Abstract Whipple’s disease is a sporadic infectious condition, with an incidence rate of approximately 1 per million individuals. The causative agent is the gram-positive bacterium Tropheryma whipplei . The disease manifests with a wide range of clinical symptoms, including non-specific presentations such as diarrhea, arthralgia, and fever, as well as the more pathognomonic lipodystrophy. This diversity in presentation poses a significant diagnostic challenge even for experienced clinicians. Our review aims to provide an updated overview encompassing the latest insights into Whipple’s disease, focusing on epidemiology, pathophysiology, genetic predisposition, clinical manifestations, diagnosis, immune reconstitution inflammatory syndrome, and treatment. Herein, we have additionally explored many of the confounding factors in the diagnosis and management of Whipple’s disease, including the variable presentations among patients colonized by Trophyrema whipplei as well as the limitations of current treatment options, and underscore the need for further research and guidelines related to this complex disease process.
Korybski et al. (2026) studied this question.