INTRODUCTION
Angioedema (AE) is characterized by swelling of the deep dermis, subcutaneous tissue, or mucous membranes. A distinction is made between histamine-mediated AE, due to histaminoliberation (anaphylactoid reaction, drug-induced, chronic idiopathic histaminic AE), and bradykinin-mediated AE (1,2). Bradykinin, similarly to histamine, is a vasodepressor that relaxes vascular smooth muscle cells, lowers blood pressure and increases vascular permeability (3). Bradykinin-mediated AE can be caused by C1 inhibitor (C1-INH) deficiency (either genetic or acquired), by genetic mutations with a normal C1-INH (like factor XII or plasminogen mutations), or by bradykinin-releasing drugs, such as angiotensin-converting enzyme inhibitors (ACEi) (4,5).
It is estimated that 0.1 to 0.7% of patients treated with ACEi develop ACEi-induced angioedema (ACEi-AE) (2,5–7). Attacks usually appear within the first 3 months of treatment, but can develop at any time during the treatment course, even several years after its initiation (6,8). As they are bradykinin-mediated, urticaria is deemed to never occur during ACEi-AE attacks. So far, there is no validated set of diagnostic criteria and no specific biomarker for ACEi-AE; and the diagnosis can only be made with certainty on a retrospective basis, in the absence of urticaria and relapse after at least 6 months of treatment discontinuation (9,10).
Thus, the initial management of a patient presenting with a first AE attack, no urticaria and ACEi treatment can be difficult, as it is not always easy to discriminate between a first attack of an undiagnosed idiopathic histaminergic AE and ACEi-AE. Few studies have tried to determine the attack characteristics that are specific to ACEi-AE; and since most of them did not follow up patients after treatment cessation, they may have mistakenly included idiopathic histaminergic AE (8,11–13).
The objective of this study was thus to report on the follow-up of patients with suspected ACEi-AE and to describe the baseline characteristics of patients and AE attacks in a population with a definitive diagnosis of ACEi-AE, confirmed by a long-term follow-up.