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Mucormycosis

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This article is about fungal infections in the nose. For COVID-19 related disease, see Black fungus (COVID-19 condition).

Mucormycosis
Other namesZygomycosis[1]
This patient presented with a case of a periorbital fungal infection known as mucormycosis, or phycomycosis.
SpecialtyInfectious diseases Edit this on Wikidata
CausesWeakened immune system
Risk factorsHIV/AIDS, diabetes mellitus, diabetic ketoacidosis, COVID -19, lymphoma, organ transplant, long-term steroid use
Treatmentamphotericin B, surgical debridement
PrognosisPoor

Mucormycosis is any fungal infection caused by fungi in the order Mucorales.[2]: 328  Generally, species in the Mucor, Rhizopus, Absidia, and Cunninghamella genera are most often implicated.[3][4]

Common sources of infections are from soil, damp walls on old buildings etc.

The disease is often characterized by hyphae growing in and around blood vessels and can be potentially life-threatening in diabetic or severely immunocompromised individuals.

"Mucormycosis" and "zygomycosis" are sometimes used interchangeably.[5] However, zygomycota has been identified as polyphyletic, and is not included in modern fungal classification systems. Also, while zygomycosis includes Entomophthorales, mucormycosis excludes this group.

The condition is informally referred to as black fungus.[6]

Types of 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 and in people who have had a kidney transplant.
  • Pulmonary (lung) mucormycosis is the most common type of mucormycosis in people with cancer and in people who have had an organ transplant or a stem cell transplant.
  • Gastrointestinal mucormycosis is more common among young children than adults, especially premature and low birth weight infants less than 1 month of age, who have had antibiotics, surgery, or medications that lower the body’s ability to fight germs and sickness. 9-10
  • Cutaneous (skin) mucormycosis: occurs after the fungi enter the body through a break in the skin (for example, after surgery, a burn, or other type of skin trauma). This is the most common form of mucormycosis among people who do not have weakened immune systems.
  • Disseminated mucormycosis occurs when the infection spreads through the bloodstream to affect another part of the body. The infection most commonly affects the brain, but also can affect other organs such as the spleen, heart, and skin.[7]

Signs and symptoms

A 47-year-old man with mucormycosis and electron micrograph of his skin showing sporangia of Mucorales fungi.[8]

Mucormycosis frequently infects the sinuses, brain, or lungs. While infection of the oral cavity or brain are the most common forms of mucormycosis, the fungus can also infect other areas of the body such as the gastrointestinal tract, skin, and other organ systems.[9] In rare cases, the maxilla may be affected by mucormycosis.[10] The rich blood vessel supply of maxillofacial areas usually prevents fungal infections, although more virulent fungi, such as those responsible for mucormycosis, can often overcome this difficulty.[10]

There are several key signs which point towards mucormycosis. One such sign is fungal invasion into the blood vessels which results in the formation of blood clots and surrounding tissue death due to a loss of blood supply.[11] If the disease involves the brain, then symptoms may include a one-sided headache behind the eyes, facial pain, fevers, nasal congestion that progresses to black discharge, and acute sinusitis along with eye swelling.[12] Affected skin may appear relatively normal during the earliest stages of infection. This skin quickly becomes reddened and may be swollen before eventually turning black due to tissue death.[11] Other forms of mucormycosis may involve the lungs, skin, or be widespread throughout the body; symptoms may also include difficulty breathing, and persistent cough. In cases of tissue death, there may be nausea and vomiting, coughing up blood, and abdominal pain.[9][12]

The symptoms of mucormycosis also depend on where in the body the fungus is growing.

Symptoms of rhinocerebral (sinus and brain) mucormycosis include:

  • One-sided facial swelling
  • Headache
  • Nasal or sinus congestion
  • Black lesions on nasal bridge or upper inside of mouth that quickly become more severe
  • Fever

Symptoms of pulmonary (lung) mucormycosis include:

  • Fever
  • Cough
  • Chest pain
  • Shortness of breath

Cutaneous (skin) mucormycosis can look like blisters or ulcers, and the infected area may turn black. Other symptoms include pain, warmth, excessive redness, or swelling around a wound.

