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Angiotensin-converting enzyme inhibitor (ACEI)–induced angioedema: Angioedema is a potentially life-threatening adverse effect of ACEI therapy, one characterized by well-demarcated swelling of the lips, face, and oropharynx (Gainer, 1996). The angioedema most commonly affects the head and neck, but the viscera can be involved as well. In some cases, ACEI therapy causes localized angioedema affecting the tongue alone (Kyrmizakis, 1998).

The estimated incidence of angioedema during ACEI treatment is 0.1-0.2%. Approximately 60% of cases occur during the first week of treatment, though several cases have been reported after several years. The incidence is up to 3 times greater in certain groups such as African Americans, in whom low levels of endogenous bradykinin heighten their sensitivity to bradykinin-related changes during ACEI therapy (Gainer, 1996).

Kininase II is the main inactivator of bradykinin and identical to angiotensin-converting enzyme (ACE). By blocking both ACE and kininase II, ACEIs inhibit the metabolism of bradykinin, a potent vasodilator and mediator of capillary leakage. Increased tissue levels of bradykinin are thought to induce angioedema. Other immunologic processes and mediators, such as histamine, substance P, and prostaglandins, may also be involved. Evidence to support this mechanism includes the increased incidence of ACEI-induced angioedema in patients with ACE-gene polymorphism and enzyme deficiencies (Vleeming, 1998).

Standard management includes airway protection and supportive treatment with antihistamines and/or corticosteroids, although no controlled studies have confirmed their efficacy (Vleeming, 1998). The clinician must realize that the use of standard allergic therapy (eg, antihistamines, corticosteroids) may not rapidly produce a significant positive effect. This blunted response to standard allergic therapy results from the pathophysiologic basis of bradykinin as the primary mediator rather than histamine. In life-threatening angioedema, epinephrine and early intubation or cricothyroidotomy may be necessary. Prophylactic endotracheal intubation may be required for airway protection. Fresh frozen plasma (FFP) may be beneficial in unresponsive cases of severe ACE-I angioedema. However, FFP treatment is associated with a risk of allergic reaction, volume overload, and the transmission of viral disease. In addition, FFP is beneficial in hereditary angioedema, in which it replaces the deficient C1 esterase inhibitor. FFP also provides additional kininase II, which breaks down accumulated bradykinin, and it provides functional enzyme to patients with enzyme defects in bradykinin metabolism (Karim, 2002).

For more information on angioedema syndrome, see the eMedicine articles (Medicine) Angioedema and (Emergency Medicine) Angioedema.

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Physical examination reveals morbid obesity and normal vital signs. The patient is sitting upright on a stretcher and leaning forward, drooling, and easily ventilating. Her voice is muffled. She has marked, nontender edema of the tongue and the floor of the mouth but not on her lips or face. No erythema, increased warmth, or induration is observed.

An emergency airway tray is placed at her bedside as an otolaryngologist performs nasopharyngolaryngoscopy; this does not reveal any edema of the uvula, hypopharynx, or vocal chords. No stridor is noted, and her lungs are clear to auscultation. The patient is given intravenous Solu-Medrol, famotidine, and diphenhydramine and admitted to the ICU. The swelling gradually improves, and no airway interventional methods are needed.