Clinical characteristics and management of pediatric egg-induced anaphylaxis: A cross-sectional study.

BACKGROUND: Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse. OBJECTIVE: To describe the clinical characteristics, management, and outcomes of pediatric egg-induced anaphylaxis. METHODS: Children presenting with anaphylaxis were recruited from 13 emergency departments as part of the Cross-Canada Anaphylaxis Registry, from which data on anaphylaxis triggered by egg were extracted. Multivariate logistic regression was used to determine factors associated with prehospital epinephrine autoinjector (EAI) use and to compare anaphylaxis triggered by egg with other triggers of food-induced anaphylaxis (FIA). RESULTS: We recruited 302 children with egg-induced anaphylaxis. The mean age was 2.6 years (SD = 3.6), and 55.3% were male. Only 39.4% had previously been diagnosed with an egg allergy. Prehospital EAI use was 32.1%, but this was not significantly lower than in other triggers of FIA (P = .26). Only 1.4% of patients required hospital admission. Relative to other triggers of FIA, patients with egg-induced anaphylaxis were significantly younger (P < .001) and exhibited more vomiting (P = .0053) and less throat tightness (P = .0015) and angioedema (P < .001). CONCLUSION: To the best of our knowledge, this is the largest published cohort of pediatric egg-induced anaphylaxis. In this cohort, prehospital EAI use was very low. In addition, we identified certain symptoms that distinguish egg-induced from other triggers of FIA. Taken together, high suspicion is crucial in identifying egg-induced anaphylaxis, given the younger patient demographic and frequent lack of FIA history.

Milk-induced anaphylaxis among children presenting to Canadian emergency departments.

BACKGROUND: Cow's milk is one of the most common and burdensome allergens in pediatrics, and it can induce severe anaphylactic reactions in children. However, data on cow's milk-induced anaphylaxis are sparse. OBJECTIVE: To describe the epidemiology of pediatric cow's milk-induced anaphylaxis and to determine risk factors for repeat emergency department (ED) epinephrine administration. METHODS: Between April 2011 and May 2023, data were collected on children with anaphylaxis presenting to 10 Canadian EDs. A standardized form documenting symptoms, triggers, treatment, and outcome was used. Multivariate logistic regression was used. RESULTS: Of 3118 anaphylactic reactions, 319 milk-induced anaphylaxis cases were identified (10%). In the prehospital setting, 54% of patients with milk-induced anaphylaxis received intramuscular epinephrine. In those with milk-induced anaphylaxis, receiving epinephrine before presenting to the ED was associated with a reduced risk of requiring 2 or more epinephrine doses in the ED (adjusted odds ratio, 0.95 [95% CI, 0.90-0.99]). Children younger than 5 years of age were more likely to experience a mild reaction compared with that in older children, who experienced a moderate reaction more often (P < .0001). Compared with other forms of food-induced anaphylaxis, children presenting with milk-induced anaphylaxis were younger; a greater proportion experienced wheezing and vomiting, and less experienced angioedema. CONCLUSION: Prehospital epinephrine in pediatric milk-induced anaphylaxis is underused; however, it may decrease risk of requiring 2 ED epinephrine doses. Milk-induced anaphylaxis in children younger than 5 years of age may be less severe than in older children. Wheezing and vomiting are more prevalent in milk-induced anaphylaxis compared with that of other foods.

Assessing Pediatric Cephalosporin Allergic Reactions Through Direct Graded Oral Challenges.

BACKGROUND: Cephalosporins, ß-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.

Managing anaphylaxis: Epinephrine, antihistamines, and corticosteroids: More than 10 years of Cross-Canada Anaphylaxis REgistry data.

BACKGROUND: Epinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse. OBJECTIVE: To establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management. METHODS: Patients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form. Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes. RESULTS: Among 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions. Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]). CONCLUSION: Our findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.

COVID vaccine evaluation of barriers and resources among families of children with diagnosed allergies.

