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Introduction: Venom immunotherapy (VIT) and adrenaline autoinjector (AAI) are important therapies in venom anaphylaxis. Adherence to VIT and AAI in patients with venom allergy has been evaluated in a few studies; however, solid data are lacking. This study aimed to evaluate VIT and AAI retrieval rates in patients with venom allergy with a special focus on adherence to treatment. Adherence was compared to subcutaneous immunotherapy (SCIT) with inhalant allergens. Methods: This was a retrospective study among patients registered for allergen immunotherapy at the Allergy Center, Odense University Hospital, Denmark, from January 1, 2010, to December 31, 2014. Data on purchased immunotherapy and AAI were obtained from the Danish National Health Service Prescription Database. Multivariable logistic regression was used to analyze if allergen, age, sex, mastocytosis, and treatment site affected adherence. Results: The 3-year adherence to VIT was 92.4% (244/264) compared to 87.4% (215/246) in SCIT with inhalant allergens, and the 5-year adherence to VIT was 84.1% (222/264) compared to 74.8% (184/246) in SCIT with inhalant allergens (p = 0.045). Females treated with VIT were more adherent than males (p = 0.45 [3-year], p = 0.008 [5-year]), whereas allergen, age, mastocytosis, or treatment site did not significantly affect adherence. Only 28.6% of patients (12/42) purchased an AAI after premature termination of VIT. Conclusion: In this register-based study, we found that the 3- and 5-year adherences to VIT and SCIT with inhalant allergens are at the upper end of the spectrum hitherto reported. Patients' 5-year adherence to VIT was higher than patients' 5-year adherence to SCIT with inhalant allergens. If VIT was prematurely terminated, less than 1/3 would have purchased an AAI. [ABSTRACT FROM AUTHOR]

Venom immunotherapy (VIT) protects up to 98% of treated Hymenoptera allergy patients from reactions with new stings. A correct diagnosis with the identification of the venom causing the allergic reaction is essential to implementing it. The knowledge of the Hymenoptera foraging habits when the sting takes place in a food environment would allow the culprit insect to be known. Images of Hymenoptera occurring in environments where there was human food were recorded in Spain, including the date of the image, the place description and its geolocation. The insects' genus and species were identified by an entomologist. Results: One hundred and fifty-five images depicting 71 insects were analyzed. The identified insects were Vespula (56), Vespa (7), Polistes (4), Cerceris (2), Bombus (1) and Apis (1). Most (97.1%) of the images were obtained in summer and early autumn, outdoors in terraces (64%). Meat was the food associated with 47.9% of the images. In protein-rich foods, Vespula was found in 89%. Conclusions: Vespula was the main Hymenoptera associated with food environments in our country (78.87%), and in most of the cases (71%), the food involved is a source of protein, such as meat or seafood. In that environment, the probability that the insect is a Vespula would be 89%. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy (AIT) was born in 1911 and great progress has been made over the last 110 years, from the invention of subcutaneous and sublingual administration to new strategies. It can be applied in respiratory allergies, such as rhinoconjunctivitis and asthma, with even long-term effects in the use of drugs, symptoms, hospitalizations and prognosis. Many protocols are described in venom allergy, but it is not yet established which is the best and further studies are needed to guide personalized treatment. The use in food allergies is growing, it determines immunological changes in a long-term process, with results that are different between adulthood and pediatric age. Sensitization to allergenic molecules is a gradual process that starts from one or a few molecules, often asymptomatic, to a polymolecular sensitization through a “molecular spreading”. New strategies in AIT have been proposed in recent years, such as the use of adjuvants and modifications of allergens, while biomarkers that allow optimization of treatment with AIT are continually being studied.

