II. Epidemiology
- Prevalence: 0.5 to 1% in U.S. and 0.3% worldwide
- Women affected 2-3x more often (account for more than three-quarters of patients)
- Twin concordance: 30 to 50%
- Peak Incidence ages 30 to 50 years (mean age of onset 48 years old)
- Associated with HLA-DR4 and HLA-DR1 haplotypes
- Associated with STAT4 gene and CD40 locus
III. Pathophysiology: Order of changes
- Immune response
- Autoantibodies to citrulline-containing endogenous Proteins (response to genetic and environmental factors)
- Synovial Macrophage and fibroblast activation
- Cytokine production and release (Interleukin-6, Tumor Necrosis Factor or TNF) results in fever, Anemia
- Lymphoctes infiltrate perivascular areas
- Musculoskeletal and vascular effects
- Synovial thickening (Pannus formation and spread)
- Neovascularization
- Local micro-Vasculitis
- Chondrocyte, Osteoclast, CD4+ Helper activity
- Endothelial proliferation
- Joint space narrowing
IV. Risk Factors
- Increased risk
- Female gender
- Family History of Rheumatoid Arthritis
- Tobacco Abuse (most significant environmental trigger)
- Relative Risk: 2.2 for more than 40 pack year smokers
- Also associated with more severe joint disease and extraarticular disease (e.g. Vasculitis, pulmonary fibrosis)
- More than 3 cups coffee daily (esp. decaffeinated)
- Decreased risk
- Women who've delivered children
- Breastfeeding
- Diets rich in fish
- References
V. Findings
VI. Course
- Self-limited (5-20%)
- Minimally progressive (5-20%)
- Progressive (60-90%)
- Early damage
- Two Years from onset:
- Joint space narrowing and erosions in 50%
- Ten years from onset:
- Young working patients are disabled: 50%
- Two Years from onset:
- Early death by multiple causes
- Women's Life Expectancy reduced by 10 years
- Men's Life Expectancy reduced by 4 years
- Early damage
VII. Diagnosis
VIII. Differential Diagnosis
- See Rheumatoid Arthritis Prediction Rule for Undifferentiated Arthritis
- See Polyarthritis
- Arthropathy of Inflammatory Bowel Disease
- Hemochromatosis
- Hepatitis B
- Hypothyroidism
- Fibromyalgia
- Gonococcal Arthritis
- Gouty Arthritis (Polyarticular)
- Lyme Disease
- Parvovirus
- Polymyalgia Rheumatica
- Psoriatic Arthritis
- Reiter's Syndrome
- Sarcoidosis
- Scleroderma
- Septic Arthritis
- Still's Disease
- Subacute Bacterial Endocarditis
- Systemic Lupus Erythematosus
IX. Labs (ARA recommended, but do not exclude diagnosis)
- Initial Labs
- Complete Blood Count with differential
- Rheumatoid Factor (Initially positive in 70%)
- Sedimentation Rate (ESR) or C-Reactive Protein (C-RP)
- Consider Anticyclic Citrullinated Peptide Antibody
- Consider Antinuclear Antibody (especially in juvenile forms as has prognostic value)
- Additional labs in preparation for rheumatic agents
- Labs needed before Steroids, TNF Inhibitors or DMARDs
- PPD with candida controls
- HBsAg
- Hepatitis C Antibody
- Markers of disease course
X. Imaging
- Obtain baseline hand and feet XRays
- May demonstrate periarticular erosive changes
- May define more aggressive disease
- See Rheumatoid Arthritis Related XRay Changes
- Chest XRay (erosions define moderate to severe disease)
XI. Management
XII. Associated Conditions
- See Rheumatoid Arthritis Extra-articular Signs
- Atlanto-axial instability
- Exercise caution with intubation
- Risk of C-Spine Fracture with Trauma
- Lymphoma (and other lymphoproliferative disorders)
- Insulin Resistance (50-60%)
-
Coronary Artery Disease
- See Cardiac Risk Management
- Rheumatoid Arthritis is now considered a coronary equivalent (similar to diabetes mellitus Cardiovascular Risk)
- Methotrexate is associated with reduced Cardiovascular Risk
- Overall Increased Mortality
- Related to cardiovascular disease, higher infection rates, Chronic Kidney Disease
- Mortality is increased as much as 1.5 to 2 fold in Rheumatoid Arthritis patients
XIII. Prognosis: Predictors of prolonged Remission (achieved in 10-50% of patients)
- Males
- Non-smokers
- Age under 40 years old
- Onset after age 65 years
- Shorter duration of Rheumatoid Arthritis
- Milder Rheumatoid Arthritis disease course
- Acute phase reactants not elevated (e.g. C-RP)
- Rheumatoid Factor negative
- Anti-Citrullinated Protein Antibody negative
XIV. Prognosis: Poor Prognostic Signs
- Hyper-acute onset (overnight onset)
- Multiple joint involvement (especially >20 joints)
- High titer Rheumatoid Factor (RF)
- HLA-DRBI 0404
- Low dose Corticosteroid resistance
- Early loss of function or young age of onset
- Higher Erythrocyte Sedimentation Rate
- Rheumatoid Arthritis Extra-articular Signs