Mucormycosis, also known as black fungus, is a severe fungal infectionLi N, Bowling J, de Hoog S, Aneke CI, Youn J, Shahegh S, Cuellar-Rodriguez J, Kanakry CG, Rodriguez Pena M, Ahmed SA, Al-Hatmi AMS, Tolooe A, Walther G, Kwon-Chung KJ, Kang Y, Lee HB, Seyedmousavi A.2024.Mucor germinans, a novel dimorphic species resembling Paracoccidioides in a clinical sample: questions on ecological strategy. mBio15:e00144-24.https://doi.org/10.1128/mbio.00144-24 that may cause fulminant fungal sinusitis, usually in people who are immunocompromised. It is mostly curable when diagnosed early. Symptoms depend on where in the body the infection occurs. It most commonly infects the nose, sinuses, eyes and brain resulting in a runny nose, one-sided facial swelling and pain, headache, fever, blurred vision, bulging or displacement of the eye (proptosis), and tissue death. Other sites of infection may include the lungs, stomach and intestines, and skin. It tends to progress rapidly and is fatal in about half of sinus cases and almost all cases of the widespread type.
It is spread by spores of molds of the order Mucorales, most often through inhalation, contaminated food, or contamination of open wounds. These fungi are common in soils, decomposing organic matter (such as rotting fruit and vegetables), and animal manure, but usually do not affect people. It is not transmitted between people. 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. Risk factors include diabetes with persistently high blood sugar levels or diabetic ketoacidosis, low white blood cells, cancer, organ transplant, iron overload, kidney problems, long-term steroids or use of immunosuppressants, and to a lesser extent HIV/AIDS.
Diagnosis is by biopsy and culture, with medical imaging to help determine the extent of disease. It may appear similar to aspergillosis. Treatment is generally with amphotericin B and surgical debridement.
Mucormycosis is usually rare. A recent rise in cases was particularly noted in India, where it may be about 80 times more common than in developed countries. People of any age may be affected, including premature infants. The disease has been reported in natural disasters, including the 2004 Indian Ocean tsunami and the 2011 Joplin tornado. During the COVID-19 pandemic, an association between mucormycosis and COVID-19 was reported, thought to result from reduced immune function during the illness or from glucocorticoid therapy for COVID-19.
Classification Generally, mucormycosis is classified into five main types according to the part of the body affected. A sixth type has been described as mucormycosis of the kidney, or miscellaneous, i.e., mucormycosis at other sites, although less commonly affected. Sinuses and brain (rhinocerebral); most common in people with poorly controlled diabetes and in people who have had a kidney transplant. 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. 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. Skin (cutaneous); after a burn, or another skin injury, in people with leukaemia, poorly-controlled diabetes, graft-versus-host disease, HIV and intravenous drug use. Widespread (disseminated); when the infection spreads to other organs via the blood.
Signs and symptoms
Signs and symptoms of mucormycosis depend on the location of the infection in the body. Infection usually begins in the mouth or nose and enters the central nervous system via the eyes.
If the fungal infection begins in the nose or sinus and extends to the 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. 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.
Fever, cough, chest pain, and difficulty breathing, or coughing up blood, can occur when the lungs are involved. A stomach ache, nausea, vomiting, and bleeding can occur when the gastrointestinal tract is involved. Affected skin may appear as a dusky reddish tender patch with a darkening centre due to tissue death. There may be an ulcer, and it can be very painful.
Invasion of the blood vessels can result in thrombosis and subsequent death of surrounding tissue due to a loss of blood supply. 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 changes in mental status or lapse into a coma.
Cause Mucormycosis is a fungal infection caused by fungi in the order Mucorales. In most cases it is due to an invasion of the genera Rhizopus and Mucor, common bread molds. Most fatal infections are caused by Rhizopus oryzae. It is less likely due to Lichtheimia, and rarely due to Apophysomyces. Others include Cunninghamella, Mortierella, and Saksenaea.
The fungal spores are present in the environment. Once inside the body, the fungus grows branch-like filaments which invade blood vessels, causing clots to form and surrounding tissues to die.
Spores can be found on items such as moldy bread and fruit, and are breathed in frequently, but cause disease only in some people. In addition to being breathed in and deposited in the nose, sinuses, and lungs, the spores can also enter the skin via blood or directly through a cut or open wound, and can also grow in the intestine if eaten. Other reported causes include contaminated wound dressings. Mucormycosis has been reported following the use of elastoplast and the use of tongue depressors for holding in place intravenous catheters. Outbreaks have also been linked to hospital bed sheets, negative-pressure rooms, water leaks, poor ventilation, contaminated medical equipment, and building works. One hypothesis suggests that the spread of fungal spores in India could be due to fumes generated from the burning of Mucorales-rich biomass, like cow dung and crop stubble.