Objective: Venom immunotherapy (VIT) is recommended as the first-line therapy in patients with Hymenoptera venom allergy. The frequency of adverse reactions and side effects during VIT has been reported at variable rates. Our study aims to investigate the factors affecting of primary bee sting allergic reactions, re-sting allergic reactions in the course of VIT, and allergic reactions due to VIT injections. Material and Method: The patients, who received VIT in the Ege University Medical Faculty, Department of Internal Medicine, Division of Allergy and Clinic Immunology, allergy outpatient clinic between January 2014 and September 2019, were reviewed retrospectively. Demographic data, basal serum tryptase (BST) levels, the severity of primary sting reactions according to Mueller classification, use of antihypertensive drugs, skin prick test and venom-specific IgE results, presence of allergic reactions after VIT injections and re-sting reactions in the field were investigated. Results: Sixty-seven (n=67, 23 F/44 M) patients with a median age (min-max) of 46 (19-66) were included. 43% (n=29) were receving VIT with Apis mellifera venom, 48% (n=32) Vespula vulgaris, and 9% (n=6) of them were receiving VIT with both venom types. In skin tests, positivity was detected with a single venom in 69% of patients, positivity was detected with double venom in 30%, and positivity with all 3 venom allergen extracts (Apis, Vespula, and Polistes) in 1% of patients. The frequency of systemic reaction during VII was higher in patients who were sensitive to two bees in skin tests (Apis + Vespula); the frequency of large who are sensitive to three bees (Apis + Vespula + Polistes) (p=0.005). The frequency of local bee-sting reactions was higher in patients using antihypertensive drugs (n=6) and the frequency of systemic reactions was higher in patients who did not use the antihypertensive drugs (p=0.001). Primary hypersensitivity reactions (HSR) of the patients were graded according to Mueller classification, and groups were compared according to the mean BST levels. While no significant difference was found between grade 2 HSR (BST: 5.21 ng/ml) and grade 3 HSR (BST: 5.10 ng/ml); the mean BST value (10 ng/ml) in patients with grade 4 reaction were significantly higher than the other groups (p=0.023). The patients were classified according to the type of VII and the groups were compared according to the mean BST levels. The BST level of the patients sensitive to both bee types (Apis+Vespula) (14.92 ng/ml) was compared to the BST level of the Vespula-only sensitive patients (6.57 ng/ml) and the BST level of the Apis-only sensitive patients only (6.09 ng/ml) ((p=0.020 vs 0.016)]. When the patients were evaluated according to the type of bee to which they were sensitive, the primary reaction, the re-sting reaction, and the reaction during VIT were compared and no significant results were found. Conclusion: The use of antihypertensive does not increase the frequency of life-threatening reactions with bee stings both during VIT and re-sting reactions in the field. During VIT; There is an increase in all reactions, especially in the dose escalation phase. Systemic reaction development during VIT is significantly higher in those with sensitivity to both venoms in skin tests. The BST value of patients who are susceptible to both venoms and whose primary reaction is Mueller class 4 should be investigated. Bee species and venom specific IgE levels do not affect the frequency of allergic reactions. [ABSTRACT FROM AUTHOR]

Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera, and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aimed to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross‐reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on available immunotherapies. Major allergens of most insects were identified, and cross‐reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy. [ABSTRACT FROM AUTHOR]

The impact on health‐related quality of life (HRQL) plays a key role for patients suffering from allergies and anaphylaxis. In this narrative review we review the HRQL in allergic patients suffering from food and venom allergy, both being the most frequent elicitors of severe allergic, potential life‐threatening reactions and provide an overview on the current knowledge and identified gaps. The data show that for food and venom allergy standardized assessment tools to measure HRQL are available and have been successfully applied. Our analysis shows that multiple factors can modulate HRQL in these patient groups. These include sociodemographic data like patients' age and sex, fear of accidental reactions but also external factors like the social environment and the appreciation of the seriousness of the condition by others. External factors may have a significant impact on HRQL and should be considered in patient‐related outcome assessments to avoid biased measurements possibly affecting the results. The assessment of the quality of life in the context of specific immunotherapy should consider lifestyle factors and ideally, the individual change in HRQL should be measured. Although there are many data indicating a negative impact on HRQL in food allergic children and their caregivers, limited data are existing from adults with food allergy and venom allergic patients from all age groups. Also, the use of standardized questionnaires should be extended to allow for a better comparability of results between studies. Therefore, translation to additional languages is necessary. Taken together, the eliciting allergen, the severity of the allergic disease but moreover multiple external factors impact the outcome in HRQL and should be considered in HRQL assessment. [ABSTRACT FROM AUTHOR]

Venom immunotherapy (VIT) protects up to 98% of treated Hymenoptera allergy patients from reactions with new stings. A correct diagnosis with the identification of the venom causing the allergic reaction is essential to implementing it. The knowledge of the Hymenoptera foraging habits when the sting takes place in a food environment would allow the culprit insect to be known. Images of Hymenoptera occurring in environments where there was human food were recorded in Spain, including the date of the image, the place description and its geolocation. The insects’ genus and species were identified by an entomologist. Results: One hundred and fifty-five images depicting 71 insects were analyzed. The identified insects were Vespula (56), Vespa (7), Polistes (4), Cerceris (2), Bombus (1) and Apis (1). Most (97.1%) of the images were obtained in summer and early autumn, outdoors in terraces (64%). Meat was the food associated with 47.9% of the images. In protein-rich foods, Vespula was found in 89%. Conclusions: Vespula was the main Hymenoptera associated with food environments in our country (78.87%), and in most of the cases (71%), the food involved is a source of protein, such as meat or seafood. In that environment, the probability that the insect is a Vespula would be 89%.

