Which of the following statements regarding rheumatoid arthritis is true?
ExplanationThe prevalence of RA is 0.8%, and females are three times more likely to be affected than males. However, as the population ages, the prevalence increases and the sex difference diminishes. RA is found throughout the world and affects people of all races. Age of onset is most commonly 35–50 years. Family studies show a clear genetic predisposition. First-degree relatives have approximately four times the expected rate of RA. Other risk factors for RA include the class II major histocompatibility antigen HLA-DR4. Approximately 70% of patients with RA have HLA-DR4. However, this association is not true in Africans or African Americans, among whom 75% do not show this allele. The role of this allele in the pathogenesis of RA remains unknown because the cause of RA is unknown. The earliest lesion in RA is microvascular injury with an increase in the number of synovial lining cells. Increased numbers of mononuclear cells are seen in the synovial lining, and this is thought to be under the control of CD4+ T lymphocytes. As the inflammation continues, the articular matrix is degraded by collagenases and cathepsins produced by the inflammatory cells. Other cytokines produced by the inflammatory cells include IL-1 and TNFα. Over time, bone and cartilage are destroyed, leading to the end-stage clinical manifestations. Rheumatoid factor (RF) is an IgM molecule directed against the Fc portion of IgG and is found in two-thirds of patients with RA. However, this molecule is found in approximately 5% of healthy persons and more than 10% of persons older than age 60. It is not known to have a role in the pathogenesis of the disease, but titers of RF are shown to be predictive of the severity of clinical manifestations or the presence of extraarticular manifestations.
