in Children
Shikha Jain
INTRODUCTION Table 1: Common causes of decreased or blurred vision in

children
Decreased vision in children should be a cause of concern for
all ophthalmologists, as well as nonophthalmologists; because <2 years >2 years
if not corrected appropriately in time, it can cause amblyopia • Cataract • Refractive errors
leading to permanent vision loss. • Congenital glaucoma • Trauma
• Strabismus • Trachoma
• Corneal opacity/corneal ulcer • Hyphema/hypopyon
NORMAL VISUAL DEVELOPMENT
• Orbital cellulitis • Iridocyclitis
Visual development is a highly complex maturation process. • Retinoblastoma
Visual system is immature at birth. Myelination of optic nerve, • Xerophthalmia
development of visual cortex, and growth of lateral geniculate
body occur over the first 2 years of life.
Visual Milestones Approach to an Infant with Decreased Vision

Pupillary light reflex is usually present after 31 weeks of History
gestation but it can be difficult to evaluate due to miosis in A careful history is essential. Antenatal history should include
newborn. A blink reflex to light is usually present several days maternal infection, radiation, drugs, or any history of trauma.
after birth. At 6 weeks of age, baby should be able to make Perinatal history should include prematurity, birth weight,
and maintain eye contact and react with facial expressions. At intrauterine growth retardation, fetal distress, meconium
2–3 months of age, a child is usually interested in bright lights staining, forceps delivery, and any history of supplemental
although premature infants may reach these landmarks later. oxygen therapy in immediate postpartum period
Disconjugate eye movements may be noted initially but should
not persist beyond 4 months. Examination
For a pediatrician, a thorough torch light examination can
Signs of Poor Visual Development yield rewarding results. Following points should be carefully
Some of the findings which should point to the examining documented:
pediatrician for a need for detailed examination and referral to • Ptosis: normally the upper lid covers one-sixth of the cornea
an ophthalmologist are: and the lower lid rests at the inferior margin of cornea. Any
• Wandering eye movements dropping of lids more than this can be classified as ptosis.
• No response to familiar faces and objects In severe ptosis, the lower margin of the lid may cover the
• Nystagmus pupil resulting in decreased vision
• Staring at bright light and forceful rubbing of eyes in a • Visual fixation of the child should be noted. This is done
visually disinterested infant (oculodigital reflex). by shining a torch light and noting the corneal reflex. The
The common causes of decreased or blurred vision in reflex should be in the center of the pupil and the child
children are given in table 1. should follow the light as it is moved to and fro
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Chapter 144: Decreased Vision in Children
Algorithm 1
Decreased vision in children
• Ocular alignment, motility, and the presence of nystagmus ASSESSMENT OF VISUAL ACUITY
or roving eye movements are important to be documented.
Monocular cover-uncover test is the most important test Infants
for detecting the presence of manifest strabismus. As one In infants it can be assessed by various methods:
eye is covered, the examiner watches for any movement • Fixation behavior: It has three components—central,
in opposite noncovered eye, such movement indicates the steady, and maintained (CSM) fixation.
presence of a tropia. Movement of covered eye in opposite {{ C: after covering one eye of the patient corneal light
direction as the cover is removed indicates a phoria that reflex is noted as the patient fixates the examiner’s light.
becomes manifest when binocularity is interrupted The light reflex should be near the center of cornea
• Cornea: any obvious corneal haze or opacity should be {{ S: steadiness of fixation as the light is held motionless
documented. It can be an indicator of glaucoma, Peters and then moved slowly
anomaly, sclerocornea, and mucopolysaccharide storage {{ M: ability to maintain alignment with both eyes as the
disorders among other causes other eye is uncovered
• Pupil: it is normally grayish black in color. White reflex of • Optokinetic nystagmus: the patient follows a moving
the pupil is known as leukocoria. object, which then moves out of the field of vision at which
Causes of leukocoria are: point the eyes move back to the original position.The reflex
• Cataract develops at about 6 months of age
• Retinoblastoma • Preferential looking: the child is presented with two
• Retinopathy of prematurity stimulus fields, one with alternating stripes and the
• Chorioretinal colobomas other with a homogeneous gray area of the same average
• Uveitis luminance as the striped field. It is based on the concept
• Toxocariasis that the child will prefer to look at the more interesting
• Tumors, e.g., hamartomas, choroidal hemangiomas. Size stripes if he/she can detect them
of the normal pupil is 3–4 cm. A dilated or a miosed pupil • Visual evoked potential: it measures acuity by assessing
may indicate some pathology, e.g., optic nerve lesion may the response of the brain to alternating black and whites
have a dilated pupil while Horner’s syndrome and some stripes or checks. Three small electrodes are placed on the
poisoning present with miosed pupil child’s head which are connected to a computer. When
• Pupillary reflex: a note should be made of the equality and the child looks at the stripes, the signal is picked up by the
briskness of pupillary responses. electrodes. 697
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Toddlers
Allen’s picture cards are used which consist of familiar objects,
e.g., cake, car, horse, duck, etc. (Fig. 1).
Preschoolers
Matching cards are used, e.g., HOTV cards, where the child has
to pick a matching card to that shown from a group of cards
(Fig. 2). Other useful tests include Landolt Rings (C) test or
Tumbling “E” test (Fig. 3).
School-aged Children
In school-aged children, Snellen’s visual acuity is usually done
(Fig. 4).
Fig. 4: Snellen’s chart
Clinical Pearl
• Use of pinhole helps to give us an estimate of best corrected
visual acuity though it can be cumbersome in children.
CONCLUSION
In conclusion, it can be said that various features picked up on
a simple torch light examination when taken in conjunction
Fig. 1: Allen picture cards
with the presenting symptoms give a fair idea of the need for
an appropriate and timely ophthalmological reference.
Key points
))
Nystagmus is an indicator of decreased vision and is not
present at birth but usually appears around 2–3 months of
age. It implies presence of at least some visual function. On
the contrary, roving eye movements suggest total or near
total blindness
))
In infants exotropia is more common as a form of abnormal
binocular alignment whereas after 1 year of age esotropia
becomes more common
))
Both direct and consensual pupillary responses are important.
If direct response is defective, it indicates lesion in optic nerve
while consensual indicates the motor pathway (oculomotor
Fig. 2: HOTV cards nerve) is defective
))
Pupillary response is normal in cortical visual impairment.
SUGGESTED READINGS
1. American Academy of Ophthalmology. Pediatric Ophthalmology and Strabismus:
Basic and Clinical Science Course. Section 6. 2007-2008.
2. Nelson LB, Olitsky SE, Harley RD (Eds). Harley’s Pediatric Ophthalmology, 5th ed.
Philadelphia, PA, USA: Lippincott Williams & Wilkins; 2005.
3. Taylor D. Pediatric Ophthalmology, 2nd ed. Cambridge, MA, USA: Blackwell
Science; 1997.
698 4. Atkinson J. Human visual development over the first 6 months of life. A review
Fig. 3: Tumbling E’s and Landolt C’s and a hypothesis. Hum Neurobiol. 1984;3(2):61-74.
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Section 18: Ear, Nose, and Throat
Chapter 145
Hearing Screening and
Management in Newborn
Atul Ahuja
Introduction Box 1: The high risk register

The importance of hearing screening in the newborn cannot List of situations where a hearing impairment can be expected:
be overemphasized. Though it is one of the most common • Family history of permanent childhood sensorineural hearing
congenital anomalies it is not obvious to the uninitiated till loss
very late (Table 1). • In utero infection such as cytomegalovirus, rubella toxoplasmosis
It is therefore surprising that the newborn screening or herpes
programs of most hospitals screen for many of the less frequent • Craniofacial anomalies, including those with morphological
conditions while omitting the newborn hearing screening. abnormalities of the pinna and ear canal
One of the reasons cited is that for a newborn to be • Neonatal indicators, specifically hyperbilirubinemia at a serum
level requiring exchange transfusion, persistent pulmonary
screened the presence of risk factors is a must. For this an High
hypertension of the newborn (PPHN) associated with mechanical
Risk Register (HRR) was used (Box 1).
ventilation, and conditions requiring the use of extracorporeal
membrane oxygenation (ECMO)
Clinical Pearl • Postnatal infections associated with sensorineural hearing loss,
including bacterial meningitis
• Almost 50% children born with hearing impairment have no • Stigmata or other findings associated with a syndrome known to
known risk factors include a sensorineural or conductive hearing loss or eustachian
• Therefore high risk register is not good enough. tube dysfunction
• Syndromes associated with progressive hearing loss such as
neurofibromatosis, osteopetrosis, and Usher syndrome
IMPORTANCE OF SCREENING THE NEWBORN • Neurodegenerative disorders, such as Hunter syndrome, or
sensory motor neuropathies, such as Charcot-Marie-Tooth
Unlike many other congenital deformities the consequences of syndrome
a hearing impairment keep worsening as the child grows older. • Parental or caregiver concern regarding hearing, speech,
Unfortunately hearing loss is not detected early as it is invisible language, and/or developmental delay
and no antenatal predictive tests. • Head trauma
• Recurrent or persistent otitis media with effusion lasting for at
Table 1: comparison of the incidence of common congenital least 3 months
anomalies
Disorder Rate per 100,000
Adrenal hyperplasia 2
Galactosemia 2 The development of speech, social development and
Phenylketonuria 3 emotional bonding of a child are dependent on normal.
During the first few months the child’s brain grows
Sickle cell disease 47
tremendously. During this period the areas of brain
Hypothyroidism 28
responsible for hearing if not stimulated consistently by sound
Down’s syndrome 100–125
are reallocated other functions (encroachment), pathways fail
Hearing impairment 200–400 to develop and the ganglion cell population decreases.
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Once this critical time period elapses even proper Automated Otoacoustic Emission (Kemp, 1978)
amplification will not help this child.
Tests the integrity of the cochlea:
It is therefore important to detect hearing loss early. Studies
A small soft tipped earpiece (with and integrated mike and
have revealed that early intervention (before 6 months of age)
speaker) is placed in the outer part of the baby’s ear; this sends
allows infants to develop normal speech and language at par
very soft clicking sounds down the ear.
with his normal hearing peers. Even children receiving help
This sound is transmitted to the tympanic membrane, the
after 7 months of age lag behind those receiving amplification
ossicles and eventually the cochlea. Within the cochlea the
before 6 months of age.
sound is picked up by the outer hair cells which start vibrating,
Traditional techniques detect hearing impairment at an
moving tectorial membrane. This in turn stimulates inner hair
average age of 2.5 years. Although children who had severe-to-
cells.
profound hearing loss or multiple disabilities were identified
The vibration of outer hair cells transfers energy back to
at or before age 2.5 years, children with mild-to-moderate
endolymph and perilymph. These vibrations are transmitted
hearing loss were often not identified until school age (i.e., 4
back along the same path through which they were conducted.
years). Studies have indicated that, as a result of the universal
These are then picked up as clicks by a microphone which
newborn hearing screening program in various countries, the
is integrated into the same earpiece.
mean age of diagnosis was 3.9 months, with a mean age of
Automated oto-acoustic emissions are fast, efficient and
intervention of 6.1 months.
objective screening test of peripheral auditory sensitivity
Another common myth amongst clinicians is that simply
(preneural cochlear function). Overcoming major hurdles in
clapping next to the infant is enough to assess the hearing.
neonatal testing.
There are major pitfalls to this technique:
However, the effectiveness of the test is reduced by
• Children can compensate for hearing loss and clapping
contamination with low-frequency ambient noise in a busy
may create a slight breeze to which the baby may react. The
nursery, vernix in the ear canal, or any middle ear pathology.
child may even react to parental expressions reactions or
Automated oto-acoustic emissions alone however may
even shadows
not be a sufficient screening tool in infants who are at risk for
• Even if this were to elicit a startle response, it does not
neural hearing loss (e.g., auditory neuropathy/dyssynchrony)
properly assess the babies hearing. As mentioned before
as they test only the cochlea, not the nerve (Fig. 1).
mild to moderate hearing loss can also be damaging to the
speech and language development of the child.
Automated Auditory Brainstem Responses
SCREENING TECHNIQUES Automated auditory brainstem response (AABR) is a rapid
electrophysiologic test that is used to assess auditory function
from the eighth nerve through the auditory brainstem. This
Clinical Pearl test was developed to supplement the results of AABR.
Though quite specific it is not as sensitive as an ABR
• Traditional techniques of bedside testing are inadequate
(Auditory Brainstem Responses/Brainstem Evoked Response
and cannot detect moderate hearing impairment, which is
Audiometry). Together with AOAE, AABR forms a very
responsible for most speech delays.
powerful screening tool in newborn and infants.
700 Fig. 1: Organ of corti
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Chapter 145: Hearing Screening and Management in Newborn
For the purpose of AABR measurements disposable surface tone beeps given. This generates an electrical response in
electrodes are placed high on the forehead and on the mastoid the auditory (neural) pathways. These responses are picked
and electrical activity traced. The stimulus is in the form of up by electrodes placed on the forehead or the vertex and
clicks [generally set at 35 dB hearing level (HL)] is delivered mastoid processes. The sum total of the electrical responses is
using small disposable earphones designed to attenuate calculated and mapped out as waveforms. These are charted
background noise. out as a function of time much like an ECG. These are usually
Automated auditory brainstem response system as the detected within 10 milliseconds of a click stimulus. These are
name suggests automatically first checks the reproducibility of consistently picked up with click stimuli in the amplitude
the wave forms, then compares the infant’s waveform with that range of 70–90 dB. These waveforms are labeled as waves
of a template. This has been developed from normative ABR I–VII, each denoting an important structure in the auditory
infant data. The results of this test are just in the form of either pathway. Though the origin of the waveforms is still being
pass or fail, and the test can be conducted in the presence of debated, the following are the most commonly accepted.
background noise. • Cochlear Nerve—I
It lacks frequency-specific information. • Cochlear Nucleus—II
The AABR test is solely a screening technique designed • Sup Olivary Nuc—III
to identify infants who require follow-up testing. It cannot be • Lat. Laminiscus—IV
used to determine the degree or nature of the hearing loss. • Inf. Colliculus—V
Automated auditory brainstem responses cannot however • Med. Geniculate—VI
detect mild hearing loss and thus should be combined with • Auditory Radiatn—VII
AOAE. Auditory brainstem response gives us a good idea about
the integrity of the auditory pathways and to some extent the
Auditory Brainstem Responses threshold of hearing; however, it should be used in conjunction
with clinical assessment and behavioral audiometry as it is not
The most common application of auditory evoked responses
a substitute for these.
is ABR audiometry. These were first described by Jewett and
Williston in 1971.
In ABR an insert phone is introduced into the external Auditory Steady State Response
auditory canal and sound inputs in the form of clicks or This is an advance over the ABR/BERA as it tests both the bone
and air conduction for four frequencies, i.e., 500, 1000, 2000, and
4000 Hz. This gives us a good idea about the sound conduction
through the middle ear system and the auditory pathways. It
allows us to assess children not assessable through behavioral
methods and since it gives us a fair idea of frequency specific
thresholds, it helps in fitting hearing aids as well.
SCREENING PROTOCOLS FOR NEWBORN

All patients with unilateral atresia, suspected/confirmed
bacterial meningitis undergo era directly.
Clinical Pearls
• If there is a delay in sound stimulation, cortical areas in the
brain get encroached and subsequent amplification does not
have the desired effect
• Unless amplification is initiated before 6 months of age an
infant does not keep up with its peers
• Hearing impairment could also be a sign of associated
syndromic disorders. Patients should have a thyroid profile, eye
exam, renal and cardiac assessment
• It is valuable to take a detailed consultation with an
experienced pediatric neurologist to assess milestone delays
and development.
Fig. 2: The auditory pathway.
701
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Algorithm 1
Suggested algorithm for workup of hearing impaired infants
AOAE, automated otoacoustic emission; AABR, automated auditory brainstem response; NICU, neonatal intensive care unit; CI, cochlear implant; OAE, otoacoustic
emission testing, ABR, auditory brainstem responses; BOR, branchiootorenal; CT, computed tomography; MRI, magnetic resonance imaging; AC, air conduction;
BC, bone conduction; ENT, ear, nose, and throat; U/L, unilateral; B/L, bilateral.
702
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Chapter 145: Hearing Screening and Management in Newborn
Key points
))
The importance of hearing assessment in neonates cannot be overemphasized
))
The traditional techniques of assessment are not very accurate and cannot detect mild to moderate hearing impairment. By the time it
becomes apparent to the parents its quite late and such children seldom catch up with their peers since amplification is started too late
))
The policy of screening neonates falling in the high risk register again is full of errors as at least 50% of congenitally hearing impaired
have no known risk factors
))
The detection of hearing loss should also alert the clinician to the possibility of associated syndromic conditions.
703
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CHAPTER 146
Hoarseness in
Pediatric Age Group
Kumud K Handa, Aru C Handa, Dilip Samal
Vocal Nodules
INTRODUCTION
Vocal nodules are by far the most common pathology causing
Hoarseness or dysphonia is defined as an abnormality in voice hoarseness in childhood with an incidence of 38–78%, which
quality that arises because of dysfunction in vocal cord vibratory causes abnormality in vibratory function of cords with
function, causing impairment in proper communication. decreased mucosal waves on stroboscopic examinations.
Normal voice is produced by the fine vibratory function of The prevalence of vocal fold nodules varies affecting 21.6%
the vocal cords that may get deranged because of structural in males and 11.7% in females. Vocal nodules are usually
abnormality of vocal cords or due to any functional deficit. bilateral and formed at the junction of anterior and mid third
Childhood hoarseness is not an uncommon entity. of vocal cords. Vocal nodule arises due to the mechanical
Although, it is an underdiagnosed entity, its prevalence trauma, injury and with secondary hyalinization at the free
may be as high as 23.4% in school-going children with boys edge of vocal cords (Fig. 1).
affected more than girls. The causes may be benign vocal cord
lesions, infections, inflammations, congenital, neurological, or Clinical Pearls
traumatic.
It may impair quality of life in regards to speech. Children • Hoarseness in children, with vocal abuse, is commonly due to
with vocal nodules, vocal fold paralysis and paradoxical vocal vocal nodules
cord movements had statistically significant pediatric voice- • It is very important to examine the larynx, even in children, to
related quality-of-life-impairments as compared to their age know the exact pathology.
matched normal counterparts as per study conducted in 2008
by Merati et al. This requires a more aggressive evaluation and
required intervention of dysphonia in pediatric ages.
ETIOLOGY
Vocal abuse plays a major role causing hoarseness in pediatric
age group. It is more commonly observed in boys, in view of
more aggressive nature as compared to girls.
The etiology of hoarseness may be:
• Benign vocal cord lesions like vocal nodule, polyp
• Vocal cord cysts, sulcus vocalis
• Juvenile laryngeal papillomatosis
• Vocal fold paresis
• Laryngopharyngeal reflux
• Acute or chronic laryngitis
• Foreign body inhalation
• Malignant lesions of larynx
• Systemic illness like hypothyroidism Fig. 1: Five-year-old child with hoarseness and cystic swelling free
• Post-surgery (Iatrogenic) edge of left true cord
CHAPTER 146: Hoarseness in Pediatric Age Group
Vocal Polyps Juvenile Laryngeal Papillomatosis

Vocal polyps are less infrequent entity, usually unilateral, Juvenile laryngeal papillomatosis (recurrent respiratory
may be pedunculated or sessile. Polyps are formed due to papillomatosis) is a benign infectious condition of larynx
phonotrauma and occur at the site of exertion of maximum due to human papilloma virus infection of serotype mainly
muscular and aerodynamic force. These are formed as a result 6 and 11. It is the most common benign neoplasm of larynx
of circulation impediment, thrombosis, exudation, edema due and second most common cause of dysphonia or hoarseness
to inflammation of the vocal cords. in children. It is more aggressive in childhood, often
requiring multiple surgical intervention. Most common age
Vocal Cord Cysts of presentation is from 2 to 4 years, with youngest reported
age is at 1 day. It has an incidence of 4.3 per 100,000 among
Vocal cord cysts usually present as unilateral submucosal
the children with an equal male and female distribution.
swelling with reduced mucosal waves on stroboscopy (Fig. 2).
It usually presents as dysphonia in early stage of disease,
but may be presented with breathing difficulty and stridor
Sulcus Vocalis when compromises the glottic airway and may require
It has epithelium invaginates and adheres to vocal ligament tracheotomy. The most common sites involved in larynx are
forming a longitudinal furrow with incomplete vocal cord midzone of the laryngeal surface of the epiglottis, the upper
closure on stroboscopy. Both are believed to be either and lower margins of the ventricle, the undersurface of the
congenital or may be acquired lesions having variable vocal folds, the carina with a common histologic feature of a
presentations of hoarseness, vocal fatigue or voice breakage. squamociliary junction sites (Fig. 4).
They have a poor response to speech therapy and may require
surgical intervention (Fig. 3). Congenital or Acquired Vocal Fold Paresis
In children it may present as dysphonia, resulting from birth
trauma or congenital anomaly involving the central nervous
system. Vocal fold paralysis may have a unilateral or bilateral
vocal cord involvement and should be differentiated from
cricoarytenoid joint dislocation. Unilateral vocal fold paresis
may remain undiagnosed, but bilateral vocal fold paresis
may present with stridor, requiring tracheostomy. It may have
spontaneous recovery, otherwise may need corrective surgical
intervention later on.
Laryngopharyngeal Reflux
It can present as hoarseness, which is more aggressively being
evaluated in recent era. Although confirming the diagnosis is
difficult, reflux laryngitis with dysphonia may be reversible
with antireflux proton pump inhibitors and prokinetic drug
treatment.
Fig. 2: Vocal cord cyst
705
Fig. 3: Sulcus vocalis Fig. 4: Juvenile papilloma (endoscopic view)
SECTION 18: Ear, Nose, and Throat
Acute or Chronic Laryngitis threatening condition. Stridor may be inspiratory, expiratory or

biphasic, depending upon the site of involvement in the larynx.
It may present as dysphonia causing vocal fold edema.
The etiology may be laryngeal papillomatosis or neoplastic
Although it has a viral etiology, may be bacterial or fungal also.
lesion.
Symptoms may worsen more with vocal abuse. It should be
Difficulty in swallowing may be associated, when laryngeal
differentiated from acute laryngotracheobronchitis or croup,
involvement because of neurologic disorder or large structural
caused by parainfluenza virus I and II.
abnormality that hampers the swallowing physiology. It may be
associated with aspiration, especially in cases of neurological
Foreign Body Inhalation disorders and laryngeal clefts.
It can cause hoarseness of acute onset with or without breathing Significant gastroesophageal reflux may present as
difficulty. On evaluation patient may have stridor along with hoarseness, but it is a difficulty entity to diagnose or ruled out
change in voice, which may need immediate intervention. reflux. Some physicians prefer an antireflux trial response for
the diagnosis of the entity.
Malignant Tumors
Malignant tumors of larynx although rare, but should be
Examination
ruled out in a pediatric patient presented with progressively It includes thorough otolaryngological examination,
worsening hoarseness with dysphagia or breathing difficulty. examination of endolarynx and voice analysis. Endolarynx is
Embryonal rhabdomyosarcoma is the most common variant, examined using 90 degree telescope or fiberoptic 2.7 or 4.0 mm
others are squamous cell carcinoma, lymphoma, muco laryngoscope. This provides information regarding structural
epidermoid carcinoma or metastatic carcinoma variant. Long vocal cord abnormality and its functional aspects also.
standing recurrent respiratory papillomatosis is known risk Although awake laryngoscopy is superior to laryngoscopic
factor in the development of malignant transformation with an evaluation under general anesthesia, in infants for proper
incidence of 2–3%. evaluation some surgeon prefer evaluation under anesthesia
without muscle relaxant. Video stroboscopic examination
Iatrogenic provides better clinical details regarding the detail mucosal
vibratory function (Fig. 5).
patient may present with change in voice following surgery. Subjective evaluation with pediatric voice handicap index
It may be due to vocal fold paresis following cardiothoracic (pVHI) and objective voice evaluation with acoustic and
surgery or may be due to cricoarytenoid dislocation. aerodynamic analysis plays an important role in evaluation
and examining response to treatment.
Clinical Pearl
Clinical Pearl
• Laryngopharyngeal reflux, despite being common, in children
is still an underdiagnosed entity • With patience, counseling, and parental cooperation good
examination of larynx are possible in most cases either by
• Neonates and infant with unilateral cord paralysis have a weak
indirect laryngoscopy or flexible laryngoscopy
cry whereas bilateral vocal cord paralysis presents with stridor.
• Direct laryngoscopy for examination under anesthesia, without
muscle relaxant, is required only in select few.
EVALUATION
Approach to a child with hoarseness needs a multidisciplinary
approach involving otolaryngologist, speech language
therapist for detailed evaluation of medical history, physical
examinations, laryngoscopic vocal cord assessment and
acoustic and aerodynamic evaluation of voice with strobo
scopic examination if needed.
History
Patient should be thoroughly studied regarding the age
of onset, i.e., since birth or later, duration of hoarseness.
Congenital lesions usually present at birth, whereas
neurological illnesses may present from birth or later on. It
may be intermittent as in reflux laryngitis or vocal abuse or
persistent as in structural laryngeal pathology. Progressively
worsening dysphonia may be because of neoplastic lesions
and juvenile papillomatosis.
When associated with noisy breathing, it should be Fig. 5: Videostroboscope for examination of the vibratory edge of
706 evaluated seriously; otherwise it may progress in to a life the vocal fold
CHAPTER 146: Hoarseness in Pediatric Age Group
ALGORITHM 1
URTI, upper respiratory tract infection; PND, paroxysmal nocturnal dyspnea, PPI, proton pump inhibitor, RRP, recurrent respiratory papillomatosis, MLS,
microlaryngeal surgery; CECT, contrast-enhanced computed tomography.
Additional test laryngeal electromyography, pH probing

may be done when there is any clinical suspicion and Clinical Pearls
requirement. • Voice therapy is mainstay of treatment for vocal nodules in
children
• It is very important to involve the family for voice therapy in
TREATMENT children.
Voice therapy: Usually it is the initial and most common form
of treatment used in treatment of dysphonia in pediatric age Surgery
group. Voice therapy for children is usually behavioral in It is done in specific conditions. Vocal polyps need micro
nature and includes family orientation, vocal hygiene and scopic laser or cold instrument excision while vocal nodules
vocal training. In children specific voice therapy techniques respond most of the times to voice therapy. It is only vocal
are associated with drawing, body movements, and hand nodules which do not respond to voice therapy that need
gestures to make them understand the goals of therapy. surgery. Vocal cord cysts mucus retention or epidermoid
Computer games and software’s like the voice therapy needs surgical excision. This may be done by laser or flap
segment in Doctor’s Speech etc. especially designed to phonomicrosurgery.
provide visual and audio feedbacks related to respiration, Recurrent respiratory papillomatosis (Juvenile papillomas)
voice quality, pitch, loudness, resonance, and articulation are needs surgical excision. Nowadays a combination of debrider
used to make voice therapy for children more interesting and debulking using a skimmer blade and CO2 laser is used for
concrete. removal of juvenile papillomas. Papillomas can recur and need
General voice therapy techniques include body relaxation, multiple surgical sittings.
breathing exercises, laryngeal manipulation, and repositioning Bilateral abductor cord paralysis may need surgical inter
in the neck. Whereas the specific techniques include resonance vention if stridor is severe. The commonly done procedures are
and vibration technique, chanting of poems and rhymes posterior laser cordectomy, Kashima procedure (disjunction
reduces the compression of laryngeal forces and increases of vocal process from the vocal cord) and endoscopic laser
reverberation in oral and nasal cavities. arytenoidectomy. 707
Unilateral cord paralysis not responding to voice therapy

may need injection or medialization thyroplasty. ))
Cause of Vocal fold paralysis in a child should be evaluated
radiologically with imaging of brain, neck and upper
mediastinum
Clinical Pearls
))
Laryngopharyngeal reflux in children is more common in
• Removal of vocal nodule without a good and adequate children than thought of
speech therapy is not advisable. Surgery reserved only for rare ))
Malignant tumors in children are less common so may get
refractory cases diagnosed late because of delay in laryngeal examination
• Repeated frequent removal of juvenile onset recurrent ))
Voice therapy may be helpful in majority of lesions causing
respiratory papillomatosis is required to prevent airway hoarseness in children.
obstruction and tracheotomy
• The aim of surgery in recurrent respiratory papillomatosis is to
provide adequate airway, functional voice with minimal scarring.
SUGGESTED READINGS
1. Akif Kilic M, Okur E, Yildirim I, Güzelsoy S. The prevalence of vocal fold nodules
in school age children. Int J Pediatr Otorhinolaryngol. 2004;68(4):409-12.
2. Chen X. Comparative research on vocal polyps and nodules. Zhonghua Er Bi Yan
KEY POINTS Hou Ke Za Zhi. 1989;24(1):53-5, 63.
3. Derkay CS. Task force on recurrent respiratory papillomas. Arch Otolaryngol Head
))
Hoarseness in pediatric age group needs proper evaluation
Neck Surg. 1995;121:1386-91.
including detailed history of duration, infection, vocal abuse,
4. Ferlito A, Rinaldo A, Marioni G. Laryngeal malignant neoplasms in children and
trauma, etc. adolescents. Int J Pediatr Otorhinolaryngol. 1999;49(1):1-14.
))
As it is difficult to get child’s cooperation so examination of 5. Gaylis B, Hayden R. Recurrent respiratory papillomatosis: progression to invasion and
larynx in children may be challenging malignancy. Am J Otolaryngol. 1991;12:104-12.
))
Vocal nodules occur due to vocal abuse or overuse and 6. Kashima H, Mounts P, Leventhal B, Hruban RH. Sites of predilection in recurrent
management includes voice therapy with or without surgery respiratory papillomatosis. Ann Otol Rhinol Laryngol. 1993;102(8 Pt 1):580-3.
))
Vocal polyps are less common in children 7. Kleinsasser O. Pathogenesis of vocal cord polyps. Ann Otol Rhinol Laryngol.
1982;91(4 Pt 1):378-81.
))
Vocal cysts do not respond to voice therapy and require
8. Merati AL, Keppel K, Braun NM, Blumin JH, Kerschner JE. Pediatric voice-related
surgical correction
quality of life: findings in healthy children and in common laryngeal disorders. Ann
))
Sulcus vocalis may be congenital or acquired requires Otol Rhinol Laryngol. 2008;117(4):259-62.
prolonged voice therapy, and the surgical results are not very 9. Morgan AH, Zitsch RP. Recurrent respiratory papillomatosis in children: a retrospective
dramatic thus requiring postoperative speech therapy also study of management and complications. Ear Nose Throat J. 1986;65:19-28.
))
Recurrent respiratory papillomatosis presents in early 10. Silverman EM. Incidence of chronic hoarseness among school-age children.
childhood with weak cry, hoarseness, and may progress on to J Speech Hear Disord. 1975;40(2):211-5.
stridor if not treated. Surgery is treatment of choice but there 11. Zur KB, Cotton S, Kelchner L, Baker S, Weinrich B, Lee L. Pediatric voice handicap index
is high chance of recurrence (pVHI): a new tool for evaluating pediatric dysphonia. Int J Pediatr Otorhinolaryngol.
2007;71(1):77-82.
708
CHAPTER 147
Otitis Media with Effusion
Anurag M Srivastava, Anil K Monga, Uday Monga
INTRODUCTION TABLE 1: Definition for otitis media
Otitis media with effusion (OME) is the chronic accumulation Middle ear Definition
of mucus within the middle ear and sometimes the mastoid condition
air cell system. It is characterized by a nonpurulent effusion MEE Fluid in the middle ear space
of middle ear that may be either mucoid or serous. Symptoms AOM MEE with symptoms and signs of inflammation
usually involve hearing loss or aural fullness but typically (i.e., otalgia, fever, irritability)
do not involve pain or fever. Otitis media with effusion can OME MEE without symptoms or signs of inflamation
occur during the resolution of acute otitis media once the
inflammation has resolved. Middle ear infections are most RAOM Three or more episodes of AOM in 6 months
common medical problem in infants and children of pre Persistent OME MEE without symptoms for more than 3 months
school age. Tympanostomy tube insertion is preferred initial AOM, acute otitis media; MEE, middle ear effusion; OME, otitis media with
procedure. Adenoidectomy should not be performed, unless effusion; RAOM, recurrent acute otitis media.
a distinct indication exists (e.g., nasal obstruction, chronic
adenoiditis). Medical Therapy to manage the mucosal aspect of
the disease will be required regardless of surgical intervention. SUBJECTIVE COMPLAINTS
The otolaryngologist should monitor patients until the Otitis media with effusion is characterized by a non-purulent
conditions resolves with medical or surgical intervention. effusion of the middle ear that may be either mucoid or serous.
Thereafter, if the patient’s hearing is normal, the paediatrician Symptoms usually involve hearing loss or aural fullness but
can provide care. typically do not involve pain or fever. In children, hearing loss
is generally mild and is often detected only with an audiogram.
DEFINITION In many children, OME may be preceded by an episode
of acute otitis media (AOM) with otalgia and fever. These
Otitis media with effusion is the chronic accumulation of secretions then become secondarily infected with bacteria—
mucus within the middle ear and sometimes the mastoid air AOM. Once the infection has resolved, it takes time for the
cell system. The time that the fluid has to be present for the epithelium to recover. So, OME will be present temporarily in
condition to be chronic is usually taken as 12 weeks. many children after an episode of AOM.
SYNONYMS CLINICAL AND FUNCTIONAL ANATOMY

Serous otitis media is also known as nonsuppurative otitis Middle ear cleft is a continuous space that extends from
media, exudative otitis media or simply “glue ear”. Other terms the nasopharyngeal orifice of the eustachian tube to the
are serous otitis media, secretory otitis media and chronic non- furthermost mastoid air cells. Three main segments are the
purulent otitis media (Table 1). eustachian tube; middle ear (tympanum); and the air cells of
Classic Theory
The classic explanation proposes that eustachian tube
dysfunction is the necessary precursor. If eustachian tube
dysfunction is persistent, a negative pressure develops within
the middle ear from the absorption and/or diffusion of nitrogen
and oxygen into the middle ear mucosal cells. If present for
long enough and with appropriate magnitude, the negative
pressure elicits a transudate from the mucosa, leading to the
eventual accumulation of a serous, essentially sterile effusion.
Newer Theories
The newer models describe the primary event as inflammation
of the middle ear mucosa caused by a reaction to bacteria
Fig. 1: Anatomy of the external and middle ear already present in the middle ear. Indeed, Bluestone and others
have shown (using radiographic evidence) that reflux up the
eustachian tube is demonstrable in children prone to otitis
the mastoid, petrosa, and related areas. Tympanic membrane
media. Furthermore, Crapko et al. demonstrated the presence
facilitates sound transfer also allow it to serve as a clinical
of pepsin in the middle ear space of 60% of children with
window into the middle ear cleft, one that permits inferences
OME. This reflux certainly may also occur in otherwise healthy
about the condition of the tympanum based on visible changes
individuals. Yilmaz et al. published a study that documented
in the color, mobility, or position (Fig. 1).
significant changes in oxidative stress in patients with OME.
Mucosal lining of the middle ear cleft varies from the thick,
The investigators demonstrated a significantly improved but
ciliated, respiratory epithelium of the eustachian tube and
not normalized level of oxidants following the placement of
anterior tympanum to the thin, relatively featureless cuboidal
ventilation tubes.
epithelium in the mastoid cells.
ETIOLOGY
OBJECTIVE FINDINGS
Otoscopic findings of inflammation in AOM may include Clinical Pearl
decreased mobility of the tympanic membrane that is
manifested by difficulty in assessing the ossicular landmarks, • OME and AOM—still one of the most researched area in otology.
yellowness and/or redness with hypervascularity, purulent
middle ear effusion (MEE), and, occasionally, bullae. This
Same flora found in AOM can be isolated in OME. With OME,
appearance clearly contrasts with that of OME.
the inflammatory process has clearly resolved, and the volume
Findings that suggest the presence of OME include
of bacteria has decreased. However, because of the similarity
observable air-fluid levels (which may be vertically oriented),
of these two conditions, reviewing the pathogenic organisms
serous middle ear fluid, and a translucent membrane with
in AOM is worthwhile.
diminished mobility.
Otitis media with effusion can also be associated with
negative pressure in the middle ear. This negative pressure is Common Pathogens
suggested by the prominence of the lateral process, a more The most common bacteria in AOM, in order of frequency, are:
horizontal orientation of the malleus, and movement only with • Streptococcus pneumoniae is found in 35% of cases, and the
negative pneumatoscopy. prevalence does not seem to vary with age; the serotypes
Occasionally, tonsillar hypertrophy can accompany most commonly isolated, in order of frequency, are 19, 23,
findings of OME. More commonly, adenoid hypertrophy is 6, 14, and 3
present. Additional findings may include turbinate bogginess, • Haemophilus influenzae is found in 20% of cases; of these
postnasal drip, rhinorrhea, and watery and/or erythematous cases, 25–45% involve beta-lactamase production, with a
eyes consistent with a concurrent upper respiratory tract clear trend of increasing resistance
infection (URTI) or environmental allergies. • Moraxella catarrhalis is found in 4–13% of cases of AOM,
with a great frequency in winter and autumn; of these
cases, 70–100% involve beta-lactamase production.
PATHOPHYSIOLOGY
Additional bacterial pathogens include Streptococcus
Otitis media with effusion can occur during the resolution pyogenes, Staphylococcus aureus, Gram-negative enteric
of AOM once the acute inflammation has resolved. Among bacteria, and anaerobes. When an effusion is present for longer
children who have had an episode of AOM, as many as 45% than 3 months, Pseudomonas species predominate.
have persistent effusion after 1 month, but this number In other more recent studies, viruses have been isolated
710 decreases to 10% after 3 months. in conjunction with bacteria in 15–20% of cases of AOM.
CHAPTER 147: Otitis Media with Effusion
Respiratory syncytial virus (RSV) and influenza virus were the PHYSICAL EXAMINATION
most frequent.
The primary difference with the pathogens in OME Otoscopic findings of inflammation in AOM may include
compared with AOM is that the frequency of S. pneumoniae decreased mobility of the tympanic membrane (which has
is not as high, and H. influenzae and M. catarrhalis are a bulging contour) manifested by difficulty in assessing
moderately more common. the ossicular landmarks, yellowness and/or redness with
• Allergy has long been recognized as one of the causative hypervascularity, purulent MEE, and, occasionally, bullae.
factors of OME. Nasotubal mucosal congestion associated This appearance clearly contrasts with that of OME.
with inhalant allergy and obstruction of the ET was Findings that suggest the presence of OME are observable
mentioned earlier. A significant association has been air-fluid levels (which may be vertically oriented), serous
reported between food allergy and serous otitis media middle ear fluid, and a translucent membrane with diminished
(SOM) and recurrent AOM is more prevalent among mobility. Extensive inflammation and purulent MEE should
children suffering from immunodeficiency. not be evident.
Some other causes are multiple: Young age, bottle feeding, Occasionally, tonsillar hypertrophy can accompany findings
crowded living conditions (including day-care centers), of OME. More commonly, adenoid hypertrophy is present,
heredity, and a variety of associated conditions including cleft especially in patients with prolonged or recurrent condi
palate, immunodeficiency, ciliary dyskinesia, Down syndrome tion. Other findings are turbinate bogginess, postnasal drip,
and cystic fibrosis. The genetic factors of otitis media have yet rhinorrhea, and watery and/or erythematous eyes consistent
to be delineated (Table 2). with a concurrent URTI or environmental allergies (Fig. 2).
EPIDEMIOLOGY DIAGNOSTIC CHALLENGES

