0801: Impact of Diagnosis and Treatment of Tropheryma Whipplei Infection in Patients with Pre-existing Chronic Inflammatory Rheumatic Diseases: Data from the National Tw-IRD Registry
Damien CAILLET PORTILLLO1, Xavier Puéchal2, Yannick Degboe1, Marie Kostine3, Alexia Michaut4, Andre Ramon5, Daniel Wendling6, Nathalie Costedoat-Chalumeau7, Pascal Richette8, Hubert Marotte9, Justine VIX10, Jean Jacques Dubost11, Sebastien Ottaviani12, Gaël Mouterde13, Anne Grasland14, Aline Frazier-Mironer15, Vincent GERMAIN16, Fabienne COURY17, Anne Tournadre11, Martin Soubrier18, Pauline Brevet19, Laurent Cavalie20, Laurent Arnaud21, Christophe Richez22, Adeline Ruyssen-Witrand23 and Arnaud Constantin24, 1Pierre-Paul Riquet University Hospital, Toulouse & Toulouse III University - Paul Sabatier, Rheumatology, Toulouse, France, 2National Referral Center for Rare Systemic Autoimmune Diseases, Cochin Hospital, Paris, France, 3Pellegrin Hospital, University Hospital of Bordeaux, Rheumatology, Bordeaux, France, 4Hospital center, Loire Vendée Ocean, Rheumatology, La Roche-sur-Yon, France, La Roche-sur-Yon, France, 5University Hospital of DIJON, Rheumatology, Dijon, France, 6CHU, University Teaching Hospital, Besançon, France, 7Inserm DR Paris 5, Paris, France, 8Department of Rheumatology, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France, 9INSERM 1059, Saint-Etienne, France, 10University Hospital of poitiers, Rheumatology, Poitiers, France, Poitiers, France, 11University Hospital of Clermont Ferrand, Rheumatology, Clermont-Ferrand, France, 12Hopital Bichat-Claude Bernard, Paris, France, 13Lapeyronie Hospital, Montpellier, France, 14Louis-Mourier Hospital, AP-HP, Colombes, Rheumatology, Colombes, France, 15APHP Hôpital Lariboisire, Paris, France, 16Pau Hospital, Rheumatology, Pau, France, Pau, France, 17Pierre-Bénite Hospital, University Hospital Lyon, Rheumatology, Lyon, France, 18Gabriel-Montpied Hospital, Clermont-Ferrand, France, 19University Hospital of Rouen, Rheumatology, Rouen, France., Le Havre, France, 20Purpan Hospital, Federal Institute of Biology (IFB), University Hospital, Toulouse, Biology, Toulouse, France, 21Hautepierre Hospital, University Hospital of Strasbourg, Rheumatology, Strasbourg, France, 22Université de Bordeaux, Bordeaux, France, 23CHU de Toulouse, Toulouse, France, 24Toulouse University Hospital, Toulouse, France
Background/Purpose: 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.
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 registry including 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), spondyloarthritis (14), psoriatic arthritis (6) and other IRDs (22). All IRD patients were treated with DMARDs, with no therapeutic response in 51% of cases, worsening of rheumatologic symptoms in 34% of cases, and occurrence of extra-articular manifestations in 27% of 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 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, high 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.
Disclosures: D. CAILLET PORTILLLO, None; X. Puéchal, Roche; Y. Degboe, None; M. Kostine, Bristol-Myers Squibb(BMS), Merck/MSD, Novartis, Janssen, Biogen; A. Michaut, None; A. Ramon, None; D. Wendling, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Merck/MSD, Pfizer, Roche, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Eli Lilly, Sandoz, Galapados, Grunenthal; N. Costedoat-Chalumeau, UCB, Roche; P. Richette, AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB; H. Marotte, AbbVie/Abbott, Amgen, Biogen, Bristol-Myers Squibb(BMS), CellTrion HealthCare, Fresenius Kabi, HealthCare, Janssen, Eli Lilly, Nordic Pharma, Novartis, Medac, Pfizer, Merck/MSD, Galapagos, UCB; J. VIX, None; J. Dubost, None; S. Ottaviani, None; G. Mouterde, None; A. Grasland, None; A. Frazier-Mironer, None; V. GERMAIN, None; F. COURY, None; A. Tournadre, AbbVie, Eli Lilly, Fresenius-Kabi, Novartis, Pfizer, Sanofi, UCB; M. Soubrier, None; P. Brevet, None; L. Cavalie, None; L. Arnaud, AstraZeneca, Novartis, GlaxoSmithKlein(GSK), Bristol-Myers Squibb(BMS), Bristol-Myers Squibb(BMS); C. Richez, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb(BMS), Galapados, GlaxoSmithKlein(GSK), Eli Lilly, Novartis, Pfizer; A. Ruyssen-Witrand, Pfizer, AbbVie/Abbott, Novartis, Eli Lilly, Janssen, Bristol-Myers Squibb(BMS), galapagos, fresenius kabi, Merck/MSD, UCB, Pfizer, Roche, Sanofi; A. Constantin, None.
