Terano Chikako, Ishikura Kenji, Hamada Riku, Yoshida Yasuhiro, Kubota Wataru, Okuda Yusuke, Shinozuka Shunsuke, Harada Ryoko, Iyoda Sunao, Fujimura Yoshihiro, Hamasaki Yuko, Hataya Hiroshi, Honda Masataka
Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.
Division of Nephrology and Rheumatology, National Center for Child Health and Development, Japan.
Nephrology (Carlton). 2018 Jun;23(6):539-545. doi: 10.1111/nep.13054.
Recently eculizumab, a monoclonal antibody to C5, was found to improve the disease course of atypical haemolytic uraemic syndrome (aHUS) and has been recommended as the first line treatment by an international consensus guideline. However, several practical issues in the use of eculizumab for the acute phase of aHUS have yet to be resolved.
Children who received eculizumab with diagnosis of aHUS between March 2010 and December 2015 at Tokyo Metropolitan Children's Medical Center were enrolled. aHUS was diagnosed according to the haemolytic uraemic syndrome (HUS) criteria after excluding Shiga toxin-inducing Escherichia coli (STEC) -associated HUS and thrombocytopaenic purpura. We retrieved and analyzed data from the electronic medical records at our institution.
We reviewed four patients with suspected aHUS. Eculizumab was discontinued in one patient in whom STEC-HUS was later diagnosed. Treatment was continued in the remaining three patients without recurrence. Practical issues included difficulty in diagnosing aHUS, particularly in the acute phase, risk of infection by encapsulated organisms, especially Neisseria meningitis, and infusion reaction. In addition to issues relating to the acute phase, discontinuing eculizumab in stable patients in the chronic phase must be considered.
Eculizumab, the first line treatment for children with aHUS, is usually effective. However, certain problems associated with its use require caution to be exercised. As clinical information on eculizumab are still very limited, and the rationale for its long-term use has yet to be established, physicians are advised to exercise care when using eculizumab to manage aHUS.
最近发现，抗C5单克隆抗体依库珠单抗可改善非典型溶血尿毒综合征（aHUS）的病程，并且已被一项国际共识指南推荐为一线治疗药物。然而，依库珠单抗在aHUS急性期使用中的几个实际问题尚未得到解决。
纳入2010年3月至2015年12月期间在东京都儿童医疗中心接受依库珠单抗治疗且诊断为aHUS的儿童。在排除产志贺毒素大肠杆菌（STEC）相关的溶血尿毒综合征（HUS）和血小板减少性紫癜后，根据溶血尿毒综合征（HUS）标准诊断aHUS。我们检索并分析了本机构电子病历中的数据。
我们回顾了4例疑似aHUS的患者。1例后来被诊断为STEC-HUS的患者停用了依库珠单抗。其余3例患者继续治疗且未复发。实际问题包括aHUS诊断困难，尤其是在急性期，感染包膜菌的风险，特别是脑膜炎奈瑟菌，以及输液反应。除了与急性期相关的问题外，还必须考虑在慢性期稳定患者中停用依库珠单抗的问题。
依库珠单抗作为aHUS患儿的一线治疗药物通常有效。然而，使用该药存在的某些问题需要谨慎对待。由于依库珠单抗的临床信息仍然非常有限，其长期使用的理论依据尚未确立，建议医生在使用依库珠单抗治疗aHUS时谨慎行事。
