Birth control pills ID’d as common trigger of HAE attacks in rare types
Swelling in 100% of women in Portuguese study tied to estrogen contraceptives
Birth control pills and other changes in hormone levels are a common trigger for swelling attacks among women with rare forms of hereditary angioedema (HAE), according to a new study of patients in Portugal.
“The main identified triggers were oral estrogen-containing contraceptives (in 24 of 24 women; 100%),” the researchers wrote, noting that, among patients of all sexes, trauma also was a frequent trigger, as seen in 68% of the patients in the study.
These findings highlight the impact that changes in estrogen levels can have for women with rare forms of the genetic disease, particularly HAE-nC1-INH, the team noted.
Fluctuations in estrogen, one of the main hormones that regulates female development and some sex characteristics, also are known to be a trigger for many women with more common types of HAE.
The study, “Hereditary angioedema with normal C1-Inhibitor: Clinical and genetic characterization of 15 Portuguese unrelated families,” was published in the journal Annals of Allergy, Asthma Immunology.
Researchers seek to describe characteristics of rare HAE types
HAE is a chronic disorder marked by recurrent swelling episodes. The most common forms, types 1 and 2, are caused by mutations in the gene that provides instructions for making a protein called C1-inhibitor.
There also are rarer forms of HAE caused by mutations in other genes, most commonly a gene called F12. These rare forms are referred to as hereditary angioedema with normal C1-inhibitor, or HAE-nC1-INH for short. Compared with the more common forms of HAE, little is known about how HAE-nC1-INH affects patients.
To learn more, a team of scientists reported on clinical data from 41 people with HAE-nC1-INH who were followed at a reference center in Portugal.
“We described the first Portuguese series of patients with genetically characterized HAE-nC1-INH, from 15 unrelated families,” the scientists wrote, noting this is one of the largest studies of this rare subtype of HAE.
Among these patients, 39 had mutations in the F12 gene, including one specific mutation that had never been reported. The other two other patients had mutations in the PLG and KNG1 genes; both of these genes had been previously linked to HAE-nC1-INH, but the specific mutations found in these individuals were new, according to researchers.
Patients with F12 mutations were predominantly female (82%). About two-thirds of these individuals had overt symptoms of HAE; the rest were identified as having the disease based on genetic testing after family members were diagnosed with HAE. Individuals who didn’t have symptoms were more commonly male, the researchers noted.
Among patients who had symptoms, the mean age at the time of the first attack was 21.3 years, and the median delay between the first HAE attack and a final diagnosis of HAE-nC1-INH due to a F12 mutation was 13.5 years.
Patients reported that swelling attacks usually lasted three or four days, and that swelling almost always affected the face. Swelling in the extremities or abdomen also was common, though less so.
HAE attacks ended in half of patients who stopped birth control pills
Clear links were seen to the effects of hormones and related treatments in female patients.
“A hormonal influence in angioedema attacks was observed in 25 (96.2%) of the 26 symptomatic females,” the researchers wrote.
“Factors … including oral estrogen-containing contraceptives … pregnancy, menstruation and hormone replacement therapy (HRT) were described as having a negative impact in our patients,” the team added.
The researchers highlighted one woman who, prior to swelling attacks, would experience erythema marginatum, which is a skin condition characterized by the appearance of round red markings. Erythema marginatum has been reported to precede attacks in some people with HAE types 1 and 2, but this has never before been reported in HAE-nC1-INH due to F12 mutation.
Factors … including oral estrogen-containing contraceptives … pregnancy, menstruation and hormone replacement therapy (HRT) were described as having a negative impact in our patients.
Nearly all symptomatic women in the study reported that they’d experienced swelling triggered by oral contraceptives, or birth control pills, containing estrogen. These HAE attacks stopping altogether following the discontinuation of the birth control pills in almost half of the cases.
“In our study, besides hormonal factors, stress and trauma were the main identified triggers,” the researchers wrote, also noting that physical injury and dental procedures were frequently reported as triggers for swelling attacks.
Of the 16 patients who’d been pregnant, six experienced a worsening of angioedema during pregnancy, including one patient whose first swelling attack occurred while pregnant. There weren’t any reports of swelling-related problems during childbirth for any of these women.
The team said future studies are important to “fully characterize” the features of HAE-nC1-INH in patients in the country.
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