Although genetic factors are important in the development of rheumatoid arthritis (RA), not all those who are genetically susceptible develop the disease. Twin studies in the United Kingdom and Australia have shown disease concordance rates in monozygotic twins of between 15 to 21%.^1,2 Earlier studies also showed only modest concordance for autoantibody and immunoglobulin production within twin pairs.^3,4 There is weak evidence, however, of an increased concordance of RA, rheumatoid factor, and other autoantibodies within spouse pairs.⁵ These observations have encouraged the search for environmental triggers, such as infection. In this issue of The Journal [The Journal of Rheumatology], for example, a report from Finland has highlighted the high prevalence of prior infection in patients newly presenting with all forms of inflammatory arthritis.⁶

Evidence that infection is the likeliest environmental trigger for RA is considered in this review: First, we look at the different ways in which infection might act as an etiological agent in RA. We then discuss whether the descriptive epidemiology of RA is consistent with an infective trigger. In conclusion, we review evidence that various specific infections play a role in the causation of the disease.

Historically, demonstrating that an infectious agent plays a key role in disease has required the fulfilment of Koch’s postulates. These derive from a model of infectious disease whereby the etiological organism has a direct and continuing role in pathogenesis. However, the relationship between infection and a disease such as RA may be more subtle and complex, and different types of experimental design and evidence may therefore be required to confirm any given organism’s role in the disease. Koch’s postulates have recently been reformulated to define the criteria that need to be fulfilled to determine whether an organism might have an etiological role in …