Chapter 286 RHEUMATOID ARTHRITIS

Frank C. Arnett

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting diarthrodial joints and frequently a variety of other organs. TheAmericanCollegeof Rheumatology revised the classification criteria for RA to guarantee uniformity in investigative and epidemiologic studies(Table 286-1). Although these seven items include the most characteristic clinical features of RA, a variety of other disorders may mimic the disease (see Differential Diagnosis andTable 286-3).

RA occurs worldwide in all ethnic groups. Prevalence rates range from 0.3 to 1.5% in most populations, but frequencies of 3.5 to 5.3% have been found in several Native American tribes (Yakima, Chippewa, Inuit). The peak incidence of onset is between the 4th and 6th decades, but RA may begin at any time from childhood (see Juvenile Chronic Arthritis) to later life. Females are two to three times more likely to be affected than males.

ETIOLOGY.

Despite intensive research over many decades, the cause of RA remains unknown. Three areas of interrelated research are currently most promising: (1) host genetic factors, (2) immunoregulatory abnormalities and autoimmunity, and (3) a triggering or persisting microbial infection.

Genetic susceptibility to RA has been clearly demonstrated. The disease clusters in families and is more concordant in monozygotic (30%) than dizygotic (5%) twins. Certain major histocompatibility complex (MHC) class II alleles (and their encoded HLA, or human leukocyte antigens) occur with increased frequency in affected individuals. Among white people of western European origin, HLA-DR4 occurs in 60 to 70% of seropositive patients with RA as compared with 25 to 30% of normal individuals. HLA-DR1 is found in the majority of HLA-DR4-negative patients and is most strongly associated with the disease in several other ethnic groups (Israelis, Asian Indians). Several subtypes of HLA-DR4 were initially defined by mixed