The Study Of Risk Factors And The Score System Of Unresponsiveness For Intravenous Immunoglobulin Therapy In Kawasaki Disease

Part I: The application of Kobayashi scoring system inpatients with Kawasaki disease in a single centerObjective To investigate the efficiency of Kobayashi scoring system in prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease.Method We retrospectively reviewed the clinical records of 624 KD patients in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2001 to January 2014, and divided them into IVIG-sensitive group and IVIG-irresponsive group.Kobayashi scoring system was applied to score for all the patients, and we would verify that all risk factors of Kobayashi scoring system in 624 KD patients and the risk stratification whether there is statistical significance. At last, the efficiency of Kobayashi scoring system in prediction of intravenous immunoglobulin unresponsiveness in Chinese patients with Kawasaki disease was analyzed.Results There were 547 cases in IVIG-sensitive group and 77 cases in IVIG-irresponsive group. According to Kobayashi Scoring system, 113 cases were divided into high-risk group(4~11 scores), and 511 cases into low-risk group(0~3 scores), and the incidence of intravenous immunoglobulin unresponsiveness in high-risk group was significantly higher than that in low-risk group. The sensitivity, specificity, misdiagnosis rate,rate of missed diagnosis and Kappa value of Kobayashi scoring system were 39%, 85%, 15%,61% and 0.198 respectively. In addition, χ2tests showed that CRP≥100mg/L, N%≥80%,Platelet ≤300×109/L and serum sodium ≤ 133mmol/L were the risk factors for intravenous immunoglobulin unresponsiveness.Conclusion The efficiency of Kobayashi scoring system in prediction of intravenous immunoglobulin unresponsiveness in our patients with Kawasaki disease was not high. In Kobayashi scoring system, CRP ≥ 100mg/L, N% ≥ 80%, Platelet ≤ 300×109/L and serum sodium≤133mmol/L were the risk factors for intravenous immunoglobulin unresponsiveness.Part II: Study on risk factors of patients with Kawasakidisease unresponsiveness to intravenous immunoglobulinObjective To investigate the risk factors of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease.Method We retrospectively reviewed the clinical records of 624 KD patients in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2001 to January 2014, and divided them into IVIG-sensitive group and IVIG-irresponsive group.Single factor analysis was performed in related factors before IVIG treatment to identify independent predictors of IVIG unresponsiveness. Receiver operating characteristic(ROC)curves were drawn to determine the optimal cut-off value and the area under the curve(AUC)of the independent predictors.Results There were 547 cases in IVIG-sensitive group and 77 cases in IVIG-irresponsive group. Single factor analysis showed that CRP, N%, HCT, serum albumin,platelet count, serum sodium, total bilirubin, pro-BNP, IL-2R and IL-10 were independent predictors of IVIG unresponsiveness, and the optimal cut-off value was 58.5(mg/L), 77.75(%),29.65(%), 33.35(g/L), 322.5(109/L), 132.9(mmol/L), 7.75(μmol/L),687.9(pg/ml), 3648.5(U/ml)and 35.6(pg/ml)respectively.Conclusion Our study confirmed that CRP, N%, HCT, serum albumin, platelet count,serum sodium, total bilirubin, pro-BNP, IL-2R and IL-10 were independent predictors of IVIG unresponsiveness.Part III: The investigation on risk scoring system in patientswith Kawasaki disease unresponsiveness to intravenousimmunoglobulinObjective To investigate and establish a new risk scoring system of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease.Method Logistic stepwise regression analysis was conducted among risk factors according to the part II to screen out high risk factors and build a logistic regression model. A simple scoring system was constructed according to the regression coefficient. The efficiency of the simple scoring system was evaluated by ROC curve and retrospective validation.Results Among the seven risk factors, HCT, serum albumin, platelet count and total bilirubin were eventually included into logistic regression model. The logistic regression model was constructed:P=ey /(1+ey),y=0.864×HCT+0.729×platelet count+0.801×serum albumin+1.275×total bilirubin. A simple scoring system was constructed on the basis of the logistic regression model:①HCT≤29.65%(0.9 points); ②platelet count≤322.5×109/L(0.7points); ③serum albumin≤33.35g/L(0.8 points); ④total bilirubin≥7.75μmol/L(1.3 points).Total scores were 3.7points, two risk strata were identified:low-risk group, with scores of 0 to1.4 points; high-risk group, with scores of 1.4 to 3.7 points. The area under the curve(AUC),the sensitivity and specificity of the simple scoring system were 0.772, 83.1% and 57.0%respectively.Conclusion Our simple scoring system showed better sensitivity but low specificity.Our study needs multicenter, large sample and prospective studies to further validate and perfect.