Exploration Of Precise Treatment Options For Children With Kawasaki Disease

Part one:The Effect of Modified Methylprednisolone Regimen in refractory Kawasaki diseaseBackground:The use of corticosteroids in Kawasaki disease(KD)is still controversial.This study is to investigate the safety and effectiveness of modified methylprednisolone(mPSL)regimen as an initial treatment for refractory KD.Methods:This is a real-world observational study.We identified refractory KD with self-developed scoring system.Patients were divided into intravenous immunoglobulin(IVIG)+mPSL group and IVIG group.Clinical outcomes and changes of coronary arteries after the treatment during a 12-week period were observed.Propensity score matching was used to analyze those patients with similar baseline characteristics.Results:In total 168 patients,with 104 patients in IVIG group and 64 patients in IVIG+mPSL group.Therapeutic response rate of IVIG+mPSL group was significantly higher than IVIG group(98.4%vs 76.0%,P<0.05).IVIG+mPSL group had shorter duration of fever and higher rate of C-reactive protein(CRP)decline than IVIG group(1.22±0.766 days vs 1.74±1.174 days;87.7%vs 81.4%;P<0.05).The luminal diameter and Z score of left circumflex artery(LCX)were significantly smaller and lower in IVIG+mPSL group than in IVIG group at week 2 and 12.Conclusion:Modified mPSL regimen has minimal side effects.It might improve initial response to IVIG and decrease the dilation of LCX for refractory KD.Part two:Personalized treatment of clopidogrel in children with Kawasaki diseaseBackground:Antiplatelet therapy after the acute stage of kawasaki disease is very important.Low-dose aspirin(3 to 5 mg/kg.d)is the main treatment.Clopidogrel is an alternative antiplatelet agent for aspirin intolerance children,and clinical evidence of clopidogrel antiplatelet therapy in children is poor.The present study aimed to explore the personalized dose of clopidogrel in children with KD.Methods:This is a real-world observational study.Children with KD who needed clopidogrel were first given a conventional dose of clopidogrel with 0.2-lmg/kg.d,and the CYP2C19 gene phenotype was tested.Antiplatelet therapy was performed according to CYP2C19 phenotype.The carriers with CYP2C19*2 or*3 genotype received dose of clopidogrel with 1-2mg/kg.d.we administered clopidogrel for 5 days and measured response by platelet aggregometry.Patients were followed up in 1,2 and 3 months,the drug efficacy and adverse events were monitored.Results:In 294 patients,120(40.8%)were classified as clopidogrel extensive metabolizers(EMs),141(48.0%)were classified as intermediate metabolizers(IMs),33(11.2%)were classified as poor metabolizers(PMs).After equal doses of clopidogrel,the platelet aggregometry in IMs and PMs group was significantly higher than PMs group(43.44 ±26.70 vs 28.16±20.85,P=0.003).The platelet aggregometry in EMs,IMs and PMs was 28.16± 20.85、40.32 ± 26.48、53.52 ± 25.80 respectively.After increasing clopidogrel doses in the IMs and PMs group,the platelet aggregometry decreased from 57.72±25.29 to 36.44±25.74,followed-up for 3 months and no serious adverse events were found.Conclusion:CYP2C19 gene polymorphism in children with KD affects the efficacy of clopidogrel.Conventional dose of clopidogrel for IMs and PMs patients cannot achieve the expected effect of inhibiting platelet aggregation and the personalized antiplatelet therapy which be performed according to CYP2C19 phenotype is safe and effective.