The Role of Mast Cells Mediators in Angioedema Without Wheals

Abstract

Angioedema is defined as localized and transient edema of the deep skin layers or the upper respiratory or gastrointestinal mucosa. Although the most common sites of involvement are the tongue, lips, face, and throat, angioedema may also occur in the extremities, genitalia, and viscera, and it can be life-threatening when affecting the upper airway. Angioedema is due to a temporary increase of the vascular permeability caused by vasoactive mediators. However, the mechanisms and the mediators involved in angioedema without wheals vary depending on the type of angioedema. The purpose of this review is to give new insights on angioedema without wheals. To facilitate the understanding of the different types of angioedema, a modified classification of angioedema without wheals from the Hereditary Angioedema International Working Group consensus is proposed. It also summarizes the pathophysiology of the main types of AE and describes the current knowledge regarding the role of the mast cell mediators involved. Finally, given that the treatment of angioedema has changed greatly in the last years, this review also describes the specific treatment options of angioedema without wheals. Gaining knowledge into these pathophysiologic mechanisms of angioedema and into the gaps in the diagnosis will allow to improve the management of these patients, avoiding fatal outcomes. Key points: - Angioedema is a localized, self-limiting, no pitting swelling that can be life-threatening and needs adequate treatment to avoid fatal outcomes. - The mechanisms and the mediators involved in angioedema without wheals may vary depending on the type of angioedema; therefore, it is important to understand the physiopathology of each type of angioedema to improve the differential diagnoses. - There is a need to develop standardized diagnostic tests to differentiate types of angioedema in order to improve management.