Clinical meaning
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by inflammation of the synovial membrane (synovitis) in multiple joints, leading to progressive joint destruction. The pathogenesis involves loss of immune tolerance, with T cells and B cells recognizing self-antigens in the synovium. CD4+ T cells activate macrophages and B cells, which produce rheumatoid factor (RF, an IgM antibody against the Fc portion of IgG) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. The inflamed synovium proliferates into an aggressive tissue called pannus, which invades and destroys articular cartilage and subchondral bone through metalloproteinase and osteoclast activity. Pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6) perpetuate the inflammatory cascade and cause systemic manifestations. Unlike osteoarthritis, RA is a symmetric polyarthritis primarily affecting small joints of the hands and feet, with characteristic morning stiffness lasting >60 minutes. Extra-articular manifestations include rheumatoid nodules, interstitial lung disease, pericarditis, scleritis, Felty syndrome (RA + splenomegaly + neutropenia), and accelerated atherosclerosis.