Middle ear infections are the most common medical problem In adults, recognizing unilateral otitis media (OME) with
in infants and children of preschool age. effusion is crucial. It must be considered a nasopharyngeal
Clinical guidelines from a joint commission of specialties mass until definitively proven otherwise. Indirect mirror exami
document that screening surveys of healthy children between nation or flexible nasopharyngoscopy should be performed.
infancy and age 5 years show 15–40% point prevalence in Imaging studies and possibly even biopsies may be indicated.
MEE. Furthermore, among children examined at regular Other neglected areas include:
intervals for 1 year, 50–60% of child care attendees and 25% • Failure to note hearing loss
of school-aged children were found to have an MEE at some • Failure to recognize a delay in language development in
point during the examination period, with peak incidence children.
during the winter months. The following are conditions that should be considered
Between 84% and 93% of all children experience at least 1 when evaluating patients with suspected OME:
episode of AOM. Furthermore, approximately 80% of children • Benign nasopharyngeal masses
have had an episode of OME when younger than 10 years. The • Nasopharyngeal carcinoma
prevalence of OME is highest in those aged 2 years or younger,
and it sharply declines in children older than 6 years.
Otitis media is more frequent in the winter months
regardless of climate, presumably due to crowding in
schools during the upper respiratory infection (URI) season.
Henderson et al. (1982) confirmed the chronologic proximity of
otitis media to URI in a day-care setting, which held regardless
of time of year.
TABLE 2: Risk factor potentially incresing incidence otitis media

Intrinsic Extrinsic
Patient age Fall/winter season
Male gender Upper respiratory infection
Atopic disease Daycare
Immune deficiency Older sibling
Palate anomaly Passive smoke exposure
Craniofacial anomalies Pacifier use in daycare
Fig. 2: Thin tympanic membrane showing fluid level
Genetic predisposition Bottle feeding
711
• Acute otitis media Free-field Testing

• Adenoid hypertrophy
In primary care, audiometry is seldom available, particularly for
• Congenital defects affecting the eustachian tube and its
younger children. Under these circumstances, the practitioner
egress
could perform free-field voice testing of hearing.
• Ciliary dyskinesia
• Immunoglobulin G (IgG) subclass deficiencies.
Tympanometry
Differential Diagnoses Tympanometry is perhaps the most useful of all tests in
association with OME. This test reveals a type B result in 43% of
• Cleft palate
cases of OME and a type C result in 47% of cases.
• Eustachian tube malfunction
Though an acoustic seal is sometimes difficult to achieve,
• Malignant tumors of the nasal cavity
bilateral tympanograms should be obtainable in the majority
• Malignant tumors of the temporal bone
(98%) of children between the ages of 3.5 and 7 years, in a
• Middle ear inflammation/infection
slightly lower percentage (90–94%) of infants 2–11 months of
• Patulous eustachian tube
age and 78–88% of infants 12–24 months of age are included.
• Sinonasal manifestations of cystic fibrosis.
According to American Academy of Family Physicians
(AAFP), the American Academy of Otolaryngology-Head
Assessment and Neck Surgery (AAO-HNS), and the American Academy
Laboratory tests have rarely been used: of Pediatrics (AAP) subcommittee on OME, audiology is a
• History taking and physical examination are sensitive necessary component of the evaluation of certain patients with
and specific enough to facilitate accurate diagnosis and this condition.
treatment of the disease The committee not only stated that initial hearing testing
• Obtaining cultures is not routine for this condition but is in can be done in a primary care setting for children aged 4 years
tympanocentesis or older, but it also stated that conventional audiometry with
• Complete blood cell (CBC) count is assessed to rule out earphones is performed with a fail criterion of more than
active infection. 20 dB HL at 1 or more frequencies (500, 1000, 2000, 4000 Hz)
in either ear.
Radiologic Studies
Plain radiography of the nasopharynx is needed to identify Language Testing
enlarged adenoids. Language testing has also been advised for children with
hearing loss (pure tone average greater than 20 dB HL on
Computed Tomography comprehensive audiometric evaluation). Testing for language
Computed tomography (CT) scanning is extremely sensitive delays is important, because communication is integral to all
but done only in rare situations. aspects of human functioning (Box 1).
Magnetic Resonance Imaging Box 1: Host factor that potentially increase the risk of
language delay with otitis media
Magnetic resonance imaging (MRI) useful in the workup for
• Eustachian tube • Neuro-developmental/
soft-tissue masses.
dysfunction behavioral issues
{{ Over cleft palate {{ Attention deficit disorder
Pneumatic Otoscopy {{ Submucous cleft palate {{ Autism, pervasive develop
American clinical practice guidelines have strongly advocated {{ Craniofacial anomaly mental delay
the use of pneumatic otoscopy as the primary diagnostic • Congenital conductive {{ Global developmental dealy
method for OME. The sensitivity of pneumatic otoscopy is 85– hearing loss {{ Mental retardation
{{ Aural stenosis/atresia {{ Chromosomal anomalies

93% and its specificity from 71% to 89%. This can be carried out
with a closed system in a handheld otoscope or with a Siegle’s {{ Ossicular malformation • Sensorineural hearing loss
pneumatic speculum, viewed with headlight illumination or • Primary language delay
microscope. Acceptable to most children, the inability to gain
a seal with the available speculum can occur in up to 20% of Tympanocentesis and Myringotomy
children aged over 18 months.
Tympanocentesis involves aspiration of effusion from the
middle ear. Tympanocentesis can serve as both a therapeutic
Video Otoscopy procedure and a diagnostic procedure.
Video recordings of otoscopy, including pneumatic otoscopy, The criterion for documentation of an MEE is myringotomy,
can be documented and used to monitor changes with time. It which has the advantage of increased exposure and better
can also be used for teaching and research purposes. suctioning relative to tympanocentesis. Only disadvantage
712
is a larger incision with a greater, although small, chance of • Adenoidectomy should not be performed, unless a
persistent perforation or otorrhea. distinct indication exists (e.g., nasal obstruction, chronic
adenoiditis)
OVERVIEW OF MEDICAL AND • Repeat surgery consists of adenoidectomy plus myringo
SURGICAL APPROACHES tomy, with or without tube insertion
• Tonsillectomy alone or myringotomy alone should not be
used to treat OME.
Clinical Pearls
• Modification of risk factors is also a form of definitive Medication
management Pharmacologic management of OME includes adminis
• Reasonable primary intervention tration of antimicrobial agents, steroids, antihistamines and
• Avoidance of passive smoking decongestants, and mucolytics.
• Breastfeeding is associated with a lower incidence of otitis
media Antimicrobial Agents
• No feeding in supine position
Otitis media with effusion demonstrates viable pathogenic
• Avoidance of exposure to large number of children
• Avoidance of Allergens. bacteria, treatment with appropriate antibiotics is reasonable,
albeit with evidence showing only short-term benefit.
Commonly used drugs are erythromycin, sulfisoxazole,
Summary of Medical Intervention amoxicillin, amoxicillin-clavulanate, and trimethoprim-
sulfamethoxazole.
The American Academy of Family Physicians (AAFP), the
American Academy of Otolaryngology-Head and Neck Surgery
Steroids
(AAO-HNS), and the American Academy of Pediatrics (AAP)
subcommittee on OME published clinical guidelines for OME: Empirical evidence indicates that steroids help in improvement
• Document the laterality, duration of effusion, and presence of OME in cases resistant to 2 weeks of antibiotics. It may be
and severity of associated symptoms at each assessment of beneficial to add intranasal steroids.
the child with OME
• Distinguish the child with OME who is at risk for speech, Antihistamines and Decongestants
language or learning problems from other children with Nasal obstruction, rhinorrhea, and sinusitis often accompany
this condition, and more promptly evaluate hearing, otitis media, and antihistamines and decongestants may be
speech, language and need for intervention in children at considered for the relief of these associated symptoms.
risk
• Manage the child with OME who is not at risk with watchful Mucolytics
waiting for 3 months from the date of effusion onset (if Used in antibiotic resistant cases.
known), or from the date of diagnosis (if onset is unknown)
• Hearing testing should be conducted when OME persists
Indications for Surgical Intervention
for 3 months or longer, or at any time that language delay,
learning problems, or a significant hearing loss is suspected Surgical intervention is indicated in cases of developmental
in a child with OME delays, particularly in the areas of speech and language
• Children with persistent OME who are not at risk should development.
be reexamined at 3–6 month intervals until the effusion is Children who need aggressive intervention include any of
no longer present, significant hearing loss is identified, or the following:
structural abnormalities of the eardrum or middle ear are • Children with permanent hearing loss independent of
suspected. OME
• Those with suspected or diagnosed speech and language
Autoinflation delay or disorder
Many studies have reported mixed results when attempting • Those with autism spectrum disorder or other pervasive
to determine if autoinflation, compared with no intervention, developmental disorders
improves effusion clearance rates. However, it is not routinely • Children with syndromes (e.g., Down syndrome) or
practiced. craniofacial disorders that include cognitive, speech and
language delays
Summary of Surgical Intervention • Those who are blind or have uncorrectable visual
The following is a verbatim summary of the AAFP, AAO-HNS, impairment
and AAP clinical guideline recommendations: • Children with cleft palate, with or without an associated
• When a child becomes a surgical candidate, tympano syndrome
stomy tube insertion is the preferred initial procedure • Children with developmental delay.
713
MYRINGOTOMY
This section will briefly review myringotomy and aspiration
of effusion and myringotomy with pressure equalization tube
(PET) insertion.
Myringotomy and Ventilation Tubes

Introduced in 1954 by Armstrong, ventilation tube insertion
has become the criterion standard and most common therapy
for chronic otitis media with effusion (COME). Improved
hearing and decreased rates of AOM are absolute benefits of
myringotomy with placement of ventilation tubes; these have
been documented multiple times. Typically, the tubes self-
extrude 9–12 months after placement.
Pressure equalization tubes are available in a variety of sizes,
shapes and materials. All are designed to permit ventilation of
the middle ear and mastoid system. Prolonged aeration of the
middle ear has been shown to reverse the mucosal hyperplasia
and metaplasia that accompany OME.
Fig. 3: Showing a tympanic membrane with grommet in situ
Complications
Overall complication rate of ventilation tubes are 11%.
• Persistent otorrhea is the most common complication,
occurring in 15% of patients and persisting as long as 1 year
in 5% Three rationales exist for the removal of the adenoids in the
• Second in frequency is tympanosclerosis, which is not treatment of OME and are discussed below.
clinically significant unless it is extensive
• Persistent perforation is seen in approximate 2% Removal because of Enlargement
cases, where it is in place longer than 18 months. This
Enlarged adenoids occlude the nasopharynx and choanae. This
complication is also known to increase with the placement
potentiates eustachian tube reflux. However, multiple studies
of tympanostomy tubes (T-tubes) that are designed to
have revealed that the result of adenoidectomy is independent
stay in the tympanic membrane longer than the typical
of adenoid size. This finding suggests that processes other than
grommet tube
simple adenoid mass are involved.
• Other lesser known complications are granulation tissue
formation, cholesteatoma and sensorineural hearing loss.
Clinical guidelines summarize a number of studies and Removal for Improvement of
state that tympanostomy tubes are recommended for initial Eustachian Tube Function
surgery, because randomized trials show a mean 62% relative
Improvement in the equilibration of positive middle ear
decrease in effusion prevalence and an absolute decrease of
pressure after adenoidectomy has been documented. In
128 effusion days per child during the next year. Hearing levels
addition, extremely large adenoids may physically occlude
improve by a mean of 6-12 dB while the tubes remain patent
the eustachian tube orifice, although Bluestone and others
(Table 4) (Fig. 3).
have shown that this is rare. The obstruction is nearly always
functional.
Adenoidectomy
Although adenoidectomy was once the principal treatment for
Removal of a Potential Source of Inflammation
OME, easy and low-risk placement of PETs is now favored.
and Infection at the Eustachian Tube Orifice
TABLE 4: Otitis media with effusion duration and tympanostomy The third and most recent rationale for adenoidectomy
tube is to remove a potential inflammatory source and the
OME duration Probability of TT presence of infection at the orifice of the eustachian tube.
spontaneous resolution When performed correctly, adenoidectomy can be used to
<3 months High No create a smooth nasopharyngeal mucosa, which decreases
the colonization of bacteria that can occur in the crypts of
3–6 months Intermediate Placed on
adenoid tissue.
individuaized basis
Complications of adenoidectomy include bleeding (0.4%),
>6 months Low Yes velopalatal insufficiency (usually temporary), and a patulous
714 TT, tympanostomy tube placement. eustachian tube.
ALGORITHM 1
Management of otitis media with effusion
*Gentle suction cleaning
Long-term Monitoring Clinical Pearls

No standard of care for the follow-up of patients with OME has
To treat or not to treat, that is the question
been established.
Most ventilation tubes stay in situ for 6–9 months and • Significant associated conductive hearing loss
are extruded naturally through ear canal. Patient should be • Occurrence in young infants, as they are unable to communicate
followed after 3 weeks after the placement of the tubes and about their symptoms and may have suppurative disease
then every 6 months thereafter, until the tubes extrude or are • An associated acute suppurative URTI
removed. • Concurrent permanent conductive/sensorineural hearing loss
Patients are instructed that if more than two episodes of • Presence of speech/language delay associated with effusion
otorrhea occur before the 6-month follow-up is scheduled, and hearing loss
they should see their otolaryngologist (ENT) instead of or in • Tinnitus, vertigo or disequilibrium
addition to their primary care physician (PCP)/pediatrician. • Alterations of tympanic membrane, such as a retraction pocket
We recommend the removal of ventilation tubes that have • Middle-ear changes, such as adhesive otitis media or ossicular
not spontaneously extruded between 18 and 24 months after involvement
placement due to the increasing risk of persistent tympanic
• Previous surgery for otitis media (e.g., tympanostomy tube
membrane perforation. placement or adenoidectomy)
The otolaryngologist should monitor patients until the
• When episodes of acute otitis media recur frequently (5–6
conditions resolves with medical or surgical intervention.
episodes/year)
Thereafter, if the patient’s hearing is normal, the primary
• Effusion that persists for 3 months or longer (i.e. chronic otitis
physician/pediatrician can provide care. If a documented
media with effusion, before consideration for tympanostomy
hearing loss is present, it should be reevaluated for severity and
tube placement)
type of management.
• Difficult as it is each patient has to be taken up for surgery
A multidisciplinary team should rigorously follow and
at his own merit considering a holistic global understanding
aggressively treat language-related developmental delays.
of the extent of the problem, the effect on quality of life and
Interventions should include the use of hearing aids, if above all possibility of sequelae and complications in later life.
justified. 715
PITFALLS 3. Cavanaugh RM. Obtaining a seal with otic specula: must we rely on an air of
uncertainty? Pediatrics. 1991;87:114-6.
Thorough investigations required for persistence of OME as in 4. Crapko M, Kerschner JE, Syring M, Johnston N. Role of extra-esophageal
children with craniofacial abnormalities. reflux in chronic otitis media with effusion. Laryngoscope. 2007;117(8):
Medical Therapy to manage the mucosal aspect of the 1419-23.
5. Engel J, Anteunis L, Chenault M. Otoscopic findings in relation to tympanometry
disease will be required regardless of surgical intervention.
during infancy. European Archives of Otorhinolaryngology. 2000;257:366-71.
Limitations of surgical management of tube placement, i.e., 6. Henderson FW, Collier AM, Sanyal MA, Watkins JM, Fairclough DL, Clyde WA Jr, et
persistent otorrhea, tympanosclerosis, persistent perforation al. A longitudinal study of respiratory viruses and bacteria in the etiology of acute
(2%), others—focal atrophy, granulation tissue formation, otitis media with effusion. N Eng J Med. 1982;306:1377-83.
cholesteatoma, and SNHL. 7. Kaleida PH. Evidence assessment of the accuracy of methods of diagnosing middle
ear effusion in children with otitis media with effusion. J Pediatr. 2004; 145(1):138.
8. Medical Research Council Multicentre Otitis Media Study Group. Sensitivity,
KEY POINTS specificity and predictive value of tympanometry in predicting a hearing
impairment in otitis media with effusion. Clinical Otolaryngology. 1999;24:
))
Secretory otitis media is non-inflammatory middle ear 294‑300.
effusion usually following acute otitis media (AOM) 9. Palmu A, Puhakka H, Rahko T, Takala AK. Diagnostic value of tympanometry in
))
Diagnosis is clinical; adults and adolescents must undergo infants in clinical practice. International Journal of Pediatric Otorhinolaryngology.
nasopharyngeal examination to exclude malignant or benign 1999;49:207-13.
tumors 10. Pichichero ME, Poole MD. Assessing diagnostic accuracy and tympanocentesis skills
in the management of otitis media. Arch Pediatr Adolesc Med. 2001;155(10):1137-
))
Antibiotics and decongestants are not helpful
42.
))
If unresolved in 1–3 months, myringotomy with tym 11. Preston K. Pneumatic otoscopy: a review of the literature issues in comprehensive
panostomy tube insertion may be needed pediatric nursing. Good Literature Review. 1998;21:117-28.
))
Myringotomy and ventilation tube insertion is a safe and 12. Rosenfeld RM, Culpepper L, Doyle KJ, Grundfast KM, Hoberman A, Kenna MA, et al.
effective way to relief middle ear dysfunction and audition Clinical practice guideline: otitis media with effusion. Otolaryngol Head Neck Surg.
loss, it should be considered to be a basic principle of therapy 2004;130(5 Suppl):S95-118.
13. Tracy JM, Demain JG, Hoffman KM, Goetz DW. Intranasal beclomethasone as an
))
Xylitol chewing gum appears to decrease rates of AOM adjunct to treatment of chronic middle ear effusion. Ann Allergy Asthma Immunol.
secondary with otitis media effusion in children going to 1998;80(2):198-206.
daycare by 25%. 14. Williams RL, Chalmers TC, Stange KC, Chalmers FT, Bowlin SJ. Use of antibiotics in
preventing recurrent acute otitis media and in treating otitis media with effusion. A
meta-analytic attempt to resolve the brouhaha. JAMA. 1993;270(11):1344-51.
SUGGESTED READINGS 15. Yilmaz T, Koçan EG, Besler HT, Yilmaz G, Gürsel B. The role of oxidants and
antioxidants in otitis media with effusion in children. Otolaryngol Head Neck Surg.
1. American Academy of Pediatrics. Otitis media with dysfunction in young children: 2004;131(6):797-803.
a comparison of 1412-29. OME guidelines.
2. Bluestone CD. State of the art: definitions and classifications. In: Liu DJ, Bluestone
CD, Klien JO, Nelson JD (Eds). Recent Advances in Otitis Media with Effusion.
Proceedings of the 3rd International Conference. Ontario: Decker and Mosby; 1984.
716
Chapter 148
Pediatric Sinusitis
Devinder Rai
Introduction that result in a viral rhinosinusitis (a diffuse mucositis

that predisposes to approximately 80% of bacterial sinus
The paranasal sinuses in childhood are difficult to evaluate infections) and allergic inflammation (that predisposes to 20%
because of the variability in size, shape, and patterns of of bacterial sinus infections). Children have 6–8 viral upper
development. However, the child’s sinuses are affected by a wide respiratory infections each year; it is estimated that 5–13% of
spectrum of conditions including congenital abnormalities, these infections may be complicated by a secondary bacterial
inflammatory, traumatic and neoplastic conditions. infection of the paranasal sinuses.
At birth, both the maxillary and ethmoid sinuses are present; Sinusitis in children is also associated with an increased
however, they are diminutive in size. Thus, they may appear to risk of complications. The complications of sinusitis may be
be opacified in infants in good health. As sinus development divided into orbital, intracranial and local complications. The
proceeds, opacification or mucous membrane thickening increased risk may be attributed to the low immunity of the
continues to be physiological till about 6 years of age. children as well as the low bone density of the lamina and the
The sphenoid sinus is underdeveloped and non- fovea ethmoidalis.
pneumatized at birth and only starts to aerate at about 3 years
of age. The varying degrees of pneumatization of the sphenoid
sinus results in three types:
CLASSIFICATION
1. Conchal According to duration of sinusitis:
2. Presellar 1. Acute Sinusitis (7 days to 4 weeks)
3. Sellar. 2. Subacute sinusitis (4–12 weeks)
The last sinus to develop is the frontal sinus, which starts 3. Chronic sinusitis (persistence of symptoms beyond 3
appearing at the age of 6 and only completes its aeration by the months).
age of 15. Depending upon the extent of aeration of the frontal According to etiology or the causative factors:
recess, which is the narrow hourglass shaped doorway leading 1. Bacterial
to the frontal sinus, Kuhn divided the cells in the recess into 2. Fungal; Fungal sinusitis is usually seen in children
four types: who are immunocompromised. Thus, the cause of
1. Kuhn Type 1—Single cell above an agger nasi cell immunocompromise if any should be searched for in any
2. Kuhn Type 2—Two or more cells above and behind agger child suffering from fungal sinusitis. The cause could be
nasi cell uncontrolled Type 1 diabetes, children undergoing steroid
3. Kuhn Type 3—Single large cell above agger nasi, therapy, HIV infection, or those suffering from neoplastic
pneumatized into frontal sinus (<50% the height of frontal conditions of the blood cells
sinus) 3. Allergic sinusitis without polyposis: children are inherently
4. Kuhn Type 4—Single large cell above agger nasi, prone to allergies, which is manifested as nasal discharge
pneumatized into frontal sinus (>50% the height of frontal and nasal obstruction leading to obstructive sleep apnea
sinus). symptoms
4. Allergic sinusitis with nasal polyposis: nasal polyposis,
being relatively common in adults is rarely seen in children.
SINUSITIS
Any child with polyposis should be further examined to
The common predisposing events that set the stage for acute rule out ciliary dyskinesia syndromes, cystic fibrosis and
bacterial sinusitis are acute viral upper respiratory infections other similar diseases.
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BACTERIOLOGY 2. Double vision in more advanced cases leading to loss of

vision in extreme cases
The usual bacteria implicated in sinusitis are Streptococcus 3. Signs indicating intracranial involvement like meningismus
pneumoniae, Haemophilus influenzae, and Moraxella and altered sensorium.
catarrhalis. Other lesser common bacteria isolated were
Staphylococcus aureus, Bacteroides, Peptostreptococcus,
Fusobacterium, and Prevotella. COMPLICATIONS
In immunocompetent children the usual fungal species There is an increased incidence of complications in pediatric
responsible are Aspergillus and Candida. However, in sinusitis due to the following reasons:
immunocompromised individuals, there is a greater incidence 1. Thinner bony septa and sinus walls
of invasive fungal sinusitis with Rhizopus and Mucor spp. 2. Greater porosity of bones
3. Larger vascular foramina
NATURAL HISTORY 4. Open suture lines.
The complications occurring in sinusitis can be divided
Usually, bacterial sinusitis occurs as sequelae of viral sinusitis. into orbital, intracranial or local complications. The incidence
Every child on an average has about 5–7 attacks of allergic of orbital complications is higher with about 75% of pediatric
rhinitis per year. The most common causative factor is viral. sinusitis cases presenting with an orbital complication. This
Due to viral rhinitis there is increased nasal discharge greater incidence of orbital complications can be attributed to
or rhinorrhea along with nasal congestion and edema of the the close relationship between the sinuses and the orbit, which
nasal mucosa. Another effect of viral infection is that there is are separated only by a thin bone, the lamina papyracea, which
ciliary dysfunction leading to impaired clearance of secretions has congenital dehiscences.
particularly in the sinuses. This leads to stasis, which over Chandler et al., divided the orbital complications into five
a period of time undergoes secondary infection leading to stages:
bacterial sinusitis along with all its signs and symptoms. 1. Stage of preseptal cellulitis
Due to the bony immaturity of the pediatric skeleton 2. Stage of orbital cellulitis
and thin intervening septa between the eye and the ethmoid 3. Stage of subperiosteal abscess
sinuses there is an increased incidence of complications in 4. Stage of orbital abscess
pediatric sinusitis. 5. Stage of cavernous sinus thrombosis.
SYMPTOMOLOGY PRESEPTAL CELLULITIS

The typical symptoms of nasal obstruction, nasal discharge This is the first stage of orbital complications of sinusitis.
and headache as seen in the adult population are rarely seen About 30% of children with sinusitis have preseptal cellulitis
among young children. Thus indirect signs are considered as as the initial presentation. The signs include eyelid edema
pointers to a possible sinusitis in infants and young children. and erythema. There is normal extraocular muscle movement
The diagnosis of pediatric rhinosinusitis is usually based and normal vision. The diagnosis of preseptal cellulitis is
on a combination of history, physical examination, laboratory based upon the characteristic clinical picture and radiological
investigation and radiological findings. finding. The radiologic findings include diffuse thickening of
The first and perhaps most common clinical indicator of the lids and conjunctiva.
sinusitis in children is similar to that of a viral upper respiratory Medical therapy is usually sufficient in preseptal cellulitis
tract infection which is refractory to supportive therapy. which consists of IV antibiotics, head end elevation and warm
According to Lusk, it is virtually impossible to differentiate compresses. Decongestant therapy consisting of mucolytics,
between an upper respiratory tract infection and rhinosinusitis topical and systemic decongestants should be instituted to
during the first 7–10 days of symptomatology. Symptoms may facilitate drainage of sinuses.
include:
1. Rhinorrhea which may be serous or mucopurulent
2. Nasal congestion ORBITAL CELLULITIS
3. Cough This stage consists of post-septal infection, which is
4. Low grade fever, malaise and irritability characterized by eyelid edema and erythema. On external
5. Dental pain. examination, chemosis and proptosis may be present.
However, in more advanced cases, there may be high- Extraocular muscle movement may or may not affect in this
grade fever and a profuse purulent nasal discharge. Always stage. Vision is normal though blurring may be present due
this should also raise the suspicion of a nasal foreign body in to proptosis. There is no discrete abscess however localized
infants. Once excluded, this may be the sign of acute sinusitis. inflammation signs are positive. Radiologically there is a low
Several warning signs point to an impending complication of attenuation next to lamina papyracea.
acute sinusitis like: Orbital cellulitis stage may be managed the same as the
718 1. Periorbital pain and swelling stage of preseptal cellulitis. However, due to advanced stage
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Chapter 148: Pediatric Sinusitis
frequent visual acuity testing and extraocular movement characteristic. However, imaging used in confirming diagnosis
testing is warranted. Surgical drainage is indicated if no consists of MRI Venogram in addition to CT scan. Cerebral
improvement or worsening of symptoms is seen after 48 hours angiography is invasive and not very sensitive to the diagnosis
of medical therapy. of cavernous sinus thrombosis.
Treatment includes early diagnosis and prompt medical
therapy consisting of IV antibiotics. Drainage of sinuses to
SUBPERIOSTEAL ABSCESS
remove the source of infection is a must and should be done
The stage of subperiosteal abscess is characterized by pus as soon as possible. The role of anticoagulants like heparin is
formation between the periorbita and the lamina papyracea. controversial. Heparin should be used only if diagnosis is made
This displaces the orbital contents downward and laterally. within a few hours. In more delayed cases anticoagulants like
On local examination there is proptosis, chemosis, and total warfarin may be tried.
ophthalmoplegia. There is thus and increased risk of residual
visual sequelae. The pus may rupture through the septum and
LOCAL COMPLICATIONS
present in the eyelids. On CT scanning there is a rim enhancing
hypodensity with mass effect adjacent to lamina. The basic premise of sinusitis is that it is always rhinologic in
Treatment consists of combined medical and surgical origin. The ideology being that rhinitis causes the nasal mucosa
approaches. Only medical therapy has a success rate of about to undergo inflammation leading to edema and blockage of
50–67%. Combined approach is successful in 95–100% of the the sinus prechambers leading to accumulation of secretions
cases. Due to the morbidity associated with loss of eye function, in them which undergo secondary infections leading to
we advocate an aggressive approach consisting of surgical sinusitis. The local complications of sinusitis are particularly
drainage along with medical therapy consisting of IV antibiotics, more common in children as compared to adults due to the
systemic and topical decongestants and supportive therapy. immature bony skeleton and incompletely closed foramina.
The surgical approach depends upon the location and In an acute case there is an incidence of frontal bone
extent of the abscess in question. In case of medical abscesses osteomyelitis, which is termed as Potts Puffy Tumor. This is
and endoscopic orbital decompression is preferred. However, in a misnomer as there is no actual tumor but a subperiosteal
case of lateral abscesses an external ethmoidectomy via lynch collection of pus in the frontal bone usually secondary to
incision or a transcaruncular approach is considered best. frontal sinusitis.
The other local complications of sinusitis in children are
mucoceles and pyoceles. Pyocele is a collection of pus within
ORBITAL ABSCESS
a walled cavity usually present in the ethmoid or the sphenoid
Orbital abscess is characterized by pus formation within orbital sinus leading to a myriad of symptoms depending on the sinus
tissues. On local examination there is exaggeration of signs involved and its surrounding structures. A similar presentation
seen in subperiosteal abscess. There is visual impairment, but when the walled cavity contains sterile fluid it is termed
which may range from blurring of vision to total visual loss. as a mucocele. Sphenoidal mucoceles are considered more
Vision loss constitutes an emergency and according to studies, dangerous due to the close proximity of the optic nerve, which
the surgeon has about 100 minutes to save the vision before passes in the posterolateral wall of the sphenoid sinus, which
the loss becomes irreversible. On CT scanning there is a rim invariably gets compressed due to the mucocele leading to
enhancing hypodensity within the orbital tissue, which may visual deficits. According to various studies once the optic
extend to the intraconal region. nerve gets involved or compressed, the surgeon has about 60
Orbital abscess with its ominous complication of minutes to decompress the nerve in order to save its function
irreversible vision loss must be treated aggressively with before irreversible functional deficits occur, leading to the
surgical drainage the primary modality of treatment in addition concept of the “golden hour”.
to medical therapy.
INTRACRANIAL COMPLICATIONS
CAVERNOUS SINUS THROMBOSIS Due to the bony immaturity, thin fovea ethmoidalis and
This dreaded complication of sinusitis is characterized numerous foramina that remain open in children till full
by formation of clots in the cavernous sinus secondary to ossification takes place there is an increased incidence of
infection because of activation of the coagulation cascade. This intracranial complications as compared to adults. The signs
condition is associated with chemosis, exophthalmos, decrease and symptoms that the children present with are also subtle,
or loss of vision, headaches or paralysis of the cranial nerves 3, thus a high degree of suspicion is needed to diagnose the
4, 5, 6. Other common signs include signs of raised intracranial intracranial complications.
tension and sepsis. Infection can spread to contralateral sinus There are five types of intracranial complications of
within 24–48 hours. sinusitis in children:
Clinical acuity and testing is paramount to diagnosis as 1. Meningitis
the signs and symptoms of cavernous sinus thrombosis are 2. Epidural abscess
719
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3. Subdural abscess rhinoscopy is a must in every case. Flexible fibreoptic

4. Brain abscess nasendoscopy is an invaluable tool in order to better assess
5. Cavernous sinus thrombophlebitis. the nasal cavity and the sinus prechambers. Laboratory
These complications can also be considered as a spectrum investigations include nasal smears for bacteriology, blood
of progression of disease. Thus the symptoms can be quite work for leukocytosis, culture and for diagnosis of sepsis. The
overlapping and confusion to the surgeon and the final gold standard for the diagnosis of acute bacterial sinusitis
diagnosis is often made radiologically. The common symptoms is the recovery of bacteria in high density (≥104 colony-
include general symptoms like fever, irritability, vomiting, forming units/mL) from the cavity of a paranasal sinus. Blood
seizures, and altered sensorium. Specific symptoms include investigations may also rule out immunodeficiency conditions
hemiparesis, visual disturbances and other neurological and ciliary dyskinesia.
deficits. Thus ruling out sinusitis is an important part of In children below 6 years of age with uncomplicated
working up a child with such symptoms even with no preceding sinusitis radiography is generally not indicated. However,
complaints of nasal discharge or obstruction. the American College of Radiology has taken the position
The most common microorganisms isolated in children that the diagnosis of acute uncomplicated sinusitis should be
include S. pneumoniae, S. aureus, Gram-negative rods, and made on clinical grounds alone. They support this position
anaerobes. by noting that plain radiographs of the paranasal sinuses are
technically difficult to perform, particularly in very young
Meningitis: Acute bacterial meningitis follows sinusitis and children. Correct positioning may be difficult to achieve
presents with all the general malaise symptoms in the child. and therefore the radiographic images may overestimate
In addition the child may have neck rigidity on examination and underestimate the presence of abnormalities within the
and photophobia. The child may also present with cranial paranasal sinuses.
nerve palsies. Upon examination, the various tests done are CT scans of the paranasal sinuses should be reserved for
the Kernig’s sign and Brudzinki’s sign. Radiologically there patients in whom surgery is being considered as a management
may be enhancement along the meninges but with no abscess strategy (strong recommendation based on good evidence and
formation. strong panel consensus).
In complicated cases, radiography is invaluable in
EPIDURAL AND SUBDURAL ABSCESS assessing the extent of disease as well as differentiating the
type of complications present. In case of a suspected intra
Due to the usual ambiguity between the two types of abscesses, cranial complication MRI may be considered as it has greater
which are close to one another, they may be considered sensitivity and specificity as compared to a CT scan.
together. They present with fever with chills and rigors, Lumbar puncture maybe considered to confirm the
headache and vomiting. Due to raised intracranial tension presence of meningitis; however, an ophthalmology consult
there may be features of papilledema upon fundoscopic must be sought prior to this invasive procedure to rule out
examination. Epidural and subdural abscess are differentiated raised ICT, as it may be fatal in such cases.
from one another radiologically. Epidural abscess presents
with a rim shaped enhancement on CT scanning, whereas
subdural abscess presents with biconvex or crescentic TREATMENT
enhancing lesions. Subdural abscess also have a higher rate of For the sake of discussion, treatment of pediatric sinusitis
residual neurological sequelae, which are present in 35–55% of can be divided into uncomplicated cases and cases with
the cases. complications. However, treatment strategies are aimed to
be aggressive due to the fulminant and rapid progression of
infection in children.
INTRACEREBRAL ABSCESS
The mainstay of treatment of acute uncomplicated
In the present antibiotic era, brain abscesses have become bacterial sinusitis is antibiotics, which may be parenteral or
extremely rare. However, if present they present the surgeon oral depending upon variables like severity, general condition
as an emergency with symptoms of altered sensorium, focal of the child. In all suspected cases of complications hospital
neurological deficits, seizures, and papilledema. There is also a admission and IV antibiotics are a must. Supportive therapy
grave prognosis as there is a 20–30% risk of mortality associated including systemic and topical decongestants is controversial
with it. On CT scanning there is hypodense lesion in the brain, once sinusitis has set in. A short burst of corticosteroids
usually in the frontal or temporoparietal lobe with peripheral may be given in atopic children to manage the symptoms
rim enhancement. but should be used with caution in fungal sinusitis. The
following treatment algorithm has been recommended by the
Subcommittee on Management of Sinusitis and Committee on
DIAGNOSIS Quality Improvement Paediatrics in 2001.
A high clinical suspicion and rapid diagnosis is a must for In complicated cases of sinusitis the treatment is more
pediatric sinusitis due to rapid progression of infection. A aggressive as compared and involves prompt radiography to
720 detailed history and clinical examination including anterior diagnose the complication. In cases of orbital complication,
ch-148.indd 720 11/22/2016 12:11:58 PM

