A cautionary tale of false-positive histoplasma urine antigen in an HIV patient: a case report

<b>Introduction.</b> Coccidioidomycosis, or Valley fever, is a fungal disease caused by <i>Coccidioides</i> species, prevalent in parts of the southwestern United States. It usually results from inhaling spores from soil and is a common cause of pneumonia in these regions. <b>Case Presentation.</b> We present a unique case of coccidioidomycosis in an immunodeficient male patient secondary to human immunodeficiency virus infection with poor adherence to anti-retroviral treatment. After presenting with non-specific symptoms and pre-syncope, he was initially diagnosed with pneumonia based on chest X-ray findings, but his symptoms failed to improve with antibiotics. He was treated for presumed pulmonary histoplasmosis following a positive histoplasma urine antigen test. However, the patient worsened clinically. Following a computed tomography scan demonstrating a large necrotic lung consolidation, fungal stain and culture of tissue biopsied through endobronchial ultrasound confirmed coccidioidomycosis. The patient received 2 weeks of liposomal amphotericin with clinical improvement before discharge with itraconazole. <b>Conclusion.</b> The histoplasma antigen test can be falsely positive due to cross-reaction with other fungal infections like blastomycosis, paracoccidioidomycosis or talaromycosis, and less frequently, coccidioidomycosis or aspergillosis. Diagnosis of coccidioidomycosis requires a high index of suspicion outside the expected geographic distribution in the appropriate clinical setting. Our case highlights the risk of false-positive antigen test results and the importance of invasive diagnostics, including bronchoscopy to obtain fungal cultures, if the diagnosis remains uncertain.