Background: Anaphylaxis is a severe systemic hypersensitivity reaction that usually has a rapid onset and can be fatal. Presentations of childhood anaphylaxis vary widely in accordance with the triggers and the patient's age, geographical region and dietary and lifestyle habits., Methods: The medical records of 177 paediatric patients diagnosed with anaphylaxis between January 2021 and January 2024, whose disease progression was monitored at a single tertiary care centre, were reviewed retrospectively., Results: The study included 177 patients diagnosed with anaphylaxis (107 males and 70 females with a median age of 48 months). The most common allergen responsible was food (53.7%). Egg allergy was the most common source of anaphylaxis, afflicting 35 patients (19.3%), while beta-lactam provoked the most common drug allergy, affecting 24 patients (13.6%). The most common organ involved was the skin (92.7%). When the patients were analysed by age group, there were more males in the infancy, preschool and school age groups, while there were more females in the adolescent group (p = 0.44). Food-induced anaphylaxis became less common with increasing age, whereas the rate of drug-induced anaphylaxis increased (p = 0.01 and p = 0.01, respectively). Cardiovascular system findings were observed more frequently in adolescents compared to other age groups (p = 0.003). Most cases stemming from a food allergy were mild, whereas most drug-induced cases were moderate or severe (p < 0.05). When severity was analysed by age group, mild cases in infants were more common than moderate to severe cases., Conclusion: The aetiological and clinical manifestations of childhood anaphylaxis vary among different age groups., Competing Interests: The authors declare no conflict of interest.

Hymenoptera stings are one of the most common causes of anaphylaxis. Vespa orientalis (red hornet) is a common and very aggressive hymenopteran endemic in central and southern areas of Iran. Allergy testing and venom immunotherapies are carried out with venom components which are expensive, have limited commercial availability, and often lack specificity. Although proteomic analysis of hymenopteran venom has been shown to be a powerful technique to identify allergens, data on the protein components of V. orientalis venom are lacking. This study was designed to characterize the allergenome profile (proteome of allergenic proteins) of this local hornet venom. Venom was extracted from V. orientalis worker venom sacs. The venom constituents were separated by two-dimensional gel electrophoresis (2DE). Protein components were blotted and probed with serum from 10 allergic patients by immunoblotting. Reactive spots were isolated and characterized by liquid chromatography with tandem mass spectrometry. A total of 195 protein spots were detected on the 2DE gels. Fifteen distinct venom proteins showed reactivity to IgE in patients' sera. Four major allergens in order of allergenicity in patients were identified as hyaluronidase, arginine kinase, phospholipase A1 (PLA1) and PLA1 magnifin. Broadening our knowledge of V. orientalis venom constituents can contribute to improvements in diagnostic and immunotherapeutic techniques, both of which are dependent on the major allergens in venom extract. This information is also potentially helpful to develop medical uses of major allergens in this venom to improve the diagnostic specificity and the efficacy of immunotherapy. [Display omitted] • Serum samples from patients allergic to Vespa orientalis venom show reaction mainly to hyaluronidase. • Three isoforms of arginine kinase show allergenicity in Vespa orientalis venom sensitized patients. • Like other vespids, enzymes with phospholipase activity are among the major allergens of red hornet venom. [ABSTRACT FROM AUTHOR]

Aim: Allergic reactions that develop after venom can be serious and fatal. The only treatment that can prevent these serious reactions is venom immunotherapy. Studies on venom immunotherapy in paediatric patients are limited. Aim of this study to evaluate the demographic data and laboratory results of paediatric patients who have received venom immunotherapy. Materials and Methods: The study included 45 patients who have received subcutaneous venom immunotherapy in Department of Paediatric Allergy and Immunology. Results: Thirty-three of the patients (73.3 %) were boys and 12 (26.7 %) were girls, the median age was 14 years (min.: 6, and max. 18). Apis mellifera venom was given to 24 (53.3 %) of 45 patients, and Guapes species venom immunotherapy was given to 21 (46.7 %) patients. While 15 (33.3 %) patients who received immunotherapy were living in Malatya, 30 patients were living in various provinces of the Eastern Anatolia region. While wide local reaction developed in 15 (33.3%) of the patients, systemic reaction developed in 3 (6.7 %) patients during venom immunotherapy. Apis mellifera prick test median diameter was determined as 4 mm and median of Apis specifc Ig E value was determined as 6 kU/L. Guapes species prick test median diameter was determined as 4 mm and median of Guapes specifc Ig E value was determined as 4 kU/L. Conclusion: Immunotherapy with Apis venom was more than Guapes venom in current study. Large local reaction was observed in 1/3 of the patients during immunotherapy. Therefore, attention should be paid in terms of systemic allergic reactions and large local reactions during immunotherapy. All necessary precautions should be taken during the immunotherapy. [ABSTRACT FROM AUTHOR]

