Whipple’s disease presenting with false-positive HIV serology: a diagnostic pitfall

Abstract

Background: Whipple’s disease is a rare systemic infection caused by Tropheryma whipplei. Its protean manifestations may mimic chronic infectious or inflammatory conditions, including HIV infection, leading to diagnostic pitfalls. Case presentation: We report the case of a 51-year-old man presenting with a one-month history of severe weight loss, chronic diarrhea, and asthenia. Initial evaluation revealed a weakly reactive fourth-generation HIV screening assay, raising concern for HIV infection; however, confirmatory HIV PCR was negative. Cross-sectional imaging showed diffuse small-bowel wall thickening, mesenteric lymphadenopathy, ascites, and pleuropericardial effusions. Upper gastrointestinal endoscopy revealed friable ulcerated duodenal mucosa with villous blunting. Duodenal biopsies demonstrated periodic acid–Schiff-positive foamy macrophages, and polymerase chain reaction confirmed Whipple’s disease. The patient received intravenous ceftriaxone followed by oral doxycycline and hydroxychloroquine, with rapid clinical improvement and no evidence of relapse at six months of follow-up. Conclusion: This case highlights Whipple’s disease as an important differential diagnosis in patients with unexplained multisystemic symptoms and discordant HIV test results. Weakly reactive HIV screening assays should be interpreted cautiously and confirmed before establishing a diagnosis of HIV infection. Early duodenal biopsy and timely initiation of CNS-penetrant antibiotic therapy are essential to improve outcomes and reduce relapse risk.