HAE

This review on hereditary angioedema (HAE) focuses on special topics regarding HAE in female patients. HAE is a bradykinin-mediated disorder, and the role of hormonal regulation of disease expression will be discussed focusing on the effect of estrogen on disease mechanism. The impact of exogenous estrogen on symptom exacerbation leads to special consideration regarding choice of contraceptives and safety of hormone replacement therapy. The effects of pregnancy and childbirth will be examined on the course of disease control. Unique considerations regarding therapeutic management for female HAE patients will be addressed, including the role of C1 inhibitor (C1-INH), ecallantide, and icatibant. Finally, this review will provide an overview of the more recently characterized HAE with normal C1-INH (HAE type III) that predominantly affects women and is in some cases associated with factor XII gene mutations.

Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by deficient or dysfunctional C1 inhibitor (C1 INH). HAE patients experience recurrent episodes of angioedema affecting the extremities, face, genitalia or submucosal edema in the abdomen or upper airway. Laryngeal attacks can be fatal. The determination of optimal therapy should be based on individualization of patient history and preferences. The parameters include attack frequency, location, severity and burden of illness on quality of life. Patients with HAE need medications for acute attacks; some also require prophylaxis. This is an overview of HAE treatments currently available in the US and how to individualize therapy for patients based on their circumstances. A literature search was performed for HAE and therapeutic modalities currently available. HAE guidelines and randomized, controlled clinical trials were evaluated. There are several options for acute and prophylactic treatment of HAE that have been approved by the Food and Drug Administration. Acute treatments include C1 INH, a replacement therapy; ecallantide, a kallikrein inhibitor; and icatibant, a bradykinin-2 receptor antagonist. Prophylactic treatments include attenuated androgens and C1 INH. These options have been proven safe and effective in clinical trials. Optimal therapy is based on the individual patients need regarding on-demand therapy and/or prophylactic therapy, short-term or long-term. Patients with HAE have individual requirements, based on the nature and frequency of past attacks, occupation, proximity to trained medical personnel, and patient preference. These factors should be used to create a patient-centered approach to management of HAE.

Hereditary Angioedema (HAE) is an autosomal dominant disorder characterized clinically by recurrent episodes of swelling involving subcutaneous tissues, gastrointestinal tract, and oro-pharyngeal area. Gene mutations are the most common genetic cause of HAE and observed in more than 90% of patients. More than 700 mutation variants have been described so far. Patients with angioedema who have no mutations in the gene for C1-INH and normal levels and activity of this inhibitor are labelled: normal C1 inhibitor HAE. These include genetic mutations in factor 12 gene, plasminogen gene, angiopoietin gene, kininogen 1, and myoferlin genes. The clinical manifestations of patients with these mutations are similar to with patients with C1-INH gene mutations. However, a later age of onset, oro-pharyngeal involvement, and higher female preponderance have been reported in these rare subtypes of hereditary angioedema. With the advent and increased accessibility of whole-exome sequencing, it is expected that new genetic defects and novel pathophysiological pathways will be identified in families with HAE of unknown cause or normal C1-INH angioedema. This review covers some of the recent advances in the field of HAE. The review focuses on pathophysiology of HAE beyond the well-known C1-INH deficiency phenotypes, including various biomarkers that can serve the diagnosis and management of these rare disorders.