Symptoms of gastrointestinal mucormycosis include:

  • Abdominal pain
  • Nausea and vomiting
  • Gastrointestinal bleeding

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. Patients with disseminated infection in the brain can develop mental status changes or coma.[13][14][15][16]

Risk factors

Predisposing factors for mucormycosis include AIDS, uncontrolled diabetes mellitus, cancers such as lymphomas, kidney failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis, energy malnutrition,[9][10] and deferoxamine therapy.[medical citation needed] Despite this, however, there have been cases of mucormycosis reported with no apparent predisposing factors present.[17]

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.[18][19][20]

Diagnosis

As swabs of tissue or discharge are generally unreliable, the diagnosis of mucormycosis tends to be established with a biopsy specimen of the involved tissue.[citation needed]

Treatment

If mucormycosis is suspected, amphotericin B therapy should be immediately administered due to the rapid spread and high mortality rate of the disease. Amphotericin B is usually administered for an additional 4–6 weeks after initial therapy begins to ensure eradication of the infection. Isavuconazole was recently FDA approved to treat invasive aspergillosis and invasive mucormycosis.[21]

After administration of either amphotericin B or posaconazole, surgical removal of the "fungus ball" is indicated. The disease must be monitored carefully for any signs of reemergence.[9][22]

Surgical therapy 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. In some cases surgery may be disfiguring because it may involve removal of the palate, nasal cavity, or eye structures.[12] Surgery may be extended to more than one operation.[9] It has been hypothesized that hyperbaric oxygen may be beneficial as an adjunctive therapy because higher oxygen pressure increases the ability of neutrophils to kill the fungus.[11]

Prognosis

In most cases, the prognosis of mucormycosis is poor and the disease has varied mortality rates depending on its form and severity. In the rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient, with a mortality rate of up to 90%.[11] Patients with AIDS have a mortality rate of almost 100%.[22] Possible complications of mucormycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.[12]

Epidemiology

Mucormycosis is a very rare infection, and as such, it is hard to note histories of patients and incidence of the infection.[9] However, one American oncology center revealed that mucormycosis was found in 0.7% of autopsies and roughly 20 patients per 100,000 admissions to that center.[22] In the United States, mucormycosis was most commonly found in rhinocerebral form, almost always with hyperglycemia and metabolic acidosis (e.g. DKA).[17] In most cases the patient is immunocompromised, although rare cases have occurred in which the subject was not; these are usually due to a traumatic inoculation of fungal spores. Internationally, mucormycosis was found in 1% of patients with acute leukemia in an Italian review.[9]

Outbreaks

Not every hospital in the USA is required to publicize details of infectious outbreaks which occur within their facilities. In 2014, details of a lethal mucormycosis outbreak[23] which occurred in 2008 emerged after television and newspaper reports responded to an article in a pediatric medical journal.[24] Contaminated hospital linen was found to be spreading the infection. A 2018 study found many freshly laundered hospital linens delivered to U.S. transplant hospitals were contaminated with Mucorales.[25]

A cluster of infections occurred in the wake of the 2011 Joplin tornado. By July 19, 2011 a total of 18 suspected cases of cutaneous mucormycosis had been identified, of which 13 were confirmed. A confirmed case was defined as 1) necrotizing soft-tissue infection requiring antifungal treatment or surgical debridement in a person injured in the tornado, 2) with illness onset on or after May 22 and 3) positive fungal culture or histopathology and genetic sequencing consistent with a mucormycete. No additional cases related to that outbreak were reported after June 17. Ten patients required admission to an intensive-care unit, and five died.[26][27]

Cutaneous mucormycosis has been reported after previous natural disasters; however, this is the first known cluster occurring after a tornado. None of the infections were found in persons cleaning up debris; instead it is believed transmission occurred through penetrating injuries inflicted by contaminated objects (e.g. splinters from a woodpile).[28]

Black fungus

Main article: Black fungus (COVID-19 condition)

During the COVID-19 pandemic, a number of cases linked to immunosuppressive treatment for COVID-19 were reported in India called covid associated mucormycosis(CAM)[29]. In Ahmedabad, 44 cases including nine deaths were reported by mid-December 2020. Cases were also reported in Mumbai and Delhi.[30] In 2021, more cases were also reported throughout India.[6] According to the reports, it has affected close to 5,000 people across the country and has an Irrefutable number of deaths.[31]

