Rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory polyarthropathy of unknown etiology that targets synovial tissues. It has a prevalence of about 1% in adults across the world. Women are twice as likely to be affected than men. Smoking and infections have been cited as risk factors, and the gene HLA DRB1 has been associated in the development of the gene.
All patients exhibit some systemic features such as fatigue, low-grade fevers, anemia, and elevated ESR or CRP. This systemic inflammatory process causes vascular endothelial damage leads to a marked increased risk for coronary artery disease and congestive heart failure.
Twin studies have shown a concordance rate of approximately 15% for monozygotic twins, giving us a clear genetic predilection for the disease, associated with the HLA DR1 gene. However, the genetic component is not enough to cause RA on its own, a trigger is often required as illustrated below.
The pathogenesis of RA is complicated. In essence it is thought that the process is initiated by an as of yet unknown trigger, that activates T helper cells (particularly TH1 and Th17) which appear to predominate in synovial tissues. These T cells secrete cytokines that drive further synovial proliferation. Humoral immunity also plays an important role, rheumatoid factor (RF), an auto antibody (IgM) is a clear serological marker and its level correlates with more severe diseases, including erosion of the bone and extra-articular features. The exact role of RF is unclear, but it is thought that RF production increases complement activation and therefore increases lysosomal enzymes, kinins and free radicals.
While synovial tissues are the primary target, the generalised inflammation involves the vascular endothelium and results in significant premature atherosclerosis. Once the process begins, the proliferation of the synovial tissues (synovitis) causes excess amounts of synovial fluid. Synovitis results in the destruction of cartilage and marginal bone and can eventually cause rupture of the joint capsule or tendons and ligaments.
Articular manifestations
RA can affect any of the synovial joints. It most commonly starts with the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) and metatarsophalangeal (MTP) joints, followed by wrists, knees, elbows, ankles, hips and shoulders (roughly in that order).