Figure 2.

Overall presentation of different causes of angioedema classified by pathophysiology mechanisms, focusing on bradikinergic or BK-mediated angioedema (BK-AE) and drug-induced forms [3,47,109]. * Hereditary angioedema (HAE) with C1-INH deficiency with low antigenic and functional C1-INH levels (HAE-1, 85% of cases), HAE due to C1-INH dysfunction (HAE-2, 10% of cases) characterized by normal or elevated antigenic but low functional C1-INH levels, and HAE with normal C1-INH (HAE-nC1-INH, 5% of cases) due to various gene mutations. ** Acquired forms of BK-AE include drug-induced AE, such as AE induced by angiotensin-converting enzyme inhibitors (ACEIs), AE due to acquired C1-INH deficiency (AAE-C1-INH), and acquired idiopathic non-histaminergic AE. *** Mast cell-mediated angioedema (MC-AE) includes allergic IgE-mediated reactions (such as AE with anaphylaxis), nonallergic non-IgE-mediated reactions (such as AE due to non-steroidal anti-inflammatory drugs or infections), AE in chronic inducible urticaria or chronic spontaneous urticaria (sometimes referred to as idiopathic histaminergic acquired AE). The diversity of mediators involved in MC-AE is reflected also by the fact that patients with chronic spontaneous urticaria may respond to treatment with omalizumab but not to H₁ antihistamines.