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Jasmine Chang,1 Leila Cattelan,2 Moshe Ben-Shoshan,3 Michelle Le,2 Elena Netchiporouk2 1Department of Medicine, McGill University, Montreal, Quebec, Canada; 2Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada; 3Division of Allergy Immunology and Dermatology, Montreal Children’s Hospital, Montreal, Quebec, CanadaCorrespondence: Elena NetchiporoukDivision of Dermatology, McGill University, 1650 Cedar Ave, Montreal, Quebec, H3G 1A4, CanadaEmail elena.netchiporouk@mail.mcgill.caAbstract: Chronic urticaria (CU) is associated with debilitating symptoms such as pruritic wheals and/or angioedema, which can significantly affect patients’ sleep, productivity and quality of life. Chronic spontaneous urticaria (CSU) is defined in cases in which no triggering factor is identified. Various guidelines directing the optimal management of CU in the adult population were published and updated overthe recent years with the most accepted and widely used being the EAACI/GA2LEN/EDF/WAO 2017 guidelines. Meanwhile, guidelines specific to the pediatric population are scarce, mainly due to the fact that high quality evidence is lacking for many treatment options in this age group. The objective of this article is to review and synthesize the existing literature regarding the management of pediatric CSU. Our review highlights evidence supporting the EAACI/GA2LEN/EDF/WAO 2017 treatment guidelines with non-sedating second-generation antihistamines (sgAHs) as the mainstay of treatment for pediatric CSU, considering their demonstrated efficacy and reassuring safety profile. Additionally, the use of omalizumab in adolescents is well supported by the current literature. There is limited data available regarding the updosing of sgAHs, omalizumab in children with CSU under 12 years of age and the treatment with cyclosporine and leukotriene receptor antagonists (LTRAs) in pediatric patients of all ages. However, the results from currently available case series and case reports are promising for omalizumab and cyclosporine use in children with CSU, although large and well-designed randomized control trials (RCTs) assessing these treatment options are needed in order to formulate strong recommendations for their use. First-generation antihistamines (fgAHs) remain commonly used in pediatric CSU treatment despite a lack of studies assessing their efficacy and safety in the pediatric population and their widely known inferior safety profile compared to sgAHs.Keywords: chronic spontaneous urticaria; CSU, chronic urticaria; CU, treatment, management, guidelines, children, pediatric

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell–driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. © 2021 GA²LEN. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Michelle Le, Sofianne Gabrielli, Sarah De Schryver, Moshe Ben-Shoshan Division of Allergy, Immunology and Dermatology, Department of Pediatrics, McGill University Health Center, Montreal, QC, CanadaCorrespondence: Michelle LeDivision of Pediatric Allergy, Clinical Immunology and Dermatology, Department of Pediatrics, McGill University Health Center, 1001 Boul. Decarie, Montreal, Quebec H4A 3J1, CanadaTel +1 514-412-4400 (23151)Fax +1 514-412-4390Email michelle.le@mail.mcgill.caBackground: Idiopathic anaphylaxis (IA) is a diagnosis of exclusion and represents a major diagnostic and management challenge. There are no current guidelines for diagnosis and management of IA. We aim to present a systematic review of the literature on adult and pediatric IA.Methods: We conducted a systematic review of original articles published in the past 22 years regarding diagnosis and management strategies of adult and pediatric IA.Results: The current proposed diagnostic approach and treatment regimens are based on a few small studies. Future large-scale studies are required. IA is a diagnosis of exclusion and should be made only after extensive evaluation excludes potential anaphylaxis triggers as well as non-allergic conditions with a similar presentation. There is currently no diagnostic consensus for IA. Furthermore, the current proposed treatment regimens are limited and rely on prophylactic treatment with antihistamines and prednisone for patients with frequent episodes. However, daily treatment with systemic steroids has well-recognized serious adverse effects. More recently, the use of biologics was suggested to benefit patients with IA, although the optimal management protocol is not yet established.Conclusion: Future studies are needed to optimize diagnosis and treatment strategies in adult and pediatric cases of IA. Omalizumab may be a promising novel therapeutic option for adult and pediatric IA.Keywords: anaphylaxis, diagnosis, management, treatment

