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Background: Ibuprofen is a main cause of drug hypersensitivity reactions in children. The gold standard for diagnosis is the drug provocation test (DPT)., Objective: We aimed to create a clinical risk-stratification tool to guide this high-risk procedure., Methods: We prospectively recruited children with suspected ibuprofen hypersensitivity between January 2017 and March 2024. Using stepwise bidirectional multivariable logistic regression, we calculated a predictive score for a positive ibuprofen DPT., Results: Eighty-two patients with a median age of 5.9 years (IQR: 3.4;11.1) had an ibuprofen DPT. Eighteen (22.0%) had a positive challenge, with an anaphylactic reaction for 11 (61.1%). The I3A score (acronym for Ibuprofen, 3As: Angioedema, Anaphylaxis, Age, Cut-off of 3) encompasses the following items: Angioedema (2 points), Anaphylaxis (1 point), and Age at reaction ≥ 10 years old (1 point). The AUC of the I3A score was 0.84 and the optimal cut-off of <3 conferred a sensitivity of 84.4% % (95% confidence interval [95%CI] 66.7-100.0%) and a specificity of 83.3% (95%CI 75.0-92.2%). The negative predictive value was estimated at 94.7% (95%CI 90.0-100.0%), and the positive predictive value at 60.0% (95%CI 46.2%-76.2%). The relative risk of reacting to challenge in the group I3A 3-4 compared to 0-2 was 11.4 (95CI% 3.62-35.7, p<0.001). Anaphylaxis following DPT was observed in 9/25 [36.0% (95%CI 16.0-56.0%)] in the high-risk group as compared to 2/57 [3.5% (95%CI 0.0-8.8%)] in the low-risk group [relative risk 10.3 (95%CI 2.4-43.5)]., Conclusion: We generated a risk stratification tool to identify children at low-risk of reacting to ibuprofen challenges. Further validation is required in external cohorts., (Copyright © 2024. Published by Elsevier Inc.)

Delayed drug hypersensitivity reactions have varied clinical phenotypes, from common maculopapular exanthem (MPE) to the rare but severe drug reaction with eosinophilia and systemic symptoms (DRESS). 1 Few studies showed cross-reactivity between R1-side chains of aminopenicillins and aminocephalosporins in delayed (T-cell-mediated) hypersensitivity with tolerability for other penicillins and cephalosporins. 2 , 3 We aim to describe a cohort of patients with confirmed delayed hypersensitivity to aminopenicillins who safely tolerate penicillin V, which has a different R1 side chain., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Reducing the burden of disease for patients and families requires being able to measure health status changes related to disease severity, control, and response to treatment over time. Patient-reported outcomes are patient perceptions of their health status. Such perceptions are critical to decision making. Some patient-reported outcome measures (PROMs) are extensive and often intended to be used only for detailed research assessments. Many PROMs, however, form critical components of valid, reliable, and responsive assessments in clinical research and routine clinical practice. The smallest score change in a PROM that would lead to different decision making by patients is called the minimally important difference. Using PROMs may also offer advantages over general questions or unvalidated tools. With the innovation of technology, the ability to chronicle disease symptoms using communication technology (mobile phone applications) has become increasingly available. Collection of real-world data in this capacity will be very useful for identifying more precise phenotypes/endotypes necessary for investigation of tailored therapies for chronic spontaneous and inducible urticaria, angioedema, and atopic dermatitis. Here, we provide an overview of PROMs that have been developed for the assessment of disease severity, control, and quality of life and that have been validated for the use of adults and children with these skin disorders., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Oral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse., Objective: We aimed to assess the long-term adherence rates to OIT protocol and the associated risk of allergic reactions., Methods: Patients who completed milk OIT and reached a maintenance dose of 200 mL of milk were surveyed biannually on their dairy consumption and occurrence of allergic reactions. A survival analysis was performed to evaluate the association between the risk of reaction and the adherence to OIT maintenance protocol., Results: The cohort consisted of 50 patients. Only 56% of the cohort adhered to the protocol, which