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Year : 2021  |  Volume : 59  |  Issue : 2  |  Page : 127-130

Mucormycosis: An epidemic amidst the pandemic

Regional Institute of Ophthalmology and Government Ophthalmic Hospital, Chennai, Tamil Nadu, India

Date of Submission08-Jun-2021
Date of Acceptance09-Jun-2021
Date of Web Publication24-Jun-2021

Correspondence Address:
Dr. Sharmila Devi Vadivelu
Department of Cornea, Regional Institute of Ophthalmology and Government Ophthalmic Hospital, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_78_21

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How to cite this article:
Vadivelu SD. Mucormycosis: An epidemic amidst the pandemic. TNOA J Ophthalmic Sci Res 2021;59:127-30

How to cite this URL:
Vadivelu SD. Mucormycosis: An epidemic amidst the pandemic. TNOA J Ophthalmic Sci Res [serial online] 2021 [cited 2021 Jul 27];59:127-30. Available from: https://www.tnoajosr.com/text.asp?2021/59/2/127/319266

In preparing for battle, I have always found that plans are useless but planning is indispensable - Dwight D. Eisenhower

Mucormycosis is an extremely aggressive fungal infection caused by fungi of the order Mucorales.[1] It usually affects diabetic, immunocompromised, and occasionally healthy patients. The COVID-19 pandemic has led to an increase in the incidence of rhino-orbital cerebral mucormycosis (ROCM). Many states have declared the disease an epidemic and have made it notifiable. The incidence of pulmonary, gastrointestinal, soft tissue, and disseminated mucormycosis in COVID patients has also been reported.

  Epidemiology Top

Mucormycosis is not a new disease, it has been present for a long time (since 1876). Although most cases originate in developing countries, it has been encountered by clinicians in developed countries also in the pre-COVID era. Rhizopus, Mucor, Lichtheimia (formerly Absidia), and Apophysomyces are the most common members of the order Mucorales that cause mucormycosis, accounting for 70%–80% of all cases.[2] Fungi of the genus Rhizopus account for the majority of clinical isolates. In patients with hematological conditions, pulmonary, followed by disseminated and rhino orbitocerebral mucormycosis, is the most common,[3] whereas in patients with diabetes, especially with ketoacidosis, rhino-orbito-cerebral mucormycosis is the most common.[4]

  Etiopathogenesis Top

Airborne fungal spores are ubiquitous and can be found on human surfaces that come in contact with air, especially on the upper and lower airway mucosa.[5] Implantation of spores in the oral and nasal mucosa with subsequent extension to the rhinocerebral region is one of the probable modes of mucormycetes infection.[6] Inhaled fungal spores which are trapped in the paranasal sinuses undergo proliferation. There is rapid progression over a few days with angioinvasion and hematogenous dissemination with fungi invading the mucosa, submucosa, blood vessels, and bony walls of the nose and paranasal sinuses. Hyperglycemia and acidosis provide an ideal environment for fungal growth and tissue invasion (fungal proliferation enhanced with iron overload).[7]

  Risk Factors Top

ROCM is a rapidly progressive infection of the orbit and central nervous system secondary to infection of the paranasal sinuses. Uncontrolled diabetes, severe neutropenia, prolonged immunocompromised state, steroid therapy, and prolonged mechanical ventilation are high risk factors for ROCM. Uncontrolled diabetes mellitus was the most common underlying disease among COVID-19-associated mucormycosis (CAM) and non-CAM patients.[8] There should be a high index of clinical suspicion in patients with comorbidities who have recently recovered from COVID-19. Song et al. reported fungal coinfections in COVID-19 patients based on a worldwide search.[9] We should keep it in mind that it can also present as a coexisting infection with COVID-19. The patients are usually managed via a multidisciplinary approach in coordination with medicine, radiology, microbiology, pathology, and ear, nose, and throat departments.

  Clinical Manifestations Top

The usual presenting complaints are nasal blockage, congestion, bloody nasal discharge, localized facial pain, numbness, unilateral excruciating headache, unilateral facial pigmentation, and blurred and double vision. An ophthalmologist should do a complete ophthalmic evaluation, including visual acuity, extraocular movements, slit-lamp biomicroscopy, and fundus examination. It is essential to look for ophthalmoplegia or vascular occlusions through the entire course of the patient's treatment.

