Rhino Cerebral Mucormycosis in Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a multisystem connective tissue disease. Patients with SLE develop cutaneous infections due to immune dysregulation and treatment with immunosuppressive agents. Deep fungal infections are rare in SLE but are important cause of morbidity. We report a case of successfully treated rhino cerebral mucormycosis (RCM) in a female patient with SLE.

Introduction

What was known?

1. Mucor mycosis is an opportunistic infection.

2. Rarely reported in SLE with a high degree of mortality.

Mucormycosis is an opportunistic infection caused by a saprophytic aerobic fungus of the Phycomycetes class. This condition was first described by Paltauf in 1885 in human beings. These ubiquitous fungi become pathogenic in man under certain conditions like immunosuppression, diabetic acidosis, antibiotic, corticosteroid, and cytotoxic therapy, with other predisposing factors like malignancy, burns, malnutrition, renal failure, and blood dyscrasias.[1] Rhino cerebral mucormycosis (RCM) is the most common clinical variant involving the paranasal sinuses and brain. The survival rate was zero before the year 1955–the pre-amphotericin era. After an advent of amphotericin, the survival rate among patients with invasive sinus disease without cerebral involvement was reported as high as 50-80%. If infection spreads to the brain, the case fatality rate can exceed 80%. The cause of death in many patients is mucormycosis itself rather than the progression of the underlying disease. Early diagnosis and multidisciplinary treatment approach only will reduce morbidity and mortality.

Case Report

A 28-year-old female presented with pallor, swelling of face and legs with history of hematuria, oliguria, and diffuse hair loss. She was suspected to have systemic lupus erythematosus (SLE) and on investigation, she had anemia (hemoglobin 7.5 gm%), leucocytosis, elevated ESR, positive ANA (1:80) and dsDNA. Her renal function tests including 24 h urinary protein were normal, except presence of RBC deposits. The renal biopsy showed diffuse proliferative glomerulonephritis with immuno fluorescence pattern consistent with lupus nephritis. She was treated with monthly pulses of injection methylprednisolone along with daily oral prednisolone. Three months later, she developed ulceration over cheek and palate with discharge of pus. She started losing weight and developed gross edema of right half of face. On examination, she had a puckered ulcer with induration over right side of cheek and a whitish plaque on hard palate [Figures 1 and 2]. She also had lagophthalmos and right-sided facial palsy. Superinfection with mucormycosis was suspected, methylprednisolone was stopped, and a therapeutic curettage done from the plaque, the histopathological examination of which showed broad irregular hyphae consistent with mucormycosis [Figure 3]. The fungal culture yielded no growth. Patient was treated with inj. amphotericin B 0.6 mg/kg/day i.v. for 1 month and she improved. However, the improvement was not consistent as there was extension of ulceration over the palate. Surgical debridement was repeated, computed tomography (CT) brain and peripheral nervous system (PNS) showed erosion of palate and maxillary antrum [Figure 4]. Maxillectomy was performed and Inj. amphotericin B continued for 21 days, and she was continuously monitored for signs of drug-induced renal toxicity. The disease was controlled and the wound healed well [Figure 5]. Patient is being followed up with no recurrence till date (3 years since diagnosis).

Figure 1.

Systemic lupus erythematosus (SLE) patient with rhino cerebral mucormycosis (RCM) showing a puckered ulcer over the cheek with indurations and edema of right cheek with facial palsy

Figure 2.

Systemic lupus erythematosus (SLE) patient with rhino cerebral mucormycosis (RCM) showing whitish plaque in the hard palate

Figure 3.

Hemotoxylin and Eosin stain histopathology of the curettage showing necrotic and edematous tissue with fungal hyphae

Figure 4.

Computed tomography (CT) brain and peripheral nervous system (PNS) showing erosion of palate and maxillary antrum

Figure 5.

After complete cure of the disease showing right sided facial palsy

Discussion

SLE is a multisystem autoimmune disease, where there is altered immune regulation and reduced protective functions of immune system. Infections are the major cause for morbidity and mortality in up to 30-50% of SLE patients.[2,3] Of the invasive fungal infections affecting patients with SLE, Cryptococcus neoformans accounted for most common fatalities in one series.[4] The overall mortality of mucormycosis was very high (88%).[5] RCM is a rare opportunistic deep fungal infection and is infrequently reported in patients with SLE. Not many reports are available where RCM in SLE patients were successfully treated. One more report of SLE with abdominal mucormycosis where intestinal resection done but did not have a follow-up.[6]

An underlying risk factor is recognized in more than 96% of mucormycosis cases including steroid therapy. Palatal erosion in mucor mycosis indicates rhinomaxillarymucormycosis,[7] can progress to RCM if left untreated, can result in carotid artery occlusion,[8] cavernous sinus thrombosis, CNS infarction secondary to fungal thrombosis leading to hemi paresis, hemiplegia, coma, and death. Other complications of RCM include CNS hemorrhage, abscess, and cerebritis.

Treatment of RCM includes reversing underlying immunocompromised states as in diabetes mellitus or withdrawal of steroids, institution of systemic anti-fungals, and urgent surgical debridement. Recovery of neurologic function can be only possible if no irreversible damage has occurred. Post-surgical disfigurement and morbidity due to RCM are very common as in our case. In our case, need for methyl prednisolone did not arise as the patient improved well after control of RCM, and there were no clinical or biochemical renal abnormality. Her ANA still remains positive in a lower dilution (1:10). However, the patient is periodically reviewed.

Conclusion

Patients with SLE have an altered protective host immune function against infection, which when challenged with immunosuppressive therapy for the control of SLE, they become more prone for infections. Unless suspected early and promptly treated, the disease and infection have deleterious effect on the patient increasing the morbidity and mortality. Mucormycosis is rare but usually having a fulminantly fatal clinical pattern. Judicious use of immunosuppressive agents to treat the disease (SLE), watchful expectancy of infections with a high index of suspicion, early diagnosis, and appropriate multi-disciplinary treatment will improve the prognosis.