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Summertime stings which--actually peak in incidence late in the season--can result in either a mild local reaction and a lesson learned, or a systemic allergic reaction with a devastating outcome. Here are strategies to help you and your patients prevent stings and their potentially devastating outcomes. [ABSTRACT FROM AUTHOR]

Systemic allergic reactions to insect stings are estimated to occur in about 1 percent of children and 3 percent of adults. In children, these reactions usually are limited to cutaneous signs, with urticaria and angioedema; adults more commonly have airway obstruction or hypotension. Epinephrine is the treatment of choice for acute anaphylaxis, and self-injection devices should be prescribed to patients at risk for this allergic reaction. Stinging insect allergy can be confirmed by measurement of venom-specific IgE antibodies using venom skin tests or a radioallergosorbent test. Patients with previous large local reactions have a 5 to 10 percent risk of experiencing systemic reactions to future stings. Patients with previous systemic reactions have a variable risk of future reactions: the risk is as low as 10 to 15 percent in those with the mildest reactions and in some children, but as high as 70 percent in adults with the most severe recent reactions. Because of demonstrated efficacy (98 percent), venom immunotherapy is recommended for use in patients who are at risk for severe systemic reactions to future insect stings. Venom immunotherapy is administered every four to eight weeks for at least five years. Immunotherapy may be needed indefinitely in patients at higher risk for recurrence of anaphylaxis after treatment is stopped. [ABSTRACT FROM AUTHOR]

Summertime stings can result in either a mild local reaction and a lesson learned, or a systemic allergic reaction with a devastating outcome. Here are strategies to help you and your patients prevent stings and their potentially devastating outcomes. [ABSTRACT FROM AUTHOR]

Background: The evaluation and management of insect sting allergy is a complex core competency taught in Allergy and Immunology fellowship programs. It is unclear whether current training on insect allergy is sufficient to meet the needs of the field and what training barriers exist., Objective: To investigate the extent of training on stinging insect allergy and factors currently impacting stinging insect allergy clinical practice through a pilot needs-assessment survey., Methods: A Web-based questionnaire was designed and sent to a 20% random sample of American Academy of Allergy, Asthma & Immunology member categories. Data were analyzed for descriptive frequencies., Results: A total of 78 responses were received (11% response rate). Respondents' mean age was 53.7 years, 52% were female, and 92.3% were physicians. The mean time since training completion was 18.4 years. During fellowship training, 95.7% were educated on stinging insect allergy, 87.1% reported conducting testing, and 82.6% ordered venom immunotherapy (VIT). During training, 50% of respondents managed 1 to 5 patients with venom allergy (38% managed > 5, and 12% none). After fellowship, 97.3% reported evaluating patients with stinging insect allergy, 90.3% report evaluating 1 to 5 patients per month, and 93.2% and 87.5% offer testing and VIT, respectively. A patient's decision to not start VIT was the most common barrier reported by 81.8%., Conclusions: In this pilot needs-assessment survey, the majority reported training and education on insect allergy during fellowship, although patient exposure was low for most. After fellowship, insect allergy evaluations increased up to 24-fold compared with fellowship training and patient-driven decisions are the most common deterrent for VIT., (Published by Elsevier Inc.)

