title: Degos disease: a C5b-9/interferon-α-mediated endotheliopathy syndrome.
abstract: Degos disease is a lethal small vessel angiopathy targeting the skin, gastrointestinal tract, and central nervous system, potentially developing in the setting of known autoimmune disease, although forme fruste primary variants exist. Its pathogenetic basis is unknown. Four cases of Degos disease were encountered in archival material, representing 2 men, ages 38 and 43 years, and 2 females, ages 48 and 2 years; 3 patients died of disease. All had characteristic skin lesions with gastrointestinal involvement; other affected organs included brain in one and pericardium and pleura in another. Skin biopsies showed pauci-inflammatory thrombogenic microangiopathy with endothelial cell injury. Extracutaneous organs demonstrated fibromucinous occlusive arteriopathy. Prominent vascular C5b-9 was seen in the skin, gastrointestinal tract, and brain. All cases had evidence of high expression of interferon-α (based on tissue expression of MXA, a type I interferon-inducible protein), endothelial tubuloreticular inclusions, and an interferon gene signature in peripheral blood mononuclear cells. The MXA expression paralleled the pattern of C5b-9 deposition. Degos disease is a distinct vascular injury syndrome whereby a dysregulated interferon-α response in concert with membranolytic attack complex deposition may contribute to the unique vascular changes. Understanding the pathophysiology of the disease process could lead to more directed therapies, including terminal complement inhibition with agents such as eculizumab.
authors.affiliation: Division of Dermatopathology, Dept of Pathology and Laboratory Medicine, Weill Cornell College of Cornell University, New York, NY 10065, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Magro
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Poe
authors.forename: Connie
authors.initials: C
authors.lastname: Kim
authors.forename: Lee
authors.initials: L
authors.lastname: Shapiro
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: Mary K
authors.initials: MK
authors.lastname: Crow
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D041981:Gastrointestinal Tract / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D008297:Male; D054853:Malignant Atrophic Papulosis / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D057049:Thrombotic Microangiopathies / Q000378:metabolism / Q000473:pathology
chemical_list: D015938:Complement Membrane Attack Complex; D016898:Interferon-alpha