Rheumatoid Arthritis

Definition

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent synovial inflammation, leading to joint destruction, deformity, and systemic manifestations.

Epidemiology

• Affects approximately 0.5–1% of the global population
• Female-to-male ratio is approximately 3:1
• Peak onset between ages 30–60 years
• Can occur at any age, including childhood (juvenile RA)
• Prevalence varies by geography and ethnicity
• Familial clustering observed, suggesting genetic predisposition
• Associated with significant morbidity and functional disability

Etiology

• Autoimmune response triggered by genetic and environmental factors
• Genetic predisposition: HLA-DR4, HLA-DR1 alleles
• Environmental triggers: smoking, infections, gut microbiome alterations
• Immune dysregulation: activation of T and B cells, cytokines (TNF-α, IL-1, IL-6)
• Synovial inflammation leading to pannus formation and joint destruction
• Hormonal factors may influence susceptibility
• Interaction of genes and environment drives chronic inflammation

Pathophysiology

• Autoimmune activation of synovial tissue and joint lining
• Inflammatory cytokines stimulate synovial proliferation and pannus formation
• Destruction of cartilage and subchondral bone via osteoclast activation
• Vascular proliferation and inflammatory cell infiltration in synovium
• Systemic inflammation can affect lungs, heart, and blood vessels
• Chronic inflammation leads to joint deformity and functional impairment
• Autoantibody production: Rheumatoid factor (RF) and anti-CCP antibodies