HAE Update: Special considerations in the female patient with hereditary angioedema

Abstract

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.

Presentation, diagnosis and treatment of angioedema without wheals: a retrospective analysis of a cohort of 1058 patients

“…during pregnancy or contraceptive treatment) [25,26]. Possibly due to its link to oestrogens, phenotypic expression of F12 gene mutations is far from being close to 100% as for those in SERPING1 that lead to C1-INH-HAE [27]. Amongst patients with FXII-HAE referred to our centre, one developed angioedema symptoms only during pregnancy and two during contraceptive pill treatment.…”

BSACI guideline for the management of chronic urticaria and angioedema

“…The benefit of progestin contraception rather than an oestrogen-progestin contraception in Type III is reported [49]. Combined oral contraception should be avoided in all women with HAE [50].…”

Urticaria and Angioedema in Pregnancy

“…Estrogen has been shown to affect the contact and coagulation systems by increasing the levels and function of factor XII, prekallikrein, kallikrein, and high molecular weight kininogen, all of which are involved in the process of bradykinin formation. Estrogens also up-regulate the expression and potentiate the activity of bradykinin receptor B 2 [39]. The influence of progesterone on the course of HAE is inconclusive.…”

“…Factors associated with a more aggressive course in pregnancy include early onset of disease in life, bearing a fetus with C1EI deficiency, and disease exacerbation during menses [39]. According to some studies, the course of disease during a previous pregnancy might predict the clinical picture in subsequent pregnancies [41•].…”