Division of Immunology, Boston Children's Hospital, 300 Longwood Avenue, Fegan 6, Boston, MA, 02115, USA.
Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Pediatr Rheumatol Online J. 2021 Mar 17;19(1):31. doi: 10.1186/s12969-021-00526-0.
Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA).
We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospective chart review of our KD population, we identified ten children treated for KD with intravenous CYC (10 mg/kg/dose) for one or two doses. Seven patients were male, the median age was 2.0 years (range 4 months - 5 years). All patients received initial IVIG between day 4-10 of illness. Other anti-inflammatory treatments administered before CYC included second IVIG (n = 9), corticosteroids (n = 10), infliximab (n = 4), cyclosporine (n = 2), and anakinra (n = 1). Median illness day at administration of the first CYC dose was 22.5 days (range:10-36 days). The primary indication for treatment with CYC for all patients was large or giant CAA and/or rapid progression of CAA. Three patients received a second dose of CYC (10 mg/kg) for progressively enlarging CAA. CAA did not progress after final CYC treatment. One patient with a history of neutropenia in infancy developed severe neutropenia 9 days after treatment with CYC, which recovered without intervention or complications. No patient developed infections or other serious toxicity from CYC.
In KD patients with severe and progressive enlargement of CAA despite anti-inflammatory therapy, CYC seemed to arrest further dilation and was well-tolerated. Future multicenter studies are needed to confirm our findings in this subgroup of KD patients.
尽管及时给予静脉注射免疫球蛋白（IVIG）治疗，一些川崎病（KD）患者仍会出现快速进展或巨大冠状动脉瘤（CAA）。
我们描述了使用环磷酰胺（CYC）治疗此类病例的经验，并回顾了 CYC 在 KD 中的应用文献。通过对 KD 患者的回顾性图表审查，我们确定了 10 名接受静脉注射 CYC（10mg/kg/剂）治疗的儿童，剂量为 1 或 2 剂。7 名患者为男性，中位年龄为 2.0 岁（范围为 4 个月至 5 岁）。所有患者在疾病第 4-10 天接受初始 IVIG 治疗。在 CYC 治疗前给予的其他抗炎治疗包括第二次 IVIG（n=9）、皮质类固醇（n=10）、英夫利昔单抗（n=4）、环孢素（n=2）和阿那白滞素（n=1）。首次 CYC 剂量给药时的中位疾病天数为 22.5 天（范围：10-36 天）。所有患者使用 CYC 的主要指征是大或巨大 CAA 和/或 CAA 的快速进展。3 名患者因 CAA 逐渐增大而接受了第二次 CYC（10mg/kg）治疗。在最后一次 CYC 治疗后，CAA 没有进一步进展。1 名在婴儿期有中性粒细胞减少症病史的患者在 CYC 治疗后 9 天发生严重中性粒细胞减少症，但未经干预或并发症自行恢复。没有患者因 CYC 发生感染或其他严重毒性。
在 KD 患者中，尽管进行了抗炎治疗，CAA 仍严重且进行性增大，CYC 似乎能阻止进一步扩张，且耐受性良好。需要进行未来的多中心研究来证实我们在 KD 患者这一亚组中的发现。
