title: 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.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg University, Mainz, Germany. Electronic address: bork@hautklinik.klinik.uni-mainz.de.
authors.forename: Konrad
authors.initials: K
authors.lastname: Bork
authors.forename: Karin
authors.initials: K
authors.lastname: Wulff
authors.forename: Günther
authors.initials: G
authors.lastname: Witzke
authors.forename: Christian
authors.initials: C
authors.lastname: Stanger
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Jochen
authors.initials: J
authors.lastname: Hardt
mesh_terms: D000799:Angioedema / Q000235:genetics*; D015331:Cohort Studies; D050718:Complement C1 Inhibitor Protein / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005174:Factor XII / Q000235:genetics / Q000378:metabolism; D005260:Female; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D009154:Mutation; D011247:Pregnancy
chemical_list: D050718:Complement C1 Inhibitor Protein; D004967:Estrogens; D006633:Histamine Antagonists; D005174:Factor XII
keywords: Angioedema; Desogestrel; Estrogens; Hereditary angioedema; Hereditary angioedema type III; Hereditary angioedema with normal C1 inhibitor; Idiopathic angioedema; Mutations in the coagulation factor XII gene; Progestins