Background: Tropheryma whipplei (Tw) infection is a rare condition, characterized by inflammatory joint symptoms in more than 75% of the cases, which can lead the physician to diagnose chronic inflammatory rheumatic diseases (IRD) and to initiate DMARDs. DMARDs are often ineffective and may reveal digestive signs, systemic manifestations or involvement of other organs. We hypothesized that treatment of Tw infection has a favorable impact on rheumatologic and extra-rheumatologic manifestations attributed to IRD.

Objectives: To validate this hypothesis, we initiated a registry with the objectives to describe the characteristics of IRD and their treatments, the diagnostic and therapeutic modalities of Tw infections and the impact of the treatment of Tw infection on the evolution of IRD and associated DMARDs.

Methods: We initiated a French National register including adult patients with pre-existing IRD, treated with DMARDs, later diagnosed with Tw infection. Cases were identified through a call for observation via the “Club Rhumatismes et inflammations” website. We collected clinical and biological data about the characteristics of IRD and their treatments, the diagnostic and therapeutic modalities of Tw infections, and the impact of the treatment of Tw infection on the evolution of IRD and associated DMARDs.

Results: Seventy-three IRD patients were included. Mean age at diagnosis was 49 years (SD +/- 10.9), with 78% of men, median IRD duration was 79 months (IQR 36; 140), including rheumatoid arthritis (31 cases), spondyloarthritis (14 cases), psoriatic arthritis (6 cases) and other IRDs (22 cases). All IRD patients were treated with DMARDs, with no therapeutic response in 51% of the cases, worsening of rheumatologic symptoms in 34% of the cases, and occurrence of extra-articular manifestations in 27% of the cases. Screening for Tw infection mainly involved saliva and stool PCR, while diagnostic modalities involved organ specific PCR and biopsies, in particular duodenal biopsies (PCR positive in 87% of cases and histology in only 38% of cases). At the time of Tw infection diagnosis, mean age was 58 years (SD +/- 10.1), all patients had joint involvement, 33% axial involvement, 11% entheseal involvement, 84% extra-articular manifestations, 93% elevated CRP, 86% hypoalbuminemia and 67% anemia. Tw infection treatment modalities (median follow-up of 22 months) mainly involved a combination of doxycycline (95%) and hydroxychloroquine (96%), with complete recovery in 79% of the cases and Tw-related deaths in 2 cases. At the same time, Tw infection treatment was associated with IRD remission in 93% of cases, with a median time to remission of 2 months (IQR 1; 4.25), leading to DMARD withdrawal in 94% of cases and corticosteroid therapy withdrawal in 65% of cases.

Conclusion: A Tw infection should be considered in IRD patients with peripheral joint involvement and inadequate response to DMARDs, particularly in the presence of extra-articular manifestations, elevated CRP and hypoalbuminemia. In such patients, positive results of screening and diagnostic tests for Tw infection may lead to the initiation of Tw infection treatment which is associated with complete recovery of Tw infection and rapid remission of the IRD, allowing DMARD and corticosteroid therapy withdrawal in most the cases.

REFERENCES:

[1]Marth T. Tropheryma whipplei infection and Whipple’s disease. The Lancet Infectious Diseases 2016;16(3):e13–22.

[2]Puéchal X. Whipple’s arthritis. Joint Bone Spine 2016;83(6):631–5.

Acknowledgements: Club Rhumatismes et Inflammations.

Disclosure of Interests: None declared.