Mucormycosis is a fungal infection caused by fungi in the order Mucorales

Mucormycosis, also known as black fungus,[3][4] is a serious fungal infection, usually in people with reduced ability to fight infections.[9][11] Symptoms depend on where in the body the infection occurs.[12][13] It most commonly infects the nose, sinuses, eye and brain resulting in a runny nose, one sided facial swelling and pain, headache, fever, blurred vision, swollen and bulging eye, and tissue death.[1][6] Other forms of disease may infect the lungs, stomach and intestines, and skin.[6]

It is spread by spores of molds of the order Mucorales, most often through inhalation, contaminated food, or contamination of open wounds.[14] These fungi are common in soils, decomposing organic matter (such as rotting fruit and vegetables), and animal manure, but usually do not affect people.[15] It is not transmitted between people.[13] Risk factors include diabetes with persistently high blood sugar levels or diabetic ketoacidosis, low white cells, cancer, organ transplant, iron overload, kidney problems, long-term steroids or immunosuppressant use, and to a lesser extent in HIV/AIDS.[7][9]

Diagnosis is by biopsy and culture, with medical imaging to help determine the extent of disease.[5] It may appear similar to aspergillosis.[16] Treatment is generally with amphotericin B and surgical debridement.[8] Preventive measures include wearing a face mask in dusty areas, avoiding contact with water-damaged buildings, and protecting the skin from exposure to soil such as when gardening or certain outdoor work.[10] It tends to progress rapidly and is fatal in about half of sinus cases and almost all cases of the widespread type.[2][17]

Mucormycosis is usually rare, affecting fewer than 2 people per million people each year in San Francisco,[8] but is now ~80 times more common in India.[18] People of any age may be affected, including premature infants.[8] The first known case of mucormycosis was possibly one described by Friedrich Küchenmeister in 1855.[1] The disease has been reported in natural disasters; 2004 Indian Ocean tsunami and the 2011 Missouri tornado.[19] During the COVID-19 pandemic, an association between mucormycosis and COVID-19 has been reported. This association is thought to relate to reduced immune function during the course of the illness and may also be related to glucocorticoid therapy for COVID-19.[4][20] A rise in cases was particularly noted in India.[21]

Contents
1 Classification
2 Signs and symptoms
3 Cause
3.1 Risk factors
4 Mechanism
5 Diagnosis
5.1 Imaging
5.2 Culture and biopsy
5.3 Other
5.4 Differential diagnosis
6 Prevention
7 Treatment
7.1 Medication
7.2 Surgery
7.3 Other considerations
8 Prognosis
9 Epidemiology
9.1 COVID-19–associated mucormycosis
10 History
10.1 Naming
10.2 COVID-19–associated mucormycosis
11 Society and culture
12 Other animals
13 References
14 Further reading
15 External links
Classification
Generally, mucormycosis is classified into five main types according to the part of the body affected.[13][22] A sixth type has been described as mucormycosis of the kidney,[1] or miscellaneous, that is mucormycosis at other sites, although less commonly affected.[22]

Sinuses and brain (rhinocerebral); most common in people with poorly controlled diabetes and in people who have had a kidney transplant.[13]
Lungs (pulmonary); the most common type of mucormycosis in people with cancer and in people who have had an organ transplant or a stem cell transplant.[13]
Stomach and intestine (gastrointestinal); more common among young premature and low birth weight infants, who have had antibiotics, surgery, or medications that lower the body’s ability to fight infection.[13]
Skin (cutaneous); after a burn, or other skin injury, in people with leukaemia, poorly controlled diabetes, graft-versus-host disease, HIV and intravenous drug use.[5][13]
Widespread (disseminated); when the infection spreads to other organs via the blood.[13]
Signs and symptoms
Signs and symptoms of mucormycosis depend on the location in the body of the infection.[6] Infection usually begins in the mouth or nose and enters the central nervous system via the eyes.[5]

If the fungal infection begins in the nose or sinus and extends to brain, symptoms and signs may include one-sided eye pain or headache, and may be accompanied by pain in the face, numbness, fever, loss of smell, a blocked nose or runny nose. The person may appear to have sinusitis.[23] The face may look swollen on one side, with rapidly progressing “black lesions” across the nose or upper inside of mouth. One eye may look swollen and bulging, and vision may be blurred.[6][23][24]

Fever, cough, chest pain, and difficulty breathing, or coughing up blood, can occur when the lungs are involved.[6] A stomach ache, nausea, vomiting and bleeding can occur when the gastrointestinal tract is involved.[6][25] Affected skin may appear as a dusky reddish tender patch with a darkening centre due to tissue death.[11] There may be an ulcer and it can be very painful.[5][7][11]

