Indian Journal of Clinical and Experimental Ophthalmology

Print ISSN: 2395-1443

Online ISSN: 2395-1451

CODEN : IJCEKF

Indian Journal of Clinical and Experimental Ophthalmology (IJCEO) is open access, a peer-reviewed medical journal, published quarterly, online, and in print, by the Innovative Education and Scientific Research Foundation (IESRF) since 2015. To fulfill our aim of rapid dissemination of knowledge, we publish articles ‘Ahead of Print’ on acceptance. In addition, the journal allows free access (Open Access) of its content, which is likely to attract more readers and citations of articles more...


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Sharma, Rajvanshi, Khurana, and Arora: Rhinoorbital mucormycosis in COVID-19 pandemic: presentation and course of disease: An observational study


Introduction

Second wave of COVID-19 pandemic in India has affected a large number of people so the associated bacterial and fungal infection cases are also high.1 Cases with symptoms and signs suggestive of rhinoorbital mucormycosis suddenly increased that was previously seldomly reported. Sen et al studied 6 patients with COVID -19 who developed rhino-orbital mucormycosis.2 Recently Sarcar et al. reported 10 cases of clinically diagnosed orbital mucormycosis with concurrent COVID-19 illness.3

The term ‘Mucormycosis’ denote the acute or subacute rapidly progressing infection caused by the angioinvasive fungi in the order of ‘Mucorales.4, 5 The ubiquitous fungi often thrive on decaying plant debris and soil. The most common genera causing human infection include Rhizopus, Lichtheimia, Apophysomyses, Mucor and Rhizomucor. The most common clinical presentation is Rhinoorbital cerebral mucormycosis. Rhinoorbital cerebral mucormycosis almost always occurs in immunocompromised individuals, including uncontrolled diabetes mellitus with acidosis or keto acidosis, steroid therapy, organ transplant recipients, chemotherapy, hematologic dyscrasias, retroviral disease and malnourishment.6

The rapidly growing saprophytic fungi release a large number of spores in the environment. These sporangiospores are commonly inhaled by the host, in hosts with normal immune status, the ciliary system directs the spores towards the pharynx, thereby eliminating them via the GI system. The spores might also get colonized in the oral mucosa, nose, throat and paranasal sinuses. Mucorales do not cause disease in host with normal immune system where phagocytosis could effectively contain the invasion and infection. When phagocytosis is impaired due to immune deficiency, the germination of spores into hyphae with resultant angioinvasion is initiated. The initial site of infection in Rhinoorbital cerebral mucormycosis is the nasal turbinates. An acute episode of sinusitis progresses into pan sinus involvement within a few days with contiguous spread to orbit, palate and brain resulting in severe tissue ischemia and necrosis due to the angioinvasive nature of the fungi. This mechanism is facilitated by high amount of Iron and Glucose in serum.7, 8, 9, 10

The presenting symptoms of rhino orbital cerebral mucormycosis include headache, facial pain, eye pain, facial numbness, diplopia with varying degrees of ophthalmoplegia, ptosis, proptosis, vision loss with and without papilloedema, nasal discharge, epistaxis and loosening of teeth. Black discoloration of skin and mucosa along with ulceration and discharge from nose and palatal mucosa are characteristic of mucormycosis.11 CT Scan can demonstrate the nature and extent of soft tissue abnormalities in the sinuses, orbits and brain. Mucosal thickening of sinuses along with opacification is often noted. MRI is more helpful over the CT in clearly delineating vascular invasion, intracranial spread and also in the assessment of early perineural spread. A T2 weighted MRI with fat saturation sequences or short T1 inversion recovery is ideal. Definite diagnosis is arrived at by tissue biopsy.6

Rhino orbital mucormycosis is an medical and surgical emergency. Amphotericin B has become the gold standard for the systemic treatment. Liposomal amphotericin B is the first choice of treatment as it crosses the blood brain barrier more effectively. Surgical debridement of local necrotic tissue (paranasal sinuses and orbital exentration) are done to reduce fungal load.6

As the patients reported in our study were mostly from rural are, the awareness about the disease and data availability was limited. Therefore our study largely represents the presentation and course of disease among rural population.

