PSMI Doctor’s

Clinical Training
Cases
10th March 2018
 Case Study 1

www.newlandsclinic.org.zw Zimbabwe
 Case Study 1

Mr RM
• 45 year old M
• Lives in Msasa Park
• 10 children with 10 different mothers
• Car dealer
• Diagnosed with HIV infection in 2008 & commenced
on ART
 Case Study 1

ART history

• D4T/3TC/NVP 2008 - 2010

• TDF/3TC/EFV 2010 - 2015
• Defaulted for 2 years and returned to care in
September 2017
 Case Study 1
Presenting complaints:
Loss of weight (> 20kg), loss of appetite, occasional
night sweats, mass in the right axilla

Examination:
Overweight (83.2 kg), apyrexial, no LN except 5cm
cystic, non-tender mass in right axilla (anteriorly)
Chest was clear & all other systems were essentially
normal
 Case Study 1

Baseline blood results:

• CD4 94
• VL 332 292 copies/ml
• FBC: Hb 11.7 WBC 5.3 Plt 301
• Sputum for GeneXpert : Negative
Chest X Ray
USS of the right axilla & anterior chest wall
 Management

• Restarted on TLE and ART counselling done for

possible switch to 2nd line
• EFV stopped after 2 weeks due to CNS toxicity &
raised SGPT
• Commenced on 2nd line ART
• Week 3 on 2nd line: presented with confusion,
sweating profusely, general body weakness
unable to walk without assistance, came in a
wheelchair
Photograph of the right axilla & chest wall
 Management

• The diagnosis of TB lymphadenitis was made & he

was commenced on TB treatment

• Patient improved dramatically and came for review

walking unaided!
 Case Study 2

www.newlandsclinic.org.zw Zimbabwe
 Case Study 2

Mr LM
• 35 year M
• Lives in Hatcliffe
• Married with 2 children (4 & 6 years), wife on ART
• Referred from Murambinda hospital with high VL on
1st line ART
• Diagnosed HIV +ve in 2010, commenced on TLE
• Defaulted in 2015 for 6 months, recommenced 1st L
 Case Study 2

Presenting complaints
• Weight loss 65 kg to 42kg
• Chronic skin lesions – right shoulder & left leg
• Sores on the buttocks
• No cough
• No fever
• No night sweats
 Case Study 2

Examination
• Wasted, pale, T 36, generalised lymphadenopathy
• Skin - hyperpigmented, indurated skin rash on right
anterior chest wall extending into axilla, fluctuant
area in right supraclavicular area, large ulcerating
lesion in the pre-tibial region of the left leg
• RS, CVS, ABD, CNS – unremarkable
• GUS – scarring from chronic HSV 2 ulceration
Skin Lesion
Cutaneous Ulcer
 Case Study 2

Differential Diagnosis
• Chronic skin infections ? cause
• Severe weight loss ? cause
• Anaemia ? cause
• Probable 1st line treatment failure

What would you do?

 Case Study 2

Investigations:
• CD4 35, VL 273 381
• Liver & renal function normal
• FBC: Hb 6.3 (MCV 89, MCH 27), WBC 5.3, Plt 492
• Serum CrAg negative
• CRP 62.5
• Aspirate: GeneXpert negative MTB
• Urinary LAM: negative
• CXR
 Case Study 2

5 days later
• Reviewed with blood, urine & CXR results
• Diagnosis of EPTB was made on basis of skin
lesions and Xray findings
• Commenced on TB treatment
 Case Study 2

Week 2 of TB treatment
• Gained 4 kg!
• Leg ulcer showing signs of healing
• Switched to 2nd line ART – ABC/3TC/ATV/r
• Continued on TB treatment but Rifampicin
changed to Rifabutin
 Case Study 2

Week 4 TB treatment & week 2 second line ART

• Gained 6 kg
• Leg ulcer healing

Week 8 TB treatment & week 6 ART

• Gained 13 kg 
• Stopped IP of TB treatment
• Leg ulcer almost healed
• Hb 8.1
 Case Study 3

www.newlandsclinic.org.zw Zimbabwe
 Case Study 3

TG
• 19 year old M
• Lives in Kadoma with his mother who is a teacher
& is on ART
• 2nd born in a family of 2
• Paternal orphan
• Diagnosed with HIV in March 2013
• Vertical transmission
 Initial visit Dec 2016

• TG had been on ART for 3½ years (TLE)

• Baseline bloods: VL 1 177 380 CD4 29

• Defaulted ART for 6 months prior to NC visit

• C/o cough & fever, was screened for TB

 Initial visit Dec 2016

• Sputum for GeneXpert negative

• CXR – scoliosis & changes consistent with

chronic lung disease

• Plan – TG was recommenced on TLE & to have

DOTS at home
CXR Dec 2016
 Management

• May 2017 (5 months later) VL 477 684, CD4 18

• Switched to 2nd line in June 2017
• Week 6 on 2nd L presented with cough, fever,
tachycardia, SOB
• Had lost 4 kgs in 4 months
• FBC: Hb 3.2 (MCV 86.8), WCC 5.10, Plt 188
• Was referred to hospital for blood transfusion
 Management

