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Issue #2, April 2021
Welcome back to The Buzz, a monthly feature of the HIVE community where we summarize recent articles with high clinical relevance for Canadian allergists, immunologists and dermatologists.
The allergists’ perspective on anaphylaxis risk with SARS-CoV-2 vaccines
In a timely editorial, Greenhawt and colleagues urge vigilance to avoid over diagnosing anaphylaxis risk in the global vaccine effort, especially given deliberate misinformation campaigns. Allergists need to balance the statistically rare events of anaphylaxis and the ability to mitigate risks, with the very real and fatal risk of SARS-CoV-2 persistence if the vaccination effort falls short. The authors note there is no conclusive proof that the polyethylene glycol (PEG) excipient in the mRNA vaccines is the source of observed anaphylactic reactions, and that PEG skin testing is often inconclusive. Overall, they state that it is harmful to restrict vaccination beyond labelled contraindications without a higher burden of proof. As many of the events in the media have not been definitively identified as true allergic events, collecting serum and evaluating for serum tryptase and complement profiles within two hours of a suspected anaphylactic event would help to further characterize the events.
Read more: [Sosido link] Greenhawt M, Abrams EM, Oppenheimer J, et al. The COVID-19 Pandemic in 2021: Avoiding Overdiagnosis of Anaphylaxis Risk While Safely Vaccinating the World [published online ahead of print, 2021 Jan 30]. J Allergy Clin Immunol Pract. 2021;S2213-2198(21)00080-5. doi:10.1016/j.jaip.2021.01.022
Emerging biologics for chronic spontaneous urticaria
Patients with chronic spontaneous urticaria (CSU) are typically treated with escalating doses of nonsedating antihistamines, followed by omalizumab. Many patients do not respond adequately to omalizumab therapy, currently their only remaining option is cyclosporin. Metz and Maurer review some of the more recently elucidated mechanisms for CSU and biologics being studied to target these mechanisms. Some are already in clinical development, such as ligelizumab (anti-IgE), dupilumab (antiIL-4Rα), and benralizumab, mepolizumab and reslizumab (anti-IL-5/-5R). Early-phase biologics targeting emerging mast cell targets, such as alarmins and G protein-coupled receptors are also reviewed. The authors are optimistic that additional biologics will become available to treat CSU in the coming years.
Read more: [Sosido link] Metz M, Maurer M. Use of biologics in chronic spontaneous urticaria - beyond omalizumab therapy?. Allergol Select. 2021;5:89-95. Published 2021 Feb 12. doi:10.5414/ALX02204E
Predictors of response and non-response in chronic spontaneous urticaria
Fok and colleagues conducted a systematic review to identify response predictors to the different types of therapies used in CSU. Seventy-three studies were included for data analysis. For antihistamines, no markers were associated with a good response, however high disease activity, C-reactive protein, Ddimer, concomitant chronic inducible urticaria (CIndU) and previous treatment with corticosteroids were associated with poor or no response. Not surprisingly, low total IgE was associated with poor or non-response to omalizumab. Positive basophil histamine release assay results and low total IgE levels were found to be markers of good response to cyclosporine.
Read more: [Sosido link] Fok JS, Kolkhir P, Church MK, Maurer M. Predictors of treatment response in chronic spontaneous urticaria [published online ahead of print, 2021 Feb 4]. Allergy. 2021;10.1111/all.14757. doi:10.1111/all.14757
Real-world analysis of omalizumab in chronic inducible urticaria
Yu and colleagues conducted a real-world retrospective analysis of CIndU patients treated with omalizumab therapy. Fifty-nine patients were enrolled, including 70% with symptomatic dermographism. Patients received 300 mg omalizumab every month for up to six months. Well controlled disease was observed in 78% of subjects, with 56% being complete responses. Complete responders were younger and had higher baseline IgE than those without a complete response. DLQI scores dropped >4 points from baseline in 83% of patients. Five patients who had achieved a complete response within 6 months of omalizumab treatment stopped their treatment and all relapsed. All
patients were successfully retreated with omalizumab and experienced complete response after the first administration. None of the patients reported adverse events resulting from omalizumab treatment.
Read more: [Sosido link] Yu M, Terhorst-Molawi D, Altrichter S, et al. Omalizumab in chronic inducible urticaria: A real-life study of efficacy, safety, predictors of treatment outcome and time to response [published online ahead of print, 2021 Jan 31]. Clin Exp Allergy. 2021;10.1111/cea.13838. doi:10.1111/cea.13838
Quantifying peanut allergen thresholds in Canadian children and young adults
Chu and colleagues calculated peanut allergen thresholds from two prospective, randomized studies (Canada-ARM1 and PISCES) in Canadian children and young adults. The analysis used Bayesian Stack Model Averaging to model thresholds. The eliciting dose in 50% of the study population (ED50), was found to be 70.58 (95% CI, 59.40-130.90) mg of peanut protein, equivalent to approximately ¼ peanut. The ED50 was higher in the Canada-ARM1 study, which enrolled an older cohort than the PISCES study. ED50 findings were similar to a published report from the UK. Further work should be undertaken to better characterize thresholds for peanut and other food allergens and understanding the mechanism
and clinical use.
Read more: [Sosido link] Chu DK, Baumert JL, Taylor SL, et al. Peanut allergen reaction thresholds during controlled food challenges in 2 Canadian randomized studies (Canada-ARM1 and PISCES) [published online ahead of print, 2021 Feb 16]. J Allergy Clin Immunol Pract. 2021;S2213- 2198(21)00189-6. doi:10.1016/j.jaip.2021.02.009
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