Insect stings can cause large local reactions (LLRs) that are IgE-mediated and associated with considerable morbidity. A risk for systemic reactions including anaphylaxis to subsequent stings has been reported and is often noted by patients and health care providers. Guidelines do not recommend venom immunotherapy (VIT) for LLRs based on the relatively low risk of anaphylaxis, but this is debated in this review. On the pro side: the risk of anaphylaxis may be higher than reported in the limited literature, especially in patients who had only 1 LLR; new species with more potent stings are spreading into new areas; the quality of life can be markedly impaired by LLRs; and VIT is generally safe and highly effective. On the con side: LLRs are benign, stings occur infrequently, VIT has significant cost, systemic reactions occur more often to VIT than to stings in patients with LLRs, and Food and Drug Administration approval and published guidelines do not recommend VIT for LLRs. In practice, shared decision-making is appropriate to incorporate knowledge of the natural history and known high-risk factors in the context of the patient's personal values and preferences., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Evaluation and management of insect sting allergy are often not straightforward when there is uncertainty about the history of reaction, the significance of test results, and the risk of severe reaction to future stings. Patients encounter misinformation about the chance of reaction and may have strong beliefs about the need for treatment. Shared decision-making encourages the clinician to listen to the patients' concerns and beliefs, share relevant information and evidence, and partner with patients to incorporate their values and preferences. This review discusses some major decision points in diagnosis and treatment of insect-allergic patients, with attention to the potential burdens or harms that are important to patients and factors that relate to patients' values and preferences concerning the choices they must make. This is especially true in patients with no history of moderate to severe sting anaphylaxis in whom the risk may be overestimated, but it can also be important in patients who underestimate the risk associated with severe sting anaphylaxis. Clinicians should become more knowledgeable about patient-important beliefs and outcomes and engage in shared decision-making to help patients understand and be comfortable with the choices they must make., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Noninjectable epinephrine to treat allergic reactions addresses an unmet need. Intranasal epinephrine is approved and a sublingual form is under development. Inhaled epinephrine is poorly studied for anaphylaxis. These forms have unknown cost-effectiveness., Objective: To evaluate cost-effectiveness of commercially available noninjectable epinephrine compared with intramuscular epinephrine for treatment of anaphylaxis., Methods: Markov cohort analyses evaluated the cost-effectiveness of noninjectable epinephrine forms. The base-case assumed exaggerated anaphylaxis fatality rates (50-fold increase) for using inhaled epinephrine given low certainty evidence in anaphylaxis and deliberately reduced fatality risk for nasal or sublingual forms (10-fold reduction) theorizing higher adherence and early use during an allergic reaction., Results: In the base-case scenario, assuming a 10-fold decreased risk in peanut allergy fatality associated with intranasal or sublingual epinephrine treatment for a severe allergic reaction (net monetary benefit [NMB], $2,189,134) vs intramuscular epinephrine use (NMB, $2,189,114), intranasal or sublingual epinephrine was the most cost-effective option (incremental cost-effectiveness ratio [ICER], $83,748/quality-adjusted life-year [QALY]), but only at a marginal annual cost of $4. Intramuscular epinephrine was cost-effective (ICER, $17,900/QALY) vs inhaled epinephrine (NMB, $2,183,531), although inhaled epinephrine reached cost-effectiveness (willingness to pay [$100,000/QALY]) if associated fatality risk fell below 2.5-fold. Substituting a single noninjectable form of epinephrine for a second injectable device (in patients prescribed 2 autoinjectors already) would be cost-effective; however, adding a supplemental noninjectable device was not cost-effective, even assuming a 10-fold risk reduction with multiple device carriage (ICER, $858,462)., Conclusion: Noninjectable routes of epinephrine can be cost-effective options provided fatality risk is not significantly elevated. Carriage of redundant epinephrine autoinjectors with noninjectable forms is not cost-effective if associated with excess cost of redundant device packs., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Shared