consisted of ingesting a minimum of 200 mL of milk at least 3 times per week. Adherent patients had a significantly reduced risk of allergic reactions as well as a reduced incidence of anaphylaxis, health care/emergency room visits, and epinephrine/antihistamine administration., Conclusions: The findings demonstrate the importance of consistent maintenance dose consumption in the management of food allergies, with regular milk consumption contributing to the maintenance of unresponsiveness and decreased risk of allergic symptoms., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Food allergies, particularly peanut, represent the predominant cause of anaphylaxis. Whereas early allergen introduction has emerged as a potential preventive strategy, the precise impact of recent guidelines on peanut-induced anaphylaxis rates in Canada remains unclear., Objective: To assess the impact of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy on peanut-induced anaphylaxis rates in Canada., Methods: Using a comprehensive longitudinal registry capturing pediatric anaphylaxis presentations to the Montreal's Children's Hospital, we compared children with and without known peanut allergy who presented with peanut-induced anaphylaxis between 2011 and 2019 inclusive, excluding data beyond 2019 owing to the Coronavirus disease 2019 (COVID-19) pandemic. We calculated rates of peanut-induced anaphylaxis presentations per 100,000 age-adjusted all-cause emergency department visits using 4-month intervals. Interrupted time series analysis was used to compare anaphylaxis rate trends before and after 2017 for children ages 0 to 2 and 3 to 17 years., Results: We examined 2,011 cases of pediatric anaphylaxis, including 429 (21%) triggered by peanuts. Compared with pre-guideline estimates, the yearly rate of change of peanut anaphylaxis rates decreased by 7.96 (95% confidence interval -14.57 to -1.36; P = .018) after 2017 among patients with new-onset anaphylaxis in children 2 years of age or younger (n = 109). No significant changes were identified for older patients ages 3 to 17, or in patients with known peanut allergy., Conclusions: Early introduction guidelines in Canada are associated with a reduced risk of new-onset peanut-induced anaphylaxis in young children within a single center in Montreal. Further research is required to assess the impact on a wider population and other food allergens., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear., Objective: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids., Methods: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach., Results: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty)., Conclusions: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice., Objecctive: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks., Methods: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU., Results: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM., Conclusions: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cephalosporins, β-lactam antibiotics, commonly cause allergic reactions., Objective: To assess the clinical characteristics and management of pediatric patients with suspected cephalosporin allergy using direct graded oral challenges (GOCs)., Methods: Children referred for suspected cephalosporin allergy at 4 Canadian clinics were recruited over 10 years. Data on demographics, clinical reaction characteristics, and management were collected through a questionnaire. Patients underwent a direct GOC (initially 10% of the treatment dose, then 90% after 20 min), and reactions were monitored 1 week postchallenge. Families were contacted annually for up to 5 years to detect subsequent antibiotic reactions. Logistic regression analysis identified factors associated with positive GOC reactions., Results: Among the 136 patients reporting cephalosporin allergy, 75 (55.1%) were males with a median age of 3.9 years (interquartile range 2.3-8.7). Cefprozil represented the most common cephalosporin linked to the index reaction (67.6% of cases). Of the 136 direct GOCs, 5.1% had an immediate and 4.4% a nonimmediate reaction, respectively. Positive GOCs conducted in children with a history of skin-limited nonsevere rashes were classified as mild, benign skin rashes. Positive GOCs were more likely in children with food allergies (adjusted odds ratio 1.14; 95% confidence interval [95% CI] 1.00-1.29)., Conclusions: Direct GOCs are safe and effective for diagnosing pediatric cases that report nonvesicular skin-limited symptoms while being treated with