Covid-Associated Mucormycosis in a Case of Wegener’s Granulomatosis: A Management Challenge

Abstract

A Gentleman in his 40s presented to us with left-sided hemifacial pain and nasal discharge for the last three days. He has been on immunosuppressive therapy for Wegener’s Granulomatosis for over five years. Crusting was seen in the Left middle meatus upon clinical examination. Based on the post-covid status, steroid therapy, KOH mount, and radiologic imaging, a provisional diagnosis of Sinonasal mucormycosis was considered. He was posted for emergency debridement followed by Liposomal Amphotericin B and steroid therapy. Surgical histopathological specimens were suggestive of Mucormycosis. Limited sinonasal disease with no intracranial, orbital, or palatal involvement was seen in a background of Wegener’s Granulomatosis, Covid, and immunosuppressive therapy. Steroids are condemned as a predisposing factor to mucormycosis. Still, the combination of Liposomal Amphotericin B and steroids was used, opening new avenues for managing mucormycosis in patients with vasculitis. The patient is well nine months post-surgery with no signs of disease relapse.

Introduction

Wegener’s Granulomatosis, now known as Granulomatosis with polyangiitis, is a necrotizing granulomatous inflammation with necrotizing vasculitis affecting small to medium-sized vessels. It is a relapsing–remitting autoimmune ANCA (antineutrophil cytoplasmic autoantibodies–associated vasculitis, primarily involving the upper and lower respiratory tract and kidneys [1]. Diagnosis requires a high index of suspicion and elevated levels of PR3-ANCA and tissue diagnosis [2].

The second wave of covid pandemic saw a massive uprise in cases of invasive fungal rhinosinusitis. Over 250 patients with Mucormycosis presented to our institute with varied presentations. Mucormycosis can occur in various forms, such as sinonasal, orbital, cerebral, pulmonary, and cutaneous mucormycosis [3]. The sinonasal tract is a standard entry route for fungal spores causing mucormycosis. Treatment includes reducing fungal load, controlling underlying comorbidities, and antifungal therapy. Surprisingly, a limited disease involvement was found in Wegener’s Granulomatosis and immunosuppressive therapy background. To the best of our knowledge, the use of steroids as a part of management in a patient with mucormycosis with a favorable outcome is undocumented in the literature.

Case Presentation

A Gentleman in his 40s presented to us with left-sided hemifacial pain and nasal discharge for the last three days. The pain was dull-boring in character, non-pulsatile, moderate in severity, with no radiation, no diurnal variation, and aggravating or relieving factors. There is no history of fever, vision loss, nasal discharge, toothache, diplopia, or addictions.

He has a history of multiple episodes of severe abdominal pain five years back, which were diagnosed to be due to Wegener’s Granulomatosis on further evaluation. His P-ANCA levels were elevated, and renal biopsy showed ANCA-associated glomerulonephritis. He was maintained on azathioprine. He developed covid pneumonia one month back and was treated using Oxygen support, steroids and Remedesvir. Azathioprine was changed to oral prednisolone to maintain Wegener’s Granulomatosis during the treatment of covid pneumonia. There is a history of azathioprine-induced anemia two years back.

He has multiple comorbidities: chronic kidney disease (S. Creatinine- 2.9), hypertension, glaucoma, benign prostatic hypertrophy, urinary stricture, and tinea cruris currently maintained on cilnidipine acetylcysteine, febuxostat, prednisolone, soda bicarbonate, tamsulosin, and timolol eye drops.

On examination, the patient was conscious, oriented to time, place, person, and obeys commands. His vitals and systemic examination were within normal limits. He had left House Brackmann grade 3 lower motor neuron facial palsy [4] and left maxillary sinus tenderness. On eye examination, visual acuity was normal, the left eye deviated laterally, and the pupil mid-dilated (history of trauma six years back followed by deviation of the left eye). The tooth and palate were normal, with no crusting or eschar over the palate. No crusting/discharge was seen in the nasal cavity upon anterior rhinoscopy. Diagnostic nasal endoscopy showed crusting and necrotic debris in the left middle meatus and deviation of the nasal septum towards the left. Middle, inferior turbinate, and floor of the left nasal cavity were normal. The right nasal cavity was unremarkable upon clinical examination.

KOH mount sample from the left nasal cavity was suggestive of broad aseptate ribbon-like hyphae suggestive of Mucormycosis. Magnetic resonance imaging showed mucosal hypertrophy in the bilateral maxillary sinus (Fig. 1). His renal function tests were deranged with elevated Serum urea levels at 86 mg/dl and serum creatinine levels at 3.39 mg/dl. The total leukocyte counts (16,700/microliter) and inflammatory markers ferritin (1409.9 ng/ml), HSCRP (60.92 mg/dl), and LDH (600 U/l) were raised, suggestive of an inflammatory etiology. HbA1c was 6.1, reflecting the patient’s non-diabetic status.

Fig. 1.

