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  • ADD TRANSITION: UNEMPLOYMENT
  • VIOXX: 2 to 11 years of age: 0.6 mg/kg to a maximum of 25 mg once daily. Pts < 40 kg, recommended to use 12.5 mg/5 mL suspension. 12 to 17 yrs, 25 mg once daily. Maximum daily dose 25 mg. Adverse Events: Upper/abdominal pain, headache, upper respiratory tract infection, pyrexia, skin/subcutaneous disorders, insomnia, dizziness, elevated hepatic enzymes, edema, pseudoporphyria.
  • MTX: ADD AE PROFILE LAST BULLET NEEDS TO BE MODIFIED

Juvenile+Rheumatoid+Arthritis+slides Presentation Transcript

  • 1. Juvenile Rheumatoid Arthritis
  • 2. Definition - JRA
    • JRA is a general term for all types of arthritis and related conditions occurring (Arthritis Foundation 2009). The primary pathology of the chronic disease is inflammation of the connective tissues and is characterized by swelling and pain.
  • 3. JUVENILE RHEUMATOID ARTHRITIS American College of Rheumatology Revised Criteria
    • Age of onset < 16 years
    • Arthritis of one or more joints
    • Duration of disease > 6 weeks
    • Other conditions which present with arthritis in childhood must be excluded
  • 4. JUVENILE RHEUMATOID ARTHRITIS Epidemiology
    • Described in all races and geographic areas
    • Incidence: 6 – 19.6 cases/100,000 children
    • Prevalence: 16-150/100,000
    • Females predominate 2:1
  • 5. Clinical Manifestations of JRA
  • 6. Symptoms and Types
    • Juvenile arthritis is characterized by major changes in the joints including inflammation, contractures and joint damage which affect mobility, strength, and endurance.
    • Nearly all children experience periods when symptoms reduce in severity or disappear but may go from symptom free to extreme pain and swelling
    • When children are symptom free they should be encouraged to participate in developmental activities
  • 7.
    • Psychological and social impacts are multidimensional as joint pain and stiffness becomes a distraction that effect concentration; medication schedules are also disruptive and have side effects – subtypes are distinguished by the number of joints involved within the first 6 months of onset:
    • Systemic arthritis: entire body is affected from high spiking fever to concomitant joint discomfort
  • 8.
      • Polyarticular arthritis: arthritis in five or more joints with major symptoms of pain in the knees, ankles, wrist, fingers, elbows and shoulders. Constant pain is prevalent
      • Pauciarticular arthritis: arthritis in four or fewer joints within the first 6 mo of onset; large joints of knee, ankle, elbow, and wrist are affected.
  • 9. ILAR Proposed Classification Criteria
    • Juvenile Idiopathic Arthritis (JIA)
    • Systemic
    • Polyarticular RF+
    • Polyarticular RF-
    • Oligoarticular
      • Persistent
      • Extended
    • Ppsoriatic arthritis
    • Enthesitis-related arthritis
    • Other arthritis
  • 10. JUVENILE RHEUMATOID ARTHRITIS Laboratory Studies: Pauciarticular Disease
    • CBC: normal
    • ESR: usually normal
    • ANA: frequently positive
    • RF: usually negative
    • Synovial fluid: class II (inflammatory)
    • X-ray findings: soft tissue swelling, periarticular osteoporosis, growth disturbance, loss of joint space
  • 11. JUVENILE RHEUMATOID ARTHRITIS Clinical features: systemic disease
    • 10-20% of patients with JRA
    • Prominent systemic symptoms: fever, rash, lymphadenopathy, hepatosplenomegaly, pericarditis, pleuritis
    • Arthritis may be absent for months to years
    • Uveitis uncommon
  • 12. JUVENILE RHEUMATOID ARTHRITIS Laboratory studies: systemic disease
    • WBC   , Hgb  , platelets  to   ,
    • ESR   to   
    • ANA and RF usually negative
    • X-rays : soft tissue swelling
  • 13. JUVENILE RHEUMATOID ARTHRITIS Extra-articular Manifestations
    • Generalized or local growth disturbances
    • Delayed puberty
    • Pericarditis, myocarditis, rarely endocarditis
    • Plural effusion, rarely
    • Pneumonitis, pulmonary fibrosis
    • Hepatitis
    • Hematuria
  • 14. Prognosis of JRA
    • Pauciarticular JRA
      • Boys may be affected in older childhood or adolescence; this may represent an early manifestation of a spondyloarthropathy.
