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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]

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]

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]

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]

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]

Copyright of Paediatria Croatica, Supplement is the property of Paediatria Croatica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Paediatria Croatica, Supplement is the property of Paediatria Croatica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

Recombinant allergens for immunotherapy aim to overcome the problems of natural extracts as they can be produced in unlimited amounts with exact physiochemical and immunological properties. These can be modified to have more favourable characteristics including reduced IgE reactivity or enhanced immunogenicity. Different types of recombinant allergens have been evaluated in clinical phase II and III trials whilst others are currently under development. In this review, we identified double-blind, placebo-controlled randomised clinical trials assessing the efficacy and safety of various recombinant allergen preparations. The majority of studies have up to now focused on cat, grass, birch, ragweed and bee venom allergens. Some studies have shown some of these preparations to be effective and well tolerated. However, there are still outstanding issues regarding optimum doses, minimising side effects and long-term effects. [ABSTRACT FROM AUTHOR]

Background:Vespa orientalis (VO) stings occasionally induce anaphylaxis. In the absence of commercial VO venom, allergists use commercial venoms for immunotherapy, despite having no indication regarding efficacy. We attempted to examine the effectiveness of immunotherapy with commercial venoms in patients with VO allergy and to identify the venom accountable for this effect. Methods: Patients who unequivocally identified VO as the culprit insect were administered venom immunotherapy with the commercial venoms available in Israel to which they had positive skin tests. Patients were also skin tested with VO venom sac extracts and, after reaching the maintenance dose, were sting challenged by a live insect. The allergenic components in the venom were determined by immunoblotting. Results: Twelve patients were recruited and, based on their skin test results, all were treated with yellow jacket (YJ) venom, either alone or combined with other venoms. All 8 patients who were sting challenged by VO demonstrated positive skin test responses to VO venom. Six of the stung patients tolerated the sting challenge uneventfully. Two patients developed minimal transient symptoms that resolved spontaneously. SDS-PAGE with patient sera suggested cross-reactivity between VO and YJ venoms at molecular weights of 39-42 kDa. Using phospholipases, antigen 5 and hyaluronidase derived from several Vespa, Dolichovespula and Vespula species, hyaluronidase is possibly accountable for inducing the allergic reaction. Conclusion: In the absence of commercial VO venom the practice of treating patients allergic to this insect with available commercial venoms seems to be efficacious and YJ venom is probably responsible for this effect. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Stings from bees and wasps can cause systemic allergic reactions in sensitized patients. However, the mystery of why some cases develop allergic reactions while others do not, remains poorly understood. We investigated whether particular human leukocyte antigen (HLA) class land class II genes contribute to the development of venom allergy. A total of 21 bee and/or wasp venom sensitive patients who had life-threatening allergic symptoms after a sting, and positive diagnostic tests (Group 1), were included in the study. Thiry-seven healthy subjects without venom allergy (Group 2) were selected as the control group HLA-class 1 (A-C) and class II (DR, DQ, DP) typing was performed by PCR-based techniques. HLA-B*l8 and HLA-Cw*07 alleles was found more frequently in Group l than in Group 2 (14.3% vs 2.7%, p=0.026, and 31% vs 14.9%, p=0.036, respectively). Furthermore, HLA-A*0l allele frequency had a trend to he higher in Group 1 than in Group 2 (14.3% vs 4.1%, p=0.055). However, the frequencies of HLA-A*03 and HLA-Cw*03 alleles were increased in Group 2 compared to Group 1 (20.3% vs 7.1%, p=0.049 and 10.8% vs 0%, p=0.024, respectively). Among HLA-class II geno- types, HLA-DQBl*03 allele was significantly increased in Group 2 (60.9% vs 38.1%, p=0.0l8), while a higher frequency of HLA-DRBl*03 and HLA-DRBl*l4 alleles showed a tendency statistically significant in Group 1(9.5% vs 1.4%, p=0.057 and 11.9% vs 2.7%, p=0.058. respectively). HLA-B*l8 and HLA-Cw*07 alleles may probably be associated with susceptibility to venom allergy, whereas HLA-A*03, HLA-Cw*03 and HLA-DQB 1*03 seem to be protective markers in a small Turkish population. [ABSTRACT FROM AUTHOR]

