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This review summarizes new research developments and clinical practice recommendations for the diagnosis and management of anaphylaxis presented in the Joint Task Force on Practice Parameters 2023 Anaphylaxis practice parameter Update. It is intended to serve as a high-level summary of the 2023 practice parameter, which makes clinically impactful recommendations based on evidence that has emerged since the 2015 practice parameter. We invite clinicians to explore the full 2023 practice parameter to understand the research methods and underlying evidence that have informed the recommendations summarized here. There are new and evolving diagnostic criteria for anaphylaxis, rules for defining elevated tryptase levels, and recognition of signs and symptoms particular to infants and toddlers. The administration of epinephrine should not be used as a surrogate to diagnose anaphylaxis. Risk factors for anaphylaxis should be assessed on a case-by-case basis. Patient counseling and shared decision-making are essential to support patients' treatment decisions and capacity to manage the risk of anaphylaxis at home and in other community settings. Activation of emergency medical services after home epinephrine administration may not be required in all cases, and patients should be engaged in shared decision-making to determine when home management may be appropriate., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Undertreatment of anaphylaxis with epinephrine continues to be an unmet need and is a particular challenge among infants and toddlers., Objective: To address this gap by identifying barriers and solutions to appropriate and timely administration of epinephrine., Methods: We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when younger than 36 months. Outcomes of interest included epinephrine use in community and health care settings to treat probable anaphylaxis., Results: Of 264 probable anaphylaxis cases, 39% of infants (aged <12 months) and 61% of toddlers (aged 12-35 months) received epinephrine at any time during the child's most severe allergic reaction (P = .001). A previous diagnosis of a food allergy was reported in 62% of cases where epinephrine was used compared with 26% of cases where epinephrine was not used (P < .001). In children with a previous diagnosis of a food allergy, epinephrine was used in 89% of those who were prescribed an anaphylaxis action plan compared with 50% of those without a plan (P = .001). The adjusted odds ratio for the association between having an anaphylaxis action plan and epinephrine use in cases of probable anaphylaxis was 5.39 (95% confidence interval, 2.18-13.30)., Conclusions: Epinephrine use at any time (including in health care settings) during probable anaphylaxis is more likely in infants and toddlers with a previously diagnosed food allergy than those without diagnosis. The provision of an anaphylaxis action plan is also associated with increased epinephrine use during probable anaphylaxis in this population., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

An accurate diagnosis of IgE-mediated allergies is necessary to inform risk management for severe allergic reactions including anaphylaxis for food, venom, and drug allergies. The most widely available laboratory test for allergy is serum-specific IgE testing, which is routinely used for food allergy and insect sting allergy. Testing for specific IgE is limited by high sensitivity and low specificity, resulting in concern regarding overdiagnosis. Testing of allergen components has led to improved diagnosis for some food and venom allergens. Additional options for laboratory tests, such as epitope analysis, basophil activation, and mast cell activation, are being investigated for their potential to optimize diagnosis and provide predictors for reaction severity and treatment response. In contrast, laboratory testing for drug allergy is more limited because to date, there are no well-validated commercial assays in the United States. Furthermore, it is important to diagnose delayed reactions to medications, because these also significantly affect decision-making regarding therapeutic options for infectious disorders. Reliable tests for both immediate and delayed drug hypersensitivity are much needed, because drug allergy labels can significantly limit treatment options for patients. Research in this area is emerging., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Numerous scoring systems have been developed to improve and standardize the diagnosis and management of acute allergic reactions and anaphylaxis; however, considerable variability exists among these systems. This review article discusses existing severity scoring systems and identifies specific knowledge gaps that remain. Future research is needed to resolve the limitations of existing grading systems, including attempting to link reaction severity with treatment advice and conducting validation studies in different clinical settings, patient populations, and geographies to promote grading system application and dissemination in both clinical care and research., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown., Methods: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo., Results: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group., Conclusions: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.)., (Copyright © 2023 Massachusetts Medical Society.)

