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Background: Until recently, immediate emergency department (ED) transfer after food-related anaphylactic reactions was recommended regardless of symptom resolution following use of an epinephrine autoinjector (EAI). We evaluated the cost-effectiveness of delayed ED transfer after EAI use in non-medical settings (watchful waiting) compared to immediate ED transfer among pediatric patients with food allergies in Canada., Methods: We developed a probabilistic Markov model of individuals starting at age of one year who are at risk of severe food-related allergic reactions requiring epinephrine. We evaluated medical costs (in 2022 Canadian dollars) and quality-adjusted life years (QALY) of each strategy over a 20-year horizon. In the base case, we assumed a tenfold increase in food allergy fatality for patients under watchful waiting, which we increased to 100- to 1,000-fold in sensitivity analysis. The analysis was conducted from the Canadian healthcare system perspective with a 1.5% annual discount rate and a willingness-to-pay (WTP) threshold of $50,000 per QALY., Results: Immediate ED transfer following EAI use resulted in a decreased risk of food allergy fatality of 9.2 × 10 - 5 over 20 years, which is equivalent to < 1 fatality per 200,000 patient-years. Watchful waiting resulted in cost savings of $1,157 per patient and a QALY loss of 7.28 × 10 - 4 ; an incremental cost per QALY saved of $1,589,854. The incremental cost per death prevented with immediate ED transfer was $12,586,613. Watchful waiting remained cost-effective in all sensitivity and scenario analyses, except under extreme increases in fatality risk of 500-fold and 1,000-fold., Conclusions: Watchful waiting for symptom re-occurrence following EAI administration in non-medical settings is cost-effective., Competing Interests: Declarations. Ethics approval and consent to participate: N/A. Consent for publication: N/A. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Neutrophils are short-lived cells of the innate immune system and represent 50-70% of the circulating leucocytes. Their primary role is antimicrobial defence which they accomplish through rapid migration to sites of inflammation followed by phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETosis). While previously considered terminally differentiated cells, they have been shown to have great adaptability and to play a role in conditions ranging from cancer to autoimmunity. This review focuses on their role in allergic disease. In particular: their role as potential amplifiers of type 1 hypersensitivity reactions leading to anaphylaxis; their involvement in alternative pathways of food and drug allergy; their role in allergic rhinitis and asthma and neutrophil dysfunction in atopic dermatitis. The use of potential biomarkers and therapeutic targets is also discussed with a view to guiding future research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered via intramuscular (IM) or subcutaneous (SC) injection. AQST-109, a sublingual film containing a prodrug of epinephrine, is in development as an alternative delivery method for the treatment of severe allergic reactions including anaphylaxis., Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine following administration of AQST-109 to epinephrine delivered by manual IM injection and epinephrine autoinjectors (EAIs)., Methods: Data were integrated from two randomized, open-label, Phase I crossover trials evaluating the pharmacokinetics and pharmacodynamics of epinephrine in 54 healthy volunteers. They had no prior medical conditions and were delivered either AQST-109 12 mg or 0.3 mg EpiPen, 0.3 mg generic EpiPen, 0.3 mg Auvi-Q and 0.3 mg manual IM injection., Results: AQST-109 yielded comparable epinephrine pharmacokinetics and similar exposure when compared to both the manual IM injection and EAIs. The median time to maximum concentration (Tmax) for AQST-109 was 15 minutes, as compared to EpiPen (10 minutes), generic EpiPen (15 minutes), Auvi-Q (30 minutes) and manual IM (50 minutes). There was also an early, rapid, and consistent increase observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) following the administration of AQST-109., Conclusion: AQST-109 delivered epinephrine with PK and PD results within the bracketed range of approved IM products. AQST-109 shows promise as an innovative, needle-free, non-device, portable and orally delivered alternative for the first-line treatment of Type I allergic reactions, including anaphylaxis., (Copyright © 2025. Published by Elsevier Inc.)

Osteoarthritis (OA) is a common condition. The treatment of knee OA aims to improve the quality of life and clinical symptoms, mainly knee pain. To develop a new treatment option, diclofenac etalhyaluronate (ONO-5704/SI-613; trade name: JOYCLU) was developed. Its anti-inflammatory and pain-relieving effects have been demonstrated. Conversely, adverse events have also been reported. Here, we report the case of a 71-year-old female who presented with anaphylaxis and prolonged allergic reactions after an intra-articular injection of JOYCLU. A basophil activation test (BAT) was performed to determine the cause of the anaphylaxis. BAT showed no positive findings. As the incidence of knee OA increases, the number of cases of JOYCLU use is expected to grow; therefore, careful administration is required. In this case, the cause was unknown by BAT. Thus, further development of appropriate testing methods is necessary. Intra-articular allergic reactions in knee OA may be modified and worsened besides normal allergic reactions; therefore, caution is required., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Studies of human IgE and its targeted epitopes on allergens have been very limited. We have an established method to immortalize IgE encoding B cells from allergic individuals., Objective: To develop an unbiased and comprehensive panel of peanut-specific human IgE mAbs to characterize key immunodominant antigenic regions and epitopes on peanut allergens to map the molecular interactions responsible for inducing anaphylaxis., Methods: Using human hybridoma technology to immortalize IgE encoding B cells from peripheral blood of subjects with severe peanut allergy, we generated a panel of naturally occurring human IgE mAbs in an unbiased manner. Isolated IgE mAbs were characterized extensively in allergen binding assays, peptide array analysis, antigenic mapping, binding kinetic analysis, serum blocking, skin testing inhibition, and functional assessment using human FcεRI transgenic mice., Results: We created a large panel of 54 peanut-specific IgE mAbs, of which 63% were specific for Ara h 2 and/or 6. Pairs of IgE mAbs with the same antigen-specificity but different binding sites were able to mediate passive systemic anaphylaxis in FcεRI transgenic mice. A single mAb targeting the repetitive motif on Ara h 2 was able to induce degranulation and anaphylaxis on its own. IgG1 switched-variant immunoglobulins of the IgE mAb inhibited patients´ IgE binding to peanut extract between 30-60% (ImmunoCAP) and reduced peanut extract-induced skin wheal sizes by 1.6-7.4 millimeters in peanut allergic patients., Conclusion: We created a molecular map of the IgE antibody response to the most important peanut allergen proteins to enable the design of new allergy immunotherapies and vaccines., (Copyright © 2025. Published by Elsevier Inc.)

Background: Human monoclonal IgE antibodies recognizing peanut allergens have recently become available, but we lack a detailed understanding of how these IgEs target allergens., Objective: To determine the molecular details of the antibody-allergen interaction for a panel of clinically important human IgE monoclonal antibodies and to develop strategies to disrupt disease causing antibody-allergen interactions., Methods: We identified candidates from a panel of epitope binned human IgE monoclonals that recognize two important and homologous peanut allergens, Ara h 2 and Ara h 6. Crystal structures were determined revealing the interfaces (antigenic sites) of exemplars of five common IgE bins., Results: Among the common antigenic sites on Ara h 2 and Ara h 6, two sites (A and B) are highly conserved between the allergens, explaining the cross reactivity of antibodies that recognize these sites. Three sites (C, D, and F) involve residues that are not conserved between the allergens. Of the five common sites, three Sites (B, C, and D) involve residues that are only near each other when the allergens are properly folded, such that these sites are conformational. Two additional sites (sites A and F) involve largely linear stretches of amino acids. Site F targeted antibody, 38B7, binds to a peptide sequence DPYSP OH S, in which hydroxylation of the last proline is critical for binding. This sequence is repeated two or three times depending on the Ara h 2 isoform, enabling 38B7 to induce anaphylaxis as a single monoclonal, without a second antibody. We have mutated key residues in each site and created a panel of hypoallergens, having reduced IgE mAb binding and lacking the ability to induce anaphylaxis in our murine model., Conclusion: We created a structural map of the IgE antibody response to the most important peanut allergen proteins to enable the design of new allergy immunotherapies and vaccines., (Copyright © 2025. Published by Elsevier Inc.)

