ANNOOR DENTAL COLLEGE

DEPARTMENT OF ORAL MEDICINE AND

RADIOLOGY

TOPIC: MUCORMYCOSIS

Submitted By,
JOEL ANTO VARGHESE
FINAL YEAR PART 1
190022139
 DEPARTMENT OF ORAL MEDICINE AND
RADIOLOGY

CERTIFICATE
This is to certify that JOEL ANTO VARGHESE with enrolment number
190022139 has successfully completed all seminars conducted by Department
of Oral Medicine and Radiology for the academic period 2023-2024.

Staff in-charge Professor and HOD

Department of Oral Medicine and
Radiology
 CONTENTS

1. Introduction
2. Etiopathogenesis
3. Clinical Features- Diagnosis
4. Investigations
5. Treatment
6. Conclusion
7. Reference

INTRODUCTION
 Mucormycosis is a life threatening, angioinvasive infection caused by
saprophytic fungi of Order Mucorales. Mucorales fungi are ubiquitous fungi.
Rhizopus oryzae is the most common organism isolated from patients with
mucormycosis.
It usually occurs in patients with uncontrolled diabetes mellitus with or
without ketoacidosis, corticosteroids treatment, organ or bone marrow
transplantation, neutropenia, malignant hematologic disorders, trauma and burns,
deferoxamine therapy in patients receiving haemodialysis. A new underlying factor
experienced in recent months is COVID-19.

Etiopathogenesis:

1. Diabetes Mellitus:

Diabetes Mellitus is known to be the underlying disease for occurrence of

mucormycosis in most cases.Diabetes prevalence has risen faster in low- and
middle-income countries than in high income countries. Uncontrolled Type II
Diabetes mellitus is the most common type in diabetes patients with
mucormycosis.

Patients with Diabetic Ketoacidosis are more prone to develop

mucormycosis due to inoculation of organism due to trauma like unhygienic dental
procedures during tooth extraction, accidents, injury. Impaired healing also plays a
vital role in inoculation of organism.

2.Solid Organ Transplantation:

Solid Organ Malignancy and associated solid organ transplantation is also an

important risk factors factor of Mucormycosis. In a review by Almyroudis et al
incidence in renal transplant recipients was 0.4–0.5, in liver recipients 4–16, in
heart recipients 8 and in lung recipients 13.7–14, all per 1000 patients.

3.Malignant Hematologic Disorders:

 Hematologic Malignancy and associated hematopoietic stem cell
transplantation is the underlying cause in countries with high income population.
Acute Myeloid Leukemia, Acute Lymphoid Leukemia, non –Hodgkin’s
Lymphoma, Myelodysplastic Syndrome are some of the related hematological
malignant disorders. Risk of Mucormycosis increases with prolonged neutropenia.

4.Treatment with Corticosteroids and Other Immunosuppressants:

Chronic Administration of immunosuppressive drugs like corticosteroids in

treatment of malignancy, transplantation, autoimmune disorders is the major risk
factor associated with mucormycosis. Minor Trauma and Impaired healing worsens
situation by exposing patients
to fungal infection.

5.Increased Iron Levels in Plasma & Deferoxamine Therapy Haemodialysis:

In normal physiological states iron is attached to ferritin in mucosal cells of

gastrointestinal tract and transferring it to plasma and deposits Iron in liver or bone
marrow. In patients suffering from Diabetes mellitus with acidosis the affinity of
protein to bind with iron is decreased causing increased levels of iron in plasma.
This causes availability of iron to Mucorales fungi.

Serum Iron may be increased in patients undergoing multiple transfusion or

dialysis due to decrease of proteins in plasma. Deferoxamine an iron chelator used
in the past for treating increased serum iron levels. It is a bacterial siderophore.
However, Mucorale Fungi utilizes Deferoxamine to acquire iron from host causing
Mucormycosis in host.