Background: In patients with hymenoptera venom allergy diagnostic tests are often positive with honey bee and Vespula venom causing problems in selection of venoms for immunotherapy. Methods: 100 patients each with allergic reactions to Vespula or honey bee stings and positive i.e. skin tests to the respective venom, were analysed for serum IgE to bee venom, Vespula venom and crossreacting carbohydrate determinants (CCDs) by UNICAP (CAP) and ADVIA Centaur (ADVIA). IgE-antibodies to species specific recombinant major allergens (SSMA) Api m1 for bee venom and Ves v5 for Vespula venom, were determined by ADVIA. 30 history and skin test negative patients served as controls. Results: By CAP sensitivity was 1.0 for bee and 0.91 for Vespula venom, by ADVIA 0.99 for bee and 0.91 for Vespula venom. None of the controls were positive with either test. Double positivity was observed in 59% of allergic patients by CAP, in 32% by ADVIA. slgE to Api m1 was detected in 97% of bee and 17% of Vespula venom allergic patients, slgE to Ves v5 in 87% of Vespula and 17% of bee venom allergic patients. slgE to CCDs were present in 37% of all allergic patients and in 56% of those with double positivity and were more frequent in bee than in Vespula venom allergic patients. Conclusions: Double positivity of IgE to bee and Vespula venom is often caused by crossreactions, especially to CCDs. IgE to both Api m1 and Ves v5 indicates true double sensitization and immunotherapy with both venoms. [ABSTRACT FROM AUTHOR]

Background Venom immunotherapy (VIT) induces long-lasting immune tolerance to hymenoptera venom antigens, but the underlying mechanisms are not yet clarified. Regulatory T cells are thought to play an important role in allergic diseases and tolerance induction during specific immunotherapy. Aim Characterize longitudinally the impact of VIT on the pool of circulating regulatory T cells. Methods Fourteen hymenoptera venom-allergic patients with severe reactions (grades III–IV) were studied before, 6 and 12 months after starting ultra-rush VIT. Freshly isolated peripheral blood mononuclear cells were surface stained with a panel of markers of T cell differentiation and intracellularly for CTLA-4 and Foxp3 and analysed by flow cytometry. foxp3 mRNA was quantified by real-time PCR. VIT responses were assessed by measuring specific IgG4 and IgE levels. Eleven individuals with no history of insect venom allergy were studied as controls. Results VIT induces a significant progressive increase in both the proportion and the absolute numbers of regulatory T cells defined as CD25bright and/or Foxp3+ CD4+ T cells. These changes are not related to alterations in the expression of activation markers or imbalances in the naïve/memory T cell compartments. foxp3 mRNA levels also increased significantly during VIT. Of note, the increase in circulating regulatory T cell counts significantly correlates with the venom-specific IgG4/IgE ratio shift. Conclusion VIT is associated with a progressive expansion of circulating regulatory T cells, supporting a role for these cells in tolerance induction. [ABSTRACT FROM AUTHOR]

Background: Despite the well-documented efficacy of Hymenoptera specific immunotherapy (SIT), there is no safe method to reliably characterise the patient level of protection. Only poor correlations between protection and allergen-specific serum immunoglobulins have been found, and a sting challenge is the only means to evaluate the efficacy of immunotherapy. Therefore, we aimed to develop a cutaneous test that measures in vivo neutralisation of the Hymenoptera venom. Materials and Methods: Twenty-four patients with wasp venom allergy were included in the study. Wasp-specific serum IgE, IgG and IgG4 were measured by ImmunoCAP. Dilutions of the individual patient sera were intradermally injected into the forearm. Then, wasp venom extract was injected into these sites to quantitatively assess the formation of wheals and flares. Results: The results show that during the course of SIT, patient sera gained the capacity to neutralise skin reactions to wasp venom extracts in vivo. The test correlated with the duration of SIT as well as with the concentration of IgG and IgG4. Conclusion: The in vivo neutralisation test may become a promising tool in allergy diagnostics as well as in monitoring the success of SIT in patients undergoing allergen SIT. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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An aerobiologic and clinical survey was conducted in Málaga, southern Spain, in order to determine fluctuations of Australian pine (Casuarina) pollen in the atmosphere of the city, and the prevalence of sensitivity in a nonatopic population. The aerobiologic survey, using a Burkard spore trap, was conducted from January 1991 to December 1994, and sensitization was ascertained by the skin prick test. The pollen season is relatively short and the pollen dispersion period occurs during October and November, mainly during the last 3 weeks of October. Diurnal patterns showed that the highest concentrations of pollen occur between 12 a.m. and 2 p.m., the most influential variables in its dispersion being temperature, sunshine, and rainfall. The prevalence of sensitization to Casuarina pollen was determined by skin prick test (SPT) in a nonatopic population ot 210 patients with a previous history of autumn rhinitis, asthma, or rhinitis asthma. Six subjects showed a positive reaction to the pollen extracts, and the presence of specific IgE was demonstrated by the conventional radioallergosorbent test (RAST ≥ 2) in five of these patients with positive SPT. [ABSTRACT FROM AUTHOR]

