Treatment for hereditary angioedema with normal C1-INH and specific mutations in theF12gene (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.

Hereditary angioedema with a mutation in the plasminogen gene

“…Tranexamic acid is a competitive inhibitor of the lysine‐binding sites in the kringle domains of PLG and plasmin. It is effective in various degrees in the long‐term prophylaxis in HAE‐C1‐INH, in HAE‐FXII, and in HAE‐PLG as mentioned in this article. The exact mode of action of antifibrinolytics in HAE, however, is not fully understood.…”

Highlights and recent developments in food and drug allergy, and anaphylaxis in EAACI Journals (2017)

“…59 Hereditary angioedema with normal C1 inhibitor and specific mutations in the F12 gene (HAE-FXII) exists, and recommendations for treatment were given from a personal experience in 72 patients. 60 Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease for which there are no available laboratory parameters to clearly define the disorder. A literature review was performed, and omalizumab was found to induce a complete remission in the 20 patients treated.…”

Clinical Utility Gene Card for hereditary angioedema with normal C1 inhibitor (HAEnC1)

“…22 and off label use has been reported. 9,25 No data are available concerning differences in clinical management, treatment response, or prognosis between patients with variants in F12 (FXII-HAE) and variant-negative patients (U-HAE).…”