See also

References

  1. ^ "Orphanet: Zygomycosis". www.orpha.net. Archived from the original on May 13, 2021. Retrieved May 13, 2021.
  2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
  3. ^ Rinaldi M.G. (1989). "Zygomycosis". Infect Dis Clin North Am. 3 (1): 19–41. doi:10.1016/S0891-5520(20)30244-0. PMID 2647832.
  4. ^ Lee F.Y.; Mossad S.B.; Adal K.A. (1999). "Pulmonary mucormycosis: the last 30 years". Arch Intern Med. 159 (12): 1301–9. doi:10.1001/archinte.159.12.1301. PMID 10386506.
  5. ^ Staff Springfield News-Leader (June 10, 2011) "Aggressive fungus strikes Joplin tornado victims" Seattle PI, Hearst Communications Inc.
  6. ^ a b "Mucormycosis: The 'black fungus' maiming Covid patients in India". May 9, 2021 – via www.bbc.com.
  7. ^ "About Mucormycosis | Mucormycosis | CDC". www.cdc.gov. January 14, 2021. Retrieved May 12, 2021.
  8. ^ Ran Yuping (2016). "Observation of Fungi, Bacteria, and Parasites in Clinical Skin Samples Using Scanning Electron Microscopy". In Janecek, Milos; Kral, Robert (eds.). Modern Electron Microscopy in Physical and Life Sciences. InTech. doi:10.5772/61850. ISBN 978-953-51-2252-4.
  9. ^ a b c d e f g Nancy F Crum-Cianflone; MD MPH. "Mucormycosis". eMedicine. Retrieved May 19, 2008.
  10. ^ a b c Auluck A (2007). "Maxillary necrosis by mucormycosis. a case report and literature review" (PDF). Med Oral Patol Oral Cir Bucal. 12 (5): E360–4. PMID 17767099. Retrieved May 19, 2008.
  11. ^ a b c d Spellberg B, Edwards J, Ibrahim A (2005). "Novel perspectives on mucormycosis: pathophysiology, presentation, and management". Clin. Microbiol. Rev. 18 (3): 556–69. doi:10.1128/CMR.18.3.556-569.2005. PMC 1195964. PMID 16020690.
  12. ^ a b c d "MedlinePlus Medical Encyclopedia: Mucormycosis". Retrieved May 19, 2008.
  13. ^ Petrikkos, George; Skiada, Anna; Lortholary, Olivier; Roilides, Emmanuel; Walsh, Thomas J.; Kontoyiannis, Dimitrios P. (February 1, 2012). "Epidemiology and Clinical Manifestations of Mucormycosis". Clinical Infectious Diseases. 54 (suppl_1): S23–S34. doi:10.1093/cid/cir866. ISSN 1537-6591.
  14. ^ Lewis, Russell E; Kontoyiannis, Dimitrios P (September 2013). "Epidemiology and treatment of mucormycosis". Future Microbiology. 8 (9): 1163–1175. doi:10.2217/fmb.13.78. ISSN 1746-0913.
  15. ^ Spellberg, Brad; Edwards, John; Ibrahim, Ashraf (2005). "Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management". Clinical Microbiology Reviews. 18 (3): 556–569. doi:10.1128/cmr.18.3.556-569.2005. ISSN 0893-8512.
  16. ^ Ribes, Julie A.; Vanover-Sams, Carolyn L.; Baker, Doris J. (April 1, 2000). "Zygomycetes in Human Disease". Clinical Microbiology Reviews. 13 (2): 236–301. doi:10.1128/cmr.13.2.236. ISSN 1098-6618.
  17. ^ a b Roden MM, Zaoutis TE, Buchanan WL, et al. (September 2005). "Epidemiology and outcome of Mucormycosis: a review of 929 reported cases". Clin. Infect. Dis. 41 (5): 634–53. doi:10.1086/432579. PMID 16080086.
  18. ^ Biswas, Soutik (May 9, 2021). "Mucormycosis: The 'black fungus' maiming Covid patients in India". BBC News. British Broadcasting Corporation. Retrieved May 11, 2021.
