Whipple’s disease in rheumatology: insights from a Portuguese multicenter series

Whipple’s disease (WD) is a rare chronic infection caused by Tropheryma whipplei, often presenting initially with musculoskeletal (MSK) manifestations that precede gastrointestinal (GI) or systemic symptoms by years. Its protean features and response to immunosuppression make it a diagnostic challenge in rheumatology. We conducted a national, multicenter, retrospective study of WD cases initially assessed for suspected rheumatic disease in Portuguese Rheumatology departments. Diagnosis was confirmed by duodenal histopathology and/or polymerase chain reaction (PCR) detection of T. whipplei. Demographic, clinical, laboratory, and therapeutic data were analyzed descriptively. Seven patients were identified (71.4% male; mean age 59.9 ± 8.2 years). The median diagnostic delay from MSK symptom onset was 4 years. MSK presentations included migratory arthritis/arthralgia (n=4), polymyalgia rheumatica-like symptoms (n=1), asymmetric sacroiliitis (n=1), and rheumatoid arthritis mimics (n=2). GI symptoms occurred in 57.1% and systemic manifestations in 85.7%, all with weight loss. One patient had central nervous system involvement. All showed anemia and elevated inflammatory markers. The median interval between MSK and extra-articular symptoms was 2.6 years. Five patients received immunosuppressive therapy; notably, earlier systemic/GI involvement occurred in those without such exposure, while the only patient treated with biologics did not develop extra-articular symptoms. WD may mimic diverse rheumatic diseases, causing diagnostic delay. A high index of suspicion is warranted in patients with refractory rheumatic symptoms, anemia, and weight loss. The observed variability in systemic progression highlights a potentially complex relationship between immunosuppression and host immune response to T. whipplei, warranting further investigation.