Chapter 148: Pediatric Sinusitis
Algorithm 1
Algorithm 2
721
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prompt surgical drainage of sinuses in addition to IV antibiotics

is recommended except in Stage 1, where the role of surgery is Key points
debatable. In Stage 3 and above surgery is a must to prevent ))
Bacterial sinusitis in children is usually preceded by viral
further complications. The norm is to do an endoscopic rhinitis, which is one of the most common diseases in children
drainage of the sinuses and also to do an orbital decompression ))
Usual bacteria implicated are S. pneumoniae, H. influenzae, and
and remove the lamina papyracea. M. catarrhalis
The treatment in intracranial complications is to first ))
The symptoms include runny nose, nasal obstruction, fever
differentiate between meningitis and frank abscess formation. and cough
This can be done by ruling out raised ICT through a retinal ))
High index of suspicion, anterior rhinoscopy and nasendo
fundoscopy. In case of an abscess formation, surgical drainage scopy is a must to diagnose pediatric sinusitis
is a must and should be done as early as possible. Drainage ))
Increased rate of complications of sinusitis in children, which
consists of removal of pus from the abscess as well as drainage may be local, orbital or intracranial
of the paranasal sinuses. Thereafter antibiotic therapy and ))
In case of complications IV antibiotics, prompt management
supportive management should continue. and imaging is a must
In cases of mucocele and pyoceles, surgical drainage ))
Surgery may be needed on an emergent basis to prevent
and decompression of the surrounding structures is the only vision loss in advanced orbital complications.
option as supportive therapy has no role it the management.
In cases of Sphenoidal lesions, which compress the optic
nerve decompression of the nerve, must be carried out in the SUGGESTED READINGS
same sitting.
1. American Academy of Pediatrics. Subcommittee on Management of Sinusitis and
Committee on Quality Improvement. Clinical practice guideline: management of
Clinical Pearls sinusitis. Pediatrics 2001;108(3):798-808.
2. Chandler JR, Langerbrunner DJ, Stevens ER. The pathogenesis of orbital
• Antibiotics in all cases of sinusitis in children less than 2 years of complications in acute rhinosinusitis. Laryngoscope. 1970;80:1414-28.
age or in those who have had a complication in the past 3. Kuhn FA. Chronic frontal sinusitis: the endoscopic frontal recess approach.
Operative Techniques Otolaryngol Head Neck Surg. 1996;7:222-9.
• Early recognition of warning signs a must for successful 4. Lusk RP, Stankiewicz JA. Pediatric rhinosinusitis. Otolaryngology—Head and
treatment and prevention of complications Neck Surgery. 1997;117(3):S53-7.
• Limited role of antihistaminics and systemic decongestants, IV 5. Mackay IS, Lund VJ. Classification and differential diagnosis of rhinosinusitis.
antibiotics is the mainstay of treatment In: Michael Gleeson (Ed). Scott Brown’s Otorhinolaryngology, 7th edition. pp.
2008;1380-6.
• Multidisciplinary team to successfully diagnose and treat
6. Miller AJ, Amedee RG. Sinus anatomy and function. In: Bailey BJ et al. (Eds).
sinusitis and its complications Otolaryngology—Head and Neck Surgery. 1(31): 413-21.
• Early radiography may remove doubt in most cases 7. Ott NL, O’Connell EJ, Hoffman AD, Beatty CW, Sachs MI. Childhood Sinusitis.
• Prompt surgical intervention is a must in case of visual deficit Mayo Clin Proc. 1991;66:1238-47.
and threatening complications. 8. Stammberger H, Lund VJ. Anatomy of the nose and paranasal. In: Gleeson M (Ed).
Scott Brown’s Otorhinolaryngology, 7th edition. pp. 2008;1315-43.
722
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Chapter 149
Stridor in Children
Arvind S Bais

It is not uncommon to come across many young anxious
parents seeking advice for their child’s problem of noisy • As the internal diameter of the infant larynx is small even
breathing. 1 mm of edema in the subglottic area narrows the airway
It is believed that less than 10% of the new born babies have to approximately 50% as compared to adults in whom no
some kind of noisy breathing and all of them do not fit into the significant change occurs.
category of congenital laryngeal stridor.
The gravity of the situation is enormous in infants. The
Clinical Pearl causes of stridor can be divided into: (A) Congenital and (B)
Acquired.
• It is important to know that no clinical entity as congenital
laryngeal stridor existing pathology in the upper airway and CONGENITAL CAUSES
needs evaluation.
• Laryngo tracheal stenosis
In clinical practice, a variety of terms are frequently used to • Laryngeal atresia
describe the noisy breathing which are given in table 1. • Laryngomalacia
It is essential to know that there are some basic differences • Tracheomalaci
• Laryngeal webs
between the larynx of an infant and adult larynx. A proper
• Laryngeal cysts
understanding which helps in treatment planning.
• Vascular abnormalities such as:
Infant larynx:
{{ Aberrant left subclavian artery
• Situated higher up in the neck close to the base of the
{{ Innominate artery compression
tongue
{{ Double aortic arch
• The size is small
• Vocal cord palsy.
• Epiglottis is infolded
• The aryepiglottic folds are large
• The internal diameter of the larynx is small ACQUIRE CAUSES
• The mucous membrane of the larynx is loosely attached
• Laryngeal trauma
especially in the subglottic region
• Fixation of the arytenoid
• The entire cartilaginous framework of the larynx is soft.
• Epiglottitis
Table 1: Terms frequently need to describe noisy breathing • Croup
• Multiple laryngeal:
Site of origin {{ Papilloma
Wheeze Intrathoracic airways • Bilateral abductor palsy of the vocal cords

Stridor Extrathoracic airways • Cystic hygroma
• Hemangioma may be congenital or acquired
Rattle Either of the above or both
• Foreign bodies in the airway, i.e., larynx, trachea, and the
Snuffle Nose and nasopharynx bronchus
ch-149.indd 723 11/24/2016 2:41:05 PM

• Reflux laryngitis. • Immediate measure requires tracheostomy following

endoscopy.
Laryngo-tracheal Stenosis • Abalation of the web by CO2 laser.
• Adopt the policy of wait and watch if the symptoms are
mild. Allow the time for growth. Laryngeal Cysts
• If severe stridor is present do tracheostomy. True congenital cysts of the larynx are extremely rare. There
• Laryngo-tracheal reconstruction can be done at a later is severe stridor endoscopy reveals cystic swilling completely
date. distorting the view of the larynx, originating from the
aryepiglottic folds. Manage by Aspiration of fluid from the cyst,
Laryngeal Atresia allow it to collapse and then followed by complete excision
of the cyst wall. The procedure is known as deroofing and
• It is usually incompatible with life.
excision.
Laryngomalacia
It is most common condition the clinical findings are as follows:
ACQUIRED CAUSES
• Type I—The epiglottis is omega shaped
• Type II—The aryepiglottic folds are foreshortened Epiglottitis
• Type III—The arytenoids have loosely attached mucous Inflammation of the supraglottic Larynx caused by H.
membrane or one may see a combination of both. influenzae type B and rarely by streptococci and pneumococci.
Asses by:
Diagnosis • Postural inspiratory stridor
Use flexible endoscope to assess the status of the larynx in • Drooling
spontaneous respiration. It is a self-limiting disease. No need • Thick mucus secretion
for tracheostomy: • High temperature.
• Occasionally supraglotto Recommended:
• Plasty in from of trimming of the soft tissues of the larynx • Pulse oximetry
may be required • Monitor arterial blood gas (ABGS)
• Symptoms usually subside by 2‒3 years of age. • Humidification
• Oxygenation
• Tracheostomy rarely done.
Clinical Pearl
• Genetic or familial incidence does occur. Reassure the parents Clinical Pearl
regarding clinical improvement over a period of time.
• There is no evidence to show that the systemic corticosteroid
is useful yet it is widely administered by pediatricians and
otolaryngologists.
Tracheomalacia
• The incidence ranges between 1 in 1,500 and 1 in 2,000
children. Diagnosis is by CT and MRI. Croup
• Bronchoscopy reveals flattening of the trachea anteriorly Most common between 6 months and 5 years of age. Commonly
or at the junction of middle and lower third of the trachea occurs in winter and is viral in origin.
use of antibiotics is recommended to prevent bronchitis.
• In severe cases surgery is indicated. Symptoms
• Inspiratory stridor
Clinical Pearl • Fever
• Barking cough.
• The parents should be advice to bring their child for regular
check-up in order to minimize unnecessary usage of antibiotics Diagnosis
and overcome anxiety. Lateral X-ray of the neck in extended position will reveal
enlarged edematous epiglottis, called as Thumb sign or a
tapered subglottic area called “steeple sign” is seen.
Laryngeal Webs
In the third month of gestation if the larynx fails to get Management
recanalized web forms. In majority of cases webs are located Always admit the child. Humidification does not give much
anteriorly and are usually thick and complete: relief. Administer nebulized adrenaline. For moderate to severe
724 • Patient presents with severe stridor cases systemic or nebulized corticosteroids is recommended.
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Chapter 149: Stridor in Children
• Proper history taking and clinical observation followed by

Clinical Pearl auscultation
• Note the type of stridor
• Repeated clinical examination is most desired intervention as • Any relationship with change of posture. Note does it gets
the clinical condition may worsen. aggravated or stops by change of posture or while feeding
• Note the duration of stridor
• Is it continuous, regular or intermittent
Foreign Bodies in the Airways • Any change in the pattern of stridor while crying
History of aspiration of foreign bodies in most of the cases • Is there any aspiration while taking feeds
occasionally no history of aspiration yet the child may have • Asses the neurodevelopmental status of the infant. It is very
violent cough, breathing difficulty, difficulty in swallowing and helpful in cases of laryngomalacia.
inspiratory stridor.
Management: Clinical Pearls
• Ensure adequate airway
• Do not classify stridor as wheeze as one may miss upper airway
• Oxygenation in severe stridor
obstructive pathology.
• Prophylactic antibiotics and systemic corticosteroids to be
given on need based cases • Always look for respiratory distress, at times even slow
• Plan for quick intervention in form of pan endoscopy, respiratory rate. There may be evidence of Hypoxia, Hypercarbia
and even cyanosis.
i.e., laryngoscopy bronchoscopy and in few cases
esophagoscopy is required because foreign bodies in the
upper end of esophagus is a common cause of unsuspected
partial airways obstruction
Abnormalities of the Cry
• Endoscopic procedure requires good team work between • In unilateral vocal cord palsy weak cry but obstructive
pediatrician otolaryngologist and anesthetist airway symptoms are missing
• Premedication is always by Atropine injection. • In bilateral vocal cord palsy the cry is weak but clear
• Spontaneous anesthesia by use of nitrous oxide, oxygen • In tracheomalacia barking cough with or without stridor is
and halothane present
• Rarely muscle relaxant may be given. • Absent or Muffled cry is noted in laryngeal web.
Instruments:
• All types of rigid pediatric laryngoscopes including
anterior commissure laryngoscope rigid bronchoscopes
with internal diameter of 2.5 mm, 3 mm, 4 mm or 6 mm Algorithm 1
with facility for ventilation telescopes with an angle of 0, 30, Workup of a child with stridor
and 70 degree and all types of foreign body removal forceps
and powerful suction apparatus is a must.
• Tracheostomy tray should be kept ready one may need it
at times.
Clinical Pearls
• In foreign bodies in the airway cases there is no viral prodrome.
• Always prefer to use rigid endoscopes as a flexible
bronchoscope fails to give the depth of the field.
SUBGLOTTIC HEMANGIOMA
• May be congenital or acquired.
• Large hemangioma produces inspiratory stridor.
• Removal by CO2 laser.
• Radiotherapy is contraindicated.
• Always look for cutaneous.
HEMANGIOMA IN SUCH CASES

In all cases of stridor the essential broad principles of approach
is as follows:
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Physical Signs ))
Flexible endoscopy is helpful for screening, but for removal of
Inspiratory stridor: foreign bodies form the airway rigid endoscopy is preferred
• Breathing is rapid ))
Never use jet ventilation anesthesia in cases of surgery of
• Recession of the suprasternal and Intercostal spaces multiple papilloma of the larynx because of seedling and
• In drawing of the epigastric region recurrence
• Flaring of the nostrils. ))
Autogenous vaccine and acyclovir do not give any benefit in
laryngeal papilloma cases
Nasal Patency Test ))
If there is delay in setting up OT trolly always intubate the child
and oxygenate
Put a small piece of cotton in front of the baby’s nostril and ))
For laryngoscopic evaluation with a rigid laryngoscope
observe for to and fro movement of cotton. Less movement on in infants never try to lift the epiglottis with the tip of
one or both sides gives an idea of nosal block. It helps in ruling laryngoscope as severe laryngeal spasm may occur. Just wait
out nosal causes of noisy breathing. for few seconds spontaneous visualization is possible because
in infants the larynx is very close to the base of the tongue
Radiology ))
If foreign body such as seed of any such object has been
removed piecemeal then always do a check bronchoscopy
• Lateral skiagram of neck in extended position is a must
before discharging the patient from the hospital as a small
• CT and MRI is very helpful in cases of stenosis and foreign bodies if left in the bronchus may cause serious
tracheomalacia complications later on
• Contrast radiography is not indicated except in cases of ))
Be careful in bronchoscopy as one may override a foreign
suspected vascular abnormalities body and nothing may be found
• Chest X-ray PA and lateral view should always be done. ))
Carina is the thinnest part of tracheobronchial tree respect
it while doing the endoscopy. A small tear may lead to
spontaneous pneumothorax
Key points
))
Never waste time in removing a foreign body especially in
))
Supraglottic lesion causes inspiratory stridor while subglottic demonstrating its location as it may slip deeper down and
pathology may cause biphasic stridor make the whole procedure difficult and time consuming
))
Clinical evaluation of the patient cannot be overemphasised, ))
Gastroesophageal reflux may play a major role in acquired
it is a must abnormalities in older children. In cases of laryngeal stenosis
))
Follow the principle of observation, palpation, and be treated first.
auscultation of the chest and neck also for any tracheal thud
))
Never hesitate to consult anesthetist for proper management
of airway, i.e., intubation, oxygenation tracheostomy and for SUGGESTED READINGS
endoscopy anesthesia
))
Monitor oxygen saturation and arterial blood gas estimation 1. Cummings CW, Richardson MA, et al., Stridor and airway management. In: David
Albert, Susanna Leighton (Eds). Otolaryngology Head and Neck surgery, 3rd
))
Ultrasonography may be needed in vocal cord palsy
edition. pp. 285-8.
))
Prefer laryngeal intubation than tracheostomy as much as 2. Cummings CW. Congenital disorders of the Larynx. Otolaryngology Head and
possible Neck surgery. pp. 262-84
))
In severe cases of stridor shift the patient to OT where all 3. Ear Nose and Throat Disorders. Mosbys Clinical Nursing Series, pp. 190-5.
facilities for anesthesia, ventilator support, tracheostomy and 4. Seiden AM, Gluckman JL, et al. Congenital disorders. In: Padhya TA, Wilson KM
endoscopy are available (Eds). Otolaryngology the Essentials. pp. 247-51.
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Chapter 150
Upper Airway Obstruction and
Sleep Related Breathing Disorders
Girish Raheja
INTRODUCTION Box 1: Clinical indicators of childhood obstructive sleep

Habitual snoring during sleep, the hallmark indicator of apnea
increased upper airway resistance, is an extremely frequent • Symptoms and signs anatomical and physiological characters
occurrence during childhood, with a median incidence of • Snoring underweight or overweight
about 10% among preschool and school-aged children, with • Witnessed apnea tonsillar hypertrophy
subsequent declines in frequency after 9 years of age. The
• Labored breathing adenoidal hypertrophy
exact polysomnographic criteria that differentiate between
• Restless sleep allergic rhinitis
innocent snoring (i.e., habitual snoring that does not lead to
gas exchange abnormalities, sleep disruption and/or to any • Mouth breathing micrognathia/retrognathia
morbid consequences), and snoring that is associated with • Impaired behavior high-arched palate
adverse consequences, have yet to be defined. Nevertheless, • Nasal blockage laryngomalacia
a consensus statement has been generated, and defines a set • Sweating during sleep neuromuscular disorder
of empiric criteria, on the basis of which we currently estimate
• Cyanosis prematurity
that of the many children with habitual snoring; approximately
2–3% will have clinically relevant disease. Therefore, the ratio • Daytime sleepiness failure to thrive
between symptomatic habitual snoring and obstructive sleep • Family history hypertension
apnea is usually between 3:1 and 5:1. • Obstructive sleep apnea
Whenever lymphoid tissue in a child occupies a
disproportionate amount of space in the oropharyngeal
region, it causes a compromise airway. The problem can be including hyperactivity, lack of stamina, poor attention spans
made more intense by associated anatomic conditions such and daytime sleepiness or tiredness (Box 1).
as craniofacial abnormalities, obesity, laryngomalacia and These disturbances in sleep are collectively called sleep
conditions with diminished neuromuscular tone as in Down related breathing disorders (SRBD). One such syndrome is
syndrome and cerebral palsy. called upper airway resistance syndrome (UARS) where a child
Tonsilar adenoid hyperplasia is often associated with upper with a significantly obstructive nose causes snoring, mouth
airway obstruction in children. During daytime these children breathing without significant apneas but a significant increase
demonstrate an altered muffled “Hot Potato” closed voice with in respiratory effort related arousal giving rise to daytime
mouth breathing, rhinorrhea and hyponasal speech. fatigue and poor performance. This is now considered akin to
It is however during sleep they exhibit signs of the full mild obstructive sleep apnea (Box 2).
spectrum of airway obstruction. This is due to the relaxation
of the oropharyngeal relaxation leading to further obstruction.
These children may usually snore loudly with cessation of
breathing for intermittent periods with sternal retraction and Children with significant obstructive sleep apnea if not treated
paradoxical movement of the chest. The negative physiological may land up with cor pulmonale, right ventricular hypertrophy,
outcome includes hypoxemia, hypercapnia and acidosis congestive heart failure, pulmonary hypertension and edema,
which leads to arousals, awakenings and a poor quality sleep. failure to thrive and are at a definitive risk for permanent
These children demonstrate a variety of behavioral problems neurologic damage and even death.
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Box 2: Symptoms and signs of obstructive sleep apnea Clinical Pearl

syndrome
• History: Headaches on awakening
{{
• Evaluation of the nasopharynx is only possible with a high quality
radiograph requiring an experienced radiology technician.
{{ Frequent snoring (≥3 {{ Daytime sleepiness
nights/week) {{ Attention-deficit/
{{ Labored breathing during hyperactivity disorder The full extent of the problem can only be diagnosed with
sleep {{ Learning problems
a full night polysomnography; however, in practical life the
{{ Gasps/snorting noises/
availability of pediatric sleep labs and the ability of the parent
• Physical examination:
observed episodes of to conduct the study with a small child in a new environment
{{ Underweight or overweight
apnea is wrought with errors and therefore most clinicians find
{{ Tonsillar hypertrophy
{{ Sleep enuresis (especially it convenient with clinical examination to interpret signs
{{ Adenoidal facies
secondary enuresis)* and symptoms as explained in literature to determine the
{{ Micrognathia/retrognathia
{{ Sleeping in a seated presence or absence of obstructive sleep apnea in children.
{{ High-arched palate In a large majority this clinical decision-making is shown
position or with the neck
hyperextended {{ Failure to thrive to be accurate. However, it may benefit a child with severe
{{ Cyanosis {{ Hypertension problems to consult with a pulmonologist and a cardiologist
*Enuresis after at least 6 months of continence.
to rule out the ore significant and dangerous complications of
obstructive sleep apnea.
The prevalence of obstructive sleep apnea in children Clinical Pearl

is 1–4% and surprisingly up to 10% of children may present
with primary snoring. Physical examination should include • Polysomnography is the gold standard for the diagnosis of
obstructive sleep apnea and disordered breathing; however, in
the patient’s weight, height, and body mass index. Detailed
the absence of availability the clinician will need to relay on his
examination should be of heart and lung, head, and neck with
clinical judgment for management of patients presenting with
special emphasis to adenoids, tonsils, mandible, and mid facial
signs and symptoms as listed in the tables 1 and box 3 text.
development. Adenoid facies is perhaps the most common
observation.
Tonsil size should ideally be scaled from 1–4. Scale 1 being In behavioral studies these children demonstrate a high
mild hypertrophy and Scale 4 would compromise more than prevalence of altered behavior such as withdrawal, anxiety,
75% of the oropharyngeal airway. The adenoid size is best emotional lability, impulsivity, hyperactivity, aggressiveness,
evaluated with a soft tissue lateral neck radiograph to assess
the anteroposterior dimension of the nasopharynx. However, Table 1: Symptoms and signs suggestive of sleep apnea
the correlation to the clinical symptoms is still effected by hypopnea syndrome in children
subjectivity.
Nighttime Daytime
Continuous snoring (not Normal
Algorithm 1 only in exacerbation)
Sleep related breathing disorders Observed respiratory Daytime oral breathing, nasal vioce,
pauses adenoid facies
Noisy breathing Tonsillar hypertrophy
Oral breathing Facial dysmorphia (retrognathia,
micrognathia, marcoglosia, midfacial
hypoplasia)
Increased respiratory Difficulty to wake up, tiredness upon
effort (supra-sternal and getting up, morning headaches,
intercostal retraction) daytime sleepiness
Nocturnal sweating Alterations in behavior (hyperactivity,
aggressiveness, irritability, low school
performance level)
Abnormal sleep posture Delayed growth and low height/
(hyper-extension of the weight development
neck)
Restless nocturnal sleep Obesity
Cyanosis Strong second heart sound
Nocturnal enuresis Systemic arterial hypertension
728 Presence of metabolic syndrome
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Chapter 150: Upper Airway Obstruction and Sleep Related Breathing Disorders
Box 3: Symptoms and signs of obstructive sleep apnea

psychosomatic presentations, social problems, etc., in com
syndrome parison with their peers.
There is some suggestion that behavioral patterns may
History: • Attention-deficit/ also be associated with reduced verbal abilities and language
• Frequent snoring (≥3 nights/ hyperactivity disorder
scores possibly a result of hypoxemia induced dysfunction
week) • Learning problems of the frontal lobe. However, this supposition needs to be
• Labored breathing during sleep Physical examination: substantiated with research in future.
• Gasps/snorting noises/ • Underweight or overweight
observed episodes of apnea
• Tonsillar hypertrophy ADENOID AND TONSIL SURGERY FOR
• Sleep enuresis (especially
secondary enuresis)*
• Adenoidal facies OBSTRUCTIVE SLEEP APNEA
• Micrognathia/retrognathia
• Sleeping in a seated position or Unfortunately there are few randomized studies in the
with the neck hyperextended • High-arched palate
efficacy of the tonsillectomy and adenoidectomy for children
• Cyanosis • Failure to thrive with obstructive sleep apnea. The most have concluded
• Headaches on awakening • Hypertension that Adenotonsillectomy should be considered first line of
• Daytime sleepiness therapy for obstructive sleep apnea provided adenotonsillar
hyperplasia is present. Outcomes appear to improve regardless
*Enuresis after at least 6 months of continence.
of the measure used and show a definite improvement of
Algorithm 2
Dignosis and management of disordered sleep in a child
SAHS, sleep apnea hypopnea syndrome; PSG, polysomnography; CPAP, continuous positive airway pressure; RP, respiratory polygraphy.
729
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Algorithm 3
Diagnosis and management of uncomplicated obstructive sleep apnea syndrome in children
OSAS, obstructive sleep apnea syndrome.

*Historical findings associated with OSAS include habitual snoring with labored breathing, observed apnea, restless sleep, daytime neurobehavioral abnormalities
or sleepiness, and others. Physical findings may include growth abnormalities, signs of nasal obstruction, adenoidal facies, enlarged tonsils, increased pulmonic
component of second heart sound, and others. Note that patients may have no abnormalities on examination.
†
Complex, high-risk patients include infants younger than 12 months and children with craniofacial disorders, Down syndrome, neuromuscular disorders (including
cerebral palsy), chronic lung disease, sickle cell disease, central hypoventilation syndromes, or genetic, metabolic, or storage disease.
‡Subspecialist refers to a physician with expertise in sleep disorders in children. This physician may be a pulmonologist, neurologist, or other physician with
experience in the management of sleep-disordered breathing in children.

§High-risk patients should be monitored as inpatients postoperatively.
llAll patients should undergo clinical reevaluation. High-risk patients should undergo objective testing.
quality of life and severity of obstruction and there related size Children with other comorbidities such as craniofacial,
and symptoms. neuromuscular, genetic, allergic abnormalities are at a higher
risk for persistent postoperative obstructive sleep apnea and
Clinical Pearls also at a higher risk of postoperative complication such as
respiratory embarrassment and residual airway obstruction.
• Tonsil size does not always correlate with severity of obstructive
Long-term follow-up shows a dramatic improvement in the
sleep apnea as determined by polysomnography
quality of life scores after adenotonsillectomy with reduction
• Primary care physician can assess adenoid size by ordering a soft in the number of upper respiratory episodes, and hospital
tissue lateral radiograph of the nasopharynx from a good center
visit and admissions. A reduction in problem behaviors and
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Chapter 150: Upper Airway Obstruction and Sleep Related Breathing Disorders
cognitive impairment was seen after adenotonsillectomy. What Are the Signs and Symptoms of Obstructive
Studies suggested that in a majority of children enuresis Sleep Apnea for the Mother to See?
resolves or improves after the surgery.
• Loud or noisy breathing, snoring or mouth breathing
Clinical Pearls during sleep
• Brief pauses in breathing during sleep or difficulty
• Adnotonsillectomy is effective in reducing physiological, breathing during sleep
behavioral, and cognitive sequelly in patients with adeno • Restless sleep (i.e., lots of tossing and turning)
tonsillar hypertrophy and obstructive sleep apnea • Sweating heavily during sleep
• Some patients with obesity develop recurrent obstructive • Bedwetting
sleep apnea after adenotensillectomy. The primary care • Sleeping in odd positions (e.g., neck hyperextended)
physician must emphasize weight reduction and continue to • Inattentiveness and lack of focus at school
monitor the signs and symptoms of obstructive sleep apnea • Excessive daytime sleepiness (e.g., child regularly falls
after surgery. asleep in school)
• Poor academic performance
• Irritable mood, aggressiveness, other behavioral problems
ADENOTONSILLECTOMY • Morning headaches.
Adenoidectomy and adenotonsillectomy remain the most
commonly performed operations in children. However, they Key points
are also the most discussed, appreciated, denounced and
least studied procedures in the history of ENT surgery. While ))
Screening for snoring should be part of routine health
the indications have changed over the decades. The essential maintenance visits in all children; if snoring is present, a more
surgery remains the same with the advent of laser, coblation, detailed evaluation should follow (good evidence; strong
high frequency diathermy, etc. The intraoperative bleeding has recommendation). Note: Obstructive sleep apnea syndrome
reduced dramatically; however, the traditional surgery with is unlikely in children who do not have habitual snoring.
blunt dissection and snare still seems to have a large number ))
Complex, high-risk patients should be referred to a
of favorable references. subspecialist (good evidence for increased surgical risk in
Adenoidectomy however has become more effective and these patients and consequent need for more complex
definitive with the introduction of nasal endoscopy coupled management; strong recommendation).
with powered instrumentation like shavers made by Zomed. ))
Patients who have cardiorespiratory failure cannot wait for
The operative and postoperative complications of hemorrhage elective evaluation. These patients are not covered in the
AAP guideline because it is expected that they will be in an
remain the most common serious problems of the surgery.
intensive care setting and managed by a subspecialist.
The incidence is reported from 0.2 to 0.22% from primary
))
The diagnostic evaluation should be thorough. The history
hemorrhage and from 0.1 to 3% for secondary hemorrhage.
and physical examination have been shown to be poor in
Fever in the first 36 hours is considered “normal”. It is important
differentiating between primary snoring and obstructive sleep
to maintain hydration in hospital and immediate postoperative apnea syndrome (strong evidence). Polysomnography is the
period. Mortality from tonsillectomy is estimated at 1/16,000– diagnostic method of choice; it is the only test that quantifies
35,000 tonsillectomies. About one-third attribute to primary sleep and ventilatory abnormalities. Other screening tech
bleeding and the majority to anesthetic mishaps. niques, such as videotaping, audiotaping, nocturnal pulse
The American Academy of Pediatrics recommends adeno oximetry, and daytime nap polysomnography, may be
tonsillectomy as the first line treatment in any child with helpful if the results are positive. However, these tests have
obstructive sleep apnea and enlargement of the tonsils and high false-negative rates, and they do not assess the severity
adenoids. A lot of parents are worried about the surgery, but of the syndrome (disease severity is useful in determining
it is actually quite safe and the benefits are significant. In some treatment and follow-up). When the results of other diagnostic
kids, however, there is residual obstructive sleep apnea after tests are negative, polysomnography should be performed;
surgery. Thus, all children with obstructive sleep apnea who additional audiotaping is necessary (strong evidence; strong
have surgery need to be followed up to see if there symptoms recommendation).
resolve and to make sure that they do not return. If symptoms ))
In most children, adenotonsillectomy is a first-line treatment
persist, a sleep study may be helpful. Alternative treatments are for obstructive sleep apnea syndrome; continuous positive
available if sleep apnea persists. Weight loss will help in obese airway pressure is an option in patients who are not
kids, and allergy treatments, intranasal steroids, orthodontic surgical candidates or do not respond to surgical treatment
(strong evidence; strong recommendation). Note: Potential
work, and continuous positive airway pressure (CPAP) can
complications of adenotonsillectomy include anesthetic-
benefit some kids.
related medical problems, pain and poor oral intake in
the immediate postoperative period, and hemorrhage.
Clinical Pearl Patients with obstructive sleep apnea syndrome may
• There are no studies to date that demonstrate significant have respiratory complications (e.g., worsening of the
negative clinical effect of tonsillectomy on the immune system. syndrome, pulmonary edema); death attributable to severe 731
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13. De Serres LM, Derkay C, Sie K, Biavati M, Jones J, Tunkel D, et al. Impact of
respiratory complications has been reported in patients adenotonsillectomy on quality of life in children with obstructive sleep disorders.
with severe obstructive sleep apnea syndrome. Risk factors Arch Otolaryngol Head Neck Surg. 2002;128(5):489-96.
for complications after adenotonsillectomy in children with 14. Farber JM. Clinical practice guideline: diagnosis and management of childhood
obstructive sleep apnea syndrome include age younger than obstructive sleep apnea syndrome. Pediatrics. 2002;110(6):1255-7.
3 years, cardiac complications of the syndrome (e.g., right 15. Gozal D, Crabtree VM, Sans CO, Witcher LA, Kheirandish-Gozal L. C-reactive
ventricular hypertrophy), severe obstructive sleep apnea protein, obstructive sleep apnea, and cognitive dysfunction in school-aged
syndrome determined by polysomnography, failure to thrive, children. Am J Respir Crit Care Med. 2007;176(2):188-93.
obesity, prematurity, recent respiratory infection, craniofacial 16. Gozal D, Kheirandish-Gozal L. Sleep apnea in children—treatment considerations.
anomalies, and neuromuscular disorders (the last two risk Paediatr Respir Rev. 2006;7(Suppl 1):S58-61.
factors are not discussed in the AAP Guideline). 17. Gozal D. Sleep-disordered breathing and school performance in children.
Pediatrics. 1998;102(3 Pt 1):616-20.
18. Kheirandish L, Goldbart AD, Gozal D. Intranasal steroids and oral leukotriene
SUGGESTED READINGS modifier therapy in residual sleep-disordered breathing after tonsillectomy and
adenoidectomy in children. Pediatrics. 2006;117:e61-6.
1. **AAO-HNS Position Statement—Treatment of Obstructive Sleep Apnea. 19. **Kribbs 1993—Objective Measurement of Patterns of Nasal CPAP Use by
2. American Thoracic Society. Standards and indications for cardiopulmonary sleep Patients with obstructive sleep apnea.
studies in children. Am J Respir Crit Care Med. 1996;153(2):866-78. 20. Marcus CL, Ward SL, Mallory GB, Rosen CL, Beckerman RC, Weese-Mayer DE,
3. Beebe DW. Neurobehavioral morbidity associated with disordered breathing et al. Use of nasal continuous positive airway pressure as treatment of childhood
during sleep in children: a comprehensive review. Sleep. 2006;29(9):1115-34. obstructive sleep apnea. J Pediatr. 1995;127(1):88-94.
4. **Bhattacharjee 2010—Adenotonsillectomy Outcomes in Treatment of 21. Marcus CL. Pathophysiology of childhood obstructive sleep apnea: current
obstructive sleep apnea in children. concepts. Respir Physiol. 2000;119(2-3):143-54.
5. Brietzke SE, Katz ES, Roberson DW. Can history and physical examination reliably 22. McColley SA, April MM, Carroll JL, Naclerio RM, Loughlin GM. Respiratory
diagnose pediatric obstructive sleep apnea/hypopnea syndrome? A systematic compromise after adenotonsillectomy in children with obstructive sleep apnea.
review of the literature. Otolaryngol Head Neck Surg. 2004;131(6):827-32. Arch Otolaryngol Head Neck Surg. 1992;118(9):940-3.
6. Brietzkes SE, Gallagher D. The effectiveness of tonsillectomy and adenoidectomy 23. Monasterio FO, Drucker M, Molina F, Ysunza A. Distraction osteogenesis in Pierre
in the treatment of pediatric obstructive sleep apnea/hypopnea syndrome: a Robin sequence and related respiratory problems in children. J Craniofac Surg.
meta-analysis. Otolaryngol Head Neck Surg. 2006;134(6):979-84. 2002;13(1):79-83.
7. **Brieztke 2006—The effectiveness of tonsillectomy and adenoidectomy in the 24. Richards W, Ferdman RM. Prolonged morbidity due to delays in the diagnosis
treatment of pediatric obstructive sleep apnea/hypopnea syndrome: A meta- and treatment of obstructive sleep apnea in children. Clin Pediatr (Phila).
analysis.Epstein 2009—Clinical Guidelines for Evaluation, Management and 2000;39(2):103-8.
long-term care of obstructive sleep apnea in adults. 25. Rosen CL, D’Andrea L, Haddad GG. Adult criteria for obstructive sleep apnea do
8. Brown KA, Laferriere A, Lakheeram I, Moss IR. Recurrent hypoxemia in children not identify children with serious obstruction. Am Rev Respir Dis. 1992;146(5 Pt
is associated with increased analgesic sensitivity to opiates. Anesthesiology. 1):1231-4.
2006;105(4):665-9. 26. Rosen GM, Muckle RP, Mahowald MW, Goding GS, Ullevig C. Postoperative
9. Carroll JL, McColley SA, Marcus CL, Curtis S, Loughlin GM. Inability of clinical respiratory compromise in children with obstructive sleep apnea syndrome: can
history to distinguish primary snoring from obstructive sleep apnea syndrome in it be anticipated? Pediatrics. 1994;93(5):784-8.
children. Chest. 1995;108(3):610-8. 27. Tauman R, Gulliver TE, Krishna J, Montgomery-Downs HE, O’Brien LM, Ivanenko
10. Chervin RD, Archbold KH, Dillon JE, Panahi P, Pituch KJ, Dahl RE, et al. Inattention, A, et al. Persistence of obstructive sleep apnea syndrome in children after
hyperactivity, and symptoms of sleep-disordered breathing. Pediatrics. adenotonsillectomy. J Pediatr. 2006;149(6):803-8.
2002;109(3):449-56. 28. Waters KA, Everett FM, Bruderer JW, Sullivan CE. Obstructive sleep apnea: the
11. Chervin RD, Ruzicka DL, Giordani BJ, Weatherly RA, Dillon JE, Hodges EK, et al. use of nasal CPAP in 80 children. Am J Respir Crit Care Med. 1995;152(2):780‑5.
Sleep-disordered breathing, behavior, and cognition in children before and after 29. **Weaver 2004—Survival of Veterans with Sleep Apnea—CPAP vs Surgery.
adenotonsillectomy. Pediatrics. 2006;117(4):e769-78. 30. **Weaver 2008—Adherence to CPAP Therapy—The Challenge to Effective
12. Cohen SR, Simms C, Burstein FD, Thomsen J. Alternatives to tracheostomy Treatment.
in infants and children with obstructive sleep apnea. J Pediatr Surg.
1999;34(1):182‑6.
Note: **Articles recommended by the American Academy of Ophthalmology-
Head and Neck Surgery
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Section 19: Orthopedics
Chapter 151
Septic Arthritis
Viraj Shingade, Mandar Agashe
INTRoDUCTION collagenases are released from the leukocytes and synovial

cells. These enzymes breakdown the cellular and extracellular
Septic arthritis continues to be one of the major causes of structures of the cartilage. The loss of glycosaminoglycans is
orthopedic disability in pediatric population. Although the first measurable change in articular cartilage, occurring as
the management is not very difficult, it usually needs a early as 8 hours after bacteria are introduced into the joint. Loss
multidisciplinary approach. Most of the neonates are either of glycosaminoglycans softens the cartilage and may cause it to
missed in diagnosis in early stages or they are managed by a be susceptible to increased wear. Collagen destruction follows
medical person single-handed and they lead to outcomes like and is responsible for visible change in cartilage appearance.
deformity and limb shortening. If diagnosis is made timely Elevation of the intracapsular pressure, thrombosis causes
and management is done by the team including neonatologist, impairment of the intracapsular vascular supply which causes
pediatrician, pediatric orthopedic surgeon, microbiologist, articular destruction. Destruction of the joint space leads to
and radiologist, most of these cases can be cured completely long-term sequelae in a significant percentage of patients. In
without any remnant deformity or disability. This chapter gives certain joints like hip, infection distends and softens joints
useful information about how to diagnose it at the earliest and capsule and may cause joint subluxation or dislocation.
what should be the approach for the treatment.
WHICH ARE THE SUSCEPTIBLE

HOW COMMON IS THE PROBLEM?
GROUPS IN NEONATES?
Septic arthritis refers to bacterial invasion of the joint space
and the subsequent inflammatory response. Septic arthritis in the neonates is seen in two distinct groups.
The incidence of septic arthritis in India is approximately One is the neonate, who is sick, premature, and needs intensive
1 in 1,500 live births. Although bone and joint infections are care. The other group is healthy neonate, who has been
quite common, the diagnosis of septic arthritis is not always discharged from the hospital and then presents 2–3 weeks later
straightforward. with bone and joint infection.
When to Suspect (Algorithm 1)?