cephalosporins., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Reports of allergic reactions to coronavirus disease 2019 (COVID-19) vaccines, coupled with an "infodemic" of misinformation, carry the potential to undermine confidence in the COVID-19 vaccines. However, no attempts have been made to comprehensively synthesize the literature on how allergic disease and fear of allergic reactions to the vaccines contribute to hesitancy., Objectives: Our aim was to review the academic and gray literature on COVID-19 vaccine hesitancy and allergic reactions., Methods: We searched 4 databases (CINAHL, PsycINFO, MEDLINE, and Embase) using a search strategy developed by content and methodologic experts. No restrictions were applied regarding COVID-19 vaccine type, country of study, or patient age. Eligible articles were restricted to 10 languages., Results: Of the 1385 unique records retrieved from our search, 60 articles (4.3%) were included. Allergic reactions to the COVID-19 vaccine were rare but slightly more common in individuals with a history of allergic disease. A fifth of the studies (13 of 60 [22%]) discussed vaccine hesitancy due to possibility of an allergic reaction. Additionally, the present review identified research on details of vaccine-related anaphylaxis (eg, a mean and median [excluding clinical trial data] of 12.4 and 5 cases per million doses, respectively) and allergic reactions (eg, a mean and median [excluding clinical trial data] of 489 and 528 cases per million doses, respectively)., Conclusion: COVID-19 vaccine acceptance among individuals living with allergy and among those with no history of allergic disease may be affected by fear of an allergic reaction. Despite the low incidence of allergic reactions to the COVID-19 vaccine, fear of such reactions is one of the most commonly cited concerns reported in the literature., (© 2023 The Author(s).)

Background: Few validated tools exist to evaluate chronic urticaria (CU) control in children. Although the Urticaria Control Test (UCT) exhibits favorable clinometric properties in adult CU, it is not yet validated in children., Objective: To evaluate the validity of the UCT for the assessment of pediatric CU., Methods: Children presenting with CU were consecutively recruited and completed both the UCT and the Children's Dermatology Life Quality Index (CDLQI) at study entry. Using the CDLQI as an anchor, we assessed the internal consistency, convergent and known-groups validity, and screening accuracy of the UCT at study entry and at follow-up., Results: A total of 52 children with CU were recruited. The UCT exhibited respectable internal consistency in the evaluation of CU (Cronbach's α, 0.73; 95% CI, 0.62-0.85). UCT and CDLQI scores strongly correlated (r = -0.74; P < .01). The UCT distinguished between different strata of disease severities established by the CDLQI (P < .01). Screening accuracy of the UCT was excellent in the discrimination of poorly controlled CU (area under the curve, 0.82). An optimal cutoff of less than or equal to 10 was determined for defining poorly controlled CU (sensitivity, 95.5%; specificity, 63.3%). Data at follow-up were consistent with data at study entry. Subgroup analyses of patients with chronic spontaneous urticaria were consistent with overall estimates of validity., Conclusions: The UCT is a valid tool for the assessment of pediatric CU and chronic spontaneous urticaria, as evidenced by the acceptable internal consistency, convergent and known-groups validity, and screening accuracy at multiple time points., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Prompt epinephrine autoinjector (EAI) use is the primary treatment for anaphylaxis. However, limited Canadian data exist on the impact of reaction location on EAI use for food-induced anaphylaxis (FIA)., Objective: We sought to investigate the setting, management, and severity of pediatric FIA., Methods: We recruited children presenting with FIA from 11 Canadian emergency departments. Patient demographics and the setting, management, and symptoms of FIA were collected by standardized questionnaire. Factors associated with prehospital EAI use and reaction severity were determined by logistic regression., Results: We recruited 3,604 children; 60.2% were male and the median age was 5.0 years (interquartile range 1.8-11.0). Among cases with a known location of FIA (85.0%), home was the most common setting (68.1%), followed by school/daycare (12.8%), other locations (11.4%; eg, park, car), and restaurants (7.4%). In the prehospital setting, EAI was