Rheumatoid arthritis and osteoarthritis (also called degenerative joint disease) are the most common forms of arthritis. Both of these chronic conditions are characterized by pain, stiffness, restricted joint motion, joint deformities, and disability, but their differences in pathogenesis, pathology, and clinical features must be distinguished because the prognosis and treatment of the two diseases differ.

RHEUMATOID ARTHRITIS

Rheumatoid arthritis is a chronic, inflammatory systemic illness with widespread involvement of connective tissue. Although rheumatoid arthritis may begin at any age, onset is usually in the fourth or fifth decade. Occurring in all parts of the world, it affects females two to three times more often than males.

The major characteristic of rheumatoid arthritis is inflammation of multiple joints (polyarthritis), usually the joints of the limbs. Although partial remissions are common, relapses and progression of active disease are common. If unchecked, the joint inflammation causes irreversible damage to the articular cartilage and bone, resulting in joint deformity and disability.

JOINT PATHOLOGY

There are one to two layers of the synovial lining cells in the synovium in normal joints, which mainly consist of two types of synovial lining cells (also called synoviocytes): type A (macrophage-like cells) and type B (fibroblast-like cells). Type C cells are synovial dendritic cells. In contrast, rheumatoid joint synovium becomes thickened, with more than three layers of synoviocytes. In addition to the synoviocytes, cell infiltrates including neutrophils, lymphocytes, and plasma cells also contribute to the synovial hypertrophy. The synoviocytes, neutrophils, and lymphocytes together constitute synovial cells, which produce numerous pathogenic molecules leading to the disease process in the rheumatoid synovium. Among the molecules are numerous cytokines that play important pathogenic roles. Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), have been extensively studied and confirmed to be pathogenic. On the basis of these proinflammatory cytokines, several biologic agents that target these cytokines have been developed and have been approved to treat rheumatoid arthritis. These agents include TNF-α inhibitors or blockers such as etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), and golimumab as well as the IL-1 antagonist anakinra (Kineret) (see later section on therapy for rheumatoid arthritis). In the rheumatoid synovium there are other cytokines, such as IL-17, IL-18, and lymphotoxin-β that could be potential therapeutic targets in the future. In addition, other molecules such as chemokines are found to be involved in the rheumatoid disease process. These chemokines bind to their receptors CXCR3 and CCR5 to recruit inflammatory cells to the sites of the joint inflammation.