Search

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.

SARS-CoV-2 has caused a worldwide pandemic that began with an outbreak of pneumonia cases in the Hubei province of China. Knowledge of those most at risk is integral for treatment, guideline implementation, and resource allocation. We conducted a systematic review and meta-analysis to evaluate comorbidities associated with severe and fatal cases of COVID-19. A search was conducted on PubMed and EmBase on 20 April 2020. Pooled estimates were collected using a random-effects model. Thirty-three studies were included in the systematic review and twenty-two in the meta-analysis. Of the total cases 40.80% (95%CI: 35.49%, 46.11%) had comorbidities, while fatal cases had 74.37% (95%CI: 55.78%, 86.97%). Hypertension was more prevalent in severe [47.65% (95%CI: 35.04%, 60.26%)] and fatal [47.90% (95%CI: 40.33%, 55.48%)] cases compared to total cases [14.34% (95%CI: 6.60%, 28.42%)]. Diabetes was more prevalent among fatal cases [24.89% (95%CI: 18.80%, 32.16%)] compared to total cases [9.65% (95%CI: 6.83%, 13.48%)]. Respiratory diseases had a higher prevalence in fatal cases [10.89% (95%CI: 7.57%, 15.43%)] in comparison to total cases [3.65% (95%CI: 2.16%, 6.1%)]. Studies assessing the mechanisms accounting for the associations between severe cases and hypertension, diabetes, and respiratory diseases are crucial in understanding this new disease, managing patients at risk, and developing policies and guidelines that will reduce future risk of severe COVID-19 disease.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GALEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast-cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic urticaria, i.e. chronic spontaneous urticaria and chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This article is protected by copyright. All rights reserved.

Background Idiopathic anaphylaxis (IA) is a diagnosis of exclusion and represents a major diagnostic and management challenge. There are no current guidelines for diagnosis and management of IA. We aim to present a systematic review of the literature on adult and pediatric IA. Methods We conducted a systematic review of original articles published in the past 22 years regarding diagnosis and management strategies of adult and pediatric IA. Results The current proposed diagnostic approach and treatment regimens are based on a few small studies. Future large-scale studies are required. IA is a diagnosis of exclusion and should be made only after extensive evaluation excludes potential anaphylaxis triggers as well as non-allergic conditions with a similar presentation. There is currently no diagnostic consensus for IA. Furthermore, the current proposed treatment regimens are limited and rely on prophylactic treatment with antihistamines and prednisone for patients with frequent episodes. However, daily treatment with systemic steroids has well-recognized serious adverse effects. More recently, the use of biologics was suggested to benefit patients with IA, although the optimal management protocol is not yet established. Conclusion Future studies are needed to optimize diagnosis and treatment strategies in adult and pediatric cases of IA. Omalizumab may be a promising novel therapeutic option for adult and pediatric IA.

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.

Type 2 immunity, illustrated by T helper 2 lymphocytes (Th2) and downstream cytokines (IL-4, IL-13, IL-31) as well as group 2 innate lymphoid cells (ILC2), is important in host defense and wound healing.1The hallmark of type 2 inflammation is eosinophilia and/or high IgE counts and is best recognized in atopic diathesis. Persistent eosinophilia, such as seen in hypereosinophilic syndromes, leads to fibrosis and hence therapeutic Type 2 inhibition in fibrotic diseases is of high interest. Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression. Development of targeted monoclonal antibodies against IL-4Rα (eg, dupilumab) led to a paradigm shift for the treatment of atopic dermatitis (AD) and stimulated research to better understand the role of Type 2 inflammation in other skin conditions. In this review, we summarize up to date knowledge on the role of Type 2 inflammation in skin diseases other than AD and highlight whether the use of Type 2 targeted therapies has been documented or is being investigated in clinical trials. This manuscript reviews the role of Type 2 inflammation in dermatitis, neurodermatitis, IgE-mediated dermatoses (eg, bullous pemphigoid, chronic spontaneous urticaria), sclerodermoid conditions and skin neoplasms.

Introduction We conducted a nationwide Canadian telephone survey on food allergy prevalence between February 2016 and January 2017, targeting vulnerable populations (New, Indigenous, and lower-income Canadians). Objective To examine the independent effect of demographic characteristics on food allergy. Methods Canadian households with vulnerable populations were targeted using Canadian Census data and the household respondent reported whether each household member had a perceived (self-reported) or probable (self-report of a convincing history or physician diagnosis) food allergy. The association between perceived and probable food allergy and demographic characteristics was assessed through weighted multivariable random effects logistic regressions. Results Children, females, Canadian-born participants, adults with post-secondary education, and those residing in smaller households were more likely to report perceived or probable food allergy. Although immigrant parents self-reported less food allergy, Canadian-born children of Southeast/East Asian immigrant versus other immigrant or Canadian-born parents reported more food allergy. Conclusion We have demonstrated clear associations between demographic characteristics and food allergy, which may provide important clues to the environmental determinants of food allergy.

