Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy.

Background: Hereditary angioedema caused by mutations in the factor XII gene is a recently described disease entity that occurs mainly in women. It differs from hereditary angioedema caused by C1 inhibitor deficiency.

Objective: To assess the clinical symptoms, factors triggering acute attacks, and treatments of this disease.

Methods: Thirty-five female patients with hereditary angioedema and the factor XII mutations p.Thr309Lys and p.Thr309Arg who came from 13 unrelated families were studied. The observation period was 8.4 years on average (range, 2-26 years).

Results: Patients had on average 12.7 +/- 7.9 angioedema attacks per year. Recurrent facial swellings occurred in all patients; skin swellings other than facial, abdominal pain attacks, tongue swellings, and laryngeal edema occurred less frequently. Some factors that triggered angioedema attacks were trauma, physical pressure, and emotional stress. Clinical symptoms started mainly after intake of oral contraceptives (17 women) or pregnancy (3 women). Exacerbation of the symptoms occurred after oral contraceptive use (8 women), pregnancy (7 women), hormone replacement therapy (3 women), intake of angiotensin-converting enzyme inhibitors (2 women), and an angiotensin 1 receptor blocker (1 woman). Effective treatments included C1 inhibitor concentrate for angioedema attacks (6 women) and, for prophylaxis, progesterone (8 women), danazol (2 women), and tranexamic acid (1 woman). No difference between mutation p.Thr309Arg and p.Thr309Lys was found.

Conclusions: Facial swelling is a cardinal symptom of this condition. Estrogens may have a great influence, but this influence is highly variable. Various treatment options are available.