title: Role of the skin biopsy in the diagnosis of atypical hemolytic uremic syndrome.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: *Professor of Pathology and Laboratory Medicine, Dermatopathologist, Director of Dermatopathology, Department of Pathology and Laboratory Medicine and †Anatomic and Clinical Pathology Resident, Weill Cornell Medical College, Cornell University, New York, NY; ‡MD-PhD Candidate, Weill Cornell Graduate School of Medical Sciences, Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY; §Research Assistant, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College of Cornell University, New York, NY; ¶Hematologist, Department of Hemostasis, Thrombosis Laboratory, The Western Pennsylvania Hospital Allegheny Health Network, Pittsburgh, PA; and #Professor of Medicine in the Division of Hematology-Oncology, Attending Physician, Department of Medicine Weill Cornell Medical College, NewYork-Presbyterian Hospital New York, NY.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Magro
authors.forename: Shabnam
authors.initials: S
authors.lastname: Momtahen
authors.forename: Joseph Justin
authors.initials: JJ
authors.lastname: Mulvey
authors.forename: Aminah H
authors.initials: AH
authors.lastname: Yassin
authors.forename: Robert B
authors.initials: RB
authors.lastname: Kaplan
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Laurence
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D065766:Atypical Hemolytic Uremic Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D015938:Complement Membrane Attack Complex / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D015938:Complement Membrane Attack Complex; D007166:Immunosuppressive Agents; C481642:eculizumab