title: Treatment for hereditary angioedema with normal C1-INH and specific mutations in the F12 gene (HAE-FXII).
abstract: Hereditary angioedema with normal C1 esterase inhibitor and mutations in the F12 gene (HAE-FXII) is associated with skin swellings, abdominal pain attacks, and the risk of asphyxiation due to upper airway obstruction. It occurs nearly exclusively in women. We report our experience treating HAE-FXII with discontinuation of potential trigger factors and drug therapies. The study included 72 patients with HAE-FXII. Potential triggers included estrogen-containing oral contraceptives (eOC), hormonal replacement therapy, or angiotensin-converting enzyme inhibitors. Drug treatment comprised plasma-derived C1 inhibitor (pdC1-INH) for acute swelling attacks and progestins, tranexamic acid, and danazol for the prevention of attacks. Discontinuation of eOC was effective in 25 (89.3%) of 28 women and led to a reduction in the number of attacks (about 90%). After ending hormonal replacement therapy, three of eight women became symptom-free. Three women with exacerbation of HAE-FXII during intake of quinapril or enalapril had no further HAE-FXII attacks after discontinuation of those drugs. Eleven women were treated with pdC1-INH for 143 facial attacks. The duration of the treated facial attacks (mean: 26.6 h; SD: 10.1 h) was significantly shorter than that of the previous 88 untreated facial attacks in the same women (mean: 64.1 h; SD: 28.0 h; P < 0.01). The mean reduction in attack frequency was 99.8% under progestins after discontinuing eOC (16 women), 93.8% under tranexamic acid (four women), and 100% under danazol (three women). For patients with HAE-FXII, various treatment options are available which completely or at least partially reduce the number or duration of attacks.
authors.affiliation: Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Bork
authors.affiliation: University Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wulff
authors.affiliation: Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Witzke
authors.affiliation: Department of Medical Psychology and Medical Sociology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hardt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D015415:Biomarkers; D018890:Chemoprevention; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use*; D018450:Disease Progression; D004967:Estrogens / Q000009:adverse effects; D005174:Factor XII / Q000235:genetics; D005260:Female; D056828:Hereditary Angioedema Type III / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D050718:Complement C1 Inhibitor Protein; D004967:Estrogens; D005174:Factor XII
keywords: hereditary angioedema; hereditary angioedema type III; hereditary angioedema with normal C1 inhibitor; specific mutations in the F12 gene; treatment