A Cautionary Tale of False Positive Histoplasma Urine Antigen in an HIV Patient: A Case Report

Introduction. Coccidioidomycosis, or Valley fever, is a fungal disease caused by Coccidioides 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. Case Presentation. We present a unique case of coccidioidomycosis in an immunodeficient male patient secondary to HIV infection with poor adherence to ART. 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 CT scan demonstrating a large necrotic lung consolidation, fungal stain and culture of tissue biopsied through EBUS confirmed coccidioidomycosis. The patient received two weeks of liposomal amphotericin with clinical improvement before discharge with itraconazole. Conclusion. 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.