Trust Your Gut: Recognizing Whipple’s Disease Beyond the Intestine

Whipple's disease is a rare, chronic, multisystemic infection caused by <i>Tropheryma whipplei (T. whipplei)</i>, classically presenting with gastrointestinal manifestations but frequently involving extraintestinal organs that may delay diagnosis. We report two cases illustrating the clinical spectrum of Whipple's disease: a 59-year-old man with malabsorption, chronic diarrhea, and weight loss, and a 44-year-old man with inflammatory polyarthralgia and constrictive pericarditis who developed gastrointestinal symptoms eight years later. In both cases, diagnosis was established by duodenal biopsy demonstrating periodic acid-Schiff (PAS)-positive macrophages and polymerase chain reaction confirmation of <i>T. whipplei</i>. Both patients were treated with intravenous ceftriaxone followed by long-term trimethoprim-sulfamethoxazole, with favorable clinical outcomes. These cases highlight the diagnostic challenges posed by atypical Whipple's disease and underscore the importance of considering this diagnosis in patients with unexplained multisystem inflammatory syndromes.