      • Leg length discrepancy from asymmetric knee synovitis and bone growth may cause flexion contractures, gait abnormalities and long-term growth abnormalities.
  • 15.
      • Eye involvement as anterior uveitis, may lead to scarring or blindness in ~ 15-20% of children.
      • Active arthritis into adulthood in 40% to 50% of patients.
      • Radiographic joint damage within 5 years.
    Prognosis of JRA
  • 16.
    • Polyarticular JRA and Systemic JRA
      • Active arthritis into adulthood : 50% to 70% of polyarticular or systemic onset JRA;
      • Long-term disabilities : 30% to 40% of children
        • Unemployment: 25% to 50% of adult JRA patients;
        • May need major surgery (joint replacement).
      • Radiographic joint damage within 2 years;
      • Mortality rate : 0.4% to 2% (greater risk with systemic JRA than with polyarticular JRA).
    Prognosis of JRA
  • 17. Before the 1990s … Pyramid Approach Traditional Approach to the Treatment of JRA Cytotoxic Drugs Disease Modifying Anti-Rheumatic Drugs (DMARDs) Intra-Articular/Oral Corticosteroids Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
  • 18.
    • Paradigm shift….
    • The trend in managing JRA is much more aggressive treatment earlier in the disease course with the goal of preventing joint damage and slowing progressive articular damage.
    Evolving Treatment of JRA Since the 1990s and into the 2000s…
  • 19.
    • Non-Selective NSAIDs
      • Aspirin, tolmetin sodium, ibuprofen, naproxen
      • Naproxen [Tablets and Suspension]
        • Indicated for patients 2 years and older with juvenile arthritis.
        • Daily dose: approximately 10 mg/kg/day as a BID dose (5 mg/kg given twice-a-day). Total daily dose is not to exceed 15 mg/kg/day.
    Treatments with Indications for JRA
  • 20.
        • Adverse events: gastrointestinal, central nervous system (headache, dizziness, drowsiness, vertigo), rash (ecchymoses, purpura), pruritus, sweating, special senses (tinnitus, visual disturbances, hearing disturbances), cardiovascular (edema, palpitations) prolonged bleeding times.
    Treatments with Indications for JRA
  • 21.
    • Non-Selective NSAIDs/COX-2 Selective Inhibitors
      • MOBIC (meloxicam) [Tablets and Suspension]
        • Indicated for the relief of the signs and symptoms of pauciarticular and polyarticular course JRA in patients 2 yrs and older.
        • 0.125 mg/kg once daily up to a maximum of 7.5 mg.
    Treatments with Indications for JRA
  • 22.
        • Adverse events: abdominal pain/upper, vomiting, diarrhea, headache, infection (rhinitis), cough, pyrexia, rash. urticaria, slight increases in systolic blood pressure.
      • VIOXX (rofecoxib) [Tablets and Suspension]
        • Withdrawn from the global market September 2004.
        • Indicated for the relief of the signs and symptoms of juvenile rheumatoid arthritis in patients 2 years and older.
    Treatments with Indications for JRA
  • 23. Treatment of JRA
    • Corticosteroids
      • Used for uncontrolled or life-threatening systemic disease;
      • Treatment of chronic uveitis as local ophthalmic drops; or
      • Intra-articular agents (Pauci- and polyarticular JRA)
      • Intermediate-acting corticosteroids: Prednisone; methyl-prednisolone (Intravenous pulse therapy for severely active JRA).
  • 24. Treatment of JRA
        • Prednisone low-dose as 0.1 to 0.2 mg/kg; higher-dose 0.25 to 1.0 mg/kg/day (maximum single dose 40 mg)
        • Adverse events: hypertension, iatrogenic Cushing’s syndrome, growth suppression, fractures, cataracts, increased susceptibility to infection.
  • 25.
    • DMARDs and Biologic DMARDs
      • Methotrexate (MTX): used when NSAIDs fail to bring relief.
        • Indicated for polyarticular JRA. MTX is the most widely used DMARD for JRA treatment.
