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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 296-302

Imaging and clinical perspectives of rhino-orbito-cerebral mucormycosis: An epidemic born out of a pandemic


Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Submission23-Jun-2022
Date of Acceptance05-Aug-2022
Date of Web Publication29-Sep-2022

Correspondence Address:
Dr. Syed M Danish Qaseem
Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mgmj.mgmj_89_22

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  Abstract 

Purpose: To study the imaging and clinical perspectives of a recent epidemic of rhinocerebral mucormycosis during the COVID-19 (coronavirus disease) pandemic in India. Materials and Methods: This retrospective study included clinical and imaging data of 24 diagnosed cases of acute rhinocerebral mucormycosis who were presented to our hospital in May 2021. The clinical profile and imaging data of the patients were documented. Results: 18 patients (75.0%) had moderate to severe COVID-19 illness with a history of oral or intravenous corticosteroid intake. 19 patients (79.2%) had presented with hyperglycemia at the time of admission. Nasal discharges with or without black crusts and facial swelling (79.2%) were the most commonly reported complaints, followed by headaches or facial pain (62.5%). All cases demonstrated the involvement of one or more paranasal sinuses in imaging, with predominantly unilateral involvement. Extra sinusoidal involvement was commonly seen, with abnormalities seen in retromaxillary and masticator space, orbit, face, oral cavity, pterygopalatine fossa, and deep spaces of the neck, cavernous sinus, and brain. Conclusion: An upsurge of mucormycosis cases during the COVID-19 pandemic appears to be closely related to uncontrolled hyperglycemia and corticosteroid therapy. Computed tomography (CT) and magnetic resonance (MR) imaging are invaluable in establishing an early diagnosis, defining the extent of disease, and helping in immediate surgical planning.

Keywords: COVID-19, corticosteroid, hyperglycemia, imaging, rhinocerebral mucormycosis


How to cite this article:
Qaseem SM, Monis M, Ibbrahim A, Khalid M. Imaging and clinical perspectives of rhino-orbito-cerebral mucormycosis: An epidemic born out of a pandemic. MGM J Med Sci 2022;9:296-302

How to cite this URL:
Qaseem SM, Monis M, Ibbrahim A, Khalid M. Imaging and clinical perspectives of rhino-orbito-cerebral mucormycosis: An epidemic born out of a pandemic. MGM J Med Sci [serial online] 2022 [cited 2022 Dec 6];9:296-302. Available from: http://www.mgmjms.com/text.asp?2022/9/3/296/357492




  Introduction Top


Rhinocerebral mucormycosis is a rare life-threatening infection caused by a class of saprophytic fungi known as Zygomycetes. Rhizopus, Absidia, and Mucor are the different genera included in the class Zygomycetes.[1] These fungi are present throughout the environment, particularly in soil and in decaying organic matter.[2]

The term zygomycosis is used to describe any invasive fungal infection caused by zygomycetes and is frequently used interchangeably with the term mucormycosis.[3] The disease is caused by the inhalation of the fungal spores present in the environment. There is a strong predilection for patients with poorly controlled diabetes and immunosuppression.

Early clinical symptoms are non-specific and include fever, sinusitis, headache, and unilateral facial swelling. The more typical features which appear later include black nasal or palatal eschars and decreased vision. A necrotic ulcer with a black eschar in the palate is the first and most common external sign.[4] The disease is rapidly progressive leading to cerebritis and cranial nerve palsies. Mucormycosis is frequently a life-threatening infection. A review of 929 published cases of mucormycosis found an overall mortality rate of 54%.[5] Early imaging and prompt and aggressive treatment is the mainstay of management.

In May 2021, when India was already battling an overwhelming second wave of Coronavirus disease 2019 (COVID-19) pandemic, there was a concomitant rise in the number of cases of rhino-orbito-cerebral mucormycosis, which is otherwise a disease of rare occurrence. The study aims to study the imaging and clinical perspectives of this recent epidemic of rhinocerebral mucormycosis during the COVID-19 pandemic in India.


