Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
J Rheumatol. 2012 Apr;39(4):864-7. doi: 10.3899/jrheum.110877. Epub 2012 Feb 15.
Kawasaki disease (KD) is an acute febrile disease in infants and young children. Five percent to 8% of cases will be complicated with coronary dilatation or aneurysm, although introduction of high-dose intravenous immunoglobulin (IVIG) therapy has provided remarkable results for reducing the frequency of cardiac involvement. We describe the results of an open-label trial of infliximab, an anti-tumor necrosis factor-α monoclonal antibody, for suppressing the progression of coronary artery lesions in cases of KD refractory to extensive IVIG therapy. Plasma exchange (PE) was available as a rescue therapy for patients refractory to infliximab.
Twenty eligible patients fulfilled the diagnostic criteria for KD, and were primarily treated with IVIG up to 4 g/kg. "Refractory to IVIG" was defined as persisting or reemerging fever > 38°C and positive fractional changes of C-reactive protein, white blood cell counts, or neutrophil counts 48 hours after IVIG infusion. These cases were treated with infliximab, 5 mg/kg, which should begin within 10 days of disease onset. PE for patients refractory to infliximab was performed with 5% albumin.
There was rapid improvement of inflammatory symptoms as well as normalization of the inflammatory markers. Sequential examination by echocardiography up to disease Day 30 revealed that the inflamed and mildly dilated coronary artery at the beginning of the study regressed to normal size in the convalescent phase. Two out of 20 patients showed incomplete improvement of inflammatory symptoms after infliximab treatment, and were provided with PE therapy, with no complications.
Eighteen of 20 patients were effectively treated with infliximab, and 2 cases were effectively treated with PE to prevent progression to coronary artery lesions. No adverse event such as anaphylactoid reaction, heart failure, severe infectious diseases, or tuberculosis was observed in this trial.
川崎病（KD）是一种发生于婴幼儿的急性发热性疾病。尽管大剂量静脉注射免疫球蛋白（IVIG）治疗显著降低了心脏受累的发生率，但仍有 5%至 8%的病例会并发冠状动脉扩张或动脉瘤。我们描述了英夫利昔单抗（一种抗肿瘤坏死因子-α的单克隆抗体）治疗川崎病患儿的开放性试验结果，该试验旨在抑制 KD 患儿对广泛 IVIG 治疗无反应的冠状动脉病变进展。对于对英夫利昔单抗无反应的患者，可采用血浆置换（PE）作为挽救性治疗。
20 名符合 KD 诊断标准的患者首先接受了高达 4 g/kg 的 IVIG 治疗。“对 IVIG 无反应”定义为 IVIG 输注后 48 小时持续或再次出现发热>38°C，且 C 反应蛋白、白细胞计数或中性粒细胞计数的分数变化呈阳性。这些患者给予英夫利昔单抗，5mg/kg，应在发病后 10 天内开始治疗。对于对英夫利昔单抗无反应的患者，采用 5%白蛋白进行 PE。
炎症症状迅速改善，炎症标志物恢复正常。在疾病第 30 天之前进行的连续超声心动图检查显示，在研究开始时炎症和轻度扩张的冠状动脉在恢复期恢复到正常大小。20 例患者中有 2 例在接受英夫利昔单抗治疗后炎症症状改善不完全，给予 PE 治疗，无并发症。
20 例患者中有 18 例接受英夫利昔单抗治疗有效，2 例接受 PE 治疗有效，预防了冠状动脉病变进展。本试验未观察到过敏样反应、心力衰竭、严重感染性疾病或结核病等不良事件。
