Angioedema due to angiotensin-converting enzyme inhibitors

Angiotensin-converting enzyme (ACE) inhibitor associated angioedema was det ected in 39 subjects (17%) of 231 consecutive patients examined in the last 5 years at our out-patient clinic for symptoms of angioedema without urtic aria. In these patients, angioedema was most commonly localized to the face . The duration of ACE-inhibitor treatment at the onset of angioedema ranged from 1 day to 8 years with a median of 6 months. The time elapsed between onset of angioedema and withdrawal of ACE-inhibitor ranged from 1 day to 10 years with a median of 10 months. Delayed diagnosis is explained by the un usual characteristics of this adverse reaction: angioedema may start years after beginning the treatment and then it recurs irregularly. Infact, ACE-i nhibitors seem to facilitate angioedema in predisposed subjects, rather tha n causing it with an allergic or idiosyncratic mechanism. Thus, while Cl-in hibitor levels are usually normal in subjects developing ACE-inhibitor-depe ndent angioedema, we found that ACE-inhibitors caused angioedema in Cl-inhi bitor-deficient patients. Because the main inactivator of bradykinin is kin inase II, which is identical with ACE, it is believed that bradykinin media tes ACE-inhibitor-dependent angioedema. We had the possibility to examine t he plasma bradykinin levels in one ACE-inhibitor-treated patient during an angioedema attack and we found very high levels, but we did not find an inc rease of break-down products of high-molecular-weight-kininogen as observed during acute attacks in hereditary angioedema. Bradykinin fell to normal l evels during remission after withdrawal of the drug. These observations ind icate that in ACE-inhibitor-induced angioedema, contrary to hereditary angi oedema, the reduction of bradykinin catabolic rate plays a predominant role . (C) 1999 Elsevier Science B.V. All rights reserved.