QOTW – “What about those of us with idiopathic angioedema? Can you do something for those of us who do not have HAE?”

May 10, 2016

Dr. C: Greetings and Happy Mother’s Day. Our mission at the “US HAEA Angioedema Center” is to improve the lives of all patients with angioedema. The idiopathic diagnostic category can be particularly distressing for patients. The term is defined as “a disease or condition that arises spontaneously or for which the cause is unknown”—in other words it comes out of the blue and we have no real answer as to why. We arrive at this diagnosis after a concerted attempt to identify any clear culprit. We are all programmed to want answers, so to be told that we do not have one can be uniquely frustrating. Clearly, we need continued research in this area. We do need to do the best we can with what we have to work with. For the present this translates into trying to identify which of the two main known culprits, histamine and bradykinin, are at the root of the swelling. This will then inform our therapeutic strategy and management. Marc, can you update our reader on our clinical approach to cases of idiopathic angioedema?

Dr R: “Idiopathic” is a word that no one likes to hear in clinical medicine. The word comes from Greek roots and literally means “one’s own suffering”. When used in the medical field it means a condition without a known or identifiable cause. Unfortunately, there are many medical conditions that fit into this category and angioedema is no exception. A large percentage of people with angioedema have this idiopathic form. It’s important with any angioedema condition to take a careful medical history and review records to look for any possible underlying reasons for the angioedema. Sometimes lab testing is indicated to exclude suspected causes. However, even with extensive testing, we often can’t pinpoint any specific reason for recurrent angioedema in some individuals. In these cases, it’s usually important to shift from ineffectively searching for a cause to finding a management plan that will treat or control the symptoms. By paying close attention to the details of the character, duration, and associated symptoms of the angioedema, an experienced specialist can often garnish clues to the biochemical pathway driving the symptoms. This is usually a histamine or a bradykinin problem. Some of our current research efforts at the Angioedema Center are aimed at the development of diagnostic tests that would more definitely tell us which of these pathways is “overactive” in each individual. This might allow us to prescribe medications with greater precision and more efficiently treat idiopathic angioedema. Until these tests-in-development are proven useful, we’re left with a “trial and error” approach of carefully constructing a treatment plan after extensive consultation with the patient, and then adjusting that plan as needed based on the response. The good news is that most of the time we can ultimately find a treatment regimen to control the angioedema symptoms in each person. So the answer to the question posed is: Yes – we can help with idiopathic angioedema, but we continue to work at finding more efficient ways to do so, and hopefully with time, we’ll be able to better explain the reasons for this frustrating problem.

Dr. C: Thank you Marc. Bruce, perhaps you could share some thoughts about idiopathic angioedema.

Dr Z: As you already pointed out, we are faced with two important and related questions when we consider making a diagnosis of idiopathic angioedema: 1) are we missing an underlying specific cause; and 2) what it the likely mechanism of swelling? The first question addresses whether the swelling is really idiopathic. This is a moving target – as we increase our knowledge, we should be able to move some idiopathic diagnoses to problems with known causes. The second question mostly revolves around whether the mechanism of swelling is histamine-mediated or bradykinin-mediated. This is important for reasons concerning both prognosis and treatment approaches. Ongoing research addressing these questions is being conducted at many centers, including the US Angioedema Center at UC San Diego. Idiopathic urticaria (hives) has been studied more extensively than histamine-mediated idiopathic angioedema, and some investigators suspect an underlying autoimmune mechanism. Whether histamine-mediated idiopathic angioedema is really similar to idiopathic urticaria, however, is an open question. In truth, we know almost nothing about the cause of histamine-mediated idiopathic angioedema. The relationship between bradykinin-mediated idiopathic angioedema and HAE with normal C1 inhibitor unknown type is a difficult question. Considering the possibility that many people may have HAE with normal C1 inhibitor but are asymptomatic, it’s not possible at the moment to exclude a heritable basis. In addition, we know that every mutation has to start somewhere, and without knowing the underlying cause, we cannot exclude a de novo mutation. In our research studies concerning HAE with normal C1 inhibitor, we definitely include a subgroup of patients with non-histaminergic idiopathic angioedema. At the moment, our ability to treat idiopathic angioedema (whether histamine-mediated or bradykinin-mediated) exceeds our understanding of these conditions. It’s not just patients who are frustrated by this diagnosis – doctors also find our lack of knowledge about it to be deeply frustrating.

Dr C: Thank you Bruce and Marc. I hope that our discussion was helpful for our reader and followers with HAE. As always there is clearly more work to be done. We look forward to hearing from you and our next “Question of the Week”.

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