S4991 Non-Caseating Granulomas and a Hidden Fungus: Disseminated Histoplasmosis in a Crohn’s Patient on Anti-Tumor Necrosis Factor Therapy

Introduction: Patients with inflammatory bowel disease receiving anti-tumor necrosis factor alpha inhibitors are at increased risk for opportunistic infections. Histoplasmosis, though uncommon, may present with nonspecific pulmonary symptoms and radiographic findings that mimic other etiologies such as hypersensitivity pneumonitis and sarcoidosis. This case highlights the diagnostic challenge of differentiating atypical infections from inflammatory or immune-mediated conditions in an immunosuppressed patient with Crohn’s disease. Case Description/Methods: A 32-year-old man with penetrating ileocolonic and perianal Crohn’s disease, maintained on infliximab, presented with a 2-month history of progressive nonproductive cough, fevers, and chills. He is a nonsmoker and denied sick contacts, recent travel, weight loss, or hemoptysis. He worked in agriculture, primarily hydroponics. On examination, he was febrile, tachycardic, and diaphoretic. Laboratory studies revealed elevated inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), positive (1→3)-β-D-glucan, and elevated serum IgE. Chest X-ray showed bilateral patchy infiltrates, and computed tomography chest revealed diffuse ground-glass opacities without lymphadenopathy or tree-in-bud opacities. The differential diagnosis included subacute hypersensitivity pneumonitis, sarcoidosis and atypical fungal infections. Abdominopelvic computed tomography revealed splenomegaly. Bronchoalveolar lavage showed chronic inflammation but no malignant cells or organisms. Lung biopsy revealed non-caseating granulomas. Bronchoalveolar lavage fungal cultures later grew Histoplasma capsulatum, and urine Histoplasma antigen was positive. The patient declined amphotericin B and was treated with oral itraconazole. Infliximab was discontinued. Over 1 year of follow-up, he had complete resolution of symptoms, normalization of imaging, and negative Histoplasma antigen. His Crohn’s disease remained stable off biologic therapy, and he is currently under re-evaluation for biologic reinitiation. Discussion: This case emphasizes the importance of considering opportunistic infections like histoplasmosis in patients with inflammatory bowel disease on biologic therapy who present with atypical pulmonary findings. Non-caseating granulomas can be misleading and are not pathognomonic for sarcoidosis or hypersensitivity pneumonitis. Occupational exposure history and comprehensive infectious workup are essential to avoid misdiagnosis. Discontinuation of immunosuppressive therapy and timely antifungal treatment led to full clinical recovery in this case.