• Week 11 on 2nd line returned with weakness, SOB &

was noted to be pale
• FBC: pancytopenia – Hb 5.5 (MCV 83.3), WBC 1.99,
Plt 98
• Peripheral smear: normocytic, hypochromic cells +
anisocytosis
• CXR: worsening of the chronic lung disease
• Cervical lymph node biopsy: reactive changes
• Serum ferritin: 2750 (NR 19 – 323)
CXR Aug 2017
Our dilemma…

• Patient with recurrent anaemia, loss of weight,

chronic lung disease

• No firm evidence for TB

• What would you do?

Graph showing TG’s recurrent anaemia

.
Hb results since initial visit
12 Week 11
10 (5.5)

8 2nd L ART commenced

6
4
2 Week 6
(3.2) Week 15
0 (4.3)
 The answer 

• September 2017 a bone marrow aspirate +

trephine biopsy was done:
o AAFBs seen as well as granuloma
o Pure red cell aplasia morphology suggestive of
parvovirus infection

• TG has been commenced on TB treatment

 Case Study 4

www.newlandsclinic.org.zw Zimbabwe
 Case Study 4
Mr LT
• 22 year M
• Lives with his mother & sister in Hatcliffe.
• Diagnosed HIV +ve in 2013 with a history of
recurrent skin rashes & enlarged parotid glands
• On examination at initial visit in 2013 he was noted
to have generalised lymphadeonapathy & tinea
corporis but nil else of note
 Case Study 4

Baseline blood results:

• CD4 3, high VL
• Normal liver & renal function
• FBC: Hb 11.7, WBC 4.3, Plt 228
 Case Study 4

• LT was not ready to commence ART

• Had a number of counselling sessions over 8 weeks
then commenced TDF/3TC/EFV
• The first 9 months of ART were unremarkable
• At week 36 the VL was 107 700
• Enhanced adherence counselling was instituted & 3
months later VL was 12 400
 Case Study 4

• LT was asked to come for 2 weekly adherence

monitoring & continued with the 1st line ART
• His mother assisted with DOTS at home
• After a further 3 months, VL was 147 326, CD4 330
• He was enrolled in adherence SG & attended for 8
weeks
• His post-group VL was 37 396
 Case Study 4

• Was switched to 2nd line - ABC/3TC/ATV/r

• Week 12 on 2nd line his VL 96
• At week 48 VL 19 962
• Despite renewed emphasis regarding adherence,
the VL was 140 131 at week 72
• He then defaulted treatment for 2 months 
 Case Study 4

• LT had found work gold panning & could not finance

his transport to return for his visits
• At week 88 he returned & was clinically well
• CD4 of 182, VL 98 035
• He was recommenced on 2nd line ART & assisted to
come for 2 weekly adherence monitoring.
• His mother said that she would assist with DOTS
 Viral Load

Wk 72
Defaulted for
2 months

Returned to care.
Recommenced on
2nd L

Wk48
Wk 0 2nd L
Wk 24
 Case Study 4

• Results at week 96 (May ‘17): CD4 429, VL 732

• Developed right sided cervical lymphadenopathy at
week 112
• No constitutional symptoms or signs of TB.
• A differential diagnosis of Non-Hodgkins Lymphoma
or TB lymphadenitis was made & a lymph node
biopsy was done
 Case Study 4

• Results of the lymph node biopsy: numerous non-

caseating granulomata composed of epithelioid
histiocytes & Langhans type giant cells consistent
with TB

• LT was commenced on TB treatment in September

2017 on a Rifabutin-containing regimen & continued
on 2nd line with DOTS at home & 2 weekly clinic
visits
 Case Study 5

www.newlandsclinic.org.zw Zimbabwe
 Case Study - TR

TR 21-year-old M
• Referred to NC in February 2017 with suspected
ART treatment failure (loss of weight & general
body weakness)
• Presenting complaints: diarrhoea, abdominal pain &
loss of weight
• Elucidation of the duration of these symptoms was
difficult ? several months duration
 ART History

• Commenced on D4T/3TC/NVP in 2010 + CMZ

prophylaxis
• Switched to TDF/3TC/EFV Jan 2015 (no blood
work)
• Defaulted treatment for 6 months in 2016 (gone
to the rural areas)
• Admitted to intermittent poor adherence to ART
 Social History