Patients can present with sinus involvement alone or orbital disease along with it. The signs of orbital disease can include conjunctival chemosis, proptosis, ptosis, reduced ocular motility, and frozen globe. Cranial nerve examination should be done and palsies have to be documented. Loss of vision and relative afferent pupillary defect can be present in orbital apex syndrome and central retinal artery occlusions. It is essential to stage them and classify whether they have a limited medial involvement, diffuse orbital involvement, orbital apex syndrome, or whether they have bilateral orbital involvement. As emphasized by many orbital surgeons, it is mandatory to do a retropulsion test to assess the severity of retrobulbar necrosis. Sometimes, there can be an involvement of the orbital apex and cavernous sinus through the pterygopalatine fossa and the anterior orbital contents may not be involved much and this is where a retropulsion test may be extremely useful. Santosh G. Honavar has proposed a good staging system to categorize the disease severity of ROCM as shown in [Figure 1].[10]
Figure 1: Staging of rhino-orbital cerebral mucormycosis

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  Investigations Top

Investigations should include a high nasal swab. Specimens should be analyzed by microscopy using 10% potassium hydroxide (KOH). For rapid diagnosis, clinicians should request for calcofluor/KOH mount. Calcofluor white stain acts as a brightener under a fluorescent microscope. On microscopy, Mucorales are seen as nonseptate fungi with right-angle branching. Mucorales are aseptate fungi, whereas Aspergillus, Fusarium, and Scedosporium species are septate fungi. Aspergillus species demonstrates acute-angle branching and Mucorales demonstrates right angle branching. Fungal culture specimens should be obtained preferably before starting antifungal therapy. Initiation of antifungals before culture reduces the chances of growing fungus on culture. The samples are cultured on agar such as Sabouraud dextrose agar and brain–heart infusion agar with antibiotics. Macroscopic and microscopic examination of cultures aids in the diagnosis of fungus. Fungal cultures should be examined biweekly for a period of 4 weeks before they are declared as negative.

Histopathology of diagnostic specimens is the most important tool and specimens can be taken during diagnostic nasal endoscopy or during endoscopic sinus surgery where sinus debridement is done. Imaging studies included magnetic resonance imaging or computed tomography scan of both the orbits, brain, and para nasal sinuses preferably with contrast. Imaging findings of inflammatory tissue infiltration adjacent to the paranasal sinuses with possible extension into the pterygopalatine fossa, infratemporal fossa, and orbit or the cavernous sinus should raise the suspicion of a mucormycosis, especially in immunocompromised patients.[11] Imaging can show an altered intensity of the orbital fat and stretching of the optic nerve in orbital disease.

  Management Top

The medical management of a proven case of ROCM is primarily with amphotericin B. It is a fungistatic agent rather than fungicidal, which leads to longer treatment duration. The use of amphotericin B may be limited by adverse effects, especially renal impairment. Use of liposomal intravenous amphotericin B (5–10 mg/kg body weight) permits treatment with higher doses than those with conventional formulations of amphotericin B without significantly increasing toxicity.[12] The drug was continued until 4–7 days after resolution of the disease. The choice of the empirical antifungal agent is extremely difficult as the triazoles, except for posaconazole, are ineffective for mucormycosis.

A combined approach of surgical debridement along with antifungals gives the patients an improved survival rate. Antifungals cannot penetrate into the dead tissue; hence, all the dead tissue should be ideally removed through Endoscopic sinus surgery with sinus debridement by an ENT surgeon. It can be combined with amphotericin lavage. Transcutaneous retrobulbar amphotericin B (TRAMB) injection (3.5 mg/ml) (off-label usage) is used for early orbital invasion with good vision and in cases where aggressive orbital debridement is not favored. Informed consent should be obtained before giving the injection. Some cases can have a transient orbital inflammation following the injection. We should also be aware of orbital compartment syndrome which can be an exceedingly rare complication following TRAMB and it has been reported in literature.