MECHANISM/PATHOPHYSIOLOGY
Clinically, septic arthritis usually presents with obvious
OF THE PROBLEM swelling of one or more joints. Symptoms include edema,
Septic arthritis usually is of hematogenous origin, but can erythema, joint effusion, and tenderness. Patients tend to keep
arise through direct inoculation. It can occur from the primary the affected joint in a position that maximizes intracapsular
seeding of the synovial membrane, secondarily from infection volume and comfort. Refusal to move an affected joint is
in the adjacent metaphyseal bone or directly from infection in referred to as pseudoparalysis and even passive movement
the adjoining epiphysis. may be painful. Systemic symptoms, such as fever, malaise,
When septic arthritis occurs, bacteria rapidly gain access to and poor appetite, are also seen in most patients. If the
the joint cavity and within a matter of hours cause synovitis and infection involves a lower extremity, the child will often have
formation of fibrinous exudates followed by areas of synovial a limp or will be unable to bear weight on the limb. A history
necrosis. Endotoxins are released. This leads to destruction of of antecedent trauma is quite common. Trauma rarely results
the synovium and cartilage matrix. Proteases, peptidases, and in a delayed limp. The clinician should elicit specific details
ch-151.indd 733 11/25/2016 5:06:25 PM

Algorithm 1
How to diagnose and treat a baby with septic arthritis
ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IV, intravenous.
regarding any traumatic event. Did the child cry and limp or What are Clinical Clues
refuse to bear weight immediately after the trauma? If the in Infants and Older Children?
answers to these questions are no and there was a period of
time between the injury and time symptoms appeared, the Typical symptoms like high grade fever, and warmth or hot
suspicion of infection should increase. extremity may not be present. Limping, refusal to walk, and
refusal to bear weight may be the earliest symptom.
WHICH ARE THE MOST COMMON

CHALLENGES IN
JOINTS INVOLVED?
DIAGNOSING SEPTIC ARTHRITIS
Knees and the hips being most commonly affected (80%),
other commonly affected joints include the ankles, wrists, Many immunocompromised children fail to have fever and
elbows, and shoulders. may show lowered white blood cell count. X-rays may be
reported as normal in early phase of the disease. Ultrasound,
bone scan, or magnetic resonance imaging (MRI) suggest a
What Are Clinical Clues for Diagnosis in Neonate? process of inflammation and effusion, but cannot diagnose
The initial presentation is with swelling of a limb or joint septic arthritis confirmatively in the early stage of disease.
and reluctance to move the limb. There may be irritability The damage to the cartilage, growth plate, and bone due to
on handling, e.g., when changing the nappies. Sometimes, avascularity and enzymatic destruction sets in very early.
the reluctance to move a limb is so severe as to cause a The cartilage destruction starts as early as 8 hours following
pseudoparalysis. Septic arthritis of the hip may cause the baby the onset of infection. The avascularity sets in within 24–48
to hold the leg flexed, abducted, and externally rotated. hours of the tamponade. The biggest challenge is, therefore,
In the fulminant form of septic arthritis, signs of bone and to control the infection and drain the joint before the damage
joint involvement may occur at the time of, or some times after takes place. Understanding the limitations of investigations
the signs of, sepsis. The babies are lethargic with or without fever, for confirmation of diagnosis, it is important that physician
do not tolerate feeds, and may have abdominal distension and should have high index of suspicion and should start treatment
jaundice. Multiple bones or joints may be involved. as earliest as possible.
734
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Chapter 151: Septic Arthritis
WHICH ARE OTHER Magnetic Resonance Imaging

DIFFERENTIAL DIAGNOSES? In selected cases, an MRI is the most sensitive. It shows changes
It includes hemarthrosis, traumatic effusion, transient of marrow edema and helps to differentiate between transient
synovitis, reactive arthritis, Lyme arthritis, juvenile rheumatoid synovitis, inflammatory arthritis, and septic arthritis by virtue
arthritis, arthritis of acute rheumatic fever, and slipped capital of changes in marrow edema and synovial lining.
femoral epiphysis.
Hematological Investigations
A routine hemogram (complete blood count) with erythrocyte
WHICH ARE THE MOST sedimentation rate (ESR) and C-reactive protein (CRP)
COMMON CAUSATIVE ORGANISMS? are usually required and helpful to diagnose and monitor
In the neonatal period, Staphylococcus aureus remains a the course of treatment. In the community setting, CRP is
common organism, but Group B β-hemolytic streptococcus useful parameter and is highly sensitive for infection. In an
and Gram-negative enteric bacilli are also frequently identified. immunocompromised child, it may not be very reliable.
No bacteria are grown from the blood or joint fluid of 50% cases Rather than a single value, changing trend in a CRP is more
of typical septic arthritis. informative.
Other contributing organisms could be methicillin- Erythrocyte sedimentation rate is not very useful in
resistant S. aureus (MRSA), Gram-negative organisms (Entero neonates, but with chronicity of infection, a decreasing trend
bacteriaceae) fungal species like Aspergillus and Candida. in ESR usually indicates subsidence of infection.
Tuberculosis and syphilis must be considered in atypical case Blood culture must be routinely performed and sometimes
contexts. it can identify the pathogen. However, the blood sample must
be promptly analyzed after collection and any contamination
must be prevented.
WHAT INVESTIGATIONS ARE Organism identification is extremely important for both
SUPPORTIVE TO CONFIRM THE DIAGNOSIS? confirmation of the diagnosis and guiding antimicrobial
selection. Needle aspiration is likely to grow an organism in
The most important diagnostic test is clinical acumen. Positive almost 50–60% of cases whereas blood cultures yield positive
changes on X-ray suggest that the disease is already in its results in one-third to little more than half of specimens.
advanced stage. Hence to diagnose the condition in its early
stage, optimum use of investigations like ultrasound and MRI
can be done. HOW TO PROCEED FOR THE MANAGEMENT
ONCE DIAGNOSIS IS MADE (Algorithm 1)?
Radiographs Early diagnosis and treatment of septic arthritis is usually
The role of plain X-ray film in the diagnosis of early bone highly effective and usually achieves a clinically normal joint.
and joint sepsis is often undervalued. It is because the most Consequently, it is essential that children with septic arthritis
sought after change is osteopenia or bone lysis, which takes are urgently referred to treatment centers and it is essential that
7–10 days to develop. Actually, deep soft tissue swelling with the latter centers commence treatment as soon as possible.
obliteration of fat plane is the earliest radiographic evidence Prompt diagnosis and treatment of septic arthritis is not only
of infection. Unlike older children, radiographic changes rewarding, but also saves the child from a lifelong disability.
appear early in neonatal age group. The thin periosteum The treatment is a team approach which involves pedia
ruptures easily, and osteolytic lesions, soft tissue swelling, trician, pediatric orthopedic surgeon, pediatric intensivist
and periosteal elevation are often seen within 7 days of (particularly in sick neonates), microbiologist, and radiologist.
onset of infection. Erosion of the cortex, cavitation in the Treatment is directed towards obtaining a rapid cure as
metaphysic or epiphysis can be seen as early as 3 days of the sequelae of septic arthritis can be quite devastating (Figs 1
onset of infection. and 2). Any suspicion of the infection in a neonate should
initiate prompt investigation to identify the site and source of
Ultrasonography the infection. Ideally, a joint or bone aspirate or positive blood
culture must be obtained before commencing antimicrobial
Ultrasonography (USG) is very useful to detect any joint
therapy. However, often this is not the case, and many
effusion and subperiosteal edema. Although USG cannot
neonates have received oral or intravenous antibiotics before
clearly differentiate between pus and synovial fluid, in
they reach the definitive treatment center. In any case, if there
experienced hands USG-guided aspiration may be very useful
is no improvement in clinical parameters within 48–72 hours
to confirm the diagnosis.
of antimicrobial administration, then surgical intervention is
mandatory.
Bone Scan Prompt surgical drainage and thorough wash of the joint
Bone scans are both sensitive and specific. They are often is necessary. Open surgical drainage of the certain joints
abnormal within 2–3 days of onset of symptoms. is essential to prevent necrosis (e.g., head of the femur or 735
ch-151.indd 735 11/25/2016 5:06:26 PM

A B
Fig. 1: A, An X-ray pelvis in an 8-year-old child who suffered septic arthritis of left hip in neonatal age group. Left femoral head shows growth
arrest and gross collapse and incongruity. B, An X-ray of knee in a 5-year-old child who suffered septic arthritis in neonatal period. There is gross
deformity and growth arrest of proximal tibia. Child had gross shortening of limb and deformity
of proper antibiotics. Involvement of pediatric orthopedic

surgeon at the onset of treatment itself is important as he
or she is the person who is going to manage the sequelae in
future. These children need long-term follow-up.
Antimicrobial therapy should commence immediately after
drainage of pus. Antimicrobial therapy is guided by Gram stain
on the aspirated pus. Up to 50% of joint aspirates are sterile in
septic arthritis, possibly because joint fluid is bacteriostatic or
because the organisms are limited to the synovium.
WHICH ANTIBIOTICS NEED TO BE GIVEN?

Since Gram-positive organisms are most frequently responsi
ble for the infection, an antibiotic that is effective against
these organisms should be started empirically. In infants and
children, a third-generation cephalosporins (e.g., cefotaxime,
ceftriaxone) are the drug of choice combined with amikacin
or gentamicin which provide coverage against many S.
aureus (methicillin-sensitive S. aureus), most streptococci,
Fig. 2: Clinical photograph of the same child whose X-ray is shown in Haemophilus influenzae, and Kingella kingae.
figure 1A suggesting gross shortening of left lower limb Linezolid, vancomycin, teicoplanin, and tobramycin
are reserved until there is a positive report to support their
use. Once an organism has been identified, coverage can be
humerus). The current trend is towards mini-invasive surgeries narrowed based on results of susceptibility testing.
(Figs 3 and 4), particularly in neonates; or arthroscopic joint
lavage rather than big incisions. Smaller joints can usually be
effectively treated by regular aspiration and rarely need open WHICH IS THE PREFERRED ROUTE
surgical drainage. OF ANTIBIOTICS?
Drainage of pus by a pediatric orthopedic surgeon
decompresses the joint with drainage of pus leading to The initiation of treatment should be with intravenous anti
increased vascularity and healing. The antibiotics which were biotics only. The oral route is preferred for maintenance phase.
not able to reach the local site due to tight compartment like
pressure are able to reach the infection site after drainage of HOW LONG ANTIBIOTICS NEED
pus. This ultimately results in rapid healing of bone and joint TO BE GIVEN?
due to clearance of tissue-destroying fluid and also due to
decrease in the tamponade effect on the delicate circulation The duration of parenteral antimicrobial therapy is a matter
around the growth plate. of debate. While the final choice is decided by the prevalent
Pus or fluid obtained during surgery must be sent for Gram pathogen in the bacteriological and culture report, the duration
736 staining and appropriate culture which helps in selection of intravenous treatment varies from 7 days to 5 weeks.
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Chapter 151: Septic Arthritis
A D
B C E
Fig. 3: A, Clinical photograph of a 25-day-old neonate with septic arthritis right hip. There is fixed flexion deformity at right hip and baby refuses to
move the right lower limb. B, An X-ray shows right hip dislocation, which is due to inflamed synovium pushing the head outside the acetabulum.
C, Joint wash of the right hip was done by mini-invasive technique using 16 G needles through multiple ports. This was followed by course of
intravenous and then oral antibiotics. D, Clinical photographs showing one and half year follow-up with full range of movement at right hip joint
and no limb length discrepancy. E, X-ray done at 15 months suggests growth is getting affected and small-sized epiphysis of right hip
A
C
B D E F
Fig. 4: A, Clinical photograph of a 28-day-old neonate with septic arthritis right hip. There is fixed flexion deformity at right hip and painful
movements of right lower limb. B, X-ray shows right hip dislocation as well as lytic changes in proximal femur. C, Joint wash of the right hip
was done by mini-invasive technique using 16 G needles through multiple ports. This was followed by course of intravenous and then oral
antibiotics. D, and E, Clinical photographs showing two and half year follow-up with full range of movement at right hip joint and no limb
length discrepancy. F, X-ray done at two and half years suggests normal recovery; no growth arrest, no limb length discrepancy 737
ch-151.indd 737 11/25/2016 5:06:26 PM

There are many studies which has proven efficacy of intensive care unit/pediatric intensive care unit room. It should
minimum 3 weeks of intravenous antibiotics followed by 2–3 be done by a person well worse with anatomy of particular
weeks of oral therapy (total 4–6 weeks). The author follows the joint (preferably by pediatric orthopedic surgeon).
regimen of 2–3 weeks of intravenous antibiotics followed by
oral antibiotics for 2–3 weeks at our center. Few studies have Is Simple Joint Aspiration Sufficient or a Joint
indicated a shortened course of appropriate antibiotics for 3 Wash Need to Be Done?
weeks is as efficacious as 6 weeks of parenteral therapy.
Close monitoring of the clinical, blood, and radiological Joint wash gives an additional advantage of reducing the
parameters is required to ensure that the treatment is effective bacterial load and thereby better chances of healing. Hence,
and the outcome satisfactory. Antibiotics can usually be whenever a pediatric orthopedic surgeon is available he
stopped by 6 weeks if the child has improved. Radiographs should be involved in the management and a thorough joint
must be taken 6 monthly to see for any sequelae which develop wash should be done rather than simple aspiration.
in future.
Based on the latest review of literature, use of intravenous What is the Role of Plaster Cast/Splints/Traction?
antibiotics till child improves clinically and starts weight Plaster cast/splints help in immobilization of the joint and
bearing, followed by oral antibiotics for 4–6 weeks seems to better healing particularly initial 1–2 weeks of treatment. Hip
be a standard regimen. The duration of antibiotics depends spica is needed in cases of septic hip dislocations to achieve the
on the clinical recovery rather than a fixed time frame. To start containment. Joint should not be immobilized for prolonged
with, an intravenous route is preferred. Once the clinical signs time to avoid stiffness. In children, traction helps in reducing
improve and CRP levels touch baseline, the antibiotic may be the pain as well as correcting the deformity. On traction,
given orally. movements need to be started as earliest as possible.
WHERE AND WHO SHOULD PERFORM Key points

THE JOINT ASPIRATION?
))
Septic arthritis is a surgical as well as medical emergency
Although older literature mentions about drainage in the ))
Prevention of sequelae by starting treatment urgently is the
emergency room, recent guidelines suggest to be done under key to success
aseptic atmosphere like operation theater or sterile neonatal ))
The treatment needs a team approach by pediatrician,
pediatric orthopedic surgeon, neonatologist, microbiologist,
and radiologist
))
Small setups where facilities are not available should refer the
Clinical Pearls patient urgently to tertiary center where treatment needs to
be started by the team on emergency basis
• Suspect septic arthritis in all neonates with decreased
movements of limb or painful movements of limb ))
Septic arthritis if untreated will cause growth plate
disturbances or damage, subsequent shortening of affected
• Suspect septic arthritis in all toddlers or children having gait
limb and lifelong deformity. Hence, the need for urgent
disturbance with history of fever
diagnosis and treatment.
• Give joint lavage as earliest as possible
• Joint lavage should be given in aseptic conditions preferably
in operation theater or sterile neonatal intensive care unit/ SUGGESTED READINGS
pediatric intensive care unit room (preferably by pediatric
orthopedic surgeon who will keep follow-up of the case 1. Curtiss PH, Klein L. Destruction of articular cartilage in septic arthritis. II. In vivo
managing sequelae in long term) studies. J Bone Joint Surg Am. 1965;47(8):1595-604.
2. Fox L, Sprunt K. Neonatal osteomyelitis. Pediatrics. 1978;62(4):535-42.
• Send joint fluid for microbiological evaluation
3. Narang A, Kumar PK. Bone and joint infection in neonates. Indian J Pediatr.
• X-rays and ultrasonography are helpful in diagnosis 1988;62:535-42.
• Empirical antibiotics should be commenced after prompt 4. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Sensitivity of erythrocyte
drainage of joint collections sedimentation rate and C-reactive protein in childhood bone and joint infections.
Clin Orthop Relat Res. 2014;468(3):861-6.
• Start antibiotics with intravenous route only
5. Rutz E, Brunner R. Septic arthritis of the hip-current concepts. Hip Int.
• Further choice of antibiotics will depend on culture report and 2009;19(Suppl 6):S9-12.
clinical course 6. Sultan J, Hughes PJ. Septic arthritis or transient synovitis of the hip in children: the
• Once clinical course is better shift to oral route of antibiotics value of clinical prediction algorithms. J Bone Joint Surg Br. 2010;92(9):1289‑93.
• Keep patient in long-term follow-up for observation of 7. Syriopoulou VP, Smith AL. Osteomyelitis and septic arthritis. In: Feigin RD,
sequelae and their subsequent management. Cherry JD, Demmler GJ, Kaplan SD, editors Textbook of Pediatric Infectious
Diseases, 2nd ed. Philadelphia, PA: WB Saunders; 1987. pp. 759-79.
738
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Chapter 152
Angular and Rotational
Deformities in Children
Taral V Nagda, Venkatadass Krishnamoorthy
INTRODUCTION Usually, it passes through the center of the knee joint. Medial
deviation of mechanical axis is seen in genu varum and lateral
Any deviation from the normal alignment of the limb in deviation is seen in genu valgum. The measure of the deviation
coronal plane is termed as angular deformity and that in of mechanical axis of lower limb from the center of knee joint is
transverse or axial plane is termed as rotational (torsional) called as “mechanical axis deviation (MAD)”. The other angles
deformity. While angular deformities are obviously seen as which needs to routinely measured are mechanical lateral-
outward or inward deviation of legs, children with rotational distal femoral angle, medial proximal tibial angle, modified
deformities often present with either in-toeing or out-toeing tibiofemoral angle (TFA), and joint line convergence angle
walking. This chapter discusses in brief the common causes of (Fig. 1).
these abnormalities and an algorithmic approach to each of
this clinical scenario. Genu Varum (Algorithm 1)
Causes of genu varum are given in box 1.
ANGULAR DEFORMITIES IN CHILDREN
Genu varum (bow legs) and genu valgum (knock knees) are
the most common angular deformities for which the child is
brought to the pediatric orthopedic clinic.
Normal Variation During Growth

Before going to the pathological genu varum and valgum, it is
important to know the normal variation during growth. Most
newborns have bow legs, with 10–15° of varus angulation. This
gradually corrects until 18–24 months of age. After 2 years,
there is valgus angulation with maximum valgus occurring
around 4 years of age. The limb usually reaches normal adult
alignment of 6–7° of valgus by around 11 years of age.
Radiological Assessment of
Alignment of Lower Limb
Full length standing radiograph of both lower limbs covering
from both the hip joints to ankle joints with patellae facing
anteriorly is the standard radiograph needed for analyzing
the angular deformities of lower limbs. This should be
standardized as management decisions are made based on LPFA, lateral proximal femoral angle; mLDFA, mechanical lateral-distal femoral
this radiograph. Mechanical axis is drawn by the line joining angle; MPTA, medial proximal tibial angle; LDTA, lateral-distal tibial angle.
the center of the femoral head to the center of tibial plafond. Fig. 1: Mechanical axis of lower limb
ch-152.indd 739 11/22/2016 12:21:30 PM

Algorithm 1 examination will have other signs of active rickets. The X-rays
Approach to a child with genu varum (bow legs) show cupping and flaring of the metaphysis with widening of
the physis. Active rickets will have to be treated with vitamin D
supplements and the deformity needs to be observed.
The children with active rickets who are not responding to
vitamin D supplements are likely to have vitamin D resistant
rickets and they need to be investigated preferably by a
pediatric endocrinologist and managed accordingly.
It is not uncommon to see children presenting with
bowlegs after the active rickets has healed. The persistent
deformity needs to be corrected to get the mechanical axis
of the lower limb to normal. Guided growth in the form of
temporary hemiepiphysiodesis with a tension band plate
(8 plate) applied on the lateral side is the preferred form of
treatment when the physes remains open. The parents must
be counseled well about the need for regular follow-up X-rays
at 3–4 monthly intervals and the need for 8-plate removal
once the deformity is corrected. In children for whom the
physes are closed or those with sick physis not responding to
guided growth, the deformity is corrected by osteotomy.
Blount’s Disease
Blount’s disease also called as tibia vara is classified into three
types based on the age of onset of the deformity.
• Infantile tibia vara: less than 3 years
• Juvenile tibia vara: 4–10 years
• Adolescent tibia vara: more than 10 years.
Infantile Blount’s disease is considered to be a disorder on
the other end of the spectrum of physiological bowing.
Box 1: Causes of genu varum Clinical Features

• Physiological genu varum • Skeletal dysplasias The two major features which helps in differentiating
• Infantile Blount’s disease • Focal fibrocartilaginous
physiologic genu varum from infantile tibia vara is that the
dysplasia child is usually obese (>95th percentile) and the presence
• Metabolic disorders
of lateral thrust while walking. This sudden lateral knee
movement with weight bearing is caused by varus instability
at the joint. This sign, though not pathognomonic of infantile
Physiological Genu Varum tibia vara, increases the level of suspicion and is an indication
Bow legs usually become prominent when the child starts for radiography, regardless of the age of the patient.
walking and the parents get concerned about the deformity.
Physiological genu varum is common in early walkers and Radiographic Findings
in obese children. In physiologic genu varum, there may be A standardized standing anteroposterior view of the lower
associated tibial intorsion. There are no other significant extremities from hip to ankle with both patellae facing forwards
positive findings on clinical examination. X-rays of the knees must be obtained. The diagnosis is based on radiographic
may show an apparent delay in the ossification of the medial changes in the proximal end of the tibia as follows (Fig 2):
side of the distal femoral and proximal tibial epiphyses or • A sharp varus angulation in the metaphysis
flaring of the medial distal femoral metaphysis. The physes • A widened and irregular physeal line medially
are normal. Majority of children less than 2 years of age have • A medially sloped and irregularly ossified epiphysis
physiological genu varum, which needs reassurance to parents • Prominent beaking of medial metaphysis with lucent
and follow-up evaluation. The genu varum that persists after cartilage islands within the beak
2 years of age is considered to be pathological and needs to be • Lateral subluxation of the proximal end of the tibia.
investigated further. Infantile Blount’s disease in early stages and young patients
can be managed by Blount’s brace, which needs to be worn
Nutritional Rickets 23 hours a day. Though the compliance rates are very poor with
Nutritional rickets is one of the most common causes for bowed brace treatment, there is good evidence in the literature that
legs in developing countries. The typical clinical scenario in early stages of the disease just braces could normalize the
740 would be a child presenting with bowed legs and on clinical mechanical axis of the limb. Persistent and severe deformities
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Chapter 152: Angular and Rotational Deformities in Children
Focal Fibrocartilaginous Dysplasia

Focal fibrocartilaginous dysplasia is a rare cause of unilateral
genu varum in an infant or toddler. Careful clinical examination
reveals that the deformity is slightly more distal than the knee
joint. On weight bearing and walking, the child may have a
lateral thrust along with associated hyperextension of the knee
which is not a feature of Blount’s disease.
Radiographic Findings
X-rays show a characteristic abrupt varus at the metaphyseal-
diaphyseal junction of the tibia, clearly not involving the physis.
There is cortical sclerosis in and around the area of the abrupt
varus on the medial cortex. A radiolucent lesion may be seen
just proximal to the area of cortical sclerosis, which probably
corresponds to the fibrocartilaginous tissue. The etiology of
this defect and the pathogenesis of the deformity are unknown.
The importance of recognizing this variation of infantile
Fig. 2: An X-ray of a child with bilateral Blount’s disease
tibia vara is that the deformity can resolve without surgery.
Surgical treatment may be necessary if the deformity progresses
or fails to resolve during a period of observation or orthotic
management.
Clinical Pearls
Pointers to pathological genu varum:
• Age more than 2 years
• Lateral thrust on walking
• Hyperextension while standing
• Acute bowing in the tibia
• Unilateral bowing.
Genu Valgum (Algorithm 2)

Causes of genu valgum are given in box 2.
A B
Valgus alignment of the lower extremities is normal in a
Fig. 3: A, Preoperative X-ray of a 7-year-old boy with bilateral child between 2 years and 6 years of age. The maximum amount
Blount’s disease and B, 2 years follow-up X-ray after osteotomy of physiologic valgus occurs between the ages of 2 years and 4
showing normal alignment of the lower limbs years, after which the alignment of the lower extremity assumes
a mild valgus femoral-tibial angle, the normal alignment in an
adult.
in late stages will require surgical correction in the form of In a younger child, X-rays are not routinely indicated.
corrective osteotomy (Fig. 3). Alignment X-rays are indicated in the following situations:
• Presence of short stature
Skeletal Dysplasia • History of trauma or infection
Children with genu varum secondary to skeletal dysplasia • Features suggestive of metabolic bone disease
usually have associated short stature. The dysplasia could • Asymmetrical genu valgum.
be either at the epiphysis, metaphysis or the diaphysis. The The rotational profile of the extremity must be evaluated
common dysplasias which present with genu varum are carefully because an apparent increase in valgus may result
achondroplasia, pseudochondroplasia and metaphyseal- from increased femoral anteversion.
chondrodysplasia (Schmid/McKusick) and hereditary
multiple exostosis. Genu varum in these children will need Idiopathic Genu Valgum
surgical correction to restore the mechanical axis. It is worth Significant genu valgum that persists after 7 years of age
while considering growth modulation or guided growth in without any identifiable underlying cause is usually labeled as
these patients while the physes are open. Those children idiopathic genu valgum. Surgical correction is indicated when
who are not ideal for growth modulation will need corrective there is significant MAD (the mechanical axis passing lateral
osteotomy. to the lateral-tibial plateau). If untreated this may lead to gait 741
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Algorithm 2
Approach to a child with genu valgum (knock knees)
over correction and development of opposite deformity. In

Box 2: Causes of genu valgum
children who present late where the physis is fused, corrective
• Physiological genu valgum • Skeletal dysplasias osteotomy is indicated.
• Metabolic • Hereditary multiple exostosis
• Post-traumatic Metabolic Disorders
Genu valgum may be presenting feature of a child with
chronic renal failure. Apart from nutritional rickets, renal
rickets must be ruled out in all children presenting with genu
valgum by doing renal function tests. Correcting the metabolic
abnormality gets the first priority in these children followed by
deformity correction later on.
Skeletal Dysplasia
Multiple hereditary exostosis, spondyloepimetaphyseal dys-
plasia, Ellis-van Creveld syndrome, and focal fibrocartilagi-
nous dysplasia are rare causes of genu valgum. The deformity
needs to be corrected when there is severe MAD irrespective
of the etiology.
Post-traumatic Genu Valgum

Proximal tibial fracture in toddlers (Cozen’s fracture) is known
to cause unilateral valgus deformity. Though the etiology of
this condition remains undetermined, there is strong evidence
A B in the literature that most of these deformities would correct
Fig. 4: A, 12-year-old girl with idiopathic genu valgum and spontaneously and hence need to be observed periodically for
improvement of the deformity.
B, 1-year follow-up X-ray after bilateral hemiepiphysiodesis
showing complete correction of deformity.
Clinical Pearl
disturbance, difficulty in running, knee discomfort, patellar Beware of unilateral deformity; it is most likely to be pathological.
malalignment, and evidence of ligamentous instability.
Growth modulation with medial hemiepiphysiodesis using
a tension band plate is currently the preferred method of ROTATIONAL DEFORMITIES IN CHILDREN
achieving correction while the physis is open (Fig. 4). However,
one must be aware that in genu valgum, correction is rapid Rotational deformities in children manifest as either in-toeing
742 and 3-monthly monitoring with X-rays is mandatory to avoid or out-toeing while walking. Parents bring their children
ch-152.indd 742 11/22/2016 12:21:31 PM

Box 3: Physiologic causes for rotational deformities Box 4: Pathological causes of rotational deformities
In-toeing Out-toeing • Cerebral palsy • Metabolic disorders
• Foot • Foot • Hereditary neurologic • Skeletal dysplasia
{{ Metatarsus adductus {{ Pes calcaneovalgus disorders—Charcot-Marie • Rigid pes planus with or
{{ Skew foot {{ Pes planovalgus tooth disease, Friedrich ataxia without tarsal coalition
• Leg • Leg • Mild tibial deficiencies • Slipped capital femoral
{{ Internal tibial torsion {{ External tibial torsion • Blount’s disease epiphysis.
• Hip • Hip
{{ Increased femoral {{ External rotation contracture
anteversion {{ Femoral retroversion Pathologic Causes for Rotational Deformities

Pathological causes for rotational deformities are given in
seeking opinion for abnormal inward or outward positioning box 4.
of the feet while walking. Though majority of the rotational
deformities in early childhood are benign and gets resolved Evaluation of Child with Rotational Deformity
spontaneously with growth, it is important to do a thorough A good history with systematic clinical examination is
clinical examination to locate the anatomical site of the recommended in all children presenting with in-toeing or
deformity. A comprehensive history along with a thorough out-toeing while walking. The following findings would point
physical examination helps in differentiating benign from towards a pathologic cause of rotational deformity:
pathologic causes of rotational abnormalities. • A hypoxic or infective event in neonatal period
• Delayed developmental milestones
Common Causes of • A family history of hip dysplasia or a neurologic disorder
Rotational Deformities in Children • Spasticity, a neurologic deficit, or signs of muscular dystrophy
• Limping or another abnormality of gait of sudden onset
Majority of the rotational anomalies in children are physiologic
• Deformities of the foot.
variations (Box 3), which resolve over a period of time. Very
rarely physiologic variations may persist or become rigid
deformities, which then would warrant a surgical intervention. The Three-step Rotational Profile (Algorithm 3)
Pathologic causes of rotational deformities need to be identified • Step 1 [foot progression angle (FPA)]: make the child walk in
and managed appropriately. a straight line and look for the FPA. Foot progression angle
Algorithm 3
Approach to a child with rotational profile
743
TFA, tibiofemoral angle; IR, internal rotation.
ch-152.indd 743 11/22/2016 12:21:32 PM

A comprehensive recording of the patient’s history

combined with a thorough physical examination are essential
for differentiating benign from pathologic causes of rotational
abnormalities. Studies present various conclusions in terms of
the age beyond which the persistence of in-toeing is abnormal.
However, the general consensus is that no natural correction of
a rotational malalignment should be expected beyond the age
of 10 years, although exceptions to this do occur.
Investigations
As benign variations in the rotational profile of the lower
extremities are quite common in children, imaging is not
routinely required in the assessment of an in-toeing or out-
toeing gait unless indicated by a clinically suspected pathology.
Fig. 5: Foot progression angle Fig. 6: Thigh foot angle It is also important to know that deformities in the rotational
or axial plane are difficult to interpret on standard two-
dimensional radiographs. Indications for supplemental radio
is the angle between the longitudinal axis of the foot and graphic imaging include the presence of leg-length discrepancy,
an imaginary line of progression of the body through space asymmetric findings, limp, pain, spasticity, recent changes in
(Fig. 5). A positive or external FPA of 0–20° is considered gait, persistence of a deformity into adolescence, and cosmetic
normal, but the angle varies with age and may necessitate concerns. Children older than 6 months who present with a leg-
observation over time and correlation with the remainder length discrepancy, an asymmetric rotational profile, or both
of the physical examination. A negative FPA indicates that should have an anteroposterior radiograph of the pelvis to rule
the child is walking with in toeing. Foot progression angle out hip dysplasia or other abnormalities of the hip.
is also an important indicator of dynamic causes of in-
toeing such as tibialis anterior overactivity Metatarsus Adductus
• Step 2 [external rotation and internal rotation (IR) at both
In metatarsus adductus, there is inward deviation of the
hip joints]: femoral anteversion is diagnosed clinically
forefoot relative to the hind foot. Metatarsus adductus is
when a child has more IR than external rotation of the hip.
the most common congenital foot deformity and it resolves
In infants, IR of the hip averages 40°, with a range of 10–60°,
spontaneously in more than 90% of children. A rigid forefoot
and external rotation averages 65° with a range of 45–90°
adduction deformity with a prominent plantar crease, which
• Step 3 [thigh foot angle (TFA)]: it is determined in the prone
often requires surgical management, is termed as “metatarsus
position as the angle between the longitudinal axis of the
varus” by some authors. For simplicity, these deformities are
foot (usually along the second ray) and the longitudinal
now classified as actively correctable, passively correctable
axis of the thigh, with the knee flexed to 90° and the
or rigid.
ankle in neutral position (Fig. 6). Factors influencing the
The clinical hallmark of the condition is medial deviation of
TFA include tibial torsion and any hind foot or forefoot
the forefoot relative to the hind foot. When the foot is viewed from
deformities. The average TFA is negative or internal by
the plantar surface, the sole of the foot appears bean shaped.
5° in infants, and becomes positive or external by 10° by
It is important to establish the degree of flexibility of the
approximately 8 years of age.
deformity. In mild cases, the foot will correct actively when the
lateral border of the foot is stimulated. In less flexible cases,
In-toeing the foot will not correct actively but can easily be corrected
The three most common causes of in-toeing are persistent passively. A rigid deformity has a medial soft-tissue crease at
femoral anteversion, internal tibial torsion, and metatarsus the tarso-metatarsal level and a medial soft-tissue contracture
adductus. In-toeing is usually the result of metatarsus that prevents passive correction of the foot.
adductus in an infant, of internal tibial torsion in a toddler, and If the metatarsus adductus is flexible and spontaneously
of femoral anteversion both in children older than 2.5 years corrects as the foot is stimulated into active eversion, it does
and in adolescents. not warrant any treatment. These mild deformities will
Among causes for out-toeing, which is less common, are resolve gradually. Parents should be reassured and shown
diminished femoral anteversion and, less frequently, femoral how to gently stretch the foot and how to stimulate it to
retroversion, external tibial torsion, pes calcaneovalgus, and achieve active correction. Passively correctable deformities
external rotational contracture of the hip. Out-toeing, when can either be casted or be maintained on a splint. Majority
seen in newborns, is often a consequence of intrauterine of the rigid deformities will be corrected by serial casting.
positioning of the foot in dorsiflexion against the shin, or Surgical intervention is indicated very rarely for those patients
calcaneovalgus. In infants and toddlers, it is often the result of with persistent deformity or those presenting late with rigid
external capsular contracture of the hip, and in older children deformities and in older patients with recurrence of the
744 the consequence of true bone torsion or pes planovalgus. deformities.
ch-152.indd 744 11/22/2016 12:21:32 PM