Background: We aimed to determine vaccine hesitancy and the main barriers associated with the 2019 novel coronavirus, SARS-CoV-2 (COVID-19) vaccination among families of children diagnosed with food/drug/environmental allergies. Methods: Between May and June 2021, we approached 146 families seen at the outpatient allergy clinic at the Montreal Children's Hospital and a community allergy practice were invited to complete an anonymous online survey on COVID-19 and vaccination attitudes and behaviour. Uni and multivariable logistic regressions were compared to estimate factors associated with vaccine hesitancy. Results: Among all patients, 24.1% reported vaccine hesitancy. The large majority of parents (95.2%) believed that vaccines work. The most common barrier to vaccination was fear of adverse side effects (57.0%). One-third of participants (31.5%) reported that a history of food, venom and drug allergy was a contraindication for COVID-19 vaccination. Fifty-nine (60.8%) participants stated that the dissemination of additional information would increase their willingness to be vaccinated. Most (96.9%) parents reported that their children's vaccinations were up to date. Hesitant families were more likely to be parents of children aged 6-10 years, be of Asian descent, report that mRNA vaccines are riskier than traditional vaccines, and report that the vaccine should not be given if the child has a history of allergic reaction to vaccines. Conclusion: Vaccine hesitancy exists mainly among certain ethnic groups and families with young children. Allergies to food, venom and drug allergy are commonly perceived as contraindications for COVID-19 vaccination. Knowledge translation activities addressing parental concerns will help increase vaccination rates.

Bridging knowledge gaps in paediatric chronic urticaria through a video-based educational tool.

BACKGROUND: There is a lack of patient educational resources about chronic urticaria (CU). AIMS: To develop and test the effectiveness of an education tool to help paediatric patients and their families better understand CU and its management. METHODS: From July 2020 to May 2022, paediatric patients with a history of CU who presented to the allergy outpatient clinics at our institution were recruited. Consenting families and patients were asked to complete five questions related to the definition, causes and management of CU at the time of presentation to the clinic. Participants were shown a 5-min animated video addressing the main knowledge gaps about CU. At the end of the video, participants were redirected to the same five questions to respond again. The scores were recorded as a proportion of correct answers (range 0·0-1·0). RESULTS: In total, 53 patients [30 girls (56·6%), 23 boys (43·4%); mean age 9·7 ± 5·1 years, range 1·4-18·5 years] were recruited. The mean baseline pre-video education questionnaire score was 0·67 ± 0·2 (range 0·2-1·0), while the mean post-video score was 0·94 ± 0·1 (range 0·4-1·0), a mean score difference of 0·27, which was statistically significant (P < 0·001). At the 1-year follow-up, 14 (26·4%) patients answered the questionnaire again to assess retention of knowledge; the mean score was 0·83 ± 0·2 (range 0·2-1·0). CONCLUSIONS: Our educational video was successful in educating patients and their families to better understand urticaria. Future studies should aim to optimize patient education through nontraditional tools such as videos, and compare knowledge gain using different methods of education.

Temporal trends in anaphylaxis ED visits over the last decade and the effect of COVID-19 pandemic on these trends.

BACKGROUND: Anaphylaxis is an acute systemic and potentially fatal allergic reaction. We evaluated trends in yearly rates of anaphylaxis in a pediatric Emergency Department (ED) in Montreal, Canada. METHODS: A prospective and retrospective recruitment process was used to find families of children who had presented with anaphylaxis at the Montreal Children's Hospital between April 2011 and April 2021. Using a uniform recruitment form, data were collected. Anaphylaxis patterns were compared to clinical triggers using descriptive analysis. RESULTS: Among 830,382 ED visits during the study period, 2726 (26% recruited prospectively) presented with anaphylaxis. The median age was 6 years (IQR: 0.2, 12.00), and 58.7% were males. The relative frequency of anaphylaxis cases doubled between 2011-2015, from 0.22% (95% CI, 0.19, 0.26) to 0.42 March 2020, the total absolute number of anaphylaxis cases and relative frequency declined by 24 cases per month (p < 0.05) and by 0.5% of ED visits (p < 0.05). CONCLUSIONS: The rate of anaphylaxis has changed over the years, representing modifications in food introduction strategies or lifestyle changes. The decrease in the frequency of anaphylaxis presenting to the ED during the COVID pandemic may reflect decreased accidental exposures with reduced social gatherings, closed school, and reluctance to present to ED.

