Primary Cutaneous Mucormycosis in Association with Diabetes Mellitus: A Rare Case
Year: 2024
Type: article
Abstract: Dear Editor, A 50-year-old hypertensive obese male presented to our outpatient department with complaints of multiple fluid-filled purplish blisters predominantly over the trunk and proximal extremities from the past two days. The lesions appeared within a few hours of intake of a single dose of bisacodyl and esomeprazole for diarrhea. A few of the blisters ruptured to form raw areas. It was associated with itching and mild tenderness. The patient was afebrile and his vitals were within normal limits. He had a history of a few episodes of developing pigmented itchy raised lesions after the intake of fexofenadine and hydroxyzine, which was suggestive of fixed drug eruption. He had been diagnosed with hypertension for the past three to four months and was taking amlodipine 10 mg on and off. On examination, the patient had multiple, well-defined, discrete, and confluent purplish erythematous fluid-filled blisters predominantly over the trunk and proximal extremities [Figure 1]. There were bright erythematous raw areas present in between. Mucosal examination was normal. All investigations including routine hematological and biochemical investigations were sent and the patient was diagnosed with uncontrolled diabetes mellitus (Hba1c – 11.2). The rest of the investigations were normal. On the basis of history, examinations, and investigations, he was diagnosed with bullous fixed drug eruption with uncontrolled diabetes and hypertension and was started on intravenous dexamethasone 8 mg injection, regular insulin 10 units before meals three times a day, neutral protamine Hagedorn (NPH) insulin 10 units twice a day after meals, oral antibiotics (amoxycillin/clavulanate 625 mg three times a day), and anti-hypertensives (amlodipine 5 mg once a day and telmisartan 40 mg once a day). Despite this, he had poor glycemic control. Within five to six days, his blisters and erosions started resolving with exfoliation. However, we noticed a tender dusky erythematous plaque of size 15×10 cm over the left upper back and the patient also started developing a high fever [Figure 2a]. He was shifted to a tapering dose of oral steroid (prednisolone 30 mg) and was immediately started on intravenous clindamycin 600 mg three times a day and piperacillin/tazobactam 4.5 g every 6 hourly but there was no improvement as the violaceous plaque kept on increasing in size. Necrotizing fasciitis was suspected. The wound was surgically debrided [Figure 2b] and debrided tissue was sent for histopathological evaluation, and bacterial and fungal culture. Bacterial culture was sterile and the wound was serially surgically debrided. Aspergillus flavus was detected on fungal culture (a common contaminant). Histopathological evaluation revealed an ulcerated epidermis with dermis showing infarction and necrosis along with aseptate, branching fungal hyphae of mucor extending up to the overlying epidermis [Figure 3]. Periodic acid–Schiff (PAS) stain for fungus was positive and suggestive of mucormycosis. The case was diagnosed as cutaneous mucormycosis and was started on injection liposomal amphotericin B 1 g once a day. However, the patient died due to shock from multiple comorbidities.Figure 1: (a) and (b) Multiple, discrete and confluent, ruptured purplish erythematous fluid-filled blisters with bright, erythematous raw areas in between predominantly over trunkFigure 2: (a) Dusky erythematous plaque of size 15 × 10 cm over left upper back. (b) Plaque after surgical debridement with no tendency to healFigure 3: (a) -Grocott methenamine silver (GMS) stain (400×) and (b) H & E stain (400×) Ulcerated epidermis with dermis showing infarction, necrosis along with aseptate, branching fungal hyphae of mucor extending up to the overlying epidermisCutaneous mucormycosis is a rare, invasive deep fungal infection caused by fungi of phylum glomeromycota, subphylum mucormycotina, with only a handful of cases reported in the literature, especially from India.[1] Cutaneous mucormycosis manifests predominantly in immunocompromised patients following trauma due to direct spore inoculation of exposed wounds. Risk factors include diabetes mellitus, hematological disorders, glucocorticoid therapy, intravenous drug abuse, and renal failure. The principal risk factor for mucormycosis in India is uncontrolled diabetes mellitus. Our patient had both risk factors for mucormycosis (uncontrolled diabetes mellitus and history of steroid use). Mucormycosis has at least six different clinical presentations—rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and miscellaneous. Cutaneous mucormycosis is the third most common manifestation (after rhinocerebral and pulmonary) and is seen in 19% mucormycosis patients.