From March 2016 through April 2017, 143 children were hospitalized for complete KD in the Kyungpook National University Children’s Hospital. Inclusion criteria were complete KD as a final diagnosis, a blood test before and 24 hours after the administration of IVIG, and agreement of the children’s guardians for the analysis of inflammatory markers using a serum left after the conventional tests. This study protocol was approved by the institutional review board (IRB no. KNUCH 2016-06-013). Written informed consents were obtained from the guardians of participating children.

IVIG was the primary treatment for all children. At the start of IVIG infusion, children without fever were immediately treated with IVIG whereas children with fever (> 38.8℃) received acetaminophen and/or ibuprofen for fever control before the infusion. If the fever control failed, single dose intravenous dexamethasone (0.1 mg/kg) was administered. IVIG-resistant KD was diagnosed when fever recurred or persisted for at least initial 36 hours after the initial infusion of IVIG. Children with IVIG-resistant KD received secondary treatment of additional IVIG and intravenous methylprednisolone (30 mg/kg). Acetylsalicylic acid was not being used as a primary treatment during the study period because the medication was not in use in the hospital due to an incident of acetylsalicylic acid-related Reye’s syndrome.

As baseline characteristics, we obtained information regarding age (months), sex, the Kobayashi score (≥ 4; high-risk for IVIG resistance)10), length of hospital stay (day), duration of fever (total [day] and from administration of IVIG to defervescence [hour]), time required to IVIG administration (hour), use of the antipyretics, and implementation of the secondary treatment. Groups were designated as per the use of dexamethasone. Outcomes included CAAs, inotropic support, hospitalization to the intensive care units, and in-hospital mortality.

We have routinely performed blood tests on the day of hospitalization and 24 hours after IVIG administration. Inflammatory markers of interest included white blood cells, erythrocyte sedimentation rate, C-reactive protein (CRP), and interleukin (IL)-6, and IL-10. The other laboratory tests were counts of neutrophils and platelets, and concentrations of hemoglobin and aminotransferases. The ILs were analyzed using the remaining serum from the above-mentioned tests which was stored at −80°C. According to the manufacturer’s instruction, a multiplex assay on the Luminex 200 Total System (Luminex Corp., Austin, TX) was used for measuring the ILs. The changes in laboratory data and cytokine concentrations before and after primary treatment were presented as delta (Δ) scores.

CAAs were evaluated by performing echocardiography twice during the hospitalization. We used the Z-score of size of the coronary artery based on aortic valve annular diameter for confirmation of CAAs11). The aortic valve annular diameters were measured with magnification in parasternal long-axis views from the inner edge of the proximal valve insertion hinge point within the arterial root to the inner edge of the opposite hinge point. Dilatation and aneurysm were defined as Z-scores of 2 to < 2.5 and ≥ 2.5, respectively5).

All statistical analyses were performed with IBM SPSS for Windows, version 25.0 (IBM Corp., Armonk, NY). Statistics were presented as medians (interquartile ranges) or numbers (%). The Mann-Whitney U-tests were used to compare the changes in values of the inflammatory markers as per the use of dexamethasone, and before and after the primary treatment. For this purpose, paired t-test and Wilcoxon signed-rank test were used. A P < 0.05 was considered statistically significant.

A total of 42 children were enrolled and divided into the 2 groups according to the use of dexamethasone as an adjunctive therapy for primary treatment: 18 children in the dexamethasone group and 24 in the control group. No differences were found between the groups in the baseline characteristics (Table 1). There were no children with CAAs, inotropic support, hospitalization to the intensive care units or in-hospital mortality.

Table 2 lists the changes in values of the inflammatory markers and the other laboratory tests. In both groups, all tests but platelet counts showed significant changes before and after the primary therapy. Among the markers with the significant changes in both groups, white blood cells, CRP, and the ILs decreased. The delta scores of CRP, IL-6, and IL-10 were significantly higher in the dexamethasone group than the control group (Table 3). The scores of the other laboratory findings showed no significant differences between the 2 groups.