Rheumatoid Arthritis Lecture Notes

Introduction to Rheumatoid Arthritis

• "Arthr-" refers to joints; "-itis" means inflammation.
• "Rheumatoid" comes from rheumatism, a musculoskeletal illness.
• Chronic inflammatory disorder mainly affecting joints and possibly other organ systems (skin, lungs).

Anatomy of a Healthy Joint

• Two bones covered with articular cartilage.
• Articular cartilage: protective cushion for smooth movement.
• Synovial Joint:
  • Connects two bones with fibrous joint capsule (continuous with periosteum).
  • Lined with synovial membrane producing synovial fluid.
  • Synovial fluid: jelly-like lubricant to reduce friction.
  • Membrane contains blood vessels and lymphatics.

Pathophysiology of Rheumatoid Arthritis

• Autoimmune Process:

  • Triggered by genetic factors (e.g., HLA-DR1, HLA-DR4) and environmental factors (e.g., cigarette smoke, pathogens).
  • Modification of self-antigens (e.g., IgG, type II collagen) through citrullination.
  • Immune cells misrecognize modified proteins, leading to autoantibody production.

• Immune Response:

  • CD4+ T-helper cells activated by antigen-presenting cells.
  • B-cells produce autoantibodies against self-antigens.
  • T-cells secrete cytokines (e.g., interferon-γ, IL-17) attracting inflammatory cells (macrophages).
  • Macrophages produce cytokines (TNF-α, IL-1, IL-6) stimulating synovial cell proliferation.

• Pannus Formation:

  • Thick, swollen synovial membrane with granulation tissue.
  • Damages cartilage, soft tissues, and erodes bone.

Mechanisms of Joint Damage

• Synovial cells secrete proteases breaking down articular cartilage.
• T-cell surface protein RANKL activates osteoclasts, leading to bone resorption.
• Autoantibodies (e.g., rheumatoid factor, anti-CCP) form immune complexes activating complement system.

Extra-Articular Manifestations

• Chronic Inflammation Effects:
  • Angiogenesis increases inflammatory cell influx.
  • Systemic effects from cytokines affecting various organs:
    • Fever (IL-1, IL-6)
    • Rheumatoid nodules (collections of macrophages and lymphocytes)
    • Vasculitis (inflammation of blood vessels)
    • Anemia (due to hepcidin production)
    • Lung fibrosis and pleural effusions.

Clinical Features

• Symmetric joint involvement (5+ joints, e.g., hands, feet).
• Commonly affected joints: metacarpophalangeal, proximal interphalangeal.
• Symptoms during flares: swelling, warmth, redness, pain, stiffness, especially in the morning.
• Typical deformities:
  • Ulnar deviation of fingers.
  • Boutonniere Deformity: flexion of proximal interphalangeal joint.
  • Swan Neck Deformity: hyperextension of proximal interphalangeal joint.
• Baker's Cyst: bulging of synovial fluid into the popliteal fossa.

Diagnosis

• Blood Tests:
  • Presence of rheumatoid factor, anti-CCP.
• Imaging Studies:
  • X-ray findings: decreased bone density, soft tissue swelling, joint space narrowing, bony erosions.

Treatment and Management

• Disease-Modifying Antirheumatic Drugs (DMARDs):
  • Methotrexate, hydroxychloroquine, sulfasalazine.
• Biologics:
  • Abatacept (T-cell suppression), rituximab (B-cell suppression).
  • TNF blockers (adalimumab, etanercept, infliximab).
  • Anakinra (blocks IL-1), tocilizumab (blocks IL-6).
• Acute Flares:
  • NSAIDs, short-term glucocorticoids.

Summary

• Rheumatoid arthritis: systemic autoimmune inflammatory disorder.
• Characterized by joint destruction, elevated rheumatoid factor, and anti-CCP levels.
• Affects multiple organs including skin, heart, blood vessels, lungs.