Can you comment about the influence of age on the frequency of angioedema attacks?

Jun 24, 2015

Dr. C: I would like to start by encouraging all of you to sign up for our patient registry and join the database. We began this project over 5 years ago and it has become a repository of information to allow us to answer questions such as these. It is invaluable to have the direct patient input. A warm thank you to all of who have registered and continue to participate.

Dr. Z: I’d also like to thank all of you who are participating in the Registry. We plan to analyze the data soon and then publish the results. This should provide a more definitive answer to this week’s question. Stay tuned!

Dr. C: Back to the question. Type I and type II HAE typically present in childhood, with 50% of patients reporting their first swelling by the age of 10 (prior to the exacerbation at puberty) and a vanishingly small percentage of patients who have an onset of symptoms after the age of 30. External factors can unpredictably influence the course of disease severity. The presumption has been that with older age, the frequency of attacks may be less severe but we really have no good longitudinal studies to draw from. Marc, you have had a broad experience in caring for HAE patients—any comments about this?

Dr R: We know from large surveys that most individuals with HAE have symptoms during childhood. Often the frequency of angioedema increases during puberty. Beyond that, there doesn’t appear to be a ‘typical course’ for HAE during adulthood. The frequency and severity of attacks can change dramatically for some people over time and remain very consistent over a lifetime for others. I have seen patients where the symptoms wane and become much less frequent after the age of 60, but that certainly is not true for everyone.

Dr. C: I do think that we have all seen substantial variability in HAE severity as patients get older. One mechanism that could account for this variability, including a decrease in severity with age, is hormonal fluctuation. This would be with particular regard to estrogen in menopausal and post-menopausal women. This is one of the many areas that we are trying to gather information on in the registry database. Hormonal replacement therapy with estrogens is contraindicated in HAE, but we still see many women being put on replacement therapy during and after menopause, which could worsen the angioedema. Any thoughts on this Bruce?

Dr. Z: I’ve certainly seen patients who were put on hormonal replacement therapy and then experienced a flare in their swelling. Like Marc, I haven’t been impressed that there is a consistent alternation in HAE severity with advancing age – which is disappointing to me as I keep hoping that there are some good things that occur with advancing years. I think that your hypothesis that changes in disease severity may be linked to natural changes in hormone levels is intriguing. We do see patients who do seem to have fewer attacks as they age, and it would be fascinating to know why this occurs. In addition to hormonal changes, I wonder if variation in stress could account for the differences? Some people experience significant reductions in stress as their children grow up and they retire. For others, aging itself can be a source of stress. We don’t understand how stress affects HAE severity, and it’s not unreasonable to envision neuro-endocrine interactions that link stress to hormonal changes.

Dr. C: I share your disappointment on the ‘advancing years’ front Bruce—I seem to be getting targeted with advertisements urging me to buy ‘anti-wrinkle’ cream. I agree with you that the issue of stress and HAE remains of considerable interest. As we discussed several weeks ago, we are about to launch a study to try to measure whether stress correlates with HAE severity. Speaking of areas where we need progress, we are now beginning to gather data on patients with HAE with normal C1 inhibitor. It does seem from the literature that this group has a later onset of disease but again we do not have sufficient insight about the natural history. Marc, you have had the opportunity to care for a number of patients with this condition— any thoughts?

Dr. R: Patients with suspected HAE with normal C1 inhibitor do appear to start swelling a little later in life than patients with type I or type II HAE. Unfortunately, we don’t really know much yet about the impact of aging on swelling in this condition.

Dr Z: We do recognize the unmet need here. I’d like to mention that the Angioedema Center along with the US HAEA and its Medical Advisory Board are organizing a workshop on HAE with normal C1 inhibitor this Fall. In addition, we’re building a special Registry for HAE with normal C1 inhibitor at the Angioedema Center so that we’ll be able to address these questions.

Dr C: Thank you both again for an interesting discussion–even though we were not actually able to provide a definitive answer. In the end it highlights that there is still much to be done in furthering our understanding of HAE. I am confident that progress will continue through our partnership with the HAEA and the patient community. I look forward to hearing from you both for our next “Question of the Week”. In closing I would like to wish all of our readers who qualify “Happy Mother’s Day”.

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