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

Am J Dermatopathol. 2015 May;37(5):349-56; quiz 357-9. doi: 10.1097/DAD.0000000000000234.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Atypical Hemolytic Uremic Syndrome / diagnosis*
  • Atypical Hemolytic Uremic Syndrome / drug therapy
  • Atypical Hemolytic Uremic Syndrome / immunology
  • Atypical Hemolytic Uremic Syndrome / pathology
  • Biomarkers / metabolism
  • Biopsy
  • Case-Control Studies
  • Complement Membrane Attack Complex / immunology*
  • Complement Membrane Attack Complex / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Microvessels / drug effects
  • Microvessels / immunology*
  • Microvessels / pathology
  • Middle Aged
  • Predictive Value of Tests
  • Skin / blood supply*
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Complement Membrane Attack Complex
  • Immunosuppressive Agents
  • eculizumab