Background: Food allergies are common among children worldwide. This occurs when the immune system has an abnormal reaction to certain foods. This reaction can range in severity from mild to severe and may lead to anaphylaxis, which can be fatal. As teachers are the first responders in managing such situations in schools, this study aims to explore and measure primary school teachers' knowledge and attitudes about food allergies and their management and review the current school policy., Methods: This cross-sectional study uses a randomly distributed online questionnaire to measure teachers' knowledge and attitudes at primary schools in Medina, Saudi Arabia., Results: The sample consisted of 383 primary school teachers. Approximately 87.5% of the participants were aware of food allergies. More than two-thirds of teachers were able to identify anaphylactic shock. Only 15.4% of the teachers knew that an epinephrine autoinjector was the first aid measurement to be taken. Additionally, 39.9% of the teachers reported that the school does not have an action plan for dealing with students with food allergies. Approximately 93.4% of the participants agreed that avoiding foods that cause allergies is important for preventing allergies., Conclusions: This study revealed teachers' good knowledge in the identification of food allergy and their symptoms, as well as the awareness of their potential severity. However, the study highlighted a significant gap in management. Most had positive attitudes toward learning about food allergies. Therefore, administration policies and strategies need to be implemented to assist in managing food allergies at school., Competing Interests: The 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., (© 2025 Aljohani, Alshamani, Aljohani, Almohammadi, Alharbi, Altarjami and Alsaedi.)

Introduction: COVID-19 vaccination has been a key intervention in reducing the severity of symptoms; however, concerns about vaccine safety, particularly regarding allergic reactions, arose early on. Healthcare workers faced the challenge of addressing these concerns to ensure safe vaccine administration. This study aimed to review the practical aspects of using allergy skin testing for COVID-19 vaccine excipients in patients with a history of allergic reactions developed following mRNA COVID-19 vaccination., Methods: A retrospective chart review was conducted for patients who reported allergic reactions after the COVID-19 vaccine and underwent allergy skin testing for COVID-19 vaccine excipients in the Adult Allergy and Immunology Service at Hamad Medical Corporation, Doha, Qatar. The testing protocol, developed based on published data during the pandemic, included skin prick (SPT) and intradermal (ID) testing using medications containing polysorbate 80 and polyethylene glycol (PEG), the primary excipients in the COVID-19 vaccines suspected of triggering allergic responses., Results: Of the 88 patients reviewed, 38 reported different types of allergic reactions following mRNA COVID-19 vaccination, with the majority being female. Anaphylaxis was reported in 21.1% of the patients, while the remaining experienced less severe allergic reactions. All patients underwent SPT and ID testing with PEG and polysorbate 80. By SPT, two patients tested positive for PEG and none for polysorbate 80. By ID, seven tested positive for polysorbate 80 and one for PEG. Among patients who experienced anaphylaxis, 50% had positive allergy test results. Twenty-three percent of patients with negative test results could receive additional vaccine doses without adverse reactions., Conclusion: Managing patients with a history of allergic reactions to the COVID-19 vaccine is challenging, as the exact mechanisms and accurate and valid allergy testing are yet to be determined. In our cohort, most patients had mild allergic reactions following vaccination. Excipients' allergy skin testing has helped to reduce vaccine hesitancy despite its questionable utility in clinical practice., Competing Interests: The 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., (© 2025 Aqel, Thalappil, Imameldin, Mudawi, Al Maslamani, Al-Khal, Mobayed, Al-Nesf and Ibrahim.)

Prescription-event monitoring (PEM) is the current gold standard for determining the risk of rare drug side-effects and comparing the risk between agents; however, spontaneous or prompted reporting schemes have low case-detection rates and exposure may be difficult to estimate. A novel method is described that allows a comparative adverse event rate between two drugs to be estimated-based on patterns of cross-reactivity-requiring only a sample of cases and no direct knowledge of drug exposure rates. Agreement was compared between the novel method and historical estimates of risk using PEM for comparative risk of rocuronium versus vecuronium anaphylaxis. The novel method was applied to a sample of patients investigated by the Western Australian Anaesthetic Drug Reaction Clinic over a 21-year period. Relative population exposure was estimated from the number of patients with either rocuronium or vecuronium anaphylaxis subsequently shown to be reactive on skin testing to both agents. This was used to correct the total number of cases of hypersensitivity triggered by each agent. Measures of spread were by bootstrap sampling. Historical estimates were gathered by literature review. Additional comparisons of agreement between estimates made by the novel method and PEM were made using cross-reactivity data and PEM rates reported in the literature. There was agreement between estimates of comparative anaphylaxis risk between the novel method and PEM. Two-hundred and twenty-eight cases of anaphylaxis were observed, 89% caused by rocuronium. Patients reactive to both agents were more likely to be female, and had a higher acute mast cell tryptase level. Patients with a history of rocuronium anaphylaxis were more likely to be reactive to one agent only (69% vs . 33%, P  < 0.01). It was estimated that rocuronium was prescribed 3.9 times more frequently than vecuronium. When the observed proportion of cases was corrected for exposure rate, the risk of rocuronium anaphylaxis was 2.2 times that of vecuronium (95% confidence interval 1.7 to 2.8). The median risk from historical estimates was 4.7 times, while the previous PEM estimate in Western Australian was 3.0 times. Using a subgroup of patients susceptible to the same side-effect of two drugs, the relative exposure rate and corrected comparative risk of an adverse effect can be estimated for a population. Using this technique, which requires assessment only of cases to estimate relative exposure rates, we have estimated that the risk of anaphylaxis from rocuronium to be 2.2 times that of vecuronium in Western Australia., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/objectives: Vaccines have been recognized as one of the most effective public health interventions. However, vaccine-associated anaphylaxis, although rare, is a serious adverse reaction. The incidence of anaphylaxis related to non-COVID-19 vaccines in adults remains underreported. This systematic review and meta-analysis aim to estimate the incidence of post-vaccination anaphylaxis across various vaccines in adults., Methods: A comprehensive literature search of PubMed, Embase, Scopus, and Web of Science identified studies on anaphylaxis following vaccination in adults (≥18 years), excluding COVID-19 vaccines. PRISMA 2020 guidelines were followed. The protocol was registered in PROSPERO in advance (ID CRD42024566928). Random-effects and fixed-effects models were used to pool data and estimate the logit proportion, with the logit-transformed proportion serving as the effect size, thereby allowing for the calculation of event rates., Results: A total of 37 studies were included in the systematic review, with 22 studies contributing to the meta-analysis, representing a combined population of 206,855,261 participants. Most studies focused on influenza vaccines ( n = 15). Across all studies, 262 anaphylactic cases were reported, with 153 cases related to influenza vaccines, followed by herpes zoster virus vaccines (38 cases) and yellow fever vaccines (29 cases). Td/Tdap vaccine had the lowest rate (0.0001 per 100,000 participants). The overall random-effects model yielded a logit proportion of -10.45 (95% CI: -12.09 to -8.82, p < 0.001), corresponding to an event rate of 2.91 events per 100,000 subjects (95% CI: 0.56 to 14.73). Sensitivity analysis showed a higher incidence for influenza, hepatitis vaccines, and in vulnerable populations., Conclusions: Anaphylaxis following vaccination in adults is rare but varies by vaccine type. Strengthened monitoring and preparedness are essential, especially in non-medical settings, to ensure a rapid response to anaphylaxis and maintain public confidence in vaccination programs.

Clinical Implications: If a cypress-sensitized patient experiences severe reactions to fruits-particularly with periorbital angioedema and cofactors present-consider testing for Pru p 7-specific IgE, even if initial tests, such as specific IgE to peach and SPT with peach extract, are negative., (Copyright © 2025. Published by Elsevier Inc.)

IgE-mediated opioid hypersensitivities, or true allergies, are rare and most adverse reactions to opioids can be attributed to side effects or to pseudo-allergies. Given that immune-mediated allergies to opioids are uncommon, literature regarding cross-reactivity among opioid classes are limited. This retrospective study aimed to determine the rates of cross-reactivity and tolerance among patients with previously documented opioid allergy or adverse drug reaction (ADR) across three opioid drug classes (natural, semisynthetic, and synthetic opioids). Patients with documented allergy(s) and/or ADR(s) to opioids were assessed for outcomes of subsequent opioid exposure during any hospital admission at a Veterans Affairs hospital over a 10-year time-period. Veterans were sorted into three cohorts based on the opioid class of the previously documented allergy or ADR. Each cohort had three study arms, one for each class of subsequent opioid exposure. A total of 1507 patients were identified with previously documented allergy or ADR to at least one opioid and at least one subsequent opioid drug exposure. No cross-reactivity among any of the opioid drug classes were found resulting in 100% re-exposure tolerance rates with all study arms. These findings could increase confidence in utilizing opioids in patients with historically documented opioid allergies or ADRs.