Bridging Knowledge Gaps in Anaphylaxis Management Through a Video-Based Educational Tool.

Introduction: We aimed to develop and test the effectiveness of an education tool to help pediatric patients and their families better understand anaphylaxis and its management, and to improve current knowledge and treatment guidelines adherence. Methods: From June 2019 to May 2022, 128 pediatric patients with history of food-triggered anaphylaxis who presented to the allergy outpatient clinics at the study institution were recruited. Consenting families were asked to complete 6 questions related to the triggers, recognition, and management of anaphylaxis at the time of presentation to the clinic. Participants were shown a 5-min animated video on the causes, presentation, and management of anaphylaxis. At the end of the video, the participants were redirected to the same 6 questions to respond again. The scores were recorded in proportion of correct answers (minimum 0.0; maximum 1.0). Results: The mean age of the patients was 5.8 ± 4.5 years (range: 0.5-18.8 years). The majority were males (70 patients; 54.7%). The mean baseline prevideo education questionnaire score was 0.76 ± 0.2 (range: 0.3-1.0), whereas the mean follow-up score was 0.82 ± 0.2 (range: 0.3-1.0). This score difference of 0.06 was statistically significant (P < 0.001). There were no significant associations between change in scores and age or gender of the participants. Conclusion: Our video teaching method was successful in educating patients and their families to better understand anaphylaxis and its management at the moment of the clinical encounter. Retention of knowledge at long-term follow-up should be assessed.

Impact of Reaction Setting on the Management, Severity, and Outcome of Pediatric Food-Induced Anaphylaxis: A Cross-Sectional Study.

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.

Skin prick test in milk allergic patients undergoing oral immunotherapy: Does the milk form used for skin tests matter?

SPT is the most commonly used confirmatory test for an IgE-mediated milk allergy. However, food SPTs are not standardized. We aimed to assess the accuracy of SPTs with extract, diluted, and undiluted milk to detect desensitization in children with milk allergy undergoing OIT. Children with milk allergy undergoing OIT and controls were recruited from Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH) and The Hospital for Sick Children (SickKids). Participants in the active arm received a weekly increase in milk until 200 ml of pure milk was tolerated. SPT using milk extract (Omega), diluted 2% milk (1:10), and undiluted milk was done at the study entry and when 200 ml of pure milk was reached. Participants in the control arm had SPT at study entry and 12 months later before they entered the active arm. Among 53 children who reached 200 ml, the median age was 12 years and 54.7% were males. The mean decrease in wheal size at 200 ml from the baseline was 3.78 mm (95%CI, 2.55-5.01), 5.05 mm (95% CI, 3.68-6.41), and 5.05 mm (95% CI, 3.29-6.80) for milk extract, diluted and undiluted milk respectively. Among 32 controls, the median age was 10 years and 62.5% were males. There was no significant change in wheal diameter over a one-year period regardless of the skin test method. Response to extract behaved similarly to whole food (Diluted and undiluted) and thus can be used to follow sensitization in the context of a desensitization program.

Tree nut-induced anaphylaxis in Canadian emergency departments: Rate, clinical characteristics, and management.

