Fungal Osteomyelitis of the Calcaneus Caused by Exophiala spp. in an Immunocompetent Child

To the Editors: Osteomyelitis is an inflammatory bone infection most caused by bacteria; however, fungal etiologies, although rare, represent a significant diagnostic and therapeutic challenge. Fungal osteomyelitis accounts for a small proportion of reported cases and is frequently associated with immunosuppression, prior surgery, trauma or disseminated infection.1 Among dematiaceous (black fungi), the genus Exophiala spp. has been described as a cause of subcutaneous and systemic infections, with occasional reports of deep tissue and bone involvement.2–4 Cases in immunocompetent hosts are exceptionally uncommon. We report the case of a 3-year-old girl, previously healthy, living in a rural area, admitted with a 20-day history of progressive pain in the left calcaneus, associated with edema, hyperemia and difficulty walking. The caregiver reported a prior puncture injury caused by a lemon tree thorn contaminated with soil. Initial outpatient management with nonsteroidal anti-inflammatory drugs resulted in no clinical improvement. On admission, the patient was afebrile and in fair general condition. Physical examination revealed localized tenderness, moderate edema and limited ankle mobility, without fistula or purulent drainage. Laboratory tests showed mild anemia (hemoglobin 10.1 g/dL), elevated C-reactive protein (3.46 mg/dL) and erythrocyte sedimentation rate of 100 mm/h. Renal function was normal. Empirical intravenous antibiotic therapy with oxacillin and clindamycin was initiated for presumed bacterial osteomyelitis. Due to a lack of response, antimicrobial therapy was escalated to vancomycin and later combined with ciprofloxacin, without significant improvement. Computed tomography of the left foot demonstrated erosion of the anterior calcaneal tuberosity and a hypodense area suggestive of abscess formation, along with adjacent soft tissue inflammation. Surgical drainage and debridement were performed, and samples were collected for microbiologic and histopathologic analysis. The histopathology revealed chronic inflammatory infiltrate, necrosis and fungal elements compatible with phaeohyphomycosis. Subsequent mycologic culture confirmed Exophiala spp., establishing the diagnosis of fungal osteomyelitis. Antibacterial therapy was discontinued, and antifungal treatment with liposomal amphotericin B (3 mg/kg/d) combined with oral itraconazole (6.5 mg/kg/d) was initiated. Amphotericin B, a polyene antifungal, binds to ergosterol in the fungal membrane, leading to cell death, but its use is limited by potential toxicity.5 Itraconazole, a triazole, inhibits ergosterol synthesis and is frequently used for long-term management due to its oral formulation and favorable safety profile.3 After 14 days of antifungal therapy, the patient demonstrated progressive clinical improvement, with reduction of pain and edema and decreased inflammatory markers (C-reactive protein 0.8 mg/dL; erythrocyte sedimentation rate 45 mm/h). Magnetic resonance imaging revealed persistent bone marrow signal changes in the calcaneus, cuboid and navicular bones, compatible with active osteomyelitis. A second surgical debridement was performed to reduce fungal burden. Culture again isolated Exophiala spp., confirming persistent local infection. The patient remained hospitalized for 28 days after initiation of antifungal therapy, evolving without complications. She was discharged on prolonged oral itraconazole for 6 months, with multidisciplinary outpatient follow-up. During follow-up, she showed full clinical recovery, normalization of laboratory parameters and progressive functional improvement. Follow-up imaging demonstrated a significant reduction of inflammatory changes, without late deformities or functional limitations. Fungal osteomyelitis remains rare and often underrecognized, particularly in immunocompetent pediatric patients. A recent systematic review highlights the predominance of Aspergillus and Candida species, with vertebral involvement being most common.1 Reports of Exophiala osteomyelitis are scarce and usually involve immunocompromised adults.2 Pediatric calcaneal osteomyelitis itself is uncommon and may present diagnostic challenges due to anatomical and vascular particularities.6 Delayed diagnosis is associated with increased morbidity and need for repeated surgical interventions.7 This case underscores the importance of considering fungal etiologies in osteomyelitis unresponsive to broad-spectrum antibiotics, even in immunocompetent children. Early microbiologic investigation and combined surgical and antifungal management were decisive for a favorable outcome. Although limited by its nature as a single case, this report contributes to the growing body of evidence on rare fungal bone infections and may assist clinicians in recognizing and managing similar presentations, as shown in Figure 1.FIGURE 1.: Characteristics of the fungus Exophiala spp. (A), pathogenesis of fungal osteomyelitis (B) and treatment (C).