Introduction: Food allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production., Methods: IgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE + plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated., Results: EBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p<0.001) and the number of IgE-producing plasma cells in PN allergic mice, accompanied by 100% inhibition of PN-induced anaphylaxis and plasma histamine release (p<0.001) without affecting IgG1 or IgG2a production. Berberine markedly suppressed IgE production, which was associated with suppression of XBP1, BLIMP1, and STAT6 transcription factors and a reduced rate of mitochondrial oxidation in an IgE-producing plasma cell line., Conclusions: EBF-2 and its active compound berberine are potent IgE suppressors, associated with cellular regulation of immunometabolism on IgE plasma cells, and may be a potential therapy for IgE-mediated food allergy and other allergic disorders., Competing Interests: X-ML received research support to her institution from the National Institutes of Health (NIH)/National Center for Complementary and Alternative Medicine (NCCAM) # 1P01AT002644725-01“Center for Chinese Herbal Therapy (CHT) for Asthma”, and grant #1R01AT001495-01A1 and 2R01 AT001495-05A2, NIH/NIAID R43AI148039, Food Allergy Research and Education (FARE), Winston Wolkoff Integrative Medicine Fund for Allergies and Wellness, the Parker Foundation and Henan University of Chinese Medicine; received consultancy fees from FARE and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Bayer Global Health LLC; received royalties from UpToDate; is an Honorary Professor of Chinese Medical University, Taichung, Taiwan; Henan University of Chinese Medicine Zhengzhou, China, and Professorial Lecture at Icahn School of Medicine at Mount Sinai, New York, NY, US; received travel expenses from the NCCAM and FARE; share US patent US7820175B2 (FAHF-2), US10500169B2 (XPP), US10406191B2 (S. Flavescens), US10028985B2 (WL); US11351157B2 (nanoBBR): take compensation from her practice at Center for Integrative Health and Acupuncture PC; US Times Technology Inc is managed by her related party; is a member of General Nutraceutical Technology LLC and Health Freedom LLC. NY received research support from the National Institutes of Health (NIH)/National Center for Complementary and Alternative Medicine (NCCAM), NIH/NIAID R43AI148039, shares US patent: US10500169B2 (XPP), US10406191B2 (S. Flavescens), US10028985B2 (WL); and is a member of General Nutraceutical Technology, LLC, and Health Freedom LLC; receives a salary from General Nutraceutical Technology, LLC. HS shares US patents: US7820175B2 (FAHF-2) and US10406191B2 (S. Flavescens), US10028985B2 (WL); is a medical consultant for General Nutraceutical Technology, LLC. KS shares US patent: US11351157B2 (nanoBBR) and received a salary from General Nutraceutical Technology LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Maskey, Srivastava, Kim, Wang, Musa, Shi, Gong, Fidan, Wang, Dunkin, Chung, Zhan, Miao, Sampson and Li.)

Purpose of Review: The goal of this review is to characterize health disparities impacting the recognition and treatment of anaphylaxis., Recent Findings: Previous research has identified major health disparities related to atopic conditions including asthma, atopic dermatitis, and food allergies (FA); however, disparities related to anaphylaxis have yet to be examined in depth. We found widespread health disparities in the incidence and severity of anaphylaxis, as well as in the management of allergies (particularly food allergies) that place individuals at risk of anaphylaxis. Sociodemographic factors are associated with numerous negative health outcomes related to anaphylaxis. We highlight several key steps that must be taken to address these disparities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The appropriate at-home management of anaphylaxis begins with patient education on recognition and treatment, especially when and how to use epinephrine. Delayed administration of epinephrine as well as having severe symptoms and needing multiple doses of epinephrine to treat symptoms are risk factors for biphasic anaphylaxis. The successful implementation of at-home management of anaphylaxis requires appropriate patient selection and an algorithmic approach that recommends activation of emergency medical services (EMS) when the patient does not adequately respond to at-home administration of epinephrine or there are extenuating patient-related circumstances. Fortunately, approximately 98% of anaphylactic episodes respond to 2 or fewer doses of epinephrine, the standard prescription used for epinephrine autoinjectors; fatal anaphylaxis is very rare, as low as 0.002 deaths/million person-years; and biphasic reactions are uncommon (∼5%), and only extremely rarely lethal. Thus, most common concerns leading to recommended EMS activation and emergency department visits after epinephrine administration are generally unsubstantiated. Furthermore, emergency department visits do not always lead to better treatment and drive health care costs higher. Open communications with patients and families regarding