administered in 36.7% of reactions at home, 66.7% in school/daycare, 40.2% in other locations, and 44.5% in restaurants. Relative to reactions occurring at school/daycare, prehospital EAI use was less likely at home (adjusted odds ratio [aOR] 0.80; 95% CI 0.76-0.84), in restaurants (aOR 0.81; 95% CI 0.75-0.87), and in other settings (aOR 0.77; 95% CI 0.73-0.83), when data were adjusted for reaction severity, sex, age, comorbidities, and province. The FIA setting was not associated with reaction severity or hospitalization., Conclusions: Prehospital EAI use was higher at school/daycare than in other settings, potentially owing to the presence of policies and training on FIA. Setting-specific interventions including educational programs and policies/laws mandating training and stocking an EAI may improve anaphylaxis recognition and treatment., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the prevalence, management, and prevalence of associated anaphylaxis of cold urticaria., Objectives: To evaluate the prevalence of cold urticaria among CIndU and chronic urticaria (CU) cases, to assess the management of cold urticaria, and to determine the prevalence of associated anaphylaxis., Methods: We searched PubMed and EMBASE for studies pertaining to cold urticaria and/or CIndU published in the past 10 years. We conducted meta-analyses to evaluate the prevalence of cold urticaria among CIndU and CU cases, the management of cold urticaria with H1-antihistamines and omalizumab, and the prevalence of associated anaphylaxis., Results: Twenty-two studies were included in the systematic review and 14 in the meta-analysis. The pooled prevalence of cold urticaria among patients with CU and CIndU was 7.62% (95% confidence interval [CI], 3.45% to 15.99%; I 2  = 98%) and 26.10% (95% CI, 14.17% to 43.05%; I 2  = 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95% CI, 92.47% to 97.54%; I 2  = 38%) of patients and omalizumab in 5.95% (95% CI , 2.55% to 13.27%; I 2  = 83%) of patients. The pooled prevalence of anaphylaxis among patients with cold urticaria was 21.49% (95% CI, 15.79% to 28.54%; I 2  = 69%)., Conclusions: Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines; few patients receive omalizumab. Anaphylaxis is common, and an epinephrine autoinjector prescription may be considered., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Food desensitization via oral immunotherapy (OIT) is gaining acceptance in clinical practice. Owing to adverse reactions, the duration of the buildup phase until a maintenance dose is achieved may be prolonged, and in a minority of cases, OIT is stopped., Objective: We aimed to assess factors associated with the probability of reaching the maintenance dose in cow's milk (CM) OIT., Methods: We collected data from patients undergoing CM OIT at the Montreal Children's Hospital, BC Children's Hospital, and Hospital for Sick Children. We compared univariable and multivariable Cox regressions to evaluate sociodemographic factors, comorbidities, clinical characteristics, and biomarkers at study entry associated with the likelihood of reaching a maintenance dose of 200 mL of CM., Results: Among 69 children who reached 4 mL of milk, the median age was 12 years (interquartile range, 9-15 years); 59% were male. Median duration of buildup phase from 4 to 200 mL was 24.0 weeks (interquartile range, 17.7-33.4 weeks). After adjusting for age and sex, higher baseline levels of specific IgE antibodies for α-lactalbumin (hazard ratio [HR] = 0.80; 95% confidence interval [CI], 0.67-0.95), β-lactoglobulin (HR = 0.86; 95% CI, 0.76-0.98), casein (HR = 0.82; 95% CI, 0.72-0.94), and total CM (HR = 0.79; 95% CI, 0.65-0.97) were associated with a decreased probability of reaching maintenance. In addition, for every 10-mL increase in CM tolerated at entry challenge, the probability of reaching maintenance increased by 10%., Conclusions: The data suggest that higher levels of CM-specific IgE decreased the likelihood of reaching maintenance, whereas an increased cumulative CM dose at entry challenge increased the likelihood. Assessing these factors before therapy may assist in predicting the success of CM OIT., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Data on the diagnostic properties of direct oral challenges without the use of skin tests in children with suspected amoxicillin allergy are sparse., Objective: Assess the use of direct oral challenges., Methods: A cohort study was conducted between March 2013 and March 2020, in Montreal and Winnipeg. All children referred with reported history