Study population
This was a retrospective study conducted in our national reference center for bradykinin-mediated AE in Lille University Hospital (CREAK, France). Eligible patients were identified by screening our consultation database using the diagnostic code for AE. They were included if they met all the following criteria: (1) confirmed diagnosis of AE; (2) treatment by ACEi concomitant to at least one AE attack; (3) normal C1-INH levels and activity; (4) baseline visit between January 1sts 2014 and December 31st, 2019; (5) at least one follow-up visit at least 6 months after ACEi cessation.
Patients whose diagnosis of ACEi-AE could readily be refuted based on baseline visit data (i.e., patients with urticaria before or during AE attacks, or with AE attacks before ACEi introduction) were excluded from the study, as there is usually no diagnostic challenge regarding the AE mechanism and no therapeutic hesitation in this situation.
The remaining patients were classified in 3 different groups based on follow-up data. Patients were classified as “undetermined AE ” if follow-up data did not allow to properly discriminate between ACEi-AE and histaminergic AE (i.e., no recurrence of AE attacks after ACEi cessation but with concomitant introduction of prophylactic treatment by antihistamine and/or corticosteroids). They were classified as “probable histaminergic AE ” if they met at least one of the following criteria: (1) recurrence of AE after the 6thmonth of ACEi withdrawal; (2) no recurrence of AE despite re-exposure to ACEi; (3) occurrence of urticaria during follow-up. They were classified as “probable ACEi-AE ” in any other cases.