Mucormycosis – Commonly known as “Black fungus”

A rare but life-threatening fungal infection, known as mucormycosis and colloquially as “black fungus”, is being detected relatively frequently among Covid-19 patients in some states of India. It mainly affects immunocompromised patients. Most of these patients were having other immunocompromised illnesses such as uncontrolled diabetes etc. and once they were infected with Covid 19, they have been treated with steroids and this has led to this devastating outcome

Mucormycosis has been diagnosed from Sri Lankan immunocompromised patients over the years and it is not uncommon among Sri Lankan patients. In 2019 we have diagnosed and successfully treated 42 patients and in 2020 it was 24 patients. Most of these patients were diagnosed with rhinocerebral mucormycosis and few were diagnosed with pulmonary mucormycosis.

So far, Sri Lanka has not diagnosed or reported COVID 19 patients with mucormycosis.

Mucormycosis is caused by moulds belonging to order Mucorales. These fungi can cause many clinical forms of mucormycosis in predisposed vulnerable individuals. It is known as the second most frequent mould infection in immunocompromised individuals. This group of organisms have a predilection for vascular invasion causing thrombosis, infarction & necrosis of surrounding tissues which has given the name “Black fungus”. It has a worldwide distribution. Found ubiquitous in soil & decomposing organic matter. It can be found in indoors & outdoors, in food items & dust.

Commonest causative agents are Rhizopus oryzae, Rhizorpus microsporus, Apophysomyces elegans, Cokeromyces recurvatus, Cunninghamella bertholletiae, Lichtheimia (Absidia) corymbifera, Rhizomucor pusillus, Saksenaea vasiformis & Syncephalastrum recemosum.

Most infections are following inhalation of spores in air. As a result, nasal sinuses & lungs are the commonest initial sites of infection. Also cutaneous, percutaneous infections have been reported following inoculation, such as traumatic disruption of skin barriers, catheter insertion sites & following injections. Cases have been reported following ingestion of contaminated food also.

Risk factors are prolonged or profound neutropaenia, diabetes mellitus (type I & II), metabolic acidosis, malnutrition, steroid usage, treatment on iron-chelating agents, on deferoxamine treatment, HSCT recipients, solid organ transplant recipients, patients with haematological malignancies, patients with burn injuries, injection drug users, widespread use of voriconazole and also some patients with no apparent immunological defects.

Certain predisposing factors are more commonly associated with certain clinical forms, such as diabetic ketoacidosis with rhinocerebral mucormycosis, haematological malignancies & transplant recipients with pulmonary mucormycosis etc.

Case fatality rate (CFR) is around 35% with no underlying predisposing cause), 44% in patients with diabetes mellitus, 66% in patients with malignancies. CFR can vary according to site of infection as well, 62% in rhinocerebral mucormycosis, 76% in pulmonary mucormycosis, 85% gastro-intestinal mucormycosis and 96% in disseminated mucormycosis. Higher survival rate among diabetes mellitus patients due to easiness of reverting underlying ketoacidosis than among malignancies. Higher CFR has observed in pulmonary mucormycosis patients due to its difficulty in diagnosing the disease.

 

Clinical manifestations include 5 major clinical forms,

rhinocerebral mucormycosis – commonest form
pulmonary mucormycosis – second most common form
cutaneous mucormycosis
gastrointestinal mucormycosis
disseminated mucormycosis

Clinical hallmark is rapid onset of necrosis & fever. Most cases progress very rapidly, death is unavoidable unless timely diagnosed & rapidly treated.

1. Rhinocerebral mucormycosis – patients can present with fever, unilateral facial swelling, unilateral headache, nasal or sinus congestion or pain & a blood-tinged nasal discharge.Characteristic diagnosed signs include necrotic black ulceration on the hard palate or nasal turbinates, ptosis, proptosis, ophthalmoplegia, loss of vision, drainage of black pus from eye/s.
   Complications include, spreading to the orbit, periorbital or perinasal swelling with progressive destruction of facial tissues. Infection can spread to brain with frontal lobe necrosis & abscess formation.
   If left untreated, this could be fatal within a week of onset of the disease.
2. Pulmonary mucormycosis – clinical presentation includes non-specific, unremitting fever, non-productive cough, (haemoptysis & pleuritic chest pain uncommon). Has a more predilection for upper lobes of the lungs, but any part of the lungs can be affected, but bilateral disease is uncommon. If left untreated could be fatal within two to three weeks.
3. Cutaneous mucormycosis – present initially with cutaneous erythema & subcutaneous swelling of the affected area. Painful lesions, febrile, raised & indurated, central necrotic ulcer with black eschar formation.
4. Gastrointestinal mucormycosis – present as necrotizing enterocolitis, all segments can be involved, more common in stomach, colon, ileum. Symptoms depend on the affected site, fever, abdominal pain, distension, vomiting & haematemesis are typical. Complications include gastric or intestinal perforation, perirenal abscesses & renal infarction.
5. Disseminated mucormycosis – commonest site of spread is brain, metastatic necrotic lesions can form in spleen, heart and any other organ.

Radiological investigations in rhinocerebral mucormycosis include,

CT scan - involvement of several sinuses (ethmoid & sphenoid), clear unilateral predilection, no air-fluid levels, thickening of sinus linings & destruction of surrounding bone

MRI – better than CT. Detects extension of infection to adjacent soft tissues of the orbit & brain

in pulmonary mucormycosis include,

CXR - chest infiltrates & nodules more frequent than consolidation or cavitation

High resolution CT scan – best (halo & air crescent sign increase risk of massive haemoptysis)

 

Laboratory investigations - Early diagnosis & adequate treatment are the mainstay of successful outcome. Specimens include,

• clinical material from necrotic lesions (in a sterile screw capped container with sterile saline) for fungal studies,
• sputum & BAL (in sterile screw capped containers) for fungal studies

All samples should be transported at room temperature to Department of Mycology, Medical Research Institute, Colombo 8

Management include, antifungal treatment (amphotericin B) should be initiated with suspected diagnosis, underlying metabolic or immunological disorder must be corrected, infected necrotic tissues & surrounding tissues should be surgically removed repeatedly. Duration of treatment depends on clinical, radiological & mycological cure

Complications include disfigurement, amputation of limbs, blindness, brain infection or death

Prevention include,

• In non-immunocompromised individuals, adequate control of diabetes mellitus, use of iron chelating agents other than desferrioxamine, limited use of aluminium containing buffers in dialysis
• In immunocompromised individuals, reduce sources of environment exposure (gardening, avoid old & contaminated food, avoid contaminated surgical dressings & syringes etc.), avoid inhalation of spores during critical periods (keep in rooms with HEPA filters)
• No antifungal prophylaxis is available