Takanori Suzuki

Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high-Na) and sodium-trace (low-Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low-Na IVIG preparations in KD children using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low-Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. We identified 42,345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p = 0.031) and IVIG resistance (17% vs. 18%, p = 0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.Conclusion: The present study suggests that high-Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study. What is Known: • For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, sodium-containing IVIG and sodium-trace IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior. What is New: • The present findings suggest that high-Na IVIG is associated with reductions in the proportions of CAAs and IVIG resistance in KD patients.

Little is known whether 2-g/kg IVIG is necessary for older children with Kawasaki disease (KD), because they could have more complications and financial burden. The purpose of this study was to compare outcomes between high- and low-dose IVIG in KD children with higher body weight (25 kg or more), using a national inpatient database in Japan from 2010 to 2017. We identified those receiving 2-g/kg and 1-g/kg IVIG as an initial treatment. Outcomes included the proportions of coronary artery abnormality (CAA) formation, IVIG resistance, adverse effects, length of stay, and medical costs. A propensity score matching analysis was conducted to compare the outcomes between the groups. We identified 1332 patients with KD and created 4:1 propensity score-matched pairs between high- and low-dose IVIG groups. There were no significant differences in the proportions of CAA (5.3% vs. 4.1%; p = 0.587), IVIG resistance, and length of stay. Medical costs were significantly higher in the high-dose group than in the low-dose group (p < 0.001).Conclusion: No significant difference was shown between the high- and low-dose IVIG groups in the proportions of outcomes, while medical costs were higher in the high-dose group. Further studies are needed to ascertain the appropriate IVIG dose in older patients with KD. What is Known: • For treatments of Kawasaki disease at any age in the acute phase, 2-g/kg single-dose intravenous immunoglobulin and aspirin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. What is New: • There was no significant difference in outcomes between children with Kawasaki disease weighing ≥ 25 kg treated with high-dose or low-dose IVIG in terms of coronary artery abnormalities, IVIG resistance, adverse effects, and length of stay, except for medical costs.

Kawasaki disease is an acute systemic vasculitis in children. Antiplatelet medicines are commonly used for Kawasaki disease to attenuate vasculitis and prevent thromboembolism; however, the mechanisms have not been elucidated. The objective of this study is to assess the effectiveness of antiplatelet medications for Kawasaki disease. We used Medline, Embase, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Ichushi) from January 1947 to August 2018. Studies describing the platelet functions of antiplatelet drugs for Kawasaki disease were included. Twenty studies met the inclusion criteria. There were no randomized controlled trials. Seven studies compared platelet aggregation ability before and after treatment. Eight studies compared platelet aggregation with that in Kawasaki disease patients without treatment. Four studies compared aggregation among different types of antiplatelet drugs or at different doses. Antiplatelet medications administered in the studies included aspirin, flurbiprofen, dipyridamole, and choline salicylate. Methods for the measurement of platelet aggregation ability varied among studies. The groups with antiplatelet treatment tended to have a decreased platelet aggregation function. The statistical analyses were impossible due to insufficient quantitative data and heterogeneity among the studies.Conclusion: The present systematic review revealed that there was insufficient evidence for the effectiveness of antiplatelet therapy for Kawasaki disease. What is Known: • Antiplatelet therapy is widely used for Kawasaki disease to mitigate cardiac complications. • The mechanisms of antiplatelet therapy for Kawasaki disease are not clarified. What is New: • This systematic review showed that the groups with antiplatelet treatment tended to have a decreased platelet aggregation function. • There is insufficient evidence for the effectiveness of antiplatelet therapy for Kawasaki disease.