Pediatric Entomophthoramycosis in the Brazilian Amazon: A Challenging Diagnosis of a Rare Fungal Infection

To the Editors: Entomophthoramycosis is a rare subcutaneous mycosis predominantly reported in tropical and subtropical regions. Infections are caused mainly by Conidiobolus spp. and Basidiobolus ranarum, which are saprophytic fungi commonly found in soil, leaf litter and the gastrointestinal tracts of amphibians, reptiles and insects. Transmission is thought to occur through minor skin trauma, insect bites, or ingestion of contaminated material.1–5 The diagnosis of entomophthoramycosis remains challenging due to limitations in both histopathological and mycological methods. Histology may show broad, sparsely septate hyphae with eosinophil-rich inflammation and Splendore–Hoeppli material, findings that are not entirely specific.1,2,6,7 Herein, we report a challenging case of entomophthoramycosis in a pediatric patient from northeastern Brazil. This is a previously healthy male child, 2 years and 3 months old, residing in the Pre-Amazon Region, who presented with periorbital edema and hyperemia in the right eye, associated with fever and prostration for approximately one month. Initially, he presented with periorbital cellulitis of bacterial etiology, undergoing antibiotic therapy (Ceftriaxone, Oxacillin and Clindamycin) for 28 days without clinical improvement. The persistence of the condition, coupled with the lack of response to conventional treatment, motivated his admission to a University Hospital. Upon admission, the patient was evaluated and prescribed clinical treatment with antibiotic therapy for suspected periorbital cellulitis complicated by a hospital-acquired bacterial infection. Vancomycin and Meropenem were initiated and administered for 12 days without clinical improvement. During this period, the patient underwent laboratory tests, which revealed hemoglobin 9.4 g/dL, hematocrit 27%, leukocytes 7890/mm3, platelets 700,000/mm3 and erythrocyte sedimentation rate of 100 mmHg. Imaging studies, including orbital and facial computed tomography, showed an expansive, amorphous, tissue-related lesion with poorly defined contours, affecting the anterior myoadipose planes of the right hemiface and malar regions, with superficial and deep involvement. The lesion area showed diffuse enhancement with intravenous contrast medium, as well as central areas lacking contrast enhancement, which may represent associated liquefied/necrotic content. The patient underwent a biopsy, with material collected for histopathological examination from facial, orbital, palpebral and nasal tissues, which revealed granulomatous inflammation characterized by multinucleated giant cells and areas of central necrosis with eosinophilic amorphous material. The inflammatory process involved fibroadipose and skeletal muscle tissues and showed similar histopathological features across all sampled sites. Special stains for infectious agents, including Grocott and periodic acid-schiff showed hyphae compatible with entomophthoromycosis. The initial antifungal treatment consisted of conventional amphotericin B 1 mg/kg/day. Subsequently, it was replaced with compounded oral itraconazole 10 mg/kg/day, allowing for safe outpatient continuity for 1 year. During outpatient follow-up, the patient progressed without visual, neurological, or scarring sequelae, using itrazonazole for a period of 1 year, undergoing monthly clinical and laboratory monitoring for adverse drug events (Fig. 1). No evidence of recurrence was observed during a 12-month follow-up period after discontinuation of antifungal therapy.FIGURE 1.: Clinical evolution documented by serial photographs obtained at admission (A and B), before antifungal therapy and after initiation of treatment with complete clinical resolution (C and D).Entomophthoromycosis is a rare fungal infection, classically described in immunocompetent adults, an increasing number of pediatric cases have been reported.1–7 The disease often presents with nonspecific clinical features, such as progressive facial swelling and mild inflammatory signs, frequently leading to an initial misdiagnosis of bacterial cellulitis and inappropriate antibiotic use.6 Infections that fail to respond to empirical antibacterial therapy should prompt consideration of alternative etiologies, particularly atypical mycobacterial and fungal infections, and warrant early collection of appropriate clinical specimens to avoid diagnostic and therapeutic delays. In this context, histopathological findings play a crucial role: the presence of granulomatous inflammation associated with eosinophils and the Splendore–Hoeppli phenomenon strongly suggests pathogens with slow replication kinetics rather than conventional pyogenic bacteria.2,6 In the present case, no fungal growth was obtained in conventional culture media, highlighting a well-recognized limitation in the diagnosis of entomophthoramycosis. Despite these limitations, the diagnosis was supported by characteristic histopathological findings, including broad, sparsely septate hyphae associated with a prominent eosinophilic inflammatory response and the Splendore–Hoeppli phenomenon on special fungal stains.1–3 In vitro susceptibility data have demonstrated reduced activity of amphotericin B against Basidiobolus and Conidiobolus species; however, clinical responses have occasionally been observed when this agent is administered alone or in combination with azole antifungals. The sustained clinical remission observed during long-term follow-up in our patient reinforces the potential effectiveness of this therapeutic approach and highlights its relevance in settings where standardized treatment protocols are lacking.1,2,4,7