The Brief Case: Cutaneous Fungal Infection in a Pediatric Patient with Newly Diagnosed Acute Lymphocytic Leukemia

Abstract

A 4-year-old male presented to the emergency department with a worsening skin lesion at the prior intravenous (i.v.) injection site on his left arm. He had been diagnosed with acute lymphoblastic leukemia (ALL) 10 days prior and was currently undergoing induction chemotherapy. The lesion was first noticed by his father 2 days earlier as a dime-sized erythematous papule with no pain or focal swelling. Physical examination revealed a painful patch with an irregular erythematous border and central dark bulla overlying the left medial epicondyle (Fig. 1A). The patient was afebrile and noted to have left cervical lymphadenopathy. No intraluminal thrombosis was identified in the left upper extremity by Doppler ultrasonography. Laboratory findings were notable for severe neutropenia, with an absolute neutrophil count (ANC) of 70 cells/l (normal range, 1,500 to 8,000 cells/l). C-reactive protein and the erythrocyte sediment rate were both within normal limits. Levels of serum 1,3-␤-D-glucan (Fungitell test; Associates of Cape Cod, East Falmouth, MA), Aspergillus galactomannan (Bio-Rad, Hercules, CA) and Histoplasma serum antigen (Mira Vista Diagnostics, Indianapolis, IN) were all undetectable. Aerobic (n ϭ 1) and anaerobic (n ϭ 1) blood cultures (VersaTrek;Trek Diagnostic Systems, Cleveland, OH) and blood isolator tubes (Wampole; Abbott, Chicago, IL) for mycobacterial (n ϭ 1) and fungal (n ϭ 1) cultures all yielded no growth.A punch biopsy of the skin lesion was performed at the same time. The tissue sample was sent to both the microbiology and the surgical pathology labs. Microscopically, it showed abundant branching, aseptate hyphae that were present intravascularly ( Fig. 1B), as well as in the dermal and subcutaneous tissue. Fungal elements were also positive by Grocott's methenamine silver (GMS) staining. Cutaneous mucormycosis was suspected. The organism grew rapidly on inhibitory mold agar (IMA) (Remel, Thermo Fisher Scientific, Waltham, MA) with cotton candy-like colonies (Fig. 1C) after 48 h of incubation at 30°C. A tape preparation of the colony with lactophenol blue stain demonstrated the presence of stolons and root-like structures (rhizoids) and the formation of sporangiophores, singly or in groups, from nodes directly above the rhizoids (Fig. 1D). The organism was identified as Rhizopus spp., and the diagnosis of cutaneous mucormycosis was confirmed.The patient was treated with surgical debridement, systemic antifungal medications (liposomal amphotericin B 5 mg/kg/day combined with caspofungin 70 mg/m 2 /day), granulocyte infusions, and granulocyte colony-stimulating factor preparations (G-CSF). He remained afebrile and stable during the whole hospitalization. His chemotherapy plan was adjusted due to invasive mucormycosis. Complete remission of ALL was achieved on day 29 of chemotherapy (day 17 of antifungal treatment). His ANC normalized 20 days after initiation of antifungal treatment, and the debrided wound healed completely with no fungal elements identified or recovered in subsequent surgical patholog...