• TR was the eldest of 2 children

• Both parents were on ART at a municipal clinic
• He was a dancer & had not disclosed his HIV
status to work colleagues or family members
• Was sexually active & stated that he consistently
used condoms
 On Examination

• Weight 37.8 kg, BMI 13.5, T 36, BP 110/70, PR 76,

RR 18
• Unwell, wasted, mild pallor, generalised LN (> 2 cm
in diameter), a 2cm x 3cm firm, raised, keratinised,
fungating lesion in the left acromio-clavicular area,
no oral lesions
• Systems examination: chest clear, CVS, abdomen &
nervous system normal
 Working Diagnosis

• Clinical evidence of treatment failure, WHO stage 3

(weight loss of >10%)
• Supported by the history of poor adherence &
treatment interruption
• The possibility of an underlying OI (TB) or
malignancy was considered
 Initial Management

• TR was counselled regarding disclosure of his

status to a treatment supporter & importance of
adherence to ART
• Prescribed TDF/3TC/EFV & Cotrimoxazole
prophylaxis
• Baseline blood investigations & biopsy of the skin
lesion was done
 Results

• CD4 16, VL 18 897

• Liver & renal function: normal
• FBC: Hb 8,5 (Hct 25, MCV 101, MCH 34); WBC 3,5
(30% L, 49% N); Plt 197
• Serum CrAg negative; TPHA negative; sputum
Xpert MTB PCR negative
CXR
CXR Report
 Histology of the Skin Lesion

“A polypoid ulcerated lesion covered by slough

overlying lobules of capillary channels set in a
haemorrhagic and oedematous stroma with a mixed
inflammatory infiltrate. The appearances are
consistent with a pyogenic granuloma.
There is no evidence of malignancy”.
 Subsequent Visits

• Seen at 2 weekly intervals, worked up for a switch

to 2nd line ART
• Developed oral (& clinically suspected
oesophageal candidiasis) & was treated with
Fluconazole 400mg d x 3 days
• In order to eliminate the possibility of occult OIs, an
abdominal & pelvic USS
• Lymph node biopsy of a right epitrochlear lymph
node
 Results

• The USS scan revealed multiple paraportal &

mesenteric lymph nodes. Abdominal & pelvic organs
were normal

• Histology of the lymph node: “non-specific reactive

changes with follicular lysis. No granulomas seen
and no evidence of malignancy”
 Further Management

• 6 weeks after initial visit was commenced on 2nd line

ART – ABC/3TC/Atazanavir/r
• Blood results at switch: CD4 20; VL 11 523 cp/ml
• Seen at 2 weekly intervals & except for 1 episode of
diarrhoea & oral candidiasis, he improved
• Stable at week 12, no further diarrhoea, but had lost
3kg
• Requested to come for monthly visits
 Further Management – Week 16
• TR complained of fatigue and was wasted
• Examination: wt loss (4kg), apyrexial, mild pallor, no
new skin lesions, small generalised LN, RS, CVS,
NS normal, abdomen - diffuse tenderness, no HSM
• CD4 count 15; VL < 20 cp/ml. FBC: Hb 8.6
(microcytic), WBC 1.3, Plt 145
• Probable IRIS but what?
• Counselled with parents, continued on 2nd line ART
• Weekly visits
 Further Management – Week 20

• A number of skin lesions were noted

• Raised, hyperpigmented, non-tender lesions
Situated on left superior orbital margin & the left
lower leg
• Biopsy of the lesion on the left lower leg was done
 Skin Lesions

Histology results: a lobular

capillary haemangioma with no
evidence of malignancy
 Further Management – Week 21

• The clinical condition deteriorated with marked

weight loss - now 31kg
• FBC: Hb 6.1, WBC 4.3, Plt 40
• Referred to Parirenyatwa hospital, presumptive
diagnosis of Kaposi sarcoma
• The KS team were not convinced
• Ordered a number of investigations
• BMAT: myelodysplasia – exclude secondary causes
i.e vitamin B12 def, RVI, drugs, etc.
What are you thinking?
Differential diagnosis of
Kaposi sarcoma
MZ Borok
Department of Medicine, UZCHS
HIV Clinicians September 2017
Differential Diagnosis

• Is this KS?
• If it is, what is the extent (staging)
• If it is not KS, what could it be?
• Do a biopsy
– HHV-8 staining
 KS Mimickers
Patch/Macule Papule Nodules

Bruises Secondary syphilis Pyogenic

granuloma
Papular pruritic Bacillary
Purpura eruption angiomatosis

Haemangiomas Basal cell Dermatofibroma

carcinoma
Naevi Squamous cell
carcinoma
Lichen planus
 KS Mimickers
Patch/Macule Papule Nodules
Bruises Secondary Pyogenic
syphilis granuloma
Papular pruritic Bacillary
Purpura eruption angiomatosis

