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Clinical manifestations and pathogenesis of hereditary angioedema

INTRODUCTION

Hereditary angioedema (HAE) is a rare genetic disorder resulting from an inherited deficiency or dysfunction of the C1 inhibitor. It is characterized by recurrent episodes of angioedema, without urticaria or pruritus, which most often affect the skin or the mucosal tissues of the upper respiratory and gastrointestinal tracts. Although the swelling is self-limited, laryngeal involvement may cause fatal asphyxiation. Untreated, this disorder was associated with a mortality rate of approximately 30 percent in the past, secondary to asphyxiation from laryngeal swelling.

Hereditary angioedema is distinguished by its lack of response to therapies for other types of angioedema, including antihistamines, steroids, and epinephrine. Effective therapies either replace the inhibitor (administration of C1-inhibitor concentrate or fresh frozen plasma) or increase its hepatic synthesis (administration of androgens).

The epidemiology, pathogenesis, genetics, clinical manifestations, and prognosis of hereditary angioedema are reviewed herein. The diagnosis and prophylactic and acute therapies of this disorder are discussed separately. (See "Diagnosis of hereditary and acquired angioedema (C1 inhibitor disorders)" and "Prevention of attacks in hereditary angioedema" and "Treatment of acute attacks in hereditary and acquired angioedema".)

EPIDEMIOLOGY

The prevalence of hereditary angioedema is estimated at 1 individual per 50,000, with reported ranges from 1:10,000 to 1:150,000 [1,2]. There are no known differences in prevalence among ethnic groups [2-4]. Men and women are affected equally, and the diagnosis is most commonly made in the second or third decade of life, although symptoms often begin earlier. (See 'Age of onset' below.)

PATHOGENESIS

The pathogenesis of the two most common forms of hereditary angioedema (ie, types I and II) results from either deficiency or dysfunction of the C1 inhibitor [5]. However, the exact mechanism(s) that lead to angioedema are not fully understood. The proinflammatory mediator bradykinin appears to be critical in the pathogenesis of HAE, and C1 inhibitor plays a role in regulating its production [6,7].
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