title: Angio-oedema induced by oestrogen contraceptives is mediated by bradykinin and is frequently associated with urticaria.
abstract: BACKGROUND
  Hereditary C1-inhibitor (C1-Inh) deficiency is associated with 'bradykinin-mediated angio-oedema' (BK-AO) and is believed not to be associated with urticaria. Acquired AO has been related to oestrogen contraceptives.
  
  
  OBJECTIVE
  To demonstrate that AO precipitated by oestrogens and characterized by nonfunctional C1-Inh is mediated by BK and to evaluate the occurrence of urticaria in these patients.
  
  
  METHODS
  A retrospective evaluation of patients referred for AO related to oestrogen was undertaken. Circulating C1-Inh, high molecular weight kininogen (HK) and enzymes involved in the metabolism of bradykinin were investigated.
  
  
  RESULTS
  Fifteen patients were included. HK cleavage concurrent to oestrogen intake was demonstrated in 10 patients with available plasma. Eight patients reported recurrent or chronic urticaria. Discontinuation of the contraceptive resulted in a return to native C1-Inh and HK in all cases studied and to normal kininogenase activity in all but one. The clinical manifestations completely disappeared in 6 patients and improved in 7 after the withdrawal of oestrogen.
  
  
  CONCLUSIONS
  Patients display extensive cleavage of HK in the plasma, which supports that AO precipitated by oestrogen contraception is BK-mediated. Recurrent urticaria may have been underestimated in this context. The presence of recurrent urticaria should not systematically rule out the diagnosis of BK-AO when the history is suggestive.
authors.affiliation: Department of Dermatology, L’UNAM University, Angers Hospital, Angers, France.
authors.forename: C
authors.initials: C
authors.lastname: Giard
authors.forename: B
authors.initials: B
authors.lastname: Nicolie
authors.forename: M
authors.initials: M
authors.lastname: Drouet
authors.forename: C
authors.initials: C
authors.lastname: Lefebvre-Lacoeuille
authors.forename: J
authors.initials: J
authors.lastname: Le Sellin
authors.forename: J-C
authors.initials: JC
authors.lastname: Bonneau
authors.forename: H
authors.initials: H
authors.lastname: Maillard
authors.forename: G
authors.initials: G
authors.lastname: Rénier
authors.forename: S
authors.initials: S
authors.lastname: Cichon
authors.forename: D
authors.initials: D
authors.lastname: Ponard
authors.forename: C
authors.initials: C
authors.lastname: Drouet
authors.forename: L
authors.initials: L
authors.lastname: Martin
mesh_terms: D000799:Angioedema / Q000097:blood / Q000139:chemically induced*; D001920:Bradykinin / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism*; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D003937:Diagnosis, Differential; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000097:blood*; D012189:Retrospective Studies; D014581:Urticaria / Q000097:blood / Q000139:chemically induced*
chemical_list: D050718:Complement C1 Inhibitor Protein; D003278:Contraceptives, Oral, Hormonal; D004967:Estrogens; D019679:Kininogen, High-Molecular-Weight; D001920:Bradykinin