HORMONALLY EXACERBATED HEREDITARY ANGIOEDEMA

In England both a mother and her daughter either suffered their first attacks of hereditary angioedema around puberty or the disease worsened around puberty when estrogen levels were rising. The main symptoms included sudden swelling and reddening of the skin. The mother is the first reported case of exacerbated symptoms of hereditary angioedema occurring premenstrually. Use of a combined oral contraceptive (OC) (Femodene) exacerbated the daughters symptoms. Symptoms improved after stopping the OC. The mother also experienced more severe and frequent attacks of symptoms while taking an OC. Acute attacks with abdominal pain diminished after OC cessation but she still suffered edema and reddening of the skin. The daughters C1 esterase inhibitor level was down to only .06 g/L in July 1988 and .09 g/L in December 1989. The mothers C1 esterase inhibitor level was < 25% of normal levels. When another daughter was 4 years old she had a C1 esterase inhibitor level < 25% of the normal range. The level of the same younger daughter in June 1990 was < 22% of the normal range. The oldest daughter was treated with Stanozolol and the mother with Danazol. The youngest daughter received Terfenidine and experienced no symptoms thereafter. Unlike other women with hereditary angioedema the mother did not experience worsening of symptoms during pregnancy. Danazol a derivative of 17-alpha-ethinyl testosterone significantly reduces plasma estradiol levels. It can increase C1 esterase inhibitor levels 3 to 4.5 times pretreatment levels and C4 levels 15 times. These cases and the literature led the dermatologists to recommend that clinicians should not administer estrogen-containing contraceptives to women known to have hereditary angioedema. It appears that progesterone-only contraceptives induce attacks of nonhereditary forms of angioedema. Much more research on the safety of hormonally-exacerbated hereditary angioedema needs to be done.