Materials and Methods

We recruited a cluster of 17 patients with signs or symptoms suggestive of rhino-orbital mucormycosis who reported to Ophthalmology and Otorhinolaryngology departments of our Government district hospital after obtaining consent from patients. Their demographic profile was noted. Clinical examination was done. Spo2, blood sugar, treatment history with O2 and steroids was recorded. CT-PNS, orbit and head were done. All the patients were referred to tertiary level centres. Patients were followed for their management and outcome. At tertiary level MRI of paranasal sinuses, orbits and brain (plain and contrast) were obtained. Endoscopic tissue biopsy was done for final diagnosis. Endoscopic sinus debridement or orbital exentration were done as per the requirement. Intravenous liposomal amphotericin B was used for the medical management.

Results

Case no. 1,2,3,4,5,10,11,12 and 17 total 9 developed symptoms during their treatment for COVID in hospital. All these patients were on intravenous steroids and O2. 7 out of these 9 patients had spo2 below 90%. All these 7 patients died within 7 days from the onset of symptoms of mucormycosis. One patient out of these 9 admitted patients had spo2 97%, had orbital exentration done and was on Amphotericin B but expired during 3rd week of treatment. Remaining one patient had orbital exentration and was on Amphotericin B till the last follow up.

Table 1

Case no.

Ag/ sex

R/U

COVID RT-PCR

COVID

Related symptoms, Spo2

Treatment with inhalational o2

Blood sugar (mg%)

Orbital symptoms and signs

Radiologic findings

Treatment received for Mucormycosis

Outcome

1

45/M

R

+ve

ICU,

Spo2 75%

+

240

RE/ orbital cellulitis

MRI –Rt. Orbital cellulitis and Optic Neuritis

Cavernous sinus thrombosis

Amph. B for 2 days

Death

2

80/F

U

+ve

ICU,

Spo2 70%

+

320

RE/Orbital cellulitis

MRI-Rt. Orbital cellulitis and Optic neuritis

Amph. B for 2 days

Death

3

75/F

R

-ve

Fever,

dyspnoea

Spo2 80%

+

285

RE/ Orbital cellulitis

NA

Amph.B

for 3 days

Death

4

45/F

U

+ve

Fever,

dyspnoea

Spo2 85%

+

280

RE/Orbital cellulitis

MRI –Rt Orbital cellulitis

RE /Orb.Ext. followed by Amph. B for 1 day

Death

5

70/ M

R

+

Fever,

Dyspnoea

Spo2 85%

+

310

RE/ Orbital cellulitis

MRI-Rt Orbital cellulitis with Optic neuritis

RE/ orb. Ext.

Death

6

45/M

R

-ve

Fever

Spo2 95%

_

500

RE/ Orbital cellulitis PL _ve

MRI – Rt. Orbital Cellulitis

Received Amphotericin B for 2 days

Death

7

65/M

R

-ve

Fever

Spo2 95%

_

500

LE/ Orbital cellulitis

MRI- Lt. Orbital cellulitis, Cavernous sinus Thrombosis

Nil

Death

8

54/F

R

_ve

Fever, breathlessness,anosmia

_

500

LE/ Orbital Cellulitis

MRI-Lt. Orbital cellulitis

On Amph. B

Impro-ved

9

70/F

R

_ve

Fever, dyspnea, Spo2 75%

-

380

LE/ C/O pain at presentation, paraesthesia ovecr Lt. heek progressed to Lt. 6th nerve palsy

