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Source: Schuna AA. Rheumatoid Arthritis. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. Accessed June 26, 2012

  • Chronic and usually progressive inflammatory disorder characterized by polyarticular symmetric joint involvement and systemic manifestations.

  • Genetic predisposition and exposure to unknown environmental antigens likely involved.

  • Involves dysregulation of humoral and cell-mediated components of immune system.
  • Immunoglobulins activate complement system, which amplifies cell-mediated immunity.
  • Activated T cells produce cytotoxins and cytokines.
  • Tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 contribute to inflammation.
  • Polymorphonuclear leukocytes release cytotoxins that damage synovium and bone.
  • Histamine, kinins, and prostaglandins cause edema, warmth, erythema, and pain.
  • Pannus formation invades cartilage and bone surfaces, producing erosions and joint destruction.
  • Process results in:
    • Loss of joint space and motion
    • Ankylosis
    • Joint subluxation
    • Tendon contractures
    • Chronic deformity

  • Estimated prevalence: 1% with no racial predilection.
  • Can occur at any age, with increasing prevalence up to seventh decade.
  • Incidence in women ~3 times greater than in men.

  • Family history
  • Sex (more common in females)
  • Age (more common in ages 40–60 years)

Signs and Symptoms

  • Nonspecific prodromal symptoms developing over weeks to months include:
    • Fatigue
    • Weakness
    • Low-grade fever
    • Loss of appetite
    • Joint pain
  • Stiffness and myalgias may precede development of synovitis.
  • Joint involvement tends to be symmetric and affect:
    • Small joints of hands, wrists, and feet
    • Elbows
    • Shoulders
    • Hips
    • Knees
    • Ankles may also be affected.
  • Joint stiffness worse in morning, lasts >30 minutes, and may persist all day.
  • Involved joint may be:
    • Swollen
    • Soft
    • Spongy
    • Warm
    • Erythematous
  • Chronic joint deformities include:
    • Swan neck deformity
    • Boutonnière deformity
    • Ulnar deviation
  • Extra-articular involvement includes:
    • Rheumatoid nodules
    • Vasculitis
    • Pleural effusions
    • Pulmonary fibrosis
    • Ocular manifestations
    • Pericarditis
    • Cardiac conduction abnormalities
    • Bone marrow suppression
    • Lymphadenopathy

Means of Confirmation and Diagnosis

Laboratory Tests

  • Normocytic, normochromic anemia
  • Thrombocytosis or thrombocytopenia
  • Leukopenia
  • Elevated erythrocyte sedimentation rate and C-reactive protein
  • Positive rheumatoid factor (60–70% of patients)
  • Positive anticyclic citrullinated peptide antibody (50–85% of patients)
  • Positive antinuclear antibodies (25% of patients)


  • Early radiologic findings may include soft-tissue swelling and periarticular osteoporosis.
    • Erosions occur later in disease.

Diagnostic Procedures

  • Aspirated synovial fluid may be turbid with leukocytosis, reduced viscosity, and normal or low glucose relative to serum concentrations.

Differential Diagnosis

  • Gout with tophi
  • Systemic lupus erythematosus
  • Osteoarthritis
  • Polymyalgia rheumatica
  • Lyme disease
  • Rheumatic fever
  • Rubella arthritis
  • Systemic vasculitis

  • Induce complete disease remission, if possible.
  • Reduce joint swelling, stiffness, and pain.
  • Preserve range of motion and joint function.
  • Improve quality of life.
  • Prevent systemic complications.
  • Slow destructive joint changes.

  • Start disease-modifying antirheumatic drug (DMARD) within first 3 months of symptom onset (...

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