Arthritis, Rheumatoid (RA)
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- Chronic systemic autoimmune inflammatory disease with symmetric polyarthritis and synovitis
- Progressive chronic inflammation leads to large and small joint destruction, deformity, decline in functional status, and premature morbidity/mortality.
- System(s) affected: musculoskeletal, skin, hematologic, lymphatic, immunologic, muscular, renal, cardiovascular, neurologic, pulmonary
- Increased age-related comorbidities
- Decreased medication tolerance; increased incidence of hydroxychloroquine-associated maculopathy and sulfasalazine-induced nausea/vomiting, NSAID-induced gastric ulcers, and corticosteroid-induced diabetes and osteoporosis
- Use effective contraception in patients taking disease-modifying antirheumatic drugs (DMARDs).
- Methotrexate, leflunomide, cyclophosphamide, and cyclosporine are teratogenic. Sulfasalazine and hydroxychloroquine are safe to use during pregnancy and breastfeeding.
- 50–80% of patients improve during pregnancy because of immunologic tolerance. Most relapse in 6 months after delivery. First episode may occur in pregnancy or postpartum.
- 25 to 30/100,000 for males
- 50 to 60/100,000 for females
- Peak age at onset is 35 to 50 years.
1% of the U.S. population
Etiology and Pathophysiology
- An insult (e.g., infection, smoking, trauma) precipitates an autoimmune reaction activating antibody-complement complexes, resulting in endothelial activation, synovial hypertrophy, and joint inflammation/damage.
- Pathogenesis is mediated by abnormal B- and T-cell interactions and cytokine overproduction (TNF and IL-6).
- Multifactorial disease with genetic, host (hormonal, immunologic), and environmental (socioeconomic, smoking) factors
- RA is 50% attributable to genetic causes. HLA-DR4 is a shared epitope in over 50% of cases.
- Monozygotic twin concordance is 15–20%, suggesting nongenetic factors also contribute.
- Individuals with HLA-DR4 and DRB1, and mutations in STAT4, CD40+ have increased relative risk.
- First-degree relatives have 2- to 3-fold increased risk.
- Smokers have elevated relative risk of 1–2%. Smoking is associated with an increased risk of developing ACPA-positive antibodies.
- Pregnancy and breastfeeding for 24 months lowers risk up to 50%.
- Women affected 3:1; difference diminishes with age.
Commonly Associated Conditions
Accelerated atherosclerosis, pericarditis, amyloidosis, Felty syndrome (RA, splenomegaly, neutropenia), interstitial lung disease, pulmonary nodules, rheumatoid nodules, vasculitis, lymphomas, and carpal tunnel syndrome