Omalizumab was recently approved by the US Food and Drug Administration for treatment of any single food allergy or multiple food allergies in children aged 1 year and older and adults. There is currently no formal guidance regarding recommended best practices for omalizumab use in food allergy, including patient selection, anticipated goals and outcomes of therapy, procedure for monitoring patients who elect to start omalizumab therapy, and ways in which omalizumab can be incorporated into the landscape of food allergy management and daily clinical practice. This work group report was developed by the food allergy therapies subcommittee of the Adverse Reactions to Foods Committee within the American Academy of Allergy, Asthma & Immunology. Consensus, evidence-based guidance regarding experts' recommendations for using omalizumab to treat children and adults with food allergy was developed by using modified Delphi methodology. In iterative fashion, a total of 8 statements regarding how to use omalizumab to treat patients with food allergy were developed by 16 clinical experts. This guidance provides the clinician with a suggested approach to patient selection, initiation of therapy, monitoring of efficacy, and long-term follow-up care. The role of preference-sensitive care is emphasized, with most statements offering care recommendations relevant to the culture and values of a particular practice setting., Competing Interests: Disclosure statement Disclosure of potential conflict of interest: A. Anagnostou reports institutional funding from Novartis; advisory board service for of Genentech, Novartis, Bryn, and Ready, Set, Food!; and consultation/speaker fees from ALK, Adelphi, Bryn, Novartis, Genentech, Medscape, Food Allergy Research and Education (FARE), MHJ, and EPG Health. J. A. Bird reports consultancy for Allergenis, DBV Technologies, FARE, Genentech, Hanimmune Therapeutics, HAL Allergy, Infinant Health, Novartis, Nutricia, and Parexel, as well as research for Aimmune, DBV Technologies, Genentech, the National Institute of Allergy and Infectious Diseases (NIAID), Novartis, Regeneron, and Siolta. S. Chinthrajah receives grant support from the Consortium for Food Allergy Research (CoFAR), NIAID, and FARE and is an advisory board member for Alladapt, Novartis, Allergenis, IgGenix, Intrommune Therapeutics, Phylaxis, and Genentech. T. E. Dribbin has received funding and is supported by NIH (K23 AI175525). D. M. Fleischer has received research support from ARS Pharmaceuticals and DBV Technologies; serves as an unpaid advisory board member for the Food Allergy and Anaphylaxis Connection Team and the National Peanut Board; receives royalties from UpToDate; and has received personal fees as a consultant to Aquestive, ARS Pharmaceuticals, Bryn Pharma, DBV Technologies, Genentech, and Nasus outside the submitted work. E. Kim reports grants to his institution from NIAID and FARE; personal fees from ALK, Ukko, Cellergy Pharma, DBV Technologies, Genentech, Hanimumme Therapeutics, Novartis, Phylaxis, Revolo Biotherapeutics; and safety review board service for Allergy Therapeutics. A. Nowak-Wegrzyn receives research support from NIAID, DBV Technologies, and Siolta Therapeutics; speaking fees from Nestle, Danone, Medscape, and Genentech; and royalties from UpToDate. In addition, A. Nowak-Wegrzyn serves as an associate editor for the Annals of Allergy, Asthma and Immunology; as director of the AAAAI board; and as chair of the medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association. M. S. Shaker is a member and cochair 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, and serves on the board of directors of the AAAAI (all views expressed are his own). W. Shreffler reports grants to his institution from NIAID, the Food Allergy Science Initiative, and FARE; contract research support to his institution from Genentech, DBV, Allergy Therapeutics, Aravax, Novartis; personal consulting fees from Aimmune, DBV, Novartis, ALK, Allergy Therapeutics, FARE; and royalty payments from UpToDate. S. Sicherer reports royalty payments from UpToDate and Johns Hopkins University Press; grants to his institution from tNIAID, FARE, and Pfizer; and personal fees from the AAAAI as deputy editor of the Journal of Allergy and Clinical Immunology: In Practice outside of the submitted work. B. P. Vickery reports grants from Alladapt, AstraZeneca, Genentech, NIAID, and Siolta; personal fees from Allergenis, Aravax, Reacta Biosciences, and Sanofi Regeneron; both grants and personal fees from Aimmune, DBV, FARE, Novartis, and Regeneron; and stock options from Moonlight Therapeutics outside the submitted work. J. Wang is a member of the Joint Task Force on Practice Parameters; receives research support from NIAID, Aimmune, DBV, and Siolta; and receives consultancy fees from ALK-Abelló, DBV, and Novartis. M. Greenhawt is a consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Takeda, Griffols, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abelló, Bryn, Genentech, and Prota; is a speaker for Genentech; 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; and is member of the Joint Taskforce on Allergy Practice Parameters. In addition, J. Wang has received honoraria for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, Kaplan, Food Allergy Research and Education, and multiple state and local allergy societies. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Adrenaline is the first line treatment for anaphylaxis and adrenaline auto-injectors (AAI) allow reliable, safe and ergonomic administration in the community. However, AAIs have significant limitations and adrenaline is often not used in anaphylaxis. Innovations to administer adrenaline via alternative routes may potentially improve usage rates and treatment effectiveness. Here, we describe the known limitations and barriers to AAI use in anaphylaxis. We then summarise current data for adrenaline devices which use alternative routes of administration for treating anaphylaxis. Several novel devices are in development, which deliver adrenaline via nasal, sublingual or transcutaneous routes. Pharmacokinetic, pharmacodynamic and safety studies have compared these treatments with AAI or intramuscular adrenaline via needle and syringe. The first non-injectable adrenaline delivery device for emergency treatment of anaphylaxis was approved in Europe and the United States. Neffy, an adrenaline nasal spray, is licensed for use in adult and paediatric patients who weigh at least 30 kg. In the near future, multiple alternatives to injectable adrenaline may be available for managing anaphylaxis, overcoming some, but not all of the limitations of AAIs., (© 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Immune checkpoint inhibitors (ICIs), such as pembrolizumab (PEM), are widely recognized for their antitumor efficacy, but they can also lead to various cutaneous adverse events (CAEs). While most CAEs can be managed with topical corticosteroids, severe cases may necessitate halting immunotherapy. The incidence of severe CAEs is notably higher in combination therapies involving ICIs than in monotherapies, emphasizing the need for stringent, long-term management strategies. This includes potential modifications or discontinuations of the combination therapy. PEM, when added to the conventional paclitaxel + cisplatin (or carboplatin) ± bevacizumab regimen, has shown significant improvements in overall and progression-free survival for patients with Stage IVB metastatic or locally uncontrolled recurrent cervical cancer. This case series retrospectively examined the incidence and management of CAEs in 19 female patients treated with this combination therapy between October 2022 and May 2023. Four patients exhibiting CTCAE grade 3 were identified. The four cases of severe CAEs involved erythema multiforme after the initial course of PEM combination chemotherapy. Notably, three patients experienced immediate hypersensitivity reactions, including anaphylaxis, during subsequent treatments. This observation underscores the necessity for rigorous dermatological monitoring of patients undergoing PEM combination chemotherapy. Such vigilance is crucial for early detection of adverse reactions and timely adjustment of treatment regimens, thereby enhancing patient safety., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Anaphylaxis affects up to 5% of people during their lifetime. Although anaphylaxis usually resolves without long-term physical consequences, it can result in anxiety and quality of life impairment. Rarely and unpredictably, community anaphylaxis can cause rapid physiological decompensation and death. Adrenaline (epinephrine) is the cornerstone of anaphylaxis treatment, and provision of adrenaline autoinjectors (AAI) has become a standard of care for people at risk of anaphylaxis in the community. In this article, we explore the effectiveness of AAIs for preventing fatal outcomes in anaphylaxis, using information drawn from animal and human in vivo studies and epidemiology. We find that data support the effectiveness of intravenous adrenaline infusions for reversing physiological features of anaphylaxis, typically at doses from 0.05 to 0.5 μg/kg/min for 1-2 h, or ~ 10 μg/kg total dose. Intramuscular injection of doses approximating 10 μg/kg in humans can result in similar peak plasma adrenaline levels to intravenous infusions, at 100-500 pg/mL. However, these levels are typically short-lived following intramuscular adrenaline, and pharmacokinetic and pharmacodynamic outcomes can be unpredictable. Epidemiological data do not support an association between increasing AAI prescriptions and reduced fatal anaphylaxis, although carriage and activation rates remain low. Taken together, these data suggest that current AAIs have little impact on rates of fatal anaphylaxis, perhaps due to a lack of sustained and sufficient plasma adrenaline concentration. Effects of AAI prescription on quality of life may be variable. There is a need to consider alternatives, which can safely deliver a sustained adrenaline infusion via an appropriate route., (© 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Objective: The cardiac return assist blanket (CRAB) has been designed to increase central venous pressure (CVP) to manage severe hypotension associated with anaphylaxis. This interventional study aimed to identify the relationship between CRAB pressure and CVP. CRAB pressure was also compared with the change in CVP associated with a straight leg raise (SLR), the Trendelenburg position, and 1 L of compound sodium lactate., Methods: Sixteen healthy, fasted volunteers were exposed to CRAB pressure at 10, 20, 30, and 40 cmH 2 O, the SLR, and 15 degrees of the Trendelenburg position. The volunteers were then fed and hydrated with 1 L of CSL over 30 minutes and the protocol was repeated., Results: The initial 10 cmH 2 O of CRAB pressure increased CVP by 3.7 mmHg (95% confidence interval 2.7, 4.7). Each subsequent 10-cmH 2 O rise in CRAB pressure increased CVP by 0.9 mmHg (95% confidence interval 0.55, 1.25). The SLR, Trendelenburg position, and 1 L of CSL increased CVP by 0.97 , 0.75 , and 0.69 mmHg, respectively., Conclusions: The CRAB controllably increases CVP, and 40 cmH 2 O of CRAB pressure increases CVP by 6.41 mmHg. The effect of the CRAB is greater than that with the SLR, Trendelenburg position, or 1 L of CSL.This trial was registered with the ANZCTR (ACTRN12621000840886: https://www.anzctr.org.au)., Competing Interests: Declaration of conflicting interestC Mitchell is the inventor of the CRAB and the owner of Coco Industries Pty. Ltd. Coco Industries Pty. Ltd. holds the patent for the CRAB and paid for any expenses associated with this study. A Jacques declares that there is no conflict of interest.

