Abstract Body (Do not enter title and authors here): Introduction Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG) is the most effective therapy for the acute phase of KD. However, some very severe cases need several additional treatments and are at risk for CALs. Several scoring systems that have tried to predict IVIG-resistant patients failed in multiethnic populations.
Aims: To develop the most effective biomarker for predicting refractory cases and determine the cut-off value for the development of the diagnostic kit.
Methods Multicenter, prospective, observational study was conducted at 49 hospitals in Japan between September 2017 and December 2023. The subjects consisted of 1310 KD patients, including Group 1 (n=50); treatment-resistant cases that required additional treatment of 3rd line or more (defined as refractory cases), and Group 2 (n=1260); cases that completed the treatment with 1st or 2nd line. Tenascin C (TN-C), Pentraxin 3 (PTX3), and Procalcitonin (PCT) values, which were selected by systematic review and a pilot study, were measured before initial treatment in each group. The cut-off value of the biomarker, which had the highest area under the curve (AUC), was determined.
Results: All three biomarker values were significantly higher in Group 1 than Group 2 (p<0.01). Median [Interquartile range] in Group 1 vs Group 2 and AUC were PTX3; 44.6 [32.3-67.9] vs 12.2 [6.9-26.9]ng/ml, AUC=0.83, PCT; 4.3 [1.9-7.8] vs 0.6 [0.2-1.9]ng/ml, AUC=0.81, TN-C; 182 [122-222] vs 123 [94-163]ng/ml, AUC=0.71. PTX3 showed the highest AUC with the cut-off value of 31.7ng/ml [95% confidence interval; 31.7-34.9]. Group 1 could be predicted by PTX3 with the sensitivity of 80%, the specificity of 82%, the positive predictive value of 13% and the negative predictive value of 99%.
Conclusions It may be possible to predict refractory KD cases with high sensitivity and specificity by PTX3 value before initial treatment, and possibly develop a diagnostic kit using PTX3 value for prediction of refractory cases.