        • Starting dose 7.5 mg/m 2 per week; maximum dose of 15 mg/m 2 per week.
        • Methotrexate compared to leflunomide (Lef): 240 JRA pts, 16-week DB + 6 mo Ext + optional 30 mo Ext in JRA; JRA Definition of Improvement > 30% (JRA DOI > 30): 89% MTX compared to 68% Lef.
    Treatment of JRA
  • 26. Treatment of JRA
        • Adverse events: stomatitis, leukopenia, nausea/ abdominal pain, gastrointestinal bleeding, anorexia, malaise, fatigue, chills and fever, headache, alopecia, rash, decreased resistance to infection, elevated hepatic enzymes.
      • Sulfasalazine
        • Indicated for polyarticular JRA who have responded inadequately to salicylates or other non-steroidal anti-inflammatory drugs.
  • 27.
        • Children 6 yrs and older: 40 - 60 mg/kg/day divided into 3 to 6 doses.
        • Maintenance dose: 30 mg/kg/day divided into 4 doses.
        • Adverse events: anorexia, headache, vomiting, gastric distress, rash, urticaria, hemolytic anemia.
    Treatment of JRA
      • ENBREL (etanercept):
        • Indicated for moderate to severe polyarticular course JRA patients 4 to 17 years of age who had an inadequate response to one or more DMARDs.
  • 28.
        • Dosage: 0.4 mg/kg/week (maximum 25 mg/ dose given twice weekly) as subcutaneous injection pre-filled syringe, 72-96 hrs. apart.
        • Adverse events: headache, nausea, abdominal pain, and vomiting. Infection was reported in 43 of 69 (62%) of JRA patients during the 3-month (open-label phase). Serious AEs reported in the study: varicella, gastroenteritis, depression/ personality disorder, cutaneous ulcer, esophagitis/ gastritis, group A streptococcal septic shock, Type 1 diabetes, soft tissue and post-operative wound infection.
    Treatment of JRA
  • 29.
    • DMARDs indicated for RA without an indication for JRA
      • Hydroxychloroquine, injectable gold, leflunomide and d-penicillamine.
    • Other Immunomodulatory or Cytotoxic Drugs
      • Indicated in RA without a JRA indication:
        • Azathioprine
        • Cyclosporine A
      • Without a RA or a JRA indication:
        • Chlorambucil
        • Thalidomide
    Treatment of JRA
  • 30.
    • Pauciarticular
      • 25% to 33% will respond to NSAIDs;
      • Patients not responsive to NSAIDS after 4 - 6 weeks with flexion contractures or leg length discrepancy  intra-articular corticosteroids.
      • Patients with extended pauciarticular JRA or small joint involvement  treat as polyarticular JRA.
    Treatment of JRA in 2008 Modified from Laxer R, Hashkes PJ. Medical Treatment of Juvenile Idiopathic Arthritis. JAMA, October 5, 2005. Vol 294, No. 13, pp 1671-1684.
  • 31.
    • Polyarticular
      • RF (-) or (+), NSAID (symptom control) alone is usually not as effective as a NSAID + DMARD.
      • NSAID trial for several weeks  add oral MTX.
      • If oral MTX is not effective  parenteral route MTX.
      • If NSAID + MTX (oral or parenteral) is not effective  anti-TNF medication.
        • No current evidence whether a combination of MTX + anti-TNF medication are more effective than only anti-TNF medication.
    Treatment of JRA in 2006 Modified from Laxer R, Hashkes PJ. Medical Treatment of Juvenile Idiopathic Arthritis. JAMA, October 5, 2005. Vol 294, No. 13, pp 1671-1684.
  • 32.
    • Systemic
      • NSAIDs 2 to 3 weeks with caution  risk of Disseminated Intravascular Coagulation (DIC), (macrophage activation syndrome);
      • Intravenous pulse methylprednisolone;
      • Oral corticosteroids 
        • Lowest effective dose;
        • Steroid sparing  immunomodulatory approach is under evaluation for steroid sparing effects.
    Treatment of JRA in 2006 Modified from Laxer R, Hashkes PJ. Medical Treatment of Juvenile Idiopathic Arthritis. JAMA, October 5, 2005. Vol 294, No. 13, pp 1671-1684.