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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).We sought to investigate the setting, management, and severity of pediatric FIA.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.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.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.

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.

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.

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.

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.

Background Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk of 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 PubMed and EMBASE were searched for studies pertaining to cold urticaria and/or CIndU published in the last 10 years. Meta-analyses were conducted to evaluate: the prevalence of cold urticaria among CIndU and chronic urticaria (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 CU and CIndU cases were 7.62% (95%CI: 3.45%, 15.99%; I2=98%) and 26.10% (95%CI: 14.17%, 43.05%; I2= 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95%CI: 92.47%, 97.54%; I2=38%) of patients and omalizumab in 5.95% (95%CI: 2.55%, 13.27%; I2=83%) of patients. The pooled prevalence of anaphylaxis among cold urticaria cases was 21.49% (95%CI: 15.79%, 28.54%; I2=69%). Conclusion Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines, with a minority of patients receiving omalizumab. Anaphylaxis is not rare, and epinephrine auto-injector (EAI) prescription may be considered.

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.

BACKGROUND Food desensitization via oral immunotherapy (OIT) is gaining higher acceptance in clinical practice. Due to adverse reactions, the duration of the build-up 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 Data was collected from patients undergoing CM OIT at the Montreal Children’s Hospital, BC Children’s Hospital, and Hospital for Sick Children. We compared uni- and multivariable Cox regressions to evaluate sociodemographic factors, co-morbidities, 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 [IQR] 9-15) and 59% were male. The median duration of build-up phase from 4 mL to 200 mL was 24.0 weeks (IQR 17.7-33.4). After adjusting for age and sex, higher baseline levels of specific IgE (sIgE) antibodies for α-lactalbumin (ALA, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.67-0.95), β-lactoglobulin (BLG, 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. Additionally, for every increase of 10 mL CM tolerated at entry challenge, the probability of reaching maintenance increased by 10%. CONCLUSION The data suggest that higher levels of CM-sIgE decreased the likelihood of reaching maintenance, while an increased cumulative CM dose at entry challenge increased the likelihood. Assessing these factors prior to therapy may assist in predicting the success of CM OIT.

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.

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.

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.

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.