Abstract Histoplasmosis and blastomycosis are dimorphic fungal infections with overlapping clinical and radiologic features, often complicating diagnosis especially in immunocompromised hosts. Expanding endemic areas likely due to cross migration and climate change and serologic cross-reactivity further blur distinctions. We present a 88-year-old woman with myasthenia gravis on mycophenolate, hyperlipidemia, and osteoporosis presented with months of progressive weakness, fatigue, and cough for 4 weeks. Chest imaging revealed bilateral infiltrates with a miliary pattern and small left pleural effusion. She denied recent travel, bird exposure, or tuberculosis risk factors. Examination showed decreased breath sounds and multiple scaly facial lesions, initially biopsied for suspected basal cell carcinoma. Serum fungal studies showed positive Histoplasma antigen (19.63 ng/mL), negative antibody (1:8), and positive Blastomyces antigen (5.87 ng/mL), consistent with antigenic cross-reactivity. Patient was unable to provde urine samples for antigen and serology testing. Bronchoalveolar lavage (BAL) demonstrated granulomatous inflammation with fungal elements consistent with Histoplasma spp. BAL PCR was positive for CMV but negative for Mycobacterium tuberculosis, Coccidioides, Aspergillus, and Pneumocystis jirovecii. Along with this she was getting worked up for a skin lesion in dermatology clinic . Later , biopsy of the jawline lesion confirmed cutaneous histoplasmosis. Although CMV PCR was positive , CMV pneumonitis was deemed unlikely given absent inclusion bodies and lack of clinical findings suggestive of CMV infection. She was started on itraconazole with close follow-up. This case highlights the diagnostic challenges of disseminated histoplasmosis in immunocompromised patients. Antigen cross-reactivity between Histoplasma and Blastomyces reported in up to 90% can confound serologic interpretation, especially when antibody titers are low due to immune suppression. Urine antigen is detected in over 90% of disseminated cases, with nearly universal antigenemia in severe disease, though sensitivity declines in subacute or chronic pulmonary forms. When extrapulmonary clues such as skin lesions, adrenal involvement, or bone marrow suppression are absent, adjunct serologic testing can improve diagnostic confidence, combining antigen and antibody testing enhances sensitivity (from 87.8% up to 97.6%) and aids differentiation from blastomycosis. While bronchoscopy with BAL provides high diagnostic yield for both organisms, it may be contraindicated in respiratory distress. In such cases, noninvasive antigen testing and recognition of systemic features remain essential for timely diagnosis and initiation of antifungal therapy. This abstract is funded by: None
Bista et al. (2026) studied this question.