Mastocytosis is a risk factor for Hymenoptera venom anaphylaxis (HVA). Current guidelines recommend measuring tryptase in patients with HVA and that those with mastocytosis pursue lifelong venom immunotherapy (VIT). Available data on HVA and mastocytosis largely derive from European single-center studies, and the prevalence of HVA with and without mastocytosis in the United States is unknown. We sought to determine the prevalence of HVA and mastocytosis in the United States using an insurance claims database and evaluate the impact of mastocytosis on VIT in patients with HVA in a US cohort. The IBM Watson Database, consisting of insurance claims from approximately 27 million US patients in 2018, was queried to identify patients with HVA and/or mastocytosis. Furthermore, a retrospective study of 161 patients undergoing VIT between 2015 and 2018 at the University of Michigan was conducted. In the IBM Watson Database, the prevalence of HVA was 167 per 100,000 (0.167%) and the prevalence of mastocytosis 10 per 100,000 (0.010%) overall and 97 per 100,000 (0.097%) among those with HVA. Mastocytosis showed a 9.7-fold increase among patients with HVA versus the general population. In the U-M cohort, 2.6% of patients with VIT had mastocytosis. Tryptase level did not correlate with venom reaction severity but was higher in patients with systemic VIT reactions. We observed a lower US HVA prevalence than previously reported. Mastocytosis was more common in US patients with HVA, though at lower rates than previously reported. In patients with VIT there was no correlation between tryptase level and reaction severity. [ABSTRACT FROM AUTHOR]

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.)

Abstract Hymenoptera stings mostly cause acute urticaria but we describe a case of CU after wasp stings which remitted during venom immunotherapy. IgE‐mechanisms have not been fully clarified in CU, except for isolated circumstances. In our case immunotherapy has played a positive role reducing immune cells reactivity and improving urticaria symptoms.

Venoms are complex mixtures of toxic compounds delivered by bite or sting. In humans, the consequences of envenomation range from self-limiting to lethal. Critical host defence against envenomation comprises innate and adaptive immune strategies targeted towards venom detection, neutralisation, detoxification, and symptom resolution. In some instances, venoms mediate immune dysregulation that contributes to symptom severity. This review details the involvement of immune cell subtypes and mediators, particularly of the dermis, in host resistance and venom-induced immunopathology. We further discuss established venom-associated immunopathology, including allergy and systemic inflammation, and investigate Irukandji syndrome as a potential systemic inflammatory response. Finally, this review characterises venom-derived compounds as a source of immune modulating drugs for treatment of disease. [ABSTRACT FROM AUTHOR]

Hymenoptera stings mostly cause acute urticaria but we describe a case of CU after wasp stings which remitted during venom immunotherapy. IgE‐mechanisms have not been fully clarified in CU, except for isolated circumstances. In our case immunotherapy has played a positive role reducing immune cells reactivity and improving urticaria symptoms. [ABSTRACT FROM AUTHOR]

Purpose of Review: To provide clinicians with an understanding of risk factors associated with fatal anaphylaxis, and to promote individualized management plans with patients based upon key aspects of their clinical history. Recent Findings: While anaphylaxis can affect a significant percentage of the general population, death from anaphylaxis remains a rare outcome. The presence of asthma and peanut or tree nut allergy is associated with higher risk for severe or fatal anaphylaxis from foods. Specific triggers (medications, venom), underlying comorbid conditions, age, and use of some medications can also impact risk and warrant different counseling and management strategies. Summary: Anaphylaxis is a rapidly progressive systemic reaction with multiple different causes and encompasses a wide degree of severity in clinical presentation and risk for future episodes. Individualized management, discussion of risk, and shared decision making should occur with each patient and in consideration of their personal risk factors. [ABSTRACT FROM AUTHOR]

Introduction: Hymenoptera venom allergy (HVA) is associated with a high risk of anaphylaxis. Effective treatment of HVA patients requires allergologists' familiarity with the latest HVA recommendations. Aim: Evaluation of current practices in HVA diagnosis in Poland. Material and methods: A survey questionnaire was conducted in 32 HVA centres in Poland. Results: The response rate was 97%. There were 1829 patients evaluated due to HVA in 2015. Sixty six percent (n = 21) of the centres used skin prick tests, out which 90% (n = 19) used 100 μg/ml of the venom extract as the highest concentration. All the centres performed intradermal tests (IDT) and serum specific IgE (sIgE), an initial diagnostic tool in 91% (n = 29). The highest venom concentration in IDT was 1 μg/ml in 75% (n = 24), 0.1 μg/ml in 16% (n = 5), 0.01 μg/ml in 3% (n = 1) and 10 μg/ml in 6% (n = 2). Baseline serum tryptase was assessed in 84% of the centres (n = 27), out of which 53% (n = 17) tested all their patients, whereas 31% (n = 10) checked only those with life-threatening reactions. In case of negative IDT/sIgE, 59% of the centres (n = 19) performed components evaluation, while 19% (n = 6) did the basophil activation test. In case of no identification of the culprit insect and sensitization to both venoms, VIT employed venom with higher sIgE. Conclusions: Most allergology centres in Poland follow HVA guidelines. We identified two inaccuracies in their HVA management including non-adequate venom concentration in IDT and a false belief in correspondence between sIgE concentration and severity of allergic reactions. [ABSTRACT FROM AUTHOR]

