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Rheumatoid Arthritis

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Rheumatoid Arthritis

  • Epidemiology
  1. Prevalence: 0.3 - 1.5% of population worldwide
  2. Women affected 2-3x more often (account for more than three-quarters of patients)
  3. Twin concordance: 30 to 50%
  4. Peak Incidence ages 30 to 50 years (mean age of onset 48 years old)
  5. Associated with HLA-DR4 and HLA-DR1 haplotypes
  6. Associated with STAT4 gene and CD40 locus
  • Pathophysiology
  • Order of changes
  1. Synovial Macrophage and fibroblast activation
  2. Cytokine production (interleukin-6, tumor necrosis factor or TNF)
  3. Lymphoctes infiltrate perivascular areas
  4. Synovial thickening (Pannus formation and spread)
  5. Neovascularization
  6. Local micro-Vasculitis
  7. Chondrocyte, Osteoclast, CD4+ Helper activity
  8. Endothelial proliferation
  9. Joint space narrowing
  10. Cytokine release (resulting in fever, Anemia)
  • Risk Factors
  1. Increased risk
    1. Female gender
    2. Family History of Rheumatoid Arthritis
    3. Tobacco abuse (most significant environmental trigger)
      1. Relative Risk: 2.2 for more than 40 pack year smokers
    4. More than 3 cups coffee daily (esp. decaffeinated)
  2. Decreased risk
    1. Women who've had children
    2. Breastfeeding
  3. References
    1. Kuder (2002) Rev Environ Health 17:307-15 [PubMed]
    2. [PubMed]
  • Course
  1. Self-limited (5-20%)
  2. Minimally progressive (5-20%)
  3. Progressive (60-90%)
    1. Early damage
      1. Two Years from onset:
        1. Joint space narrowing and erosions in 50%
      2. Ten years from onset:
        1. Young working patients are disabled: 50%
    2. Early death by multiple causes
      1. Women's Life Expectancy reduced by 10 years
      2. Men's Life Expectancy reduced by 4 years
  • Labs (ARA recommended, but do not exclude diagnosis)
  1. Initial Labs
    1. Complete Blood Count with differential
    2. Rheumatoid Factor (Initially positive in 70%)
    3. Sedimentation Rate (ESR) or C-Reactive Protein (C-RP)
    4. Consider Anticyclic citrullinated peptide Antibody
    5. Consider Antinuclear Antibody (especially in juvenile forms as has prognostic value)
  2. Additional labs in preparation for rheumatic agents
    1. Liver Function Tests
    2. Renal Function tests
  3. Labs needed before Steroids, TNF Inhibitors or DMARDs
    1. PPD with candida controls
    2. HBsAg
    3. Hepatitis C Antibody
  4. Markers of disease course
    1. C-Reactive Protein (C-RP)
    2. Erythrocyte Sedimentation Rate
    3. Wrist XRay or Ankle XRay
    4. Anticyclic citrullinated peptide Antibody
  • Imaging
  1. Obtain baseline hand and feet XRays
    1. May demonstrate periarticular erosive changes
    2. May define more aggressive disease
  2. See Rheumatoid Arthritis Related XRay Changes
  3. Chest XRay (erosions define moderate to severe disease)
  • Associated Conditions
  1. See Rheumatoid Arthritis Extra-articular Signs
  2. Atlanto-axial instability
    1. Exercise caution with intubation
    2. Risk of C-Spine Fracture with Trauma
  3. Lymphoma
  4. Insulin Resistance (50-60%)
  5. Coronary Artery Disease
    1. See Cardiac Risk Management
    2. Rheumatoid Arthritis is now considered a coronary equivalent (similar to Diabetes Mellitus cardiovascular risk)
      1. Kaplan (2006) Curr Opin Rheumatol 18:289–97 [PubMed]
    3. Methotrexate is associated with reduced cardiovascular risk
      1. Westlake (2010) Rheumatology 49: 295-307 [PubMed]
  • Prognosis
  • Predictors of prolonged Remission (achieved in 10-50% of patients)
  1. Males
  2. Non-smokers
  3. Age under 40 years old
  4. Onset after age 65 years
  5. Shorter duration of Rheumatoid Arthritis
  6. Milder Rheumatoid Arthritis disease course
  7. Acute phase reactants not elevated (e.g. C-RP)
  8. Rheumatoid Factor negative
  9. Anti-citrullinated protein Antibody negative
  • Prognosis
  • Poor Prognostic Signs
  1. Hyper-acute onset (overnight onset)
  2. Multiple joint involvement (especially >20 joints)
  3. High titer Rheumatoid Factor (RF)
  4. HLA-DRBI 0404
  5. Low dose Corticosteroid resistance
  6. Early loss of function or young age of onset
  7. Higher Erythrocyte Sedimentation Rate
  8. Rheumatoid Arthritis Extra-articular Signs