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Angela Mulé, Catherine Prattico, Adnan Al Ali, Pasquale Mulé, Moshe Ben-Shoshan Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children’s Hospital, McGill University Health Centre, Montreal, QC, CanadaCorrespondence: Moshe Ben-Shoshan, Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children’s Hospital, McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC, H4A 3J1, Canada, Tel +1 514 412-4400, Fax +1 514 412-4288, Email moshebenshoshan@gmail.comAbstract: Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE mediated food allergy that presents with delayed gastrointestinal symptoms after ingestion of the trigger food. The data regarding FPIES are sparse, despite being recognized as a distinct clinical entity. This narrative review presents the characteristics of this disorder in the pediatric population, as well-standard diagnostic and management protocols. FPIES can be classified into acute and chronic subtypes, and some cases may develop into an IgE-mediated allergy. Given that skin prick tests and specific IgE levels are negative in the majority of cases, diagnosis relies on clinical history and oral food challenges. Management involves elimination diets, assessment of tolerance through oral food challenges, and rehydration in the event of a reaction. Future research should focus on improving diagnostic methods, illustrating underlying pathogenesis and biomarkers, and assessing long-term natural history. Increased knowledge and awareness for FPIES are required.Keywords: FPIES, non-IgE mediated food allergy, oral food challenge, elimination diet

The Chronic Angioedema Registry (CARE) is an international disease registry that aims to improve patient care for recurrent angioedema. It collects data through questionnaires completed by physicians and patients to assess disease control, quality of life, and treatment responses. However, the outcomes may not apply to less severe cases typically seen in primary care or community settings, and the findings may not be generalizable to patients from diverse ethnic backgrounds. The document also lists conflicts of interest for authors involved in the CARE study, who have disclosed financial relationships with pharmaceutical companies and other organizations. The study received approval from the Ethics Committee of Charité—Universitätsmedizin Berlin. [Extracted from the article]

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 over the 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

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 10 years 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

Summary: Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle‐aged women. It usually lasts for several years (> 1 year in 25–75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1‐antihistamines, even at higher doses, and third‐ and fourth‐line therapies (omalizumab and ciclosporin) control the disease only in two‐thirds of H1‐antihistamine‐resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health‐related quality of life (HRQoL), particularly when CSU is associated with angio‐oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio‐oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550. Plain language summary available online [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Omalizumab (Xolair®) is an anti‐IgE monoclonal antibody, which may benefit adults with systemic mastocytosis. We report effective treatment with omalizumab in two toddlers with severe diffuse cutaneous mastocytosis. Our cases offer preliminary evidence to support the safe use of omalizumab in paediatric patients with cutaneous mastocytosis. [ABSTRACT FROM AUTHOR]

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Background. Studies suggest that the rising prevalence of food allergy during recent decades may have stabilized. Although genetics undoubtedly contribute to the emergence of food allergy, it is likely that other factors play a crucial role in mediating such short-term changes. Objective. To identify potential demographic predictors of food allergies. Methods. We performed a cross-Canada, random telephone survey. Criteria for food allergy were self-report of convincing symptoms and/or physician diagnosis of allergy. Multivariate logistic regressions were used to assess potential determinants. Results. Of 10,596 households surveyed in 2008/2009, 3666 responded, representing 9667 individuals. Peanut, tree nut, and sesame allergy were more common in children (odds ratio (OR) 2.24 (95% CI, 1.40, 3.59), 1.73 (95% CI, 1.11, 2.68), and 5.63 (95% CI, 1.39, 22.87), resp.) while fish and shellfish allergy were less common in children (OR 0.17 (95% CI, 0.04, 0.72) and 0.29 (95% CI, 0.14, 0.61)). Tree nut and shellfish allergy were less common in males (OR 0.55 (95% CI, 0.36, 0.83) and 0.63 (95% CI, 0.43, 0.91)). Shellfish allergy was more common in urban settings (OR 1.55 (95% CI, 1.04, 2.31)). There was a trend for most food allergies to be more prevalent in the more educated (tree nut OR 1.90 (95% CI, 1.18, 3.04)) and less prevalent in immigrants (shellfish OR 0.49 (95% CI, 0.26, 0.95)), but wide CIs preclude definitive conclusions for most foods. Conclusions. Our results reveal that in addition to age and sex, place of residence, socioeconomic status, and birth place may influence the development of food allergy. [ABSTRACT FROM AUTHOR]

Cochlear dysplasia is a rare congenital anomaly. However, early detection of this anomaly can prevent serious consequences. We describe three cases of cochlear dysplasia that presented with recurrent meningitis and cerebro-spinal fluid (CSF) leak in children in which early diagnosis prevented further complications. [ABSTRACT FROM AUTHOR]

Summary: Omalizumab (Xolair®) is an anti‐IgE monoclonal antibody, which may benefit adults with systemic mastocytosis. We report effective treatment with omalizumab in two toddlers with severe diffuse cutaneous mastocytosis. Our cases offer preliminary evidence to support the safe use of omalizumab in paediatric patients with cutaneous mastocytosis. [ABSTRACT FROM AUTHOR]