risks and benefits of at-home management and observation versus EMS activation and emergency department evaluation after epinephrine administration for anaphylaxis are essential. However, we believe the data indicate that it is time to reconsider the often used and taught approach that recommends EMS activation whenever epinephrine is used., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively., Objective: We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility., Methods: We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale., Results: The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices., Conclusions: We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Anaphylaxis is a systemic allergic reaction that can be caused by food, drugs, insect bites, or unknown triggers in infants and toddlers. Anaphylaxis rates are increasing. Infants and toddlers may have increased exposure to known and unknown allergens, decreased ability to describe their symptoms, and an expanded differential diagnosis for consideration on presentation. The most common symptoms in these age groups are cutaneous and gastrointestinal. Age-specific language may be helpful for caregivers to identify and describe the symptoms of anaphylaxis in infants and toddlers. Long-term management of anaphylaxis includes allergy evaluation to guide avoidance and assess prognosis and education on allergic reaction management; this incorporates the prescription of epinephrine autoinjector and provision of an allergy emergency plan., Competing Interests: Disclosure N. Ramsey – Nothing to disclose, J. Wang receives research support from the NIAID, Aimmune, DBV Technologies, and Regeneron, and has received consultancy fees from ALK Abello, DBV Technologies, and Genentech., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Food allergy is an immune-mediated disease and must be differentiated from other adverse effects related to food that are non-immune mediated. Symptoms of immunoglobulin (Ig) E-mediated allergy can range from mild to severe, and life-threatening anaphylaxis may occur. Current recommended strategies for diagnosis include the use of skin prick tests, allergen-specific serum IgE, and/or oral food challenges. Management entails allergen avoidance and appropriate treatment of allergic reactions should accidental ingestions occur. Treatment approaches under investigation include immunotherapy as well as biologics and novel vaccines. Attention has also recently focused on implementing strategies for prevention of food allergy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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

Background: There is no widely adopted severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions, thus limiting the ability to optimize and standardize management practices and advance research., Objective: The aim of this study was to develop a severity grading system for acute allergic reactions for use in clinical care and research., Methods: From May to September 2020, we convened a 21-member multidisciplinary panel of allergy and emergency care experts; 9 members formed a writing group to critically appraise and assess the strengths and limitations of prior severity grading systems and develop the structure and content for an optimal severity grading system. The entire study panel then revised the grading system and sought consensus by utilizing Delphi methodology., Results: The writing group recommended that an optimal grading system encompass the severity of acute allergic reactions on a continuum from mild allergic reactions to anaphylactic shock. Additionally, the severity grading system must be able to discriminate between clinically important differences in reaction severity to be relevant in research while also being intuitive and straightforward to apply in clinical care. Consensus was reached for all elements of the proposed severity grading system., Conclusion: We developed a consensus severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions. Successful international validation, refinement, dissemination, and application of the grading system will improve communication among providers and patients about the severity of allergic reactions and will help advance future research., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Food allergy management in child care centers and schools is a controversial topic, for which evidence-based guidance is needed. Following the Grading of Recommendations Assessment, Development, and Evaluation approach, we conducted systematic literature reviews of the anticipated health effects of selected interventions for managing food allergy in child care centers and schools; we compiled data about the costs, feasibility, acceptability, and effects on health equity of the selected interventions; and we developed the following conditional recommendations: we suggest that child care centers and schools implement allergy training and action plans; we suggest that they use epinephrine (adrenaline) to treat suspected anaphylaxis; we suggest that they stock unassigned epinephrine autoinjectors, instead of requiring students to supply their own personal