What is Kawasaki Disease? • Idiopathic multisystem disease characterized by vasculitis of small & medium blood vessels, including coronary arteries
Diagnostic Criteria • Fever for at least 5 days • At least 4 of the following 5 features: • Changes in the extremities • Edema, erythema, desquamation 2. Polymorphous exanthem, usually truncal 3. Conjunctival injection 4. Erythema&/or fissuring of lips and oral cavity 5. Cervical lymphadenopathy • Illness not explained by other known disease process Modified from Centers for Disease Control. Kawasaki Disease. MMWR 29:61-63, 1980
Atypical or Incomplete Kawasaki Disease • Present with < 4 of 5 diagnostic criteria • Compatible laboratory findings • Still develop coronary artery aneurysms • No other explanation for the illness • More common in children < 1 year of age • 2004 AHA guidelines offer new evaluation and treatment algorithm
Phases of Disease • Acute (1-2 weeks from onset) • Febrile, irritable, toxic appearing • Oral changes, rash, edema/erythema of feet • Subacute (2-8 weeks from onset) • Desquamation, may have persistent arthritis or arthralgias • Gradual improvement even without treatment • Convalescent (Months to years later)
AHA classify coronary arteries aneurysms Small (5 mm internal diameter), medium (5 to 8 mm internal diameter), or giant (8 mm internal diameter). The Japanese Ministry of Health Classify coronary arteries asabnormal the internal lumen diameter is 3 mm in children 5 years old or 4 mm in children 5 years old; the internal diameter of a segment measures 1.5 times that of an adjacent segment;
Abnormal coronary artery Diameter of CA /BSA
Coronary Artery Involvement in Children With Kawasaki Disease: Risk Factors
ASAI 9/23 điểm : high risk
ĐIỀU TRỊ ASPIRIN • AHA-2004: 80-100 mg/kg. • Pediatrics-1995: meta-analysis.
ASPIRIN vs IVIG TỈ LỆ TỔN THƯƠNG MẠCH VÀNH
CORTICOID • Initial CORTICOID vs ASPIRIN. • Initial CORTICOID+ ASPIRIN+ IVIG vs ASPIRIN+IVIG. • Resistance IVIG.
IVIG+ASPIRIN vs IVIG+ASPIRIN+ METHYPREDNISOLON Randomized Trial of Pulsed Corticosteroid Therapy for Primary Treatment of Kawasaki Disease. N Engl J Med 2007;356:663-75. - 30 mg/kg over 2 to 3 hours - IVIG 2g/kg. - Aspirin 80-100mg/kg.
Effect and result • Response with IVIG : 90 % • No response with IVIG : 10 %
Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki disease. Circulation 2006;113;2606-2612; published online May 30, 2006; http://circ.ahajournals.org/cgi/content/full/113/22/2606. Kobayashi-2006
Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki disease. Circulation 2006;113;2606-2612; published online May 30, 2006; http://circ.ahajournals.org/cgi/content/full/113/22/2606. TIÊN ĐÓAN TỔN THƯƠNG MẠCH VÀNH
ANTI IVIG • IVIG ONLY 2 g/kg (evidence level C). • STEROID ONLY. • PULSE STEROID + IVIG: Hashino et al + RCT. • 17 patients who did not respond to an initial infusion of 2 g/kg IVIG plus aspirin followed by an additional IVIG infusion of 1 g/kg. • Randomized to receive either a single additional dose of IVIG (1 g/kg) or pulse steroid therapy. • RESULT: • Patients in the steroidgroup had a shorter duration of fever and lower medical costs. • No significant difference in the incidence of coronary arteryaneurysms was noted between the 2 groups, but power to detect a difference was limited.
KHÁNG IVIG AHA-2004 recommends • Steroid treatment berestricted to children in whom 2 infusions of IVIG have been ineffective in alleviating fever and acute inflammation (evidence level C). • The most commonly used steroid regimen is intravenous pulse methylprednisolone, 30 mg/kg for 2 to 3 hours, administered once daily for 1 to 3 days.
Acute Kawasaki Disease: Conclusion for Treatment ( AHA 2004) IVIG: 2g/kg as one-time dose Beneficial effect 1st reported by Japanese Mechanism of action is unclear Significant reduction in CAA in pts treated with IVIG plus aspirin vs. aspirin alone (15-25%3-5%)
Acute Kawasaki Disease: Treatment IVIG 70-90% defervesce & show symptom resolution within 2-3 days of treatment Retreat those with failure of response to 1st dose or recurrent symptoms Up to 2/3 respond to a second course
Acute Kawasaki Disease: Treatment Aspirin High dose (80-100 mg/kg/day) until afebrile x 48 hrs &/or decrease in acute phase reactants Need high doses in acute phase due to malabsorption of ASA Dosage of ASA in acute phase does not seem to affect subsequent incidence of CAA
Acute Kawasaki Disease: Treatment Aspirin Decrease to low dose (3-5 mg/kg/day) for 6-8 weeks or until platelet levels normalize ( evidence level C). No evidence /effect on CAA when used alone Due to potential risk of Reye syndrome instruct parents about symptoms of influenza or varicella
In case of persistent or recrudescent fever: Repeat dose of IVIG 2 g/kg as single infusion; consider IV methylprednisolone 30 mg/kg once a day; may be repeated as necessary up to a total of three doses