Rheumatoid Arthritis - RA

Rheumatoid Arthritis - RA

 

Rheumatoid arthritis (RA) is the most common inflammatory arthritis worldwide.

Epidemiology

  • Incidence
    • 25/100,000 men
    • 54/100,000 women
  • Peak age – 30-50 years
  • Gender – F>M

Etiology

  • Genetics
    • 30% concordance for twins
    • 80% of Caucasians with RA express HLA-DRI or DR4 subtypes

Risk Factors

  • Family history
  • Smoking
  • Silicate exposure

Pathophysiology

  • Joint damage begins with proliferation of synovial macrophages and fibroblasts
  • Neovascularization follows
  • Inflamed synovial tissue grows irregularly, forming pannus tissue
  • Pannus invades cartilage and bone with joint destruction

Clinical Presentation

  • Constitutional manifestations
    • Weakness
    • Fatigue
    • Anorexia
    • Low-grade fever
  • Joints
    • Pain and stiffness in multiple joints
      • Wrist and proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints affected most commonly
      • Joints are puffy and warm
  • Extra-articular involvement
    • Anemia
    • Joint and spine disease
      • Cervical spine disease due to instability of atlas on axis
      • Joint deformity (swan neck, boutonnière)
    • Ocular disease – episcleritis
    • Cardiopulmonary disease
      • Interstitial fibrosis
      • Lung nodules that cavitate
      • Pericarditis may occur in 1/3 of patients
    • Rheumatoid nodules – may resolve
    • Vasculitis – small and medium vessel disease
  • Complications
    • Cancer
      • Often secondary to therapy
        • Lymphoma, leukemia most common
    • Cervical atlanto-axial dislocation

Diagnosis

  • American College of Rheumatology criteria – at least 4 required for diagnosis
    • Morning stiffness – for at least 1 hour over a period of at least 6 months
    • Arthritis of 3 or more joints – from wrist, PIP, MCP, elbow, knee, ankle, metatarsophalangeal (MTP)
    • Hand joint involvement – wrist, MCP, PIP
    • Symmetric arthritis – same joints as arthritis
    • Rheumatoid nodules – subcutaneous nodules around joints
    • Positive rheumatoid factor
    • Radiographic changes – erosions or loss of density of joints
  • Laboratory testing
    • Complete blood count with differential
    • Erythrocyte sedimentation rate (ESR) – often increased >30 mm/hr
    • C-reactive protein (CRP)
    • Rheumatoid factor (RF) IgM
      • Negative in 30% in early onset RA
      • Present in 5-10% of healthy individuals, prevalence increases with age
      • Not specific for RA; however, present in systemic sclerosis, hepatitis C, cryoglobulinemia and systemic lupus erythematosus
    • Anti-cyclic citrullinated peptide (CCP) IgG antibody
      • More than 98% specific, positivity supports the diagnosis of RA
      • As a screening method for RA, the IgM-RF and the CCP assays are superior to other RF isotypes
      • CCP can be detected in up to 38.4% of IgM-RF negative sera
      • The presence of anti-CCP and IgA-RF may predict the development of RA
      • Anti-CCP antibodies are associated with RF positive polyarticular course of juvenile idiopathic arthritis (JIA)
    • Rheumatoid factor isotypes
      • RF IgA in combination with anti-CCP may predict radiological damage in RA

Differential Diagnosis

  • Infectious arthritis
  • Reactive arthritis
  • Seronegative spondyloarthropathies
  • Connective tissue disease
  • Fibromyalgia
  • Polyarticular gout
  • Thyroid disease
  • Hemochromatosis

Treatment

  • Aggressive use of disease-modifying antirheumatic drugs (DMARDS) to prevent damage in addition to NSAIDs