KD is an acute febrile systemic vasculitis that affects small- or medium-sized arteries, especially the coronary arteries. In China, approximately 9.1 to 21.5% of KD patients develop CALs [14–17]. In our study, 18.2% of KD patients developed CALs. Studies indicated that IVIG resistance KD patients represent a higher risk of developing CALs [3, 5, 18]. And it is confirmed by our research. The incidence of CALs in IVIG resistance group (36.7%) was much higher than that in non-resistance group (16.6%) (P < 0.001). Therefore, early and accurate identification of IVIG resistance KD patients is of great significance.
This study evaluated the efficacy of six popular scoring systems for predicting IVIG resistance in a group of KD patients in east China. We found that, compared with other three scoring systems, the Kobayashi scoring system proposed in Japan, Lan and Yang scoring systems proposed in China performed better for Chinese children. The sensitivity of the Kobayashi, Lan and Yang scoring systems is 66.7%, 68.3% and 65.0% respectively, and specificity is 79.2%, 73.0% and 76.4% respectively.
The Kobayashi scoring system was proposed in Japan enrolled 528 KD patients. The sensitivity and specificity of this system for predicting IVIG resistance were reported as 86% and 68% respectively in the initial study. However, when applied in Caucasian children [19, 20], this scoring system showed poor efficacy. This may be related to genetic factors. Several studies have demonstrated the association of KD with genetic variants of inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene [21, 22]. Therefore, KD patients with different genetic backgrounds may have different risks of IVIG resistance. While results from China diverse. Huang, et.al [23] retrospectively analyzed 84 KD patients in Taiwan, China reported a sensitivity and specificity of the Kobayashi score of 37.5% and 86.8% respectively. Song, et.al [24] conducted a study of 1163 KD patients in Beijing, China reported a sensitivity and specificity of the Kobayashi score of 16% and 85% respectively, meaning that most IVIG resistance KD children would be missed in a similar population. Nevertheless, Liu, et.al [25] conducted a study of total 346 Chinese patients found the Kobayashi score were significantly higher in the IVIG-resistant KD group than non-resistant group. Two reasons may explain the performance differences of Kobayashi scoring system among Chinese children. The first may be related to the small sample size of patients included in the study of Huang and his colleagues. Another may be due to the way the data was collected. All laboratory indicators collected in both our study and Liu's study were the highest/lowest values collected prior to initial IVIG treatment. However, this was not mentioned in the study of Song and Huang. To sum up, we can speculate that Kobayashi scoring system could be a good choice for Chinese KD patients.
The Lan and Yang scoring systems enrolled 1655 and 2102 Chinese KD patients, respectively. The sample sizes of these two were much larger than Formosa, another Chinese scoring system we included. The sample size of Formosa was only 248. This might explain why Formosa, also a Chinese scoring system, is less sensitive and specific than Lan and Yang. Both Lan and Yang scoring systems were established in 2018. To our knowledge, no one except us has demonstrated good specificity and sensitivity of these two scoring systems in the Chinese population.
At the same time, we conducted a binary logistic regression to analyze significance indicators to determine risk factors of IVIG resistance. All independent variables that reached a significance level of < 0.05 in the univariate analysis were included. Our study discovered that NE% ≥ 72.3% was an independent risk factor associated with IVIG resistance. The ROC curve demonstrated an area under the receiver operating characteristic curve of 0.77, with a sensitivity of 78.3% and a specificity of 69.0%. NE% was included in Formosa, Kobayashi, Lan and Yang scoring systems, with cutoff point at 60%, 80%, 80% and 70% respectively. And this predictive risk factor was later proved to be effective predictors in IVIG resistance in our country [26–28]. High levels of NE% probably reflected the severity of ongoing inflammation in patients with KD.
Meanwhile, our study showed that CRP level was significantly higher in the IVIG-resistant KD group than non-resistant group (P = 0.001). CRP is an acute inflammatory protein that increases when inflammation. Previous studies revealed that many proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, elevated during the acute phase of the KD and was associated with the activation of vascular endothelial cells, which may lead to varying degrees of vascular wall inflammation and occurrence of CALs [29, 30]. In conclusion, more consideration should be considered for KD patients with high NE%.