Fig. 21.34 ), knees, lower lumbar and cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first carpometacarpal joints, and first tarsometatarsal joints. Heberden nodes, prominent osteophytes at the distal interphalangeal joints, are common in women (but not in men). With time, joint deformity can occur, but unlike rheumatoid arthritis (discussed next), joint fusion does not take place (
Fig. 21.35). The level of disease severity detected radiographically, however, does not correlate well with pain and disability. There are still no satisfactory means of preventing primary OA, and there are no effective methods of halting its progression. Therapy includes management of pain, NSAIDs to reduce inflammation, intra-articular corticosteroids, activity modification, and, for severe cases, arthroplasty.
Rheumatoid arthritis (RA) is a chronic inflammatory disorder of autoimmune origin that principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis. RA often progresses to the destruction of the articular cartilage and, in some cases ankylosis (adhesion) of the joints. Extraarticular lesions may occur in the skin, heart, blood vessels, and lungs. The prevalence in the United States is approximately 1%, and it is three times more common in women than in men. The peak incidence is in the third through fifth decades of life.
As in other autoimmune diseases, genetic predisposition and environmental factors contribute to the development, progression, and chronicity of the disease. The pathologic changes are mediated by antibodies against self-antigens http://ebooksmedicine.net
Fig.21.33Osteoarthritis.(A)Histologicdemonstrationofthecharacteristicfibrillationofthearticularcartilage.(B)Eburnatedarticularsurfaceexposing subchondralbone(1),subchondralcyst(2),andresidualarticularcartilage(3).
and inflammation caused by cytokines, predominantly secreted by CD4+
T cells (Fig. 21.36
CD4+ T helper (TH) cells may initiate the autoimmune response in RA by reacting with an arthritogen, perhaps microbial or a chemically modified self-antigen. The T cells produce cytokines that stimulate other inflammatory cells to effect tissue injury:
IFN-γ from TH1 cells activates macrophages and synovial cells.
IL-17 from TH17 cells recruits neutrophils and monocytes.
Fig.21.34Severeosteoarthritisofthehip.Thejointspaceisnarrowed,andthereissubchondralsclerosiswithscatteredovalradiolucentcystsandperipheralosteophytelipping(arrows).
RANKL expressed on activated T cells stimulates osteoclasts and bone resorption.
TNF and IL-1 from macrophages stimulate resident synovial cells to secrete proteases that destroy hyaline cartilage.
Of these, TNF has been most firmly implicated in the pathogenesis of RA, and TNF antagonists have proved to be effective therapies for the disease (see later).