Hereditary angioedema (HAE) is characterized by recurrent edema attacks in various organs causing discomfort and pain [1]. Managing and preventing recurrent attacks in patients with HAE is a clinical challenge that becomes considerably more complicated during pregnancy. The present report describes the management of a patient with type I HAE over the course of two pregnancies. The patient provided consent for publication. The patient had been diagnosed with type I HAE at 15 years of age and the disease was controlled with danazol. At 33 years of age the patient expressed an interest in trying to conceive, and danazol was discontinued. After conception, the patient experienced an increased frequency and severity of HAE attacks, occurring every 5–7 days in her first and second trimesters. The majority of these attacks were abdominal, causing severe pain and vomiting. These attacks were successfully managed in the emergency department with an intravenous infusion of 1500–2000 U of purified C1 esterase inhibitor (Berinert; CSL Behring, King of Prussia, PA, USA), analgesics, and antiemetics. The patient was hospitalized twice during the first trimester and once during the second trimester owing to persistent abdominal symptoms that did not completely resolve with management in the emergency department. In the third trimester, the patient started receiving 1500 U of C1 inhibitor (C1-INH) every 5 days as prophylactic therapy and had no further HAE attacks. At term, the patient was treated with a prophylactic dose of C1-INH given prior to induction for a vaginal delivery of a healthy male neonate weighing 2780 g that was HAE-negative on further testing. After delivery, the patient was restarted on danazol 100 mg twice daily for prevention of HAE attacks and thus was unable to breastfeed. Two years after her first delivery, the patient discussed with her physicians and planned for a second pregnancy. She discontinued danazol and initiated C1-INH prophylactic therapy (initially 500 U weekly and then increased to 1000 U weekly). A portacath catheter was inserted to facilitate recurrent intravenous administration of C1-INH. Once she became pregnant, the patient developed weekly HAE attacks despite prophylactic C1-INH infusions. On 5 separate occasions the patient attended the emergency department for treatment with C1-INH (1500–2000 U), analgesics, and antiemetics. This increase in her disease activity resulted in her prophylactic regimen being changed from 1000 U twice weekly, to 1500 U twice weekly, to a maximum dose of 2000 U twice weekly by the end of the first trimester (Table 1). The titration of the C1-INH dose resulted in a gradual decline in frequency and severity of HAE attacks, decreasing to every 2–3 weeks by the third trimester without any emergency department treatment needed. At delivery, the patient was treated with 1000 U of C1-INH prior to induction of labor, and vaginally delivered an HAE-positive male neonate weighing 2550 g without complication. After delivery, the patient breastfed for 24 hours before restarting danazol. The frequency of HAE attacks has been shown to increase as pregnancy progresses, with a higher rate in the third trimester [2,3]. In the present case, the patient's initial increase in attack frequency and severity over the first two trimesters of her initial pregnancy suggests that she was likely to exhibit a further increase in the frequency and severity of HAE attacks during the third trimester. During her first pregnancy, the initiation of a prophylactic regimen with C1-INH during the third trimester was able to prevent the recurrence of further attacks for the remainder of the pregnancy. During her second pregnancy, the patient once again displayed a high level of disease activity with pregnancy, which also increased as the pregnancy progressed. However, unlike in the first pregnancy, in the second pregnancy HAE attacks were not completely controlled with C1-INH despite an even more aggressive prophylactic regimen (Table 1). The etiology to this increased dosing requirement and decrease in efficacy is likelymultifactorial, but may at least be partially due to the HAE-positive status of the child during the second pregnancy compared with the first pregnancy, where the child was HAE-negative [2,3]. Attenuated androgens are effective agents in preventing angioedema attacks in most patients with HAE; however, they are teratogenic and must be discontinued in pregnancy. In the most recent recommendations from an international consensus on the treatment of HAE, C1-INH was concluded to be the safest prophylactic agent available during pregnancy [4]. The present case emphasizes not only the utility of a long-term prophylactic regimen with C1-INH during pregnancy, but also the importance of a personalized approach to the dosing regimen, titrating dose, and frequency of infusion with the patient's frequency and severity of attacks. With regard to dosing regimens for long-term prophylaxis during pregnancy, the maximum dosing reported in the present case—2000 U of C1-INH twice weekly—appears to be the highest ever reported in the literature.
Read full abstract
Jun 1, 2013
D Aletaha + 2
Open Access