decision-making (SDM) is an increasingly implemented patient-centered approach to navigating patient preferences regarding diagnostic and treatment options and supported decision-making. This therapeutic approach prioritizes the patient's perspectives, considering current medical evidence to provide a balanced approach to clinical scenarios. In light of numerous recent guideline recommendations that are conditional in nature and are clinical scenarios defined by preference-sensitive care options, there is a tremendous opportunity for SDM and validated decision aids. Despite the expansion of the literature on SDM, formal acceptance among clinicians remains inconsistent. Surprisingly, a significant disparity exists between clinicians' self-reported adherence to SDM principles and patients' perceptions of its implementation during clinical encounters. This discrepancy underscores a fundamental issue in the delivery of health care, where clinicians may overestimate their integration of SDM, while patients' experiences suggest otherwise. This review critically examines the factors contributing to this inconsistency, including barriers within the health care system, clinician attitudes and behaviors, and patient expectations and preferences. By elucidating these factors in the fields of food allergy, asthma, eosinophilic esophagitis, and other allergic diseases, this review aims to provide insights into bridging the gap between clinician perception and patient experience in SDM. Addressing this discordance is crucial for advancing patient-centered care and ensuring that SDM is not merely a theoretical concept but a tangible reality in the., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians., Objective: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab., Methods: A systematic review of the literature was performed, and an expert Delphi Panel was assembled., Results: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective., Conclusion: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity., Competing Interests: Disclosures J.A.L. served as consultant for ARS, Aquestive, Bryn, ALK, and Novartis and Co-Chair Joint Task Force for Practice Parameters; received research money to institution from DBV and adjudication for Abvie and Siolta. T.E.D. the project described was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH), under Award Number 2UL1TR001425 - 05A1; the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. E.M.A. is and employee of Public Health Agency of Canada, but the views in any paper are her own and not those of Public Health Agency of Canada. Board member of the Canadian Society of Allergy and Clinical Immunology and Head of Allergy Section, Canadian Pediatric Society. A.A. received institutional funding (Novartis) and consultation/speaker fees (ALK, EPG Health, MJH, Adelphi, Genentech, FARE, and Medscape) and served as advisory board member (Ready, Set, Food; Novartis; and Genentech). K.G.B. received grants from NIH (R01AI150295), AHRQ (R01HS029319), and Thermo Fisher Scientific and royalties from UpToDate and is consulting for Denali Therapeutics. M.B. serves as investigator and advisory board member for Regeneron and Sanofi. N.M.C. serves as clinical investigator; received research support from AstraZeneca, Genentech, and Kenota Health; serves as advisor, consultant, and/or speaker for Amgen, ARS Pharma, AstraZeneca, Blueprint Medicines, Bryn Pharma LLC, Freed AI, Genentech, GSK, Hikma, Incyte, Novartis, Regeneron, and Sanofi. D.B.K.G. is a consultant for Novartis, Aquestive, CellDex, and Kokua; received clinical trials support from Genentech, Novartis, Pfizer, GSK, Merck, Regeneron, Allergy Therapeutics, Eli Lilly, and AstraZeneca and royalties from UpToDate. N.L.H. is a speaker for Adma Bio and Takeda; speaker and advisor for Pharming, Horizon/Amgen, Horizon; advisory board member and speaker for Pharmaceuticals/Amgen. M.G.L. received research money to institution from Regeneron. S.S.M. is speaker for Genentech, Regeneron/Sanofi, GSK, and AstraZeneca and received grant from Takeda. J.J.O. consultant/advisor: GSK, Aquestive, Amgen, and ARS; adjudication/DSMB: AZ, Novartis, GSK, Sanofi, and AbbVie; reviewer/editor and executive editor: Annals of Allergy, Asthma & Immunology; reviewer: UpToDate; executive editor: Medscape; research/grants: NIH. A.R. speakers bureau member for Sanofi/Regeneron, GSK, and AstraZeneca. N.L.R. received funding from the Jeffrey Modell Foundation (58293-I), the NIH (R21AI164100), and Takeda Pharmaceuticals; is consultant for Takeda, Pharming Healthcare, and CSL Behring; received royalties from Wolters Kluwer and UpToDate. L.S. is clinical investigator for Regeneron and DBV Technologies and advisor for Sanofi and Leo pharmaceuticals. M.S.S. is