A Recurrent Blood Culture–Negative Endocarditis Revealing Whipple’s Disease

BACKGROUND: Blood culture-negative infective endocarditis (BCNIE) represents a diagnostic and therapeutic challenge. The main reasons for negative blood cultures are prior antibiotic exposure, fungal infection, or infection with fastidious bacteria. CASE SUMMARY: Here, we describe the case of a 61-year-old patient with recurrent BCNIE initially diagnosed as rheumatoid arthritis but ultimately diagnosed as Whipple's endocarditis. DISCUSSION: Whipple's disease is a rare, chronic, multisystemic infection that may relapse if diagnosis is delayed. Whipple's endocarditis is often misdiagnosed, and its treatment remains empirical. This case shows all the typical features, with misdiagnosis causing a delay in identifying the underlying cause of BCNIE and leading to relapse before the initiation of appropriate treatment. TAKE-HOME MESSAGES: In the presence of BCNIE, Whipple's disease should always be considered as a potential underlying cause. Prolonged antibiotic therapy appears to reduce the risk of relapse, although close clinical monitoring is recommended as relapses have been reported.