D107-04 Hemophagocytic Lymphohistiocytosis Triggered by Blastomycosis in an Immunocompetent Host

Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome from uncontrolled immune activation, characterized by fever, cytopenias, hepatosplenomegaly, and multiorgan dysfunction. In adults, secondary HLH (sHLH) may be a result of infections, malignancies, autoimmune disorders, or drugs. We present a case of disseminated Blastomyces infection causing HLH in an immunocompetent man. Case Presentation A 63-year-old man with hypertension, hyperlipidemia, and a 70-pack-year smoking history presented with one week of progressive weakness, recurrent falls, and a productive cough. He was tachycardic with leukocytosis (14.5 × 109/L), hyponatremia (125 mmol/L), and elevated liver enzymes. His initial CT chest showed left lower lobe infiltrate. Despite broad-spectrum antibiotics, he had persistent fevers and worsening anemia (hemoglobin 12.2→6.8 g/dL). Laboratory evaluation was significant for ferritin 40,000 ng/mL, LDH 1578 U/L, elevated soluble IL-2 receptor and CXCL9, and rare hemophagocytosis on bone marrow biopsy, meeting 5 of 8 HLH-2004 diagnostic criteria. Initial bacterial and fungal antibody studies were negative; however, repeat antigen testing resulted in positive Blastomyces urine antigen. Klebsiella Pneumoniae was also isolated from bronchoalveolar lavage, suggesting a dual infectious trigger. The patient was treated with itraconazole and high-dose corticosteroids, resulting in defervescence, improvement of cytopenias, and full clinical recovery. PET/CT excluded occult malignancy. Discussion This case illustrates the diagnostic complexity of HLH in adults, particularly in the context of overlapping bacterial and fungal infections. Viral etiologies, particularly Epstein-Barr virus (EBV), account for approximately 30-40% of adult sHLH cases, whereas fungal infections represent 1% of infectious triggers, making them exceedingly rare. Blastomyces dermatitidis, a dimorphic fungus endemic to the Midwest, typically manifests as pulmonary or disseminated disease but only rarely provokes HLH. Fewer than ten adult cases have been described to date. Reported mortality for infection-associated HLH remains as high as 40-60%. The proposed mechanism involves macrophage and T-cell overactivation with cytokine storm and extreme hyperferritinemia. Bacterial coinfection may amplify immune dysregulation and obscure the fungal etiology. Our case adds to the limited literature on blastomycosis-associated HLH, emphasizing the need to consider endemic mycoses in patients with unexplained systemic inflammation, even in immunocompetent hosts. This abstract is funded by: NONE