Do cytokines correlate with refractory Kawasaki disease in children?

Background: Kawasaki disease (KD) is a type of pediatric vasculitis. Ten to twenty percent of children with KD do not respond to initial intravenous immunoglobulin (IVIG) treatment which called refractory Kawasaki disease. If untreated, approximately 15-25% of KD patients have complications. Therefore, it is important to predict whether KD is resistant to IVIG at an early stage. The aim of this study was to determine whether cytokines are predictors of refractory KD in children.

Methods: We retrospectively reviewed the medical records of 265 children diagnosed with KD who received IVIG within 10 days of fever onset at Beijing Children's Hospital. Refractory Kawasaki disease was defined as persistent or recrudescent fever beyond 36 h after IVIG. Before IVIG and 3 days after temperature normalization following IVIG treatment, the concentrations of cytokines in the serum including interferon gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-4 (IL-4), interleukin-2 (IL-2) and other conventional inflammatory mediators including white blood cells counts (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and albumin were detected. The patients were divided into 2 groups: IVIG-sensitive group and refractory group.

Results: Of the 265 patients, 47 (17.7%) were refractory. After treatment with IVIG, the serum levels of IFN-γ, TNF-α, IL-10 and IL-6 in both groups were significantly lower than those before treatment (P < 0.05). Before treatment, the serum levels of IFN-γ, TNF-α, IL-10 and IL-6 in refractory group were significantly higher than those in IVIG-sensitive group (P < 0.05). There were no significant differences in IL-4 or IL-2 levels between the 2 groups. The results of logistic regression analysis showed that IFN-γ, IL-6, fever duration and serum albumin were independent risk factors for refractory KD. The area under the receiver operating characteristic curve (ROC curve) for IFN-γ was 0.781, and the cut-off value for refractory was 7.37 pg/ml, while the area under the ROC curve for IL-6 was 0.837, and the cut-off value for refractory was 70.13 pg/ml.

Conclusions: IFN-γ and IL-6 were independent risk factors for refractory Kawasaki disease in children. KD patients with serum levels of IFN-γ above 7.37 pg/ml and IL-6 above 70.13 pg/ml before treatment were prone to refractory.