member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma, and Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); has participated in research that has received funding from DBV. J.M.S. received grant support from and is consultant for Regeneron/Sanofi. C.A.S. recipient of a AAAAI Foundation Faculty Development Award. The views expressed in this work are the responsibility of the authors and do not necessarily represent the official views of the AAAAI. D.R.S. is consultant to ARS. J.W. received research support from NIAID, Aimmune, DBV Technologies, and Siolta and consultancy fees from ALK Abello, DBV Technologies, and Novartis. M.J.G. is consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Sanofi/Regeneron, Nutricia, Novartis, Acquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma, and Immunology; is member of the Joint Taskforce on Allergy Practice Parameters; received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, Kaplan, Food Allergy Research and Education, and multiple state/local allergy societies. The remaining authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergist-immunologists use serologic peanut allergy testing to maximize test sensitivity and specificity while minimizing cost and inconvenience. Recent advances toward this goal include a better understanding of specific IgE (sIgE) and component testing, epitope-sIgE assays, and basophil activation testing. Predicting reaction severity with serologic testing is challenged by a range of co-factors that influence reaction severity, such as the amount and form of any allergen consumed and comorbid disease. In 2020, the Allergy Immunology Joint Task Force on Practice Parameters recommended Ara h 2-sIgE as the most cost-effective diagnostic test for peanut allergy because of its superior performance, when compared with skin prick testing and serum IgE. Basophil activation testing, a functional test of allergic response not evaluated in the Joint Task Force on Practice Parameters guideline, is a promising option for both allergy diagnosis and prognosis. Similarly, epitope-sIgE testing may improve prediction of reaction thresholds, but further validation is needed. Despite advances in food allergy testing, many of these tools remain limited by cost, accessibility, and feasibility. In addition, there is a need for further research on how atopic dermatitis may be modifying serologic food allergy severity assessments. Given these limitations, allergy test selection requires a shared decision-making approach so that a patient's values and preferences regarding financial impact, inconvenience, and psychological effects are considered in the context of clinician expertise on the timing and use of optimized testing., Competing Interests: Disclosures Dr Golden is a consultant for Novartis, Aquestive, and Kokua and has received clinical trials support from Genentech, Novartis, Pfizer, GlaxoSmithKline, Merck, Regeneron, and AstraZeneca. Dr Brough reports receiving research grants from the NIH (NIAAD) and speaker fees from DBV Technologies. Dr Santos reports receiving grants from Medical Research Council (MR/M008517/1; MC/PC/18052; and MR/T032081/1), Food Allergy Research and Education, the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID and NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust, and the NIHR through the Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; receiving personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; and receiving research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); and has participated in research that has received funding from DBV. Dr Conway has no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, & Immunology (views expressed are his own); and has participated in research that has received funding from DBV. Dr Golden is a consultant for Novartis, Aquestive, and Kokua; and has received clinical trial support from Genentech, Novartis, Pfizer, GlaxoSmithKline, Merck, Regeneron, and AstraZeneca. Dr Lieberman is a member and co-chair of the Joint Task Force on Practice Parameters; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of the American Board of Allergy and Immunology; serves as an advisor consultant for ARS, Bryn, and Aquestive; serves on the adjudication/DSMB for AbbVie and Siolta; and is an investigator (money to institution) for Novartis and DBV. Dr Greenhawt is a consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma & Immunology; is a member of the Joint Taskforce on Allergy Practice Parameters; and has received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, and multiple state/local allergy societies. Dr Lee is on the editorial boards of Pharmacology Research and Perspectives, Frontiers in Oncology, Frontiers in Pharmacology, Kidney and Blood Pressure Research, and BMC Medical Education. He is the owner and creator of Pharmacology World LLC which generates royalties.