The present study showed an intersting link between the chronic diarrhea and the risk of furher RA development and that too mainly among ever-smokers. 

The objective of the study was to estimate the relationship between the gastrointestinal disorders and risk of further RA) development.

The french prospective cohort included 98995 healthy women since 1990. The questionnaires related to health information and lifestyles were completed by all the participants. In 1993, the third questionnaire was sent to the participants for estimating gastrointestinal disorders. Cox proportional hazards regression model with age as the time scale was utilized to find the hazard ratio and 95% CIs for incident RA. The models were adjusted for age, known risk factors of RA like smoking and possible cofounders.

Out of the 65454 cases, five hundred thirty proved incident RA cases were diagnoses post 11.7 years of the study baseline. Compared to patients with no gastrointestinal problems, chronic diarrhea was found to be linked with a higher risk of RA development, independently of dietary habits or dysthyroidism. Also, the association was even stronger in ever-smokers. However, there was no link between the risk of RA and constipation or alternating constipation/diarrhea.

A significant association was noted between chronic diarrhea and increased risk of further development of RA, mainly among ever-smokers. These findings go well with the mucosal origin hypothesis of RA, where an early association between smoking and intestinal imbalance has been noted to increase the emergence of autoimmunity, resulting in the development of clinical disease at a later stage.