of benign reactions (ie, limited to the skin with no mucosal lesions and no vesicles) to amoxicillin were recruited and a 2-step graded oral challenge (GOC) was conducted. Data were collected on demographic characteristics, clinical characteristics, and comorbidities. Eligible children were followed to assess reactions to subsequent use of amoxicillin and to assess the safety of cephalexin use in children with a positive GOC., Results: Among 1914 children recruited, 1811 (94.6%) tolerated the GOC, 42 (2.2%) developed mild immediate reactions, and 61 (3.2%) developed mild nonimmediate reactions. Among 265 participants who had a negative GOC and reused amoxicillin, 226 (85.3%) reported tolerance and 39 (14.7%) had mild cutaneous reactions. Chronic urticaria (adjusted odds ratio [aOR], 1.16; 95% CI, 1.09-1.23) and an index reaction occurring within 5 minutes of exposure (aOR, 1.09; 95% CI, 1.04-1.14) were associated with immediate reactions during the GOC. Symptoms lasting longer than 7 days (aOR, 1.05; 95% CI, 1.02-1.09) and parental drug hypersensitivity (aOR, 1.04; 95% CI, 1.03-1.06) were associated with nonimmediate reactions. Among those reacting to the GOC, 12.5% reacted with mild cutaneous reactions to cephalexin challenge., Conclusions: Direct GOCs are an accurate and safe confirmatory to establish true hypersensitivity among children reporting benign reactions to amoxicillin., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In the western world, up to 10% of the general population and more than 15% of hospitalized patients report penicillin allergy. After a comprehensive evaluation, more than 95% of patients who report a penicillin allergy can subsequently tolerate this antibiotic. Traditionally, the most widely accepted protocol to evaluate beta-lactam (BL) allergy consisted of skin testing (ST) followed by a drug provocation test (DPT) in ST-negative patients. DPT is the gold standard for proving or excluding BL allergy and is considered the final and definitive step in the evaluation. Recently, studies have been published that support the use of direct DPTs without preceding ST for both pediatric and adult patients who report a low-risk historical reaction to BLs. However, these studies use various risk-stratification criteria to determine eligibility for a direct DPT. A standardized protocol for DPT is also lacking. In this review, we assess the current literature and evidence for performing direct DPT in the pediatric and adult populations. On the basis of this evidence, we also present risk-based algorithms for the evaluation of BL allergy in pediatric and adult populations based on a description of the historical reaction., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Data are sparse regarding the clinical characteristics and management of fruit-induced anaphylaxis., Objective: To assess clinical characteristics and management of patients with fruit-induced anaphylaxis and determine factors associated with severe reactions and epinephrine use., Methods: Over 9 years, children and adults presenting with anaphylaxis to seven emergency departments in four Canadian provinces and patients requiring emergency medical services in Outaouais, Quebec were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized form documenting symptoms, triggers, and management was collected. Multivariate logistic regression was used to identify factors associated with severe reactions and epinephrine treatment in the pre-hospital setting., Results: We recruited 250 patients with fruit-induced anaphylaxis, median age 10.2 years (interquartile range, 3.6-23.4 years); 48.8% were male. The most common fruit triggers were kiwi (15.6%), banana (10.8%), and mango (9.2%). Twenty-three patients reported having eczema (9.3%). Epinephrine use was low in both the pre-hospital setting and the emergency department (28.4% and 40.8%, respectively). Severe reactions to fruit were more likely to occur in spring and among those with eczema (adjusted odds ratio [aOR] = 1.12, 95% confidence interval [CI], 1.03-1.23; and 1.17, 95% CI, 1.03-1.34, respectively). Patients with moderate and severe reactions (aOR = 1.23; 95% CI, 1.06-1.43) and those with a known food allergy (aOR = 1.38; 95% CI, 1.24-1.54) were more likely to be treated with epinephrine in the pre-hospital setting., Conclusions: Severe anaphylaxis to fruit is more frequent in spring. Cross-reactivity to pollens is a potential explanation that should be evaluated further., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Community use of epinephrine for