autoinjectors to be stored on site for designated at-school use; and we suggest that they do not implement site-wide food prohibitions (eg, "nut-free" schools) or allergen-restricted zones (eg, "milk-free" tables), except in the special circumstances identified in this document. The recommendations are labeled "conditional" due to the low quality of available evidence. More research is needed to determine with greater certainty which interventions are likely to be the most beneficial. Policymakers might need to adapt the recommendations to fit local circumstances., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: Anaphylaxis remains difficult to diagnose and epinephrine underused., Objective: To better understand the thoughts of pediatricians regarding when acute allergic reactions constitute anaphylaxis and when epinephrine should be given by conducting an anonymous online survey., Methods: The survey consisted of 8 case-based scenarios of allergic reactions with the following 2 questions on each case: (1) does this case represent anaphylaxis? and (2) if this patient immediately presented to you, would you treat the patient with epinephrine during the reaction?, Results: A total of 1001 responses were analyzed. When assessing all cases combined, there was discordance in whether a case represented anaphylaxis and administration of epinephrine was warranted in 8% of the cases. An average of 5% of all the respondents suggested that the case represented anaphylaxis but would not warrant epinephrine, whereas an average of 3% suggested that the case did not represent anaphylaxis but that epinephrine was warranted., Conclusion: The results of this survey reveal that there is discordance among pediatricians on when an allergic reaction is considered anaphylaxis and when epinephrine is warranted. These data highlight the need for continued improvement of the definition of anaphylaxis and continued need for education regarding the diagnosis and management of anaphylaxis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recognizing anaphylaxis in infants and toddlers can be challenging for health care providers and caregivers, and current diagnostic criteria and anaphylaxis action plans do not specifically address this younger population., Objective: To describe symptoms and signs observed by primary caregivers of infants and toddlers during severe food-induced allergic reactions., Methods: We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when less than 36 months of age. Respondents who were present during the child's most severe reaction were asked to report symptoms and signs observed. The survey asked about infant- and toddler-specific symptoms and signs in lay language for caregivers. Data were compared with patient-reported data from past studies to identify distinct patterns among the younger population., Results: The survey was completed for 374 children (193 infants, 181 toddlers). The most common symptoms and signs reported were skin reactions (90%), facial and extremity swelling (59%), gastrointestinal issues (51%), and coughing/wheezing (45%). Infants (aged <12 months) more frequently experienced skin reactions, skin mottling, and ear pulling/scratching or putting fingers in ears, as compared with toddlers (aged 12-35 months). Toddlers experienced throat itching and coughing/wheezing more frequently than infants., Conclusions: Anaphylaxis presentation demonstrates similarities and differences in infants and toddlers. Modifying the terminology used in the current criteria allowed for reporting of symptoms and signs of anaphylaxis that are more common in infants and toddlers. Diagnostic criteria, clinical guidelines, and anaphylaxis action plans may be enhanced to address this young, often nonverbal, population., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous guidance on infant anaphylaxis largely relied on data from older children and adults. Infants are a unique subgroup, which presents specific challenges because infants are unable to verbalize symptoms, although the magnitude of underrecognition is not well studied. Data show that strict avoidance of allergens is difficult to achieve in the infant age group and a source of stress and anxiety for their caregivers. Recent studies suggest that infant anaphylaxis is less severe than in older children, which could greatly assist with implementation of food allergy prevention and treatment. New evidence from clinical trials and observational and real-world studies show that infant anaphylaxis is rare on first ingestion of a new food and typically not severe when it occurs, which parents may not be aware of when preparing to introduce peanut or other common food allergens to infants for the purpose of prevention. The better safety and efficacy of oral immunotherapy in infants and preschoolers could help prevent undesired psychosocial consequences of longstanding food allergy such as anxiety, bullying, and poor quality of life. Evidence from recent years on the lower risk of infant anaphylaxis and its severity could move allergy practice toward the confidence that regular, long-term ingestion provides., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts., Objective: