Rheumatoid Arthritis for the American Board of Internal Medicine (ABIM) Exam

Overview of Rheumatoid Arthritis (RA)

Definition: RA is a chronic, systemic autoimmune disease causing inflammation of synovial joints, leading to cartilage destruction, joint deformity, and systemic manifestations.

Pathophysiology

Autoimmune Mechanisms: Autoantibody production (e.g., RF, anti-CCP) leads to synovial inflammation and joint destruction.
Cytokine Activity: Elevated levels of TNF-alpha, IL-1, and IL-6 mediate joint inflammation and damage.
Synovial Pannus Formation: Proliferation of synovial tissue results in erosion of cartilage and bone.

Risk Factors

Genetic Predisposition: Strong association with HLA-DR4 and other genetic markers.
Gender and Age: Women are affected more frequently; peak incidence occurs between ages 40-60.
Environmental Factors: Smoking is a significant risk factor and is associated with more severe disease.

Symptoms and Signs

Symmetric Polyarthritis: Primarily affects small joints (MCP, PIP, wrists) and large joints (knees, ankles); spares DIP joints.
Morning Stiffness: Lasts >1 hour and improves with physical activity.
Joint Swelling and Tenderness: Warm, swollen joints with decreased range of motion.
Systemic Symptoms: Fatigue, low-grade fever, weight loss, and generalized malaise.
Rheumatoid Nodules: Subcutaneous, firm nodules typically found over pressure points or extensor surfaces.

Extra-Articular Manifestations

Pulmonary: Interstitial lung disease, pleural effusion, and rheumatoid nodules in the lungs.
Cardiovascular: Pericarditis, myocarditis, and increased risk for atherosclerosis and coronary artery disease.
Ocular: Sjögren's syndrome (secondary dry eyes and mouth), episcleritis, and scleritis.
Hematologic: Anemia of chronic disease, thrombocytosis, and Felty’s syndrome (RA, splenomegaly, neutropenia).

Diagnosis

Rheumatoid Factor (RF): Positive in ~70-80% of RA patients; not specific to RA.
Anti-Cyclic Citrullinated Peptide (Anti-CCP): High specificity and sensitivity for RA, often present early in disease.
ESR and CRP: Elevated markers of inflammation.

X-rays: Early findings include periarticular osteopenia and soft tissue swelling; later stages show joint space narrowing and erosions.
MRI and Ultrasound: Useful for detecting synovitis and early erosive disease.

Management

Exercise and Physical Therapy: Maintain joint flexibility and strength, prevent deformities.
Occupational Therapy: Joint protection techniques and assistive devices.

NSAIDs and Corticosteroids: For short-term symptom relief; not for long-term monotherapy.
Conventional DMARDs: Methotrexate is the first-line agent; others include sulfasalazine, hydroxychloroquine, and leflunomide.
Biologic DMARDs: TNF inhibitors (etanercept, adalimumab), IL-6 inhibitors (tocilizumab), and others used in patients with inadequate response to conventional DMARDs.
JAK Inhibitors: Target the JAK-STAT pathway (e.g., tofacitinib) for patients with refractory disease.

Surgical Intervention: Joint replacement for severe joint damage or functional limitation.

Essential Points

Early Aggressive Treatment: Start DMARDs early to prevent joint destruction and maintain function.
Monitor for Comorbidities: RA increases risk for cardiovascular disease, osteoporosis, and infection; assess and manage comorbid conditions.
Tailored Therapy: Treatment should be individualized based on disease activity, patient preference, and comorbidities.
Regular Monitoring: Monitor disease activity and medication side effects regularly to adjust therapy accordingly.