[2] Cutaneous mucormycosis can be classified as primary and secondary. In primary disease, the skin is infected by direct inoculation and in secondary form, by dissemination from other locations, more commonly from a rhinocerebral infection. It develops when there is a disruption of the normal protective cutaneous barrier. This is usually the result of trauma, which leads to direct inoculation of spores into the skin. When the host has no underlying diseases and the barrier disruption is minor, the infection may be contained if diagnosed early. However, when the patient has sustained a major trauma or there is major barrier disruption like in our patient with large eroded areas due to blisters, along with comorbid conditions such as uncontrolled diabetes or corticosteroid use, it leads to an immune-deficient state, predisposing to the development of mucormycosis.[3] Diagnosis of cutaneous mucormycosis can be difficult as initial symptoms are often non-specific and can mimic a variety of infectious skin diseases. Initially, the lesions are erythematous to purple indurated plaques that become necrotic with an erythematous halo, which can develop into an eschar. Other presentations include targetoid lesions, tender nodules, ulcers, purpuric lesions, and swollen and scaly plaques. In cases of nosocomial infections, symptoms such as erythema and pain progressing quickly to necrosis are commonly observed, as was seen in our case.[4] The upper and lower extremities are the most common sites of cutaneous mucormycosis as they are more prone to trauma, but any area of skin could be affected. In the majority of the cases, the infection progressed rapidly, sometimes leading to gangrene and hematogenous dissemination.[3] Primary cutaneous mucormycosis should be differentiated from aspergillosis and synergistic gangrene caused by bacterial infections. When targetoid lesions appear, the differential diagnoses include autoimmune disorders, drug reactions, infections, infiltrative diseases, and neoplastic disorders. In some cases, it can mimic tinea corporis or pyoderma gangrenosum. Early detection of fungus is important for initiating prompt antifungal treatment and improving the outcome. This can be attained by direct KOH microscopic examination, which reveals the presence of aseptate, hyaline hyphae, 5 μm wide and 20 to 50 μm long, with irregular branching at right angles. Common histopathological findings of cutaneous mucormycosis include edema, thrombosis, infarctions, necrosis, and an inflammatory reaction that includes polymorphonuclear cells, plasma cells, and eosinophils. Thick, hyaline, aseptate, and bifurcated hyphae may be seen with hematoxylin and eosin stain but are best visualized with periodic acid-Schiff and Grocott methenamine silver stains.[5] Fungal cultures are performed on Sabouraud and potato dextrose agar media, and they are positive in half of the cases. For precise identification of the fungus, new molecular tests can be used that target the 18S ribosomal DNA and are highly specific with no cross-reactivity with other filamentous fungi.[6] A multidisciplinary approach is necessary to improve survival in cutaneous mucormycosis. This should include extensive surgical debridement, antifungal therapy, correction of the underlying metabolic or impaired immunological status, and control of other concomitant infections. The antifungal of choice is deoxycolate amphotericin B (d-AmB); however, it is often substituted by lipid formulations because of their better safety profile. In order to increase the survival rate, treatment must be started in the first five days after clinical diagnosis. In immunocompromised patients, the recommended doses for d-AmB are 1–1.5 mg/kg/day, for liposomal amphotericin B (L-AmB), 5–10 mg/kg/day, and for amphotericin B lipid complex 5 mg/kg/day.[4] The prognosis of cutaneous mucormycosis is dependent upon the timing of therapeutic intervention and the degree of the underlying immunodeficiency of the patient. The aggressive course of the mucormycosis presented in our case displays that a high level of suspicion is required for a prompt clinical diagnosis in order to improve the outcome. Where available, new molecular tests should be used to expedite diagnosis. Manifestation of mucormycosis usually appears at a late or terminal stage of the underlying disease and a fatal course may often not be possible to abrogate, regardless of early diagnosis and successful mucormycosis treatment. Early sample harvesting for microbiological diagnosis, radical surgical debridement, and intravenous antifungal therapy are crucial for the eradication of mucormycosis and patient recovery. Hence, in immunocompromised patients with cutaneous infections of any kind, a level of suspicion for mucormycosis infections should be maintained. The existing data on mucocutaneous mucormycosis are sparse, especially in India and a limited number of cases have been documented and described properly. Herein, we present a case of cutaneous mucormycosis in a 50-year-old male with uncontrolled diabetes mellitus and hypertension who was admitted for the management of generalized bullous fixed drug eruption. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Authors: Vibhu Mendiratta, Damini Verma, Anjali Birla, Divya Jyoti, Smita Singh
Institution: Lady Hardinge Medical College
Language: English
Topic: Skin Diseases and Diabetes
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4400918436