Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema

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Clinical features of angiotensin-converting enzyme inhibitor–associated angioedema

Angioedema is characterized by self-limited, nonpitting edema of vascular origin. The most common sites of involvement in ACE inhibitor–associated angioedema are the lips, tongue, and face (Fig. 1) [5], [6], [7]. Pruritis and urticaria, seen in hypersensitivity reactions, typically do not accompany ACE inhibitor–associated angioedema. Rarely, ACE inhibitor–associated angioedema may involve the bowel wall [8]. In such cases, patients present with nausea and vomiting, abdominal pain, diarrhea, or

Epidemiology of angiotensin-converting enzyme inhibitor–associated angioedema

The reported incidence of ACE inhibitor–associated angioedema varies from 0.1% to 0.7%, calculated from postmarketing surveillance or epidemiologic studies, to as great as 2.8% to 6% when ascertained prospectively in clinical trials [10], [21], [22]. Black Americans have an incidence of ACE inhibitor–associated angioedema that is four to five times that of white Americans [7], [12], [23]. Smoking, increasing age, and female gender are also associated with increased risk for ACE

Mechanisms of angiotensin-converting enzyme inhibitor–associated angioedema

The mechanism or mechanisms of ACE inhibitor–associated angioedema remain to be elucidated, but the clinical presentation of ACE inhibitor–associated angioedema may provide clues to its causation. As noted earlier, ACE inhibitor–associated angioedema frequently occurs after prolonged exposure; furthermore, it may remit spontaneously and recur after prolonged time intervals [27]. This pattern excludes a typical allergic or immediate hypersensitivity mechanism and suggests that some concurrent

Future directions

Ultimately, verification of a role for bradykinin, substance P, or any other vasoactive peptide substrate of ACE in the pathogenesis of ACE inhibitor–associated angioedema will require clinical studies assessing the effect of specific peptide receptor antagonists on the resolution of angioedema. Such studies are difficult to conduct because of the remitting and relapsing pattern of ACE inhibitor–associated angioedema. Drugs that inhibit DPPIV are currently under development for the treatment of

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    This work was supported by NIH Grants HL079184 and HL076133 and National Center for Research Resources Grant RR-00095.

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