Estrogen-dependent inherited angioedema

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Abstract

Classic forms of hereditary angioedema are characterized clinically by recurrent episodes of angioedema, biochemically by reduced C1 inhibitor level and/or function, and genetically by a heterogeneous group of mutations in the C1 inhibitor gene that have an autosomal dominant mode of transmission. Androgens and estrogens have significant clinical effects in patients with hereditary angioedema, and tend to have antagonist effects of the levels of C1 inhibitor protein. Androgens increase the levels of C1 inhibitor protein, reduce attacks of angioedema, and thus are an important therapy for patients. The mechanisms by which the sex steroid hormones achieve these effects are not understood. The recent recognition of a novel estrogen-dependent form of angioedema may offer important insights into the mechanisms by which the sex hormones exert their effects, and the pathogenesis and treatment of both estrogen-dependent and classic forms of hereditary angioedema.

Section snippets

Background: hereditary angioedema, the C1 inhibitor gene, and the effects of sex hormones

Classic forms of hereditary angioedema are characterized by recurrent episodes of angioedema which may involve the limbs, face, airway or gastrointestinal tract [1], [2]. Symptoms occur because of inadequate C1 inhibitor function, which ultimately results in the generation of kinins (bradykinin and/or complement-derived kinin-like peptide), and possibly other vasoactive substances, leading to angioedema [3], [4].

Clinically, two broad categories of HAE are recognized: type I, in which there are

Estrogen-dependent inherited angioedema

The discovery of a family with typical symptoms of angioedema restricted to conditions of high estrogen levels [28] afforded a unique opportunity to investigate the effects of this hormone on the generation of angioedema. The index family, consisting of members of three generations, presented with features identical to classic HAE, but occurring only during pregnancy, use of oral contraceptives, or use of estrogen replacement therapy. Episodes of angioedema affected the face, extremities,

Conclusions

The discovery of estrogen-dependent and estrogen-associated inherited angioedema is an important milestone. A better understanding of the mechanisms operative in estrogen-dependent inherited angioedema will have important implications for our affected patients regarding both diagnosis and treatment. In addition, a better understanding of the processes involved in the estrogen-dependent and estrogen-associated forms of angioedema may lead to additional insights and/or treatment options for

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