Rheumatoid Arthritis for USMLE Step 2 / COMLEX-USA Level 2
Overview of Rheumatoid Arthritis (RA)
- Definition: RA is a chronic autoimmune disease that primarily affects the synovial joints, leading to inflammation, joint destruction, and systemic symptoms.
Pathophysiology
- Autoimmune Mechanism: Inflammation in the synovium due to autoantibodies (e.g., rheumatoid factor and anti-CCP).
- Pannus Formation: Inflammatory granulation tissue (pannus) develops, which invades and erodes cartilage and bone.
- Cytokine Involvement: Key inflammatory cytokines include TNF-alpha, IL-1, and IL-6, contributing to joint damage and systemic effects.
Risk Factors
- Genetics: Strongly associated with HLA-DR4 and HLA-DR1.
- Gender: More common in females (3:1 ratio).
- Smoking: Increases risk and severity; associated with poorer prognosis.
- Age: Commonly presents in middle age (30-50 years).
Symptoms and Signs
- Symmetric Polyarthritis: Symmetrical involvement of small joints (MCP, PIP, wrists) and large joints (knees, elbows, shoulders).
- Morning Stiffness: Lasts >1 hour and typically improves with activity.
- Joint Swelling and Tenderness: Warm, swollen joints with decreased range of motion and pain.
- Deformities: Chronic disease can lead to ulnar deviation, swan neck deformities, and boutonniere deformities.
Extra-Articular Manifestations
- Rheumatoid Nodules: Firm, subcutaneous nodules typically over bony prominences or extensor surfaces.
- Pulmonary: Interstitial lung disease, pleural effusions, and rheumatoid nodules in the lungs.
- Cardiovascular: Increased risk of atherosclerosis, pericarditis, and myocarditis.
- Ocular: Episcleritis, scleritis, and secondary Sjögren’s syndrome (dry eyes and mouth).
- Hematologic: Anemia of chronic disease, thrombocytosis, and risk of Felty's syndrome (RA, splenomegaly, neutropenia).
Diagnosis
- Laboratory Tests:
- Rheumatoid Factor (RF): Present in ~70-80% of patients but not specific.
- Anti-Cyclic Citrullinated Peptide (Anti-CCP): Highly specific for RA and can predict more aggressive disease.
- ESR/CRP: Elevated as markers of inflammation and disease activity.
- Imaging:
- X-ray Findings: Early joint space narrowing, soft tissue swelling, periarticular osteopenia; erosions seen in later stages.
- Ultrasound/MRI: Detect early synovitis, effusions, and bone erosions.
Management
- Initial Symptomatic Relief:
- NSAIDs: For pain and inflammation control but do not alter disease progression.
- Corticosteroids: Used for acute flare management or bridging while waiting for DMARDs to take effect.
- Disease-Modifying Antirheumatic Drugs (DMARDs):
- Methotrexate: First-line DMARD due to efficacy and long-term benefits.
- Other DMARDs: Hydroxychloroquine, sulfasalazine, leflunomide.
- Biologic Agents:
- TNF Inhibitors: Etanercept, infliximab, adalimumab, and others for patients with moderate to severe disease unresponsive to conventional DMARDs.
- Other Biologics: IL-6 inhibitors (e.g., tocilizumab), JAK inhibitors (e.g., tofacitinib).
- Non-Pharmacologic Interventions:
- Physical and Occupational Therapy: Improve joint function, flexibility, and patient education on joint protection.
Essential Points
- Early Aggressive Treatment: Initiation of DMARDs early in the disease course is critical to prevent joint damage and disability.
- Distinguishing RA: Characteristic features include symmetric polyarthritis, prolonged morning stiffness, and extra-articular manifestations.
- Monitoring and Adjusting Therapy: Regularly assess disease activity, adjust treatment accordingly, and monitor for side effects of long-term therapy (e.g., liver toxicity with methotrexate).
- Systemic Disease Consideration: RA is a multisystem disease; consider extra-articular manifestations when managing patients.