Mucormycosis: Pathogenesis, Clinical Features, and Treatment

By Nisha Rijal •  Updated: 05/22/22 •  7 min read
Mucormycosis etiological agent

Mucormycosis, previously called ‘zygomycosis’, also known as ‘black fungus disease ‘in online or print media after its epidemic in India during the COVID-19 pandemic, is a serious but rare fungal infection caused by the mucormycetes group of fungi. It is a rapidly destructive necrotizing fungal infection usually seen in diabetics and also in other immunocompromised patients. The group includes fungi belonging to the genera Lichtheimia, Mucor, Rhizomucor, Cunninghamella, Saksenaea, Apophysomyces, Cokeromyces, Actinomucor, and Syncephalastrum.

Black fungus is a ‘misnomer’ because Mucorales are hyaline fungi. There are already categories of black fungi already described in the medical literature causing tinea nigra, chromoblatomycosis, phaeohyphomycosis.

Rhizopus arrhizus (formerly Rhizopus oryzae) is the most common etiological agent. It is the third invasive mycosis in order of importance after candidiasis and aspergillosis and has an overall mortality rate of 50%.

It is caused by exposure to mucor which is ubiquitous in environment and is found in soil, plants, manure, decaying fruits and vegetables, air and even as commensal in the nose and mucus of healthy people.

Risk group

People with a weakened immune system are at higher risk of acquiring mucormycosis. Factors predisposing to the infection include conditions such as;

Immunocompetent patients can also be affected, when the spores of the fungus are directly inoculated in the skin, as a result of trauma or burns.

Pathogenesis

Mucormycetes enter the body either by inhalation of airborne spores, percutaneous inoculation or ingestion. Once the spores reach the lungs or subcutaneous tissues, they are destroyed by the first line of defence, mononuclear and polynuclear phagocytes in healthy individual.

Pathogenesis of pulmonary mucormycosis (Image source)

But when an immunocompromised host breathes in the spores of mucormycetes, the defence system is hampered, and it cause an infection commonly in the lungs or sinuses, which can spread to other parts of the body and cause disseminated infection.

Clinical manifestations

Since mucormycosis affects many parts of the body, clinical manifestations are classified depending upon the site of infection and symptoms depend upon the part affected.

Rhinocerebral mucormycosis

Rhinocerebral (sinus and brain) mucormycosis is an infection in the sinuses that can spread to the brain. This form of mucormycosis is most common in people with uncontrolled diabetes mellitus, kidney transplant and leukaemia, but is rare in solid-organ or haematopoietic stem-cell recipients and occasional in patients with HIV infection.

Clinical manifestations may start with necrosis of the palate or sinuses, which may progress towards the orbit before reaching intra-cranial structures.

Symptoms of rhinocerebral (sinus and brain) mucormycosis include:

Pulmonary (lung) mucormycosis

Invasion of the lung is the second most common clinical manifestation and follows the inhalation of spores. It is the common type of mucormycosis in people with hematological malignancy with neutropenia and in organ transplant or a stem cell transplant cases.

Symptoms of pulmonary (lung) mucormycosis include:

It is difficult to differentiate between invasive aspergillosis and pulmonary mucormycosis. Both show similar symptoms and on radiological presentation vascular invasion and thrombosis, followed by tissue necrosis, is seen in both cases.

Gastrointestinal mucormycosis

Gastrointestinal mucormycosis occurs through ingestion of spores possibly from fermented milk, dried bread products, fermented porridges, and alcoholic beverages derived from infected corn. It can also be contracted from from infected tongue depressors at physician clinics.

Gastrointestinal mucormycosis most commonly affects stomach, followed by colon, small intestine and oesophagus.

Symptoms of gastrointestinal mucormycosis include:

Cutaneous (skin) mucormycosis

Cutaneous mucormycosis is often acquired by direct inoculation, through breaks in the skin (eg after surgery, burns, motor vehicle accidents) by contaminated dressings, and insulin injection sites. Outbreaks of mucormycosis in healthcare centers are common due to contaminated adhesive tape, wooden tongue depressors, ostomy bags, and building construction contamination.

Pathogenesis of Wound Related Mucormycosis (Image source).

This is the most common form of mucormycosis among immunocompetent host.

Cutaneous mucormycosis can be classified as primary and secondary.

The most affected areas of the skin are the arms and legs. Other locations include the scalp, face, thorax, back, abdomen, perineum, breast, neck and gluteal area.

Symptoms of cutaneous mycormycosis

Disseminated mucormycosis (DM)

Disseminated mucormycosis (DM) often involves two or more non continuous organ systems. The infection spreads through the bloodstream and affects the brain, but also can affect other organs such as the spleen, heart, kidney and skin.

Disseminated cutaneous mucormycosis is exceedingly rare and deadly, with a mortality rate of 90–100%

Symptoms are non-specific and varies depending on the site of attack. For e.g Patients with disseminated infection in the brain can develop mental status changes or coma whereas dissemination to the skin results in erythematous lesions.

Other clinical manifestations:

Treatment of mucormycosis

The successful treatment of mucormycosis depends on 1) early diagnosis of mucormycosis; 2) reversal of underlying predisposing risk factors, if possible; 3) surgical debridement (extensive surgical debridement is must for removing the necrotic tissue for better circulation and penetration of antifungal drugs) where applicable, and 4) prompt antifungal therapy.

For monotherapy options,

Fluconazole, voriconazole, and itraconazole do not have reliable activity against mucormycosis

Combination therapy

References and further readings:

  1. E. Bouza, P. Munoz and J. Guinea 2006 Mucormycosis: an emerging disease? Clin Microbiol Infect; 12 (suppl 7): 7–23
  2. https://www.cdc.gov/fungal/diseases/mucormycosis/html
  3. Castrejón-Pérez, A. D., Welsh, E. C., Miranda, I., Ocampo-Candiani, J., & Welsh, O. (2017). Cutaneous mucormycosis. Anais brasileiros de dermatologia92(3), 304–311. https://doi.org/10.1590/abd1806-4841.20176614
  4. Spellberg, B., & Ibrahim, A. S. (2010). Recent advances in the treatment of mucormycosis. Current infectious disease reports12(6), 423–429. https://doi.org/10.1007/s11908-010-0129-9.

Nisha Rijal

I am working as Microbiologist in National Public Health Laboratory (NPHL), government national reference laboratory under the Department of health services (DoHS), Nepal. Key areas of my work lies in Bacteriology, especially in Antimicrobial resistance.

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