Recognizing and managing hereditary angioedema
ABSTRACTHereditary angioedema is a rare but life-threatening disease characterized by recurring attacks of swelling of any part of the body, without hives. Prompt recognition is critical so that treatment can be started to minimize morbidity and the risk of death. Drugs have recently become available to prevent and treat acute attacks.
KEY POINTS
- Swelling in the airways is life-threatening and requires rapid treatment.
- Almost half of attacks involve the abdomen, and abdominal attacks account for many emergency department visits, hospitalizations, and unnecessary surgical procedures for acute abdomen.
- Acute attacks can be managed with plasma-derived or recombinant human preparations of C1 inhibitor (which is the deficient factor in this condition), ecallantide (a specific plasma kallikrein inhibitor), or icatibant (a B2 bradykinin receptor antagonist).
- Short-term prophylaxis may be used before events that could provoke attacks (eg, dental work or surgery). Long-term prophylaxis may be used in patients who have frequent or severe attacks or require more stringent control of their disease. Plasma-derived C1 inhibitor is both safe and effective when used as prophylaxis. Attenuated androgens are effective but associated with many adverse effects.
SPECIAL CHALLENGES IN WOMEN
Women with hereditary angioedema have more frequent attacks and generally a more severe disease course than men.12 Optimizing care for women is challenging because hormonal changes often cause the disease to flare up in menarche, pregnancy, lactation, and menopause. Women also have a higher rate of discontinuing long-term androgen therapy because of side effects, including virilization and menstrual irregularities. Spironolactone (Aldactone) 100 to 200 mg daily can be used to control hirsutism.33
Contraception
Because estrogen can trigger attacks, progesterone-only formulations, intrauterine devices, or barrier methods are recommended for contraception.33 Progesterone-only pills are preferred and improve symptoms in more than 60% of women. Etonogestrel, another alternative, is available as an implant (Implanon) or vaginal ring (Nuvaring). Intrauterine devices are generally well tolerated, and no prophylaxis is needed during placement. The progesterone-eluting intrauterine device (Mirena) could be beneficial.34
Pregnancy and lactation
Pregnancy and lactation pose particular challenges. Anabolic androgens are contraindicated during pregnancy as well as during breastfeeding because they can be passed on in breast milk. Women receiving androgen prophylaxis should understand that they can still ovulate and need contraception if they are sexually active.34 Patients on attenuated androgens who desire pregnancy should discontinue them 2 months before trying to conceive.
Changes in attack patterns can be unpredictable during pregnancy. Attacks tend to be more severe during the first trimester and more frequent during the third. Due to its safety and efficacy, plasma-derived C1 inhibitor has become the treatment of choice for on-demand or prophylactic treatment during pregnancy and lactation. Antifibrinolytics are considered only when plasma-derived C1 inhibitor is not available.31 Ecallantide and icatibant have not been studied in pregnancy. If neither plasma-derived C1 inhibitor nor antifibrinolytics are available, fresh-frozen plasma or solvent-and-detergent-treated plasma can be used.
Short-term prophylaxis should be considered before amniocentesis, chorionic villous sampling, and dilation and curettage. Delivery should take place in a facility with rapid access to plasma-derived C1 inhibitor as well as consultants in obstetrics, anesthesiology, and perinatology. Although plasma-derived C1 inhibitor should be available at all times during labor and delivery, its prophylactic use is not required unless labor and delivery are particularly traumatic, the underlying hereditary angioedema is very severe, or if forceps, vacuum delivery, or cesarian section is performed. Close monitoring is recommended for at least 72 hours after routine vaginal delivery and for 1 week after cesarian section.
CONCLUSION
The goals of hereditary angioedema treatment are to alleviate morbidity and mortality associated with the disease and to improve the patient’s quality of life. Achieving these goals requires timely diagnosis, patient education, and careful selection of therapeutic modalities that are individualized to the needs of that patient. Treatments have advanced greatly in the last 4 years, and new medications for both the acute and chronic symptoms of hereditary angioedema have shown great promise.
Acknowledgment: K.T. is funded by National Institutes of Health grant T32 AI 07469.