MRI-+ve

Nil

Death

10

70/F

R

+ve

Fever,

Spo2 90%

+

340

LE/Pain, paresth-esia Lt. Cheek

CT PNS-Pansinusitis

Sinus debridement followed by Amph. B

Impro-ved

11

60/M

U

+ve

Fever

+

199

LE/Proptosis and chemosis

CT PNS-Pansinusitis,

MRI- +ve

LE/ Orb. Ext. followed by Amph. B

Death

12

50/M

R

+ve

Admitted in ICU Spo2 54%

+

360

LE/ Eyelid swelling

Progressed to orbital cellulitis

NA

Received Amphotericin B for 2 days

Death

13

50/M

R

NA,__-ve after death

NIL

_

240

RE/ Orbital cellulitis

MRI - +ve

Nil

Death

14

61/F

R

+ve

Fever

+

70

RE/ Sudden loss of vision, PL_ve

CT PNS- Maxillary sinusitis

Oral Fluconazole

Unchanged

15

65/F

R

_ve

Fever

CRP- 53

Spo2 95%

+

400

B/L Orbital cellulitis with facial swelling and eschar over lt. cheek

MRI- +ve

Amph. B

For 1 day

Death

16

34/M

U

NA

Fever, vomiting

_

123

B/L conjunctival congestion

CT PNS –Sphenoidal sinusitis

On Amph. B

Improved

17

62/M

R

+ve

Fever

+

320

LE/ Orbital cellulitis

MRI- Rhino orbital mucormycosis

LE/ Orb. Ext. followed by Amph. B

Improved

[i] Ag-Age, M-Male, F-Female, R- Rural, U- urban, MRI- +ve=MRI- +ve for Rhinoorbital mucormycosis, RE-Righteye, LE-Left eye, Orb. Ext.-Orbital Exentration, Amph.B- Liposomal Amphotericin B

8 patients presented in OPD, they did not have history of treatment with O2. 6 out of these 8 patients were on oral steroids. 5 out of these 8 OPD patients had orbital cellulitis at presentation. 4 of these 5 died within 1 week while on treatment for mucormycosis. One out of these 8 patients had acute presentation with right orbital cellulitis and nasal bleeding, blood sugar was 240mg/dl and spo2 was 95%. MRI was positive for rhinoorbital mucormycosis. He had no history of any type of illness or treatment in the past. He died before having any treatment for mucormycosis. Duration of his onset of symptoms and death was only 4 days. RT-PCR done after death was negative. Another one patient was 34 yr male with vomiting, diarrhea and bilateral conjunctival congestion at presentation. CT-PNS showed sphenoidal sinusitis. His blood sugar level was 123 mg/dl and spo2 was 97%. He was immediately referred; was diagnosed to have rhino orbital mucormycosis and was managed accordingly with Intravenous Amphotericin B. This patient survived and improved with timely intervention.

Observations

Total 17 patients were enrolled in our study. 13 (76.4%) patients were from rural area and remaining 4 (23.5%) were from urban area.

Figure 1
https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/1f7ecdba-3515-4d79-803a-53bef87250cf/image/2332812b-9e58-4b4a-bb5e-ab5f267adf69-uimage.png

Mean age of presentation was 58.88 years

9 /17 (52.9%) of patients were already admitted in COVID wards and developed mucormycosis during treatment of COVID. Other 8/17 (47.05%) cases, reported in OPD and never had treatment with inhalational O2. Therefore role of inhalational O2 in causing rhinoorbital mucormycosis remains doubtful in our study.

6 patients had RT-PCR report negative but developed symptoms and signs of Rhino orbital mucormycosis in due course. 2 patients did not get RT- PCR test done. It shows that patients can develop associated complications of COVID 19 even if they are reported negative in RT- PCR.

Figure 2
https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/1f7ecdba-3515-4d79-803a-53bef87250cf/image/fe5279dc-9490-406b-8992-87485aef8955-uimage.png

12 enrolled patients (12/17 i.e 70.5%) died and 5 patients survived till the last follow up in our study. This denotes a high death rate in mucormycosis patients. Out of 12 patients who died 10 (90.9%) had orbital cellulitis at presentation. Out of these 10 cases 2 cases presented in OPD; were immediately refered to higher centre but died before receiving any treatment for mucormycosis. 2 cases out of these 10 had orbital exentration followed by liposomal amphotericin B, 5 had received amphotericin B for 2-3 days and remaining 1 died at home within 7 days without receiving any treatment. This shows poor prognosis of patients once orbital cellulitis sets in.