  Materials and methods Top


We retrospectively evaluated the clinical and imaging data of 24 diagnosed cases of patients with acute rhinocerebral mucormycosis who had presented to our hospital in May 2021. The study was conducted after obtaining due approval from the institutional ethics committee. Informed consent was also obtained from all the patients undergoing the study. No identifying patient details are contained within this manuscript.

The clinical history and symptomatology of the patients were documented. The course and duration of a preceding or ongoing COVID-19 illness were recorded. A positive real-time reverse transcription–polymerase chain reaction test (RT-PCR test) or HRCT chest imaging features typical of COVID-19 infection (CO-RADS 5 category) was taken as evidence for the COVID-19 illness. History of associated illnesses particularly diabetes mellitus and immunosuppressive conditions were also taken.

The extent of the disease was evaluated based on computed tomography (CT) and magnetic resonance (MR) CT and MRI findings. All 24 patients had undergone non-contrast CT imaging followed by MRI. Contrast-enhanced MRI examination was done in 20 patients (No intravenous contrast was given in 4 patients due to deranged renal profile). CT scan had been performed on 128 Slice GE REVOLUTION CT scanner or 16 Slice SIEMENS CT scanner using routine PNS protocol. MR Imaging had been performed on 1.5T MAGNETOM AVANTO, SIEMENS MR Scanner. The appearance and enhancement of the nasal turbinates and sinus were recorded. Involvement of extra sinus structures like retroantral and masticator space, orbit, face, pterygopalatine fossa, and brain was noted. Involvement of vascular structures including cavernous sinuses and ICA was also looked for. All images were reviewed by two independent radiologists with 30 and 15 years of experience. Fungal cultures had been obtained in all the cases for the confirmation of diagnosis.


  Results Top


Demographic and clinical data

The study group included 24 patients (19 males and 5 females). The age group of patients ranged from 18 to 78 years, with the majority above 40 years (71%).

20 patients (87.5%) had a prior or ongoing COVID-19 illness, diagnosed either based on a positive RT-PCR test or HRCT chest imaging features typical of COVID-19 infection. 18 patients (75.0%) had moderate to severe COVID-19 illness. and 2 patients (8.3%) had only mild COVID-19 illness.

Those with a history of moderate to severe COVID-19 illness (18 patients, 75.0%) had also received a course of oral or intravenous corticosteroids. 19 patients (79.2%) of rhinocerebral mucormycosis had presented with significantly elevated blood sugar levels (hyperglycemia) at the time of admission.

Nasal discharge with or without black crusts (19 patients, 79.2%) and facial swelling (19 patients, 79.2%) were the most commonly reported complaints followed by headache or facial pain (15 patients, 62.5%). Mild to moderate fever was seen in 14 patients (58.3%). 12 patients (50%) had presented with decreased vision. Altered sensorium was seen in 6 patients (25%). Epistaxis was seen in 4 patients (16.7%). On clinical examination, 22 patients (91.6%) had evidence of necrotic ulcer on either of these structures- turbinates, nasal septum, or palate- with visualization of necrotic debris or black crusts in the nasal cavity. 7 patients (29.2%) had cranial nerve palsy(s).

Imaging findings

All cases demonstrated the involvement of one or more paranasal sinuses on CT and MRI. Maxillary sinus was the most commonly involved sinus (87.5%), followed by ethmoidal sinuses (79.2%). Multiple sinuses were commonly involved. Unilateral involvement was more common than bilateral involvement. Imaging features were in the form of mucoperiosteal thickening, air-fluid levels, or complete opacification of sinuses. The patterns of paranasal sinus involvement have been described in [Table 1].
Table 1: Imaging features of paranasal sinus involvement on CT and MRI in patients with rhino-orbital mucormycosis (n = 24)

