Chronic Diarrhea Associated With Increased Risk for Incident Rheumatoid Arthritis in Women

elderly woman with stomach pains, gastrointestinal
Women with chronic diarrhea may be at increased risk of developing rheumatoid arthritis, particularly if they have a history of smoking.

Women with chronic diarrhea may be at increased risk of developing rheumatoid arthritis (RA), according to study data published in Rheumatology. The association between diarrhea and RA risk was particularly pronounced among women who reported past or current smoking.

Understanding the potential associations between an imbalance in gut microbiota and RA, researchers used data from a prospective cohort of healthy French women enrolled in a national insurance policy (N=98,995) to examine whether chronic diarrhea is linked to RA risk. Women born between 1925 and 1950 were mailed questionnaires that asked them to report their health status. Since 1990, biennial questionnaires have been administered to the same cohort to gather information on their health and lifestyle. The present study used data from the 1993 questionnaire as a baseline metric, which captured gastrointestinal symptoms, including diarrhea and constipation.

Data from women who completed the 1993 questionnaire were examined for cases of incident RA, which were identified from answers to the inflammatory disease section of subsequent questionnaires. Cox regression models were used to calculate the hazard ratios (HRs) for incident RA in women with and without normal gastrointestinal transit. Models were adjusted for age, smoking status, and other known RA risk factors.

Questionnaire responses from 65,424 women were used in the analyses, with a total of 1,329,562 person-years of follow-up. Mean age at baseline was 52.6±6.5 years. At baseline, 46,598 women (71.2%) self-described their gastrointestinal transit as normal, 1835 (2.8%) reported diarrhea, 9173 (14.0%) reported constipation, and 7818 (12.0%) reported alternating diarrhea and constipation.

Overall, 530 cases of incident RA were reported after a mean of 11.7±5.9 years of follow-up. Compared with normal gastrointestinal transit, chronic diarrhea was significantly associated with incident RA in the age-adjusted regression model (HR, 1.70; 95% CI, 1.13-2.58). This association remained significant after adjustments for passive smoking in childhood, educational level, and body mass index (HR, 1.68; 95% CI, 1.11-2.53).

In regression models stratified by smoking status, the association between chronic diarrhea and RA risk only remained among individuals who reported ever smoking (HR, 2.21; 95% CI, 1.32-3.70). Among women who had never smoked, chronic diarrhea was no longer significantly associated with incident RA (HR, 1.15; 95% CI, 0.57-2.33). Sensitivity analyses that removed incident cases diagnosed within 2, 5, and 10 years of follow-up produced similar results.

These data suggested that chronic diarrhea may be associated with subsequent RA development, particularly among women who reported current or past smoking. As study limitations, investigators noted that gastrointestinal symptoms were ascertained by self-report rather than medical record review. In addition, all women were in middle to late adulthood, which may limit generalizability to younger women.

Further study is necessary to explore the role of chronic diarrhea in the pathogenesis of RA. “These data fit with the mucosal origin hypothesis of RA, where interaction between intestinal dysbiosis and smoking could occur at an early stage to promote emergence of autoimmunity, followed years later by clinical disease,” the investigators wrote.


Nguyen Y, Mariette X, Salliot C, Gusto G, Boutron-Ruault M-C, Seror R. Chronic diarrhoea and risk of rheumatoid arthritis: findings from the French E3N-EPIC cohort study [published online May 17, 2020]. Rheumatology (Oxford). doi:10.1093/rheumatology/keaa133