Background: In many countries, neuro-muscular blocking agents (NMBAs) are the first cause of perioperative anaphylaxis. Epidemiological studies identified pholcodine, a quaternary ammonium-containing opiate as one of the sensitization sources. However, NMBA anaphylaxis exists in countries where pholcodine was unavailable, prompting the hypothesis of other sensitizing molecules, most likely quaternary ammonium compounds (QACs). Indeed, QACs are commonly used as disinfectants, antiseptics, preservatives, and detergents. Occupational exposure to QACs has been reported as a risk factor for NMBA anaphylaxis, but little is known about the sensitization mechanism and the capacity of these molecules to elicit an immune response. We aimed to establish the immunogenicity of QACs representative of the main existing chemical structures., Methods: We measured the sensitization potential of seven QACs (two polyquaterniums, three alkyl-ammoniums and two aromatic ammoniums) by using two standard dendritic cells (DCs) models (THP-1 cell line and monocyte derived-dendritic cells). The allergenicity of the sensitizing compounds was further tested in heterologous and autologous T-cell-DC co-culture models., Results: Amongst the seven molecules tested, four could modulate activation markers on DCs, and thus can be classified as chemical sensitizers (polyquaterniums-7 and -10, ethylhexadecyldimethylammonium and benzethonium). This activation was accompanied by the secretion of pro-inflammatory and maturation cytokines. Furthermore, activation by polyquaternium-7 could induce T-cell proliferation in heterologous and autologous coculture models, demonstrating that this molecule can induce a specific CD4 + T cell response., Conclusions: We provide evidence at the cellular level that some QACs can elicit an immune response, which could be in line with the hypothesis of these molecules' role in NMBA sensitization., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

A 52-year-old man presented to our department with generalized erythema, watery stools, and vomiting 30 min after ingesting coconut, oatmeal, and vegetable juice. On arrival, his blood pressure was 120/79 mm Hg, heart rate was 126 beats per min, blood oxygen saturation was 96%, and lip cyanosis was observed. The patient experienced diffuse redness throughout the body and was diagnosed as having severe anaphylaxis. A skin prick test for the leftover coconut, oatmeal, and vegetable juice, which the patient had consumed immediately before the onset of symptoms, showed a positive reaction only to the leftover oatmeal. Direct microscopic examination of the leftover oatmeal revealed numerous insect bodies that appeared as booklice. Using Western blot analysis and quantitative polymerase chain reaction, Lip b 1, a specific antigen for Liposcelis bostrychophila (badonnel), an indoor pest that inhabits various places and feeds on various indoor materials, including stored foods, was detected only in the extract of the leftover oatmeal. Based on these results, we identified an insect body infesting oatmeal, L. bostrychophila. The serum level of L. bostrychophila-specific immunoglobulin antibodies was higher than the cutoff value; therefore, we identified the disease as anaphylaxis caused by accidental ingestion of L. bostrychophila that infested the oatmeal stored in the container. We report the first case of L. bostrychophila-infested oatmeal as an orally ingested allergen in Japan., (© 2024 Japanese Dermatological Association.)

