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Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food-induced hypersensitivity disorder that occurs mostly in infants. Long considered a rare disease, a recent increase in physician awareness and publication of diagnosis of guidelines has resulted in an increase in recognized FPIES cases. We aimed to conduct a systematic review of FPIES studies in the past 10 years. A search was conducted on PubMed and Embase in March 2022. Our systematic review focused on 2 domains: (1) the most reported FPIES food triggers; and (2) the resolution rate and median age at resolution of patients with FPIES. We found that cow’s milk was the most reported trigger globally. Patterns of the most common triggers varied by country, with fish being one of the most common triggers in the Mediterranean region. We also found that the rate and median age of resolution varied by trigger. Patients with FPIES to cow’s milk acquired tolerance at a younger age (most by age 3 years), while fish-FPIES was more persistent (mean resolution by age 37 months–7 years). Overall, many studies found a resolution rate of 60% for any food.

Within the broad category of adverse drug reactions in children, there has been a recent focus specifically on the evaluation of children with antibiotic allergy, in particular, beta-lactam allergy. The potential consequences of being labeled beta-lactam allergy are increasingly recognized. Appropriate evaluation of children with suspected reactions to antibiotics is essential as it is increasingly being recognized that the label of “penicillin allergy” is associated with adverse health and economic outcomes. This review will focus on the 3 main classes of antibiotics reported to cause allergic reactions in children: beta lactams (penicillin derivatives and cephalosporins), macrolides, and sulfonamides. This article is a narrative review of the prevalence, diagnosis, and management of different types of antibiotic allergies in children. Our review reveals that antibiotic allergy is often overreported and not appropriately diagnosed in the pediatric age groups. There is a recent shift in the diagnostic paradigm from the use of skin tests and if negative challenges to the use of challenge only in the pediatric age group. Larger studies to establish the usefulness and safety of this new approach as well as updated guidelines are needed.

Background: Studies suggest an increase in food allergy prevalence over the last decade, but the contributing factors remain unknown. The aim of this study was to evaluate the association between the most common food allergies and atopic history, sociodemographic characteristics and lifestyle habits. Methods: We conducted a case-control study nested within the SPAACE study (Surveying Prevalence of Food Allergy in All Canadian Environments) - a cross-Canada, random telephone survey. Cases consisted of individuals with probable food allergy (self-report of convincing symptoms and/or physician diagnosis) to milk, egg, peanut, tree nut, shellfish, fish, wheat, soy, or sesame. Controls consisted of nonallergic individuals, matched for age. Cases and controls were queried on personal and family history of atopy, sociodemographic characteristics and lifestyle habits. Multivariate logistic regression was used to evaluate the association between atopy, sociodemographic characteristics and lifestyle habits with probable food allergy. Results: Between September 2010 and September 2011, 480 cases and 4,950 controls completed the questionnaire. For all 9 allergens, factors associated with a higher risk of probable allergy were as follows: (1) personal history of eczema (in the first 2 years of life), asthma or hay fever (odds ratio, OR 2.3, 95% CI 1.6-3.5; OR 2.8, 95% CI 2.2-3.6, and OR 2.3, 95% CI 1.8-3.0, respectively), (2) maternal, paternal or sibling's food allergy (OR 3.7, 95% CI 2.5-5.6; OR 3.0, 95% CI 1.8-5.1, and OR 3.1, 95% CI 2.2-4.2), (3) high household income (top 20%; OR 1.5, 95% CI 1.2-2.0). Males and older individuals were less likely to have food allergy (OR 0.7, 95% CI 0.6-0.9, and OR 0.99, 95% CI 0.99-1.00). Eczema in the first 2 years of life was the strongest risk factor for egg, peanut, tree nut and fish allergy. Conclusions: This is the largest population-based nested case-control study exploring factors associated with food allergies. Our results reveal that, in addition to previously reported factors, eczema in the first 2 years of life is consistently associated with food allergies.

