Arthritis, Rheumatoid (RA)

Arthritis, Rheumatoid (RA) is a topic covered in the 5-Minute Clinical Consult.

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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

Geriatric Considerations
Decreased medication tolerance; increased incidence of hydroxychloroquine-associated maculopathy and sulfasalazine-induced nausea/vomiting, NSAID-induced gastric ulcers, and corticosteroid-induced diabetes and osteoporosis

Pregnancy Considerations
  • 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, interleukin-6 [IL-6]).
  • Multifactorial disease with genetic, host (hormonal, immunologic), and environmental (socioeconomic, smoking) factors

  • Rheumatoid arthritis (RA) is 50% attributable to genetic causes. HLA-DR4 is a shared epitope in >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.

Risk Factors

  • First-degree relatives have 2- to 3-fold increased risk.
  • Smokers have elevated relative risk. Smoking is associated with an increased risk of developing anticitrullinated protein antibody (ACPA)-positive antibodies.
  • Pregnancy and breastfeeding 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, carpal tunnel syndrome

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