6.COVID -19:

Corona Virus disease (COVID-19) pandemic caused by Severe Acute

Respiratory Syndrome Virus (SARS CoV-2) along with associated emergence of
Mucormycosis is increased in recent days. Poorly controlled diabetes mellitus and
other comorbidities are major risk factors. Also use of Corticosteroids critical
COVID-19 patients causes well known risk factor for Mucormycosis.

7. Other Predisposing Factors:

 Other causes may include IV drug use, renal failure, AIDS, liver diseases,
alcoholism. Health Care associated issues like use of non-sterile products is most
commonly suspected cause of infection. Bandages, adhesives, nitroglycerine
patches, contaminated linen, osteotomy bags and various medical devices, such as
catheters, insulin pumps and finger sticks, and insertion of tubes, tooth extractions
and surgery may be a carrier factor. Minor Trauma like animal bite or major
trauma like surgery, motor vehicle accidents may also be a cause for
mucormycosis.

Clinical features – Diagnosis:

The clinical hallmark of Mucormycosis is tissue necrosis resulting from

vascular invasion causing thrombosis and tissue infarction. Diplopia in a
neutropenic patients affected with diabetes mellitus or COVID-19 is an alarming
sign for Mucormycosis. However necrotic eschar does not preclude the diagnosis.
The Warning signs presented in patients with Mucormycosis are:
1. Pain
2. Proptosis
3. Periorbital Swelling
4. Orbital apex Syndrome
5. Palatine Ulcers
6. Blackish or Brownish discharge from nose
Prolonged fever, not responding to broad spectrum antibiotics, is usually present.
Non-productive cough is a common symptom, whereas hemoptysis,
pleuritic chest pain and dyspnea are less common.

Clinically the various types of mucormycosis seen are:

1. Rhinocerebral Mucormycosis
2. Pulmonary Mucormycosis
3. Cutaneous Mucormycosis
4. Gastrointestinal Mucormycosis
5. Palatal Mucormycosis
6. Miscellaneous

1.RHINOCEREBRAL MUCORMYCOSIS
 Rhinocerebral mucormycosis is the most common form of the disease. The initial
onset of rhinocerebral mucormycosis begins with sinusitis or periorbital cellulitis
with eye or facial pain and facial numbness, succeeded conjunctival inflammation,
blurry vision and soft tissue swelling. Fever may or may not be present. If left
untreated, infection usually spreads from the ethmoid sinus to the orbit, resulting in
loss of extraocular muscle function and proptosis in the contralateral eye, with
resulting bilateral proptosis, chemosis, vision loss, and ophthalmoplegia.

2.PULMONARY MUCORMYCOSIS

Pulmonary Mucormycosis of occurs most commonly in leukemic patients who are

receiving chemotherapy or patients undergoing hematopoietic stem cell
transplants.
Symptoms of pulmonary mucormycosis include dyspnoea, cough, and chest pain.
Radiographically, a variety of findings may be present, including, in descending
order of frequency: lobar consolidation, isolated masses, nodular disease, and
cavitation.

3.CUTANEOUS MUCORMYCOSIS
 Cutaneous Mucormycosis occurs in patient with disruption of the normal
protective cutaneous barrier. The agents of mucormycosis are typically incapable
of penetrating intact skin. However, burns, traumatic disruption of skin like
laceration and persistent maceration of skin enables the organisms to penetrate into
deeper tissues. For example, traumatic implantation of soil, due to a motor vehicle
accident or penetrating injury with plant material like a thorn or piece of stick.

4.GASTROINTESTINAL MUCORMYCOSIS

Gastrointestinal mucormycosis is rare. It mainly occurs in patients who are

extremely malnourished

5.PALATAL MUCORMYCOSIS
Palatal Mucormycosis may be presented with bilateral maxillary sinus tenderness
and an ulcerative hard palate lesion with necrosis. Palatal ulceration, necrosis, and
perforation can also be seen.

