Description

• Chronic systemic inflammatory disease with symmetric polyarthritis and synovitis of unknown cause
• Hallmarks include involvement of large and small joints with joint pain and swelling.
• Progressive chronic inflammation leads to joint destruction, deformity, and decline in functional status.
• System(s) affected: Musculoskeletal; Skin; Hematologic; Lymphatic; Immunologic; Muscular; Renal; Cardiovascular; Neurologic; Pulmonary

• Increased contribution/interaction of age-related comorbidities; pericarditis, septic arthritis, Sjögren syndrome are more common
• Less tolerance to drugs; increased incidence of hydroxychloroquine-associated maculopathy, D-penicillamine rash, and sulfasalazine-induced nausea/vomiting

• Use effective contraception with disease-modifying antirheumatic drugs (DMARDs). Modify regimen with pregnancy or breastfeeding.
• Labor/Delivery pose no serious problems, unless there is severe mechanical joint disease.
• >75% improve during pregnancy, but relapse in 6 months. First episodes may occur in pregnancy.

Epidemiology

• Incidence of RA is ~3 cases per 10,000.
• Women are affected ~3–5× more than males:
  • Female > Male (2–3:1; overall incidence and prevalence of articular manifestations).
• Peak age is 35–50 years.

Prevalence
US population: 0.5–1.5% (1). Affects all populations with increased prevalence in Native Americans

Risk Factors

• HLA genes contribute to 30–50% genetic risk.
• Family history: 1st-degree relative has 2–3-fold increased risk
• Native American ethnicity
• History of smoking has shown an increased prevalence of RA.

• Genetic factors account for ~50% of development of RA.
• Monozygotic twin concordance 15–20%, implying nongenetic roles contributing to development of RA
• 1st-degree relatives have 1.5-fold higher risk than the general population of developing RA.
• HLA-DR4+ persons have increased relative risk of 4–5×.

Pathophysiology

Pathogenesis is not completely known, but is postulated to be triggered by an insult such as infection that precipitates an initial autoimmune reaction. Systemic disorder primarily affecting synovial tissues whereby antibody-complement complex activation leads to synovial hypertrophy and joint inflammation. Pathogenesis mediated by abnormal B- and T-cell interactions.

Etiology

Multifactorial based on genetic, host (hormonal, immunologic), environmental (socioeconomic, smoking) factors

Commonly Associated Conditions

• Sjögren syndrome, Felty syndrome, amyloidosis
• Increased incidence of infections, lymphomas, and renal and cardiovascular disease
• Anemia, scleritis, pulmonary fibrosis, kidney disease, and peripheral neuropathy