Aim: Venom allergy is an important health problem because of life-threatening reactions and impaired quality of life. The only treatment that can prevent the risk of a subsequent systemic sting reaction is venom immunotherapy. Additionally, there has been limited report about Hymenoptera venom immunotherapy practice from Turkey. In our clinic, which is an important allergy center in Turkey, we aim to share the clinical characteristics of venom immunotherapy patients and to raise awareness by sharing our experience about venom immunotherapy. Materials and Methods: Between December 2012 and February 2019, adult patients who underwent venom immunotherapy in Uludag University Faculty of Medicine, Department of Immunology and Allergic Diseases outpatient clinic were evaluated. The sociodemographic characteristics of the patients, re-stings and reaction type during venom immunotherapy were recorded. Results: A total of 52 patients (44.2% female, 55.8% men; mean age= 48.4 ± 12.9 years) were included. From a total of 52 patients, 41 (78.8%) received VIT with honey bee, 8 (15.4%) with wasp and 3 (5.8%) with honey bee and wasp. Only 4 (7.7%) patients developed systemic reactions due to venom immunotherapy. During the venom immunotherapy period, 19 (36.5%) patients were re-stung by the culprit bee and none of them had any systemic allergic reactions. Conclusions: Our data is consistent with previous literature regarding safety and effectivenes of venom immunotherapy. We believe that any effort increasing knowledge of venom allergy is important. [ABSTRACT FROM AUTHOR]

Phospholipase A1 (PLA1) is one of the three major allergens identified in the venom of P. paulista (Hymenoptera: Vespidae), a clinically relevant wasp from southeastern Brazil. The recombinant form of this allergen (rPoly p 1) could be used for the development of molecular diagnostic of venom allergy. Early attempts to produce rPoly p 1 using Escherichia coli BL21 (DE3) cells rendered high yields of the insoluble rPoly p 1 but with low levels of solubilized protein recovery (12%). Here, we aimed to improve the production of rPoly p 1 in E. coli by testing different conditions of expression, solubilization of the inclusion bodies and protein purification. The results showed that the expression at 16 °C and 0.1 mM of IPTG increased the production of rPoly p 1, still in the insoluble form, but with high solubilized protein yields after incubation with citrate–phosphate buffer with 0.15 M NaCl, 6 M urea, pH 2.6 at 25 ºC for 2 h. The venom allergen was also cloned in pPICZαA vector for soluble expression as a secreted protein in Pichia pastoris X-33 cells, rendering almost undetectable levels (nanograms) in the culture supernatant. In contrast, a sevenfold increase of the solubilized and purified rPoly p 1 yields (1.5 g/L of fermentation broth) was obtained after improved production in E. coli. The identity of the protein was confirmed with an anti-His antibody and MS spectra. Allergen-specific IgE (sIgE)-mediated recognition was evaluated in immunoblotting with sera of allergic patients (n = 40). Moreover, rPoly p 1 showed high levels of diagnostic sensitivity (95%). The optimized strategy for rPoly p 1 production described here, will provide the amounts of allergen necessary for the subsequent protein refolding, immunological characterization steps, and ultimately, to the development of molecular diagnostic for P. paulista venom allergy. [ABSTRACT FROM AUTHOR]

This insect venom allergy is a special form of allergy because it carries a high risk of developing Anaphylaxis, the most severe, life-threatening form of allergic reaction. This is one of the most dangerous allergies. It is a major problem in modern allergy because it is still under-diagnosed in its pathomechanism, diagnosis and treatment.In the care of this group of patients, it is important to treat, educate patients, teach them the Principles of prevention, use drugs for immediate intervention, and most of all, the adrenaline. These tasks should cover all staff Responsible for the care of the patient both physicians, psychologists and nurses.