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.

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.

Chronic urticaria (CU) in children as in adults is characterized by the presence of itchy wheals, angioedema, or both daily or almost daily for at least 6 weeks. Most cases of urticaria in the pediatric age group are acute [1–4]. CU is sub-classified as spontaneous (occurring without a known trigger) or inducible. There are also cases of spontaneous and inducible forms that co-exist. The chronic subtypes occur continuously but also recurrently, often in association with infections. In this chapter we will touch briefly on the clinical presentation, diagnosis, and management of acute urticaria in children. However, our primary goal is to highlight key findings regarding the epidemiology, diagnosis, and management approach of pediatric CU. In addition, we will summarize the data regarding the management of CU in pregnancy and lactation.

The vast majority of individuals labelled as allergic are not deemed truly allergic upon appropriate assessment by an allergist. A label of beta-lactam allergy carries important risks for individual and public health. This article provides an overview of beta-lactam allergy, implications of erroneous beta-lactam allergy labels and the impact that can be provided by structured allergy assessment. We provide recommendations on how to stratify risk of beta-lactam allergy, beta lactam challenge protocols as well as management of patients at high risk of beta-lactam allergy.

Food-induced allergic reactions are diagnosed through corroboration of a suggestive clinical history with appropriate confirmatory tests. The major confirmatory tests include skin prick tests and serum specific immunoglobulin E (sIgE) levels. When the diagnosis is inconclusive, oral food challenges are performed (1).

Background Children are often diagnosed with an antibiotic allergy, with little investigation to confirm whether it is a true allergy. Recent studies support the use of oral challenges to confirm antibiotic allergy. Yet, little is known about families' perceptions of these challenges, or experiences of living with a misdiagnosis, often for many years. Objective To describe how families with a child previously labelled as "antibiotic allergic," but who has subsequently been delabelled, perceive the experience of misdiagnosis and subsequent delabelling. Methods We performed semi-structured interviews with parents whose children had recently completed a graded oral challenge for antibiotic allergy. Interview transcripts were analysed concurrently, but independently, by two investigators, using content analysis. Results A total of 15 parents (14 individual interviews; 1 mother-father dyad) participated. Children were, on average, 5.04 ± 4.5 years and were first diagnosed in infancy (mean age: 1.82 ± 1.48 years) subsequent to a rash (14/14; 100%), and commonly at a walk-in clinic (6/14; 42.9%). We identified four themes: (1) A red, raised rash results in a quick diagnosis despite a lack of testing, (2) sensitive care allays concerns, (3) delabelling brings relief, but also mystery and calls for proper diagnoses, and (4) quick diagnoses are reckless, but manageable through downward comparisons. Conclusion and clinical relevance These findings underscore the importance of a careful physical examination and clinical history of the patient, but also an ongoing dialogue to support families, both of which would ideally begin at the time of initial investigation.

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.

BACKGROUND: It is not established whether the risk of anaphylaxis induced by peanuts or tree nuts in children increases at specific times of the year. We aimed to evaluate the risk of peanut-and tree-nut–induced anaphylaxis during certain cultural holidays in Canadian children. METHODS: We collected data on confirmed pediatric cases of anaphylaxis presenting to emergency departments in 4 Canadian provinces as part of the Cross-Canada Anaphylaxis Registry. We assessed the mean number of cases per day and incidence rate ratio (IRR) of anaphylaxis induced by unknown nuts, peanuts and tree nuts presenting during each of 6 holidays (Halloween, Christmas, Easter, Diwali, Chinese New Year and Eid al-Adha) versus the rest of the year. We estimated IRRs and 95% confidence intervals (CIs) using Poisson regression. RESULTS: Data were collected for 1390 pediatric cases of anaphylaxis between 2011 and 2020. Their median age was 5.4 years, and 864 (62.2%) of the children were boys. During Halloween and Easter, there were higher rates of anaphylaxis to unknown nuts (IRR 1.66, 95% CI 1.13–2.43 and IRR 1.71, 95% CI 1.21–2.42, respectively) and peanuts (IRR 1.86, 95% CI 1.12–3.11 and IRR 1.57, 95% CI 0.94–2.63, respectively) compared to the rest of the year. No increased risk of peanut- or tree-nut–induced anaphylaxis was observed during Christmas, Diwali, Chinese New Year or Eid al-Adha. Anaphylaxis induced by unknown nuts, peanuts and tree nuts was more likely in children aged 6 years or older than in younger children. INTERPRETATION: We found an increased risk of anaphylaxis induced by unknown nuts and peanuts during Halloween and Easter among Canadian children. Educational tools are needed to increase awareness and vigilance in order to decrease the risk of anaphylaxis induced by peanuts and tree nuts in children during these holidays.

