Tamoxifen, a Trigger Factor of Hereditary Angioedema with Normal C1-INH with a Specific Mutation in the F12 Gene (HAE-FXII)

Rationale: In hereditary angioedema with normal C1 inhibitor with a specific F12mutation (HAE-FXII) various trigger factors are known. Tamoxifen is a selective estrogen-receptor modulator (SERM) used in the treatment of breast cancer.

Methods: A patient with a trigger factor hitherto unknown for angioedema attacks of HAE-FXII is reported.

Results: In a now 71 year-old women the family history was negative for angioedema. At age 23 she had three lip swellings during the second and third trimester of her second pregnancy. At age 25 she took an estrogen-containing oral contraceptive for three month and developed another lip swelling. Then she was symptom-free until the age of 68. At the age of 67 a breast carcinoma was diagnosed. The patient underwent surgery and radiation therapy. Subsequently she received tamoxifen for a period of 36 months. Under tamoxifen the patient had 12 severe tongue swellings, partly associated with swelling of the floor of the mouth and the pharynx. Six of the swellings made a hospital stay necessary, two of them an ICU stay. During the last 4 months of the tamoxifen medication the swellings occurred every 3 weeks. The patient had normal values for C1-INH function and protein and C4 in plasma. In the F12gene the mutation p.Thr328Lys was found. The diagnosis of HAE-FXII was established. After discontinuation of tamoxifen the patient immediately became symptom-free. Since then the patient had no further swellings, for one year until now.

Conclusions: Tamoxifen can cause severe angioedema attacks in patients with HAE-FXII.