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary., Competing Interests: Disclosures The JTFPP members and workgroup members’ conflict of interest disclosure forms can be found at www.allergyparameters.org. Dr Golden: clinical trial support from Genentech, ThermoFisher, Novartis, Pfizer, GlaxoSmithKline, and Regeneron; consulting fees from Aquestive, Novartis, ThermoFisher, ALK-Abello, Allergy Therapeutics; and royalties from UpToDate. Dr Wang: clinical trials support (money to institution) from NIH, Aimmune, DBV Technologies, Regeneron, and Siolta; consulting fees from ALK-Abello, Jubilant HollisterStier; and royalties from UpToDate. Dr Waserman: consulting fees from GlaxoSmithKline, Novartis, CSL Behring, Pfizer Canada, Sanofi Canada, AstraZeneca, Takeda, ALK-Abello, Teva, Medexus, MiravoHealth, Mylan, Bausch Lomb, AbbVie, Avir Pharma, and Leo Pharma; research funding from Pfizer Canada, ALK-Abello, Aimmune; and president of Canadian Allergy, Asthma and Immunology Foundation. Dr Akin: consulting fees from Blueprint Medicine, Cogent, and Novartis; research support from Blueprint Medicines and Cogent; and royalties from UpToDate. Dr Campbell: consulting fees from Bryn and royalties from UpToDate. Dr Ellis: advisory boards for ALK-Abello, AstraZeneca, Aralez, Bausch Health, Leo Pharma, Merck, Novartis, and Pfizer; speakers’ bureaus for ALK-Abello, AstraZeneca, Miravo, Medexus, and Mylan; research support (paid to institution) from ALK-Abello, Aralez, AstraZeneca, Bayer LLC, Medexus, Novartis, and Regeneron; independent consultant to Bayer LLC and Regeneron; and royalties from UpToDate. Dr Greenhawt: consultant for Aquestive; advisory boards for DBV Technologies, Sanofi/Regeneron, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, and Prota; scientific advisory council (unpaid) for the National Peanut Board and medical advisory board (unpaid) of the International Food Protein Induced Enterocolitis Syndrome Association; Working Group Member of the Brighton Collaboration Criteria Vaccine Anaphylaxis; senior associate editor for Annals of Allergy, Asthma & Immunology; member of the Joint Task Force on Allergy Practice Parameters; and speaker honoraria from ImSci, MedLearningGroup, RMEI Medical Education and multiple state/local allergy societies. Dr Lang: honoraria, consultant, and/or clinical research support from AstraZeneca, Genentech, Novartis, and Sanofi-Regeneron; Guest Associate Editor of JACI:In Practice; and editorial board of DynaMed. Dr Ledford: contributor to UpToDate for Perioperative Anaphylaxis; contributing editor for Ask the Expert (AAAAI); research support from AstraZeneca and Novartis (paid to institution); consultant for AstraZeneca; speaker bureau/honoraria from AstraZeneca, Genentech, GlaxoSmithKline, and Sanofi/Regeneron; and legal opinion indoor fungal exposure, drug allergy, anaphylaxis. Dr Lieberman: contracted research (paid to institution) for Aimmune, DBV, Regeneron, and Novartis; adjudication/DSMB for AbbVie and Siolta; consultant/advisor for Aquestive, ALK-Abello, Novartis, and DBV. Dr Oppenheimer: Executive Editor of Annals of Allergy, Asthma & Immunology; reviewer for UpToDate; adjudication and data safety monitoring board for AstraZeneca, GlaxoSmithKline, and Sanofi; consultant for GlaxoSmithKline, Aquestive, and Aimmune; NIH grant for the IDEA study. Dr Shaker: editorial board of The Journal of Allergy and Clinical Immunology: In Practice; associate editor of Annals of Allergy, Asthma & Immunology; member of the Joint Task Force on Practice Parameters; and research support from DBV. Dr Wallace: consulting fees from AbbVie, Bryn, Sanofi, and Kaleo. Dr Abrams: employee of Public Health Agency of Canada (PHAC); views expressed are my own and not those of PHAC. Dr Bernstein: principal investigator, consultant, and speaker for Novartis, Genentech, AstraZeneca, Sanofi Regeneron, Takeda/Shire, CSL Behring, Pharming, BioCryst, and Merck; consultant for Kalvista, Ionis, Celldex, Allakos, Amgen, Biomarin, and Blueprint Medicine; principal investigator and speaker for GlaxoSmithKline; speaker for Optinose; consultant for Ono, Astria, Incyte, Cycle, and Escient; and royalties from UpToDate, British Medical Journal, Taylor & Francis, and Elsevier. Dr Stukus: consultant for ARS Pharmaceuticals, Before Brands, Novartis, and ParentMD; research support from DBV Technologies; social media editor for the AAAAI; member, board of regents for the ACAAI; and Associate Editor, Annals of Allergy, Asthma & Immunology. Heather Cruickshank: grant support from AllerGen NCE and medical writer for Healthline Media. The remaining authors have no conflicts of interests to report., (Copyright © 2023. Published by Elsevier Inc.)