Our aim was to develop consensus definitions for clinically relevant anaphylaxis outcomes by utilizing a multidisciplinary group of clinical and research experts in anaphylaxis., Methods: Using Delphi methodology, we developed agenda topics and drafted questions to review during monthly conference calls. Through online surveys, a 19-member panel consisting of experts in allergy and/or immunology and emergency medicine rated their level of agreement with the appropriateness of statements on a scale of 1 to 9. A median value of 1.0 to 3.4 was considered inappropriate, a median value of 3.5 to 6.9 was considered uncertain, and a median value of 7.0 to 9.0 was considered appropriate. A disagreement index was then calculated, with values less than 1.0 categorized as "consensus reached." If consensus was not reached after the initial survey, subsequent surveys incorporating the aggregate de-identified responses from prior surveys were sent to panel members. This process was repeated until consensus was reached or 4 survey rounds had been completed, after which the question was categorized as "no consensus reached.", Results: The panel developed outcome definitions for persistent, refractory, and biphasic anaphylaxis, as well as for persistent and biphasic nonanaphylactic reactions. There was also consensus among panel members regarding the need to develop an anaphylaxis severity grading system., Conclusion: Dissemination and application of these definitions in clinical care and research will help standardize the terminology used to describe anaphylaxis outcomes and serve as the foundation for future research, including research aimed at development of an anaphylaxis severity grading system., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Epinephrine is the agreed-upon first line treatment for anaphylaxis, yet it continues to be underused by patients/caregivers and providers alike., Recent Findings: There are unfortunately limited data on how epinephrine can best be utilized in anaphylaxis, which hinders how best to inform patients and providers. Studies reporting underuse suggest various barriers and themes on why this may happen., Summary: Continued education of patients, caregivers, and providers is needed; however, is not likely to be enough to close the gap. Thus, novel studies on how to increase use; increase availability in a cost-effective manner; and newer, effective delivery routes are still needed.

Background: Studies assessing food-induced allergic reactions and prehospital treatments in infants and young children are scarce., Objective: To describe differences in clinical characteristics in children aged 0 to 4 years presenting to the emergency department (ED) with food allergy (FA) reactions and investigate the association between prehospital epinephrine use and clinical outcomes., Methods: Retrospective cohort study of FA ED visits in Kaiser Permanente Northern California from January 2016 to December 2018. Charts were assessed on whether anaphylaxis criteria were met, and outcomes were reviewed after prehospital and ED treatments., Results: A weighted cohort of 1518 children presenting with FA to the ED was evaluated. Infants presented with respiratory symptoms less often than did children age 1 and ages 2 to 4 years (6.8%, 16.1%, and 23.9%, respectively; P < .01), more frequently following first ingestion of offending food (74.8%, 44.2%, and 18.4%, respectively; P < .001), and with egg as the most common trigger (33.8%, 8.6%, and 5.3%, respectively; P < .001). Children younger than age 2 years had a tendency toward meeting anaphylaxis criteria less frequently than older children (31.3% vs 42.2%; P = .06), with ED epinephrine given in 12.6% overall. Prehospital epinephrine was given in 152 patients and was associated with a higher likelihood of admission for observation (adjusted odds ratio, 2.6; 95% CI, 1.0-6.5) but a lower likelihood of ED epinephrine treatment (adjusted odds ratio, 0.2; 95% CI, 0.1-0.5)., Conclusions: Infants treated in the ED for FA reactions presented differently than older children. Most infants presented after first-known ingestion of offending foods. Overall, ED epinephrine use was low necessitating additional education to recognize and treat anaphylaxis in the ED., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To review GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methods and discuss the clinical application of conditional recommendations in clinical guidelines, specifically in the context of anaphylaxis., Data Sources: Articles that described GRADE, evidence synthesis, evidence to recommendation frameworks, and shared decision making were used to discuss conditional recommendations of the 2020 Anaphylaxis GRADE guideline., Study Selections: A narrative review detailing concepts of GRADE and approaches to translate conditional recommendations to individualized and contextualized patient care., Results: GRADE methods encourage a nuanced relationship between certainty of evidence and strength of recommendations. Strength of recommendation must incorporate key factors, including the balance between benefits and harms, patient values and