6.MISCELLANEOUS

Mucorale Infection can occur in any body site. Miscellaneous expressions of

Mucormycosis includes Endocarditis, Osteomyelitis, Peritonitis, Renal
Mucormycosis.
Tissue Necrosis is hallmark of mucormycosis but presentation and
syndrome-oriented approach lacks sensitivity and specificity. Early
Diagnosis of Mucormycosis is of utmost importance as it has influence on its
management.

INVESTIGATION

Lab Investigation involves microscopic examination and visual

examination of histopathologic culture, serology and molecular assays. A
confirmatory diagnosis of mucormycosis is made from biopsies of affected
tissues or bronchoalveolar lavage. A definitive diagnosis is based on the
demonstration of fungal hyphae typical for mucoromycetes species in biopsies of
affected tissues, or bronchoalveolar lavage in patients with pulmonary
mucormycosis. Selection of tissue site for biopsy is of utmost importance because
it can be used to distinguish the presence of species as a pathogen or as a culture
contaminant.

Direct microscopy:
For a rapid diagnosis of mucormycosis, direct microscopy of Potassium
Hydroxide wet mounts can be used usually accompanied with fluorescent
brighteners like Blankophor and Calcofluor White for accurate diagnosis. When
fluorescent brighteners are used Fluorescent Microscope are used. Routine
hematoxylin and Eosin stains can be used for demonstrating only the cell wall with
no structures inside.
Mucorales genera produce typically non-pigmented, wide (5–25 µm), thin-walled,
ribbon-like hyphae with no or few septations (pauciseptate) show an irregular,
ribbonlike appearance and right-angle branching. Routine hematoxylin and Eosin
stains can be used for demonstrating only the cell wall with no structures inside.

Culture:
Culture on Sabouraud Agar with an antibacterial agent but without
cycloheximide, on which fungi grow easily. After incubation for 3-4 days on
Sabouraud agar at 30-37C, the colonies are grey – white with a thick, cottony,
fluffy surface. However, culture, has low sensitivity, as it can be falsely negative.
This can be attributed to a number of reasons, such as grinding or homogenization
of tissue specimens, which may destroy the delicate hyphae of mucoromycetes, or
even a lack of expertise

Proper sampling and handling of the specimens before examination are a

prerequisite for an optimal yield. Therefore, upon suspicion of a case, good
communication and close collaboration between clinicians and the microbiology
laboratory is essential to ensure that all steps of the diagnostic procedure will be
taken properly.

Serology:
Presently, there are no commercially available antigen markers to detect
Mucorales. Mucorale specific Antigen or any other surrogate diagnostic markers
will be of the subject of further studies. There is a specific antigen marker named
galactomannan for Aspergillus. However, Galactomannan testing in blood and
bronchoalveolar lavage in haematology patients or patients with compatible chest
CT imaging results may be used to decrease the likelihood of mucormycosis.

Molecular methods:
 Serum Mucorales PCR has been shown to be a highly reliable tool for the
diagnosis of invasive mucormycosis in immunocompromised patients. Several
Studies are going in this field of Molecular assays.
According to Millon et al. in a study using three qPCR [for Absidia
corymbifera (Lichtheimia), Mucor/Rhizopus and Rhizomucor 18S ribosomal RNA
genes] on sera of mucormycosis patients showed that this method was highly
sensitive, had a low detection level and could detect infection 3–68 days earlier
than the conventional methods.

Metabolomics-Breath Test
Koshy et al. examined breath volatile metabolite profiles, using the three
Mucorales species, by thermal desorption gas chromatography/tandem mass
spectrometry. Mice infected with Aspergillus fumigatus were used as controls.
They also analyzed breath volatile metabolites from five patients. The findings
showed that the three Mucorales species had distinct breath profiles.

