Notes on Rheumatoid Arthritis Lecture

Introduction to Rheumatoid Arthritis (RA)

• Definition: RA is a chronic, inflammatory autoimmune disorder primarily affecting the joints but can also involve other organ systems.
• Etymology:
  • "Arthr-" refers to joints.
  • "-itis" means inflammation.
  • "Rheumatoid" stems from rheumatism, which refers to musculoskeletal illnesses.

Joint Anatomy

• Healthy Joint Structure:
  • Consists of two bones covered with articular cartilage for smooth gliding.
• Synovial Joint Characteristics:
  • Fibrous joint capsule connecting two bones.
  • Synovial membrane lines the capsule, produces synovial fluid, and removes debris.
  • Synovial fluid resembles the jelly-like part of a chicken egg, lubricating the joint.

Pathophysiology of RA

• Autoimmune Trigger:
  • Interaction between genetic factors (e.g., HLA-DR1, HLA-DR4) and environmental triggers (e.g., cigarette smoke, pathogens).
  • Modification of self-antigens (e.g., IgG, type II collagen) through citrullination (conversion of arginine to citrulline).
• Immune Response:
  • Modified proteins are recognized as non-self by immune cells, leading to an immune response.
  • Activation of CD4+ T-helper cells leads to B-cell proliferation and autoantibody production.
• Joint Inflammation:
  • Inflammatory cytokines (e.g., interferon-γ, IL-17) recruit macrophages.
  • Increased synovial cells form a pannus, damaging cartilage and eroding bone.
  • RANKL increases osteoclast activity, leading to bone breakdown.

Antibodies in RA

• Rheumatoid Factor (RF): IgM antibody targeting altered IgG antibodies.
• Anti-Cyclic Citrullinated Peptide (CCP) Antibody: Targets citrullinated proteins.
• Immune Complexes: Accumulate in synovial fluid, activate the complement system, promoting inflammation.

Extra-Articular Manifestations

• Systemic Involvement:
  • Inflammatory cytokines affect various organs, leading to symptoms such as:
    • Fever, malaise, muscle weakness.
    • Rheumatoid nodules in skin, lungs, heart, and eyes.
    • Vasculitis leading to atherosclerosis.
    • Liver produces hepcidin, affecting serum iron levels.
    • Pulmonary fibrosis and pleural effusions.
• Felty Syndrome: Triad of RA, splenomegaly, and granulocytopenia leading to severe infections.

Clinical Presentation

• Joint Symptoms:
  • Affects multiple joints symmetrically (e.g., hands, feet).
  • Joints are swollen, warm, red, and painful during flares.
  • Stiffness occurs, especially in the morning or after inactivity.
• Common Deformities:
  • Ulnar deviation of fingers.
  • Boutonniere Deformity: Flexion of proximal interphalangeal joint, hyperextension of distal interphalangeal joint.
  • Swan Neck Deformity: Hyperextension of proximal interphalangeal joint, flexion of distal interphalangeal joint.

Diagnosis and Management

• Diagnosis:
  • Blood tests for RF and anti-CCP antibodies.
  • Imaging (X-ray) shows decreased bone density, soft tissue swelling, joint space narrowing, and erosions.
• Long-term Management:
  • Disease-Modifying Antirheumatic Drugs (DMARDs): Methotrexate, hydroxychloroquine, sulfasalazine.
  • Biologic Response Modifiers: Abatacept (T-cell suppression), rituximab (B-cell suppression), TNF blockers (adalimumab, etanercept, infliximab), IL-1 (anakinra), IL-6 (tocilizumab).
  • Acute Flares Treatment: NSAIDs and short-term glucocorticoids.

Summary

• RA is a systemic inflammatory disorder of autoimmune origin, characterized by:
  • Progressive, symmetric joint destruction, primarily in the wrists and fingers.
  • Potential effects on skin, heart, blood vessels, and lungs.
  • Elevated RF and anti-CCP antibodies.