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Angioedema with ACEI/ARB cross reactivity

Angioedema in most cases is shown to be idiopathic, but may also behereditary or acquired. The main symptom of angioedema is swelling beneath theskin such as the deep dermis or subcutaneous tissue and is considered aconsequence of vascular leakage.1 It may be caused by an allergic reaction in

which mast cells, as well as many other immune-mediated cells such asmacrophages, dendritic cells, monocytes, eosinophils, lymphocytes and endotheliacells, have been shown to be involved in its pathogenesis. In many cases, the causeof angioedema is not able to be determined, however medications such asangiotensin-converting enzyme inhibitors have been associated with causing thisallergic reaction. Other causes may include insect bites, pollen, animal dander, andfoods such as berries, shellfish, or eggs to name a few. Swelling typically occursaround the eyes and lips, and welts may also develop on the surface of the skin.1,2

Some other symptoms that may be associated with angioedema includeabdominal cramping, difficulty breathing, and swollen eyes, mouth, nose or throat.Mild symptoms typically do not warrant treatment, however difficulty breathing is

an emergency situation that will need prompt intervention, likely with epinephrine.Some medications other than epinephrine that may be used to treat angioedemainclude antihistamines or anti-inflammatory medications such as corticosteroids.Other than with cases of anaphylaxis in which there would be difficulty breathingand intubation may even be necessary, when breathing is not impaired it is usuallyharmless and goes away within a few days.2

Angioedema may occur after the first dose of an ACE inhibitor, or atany time during the course of therapy. 3,5 There is a higher risk forangioedema with regards to race in African American patients compared toCaucasians with the adjusted relative risk being about 3-4.5.3 Themechanism of ACE inhibitor induced angioedema is hypothetically linked toits mechanism of interfering with the breakdown of bradykinin, and is notconsidered to be drug-specific (i.e may occur with any agent in this class).4

The exact mechanism of angioedema associated with ACE inhibitors has notbeen determined however, since no definitive increase in bradykinin plasmaconcentrations during attacks of angioedema have been shown.Angioedema manifested by recurrent episodes of facial swelling will resolveupon withdrawl of the ACE inhibitor.5

Since ACE inhibitor-induced anaphylaxis has been proposed due toaccumulation of bradykinin, many assume that angiotensin II receptorantagonists wouldnt cause this type of reaction. Yet there has been a reportof angioedema in a 52-year old man within 30 minutes of first dose oflosartan 50mg, and another single case mentioned in losartans packageinsert (1 case among 4,058 patients).6 Also, an international safety updatereported 13 cases of angioedema based on 200,000 patients.7

References:

1. Kaplan AP. Urticaria and angioedema. In: Adkinson Jr, NF. Middleton's Allergy: Principle andPractice. 7th ed. Mosby; 2009:1061-81.

2. MedlinePlus Medical Encyclopedia3. DRUGDEX (micromedex)-ace inhibitors

4. Byrd JB, Adam A. Angiotensin-converting enzyme inhibitor-associated angioedema. ImmunolAllergy Clin North Am. Nov 2006;26(4):725-37..

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5. Meylers side effects of drugs . 15th edition 2006 editor JK Aronson. Oxford, UK angiotensin-converting enzyme inhibitorsp231

6. Acker CG, Greenberg A. Angioedema induced by the angiotensin II blocker losartan. N Engl JMed 1995;333(23):1572.

7. Hansson L. Medical and cost-economy aspects of modern antihypertensive therapy-withspecial reference to 2 years of clinical experience with losartan. Blood Press Suppl 1997;1:52-5.