Risk factors Predisposing factors for mucormycosis include immune deficiencies, a low neutrophil count, and metabolic acidosis. Risk factors include poorly controlled diabetes mellitus (particularly DKA), organ transplant, iron overload, such cancers as lymphomas, kidney failure, liver disease, severe malnutrition, and long term corticosteroid and immunosuppressive therapy. Other risk factors include tuberculosis (TB), deferoxamine and to a lesser extent HIV/AIDS. Cases of mucormycosis in fit and healthy people are less common.
Corticosteroids are commonly used in the treatment of COVID-19 and reduce damage caused by the body's immune response to the virus. They suppress the immune system and increase blood sugar levels in both diabetic and non-diabetic patients. These effects may increase a person's vulnerability to developing a case of mucormycosis.
Mechanism Most people are frequently exposed to Mucorales without developing the disease. Mucormycosis is generally spread by breathing in, eating food contaminated by, or getting spores of molds of the Mucorales type in an open wound. It is not transmitted between people.
The precise mechanism by which people with diabetes mellitus become susceptible is unclear. In vivo, a high sugar level alone does not permit the growth of the fungus, but acidosis alone does. People with high sugar levels frequently have high iron levels, also known to be a risk factor for developing mucormycosis. In people taking deferoxamine, the iron removed is captured by siderophores on Rhizopus species, which then use the iron to grow.
Diagnosis No blood test can confirm the diagnosis. Diagnosis requires identifying the mold in the affected tissue by biopsy and confirming it with a fungal culture. Because the causative fungi occur all around and may therefore contaminate cultures underway, a culture alone is not decisive. Tests may also include culture and direct detection of the fungus in lung fluid, blood, serum, plasma, and urine. Blood tests include a complete blood count to look specifically for neutropenia. Other blood tests include iron levels, blood glucose, bicarbonate, and electrolytes. Endoscopic examination of the nasal passages may be needed.
Imaging Imaging is often performed, such as CT scan of lungs and sinuses. 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 do not confirm mucormycosis. A reverse halo sign in a person with a blood cancer and low neutrophil count is highly suggestive of mucormycosis. CT scan images of mucormycosis can be useful to distinguish mucormycosis of the orbit and cellulitis of the orbit, but images may appear identical to those of aspergillosis. MRI may also be useful. Currently, MRI with gadolinium contrast is the investigation of choice in rhinoorbito-cerebral mucormycosis.
Culture and biopsy To confirm the diagnosis, biopsy samples can be cultured. Culture from biopsy samples does not always give a result as the organism is very fragile. Microscopy can usually determine the genus and sometimes the species but may require an expert mycologist. The appearance of the fungus under the microscope can vary but generally shows wide (10–20 micron), ribbon-like filaments that generally do not 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.
Other Matrix-assisted laser desorption/ionization may be used to identify the species. A blood sample from an artery may be useful to assess for metabolic acidosis.
Differential diagnosis Other filamentous fungi may however look similar. It may be difficult to differentiate from aspergillosis. Other possible diagnoses include anthrax, cellulitis, bowel obstruction, ecthyma gangrenosum, lung cancer, clot in lungs, sinusitis, tuberculosis and fusariosis.
Prevention Preventive measures include wearing a face mask in dusty areas, washing hands, avoiding direct contact with water-damaged buildings, and protecting skin, feet, and hands where there is exposure to soil or manure, such as gardening or certain outdoor work. In high-risk groups, such as organ transplant patients, antifungal drugs may be given as a preventative.
Treatment Treatment involves a combination of antifungal drugs, surgically removing infecting tissue, and correcting underlying medical problems, such as diabetic ketoacidosis. One of the leading experts is Dr. Thomas J. Walsh. He helped develop GM-CSF which stimulates the maturation, differentiation, and, critically, the activation of neutrophils and macrophages to fight fungal infection and can help develop a plan of action.
Medication Once mucormycosis is suspected, amphotericin B at an initial dose of 1 mg is initially given slowly over 10–15 minutes into a vein, then given as a once daily dose according to body weight for the next 14 days. It may need to be continued for longer. Isavuconazole and Posaconazole are alternatives.
Surgery Surgery can be very drastic, and, in some cases of disease involving the nasal cavity and the brain, removal of infected brain tissue may be required. Removal of the palate, nasal cavity, or eye structures can be very disfiguring. Sometimes more than one operation is required.
Other considerations