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 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.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; PCONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

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.

_To the Editor:_ Previously, we identified the HLA region as a risk factor forpeanut allergy (PA); this observation is supported further by 2 independent genome-wide association studies (GWASs). The HLA class II genes (including HLA-DR, HLA-DQ, and HLADP) encode molecules involved in presentation of extracellular antigens, such as peanut allergens, to T lymphocytes, which in turn mediates B-cell antibody production.We used the Canadian Peanut Allergy Registry (CanPAR) and the Busselton Health Study to conduct the largest GWAS for PA to date. Here we report analysis of the HLA region and a meta-analysis with data from 6 additional studies, which confirms and narrows the region of interest to HLA-DQB1 and establishes independence from asthma loci. [...]

Objective Limited evidence suggests a potentially increased risk of allergic conditions in offspring born to women with systemic lupus erythematosus (SLE). In a large population-based study, we aimed to determine if children born to mothers with SLE have an increased risk of allergic conditions compared to children born to mothers without SLE. Methods Using the Offspring of SLE Mothers Registry, we identified children born live to mothers with SLE and their matched controls, and ascertained the number of allergic conditions (asthma, allergic rhinitis, eczema, urticaria, angioedema, and anaphylaxis) based on ≥1 hospitalization or ≥1 or 2 physician(s) visit(s) with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetrics complications, calendar year of birth, sex of the child, and maternal medication. Results There were 509 women with SLE who had 719 children, while 5,824 matched controls had 8,493 children. The mean ± SD followup period was 9.1 ± 5.8 years. Compared to controls, more children born to mothers with SLE had evidence of allergic conditions (43.9% [95% confidence interval (95% CI) 40.4-47.6] versus 38.1% [95% CI 37.0-39.1]). In multivariate analysis (n = 9,212), children born to mothers with SLE had an increased risk of allergic conditions versus control children (odds ratio 1.35 [95% CI 1.13-1.61]). Conclusion Compared to children from the general population, children born to women with SLE may have an increased risk of allergic conditions. Genetics, shared environmental exposures, as well as in utero exposure to maternal autoantibodies and cytokines may mediate this increased risk.

Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and clinical manifestations such as infections, autoimmunity, and malignancy. We sought to determine if responsiveness to interleukin-21 (IL-21), a key cytokine for B cell differentiation, correlates with distinct clinical phenotypes in CVID. CVID subjects were recruited through the Canadian Primary Immunodeficiency Evaluative Survey registry. Peripheral blood mononuclear cells were cultured with anti-CD40 ± interferon-gamma, interleukin-4 (IL-4), IL-21, and/or IL-4+IL-21. B cell subpopulations and IgG production were determined at baseline and day 7 by flow cytometry and ELISA. Clinical complications were compared using contingency tables. CVID subjects exhibited decreased CD27+ B cells and IgG production after 7 days of stimulation with anti-CD40+IL-21 (p 2% class-switched memory B cells at baseline. The IL-4 and IL-21 in vitro assays distinguish two groups of CVID subjects and can be used with baseline B cell subpopulation phenotyping to better identify patients experiencing more vs. fewer clinical non-infectious complications and potentially to modulate therapy.

PURPOSE OF REVIEW Antibiotic allergy is commonly reported and often challenging to evaluate. This review highlights recent developments in our understanding of antibiotic allergy, primarily surrounding evaluation, and diagnosis of antibiotic allergy. We provide historical context to establish a framework, lending relevance to the latest studies. RECENT FINDINGS Clinicians have typically employed skin testing as a first step in the diagnosis of drug allergy, reserving drug provocation challenge, the gold standard for diagnosis, for those with negative skin tests. Although skin tests have a good negative predictive value, the positive predictive value has never been established. An increasing amount of research is demonstrating that drug provocation challenge is well tolerated as the initial evaluation in patients with non-life-threatening reactions to antibiotics. This research also calls into question the value of skin testing in these patients. SUMMARY Skin testing has long been used as the initial investigation in the diagnosis of drug allergy. New research supports that this may not be necessary in all patients, particularly those with non-life-threatening reactions. Further research into the validity of skin testing is required, along with the development of new diagnostic tests for antibiotic allergy.