Background: Acetaminophen is the most commonly used antipyretic in children. However, there are limited data assessing hypersensitivity reactions related to acetaminophen usage. Objectives: To conduct a systematic review to characterize reported reactions to acetaminophen in adults and children, and perform a meta-analysis to assess the prevalence of acetaminophen hypersensitivity in children with a suspected acetaminophen allergy. Methods: We performed a systematic review of studies reporting hypersensitivity reactions to acetaminophen by searching 2 electronic databases. From the selected studies, we included those assessing the prevalence of acetaminophen hypersensitivity by performing oral challenge in our meta-analysis. Results: Eighty-five studies were included in the systematic review, assessing a total of 1,030 participants. Immediate (within 1 h of exposure) hypersensitivity reactions were reported in > 25% of the articles, while cutaneous nonimmediate reactions were similarly reported in about 25% of the articles. The remaining articles reported Steven-Johnson syndrome/toxic epidermal necrolysis, fixed drug eruptions, and cross-intolerance reactions. Five pediatric studies were included in our meta-analysis. The prevalence of acetaminophen hypersensitivity reaction among children undergoing oral challenge was 10.1% (95% confidence interval 4.5–15.5). Conclusion: Future studies assessing the risk of immediate and nonimmediate hypersensitivity reactions to acetaminophen and elucidating the mechanism of acetaminophen hypersensitivity reactions are required.

Background: While a central role for the T helper (Th) 1/Th2 axis in food allergy has been established, the Th17 response in food-allergic humans has not been addressed. Methods: Th17 responses in 18 peanut-allergic children, who were also allergic to at least one additional food allergen, were assessed relative to 15 age-matched healthy controls. To account for the atopy background in the allergic children, 7 atopic, but not food-allergic, individuals and their age-matched controls were included in this study. PBMCs were analyzed by flow cytometry ex vivo or were stimulated in vitro with peanut allergens, gliadin, or tetanus toxoid followed by analysis of proliferation and cytokine production in antigen-responsive cells. Results: We observed a significantly lower interleukin (IL) 17 production in CD4+ T cells of food-allergic individuals ex vivo (p < 0.02). In vitro, we found that IL-17 production in CD4+ T cells in response to all antigens tested was significantly impaired in food-allergic subjects compared to healthy controls (Ara: p < 0.005; gliadin: p < 0.004; TT: p < 0.03). No significant differences were observed between atopic and nonatopic individuals with no food allergy. Conclusion: Our results thus reveal a systemic, non-allergen-specific defect in Th17 responses to antigen stimulation in food allergic individuals, suggesting a role for Th17 cells in the control of food allergy and implicating IL-17 as a potential biomarker for tolerance to food antigens.

Background: The basophil activation test (BAT) using CD63 expression is a sensitive and specific tool for the diagnostic workup of autoimmune chronic spontaneous urticaria (CSU). The definition of a positive BAT is directly dependent on the reference range and the cutoff values established in control populations. As of now, the pediatric reference range and cutoff values of the CD63 BAT remain to be established. Methods: In this study, we analyzed CD63 expression in 80 children (1-17 years old) without chronic urticaria (i.e., controls) and compared the values to those of a pediatric cohort of 105 CSU patients and 23 physical urticaria (PU) patients. Results: Based on the log-normal distribution of CD63 values in control subjects, the reference range and the cutoff for positive CD63 BAT values was established to be 1.2-1.8% (95% CI) and 1.8%, respectively. Children with CSU showed significantly elevated and significantly increased BAT values compared to healthy controls (Wilcoxon rank test p value Conclusions: Our study provides, for the first time, reference and cutoff values for the CD63 BAT in children. Our findings show that positive CD63 BAT are common in children with CSU and linked to a high disease activity.

Background: The Cross-Canada Anaphylaxis Registry (C-CARE) assesses the triggers and management of anaphylaxis and identifies predictors of the development of severe allergic reactions and of epinephrine use. Here, we present data from an urban adult tertiary care emergency department (ED) in Montreal, Canada. Methods: Potential anaphylaxis cases were identified using ICD-10 codes related to anaphylaxis or allergic reactions. Putative cases underwent chart review to ensure they met anaphylaxis diagnostic criteria. Demographic, clinical and management data were collected. Multivariate logistic regressions were conducted to assess the effect of demographic characteristics, triggers, and comorbidities on severity and management of reactions. Results: Among 37,730 ED visits, 0.26% (95% CI 0.21, 0.32) fulfilled the definition of anaphylaxis. Food was the suspected trigger in almost 60% of cases. Epinephrine was not administered in almost half of moderate-to-severe cases, and similar numbers of individuals with moderate-to-severe reactions were not prescribed an epinephrine autoinjector. Reaction to shellfish was associated with more severe reactions (OR 13.9; 95% CI 2.2, 89.4). Older individuals and those not receiving steroids were more likely managed without epinephrine (OR 1.04; 95% CI 1.01, 1.07 and OR 2.97; 95% CI 1.05, 8.39, respectively). Conclusions: Anaphylaxis accounted for a substantial number of ED visits in adults, and the most common trigger was food. There is non-adherence to guidelines recommending epinephrine use for all cases of anaphylaxis. We postulate that this may be related to concerns regarding the side effects of epinephrine in adults.