Diagnostic and Therapeutic Management of Hereditary Angioedema Due to C1-Inhibitor Deficiency

The Italian Experience

Mauro Cancian


Curr Opin Allergy Clin Immunol. 2015;15(4):383-391. 

In This Article

Abstract and Introduction


Purpose of review Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare disease, with a reported prevalence of about 1 : 50 000. C1-INH-HAE causes disabling symptoms, which may be life-threatening if swelling affects upper airways. Diagnostic procedures are now well established and the role of bradykinin as the main mediator of plasma outflow eliciting angioedema formation has been clearly elucidated.

Recent findings Increased understanding of the pathogenesis of C1-INH-HAE allowed in recent years the development of new drugs targeted to inhibit bradykinin synthesis (Ecallantide) or activity (Icatibant). At the same time, a recombinant C1-INH concentrate (Ruconest) was produced from the milk of transgenic rabbits and two plasma-derived C1-INHs (Berinert, Cinryze) underwent controlled trials to obtain marketing authorization. In 2012, an Italian network for C1-INH-HAE (ITACA) was established by physicians of 17 HAE reference centres to collect data from Italian patients and to homogenize and improve the diagnostic and therapeutic approach to the disease.

Summary Although there is a widespread agreement on therapeutic goals and treatment of C1-INH-HAE acute attacks, different approaches to prophylaxis are still present among HAE experts. The clinical experience of ITACA on a large population of C1-INH-HAE patients followed for several years may help in identifying the most effective strategies for the management of the disease.


Hereditary angioedema (HAE), whose clinical picture was originally described by William Osler in 1888,[1] is a rare condition transmitted in an autosomal-dominant genetic pattern as shown by Crowder and Crowder.[2] Fifty years later, it became evident that the disease might be caused by a defect in the C1 esterase inhibitor (C1-INH), either as reduced C1-INH plasma levels (C1-INH-HAE type I) or as qualitative deficiency (C1-INH-HAE type II).[3,4] The pathogenesis of this disease was clarified thereafter with prominent role of the contact system eventually leading to bradykinin release.[5–8] More recently, a novel type of HAE with normal C1-INH (nC1-INH-HAE), not addressed in this manuscript, has been identified.[9,10]

After the first report of an Italian family with C1-INH-HAE in 1973,[11] the number of diagnoses has progressively grown throughout the Country and in 2007 a panel of experts gathered to release the first national guideline for diagnosis and treatment of C1-INH-HAE.[12] Thenceforth, Italian centres dedicated to HAE under patronage of the Italian Hereditary Angioedema Patients' Association (http://www.angioedemaereditario.org) convened and in 2012 established the Italian network for C1-INH-HAE (ITACA), which is now based on 17 centres[13] with homogeneous protocols and facilities to diagnose and treat patients with C1-INH-HAE.

The aim of this article was to describe the ITACA approach to C1-INH-HAE, based on results of controlled trials, recent guidelines or consensus statements and long-standing, fully shared Italian clinical experience in real-life on more than 1000 patients.