  19. ^ Koehler, Philipp; Bassetti, Matteo; Chakrabarti, Arunaloke; Chen, Sharon C A; Colombo, Arnaldo Lopes; Hoenigl, Martin; Klimko, Nikolay; Lass-Flörl, Cornelia; Oladele, Rita O; Vinh, Donald C; Zhu, Li-Ping (December 2020). "Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance". The Lancet Infectious Diseases. doi:10.1016/s1473-3099(20)30847-1. ISSN 1473-3099.
  20. ^ Garg, Deepak; Muthu, Valliappan; Sehgal, Inderpaul Singh; Ramachandran, Raja; Kaur, Harsimran; Bhalla, Ashish; Puri, Goverdhan D.; Chakrabarti, Arunaloke; Agarwal, Ritesh (May 1, 2021). "Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature". Mycopathologia. 186 (2): 289–298. doi:10.1007/s11046-021-00528-2. ISSN 1573-0832. PMC 7862973. PMID 33544266.
  21. ^ Lyndsay Mayer. "Mucormycosis". Food and Drug Administration. Retrieved April 5, 2017.
  22. ^ a b c Rebecca J. Frey. "Mucormycosis". Health A to Z. Archived from the original on May 18, 2008. Retrieved May 19, 2008.
  23. ^ Catalanello, Rebecca (April 16, 2014). "Mother believes her newborn was the first to die from fungus at Children's Hospital in 2008". NOLA.com.
  24. ^ "5 Children's Hospital patients died in 2008, 2009 after contact with deadly fungus". We acknowledge that Children's Hospital is Hospital A in an upcoming article in The Pediatric Infectious Disease Journal. The safety and well-being of our patients are our top priorities, so as soon as a problem was suspected, the State Health Department and CDC were notified and invited to assist in the investigation. The hospital was extremely aggressive in trying to isolate and then eliminate the source of the fungus.
  25. ^ Sundermann, Alexander; et al. (2018). "How Clean Is the Linen at My Hospital? The Mucorales on Unclean Linen Discovery Study of Large United States Transplant and Cancer Centers". Clinical Infectious Diseases. 68 (5): 850–853. doi:10.1093/cid/ciy669. PMC 6765054. PMID 30299481.
  26. ^ Williams, Timothy (June 10, 2011) Rare Infection Strikes Victims of a Tornado in Missouri. New York Times.
  27. ^ Neblett Fanfair, Robyn; Benedict, Kaitlin; Bos, John; Bennett, Sarah D.; Lo, Yi-Chun; Adebanjo, Tolu; Etienne, Kizee; Deak, Eszter; Derado, Gordana; Shieh, Wun-Ju; Drew, Clifton; Zaki, Sherif; Sugerman, David; Gade, Lalitha; Thompson, Elizabeth H.; Sutton, Deanna A.; Engelthaler, David M.; Schupp, James M.; Brandt, Mary E.; Harris, Julie R.; Lockhart, Shawn R.; Turabelidze, George; Park, Benjamin J. (2012). "Necrotizing Cutaneous Mucormycosis after a Tornado in Joplin, Missouri, in 2011". New England Journal of Medicine. 367 (23): 2214–25. doi:10.1056/NEJMoa1204781. PMID 23215557.
  28. ^ Fanfair, Robyn Neblett; et al. (July 29, 2011). "Notes from the Field: Fatal Fungal Soft-Tissue Infections After a Tornado – Joplin, Missouri, 2011". MMWR Weekly. 60 (29): 992.
  29. ^ "CAM- covid associated mucormycosis".{{cite web}}: CS1 maint: url-status (link)
  30. ^ "'Black' Fungal Disease that Causes Blindness, Death Strikes Guj after Covid-19; Kills 9 in Ahmedabad". News18. December 18, 2020. Retrieved December 18, 2020.
  31. ^ May 21, Timesofindia; 2021; Ist, 15:11. "Black fungus infection stalks states: 5,500 cases, 126 lives lost | India News - Times of India". The Times of India. Retrieved May 21, 2021. {{cite web}}: |last2= has numeric name (help)CS1 maint: numeric names: authors list (link) CS1 maint: url-status (link)
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