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Nasal involvement was seen in the form of hypertrophy or necrosis of turbinates and fluid collections in the nasal cavity and meati, predominantly with unilateral involvement. 8 cases (33.3%) demonstrated areas of hypo- or non-enhancement involving turbinates (black turbinate sign), septum, or nasal mucosa along the floor of the nasal cavity [Figure 1]. Septal perforation was visible on CT in 1 case.
Figure 1: Sinonasal and orbital changes in mucormycosis

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Extra sinus spread was seen in all the cases except one presenting with sinonasal involvement alone. Extrasinus involvement was seen in retromaxillary and masticator space, orbit, face, oral cavity, pterygopalatine fossa, and deep spaces of the neck, cavernous sinus, and brain [Table 2]. Extrasinus involvement in the spaces of the face and neck was seen in 17 patients (70.8%) in the form of soft tissue edema and fat stranding. Two cases with the extensive disease showed involvement of ipsilateral parapharyngeal and carotid space [Figure 2]. Orbital involvement was seen in 10 patients (41.7%) in the form of inflammatory fat standing in the intra- and extraconal spaces, recti muscle edema, proptosis, and optic nerve involvement [Figure 1]. Severe proptosis with stretching of the optic nerve and posterior coning (deformity) of the ocular globe, the so-called guitar pick sign [Figure 3], was associated with acutely raised intraocular pressures, and was seen in 5 cases (20.8%). The formation of the intra-orbital subperiosteal abscess was seen in 5 cases (20.8%). The medial rectus was the most commonly involved muscle in the orbit. On MRI, optic nerve involvement was seen in 4 cases (16.7%). Erosion of the hard palate with extension into the oral cavity was seen in 2 cases (8.3%). Bony involvement was seen in the form of bone erosion or rarefaction and was seen in 7 cases (29.1%).
Table 2: Sites of extrasinusoidal involvement in patients with rhino-orbital mucormycosis in order of frequency (n = 24)

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Figure 2: Extra- sinusoidal involvement in mucormycosis

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Figure 3: Guitar-pick sign in mucormycosis

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Intracranial involvement was seen in 6 cases (25.0%). A focal area of dural thickening with features of cerebritis was seen in 3 cases (12.5%). No case of the frank intracerebral abscess was seen. Brain infarcts were seen in 4 patients (16.7%). Dural-based collections were seen in 2 cases (8.3%) [Figure 4]. Vascular complications were in the form of thrombosis of cavernous sinus thrombosis or internal carotid artery. Cavernous sinus involvement was seen in 3 cases (12.5%) and ICA involvement in 2 cases (8.3%) [Figure 5].
Figure 4: Intracranial complications in mucormycosis

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Figure 5: Vascular complication in mucormycosis

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  Discussion Top


Rhinocerebral mucormycosis is a rare life-threatening infection caused by a class of saprophytic fungi known as zygomycetes.

The term zygomycosis is used to describe any invasive fungal infection due to zygomycetes and is frequently used interchangeably with the term mucormycosis.

Distinct patterns of involvement include rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated forms. Rhinocerebral involvement is the most common form and the disease is mainly acquired by inhalation of the fungal spores present in the environment. There is a strong predilection for patients with poorly controlled diabetes and immunosuppression. An important feature of the disease is its angio-invasive nature and its tendency to invade blood vessels causing thrombosis and necrosis of infected tissues.[3] The disease is rapidly progressive and is frequently a life-threatening infection. Early imaging to know the complete extent of disease followed by wide surgical resection of necrotic areas and systemic antifungal therapy (amphotericin based) remains the mainstay of management.[6]

We found that the disease was more commonly seen in adult males. Nearly 87% of patients had prior or ongoing COVID-19 illness. Most of them had suffered from moderate to severe infection and had received a course of oral or intravenous corticosteroids. 79.2% of the cases also had hyperglycemia at the time of presentation. This is consistent with the previous studies that have found that the presence of diabetes is associated with increased chances of acquiring rhino-orbital mucormycosis.[7] Corticosteroids are known to have inhibitory effects on a broad range of immune responses.[8] as well as induce hyperglycemia. The temporal correlation between rampant use of corticosteroids in the treatment of patients suffering from COVID–19 pneumonia and a surge in the number of patients with features of mucormycosis points toward a possible association.