preferences, and resource allocation (costs), with equity, feasibility, and acceptability also often included as considerations. GRADE guidelines provide recommendations that are characterized by directionality (for or against) and strength (strong or conditional). A conditional recommendation is tailored to context and primarily applied through a lens of patient preferences related to the likelihood of outcomes of importance and a shared decision-making approach. Although the 2020 Anaphylaxis GRADE guideline better informs the practice of anaphylaxis prevention through (1) identification and mitigation of risk factors for biphasic anaphylaxis and (2) evaluation of the use of glucocorticoid and/or antihistamine pretreatment, all GRADE recommendations, although directional, are conditional and as such should not be universally applied to every circumstance., Conclusion: Clinical guidelines provide an important opportunity to critically appraise evidence and translate evidence to practice. Patients, practitioners, and policy makers should appreciate the strength of recommendation and certainty of evidence and understand how this affects guideline applicability and implementation., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Peanut allergy is a potentially severe and lifelong allergy, with few effective treatments or preventive measures., Objective: To convene an expert panel of allergists, pediatricians, and advocates to discuss and highlight unmet needs in the prevention and management of peanut allergies., Methods: Literature searches of PubMed were performed. The panel evaluated published data on the prevention of peanut allergy, treatment of existing peanut allergy, and management of reactions after unintentional peanut exposures., Results: The following key unmet needs in the prevention and management of peanut allergy were identified: (1) enhancing and optimizing implementation of early peanut introduction as a means of preventing the development of peanut allergy, (2) developing knowledge translation strategies regarding the safety and efficacy data for current and emerging immunotherapies for peanut-allergic children to support their use in clinical practice, and (3) promoting understanding of true exposure risk in allergic individuals and ensuring access to epinephrine for unintentional exposures that provoke severe reactions. Practitioners should help educate caregivers about the actual risks associated with peanut allergy and its prevention and management so that treatment decisions can be evidence based rather than fear based. Support tools are needed to help address caregiver goals, expectations, and psychological barriers, as well as identify facilitators for prevention and treatment strategies., Conclusion: There are significant unmet needs in our understanding of peanut allergy; addressing these needs will help to enhance understanding of how to most effectively prevent and treat peanut allergy, as well as educate the food-allergic and nonallergic community regarding current evidence-based practices., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Anaphylaxis is a severe and potentially life-threatening allergic reaction. Since its discovery over 100 years ago, research has led to great strides in describing pathophysiologic mechanisms of anaphylaxis; however, there is still imprecision regarding its definition and a lack of reliable, confirmatory testing. In this paper, we review definitions of anaphylaxis, highlighting studies examining the utility of the current clinical consensus definition. In addition, we evaluate current difficulties and limitations for both providers in acute care settings managing episodes and allergists evaluating patients after an episode has resolved. Finally, we provide an algorithm for outpatient evaluation of patients with a history of possible anaphylaxis., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The aim of this review is to describe effective management strategies in nursery or school based upon research findings., Recent Findings: The prevalence of food allergy and number of emergency department visits for food-related anaphylaxis are increasing in children and adolescents. As there is currently no cure, the most effective strategy to decrease allergic reactions is food allergen avoidance. However, allergic reactions are inevitable in both food allergic children as well as in first-time reactors. Misconceptions exist on the safety of products with advisory labels and questions remain on whether school-wide bans decrease the risk of allergic reactions in school. Recent legislation has prompted schools to consider requiring unassigned epinephrine autoinjectors to better manage those who have allergic reactions in nursery or school., Summary: A collective effort is required to keep children with food allergies safe at school. Families, healthcare providers, and school personnel should be informed on food allergen avoidance strategies, symptoms consistent with allergic reactions and anaphylaxis, how to respond to allergic reactions, and the impact the diagnosis of food allergy may have on quality of life for affected children and their families.