Discussion

15 (82.3%) cases had high blood sugar at presentation. Our finding correlates with the fact that mucormycosis infection is facilitated by high blood sugar.7, 8, 9

Our finding of high mortality among orbital cellulitis patients is similar to that of study done by Asim V et al.12 Who described that fungal orbital cellulitis has high mortality despite aggressive treatment.

4 patients who were alive and had improved after referral to higher centre had only initial symptoms and signs suggestive of Rhino orbital mucormycosis at presentation; were immediately referrd and were treated accordingly. This underlies the importance of early diagnosis and treatment.

The early flag sign and symptoms reported in our study were:

  1. Paresthesia over cheek and ipsilateral eye pain

  2. Bilateral conjunctival congestion

  3. Eye lid swelling

  4. Headache

Any patient with these symptoms must have CT PNS done ; if CT PNS shows mucosal thickening in any of the paranasal sinuses immediate further management must be done.

Conclusion

Rhinoorbital mucormycosis showed aute onset and rapid progression in all the patients. High index of suspicion is necessary for early diagnosis and treatment to avoid high mortality and morbidity as it showed acute onset and rapid progression even in patients with mild symptoms of COVID. Prevention of COVID infection especially in patients with Diabetes remains the only way to avoid associated mortality, morbidity, social and economic upheavals. Wide social awareness about the preventive measures, early symptoms and available management is of paramount importance especially in rural and remote areas of India.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgement

We would like to acknowledge support of Dr. Anju Kochar, SP Medical College and Hospital, Bikaner for providing follow up details of our patients.

References

1 

S Mehta A Pandey Rhino orbital mucormycosis associated with COVID 19Cureus2020129e10726

2 

M Sen S Lahane TP Lahane R Parekh SG Honavar Mucor in a Viral Land: A Tale of Two PathogensIndian J Ophthalmol202169224452

3 

S Sarkar T Gokhale SS Choudhury AK Deb COVID-19 and orbital mucormycosisIndian J Ophthalmol202169410024

4 

WC Harrill MG Stewart AG Lee Chronic rhinocerebral mucormycosisLaryngoscope19961061012927

5 

ZK Xia WL Wang RY Yang Slowly progressive cutaneous, rhinofacial and pulmonary mucormycosis caused by Mucor irregularis in an immunocompetent womanClin Infect Dis20135679935

6 

AK Kumar V Gupta Rhino orbital cerebral MucormycosisStat pearls. Treasure Island (FL)2021https://www.ncbi.nlm.nih.gov/books/NBK557429/

7 

AS Ibrahim DP Kontoyiannis Update on mucormycosis pathogenesisCurr Opin Infect Dis201326650815

8 

A Mallis SN Mastronikolis SS Naxakis AT Papadas Rhinocerebral mucormycosis: an updateEur Rev Med Pharmacol Sci2010141198792

9 

MN Gamaletsou NV Sipas E Roilides TJ Walsh Rhinoorbital cerebral mucormycosisCurr Infect Dis Rep20121442334

10 

RP Maurya Post COVID-19 Mucormycosis: What is role of iron and iron chelating agents?Indian J Clin Exper Ophthalmol2020644789

11 

R Kulkarni UK Misra U K, C Meshram D Kochar M Modi VY Vishnu Epidemic of mucormycosis in COVID 19 pandemicAnn Indian Acad Neurol202110.4103/aian.AIAN_421_21

12 

AV Farooq RM Patel AY Lin P Setabutr J Sartori VK Aakalu Fungal Orbital Cellulitis: Presenting Features, Management and Outcomes at a Referral CenterOrbit2015343152910.3109/01676830.2015.1014512



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Article type

Original Article


Article page

624-629


Authors Details

Maya Sharma*, Seema Rajvanshi, Sunita Khurana, Rajkumar Arora


Article History

Received : 16-06-2021

Accepted : 06-07-2021

Available online : 03-01-2022


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