We found that sinonasal changes in mucormycosis were seen in the form of opacification of one or more paranasal sinuses predominantly with unilateral involvement and maxillary sinus being the most commonly involved sinus. Herrera et al. have reported similar sinonasal changes on imaging.[9] T2 iso to a hypointense lesion on MRI is characteristic and is related to the presence of fungal elements. We found heterogeneous enhancement with non-enhancing sinus mucosa in 25% of the cases. This pattern of involvement has been reported by Horger et al, in which a case of rhinocerebral mucormycosis was described with areas of nonenhancement.[10] A similar change in the nasal cavity in the form of a black turbinate sign has been reported as an early MR imaging finding of nasal mucormycosis.[11]

Extra sinus spread was seen in nearly all the cases with retromaxillary, masticator space, and orbits being the common sites. Mnif et al. in their study found aggressive inflammatory changes in sinuses and orbits in patients with mucormycosis and suggested that the presence of orbital cellulitis and sinusitis in the background of immunosuppression should prompt the diagnosis of mucormycosis.[12] The posterior coning (deformity) of the ocular globe, the so-called guitar pick sign, seen in 21% of our cases is non-specific and is seen in various acute intra-orbital pathologies. The sign is associated with acutely raised intra-orbital pressures.[13] Optic neuritis was seen in 17% of our cases. Bone erosions or rarefaction were seen in only 29% of our cases despite the aggressiveness of the disease. This is attributed to the angioinvasive nature of the disease where the spread occurs along vascular pathways leading to extrasinusoidal involvement with intact bones. Bone involvement and skull base osteomyelitis are generally seen only late in the disease.[14] Thus, in a proper clinical setting, features of early extrasinusoidal involvement (particularly in absence of bone erosions) are a good imaging indicator of mucormycosis.

Intracranial involvement was seen in nearly a quarter of our cases. Spread to the brain may occur via orbital apex, orbital vessels, or cribriform plate.[15] Mucormycosis invades the walls of blood vessels leading to vascular thrombosis and infarctions.[16] Other forms of involvement include cerebritis, meningitis, cavernous sinus involvement, and extradural or intracerebral abscess formation.

The present study has certain limitations, the main weakness being a sample size not large enough to determine the statistical significance of the results. However, this is a single-institutional study representing an initial group of patients with the diagnosis of rhinocerebral mucormycosis, an emerging epidemic during the COVID-19 pandemic. The study may serve as a good reference for a quick response for other places. Nevertheless, one should be cautious against over-interpretations based on this study alone and future studies should be conducted with a larger number of patients for a better understanding of the disease. Secondly, no comparison was done between patients with mucormycosis who had past or ongoing COVID-19 illness and those without COVID-19 infection. Thirdly, although we found a possible association between rampant use of corticosteroids in the COVID-19 pandemic and increased incidence of mucormycosis, the sample data is small to establish a definite relationship. Also, the comparison could not be made with the control group of patients with mucormycosis who had not received corticosteroid therapy. We did not evaluate the severity of the mucormycosis disease about the blood sugar levels or corticosteroid doses administered due to limited data being available in the retrospective approach. We could not evaluate the outcome of the disease, many of the patients were still under treatment.


  Conclusion Top


Mucormycosis is a life-threatening infection and requires immediate and robust management. CT and MR imaging are invaluable in establishing an early diagnosis while awaiting confirmation by the culture which takes weeks. In an appropriate clinical background, imaging features of early extrasinusoidal spread particularly in absence of bone erosion is a good indicator of angioinvasive mucormycosis. CT and MR imaging also helps in evaluating the actual extent of disease and its complications which is crucial for surgical planning. Follow-up imaging is required to decide the further course of management. The recent upsurge in mucormycosis cases during the COVID-19 pandemic appears to be closely related to uncontrolled hyperglycemia and corticosteroid therapy. Prompt identification and correction of hyperglycemia and prudent use of corticosteroid therapy in COVID-19 patients may help in checking this superadded infection in COVID-19 patients. The relationship between mucormycosis and COVID-19 may be evaluated in future studies as it may have significant clinical implications.