Immune-mediated reactions to dairy products may vary depending on the mammalian source. We present a case of anaphylaxis to goat/sheep's milk with tolerance to cow’s milk. A 4-year-old boy of Eastern European descent presented with gastrointestinal and respiratory symptoms within minutes after eating a goat/sheep’s milk-derived food product. The tryptase level measured 1 hour post initial symptoms and 1 month after the allergic reaction were 14.6 µg/L and 5.1 µg/L, respectively (norm: 0.0–13.5 µg/L), confirming the diagnosis of anaphylaxis. A skin prick test performed 1 month after the reaction was highly positive for goat/sheep’s milk, but negative for cow’s milk. Skin prick tests may establish a life-threatening goat/sheep’s milk allergy. Goat/sheep’s milk allergy should always be considered in cow’s milk-tolerant patients who present with an allergic reaction to dairy products, or when undergoing/have completed of oral immunotherapy for cow’s milk allergy.

BackgroundOral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice.ObjectiveTo develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management.Materials and methodsRecommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations.ResultsThe deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients’ needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations.ConclusionsThis innovative CPG methodology was guided by patients’ perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Amoxicillin is the most common antibiotic prescribed in children with increasing use over time. While up to 10% of children are labelled as amoxicillin allergic, most children can tolerate amoxicillin after allergy evaluation. It is well documented that the label of amoxicillin allergy in children is associated with adverse health outcomes such as antibiotic-resistant infections. However, it remains controversial how best to assess children for amoxicillin allergy. While in general it is recommended that skin testing be done prior to drug provocation test in the evaluation of amoxicillin allergy, there is increasing evidence that drug provocation testing could be done in lower risk children without skin testing prior. The goal of this article as a narrative review is to review the strengths and limitations of skin testing prior to drug provocation test in children who have a history of either immediate or non-immediate, reactions to amoxicillin.

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.

Objectives To determine the recurrence rate of anaphylaxis in children medically attended in an emergency department (ED), we performed a prospective cohort study to evaluate prehospital and ED management of children with recurrent anaphylaxis and to assess factors associated with recurrent anaphylaxis. Study design As part of the Cross-Canada Anaphylaxis Registry, parents of children with anaphylaxis identified prospectively in 3 EDs and through an emergency medical response service were contacted annually after presentation and queried on subsequent reactions. Cox regression analysis determined factors associated with recurrence. Results Among 292 children who were registered as having had medical attended anaphylaxis, 68.5% completed annual follow-up questionnaires. Forty-seven patients experienced 65 episodes of anaphylaxis during 369 patient-years of follow-up. Food was the trigger in 84.6% of cases, and epinephrine was used in 66.2%. In 50.8%, epinephrine was used outside the health care facility, and 81.7% were brought to a health care facility for treatment. Asthma, reaction triggered by food, and use of epinephrine during the index episode increased the odds of recurrent reaction. Patients whose initial reaction was triggered by peanut were less likely to have a recurrent reaction. Conclusions We report a yearly anaphylaxis recurrence rate of 17.6% in children. There is substantial underuse of epinephrine in cases of anaphylaxis. Educational programs that promote effective avoidance strategies and prompt use of epinephrine are required.