It has been 3 years since the coronavirus disease 2019 (COVID-19) pandemic was initially declared, and 2 years have passed since the first COVID-19 vaccines were introduced. Since then, 13.2 billion COVID-19 vaccine doses have been administered worldwide, largely with multiple doses of messenger RNA vaccines. Although mild local and systemic adverse effects after COVID-19 vaccination are common, serious adverse effects following immunization are rare, particularly when compared with the large number of vaccine doses administered. Immediate and delayed reactions are relatively common and present similarly to allergic and hypersensitivity reactions. Despite this, reactions generally do not commonly recur, cause sequelae, or contraindicate revaccination. In this Clinical Management Review, we provide an updated perspective of COVID-19 vaccine reactions, their spectrum and epidemiology, and recommended approaches to evaluation and management., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. 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.)

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.)

Diagnostic testing of patients who present for evaluation of insect venom allergy can involve many levels of investigation. A detailed initial history is critical for diagnosis and prognosis. The severity of previous sting reactions and the presence or absence of urticaria or hypotension predict severe future sting reactions and underlying mast cell disorders. Venom skin tests and specific IgE measurement can confirm the diagnosis but have limited positive predictive value for the frequency and severity of future sting reactions. Testing for serum IgE to recombinant venom component allergens can distinguish true allergy from cross-reactivity to honey bee and yellowjacket venoms. Basophil activation tests can improve the detection of venom allergy and predict the severity of reactions and the efficacy of venom immunotherapy but are limited in availability. An elevated basal serum tryptase level is an important marker for severe sting anaphylaxis and underlying mast cell disorders (eg, hereditary α-tryptasemia and clonal mast cell disease). When there is high suspicion (eg, using the Red Espanola de Mastocytosis score), bone marrow biopsy is the definitive tool to characterize mast cell disorders that are associated with the most severe outcomes in patients with insect sting allergy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Venom immunotherapy has been utilized to treat Hymenoptera venom allergy since the 1920s. Over the last century, significant advances in the fields of immunology and genetics have led to improvements in the practice of venom immunotherapy. This review encompasses recent advances in the use of venom immunotherapy to provide precise, patient-centered care., Recent Findings: Research about the mechanism of action of venom immunotherapy continues to highlight the modification of both the innate and adaptive immune systems. Molecular techniques have allowed for the identification of specific venom allergens to improve the diagnostic accuracy and safety of venom immunotherapy. Research continues to support the safety of accelerated schedules which can impact the cost, adherence, and quality of life for patients receiving this treatment modality. Finally, significant advances have led to the elucidation of risk factors that place patients at risk for reactions during and after venom immunotherapy. Creation of risk profiles for venom-allergic patients can thus inform the process of immunotherapy in order to provide personalized and precise care., Summary: Significant progress in the use of venom immunotherapy makes the practice a dynamic and active field for continued research. Future research needs to build on these recent advances to continue to optimize and enhance this life-saving treatment., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023.)

