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Abstract

Aspergillus and other hyaline septate molds are opportunistic pathogens capable of causing severe, potentially fatal infections, particularly in immunocompromised hosts. Cutaneous involvement may occur via direct inoculation or hematogenous dissemination from a visceral focus. Angioinvasion, characterized by vascular endothelial invasion and thrombosis, is a hallmark of tissue destruction. We present an immunocompromised patient with B-cell acute lymphoblastic leukemia who developed a rapidly progressive purpuric lesion on the hand. Biopsy demonstrated non-pigmented septate hyphae within dermal vessels and associated purpura. While the histologic pattern suggested vascular spread, deeper sections revealed a retained wood splinter at the site. The lesion progressed with expanding necrosis, necessitating surgical debridement. Intravenous amphotericin B led to complete resolution without evidence of dissemination. Tissue culture yielded an Aspergillus species other than A. fumigatus, and fungal next-generation sequencing identified Aspergillus nidulans as the predominant pathogen. Histologically, Aspergillus and other hyaline molds appear as septate, acutely branching hyphae. Definitive diagnosis requires culture or molecular testing. Local invasion begins with adherence to damaged epithelium or exposed extracellular matrix, followed by enzymatic tissue degradation via proteases, lipases, elastases, phospholipases, and metalloproteases. Angioinvasion results from mechanical and enzymatic penetration of vascular endothelium, leading to thrombosis, ischemic necrosis, and potential systemic spread. Additional virulence factors include antioxidant enzymes that neutralize oxidative killing and, in some species, biofilm formation on medical devices. This case highlights the diagnostic complexity of cutaneous angioinvasive Aspergillus in the setting of a penetrating foreign body. Recognition of direct inoculation as a potential source can guide timely surgical and antifungal intervention, improving outcomes.