IgE and mast cells play key roles in the pathophysiology of allergic diseases. In 2003, omalizumab was the first anti-IgE mAb licensed in the United States when initially US Food and Drug Administration-approved for the treatment of allergic asthma. Since that time, the number of US Food and Drug Administration-approved indications for treatment with omalizumab has grown to include chronic spontaneous urticaria, chronic rhinosinusitis with nasal polyps, and food allergy. Although omalizumab is generally considered relatively safe and well tolerated, a number of safety concerns have been raised since its initial approval. These concerns focus on specific adverse events of interest, including anaphylaxis, pregnancy, malignancy, cardiovascular events, and infections. For each of these issues, data from clinical trials and postmarketing surveillance have been evaluated extensively. In this review, we examine these safety data, provide context for safety and risk assessments, and summarize a safety profile for each of the adverse events of interest. In doing so, we aim to provide a resource for shared decision making when treatment with omalizumab is being considered., Competing Interests: Disclosure statement Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Sugammadex hypersensitivity is an emerging safety concern. We aimed to describe the clinical and diagnostic features of perioperative hypersensitivity to sugammadex, and secondarily to provide an estimate of perioperative sugammadex hypersensitivity incidence in Australia., Methods: We retrospectively analysed cases of hypersensitivity to sugammadex diagnosed by positive intradermal or skin prick testing at six perioperative allergy clinics in Australia. We included all grades of hypersensitivity and compared life-threatening with non-life-threatening presentations. Incidence of hypersensitivity events was estimated relative to the estimated number of sugammadex administrations across two health services between January 1, 2010 and June 30, 2023., Results: Thirty cases were included (15 life-threatening and 15 non-life-threatening). The most common clinical signs were hypotension (n=25, 83.3%) and flushing/erythema (n=21, 70%). The median time to recognition of hypersensitivity was 5 (interquartile range 2-7.5) min. Five cases were recognised 10-30 min after administration. Serum tryptase was measured in 28 (93.3%) patients. Tryptase was positive in 15 (100%) life-threatening cases and nine (69.2%) non-life-threatening cases. The estimated incidence of sugammadex hypersensitivity was 0.004% (95% confidence interval 0.002-0.008%)., Conclusions: Sugammadex hypersensitivity presents similarly to other causes of perioperative hypersensitivity, however recognition can be delayed. The combination of positive serum tryptase and positive skin tests suggests an IgE-mediated mechanism of hypersensitivity. The estimated incidence of sugammadex hypersensitivity in Australia is lower than earlier reports., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The rate of diagnosis of mast cell activation syndrome (MCAS) has increased since the disorder's original description as a mastocytosis-like phenotype. While a set of consortium MCAS criteria is well described and widely accepted, this increase occurs in the setting of a broader set of proposed alternative MCAS criteria., Objective: Effective diagnostic criteria must minimize the range of unrelated diagnoses that can be erroneously classified as the condition of interest. We sought to determine if the symptoms associated with alternative MCAS criteria result in less concise or consistent diagnostic alternatives, reducing diagnostic specificity., Methods: We used multiple large language models, including ChatGPT, Claude, and Gemini, to bootstrap the probabilities of diagnoses that are compatible with consortium or alternative MCAS criteria. We utilized diversity and network analyses to quantify diagnostic precision and specificity compared to control diagnostic criteria including systemic lupus erythematosus, Kawasaki disease, and migraines., Results: Compared to consortium MCAS criteria, alternative MCAS criteria are associated with more variable (Shannon diversity 5.8 vs 4.6, respectively; P = .004) and less precise (mean Bray-Curtis similarity 0.07 vs 0.19, respectively; P = .004) diagnoses. The diagnosis networks derived from consortium and alternative MCAS criteria had lower between-network similarity compared to the similarity between diagnosis networks derived from 2 distinct systemic lupus erythematosus criteria (cosine similarity 0.55 vs 0.86, respectively; P = .0022)., Conclusion: Alternative MCAS criteria are associated with a distinct set of diagnoses compared to consortium MCAS criteria and have lower diagnostic consistency. This lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses., Competing Interests: Disclosure statement Suported by the Bill and Melinda Gates Foundation (OPP1113682 to P.K.); the National Institute of Allergy and Infectious Diseases (NIAID) grants U19AI057229 and U19AI67903; NIAID contract 75N93022C00052; Department of Defense contracts W81XWH1910235 and W911NF2320019; and the National Institute of Child Health and Human Development (grant K12HD000850). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of anaphylaxis is increasing worldwide. However, there is a lack of data on anaphylaxis trends in Türkiye. This study aims to analyse trends in anaphylaxis-related emergency department (ED) visits and examines factors associated with fatal anaphylaxis in Türkiye., Methods: We retrospectively analyzed data from Türkiye's Ministry of Health database from 2015 to 2022. Codes from the International Classification of Diseases, 10th revision (ICD-10), were used to identify anaphylaxis., Results: During the study period, a total 21,370 ED admissions for anaphylaxis were identified, and anaphylaxis admissions increased 1.23-fold from 3.90 to 4.79 per 10 5 population per year. The anaphylaxis trigger was unknown in 79.9% of cases, followed by drugs (11.7%), food (5.7%) and venom (2.7%). Epinephrine was administered in 49.6% of cases, and a total of 424 patients (2.1% of total cases) died. The frequency of intensive care unit (ICU) hospitalization increased 6.0-fold from 2015 to 2021, and age-adjusted average-weighted mortality rate for anaphylaxis was 0.66 per million. Older age, presence of asthma, and ICU hospitalization were found to be significantly associated with fatal anaphylaxis (p < 0.001 for all). Frequencies of death were 9.1% for venom anaphylaxis, 1.2% in drug anaphylaxis, and 0.2% for food anaphylaxis. Epinephrine autoinjector (EAI) was prescribed for 6.9% of all patients., Conclusions: This is the first study of ED admissions for anaphylaxis using a large, nationwide data from Türkiye. Increasing numbers of ED admissions, ICU hospitalizations and mortality show that anaphylaxis is an important public health issue in Türkiye., Competing Interests: None., (© 2024 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organization.)

Excipients have been identified as 'inert' substances that often enhance the non-pharmacological aspects of a medication. However, recent clinical evidence elucidates their potential in inducing anaphylaxis and indicates that they are often overlooked as potential allergens in routine clinical practice. The aim of the study was to assimilate published evidence on excipient-induced allergies associated with the use of oral medications and to underline their potential as potent allergens. A systematic literature search of MEDLINE, EMBASE and International Pharmaceutical Abstracts databases was performed for case reports published from inception to June 2024. Studies were excluded if they were animal and laboratory studies or not published in English, full-text articles were unavailable, and they lacked essential information. This systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Polyethylene glycol was the most prevalent allergenic excipient, followed by colouring agents. Clinical manifestations exhibited wide variability ranging from mild to life-threatening reactions, and the most common presentations were urticaria and angioedema. Most patients recovered spontaneously after withdrawal of the offending agent with less than half necessitating additional drug interventions and only a single instance of reported fatality, which cannot be attributed to the excipient alone. Despite being labelled as inert, excipients pose a significant threat for the development of allergic reactions. Simple measures such as increased awareness among patients and healthcare professionals, comprehensive history taking, reviewing medication compositions and improved patient awareness regarding potentially allergenic excipients can aid in avoiding these readily preventable reactions., (© 2024 Royal Australasian College of Physicians.)

Aim: A retrospective study will review episodes of anaphylaxis during bee venom immunotherapy (BVIT) in children, any modifications made to the dosing schedule, and the subsequent outcomes over a nine-year period in Western Australia., Methods: Patient demographics, dose eliciting anaphylaxis during BVIT, modifications made to BVIT regimen following anaphylaxis (i.e., continuation, modification, or cessation), and the subsequent outcomes were collected for children commenced on BVIT from 1st September 2012 to 31st August 2021., Results: A total of 624 children were commenced on BVIT from 2012 to 2021. 12/624 (1.9%) did not complete the recommended duration of BVIT, the majority of which were due to poor compliance. 33 children (5.2%) developed anaphylaxis. 2/33 children (6.0%) experienced anaphylaxis on multiple occasions, resulting in 36 separate episodes of anaphylaxis. Most of the anaphylactic episodes occurred on Day 1 of BVIT (56%). 23/35 children (65.7%) developed anaphylaxis during the build-up phase and 12/35 children (34.3%) developed anaphylaxis during the maintenance phase. For those who experienced anaphylaxis in the build phase, 6/23 children (26.0%) continued with immunotherapy on the same day, and 5/6 of these children (83.3%) tolerated the same-day continuation of immunotherapy; 17/23 children (73.9%) ceased immunotherapy and restarted on another day, with 11/17 children (64.7%) tolerating cessation and recommencement of the regimen on another day. For those who developed anaphylaxis during the maintenance phase, 6/12 children (50.0%) tolerated ongoing immunotherapy., Conclusions: Children who experience anaphylaxis during the build-up phase of BVIT showed a low risk of further anaphylaxis with proceeding immunotherapy on the same day. Children who experience anaphylaxis during the maintenance phase of BVIT appear less likely to tolerate ongoing immunotherapy due to the recurrence of anaphylaxis., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Irinotecan is a topoisomerase I inhibitor used for the treatment of various cancers, such as gastrointestinal, pancreatic, pulmonary, ovarian, and cervical cancers. Among chemotherapy agents, it represents a rare trigger of drug hypersensitivity reactions, with few cases being reported until today. Methods: -induced grade IV (WAO classification) anaphylaxis. An IgE-mediated reaction was confirmed in our case, as evidenced by a positive intradermal skin test result, and we carried out a successful desensitization protocol, given irinotecan -induced grade IV (WAO classification) anaphylaxis. An IgE-mediated reaction was confirmed in our case, as evidenced by a positive intradermal skin test result, and we carried out a successful desensitization protocol, given irinotecan's indispensability in the treatment regimen. Our case underscores the fact that in such situations where the culprit drug is also the only therapeutic option available for such a patient, implementing a desensitization protocol may represent the only viable approach to ensure safe and successful dosing. Results: A comprehensive review of the literature was also conducted to assess previously reported irinotecan -induced hypersensitivity reactions, the utility of skin tests in identifying sensitisation to irinotecan , and the existing desensitization protocols. We found a total of seventeen cases of hypersensitivity reactions to irinotecan in the literature, out of which four provided the skin test results obtained and six performed desensitization protocols for irinotecan . Conclusions: Our literature review highlights that skin testing and desensitization protocols can provide suitable solutions for managing hypersensitivity reactions to irinotecan .