These profiles distinguished the infections from each other and from aspergillosis,
therefore this method can be employed to diagnose fungal infection noninvasively.
This could be used in a high-risk population such as patients with neutropenia due
to treatment for leukemia or those undergoing hematopoietic cell transplantation.
This method seems to be convincing, but needs further research.

TREATMENT
Management of Mucormycosis includes
1. Rapidity of Diagnosis
2. Reversal of Underlying Conditions
3. Appropriate Antifungal Therapy
4. Appropriate Surgical Debridement

Antifungal Therapy:
Amphotericin B is the first-line drug of choice, posaconazole and isavuconazole
are also a part of effective treatment. The drawbacks in treating mucormycosis
in India are a gap in treatment protocol and the financial constraints of patients that
they cannot afford liposomal Amphotericin B. In addition to it, systemic
antifungals should be added to first-line management. There is a strong
recommendation of high dose liposomal amphotericin B along with the adequate
dosage of intravenous isavuconazole and posaconazole.
COVID – 19 patients
 Severely ill patients (admitted in ICU, required mechanical ventilation, long hospital
stay)
Risk Factors
Trauma, Diabetes mellitus, Corticosteroids use, Solid organ transplantation, Prolonged
Neutropenia, Haematological
Malignancy
Direct Microscopy
Using fluorescent brightener and histopathology with special stains (eg.: PAS & GMS)
Findings: Non – Septate/ Pauci-Septate; Ribbon like hyphae at least 6-16microns wide
CULTURE
Routine Media at 30C and 37C
Findings: Cottony white or Greyish black colony
Molecular
identification PCR
based assays
Primary Prophylaxis with Posconazole
First Line of Treatment Am B Lipid Complex, Liposomal Am B,
Posconazole Oral Suspension Surgical Treatment
Adjunctive Therapy (if needed)

Surgical Treatment:

Diagnosis of mucormycosis states an immediate and complete surgical

intervention. Early diagnosis in clinical examination is helpful because small, focal
lesions can be easily excised before they progress into critical structures. The
classical sign of angioinvasion prevents the entry of antifungal drug to the infection
site.
Surgical Debridement becomes necessary because of the massive amount of
tissue necrosis during the progression of infection which may not be prevented by
the killing the organism using antifungal therapy alone. In most cases the infection
is progressive in nature until management with antifungal therapy and surgical
debridement is done at right time.

Iron Chelators:
Iron Overload plays an important role in developing Mucormycosis. Iron
Chelators can be used as an adjunctive therapy for Mucormycosis. Unlike
Deferoxamine which supports the growth of Mucorales in presence of Iron, other
Iron Chelators like Deferiprone and Deferasirox did not allow organisms to take up
iron.

Other Adjunctive Therapy:

Hyperbaric Therapy can be used as adjunct along with surgical and antifungal
therapy. Adjunctive Cytokine Therapy is another treatment area need to be
researched for treating mucormycosis.The mortality rate is low in patients treated
with a combination of Amphotericin B and surgical debridement of the
infected tissue than patients treated with Amphotericin B alone.

Conclusion:
Mucormycosis is rare and destructive fungal disease which can affect any organ in
the human body. Clinical Hallmark signs are angioinvasion resulting in tissue
necrosis or infarction. Patients with poorly controlled diabetes mellitus with or
without acidosis, corticosteroid treatment, organ or bone marrow transplantation,
neutropenia, malignant hematologic disorders, trauma and burns, deferoxamine
therapy in patients receiving haemodialysis are majorly affected by Mucormycosis.

In recent months, incidence of mucormycosis has steeply increased in

COVID affected patients with comorbidities and also patients who had rigorous
corticosteroid therapy. Rhinocerebral Mucormycosis is the most common type of
Mucormycosis. Present investigatory procedures lacks sensitivity and specificity.
Early diagnosis and management reduce risk in most cases. Management includes
antifungal therapy, surgical debridement and adjunctive therapy. A combination of
antifungal therapy and surgical debridement is known to result in good prognosis