JOURNAL OF EVIDENCE BASED MEDICINE AND HEALTHCARE

SEARCH ARTICLES

Year : 2021 Month : October Volume : 8 Issue : 40 Page : 3464-3469.

Study of Clinical Findings and Treatment Outcomes of Rhino-Orbital-Cerebral Mucormycosis at a Tertiary Care Center in Central India

Kavita Anand Dhabarde1, Pallavi Madhusudan Doble2, Nehali Sureshchandra Pant3, Nisha Vilas Rahul4

1, 2, 3, 4 Department of Ophthalmology, Government Medical College, Nagpur, Maharashtra, India.

CORRESPONDING AUTHOR

Dr. Pallavi Madhusudan Doble, C/o. Madhusudan Dolbe, Ward No. 16, Behind Bus-stop, Near APMC, Karanja (Ghadge), District Wardha-442203, Maharashtra, India.
Email : pallavidoble23@gmail.com

ABSTRACT

Background

Mucormycosis is a potentially lethal angioinvasive fungal infection. Increasing incidence of rhino-orbital-cerebral mucormycosis in setting of corona virus disease-19 (COVID-19) during second wave in India and elsewhere has become a matter of immediate concern. This study was done to assess the clinical findings and treatment outcomes of rhino-orbital-cerebral-mucormycosis presenting to a tertiary care center in central India.

 

Methods

This is a longitudinal study. We observed 38 COVID-19 associated mucormycosis cases. Their demographic data, clinical manifestations, underlying systemic conditions, microbiological and radiological reports, medical treatments and surgical interventions were recorded and analysed.

 

Results

Common ocular presenting features were ophthalmoplegia (68 %), proptosis (44 %), periorbital swelling (13 %), diminution of vision (37 %), central retinal arterial occlusion (2.5 %), optic atrophy (2.5 %). Visual acuity at 1 month after surgery was compared with that at presentation and was found unchanged in 27 patients, improved in 3 patients and deteriorated in 6 patients. Functional outcome was evaluated in terms of ocular movements, and it was found that ocular movements were same as presentation in 30 patients, improved in 3 patients and deteriorated in 3 patients at follow up one month after surgery. Radiological outcome was evaluated, and it was found that residual disease was present in 4 patients and absent in 32 patients. Mortality was found in 2 patients at 1 month follow-up period.

 

Conclusions

Early diagnosis, blood sugar levels control, urgent systemic antifungal therapy and sinus debridement surgery are lifesaving in cases of COVID-19 associated mucormycosis.

 

Keywords

Mucormycosis, COVID-19, Diabetes Mellitus, Ophthalmoplegia, Orbital Apex Syndrome, Orbital Cellulitis, Proptosis

BACKGROUND

Mucormycosis is an acute, fulminating, often fatal fungal infection caused by fungi of family Mucoraceae and is seen in diabetic and immunocompromised patients.1,2 Mucormycosis is categorized as rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, or disseminated, depending upon organ involvement; the most common form is rhino-orbital-cerebral. The incidence of mucormycosis has rapidly increased in the setting of COVID 19 and has become the matter of immediate concern. The fungal hyphae of Mucoraceae family are angioinvasive, invades blood vessels, causes necrotizing vasculitis and thrombosis resulting in extensive tissue infarcts and necrosis.3 The disease usually starts in the nose and sinuses after inhalation of fungal spores. It proliferates and spreads to the paranasal sinuses (sino-nasal mucormycosis), and then to the orbit by direct extension or through hematogenous route (sino-orbital mucormycosis). It can also spread to the brain (sino-orbital-cerebral mucormycosis). Although primary site of inoculation is nose and paranasal sinuses, the patients usually initially present to the ophthalmologists with ocular signs and symptoms.4 Diabetes mellitus, use of corticosteroids, broad spectrum antibiotics and other immunosuppressive agents for treatment of moderate to severe cases of COVID-19, excessive stress of infection, long term O2 therapy, inability to maintain nasal and oral hygiene during the course of treatment are some of the risk factors suspected to contribute to COVID associated rhino-orbital-cerebral mucormycosis.5,6,7

Systemic amphotericin B with surgical debridement of sinuses and control of systemic conditions remains the mainstay of treatment.8,9,10,11 In this study, we have observed and evaluated clinical characteristics and treatment outcomes of 38 cases of COVID associated rhino-orbital-cerebral mucormycosis.

