Predictors Of Intravenous Immunoglobulin Resistance And Coronary Artery Lesions In Kawasaki Disease

Objective:The objective of this study was to analyze and evaluate the risk factors of intravenous immunoglobulin (IVIG) resistance and Coronary artery lesions (CALs) in patients with Kawasaki disease (KD).Methods:We retrospectively reviewed the medical data of patients diagnosed with KD at the Children’s Hospital, Zhejiang University School of Medicine, from May 2010 to May 2014. Both in complete KD (cKD) and incomplete KD (KD) patients, the laboratory data were compared between IVIG-resistant group and IVIG-responsive group, as well as between coronary artery lesions (CALs+) group and without coronary artery lesions (CALs-) group. In addition, those parameters which had statistical differences were performed with multivariable logistic regression analysis to evaluate the relative risk of each parameter, and cutoff values of Receiver operating characteristic (ROC) curves were used to calculate the sensitivity and specificity.Results:(1) A total of 560 KD patients were enrolled in this study, including 410 cKD patients and 150 iKD patients. Both the incidences of IVIG-resistant and CALs in iKD group were significant higher than in cKD group (7.32%vsl7.33%, P<0.01; 23.17%vs38.67%, P<0.01; respectively). Additionally, the total incidence of CALs in patients with IVIG-resistant (27/56,48.2%) was significantly higher than patients responsive to IVIG (126/504,25%) in our research(P<0.01).(2) The IVIG-resistant group had significantly higher levels of white blood cell count (WBC), proportion of neutrophils (N%), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6(IL-6), IL-10 and lower levels of Albumin (ALB) compared to IVIG-responsive group both in cKD and iKD patients(P<0.05 or P< 0.01). When ALB<32g/L, the diagnosis sensitivity and specificity for predicting IVIG-resistant in cKD patients were 72% and 83.19%, respectively; while the sensitivity and specificity in iKD patients were 42.86% and 92.73%, respectively.The hemoglobin (HB) value was significantly lower in the IVIG-resistant group than in the IVIG-responsive group (P=0.002) in iKD patients; and when HB<110g/L, the diagnosis sensitivity and specificity for predicting IVIG-resistant were 80% and 54.1%, respectively. In cKD patients, the N-terminal pro-brain natriuretic peptide (NT-proBNP) value of the IVIG-resistant group was significantly higher than the IVIG-responsive group (P=0.002). In cKD patients, NT-proBNP levels had a sensitivity of 73.91% and a specificity of 76.43% for predicting IVIG-resistant at a cutoff point of >1300pg/ml. In iKD patients, IL-6 levels had a sensitivity of 70.59% and a specificity of 66.28% for predicting IVIG-resistant at a cutoff value of>25 pg/ml, and had a sensitivity of 52.94% and a specificity of 93.02% at a cutoff value of> 120 pg/ml.(3) In cKD group, patients with CALs had the significantly higher levels of WBC, ESR and CRP and lower levels of HB and ALB compared to KD patients without CALs. In iKD group, the levels of WBC, ESR were significantly higher in patients with CALs compared to KD patients without CALs. When WBC> 14.25X 109/L, the diagnosis sensitivity and specificity for predicting CALs in cKD patients were 62.11% and 58.92%, respectively; while the sensitivity and specificity in iKD patients were 42.86% and 92.73%, respectively. In cKD patients, ESR levels had a sensitivity of 53.26% and a specificity of 64.14% for predicting CALs at a cutoff point of>75 mm/h. In KD patients, ESR levels had a sensitivity of 61.82% and a specificity of 65.12% for predicting CALs at a cutoff point of>75 mm/h. When ALB<30g/L, the diagnosis sensitivity and specificity for predicting CALs in cKD patients were 23.26% and 90.65%, respectively.Conclusion:1. Both the incidences of IVIG-resistant and CALs in iKD group were significantly higher man in the cKD group (P<0.01).2. IVIG-resistant is a high risk factor of CALs in patients with KD3. In cKD patients, higher levels of WBC、N%、CRP、ESR、NT-proBNP、IL-6、 IL-10 and lower levels of ALB were independent risk factors of IVIG-resistant. The levels of NT-proBNP and ALB had very high sensitivity and specificity for predicting IVIG-resistant. NT-proBNP levels had a sensitivity of 73.91% and a specificity of 76.43% for predicting IVIG-resistant at a cutoff point of>1300pg/ml. When ALB<32g/L, the diagnosis sensitivity and specificity for predicting IVIG-resistant in cKD patients were 72% and 83.19%, respectively.4. In iKD patients, higher levels ofWBC、N%、CRP、ESR、IL-6、IL-10 and bwer levels of HB、ALB were independent risk factors of IVIG-resistant. In iKD patients, IL-6 levels had a sensitivity of 70.59% and a specificity of 66.28% for predicting IVIG-resistant at a cutoff value of>25 pg/ml; and had a very high specificity of 93.02% but with low sensitivity of 52.94% at a cutoff value of>120 pg/ml.5. Higher levels of WBC、CRP、ESR and lower levels of HB、ALB were independent risk factors of CALs, but the diagnostic sensitivity and(or) specificity were very low.