Haemangiomas Basal cell Dermatofibroma

carcinoma
Naevi Squamous cell
carcinoma
Lichen planus
 KS Mimickers
Patch/Macule Papule Nodules
Bruises Secondary Pyogenic
syphilis granuloma
Papular pruritic Bacillary
Purpura eruption angiomatosis

Haemangiomas Basal cell Dermatofibroma

carcinoma
Naevi Squamous cell
carcinoma
Lichen planus
Biopsy is needed to confirm
diagnosis of KS
 Further Management – Week 21

• On further discussion with the physicians & review

of the histological specimens with the pathologists,
a diagnosis of bacillary angiomatosis was made

• Unfortunately the patient demised prior to

commencement of antibiotic therapy
Bacillary Angiomatosis
Bacillary angiomatosis
• Definition
• Vascular proliferation following infection with
Bartonella species
• Mainly in severely immunocompromised patients
• Wide age range
• Pathophysiology
• Gram negative rod, fastidious on culture
• Bartonella quintana and B. henselae
• Systemic infection – almost all organs affected
• Causes angiogenesis
Bacillary angiomatosis
• Transmission
oDomestic cats are the reservoir
oCat bites or scratches
oBites from cat fleas or human body louse (Pediculus
humanus)
• Symptoms and signs
oMost patients are HIV+ with CD4<200 cells/µL
oDuration of symptoms usually several months before
presentation
oSymptoms depend on the organ involved
oConstitutional symptoms of fever/chills/sweats/anorexia
and LOW
oTypically raised red or purple lesions on skin or
subcutaneous
Bacillary angiomatosis

• Signs – variable morphologic appearance

• Raised cutaneous red or purple lesions which
bleed easily
• Solitary or multiple, 1 - >1000
• May ulcerate, crust, discharge, often tender
• Associated lymphadenopathy
• Occasionally regress
• Skin disease may be a marker of visceral disease
• May affect mucosal surfaces including the mouth,
conjunctiva, nose, perineum
Bacillary angiomatosis

•Differential diagnosis is wide

•BA and KS may co-exist
 Bacillary angiomatosis
• Diagnosis
oBiopsy
oEndoscopy
oBronchoscopy

• Histology – vascular proliferation with neutrophils

adjacent to proliferation of blood vessels and
masses of bacteria, demonstrated by modified silver
stain (Warthin-Starry stain)
• Plump endothelial cells lining blood vessels
• PCR in tissue may demonstrate Bartonella DNA
BA - Pathology
KS Pathology
BA - Diagnosis continued

• ELISA - may demonstrate IgM or IgG antibodies

• IFA – demonstrates IgG, titre of >1:256 strongly
suggests active or recent infection
• Blood cultures
• CONVINCING EVIDENCE:
POSITIVE CULTURE/POSITIVE HISTOPATHOLOGY

• Imaging studies - X-rays, CT, MRI

 Management
• Antibiotics – doxycycline 100mg bd or erythromycin 500mg
qid, orally
• May use iv if liver or bone involvement, ?add rifampin for
CNS or life threatening disease
• Use doxycycline + 14 days of iv gentamicin for bacteraemia
• Optimal duration of therapy not known – at least 3 months
for skin lesions, longer with bony, visceral and liver lesions
• A Jarisch-Herxheimer reaction may occur on initiation of
treatment
• If relapses occur, re-start therapy, use till CD4 is >200 for at
least 6 mths
• Start ART after 2-4 weeks of antibiotics if CNS or eye disease
present, to avoid IRIS
Outcome
• Prognosis
• Excellent, most resolve completely
• Prognosis depends on early detection and degree
of immune compromise
• May be progressive and fatal if untreated

• Prevention
• Treat bedding and clothing
• Control flea infestations in cats
• Avoid cat scratches/contact especially if CD4 <200
• Antibiotic prophylaxis is not recommended
After 1 month After 3 months..
References

• Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents.

Guidelines for the prevention and treatment of opportunistic infections in
HIV-infected adults and adolescents: recommendations from the Centers for
Disease Control and Prevention, the National Institutes of Health, and the
HIV Medicine Association of the Infectious Diseases Society of America.
Bartonellosis. May 7, 2013;1-416.
• Levy, G, Nayler, P. SAMJ 1993 Nov; 83(11): 855
• Chitsike, I, Muronda, C. CAJM 1997 Aug; 43(8):238
• Forrestel, AK, et al. JIAPAC 2015; vol 14 issue: 1: 21-25

DISCUSSION
 Discussion

• These 4 cases illustrate the complexities that arise

when diagnosing TB in HIV infected patients
• Case study 1: normal CXR (skin)
• Case study 2: normal CXR (skin + osteomyelitis)
• Case study 3: bone marrow biopsy required
• Case study 4: no constitutional signs/symptoms
(lymph node)