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.