title: Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A Mimic of Childhood Granulomatosis With Polyangiitis.
abstract: OBJECTIVE
  The type I interferonopathies comprise a recently recognized group of mendelian diseases characterized by an upregulation of type I interferon signaling. These monogenic phenotypes include classic Aicardi-Goutières syndrome and syndromic forms of systemic lupus erythematosus, including familial chilblain lupus and spondyloenchondrodysplasia. Dermatologic features provide a major diagnostic clue to this disease grouping, as exemplified by the recently described stimulator of interferon genes-associated vasculopathy with onset in infancy (SAVI) caused by gain-of-function mutations in TMEM173.
  
  
  METHODS
  We describe a male child who, from the age of 2 months, had significant cutaneous disease that manifested as red violaceous plaques of the cheeks, nose, ears, fingers, and toes that progressed to gangrenous necrosis. In addition to his severe cutaneous vasculopathy, he experienced recurrent fevers, interstitial lung disease, and failure to thrive. His clinical syndrome was refractory to multiple immunosuppressive therapies. Evidence of marked upregulation of type I interferon signaling was observed in peripheral blood, and genetic testing identified a de novo germline mutation in TMEM173, confirming a diagnosis of SAVI 7 years after the onset of his disease.
  
  
  CONCLUSIONS
  This observational report describes a new case of SAVI, a recently defined monogenic inflammatory phenotype, that exemplifies an emerging group of disorders related to primary upregulation of type I interferon signaling.
authors.affiliation: Department of Dermatology, St Eloi Hospital, CHRU Montpellier, Montpellier, France2University of Montpellier I, Montpellier, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Munoz
authors.affiliation: University of Montpellier I, Montpellier, France3Department of Pediatrics, Arnaud de Villeneuve Hospital, CHRU Montpellier, Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Rodière
authors.affiliation: Institut Imagine, Necker Hospital for Sick Children, Paris, France5Paris Descartes University, Paris, France6INSERM UMR 1163, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Jeremiah
authors.affiliation: Institut Imagine, Necker Hospital for Sick Children, Paris, France5Paris Descartes University, Paris, France6INSERM UMR 1163, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Oojageer
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.affiliation: Paris Descartes University, Paris, France8Department of Virology, Cochin Hospital AP-HP, Paris, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Rozenberg
authors.affiliation: Institut Imagine, Necker Hospital for Sick Children, Paris, France5Paris Descartes University, Paris, France6INSERM UMR 1163, Paris, France7Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manch.
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
authors.affiliation: Department of Dermatology, St Eloi Hospital, CHRU Montpellier, Montpellier, France2University of Montpellier I, Montpellier, France9INSERM U1058, Montpellier, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Bessis
mesh_terms: D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D007370:Interferon Type I / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D017445:Skin Diseases, Vascular / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation; D000099197:STING Protein
chemical_list: D007370:Interferon Type I; D008565:Membrane Proteins; C532857:STING1 protein, human; D000099197:STING Protein