 

Objectives

Primary Objective

To study clinical findings and treatment outcomes of rhino-orbital-cerebral mucormycosis.

 

Secondary Objective

To compare treatment outcomes of rhino-orbital-mucormycosis with computed tomography (CT) severity score.

METHODS

A longitudinal study of thirty-eight cases of COVID-19 associated rhino-orbital-cerebral mucormycosis presenting to tertiary care center in central India from 1st May 2021 to 31st May 2021 was performed. Their clinical presentations, laboratory investigations and treatment received were analyzed. Comprehensive workup at presentation included detailed history regarding COVID treatment, comprehensive ocular examination (visual acuity, anterior segment evaluation, posterior segment evaluation, ocular movements), otorhinolaryngological and neurological examination to assess the severity of the disease. Depending upon CT severity score (CTSS) during the course of COVID 19 disease, patients were categorized into mild (CTSS - < 8), moderate (CTSS - 8 - 15), and severe cases (CTSS >15).

Diagnosis of mucormycosis was made on the basis of CT scan/magnetic resonance imaging (MRI) of paranasal sinuses, orbit and brain [Figure 2(d)], demonstration of fungal hyphae on KOH preparations, lactophenol cotton blue staining and PAS staining [Figure 2 (a, b, c)] of specimens obtained from nasal cavity and paranasal sinuses. Mucormycosis was defined by clinico-radiological suspicion with visualisation of broad branched aseptate fungal hyphae on KOH mount direct microscopy and histopathology specimen by fungal stains. All patients received intravenous amphotericin B as soon as diagnosis of mucormycosis was done in a dose of 1 mg/kg/day. Renal functions were monitored. Diabetes was controlled with insulin therapy. Trans-nasal endoscopic radical debridement of involved sinuses was done in all patients and specimen was obtained and sent for histopathology and culture. Endoscopic debridement of sinuses along with orbital decompression and orbital exenteration was done depending upon the involvement of sinuses and orbit in radiological reports.

Patients were followed up for a period of 1 month. Treatment outcome was measured in terms of visual, functional, radiological outcome and mortality at 1 month post-operatively. Visual outcome was evaluated in terms of unchanged, improved or deteriorated visual acuity as compared to that at presentation. Functional outcome was evaluated in terms of unchanged, improved or deteriorated ocular movements as compared to that at presentation. Radiological outcome was evaluated in terms of presence or absence of residual disease.

 

Statistical Analysis

Statistical analysis was done using chi-square test to assess association between treatment outcome of COVID-19 associated mucormycosis and severity of COVID-19 disease based on CT severity score. Visual outcome, functional outcome and radiological outcomes were compared with CT severity scores of the patients (during the course of COVID-19 disease).

RESULTS

There were 38 patients in total which included 28 male and 10 females with mean age of 49.3 years (range 21 to 73 years). Lag time between the onset of symptoms and presentation was 2 to 15 days. 27 patients (71 %) had type 2 diabetes mellitus of which 10 were recently diagnosed with diabetes mellitus (37 %) and 17 patients were known cases of diabetes with duration of diabetes ranging from 3 years to 10 years, out of which 3 patients were on irregular medications. 15 patients (40 %) were known cases of systemic hypertension and were receiving anti-hypertensive treatment. 1 patient was human immunodeficiency virus (HIV) positive receiving anti-retroviral therapy, 1 patient was HBsAg positive. Of the 38 patients, 30 patients (78.9 %) were given systemic steroid as a part of treatment for COVID 19 disease. Out of these 30 patients, 23 patients (77 %) received injectable intra-venous methylprednisolone for a period ranging from 5 to 15 days, 7 patients (23 %) received oral prednisolone. Oxygen therapy was given to 16 patients (42 %) during hospital stay as a part of COVID-19 treatment. Injection remdesivir was given to 16 patients (42 %) as a part of COVID-19 management. Based on CT severity score, 16 mild cases, 15 moderate cases and 7 severe cases of COVID 19 infection were noted. Common ocular presenting features were ophthalmoplegia 26 cases (68 %), proptosis 17 cases (44 %), orbital cellulitis 5 cases (13 %), diminution of vision 14 cases (37 %), central retinal arterial occlusion 1 case (2.5 %), optic atrophy 1 case (2.5 %) [Table 1]. Photographs of clinical presentations of two patients, one with ophthalmoplegia and other with orbital cellulitis are shown in figure 1.