Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Université Paris VII, Pediatric Nephrology Department, Paris, France.
Orphanet J Rare Dis. 2011 Sep 8;6:60. doi: 10.1186/1750-1172-6-60.
Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently, without unquestionable demonstration of efficiency. There is a high risk of post-transplant recurrence, except in MCP-HUS. Case reports and two phase II trials show an impressive efficacy of the complement C5 blocker eculizumab, suggesting it will be the next standard of care. Except for patients treated by intensive plasmatherapy or eculizumab, the worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of survivors do not recover renal function. Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early.
溶血性尿毒症综合征（HUS）的定义为机械性溶血性贫血、血小板减少和肾功能损害三联征。非志贺毒素 HUS（aHUS）定义为非志贺毒素 HUS，即使一些作者包括因肺炎链球菌或其他原因引起的继发性 aHUS，aHUS 仍表示补体替代途径调节紊乱引起的原发性疾病。aHUS 在儿童中占 HUS 的 5-10%，但在成人中占多数。补体 aHUS 的发病率尚不清楚。然而，已经报道了超过 1000 例因补体异常而接受检查的 aHUS 患者。发病年龄从新生儿期到成年期。大多数患者表现为溶血性贫血、血小板减少和肾功能衰竭，20%有肾脏外表现。2-10%的患者死亡，1/3 的患者首次发作进展为终末期肾衰竭。半数患者有复发。约 20-30%、5-15%、4-10%和 3-5%的患者分别存在编码补体调节蛋白因子 H、膜辅助蛋白（MCP）、因子 I 或血栓调节蛋白的基因突变，2-10%和 1-4%的患者存在 C3 转化酶蛋白、C3 和因子 B 的基因突变。此外，6-10%的患者存在抗因子 H 抗体。aHUS 的诊断依赖于 1）无相关疾病 2）无志贺毒素 HUS 标准（粪便培养和 PCR 检测志贺毒素；血清抗脂多糖抗体检测） 3）无血栓性血小板减少性紫癜标准（血清 ADAMTS13 活性>10%）。需要检查补体系统（C3、C4、因子 H 和因子 I 血浆浓度、白细胞上的 MCP 表达和抗因子 H 抗体；遗传筛查以识别危险因素）。该病约 20%的家系为家族性，呈常染色体隐性或显性遗传方式。由于疾病的外显率为 50%，遗传咨询较为困难。血浆疗法一直是一线治疗方法，目前尚无确切的疗效证据。除 MCP-HUS 外，移植后复发风险较高。病例报告和两项 II 期试验表明，补体 C5 抑制剂依库珠单抗具有显著疗效，提示其将成为下一个治疗标准。除接受强化血浆疗法或依库珠单抗治疗的患者外，因子 H-HUS 的预后最差，死亡率可达 20%，50%的幸存者无法恢复肾功能。一半的因子 I-HUS 进展为终末期肾衰竭。相反，大多数 MCP-HUS 患者保留了肾功能。如果早期治疗，抗因子 H 抗体-HUS 的预后良好。