Non-specific Lipid Transfer proteins (nsLTPs) are relevant allergens of several pollens and plant foods. Sensitization to nsLTPs is not typical in our region. Still, it has become an increasingly common cause of IgE-mediated food allergies and food-induced anaphylaxis in Northern Europe in recent decades. No in-depth studies describe the prevalence of sensitization of molecular components to nsLTPs in Lithuania. This study aimed to determine the sensitization profile of atopic patients at the Immunology and Allergy Department of Kauno Klinikos to the components of nsLTPs, using molecular allergen component analysis. Sixty Lithuanian adults with symptoms of allergic rhinitis and/or allergic asthma and/or food allergies were included into the study. Specific immunoglobulin E (IgE) levels were measured using two in vitro techniques: allergen extract and molecular component analysis. Results showed that 25% of subjects were sensitized to nsLTP-containing allergen sources, mostly to Zea m 14, Mal d 3, Vit v 1, and Art v 3. The median amount of total IgE was higher in nsLTP-sensitized patients than in nsLTP-nonsensitized patients. Based on Cohen's Kappa and McNemar tests, the results of allergen extract and component analysis tests do not always agree, especially when we determine the sensitization to allergen sources containing nsLTPs. Molecular allergen component analysis could be the first choice in determining detailed sensitization to nsLTPs in patients who experienced anaphylaxis of unknown origin.

Pollen-food allergy syndrome is an IgE-mediated allergic reaction arising from cross-reactive homologous allergens found in both food and pollen. Allergens, such as pathogenesis-related protein class 10 and profilin, usually trigger oropharyngeal itching and numbness in patients, whereas lipid transfer proteins tend to induce anaphylaxis. This article presents a case study of an individual with Artemisia pollen allergy who experienced anaphylaxis after consuming red fruit ginseng, a perennial herb belonging to the Campanulaceae family. This study revealed a novel allergen component mediating cross-allergy between Artemisia pollen and food, fructose-bisphosphate aldolase, which has not been documented in the literature concerning the pollen-food allergy syndrome. Fructose-bisphosphate aldolase tends to induce anaphylaxis in patients with Artemisia pollen-allergy and warrants clinicians' attention., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Li et al.)

Background: Peripheral Inserted Central Catheter (PICC) is a commonly utilized medical device for long-term intravenous therapy in healthcare settings. However, there has been a notable increase in anaphylaxis associated with PICC catheterization, which should not be neglected., Aims: The purpose is to raise awareness about the occurrence of anaphylaxis or anaphylactoid reactions associated with PICC and to emphasize the need to explore effective methods to prevent this emergency event in the future., Method: This retrospective observational study was conducted at Sun Yat-sen University Cancer Center between January 2021 and August 2023., Results: 0.10% (13 out of 12,612) of cancer patients suffered from anaphylactic reactions during PICC catheterization. The duration time of anaphylaxis or anaphylactoid reactions was approximately 8 min, with a range of 5-10 min. The signs and symptoms combined with respiratory and cardiovascular system symptoms. Most patients were relieved spontaneously by oxygen inhalation and completed catheterization after their symptoms were alleviated., Conclusion: The increasing incidence of anaphylaxis related to PICC catheterization necessitates greater awareness among healthcare providers. Further research is needed to identify the exact culprits during PICC insertion and develop effective strategies for preventing anaphylactic reactions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Anaphylaxis is an acute, potentially fatal systemic hypersensitivity reaction with varied mechanisms and clinical presentations. Although prompt recognition and treatment of anaphylaxis are imperative, both patients and healthcare professionals often fail to recognize and diagnose its early signs. Clinical manifestations vary widely, however, the most common signs are cutaneous symptoms, including urticaria and angioedema. Immediate intramuscular administration of epinephrine into the anterolateral thigh is first-line therapy, and is always safe even if the diagnosis is uncertain. The mainstays of long-term management include specialist assessment, allergen avoidance measures, and the provision of an epinephrine auto-injector with an individualized anaphylaxis emergency plan. This article provides an overview of the causes, clinical features, diagnosis, and acute as well as long-term management of anaphylaxis., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval and consent to participate are not applicable to this review article. Consent for publication: Not applicable. Competing interests: Dr Elissa M. Abrams is an employee of Public Health Agency of Canada (PHAC); views expressed are her own and not those of PHAC. She is Section Head for Anaphylaxis/Food Allergy, and a Member of the Canadian Society of Allergy and Clinical Immunology (CSACI). Dr. Waleed Alqurashi has received grant funding from the Canadian Institute for Health Research. Dr. David A. Fischer is a previous President of the Canadian Society of Allergy & Clinical Immunology (CSACI). He has received consulting fees and honoraria for continuing education from AstraZeneca, GSK, Bausch Health, Valeo, AbbVie, Takeda, ALK, Pfizer, Aralez, Merck, Novartis, Sanofi, Pediapharm and Teva Pharmaceuticals. Dr. Timothy K. Vander Leek has participated in advisory boards and has received consulting fees and honoraria from Aralez/Miravo, Bausch Health, and Covis Pharma. Dr. Anne K. Ellis has participated in advisory boards for ALK-Abello, AstraZeneca, Bausch Health, LEO Pharma, Miravo, Merck, Novartis, has been a speaker for ALK-Abello, AstraZeneca, Bausch, Miravo, Medexus, Mylan, Novartis, Pfizer, Sanofi, StallergenesGreer and Regeneron. Her institution has received research grants from ALK Abello, Aralez, AstraZeneca, Bayer LLC, Medexus, Novartis, Sanofi and Regeneron. She has also served as an independent consultant to Bayer LLC, Pharming, and Regeneron. About this supplement: This article has been published as part of Allergy, Asthma & Clinical Immunology, Volume 20 Supplement 03, 2024: Practical Guide for Allergy and Immunology in Canada 2024. The full contents of the supplement are available at https://aacijournal.biomedcentral.com/articles/supplements/volume-20-supplement-3 ., (© 2024. The Author(s).)

Background: Management of patients with food allergies is complex, especially in cases of patients with multiple and potentially severe food allergies. Although international guidelines exist for food allergy management, the role of the allergist in the decision-making process is key., Objective: Our aim was to investigate the management patterns and educational needs of practicing allergists treating patients with food allergies., Methods: An online survey was e-mailed to United States-based practicing allergists (N = 2833) in November-December 2021. The allergists were screened for managing 1 or more patients (including ≥25% pediatric patients) with food allergies per month. The allergists responded to questions regarding food allergy management in response to 2 hypothetical pediatric case studies, their familiarity with available guidelines and emerging treatments, and their future educational preferences. A descriptive analysis of outcomes was conducted., Results: A total of 125 responding allergists (4.4%) met the eligibility criteria and completed the survey. The allergists prioritized written exposure action plans, patient-caregiver communication, prevention of serious reactions, and consideration of both food allergy severity and allergic comorbidities in the management of patients with food allergies. With regard to recommending biologics in the future, the allergists identified patient history of anaphylaxis and hospitalizations, food allergy severity, and allergic comorbidities as all being important factors to consider when deciding on appropriate treatment options. The allergists noted their ongoing educational needs, especially for current and emerging treatments for food allergies., Conclusion: With the treatment landscape for food allergies evolving rapidly, the decision-making priorities and continuing educational needs of allergists will be important in optimizing the management of patients with food allergies., Competing Interests: Conducted by CE Outcomes, LLC, with support from Genentech, Inc, a member of the Roche Group. Disclosure of potential conflicts of interest: A. Anagnostou reports receiving institutional funding from Aimmune, Mike Hogg Foundation and Novartis; serving as an advisory board member for DBV Technologies and Novartis; receiving consultation and/or speaker fees from Adelphi, Aimmune, ALK, and Genentech, Inc. M. Greenhawt reports being a consultant for Aquestive; serving as an advisory board member for Aquestive, ALK-Abelló, Allergy Therapeutics, AstraZeneca, Bryn Pharma, DBV Technologies, Novartis, Nutricia, and Prota; serving as an unpaid member of the scientific advisory council for the National Peanut Board; sitting on the medical advisory board of the International Food Protein–Induced Enterocolitis Syndrome Association; serving as a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; acting as senior associate editor for the Annals of Allergy, Asthma, and Immunology; and serving as a member of the Joint Task Force on Allergy Practice Parameters. J. A. Lieberman reports serving as an advisory board member for Aquestive; sitting on the data and safety and monitoring board and/or adjudication committee for AbbVie and Siolta; acting as a consultant for ALK, Bayer, DBV, and Novartis; and serving as a board member for the American Board of Allergy and Immunology and Joint Task Force for Practice Parameters. C. E. Ciaccio reports providing research support from the Duchossois Foundation, Food Allergy Research and Education (FARE), National Institutes of Health, and Paul and Mary Yovovich; and serving as an advisory board member for Clostrabio, Genentech, Inc, and Siolta. S. B. Sindher reports receiving grants from Aimmune, Consortium for Food Allergy Research (CoFAR), DBV, the National Institute for Allergy and Infectious Diseases (NIAID), Novartis, Regeneron, and Sanofi and serving as an advisory board member for Genentech, Inc. B. Creasy, K. Baran, and S. Gupta are employees of Genentech, Inc, and stockholders in Roche. A. Nowak-Wegrzyn reports receiving research support from Astellas, Danone, DBV, the NIAID, and Nestlé; receiving consultancy fees from Gerber Institute, Novartis, and Regeneron; acting as deputy editor for Annals of Allergy, Asthma, and Immunology; and serving as chair of the medical advisory board of the International Food Protein–Induced Enterocolitis Syndrome Association., (© 2024 The Author(s).)