Background: Recent acute anaphylaxis guideline updates have identified remaining unmet needs based on currently available therapeutic options as a critical focus., Objective: We compared the pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of intranasal epinephrine with intramuscular epinephrine administered by autoinjector and manual syringe., Methods: An open-label, 3-period crossover study was conducted in 116 healthy adult volunteers to assess the bioavailability of a single 13.2 mg intranasal dose of epinephrine compared to a 0.3 mg intramuscular autoinjector and a 0.5 mg manual syringe. Patients with epinephrine concentrations of 50, 100, and 200 pg/mL at 10, 20, 30, and 60 minutes after dosing were also evaluated., Results: Pharmacokinetic parameters for the 13.2 mg intranasal dose exceeded those of the 0.3 mg autoinjector with a rapid and higher maximum observed concentration (intranasal, 429.4 pg/mL; autoinjector, 328.6 pg/mL) and greater systemic exposure (AUC 0-360 ; intranasal, 39,060 pg∙min/mL; autoinjector, 17,440 pg∙min/mL). Similar results were observed compared to the 0.5 mg manual syringe. Pharmacokinetic parameters for opposite-nostril and same-nostril dosing were higher than both intramuscular doses, except time to reach maximum observed concentration, which was bracketed between the 2 intramuscular doses (intranasal opposite and same nostril, 20 minutes; autoinjector, 14.9 minutes; manual syringe, 45 minutes). Similar effects on blood pressure and heart rate were observed for intranasal and autoinjector administration. Intranasal epinephrine was safe and well tolerated. No serious or unexpected adverse events were reported, confirming results from earlier clinical studies., Conclusions: Bidose epinephrine spray addresses the unmet medical and patient needs for a needle-free, convenient, and effective dose-delivery system for self-administration of epinephrine that is as good as or better than the 0.3 mg autoinjector., Competing Interests: Supported by Bryn Pharma LLC. Disclosure of potential conflict of interest: D. A. Dworaczyk reports a relationship with Bryn Pharma LLC that includes employment, equity or stocks, and travel reimbursement. A. L. Hunt, M. Di Spirito, M. Lor, M. J. Lamson, J. Pollock, and T. Ward report a relationship with Celerion Inc that includes employment. K. L. Dretchen reports a relationship with Mesa Science Associates that includes employment and equity or stocks., (© 2023 The Author(s).)

Background: Large local reaction to Hymenoptera stings is usually defined as a swelling >10 cm which lasts longer than 24 hours, sometimes associated with erythema, pruritus and blisters. Currently, the risk of subsequent systemic reactions after re‐stings is considered low (2%‐15%). Therefore, a diagnostic workup in case of large local reaction is often judged unnecessary, as well as adrenaline auto‐injector and venom immunotherapy prescription. The aim of this study was to prospectively evaluate the outcome of re‐stings in a real‐world setting, in patients with a history of one previous large local reaction. Methods: We consecutively enrolled patients who experienced their first large local reaction (as per EAACI definition), treated with antihistamine and steroids. They were followed for field re‐stings and assessed for risk of subsequent systemic reactions. Results: We enrolled 662 patients. Out of the 225 re‐stung subjects, 24% did not experience reactions, 52% reported a second large local reaction and 24% had systemic reactions. The risk of subsequent systemic reactions was higher in case of skin test reactivity to Apis mellifera or Vespula species (OR 2.1 and 3.8, respectively), in particular if positive at 0.001 µg/mL concentration (OR 13.4 and 16.5, respectively). Conclusions: Systemic reactions, after a previous large local reaction, occur more frequently than that reported by literature. After analysing the predictive role of large local reactions for systemic reactions, we demonstrated that an accurate diagnostic workup may be considered, particularly skin tests. Further studies in different countries are needed to confirm these results and large local reaction management. [ABSTRACT FROM AUTHOR]

Introduction: Venom immunotherapy treatment (VIT) is the only causal treatment of hymenoptera venom anaphylaxis, which aims to provide long-lasting immunoprotection against severe reactions to subsequent stings. Aim: To reassess the compliance of VIT procedures in the Polish allergy centres with the European guidelines. Material and methods: A structured questionnaire survey conducted in all 33 VIT-centres. The response rate was 94%. Results: The ultrarush initial protocol was the most common protocol (71%, n = 22), usually lasting for 3.5 h (50%, n = 7). The most frequent (36%, n = 11) time interval from the initial to the first maintenance dose (MD) was 14 days, ranging from 7 to 35 days. All centres used an MD of 100 µg. The most frequent time interval between subsequent MDs was 4 weeks (58%, n = 18). Five years' of VIT was declared by 71% (n = 22). Before the termination of treatment, more than half of the centres (58%, n = 18) performed sIgE and almost half (42%, n = 13) performed skin tests. To confirm VIT efficacy, few centres (26%, n = 8) conducted the sting challenge. About half of centres provided the patients with an adrenalin auto-injector both at the time of initial diagnostics and at the end of treatment. More than half (55%, n = 17) used antihistamines in all patients. Almost half (45%, n = 14) declared to stop treatment with ß-blockers and almost one fourth (23%, n = 7) discontinued angiotensin-converting-enzyme inhibitors. Conclusions: In the most important procedures, there is a very high compliance with the guidelines. In the areas where the guidelines are not precise, we observed a large spread of results. [ABSTRACT FROM AUTHOR]