BACKGROUND: Data are sparse regarding tree nut-induced anaphylaxis (TNA). OBJECTIVE: To characterize rate, clinical characteristics, and management of TNA in children (0-17 years old) across Canada and evaluate factors associated with severe reactions and epinephrine use. METHODS: Between April 2011 and May 2020, data were collected on children presenting to 5 emergency departments in Canada. Multivariate logistic analysis was used to evaluate factors associated with severe reactions (stridor, cyanosis, circulatory collapse, or hypoxia) and epinephrine use. RESULTS: Among 3096 cases of anaphylaxis, 540 (17%) were induced by tree nut. The median age was 5.2 (interquartile range, 2.5-9.5) years and 65.4% were of male sex. Among all reactions, 7.0% were severe. The major tree nuts accounting for anaphylaxis were cashew (32.8%), hazelnut (20.0%), and walnut (11.5%). Cashew-induced anaphylaxis was more common in British Columbia (14.0% difference [95% confidence interval (CI), 1.6-27.6]) vs Ontario and Quebec, whereas pistachio-induced anaphylaxis was more common in Ontario and Quebec (6.3% difference [95% CI, 0.5-12.2]). Prehospital and emergency department intramuscular epinephrine administration was documented in only 35.2% and 52.4% of cases, respectively. Severe reactions were more likely among of male sex (adjusted odds ratio [aOR], 1.05 [95% CI, 1.01-1.10]), older children (aOR, 1.00 [95% CI, 1.00-1.01]), and in reactions triggered by macadamia (aOR, 1.27 [95% CI, 1.03-1.57]). CONCLUSION: Different TNA patterns in Canada may be because of differences in lifestyle (higher prevalence of Asian ethnicity in British Columbia vs Arabic ethnicity in Ontario and Quebec). Intramuscular epinephrine underutilization urges for epinephrine autoinjector stocking in schools and restaurants, patient education, and consistent policies across Canada.

Sesame-induced anaphylaxis in pediatric patients from the cross-Canada anaphylaxis registry.

BACKGROUND: Sesame can cause severe allergic reactions and is a priority allergen in Canada. OBJECTIVE: To assess clinical characteristics and management of pediatric sesame-induced anaphylaxis and identify factors associated with epinephrine treatment. METHODS: Between 2011 and 2021, children with sesame-induced anaphylaxis presenting to 7 emergency departments (ED) in 4 Canadian provinces and 1 regional emergency medical service were enrolled in the Cross-Canada Anaphylaxis Registry. Standardized recruitment forms provided data on symptoms, severity, triggers, and management. Multivariate logistic regression evaluated associations with epinephrine treatment pre-ED and multiple epinephrine dosages. RESULTS: Of all food-induced anaphylactic reactions (n = 3279 children), sesame accounted for 4.0% (n = 130 children), of which 61.5% were boys, and the average (SD) age was 5.0 (4.9) years. Hummus containing sesame paste triggered 58.8% of reactions. In the pre-ED setting, 32.3% received epinephrine, and it was more likely to be used in boys (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.08-1.50) and those with a known food allergy (aOR, 1.36; 95% CI, 1.11-1.68]). In the ED, 47.7% of cases received epinephrine, with older children more likely to receive multiple epinephrine doses (aOR, 1.00; 95% CI, 1.00-1.02). CONCLUSION: In Canada, hummus is the major trigger of sesame-induced anaphylaxis. Knowledge translation focused on prompt epinephrine use and product-labeling policies are required to limit sesame reactions in communities.

Seafood-induced anaphylaxis in children presenting to Canadian emergency departments: Rates, clinical presentation, and management.

BACKGROUND: There is a lack of data on seafood-induced anaphylaxis in children in Canada. OBJECTIVE: To evaluate the rate, clinical features, and management of seafood-induced anaphylaxis in children presenting to emergency departments across Canada. METHODS: Children with anaphylaxis were recruited at 6 emergency departments between 2011 and 2020 as part of the Cross-Canada Anaphylaxis REgistry. A standardized form documenting symptoms, triggers, comorbidities, and management was used to collect data. RESULTS: There were 75 fish-induced and 71 shellfish-induced cases of suspected anaphylaxis, most of which were caused by salmon and shrimp, respectively. Mucocutaneous symptoms were most common, whereas respiratory symptoms were associated with patients with fish-induced reactions who have comorbid asthma (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.02-1.36). Prehospital epinephrine was underused (<35%), whereas in-hospital epinephrine was given to less than 60% of the patients. Among those with a known fish or shellfish allergy, prehospital epinephrine use was associated with known asthma (aOR 1.39 [95% CI, 1.05-1.84] and aOR 1.25 [95% CI, 1.02-1.54], respectively). Among children who were assessed by either skin test or specific immunoglobulin E, 36 patients (76.6%) with suspected fish-induced anaphylaxis and 19 patients (51.4%) with suspected shellfish-induced anaphylaxis tested positive. CONCLUSION: Prehospital epinephrine is underused in the management of seafood-induced anaphylaxis. Among children with known seafood allergy, prehospital epinephrine use is more likely if there is a known asthma comorbidity.

