Rheumatoid arthritis (RA) causes premature mortality, disability and compromised quality of life in the industrialized and developing world (1). Rheumatoid arthritis is a systemic inflammatory disease which manifests itself in multiple joints of the body. The inflammatory process primarily affects the lining of the joints (synovial membrane), but can also affect other organs. The inflamed synovium leads to erosions of the cartilage and bone and sometimes joint deformity. Pain, swelling, and redness are common joint manifestations. Although the causes are unknown, RA is believed to be the result of a faulty immune response. RA can begin at any age and is associated with fatigue and prolonged stiffness after rest. There is no cure for RA, but new effective drugs are increasingly available to treat the disease and prevent deformed joints. In addition to medications and surgery, good self-management, including exercise, are known to reduce pain and disability.

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The etiology, or cause, of RA is unknown. Many cases are believed to result from an interaction between genetic factors and environmental exposures.

Socio-demographics: The incidence of RA is typically two to three times higher in women than men. The onset of RA, in both women and men, is highest among those in their sixties(2)

Genetics: There is longstanding evidence that specific HLA class II genotypes are associated with increased risk. Most attention has been given to the DR4 and DRB1 molecules of the major histocompatability complex HLA class II genes. The strongest associations have been found between RA and the DRB1*0401 and DRB1*0404 alleles (12). More recent investigations indicate that of the more than 30 genes studied, the strongest candidate gene is PTPN22, a gene that has been linked to several autoimmune conditions(12).

Modifiable: Several modifiable risk factors have been studied in association with RA including reproductive hormonal exposures, tobacco use, dietary factors, and microbial exposures.

Smoking Among these risk factors, the strongest and most consistent evidence is for an association between smoking and RA. A history of smoking is associated with a modest to moderate (1.3 to 2.4 times) increased risk of RA onset (2). This relationship between smoking and RA is strongest among people who are ACPA-positive (anti-citrullinated protein/peptide antibodies), a marker of auto-immune activity (12).

Reproductive and breastfeeding history Hormones related to reproduction have been studied extensively as potential risk factors for RA:

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CDC - Arthritis - Basics - Definition - Rheumatoid Arthritis