Venom allergy may be life-threatening allergic reaction. Systemic allergic reactions occur with a frequency of 7.5% in adults and 3.4% in children. Since the risk of systemic reactions is a constant risk, it is necessary to prevent the continuing availability of symptomatic medications - adrenaline, antihistamines and corticosteroid injectors, which greatly affects the quality of life of a patient. The only form of treatment that effectively reduces the risk of future systemic responses is venom immunotherapy. This paper presents the latest guidelines in the diagnosis and treatment of venom allergy and discusses the efficacy, safety and efficacy of venom immunotherapy. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a clinical emergency which could be life-threatening and all physicians caring for children should be familiar with its management. The objective of this review is to remind of the pathophysiology of anaphylactic reaction, describe symptoms and diagnostic criteria as well as describe particular forms of anaphylaxis. Rapid recognition of symptoms and early administration of adrenaline are crucial for the disease outcome. Allergy assessment is mandatory in all children with a history of anaphylaxis. A tailored anaphylaxis management plan is required for these patients and it includes instructions on allergen avoidance and selfinjectable adrenaline administration in case of a recurrence of allergic reaction. [ABSTRACT FROM AUTHOR]

This study evaluates adherence to adrenaline autoinjector prescriptions in a cohort of well‐characterized anaphylaxis patients. The overall retrieval rate was 76% with the highest rate in patients with severe anaphylaxis. Special attention is needed in patients with unknown elicitors and in young adults, comprising the largest proportion of non‐adherent patients. Trial registration No intervention performed. Retrospective data used with permission from the Danish Data Protection Agency and Regional Committees on Health Research Ethics [ABSTRACT FROM AUTHOR]

This special edition in I Frontiers in Immunology i (Research Topic - "Anaphylaxis") embraces some key areas in anaphylaxis, and provides an opportunity to appraise regarding IgE and non-IgE mediated anaphylaxis, immunological mechanisms underlying hymenoptera venom immunotherapy (VIT), clinical utility of serum tryptase measurements in anaphylaxis, novel biomarkers, anaphylaxis in the elderly, refractory anaphylaxis, and peri-operative anaphylaxis during general anesthesia (GA). Allergen-specific immunotherapy is effective in IgE mediated allergy including allergic rhinitis, bee, and wasp venom allergy and food allergy ([6]). Several cases of spontaneous anaphylaxis in adults may unfold in time as an IgE mediated allergy to a "hidden allergen." Another important development in our understanding of anaphylaxis has been in relation to peri-operative anaphylaxis during GA, refractory anaphylaxis and anaphylaxis in the elderly. [Extracted from the article]

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.)

Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data‐driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three‐grade‐based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice. [ABSTRACT FROM AUTHOR]

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Background: A major problem of venom-specific immunotherapy (VIT) is the absence of reliable parameters for deciding treatment discontinuation. Aim of the Study: Intracutaneous tests (ICTs), the basophil activation test (BAT), specific IgEs (sIgEs) and blocking factor (BF) activity were measured during VIT. We made an evaluation by means of a protective index (PI) including ICT, BAT and BF values. Material and Methods: A population of 45 patients who had experienced a systemic reaction after an insect sting were tested before VIT (T0), at 1 week (T1w), at 10 weeks (T10w) and at 21 weeks (T21w), and, for a subgroup of 17 patients, at 3-5 years (T3-5y). Basophil activation (expressed in % CD63 and in the area under the curve) and BF activity were measured by flow cytometry using the CCR3/CD63 protocol. Results: The first 21 weeks of follow-up showed no significant variation in the ICT, sIgE and BAT measurements, except for BAT, by eliminating weak negative anti-IgE responses. In these conditions, the decrease in basophil activation was significant at T10w (p = 0.009) and T21w (p = 0.009). Increased BF activity was also significant at T10w (p = 0.008) and T21w (p = 0.002). The PI threshold calculated from the mean ± 3 standard errors (SE) was 64.8 (14.7 ± 16.7, n = 25) at T0. PI increase was significant at T3--5y (3,430 ± 6,282; p < 0.001). Conclusion: VIT induced a significant decrease in ICT values and basophil activation, along with an increase in serum BF activity, significant after 10 weeks of VIT. Evaluated in a larger population, the PI could represent a new tool for the clinico-biological follow-up of VIT efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Venom immunotherapy (VIT) is the only efficient prevention for sting-induced anaphylaxis, but its application is not without risks and needs precautions and standardization. European guidelines were proposed in 2005, but recent practice surveys and more recent knowledge raise the need for an update. The aim of this study was to analyze VIT practices in France, based on previous surveys in Europe but also extended to outcome event management.Material and Methods: A paper questionnaire was sent widely to persons involved in venom treatment.Results: Eighty-six responses could be included from physicians actively involved in VIT induction evenly distributed in France. The survey shows that VIT was engaged from grade III down to grade I reactions, starting preferentially with the ultra-rush protocol. Premedication was used by 42% only and risks induced by co-treatment with β-blockers were well known but not with angiotensin-converting enzyme inhibitors. However, side effects were very variably managed from arrest to enhancement in doses, time-delay or duration. Similarly, we observed a large discrepancy in treatment evaluation (skin tests, biology, timing and interpretation), decision making for treatment termination (when and how long to be prolonged) and post-treatment follow-up (adrenaline kit, event record) as well as procedures in case of late relapse (new induction, different doses).Conclusions: Our study shows that most recommendations were fully or partially followed and may need reminding, but many points need to be completed or updated with new tools and knowledge acquired during the last 10 years. [ABSTRACT FROM AUTHOR]

