title: Angioedema Triggered by Medication Blocking the Renin/Angiotensin System: Retrospective Study Using the French National Pharmacovigilance Database.
abstract: BACKGROUND
  Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database.
  
  
  METHODS
  The national MedDRA database was searched using the term "angioedema". Patients were included if they met the clinical criteria corresponding to bradykinin-mediated AE, if their C1-inhibitor levels were normal, and if they were treated with an ACEi or an ARB.
  
  
  RESULTS
  7998 cases of AE were reported between 1994 and 2013. Among these, 112 met the criteria for bradykinin-mediated AE with normal C1-inhibitor levels. On the 112 drug-AE, patients were treated with an ARB in 21% of cases (24 patients), or an ACEi in 77% of cases (88 patients), in combination with another treatment in 17 cases (mTORi for 3 patients, iDPP-4 for 1 patient, hormonal treatment for 7 patients). ENT involvement was reported in 90% of cases (tongue: 48.2%, larynx: 23.2%). The median duration of treatment before the first attack was 720 days, and the mean duration of attacks was 36.6 h. Forty-one percent (19/46) of patients relapsed after discontinuing treatment.
  
  
  CONCLUSIONS
  Angioedema triggered by medication blocking the renin/angiotensin system is rare but potentially severe, with a high risk of recurrence despite cessation of the causative drug.
authors.affiliation: Internal Medicine Department, Grenoble University Hospital, Grenoble, France. cfaisant@chu-grenoble.fr.|Grenoble Alps University, Grenoble, France. cfaisant@chu-grenoble.fr.|Clinique Universitaire de Médecine Interne, CHU de Grenoble, Hopital Michallon CS10217, 38043, Grenoble, Cedex 09, France. cfaisant@chu-grenoble.fr.
authors.forename: Charles
authors.initials: C
authors.lastname: Faisant
authors.affiliation: Internal Medicine Department, Rouen University Hospital, Rouen, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Armengol
authors.affiliation: Internal Medicine Department, Grenoble University Hospital, Grenoble, France.|Grenoble Alps University, Grenoble, France.|French National Reference Centre for Angioedema (CREAK), Grenoble, France.|Inserm-UJF-CEA-CNRS Unit 1036, IRTSV, CEA Grenoble, Grenoble, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouillet
authors.affiliation: Internal Medicine Department, Grenoble University Hospital, Grenoble, France.|French National Reference Centre for Angioedema (CREAK), Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boccon-Gibod
authors.affiliation: Pharmacovigilance Department, Grenoble University Hospital, Grenoble, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Villier
authors.affiliation: Internal Medicine Department, Rouen University Hospital, Rouen, France.|Inserm U1096, Rouen, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lévesque
authors.affiliation: Pharmacovigilance Department, Lyon University Hospital, Lyon, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Cottin
authors.affiliation: Pharmacovigilance Department, Rouen University Hospital, Rouen, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Massy
authors.affiliation: Internal Medicine Department, Rouen University Hospital, Rouen, France.|Inserm U1096, Rouen, France.
authors.forename: Ygal
authors.initials: Y
authors.lastname: Benhamou
mesh_terms: D000368:Aged; D000799:Angioedema / Q000139:chemically induced / Q000453:epidemiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001920:Bradykinin / Q000008:administration & dosage* / Q000009:adverse effects; D016208:Databases, Factual; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D060735:Pharmacovigilance; D012008:Recurrence; D012084:Renin-Angiotensin System / Q000187:drug effects; D012189:Retrospective Studies; D028761:Withholding Treatment
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001920:Bradykinin
keywords: Angioedema; angiotensin II antagonist; angiotensin converting enzyme inhibitor; bradykinin