Role of the skin biopsy in the diagnosis of atypical hemolytic uremic syndrome

Cynthia M. Magro, Shabnam Momtahen, Joseph Justin Mulvey, Aminah H. Yassin, Robert B. Kaplan, Jeffrey C. Laurence

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)349-359
Number of pages11
JournalAmerican Journal of Dermatopathology
Volume37
Issue number5
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • aHUS
  • atypical hemolytic uremic syndrome
  • eculizumab

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Dermatology

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