Conventional T cells have historically been linked to exacerbating allergy. By efficiently generating primarily TH2 cells, allergens skew the immune response to produce IL-4, IL-13, and IgE. Previously, CD1a-responsive T cells were shown to functionally respond to bee and wasp venom allergens. In this issue of the European Journal of Immunology, Subramaniam et al. [ Eur. J. Immunol. 2016. 46: 242-252] show that more functionally active CD1a-restricted cells are present in bee venom-allergic patients than in healthy patients. Additionally, the authors show that these cells are not as frequently found in individuals receiving venom immunotherapy. Consequently, this study implicates CD1a-reactive cells as the primary responders to venom allergy, which considerably regulate the downstream immune response. [ABSTRACT FROM AUTHOR]

The role of CD1a-reactive T cells in human allergic disease is unknown. We have previously shown that circulating CD1a-reactive T cells recognize neolipid antigens generated by bee and wasp venom phospholipase, and here tested the hypothesis that venom-responsive CD1a-reactive T cells associate with venom allergy. Circulating T cells from bee and wasp venom allergic individuals, before and during immunotherapy, were exposed to CD1a-transfected K562 cells in the presence of wasp or bee venom. T-cell response was evaluated based on IFNγ, GM-CSF, and IL-13 cytokine production. Venom allergic individuals showed significantly higher frequencies of IFN-γ, GM-CSF, and IL-13 producing CD1a-reactive T cells responsive to venom and venom-derived phospholipase than healthy individuals. Venom-responsive CD1a-reactive T cells were cross-responsive between wasp and bee suggesting shared pathways of allergenicity. Frequencies of CD1a-reactive T cells were initially induced during subcutaneous immunotherapy, peaking by weeks 5, but then reduced despite escalation of antigen dose. Our current understanding of venom allergy and immunotherapy is largely based on peptide and protein-specific T cell and antibody responses. Here, we show that lipid antigens and CD1a-reactive T cells associate with the allergic response. These data have implications for mechanisms of allergy and approaches to immunotherapy. [ABSTRACT FROM AUTHOR]

Within the Apidae, the largest family of bees with over 5600 described species, the honeybee is the sole species with a well studied venom proteome. So far, only little research has focused on bumblebee venom. Recently, the genome sequence of the European large earth bumblebee ( Bombus terrestris ) became available and this allowed the first in-depth proteomic analysis of its venom composition. We identified 57 compounds, with 52 of them never described in bumblebee venom. Remarkably, 72% of the detected compounds were found to have a honeybee venom homolog, which reflects the similar defensive function of both venoms and the high degree of homology between both genomes. However, both venoms contain a selection of species-specific toxins, revealing distinct damaging effects that may have evolved in response to species-specific attackers. Further, this study extends the list of potential venom allergens. The availability of both the honeybee and bumblebee venom proteome may help to develop a strategy that solves the current issue of false double sensitivity in allergy diagnosis, which is caused by cross-reactivity between both venoms. A correct diagnosis is important as it is recommended to perform an immunotherapy with venom of the culprit species. [ABSTRACT FROM AUTHOR]

Stinging insect allergy is a relatively common medical problem, responsible for an estimated 40 fatalities per year in the USA and considerable anxiety and lifestyle modification. There are no criteria to identify people at risk of initial venom anaphylaxis. Reactions may occur at any age and are unrelated to the time interval of prior venom exposure. There is an approximate 60% re-sting reaction rate in people who have had sting anaphylaxis and have positive venom skin tests. Re-sting reactions are more likely to occur in adults than in children and in people who have had more severe anaphylactic symptoms. Positive venom intradermal skin tests confirm the diagnosis of potential stinging insect allergy in people who have had sting reactions. Venom immunotherapy provides almost 100% protection from further sting reactions. It is recommended for all people who have had venom anaphylaxis and have positive skin tests, except for children who have dermal reactions only. Details of venom dosing are well established. The adequate duration of venom immunotherapy is still an unresolved issue. Conversion to a negative skin test appears to be an absolute criterion to discontinue treatment. In the presence of a persistent positive skin test, 3–5 years of immunotherapy is generally sufficient. People who have had severe reactions, such as loss of consciousenss, may require indefinite therapy.