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

**Authors:** Mohammad Z. Khrais, Jake Smith, Tanmay Gandhi, Shahrukh Arif, Juan Carlos Rico

PMC · DOI: 10.1099/acmi.0.000929.v3 · Access Microbiology · 2025-05-28

## TL;DR

An HIV patient was mistakenly diagnosed with histoplasmosis due to a false-positive test, but was later correctly diagnosed with coccidioidomycosis after invasive testing.

## Contribution

Highlights the risk of false-positive histoplasma antigen tests in diagnosing fungal infections and emphasizes the need for invasive diagnostics in ambiguous cases.

## Key findings

- A false-positive histoplasma urine antigen test led to misdiagnosis of histoplasmosis in an HIV patient.
- Coccidioidomycosis was confirmed through bronchoscopy and fungal culture after clinical worsening on initial treatment.
- False positives can occur due to cross-reactions with other fungal infections like blastomycosis or paracoccidioidomycosis.

## Abstract

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 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.

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.

## Linked entities

- **Diseases:** Coccidioidomycosis (MONDO:0005706), Valley fever (MONDO:0005706), pneumonia (MONDO:0005249), histoplasmosis (MONDO:0018312), blastomycosis (MONDO:0005672), paracoccidioidomycosis (MONDO:0005894), aspergillosis (MONDO:0005657)
- **Species:** Coccidioides (taxon 5500)

## Full-text entities

- **Diseases:** pulmonary histoplasmosis (MESH:D006660), aspergillosis (MESH:D001228), necrotic (MESH:D009336), pneumonia (MESH:D011014), immunodeficient (MESH:D007153), syncope (MESH:D013575), Coccidioidomycosis (MESH:D003047), blastomycosis (MESH:D001759), human immunodeficiency virus infection (MESH:D015658), fungal (MESH:D009181), paracoccidioidomycosis (MESH:D010229), talaromycosis (MESH:C000656865)
- **Chemicals:** itraconazole (MESH:D017964), amphotericin (MESH:D000666)
- **Species:** Histoplasma (genus) [taxon 5036], Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676], Coccidioides (genus) [taxon 5500]

## Full text

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## Figures

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## References

18 references — full list in the complete paper: https://tomesphere.com/paper/PMC12120142/full.md

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Source: https://tomesphere.com/paper/PMC12120142