Rheumatoid Arthritis Epidemiology

Definition

  • Chronic symmetrical polyarthritis of unknown origin

Epidemiology

  • Worldwide distribution & affects all races & ethnic groups
  • Most common inflammatory arthropathy
    • 3% of population
    • M:F – 1:3
    • Annual incidence of 2-4/ 10 000 adult population
  • Peak age 4th-6th decade
    • Peak onset 40 years
  • Increasing in West
  • Life span ↓ 3-18 years

Aetiology

  • Unknown cause
  • Cell mediated immune response
  • Postulated combination of genetic susceptibility & environmental trigger
  • External trigger
    • ? Infection
    • Viral aetiology suggested due to synovitis similar to RA in patients with
      • Hepatitis B
      • Ross river virus
      • Rubella
    • Abnormal immune response in RA patients to EBV
    • Mycobacteria & Lyme disease related but no bacteria isolated from the joints in septic arthritis
    • Can induce arthritis in rats with immunisation with
      • Streptococcal cell walls
      • Soluble type II collagen
      • Freunds adjuvant
  • Genetic susceptibility
    • Associated with HLA DR4
      • 70% Rheumatoid Arthritis
      • 30% Normal
    • 80% of patients with RA are HLA DW4 and/ or D4 positive
    • Concordance amongst identical twins is 30%
    • Some large series suggest incidence of RA in first degree relatives twice that of chance alone
  • Exogenous agent alters IgG to become antigenic
  • Helper T cells activate B Cells to become plasma cells
  • Plasma Cells produce Rheumatoid Factors (IgM usually) directed against IgG
  • Synovium acts as lymphoid organ
    • Local helper T cells activated
    • Local plasma cells produce RF
  • Antibody-Antiglobulin complexes formed
    • Stimulates complement
  • Secondary destructive inflammatory cascade
  • Rheumatoid Factor
  • Antiglobulin directed at Fc region of IgG
    • Production of antigens on surface of IgG suggested to be due to infective or other trigger
  • Usually IgM but heterogeneous
    • Can be IgM, IgG, IgA or IgE
  • Seen in 80% with Rheumatoid Arthritis
  • Incidence of RF positivity ↑ with duration of active synovitis
  • Correlation with
    • Long standing disease
    • Sustained activity
    • Nodules
    • Erosions
    • Extraarticular manifestations
  • ? Role in pathogenesis
  • Synthesised locally in subsynovial tissue & demonstrable in plasma cell by immunofluorescence & as eosinophilic bodies on H & E (Russell Bodies)
  • Synovium thus acts as lymphoid tissue like spleen & lymph nodes
  • Detected with Latex Agglutination
    • Use latex particles with human IgG adsorbed to surface
    • Various dilutions of test sera to agglutinate the complexes
    • Titre is highest dilution that agglutinates
    • 1:80 is positive
  • High Titre » Severe Disease
  • May also be present in
    • Elderly (incidental)
    • Infection
    • Autoimmune Disease
    • Chronic liver disease
    • Multiple Myeloma & other Lymphoproliferative disorders (5-10%)