Background: Although school health care professionals are integral to the management of students with food allergy, their views on school food allergy policies have not yet been reported., Objective: To characterize food allergy policies currently being used in schools and their utility and potential barriers to implementation from the perspective of school health care professionals., Methods: An electronic survey was disseminated to school nurses at the 2016 National Association of School Nurses meeting and through the Allergy and Asthma Network listserv. Frequencies were calculated to describe participant characteristics and responses. Unadjusted associations were examined using χ 2 tests; adjusted associations were examined using multiple logistic regression models., Results: A total of 242 completed surveys were included in the analysis. Thirty-two percent of nurses reported an allergic reaction in their school in the past year. Most schools used a variety of policies, including anaphylaxis training for staff (96.7%), stock epinephrine availability (81.7%), designated lunch areas (62.2%), and food guidelines for classrooms (61.8%). Barriers to implementation included financial, time, and attitudinal considerations. Schools with pre-K or kindergarten students had higher odds of having designated lunch areas (adjusted odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0-4.1; P < .05). The odds of having emergency epinephrine available were higher in schools with a full-time nurse (OR, 2.6; 95% CI, 1.1-6.3; P < .05) and in schools reporting at least 1 severe reaction in the past year (OR, 3.2; 95% CI, 1.2-8.5; P < .05)., Conclusion: With one-third of school nurses reporting an allergic reaction in the past year, schools use many strategies to minimize allergen exposures and increase anaphylaxis preparedness. Most school nurses favor these policies and acknowledge barriers to implementation., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Anaphylaxis and food allergy management in childcare facilities and schools are growing challenges. An increasing number of children experience severe allergic reactions on school grounds as evidenced by reports of epinephrine use. Data also suggest that the prevalence of food allergy may be increasing, with a large percentage of school-aged children at risk for anaphylaxis. Moreover, anaphylaxis may occur for the first time in a previously undiagnosed child at school or childcare setting, suggesting that general preparedness is essential. Management includes strategies for minimizing the risk of reactions and allergen exposures as well as readiness to recognize and treat allergic reactions of any severity. The primary objective of this report is to offer health care providers an overview of relevant evidence, resources, and expert opinion to assist with developing interprofessional collaborative counsel on school food allergy management and anaphylaxis preparedness with families, schools, and childcare settings. We present the current evidence base, suggest resources, and highlight areas of current controversy that warrant further study., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess time trends in food allergy diagnoses, epinephrine autoinjector (EAI) prescriptions, and EAI administrations in the school setting., Study Design: In this retrospective study, deidentified student data from the New York City Department of Health and Mental Hygiene, which oversees >1 million students in 1800 schools, were provided to investigators. Data from school years 2007-2008 to 2012-2013 pertaining to diagnoses of food allergy, student-specific EAI orders, and EAI administrations among students in New York City were analyzed for trends over time, via the use of ORs and χ 2 calculation., Results: The prevalences of providing physician documentation of food allergy and EAI orders, and the incidence of EAI administrations, all increased approximately 3-fold over the years of the study. Of 337 EAI administrations, more than one-half used stock EAI, and three-quarters were for students without a student-specific order preceding the incident., Conclusions: The rise in food allergy diagnoses, EAI prescriptions, and EAI administrations suggest either a true increase in allergic disease, increased reporting, and/or, in the case of EAI administrations, increased appropriate use. As the majority of EAI administrations used stock supply, availability of nonstudent-specific stock EAI appears vital to management of anaphylaxis in schools. Collaboration between physicians, families, and schools is needed to identify students at risk for severe allergic reactions and to ensure preparedness and availability of EAI in the event of anaphylaxis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Anaphylaxis is a potentially life-threatening, severe allergic reaction. The immediate assessment of patients having an allergic reaction and prompt administration of epinephrine, if criteria for anaphylaxis are met, promote optimal outcomes. National and international guidelines for the management of anaphylaxis, including those for management of allergic reactions at school, as well as several clinical reports from the American Academy of Pediatrics, recommend the provision of written emergency action plans to those at risk of anaphylaxis, in addition to the prescription of epinephrine autoinjectors. This clinical report provides information to help health care providers understand the role of a written, personalized allergy and anaphylaxis emergency plan to enhance the care of children at risk of allergic reactions, including anaphylaxis. This report offers a comprehensive written plan, with advice on individualizing instructions to suit specific patient circumstances., (Copyright © 2017 by the American Academy of Pediatrics.)