Traveling to different regions, one might encounter a species to which they have a known allergy, or other related and unrelated species. A first-time systemic reaction can occur while on vacation, even in those with previous asymptomatic stings. Three main groups of Hymenoptera are responsible for most sting reactions. Honey bee species are virtually identical around the world. Among social wasps (family Vespidae), the yellowjacket (genus Vespula and Dolichovespula) and hornet (genus Vespa) venoms have almost complete cross-reactivity, whereas paper wasp (genus Polistes) venoms show only partial cross-reactivity with other vespid venoms. Venom immunotherapy (VIT) confers 80% to 95% protection against related insects, though isolated species of paper wasps and yellowjackets exist in every country that may be distinct from the ones at home. Those allergic to imported fire ants (genus Solenopsis) in the United States should not react to other ant species around the world. Stinging ants belong to several unrelated subfamilies in different geographic regions, which do not have cross-reactive venom. The chances of encountering specific species of Hymenoptera at a traveler's destination vary by location, planned activities, and season. In this article, we discuss special considerations for traveling, including distribution of stinging insects around the world, risk factors for more severe reactions, ways to prepare for a trip, and when allergist examination or treatment may be helpful before travel., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In the past 10 years, anaphylaxis has grown into its own special area of study within Allergy-Immunology, both at the bench and at the bedside. This review focuses on some of the most clinically relevant advances over the past decade. These include simplified and more inclusive diagnostic criteria for adults and children, uniform definition of biphasic anaphylaxis, and improved systems for objective severity grading. Studies reported in the past decade have led to improved understanding of normal and abnormal regulation of mast cell function, translating into better diagnostic and therapeutic approaches to patients with anaphylaxis. Research has provided improved recognition and treatment of mast cell disorders and has identified a new condition, hereditary α-tryptasemia, that may impact anaphylactic syndromes. We have learned to recognize new causes (α-gal), new pathways (Mas-related G protein-coupled receptor-X2), and many risk factors for severe anaphylaxis. The stability of epinephrine in autoinjectors was reported to be very good for several years after the labeled expiry date, and it can tolerate freezing and thawing. Repeated and prolonged exposure to excessive heat leads to degradation of epinephrine activity. New treatments to prevent severe anaphylaxis have been described, using new ways to block the IgE receptor or modulate intracellular signaling pathways., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01-0.52) and specificity 0.97 (95%CrI 0.9-1). PEG test sensitivity was 0.02 (95%CrI 0.00-0.07) and specificity 0.99 (95%CrI 0.96-1). PS test sensitivity was 0.03 (95%CrI 0.00-0.0.11) and specificity 0.97 (95%CrI 0.91-1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00-0.08) and specificity was 0.98 (95%CrI 0.95-1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Venom immunotherapy (VIT) with Hymenoptera venom extracts is highly effective in preventing large local, systemic allergic, and anaphylactic reactions to insect stings. VIT is not required for patients with cutaneous systemic or large local allergic reactions to stings because it is uncommon for reactions to become more severe. The clinical history, with confirmatory skin or serum tests for venom IgE, can clarify the risk for future anaphylaxis and the need for VIT. For initial treatment, rush regimens are recommended because they have the same or less risk of systemic reactions than slower traditional regimens. VIT is relatively safe with a low incidence of systemic reactions. Injection-site reactions can be bothersome but do not predict systemic reactions to venom injections. Patients who need VIT should be screened for baseline serum tryptase and possible underlying mast cell disorders. VIT can be discontinued after five years in most patients, but those with known high-risk factors should continue VIT indefinitely.

Importance: Vaccination against SARS-CoV-2 is a highly effective strategy to prevent infection and severe COVID-19 outcomes. The best strategy for a second dose of vaccine among persons who had an immediate allergic reaction to their first SARS CoV-2 vaccination is unclear., Objective: To assess the risk of severe immediate allergic reactions (eg, anaphylaxis) to a second dose of SARS-CoV-2 mRNA vaccine among persons with immediate allergic reactions to their first vaccine dose., Data Sources: MEDLINE, Embase, Web of Science, and the World Health Organization Global Coronavirus database were searched from inception through October 4, 2021., Study Selection: Included studies addressed immediate allergic reactions of any severity to a second SARS-CoV-2 vaccine dose in persons with a known or suspected immediate allergic reaction (<4 hours after vaccination) after their first SARS-CoV-2 vaccine dose. Studies describing a second vaccine dose among persons reporting delayed reactions (>4 hours after vaccination) were excluded., Data Extraction and Synthesis: Paired reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects models were used for meta-analysis. The GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach evaluated certainty of the evidence., Main Outcomes and Measures: Risk of severe immediate allergic reaction and repeated severe immediate allergic reactions with a second vaccine dose. Reaction severity was defined by the reporting investigator, using Brighton Collaboration Criteria, Ring and Messmer criteria, World Allergy Organization criteria, or National Institute of Allergy and Infectious Diseases criteria., Results: Among 22 studies of SARS-CoV-2 mRNA vaccines, 1366 individuals (87.8% women; mean age, 46.1 years) had immediate allergic reactions to their first vaccination. Analysis using the pooled random-effects model found that 6 patients developed severe immediate allergic reactions after their second vaccination (absolute risk, 0.16% [95% CI, 0.01%-2.94%]), 232 developed mild symptoms (13.65% [95% CI, 7.76%-22.9%]), and, conversely, 1360 tolerated the dose (99.84% [95% CI, 97.09%-99.99%]). Among 78 persons with severe immediate allergic reactions to their first SARS-CoV-2 mRNA vaccination, 4 people (4.94% [95% CI, 0.93%-22.28%]) had a second severe immediate reaction, and 15 had nonsevere symptoms (9.54% [95% CI, 2.18%-33.34%]). There were no deaths. Graded vaccine dosing, skin testing, and premedication as risk-stratification strategies did not alter the findings. Certainty of evidence was moderate for those with any allergic reaction to the first dose and low for those with severe allergic reactions to the first dose., Conclusions and Relevance: In this systematic review and meta-analysis of case studies and case reports, the risk of immediate allergic reactions and severe immediate reactions or anaphylaxis associated with a second dose of an SARS-CoV-2 mRNA vaccine was low among persons who experienced an immediate allergic reaction to their first dose. These findings suggest that revaccination of individuals with an immediate allergic reaction to a first SARS-CoV-2 mRNA vaccine dose in a supervised setting equipped to manage severe allergic reactions can be safe.

