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 days At least of the following features: Changes in the extremities  Edema, erythema, desquamation Polymorphous exanthem, usually truncal Conjunctival injection Erythema&/or fissuring of lips and oral cavity 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 < of diagnostic criteria Compatible laboratory findings Still develop coronary artery aneurysms No other explanation for the illness More common in children < 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 mm internal – diameter), – or giant (8 mm internal diameter) • The Japanese Ministry of Health Classify coronary arteries as abnormal • the internal lumen diameter is mm in children years old or mm in children 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 12 000/mm3; (2) platelet count 350 000/mm3; (3) CRP 3; (4) hematocrit 35% (5) albumin 3.5 g/dL; (6) age 12 months; (7) male sex ≥ 4/7 : high risk Dilated CA in 30 days Dilated CA in 60 days IVIG (2G/KG/D) < IVIG 1G/KG < ASA IVIG (2G/KG/D) < IVIG 1G/KG < ASA IVIG HIGH DOSE + ASA HIGH DOSE = IVIG HIGH DOSE + ASA LOW DOSE IVIG HIGH DOSE + ASA HIGH DOSE = IVIG HIGH DOSE + ASA LOW DOSE 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 to 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 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 g/kg IVIG plus aspirin followed by an additional IVIG infusion of 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 groups, but power to detect a difference was limited KHÁNG IVIG AHA-2004 recommends 1.Steroid treatment berestricted to children in whom 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 to hours, administered once daily for to 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 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 [...]... 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... 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. .. 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. .. 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... 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... 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 Đ AN TỔN THƯƠNG MẠCH VÀNH ANTI IVIG...ASAI Symtomps 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Sex Age Days of fever Recurrent fever Recurrent rash Recurrent bong da Anemie (Hb < 10g/dL) WBC(X 103/ mm3) VS(mm) VS and PLT high for a long time(months ) Enlarge CI Abnormal rymth Ischemic myocady pericarditis 0 điểm 1 điểm Nữ ≤1 < 14 < 26 < 60 1 14 -15... 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 ... điểm 1 điểm Nữ ≤1 < 14 < 26 < 60 1 14 -15 ≥ 9/23 điểm : high risk + 26 – 30 60 – 100 2 điểm ≥ 16 + + + > 30 > 100 >1 + + + + + ĐIỀU TRỊ ASPIRIN • AHA-2004: 80-100 mg/kg • Pediatrics-1995: meta-analysis Control Ratio Dilated CA after 30 days (n=2547) After 60 days (n=4151) ASA 22.8% ( 95% CI: 20.6-25%) 17.1%(95% CI: 13.6-20.7%) ASA+IVIG 1g/kg 17.3%(95% CI: 14.320.2%) 10.3%( 95% CI: 8.3-12.3%)