Tibial Torsion anteversion of 40°, which diminishes to approximately 12–16° at

skeletal maturity, resolving at a rate of approximately 1.5° per
Tibial torsion is defined by the angular difference between the
year. This “normalization” with growth is usually achieved by
transmalleolar axis and the bicondylar axis of the knee. Medial
approximately 8–10 years of age.
tibial torsion is most apparent when infants first begin to
The child sits with the limbs in the W position, walks with an
walk. This contributes to physiologic genu varum, which often
in-toeing gait with the patella medially rotated and runs in an
presents in toddlers younger than 2.5 years. A slightly externally
awkward pattern. The appearance while running is described
rotated hip combined with an internally rotated tibia will give
as egg-beater pattern and the walking is described as pigeon-
the appearance of genu varum even if the knee is normal in
toed gait. Tripping as a result of crossing the feet may occur in
the coronal plane. This “apparent genu varum” is frequently
some children.
confused with true infantile tibia vara (Blount’s disease), but
Clinical examination reveals increased internal rotation
can usually be differentiated from the latter by serial physical
and decreased external rotation. Imaging is not routinely
examinations done over a period of a few months. If torsion
indicated, unless there is asymmetrical version. A computed
alone is present, the knee with the patella facing forward has
tomography scan or magnetic resonance imaging is needed
an orientation that ranges from neutral to slight valgus. Classic
to exactly measure the amount of version and this is only
tibial torsion usually improves spontaneously, whereas true
indicated for surgical planning rather than as a diagnostic aid.
Blount disease tends to progress to greater varus deformity.
Majority of the children resolve spontaneously and the
External tibial torsion, which is less common than classic tibial
parents need to be reassured and also counseled to encourage
torsion, has a greater potential for persistence into adolescence.
their child sit cross-legged and avoid “W sitting”. In a select
Physical examination of the lower extremities is normal or
group of children with persistent increased femoral anteversion
may show physiologic genu varum and negative TFA. Medial
(IR >80°) with severe cosmetic and functional limitation de-
tibial torsion resolves spontaneously and hence does not need
rotation osteotomy of the proximal femur is indicated to
any treatment. Efforts aimed at changing the torsional profile
correct the deformity.
of a long bone with an orthosis or other splint is generally
ineffective. It is better to avoid such devices as there is a
possibility of creating a second deformity through the joints.
Clinical Pearls
Due to the benign natural history of the condition and • In-toeing is more common than out-toeing
the generally unattractive and ineffective nature of orthotic • Majority of rotational anomalies resolve with growth
management, observation and parental education are the • No role for orthotics
main forms of treatment of tibial torsion. A small segment • Corrective osteotomy only after 10 years of age.
of the population with severe (>2 standard deviation above
the mean) medial tibial torsion that does not resolve
spontaneously may need treatment. On the other hand,
excessive external tibial torsion might not resolve and,
Key points
therefore, might need treatment at a later age. In either case, ))
Many children with angular and rotational deformities can
moderate-to-severe deformities that fail to resolve should have physiological malpositions which correct over time
alert the orthopedist to the possibility of an underlying ))
Angular deformities in a child who has at least 2 years of growth
neurologic problem, such as cerebral palsy. left are treated with guided growth using growth modulation
Surgical management by rotational osteotomy may plate
therefore be necessary in the rare situation in which the ))
Corrective osteotomies may be needed for angular
child has persistent functional or cosmetic problems after deformities where less than 2 years of growth is remaining
8 years of age. Rotational tibial osteotomies should probably or guided growth is contraindicated and for correction of
be performed only in a child with a persistent deformity pathological rotational deformities
exceeding 15° internal FPA or 30° external FPA at age 8 years ))
Encourage dual protection for pregnancy and sexually
or older, thereby ensuring that no other rotational change or transmitted infection.
gait accommodation is likely to occur, and in whom definite
functional and psychological disturbances appear to be
present. SUGGESTED READINGS
1. Herring JA. Tachdjian’s Pediatric Orthopaedics: From the Texas Scottish Rite
Femoral Anteversion Hospital for Children. 5th ed. Philadelphia, PA: Saunders-Elsevier; 2013.
2. Lovell WW, Winter RB, Morrissy RT, Weinstein SL. Lovell and Winter’s Pediatric
Femoral version is defined as the angular difference between
Orthopaedics. 6th ed. Philadelphia, PA, USA: Lippincott Williams & Wilkins; 2006.
the axis of the femoral neck and the transcondylar axis of the 3. Joseph B, Nayagam S, Loder RT, Torode I. Paediatric Orthopaedics: A System of
knee. Medial femoral torsion is a common clinical problem Decision-Making. London, United Kingdom: CRC Press, Taylor & Francis Group;
during early childhood. It is twice as common in girls as in 2009.
boys. Normally, children are born with an average femoral 4. Staheli LT. Rotational problems in children. J Bone Joint Surg Am. 1993;75:939‑49.
745
ch-152.indd 745 11/22/2016 12:21:33 PM

Chapter 153
Approach to a
Child with a Limp
Sandeep A Patwardhan, Anirban Chatterjee, Arjun A Dhawale
INTRODUCTION common causes of limp in different age groups are shown in

box 2. A detailed history, physical examination, laboratory
A limp is any deviation from the normal gait pattern. The tests, and imaging are necessary for making a diagnosis.
incidence of limping in children is unknown. A child walking Common tests are shown in table 1.
with an abnormal gait pattern is a cause of concern for parents
and the attending pediatrician. As a number of conditions may
be the cause of a limp, a systematic approach is needed for
HISTORY
appropriate treatment to be initiated. The importance of obtaining a detailed history from the
child or parents cannot be overemphasized. Some of the
important questions to be answered are: is the onset acute,
DIAGNOSIS
insidious, or chronic? Is the limp persistent or periodic,
Abnormal gait can be antalgic (Algorithm 1) or nonantalgic. static or progressive and if there are any systemic symptoms
Common abnormal gait patterns are shown in box 1 and like fever or weight loss. If there is pain, is it localized and
Algorithm 1
Algorithm for antalgic gait
WBC, white blood cell; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; RBC, red blood cell; DD, differential diagnosis; MRI, magnetic resonance imaging.
ch-153.indd 746 11/22/2016 12:30:07 PM

Chapter 153: Approach to a Child with a Limp
Box 1: Common abnormal gait patterns Table 1: Tests for diagnosis
Short limb gait Antalgic gait Test Condition

• When limb length discrepancy • Short stepping Complete blood count Polymorphs increased in infective
(LLD) >5% • Reduced stance time on
or inflammatory pathologies
• Toe walk/shoulder drops on affected side
same side • Spine pain C-reactive protein Level increased in infective or
• Compensatory knee bend on • Slow stiff gradual movement inflammatory pathologies
contralateral side to avoid jarring Erythrocyte Level increased in infective or
Trendelenburg gait sedimentation rate inflammatory pathologies
• Weak abductors, abnormal
fulcrum Synovial fluid analysis Septic arthritis: leukocyte count
• Pelvis drops on opposite side increased (>50,000/cmm), turbid
• Compensatory leaning on synovial fluid; transient synovitis:
affected side leukocyte count increased
(<15,000/cmm), clear synovial fluid
Synovial fluid culture Septic arthritis: growth; transient
Box 2: Common causes of limp in different age groups synovitis: no growth
Toddlers 1–3 years Adolescents 11–15 years Throat culture Acute rheumatic fever: group A
• Mild pain • Mild to moderate streptococci
{{ Transient synovitis (hip) {{ Slipped capital Blood culture Positive in infective pathologies
{{ Toddlers fracture femoral epiphysis
{{ Seronegative {{ Residual hip dysplasia
spondyloarthropathy {{ Chondrolysis (hip)

• Infective: continuous pain, not relieved by NSAIDs, night
• Severe and night pains {{ Overuse syndromes
pain could be due to chronic granulomatous diseases like
{{ Septic arthritis (hip, knee, ankle) {{ Osteochondritis tuberculosis
{{ Tumors dissecans • Tumor: relentless pain, not relieved by medication; night
• Painless {{ Tarsal coalitions pain—possible tumor, benign or malignant with the
{{ Cerebral palsy {{ Seronegative exception of osteoid osteoma, where pain relief is known
{{ Muscular dystrophy spondyloarthropathy with ibuprofen.
{{ Coxa vara (hip) • Severe
{{ Developmental dysplasia of {{ Sickling crisis
{{ Malignant tumors
CLINICAL EXAMINATION
the hip
{{ Torsional problems {{ Osteomyelitis It should be noted whether the child walked in or was carried
Child 4–10 years • Painless into the consulting room or walked in. If the child walked in
• Mild {{ Tethered cord (spine)
then some observation of the gait is possible even before a
{{ Transient synovitis hip {{ Cerebral palsy
detailed clinical examination.
{{ Legg-Calvé-Perthes {{ Other neurological
To properly analyze the gait, the child should be undressed
{{ Discoid meniscus (knee) conditions and made to walk along a corridor, run, and get up from sitting/
{{ Limb length
• Severe squatting position, provided it is painless. In case the limp is
{{ Septic arthritis (hip, knee, ankle) discrepancy
acute in origin and painful, then such a detailed visual analysis
{{ Leukemias
of gait may not be performed. While the child is walking, one
{{ Tumors
needs to observe the trunk, the pelvis, hips, knees, and the
• Painless ankle foot complex individually. One also needs to observe the
{{ Limb length discrepancy
shoes, especially the wear characteristics of the heel and sole.
{{ Tethered cord (spine)
{{ Cerebral palsy
{{ Muscular dystrophy
Local Examination
{{ Coxa vara (hip) At the end of the history and examination of the gait, one
{{ Developmental dysplasia of should have narrowed down the differential diagnosis (DD)
the hip and also mentally decide which limb, which bone or which
{{ Torsional problems joint needs to be examined in more detail. To avoid missing
out any subtle signs, examination should include the spine
and lower extremities including hip joints, knee joints, and
what its aggravating and relieving factors are. Some examples ankle-foot complex with the child suitably undressed. A useful
are: dictum to follow for local examination of a part is look, feel,
• Mechanical: pain on loading, relieved by rest move, measure, and perform (special tests).
• Inflammatory: continuous pain but relieved by nonsteroidal Focal examination should be done if infection or trauma is
anti-inflammatory medicines (NSAIDs) suspected. 747
ch-153.indd 747 11/22/2016 12:30:08 PM

Clinical Pearls
• Onset, duration, and progress of limp and associated or
absence of pain must be elicited clearly
• Origin of pathology in a limping child may be from the
foot to the spine
• Think of the most common conditions first according to
age.
Transient Synovitis
Transient synovitis is commonly seen in children aged 3–8 years
with acute onset of hip pain and limping with a decreased range
of movements. Often, there is a history of a preceding viral
illness. Ultrasound findings of joint effusion with no elevation A B
of C-reactive protein and erythrocyte sedimentation rate (ESR) Fig. 1: Periosteal reaction of the tibia, the differential diagnosis could
with a normal or slight elevation in white blood cell count help be osteomyelitis, healing fracture, or Caffey’s disease.
corroborate the diagnosis. Treatment is observation, rest, and
analgesics. are common injuries and are diagnosed with appropriate
radiographs. Treatment depends on the location and type
Septic Arthritis of fracture and the age of the patient. Closed treatment of
Septic arthritis can occur at any age from the neonatal long bone fractures with casting or elastic nailing is usually
period. There is an acute onset of pain, limping, and fever the norm. Epiphyseal injuries and joint injuries should be
with restricted hip range of movements. Differentiation from identified with a thorough local examination and if suspected
transient synovitis is based on history of fever, inability to bear then an magnetic resonance imaging is useful.
weight, elevated ESR, and leukocytosis (>12,000 cells/mL). The
probability of a diagnosis of septic arthritis increases with the Limb Length Discrepancy
number of criteria present; ultrasound to assess joint effusion Children with a limb length discrepancy (LLD) will toe
and synovial thickening. Radiographs, although not helpful walk on the shorter side. The shortening may be due to
in the early stages, identifies associated osteomyelitis, soft- developmental dysplasia of the hip (DDH), congenital short
tissue swelling, or hip subluxation. Early intervention with femur, postinfective physeal growth arrest, or hemimelia
hip arthrotomy and 6 weeks of antibiotic coverage as per the (Fig. 2). Apart from treatment of the primary pathology, a
culture sensitivity is the standard of care. lower extremity scanogram will document the LLD. Treatment
is usually a shoe raise and observation for a difference of up
Osteomyelitis
Osteomyelitis in children usually occurs as a result of
hematogenous spread of bacteria. The most common organism
is Staphylococcus aureus, with incidence of methicillin-
resistant S. aureus (MRSA) increasing. The child will present
with fever, limping, localized swelling, and tenderness.
Although metaphyseal involvement is more common, the
diaphysis may be involved less often. In acute osteomyelitis,
early radiographs may only show soft-tissue swelling and
radiographs after a few weeks will show periosteal reaction
(Fig. 1) and bone destruction. A 6-week course of appropriate
antibiotics is initiated after obtaining blood cultures and local
cultures after surgical drainage.
Fracture
Children with trauma to the lower extremity may present with
a limp. These could commonly occur while playing or due
748 to motor vehicle accidents. Fractures of the femur and tibia Fig. 2: Limb length discrepancy in a child with fibular hemimelia
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Chapter 153: Approach to a Child with a Limp
to 2 cm. For a greater LLD, lengthening of the short limb with

an external fixator or an epiphysiodesis of the contralateral
extremity are options after serial documentation of the
discrepancy.
Developmental Dysplasia of Hip

Incidence of neglected DDH is higher in India and other
developing countries due to the absence of screening programs
and unequal distribution of healthcare facilities and personnel
in urban and rural areas. This often results in a missed diagnosis
of DDH and children present with a limp (Fig. 3). Diagnosis
of DDH in a child of walking age can be made clinically on
hip examination by eliciting a telescopy sign and restricted
abduction with LLD. The pelvis anteroposterior radiograph will
confirm the diagnosis of DDH. Treatment depends on the age
of the child. After walking age, open reduction is necessary and
may be combined with a femoral and acetabular osteotomy to Fig. 4: Perthes disease of the right hip in an 11-year-old male with
relocate the head into the acetabulum. extrusion and flattening of the head
Slipped Capital Femoral Epiphysis

6 and 11 years. The prognosis is better in younger children
Slipped capital femoral epiphysis is more common in
due to the better remodeling potential of the capital femoral
overweight adolescent boys. Onset of limp and pain could be
epiphysis. Although many theories have been postulated, the
insidious in stable slips or acute with inability to bear weight
etiology is not well defined. The pelvis radiograph will show
in unstable slips. Some patients may complain of knee pain
collapse or extrusion depending on the stage of the disease
(due to referred pain). Patients will have restricted range of
(Fig. 4). Treatment depends on the age of the patient and stage
hip movements, with obligatory external rotation on flexion
of the disease, the principle being to contain the hip with an
and restricted internal rotation. Anteroposterior and lateral
abduction cast, femoral varus osteotomy, or an acetabular
hip X-rays are diagnostic of the slip. Bilateral involvement
shelf procedure.
could occur. An endocrinology workup should be completed.
Treatment is dependent on the degree of slip and usually
involves surgery with in-situ pinning for mild-to-moderate Osteoid Osteoma
slips and management of any underlying endocrinological The child will present with boring pain in the extremity with
condition, if present. worsening at night and typically NSAIDs will relieve the pain.
A computed tomography scan can confirm the diagnosis
Perthes Disease with a sclerotic ring surrounding a nidus being the classical
radiographic appearance. Treatment is image-guided
Legg-Calvé-Perthes disease usually presents with a painful limp
radiofrequency ablation or surgical excision.
with restricted internal rotation of the hip in children between
Juvenile Arthritis
Juvenile arthritis is an important DD in a child with a limp
who presents with pain in the knee, ankle, or subtalar joints.
Swelling with some restriction of movement will be present
along with an elevated ESR and antinuclear antibody positive
titer, although this may often be negative. Orthopedic inter
vention is rarely needed.
Clinical Pearls
What to tell the parents?
• A limp is often the tip of the iceberg
• Investigations are necessary to prove diagnosis or rule out
sinister pathology
• Surgical intervention is very often required, especially in
painless limps to prevent future problems.
Fig. 3: Developmental dysplasia of the hip 749
ch-153.indd 749 11/22/2016 12:30:08 PM


A referral to a pediatric orthopedic specialist is warranted if 1. Aronsson DD, Loder RT, Breur G, Weinstein SL. Slipped capital femoral epiphysis:
there is a mild painful limp, not responsive to conservative current concepts. J Am Acad Orthop Surg. 2006;14(12):666-79.
therapy for more than 10 days; if the limp is associated with 2. Boscainos PJ, Cousins GR, Kulshreshtha R, Oliver TB, Papagelopoulos PJ.
Osteoid osteoma. Orthopedics. 2013;36(10):792-800.
severe pain, especially at night; if there is a persistent limp with
3. Flynn JM, Widmann RF. The limping child: evaluation and diagnosis. J Am Acad
all basic investigations normal, and if an obvious orthopedic
Orthop Surg. 2001;9(2):89-98.
abnormality is diagnosed on investigations. 4. Gill KG. Pediatric hip: pearls and pitfalls. Semin Musculoskelet Radiol.
2013;17(3):328-38.
Key points 5. Herring JA. Tachdjian’s Pediatric Orthopaedics: From the Texas Scottish Rite
Hospital for Children, 5th ed. Philadelphia: Saunders-Elsevier; 2013.
))
Onset, duration, progress, and associated symptoms and age 6. Kocher MS, Mandiga R, Zurakowski D, Barnewolt C, Kasser JR. Validation of a
of a limping child are your most valuable diagnostic criteria clinical prediction rule for the differentiation between septic arthritis and transient
synovitis of the hip in children. J Bone Joint Surg Am. 2004;86-A(8):1629-35.
))
Supportive and relevant investigations will lead to accuracy
7. Sawyer JR, Kapoor M. The limping child: a systematic approach to diagnosis. Am
in management
Fam Physician. 2009;79(3):215-24.
))
Early and timely referral significantly affect outcome 8. Shah H. Perthes disease: evaluation and management. Orthop Clin North Am.
))
Unilateral painless limp should never be ignored 2014;45(1):87-97.
))
Bilateral limp usually indicative of as generalized or systemic 9. Sultan J, Hughes PJ. Septic arthritis or transient synovitis of the hip in children: the
involvement or bilateral pathology which requires correct value of clinical prediction algorithms. J Bone Joint Surg Br. 2010;92(9):1289‑93.
prioritization of problems. 10. Weinstein SL, Mubarak SJ, Wenger DR. Developmental hip dysplasia and
dislocation: Part II. Instr Course Lect. 2004;53:531-42.
750
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Chapter 154
Pulled Elbow, Growing Pains,
and Flatfoot
Premal Naik, Hitesh B Chauhan
PULLED ELBOW • Child’s forearm or hand is held firmly by a parent as the

child attempts to run away
Pulled elbow is a common injury in children under the age of 5 • Child is lifted by an adult from the ground by his/her hands
years. It is a minor soft-tissue injury of the radiohumeral joint • Child may be lifted by the hand from a lying or sitting
caused by sudden traction on the hand, wrist, or forearm. position or may be swung around by the hands/wrist while
playing.
Incidence
Five percent of all upper limb injuries less than 10 years age: Pathology
• Boys more than girls Traction on pronated forearm with extended elbow → partial
• Left more than right. escape of radial head from annular ligament → pulled elbow
Mechanism of Injury Clinical Features (Algorithm 1)

Forcible traction applied to the child’s pronated hand or wrist Child presents with painful dangling arm (infant will present
with the elbow extended; common circumstances, which leads with pseudoparalysis), child does not use the affected limb
to such traction injury, are: for holding objects, keeps the elbow extended and forearm
Algorithm 1
Algorithm for pulled elbow patient
ch-154.indd 751 11/22/2016 5:01:28 PM

pronated, and resists supination of forearm. There is no Algorithm 2

obvious tenderness, edema, or deformity at elbow. Algorithm for growing pains
Investigations
Pulled elbow is a clinical diagnosis, but when the mode of
trauma and history are not corroborative, X-ray is indicated.
Treatment
Reduction Maneuver
• Hold the child’s wrist with one hand and with other hand
support the elbow and palpate the radial head → supinate
the forearm with upward push on the radial head → click is
felt with radial head reduction
• Sometimes pronation and flexion of elbow is also required JIA, juvenile idiopathic arthritis; S. CPK, serum creatine phosphokinase.
for reduction
• Click signals successful reduction, the child will be playful
and will use the arm after sometime • Pain is most commonly in calf and ankle region and
• If the child is not using arm immediately, should be sent sometimes is so severe that child cries with pain
home with analgesics and should be called the next day. • Few children demand massaging for relief of pain
• Primarily involves lower extremities and is mostly bilateral
Precautions • Typically child resumes normal activity next day.
An important aspect in the management of pulled elbow is to
On Examination
advise the parents to avoid traction on the child’s arm. They
should not pull child from hands or wrists. Parents should be • Normal walking pattern without limp
advised to discuss this with neighbors and relatives who are • No local tenderness or swelling in joints and muscles
expected to handle the child any time. • No muscular spasticity or restriction of joints movements
• No wasting or neurological deficit. Gower test will be
Clinical Pearl negative
• No limb length discrepancy or limb wasting.
• Look for mode of trauma or mechanism of injury, age of
the child, absence edema or deformity at elbow, pronation Investigations
attitude of forearm, and presence of previous history of similar
If history is not corroborative, any other condition should be
complaints → clinically pulled elbow → reduction maneuver
ruled out with X-rays and blood investigations.
→ feel click → dramatic improvement in movements → no
immobilization required.
Differential Diagnosis
If there is history of trauma and excessive exertion with local
GROWING PAINS (Algorithm 2) bony tenderness, rule out stress fracture with X-ray. Tumor-
These are idiopathic benign pains or discomfort in children. like osteoid osteoma, osteogenic sarcomas, or Ewing’s give
rise to night pain, but are more aggressive and associated with
Incidence localized swelling, tenderness and limb wasting.
• Fifteen to thirty percent of all children
• More common in girls.
Management
After ruling out any other cause of pain, diagnosis of growing
Etiology pains is considered.
No specific treatment, hot fomentation, massage, and
Idiopathic in nature, no documented cause has been discovered.
analgesic may help.
Most importantly, parents should be reassured and made
Clinical Features to understand that growing pain are self-limiting and will
Growing pain is a diagnosis of exclusion. All other causes of leg subside in due course of time. One can be made to understand
aches are to be excluded before stamping it as growing pain. relation of pain with sudden increase in height of their child
• History is typically vague and of long duration (growth spurt) in last few months.
• Not associated with any functional disability Relapse may occur in next growth spurt. If any other
• Usually occurs at night (just before going to sleep). symptoms like swelling, wasting, and fever develop on follow-
752 Occasionally child may get up from sleep due to pain up, child should be subjected to further investigation.
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Chapter 154: Pulled Elbow, Growing Pains, and Flatfoot
• Rigid flatfoot: arch is absent all the time, whether child is

Clinical Pearl bearing weight or not. It may be due to:
{{ Tarsal coalition
Long and vague history, bilateral lower extremity, night pain,
{{ Juvenile chronic arthritis
mainly calf and ankle, normal activities next day, no clinical
findings → no radiological findings → diagnosis of exclusion → • Neuromuscular flatfoot: flatfoot secondary to muscular
reassurance, diversion of mind, relapses may occur → look for imbalance, weakness or spasticity. Common causes are:
warning signals. {{ Cerebral palsy
{{ Spina bifida.
FLATFOOT Differential Diagnosis

Other conditions which give similar appearance as of flatfoot
Absence of medial longitudinal arch of foot is known as flatfoot are:
(Algorithm 3). • Congenital vertical talus
• Accessory navicular.
Incidence
It occurs approximately 20–30% of general population. Clinical Features
• Primarily parents complaint of awkward appearance of
Classification foot, uneven shoe ware, or sometimes pain
• Flexible flatfoot: arch is absent when patient bears weight • Family history may be positive: parents tend to have joint
but appears off weight. It is be due to hyperlaxity of laxity and sometimes flatfeet as well. Tarsal coalitions can
ligaments (Fig. 1) be autosomal dominant or recessive
• Many parents are bothered about future participation in
Algorithm 3 sports and army recruitment.
Algorithm for flatfoot patient
Examination
• In flexible flatfeet: arch disappears on standing, and
reappears on taking weight off. Arch also reappears when
patient stands on toes (Fig. 2)
• Wind up test or Jack toe raising test: in flexible flatfoot,
arch can be reproduced by extending great toe at
metatarsophalangeal joint (Fig. 3)
• General assessment of signs of hyperlaxity should be
looked for hyperextension of elbows, thumb touching to
forearm, knee hyperextension
• In rigid flatfeet, arch is always absent, on or off weight.
Extension of great toe or standing on toes does not form
arch
• Movements of the hindfoot are restricted in rigid flatfeet
and free in flexible flatfeet
• Heel is in valgus and corrects on tiptoeing in flexible feet
CT, computed tomography.
753
Fig. 1: Patient with flexible flatfoot Fig. 2: Same patient showing good arch on tip toe
ch-154.indd 753 11/22/2016 5:01:29 PM

Clinical Pearl
• Absence of medial longitudinal arch, complaining of awkward
feet and gait pattern, uneven shoe wear and tear, sometimes
pain → Look for hyperlaxity, hindfoot movements, presence of
arch off weight, jack toe raising test, neurological examination
→ Absence of radiological signs → Reassurance, barefoot
walking, rigid arch support for pain
Key points
Fig. 3: Same patient showing good arch on extension of great toe ))
Commonly loss of medial longitudinal arch
))
Changes in the hindfoot movement
))
Associated with hyperlaxity
• Tendo achilles tightness should be looked for ))
Differentiate from tarsal coalition and neurological flatfeet
• Detailed neurological examination if any suggestive ))
Forcible traction in pronation is the common mechanism
findings are present. ))
Painful nonusage of arm results
))
Reduce on outpatient department (OPD) basis two gentle
Investigations attempts
• In flexible flatfeet, no investigations are required, clinical ))
Reduction click gives dramatic relief
diagnosis is adequate ))
Cause is idiopathic
• In rigid flatfeet, X-rays and computed tomography scan are ))
Commonly calf pain at night
helpful to rule out tarsal coalitions. ))
Stretching exercises and hydration maximum relief.
Management
• In flexible flatfeet: SUGGESTED READINGs
{{ Parents are reassured regarding benign nature of
1. Evans AM. Growing pains: contemporary knowledge and recommended practice.
deformity J Foot Ankle Res. 2008;1(1):4.
{{ Promote bare feet walking in sand and garden 2. Fabry G. Clinical practice. Static, axial, and rotational deformities of the lower
{{ Special shoes have no role in management of flexible extremities in children. Eur J Pediatr. 2010;169(5):529-34.
flatfeet (in fact early shoe wearing in city kids is found 3. Harris EJ, Vanore JV, Thomas JL, Kravitz SR, Mendelson SA, Mendicino RW, et al.
Diagnosis and treatment of pediatric flatfoot. J Foot Ankle Surg. 2004;43(6):341-73.
to have high incidence of flatfeet compared to rural
4. Irie T, Sono T, Hayama Y, Matsumoto T, Matsushita M. Investigation on 2331 cases
children walking bare feet) of pulled elbow over the last 10 years. Pediatr Rep. 2014;6(2):5090.
{{ Arch support only if severe shoe wear and feet pain 5. Krul M, van der Wouden JC, van Suijlekom-Smit LW, Koes BW. Manipulative
{{ Rarely surgery is advised for failed conservative interventions for reducing pulled elbow in young children. Cochrane Database
treatment Syst Rev. 2009;(4):CD007759.
• In tarsal coalitions: initially, conservative treatment in 6. Mohanta MP. Growing pains: practitioners’ dilemma. Indian Pediatr. 2014;51(5):
379-83.
form of cast followed by splints and arch support is given. If 7. Mosca VS. Flexible flatfoot in children and adolescents. J Child Orthop.
it fails then bar excision surgery is required 2010;4(2):107-21.
• In neuromuscular flatfeet: Initial conservative treatment is 8. Petersen H. Growing pains. Pediatr Clin North Am. 1986;33(6):1365-72.
orthosis. If it fails than surgery in form of muscle balancing 9. Weiser P. Approach to the patient with noninflammatory musculoskeletal pain.
or arthrodesis is required. Pediatr Clin North Am. 2012;59(2):471-92.
754
ch-154.indd 754 11/22/2016 5:01:29 PM

CHAPTER 155
Clubfoot Treatment:
Current Concepts
Rujuta Mehta, Alaric J Aroojis
INTRODUCTION Box 1: Multifactorial inheritance system

Clubfoot is the one of the most frequent congenital deformity Most common etiology
seen by a pediatrician and referred to a pediatric orthopedic • Idiopathic
surgeon. Recent estimates say over 50,000 children are born • Neuromuscular etiology
with clubfoot in India. Over 3,700 children are born with • Syndromic/genetic etiology, e.g.:
clubfoot in Maharashtra which means one in every 500 live {{ Arthrogryposis multiplex congenita
birth is a clubfoot. Significant advances have been made over {{ Streeter’s dysplasia (constriction band syndrome)
{{ Secondary to decrease of size of the uterus resulting from

the last few decades regarding the treatment of clubfoot. This
chapter will give the reader an overview of diagnosis and early rupture of amnion with chorion remaining intact
management in concurrence with the changing scenario and Rarer syndromic etiology
shift back to conservative treatment in view of recent successes • Autosomal dominant: whistling face/Freeman-Sheldon
vis-a-vis state of the art management. syndrome (craniocarpotarsal syndrome)
• Autosomal recessive:
{{ Diastrophic dwarfism (micromelia)
DEFINITION {{ Joint contracture, scoliosis, thumb deformities, congenital
talipes equino varus

The term congenital talipes equino varus (CTEV) aptly {{ Larson syndrome
describes the complex amalgamation of the following {{ Down’s syndrome
deformities of the entire foot: congenital, from birth; talipes, {{ Mobius syndrome
foot; equino, equinus posture of the foot complex (like a
horse’s heel) excessive plantar flexion; and varus, inversion
and subluxation on talonavicular joint.
ETIOLOGY
Multifactorial inheritance system due to intrauterine
environment factor leads to idiopathic CTEV (Box 1).
PATHOLOGY
Bony and soft-tissue pathology coexist in clubfeet (Fig. 1).
It is a deformation occurring during the second trimester of
pregnancy and not an embryonic malformation except in the
teratologic variety. Congenital clubfoot is a complex three-
dimensional deformity having four components: (i) equinus,
(ii) varus, (iii) adductus, and (iv) cavus. The tarsal bones,
which are mostly made up of cartilage, are in the most extreme Fig. 1: Dissected fetal clubfoot showing typical bony and
positions of flexion, adduction and inversion at birth. The talus soft-tissue pathology
SECTION 19: Orthopedics
is in severe plantarflexion, its neck is deflected medially and tendo-Achilles at the final step of correction. This technique of
plantarward, and its head is wedge-shaped. The navicular is manipulation and casting is based on anatomical studies and
severely medially displaced, in close apposition to the medial a biomechanical understanding of the “kinematic coupling”
malleolus and articulates with the medial surface of the head of the subtalar joint. It corrects all elements of the deformity,
of the talus. The calcaneus is adducted, plantarflexed and resulting in a functional, pain free, looking plantigrade foot
inverted under the talus. The forefoot is in some pronation, with good mobility, without calluses, and without the need
causing the plantar arch to be more concave (cavus). The for wearing special or modified shoes. Foot examination and
calcaneocuboid joint is deviated posteromedially. The deltoid, corrective manipulations are best done with the baby resting
tibionavicular ligament and the tibialis posterior tendon are on the mother’s lap. When applying the plaster cast, the baby is
thickened and merge with the short plantar calcaneonavicular placed at one end of the table to provide room for the mother
ligament. The ligaments of the posterior and medial aspects and assistant on either side. It is best if the baby is breastfed
of the ankle and tarsal joints are very thick and taut, thereby through the treatment.
severely restraining the foot in equinus and the navicular and
calcaneus in adduction and inversion. There is an excessive Results of the Ponseti Method of Clubfoot Treatment
pull of the tibialis posterior abetted by the gastrocsoleus, the The Ponseti method is a safe and effective treatment for
tibialis anterior and the long toe flexors. congenital idiopathic clubfoot and radically decreases the
need for extensive corrective surgery. it is the most effective
HISTORY AND PHYSICAL EXAMINATION method for children less than 1 or 2 years of age (Fig. 3).
The orthopedic officer must have a sensitive and kind approach Clinical Pearls
to babies. After a general examination to rule out nonidiopathic
clubfeet, parents must be reassured that their baby’s deformity • Treatment can begin as early as first week of life
will be corrected in a few weeks. The baby will have a normal- • Complex deformity yields better under influence of relaxin
looking and functional foot throughout life as long as they are with serial casts
faithful to all the details of the treatment program. Radiographs • Deformity is corrected within few weeks
are not necessary. • Adherence to protocol is a must.
MANAGEMENT Treatment after Independent

Treatment of clubfoot as a generic term cannot be clubbed Walking is Achieved
together. It is therefore subdivided as follows:
Various surgical modalities exist for addressing all grades of
• Treatment in the prewalking age
severity of clubfeet in the post-walking age group:
• Treatment after independent walking is achieved.
• Open surgery: soft-tissue releases and tendon transfer
• Bony surgery
Treatment in the Prewalking Age • Fixators.
The most widely practiced current standard of care for The axiom “No two clubfeet are exactly the same” is well
treatment of clubfeet in the first 6 months of life is the Ponseti accepted now and therefore the corollary that the surgical
method of treatment (Fig. 2). This is a combination of weekly treatment has to be catered to the type and need of each case
plastering and a semi-invasive procedure of tenotomy of the what is known as “A la carte” approach.
A B C
756
Fig. 2: Technique of Ponseti casting. Note the supination of the forefoot while it is being abducted
CHAPTER 155: Clubfoot Treatment: Current Concepts
A B
C D
Fig. 3: Result of Ponseti method of treating clubfoot in a 1-week-old neonate. The deformity is fully corrected after five serial
manipulations and casting followed by a percutaneous tendo-Achilles tenotomy
Open Surgery: Soft-tissue Releases • Lengthening of three tendons:

{{ Tendo-Achilles
Failures of conservative treatment or late presentations after
{{ Tibialis posterior
the age of 1 or 2 years usually mandate surgical release. Several
{{ Flexors digitorum and hallucis.
operations have been described for this condition since early
Results of this surgery are highly gratifying and long-
1930s. The most widely followed surgery is a posteromedial
lasting (Fig. 4), but not without their share of complications
release popularized by Vincent Turco in the 1960-70s after he
and morbidity.
published his original monograph with a 16-year follow-up. This
surgery addresses almost all the deforming pathoanatomical
structures on the anterior medial and posterior aspects of the Open Surgery: Tendon Transfer
foot and their abnormal interrelationships. The salient features Tendon transfers are indicated for age groups above 3–5 years
of this surgery are as follows: mainly for residual uncorrected components of clubfoot
• Release of three joints: deformities. Tibialis transfer to the medial cuneiform bone is
{{ Ankle indicated for dynamic supination and persistent metatarsus
{{ Subtalar adductus deformity, which particularly occurs with relapses of
{{ Talonavicular the conservative or Ponseti method of plastering.
• Release of three ligament groups:
{{ Talocalcaneonavicular, spring ligament, and plantar Bony Surgery
fascia The incidence of bony surgeries has plummeted in recent
{{ Superficial deltoid or talocalcaneal years, particularly with the colossal success of conservative
{{ Calcaneofibular and talofibular. techniques; however, it deserves mention.
757
A B
C D
Fig. 4: Steps and result of posteromedial release surgical open release for a 17-month-old boy
• Osteotomies: particularly for hind- and midfoot correction been analogous to an external version of Ponseti principles
above the age of 5 years, after majority of the tarsal bones which gradually unlocks the talus and brings about a complete
have ossified correction of all components of clubfoot, however, complex the
• Talectomy/naviculectomy: this is a surgery with a very deformity. Fixators are invaluable for neglected and relapsed
select place for the treatment of severe arthrogrypotic feet and rigid clubfeet, particularly 3–14 years (Fig. 5).
where the deformity is so severe and no other operation Clubfoot is referred at any age and treatment can be
can work so as to prevent plantigrade shoe wear instituted irrespective of age of referral. A simple flowchart on
• Triple arthrodesis: this is a salvage procedure done at or treatment of clubfoot treatment is depicted in algorithm 1.
around skeletal maturity for very severe or recalcitrant
clubfeet, for the purpose of relieving pain or to facilitate
normal shoe wear. ROLE OF EXERCISES AND SPLINTS
Any method of CTEV correction requires maintenance of
Fixators correction and sustaining the same till skeletal maturity. This
In 1989, Dr BB Joshi from Mumbai, India, started using an is achieved by using special footwear in the form of ankle-foot
indigenous external fixation system for gradual distraction of orthosis or stiff medial border shoes mounted on an abduction
multiplanar deformities of clubfoot. The frame is essentially bar with external rotation correction. These are essentially
constructed on K-wires fixing three segments: (i) tibial, (ii) static devices and need to be supplemented with active and
calcaneal, and (iii) metatarsal. These three segments are then assisted active exercises and stimulation of the muscles of the
interconnected using clamps, rods, and distraction assemblies lateral aspect of the foot regularly several times a day over a
are used at altering rhythms in a differential fashion, i.e., number of years. The importance of a regular follow-up and
medial more than equinus more than lateral. The process has prevention of relapse thus cannot be overemphasized.
758
CHAPTER 155: Clubfoot Treatment: Current Concepts
A B
C D
Fig. 5: Deformity, frame and result of external fixation system for neglected clubfoot
ALGORITHM 1
Clubfoot treatment
759

