ACE inhibitor-induced angioedema T73.3

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 01.08.2022

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Acquired bradykinin-mediated angioedema without C1-INH deficiency; angioedema acquired, ACE-induced; RAE; RAE Angioedema

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Occurrence of angioedema after taking ACE inhibitors or angiotensin II receptor blockers (AT2RB). The latency period between drug intake and initial manifestation of the edema is highly variable (on average 2-3 years; about 2/3 of angioedema occurs within the first 3 months). In some cases, angioedema only develops in connection with a relevant infection or in combination with other drugs (e.g. diuretics, antidiabetics or even antibiotics). Due to the large number of medications taken, it is not always possible to clearly assign the ACE inhibitor etiologically and/or chronologically. Angioedema has also been reported in connection with dipeptidyl peptidase IV inhibitors (saxagliptin) and neprilysin inhibitors (sacubitrile).

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incidence 400-700/100,000 (0.4-0.7%); purely arithmetically, around 20,000-35,000 cases/year would be expected in Germany. In about 20% of these patients, the angioedema is severe, making an inpatient stay necessary.

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ACE inhibitors inhibit the breakdown of bradykinin, which leads to increased production of bradykinin in plasma and tissue. In rare cases, angioedema can also occur under AT-1 blockers.

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In contrast to HAE ( hereditary angioedema), RAE almost always manifests in the head and neck region.

Clinical features
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Edema occurs several months after initiation of therapy; however, it also occurs after years of problem-free use (2-3 years on average). Bradykinin levels are elevated during the attack. The cough induced by ACE inhibitors is not a precursor of angioedema.

The clinic of RAE angioedema is treacherous, as it not infrequently begins as harmless mucosal edema but develops into marked edema after hours. It is not uncommon for the laryngeal and pharyngeal areas to be affected. Swelling resolves after 24-72 hours but may persist for up to 5 days. Infestation of the hands, feet, and gastrointestinal tract is also possible.

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Clinical picture and anamnesis is diagnostic. Other forms of angioedema must be excluded (see below)

Differential diagnosis
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Angioedema of a different etiology (see below angioedema).

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Discontinuation of the ACE inhibitor!

Angioneurotic edema usually resolves within 1-5 days after discontinuation of the ACE inhibitor or AT-II receptor blocker.

In case of a vital threatening laryngeal edema, immediately secure the airway (initiation of immediate intensive care measures - sedation, analgesia, intubation if necessary, tracheostomy; circulatory stabilization; see also below Shock, anaphylactic).

Immediate administration ofC1 inactivator concentrate i.v.: 20IE/kg bw Berinert P.

Alternative: Icatibant (Firazyr), a synthetically produced decapeptide (protein fragment) is the most potent antagonist of the bradykinin B2 receptor to date. To date, Icatibant has only been approved by the EMA for the symptomatic treatment of acute attacks of hereditary angioedema in adults with C1 esterase inhibitor deficiency. Applications outside of this indication can currently only be made in off-label use. The use of Icatibant (30mg s.c.) leads to a prompt improvement of angioedema in a smaller study (n=12).

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Note: Antiallergic therapy is not effective in this form of angioedema.

Angioedema is also induced by renin inhibitors.

In ACEI-induced angioedema, switching to an AT1 receptor blocker is not a solution to the problem, as these can also cause angioedema (although less frequently than ACEI).

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Last updated on: 01.08.2022