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

Treatment

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

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