Adil Adatia,1 Ann Elaine Clarke,2 Yarden Yanishevsky,3 Moshe Ben-Shoshan4 1Department of Medicine, University of Alberta, Edmonton, 2Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, 3Section of Allergy and Clinical Immunology, Department of Pediatrics, University of Alberta, Edmonton, AB, 4Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children’s Hospital, McGill University Health Centre, Montreal, QC, Canada Abstract: Sesame is an important global allergen affecting ~0.1% of the North American population. It is a major cause of anaphylaxis in the Middle East and is the third most common food allergen in Israel. We conducted a systematic review of original articles published in the last 10years regarding the diagnosis and management of sesame allergy. Skin prick testing appears to be a useful predictor of sesame allergy in infants, although data are less consistent in older children and adults. The diagnostic capacity of serum-specific immunoglobulin E is poor, especially in studies that used oral food challenges to confirm the diagnosis. Double-blind, placebo-controlled food challenge thus remains the diagnostic gold standard for sesame allergy. The cornerstone of sesame allergy management is allergen avoidance, though accidental exposures are common and patients must be prepared to treat the consequent reactions with epinephrine. Novel diagnostic and treatment options such as component-resolved diagnostics, basophil activation testing, and oral immunotherapy are under development but are not ready for mainstream clinical application. Keywords: sesame allergy, skin prick testing, specific IgE, component-resolved diagnostics, epinephrine autoinjector

Alison YM Lee,1 Paul Enarson,2 Ann E Clarke,3 Sébastien La Vieille,4 Harley Eisman,5,6 Edmond S Chan,7 Christopher Mill,7 Lawrence Joseph,8 Moshe Ben-Shoshan9 1Pediatric Residency Program, Department of Pediatrics, University of British Columbia, BC Children’s Hospital, 2Division of Emergency Medicine, Department of Pediatrics, University of British Columbia, Vancouver, BC, 3Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, 4Food Directorate, Health Canada, Ottawa, ON, 5Emergency Department, 6Department of Pediatrics, Montreal Children’s Hospital, Montreal, QC, 7Division of Allergy and Immunology, Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, BC, 8Department of Epidemiology and Biostatistics, McGill University, 9Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children’s Hospital, Montreal, QC, Canada Background: There are no data on the percentage of visits due to anaphylaxis in the emergency department (ED), triggers, and management of anaphylaxis across different provinces in Canada. Objective: To compare the percentage of anaphylaxis cases among all ED visits, as well as the triggers and management of anaphylaxis between two Canadian pediatric EDs (PEDs). Methods: As part of the Cross-Canada Anaphylaxis Registry (C-CARE), children presenting to the British Columbia Children’s Hospital (BCCH) and Montreal Children’s Hospital (MCH) EDs with anaphylaxis were recruited. Characteristics, triggers, and management of anaphylaxis were documented using a standardized data entry form. Differences in demographics, triggers, and management were determined by comparing the difference of proportions and 95% confidence interval. Results: Between June 2014 and June 2016, there were 346 visits due to anaphylaxis among 93,730 PED visits at the BCCH ED and 631 anaphylaxis visits among 164,669 pediatric visits at the MCH ED. In both centers, the majority of cases were triggered by food (BCCH 91.3% [88.7, 94.0], MCH 82.4% [79.7, 85.3]), of which peanuts were the most common culprit (24.7% [20.9, 29.9] and 19.0% [15.8, 22.7], respectively). Pre-hospital administration of epinephrine (BCCH 27.7% [23.2, 32.8], MCH 33.1% [29.5, 37.0]) and antihistamines (BCCH 50.6% [45.2, 56.0], MCH 47.1% [43.1, 51.0]) was similar. In-hospital management differed in terms of increased epinephrine, antihistamine, and steroid use at the BCCH (59.2% [53.9, 64.4], 59.8% [54.4, 65.0], and 60.1% [54.7, 65.3], respectively) compared to the MCH (42.2% [38.3, 46.2], 36.2% [32.5, 40.1], and 11.9% [9.5, 14.8], respectively). Despite differences in management, percentage of cases admitted to the intensive care unit was similar between the two centers. Conclusion: Compared to previous European and North American reports, there is a high percentage of anaphylaxis cases in two PEDs across Canada with substantial differences in hospital management practices. It is crucial to develop training programs that aim to increase epinephrine use in anaphylaxis. Keywords: anaphylaxis, emergency department, epinephrine, triggers of anaphylaxis, management