Background: Botulinum toxin type A (BTA) is a protein produced by Clostridium botulinum bacteria. It is the most widely used among botulinum toxin types, and it is recommended for the treatment of many clinical conditions, including muscle hyperactivity syndromes and for esthetic indications too. BTA is generally considered safe, and the most reported adverse events (AEs) include eyelids ptosis, immunogenicity, neuromuscular disorders and hypersensitivity reactions. In addition, serious idiosyncratic AEs, such as anaphylactic shock, have been highlighted., Objective and Methods: Taking into account that BTA skin toxicity has been already investigated recently by our research group and that, in many cases, the BTA-induced skin toxicity represents a symptom of an hypersensitivity reaction, the aim of the present study was to better characterize cases of anaphylaxis occurring after intramuscular administration of BTA by analyzing Individual Case Safety Reports (ICSRs) sent to the EudraVigilance database., Results: A total of 86 ICSRs, covering 449 Preferred Terms, reporting BTA as suspected drug and "anaphylactic reaction," "anaphylactic shock," "anaphylactoid reaction" or "anaphylactoid shock" as ADR were suitable for our analysis. The majority of patients who experienced BTA-induced anaphylaxis were female (89.5%) and mostly belonged to the age group 18-64 years. The most common outcome was "recovered/resolved," while the seriousness criteria was mostly reported as "caused/prolonged hospitalization.", Conclusion: Our results showed that anaphylactic reactions may occur after esthetic use of BTA; thus, a close monitoring before, during and after BTA intramuscular injection is highly recommended in order to prevent the occurrence of this event and ensure an appropriate management of the patients receiving this drug., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266., Competing Interests: Declarations. Conflict of Interest: The authors declare that they have no conflicts of interest to disclose. The authors confirmed that the research was conducted in the absence of any financial or commercial relationships that could be considered as a potential conflict of interest. Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed Consent: For this type of study, informed consent is not required., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Food allergy has been shown to negatively impact children's mental health and quality of life. However, its impact on school performance is unknown., Objective: We aimed to investigate whether food allergy, severe and nonsevere, is associated with school performance when accounting for measured and unmeasured familial factors., Methods: This was a register-based cohort study, with sibling controls, including all children born in Sweden 2001-5 (n = 456,164) with food allergy information based on hospital visits and prescriptions, grades, and national test results from all Swedish schools and confounders. Primary exposure was food allergy severity (none, nonsevere, or severe) in school years 7-9, and the primary outcome was total grades from year 9, with secondary exposures/outcomes also at younger ages. The primary outcome was analyzed by linear regression and, for sibling/twin control analyses, fixed effect linear regression. Results were replicated in a twin cohort (n = 31,609)., Results: In unadjusted and analyses adjusted for measured confounders, children with severe food allergy appeared to have better total grades than children without food allergy (β unadjusted  = 10.6 [95% confidence interval (CI), 8.6, 12.6] and β adjusted  = 5.5 [95% CI, 3.7, 7.4]). When also adjusting for unmeasured confounders shared by siblings, the difference was close to null and statistically nonsignificant (β sibling  = 1.6 [95% CI, -1.5, 4.7]; for nonsevere food allergy, β sibling  = -0.0 [95% CI, -2.2, 2.1]). The twin cohort results were similar., Conclusions: We found no consistent evidence of a negative effect of food allergy, either severe or nonsevere, on school performance when adjusting for measured and unmeasured confounders shared by siblings., Competing Interests: The Swedish Twin Registry is managed by 10.13039/501100004047Karolinska Institutet and receives funding through the 10.13039/501100004359Swedish Research Council under grant 2017-00641. Financial support was provided from the 10.13039/501100004359Swedish Research Council (grants 2018-02640 and 2023-02327), the Strategic Research Program in Epidemiology at 10.13039/501100004047Karolinska Institutet, the Swedish Heart–Lung Foundation (grants 20180512 and 20210416), the 10.13039/501100010234Swedish Asthma and Allergy Association Research Fund (grant 2020-0008), and the Foundation Frimurare Barnhuset in Stockholm. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Authors.)

Background: Understanding the trends of anaphylaxis and risk factors associated with its recurrence is essential for the effective management and prevention of this condition., Objective: This study aimed to analyze the prevalence trends of anaphylaxis and identify risk factors for recurrence, with a focus on the influence of neighborhood deprivation and comorbidities, across all age groups., Methods: We conducted a retrospective administrative cohort study on anaphylaxis utilizing the National Health Insurance-National Sample Cohort (NHIS-NSC) database in Korea (2002-2019). Anaphylaxis was defined with ICD-10 codes for the diagnosis combined with prescription codes. The Neighborhood Deprivation Index was used to identify the risk of recurrent anaphylaxis. Trends in the annual prevalence and recurrence of anaphylaxis were assessed through joinpoint regression and Cox proportional hazard models., Results: Out of the 1,137,861 individuals studied, 37,012 (3.25%) cases of anaphylaxis were identified. Among these, 5783 individuals (15.6%) experienced a recurrence, half of them experiencing it within the first year after the initial episode. The highest incidence of anaphylaxis was observed in children and adolescents, followed by middle-aged adults. A rapid increase in anaphylaxis cases was observed from 2002 to 2006 (Annual Percentage Change [APC], 33.2), followed by a more gradual increase until 2013 (APC, 12.8), and a stable trend from 2013 to 2019 (APC, 0.61). Males and adult age groups exhibited an increased risk of recurrence. Living in an area with neighborhood deprivation and the presence of comorbid conditions were associated with increased recurrence risk., Conclusions: The increasing prevalence of anaphylaxis and its association with certain risk factors calls for targeted intervention. Addressing neighborhood deprivation and comorbid conditions may aid in reducing the recurrence and overall burden of anaphylaxis., Competing Interests: The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be interpreted as potential conflicts of interest., (© 2024 The Author(s).)

The aim was to describe cases of anaphylaxis following the Attenuated Dengue Vaccine (TAK-003) in Brazil, from March 1, 2023, to March 11, 2024. A descriptive study of anaphylaxis cases following TAK-003 was conducted, as reported in the National System of Surveillance of Adverse Events Following Immunization (AEFI). Percentages and notification rates of AEFI per million doses administered (DA) were calculated. In total, 380,358 doses of TAK-003 were administered, and 626 AEFI were reported. Of these, 85 were cases of immediate hypersensitivity, with 24 (63.1 cases per million) being anaphylaxis, including three anaphylactic shock. For 10 (41.7 %) cases, reactions began within 15 min after vaccination. No deaths related to anaphylaxis were reported. In light of the safety signal identification (increased frequency of anaphylaxis post-dengue vaccination), the Ministry of Health of Brazil published recommendations for intensifying actions for safe vaccination, including healthcare professional training and post-vaccination observation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Diclofenac etalhyaluronate, an active pharmaceutical ingredient in JOYCLU ® (JCL), serves as a joint function improvement agent in knee and hip osteoarthritis patients. However, frequent cases of anaphylaxis induced by JCL administration have been reported. Recent clinical research suggests the potential utility of the basophil activation test (BAT) in predicting JCL-induced anaphylaxis. Nonetheless, the BAT is deemed impractical for routine diagnostic testing due to complex procedures involving whole blood stimulation and flow cytometry-based analyses. In the study reported here, an IgE crosslinking-induced luciferase expression (EXiLE) test which uses patient sera without complicated procedures, was performed with patients who had received JCL, with or without subsequent anaphylactic symptoms. The results of this test were then compared with those of the BAT reported in a clinical research study. Of the six BAT-positive JCL-induced anaphylaxis-experienced patients, four were positive in the EXiLE test and all non-experienced patients were negative in both the BAT and EXiLE tests, thus illustrating a high concordance rate of 92.3%. Further validation of testing conditions is expected to improve these rates. Notably, complement inactivation treatment led to a positive EXiLE result in a BAT-negative patient. In conclusion, it appears that the EXiLE test exhibits promise as an alternative to BAT for predicting JCL-induced anaphylaxis, and in so doing offers a simpler diagnostic approach.

