Antihistamine-resistant angioedema in women with negative family history: estrogens and F12 gene mutations.

Abstract

BACKGROUND:

In women with sporadic recurrent angioedema with an unknown cause who are unresponsive to antihistamines and have normal C1 inhibitor activity and a negative family history of angioedema, it is unclear whether they have idiopathic angioedema or hereditary angioedema with normal C1 inhibitor, and what impact exogenous estrogens have on their angioedema.

METHODS:

A cohort of 147 women was analyzed for F12 exon 9 mutations and for the influence of oral contraceptives, hormonal replacement therapy, and pregnancy on their angioedema.

RESULTS:

A total of 142 women had idiopathic angioedema unresponsive to antihistamines. Five women had an F12 mutation and thereby hereditary angioedema with F12 mutations. Among the women with idiopathic angioedema, 63 had never taken estrogens. There was no estrogen impact in 42 women, a moderate impact in 15 women, and a severe impact in 22 women. The type and dose of estrogens did not differ in women with and without an estrogen impact. In 5 women, idiopathic angioedema disappeared after desogestrel use. Among the 5 women with hereditary angioedema with F12 mutations, angioedema symptoms occurred during 4 pregnancies, whereas no symptoms occurred during any of the 58 pregnancies in women with idiopathic angioedema.

CONCLUSIONS:

Women with recurrent angioedema unresponsive to antihistamines may have idiopathic angioedema or, more rarely, hereditary angioedema with F12 mutations. Both conditions may be provoked or aggravated by exogenous estrogens. In idiopathic angioedema, treatment with progestins may be helpful.

• Authors: Konrad Bork, Karin Wulff, Günther Witzke, Christian Stanger, Peter Lohse, Jochen Hardt
• Journal: The American journal of medicine (Am J Med) Vol. 126 Issue 12 Pg. 1142.e9-14 (Dec 2013) ISSN: 1555-7162 [Electronic] United States
• PMID: 24262729 (Publication Type: Journal Article)
• Copyright: Copyright © 2013. Published by Elsevier Inc.

Chemical References

• Complement C1 Inhibitor Protein
• Estrogens
• Histamine Antagonists
• Factor XII

Topics

• Angioedema (genetics)
• Cohort Studies
• Complement C1 Inhibitor Protein (genetics, metabolism)
• Estrogens (metabolism)
• Factor XII (genetics, metabolism)
• Female
• Histamine Antagonists (pharmacology)
• Humans
• Mutation
• Pregnancy