Alison YM Lee,1 Paul Enarson,2 Ann E Clarke,3 Sébastien La Vieille,4 Harley Eisman,5,6 Edmond S Chan,7 Christopher Mill,7 Lawrence Joseph,8 Moshe Ben-Shoshan9 1Pediatric Residency Program, Department of Pediatrics, University of British Columbia, BC Children’s Hospital, 2Division of Emergency Medicine, Department of Pediatrics, University of British Columbia, Vancouver, BC, 3Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, 4Food Directorate, Health Canada, Ottawa, ON, 5Emergency Department, 6Department of Pediatrics, Montreal Children’s Hospital, Montreal, QC, 7Division of Allergy and Immunology, Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, BC, 8Department of Epidemiology and Biostatistics, McGill University, 9Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children’s Hospital, Montreal, QC, Canada Background: There are no data on the percentage of visits due to anaphylaxis in the emergency department (ED), triggers, and management of anaphylaxis across different provinces in Canada. Objective: To compare the percentage of anaphylaxis cases among all ED visits, as well as the triggers and management of anaphylaxis between two Canadian pediatric EDs (PEDs). Methods: As part of the Cross-Canada Anaphylaxis Registry (C-CARE), children presenting to the British Columbia Children’s Hospital (BCCH) and Montreal Children’s Hospital (MCH) EDs with anaphylaxis were recruited. Characteristics, triggers, and management of anaphylaxis were documented using a standardized data entry form. Differences in demographics, triggers, and management were determined by comparing the difference of proportions and 95% confidence interval. Results: Between June 2014 and June 2016, there were 346 visits due to anaphylaxis among 93,730 PED visits at the BCCH ED and 631 anaphylaxis visits among 164,669 pediatric visits at the MCH ED. In both centers, the majority of cases were triggered by food (BCCH 91.3% [88.7, 94.0], MCH 82.4% [79.7, 85.3]), of which peanuts were the most common culprit (24.7% [20.9, 29.9] and 19.0% [15.8, 22.7], respectively). Pre-hospital administration of epinephrine (BCCH 27.7% [23.2, 32.8], MCH 33.1% [29.5, 37.0]) and antihistamines (BCCH 50.6% [45.2, 56.0], MCH 47.1% [43.1, 51.0]) was similar. In-hospital management differed in terms of increased epinephrine, antihistamine, and steroid use at the BCCH (59.2% [53.9, 64.4], 59.8% [54.4, 65.0], and 60.1% [54.7, 65.3], respectively) compared to the MCH (42.2% [38.3, 46.2], 36.2% [32.5, 40.1], and 11.9% [9.5, 14.8], respectively). Despite differences in management, percentage of cases admitted to the intensive care unit was similar between the two centers. Conclusion: Compared to previous European and North American reports, there is a high percentage of anaphylaxis cases in two PEDs across Canada with substantial differences in hospital management practices. It is crucial to develop training programs that aim to increase epinephrine use in anaphylaxis. Keywords: anaphylaxis, emergency department, epinephrine, triggers of anaphylaxis, management

β-lactam antibiotics are the most widely used group of antibiotics, given their effectiveness for the most common bacterial pathogens and their relatively low price. Adverse reactions, mainly cutaneous, are often reported to be associated with their use and hence, less effective and usually more costly alternative antibiotics are prescribed. However, it is not clear what is the risk of immediate immune-mediated (i.e. developing within one hour of administration) and potentially life-threatening reactions among those using β-lactam antibiotic. We conducted a systematic review to assess the prevalence of immediate adverse reactions to β-lactam antibiotics, specifically penicillin derivatives, in patients with a reported adverse reaction to β-lactam antibiotics. In addition, we determined the effect of age on the prevalence of immediate reactions. Assessing the true risk of using β-lactam antibiotics in patients with a reported allergy could prevent physicians from unnecessarily discouraging the use of β-lactam antibiotics. We conducted a systematic review and a meta-analysis using the PubMed, OVID, and Embase databases of work published in English and in French in the last 5 years. Studies were only eligible if they established the prevalence of immediate penicillin reactions with skin testing or challenges in case of negative skin tests. The meta-analysis was conducted using Stata version 12.0. The prevalence of immediate reactions to penicillin derivatives in patients reporting a β-lactam hypersensitivity is 1.98% (95%CI; 1.35%, 2.60%) in the pediatric (under 18 years old) group, 7.78% (95%CI; 6.53%, 9.04%) in the adult group, and 2.84% (95%CI; 1.77%, 3.91%) in the combined group, as tested in various studies, using skin tests and oral challenges. The I(2) value ranged between 87.2% and 97.0%. Our results indicate that the prevalence of immediate reactions is higher in adults than in children. However, wide confidence intervals and a large study heterogeneity preclude conclusive estimates.

Patent blue V dye (PBV) is frequently used as a perioperative drug for lymphangiography, as well as a food additive. Hypersensitivity to PBV is poorly documented in adults and had not been previously described in children. The diagnosis of PBV allergy depends on corroboration of history consistent with an IgE-mediated reaction and confirmatory skin tests. We present in this paper a paediatric case of PBV anaphylaxis and of biphasic reaction that exemplifies the challenges involved in diagnosing and managing this rare but potentially life-threatening allergic reaction.

IgE-mediated milk allergy is a frequent food allergy that presents with various symptoms usually within 2 h after exposure Prompt diagnosis and management with intramuscular epinephrine is paramount Biphasic anaphylactic reactions can be seen especially when there is a delay in epinephrine administration and more severe presentations Comparing tryptase levels during reaction with baseline levels can confirm the diagnosis of anaphylaxis

STAT1 gain-of-function is a heterogeneous disease with broad clinical manifestations namely susceptibility to bacterial infections, recurrent mucocutaneous viral infection with HSV and VZV