Iatrogenic angioedema associated with ACEi, sitagliptin, and deficiency of 3 enzymes catabolizing bradykinin

Eur Ann Allergy Clin Immunol. 2014 May;46(3):119-22.


New concepts of idiopathic and iatrogenic angioedema underline the role of bradykinin, and the importance of catabolizing enzymes. A case is described of Angiotensin converting enzyme inhibitor (ACEi) and sitagliptin induced angioedema, where AO attacks decreased after the withdrawal of lisinopril but resolved only after the withdrawal of sitagliptin, an inhibitor of dipeptylpeptidase IV. ACE, aminopeptidase P and carboxypeptidase N were decreased down to 17%, 42%, 64% of median references values, and remained low one year after the interruption of these drugs: 56%, 28% and 50%, respectively. The combined deficiency of APP and CPN might enhance the inhibiting effect of the DPP IV inhibitor. The fact that this triple deficiency remained latent before and after the treatment indicates that searching for latent enzyme deficiencies should be carried out when there is intention to treat with a combination of drugs interfering with the bradykinin metabolism.

Keywords: Iatrogenic angioedema; bradykinin; enzyme deficiency.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / complications*
  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Amino Acid Metabolism, Inborn Errors / enzymology
  • Aminopeptidases / deficiency*
  • Angioedema / chemically induced*
  • Angioedema / diagnosis
  • Angioedema / enzymology*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Bradykinin / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Down-Regulation
  • Drug Interactions
  • Humans
  • Iatrogenic Disease*
  • Lisinopril / adverse effects*
  • Lysine Carboxypeptidase / deficiency*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / deficiency*
  • Polypharmacy
  • Pyrazines / adverse effects*
  • Risk Factors
  • Sitagliptin Phosphate
  • Time Factors
  • Triazoles / adverse effects*


  • Angiotensin-Converting Enzyme Inhibitors
  • Dipeptidyl-Peptidase IV Inhibitors
  • Pyrazines
  • Triazoles
  • Lisinopril
  • Aminopeptidases
  • X-Pro aminopeptidase
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Lysine Carboxypeptidase
  • Bradykinin
  • Sitagliptin Phosphate

Supplementary concepts

  • Carboxypeptidase N Deficiency