HAE and Misconceptions

Dr. C: Happy New Year to everyone--welcome back to the QOTW.

I think our readers question introduces a topic that resonates with almost everyone with HAE. As we have discussed there is still an unfortunate delay in establishing a diagnosis—on average 9 years in the US. Physicians often will jump to the common things occur commonly conclusion. So if you see swelling it must be an allergy, if you have abdominal pain you could have appendicitis or ‘irritable bowel, if your throat is swelling it must be anaphylaxis. These picks will be correct most of the time. HAE however is an ultra rare disease that for many physicians is just not on their radar. Marc, what experience have you had to share with our reader?

Dr. R: There are many challenges that can crop up for people during their journey with HAE. In my experience, however, there are three issues that most commonly cause problems. The first is the issue of a correct diagnosis, as pointed out by this question. HAE symptoms are often mistaken for other medical conditions – the skin or airway swelling is attributed to an "unknown allergic reaction (a suspected phantom food, medication, or insect sting/bite) or some unidentified trauma, and the abdominal pain is ascribed to any number of conditions affecting the GI tract or reproductive systems. HAE is typically very far down the list of possible causes or never even considered as a diagnosis because many physicians are unfamiliar with rare conditions. So proper testing to get to the correct diagnosis is a major obstacle.

Dr C: I agree, trying to push the symptoms that individuals with HAE suffer with into the wrong box is a huge problem. Bruce, what are your thoughts regarding the frequent misdiagnosis of HAE and what can we do about it?

Dr. Z: Confusing HAE with an entirely different problem is certainly the original sin in HAE. I think that there are two reasons for this misconception. The first is the rare nature of the disease, as you mentioned. The second, however, is the failure of many physicians to carefully listen to their patients. For this reason, I chose many years ago to re-focus my efforts from educating physicians to enabling patients. In my opinion, the US HAEA has played a key role in improving HAE diagnosis in the USA, substantially increasing the likelihood that a patient with HAE will receive the correct diagnosis in a timely manner. That said, its important to recognize that most of this progress has been for HAE due to C1 inhibitor deficiency. HAE with normal C1 inhibitor remains difficult to diagnosis despite our best efforts, although I expect that to change soon.

Dr C: I agree, the HAEA advocating for patients has been the greatest force in changing the landscape for HAE recognition and care. It has really brought us to where we are today. I am also hopeful that the accelerated progress that we have seen for HAE with normal C1 inhibitor will continue in the coming year. Marc perhaps you could turn to some of the common misconceptions in the medical community referred to by our reader.

Dr. R: The second misconception is the underlying pathophysiology of HAE as most physicians will not be familiar with the C1INH-kallikrein-bradykinin pathway. In medical training, doctors generally learn that "angioedema equals allergy. This simple rule is true about 90% of the time, but for the individual with HAE, this rule leads down the entirely wrong path, resulting in ineffective treatment and a great deal of suffering. So the misconception that all that swells is allergy can cause issues even after the diagnosis of HAE is made.

Dr. C: Certainly, and the consequence of this misconception translates into mistreatment. For individuals with HAE applying the therapies that would be effective for allergy, anaphylaxis or an abdominal emergency will only delay the use of effective therapy with heightened morbidity or even mortality as a consequence. The high price of this particular misconception has been demonstrated by Dr. Bork who identified a strong correlation with the risk of dying from a laryngeal attack and the lack of a defined diagnosis of HAE. Once we know what we are dealing with HAE, the therapeutic options that prevent the generation or action of kinin (the mediator of swelling) are then incorporated into the management. Bruce, I see that you are eager to wade in here.

Dr. Z: Lets not ignore the related possibility that expert physicians can incorrectly label an observation as a misconception. A little humility is in order. We still dont understand fundamental issues such as what provokes HAE attacks or why an attack ends when it does. HAE was initially called hereditary angioneurotic edema based on observation of affected patients, but once we learned the underlying biochemistry of HAE, we appropriately dropped neurotic from the name. Yet the role of stress in HAE is undeniable and were only now beginning to seriously study how stress interacts with the kinin system. Similarly, we repeatedly state that HAE is not a food allergy, but we dont know whether foods can trigger attacks through non-allergic mechanisms. We will also be investigating both of these questions more closely in 2016.

Dr. C: I certainly agree, there is much that we have yet to understand with HAE - I look forward to sharing the results of these investigations in the coming year. Another unfortunate characteristic shared by some physicians is that if my treatment isnt working the patient must be the problem. In other words the patients failure to respond to a selected management is either the result of malingering with regard to reporting symptoms ie. crazy or neurotic, seeking drugs for pain or deriving some secondary gain from embracing illness. It is important to feel that you physician is trying to partner with you to find the answers for any illness. If that is not the case it is best to try and find someone else who will be your advocate—again the HAEA is a tremendous resource here. Marc, would you like to discuss some of the consequences for patients with HAE that can result from a lack of knowledge of this disease or misconceptions about HAE?

Dr. R: The third misconception I often see is an underestimation of the debilitating and life threatening nature of HAE. I think this is true for health care providers but also sometimes for patients and families. Im reminded of this every week in seeing patients and discussing their symptoms, treatment plans, and occasional complications of HAE. With a number of effective medications available now, we typically have the tools to prevent major HAE catastrophes, but theres also a risk of being lulled into a false sense of security that managing HAE is easy. It remains a challenge for many people and underestimating the risks and complexities sometimes leads to major problems. With continued research progress, perhaps it will become simpler and easier to manage HAE, but in the meantime we must continue to work at educating the medical community on the necessary recognition, diagnosis, and specialized treatment.

Dr. Z: Id like to echo Marcs comment. It is so discouraging to see physicians and even patients settle for less than a normal life. The concept that HAE will interfere with a patients ability to lead a normal life is a misconception that we need to recognize and overcome. Im tremendously excited about the new tests and new drugs that will be coming. Although Im certainly a bit naïve, I hope that we will soon reach the point where we can and will effectively diagnose and treat HAE in a manner that allows all patients to reach their full potential. I do recognize that there are many additional misconceptions we havent had the time to discuss today and that the path forward will not be easy.

Dr. C: Thank you Bruce and Marc—I believe that we all share the same hope that pervades the HAE community that a normal life is on the horizon. We need to continue to work together to achieve this fundamental goal. I hope that this discussion will lead the way forward to avoid the misconceptions and misdiagnosis surrounding HAE as we enter a new and better year for all. We look forward to hearing from you and our next Question of the Week.