Rheumatoid Arthritis : Pathophysiology, Diagnosis, and Treatments
Rheumatoid arthritis (RA) is a chronic and usually progressive inflammatory disorder of unknown etiology characterized by polyarticular symmetric joint involvement and systemic manifestations.
RA results from a dysregulation of the humoral and cell-mediated components of the immune system. Most patients produce antibodies called rheumatoid factors; these seropositive patients tend to have a more aggressive course than patients who are seronegative.
Immunoglobulins can activate the complement system, which amplifies the immune response by enhancing chemotaxis, phagocytosis, and release of lymphokines by mononuclear cells that are then presented to T lymphocytes. The processed antigen is recognized by the major histocompatibility complex (MHC) proteins on the lymphocyte surface, resulting in activation of T and B cells.
Chronic inflammation of the synovial tissue lining the joint capsule results in tissue proliferation (pannus formation). Pannus invades cartilage and eventually the bone surface, producing erosions of bone and cartilage and leading to joint destruction. The end results may be loss of joint space, loss of joint motion, bony fusion (ankylosis), joint subluxation, tendon contractures, and chronic deformity.
Laboratory abnormalities that may be seen include normocytic, normochromic anemia; thrombocytosis or thrombocytopenia; leukopenia; elevated erythrocyte sedimentation rate (ESR); positive rheumatoid factor (60% to 70% of patients); and positive antinuclear antibodies (ANA) (25% of patients).
Examination of aspirated synovial fluid may reveal turbidity, leukocytosis, reduced viscosity, and normal or low glucose relative to serum concentrations.
– NonPharmacologic Therapy
Adequate rest, weight reduction if obese, occupational therapy, physical therapy, and use of assistive devices may improve symptoms and help maintain joint function.
Patients with severe disease may benefit from surgical procedures such as tenosynovectomy, tendon repair, and joint replacements.
– Pharmalogic Theraphy
A disease-modifying antirheumatic drug (DMARD) should generally be started within the first 3 months of symptom onset. DMARDs should be used in all patients except those with limited disease or those with class IV disease in whom little reversibility is expected. Early use of DMARDs results in a more favorable outcome and can reduce mortality.
First-line DMARDs include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. The order of agent selection is not clearly defined. Hydroxychloroquine or sulfasalazine may be used initially in mild disease, but methotrexate is often chosen initially in more severe cases because of long-term data suggesting superior outcomes than other DMARDs and lower cost than biologic agents. Leflunomide appears to have long-term efficacy similar to methotrexate.