Cullinan Noelle, Gorman Kathleen Mary, Riordan Michael, Waldron Mary, Goodship Timothy H J, Awan Atif
The Department for Paediatric Nephrology & Transplantation, The Children's University Hospital, Dublin 1, Ireland; and
The Department for Paediatric Nephrology & Transplantation, The Children's University Hospital, Dublin 1, Ireland; and.
Pediatrics. 2015 Jun;135(6):e1506-9. doi: 10.1542/peds.2014-3503. Epub 2015 May 4.
Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated against invasive meningococcal infection before beginning eculizumab therapy and take appropriate antibiotic prophylaxis during treatment, and we suggest that vaccine responses should be checked and followed annually. Clinicians need to maintain a high index of suspicion for invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis provides complete protection in patients on eculizumab therapy. The appropriate dosage of eculizumab needed to achieve remission in aHUS in the pediatric population is unknown. Having achieved remission in our patient, we monitor eculizumab and CH50 levels to evaluate ongoing blockade of the terminal complement cascade. Such information may help guide dosing intervals in the future.
非典型溶血性尿毒症综合征（aHUS）由补体系统失调引起，导致补体过度激活。一种人源化抗C5单克隆抗体依库珠单抗自2011年起可用于治疗aHUS。这种新药在儿科人群中的长期安全性和疗效仍在评估中。我们报告一名携带CFH/CFHR3杂交基因的儿童，尽管接受了血浆置换的最佳治疗仍多次复发疾病，于2010年8月开始接受依库珠单抗治疗。在52个月的随访中她未再复发，且治疗耐受性良好。已认识到该治疗期间发生脑膜炎球菌病的风险。尽管接种了脑膜炎球菌病疫苗并进行了适当的抗生素预防，我们的患者在治疗30个月时仍发生了脑膜炎球菌菌血症。她表现为非特异性症状，但经适当治疗后康复且无后遗症。我们建议儿童在开始依库珠单抗治疗前接种侵袭性脑膜炎球菌感染疫苗，并在治疗期间进行适当的抗生素预防，我们还建议应每年检查并跟踪疫苗反应。临床医生需要对侵袭性脑膜炎球菌病保持高度怀疑。疫苗接种和抗生素预防均不能为接受依库珠单抗治疗的患者提供完全保护。在儿科人群中使aHUS缓解所需的依库珠单抗适当剂量尚不清楚。在我们的患者实现缓解后，我们监测依库珠单抗和CH50水平以评估终末补体级联的持续阻断情况。此类信息可能有助于指导未来的给药间隔。
