Rheumatoid Arthritis (RA)

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. http://accesspharmacy.com/content.aspx?aid=7997207. 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

• The 2010 Rheumatoid Arthritis Classification Criteria include 6 parameters intended to diagnose disease earlier to enable disease-modifying treatments sooner to prevent erosive damage and improve outcomes.

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)

Imaging

• 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 (Figure 1).
• Nonsteroidal anti-inflammatory drugs ...