Role of the Skin Biopsy in the Diagnosis of Atypical Hemolytic Uremic Syndrome
Role of the Skin Biopsy in the Diagnosis of Atypical Hemolytic Uremic Syndrome
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DOI：
10.1097/dad.0000000000000234
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发表时间：
2015-05-01
影响因子：
1.1
通讯作者：
Laurence, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Magro, Cynthia M.;Momtahen, Shabnam;Laurence, Jeffrey C.
引言：非典型溶血性尿毒症综合征（阿胡斯）是一种典型的血栓性微血管病，可归因于补体失调。在没有补体抑制的情况下，发生进行性临床恶化。作者推测正常皮肤活检可通过显示C5 b-9血管沉积来证实阿胡斯的诊断。材料和方法：对22例aHUS患者和22例非阿胡斯患者的正常皮肤活检进行常规光镜和免疫荧光研究。通过免疫荧光和化学方法对血管C5 b-9沉积进行评估。活检主要从前臂和/或三角肌获得。结果：阿胡斯的经典功能的患者表现出阴险的微血管变化，包括松散的管腔血小板血栓，除了在2例患者中，其中一个引人注目的血栓形成血管病变是明显的活检指溃疡。确定了膜攻击复合物/C5 b-9的广泛微血管沉积，不包括1例在活检前开始使用依库珠单抗的患者。在7例随访可用的患者中，5例患者对依库珠单抗表现出极好的治疗应答。没有阿胡斯诊断性临床特征的患者未能显示出显著的补体血管沉积，除了2例血栓性血小板减少性紫癜患者，包括其中1例确定了因子H突变。在阿胡斯是重要诊断考虑因素的临床环境中，广泛的C5 b微血管沉积9支持阿胡斯或伴有补体失调的血栓性血小板减少性紫癜患者子集的诊断;显著的血管C5 b-9沉积预测对依库珠单抗的临床反应性。
Introduction: Atypical hemolytic uremic syndrome (aHUS) is a prototypic thrombotic microangiopathy attributable to complement dysregulation. In the absence of complement inhibition, progressive clinical deterioration occurs. The authors postulated that a biopsy of normal skin could corroborate the diagnosis of aHUS through the demonstration of vascular deposits of C5b-9.Materials and Methods: Biopsies of normal skin from 22 patients with and without aHUS were processed for routine light microscopy and immunofluorescent studies. An assessment was made for vascular C5b-9 deposition immunohistochemically and by immunofluorescence. The biopsies were obtained primarily from the forearm and/or deltoid.Results: Patients with classic features of aHUS showed insidious microvascular changes including loose luminal platelet thrombi, except in 2 patients in whom a striking thrombogenic vasculopathy was apparent in biopsied digital ulcers. Extensive microvascular deposits of the membrane attack complex/C5b-9 were identified, excluding 1 patient in whom eculizumab was initiated before biopsy. In 5 of the 7 patients where follow-up was available, the patients exhibited an excellent treatment response to eculizumab. Patients without diagnostic clinical features of aHUS failed to show significant vascular deposits of complement, except 2 patients with thrombotic thrombocytopenic purpura including 1 in whom a Factor H mutation was identified.Conclusions: In a clinical setting where aHUS is an important diagnostic consideration, extensive microvascular deposition of C5b-9 supports the diagnosis of either aHUS or a subset of thrombotic thrombocytopenic purpura patients with concomitant complement dysregulation; significant vascular C5b-9 deposition predicts clinical responsiveness to eculizumab.