Rheumatoid Arthritis

Anika Morgado

Background

  • Chronic systemic inflammatory disorder of synovial joints, typically polyarticular, that results in proliferation of synovial tissue and consequent loss of articular cartilage and juxta-articular bone
  • Incidence: most often onset around 30-60y; female:male ratio of ~3:1.
  • Etiology: genetic (particularly specific HLA-DR4 and DR1 haplotypes) + environmental (e.g. smoking) triggers autoantibody formation (i.e. RF and anti-CCP) within the synovium, resulting in innate and adaptive immune cell infiltration
  • May be classified as seropositive (RF or anti-CCP present) or seronegative; seropositive is typically more severe joint disease, increased risk of extra-articular manifestations, stronger heritability

Presentation

  • Usually insidious onset of polyarticular, often symmetric joint pain and swelling; often with morning stiffness (i.e. >30min) - Classically affects MCPs, PIPs, wrists, ankles, MTPs, knees
    • Classically spares DIPs and axial skeleton (except for C1-C2 in severe disease)
    • Constitutional symptoms: fatigue, widespread pain, comorbid psychiatric disease (depression)
  • Extra-articular manifestations (primarily in seropositive RA only)
    • Osteopenia, rheumatoid nodules (usually on skin but can form anywhere including lungs), sicca symptoms, scleritis, ILD, constrictive pericarditis, rheumatoid vasculitis, anemia, neutropenia (associated splenomegaly)
    • RA is an independent risk factor for CAD

Evaluation

  • Clinical diagnosis based on symptoms as above with physical exam concerning for active synovitis/inflammatory joint changes; supported by serologic and imaging findings
    • MCP subluxation, ulnar deviation, Swan and Boutonnieres deformities are late findings of untreated RA
    • 2010 ACR/EULAR classification criteria are less helpful (only 50% specific; nearly any inflammatory polyarthritis will meet criteria)
  • Serologic workup: anti-CCP (95% specificity), RF (75-80% sensitivity and specificity), ESR/CRP (tends to correlate with disease activity), CBC (anemia or thrombocytosis); CMP, Hep B/C, TB screen for treatment planning
  • Extra-articular manifestations (primarily in seropositive RA only)
    • RF is nonspecific; can be seen in any disease with chronic stimulation of humoral immune system (HBV, HC, Sjogren’s, lymphoma, cryoglobulinemia)
    • Overall poor sensitivity; up to 20% of patients are seronegative
  • Imaging:
    • Baseline plain films of hands/feet; early changes include soft tissue swelling and periarticular osteopenia; late changes include marginal erosions and joint space narrowing
    • Consider MRI and/or MSK ultrasound to detect early synovitis/ erosions

Management

  • Goal of treatment: achieve early remission or low-disease activity to improve symptoms, prevent joint damage, and reduce long-term cardiovascular morbidity. Ideal response is 50% effective at 3 months and 90-100% effective at 6 months
    • 1st line: MTX 15-25mg weekly (with folate); may use with NSAIDs and/or steroids temporarily to rapidly reduce disease activity until DMARDs take effect (~2-6 months)
    • 2nd line: no clear guidelines, often dependent on patient-specific factors. Consider TNF inhibitors (usual preferred 2nd line agent), rituximab (particularly in seropositive disease), abatacept (particularly in the elderly), tocilizumab (especially if systemic symptoms), JAK inhibitors (if patient strongly prefers oral agent; avoid if history of DVT/PE or CAD)
    • If resource-limited or biologics are contraindicated, consider HCQ, sulfasalazine, and/or leflunomide (often in combination)
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