Epidemiology and distribution
Mucormycosis is caused by environmental moulds that are present worldwide, including the Rhizopus, Apophysomyces, Mucor, and Lichtheimia

species. Mucormycosis has recently gained attention due to an epidemic in India, where thousands of instances have been recorded in the aftermath of India’s second wave of COVID-19 infections, drawing attention to this devastating yet often overlooked condition. Indeed, due to the disease’s rarity, large, randomized clinical studies are challenging to undertake, and the majority of the current data on epidemiology, diagnosis, and management comes from case reports and case series. ⁽¹⁾

Risk factors 

Fungal spores are naturally prevalent in the environment, and in a healthy immunocompetent human, the immune system prevents them from causing illness. However, when the body’s defense mechanisms are compromised, such as in patients with diabetes mellitus, neutropenia, organ transplant recipients, and other immune-compromised states, these fungal spores can easily invade the body, causing a severe systemic infection with a 45-80% fatality rate. In high-income nations, haematological malignancies are the most prevalent underlying condition, while 
uncontrolled diabetes is the most common in developing countries. (1)

Symptoms 

The most common clinical presentations of mucormycosis are rhino-orbito-cerebral, pulmonary, cutaneous, and disseminated. The most frequent symptom is a sinus infection, which is accompanied by nasal congestion, discharge, and discomfort. A fever and headache are also possible. 

If the infection progresses beyond the sinuses, symptoms may include tissue necrosis of the palate, rupture of the septum between the nostrils, perinasal oedema, and erythema of the skin overlaying the sinus and the eye socket.

Diagnosis and treatment

Because the infection is typically very aggressive and rapidly progressing, suspected mucormycosis needs immediate treatment as delayed treatment initiation is associated with greater mortality. To maximize survival rates, quick diagnostic and therapeutic action is required, including the early engagement of a multidisciplinary medical, surgical, radiological, and laboratory-based team. ⁽²⁾ A strong index of suspicion, identification of host determinants, and early assessment of clinical symptoms are all requirements for the diagnosis of mucormycosis. Direct microscopy of clinical specimens, particularly with optical brighteners such Blankophor and Calcofluor White, provides a rapid presumptive diagnosis of mucormycosis. In addition to microscopy, histopathology and culture of different clinical specimens are the pillars of diagnosing mucormycosis. Enzyme-linked immunosorbent assays, immunoblots, and immunodiffusion tests have all been tried with varying degrees of success. ⁽³⁾

Conventional polymerase chain reaction (PCR), restriction fragment length polymorphism analyses (RFLP), DNA sequencing of specific gene areas, and melt curve analysis of PCR products are all examples of molecular-based tests that can be used either for detection or identification of Mucorales. Most molecular assays target either the internal transcribed spacer or the 18S rRNA genes. In terms of specimens, various studies have employed paraffin-embedded, formalin-fixed, or fresh tissue samples, with varying results. However, current efforts in molecular diagnostics from blood and serum have provided promising clinical evidence. When compared to culture, molecular-based diagnosis from serum resulted in earlier diagnosis and verified the culture-proven cases. Therefore, molecular-based diagnostic tests are currently suggested as helpful add-on tools that supplement traditional diagnostic techniques. ^{(4, 5, 6)}. A multimodal approach is required for the successful management of mucormycosis. This includes early administration of active antifungal agents at the optimal dose, reversal or discontinuation of underlying predisposing factors (if possible), complete removal of all infected tissues, and the use of various adjunctive therapies. ⁽⁷⁾

^References

1. Steinbrink JM, Miceli MH. Mucormycosis. Infect Dis Clin North Am. 2021 Jun;35(2):435-452. doi: 10.1016/j.idc.2021.03.009. PMID: 34016285.
2. Hsin-Yun Sun, MD, Prof Nina Singh, MD. Mucormycosis: its contemporary face and management strategies. The Lancet, Infectious Diseases. Volume 11, Issue 4, P301-311, April 01, 2011. Doi: https://doi.org/10.1016/S1473-3099(10)70316-9
3. Skiada A, Lass-Floerl C, Klimko N, Ibrahim A, Roilides E, Petrikkos G. Challenges in the diagnosis and treatment of mucormycosis. Med Mycol. 2018 Apr 1;56(suppl_1):93-101. doi: 10.1093/mmy/myx101. PMID: 29538730; PMCID: PMC6251532.
4. Guinea J, Escribano P, Vena A, Muñoz P, Martínez-Jiménez MDC, Padilla B, Bouza E. Increasing incidence of mucormycosis in a large Spanish hospital from 2007 to 2015: Epidemiology and microbiological characterization of the isolates. PLoS One. 2017 Jun 7;12(6):e0179136. doi: 10.1371/journal.pone.0179136. Erratum in: PLoS One. 2020 Feb 12;15(2):e0229347. PMID: 28591186; PMCID: PMC5462442.
5. Ino K, Nakase K, Nakamura A, Nakamori Y, Sugawara Y, Miyazaki K, Monma F, Fujieda A, Sugimoto Y, Ohishi K, Masuya M, Katayama N. Management of Pulmonary Mucormycosis Based on a Polymerase Chain Reaction (PCR) Diagnosis in Patients with Hematologic Malignancies: A Report of Four Cases. Intern Med. 2017;56(6):707-711. doi: 10.2169/internalmedicine.56.7647. Epub 2017 Mar 17. PMID: 28321075; PMCID: PMC5410485.
6. Millon L, Herbrecht R, Grenouillet F, Morio F, Alanio A, Letscher-Bru V, Cassaing S, Chouaki T, Kauffmann-Lacroix C, Poirier P, Toubas D, Augereau O, Rocchi S, Garcia-Hermoso D, Bretagne S; French Mycosis Study Group. Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF). Clin Microbiol Infect. 2016 Sep;22(9):810.e1-810.e8. doi: 10.1016/j.cmi.2015.12.006. Epub 2015 Dec 17. PMID: 26706615.
7. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, Lass-Flörl C, Calandra T, Viscoli C, Herbrecht R. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017 Mar;102(3):433-444. doi: 10.3324/haematol.2016.152900. Epub 2016 Dec 23. PMID: 28011902; PMCID: PMC5394968.