1. Cooper DM, Dietz FR. Treatment of idiopathic clubfoot. A thirty-year follow-up note.
What to tell the parents? J Bone Joint Surg Am. 1995;77(10):1477-89.
• Treat early 2. Kite JH. The Clubfoot. New York, NY, USA: Grune & Stratton; 1964.
• Maintain serial casting and bracing protocol 3. Laaveg SJ, Ponseti IV. Long-term results of treatment of congenital club foot.
• Correct treatment will ensure full correction of deformity and J Bone Joint Surg Am. 1980;62(1):23-31.
good function 4. Morcuende JA, Weinstein SL, Dietz FR, Ponseti IV. Plaster cast treatment of clubfoot:
• Surgery when indicated can give good results the Ponseti method of mani pulation and casting. J Pediatr Orthop B. 1994;B(3):161-
• Postoperative bracing and rehabilitation has a vital role. 7.
5. Ponseti IV. Congenital Clubfoot. Fundamentals of Treatment. Oxford, United Kingdom:
Oxford University Press; 1996.
6. Turco VJ. Surgical correction of the resistant club foot. One-stage posteromedial
KEY POINTS
release with internal fixation: a preliminary report. J Bone Joint Surg Am.
))
Clubfeet vary in severity and presentation 1971;53(3):477-97.
))
Early conservative treatment in the form of serial Ponseti casts 7. Warrier SS, Joshi BB. Use of external fixators for virgin and neglected club feet.
is highly successful Speaker Hand Out POSI. 2000. pp. 83-88.
))
Recurrences are amenable to successful treatment too
))
Neglected or resistant feet over the age of 1 or 2 years may be
treated with surgery.
760
Chapter 156
Developmental Dysplasia of the Hip
Jayanth S Sampath, Rujuta Mehta
SPECTRUM OF Developmental neonates resolve spontaneously, this is termed physiological

dysplasia of the hip instability.
Developmental dysplasia of the hip (DDH) is a term used to Clinical Pearl

describe a spectrum of conditions where the hip joint fails to A significant number of clinically unstable hips (Barlow positive)
develop normally during childhood. In the past, descriptions resolve spontaneously in the first few weeks of life. This is termed
such as congenital dislocation of the hip were used. The term physiological instability. Hip ultrasound scan is mandatory in
hip dysplasia is also commonly used. All of the above terms such cases.
refer to the same condition.
CAUSES AND RISK FACTORS

INCIDENCE OF Developmental
dysplasia of the hip Teratologic dislocations are caused by neuromuscular
conditions such as arthrogryposis multiplex congenita, spina
The widely quoted figure of 1–2 cases of dislocation per 1,000 bifida, Larsen syndrome, and diastrophic dysplasia. A specific
live births is an approximation. The reported incidence of cause may not be readily identifiable in typical dislocations.
DDH in the literature is influenced by genetic and racial A positive family history in first-degree relatives increases the
factors, cultural practices (tight swaddling of neonates risk of DDH. Wynne Davies reported a risk of 6% with 1 affected
amongst Native Americans), experience and training of the sibling, 12% risk with an affected parent, and 36% when a
examiner, diagnostic criteria applied and age of the child at parent and a sibling are affected. Other risk factors for DDH,
presentation. The incidence of neonatal hip instability may be relative risk, and the presumed pathogenetic mechanisms are
as high as 1 in 100. Since the vast majority of unstable hips in summarized in table 1.
Table 1: Risk factors for developmental dysplasia of the hip, relative risk, and the presumed pathogenetic mechanisms
Risk factor Relative risk Mechanism
Breech presentation* 5–6 times (greater risk if Frank breech with hip flexion Intrauterine compression, though preterm breech
and knee extension) babies also at risk
“Clicky” hips at birth 8 times compared to normal hip examination at birth —
Birth order >50% of developmental dysplasia of the hip in first born Tight uterus
Girls 3–6 times greater than boys Greater susceptibility in girl babies to the maternal
hormone; relaxin causes ligamentous laxity
Side affected Left:right ratio of 3:1 Left occipitoanterior position causes the left hip to
rest against the mother’s spinal column
Oligohydramnios Higher risk if clinically significant, low risk if diagnosis Intrauterine compression
made on sonography
Postural foot deformity Risk varies from 1 in 27 for postural talipes to 1 in 5 for Extraneous compression of the hip on the affected
calcaneovalgus feet side
*Successful external cephalic version for breech presentation reduces, but does not abolish developmental dysplasia of the hip risk. Ultrasound screening of the
hips for babies in this category is recommended.
ch-156.indd 761 11/25/2016 5:07:59 PM

DIAGNOSING Developmental
dysplasia of the hip
Clinical Examination
There are no pathognomonic physical findings in DDH which
will help the clinician make a reliable diagnosis at any age and
in every child. Considerable skill, experience, and patience
are therefore essential if an accurate diagnosis is to be made.
The clinical features suggestive of DDH change as the child
becomes older. An age-specific approach, therefore, needs to
be adopted when examining the child with suspected DDH.
At or soon after birth (first few weeks of life), Barlow
and Ortolani tests are provocative maneuvers with high
specificity for DDH. They should be performed in every child
at or soon after birth. Barlow test detects an enlocated hip
which dislocates from the acetabulum, whereas the Ortolani Fig. 2: A positive Galeazzi test
is a “relocation” test which diagnoses a dislocated hip as it
reduces back into the acetabulum. Other clinical signs which
Table 2: Clinical features of developmental dysplasia of the
are associated with DDH include asymmetrical groin creases
hip at different ages
(Fig. 1), a positive Galeazzi test (Fig. 2) and limb length
discrepancy. Reduced hip abduction (<60°) is a sensitive Age Signs and symptoms of DDH
clinical indicator of DDH in children over the age of 3 months. 0–3 months • Barlow and Ortolani test
Developmental dysplasia of the hip should be borne
3–12 months • Reduced hip abduction
in mind when examining a child with a limp or waddling
• Leg-length discrepancy
gait. An important principle in the diagnosis of DDH is to
detect asymmetry in the limbs (length, range of movement, • Galeazzi test
etc.). However, it is worth remembering that bilateral DDH • Asymmetrical groin crease
is frequently missed due to lack of asymmetry. Table 2 • Barlow/Ortolani tests may become negative by
summarizes the clinical features of DDH at different ages. age 3 months
12 months • Leg-length discrepancy
Clinical Pearl and above • Painless limp
• Waddling gait (bilateral DDH)
All newborns, irrespective of risk factors, should undergo a careful
DDH, developmental dysplasia of the hip.
examination of the hip by a pediatrician at or soon after birth.
Barlow and Ortolani tests should be performed and the results
clearly documented. Investigations
Though clinical tests for DDH have high specificity (>90%), they
lack sensitivity particularly in neonates and infants (around
60% only). By no means does a normal clinical examination
rule out DDH. The clinician should, therefore, select an
investigation which will conclusively confirm or rule out DDH.
The choice of test again depends on the age of the child.
Children 0–4 months of age: ultrasound scanning of the hips
using the Graf (static) and Harcke (dynamic) methods is
recommended in children younger than 4 months.
In the Graf method, a and b angles are calculated and these
angles guide treatment. The alpha angle is an indicator of the
extent of development of the bony acetabulum (bony roof ).
The b angle is an indicator of development of the cartilaginous
roof (Fig. 3).
The Graf method is precise and has been standardized
to a high degree. Specific training in ultrasound scanning
for hip dysplasia is necessary in order to obtain good quality
ultrasound scans.
Ideally, all newborn babies should undergo a hip ultrasound
762 Fig. 1: Asymmetric groin creases scan. Though practiced in certain parts of Europe, Universal
ch-156.indd 762 11/25/2016 5:08:00 PM

Chapter 156: Developmental Dysplasia of the Hip
Fig. 3: Ultrasonography of subluxation of hip Fig. 4: An X-ray of developmental dysplasia of the hip
Neonatal Ultrasound Hip Screening cannot be justified due WHAT ARE THE TREATMENT OPTIONS?
to cost, logistical hurdles and the relatively low incidence of
abnormal hips requiring treatment. As mentioned earlier, many Treatment of DDH is entirely dependent on the age of the child.
physiologically immature hips will resolve spontaneously by 6 The younger the child at diagnosis, the less the intervention
weeks of age. Universal screening may result in overtreatment required. It is, therefore, important that the diagnosis is made
of immature hips and the possibility of iatrogenic complications as soon after birth as possible.
such as avascular necrosis of the femoral head. Figure 5 summarizes the treatment options for DDH at
Selective ultrasound hip screening based on risk factors different ages. Note that the treatment becomes progressively
for DDH has been implemented more widely in the United more invasive with increasing age at treatment.
Kingdom, United States, and other developed nations.
Common indications and the timing of ultrasound screening Pavlik Harness
are summarized in table 3. This is the least invasive method and, therefore, the most
Children older than 4 months: a good quality anteroposterior patient friendly. The harness can be used from birth to the age
X-ray of the pelvis will clearly demonstrate the problem in the of approximately 4 months. The baby can kick both legs freely
vast majority of cases. Various lines are drawn on the X-ray by within the harness and it does not interfere with normal growth
orthopedic surgeons as illustrated but these are probably of of the baby (Fig. 6).
little interest to pediatricians (Fig. 4). Once the baby has been placed in a harness, ultrasound
Briefly, the Hilgenreiner’s (horizontal) line and Perkin’s scans must be repeated every week until the hip is anatomically
(perpendicular) line result in four quadrants. The normal hip located back in the hip joint. This may take 2–4 weeks. Average
lies in the inner-lower quadrant. time in the harness is likely to be between 10 weeks and
Table 3: Common indications and the timing of ultrasound

screening
Indication Timing of ultrasound
• Positive Barlow-Ortolani tests Immediate
• Clicky hip
• Reduced hip abduction
• Leg-length discrepancy
• Breech 6–9 weeks postnatal
• Oligohydramnios (to avoid overtreatment
• Twins of physiologically
immature hips)
• Positive family history in first degree
relatives
• Postural foot deformity
(e.g., calcaneovalgus foot)
• Clubfoot (congenital talipes equino Fig. 5: Treatment options for developmental dysplasia of the hip at
varus) different ages 763
ch-156.indd 763 11/25/2016 5:08:00 PM

Medial Open Reduction

This is a minimally invasive procedure undertaken in children
under 18 months of age. There are numerous advantages
with this procedure compared to a traditional “anterior open
reduction”. The operation is performed through a small incision
in the groin and, therefore, not visible to the outside. There is
minimal blood loss and less postoperative pain.
The medial open reduction is also referred to as “assisted
closed reduction” or “relaxed closed reduction”. This term is
used because a forcible closed reduction causes damage to the
blood supply of the femoral head and poor long-term results.
Medial open reduction is followed by immobilization in
a hip spica cast for 4–6 months. Long-term results of medial
open reduction have proven that this is a minimally invasive
procedure that is safe and effective.
Anterior Open Reduction with

Femoral and Pelvic Osteotomy
This procedure is typically used in children older than
Fig. 6: Baby with Pavlik harness 18 months who have been walking for a period of time on
the dislocated hip. When a child walks on a dislocated hip,
12 weeks. In the vast majority of babies under 3 months (90% the capsule enlarges and becomes quite lax. This enlarged
or more), treatment with the Pavlik harness is successful and capsule needs to be tightened up in order to prevent the hip
results in radiographically normal hips when assessed at 5 from re-dislocating after surgery. The anterior open reduction
years of age. procedure is designed to address this particular problem
of a capacious and redundant capsule. The anterior open
Clinical Pearl reduction is performed through a “bikini” incision. There are
several tight structures (muscles, tendons, and ligaments)
In summary, early diagnosis (soon after birth) and Pavlik harness that are divided or lengthened. The hip joint is relocated and
treatment should be considered as the gold standard in the capsule repaired to keep the joint in place. Typically, the
managing hip dysplasia. shallow socket (acetabulum) is also corrected by means of a
pelvic osteotomy wherein the socket is divided and reset in
Complications of Pavlik harness include avascular necrosis the correct alignment. In addition to the pelvic osteotomy, a
of the femoral head and transient femoral nerve palsy. These femoral osteotomy is also sometimes required.
can be minimized through proper attention to technique
Neglected Developmental Dysplasia of
during harness application.
the Hip in the Older Child (Figure 7)
Closed Reduction and Unilateral neglected DDH can be treated safely up to the age
of 8 years. The upper limit of age for treatment of bilateral
Hip Spica Application
If the child is older than 6 months at diagnosis, Pavlik
harness is not appropriate. In this group (6–12 months), an
arthrogram will be necessary. A short general anesthetic is
given. A radiopaque dye is also instilled into the hip joint to
provide contrast. If the hip can be reduced without undue
force, a hip spica is applied. The term closed reduction refers
to reducing a dislocated joint without the need for an incision.
This is in contrast to an open reduction where an incision is
necessary. The total period in the spica ranges from 2 months
to 6 months.
In a dislocated hip, concomitant acetabular dysplasia
(shallow acetabulum) is almost always present. Children
less than 18 months of age possess considerable remodeling
capacity and early reduction of the hip typically results in
spontaneous resolution of the acetabular dysplasia. In children
older than 18 months at presentation, an additional procedure
764 in the form of a pelvic osteotomy is usually required. Fig. 7: Hyperlordosis
ch-156.indd 764 11/25/2016 5:08:00 PM

Chapter 156: Developmental Dysplasia of the Hip
Algorithm 1
))
Surgical treatment is indicated postwalking and can have a
Management of developmental dysplasia of the hip successful outcome
))
Various options are available for the neglected DDH, surgically
))
All varieties of DDH should be treated to eliminate the lurch
and prevent secondary osteoarthritis, and problems with the
lumbar spine which may occur if left untreated
))
First screening for developmental DDH clinical in neonatal
intensive care unit, Barlow’s and Ortolani test
))
Hips with persistent instability at 1 month need to be treated.
SUGGESTED READINGS
1. Barlow TG. Early diagnosis and treatment of congenital dislocation of the hip.
J Bone Joint Surg. 1962;44-B(2):292-301.
2. Dunn PM. The anatomy and pathology of congenital dislocation of the hip. Clin
Orthop Relat Res. 1976;(119):23-7.
3. Gage JR, Winter RB. Avascular necrosis of the capital femoral epiphysis as a
complication of closed reduction of congenital dislocation of the hip. A critical
review of twenty years’ experience at Gillette Children’s Hospital. J Bone Joint
Surg Am. 1972;54(2):373-88.
4. Graf R. Classification of hip joint dysplasia by means of sonography. Arch Orthop
Trauma Surg. 1984;102(4):248-55.
6. Harcke HT, Kumar SJ. The role of ultrasound in the diagnosis and management
of congenital dislocation and dysplasia of the hip. J Bone Joint Surg Am.
neglected DDH is approximately 5 years. In children older than 1991;73(4):622-8.
these age thresholds, there is unacceptably high incidence of 7. Klisic PJ. Congenital dislocation of the hip--a misleading term: brief report.
iatrogenic complications which compromises the eventual J Bone Joint Surg Br. 1989;71(1):136.
8. Laurenson R. The acetabular index: a critical review. J Bone Joint Surg.
outcome.
19589;41-B:702.
9. Mubarak S, Garfin S, Vance R, McKinnon B, Sutherland D. Pitfalls in the use of the
Pavlik harness for treatment of congenital dysplasia, subluxation, and dislocation
Clinical Pearl of the hip. J Bone Joint Surg Am. 1981;63(8):1239-48.
The key to successful management of developmental dysplasia 10. Ortolani M. Congenital hip dysplasia in the light of early and very early diagnosis.
of the hip is to identify risk factors for DDH in the newborn, Clin Orthop Relat Res. 1976;(119):6-10.
confirm the diagnosis by hip ultrasound scan and institute early 11. Severin E. Contribution to the knowledge of congenital dislocation of the hip joint:
late results of closed reduction and arthrographic studies of recent cases. Acta
appropriate treatment.
Chir Scand. 1941;84(Suppl 63):1-142.
12. Strayer LM. Embryology of the human hip joint. Clin Orthop Relat Res.
1971;74:221-40.
13. Suzuki S, Yamamuro T. Correlation of fetal posture and congenital dislocation of
Key points the hip. Acta Orthop Scand. 1986;57(1):81-4.
14. Wenger DR. Congenital hip dislocation: techniques for primary open reduction
))
Prewalking dysplasia of the hip (DDH) treatment is more
including femoral shortening. Instr Course Lect. 1989;38:343-54.
successful than postwalking. A painless unilateral limp or a
bilateral waddle in a child must always be investigated for
DDH
765
ch-156.indd 765 11/25/2016 5:08:01 PM

INDEX_.indd 766 11/30/2016 5:36:05 PM
Index
Page numbers followed by f refer to figure and t refer to table.
A Administer antibiotic therapy 160 Alkalinization 22

Abdomen 215, 633 Adolescent anemia, development of 81 Allergic
mottling of 618 Adrenal disease 87, 527 bronchopulmonary aspergillosis 300, 328
tenderness of 618 Adrenal hyperplasia, congenital 343, 537, 549, reaction 37, 186, 310
Abdominoscrotal hydroceles 640 550, 553, 561, 667 Allergy 193
Abetalipoproteinemia 431 Adrenaline 141 Alloimmune thrombocytopenia, neonatal 40
ABO/Rh incompatibility 43, 276 nebulized 310 Alport syndrome 483
Abscess 237 Adrenoleukodystrophy 402 Alveolar hypoventilation 157
cerebellar 429 Adrenomyeloneuropathy 443 Ambiguous genitalia 549, 553
epidural 719, 720 Aerophagia 616 Amenorrhea 87
intracerebral 720 Air American Academy of Family Physicians 712,
retropharyngeal 310 bronchogram 9f 713
subdural 720 leak syndromes 13 American Academy of Pediatrics 44, 324, 712,
subperiosteal 238, 719 movement 130 713
Acanthocytes 265 travel 350 American College of Preventive Medicine 102
Acellular pertussis 116 Airway 163, 174, 176, 180, 209, 213, 217, American College of Radiology 594
Acetaminophen 219 224 Amino acid disorders 459
Acid assessment of 130, 183 Aminophylline 320
disorders, organic 545 breathing, circulation 145, 165, 195 intravenous 321
fast bacilli 360 disability, exposure 135, 188 Ammonia 227
Acidemia clearance Amniotic fluid
isovaleric 528 methods 329 index 491
organic 48 techniques 329 volume 643
propionic 528 diseases 338 Amoebic colitis 377
Acidosis 8 disorders, upper 13 Amphetamine 344
Acidurias, organic 459 edema 141 Anaerobic infections 223
Acne 87 hydration 329 Analgesia
adolescent 668 management 161, 310 local 215
development of 537 obstruction 5, 131, 139f systemic 215
infantile 667 degree of 317 Analgesics 194
mid-childhood 667 lower 131, 158, 160 Anaphylaxis 186
neonatal 667 upper 130, 158, 186 management of 159t, 183
pediatric 667 patency, assessment of 303 Androgen 519
preadolescent 668 pressure, mean 17, 18, 147, 197, 226 aromatization of 532
treatment 668, 669 resistance syndrome, upper 727 blocking action of 90
vulgaris 667 sounds 131 insensitivity syndrome 250, 532-534, 549,
Acquired immunodeficiency syndrome 71, abnormal 193 640
270, 280, 533, 672 Alagille syndrome 655 receptor antagonism 532
Activated partial thromboplastin time 41, 270, Alanine transaminase 381 secreting tumors 667
289-292, 294-297, 297t, 593 Alarm therapy 502 Anemia 34, 36, 80-82, 260, 261, 264, 264f, 267,
Adenoid hypertrophy 712 Alcohol 77, 124 272, 273, 273t, 276, 280, 517
Adenoidectomy 714 abuse 96 adolescent 79
Adenosine Aldosterone aplastic 35, 275
diphosphate 298, 543 antagonist 91 cause of 80, 264, 272
triphosphate 543 estimation 344 chronic 35, 515
Adenotonsillectomy 731 level 470 classification of 35t, 272
Adenovirus 322 Alexander’s disease 400 degree of 272
Adiposity, markers of 520 Alkali therapy 336 development of 260
INDEX_.indd 767 11/30/2016 5:36:06 PM

diagnosis of 81, 261, 272 second-line 408 Asphyxia 8

hemolytic 79 therapy 410 antenatal 32
hypoplastic 35 toxicity 154 perinatal 13, 28, 68t
megaloblastic 262f, 265f Antifungal agents 674 Aspirations, recurrent 25
normocytic 276 Antihepatitis C virus 481 Asthma 149, 341, 661
normochromic 275 Antihistamine, intravenous 224 acute severe 319t
nutritional 35, 79, 80 Antihistaminics, topical 689 course of 318
pernicious 80 Antihypertensive drugs 478 exacerbations of 319
persistent 260 Antimicrobial therapy 247 management 160t, 320
prevalence of 272 Anti-Mullerian hormone 551, 553, 554 predictive index 312
prevention of 37, 82f Antineutrophil cytoplasmic antibodies 301, prevalence of 317
severe 79 474, 481, 482, 579, 606 severity assessment, acute 318t
severity of 79t, 264 Antinuclear antibodies 270, 474, 481, 482, 574- Astrocytoma, cerebellar 433
sideroblastic 266 576, 582, 594, 595, 606, 607 Asymptomatic hypoglycemia, management
treatment of 55, 82 Antiphospholipid antibody 288 of 48
types of 261 Antipyretics 166, 168 Ataxia 151, 410, 427, 432, 433
Anesthesia, general 613, 635 Antirabies vaccines 124, 125 attacks of 430
Aneurysm formation 579f Antiretroviral causation of 427t
Angelman’s syndrome 398t drug 250 cerebellar 428, 428t, 431, 432
Angioedema 141 prophylaxis 251 chronic 430
Angiotensin Antiscorpion venom 185 hereditary 431
converting enzyme 336, 533 Antisnake venom 183, 223, 225 intermittent 430
inhibitors 335 Antistreptolysin O 474, 477, 574 progressive 432
receptor blockers 349, 563 Anti-tissue transglutaminase 360 telangiectasia 431, 432
Angular stomatitis 263f, 359 Antitubercular therapy 360, 363 vestibular 428
Animal bite 123, 126 Anxiety disorders 102, 106 with oculomotor apraxia, types of 432t
wound, management of 124 Aorta 29 Atelectasis 131, 246
Anisocytosis 272 coarctation of 60, 332, 333, 336, 515 Atopy 312
Ano fissure 376f severe coarctation of 60 Atresia, laryngeal 723, 724
Anogenital ratio 551 Aortic arch Atrial fibrillation 153
Anomalous pulmonary venous interruption of 60 Atrophic testis 622
connection 332 Aphasia 151 Atrophy, testicular 627
Anorchia, congenital 532 Apnea 5, 54 Attention deficit hyperactivity disorder 84, 96,
Anorectal malformation 58 causes of 5, 7 111, 501
Antenatal hydronephrosis frequency of 7 Atypical wheezing, causes of 313t
definition of 642t time of 5 Auditory pathway 701f
isolated 493, 494 Apneic episodes, recurrent 15 Autism spectrum disorders 457
Anti-HIV antibodies, detection of 252 Appendicitis, acute 616 Autoantibody 600
Antiacetylcholine receptor 426 Apraxia, oculomotor 431 Autoimmune 664, 666
Antiallergics 194 Arrhythmia 136, 178, 224, 333 disease 253, 269
Antiandrogens 91 Artemether combination therapy 233 hemolytic anemia 276
Antibiotic 55, 196, 324, 611 Arterial blood thyroid disease 529
broad-spectrum 277 gas 6, 9, 18, 25t, 140, 174, 227, 233, 325, 381 Automated otoacoustic emission 700
dosage of 248, 277 pressure 164 Autonomic nervous system dysfunction 155
first line 55 Arterial carbon dioxide, partial pressure of 17, Autosomal dominant disorder 261
intravenous 488t 21, 22 recessive disorder 431-433
prophylaxis 647 Arterial hypertension, pulmonary 334, 350 Azathioprine 663
rational use of 329 Arterial oxygen, partial pressure of 17, 21 Azithromycin 478
role of 179 Arteriovenous fistula, systemic 333
route of 736 Artery, pulmonary 342 B
therapy 237, 238, 238 Arthritis 573, 603, 735
duration of 238 acute 564, 566 Bacillary dysentery 377
Antibodies 527 juvenile 749 Bacillus Calmette-Guérin 280, 584
Anticholinergics 319, 454, 503 chronic 753 vaccine 116
Anticonvulsant 148, 194 idiopathic 420, 565, 566, 568, 569, 571, Bacteremia, treatment of 161
therapy 537f 574-576, 603, 607, 608 Bacteria, role of 322
Antideoxyribonuclease 477, 575 postinfectious 564 Bacterial infection, serious 166, 228
Antidepressants 521 reactive 564, 565, 735 Bacterial pharyngitis, complication of 310
Antidiuretic hormone 470, 504 traumatic 575 Bag mask ventilation 158
Anti-double stranded deoxyribonucleic Arthrodesis, triple 758 Barium 653
acid 595 Arthrogryposis multiplex congenital 716 enema 633
Antiepileptic 409, 521 Arytenoid, fixation of 723 Barking cough 139, 724
drug 147, 201, 406, 408, 410, 410t, 414, 416, Aspartate aminotransferase 523 Barlow chart 177t
418 Aspartate transaminase 381 Barovolutrauma 23
768 first-line 408-410 Aspergillus 609 Barrel shaped chest 24
INDEX_.indd 768 11/30/2016 5:36:06 PM

Index
Bartter’s syndrome 470 reduction of 346 paradoxical 213

Base-line lung function 330 products 179, 198 patterns, abnormal 147
Bassen-Kornzweig disease 432 smear, peripheral 81 spontaneous 2
Becker’s nevus 670 sugar 5, 51, 68, 227, 232 work of 15, 188, 189, 195, 196, 206
Bee sting 186 transfusion 37, 81, 206 Breathlessness 61, 132, 328, 330
Benzodiazepine 410, 429 urea 30 cause of 133t
Benzoyl peroxide 667, 668 nitrogen 227, 344, 406 Breech delivery 516
Betamethasone 663 volume, total 216 Bronchiectasis
Bijvoet’s nomogram 507f Bloodstream infections, catheter-related 247 causes of 327, 327t
Bile ductular proliferation 657 Blount’s disease 522, 740 management of 327
Biliary Blue rubber bleb nevus syndrome 374f pathophysiology of 327
atresia, extrahepatic 655, 658f, 660 Bluish black hemangiomas 374f prognosis of 330
hypoplasia 655 Body Bronchiolitis 322, 323, 325
Bilirubin encephalopathy 50 homeostasis 189 acute 323
Biotinidase deficiency 50, 430, 528 mass index 520 course of 325
Birth asphyxia 47, 431 part of 231 management of 160, 322-324
trauma 677 temperature 168 pathology of 323
Biting animal, observation of 123 Bone severity of 322t
Bladder 344 greater porosity of 718 treatment of 323, 324t
injury 215 growth plate of 235 Bronchoalveolar lavage 313, 328
Bleeding 40, 246 marrow 270 Bronchodilators 160, 324, 329
causes of 39, 40t, 632 aspiration 274 Bronchopulmonary dysplasia 16, 17, 23, 24t,
disorder 269, 677 examination 36 25, 25t, 27, 29
dyscrasias 677 infiltration 80 diagnostic criteria 23t
gums 223 suppression 35 pathogenesis 24
neonate 39-41 ossification of 97 clinical features 24
per rectum 617 pains 505 differential diagnosis 25
per-rectal 632 scan 735 treatment strategies 25
signs of active 369f Bony Bronchoscopy 141, 328
site of 269 acetabulum 762 Bronchospasm, severe 24
time 289, 292 surgery 756, 757 Brown Sequard syndrome 441
Blepharitis 675, 677 Borrelia burgdorferi 145, 437 Brucella 145
Blepharoconjunctivitis 675 Botulism 419, 420 Bulbar conjunctival telangiectasia 432f
Blindness Bovine or cow’s milk protein allergy 353 Bulbar palsy 223
bilateral 678 Bow legs 739, 740 Bullae, aspiration of 224
congenital 457 Bowel perforation, small 215 Burn 344, 414
Blood Bradycardia 153, 557 classification system, modern 175
ammonia 154 Brain 431 depth, categories of 175t
borne bacteria 235, 239 abscess 145, 720 outpatient management of minor 178
components 224 congenital malformations of 430 prevention of 180
culture 51, 55, 56, 66, 228, 229, 233 dysfunction 150 treatment of 179
reports of 7 inflammation of 144
exchange transfusion 57 injury 154 C
filled bullae 223 acquired 460
flow 136 degree of 52 Cabot’s ring 266
cerebral 211 protection 63 Caffeine therapy 26
pulmonary 59, 60 Brainstem Caffey’s disease 748f
gas 51, 232 dysfunction 150 Calcium 406
target 17t glioma 433 channel blockers 478
glucose 47, 66 malformations 424 levels 68
level 48 Breast Caliectasis 642
monitoring of 529 cancer 73, 533 Campylobacter jejuni 421
group 36 ultrasonography 533 Canavan’s disease 400
loss 32, 260 Breastfeeding, duration of 522 Cancer
maldistribution of 136 Breath prevention 90
monitoring of 21 child short of 189 testicular 624
mononuclear cells, peripheral 251 shortness of 317, 616 Candida albicans 609
pressure 32t, 61, 73, 147, 163, 205, 207, 210, Breathing 130, 163, 171, 174, 176, 180, 209, Cannula, intravenous 194
335, 345, 495, 534, 551, 590 213, 217, 224, 226, 303, 317, 323 Capillary hydrostatic pressure 141
adequate 437 adequacy of 171 Capillary refill time 136, 191, 196, 335
diastolic 207, 343 cessation of 5 Capsid antigen, viral 254
high 521 disordered control of 158, 161 Carbamazepine 410, 429
measurement of 58, 523 disorders 727 Carbohydrate
monitoring 172 sleep related 727, 728 deficient glycoprotein syndrome 433
noninvasive 17, 22, 174 evaluation of 130 metabolism, disorders of 545 769
INDEX_.indd 769 11/30/2016 5:36:06 PM

Carbon dioxide 205 vermian hypoplasia 431 Chorea

partial pressure of 226 Cerebral causes of 455
pressure of 15 arteriopathy, transient 437 pathophysiology of 455
Carbon monoxide 179, 219 herniation Chorioretinal colobomas 697
poisoning 154 syndrome 212 Choroidal hemangiomas 697
Cardiac signs of 232 Chromosome 394, 430t, 432, 433, 544, 549
congestive 131 palsy 623 Chronic disease 278, 663
disease 341 ataxic of 430, 431 anemia of 80, 274
failure 60, 344 dystonic 456 prevention 90
impulse 61 perfusion pressure 147, 209-211 Ciliary dyskinesia 712
index 197 vasculitis 154 Circulatory disease, past 73
pump dysfunction 136 Cerebrospinal fluid 51, 57, 167, 211, 229, 233, Cleft palate 712
structure 206 247, 421, 446, 459 Clomiphene 534
surgeries 349 Certain neurodegenerative disorders 398 Clostridium welchii sepsis 265
transplant 207 Cervical Clot retraction 292
Cardiogenic mucosa 74 Clotting time 292
pulmonary edema 160, 161 spine 214 Clubfoot treatment 756, 759
shock 32, 60, 204, 206 Cervico-vertebral anomalies, congenital 420 Coagulation screening tests, abnormal 296
causes of 206 Cetrimide solution 124 Coagulopathy 378, 382
management of 205, 206 Chapel Hill consensus conference 579 Cobolamine metabolism defects 528
pathophysiology of 205 Chemical injury 176, 267 Cobra 183
Cardiomyopathy Chemotherapy 149 Cocaine 344
dilated 332, 333, 336, 337 Chest 215, 341, 385, 664 Cognitive
hypertrophic 562 compression 1, 2 behavior therapy 104, 107, 114
Cardiopulmonary diameter of 3 decline 410
disorders 13 expansion 130 performance 427
resuscitation 130, 159, 190, 191, 224 infections, recurrent 27 Cold
Cardiovascular disease 90, 93f, 241, 344 movement of 189 chain 125
Caroli’s disease 655 pain 338, 340-342 intolerance 557
Cataract 697 cardiac origin of 338 Collagen
Catastrophic epilepsy syndromes 416 causes of 338, 339 disorders 237
Catch-up vaccination 116 symptoms of 340 vascular disease 338, 341
Catecholamine 344 physiotherapy 325, 329 Colonic polyp 376f, 635
excess 343 retraction of 8 Coma, causes of 227t
use of 195 ultrasonography of 610 Community 261
Catheters, suction 1 wall acquired pneumonia 13
Cavernous sinus expansion 131 Complete androgen insensitivity
thrombophlebitis 720 movement 213 syndrome 250, 552
thrombosis 718, 719 X-ray 6, 10f, 18, 24, 55, 61, 334 Complete blood
Celiac disease 359, 361, 557 Chicken pox 232 cell 712
treatment of 361 Child count 6, 55, 66, 140, 160, 162, 165, 174, 229,
Cell abuse 95, 209 232, 236, 242, 253, 259, 264, 270, 289,
aplasia, pure red 275 intrafamilial 94 291, 294, 296, 323, 344, 350, 406, 483,
culture rabies vaccine 124, 125 signs of 516 574, 656
evaluation of 281 incestuous abuse 94 Compressive myelopathy 420
target 266 sexual abuse 97 Conduct disorder 96, 110
volume, packed 273 Childhood Congenital
Cellular immunodeficiency 281 functional abdominal pain blockage, management of 689
Central bronchus, dilated 328 syndrome 390 disorders 276
Central cord syndrome 441, 442 obesity hemolytic anemia 267
Central nervous system 8, 144, 171, 184, 246, causes of 521 hyperinsulinism, treatment for 547
303, 344, 419, 437, 491, 521, 522, 536 management of 520 nasolacrimal duct, management of 690
disorders 13 vasculitis 579 Congestive heart failure 304, 332-334, 336, 337
function 189 classification of 578 broad classification 332
Central venous Chlamydia 98 subacute 335
oxygen saturation 206 Chlorhexidine gluconate 124 treating refractory 336
pressure 164, 197, 205 Chloroxylenol 124 types 334
Centripetal fat distribution 561 Choanal atresia 14 Conjugated hyperbilirubinemia cholestasis,
Cephalic pustulosis pustules, neonatal 667 Cholangiogram, intraoperative 657, 658f causes of 656
Cephalohematoma 34, 35 Cholangitis 659 Conjunctiva 687
Cerebellar Choledochal cyst 655, 657f, 658f examination of 689
ataxias, acute 428 Cholera vaccine 119, 120 Conjunctivitis 605, 676
dysfunction 427 Cholestasis 658 allergic 677, 688
hypoplasia, congenital 431 intrahepatic 656 bacterial 676
770 peduncle, superior 431 Cholestatic neonate 656 chemical 677
INDEX_.indd 770 11/30/2016 5:36:06 PM