the treatment of anaphylaxis is low. Knowledge of rates of epinephrine use in the pre-hospital setting along with identification of barriers to its use will contribute to the development of policies and guidelines., Objectives: A search was conducted on PubMed and Embase in April 2020. Our systematic review focused on 4 domains: (1) epinephrine use in the pre-hospital setting; (2) barriers to epinephrine use in the pre-hospital setting; (3) cost evaluation and cost-effectiveness of epinephrine use; and (4) programs and strategies to improve epinephrine use during anaphylaxis., Methods: Two meta-analyses with logit transformation were conducted to: (1) calculate the pooled estimate of the rate of epinephrine use in the pre-hospital setting among cases of anaphylaxis and (2) calculate the pooled estimate of the rate of biphasic reactions among all cases of anaphylaxis., Results: Epinephrine use in the pre-hospital setting was significantly higher for children compared with adults (20.98% [95% confidence interval (CI): 16.38%, 26.46%] vs 7.17% [95% CI: 2.71%, 17.63%], respectively, P = .0027). The pooled estimate of biphasic reactions among all anaphylaxis cases was 3.92% (95% CI: 2.88%, 5.32%). Our main findings indicate that pre-hospital use of epinephrine in anaphylaxis remains suboptimal. Major barriers to the use of epinephrine were identified as low prescription rates of epinephrine autoinjectors and lack of stock epinephrine in schools, which was determined to be cost-effective. Finally, in reviewing programs and strategies, numerous studies have engineered effective methods to promote adequate and timely use of epinephrine., Conclusion: The main findings of our study demonstrated that across the globe, prompt epinephrine use in cases of anaphylaxis remains suboptimal. For practical recommendations, we would suggest considering stock epinephrine in schools and food courts to increase the use of epinephrine in the community. We recommend use of pamphlets in public areas (ie, malls, food courts, etc.) to assist in recognizing anaphylaxis and after that with prompt epinephrine administration, to avoid the rare risk of fatality in anaphylaxis cases., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents., Objective: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals., Methods: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics., Results: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm., Conclusions: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Oral immunotherapy (OIT) provides an active treatment option for patients with food allergies. OIT may improve quality of life and raise the threshold at which a patient with food allergy may react to an allergen, but it is a rigorous therapy that requires a high degree of commitment by the clinician, patients, and families. Recent guidelines from the Canadian Society for Allergy and Clinical Immunology have provided a framework for the ethical, evidence-based, and patient-oriented clinical practice of OIT, and the European Academy of Allergy, Asthma, and Immunology guidelines have also recommended that OIT can be used as a potential treatment. The recent Food and Drug Administration approval of an OIT pharmaceutical has accelerated the adoption of OIT. This review provides a summary of the recent Canadian Society for Allergy and Clinical Immunology guidelines and a consensus of practical experience of clinicians across the United States and Canada related to patient selection, office and staff preparation, the general OIT process, OIT-related reaction management, and treatment outcomes., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Serum sickness-like reactions (SSLRs) are defined by the presence of rash (primarily urticaria) and joint complaints (arthralgia/arthritis) that are believed to occur due to a non-IgE-mediated response to medications. However, similar reactions can occur due to viral infections, and it can be difficult to distinguish between the two. This may lead to unnecessary avoidance of the culprit antibiotic., Objective: We aimed to evaluate children presenting with suspected SSLRs through a graded oral challenge (GOC)., Methods: All children referred to the Montreal Children's Hospital for potential antibiotic allergy (β-lactam or other antibiotics) and a clinical presentation compatible with SSLR were recruited for the study between March 2013 and February 2020. A standardized survey with questions on treatment, symptoms, and associated factors was completed, and a GOC (10% and subsequently 90% of the oral