Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Pediatrics. 2013 Jan;131(1):e331-5. doi: 10.1542/peds.2012-0903. Epub 2012 Dec 10.
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe clinical manifestation, frequent recurrence, and poor long-term prognosis. It is usually caused by abnormalities in complement regulation. We report 2 cases of children affected by a catastrophic extrarenal complication. A 4-year-old Indian girl developed gangrene of the finger tips 2 days after initial presentation of aHUS. Factor H autoantibodies were identified. Renal function continued to decline despite daily plasma exchanges, and she was started on peritoneal dialysis 5 days after admission. The distal tips of the left hand remained gangrenous with a line of demarcation. Three weeks later, she did not return for follow-up and died at home because of dialysis-related complications. An Arabic girl developed end-stage renal disease due to aHUS in the fourth month after birth. A de novo activating C3 mutation was found. At age 9 months, she suddenly developed ischemic changes in fingers of both hands and several toes. The lesions progressed, and several finger tips became gangrenous despite intense plasma exchange therapy. The decision was made to administer complement blocking therapy with the C5 antibody eculizumab. All nonnecrotic digits rapidly regained perfusion. The 3 already gangrenous fingers healed with loss of the end phalanges. During maintenance, eculizumab aHUS activity subsided completely and some late recovery of renal function was observed. aHUS may present by thrombotic macroangiopathy of small peripheral arteries. Eculizumab appears effective in preserving tissue viability if administered before gangrene occurs and should be considered as first-line rescue therapy in such cases.
非典型溶血尿毒症综合征（aHUS）是一种临床表现严重、频繁复发、预后不良的血栓性微血管病，通常由补体调节异常引起。我们报告了 2 例儿童受灾难性肾外并发症影响的病例。一名 4 岁印度女孩在出现 aHUS 后 2 天出现指尖坏疽。鉴定出因子 H 自身抗体。尽管每天进行血浆置换，肾功能仍持续下降，入院后 5 天开始进行腹膜透析。左手远端指尖仍呈坏疽状，有一线状分界。3 周后，她未回来随访，因透析相关并发症在家中死亡。一名阿拉伯女孩在出生后第 4 个月因 aHUS 发展为终末期肾病。发现新出现的 C3 激活突变。9 个月大时，她的双手和几个脚趾突然出现缺血性改变。病变进展，尽管进行了强烈的血浆置换治疗，几个指尖仍发生坏疽。决定给予 C5 抗体依库珠单抗进行补体阻断治疗。所有未坏死的手指迅速恢复灌注。已经坏疽的 3 个手指因末端指骨缺失而愈合。在维持治疗期间，依库珠单抗 aHUS 活性完全消退，并观察到肾功能的一些迟发性恢复。aHUS 可能表现为小外周动脉的血栓性大血管病。如果在坏疽发生前给予依库珠单抗，它似乎可有效保存组织活力，应考虑将其作为此类情况下的一线抢救治疗。
