Chronic Spontaneous Urticaria Learning Zone
Transcript: CSU with isolated angioedema
Karsten Weller, MD
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- Yeah, hello, and welcome to this case study of the CSU Learning Zone on the diagnosis and treatment of chronic spontaneous urticaria with isolated angioedema. I'm Karsten Weller from the Institute of Allergology at Charité in Berlin. So let us start with a typical clinical case. It is about a male patient, 32 years old, with recurrent angioedema around every 2-3 weeks for 18 months. His angioedema typically affect the eyes, the lips, or the tongues, but the patient never reported to have wheals. His treatment was H1 antihistamines, but unfortunately, without any effect. Recurrent angioedema, as in this example, is a common clinical problem, and most commonly appears in the context of CSU. CSU in general can have very different phases. Patients may suffer from wheals only, from angioedema only, or from both symptoms, but up to 10% of CSU patients only show recurrent angioedema, which is also known as CSU with isolated angioedema. Depending on this symptom pattern of wheals, angioedema, or both, the differential diagnosis are different and other key questions need to be asked and are the key diagnostic measures need to be done in order to identify the correct diagnosis. When a patient only presents with recurrent angioedema, there are four different possibilities.
The first possibility is that the patient has CSU or one of the chronic inducible urticarias, for example, delayed pressure urticaria. Or the second possibility is that the patient has bradykinin-mediated angioedema, which means hereditary angioedema driven by C1 inhibitor deficiency or ACE inhibitor-induced angioedema, so angioedema induced by drug treatment. The therapeutic approach is completely different for these disorders, and this is important, therefore, it is very important to make an accurate diagnosis here and to avoid an unnecessary delay of sufficient treatment for those mostly highly burdened patients. So this is how to best proceed. The first key questions we should ask is, do the patients take ACE inhibitors? And here it is important to have in mind that ACE inhibitor-induced angioedema may still occur after years of treatment. If the patients take ACE inhibitors, these of course need to be stopped. But in addition, patients should be asked for the presence of hereditary angioedema. Here, two important hints from the patient's history are that other family members may also be affected and/or the patients also suffer from recurrent abdominal attacks. Abdominal attacks typically do not occur in chronic spontaneous urticaria. And then these key questions should be complemented by a key diagnostic measure, and this is the determination of C1 inhibitor level and function in the patient's serum. If C1 inhibitor is low, a hereditary or acquired C1 inhibitor deficiency is proven.
When there is, however, no hint for ACE inhibitor intake or C1 inhibitor deficiency, the diagnosis of chronic urticaria can be made. The only question that now still needs to be addressed is if the patients can make their angioedema come or not, or in other words, if these are inducible or not. With this, we can usually well distinguish CSU from chronic inducible urticarias. In our clinical case, the key diagnostic questions and measures revealed no ACE inhibitor intake, no family history for angioedema, and normal levels for C1 inhibitor and normal function of C1 inhibitor. In addition, the patient clearly reported that angioedema only occurs spontaneously and are not inducible, so that the diagnosis of CSU with isolated angioedema could be made. So what are the next diagnostic steps? For physician involved in the treatment of CSU, deciding which further tests are useful can be challenging and unnecessary investigations are usually associated with considerable costs. The current guidelines suggest only very few routine laboratory tests for our CSU patients, including isolated angioedema, and these are a differential blood count, an ESR and/or a CRP determination. We should look for total IgE levels and IgG antibodies against TPO. An extended programme should only be performed if this is suggested by the patient history. So overall, the recommended routine laboratory for CSU is quite easy and limited, and it's the same for all clinical patterns of CSU. Now, after the diagnosis of CSU is clear and secured, it is important to get the best possible insight in the patient's current disease status. This is not trivial because the patients usually appear to consultations without any symptoms at that moment, and we also do not have any biomarkers available.
So we need to fully rely on the patient perspective. And here it is important to capture this with valid and reliable tools, patient-reported outcome measures, PROMs. For patients with isolated angioedema, PROMs can be used to monitor disease activity, quality of life impairment, and disease control. The Angioedema Activity Score assesses angioedema activity, the Angioedema Quality of Life Questionnaire, the impact of the disease, and the Angioedema Control Test is a tool to determine disease control. The Angioedema Control Test, AECT, is the currently easiest of these PROMs and can be used to get a quick overview on the current disease situation. It contains of four questions on the past four weeks with five answer options each, and each question is scored from 0-4 points. The higher the score, then the higher the level of disease control. A score of 10 points or higher indicates well controlled angioedema, while a score of 9 or lower suggests poorly controlled disease. So we have a clear result after the AECT is done. In our clinical case, the patients report to have had angioedema often in the last four weeks, and that his quality of life was much affected by angioedema. In addition, he reports that the unpredictability of angioedema bothered him much and that this angioedema has not at all been controlled by his therapy. So in summary, this patient reaches 1 plus 1 plus 1 plus 0 points, so in total 3 points, which clearly indicates insufficiently controlled disease and the need for a treatment adjustment. When looking at the guidelines, the treatment recommendations, the treatment algorithm for chronic spontaneous urticaria patients with isolated angioedema is not different from all other CSU patients.
The first-line treatment are second generation H1-antihistamines in regular or up to four times increased doses. If this is not sufficient, the addition of omalizumab is recommended. If an adequate control is also not achieved with this approach, omalizumab can be replaced by cyclosporine in this third line. And in parallel, to ensure a timely and best possible treatment for the patient, a specialist referral should be considered, particularly if patients are not sufficiently treated with antihistamines. With this algorithm, really most of the patients can be treated very well. And when we get back to our clinical case, remember this patient with isolated angioedema was insufficiently controlled with antihistamines. The addition of omalizumab would be the next therapeutic step. So with this, in summary, the taking home points, we can say CSU is defined as a spontaneous appearance of wheals, angioedema, or both for more than six weeks. It is important to note that in up to 10% of patients, angioedema is a primary manifestation of their disease. In addition, an accurate and fast diagnosis is important to avoid delays in providing an effective treatment because these patients very commonly have a high disease burden. In patients with isolated angioedema, the patient history and diagnostic tests should focus on the exclusion of bradykinin-mediated angioedema, meaning ACE inhibitor-induced angioedema and C1 inhibitor deficiency-driven angioedema or hereditary angioedema, because these have different treatment options that 'cause the CSU treatment doesn't work in these patients and vice versa. Importantly, also additional routine laboratory test as well as a treatment algorithm for CSU patients with isolated angioedema is identical to those of all other CSU patients.
And finally, patient-reported outcome measures, PROMs, such as the AECT, for example, should be assessed from a first patient visit, and they help us really to monitor disease activity, impact, and control, and can back our treatment decisions. And they are really the only way to reliably capture the patient's disease status since reliable biomarkers are not available yet. And this is the final slide. I hope you got important insights in the diagnosis and treatment of this important population of patients with isolated angioedema and enjoyed this episode. Thank you for watching.
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