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.)

Hymenoptera stinging insects are common culprits for allergic reactions. Anaphylaxis to insect stings can be life threatening and is associated with a significant risk of recurrence. Insect allergy requires referral to an allergist/immunologist for education and for diagnostic evaluation that will direct further management and treatment. Venom immunotherapy is safe and effective; it prevents sting anaphylaxis in up to 98% of patients. Potential risk factors for side effects during testing and treatment should be assessed for every patient to mitigate risk and to guide treatment recommendations and the duration of immunotherapy., Competing Interests: Disclosure K.E. Adams has nothing to disclose. J.M. Tracy serves on the advisory boards for Pharming, Biocrist, and Thermo-Fischer; Honoraria: UptoDate. D.B.K. Golden serves on the speaker bureau for Genentech; as a consultant to ALK, Stallergenes, Allergy Therapeutics, Kaleo, and Aquestive; as a section editor for UpToDate and receives clinical trials support from Genentech, Novartis, and Allergy Therapeutics., (Published by Elsevier Inc.)

Optimal evidence-based clinical practice requires systematic summaries of the best available evidence, including ratings of the quality of that evidence, and is facilitated by the availability of trustworthy guidelines. In this review, we describe the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rating quality of evidence and moving from evidence to recommendations using examples from allergy-immunology. GRADE focuses on systematic summaries of the best evidence, systematic reviews and trustworthy guidelines, and emphasizes a structured approach to determining quality (certainty) of bodies of evidence, absolute magnitude of effects of desirable and undesirable consequences (benefits and harms), and use of evidence to develop clinical recommendations. Adopted by over 110 organizations worldwide, including the American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters, GRADE is foundational to the optimal interpretation of research evidence and its application in clinical practice. This review supports the clinician's ability to find and use the information in GRADE guidelines to help care for patients in the clinic., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by 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.)

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil ® Bee and Wasp. Venomil ® is provided as a freeze-dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister-Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.

Purpose of Review: This review describes improvement in diagnostic accuracy, prediction of outcomes, identifying high-risk factors, and refinements of treatment that continue to evolve over the past 5-10 years., Recent Findings: The risk of anaphylaxis is relatively low (< 5%) in patients with previous large local reactions or strictly cutaneous systemic reactions, but much higher in those with moderate-to-severe anaphylaxis (40%-70%) or mastocytosis (> 90%). Use of recombinant venom allergens and basophil activation tests may improve diagnostic accuracy. Elevated serum tryptase (and possible mastocytosis) occurs in 10% of patients with insect sting allergy, and in 25% of those with hypotensive reactions. Rush VIT is proven safe and rapidly effective. There are known high-risk factors that justify treatment beyond 5 years. Diagnostic accuracy and prediction of risk have improved in recent years. There are still knowledge gaps related to prediction and management of risk with current diagnostic and therapeutic modalities.