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RA risk lower after urinary and gut infections

But respiratory infections have no effect on risk of developing the disease

Louise Prime

Thursday, 05 February 2015

People may be less likely to develop rheumatoid arthritis if they have recently suffered urogenital or gut infections, research has shown – but respiratory infections have no such effect. Authors of the study*, published today in Annals of the Rheumatic Diseases, suggest this could be because of links between bacteria in the gut, the use of different types of antibiotics, and the inflammatory process.

Between 1996 and 2009 in Sweden, 6,401 women and men (with a mean age of 52 years) had enrolled in a population-based case-control study of rheumatoid arthritis, in which the cases were people newly diagnosed with RA. At enrolment, all participants had been asked whether in the preceding two years they had had gastroenteritis, urinary tract infection, genital infection, prostatitis, sinusitis, tonsillitis and pneumonia. Researchers analysed data from this study to look for associations between recent infection, and the development of RA.

They found that recent gastrointestinal and urogenital tract infections (i.e. in the past two years) were associated with a significantly lowered risk of RA (odds ratios 0.71 for gastroenteritis, 0.78 for urinary tract infections and 0.80 for genital infections). Having recently had all three types of infection halved the risk of developing RA (OR 0.50). Adjusting for smoking and socioeconomic factors barely affected these results.

There was a non-significant but similar degree of risk reduction (OR 0.64) associated with prostatitis; sinusitis, tonsillitis or pneumonia had no effect on risk of developing RA.

The study authors acknowledged that because their study was observational, they couldn’t make definitive conclusions about cause and effect. But they suggested several possible biological mechanisms underlying their results. One is that a decreased prevalence of infections might indicate a strong capacity for immune activation in general at mucosal surfaces that could, in some as-yet unknown way, be linked to protection against RA. They added: “A second, and partly related, potential explanation would be that infections in the gut and urinary tract may change the composition of the microbiome and that such a change would influence the susceptibility to RA … [recent] reports from basic science suggest that changes in the gut microbiome may play a role in the pathogenesis of RA.”

They also pointed out that that the sites of infections that conferred a decreased risk of RA in their study are primarily infected with gram-negative bacteria, while those sites in which infections did not confer a decreased risk are primarily infected with gram-positive bacteria. They said: “Both sulfa (sulfasalazine) and tetracycline drugs, used for gram-negative infections at these particular sites, have in double-blind randomised clinical trials published before the era of ‘biologic’ treatments in RA been shown to be effective against RA.”


* Sandberg M E C, et al. Recent infections are associated with decreased risk of rheumatoid arthritis: a population-based case-control study. Ann Rheum Dis 2015; doi:10.1136/annrheumdis-2014-206493

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