How we manage persons with hereditary angioedema

Abstract

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling that can result in significant morbidity and even mortality. Several novel therapies introduced since 2008 have dramatically transformed the approach to management. In this review we will discuss the current understanding of the pathophysiology of HAE, diagnostic evaluation of recurrent angioedema without urticaria, and the therapeutic approach to HAE. We advocate taking an integrative approach to care in order to normalize the lives of affected patients.

Hereditary angioedema: Looking for bradykinin production and triggers of vascular permeability

“…In many monogenic diseases, although the causal target gene is well known, individuals carrying the same causal mutation either do not always develop the disorder, an effect called incomplete penetrance, or do not present the same clinical symptoms, a phenomenon known as variable expressivity. All types of HAE are inherited as autosomal‐dominant traits with incomplete penetrance and little or no genotype‐phenotype correlation has been detected . Indeed, patients with HAE carrying the same mutation exhibit large variability of frequency and severity of symptoms, even among siblings.…”

“…All types of HAE are inherited as autosomal-dominant traits with incomplete penetrance and little or no genotype-phenotype correlation has been detected. 16 Indeed, patients with HAE carrying the same mutation exhibit large variability of frequency and severity of symptoms, even among siblings. As a result, the clinical expression is characterized by a large inter-and intra-familial heterogeneity in regard to the age at disease onset, the number of attacks, triggers of acute episodes, the severity and localization of oedema, and prodromal signs and symptoms.…”

Long-term prophylaxis therapy in patients with hereditary angioedema with C1 inhibitor deficiency

“…First, all patients should have a comprehensive management plan that should be reviewed periodically for treatment effectiveness, safety, and adherence. 13,57 Second, all patients should have ondemand treatment on hand regardless of whether they are receiving prophylaxis therapy because even patients receiving the most effective prophylaxis therapies are at risk of having an attack. [11][12][13] Third, prophylaxis therapy should be discussed as a potential treatment option for each patient.…”

Gene therapy for C1 esterase inhibitor deficiency in a Murine Model of Hereditary angioedema

“…Treatment strategies for HAE are targeted to treating acute attacks with on‐demand therapy or preventing attacks with prophylactic therapy . Acute HAE attacks can be managed with early therapeutic intervention by administration of plasma‐derived C1INH (Berinert ® , CSL Behring GmbH, Marburg, Germany), recombinant C1INH (Ruconest ® , Pharming Group N.V., Netherlands), kallikrein inhibitor (Kalbitor ® , Dyax Corp, Burlington, MA), or inhibition of the bradykinin receptor (Firazyr ® , Shire Orphan Therapies, Inc., Lexington, MA) .…”