Index
chlamydial 678 C-reactive protein 55, 66, 229, 236, 239, 241, Deoxyribonucleic acid 251, 275, 396
enteroviral 677 242, 246, 254, 304, 350, 360, 564, 602, 610, Depression 77, 101, 102
gonococcal 677 735 adolescent 101
infectious 675 Creatine phosphokinase 425 major 106, 108
mild 323 Creatinine 344 management of 104
neonatal 677 kinase 599, 600 signs of 103
purulent 678 Crescentic glomerulonephritis 483 treatment of 105
viral 676, 676t Cricothyrotomy 158 Depressive disorder
Connective tissue Crohn’s disease 359, 362t, 364, 376f, 378 major 105, 107
disease 571 Croup 139f, 140f treatment 105
disorders 437 diagnosis of 140 Dermal melanocytosis 670
Consanguinity 523, 529 management of 142t, 160t Dermatitis
Consciousness severity assessment 140t atopic 661
Child’s state of 189 severity of 140, 309 eczematous 662
level of 138, 155, 166, 172, 183, 213, 317 Cryptogenic epilepsy syndromes 415 Dermatomyositis 419
loss of 186, 209, 210 Cryptorchidism 622-623 juvenile 566, 598, 598f, 600
recovery of 201 Cubital fossa 661 Desmopressin acetate 502
Consensual sex 94 Cushing syndrome 343, 515, 523, 524, 561 Dexamethasone 141
Constipation 557, 616, 617 Cutaneous polyarteritis nodosa 581 dose of 141
chronic 617 Cyanosis 59, 61 Diabetes 8, 73, 136, 149, 341, 346
Constitutional obesity 520, 521 cardiac 60t insipidus 253, 470, 504
Continuous positive airway pressure 1, 5, 6, 9, central 205 mellitus 521, 526, 527, 528, 557, 666
11, 13-15, 17, 25, 36, 63, 195, 324, 325 Cyanotic congenital cardiac disease 21 neonatal 529
application of 158 Cyclooxygenase, use of 30 permanent neonatal 528
delivery of 15 Cyclosporine 344, 663 transient neonatal 528, 667
Contraception 71 topical 689 prevention 90
Conversion disorder 419 Cystic adenomatoid malformation, Diamond-Blackfan anemia 263f
Convulsion 344, 346 congenital 13 Diaphragmatic hernia, congenital 13, 14, 18
Cysts Diarrhea 224, 261, 420, 617
Convulsive disorders 155
cluster of 328 chronic 352, 355, 358
Cool pale diaphoretic skin 193
laryngeal 723, 724 infectious 632
Cool-mist therapy 142
Cytomegalovirus 36, 37, 264, 278, 279, 381, 656 intractable 356t, 529
Coomb’s test 44, 267
Cytoplasmic antineutrophil cytoplasmic management of chronic 360
Cord
antibody 474 repeated 277
clamping 1
Diastolic dysfunction 204, 562
hemisection of 441
prolapse 50 D Diastrophic dysplasia 761
Diazoxide 530
syndrome 443 Dacryocystorhinostomy 690 Diethylcarbamazine 301
Core temperature monitoring 172 Danazol 534 Diethylene triamine pentaacitic acid 493, 494
Cornea 687 Dancing eyes 457 Diethylstilbestrol 623
perforation of 678 Dancing feet 457 DiGeorge syndrome 277
Corneal Dandy-Walker syndrome 430 Dihydrotestosterone 553, 554
abrasion 675, 677 Deafness, congenital 457 Dimercaptosuccinic acid 486, 489, 644, 646
light reflex 697 Deamidated gliadin peptide 361 Diphenhydramine 454
Cornstarch, use of 545 Deep mucus layer 687 Diphtheria antitoxin 310
Coronary artery disease 332 Deep partial thickness burns 176f Diphtheria pertussis tetanus vaccine 366,
Coronavirus 322 Deep tendon reflexes 440 349
Corrosive Deep vein thrombosis 198 Diplopia 682
ingestion 385 Deformity Disability 192
injury 384 angular 739 assessment 215
types of 384 complete correction of 742 Disconnective surgery 416t
Corticosteroid 26, 141, 155, 320, 324, 419 in children, rotational 742 Disseminated intravascular coagulation 55,
inhaled 312, 329 rotational 743 182, 184, 245, 265, 269, 276, 284, 287, 291,
systemic 324 Dehydration 294-297
topical 674 episodes of 504 Diurnal dystonia 454
Cosmetic problem of 323 Dog bite 420
signs 90 recurrent 470 Double stranded deoxyribonucleic acid 594
symptoms 90 Dehydroepiandrosterone 532, 535, 554 Down’s syndrome 84, 420, 430, 557
Cotrimoxazole prophylaxis 252 Delivery, methods of 16 Downes’ score 9t
Cough 341, 348, 616 Demyelination 437, 438 Drop attacks 405
bouts of 317 Dend syndrome 528 Drowsiness 410
Cover test 693 Dengue, rash of 243 Drug 1, 2, 5, 26t, 60, 77, 96, 98, 148, 173 229,
Cozen’s fracture 742 Dennie Morgan fold 662 246, 253, 261, 335, 337, 344, 412, 414, 415,
Cranial nerve palsies 155 Dental procedure 350 417, 418, 521, 532
Craniocervical junction lesions 425 Deoxyribonuclease 324 Drug-refractory epilepsy, complication of 414 771
INDEX_.indd 771 11/30/2016 5:36:06 PM

Duodenal thoracis 609 second dose of 224

hematoma 215 Encephalitis 132, 144, 678 Epiphora 688
obstruction 619f enteroviral 155 Episcleritis 675
Dysautonomia, familial 344 syndrome Episodic
Dyselectrolytemia 5, 149, 444 acute 144, 231, 233, 234, 444 ataxia, hereditary 430, 430t
Dysfunctional uterine bleeding 87 causes of acute 232 phenomena 405
Dyshormonogenesis 515 treatment of 155 viral wheeze 312
Dyslipidemia 92 viral 231, 233 Epistaxis 223
prevalence of 522 Encephalomyelitis, acute disseminated 144, Epsilon aminocaproic acid 291
Dysmenorrhea, relief of 72 419, 429, 437, 460 Epstein-barr virus 145, 269, 285, 569
Dysmorphic Encephalopathy 459 Erythema 668
red blood cell 481f acute 459, 461t Erythematous plaques 661
syndromes 521 enteric 155 Erythrocyte sedimentation rate 236, 239, 254,
Dysmorphism 433, 522 episodes of 232 304, 360, 361, 564, 574, 576, 586, 735, 748
Dyspepsia, functional 389 hypoxic 149 Erythromycin 478, 667
Dysphonia, dystonic 453 neonatal 13 Erythropoietin
Dysplasia recurrent 154 reduced 80
ectodermal 253 syndrome, acute 445, 446 transient deficiency of 35
metaphyseal 463, 464 End-expiratory pressure, positive 16, 17, 63, Escherichia coli 236, 488
Dyspnea 186 160 sepsis 545
progression of 304 Endocardial fibroelastosis 333 Estradiol, level of 538
Dystonia 151 Endocarditis Estrogen
acute 453 infective 333, 337, 566, 576 action of 532
form of 231 prophylaxis, infective 350 effect, signs of 538
lingual 453 Endocrine 521 receptor agonism 532
musculorum deformans 454 diseases 521 Ethanol 219
paroxysmal 453, 454 function 344 Ethylcysteine 493, 494
primary 454 hypertension 560, 562 Ethylene glycol 219
secondary 454 Endogenous eczema, non-contagious 661 Ethylenediamine tetraacetic acid 294
severe 455f Endometrial glands, regression of 72 Eustachian tube
Dystopia canthorum 664 Endophthalmitis 675 function 714
Dystrophy, myotonic 426 Endotracheal intubation 157, 170, 309 malfunction 712
Dysuria 616, 617 End-stage renal disease 589 Exacerbations, acute 674
Entamoeba histolytica 609 Excessive sweating 344
E Enterovirus 322
Enuresis 500
Exfoliative dermatitis 529
Expiratory flow, peak 318
Ear Envenomation 181 Extracellular fluid 470
effusion, middle 710 signs of 224 Extracorporeal membrane oxygenation 22,
infection, middle 712 Enzyme, deficiencies of 544 198, 336, 699
inflammation, middle 712 Enzyme-linked immunosorbent assay 281, Extrahepatic
Eating disorders 96 481, 595 biliary atresia, treatment in 660
Ebstein anomaly 333 Eosinophilia 299-301, 301t portal venous obstruction 369
Ectopic testis 622 syndrome 300 Extubation, chances of 7
Eczema, atopic 661 Ependymoma 433 Eye movements, wandering 696
Edema 61, 512 Epidermal Eyelid
angioneurotic 159, 310 barrier dysfunction 661 edema of 262
inflammatory 140, 140f nevi 670 hygiene 677
pulmonary 21, 142, 164, 478 Epididymis, appendix of 631f Eyes, deviation of 691
subgaleal 140f Epididymo-orchitis 629, 630
Elbow, pulled 751
Electrical burns 176
Epiglottitis 139f, 140f, 141, 310, 723
Epilepsy 404, 405, 408, 412
F
Electrocardiogram 163, 184, 201, 319, 320 death in 414 Facial
Electroencephalogram 51, 148, 202 disease 408 hemiparesis 344
Electrolytes 178, 344 drug treatment of 409 muscle 405
Electron microscopy 478 medical management of 408 purpura, development of 39
Elliptocytosis 35 pseudorefractory 415 Facies 261
Ellis-Van Creveld syndrome 742 pyridoxine-dependent 50 hemolytic 262f
Embryo vaccine 125 refractory 414 Fanconi’s anemia 262f, 263f
Emesis 172 remission of 405 Fanconi’s syndrome 466, 505
Emotions, control of 107 surgeon 415 Fasciotomy 224
Empiric therapy 153 surgery 416 Fasting blood sugar 344
Empyema 149, 609, 610, 612 resective 416 Fatal
management of 611 syndrome 51, 408 asthma 317, 318
stages of 610t Epinephrine disease 125
772 subdural 153 nebulized 141 meningitis 678
INDEX_.indd 772 11/30/2016 5:36:06 PM

Index
Fatigue 557, 558, 672 Flexors digitorum 757 functional 389

diaphragmatic 14 Fluid endocospy, upper 356, 368f, 369f, 378
Fatty acid 672 adequacy of 196 symptoms 220t, 651
oxidation 543, 546-548 amount of 163 tract 223, 299, 469
defects 48 intravenous 47 Gastroscopy 634
disorders 459, 545 refractory shock 196 Gaucher’s disease 402
Febrile child, management of 168 restriction, moderate 30 Genetic
Febrile encephalopathy resuscitation 36, 178 disorders 623
acute 144-146, 149t, 151t, 152t, 444, 446 therapy 163 influences 500
causes of acute 445 Fluorescein dye disappearance test 689 Genital
Febrile systemic infections, acute 677 Fluorescence in situ hybridization 301, 424, bleeding 73
Feeding disorders 522 552 herpes 97
Female condoms 72t Fluoroscopy 653 Genitalia
Femoral Focal fibrocartilaginous dysplasia 741, 742 atypical 561
anteversion, persistent 744 Focal sensory attacks, transient 405 examination of 97
arterial thermodilution 197 Folinic acid-responsive seizures 50 external 672
epiphysis, slipped capital 749 Follicle stimulating hormone 89, 534, 535, 540, Genitourinary tract tumors 257
pulses, weak 61 554, 623 Genu valgum 522, 739, 741, 742
Fertility 627 Food and Drug Administration 105, 315 causes of 742
Fetal Food protein allergy, management of 354 idiopathic 741, 742
distress 50, 696 Foot progression angle 743, 744 post-traumatic 742
echocardiography 59, 350 Foul smelling 32 Genu varum 740
intervention 643 Fowler position 335 causes of 739, 740
urinary tract 491 Fractionated serum bilirubin Germ cell
Fetomaternal transfusion 34 concentration 656 malignancy 553
Fetoplacental transfusion 34 Fracture 214, 522 tumors, extragonadal 257, 532
Fever 166, 224, 243, 246, 341, 348, 504, 574, pelvis 214 Gestational age 47, 515, 546
576, 616, 617, 724 splinting of 163 Gestational diabetes mellitus 50
acute 168 Free fatty acid 401t, 530, 543 treatment of 524
assessment of 166 Fresh frozen plasma 42, 224, 291, 292, 378, 382 Glasgow Coma Scale 145, 190, 192, 193, 209,
causes of 167t Fresh neurological deficits 413 211t, 214, 232
central 246 Friedreich’s ataxia 431, 432 modified 193
control 194 Fructose-1,6-biphosphatase deficiency 545 Glomerular
degree of 149 Fundus, diameters of 539 basement membrane 474, 475
enteric 152, 254 Fungal sepsis 54, 57 bleeding 480
infectious causes of 246 Furosemide 478 filtration rate 476, 477, 494, 497, 505, 507,
nature of 166 646
noninfectious causes of 246 G hematuria 480, 483
of unknown origin 253, 255 Glomerulonephritides, infectious 478
causes of 253 Gait patterns, abnormal 747 Glomerulonephritis 343, 473, 476, 481
percentage of 241 Galactorrhea 539 acute 473, 474
phobia 169 Galactose-1-phosphate uridyltransferase 545 postinfectious 473, 477, 478f
severity of 169 Galactosemia 48 poststreptococcal 473, 476-479
treatment of 168 Galeazzi test 762f membranoproliferative 481, 482, 498
Fibrin degradation product 270, 291 Gallbladder 657f postinfectious 473
Fibrinogen 297 disease 73 post-streptococcal acute 476f
degradation products 184, 297 stone 657 Glucokinase, mutations of 544
Fibrinolysis inhibitors 297 Gallstone disease 522, 523 Gluconeogenesis 530
Fibrinolytic system 39 Gamma-glutamyl transpeptidase 381 Glucose 406
Fibrocalculus pancreatic diabetes 527 Ganglia lesions, bilateral 461t 6-phosphate dehydrogenase 35, 261
Fibromuscular dysplasia 343 Gangrene infection 223 deficiency 381
Fibrosis Gas exchange abnormalities of 5
cystic 314, 327 assessment of 318, 323 complete blood count cultures 201
peribronchial 328 optimize 163 estimation, methods of 47
Fibular hemimelia 748f Gastric homeostasis 542, 543
Fine needle aspiration cytology 559 decompression 213 infusion rate 47
Fissure in ano 632, 634 lavage 173, 221 infusion, intrapartum 47
Fistula, bronchopleural 610 Gastroenteritis 348, 620 ratio fluid/plasma 610
Flaccid Gastroenteropathy, eosinophilic 632 storage of 526
paralysis 223, 419 Gastroesophageal reflux 27, 140, 318, 328 supply of 542
quadriplegia 223 disease 5, 304, 314, 328, 391 transporter deficiency 50
Flap phonomicrosurgery 707 bleeding 366, 367, 368t, 371 Glutamate dehydrogenase 543
Flatfoot 522, 753 control upper 370t Glutamic acid decarboxylase 526
rigid 753 lower 378, 379, 632 Gluten-free diet 361
Flexible flatfeet 753 disorder 389t Glycemic control 198 773
INDEX_.indd 773 11/30/2016 5:36:06 PM

Glycogen structural 59, 340 Hemolytic uremic syndrome 73, 266f, 269,
storage 426 valvular 332, 333 270, 276, 294, 497, 611
disorder 400, 545, 546 congenital 8, 32, 58, 58t, 60, 61, 136, 149, Hemophilia 237
stores, depletion of 543 204, 206, 233, 324, 332, 333, 339, 345, Hemorrhage 164, 344
Glycosylation, congenital disorder of 431, 433 350, 425 adrenal 34
Gonadal maturation 535 failure 60, 340 cerebellar 429
Gonadotropin acute ongestive 336 control 214
regulation of 535 acute primary 336 internal 276
release of 535 decompensated 336 intracranial 34, 50, 223
Gonadotropin-releasing hormone 89, 535, 540 management of 62 intraventricular 1, 5, 6, 8, 30, 36
agonist analog test 539 management of congestive 332 pulmonary 13, 39, 55
Gonorrhea 98 primary 336 subconjunctival 675, 677
Gower test 752 signs of 340 subgaleal 34
Graft versus host disease 37 lesion, congenital 58t Hemorrhagic
Granulomatosis 576 obstruction 60 causes 80
Granulomatous polyangiitis 581 palpitations 186 signs 224
Graves’ disease 558 rate 2, 5, 6, 55, 61, 135, 163, 165, 196t, 204, Hemostasis 39
Great vessels, transposition of 59 205, 214, 335 Hemostatic system 40t
Ground glass appearance 9f normal 192t components of 39, 40t
Growth failure 27, 521, 522 pattern, abnormal 32 Hemothorax 131
Growth hormone 518t, 519, 521, 542, 544, 548 size of 206 Henoch-Schönlein purpura 291, 294, 295, 344,
deficiency 514, 515, 519 sounds 61 474, 479, 481, 497, 566, 576, 578, 581, 582,
insensitivity syndromes 515 surgery 350 589, 590
stimulation test 518 Heat intolerance 558 management of 590
therapy 515, 519 Heinz body 266 palpable 375f
Growth parameters, assessment of 523 Helicobacter pylori 437 Hepatic
Growth plate disturbances 238 Helminthiasis 80 coma 444
Growth velocity, monitoring of 514 Hemangioblastoma, cerebellar 433 disease 176
Guanosine triphosphate 543 Hemangioma 632, 723, 725 duct 658f
Guillain-Barré syndrome 344, 419-421, 421t, subglottic 725 dysfunction, causes of 523
429 Hemarthrosis 735 encephalopathy 155, 460
Gum hypertrophy 263f Hematochezia 632 injury 215
Gunshot injury 211 Hematoma, extradural 209 transaminases 253
Gynecomastia 532, 533 Hematuria 36, 345, 480, 484 Hepatitis 300
causes of 532, 533 benign familial 483 A
familial 532 causes of 481t vaccine 118
extraglomerular 480, 481t virus 381
H gross 480, 482 B 98
microscopic 479, 482 surface antigen 381, 482, 564
Haemophilus influenzae 116, 228, 241, 281, Hemianopia, temporal 685f vaccine 116
310, 328, 602, 676, 710, 736 Hemiconvulsion-hemiplegia-epilepsy virus 479
Hair loss 410, 664 syndrome 435 C virus 479
Harrison’s sulcus 464 Hemiepiphysiodesis, bilateral 742 E virus 381
Hartnup disease 430 Hemiparesis 151, 346 neonatal 656, 658
Hashimoto’s encephalopathy 154 abrupt onset of 436 Hepatocyte transplantation 382
Head Hemiplegia 435 Hereditary exostosis, multiple 752
injury 132, 209, 414 congenital 435 Hereditary giant platelet syndromes 270
classification of 209 recurrent 438 Hernia 637, 639, 639t, 640, 640f
traumatic 221 Hemiplegic migraine, familial 438 bilateral 640
posture Hemodialysis 221 diaphragmatic 9, 21
abnormal 680, 684 Hemodynamic support, management of 197 inguinal 623, 637, 638
components of 680 Hemoglobin 197, 260 inguinoscrotal 637
interpretation of 680 concentration 157 management of 638
trauma 215, 536 mean corpuscular 260, 264, 272, 273 open repair of 640
Headache 344, 346, 536, 560 distribution width 265 Herniation syndromes 151t, 155
severe 516 electrophoresis 81 Herpes infections 279
Healing fracture 748f level of 276 Herpes simplex 656
Hearing disability 84 normal 34t encephalitis 144, 231
Heart low 80 viral conjunctivitis 678
block 332, 333 mean corpuscular 260, 264, 273 virus 98, 145, 228, 278
defect, congenital 166 synthesis 80 Herpes zoster 118
disease 341, 350, 515 value of 264 Heterochromia iridis 664
acyanotic 61t Hemoglobinuria 224, 480 Heterogeneous papulopustular acneiform 667
functional 332 Hemogram 36, 44, 517 Heterophoria 691
774 ischemic 523 Hemolysis 478 Heterotropia 692
INDEX_.indd 774 11/30/2016 5:36:06 PM

Index
Heterozygosity, loss of 544 neonatal 43 ketotic 545

Hexokinase deficiency 35 direct 656 neonatal 544
Hip unconjugated 43t refractory 48
developmental dysplasia of 761, 763f, 765 Hypercalciuria, idiopathic 483 symptoms of 221, 545, 545t
dysplasia of 748, 749 Hypercapnia, permissive 26 treatment of 547
spica application 764 Hypercarbia 158 persistent 542
subluxation of 763f signs of 132 Hypogonadism, primary 623
Hirschsprung disease 664 Hyperekplexia 406 Hypokalemia 419, 420
Hirsutism 87, 90, 667 Hypereosinophilic syndrome 299, 301 metabolic 508
management of 91 Hyperglycemia 198, 460, 526-527, 530, 531 Hypomagnesemia 50
medical management of 90, 91 effects of 526 Hypomelanosis 664
treatment of 90 symptoms of 526, 528, 531 Hypomelanotic macules 666
Hoarseness, characteristic signs of 139 treatment of 55 Hyponasal speech 727
Homovanillic acid 259 Hyperinflation 16 Hyponatremia 50, 471, 505, 546
Hormonal Hyperinsulinism 546, 547 correction of 460
contraceptives 72t congenital 544 Hypoparathyroidism 527
combined 73 management of 548t Hypophonia 424
Hormone 539 Hyperkalemia 505 Hypophosphatasia 463, 464
adrenocorticotropic 544 Hyperkinetic disorder 102 Hypophosphatemia 419
deficiencies 544 Hyperlacrimation 687 Hypophosphatemic rickets, familial 463
isolated 544 Hyperlordosis 764f Hypopigmentation 664, 666
Horn cell disease, anterior 419 Hypernatremia 50, 471, 498 Hypopituitarism 666
Host defense, reduction of 179 Hyperoxia 26 congenital 48
Howell-Jolly bodies 267 Hyperparathyroidism 343 Hypoplasia, cerebellar 430
Human chorionic gonadotropin 532, 534, 538, Hyperpigmentation 428 Hypoplastic
552-554 post-inflammatory 668 alae nasi 664
stimulation test 552 Hyperprolactinemia 73 left heart syndrome 60, 333
Human diploid cell vaccine 125 Hyper-reactive airway disease 27 Hypotension 35, 137t, 192t, 215, 224
Human immunodeficiency virus 37, 98, 145, Hypertension 18, 73, 92, 153, 343-345, 345t, Hypothalamic disorders 557
236, 250, 253, 264, 269, 270, 275, 277, 279, 505 Hypothermia 8
280, 283, 359, 533, 564, 569, 672 classification of 346, 346t Hypothyroidism 515, 556-558, 666
child transmission of 252 drug treatment of 347tt congenital 556
diagnosis of 251, 252 endocrine causes of 560 signs of 557
infection 117, 120 evaluation, primary 344 stigmata of 537
Human leukocyte antigen 361, 564, 574, 607 intracranial 523 Hypotonia 54, 423, 426, 427
Human metapneumovirus 322 nonpharmacological management of 345 benign congenital 425
Human papillomavirus 71, 98 pill induced 73 central 425
vaccine 118 primary 344 cerebral 424
Human rabies immunoglobulins 124 pulmonary 20, 163, 337 infantile 523
Hyaline membrane disease 8, 12, 313 secondary 346 neonatal 426
Hyaluronidase 477 symptomatic 346 peripheral 425t
Hydrocele 639, 639t systemic 343 cause of 425
management of 638 transient 344 Hypoventilation
right 639f Hypertensive encephalopathy 460 central 157
Hydrocephalus 670 Hyperthermia, correction of 303 syndrome 522
Hydrocortisone 663 Hyperthyroidism 343, 532, 556, 558 Hypovolemia 163
intravenous 224 treatment of 558 Hypovolemic shock
Hydronephrosis 343, 491, 492, 496, 505, 642 Hypertonic saline 148, 160 management of 164, 165
antenatal 492, 493, 493t, 642, 643 Hypertrophic obstructive cardiomyopathy 342 nonhemorrhagic causes of 162
bilateral 644 Hypertrophy, adenotonsillar 501 Hypoxemia 158
grading of 642t Hyperventilation test 21 refractory 161
grading systems 492t Hypervolemia 344 signs of 132
severe 494 Hyphae 664 Hypoxia 149, 215
unilateral severe 494 Hypnogenic dystonia, paroxysmal 454 correction of 21
Hydrops fetalis 32 Hypocalcemia 37, 50, 546, 460 perinatal 67
Hydroxyindoleacetic acid 107 late onset 52 Hypoxic ischemic encephalopathy 13, 50, 68,
cystic hygroma 723 treatment of 55 68t
Hyperactive reticuloendothelial system 80 Hypochondroplasia 519
Hyperaldosteronism 470 Hypocomplementemia, persistent 478
Hyperammonemia 155 Hypoglycemia 5, 8, 47, 50, 226, 529, 542, 543,
I
Hyperandrogenism 87 546 Ibuprofen 30
severe 87 accelerated 545 Ichthyosis vulgaris 662
Hyperbilirubinemia asymptomatic 48t Ileocecal valve, edema of 652
conjugated 660 cause of 543, 545 Iliac fossa empty, right 652f
direct 658 correction of 303 Immunedeficiency, warning signs of 278 775
INDEX_.indd 775 11/30/2016 5:36:06 PM

Immunization 115 Intestinal obstruction 616, 621 Kasai portoenterostomy 659

active 124 signs of 652f Kashima procedure 707
Immunodeficiency 359 Intra-abdominal testis 553 Kawasaki disease 254, 339, 341, 568, 569, 571,
disorder 269 Intracellular fluid 471 576, 584, 585
primary 278 Intracranial pressure 147, 209-211, 226, 227, management of 587
severe combined 355 232, 233, 344, 670 Keratitis 675
states 355 management of raised 161, 381 interstitial 606
management of 362 signs of raised 147 Keratosis pilaris 662
Immunofluorescence 477 Intraperitoneal bladder rupture 216 Ketoacidosis, diabetic 149, 527
Immunoglobulin 381, 595 Intrauterine Ketoconazole 667, 674
A 360, 361, 473, 481, 482, 589 devices 71, 74, 74f Ketogenic diet 409, 416, 417t
nephropathy 483 growth retardation 696 Ketone bodies, formation of 543
administration of 124 infections 261, 276 Kidney 344, 481
E 300, 322, 353 myocarditis 333 disease, chronic 233, 515
G 280, 360, 517, 712 Intravenous fluids, maintenance 155 disruption 215
intravenous 57, 584, 586, 587 Intubation 2, 226t function test 233, 259, 481, 482
M 360 surfactant-extubation 15, 26 injury
therapy, intravenous 429 Intussuception, treatment of 652 acute 304, 478, 497, 499
Indian black scorpion 184f Intussusception 632, 651, 651f management of acute 499
Infection management of 654 perfusion 136
focus of 228, 229 Iodine, radioactive 558 reflux 649
intracranial 50 Ipex syndrome 529 Kinesigenic
prevention of 63 Ipratropium bromide, doses of 320 choreoathetosis 406
recurrent unusual 277 Iridocyclitis 675 dystonia, paroxysmal 454
severity of 247 Iritis 675 Kinsbourne syndrome 429
sign of 349 Iron 219 Klebsiella 236, 488
site of 197 binding capacity, total 274 Kleihauer-Betke test 36
Infectious deficiency 80, 263 Klinefelter’s syndrome 84, 532, 549
diseases 228 anemia 79-81, 260, 262f, 263f, 264, 265f, Knee
pneumonia, acute 160 274t movement of 523
Infertility 87 anemia, management of 82 X-ray of 522
management of 91, 92t therapy 36 Knock knees 739, 742
Infiltrative disorders 270, 532 Irritable bowel syndrome 389, 390 Koilonychia 263f
Inflammatory bowel disease 356, 359, 360, Ischemic stroke, arterial 435, 436 Korotkoff sound 560
363t, 364t, 365, 374, 378, 391, 569, 571, 574, Islet cell adenoma 545 Krait, common 181, 183
576, 607, 608 Isolated neutropenia, causes of 282t Krimsky prism bar reflex test 693
Inflammatory disorders, chronic 519 Isotonic magnesium sulfate, nebulized 321
Inflammatory polyps, juvenile 635 Isotretinoin 667 L
Inflammatory polyradiculoneuropathy,
acute 421 Lacrimal
Influenza vaccine 119, 120 J drainage system 687
Inguinal Japanese encephalitis 144, 444 gland 687
hernia, direct 637 vaccine 119, 120 pump failure 688
pouch, superficial 623 Jaundice 35, 43, 522, 655, 656 puncta 687, 689
Injuries, abdominal 214 management of neonate with 659 sac 687, 689
Injury, intracerebral 215 neonatal 655 system 687
Inotropes, use of 198 pathological 655, 655t Lactate dehydrogenase 274, 276, 599, 600
Inspiratory pressure, peak 16, 17 surgical 656 Lactose intolerance, secondary 355
Institution of Adequate Standard Therapy 317 treatment of 44t, 45t Lamina papyracea 722
Insulin Jaw thrust 157 Lamotrigine 410, 521
pump 529 Joint aspiration 738 Laparotomy 634, 635
resistance 87, 521, 527 Joint pain 253, 616 Larsen syndrome 716
management of 92 monoarticular 603 Laryngeal
secretion 543f Jones dye test 689 manipulation 707
vesicles, exocytosis of 543 Joubert’s syndrome 424, 430 mask airway 157, 170, 174, 194
Insulinoma 545 Jugular venous papillomatosis, juvenile 704, 705
Intensive care unit 160, 246, 314, 325, 366, 530 distension 204 stridor, congenital 723
neonatal 11, 13, 64, 67, 526, 530 pressure 333 webs 723, 724
Intensive Psychiatric Care Unit 165 Juvenile ankylosing spondylitis 568, 569 Laryngismus stridulus 142
International League Against Epilepsy 404 Laryngitis
International Study of Kidney Disease 594 acute 706
Interphalangeal joints, dorsum of 428 K chronic 704
Interstitial emphysema, pulmonary 18 Kala azar 253 Laryngomalacia 310, 723, 724
Intestinal lymphangiectasia, management Kallmann syndrome 532 Laryngoscopy 141
776 of 361 Karyotype, abnormal 624 Laryngo-tracheal stenosis 723, 724
INDEX_.indd 776 11/30/2016 5:36:06 PM

Index
Laryngotracheitis 139 carcinoma of 532 MeCkel’s diverticulum 634, 654, 654f

Laryngotracheobronchitis 139, 309 cysts, congenital 13 Meconium aspiration syndrome 8, 10f, 11, 13,
Legg-Calvé-Perthes disease 749 damage, major 16 14, 16-18
Legionellosis 152 disease management of 18
Leigh disease 50 chronic 13, 14, 23, 322, 324 Meconium peritonitis, infected 616f
Lentigo simplex 670 parenchymal 20 Meconium stained
Lepromatous pole 664 injury amniotic fluid 18, 32
Leptocytes 266 prevent 13 liquor 3, 8
Leptospira 145 transfusion associated acute 37 Medialization thyroplasty 708
Lethargy 54 involvement, bilateral 330 Medroxyprogesterone acetate 73
episodes of 317 protection 63 Medullary nephrocalcinosis 507f
Leucine sensitive hypoglycemia 544 tissue disease 158, 160 Medulloblastoma 433
Leukemia 237 Lupus nephritis 478, 481 Megakaryocytes 269
acute promyelocytic 263f Luteinizing hormone 72, 540, 554, 623, 535, Melanin, biosynthesis of 664
infiltration 344 667 Melanocytic nevus, congenital 670, 671
Leukocyte adhesion Lyme Meningeal
defect testing 281 arthritis 735 irritation 150
deficiency 281 disease 145 signs 446
Leukocytosis 748 Lymph node 291 Meningitis 132
peripheral 446 palpable 558 bacterial 233
Leukodystrophy 400 Lymphadenitis 142 Meningococcal vaccine 119, 120
metachromatic 402 Lymphadenopathy 264, 264f Meningoencephalitis 84, 444
Leukomalacia, periventricular 5 regional 224 viral 155
Leukopenia 151 Lymphangiectasia, intestinal 359 Meningomyelocele 638
Leukotriene receptor antagonist 315 Lymphocytic leukemia, acute 294 Menses, control of irregular 91
Levator palpebrae superioris 686 Lymphocytic variant hypereosinophilic Menstrual problems 8790t
Levetiracetam 201, 410 syndrome 300 adolescents 87
Levonorgestrel 73 Lymphoma 264f Mental
Leydig cell 535, 623 Lymphonodular hyperplasia 632 disorders 101
tumors 538 Lysosomal storage disorders 402 health
Limb issues 102
gait, short 747 M providers 103
length discrepancy 747, 748, 748f maturity 97
musculature, hypoplasia of 664 Macrocytic anemia 267, 275 status 163, 192, 193
upper 585f Macules, hypopigmented 664-666 Mercaptoacetyltriglycine 493, 494
Lipoprotein Maculopapular rash 243t Mercury 219
high density 523 Magnesium 51 Mesenteric lymphadenitis 620
low density 523 sulfate 320 Mesobuthus tamulus 184
Listeria 145 nebulized 320 scorpion sting 185
monocytogenes 228 Malabsorption syndromes 261, 515, 517 Metabolic acidosis 35, 505
Lithium 219 Malaria 37, 264f hyperchloremic 505
Liver 215 control 82 Metabolic alkalosis 505, 508
assist devices 382 suggestive of 269 hypokalemic 505
biopsy 657 Malarial parasite 36, 227, 253 Metabolic disorders 48, 148, 276, 430-432
disease 233, 515, 532 Malassezia Metabolic substrate, use of 162
active 73 furfur 672 Metabolic syndrome 93f, 520
acute 381 globosa 672 Metabolic therapy 22
chronic 149 hydrolyze 672 Metaiodobenzylguanidine 562
disorders 266 restricta 672 Metformin 91
dysfunction 410, 545 Male condom 73 Methanol 219
enzymes 656 Male-limited precocious puberty, familial 537 Methemoglobin 219
failure, acute 380, 381, 381t Malnutrition 516 Methicillin resistant Staphylococcus
function 517 Maple syrup urine disease 430 aureus 236, 239, 248, 603, 748, 735, 736
test 174, 219, 227, 232, 594, 656 Marinesco-Sjogren syndrome 431, 432 Methotrexate 663
transplantation 382, 660 Marrow suppression, causes of 264 Methylation, loss of 528
Loop diuretics 478 Mast cell stabilizers 689 Methylmalonic acidemia 528
Loose motions 616, 617 Maternal Microcytic, hypochromic anemia 267, 274
Low birth weight 1, 50, 343, 528 chorioamnionitis 32 Micronutrient deficiency 515
Low dose dexamethasone suppression diabetes mellitus 491 Microphallus 544
test 554 infection 696 Micturating cystourethrogram 344, 486, 489,
Lower chest pain, cause of 338 mortality, high 81 493, 494, 496, 646
Lower limb, alignment of 739 Maxillofacial injury 213 Midgut volvulus 617
Lumbar puncture 55, 152, 153, 229, 406 McCune-Albright syndrome 536, 538f Mid-intestinal obstruction 619f
Lung 157 Measles 115, 117 Mid-parental height 514
blood flow 334 Mechanical breaths, adequacy of 17 Migraine 73, 438 777
INDEX_.indd 777 11/30/2016 5:36:07 PM

abdominal 390 Myelodysplastic syndrome 273, 275 respiratory distress, management of 11

basilar 429 Myelomeningocele 623 resuscitation 1
Milk protein allergy 632 Myelopathy program 6
Miller Fisher syndrome 429 acute 419, 442t sclerosing cholangitis 655
Mitochondrial chronic 442t seizures 50, 50t, 52, 52t
diseases 419 Myeloperoxidase 583 familial 51
disorders 400 Myeloproliferative variant hypereosinophilic shock, management of 32, 33
Mitral regurgitation 332, 336 syndrome 300 sleep myoclonus, benign 448
Monoamine oxidase inhibitors 106 Myocardial surgical jaundice, causes of 655
Monoarhritis 573, 574 blood flow 340 Neoplastic diseases 300
causes of 564 contractility 207 Nephrectomy 495
chronic 564 dysfunction 8, 163, 204 Nephritic syndrome 474t
Mononucleosis function 206 unresolving 478
infectious 264, 270 infarction 72, 184 Nephritis, endocarditis associated 478
syndrome 254 Myocarditis 149, 332, 333 Nephritogenic streptococcal antigens 475
Mood disorders, prevalence of 522 viral 333, 337 Nephrology 579
Mood swings 410 Myoclonus 151 Nephropathy, reflux 343
Moraxella catarrhalis 328, 710 Myoglobinuria 224 Nephrotic range 479
Morbidity, causes of 195 Myotonic dystrophy, congenital 425 Nephrotic syndrome 339, 474t, 510, 512t
Mortality, chances of 196 Myringotomy 712, 714 causes of 510
Mosaic perfusion 328 tube 714 childhood 510, 511
Mother-to-child transmission 250 complications of 512t
Motor attacks, transient focal 405 N management of 510
Motor dysfunction, chronic 448 Nerve disorders, peripheral 426
Motor fusion 681 N-acetyl cysteine 381 Nervous system 123
Motor neuron Nails, staining of 9 Neuritis, traumatic 419, 421t
gene, survival 425 Naja naja 181 Neuroacanthocytosis 457
lower 440, 448 Naloxone 172 Neuroblastoma 237, 343
lesions 440 role of 3 Neurocutaneous melanosis 670
upper 440, 441, 448 Nasal Neurodegenerative disorders 396, 397t, 398,
Motor unit disorders 425 cavity, malignant tumors of 712 399, 400t, 401, 401t
Motor visual system 682 decongestion 324 Neuroendocrine systems 108
Mouth, suction of 2, 4 intermittent positive pressure Neuroglucopenic symptoms 546
Movement disorder 51, 51t, 449, 449t, 450t inhibitors 320 Neuromuscular
categorization of 448, 449 patency test 726 blockade 223
causes of 450 root, broadening of 664 disease 136
drug induced 450, 451t septum damage 15 disorders 13
paroxysmal 448, 454 intermittent flatfoot 753
Moyamoya mandatory ventilation 5, 6 junction 224
disease 343 positive pressure ventilation 13, 16 transmission, disorders of 419
syndrome 437 continuous positive airway pressure 15, 17 weakness 131
Mucoid discharge 677 Nasolacrimal duct 677, 687, 689 Neuropathy, peripheral 419, 432
Mucolytics 324, 713 block 689 Neuropsychiatric abnormalities 460
Mucopolysaccharidosis 402, 463 congenital obstruction of 689 Neuroregression, symptom of 397
Multicystic dysplastic kidney 495 Nasopharyngeal Neurotoxic
Multidrug resistance tuberculosis 360, 364 airway 158t bites 183
Multifactorial inheritance system 755 aspirate 154 signs 224
Multiple sclerosis, childhood 429 carcinoma 711 Neurotoxicity 43
Mumps 115, 117 masses, benign 711 Neurotransmission, disruption of 144
Murmur 59, 61 Nausea 522 Neutrophils, hypersegmented 265f
Muscle Neck swelling 420 Nevomelanocytic cells 670
accessory 131, 309, 317, 323 Necrosis infection 223 Nevus
biopsy 600 Necrotizing enterocolitis 5, 29, 30, 37, 526, anemicus 664
disorders 419, 426 531, 547 depigmentosus 664
enzymes 599 Nefazodone 106 sebaceous 670
strength, assessment of 150 Neisseria spilus 670
stretch reflexes 420 gonorrhoeae 677 Newborn gender assignment 552
tenderness 420 meningitidis 228 Nitric oxide 22
tone 136 Neonatal inhaled 18, 22, 26
Muscular dystrophy, congenital 425 diabetes mellitus, management of 529 Nitroglycerine 185
Myasthenia gravis 419, 420 hepatitis, idiopathic 655 Nitroprusside 337
Myasthenic syndromes 426 hyperbilirubinemia, management of N-methyl-d-aspartate receptor 460
Mycobacterium tuberculosis 145, 254, 611 unconjugated 45 Nocturnal bladder capacity 502
Mycophenolate mofetil 663 hypoglycemia, management of 48 Nocturnal enuresis 500, 501, 503
778 Mycoplasma pneumoniae 145, 152, 437 jaundice, causes of 655 primary 501
INDEX_.indd 778 11/30/2016 5:36:07 PM