MRI Image suggestive of mucosal hypertrophy in bilateral maxillary sinuses (Black arrow)

Treatment

A provisional diagnosis of Post covid sinonasal mucormycosis based on the post covid status, high dose steroid therapy, high clinical suspicion, KOH mount, and radiological imaging was made. He was posted for emergency debridement. The left maxillary sinus was filled with necrotic mucosa and debris; endoscopic middle meatus antrostomy was done through the sublabial Caldwell Luc’s approach for adequate exposure along with anterior and posterior ethmoid sinus clearance. After the middle meatus antrostomy, hypertrophic mucosa was seen in the right maxillary sinus. Necrotic debris and mucosa were sent for intraoperative KOH mount, which was suggestive of broad aseptate ribbon-like hyphae confirming the diagnosis of mucormycosis (Figs. 2 and 3). Medicine consultation advised continuing steroid therapy post-surgery to prevent relapse of Wegener’s Granulomatosis. Nephrology consultations in view of deranged renal function test advised a renal adjusted dose of 3–5 mg/kg body weight/day of Liposomal Amphotericin B to be given over 3–4 weeks along with oral prednisolone. He was discharged on tab prednisolone and nasal douching with isotonic nasal spray and saline spray after a 3.5 g cumulative dose of Liposomal amphotericin B.

Fig. 2.

KOH mount microscopy suggestive of Broad aseptate ribbon-like hyphae (Black arrow)

Fig. 3.

Necrotic debris in Left maxillary sinus

Outcome and Follow-Up

The patient is doing well post-surgery; histopathology showed areas of necrosis, hemorrhage, and dense neutrophilic infiltrate with broad aseptate hyphae suggestive of mucormycosis. He was kept on regular follow-up and is doing well until nine months with no crusting and discharge and normal mucosalisation in the nasal cavity (Fig. 4). A CT scan was done five months postoperatively and showed no residual or recurrent disease signs.

Fig. 4.

Nine months Postoperative Nasal endoscopy image depicting a well-healed healthy cavity

Discussion

It is the first case report describing Covid-associated mucormycosis in Wegener’s Granulomatosis. Previous reports describe sinonasal, cutaneous, and pulmonary mucormycosis in Wegener’s Granulomatosis, but no study has been published describing mucormycosis in a Post Covid patient with Wegener’s Granulomatosis [5–7].

A multidisciplinary approach is essential for managing mucormycosis; patients usually suffer from multiple comorbidities. Liposomal Amphotericin B, the drug of choice for mucormycosis, has nephrotoxic effects and leads to electrolyte imbalances and deranged creatinine levels. Its use in Chronic kidney disease requires careful dose titration and regular monitoring of renal function tests. A lower dose of 3–5 mg/kg/day, contrary to the recommended dose of 5-10 mg/kg/day, was used after careful discussion with a nephrologist. Diabetes is a common risk factor for mucormycosis, and its absence supports Wegener’s and covid as the underlying cause of mucormycosis.

Wegener’s Granulomatosis and Covid 19 necessitate steroids and immunosuppressants for disease control and prognostic benefit. Steroids are a double-edged sword as underdosing can lead to a relapse of Wegener’s, and overdosing will cause a flare-up in mucormycosis. Oral steroids were continued throughout the course of the disease with regular monitoring by a physician. Limited disease involvement was seen despite active immunosuppressive therapy, vasculitis, and post covid status challenging the role of steroids in the causation of Mucormycosis.

Treatment requires adequate antifungal therapy using Liposomal Amphotericin B, surgical debridement, and control of underlying comorbidities. IVIG has been used previously to control mucormycosis in a patient with Wegener’s Granulomatosis. The use of oral steroids and low dose LAMB in a patient with mucormycosis and Wegener’s Granulomatosis with successful treatment outcome is previously undocumented in the literature and requires further evaluation.

Learning Points

• It is a case of Mucormycosis in a post covid patient with Wegener’s Granulomatosis posing management challenges.

• A multidisciplinary approach is required to achieve appropriate outcomes in complex cases with multiple comorbidities

• Limited disease involvement was seen despite immunosuppression favoring widespread disease.

• The use of steroids in a patient with mucormycosis seems counterintuitive but is essential and a unique feature of this case report.

Patient’s Perspective

It started five years back with a stomach ache; I went to consult a nearby doctor, and he ran some tests, which revealed an abnormality in my kidney function tests, I was referred to a tertiary health care center for further evaluation, and eventually, I was diagnosed to have Wegener’s Granulomatosis, a disease of the blood vessels. The treatment cost was relatively high, involving frequent visits to a nephrologist.

It had been five years, and I was well adjusted to my new life when I noticed pain and swelling on the left side of my face. The television was running news about a disease called the “black fungus” with a rapid rise in cases in people who suffered from Covid 19, and I decided to get myself checked for this new disease. The doctors took samples from my nose, did a CT scan, and confirmed my fears. I was suffering from the dreaded black fungus and needed hospitalization for about a month. Around 250 patients like me were admitted to different wards in the hospital.

I was taken for surgery and was started on medication. Everyone around me was feverish and suffering from reactions after taking the drug. I was told I had to take medicine for at least three weeks. There was a time when daily 10–15 doctors from different specialties used to see me owing to my Wegener’s Granulomatosis requiring adjustments in the dose. Many patients around me lost their eyes and palate to this disease. Thanks to the efforts of doctors and nursing staff, I tolerated the treatment well and was discharged after a month; I was called for regular checkups, initially weekly, then monthly. Till now, I am recovering well with no signs of black fungus as per my doctors.

Author Contributions

AA and RDA: Cocept,design, Literature search,Writing; AA AND RDA: Concept, Analysis and/or interpretations; NMN and RDA: Supervision, Critical Review.

Funding

No funding was received to assist with the preparation of this manuscript.

Declarations

Conflict of interest

The authors have no conflict of interest.

Human and Animal Rights

The research involves human participants, and well informed consent was taken from each individual. The exemption from the ethical committee review was obtained in view of the retrospective study (Letter no:2861/IEC-AIIMSRPR/2023.)