Rheumatoid Arthritis for USMLE Step 1 / COMLEX-USA Level 1
Overview of Rheumatoid Arthritis (RA)
- Definition: RA is a chronic autoimmune disease characterized by inflammation of synovial joints, leading to joint destruction, deformity, and systemic manifestations.
Pathophysiology
- Autoimmunity: An autoimmune response leads to the formation of immune complexes, resulting in synovial inflammation.
- Pannus Formation: Proliferation of granulation tissue (pannus) in joints invades cartilage and bone, leading to joint destruction.
- Cytokines and Mediators: TNF-alpha, IL-1, and IL-6 are central to inflammation and joint damage.
Risk Factors
- Genetics: HLA-DR4 and HLA-DR1 are associated with an increased risk.
- Gender: More common in females.
- Smoking: Strongly associated with increased risk and severity.
- Age of Onset: Usually presents between ages 30-50.
Symptoms and Signs
- Symmetric Polyarthritis: Affects multiple joints symmetrically, typically involving the small joints of the hands (MCP, PIP), wrists, knees, and feet.
- Morning Stiffness: Lasts >1 hour and improves with movement (in contrast to osteoarthritis).
- Joint Swelling, Pain, and Tenderness: Warm, swollen, and tender joints; reduced range of motion.
- Deformities: Advanced RA can lead to ulnar deviation, swan neck deformities, and boutonniere deformities.
Extra-Articular Manifestations
- Rheumatoid Nodules: Subcutaneous, firm nodules found over extensor surfaces or pressure points.
- Pulmonary: Interstitial lung disease, pleuritis, and pulmonary nodules.
- Cardiovascular: Pericarditis and increased risk of coronary artery disease.
- Hematologic: Anemia of chronic disease and potential splenomegaly (e.g., Felty's syndrome).
Diagnosis
- Laboratory Findings:
- Rheumatoid Factor (RF): Present in ~70-80% of patients; not specific.
- Anti-Cyclic Citrullinated Peptide (Anti-CCP): Highly specific for RA and can be detected early.
- Elevated ESR/CRP: Markers of inflammation.
- Imaging:
- X-ray Findings: Early joint space narrowing, periarticular osteopenia, and later, erosions and deformities.
Management
- NSAIDs: Provide symptomatic relief but do not alter disease progression.
- Glucocorticoids: Short-term use for acute flare control.
- Disease-Modifying Antirheumatic Drugs (DMARDs):
- Methotrexate: First-line DMARD; inhibits folate metabolism.
- Other DMARDs: Sulfasalazine, hydroxychloroquine, leflunomide.
- Biologic Agents: Target TNF-alpha (e.g., etanercept, infliximab) or other cytokines for patients unresponsive to conventional DMARDs.
Essential Points
- Early Intervention: Initiating DMARDs early helps prevent joint damage and disability.
- Inflammatory Nature: Morning stiffness and systemic symptoms distinguish RA from non-inflammatory arthritis like osteoarthritis.
- Multi-System Involvement: RA can affect multiple organ systems, including the lungs, cardiovascular system, and skin.
- Role of Anti-CCP: High specificity for RA, making it a key diagnostic tool.