Distinct conditions support a novel classification for bradykinin-mediated angio-oedema

Dermatology. 2015;230(4):324-31. doi: 10.1159/000371814. Epub 2015 Feb 20.


Background: Angio-oedema (AO) can be attributable to bradykinin (BK) accumulation, as is the case for prototypical hereditary AO (HAO) due to C1 inhibitor (C1-INH) deficiency. However, our clinical experience in a reference centre has shown that some patients display a clinical history suggestive of HAO, but exhibit normal C1-INH function, have no mutation in the causative genes associated with HAO (SERPING1, F12), and report no intake of drugs known to promote AO.

Objective: We sought to determine the frequency and distribution of different AO subtypes suspected to be BK-mediated AO (BK-AO) and defined by clinical, history and biological criteria (enzyme activities implicated in BK formation and catabolism).

Methods: The files of all patients referred to our centre for suspected BK-AO were retrospectively analysed.

Results: The distribution of patients (n = 162) was 16 and 4% with a hereditary deficiency of C1-INH or a gain of factor XII function, respectively, 29% with iatrogenic BK-AO, 21% with non-iatrogenic defective kininase activity and 30% with idiopathic increased kinin formation.

Conclusion: BK-AO may be caused by multiple inherited or acquired factors triggering BK accumulation. Therefore, we propose a novel typology for BK-AO based on the imbalance of production/catabolism of BK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amidohydrolases / metabolism
  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Angioedema / classification*
  • Angioedema / etiology
  • Angioedema / metabolism*
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Bradykinin / metabolism*
  • Child
  • Child, Preschool
  • Complement C1 Inactivator Proteins / genetics
  • Complement C1 Inhibitor Protein / metabolism*
  • Factor XII / genetics
  • Female
  • Hereditary Angioedema Types I and II / complications
  • Hereditary Angioedema Types I and II / enzymology
  • Hereditary Angioedema Types I and II / genetics
  • Hormones / adverse effects
  • Humans
  • Lysine Carboxypeptidase / metabolism
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / metabolism
  • Polymorphism, Single Nucleotide
  • Recurrence
  • Retrospective Studies
  • Urticaria / etiology
  • Young Adult


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • Hormones
  • SERPING1 protein, human
  • Factor XII
  • Aminopeptidases
  • X-Pro aminopeptidase
  • Peptidyl-Dipeptidase A
  • Lysine Carboxypeptidase
  • Amidohydrolases
  • amidase
  • Bradykinin