Andrew W O'Keefe,1,2 Sarah De Schryver,1 Jennifer Mill,3 Christopher Mill,3 Alizee Dery,1 Moshe Ben-Shoshan1 1Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada; 2Department of Pediatrics, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada; 3Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada Abstract: It is reported that 6% of children and 3% of adults have food allergies, with studies suggesting increased prevalence worldwide over the last few decades. Despite this, our diagnostic capabilities and techniques for managing patients with food allergies remain limited. We have conducted a systematic review of literature published within the last 5 years on the diagnosis and management of food allergies. While the gold standard for diagnosis remains the double-blind, placebo-controlled food challenge, this assessment is resource intensive and impractical in most clinical situations. In an effort to reduce the need for the double-blind, placebo-controlled food challenge, several risk-stratifying tests are employed, namely skin prick testing, measurement of serum-specific immunoglobulin E levels, component testing, and open food challenges. Management of food allergies typically involves allergen avoidance and carrying an epinephrine autoinjector. Clinical research trials of oral immunotherapy for some foods, including peanut, milk, egg, and peach, are under way. While oral immunotherapy is promising, its readiness for clinical application is controversial. In this review, we assess the latest studies published on the above diagnostic and management modalities, as well as novel strategies in the diagnosis and management of food allergy. Keywords: skin prick testing, oral challenge, specific IgE, component testing, oral immunotherapy, epinephrine autoinjector

We report a case of serum sickness-like reaction (SSLR) in a 15-month-old boy following oral amoxicillin therapy for an acute otitis media. While symptoms of SSLR improved with a non-steroidal anti-inflammatory (NSAID) and oral corticosteroids, he developed a duodenal ulcer. A nasopharyngeal PCR was positive for Influenza A virus during active disease. A graded challenge to amoxicillin conducted subsequently was negative. It is important to consider infectious causes for SSLR and incorporate proton pump inhibitors if NSAIDs and corticosteroids are used simultaneously to prevent gastric complications. Graded oral challenge to the suspected culprit medication proved to be safe in this case and future large scale studies exploring its role in establishing drug related SSLR in patients are required.

Background: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. Objective: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. Materials and methods: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. Results: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients’ needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. Conclusions: This innovative CPG methodology was guided by patients’ perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Introduction: the COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim: to understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. Materials and methods: our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results: the COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. Conclusions: the COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation., Novartis; Sanofi; Menarini Universidad Espiritu Santo; Takeda; Allakos; AstraZeneca; CSL Behring; Genentech; Pharming; GSK; Shire/Takada; BioCryst; ResTORbio; Pearl Therapeutics, CVS Health; Law offices of Levin; Riback; Adelman; Flangel; Vedder Price; Fresenius; Taiho; Kyowa Kirin; Tanabe; Korin; Uriach Pharma; Instituto Carlos III FEDER; Menarini; Amgen; Thermo Fisher; Avene; ALK‐Abello; Bencard/Allergy Therapeutics; Celgene; Allergopharma; Faes Farma; AbbVie; Janssen; Leo Pharma; Lilly; Roche; Genesis; Menlo Therapeutics; UCB; Pfizer; Almirall; Galderma; Allergika; Beiersdorf; Biocryst; Biogen Idec; BMS; Boehringer‐Ingelheim; Eli‐Lilly; Galderma; Hexal; Klosterfrau; LEO‐Pharma; LETI‐Pharma; L´Oreal; Medice; Octapharma; Pflüger; Pharming; Regeneron; Shire; ALK‐Abello; Fraunhofer‐IZI Leipzig; Hautnetz Leipzig/Westsachsen; MSD; HAL‐Allergy; Bencard; Nestle; Nutricia; Bayer Health Care; FAES; Henkel; Allakos; Argenx; Genentech Menarini; Moxie; Aralez; Celldex