Rheumatoid Arthritis Health Article

Definition/epidemiology

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by symmetric inflammatory polyarthritis and varying degrees of extraarticular involvement. A chronic fluctuating course of the disease is experienced by most patients that may result in joint destruction, deformity, disability and premature death. ^1–4 Major economic and emotional disabilities can result from RA and can have a significant impact on patients’ families and loved ones. More than 9 million physician visits and more than 250,000 hospitalizations occur in the United States each year because of RA. ^{5, ,6}

RA affects 1% of the adult population in the United States, with women affected 2 to 3 times more often than men. The prevalence increases with age. Despite extensive research, the etiology of RA remains unknown; however, most investigators believe that a combination of genetic, environmental, hormonal, and reproductive factors is important. RA probably occurs in a genetically susceptible person with an abnormal immune response to an undetermined antigen(s). Genetic studies have shown that RA is strongly linked to HLA-DRB 10404 and - DRB 10401. ^{5, ,6}

Pathophysiology

The main target of inflammation is the synovial lining of diarthrodial joints. The earliest changes in the synovial membrane are seen in the capillaries and small blood vessels. There is proliferation of the lining cells and early infiltration by T lymphocytes. Later, there is diffuse infiltration with B and T lymphocytes, macrophages, and plasma cells. The synovial membrane undergoes hyperplastic thickening with the proliferation of lining cells and fibroblasts and formation of new blood vessels. This granulation tissue called "pannus" invades the cartilage and subchondral bone and is primarily responsible for the destruction of joint structures in RA. ^{1–4 ,7}

Immune complexes in the synovial tissue activate the complement system, which then participates in the inflammatory process. Kinins, prostaglandins, and other mediators increase the permeability of blood vessels and attract leukocytes and lymphocytes into the joint. Neutrophils and macrophages ingest immune complexes and release enzymes that degrade articular cartilage and joint structures. Rheumatoid factor (RF) and possibly other autoantibodies produced locally in the synovium participate in the formation of pathogenic immune complexes. ^{1–4 ,7}

T-cells are the major infiltrating lymphocytes in the rheumatoid synovium. Many autoantigens are targeted by the immune system in RA and some autoantigens are T-cell targets. Activated T-cells proliferate, expand, and stimulate monocytes, macrophages, and synovial fibroblasts to secrete cytokines, including interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α). Both cytokines stimulate mesenchymal cells to secrete matrix metalloproteinases that destroy cartilage and bone. Activated T-cells stimulate B-cells to produce immunoglobulins, including RF. ^{1–4 ,7}

Venules and small blood vessels become occluded by hypertrophied endothelial cells: fibrin, platelets, and inflammatory cells. The decreased circulation along with the increased metabolic demands of hypertrophy and hyperplasia results in hypoxia and metabolic acidosis. Acidosis stimulates the release of hydrolytic enzymes from synovial cells into the surrounding tissue, causing erosion of articular cartilage as well as inflammation of ligaments and tendons. ^{1–4 ,7}

Clinical Presentation

The onset of RA is usually insidious, occurring over a period of several weeks or months, but in 10% to 15% of patients there is an acute onset. The initial symptoms include general systemic manifestations of inflammation, weakness, weight loss, malaise, fatigue, anorexia, aching, and stiffness. Localized symptoms include painful, tender, swollen joints. Morning stiffness lasts for as long as 1 to 2 hours. ^{1–4 ,8}

The small joints of the hands, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, wrists and small joints of the feet, and metatarsophalangeal (MTP) joints are commonly affected initially. Joint involvement is bilateral and symmetric. The hips, knees, ankles, and shoulders may also be involved. ^{1–4 ,8}