Kawasaki Disease: An Update of diagnosis and treatment

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: 1.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 as abnormal 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

Harada et al – risk score (1) white blood cell count /mm3; (2) platelet count /mm3; (3) CRP 3; (4) hematocrit 35% (5) albumin 3.5 g/dL; (6) age 12 months; (7) male sex.  4/7 : high risk

ASAI Symtomps0 điểm1 điểm2 điểm 1.Sex 2.Age 3.Days of fever 4.Recurrent fever 5.Recurrent rash 6.Recurrent bong da 7.Anemie (Hb < 10g/dL) 8.WBC(X 10 3 / mm 3 ) 9.VS(mm) 10.VS and PLT high for a long time(months ) 11.Enlarge CI 12.Abnormal rymth 13.Ischemic myocady 14.pericarditis Nữ  1 < 14 - < 26 < 60 < 1 - Nam > – –  16 + > 30 > 100 >1 +  9/23 điểm : high risk

ĐIỀU TRỊ ASPIRIN AHA-2004: mg/kg. Pediatrics-1995: meta-analysis. ControlRatio Dilated CA after 30 days (n=2547)After 60 days (n=4151) ASA22.8% ( 95% CI: %) 17.1%(95% CI: %) ASA+IVIG 1g/kg17.3%(95% CI: %) 11.1%(95% CI: %) ASA+IVIG >1g/kg10.3%( 95% CI: %) 4.4% (95% CI: 2.8-6%) ASA+ IVIG >1g/kg lieàu duy nhaát 2.3%(95% CI: %)2.4%(95% CI: %) IVIG >1g/kg + ASA <80 mg/kg 13%(95% CI: 9-17%)4.8%(95% CI: %) IVIG >1g/kg +ASA >80mg/kg 9.1% (95% CI: %)4%(95% CI: %)

Dilated CA in 30 daysDilated CA in 60 days IVIG (2G/KG/D) < IVIG 1G/KG < ASA IVIG HIGH DOSE + ASA HIGH DOSE = IVIG HIGH DOSE + ASA LOW DOSE IVIG (2G/KG/D) < IVIG 1G/KG < ASA IVIG HIGH DOSE + ASA HIGH DOSE = IVIG HIGH DOSE + ASA LOW DOSE

ASPIRIN vs IVIG IVIG+ASPIRIN -IVIG HIGH DOSE -IVIG LOW DOSE ASPIRIN TỈ LỆ TỔN THƯƠNG MẠCH VÀNH

CORTICOID 1.Initial CORTICOID vs ASPIRIN. 2.Initial CORTICOID+ ASPIRIN+ IVIG vs ASPIRIN+IVIG. 3.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: mg/kg over 2 to 3 hours - IVIG 2g/kg. - Aspirin mg/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; ; published online May 30, 2006; Kobayashi-2006

Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki disease. Circulation 2006;113; ; published online May 30, 2006; 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 1.Steroid treatment berestricted to children in whom 2 infusions of IVIG have been ineffective in alleviating fever and acute inflammation (evidence level C). 2.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 1 st 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 1 st dose or recurrent symptoms  Up to 2/3 respond to a second course

Acute Kawasaki Disease: Treatment Aspirin –High dose ( 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