Target lesions in a neutropenic patient

Abstract

A 25-year-old male with a past medical history of Down’s syndrome was admitted for chemotherapy for relapsed acute lymphocytic leukemia. After 7 days of chemotherapy, he became profoundly neutropenic (absolute neutrophil count of \300 cells/mm) and febrile. Empiric intravenous vancomycin and cefepime were initiated for neutropenic fever. Intravenous micafungin was added when fever persisted. Multiple sets of blood cultures were negative. CT scans of chest, abdomen and pelvis did not reveal the infectious source of persistent fever. After 4 weeks of neutropenia, the patient developed several painful erythematous papular skin lesions beginning on the right lower forearm. Lesions spread rapidly to other extremities (Fig. 1a), face and trunk over a few days; some of these developed necrotic hemorrhagic centers (Fig. 1b). Multiple skin punch biopsies were obtained. Intravenous amphotericin B lipid complex (5 mg/kg every 24 h) and intravenous voriconazole (6 mg/kg every 12 h for 2 doses, followed by 4 mg/kg every 12 h) were administered for suspected invasive fungal infection, awaiting diagnostic confirmation. Skin biopsy revealed multiple septated hyphae branching at acute angles (Fig. 1c), with evidence of frank angioinvasion (Fig. 1d). Skin tissue cultures were positive for Fusarium solani; blood cultures remained negative. Absolute neutrophil counts did not recover and his condition continued to deteriorate. The patient eventually succumbed to multi-organ failure from disseminated fusariosis 8 days after initiation of antifungal therapy. Fusarium spp. are ubiquitous in the environment and widely distributed in soil, plants and air. Disseminated Fusarium infections occur almost exclusively in neutropenic patients with hematologic malignancies, typically among patients with leukemia receiving induction chemotherapy or hematopoietic stem cell transplantation [1, 2]. Invasive fusariosis most commonly manifests as persistent fever refractory to antimicrobial treatment. Skin lesions are often the only clinical manifestation and source of diagnostic material in majority of patients with disseminated fusariosis [2, 3]. Prolonged ([1 week) and profound neutropenia (absolute neutrophil count 500 cells/mm) is the major risk factor for invasive disseminated fusariosis [2, 3]. Cutaneous manifestations of disseminated disease usually begin as multiple erythematous tender macules or nodules (Fig. 1a) [3–5]. These skin lesions are found more commonly on the arms and legs than on the trunk [3]. Some of the cutaneous lesions may progress to a central eschar with a surrounding erythematous base, resulting from angioinvasion of Fusarium spp., giving the lesions target-like appearance (Fig. 1b). Several lesions may coalesce forming a large area of hemorrhage resembling ecthyma gangrenosum [3]. It is not uncommon to see several lesions at varying stages of evolution simultaneously. Recognition of these distinctive cutaneous lesions provides critical clinical clues of disseminated Fusarium infection, which can have a significant influence on early and aggressive therapy. Skin punch biopsies should be performed expeditiously for immediate frozen section, routine histology and cultures to identify the fungal Z. Min (&) Department of Medicine, Division of Infectious Diseases, Allegheny General Hospital, 420 East North Avenue, East Wing, Suite 407, Pittsburgh, PA 15212, USA e-mail: zmin@wpahs.org