Background: Previous studies report epinephrine use for positive oral food challenges (OFCs) to be 9-11% when generally performed to determine outgrowth of food allergies. Epinephrine use for positive OFCs performed as screening criteria for enrollment in therapeutic trials for food allergy has not been reported., Objective: The objective of this study was to assess the characteristics and treatment for positive OFCs performed for screening subjects for food therapeutic trials., Methods: Retrospective review of positive screening OFCs from 2 treatment trials, food allergy herbal formula-2 (n = 45) and milk oral immunotherapy (n = 29), conducted at the Icahn School of Medicine at Mount Sinai was performed., Results: The most common initial symptom elicited was oral pruritus, reported for 81% (n = 60) of subjects. Overall, subjective gastrointestinal symptoms (oral pruritus, throat pruritus, nausea, abdominal pain) were most common (97.3% subjects), followed by cutaneous symptoms (48.7%). Of the 74 positive double-blind, placebo-controlled food challenge, 29 (39.2%) were treated with epinephrine; 2 of these subjects received 2 doses of epinephrine (6.9% of the reactions treated with epinephrine or 2.7% of all reactions). Biphasic reactions were infrequent, which occurred in 3 subjects (4%)., Conclusions: Screening OFCs to confirm food allergies can be performed safely, but there was a higher rate of epinephrine use compared with OFCs used for assessing food allergy outgrowth. Therefore, personnel skilled and experienced in the recognition of early signs and symptoms of anaphylaxis who can promptly initiate treatment are required., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Studies show that anaphylaxis is under-recognized and epinephrine (adrenaline) is under-used by medical personnel as well as patients and their families. This study assesses the knowledge of food-induced anaphylaxis diagnosis and management across different populations of providers and caregivers and other interested respondents., Methods: An online survey embedded in a case discussion of food-induced anaphylaxis was distributed by Medscape to registered members., Results: A total of 7822 responders who started the activity chose to answer at least some of the questions presented (response rate 39.5%). Over 80% of responders in all groups correctly identified the case of anaphylaxis with prominent skin and respiratory symptoms; however, only 55% correctly recognized the case without skin symptoms as anaphylaxis. Only 23% of responders correctly selected risk factors for anaphylaxis, with physicians significantly more likely to choose the correct answers as compared to allied health, other health professionals, and medical students (p < 0.001). Ninety-five percent selected epinephrine (adrenaline) as the most appropriate treatment for anaphylaxis, and 81% correctly indicated that there are no absolute contraindications for epinephrine (adrenaline) in the setting of anaphylaxis. When presented a case of a child with no documented history of allergies who has symptoms of anaphylaxis, more physicians than any other group chose to administer stock epinephrine (adrenaline) (73% vs. 60%, p < 0.001)., Conclusion: Specific knowledge deficits for food-induced anaphylaxis persist across all groups. Further educational efforts should be aimed not only at the medical community but also for the entire caregiver community and general public, to optimize care for food allergic individuals., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: To describe the development of a novel treatment for food allergy, named the food allergy herbal formula-2 (FAHF-2), that is based on traditional Chinese medicine., Recent Findings: FAHF-2 has proven to be well tolerated and effective for the treatment of food allergies in murine models of peanut and multiple food allergies. These results are accompanied by evidence of favorable immune modulation, and the effects are persistent after the discontinuation of treatment. Early clinical trials demonstrate the safety and tolerability of this formula in individuals with food allergies. An ongoing Phase II clinical trial will evaluate the efficacy of FAHF-2 in protecting individuals from allergen-induced allergic reactions during oral food challenges., Summary: FAHF-2 is an herbal formula that has a high safety profile and has shown to prevent anaphylaxis in murine models of food allergy. Similar findings in clinical trials could bring a novel treatment for food allergies.

Anaphylaxis is a life-threatening allergic reaction, and food is one of the most common responsible allergens in the outpatient setting. The prevalence of food-induced anaphylaxis has been steadily rising. Education regarding food allergen avoidance is crucial as most of the fatal reactions occurred in those with known food allergies. The lack of a consensus definition for anaphylaxis has made its diagnosis difficult. Symptoms affect multiple organ systems and include pruritus, urticaria, angioedema, vomiting, diarrhoea, abdominal cramps, respiratory difficulty, wheezing, hypotension, and shock. Prompt recognition of anaphylaxis is essential as delayed treatment has been associated with fatalities. Although epinephrine is accepted as the treatment of choice, timely administration does not always occur, partly due to a lack of awareness of the diagnostic criteria. Several novel tools are currently being investigated, which will potentially aid in the diagnosis and treatment of food-induced anaphylaxis.