Ethical consideration

Approval/clearance for undertaking the proposed research study on “Imaging and Clinical Perspectives of Rhino-Orbito-Cerebral Mucormycosis: An Epidemic Born Out of a Pandemic” was obtained from the Institutional Ethics Committee, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh- 202002, Uttar Pradesh, India, vide their letter no. IECJNMC/467 dated 19.10.2021.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hibbett DS, Binder M, Bischoff JF, Blackwell M, Cannon PF, Eriksson OE, et al. A higher-level phylogenetic classification of the fungi. Mycol Res 2007;111:509-47.  Back to cited text no. 1
    
2.
Richardson M The ecology of the zygomycetes and its impact on environmental exposure. Clin Microbiol Infect 2009;15 Suppl 5:2-9.  Back to cited text no. 2
    
3.
Kontoyiannis DP, Lewis RE Invasive zygomycosis: Update on pathogenesis, clinical manifestations, and management. Infect Dis Clin North Am 2006;20:581-607.  Back to cited text no. 3
    
4.
Khanna JN, Natarajan S, Galinde J Rhinocerebral Mucormycosis – An emerging threat. J Oral Maxillofac Surg Med Pathol 2015;27:550-7.  Back to cited text no. 4
    
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Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis 2005;41:634-53.  Back to cited text no. 5
    
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Rogers TR Treatment of zygomycosis: Current and new options. J Antimicrob Chemother 2008;61 Suppl 1:i35-40.  Back to cited text no. 6
    
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Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, et al. A prospective multicenter study on mucormycosis in india: Epidemiology, diagnosis, and treatment. Med Mycol 2019;57:395-402.  Back to cited text no. 7
    
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McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers WH, Dhabhar FS, et al. The role of adrenocorticoids as modulators of immune function in health and disease: Neural, endocrine and immune interactions. Brain Res Brain Res Rev 1997;23:79-133.  Back to cited text no. 8
    
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Herrera DA, Dublin AB, Ormsby EL, Aminpour S, Howell LP Imaging findings of rhinocerebral mucormycosis. Skull Base 2009;19:117-25.  Back to cited text no. 9
    
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Horger M, Hebart H, Schimmel H, Vogel M, Brodoefel H, Oechsle K, et al. Disseminated mucormycosis in haematological patients: Ct and Mri findings with pathological correlation. Br J Radiol 2006;79:e88-95.  Back to cited text no. 10
    
11.
Safder S, Carpenter JS, Roberts TD, Bailey N The “black turbinate” sign: An early Mr imaging finding of nasal mucormycosis. Ajnr Am J Neuroradiol 2010;31:771-4.  Back to cited text no. 11
    
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Mnif N, Hmaied E, Oueslati S, Rajhi H, Hamza R, Marrakchi M, et al. [Imaging of rhinocerebral mucormycosis]. J Radiol 2005;86:1017-20.  Back to cited text no. 12
    
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Nguyen VD, Singh AK, Altmeyer WB, Tantiwongkosi B Demystifying orbital emergencies: A pictorial review. Radiographics 2017;37:947-62.  Back to cited text no. 13
    
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Chan LL, Singh S, Jones D, Diaz EM Jr, Ginsberg LE Imaging of mucormycosis skull base osteomyelitis. Ajnr Am J Neuroradiol 2000;21:828-31.  Back to cited text no. 14
    
15.
Sheman DD, Burkat CN, Lemke BN Orbital Anatomy and Its Clinical Applications. Philadelphia, PA: Lippincott-Raven; 1992.  Back to cited text no. 15
    
16.
Thajeb P, Thajeb T, Dai D Fatal strokes in patients with rhino-orbito-cerebral mucormycosis and associated vasculopathy. Scand J Infect Dis 2004;36:643-8.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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