HAE in women, pregnancy, and children
“With children, we have to set them up for success rather than a life of anxiety and depression and worry about having a genetic disorder.”
Professor Connie Katelaris summed up her view on how to support children with HAE in a single sentence. Her presentation, the final one from our experts, took in the situation of mothers and pregnant women with HAE, too.
Children with HAE
Starting with children, she told the audience that between half and three-quarters of children with HAE have their first HAE attack by the age of 12, and 90% will have had one by the age of 20. This means, she said, that this is a disease that manifests in childhood, and the way in which those early years are managed is really important for the rest of the child’s life.
The earlier the disease starts can be linked to more severe HAE, she said, but females also tend to show symptoms sooner in life.
Diagnosis in children can be delayed, she said, because there is a low awareness of the condition. In the case of abdominal symptoms, these can be attributed to much more common causes of recurrent abdominal pain in children, like appendicitis.
Professor Katelaris stressed that children often have prodromal symptoms, such as a non-itchy raised rash. These sometimes occur long before a first swelling attack. The actual attacks themselves are exactly the same types as in adults. The most common locations are the abdomen or the hands and feet. Laryngeal attacks are thankfully rare, she told the audience, but they do occur and are concerning because of the small size of a child’s windpipe. All throat or laryngeal attacks are an immediate emergency, she said, as the airway can be compromised much more quickly in a child.
Moving to diagnosis, Professor Katelaris outlined the importance of medical and family history. Biochemical marker tests are measured, but in her view, genetic tests aren’t usually necessary except for the very rare form, HAE with normal C1-inhibitor. For a typical presentation, family history, and biochemical markers, there is no need for genetic testing of a child.
After diagnosis, she recommends 2-3 visits with the doctor to go through everything, which includes:
- Pointers on recognizing attacks
- Discussing prodromal symptoms and trigger factors
- Treatment and management options (where this luxury exists), with input from parents, caregivers, and the patient if they are old enough
- Getting a written management plan so everyone knows what is agreed. This can also be helpful for doctors in the emergency department, Professor Katelaris noted.
- The national HAE organization and the importance of joining
- Equipping the child with the skills and knowledge to understand the condition, explain it to others, and manage any anxiety
Touching briefly on treatment, Professor Katelaris noted that not everyone in the audience had access to HAE-specific therapies and hoped that would change in the coming years. Whether you have or don’t have effective treatment, she said, there is a great deal we can do for children. A key part is to help them make sensible choices. Using sports as an example, she mentioned a patient who was a very aggressive player in a contact sport, which meant he ended every game with a swelling, making it not a great choice. Talking about something in which you can succeed and not be impaired by HAE is really important.
Hearing and addressing the worries every child with HAE had was also important to Professor Katelaris. She asks all young patients to tell her what they’re worried about; sometimes, it’s sleeping over at a friend’s house for fear of an attack, or being embarrassed for their friends to see their hand or foot swollen. Professor Katelaris suggested that managing anxiety is very important and should be part of overall healthy living (with or without HAE). This, for her, involved a good diet, good sleep, and good exercise.
Help yourself to get good sleep; have a regular bedtime, with no phones or devices before bed. Perhaps reading a book and learn how to relax from the day’s activities.
Another good practice is to look at the family dynamics, Professor Katelaris counseled. If parents are overly anxious or worried, especially if they also have HAE, a child will learn to feel the same way. A more balanced attitude will help the child see a better way to approach a lifelong disease with less anxiety.
Mentioning triggers, Professor Katelaris highlighted that climbing trees and having falls may lead to attacks, but it’s a normal part of childhood. Children also get lots of common infections. This can’t be stopped, but making sure children with HAE get all the immunizations that are available will really help. The number 1 trigger was, she said, stress. We all have stress, she said, but increased disease activity leads to anxiety, which in turn can lead to increased risk of another attack. If you have a child with HAE who is more nervous or anxious, they might need some psychological support. Evidence does indeed suggest that children who have attacks tend to have higher anxiety traits.
With treatment, Professor Katelaris was clear that more clinical trials are needed in young children. They are coming, she suggested, but more needs to be done. Her priority was to get prophylactic treatment to children, as it makes a massive difference to their lives.
Women with HAE
Professor Katelaris made clear that women have more frequent and often more severe HAE attacks, with a higher need for hospitalization.
In a survey of 150 women with HAE, two-thirds stated that the condition worsened during puberty, and 80% reported more attacks if they took contraceptive pills containing estrogen. HAE attacks are often triggered by the menstrual cycle, she said.
‘Why are women so affected?’ she asked. Estrogen, a female hormone, impacts the cycle, which leads to increases in bradykinin, which, she remarked, we remember from earlier being the cause of leaky blood vessels and subsequent swelling. Monthly periods and problems such as undiagnosed endometriosis can trigger abdominal attacks.
There are oral contraceptives that do not contain estrogen, and intrauterine devices (IUDs) and barrier methods don’t seem to be an issue. In women who want to become pregnant, Professor Katelaris cautioned the need for planning. The medications the individual might be on could be a problem if they become pregnant. There is also the opportunity for genetic counseling.
Fertility is not affected by HAE, according to Professor Katelaris. Women using IVF may find that the hormonal injections can be a real trigger for attacks. Short-term prophylaxis, where available, would be good for these women, said Professor Katelaris.
Pregnant women with HAE are also diverse. In some pregnant women HAE worsens, but in others it gets better.
Professor Katelaris said that, unsurprisingly, abdominal attacks are the most frequent for pregnant women. C1-inhibitor concentrate is the only treatment recommended for women who are pregnant or breastfeeding, Professor Katelaris confirmed. There is no recommendation for routine prophylaxis before an uncomplicated birth, she said, but there should be acute treatment available regardless of the type of birth.
Breastfeeding can lead to increased attacks, and tranexamic acid and androgens are to be avoided in breastfeeding, Professor Katelaris told the audience.
Moving on to another stage in a woman’s life, Professor Katelaris discussed the impact of menopause on HAE. She reported that in 1 study of post-menopausal women with HAE, 55% of women reported no change, 13% reported improvement, and around a third reported a worsening of symptoms. In treating menopausal symptoms, Professor Katelaris expressed caution about estrogen replacement, suggesting it should be avoided and that progesterone can be used. Non-hormonal treatments are not an issue, she said.
Finally, Professor Katelaris spoke about HAE with normal C1-inhibitor, as women are far more affected by the condition than men. The face, tongue, and upper airway are usually more affected, with abdominal attacks less common. Estrogen has an even greater effect, according to the Professor. There is a lack of trials on treatment. Icatibant works but is slower, according to a case series, and there are cases where tranexamic acid has been reported to be beneficial, she concluded.
