Rheumatoid Arthritis for USMLE Step 3 / COMLEX-USA Level 3
Overview of Rheumatoid Arthritis (RA)
- Definition: RA is a chronic autoimmune disorder characterized by persistent synovial inflammation leading to joint destruction, pain, and systemic symptoms.
Pathophysiology
- Autoimmune Mechanism: Immune dysregulation causes synovial inflammation, proliferation (pannus formation), and joint damage.
- Cytokine Activity: Key cytokines involved include TNF-alpha, IL-1, and IL-6, which contribute to inflammation and joint destruction.
- Pannus Formation: Invasive tissue that erodes cartilage, bone, and surrounding structures.
Risk Factors
- Genetics: HLA-DR4 and HLA-DR1 association increases susceptibility.
- Gender: Females are more commonly affected (3:1 female-to-male ratio).
- Age: Typically presents between ages 30-50.
- Environmental Factors: Smoking is strongly linked to disease risk and severity.
Symptoms and Signs
- Symmetric Joint Involvement: Affects small joints (MCP, PIP, wrists) and large joints (knees, shoulders) with sparing of the DIP joints.
- Morning Stiffness: Lasts >1 hour, improving with activity throughout the day.
- Joint Swelling and Tenderness: Warmth, swelling, and tenderness of affected joints; decreased range of motion.
- Joint Deformities: Advanced disease can cause ulnar deviation, swan neck deformities, and boutonniere deformities.
Extra-Articular Manifestations
- Rheumatoid Nodules: Firm, subcutaneous nodules commonly over pressure areas or extensor surfaces.
- Pulmonary: Interstitial lung disease, pleural effusion, and rheumatoid lung nodules.
- Cardiovascular: Pericarditis, myocarditis, increased risk of atherosclerosis and coronary artery disease.
- Ocular: Episcleritis, scleritis, and secondary Sjögren’s syndrome (dry eyes and mouth).
- Hematologic: Anemia of chronic disease, thrombocytosis, and Felty’s syndrome (RA, splenomegaly, neutropenia).
Diagnosis
- Laboratory Studies:
- Rheumatoid Factor (RF): Positive in ~70-80% of RA cases but not specific.
- Anti-Cyclic Citrullinated Peptide (Anti-CCP): High specificity for RA and associated with severe disease.
- ESR/CRP: Elevated in active disease, indicating inflammation.
- Imaging Studies:
- X-ray: Early changes include periarticular osteopenia and soft tissue swelling; advanced disease shows joint space narrowing and erosions.
- Ultrasound/MRI: Helpful in detecting early synovitis, effusions, and erosions.
Management
- Symptomatic Relief:
- NSAIDs: For pain and inflammation but do not alter disease progression.
- Glucocorticoids: Low-dose oral or intra-articular for short-term control or bridging to DMARDs.
- Disease-Modifying Antirheumatic Drugs (DMARDs):
- Methotrexate: First-line DMARD for slowing disease progression and joint damage.
- Other DMARDs: Leflunomide, sulfasalazine, hydroxychloroquine.
- Biologic Agents:
- TNF Inhibitors: Etanercept, adalimumab, infliximab; used for moderate to severe RA not responsive to conventional DMARDs.
- Other Biologics: IL-6 inhibitors (tocilizumab), B-cell depleting agents (rituximab).
- JAK Inhibitors: Tofacitinib for patients unresponsive to TNF inhibitors.
- Non-Pharmacologic:
- Physical and Occupational Therapy: Focus on maintaining joint function, flexibility, and education on joint protection.
Essential Points
- Early and Aggressive Therapy: Early use of DMARDs can prevent joint destruction and improve long-term outcomes.
- Monitoring Disease Activity: Regular follow-up to assess disease activity and side effects of long-term therapy.
- Holistic Management: RA is a systemic disease; address extra-articular manifestations, comorbidities (e.g., cardiovascular risk), and psychosocial support.
- Combination Therapy: Often necessary for disease control, especially in moderate to severe cases.