Early exenteration is done in cases where there is an advanced orbital disease and where retropulsion test is firm to hard indicating necrosis of periorbital and orbital tissues. Clinicoradiological features coupled with microbiological confirmation or histopathological evidence are essential to categorize a patient as proven ROCM and it is mandatory if a patient is taken for exenteration.

  Conclusion Top

The exact prevalence of mucormycosis in India is unknown, though the estimated prevalence is much higher than that in developed countries. The possible reason for the high prevalence is the abundant presence of Mucorales in the community and hospital environment, large number of susceptible hosts especially diabetics, and the neglect for regular health checkups of Indian population. A considerable number of patients are ignorant of diabetes status till they acquire mucormycosis.[13] Is the delta variant associated with an increase in sugar levels which can be a predisposing factor for mucormycosis? Researchers are working on these areas and we are yet to get solid evidence.

It may be possible to reduce the incidence of ROCM in the setting of COVID-19 by optimizing the indications for systemic corticosteroids, judicious use of tocilizumab, proactive metabolic control, and by minimizing the patient exposure to potential sources of infection.[8]

Having a high index of suspicion, early investigations and diagnosis, proper clinical staging, prompt institution of antifungal therapy, surgical debridement whenever necessary, identifying progression, and above all a good multidisciplinary team approach can help us win the battle against this deadly fungus.

  References Top

Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SC, Dannaoui E, Hochhegger B, et al. Global guideline for the diagnosis and management of mucormycosis: An initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019;19:e405-21.  Back to cited text no. 1
Gomes MZ, Lewis RE, Kontoyiannis DP. Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species. Clin Microbiol Rev 2011;24:411-45.  Back to cited text no. 2
Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis 2000;30:851-6.  Back to cited text no. 3
Espinel-Ingroff A, Oakley LA, Kerkering TM. Opportunistic zygomycotic infections. A literature review. Mycopathologia 1987;97:33-41.  Back to cited text no. 4
Lackner A, Stammberger H, Buzina W, Freudenschuss K, Panzitt T, Schosteritsch S, et al. Fungi: A normal content of human nasal mucus. Am J Rhinol 2005;19:125-9.  Back to cited text no. 5
Righi E, Giacomazzi CG, Lindstrom V, Albarello A, Soro O, Miglino M, et al. A case of Cunninghamella bertholettiae rhino-cerebral infection in a leukaemic patient and review of recent published studies. Mycopathologia 2008;165:407-10.  Back to cited text no. 6
Mankekar GS, Mehta R, Nuss DW. Orbito-Rhinocerebral Syndrome. In: Turgut M, Challa S, Akhaddar A, editors. Fungal Infections of the Central Nervous System. Cham: Springer; 2019.  Back to cited text no. 7
Patel A, Agarwal R, Rudramurthy SM, Shevkani M, Xess I, Sharma R, et al. MucoCovi Network3. Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India. Emerg Infect Dis 2021;27. doi: 10.3201/eid2709.210934. Epub ahead of print. PMID: 34087089.  Back to cited text no. 8
Song G, Liang G, Liu W. Fungal co-infections associated with global COVID-19 pandemic: A clinical and diagnostic perspective from China. Mycopathologia 2020;185:599-606.  Back to cited text no. 9
Honavar SG. Code Mucor: Guidelines for the diagnosis, staging and management of rhino-orbito-cerebral mucormycosis in the setting of COVID-19. Indian J Ophthalmol 2021;69:1361-5.  Back to cited text no. 10
  [Full text]  
Raab P, Sedlacek L, Buchholz S, Stolle S, Lanfermann H. Imaging patterns of rhino-orbital-cerebral mucormycosis in immunocompromised patients: When to suspect complicated mucormycosis. Clin Neuroradiol 2017;27:469-75.  Back to cited text no. 11
Pagano L, Valentini CG, Caira M, Fianchi L. ZYGOMYCOSIS: Current approaches to management of patients with haematological malignancies. Br J Haematol 2009;146:597-606.  Back to cited text no. 12
Prakash H, Chakrabarti A. Epidemiology of mucormycosis in India. Microorganisms 2021;9:523.  Back to cited text no. 13


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