Index
Nocturnal polyuria 500 inflammation 687 Oxygen 55, 303, 319

Nodular lymphoid hyperplasia cow’s-milk muscles 453 adequacy of 212
protein allergy 377f surface disease 687 administration of 158, 323
Nodular rash 243, 245 torticollis 683t delivery 158
Nonaccidental injury 460 Oculocutaneous albinism 664 adequacy of 206
Nonalcoholic fatty liver disease 521 Olanzapine 521 method of 15
Nonbilious vomiting 615 Oligoarthritis 564 generation of 526
Noncompressive myelopathy 442 Oligoarticular partial pressure of 226
Non-cycline antibiotics 667 arthritis, acute onset 566 release of 37
Nonepileptic attack disorder 405, 415 juvenile idiopathic arthritis, chronic 565 role of 3
Nonexudative conjunctivitis sparing Oligomenorrhea 87 saturation 58, 61
limbus 585f Omalizumab 663 arterial 17, 163
Nonfamilial neonatal seizures, benign 51 Omental torsion, idiopathic 620f target 3t
Nonketotic hyperglycinemia 50 Omentum 637 status 213
Nonmegaloblastic macrocytic anemia, causes Ophthalmia neonatorum 677, 688, 688t supplemental 159
of 275 Ophthalmic evaluation 344 supplementation 323
Nonmonosymptomatic enuresis 500 Ophthalmoplegia 182 supply 336
Non-nucleated cells 269 Opioid ingestion 154 therapy 13, 14, 309, 324
Non-nutritional rickets 466 Opisthotonus 150 supplemental 696
Nonophthalmologists 696 Opportunistic infections 252
Nonpalpable testis 625 Oppositional defiant disorder 96, 110, 114 P
Nonpoisonous snake 181t Opsoclonus myoclonus syndrome 429
Nonprogressive cerebellar ataxias, Optic fundi, examination of 538 Pain 136
chronic 430 Optic nerve, myelination of 696 abdominal 97, 522, 620t, 621
Non-purulent otitis media, chronic 709 Optokinetic nystagmus 697 acute abdominal 615, 616t, 618t
Nonscalp seborrheic dermatitis 674 Oral categories of 615
Nonsteroidal anti-inflammatory drug 329, antibiotics 488t chronic abdominal 389, 391, 391t
336, 349, 481, 564, 571 candidiasis 278 local 215
Noonan syndrome 519 contraceptive pills 73, 91, 344 management of functional 391
Norepinephrine 202 glucose tolerance test 526 mild 747
Norgestrel 73 polio vaccine 116 musculoskeletal 341
Normocytic anemia, causes of 275 rehydration solution 165 periorbital 718
Normovolemia, sign of 211 tetracyclines 667 pleuritic 341
Nosocomial infections 24, 155 Orbicularis muscle, weakness of 688 preceding vomiting 615
prevention of 26 Orbital abscess 719 pulmonary 341
treatment of 247 stage of 718 reactions of 186
Nostrils, flaring of 726 Orbital cellulitis 718 referred 615
Nuclear membrane, remnants of 266 stage of 718 relief 179, 349
Nursery school syndrome 314 Organ severe 747
Nutrition 63, 66, 198 dysfunction 198 shoulder 341
strategies, aggressive 26 failure, recognition of 198 visceral 615
Nutritional therapy 524 transplant, solid 345 Palamnaeus swammerdami 184
Nystagmus 683, 686 Organophosphate poisoning 419 Palpitation, episodes of 561
Ornithine transcarbamylase deficiency 430 Pancreatic injury 215
Pandora’s box 615
O Oromandibular dystonia 453
Oropharyngeal airway 158, 170, 174 Papilledema 153
Obesity 343, 520, 522, 522t, 524 Oscillatory ventilation 22 Papilloma, juvenile 705f
abdominal 520 Osteoarthritis 522 Pappenheimer bodies 267
cause of 521, 521t, 522, 523t Osteoarticular infections, acute 601-604 Papulosquamous
childhood 520 Osteoid osteoma 749 inflammatory disorder, chronic 672
complications of 521t, 523, 523t Osteomyelitis 237, 575, 601, 748, 748f lesions 674
effects of 522 acute 235, 236t, 239 Parainfluenza virus 139, 322
form of 521 causes of 236 Paralysis 14
hypothalamic 521 chronic 238 Paraparesis, acute 420
monogenic 521 evaluation of 237, 239 Paraplegia 442
onset of 522 management of acute 239 acute 420
Obsessive compulsive disorder 104, 105 treatment of 237 Parathyroid hormone 465
Obstruction, degree of 308, 322 Osteopetrosis 262 Parenchymo-pleural fistula 610
Obstructive Osteosclerosis 73 Parenteral nutrition, total 66, 387
lung disease 14 Otitis media 709, 709t, 711t, 714t, 715 Parietal pain 615
sleep apnea 523, 727, 729 acute 709, 712 Parkinson’s disease, juvenile 456
childhood 727 unilateral 711 Paroxetine 521
syndrome 730 Ovarian Paroxysmal
Ocular size 88 dystonic choreoathetosis, familial 454
head posture 683t torsion 616 nocturnal hemoglobinuria 295 779
INDEX_.indd 779 11/30/2016 5:36:07 PM

torticollis, benign 448 Pimecrolimus 663 microscopic 581

vertigo, part of benign 428 Pituitary Polyarteritis nodosa 478, 571, 578, 582
Patent ductus arteriosus 5, 17, 24, 28, 29, 60, disease 87 childhood 581
332 disorder 532 Polyarthritis 568, 569, 569t, 570t, 576
management of 29 hormone deficiencies 544 diagnosis of 576t
Patulous eustachian tube 712 Pityriasis treatment of 571t
Pediatric alba 662 Polycystic kidney disease 343
acute liver failure, causes of 382 versicolor 664, 674 Polycystic ovarian syndrome 87-88, 88t, 89, 90,
advanced life support 191 Placenta 90t, 91-93, 521, 527
airway, structure of 214 examination of 35 management of 90
disorders 514 level of 34 Polycythemia 47
epiphora 687 Placental Polydipsia causing constipation 504
head trauma 210 abruption 50 Polymerase chain reaction 153, 229, 251, 281,
hypertension 345 anomalies 32 360, 381
intensive care unit 190, 196, 202, 210, 318, Plant toxins 145 Polymorphonuclear leukocytosis 224
320 Plantar fascia 757 Polymyositis 419, 598
movement disorders 448 Plasma Polysaccharide vaccine 115, 117
sinusitis 717 aldosterone concentration 562 Polysynaptic pathways, interruption of 144
viral respiratory tract illness, primarily 139 amino acids 401t Polytherapy 410
Pedophile 94 estimation of 530 Polyuria 504
Pelvic glucose 542 Pompe’s disease 426
inflammatory disease 621 organic acids 401t Popliteal fossa 661
osteotomy 764 protein losses 162 Porphyria 344
Pelvi-ureteric junction 391 renin activity 554, 562, 649 Postexposure prophylaxis 120, 123, 123t, 124
obstruction 491, 493, 495, 643 therapies 198 Postrabies-vaccine encephalomyelitis 420
Pencil-point sign 141f Plasminogen Poststreptococcal
Perifollicular papules 674 activator inhibitor 1 297 glomerulonephritis 344, 475f, 481
Perinatal torsion 631 Plasmodium falciparum 145, 444 reactive arthritis 566, 569
management of 631 Plasmodium malarial 473b Potassium 469
Periodic paralysis 419, 420 Platelet 39 abnormality 472
hypokalemic 419, 420 aggregation study 291t hydroxide
Peripheral oxygen, saturation of 205 concentrate 41 microscopy 664
perfusion, adequacy of 192 dysfunction 291t mount 674
smear, examination of 273 function analyzer 298 imbalances 469
Peritonitis, neonatal 618f production of 269 management of 471
Periumbilical pain 615 range of 269 Pott's spine 442
Periungual desquamation 585f sequestration of 269 Prader’s staging 551f
Persistent Pleural Prader-Willi syndrome 424, 519, 523
causes of 547 cavity drainage, timing of 611 Precocious puberty 535, 537, 540
hypoglycemia, 543, 544, 546, 548 fluid analysis 611 causes of 536
management of 547 Pneumatic otoscopy 712 central 535, 540
Persistent Mullerian duct syndrome 554 Pneumococcal gonadotropin-dependent 537f, 540
Persistent pulmonary hypertension 13, 18, diseases, prevention of 117 peripheral 535
20, 21 polysaccharide vaccine 117 types of 535
management of 22 vaccines 117 Precordium, active 21
Personality disorder 96 Pneumonia 6, 12, 149, 160, 228 Prednisolone, dose of 141
Perthes disease 749, 749f aspiration 8, 155 Premature ovarian failure 89t
Pertussis vaccine 116 bacterial 25, 610 thelarche 537f
Pes calcaneovalgus 744 congenital 8, 13, 10f Prematurity
Peutz Jegher’s syndrome 374f viral 25 anemia of 35
Pharynx, infection of 97 Pneumothorax 3, 11, 11f, 14, 15, 131, 142, 149 apnea of 5, 6, 13, 16
Phenobarbitone 410, 429 bilateral 11 Preseptal cellulitis 718
Phenothiazines 429 Poison elimination 172 stage of 718
Phenotypes, classification of 313t Poisoning Prism bar cover test 693
Phenylketonuria 556 causes of 170 Probiotics 663
Phenytoin 410 management of 170, 174 Procalcitonin 55
overdose of 429 Poisonous snakes 181t, 183 Processus vaginalis 618f, 637, 639
Pheochromocytoma 343, 561 Poisons, ingestion of 304 Procoagulant system 39
Phlebotomy losses 37 Polio vaccine, inactivated 116 Prophylactic
Phosphate, tubular reabsorption of 507 Poliomyelitis 344, 421t antibiotics 494, 660
Phosphoenolpyruvate carboxykinase vaccine-associated 419 iron therapy 37
deficiency 545 Poliosis 664 Prophylaxis, regular 315
Phosphoglycerate kinase deficiency 266 Poliovirus vaccines 116 Propionibacterium acnes 668
780 Phytanic acid oxidase, deficiency of 432 Polyangiitis 576 Propylene glycol 674
INDEX_.indd 780 11/30/2016 5:36:07 PM

Index
Prostaglandin E1 335 R replacement therapy 198

Protein sinus splitting 642
catabolism of 526 Rabies 123, 124, 420 tubular
glycosylation of 526 immunoglobulins 124 acidosis 466, 504-506
loss of 163 dose of 124 disorders 504, 504t, 505, 505f
Proteinuria 484 infection 123 tumor 343
Proteolytic enzymes 235 vaccine 120 vein thrombosis 343
Proteus 488 intradermal 125 Renin-angiotensin system 344
Prothrombin time 41, 219, 270, 289, 290-292, Rachitic Respiration 163
294-296 dwarfism 463, 464 assessment of 2
Prothrombotic disorders 437 rosary 464 paradoxical 424
Proton pump inhibitors 367, 370, 387 Radionuclide bone scanning 237 Respiratory
Proximal Rapid-onset diarrhea 186 disorders, surgical 13
bile ducts 658f Rash 243 distress 8, 24, 130-132, 132t, 149, 157, 158t,
tibial fracture in toddlers 742 peripheral 243, 244, 244t 193, 334, 341, 522, 523
Prune belly syndrome 623 purpuric 243, 245, 245t causes of 130, 303, 304
Pruritic types of 243 degree of 139, 309
dermatitis 661 Rasmussen’s encephalitis 409 severe 309
erythematous 664 Recombinant human erythropoietin 37 severity of 9, 10, 309
Pruritis 186 Rectal sign of 131
Pseudohermaphroditism 549 polyp 632, 635 syndrome 8, 9f, 11, 13, 16, 17, 21, 24, 28,
Pseudohypoaldosteronism 470 prolapse 636 531
Pseudohypoparathyroidism 456f, 521 varices 376f acute 133, 160, 161
Pseudomonas aeruginosa 236, 328 Red blood cell 34, 37, 79, 260, 265, 272, 273, management of 17
endobronchial infection 329 294, 474, 480, 480f, 634 failure 14, 54, 132, 157, 158t, 193
Psychomotor morphology 36, 44, 265 sign of 131, 309
regression 396, 398 packed 163 paralysis 182, 224
retardation 433, 547 Red cell problem, types of 158
causes of 396 distribution width 264, 272-274 rate 61, 130, 135, 165, 205, 335
Puberty indices 264 normal 191t
end of 517 release of 260 support 13, 65
normal 535 Red eye, causes of 675, 675t noninvasive 14
sequence of 536 Red flag signs 314, 389 modes of 13
sign of 535 Red scorpion 184f system, function of 157
stages of 535 Reflex tract
Pubic hair 667 grade of 649 infection
Puffy pale face 557 laryngopharyngeal 704, 705 lower 349
Pulmonary pupillary 697 upper 314, 323, 348, 675, 689, 710
edema 184 Refractory congestive heart failure, Respiratory syncytial virus 322, 326, 711
function test 328, 338 management of 336 immunoprophylaxis 326t
Pulse 58 Refractory hypoglycemia Resuscitation, initial steps of 3
contour cardiac output 197 management of 48 Reticulocyte
evaluation of 135 treatment of 49 count 44, 81, 264, 265
oximetry 130, 335 Refsum disease 431, 432 number of 272
peripheral 61, 214 Rehabilitation 98 production index 272
pressure 136, 214 Renal production of 273
narrow 193 anomalies, antenatal 491, 492 Reticulocytosis 265
quality 135 arteriography 344 Retinal vasculitis 606
wave Doppler main pulmonary artery 29 artery stenosis 343 Retinoblastoma 697
Pupillary biopsy 344, 477, 477t, 483, 510, 511, 595 Retinoids, topical 667
light reflex 696 calculi 505 Retinopathy, rates of 14
reactions 693 colics 616 Retractions, severity of 189, 191t
response, abnormal 147 disease 136, 149, 345 Reye’s syndrome 145, 149, 444
Pus 735 endocarditis associated 479 Rheumatic
Pyelogram, intravenous 493 disorders 515 diseases 575
Pyelonephritis 254, 343, 344, 616 dysplasia 343 fever 332, 333
Pyramidal signs 151 failure 270, 346, 466 acute 569, 571, 576, 735
Pyridoxine 672 acute 69, 224 heart disease 149, 332, 336
Pyruvate dehydrogenase deficiency 50, 430 chronic 343, 495, 519 Rheumatoid
Pyruvate kinase deficiency 35 function 335, 517 arthritis, juvenile 253, 735
Pyuria, degree of 247 test 174, 232 factor 574-576
involvement 479 Rhinitis, allergic 661
pelvis Rhinorrhea, symptoms of 309
Q anteroposterior 642 Rhinovirus 322
Quadriplegia 344 diameter, anteroposterior 492, 493 Rhombencephalosynapsis 431 781
INDEX_.indd 781 11/30/2016 5:36:07 PM

Ribavirin 160, 325, 672 management of 56, 57, 336 origin of 204
Ribonucleic acid 232 neonatal 54 pathophysiology of 31
Ribosomes, remnants of 267 severe 196 phase of 207
Rickets 463, 466 signs of early 241 recognition of 135, 138
hypophosphatemic 466, 515 symptoms of 55 reversal of 198
nutritional 463, 465, 740 treatment of 36 sign of 192
oncogenic 467 Septal defect, atrioventricular 60, 332 state of 181
refractory 505 Septic symptoms of 147
treatment of 467t arthritis 238, 565, 575, 601,. 733, 734, 737, types of 31, 135, 137t
Ringer’s lactate 163 748 Short stature
Roger syndrome 527 screen 56 cause of 514, 515
Rotational deformities, pathological causes shock 32, 195 familial 514
of 743 management of 196 glucocorticoid induced 519
Rotavirus 117 neonatal 13 idiopathic 519
vaccines 117 Septicemia, meningococcal 677 Shunt nephritis 479
Rubella 36, 656 Serotonin, levels of 107 Sickle cell
vaccine 117 Serotonin-norepinephrine reuptake anemia 80, 236-238
Russell’s viper 181, 183 inhibitors 105, 106 disease 73, 117, 266f, 339, 340, 341, 437
Serum Sinovenous thrombosis 436
S alkaline phosphatase 464 Sinus
ammonia 48 bradycardia 184
Salbutamol, puffs of 319 bilirubin 36, 43, 44, 81 tachycardia 184
Salicylates 219 value tends, total 43 venous thrombosis 437
Salmonella typhi 145 calcium 51 Sinusitis 717
Sangstaken-Blakemore tube 370 normal 505 acute 717
Scabietic eczema 661 chemistry panel 533 chronic 717
Scalds 176 cortisol 344 subacute 717
Scalp seborrheic dermatitis 674 creatinine 30, 406, 517 Sjögren’s syndrome 32
Sciatic neuritis, traumatic 420 electrolytes 5, 406 Skeletal
Sclerema 55 glutamic pyruvic transaminase 517 defects 58
Scleritis 605t insulin level 48 dysplasia 515, 519, 741
therapy of 606t transferrin receptor assay 274 Skin 261
Sclerosis, multiple 437, 443 Sex coloration of 189
Sclerotherapy, endoscopic 367, 369 development, disorder of 250, 549, 550, coolness of 171
Scorpion 550t, 553, 554 dermis of 125
antivenom 185 hormone-binding globulin 89, 532 healing 350
sting 184 steroids, dose of 514 observation of 398
management of 185 Sexual patchy discoloration of 136
Scrotal edema, idiopathic 629, 630 abuse 94, 96, 99, 537 purpura 616t
Scrotum adolescent 94, 99 rash, eczematous 529
acute 629 signs 97t scar, nature of 348
examination of 629 activity 74 temperature of 136
Sebaceous assault 95, 632 Sleep apnea hypopnea syndrome 728t
gland 672 offence of 99 Sleep
hyperplasia 668 physical indicator of 97 deprivation 672
Seborrheic dermatitis 661, 672, 674 exploitation 95 disorder 344, 406
Segawa syndrome 454 gratification 95 Smooth muscle hamartoma 670
Seizure disorder 149, 232 grooming 95 Snake
Selenium sulfide 674 offenses, variety of 95 bite 181, 419
Semen 97 Sexual maturity rating 535 envenomation 420
Sensations, primary 440 classification of 536t management of 183
Sensorineural hearing loss, congenital 664 Sexually transmitted diseases 98 species of 181
Sensorium 214 prophylaxis of 98 Sodium 469
Sensory Shigella encephalopathy 149 abnormality 472
ataxia 427 Shock 31, 47, 55, 60, 135, 193, 196f, 224, 333 bicarbonate, administration of 173
cause of 427 severity of 135 cromoglycate 689
level 440 causes of 60 fractional excretion of 498
symptoms 421 distributive 32 imbalances 469
visual system 682 early recognition of 135 management of 471
Sepsis 9, 47, 54t, 55, 195, 382 hemorrhagic 164 nitroprusside 185
bacterial 54 hypotensive 136 infusion 478
classification of 54t hypovolemic 32, 162, 163 valproate 410
diagnosis of 198 management of 206 Soft tissue
episodes of 278 general 163 mass 652f
782 late onset 54 neonatal 31, 32, 32t, 33t pathology 755f
INDEX_.indd 782 11/30/2016 5:36:07 PM

Index
releases 757 Steroidogenic acute regulatory T

Sore throat 420 protein 250
Sounds, abnormal 131t Steroid-resistant disease 511 Tachycardia 147, 193
Spasmodic croup 142 Steroid-sensitive nephrotic syndrome, Tachycardiomyopathy 332
Spasmus nutans 448 treatment of 512t Tachypnea 193
Spastic Stevens-Johnson syndrome 344, 410 mild 54
paraplegia 440 Stillbirth, cause of 67 progressive 138
causes of 442 Stomatocytosis 35 quiet 131
hereditary 443 Strabismus 691, 692 transient 8, 10f, 11
quadriplegia 537f torsional 691 Tacrolimus 344, 663
Takayasu’s arterirtis 343
Spherocytosis, hereditary 35, 266f Strawberry tongue 585f
Talipes equino varus, congenital 755
Spina bifida 670, 716 Streptococcus pneumonia 241, 328, 609, 611,
Tamoxifen 534
Spinal 676, 710
Tanner whitehouse 3 517
arteriovenous malformations, Streptococcus pyogenes 609, 710
Tap sign 184
intramedullary 443 Streptokinase 477
Tardive dystonia 453, 454
cord 426 Streptozyme test 477
Tarsal coalition 753
disorders, intramedullary 441t Stress 343
Tear drop cells 266
disorders, types of 441 disorder, post-traumatic 114
Tear, secretion of 687
injury 215, 419 hyperglycemia 526, 530
Telangiectasia 431
ischemia 419 psychological 672
Temporal bone, malignant tumors of 712
syndromes 441, 442t ulcer prophylaxis 198 Tendo-Achilles 757
transection of 441f Stridor 311, 723 Testicular
tumors 443 cause of 308, 308t descent, normal 622
disease, intramedullary 441 inspiratory 139, 724 torsion 616, 623
muscular atrophy 425 onset of 309 trauma 532, 533, 623, 631
tenderness 420 Stroke vessels, mobility of 626
trauma 420 causes of 437 Testis 624, 631f
Spine movement, painful 420 childhood 435 appendages of 631
Spironolactone 91 ischemic 438 descends 637
Splanchnic pain 615 perinatal 435 enlargement of 538
Spleen 215 Subperiosteal abscess, stage of 718 palpable 625
Splenectomy 149 Suicide 77, 106, 107, 108 retractile 622, 627
Splenic acceptability of 108 surgery in undescended 625
dysfunction 117 acts of 106 torsion of 630
injury 215 behavior 108 undescended 622, 640
Spondyloepimetaphyseal dysplasia 742 reporting of 108 Testosterone 553, 554
Spring ligament 757 Sulcus vocalis 704, 705 action of 91, 532
Spur cell 265 Sulfamethoxazole 603 production of 91, 532
Squamous cell carcinoma 706 Sulfite oxidase deficiency 50 Tetanus 116
Squint 692 Sulfonylurea receptor 543 toxoid 116, 215, 224
concomitant 683 Supplementary oxygen, administration of 3 Tethered cord syndrome 443
incomitant 682 Supraglottic Tetralogy of Fallot 59
paralytic 686 edema 140f Thalassemia 80
Stable oxygen requirement 27 larynx 724 intermedia 262f
Staphylococcal pneumonia 11 region 139 major 267f
Staphylococcus aureus 197, 236, 310, 328, 479, Suprapubic aspiration 487 Thelarche, duration of 538
609, 710, 735, 748 Supraventricular tachycardia 184, 205, 206, Theophylline 219
Staphylococcus epidermidis 479 332 Therapeutic hypothermia 3, 69
Status asthmaticus, treatment of 321 Swelling 348 use of 148
Status epilepticus 52, 201, 405, 414, 415 inguinoscrotal 637 Thermal injury 141
management of 201 of scrotum 629 Thoracotomy, open 613
non-convulsive 145 Sympathetic nervous system 560 Thorax 463
Steatorrhea 432 Syndromic hypotonia 424 Throat swab 154
Steeple sign 141f Synophrys 664 Thrombin clotting time 290
Stenosis Synovial fluid 735 Thrombocytopenia 40, 41, 55, 151, 269, 270,
aortic 60, 332, 336 Synovitis, transient 735, 748 289, 375f, 478
pulmonary 59 Syphilis 98 acquired 632
Steroid 160, 713 Systemic disease 419, 425 causes of 269
adrenal 552 signs of 561 immune 294, 296
antenatal 26 Systemic disorder, signs of 448 isolated 269, 270
eye drops 677 Systemic lupus erythematosus 32, 73, 276, management of 41
intake of 523 288, 291, 343, 481, 497, 566, 568, 569, 571, Thrombocytopenic purpura
nebulized 314 574, 574, 592, 593, 593f, 594, 599 idiopathic 288, 291
therapy 197 treatment of 596 immune 269, 270 783
INDEX_.indd 783 11/30/2016 5:36:07 PM

Thrombophilia 73 Trauma 149, 213, 232, 237, 339, 344, 675 output 163, 215, 335
Thrombophlebitis 246 abdominal 621 maintain 163
Thromboplastin time, partial 219, 290 laryngeal 723 retention of 210
Thrombotic thrombocytopenic purpura 73, Trendelenburg gait 747 test 485
269 Triamcinolone 663 Urolithiasis 481
Thyroid Trichinosis 419 Ursodeoxycholic acid 660
disease 558, 666 Trichomonas 97, 98 Urticaria 224
disorders 556 Tricuspid atresia 59 Urticarial rash 243, 245, 245t
dysfunction 527 Tricyclic antidepressants 105, 106 Uveitis 606, 607, 697
function 557, 558 Triiodothyronine, serum 557 classification of 606t
test 517 Trimethoprim 603
nodule 558 Trivalent influenza vaccine 119 V
screening, universal 556 Truncus arteriosus 332
stimulating hormone 523, 533, 540, 556, 557 Tuberculoid pole 664 Vaccine
Tibia vara 740 Tuberculosis 254, 279, 313, 328, 356, 360, 391, preventable deaths 127
infantile 740 565, 571, 574, 592 regimen, intradermal 125
juvenile 740 abdominal 363, 364t types of 115
Tibia, periosteal reaction of 748f suggestive of 152 Vaginal candidiasis 526
Tibial torsion 745 Tuberculous meningitis 144, 232, 447 Vagus nerve stimulation 416
internal 744 Tuberous sclerosis 664 Vanillylmandelic acid 259, 344
Tibiofemoral angle 739 Tubular necrosis, acute 344, 498 Variceal
Tick-bite paralysis 419 Tumor 405, 409 bleeding, acute 370
Tinea cruris 674 adrenal 532 ligation, endoscopic 367, 369
Tissue cerebellar 431, 433 Varicella
perfusion 157 malignant 706 disease 118
plasminogen activator 437 necrosis factor-α 587 vaccines 349
transglutaminase 361 Turner’s syndrome 84, 515, 519, 549, 553, 557 zoster virus 420
antibody 361 Tympanocentesis 712 Vascular injury, site of 269
Todd’s paralysis 438 Tympanometry 712 Vasculitis 460
Todd’s paresis 404 Typhoid vaccine 118 childhood 578-580
Toddler’s diarrhea 355 disorder, systemic 460
syndrome 561
Tongue 147, 157, 159 U Vasoactive drugs 196, 207, 207t
bald 263
fasciculations 424 Ulcer bleeds 377 Vaso-cardioactive drugs 207
strawberry 244t, 585f Ulcerative colitis 359, 362t, 378 Venereal diseases 97
Topical steroids 663 Umbilical artery catheter 66 Venezuelan equine encephalitis 232
eye drops 689 Undescended testis, treatment for 626 Venom
Torsion Upper airway obstruction, acute 159t hemorrhagic effects of 223
duration of 630 Upper gastrointestinal bleeding, causes suction of 183
dystonia, idiopathic 406, 454 of 367t Venous blood gas 165, 517
Torticollis 215, 453 Urea cycle disorders 459 Ventilation 16, 18, 55
Tourette syndrome 456 Ureaplasma urealyticum 24 adequacy of 189
Toxemia, signs of 236 Uremia 155 conventional 16
Toxic 488 Ureter 344, 481 invasive 13
exposures Urethral valves 491, 495, 642 mechanical 16, 213, 224
management of 173t Urge syndrome 503 modes of 16
typical of 217 Uric acid 344 positive pressure 1, 2, 6
oxygen radicals 235 Urinalysis 498, 618, 619 pressure support 16
synovitis 575 Urinary 344 strategies 16, 27t
Toxidrome 171t, 219t bilirubin 656 tube 714
Toxin elimination 172 calcium 482 use of invasive 15
Toxocariasis 697 microalbuminuria 344 Ventricular septal defect 60, 332
Toxoplasma 36 potassium 470 Ventriculoperitoneal shunts 640
Toxoplasmosis 36 tract dysfunction, lower 649 Vermian hypoplasia 430
Tracheitis, bacterial 141 tract infection 97, 166, 167, 228, 254, 345, Vernal keratoconjunctivitis 688
Tracheoesophageal fistula 14 482, 485, 486, 489, 489t, 491, 644, 646, Vero-cell rabies vaccine, purified 125
Tracheomalacia 723, 724 649 Vertical talus, congenital 753
Tracheostomy 158 recurrent 277 Vertigo, attacks of 428
Transcutaneous oxygen 21 symptoms of 649 Very low birth weight 13, 23, 37, 63, 530
Transient hypoglycemia, causes of 543 tract, lower 500 Vesicoureteral reflux 166, 491, 493, 494, 642
Transjugular intrahepatic portosystemic Urine 154, 344, 470 Vesico-ureteric
shunt 367, 370 analysis 630 junction obstruction 491
Transphyseal blood vessels 235 calcium, spot 509 reflux 649
Transtubular potassium gradient 470, 508 dipstick 487 management of 646, 648 649
784 Transverse myelitis 419, 420, 421t examinations, multiple centrifuged 480 Vesiculobullous rash 243, 245, 245t
INDEX_.indd 784 11/30/2016 5:36:07 PM

Index
Vestibular dysfunction 427 bilateral abductor palsy of 723 Whole blood clotting
Video-assisted thoracoscopic surgery 612 cyst 704, 705 test 183
Violaceous striae 521 laryngoscopic 706 time 223
Viper 223 palsy 311, 723 Whole bowel irrigation 173, 221
saw-scaled 181, 183f Vocal fold paresis 704 Whole cell pertussis vaccine 116
Viral acquired 705 Wilms’ tumor 256
croup, treatment of 310 Vocal nodules 704 Wilson disease 523
disease 142 Voltage-gated potassium channel 460 Wiskott-Aldrich syndrome 269, 270
encephalitis, acute 231 Vomiting 224, 344, 346, 504, 615-617, 621 Wolcott-Rallison syndrome 529
Virilization 87 preceding pain 615 Wolfram syndrome 527
signs of 538 von Hippel-Lindau disease 433 Wound
Viruses 323 von Willebrand
care 178, 179, 348
Vision, blurred 182 disease 270, 291, 294-296
management 124t
Visual factor 296-298
open 213
cortex, development of 696 antigen 298
suturing of 124
development 696 Vulva, bruising of 97
Wright stain 480
normal 696 Writer’s cramp 453
signs of poor 696 W
evoked potential 697
system 696
Waardenburg syndrome 664
Waist circumference 520
X
Vital organs, perfusion of 189 Warm humidified oxygen 213 Xerocytes 266
Vitamin West Nile encephalitis 232
B12, deficiency of 443
B2 672
Wheeze
cause of 314
Y
B6 672 multiple-trigger 312 Yellow fever vaccine 120
D dependent rickets 464, 467 type of 314
D toxication 344
E, deficiency of 431, 432
White blood cell 167, 229, 230, 242, 254, 272,
273, 294, 322, 574, 601
Z
K deficiency bleeding 40 count 228, 618 Zinc pyrithione 674
Vocal cord 453 White coat hypertension 343 Zoonotic disease 123
785
INDEX_.indd 785 11/30/2016 5:36:07 PM

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Algorithms in

Nitin K Shah MD DCH DNB

The Health Sciences Publisher

© 2017, Jaypee Brothers Medical Publishers

Algorithms in Pediatrics / Anand S Vasudev, Nitin K Shah

First Edition: 2017

Ashish Mehta MD DCH Usha Pratap MD MRCP Varinder Singh MD FRCPCH

Mohan K Abraham MS MCh Atul Ahuja MS Arvind S Bais MS FIMSA

Shalu Gupta MD Aspi J Irani MD DCH Nachiket M Joshi MBBS

Ram G Holla MD DM Ganesh S Jevalikar MD DNB PDCC Rakesh Kumar

Nitin Pant MS MCh Baldev S Prajapati MD DPed FIAP Arun G Roy MD DM

Nidhi Sugandhi MS MCh Soumya Tiwari MD M Vijayakumar MD DCH DM FIAP

Pramod Jog MD DNB FIAP

Section 1: Neonatology 13. Neonatal Seizures 50

5. Persistent Pulmonary Section 2: Adolescence

8. Neonatal Shock 31 20. Adolescent Anemia 79

9. Anemia in Neonate 34 21. Academics and Career Choices in

24. Adolescent Depression/Suicidal 38. Approach to Burns in Children 175

Section 5: Intensive Care

27. Missed Immunization 121 41. Septic Shock 195

28. Animal Bites 123 42. Status Epilepticus 201

44. Head Injury in Infants and Children 209

37. Approach to Poisoning in Children 170 51. Acute Osteomyelitis 235

52. Algorithmic Approach to Short Section 8: Pulmonology

54. Approach to Managing New Onset 67. Assessing and Managing

55. Infant Born to Human Immunodeficiency 68. Recurrent Wheezing in

70. Management of Bronchiolitis 322

65. Algorithmic Approach to 77. Chronic Diarrhea in Children

80. Acute Liver Failure 380 Section 12: Nephrology

Section 11: Neurology 98. Acute Glomerulonephritis 473

90. Approach to Ataxia 427 Section 13: Endocrinology

109. Gynecomastia in Children 532 Section 15: Pediatric Surgery

114. Endocrine Hypertension in Children 560 129. Per-rectal Bleeding 632

130. Inguinal Hernia 637

118. Childhood Vasculitis 578

122. Approach to Juvenile Dermatomyositis 598 137. Pediatric Acne 667

Section 17: Ophthalmology 149. Stridor in Children 723

141. Compensatory Head Posture 680

153. Approach to a Child with a Limp 746

INTRODUCTION Identifying High Risk Delivery

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an understanding of the relevant neonatal data and ethical

Where? Mother Supervised in Neonatal intensive

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INTRODUCTION Clinical Pearls

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• Serum phenobarbitone level base as loading dose over 30 minutes followed by

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tachycardia and feed intolerance as compared to • Supportive care:

• Continuous positive airway pressure: continuous positive

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INTRODUCTION • Surgical causes: pneumothorax, congenital malformation

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Table 1: Score for respiratory distress (Downes’ score)

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Fig. 3: Chest X-ray showing infiltrates in right lower lung which is

Bronchopulmonary dysplasia • Pneumothorax may be diagnosed by auscultation, trans

INTRODUCTION Table 1: National Institute of Health definition: broncho

Hypovolemic shock {{ Inborn error of metabolism (glycogen storage disease, muco