A chronic multisystem disease of unknown etiology characterized by persistent inflammatory synovitis, usually involving peripheral joints in a symmetric fashion. Although cartilaginous destruction, bony erosions, and joint deformity are hallmarks, the course of RA can be quite variable. An association with HLA-DR4 has been noted; both genetic and environmental factors may play a role in initiating disease. The propagation of RA is an immunologically mediated event in which joint injury occurs from synovial hyperplasia; lymphocytic infiltration of synovium; and local production of cytokines and chemokines by activated lymphocytes, macrophages, and fibroblasts.