Latex allergy, or natural rubber latex allergy (NRLA), is a global health concern, even among the pediatric population, with symptoms varying in severity from mild to potentially life-threatening. Latex is derived from the Hevea Brasiliensis tree, producing twelve million tons annually for use in various everyday and medical products. Despite efforts to mitigate NRLA, its prevalence remains high, especially in at- risk groups such as children with spina bifida. Clinical manifestations include immediate and delayed symptoms, even anaphylactic reactions. Diagnosis involves a detailed medical history and specific tests. Prevention focuses on avoiding exposure, especially in medical and educational settings. Treatment, including immunotherapy, exhibits variable efficacy. NRLA has a strong negative impact on children's quality of life. The objective of this publication is to provide updated information and practical tools for the pediatrician's and allergist's practice., (Sociedad Argentina de Pediatría.)

In very cold environments, it may be burdensome or impossible for the polar medic to prevent medicines from freezing. We sought to investigate whether orientation affected the risk that glass ampoules of 1 in 1000 adrenaline, an important emergency drug, would break during freezing and subsequent thawing. Ampoules of adrenaline were orientated either upright, horizontally or inverted. They were exposed to freezing temperatures (-25°C or -80°C) and then allowed to thaw. A crossover design was used whereby the orientation of unbroken ampoules was changed for the next trial. No ampoules broke when frozen at -25°C and then thawed. When this was repeated at -80°C, ampoules reliably broke unless they were upright with no liquid in the top part of the ampoule. Upright orientation prevents the breakage of glass ampoules of 1 in 1000 adrenaline rapidly frozen at -80°C. The polar medic may consider storing ampoules upright if they are to be exposed to very low temperatures.

Purpose of Review: Biphasic anaphylaxis is a variant of anaphylaxis characterized by recurrence of symptoms after initial resolution of anaphylaxis. It was first described in the mid 1990s by Popa and Lerner. Our understanding of the pathophysiology and epidemiology of the condition has advanced considerably since then. The purpose of this manuscript is to review the literature surrounding biphasic anaphylaxis while highlighting key works and recent advances., Recent Findings: Prior studies have estimated biphasic anaphylaxis occurs in 0.4-20% of anaphylaxis episodes. The wide range may be related to differences in anaphylaxis diagnostic criteria which was inconsistent across studies. Recently identified risk factors for occurrence of biphasic anaphylaxis include severe initial symptoms including hypotension or hypoxia, delay in epinephrine use, and greater than one dose of epinephrine required to treat symptoms. Despite our progress to better understand biphasic anaphylaxis, there remain gaps in the literature. This article aims to review the recent literature including, epidemiology, risk factors, and management of biphasic anaphylaxis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Arylpropionic acid derivatives (APs) are the main triggers of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Data on clinical patterns and risk factors for AP hypersensitivity in children are quite limited., Aim: To assess the clinical characteristics and potential risk factors for proven AP hypersensitivity in children., Method: Patients with a history of AP hypersensitivity were retrospectively assessed using a standardized diagnostic algorithm. Children with confirmed hypersensitivity were defined as selective responders or cross-intolerants based on the result of drug provocation tests and further categorized according to the EAACI/ENDA classification. A multivariable logistic regression analysis was performed to analyze the potential risk factors for proven AP hypersensitivity., Results: A total of 166 patients (51.2% male, median age of six years) with a history of AP hypersensitivity were included. Ibuprofen (89.2%) was the most frequently reported AP in the patients' histories. The reported hypersensitivity of 40 (22.4%) patients was confirmed by diagnostic testing: eight (13.6%) patients with a history of reaction only to APs and 32 (29.9%) patients with a history of reactions to multiple NSAIDs, including chemically unrelated NSAIDs in addition to APs. Five (12.5%) patients were classified as selective responders and 35 (87.5%) were cross-intolerants. Overall, five (12.5%) of the confirmed cases could not be categorized according to the EAACI/ENDA classification. Older age (aOR: 1.11, 95% CI 1.02-1.21, p = 0.015), chronic urticaria as an underlying disease (aOR: 2.87, 95% CI 1.09-7.54, p = 0.033) and a history of anaphylaxis (aOR: 7.84, 95% CI 1.86-33.04, p = 0.005) were related to confirmed AP hypersensitivity., Conclusion: Almost a quarter of children and adolescents were confirmed to have AP hypersensitivity. Older age, the presence of chronic urticaria and a history of anaphylaxis were potential risk factors for proven AP hypersensitivity., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

It has previously been shown that EpiPen® autoinjectors are likely to activate normally following up to five excursions to -25°C but data about the post-freezing performance of other brands of adrenaline autoinjectors has not previously been published. Additionally, conditions experienced by polar medics may be substantially colder than this and the performance of adrenaline autoinjectors following more extreme freeze-thaw cycles remains uncharacterised. Investigators in Antarctica and the United Kingdom performed laboratory testing on two brands of adrenaline autoinjector, EpiPen® and Jext® (12 devices of each type). A single freeze-thaw cycle involved freezing the device to -80°C then allowing it to come to room temperature. Devices were exposed to 0, 1, 5 or 15 freeze-thaw cycles. The mass of liquid ejected from each device, when activated, was then measured. No significant differences in the mass of the liquid ejected was found between the test groups. Multiple freeze-thaw cycles to -80°C are unlikely to significantly impact the amount of adrenaline solution expelled from EpiPen® and EpiPen® autoinjectors. This preliminary finding encourages further work investigating the safety and effectiveness of adrenaline autoinjectors after exposure to very low temperatures. This information would be valuable for future polar medics planning and delivering medical provision in extreme environments.

Incidences of multiple bee stings have been increasing globally; the substantial amount of bee venom injected in such incidents can result in anaphylactic shock, rhabdomyolysis and renal failure, proving fatal in some cases. While anaphylactic reactions are more common and have established treatment protocols, inflammatory response induced by the venom demands a tailored approach. Here we report a case of a 70-year-old male in India who succumbed from approximately 500 bee stings. Based on our literature review, this case stands out as one of the first reported fatalities caused by 500 bee stings in our country. The unidentified species of bees in this case makes management of such bee venom-related toxic reactions more difficult. This report emphasises the importance of prompt and appropriate interventions., Competing Interests: Declaration of conflicting interestsThe authors declare that we have no conflict of interest with respect to the research, authorship and/or publication of this article.

Background: Standard of care for anaphylaxis treatment is intramuscular (IM) epinephrine. An epinephrine nasal spray (ENS) is under development as an alternative form of administration., Objective: To compare the pharmacokinetic and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine autoinjector., Methods: Data from 4 open-label phase 1 crossover studies conducted in healthy adults were pooled to determine the pharmacokinetic and PD profile of a single 13.2 mg ENS dose delivered by 2 consecutive sprays of 6.6 mg each in opposite (n = 224 doses) or the same nostril (n = 75 doses) compared with the 0.3 mg IM autoinjector (n = 215 doses). Each participant served as their own control. Blood samples and vital signs were collected predose and at multiple intervals from 0 to 360 minutes postdose., Results: ENS rapidly increased the plasma epinephrine concentration, with levels that were overall greater than IM autoinjector. Median (range) time to maximum plasma epinephrine concentration with ENS opposite nostrils, ENS same nostril, and IM autoinjector was 25.1 (1.3-362.1), 20.1 (3.0-120.2), and 20.0 (1.0-121.3) minutes, respectively. The area under the plasma concentration-time curve for 0 to 360 minutes was significantly higher with ENS than with the IM autoinjector (geometric mean ratio [90% CI], 155% [140%-172%] with ENS opposite nostrils, 159% [138%-182%] with ENS same nostril). The PD effects on heart rate and blood pressure were similar in pattern and magnitude among all 3 treatment groups., Conclusions: ENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM autoinjector and with a similar PD effect., (Copyright © 2024. Published by Elsevier Inc.)