Demographic and clinical characteristics of patients with hereditary angioedema in Canada.

BACKGROUND: Data on the clinical and demographic features of Canadian patients with hereditary angioedema (HAE) are lacking. OBJECTIVE: To describe the clinical and demographic features in a large Canadian HAE cohort and compare them with patients with HAE in other countries. METHODS: An online questionnaire was distributed to the members of 2 Canadian HAE patient groups to collect information on demographics and HAE clinical characteristics. All participants 18 years of age or older with HAE type I or II were eligible. Frequency, location, prodromes, and triggers of HAE attacks, including types of HAE treatment, were characterized. RESULTS: Among the 90 participants who completed the online survey, 57% self-identified as having HAE type 1 and 26% HAE type II. The average diagnostic delay was 11 years. In the preceding 6 months, 24% of the participants had no attacks and 35% experienced greater than 5 attacks. The most frequently affected regions of the body were the abdomen (83%), arms orlegs (63%), face (41%), and larynx or throat (41%). Approximately 87% of the participants reported having access to C1 inhibitor at home, and 69% reported using it for long-term prophylaxis. CONCLUSION: Canadian patients with HAE share common clinical characteristics with patients with HAE in other countries. They had a delay in HAE diagnosis and a high burden of disease, as indicated by the high frequency of attacks in the preceding 6 months. This study provides a better understanding of the demographic and clinical characteristics of Canadian patients with HAE.

Elevated Cow's Milk-Specific IgE Levels Prior to Oral Immunotherapy Decrease the Likelihood of Reaching the Maintenance Dose.

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), ß-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.

Establishing Amoxicillin Allergy in Children Through Direct Graded Oral Challenge (GOC): Evaluating Risk Factors for Positive Challenges, Safety, and Risk of Cross-Reactivity to Cephalosporines.

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.

Trained immunity induced by in vivo peptide-based STAT6 inhibition prevents ragweed allergy in mice.

BACKGROUND: Trained immunity is the ability of the innate immune system to form immune memory responses to provide support the formation of appropriate adaptive responses. Allergic airways disease (AAD) is a maladapted immune response to allergens, initiated and maintained by the type 2 (T2) inflammatory pathway. It is predicated by the elaboration of cytokines IL-4 and IL-13 and follows activation of the STAT6 transcription factor. OBJECTIVE: To investigate the role of trained immunity in mucosal immune responses following neonatal vaccination with the STAT6 inhibitory peptide (STAT6-IP), in preventing the development of ragweed-induced AAD. METHODS: We demonstrate that transfer of CD4+ T cells or dendritic cells (DC) from STAT6-IP vaccinated wild-type BALB/c mice to naïve mice, that were subsequently chronically exposed to sensitizing doses of ragweed allergen, is sufficient to prevent development of T2 responses in recipients. RESULTS: Our results demonstrate significant reductions in; airways hyperresponsiveness (AHR); ragweed-specific IgE; pulmonary inflammation; T2 cytokines; and inflammatory gene expressions in recipient mice. Expression of IDO, TGFß and T regulatory cells were all significantly increased. Anti-TGFß treatment during the ragweed sensitization phase re-constituted the pro-inflammatory T2 immune response. We show that tolerance can be attained via DC trained in the STAT6-IP-mediated tolerant milieu. This effect is not restricted to a particular allergen and does not require antigen-mediated T cell activation prior to transfer. CONCLUSION: Adoptive transfer experiments suggest that STAT6-IP treatment trains dendritic and cells to mediate tolerant immunity to chronic ragweed exposure in the airways. This indicates that early transient STAT6-inhibition constitutes an effective immunomodulatory airways allergy preventative strategy.

Fruit-Induced Anaphylaxis: Clinical Presentation and Management.

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.