Hereditary Angioedema.

Copyright © 2020 Massachusetts Medical Society. Hereditary angioedema is a rare, potentially life-threatening disorder characterized by attacks of cutaneous and submucosal swelling. Quincke first described its clinical presentation, and Osler’s recognition of the autosomal dominant inheritance pattern followed in 1888.1 The initial name of the disorder, “hereditary angioneurotic edema,” conveyed the bias that it devolved from neurosis. Over the past 40 years, scientific investigations have identified the fundamental defect of hereditary angioedema as a deficiency of functional C1 inhibitor protein, a protease inhibitor in the serpin superfamily,2,3 and have established that bradykinin is the biologic mediator of swelling.4,5 In 2000, hereditary angioedema with normal C1 inhibitor levels was described, for which molecular mechanisms are emerging.6,7 Despite progress in unraveling the pathophysiology of hereditary angioedema, a delay in proper diagnosis and a paucity of effective therapeutic approaches have hampered effective management of the disease until recently. Advances envisioned in 2008,8 however, have now been realized, with insights from basic research translated into novel therapies. This article reviews the progress made during the past decade in elucidating the pathophysiological mechanisms of hereditary angioedema and the subsequent development of targeted treatments for the disorder, with anticipated reductions in morbidity and mortality and an improved quality of life. The clinical vignette below illustrates the profound effect of these treatments.