**1. Introduction: definition of angioedema and differentiation between histaminergic and bradykininergic angioedema**

The term "angioedema" (AE) is defined as localized and transient subcutaneous and/or submucosal swelling (which may affect the gastrointestinal, respiratory, or genitourinary tract) [1, 2]. It occurs when there is vasodilation with consequent increase in capillary permeability and extravasation of fluid into the interstitial space [2, 3].

A variety of inflammatory mediators have been described that can lead to this process, such as histamine, prostaglandins, leukotrienes, and bradykinin [4]. The most frequent type of AE is produced by histamine release, as a consequence of mast cell activation, and is called "histaminergic angioedema."

It includes allergic reactions, but also idiopathic AE in the context of chronic spontaneous urticaria [5]. Histaminergic AE can be associated to urticaria [6], is usually erythematous, warm, and pruritic, and is responsive to treatment with antihistamines [7]. The clinical expression of urticarial lesions is mainly a consequence of inflammation and edema of the upper dermis, whereas swellings are located in the deep dermis and even in the subcutane‐ ous tissue.

Another important type of AE is produced by an increase in bradykinin (BK). This AE type is non‐erythematous, non‐pruritic, cold, non‐responsive to antihistamines and urticaria is not associated [7]. This subgroup is known as bradykininergic angioedema (BK‐AE).