Invasion into the blood vessels can result in thrombosis and subsequent death of surrounding tissue due to a loss of blood supply.[7] Widespread (disseminated) mucormycosis typically occurs in people who are already sick from other medical conditions, so it can be difficult to know which symptoms are related to mucormycosis. People with disseminated infection in the brain can develop mental status changes or coma.[26][27]

Cause
Mucormycosis is a fungal infection caused by fungi in the order Mucorales.[5] In most cases it is due to an invasion of the genera Rhizopus and Mucor, common bread molds.[28] Most fatal infections are caused by Rhizopus oryzae.[16] It is less likely due to Lichtheimia, and rarely due to Apophysomyces.[29] Others include Cunninghamella, Mortierella, and Saksenaea.[5][30]

The fungal spores are in the environment, can be found on for instance moldy bread and fruit and are breathed in frequently, but cause disease only in some people.[5] In addition to being breathed in to be deposited in the nose, sinuses and lungs, the spores can also enter the skin via blood or directly through a cut or open wound, or grow in the intestine if eaten.[13][30] Once deposited, the fungus grows branch-like filaments which invade blood vessels, causing clots to form and surrounding tissues to die.[5] Other reported causes include contaminated wound dressings.[5] Mucormycosis has been reported following the use of elastoplast and the use of tongue depressors for holding in place intravenous catheters,[5] Outbreaks have also been linked to hospital bed sheets, negative-pressure rooms, water leaks, poor ventilation, contaminated medical equipment, and building works.[31]

Risk factors
Predisposing factors for mucormycosis include conditions where people are less able to fight infection, have a low neutrophil count or metabolic acidosis.[11][9] Risk factors include poorly controlled diabetes mellitus (particularly DKA), organ transplant, iron overload, cancers such as lymphomas, kidney failure, long term corticosteroid and immunosuppressive therapy, liver disease and severe malnutrition.[30][10

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] Other risk factors include tuberculosis (TB),[19] deferoxamine[1] and to a lesser extent HIV/AIDS.[1][7] Cases of mucormycosis in fit and healthy people are rare.[7]

Corticosteroids are commonly used in the treatment of COVID-19 and reduce damage caused by the body’s own immune system during a coronavirus infection. They are immunosuppressant and increase blood sugar levels in both diabetics and non-diabetic patients. It is thought that both these effects may contribute to cases of mucormycosis.[32][33][20]

Mechanism
Most people are frequently exposed to Mucorales without developing the disease.[30] Mucormycosis is generally spread by breathing in, eating food contaminated by, or getting spores of molds of the Mucorales type in an open wound.[14] It is not transmitted between people.[13]

The precise mechanism by which diabetics become susceptible is unclear. In vivo, a high sugar alone does not permit the growth of the fungus, but acidosis alone does.[1][7] People with high sugars frequently have higher iron levels, also known to be a risk factor for developing mucormycosis.[7] In people on deferoxamine, the iron removed is captured by siderophores on Rhizopus species, which uses the iron to grow.[34]

Diagnosis
There is no blood test that can confirm the diagnosis.[35] Diagnosis requires identifying the mold in the affected tissue by biopsy and confirming it with a fungal culture.[8] Because the causative fungi occur all around, a culture alone is not decisive.[5] Tests may also include culture and direct detection of the fungus in lung fluid, blood, serum, plasma and urine.[19] Blood tests include a complete blood count to look specifically for neutropenia.[35] Other blood tests include iron levels, blood glucose, bicarbonate, and electrolytes.[35] Endoscopic examination of the nasal passages may be needed.[35]

Imaging
Imaging is often performed, such as CT scan of lungs and sinuses.[36] Signs on chest CT scans, such as nodules, cavities, halo signs, pleural effusion and wedge-shaped shadows, showing invasion of blood vessels may suggest a fungal infection, but does not confirm mucormycosis.[16] A reverse halo sign in a person with a blood cancer and low neutrophil count, is highly suggestive of mucormycosis.[16] CT scan images of mucormycosis can be useful to distinguish mucormycosis of the orbit and cellulitis of the orbit, but imaging may look identical to those of aspergillosis.[16] MRI may also be useful.[37] Currently, MRI with gadolinium contrast is investigation of choice in rhinoorbito cerebral mucormycosis.[citation needed]

Culture and biopsy
To confirm the diagnosis, biopsy samples can be cultured.[12][35] Culture from biopsy samples does not always give a result as the organism is very fragile.[16] To precisely identify the species requires an expert.[16] The appearance of the fungus under the microscope will determine the genus and species.[35] The appearances can vary but generally show wide, ribbon-like filaments that generally don’t have septa and that unlike in aspergillosis, branch at right angles, resembling antlers of a moose, which may be seen to be invading blood vessels.[11]