Hereditary angioedema in women.

Hereditary angioedema in women.

Carl Stuart.

Stuart Medical Series.

The full item was published in the Journal Allergy, Asthma & Clinical Immunology; July 28, 2010; Volume 6, Issue Number 17; pages 1-4. The author of this article is Laurence Bouillet.

Review.

Hereditary angioedema is an autosomal dominant disorder that affects both males and females. According to professor Bork, females have more symptomatic episodes than males. This preponderance of clinical symptoms in females is caused by hormonal factors. This explains why there is a variation in attack rates during the different phases of a female life cycle. Female hormones have been shown to exacerbate the symptoms of HAE (Hereditary angioedema). McGlinchey has shown that HRT (hormone replacement therapy) provokes an emergence of angioedema symptoms.

Female sex hormones have been implicated in bradykinin-mediated HAE, since they cause an increase in the rate of production of bradykinin (a vasodilator). Progesterone causes an increase in Kallikrein cDNA (complementary DNA) level. Oral contraceptives have been shown to increase the plasma levels of fibrinolytic proteins in healthy women. This increase is caused by oestrogen. The resultant fibrinolysis consumes most of the C1 inhibitor, thus causing C1 inhibitor deficiency and the consequent angioedema symptoms. HRT has been shown to produce similar results in healthy women. A study done by Visy et al showed a positive correlation between the rate of angioedema attacks and the serum levels of progesterone and oestradiol.

Findings.

There are three patterns of HAE in females. These patterns are stated below:

1.     Oestrogen-dependent: The patient shows symptoms of type III HAE only when pregnant or after using combined contraceptive pills.

2.     Oestrogen-sensitive: The symptoms of any type of HAE are exacerbated after intake of combined contraceptive pills or during pregnancy.

3.     Oestrogen-independent: Neither pregnancy nor use of combined oral contraceptives causes an exacerbation of angioedema symptoms.

The mutations in F12 gene which causes Type III HAE were identified in 2006 by Cichon (et al) and Dewald (et al). Bork stated that facial oedema occurs only in Type III HAE. BioMed Central reported that among female HAE patients, 23% of angioedema attacks are oestrogen-dependent, and 54.5% are oestrogen-sensitive. Thus, the following should be considered during the management of a female HAE patient:

1.     Contraception method: Combined contraceptive pills are contraindicated. The best alternatives are progesterone pills and intrauterine devices.

2.     Management of pregnancy: The rate of angioedema attacks increases in the third trimester. Tranexamic acid is used for background treatment, but there is an absolute contraindication for Danazol. The most appropriate treatment in this situation is C1 inhibitor concentrates.

3.     Delivery method: The delivery method can either be spontaneous vertex delivery or caesarean section. Severe episodes of angioedema during labor can be managed by intravenous infusion of 20U/Kg C1 inhibitor concentrates. Epidural analgesia must be used during deliveries.

4.     Lactation: Only C1 inhibitor concentrates can be used to manage severe angioedema. During lactation, Danazol, Icatibant and Tranexamic acid are contraindicated.

5.     Menopause: The pattern of the disease is not affected by menopause. HRT is not used because it worsens the condition.

6.     Breast cancer: Tamoxifen is contraindicated. C1 inhibitor concentrates, attenuated androgens and Tranexamic acid can be used for short-term prophylaxis. Antifibrinolytics are the best option for long-term prophylaxis. Attenuated androgens have adverse effects (such as virilisation, mammary hypotrophy, hirsutism, alopecia, dysmenorrhea, acne and weight gain) if they are used for long-term prophylaxis.

The information contained in this paper is important to the general public because:

1.     It states why HAE symptoms are more common in females than males.

2.     It states the management strategies that can be used in HAE patients.

Laurence Bouillet links his paper to other scholarly and peer-reviewed works. Moreover, he states the importance of this paper to the general public when he states the indicated drugs and the contraindicated drugs that must be used or avoided (respectively) during the management of a female HAE patient.