Lisinopril induced angioedema
Question:
4/24/2023
A 38-year-old male on lisinopril developed throat angioedema in March 2023 necessitating ED visit and two-day ICU stay. Responsive to epinephrine within minutes. No tracheostomy required. No recurrence of angioedema since being off lisinopril. Primary physician wants to be able to use amlodipine or thiazide in the future. He requests testing. Literature search indicates small risk of angioedema with both of the above medications, higher risk of angioedema with higher dose of amlodipine. Question is how to test. He declines to take any other antihypertensive without some testing. Considering a graded dose challenge in office, although doubt that would definitively rule out chance of angioedema with each agent, would just make more likely the patient would be willing to take the antihypertensive. Appreciate input from the expert panel.
Answer:
As you know ACE inhibitors block the effects of the enzyme angiotensin converting enzyme (ACE), impacting the degradation of bradykinin. High levels of bradykinin stimulate vasodilation and increase vascular permeability of the postcapillary venules, allowing for plasma extravasation into the submucosal tissue, leading to angioedema. There are no lab tests to confirm angioedema is due to the ACE Inhibitor, however ordering a Complement C4 is reasonable to rule out underlying occult process. If C4 is low then proceed with further complement studies including C1q, C1 esterase level &C1 esterase function to assess for HAE and AAE.
There are case reports of angioedema associated with amlodipine. Angioedema associated with calcium channel blockers is uncommon and the mechanism is unknown. Kuruvilla et al. (1) present a case report and provide a table of other reported cases. Likewise, there are reported cases of angioedema associated with thiazide diuretics, some of which IgE mediated.
Drug testing and/or oral challenge is not warranted, and a negative test does not rule out angioedema in the future. Because of the severity of the event, I do feel assessing complement is reasonable. Obviously approach this with shared decision making. Your patient may feel better if he is observed with his initial dose or if preferred, a graded challenge.
1) Kuruvilla ME, Sanan N. Amlodipine-induced angioedema: An unusual complication of a common medication. Allergy Rhinol (Providence). 2018 Apr 6;9:2152656718764139. doi: 10.1177/2152656718764139. PMID: 29977650; PMCID: PMC6028154.
Jeffrey G. Demain, MD, FAAAAI