Disseminated Fusariosis, Leukemia Cutis, and Acute Sinus Disease in Prolonged Neutropenia from Acute Myeloid Leukemia

BackgroundPatients with acute myeloid leukemia (AML) and prolonged neutropenia are at high risk for invasive fungal infections such as fusariosis, which represents the second most common pathogenic mold infection in this population. Disseminated fusariosis carries mortality rates of 50–80% in immunocompromised patients, with persistent neutropenia being the most critical factor associated with poor outcomes.Case PresentationA 62-year-old man with systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) and myelodysplastic syndrome (MDS) progressing to AML presented with two weeks of headache, sinus pressure, nasal congestion, right neck swelling, and worsening left lower-extremity pain. His hematologic disease was complicated by >6 months of transfusion-dependent pancytopenia, recurrent neutropenic infections, extended-spectrum-lactamase (ESBL) Escherichia coli bacteremia, liver abscess, nodular pneumonia, and neutropenic colitis. Prior therapies included avapritinib, decitabine/venetoclax, and enrollment in a vyxeos-gliteritinib clinical trial; he remained profoundly neutropenic (absolute neutrophil count [ANC] <20). Examination revealed numerous necrotic nodular skin lesions; biopsy grew Fusarium. Imaging showed new and worsening pulmonary nodules, and subsequently demonstrated multiple lung, spleen, and kidney lesions consistent with disseminated fusariosis, with the lungs suspected as the primary site of infection. Labs confirmed severe pancytopenia (WBC 0.28), mild acute kidney injury (AKI); blood cultures remained negative. Bronchoalveolar lavage (BAL) testing and Karius sequencing identified Fusarium solani. Concomitantly, multifocal painful nodules and right sternocleidomastoid enlargement were attributed to leukemia cutis, supported by progression of blasts to 30-35%. His presentation reflected overlapping disseminated mold infection and leukemic infiltration. He was managed with liposomal amphotericin B, voriconazole, and terbinafine, along with meropenem and vancomycin. Due to Fusarium’s high azole and amphotericin minimum inhibitory concentrations (MICs) at our institution, fosmanogepix was requested but anticipated to arrive in two weeks. GM-CSF was added to augment neutrophil recovery; however, despite maximal therapy, he developed progressive respiratory failure and expired on mechanical ventilation before fosmanogepix became available.ConclusionThis case illustrates the devastating impact of invasive fusariosis in patients with hematologic malignancies and prolonged neutropenia. Early recognition of the clinical triad of respiratory involvement, severe myalgia, and skin lesions may suggest Fusarium etiology in severely neutropenic patients. Successful management requires prompt diagnosis, appropriate combination antifungal therapy, and most critically, neutrophil recovery, which represents the single most important prognostic factor.