antibiotic dose) was conducted. Patients with a negative GOC were contacted annually to query on subsequent antibiotic use., Results: Among 75 patients presenting with suspected SSLRs, the median age was 2.0 years and 46.7% were males. Most reactions were attributed to amoxicillin. Among the 75 patients, 2.7% reacted immediately (within 1 hour) to a GOC and 4.0% had a nonimmediate reaction. Of the 43 patients successfully contacted, 20 reported subsequent culprit antibiotic use of whom 25.0% had a subsequent mild reaction (macular/papular rash)., Conclusions: This is the first and largest pediatric study to assess SSLR using a GOC. Our findings suggest that using a GOC is safe and appropriate for differentiating between β-lactam-induced SSLR and viral exanthem in this population., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Studies assessing the use of antihistamines and corticosteroids for the treatment of anaphylaxis have not supported a conclusive effect., Objective: To assess prehospital management of anaphylaxis by measuring the effect of epinephrine use compared with antihistamines and corticosteroids on negative outcomes of anaphylaxis (intensive care unit/hospital ward admission, multiple doses of epinephrine in the emergency department [ED], and intravenous fluids given in the ED)., Methods: The Cross-Canada Anaphylaxis Registry is a cohort study that enrolls anaphylaxis cases presenting to EDs in 5 Canadian provinces over a 6-year period. Participants were recruited prospectively and retrospectively and were excluded if the case did not meet the definition of anaphylaxis., Results: A total of 3498 cases of anaphylaxis, of which 80.3% were children, presented to 9 EDs across Canada. Prehospital treatment with epinephrine was administered in 31% of cases, whereas antihistamines and corticosteroids were used in 46% and 2% of cases, respectively. Admission to the intensive care unit/hospital ward was associated with prehospital treatment with corticosteroids (adjusted odds ratio, 2.84; 95% confidence interval [CI], 1.55, 6.97) while adjusting for severity, treatment with epinephrine and antihistamines, asthma, sex, and age. Prehospital treatment with epinephrine (adjusted odds ratio, 0.23; 95% CI, 0.14, 0.38) and antihistamines (adjusted odds ratio, 0.61; 95% CI, 0.44, 0.85) decreased the likelihood of receiving multiple doses of epinephrine in the ED, while adjusting for severity, treatment with corticosteroids, asthma, sex, and age., Conclusions: Prompt epinephrine treatment is crucial. Use of antihistamines in conjunction with epinephrine may reduce the risk of uncontrolled reactions (administration of 2 or more doses of epinephrine in the ED), although our findings do not support the use of corticosteroids., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: This study focuses on the side effects of cow's milk oral immunotherapy (CM-OIT) using consensus definitions of food-induced anaphylaxis., Objective: To evaluate the risk of allergic reactions (ARs) and to identify risk factors associated with higher risk of anaphylactic ARs (AARs) during CM-OIT in children., Methods: Clinical charts of children receiving CM-OIT were carefully reviewed. ARs were defined as single-organ ARs, and AARs were defined as involvement of 2 organ systems and/or hypotension in response to CM protein. Descriptive statistics were used to represent demographics, occurrence, reaction characteristics, and comorbidities. Poisson analysis was performed to evaluate risk factors associated with AARs., Results: Among 41 children undergoing CM-OIT, 11 discontinued the treatment (N = 26.8%). The mean age at challenge was 12.1 years (standard deviation [SD], 3.6) and half were male (56.1%). The mean number of AARs per patient was 6.0 (SD, 3.5) versus a mean of 17.4 (SD, 11.9) non-AARs per patient. Among withdrawals from OIT, the mean number of AARs per patient was 8.3 versus 5.1 in nonwithdrawals. AARs were more frequent in children with higher specific IgE (sIgE) for α-lactalbumine and casein at baseline (1.11 [95% confidence interval (CI): 1.01, 1.22] and 1.01 [1.0, 1.03], respectively). Children with resolved eczema and higher sIgE for β-lactoglobuline at baseline (0.13 [95% CI: 0.04, 0.46] and 0.96 [95% CI: 0.94, 0.99], respectively) were less likely to develop AARs., Conclusions: Although the majority of ARs during OIT are nonanaphylactic, AARs occur frequently. Children with higher sIgE for α-lactalbumine and casein at baseline seem to be at higher risk for AARs during OIT., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Anaphylaxis