Logical Approach to a Patient Presenting with Recurrent Angioedema Attacks

？？Abstract Angioedema is described as local, restricted noninflammatory edema as a result of augmented plasma leakage fromthe capillaries situated in the profound layers of the skin andthe mucosae. The major mediators such as histamine and bradykinin play a role in the pathophysiology of most of the angioedema cases. According to these mediators, angioedema is essentially classified as histaminergic or bradykininergic. Angioedema can be observed with wheals as anindicator of urticaria, and this type is often associated withhistaminergic (allergic, IgE-mediated) type. Histaminergicangioedema is the most common type of angioedema. Angioedema is categorized into either acute (symptoms lasting less than 6 weeks) or chronic (lasting more than 6 weeks) form. It is further characterized into angioedema manifesting with or without wheals. Angioedema with wheals may be acute, chronic, spontaneous or inducible. Angioedema without wheals (AEWOW) is still seen in approximately 10% of urticaria patients, but it can also take place as a discrete entity. In 2014 Hereditary Angioedema International Working Group classification, AEWOW is mainly categorized into hereditary and acquired types. Hereditary AEWOW forms are as follows: Hereditary angioedema (HAE) with genetic C1 inhibitor (C1-INH) deficiency,HAE with normal C1-INH but with Factor XII gene mutation, and unknown HAE; acquired forms of AEWOW have4 subtypes. Acquired C1-INH deficiency, angiotensin converting enzyme inhibitor (ACE-i) induced, idiopathic histaminergic and idiopathic non-histaminergic angioedema. From these types, just idiopathic histaminergic is histaminergic, the others are bradykininergic angioedemas. Hereditary angioedema is a rare congenital disease mainly attributable to the SERPING1 gene mutations, programmingthe C1-INH protein that yields to plasma deficiency, resulting in recurrent attacks of severe angioedema. As of 2018,over 490 different mutations were demonstrated in the region of C1-INH gene (SERPINGI). It is now known thatC1-INH deficiency excites the plasma contact (kallikreinkinin) system, which ultimately results in bradykininover production. After the year 2000, the most recent development in the field of HAE, 3 new types of HAE with “normal” C1-INH were reported. Several abnormalities in thegenes of Factor XII, Angiopoietin-1 and Plasminogen havebeen identified in this novel disease entity. Due to obviousin consistency of clinical pictures, complete understanding of recurrent angioedema phenotypes and the underlying mediator of symptoms are essential for precise diagnosis