due to unknown trigger (AUT) is anaphylaxis not explained by a proved or presumptive cause or stimulus at the time of the reaction. Research describing the management and follow-up of AUT is limited., Objective: To assess and compare the demographic and clinical characteristics and the management of adult and pediatric AUT cases across Canada., Methods: Participants were identified between 2011 and 2018 in emergency departments at 8 centers across Canada as part of the Cross-Canada Anaphylaxis Registry. A standardized form documenting the reaction and management in children and adults was completed. Patients were contacted for follow-up to determine assessment by an allergist., Results: A total of 295 AUT cases (7.5%) were recruited among 3,922 cases of anaphylaxis. In the prehospital setting, children (adjusted odds ratio [aOR], 1.20; 95% CI, 1.05-1.37) and those with a known food allergy (aOR, 1.14; 95% CI, 1.02-1.28) were more likely to receive treatment with epinephrine. Children were also more likely to be assessed by an allergist after their reaction (aOR, 1.43; 95% CI, 1.13-1.81) and were more likely to have an identified trigger for their reaction (aOR, 1.35; 95% CI, 1.07-1.70). Among patients contacted for follow-up, food was identified as the cause of reaction in 11 of 76 patients. A new food allergy was diagnosed in 4 patients (2 children and 2 adults)., Conclusions: Our findings highlight important differences between management and follow-up of adult and pediatric AUT cases. It is crucial to follow up all cases of AUT and establish appropriate treatment and management guidelines., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

There are substantial knowledge gaps related to diagnosis and management of pediatric cases of chronic urticaria, and in particular chronic spontaneous urticaria (CSU). In this article we aimed to review the diagnosis and management of chronic urticaria in children and CSU in particular. We conducted a systematic review of articles published in English and French on pediatric CSU management in the last 10 years. We included experimental studies (eg, randomized controlled trials), other experimental designs (eg, nonrandomized methods of assignment, controlled before-after studies, and interrupted time series), and observational studies (eg, prospective or retrospective cohort studies, cross-sectional studies, case-control studies, and case reports). Our findings highlight the efficacy of second-generation antihistamines for the treatment of CSU in children and supports the use of omalizumab for more severe cases. However, our study also reveals severe knowledge gaps related to the best management strategy in children with more severe/refractory cases of CSU. Future studies are required to establish the beneficial effect of high doses of second-generation antihistamines as well as the effectiveness and safety of omalizumab and other biologics in young children., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Epinephrine is the first-line treatment for anaphylaxis. Despite this, there have been identified gaps in the management of anaphylaxis including infrequent or delayed use of epinephrine for acute allergic reactions, as well as inadequate epinephrine autoinjector (EAI) training, and prescription rates of these devices for patients at risk. This paper reviews new data, and new problems in recently published literature on EAIs. A database search was conducted for publications between January 2015 and February 2017 using keywords related to EAIs including their functionality and features, carriage, prescription rates, barriers, and side effects. Eligibility criteria included patients at risk for anaphylaxis, caregivers, and health care professionals. Experimental studies and observational studies were included. Of 1,737 potentially relevant articles, 19 were used for analysis. These articles addressed specific aspects of an EAI, including (1) information on features and functionality; (2) prescriptions; (3) training on their use; and (4) carriage and use at the time of reaction by patients, schools, camps, emergency departments, and paramedics. Our review highlights that existing gaps in anaphylaxis management remain unaddressed. Patient needs are largely unmet, and very few studies are being designed to clarify and instill best practice, and to determine how to increase adherence to existing anaphylaxis guidelines through integrated knowledge translation strategies., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)