Recent findings have clarified major steps in the differentiation and maturation pathways of mast cells and basophils in relation to other cells in the immune system which are involved in the allergic response, such as eosinophiis and mononuclear phagocytes. This review aims to summarize the basic facts and major recent advances in this field. The controversy appears to have been resolved, at least in part, by the demonstration of a role for basophils in human allergy in that basophilic granulocytes bearing lineage-specific surface markers invade the tissues during the late-phase allergic response in the airway mucosa.

The IgE response, the involvement of the different penicillins available for therapeutic use, and the specificity of the IgE antibodies found in a group of penicillin-allergic subjects from Italy were studied. Thirty subjects with a history of allergic reactions to penicillins were studied. In vivo and in vitro specific IgE antibodies were determined to different penicillin determinants. Fifteen subjects developed anaphylactic responses and the remainder urticaria and angioedema. The drug most frequently involved in the patients' allergic reactions was ampicillin (AMP). The benzylpenicilloyl (BPO) skin test was positive in 16 (53.3%) patients, whereas 23 (76.6%) patients were positive to minor determinant mixture (MDM), benzylpenicillin (PG), AME or amoxicillin (AX). When classified according to initial reaction type, most anaphylactic patients (93.3 %) were associated with minor determinant reactivity, whereas most urticaria patients (80%) reacted to BPO. RAST results for the anaphylactic and urticaria subgroups were similar. RAST inhibition showed that most sera contained highly cross-reactive IgE antibodies. There was evidence of a specific response to AX and PG (one patient each). These data show that in a population of penicillin-allergic patients from Italy, AMP was the main drug inducing the allergic reactions In skin tests and RAST, patients exhibited heterogeneous IgE responses with little indication of specific reactivity to AMP. [ABSTRACT FROM AUTHOR]

We evaluated the immunogenicity and antigenicity of a formula based on partially hydrolyzed cow's milk whey protein in infants at risk of atopy and in controls. Total IgE and specific IgE, IgG, and IgG4 subclass antibodies against egg albumin and cow's milk α-lactalbumin, casein, and β- lactoglobulin were measured by radiommunoassay of cord blood and of peripheral blood at 5 days and 6 months of life in five groups of infants: 16 breast-fed infants at risk of atopy (group 1), 21 partially hydrolyzed whey formula-fed infants at risk of atopy (group 2), 14 formula-fed infants at risk of atopy (group 3), 10 breast-fed control infants (group 4), and 13 formula- fed control infants (group 5), Total IgE concentration was significantly lower in group 2 at 6 months than in groups 3 and 5 infants and similar to that observed in groups 1 and 4 infants. The concentration of specific antiegg and anti-cow's milk protein IgG and of specific anti-cow's milk a-lactalbumin and β-lactoglobulin IgG4 subclass antibodies was significantly reduced in group 2 as compared to group 3 infants and similar to that found in breast-fed infants. in conclusion, the partially hydrolyzed formula was less immunogenic, and antigenic than a traditional formula and was as immunogenic and antigenic as breast milk. [ABSTRACT FROM AUTHOR]

For the diagnosis of IgE-mediated (immediate) hypersensitivity to natural rubber latex (NRL), skin prick testing with extracts of latex gloves has been widely used, but such extracts are difficult to standardize. The, present study aimed to produce on an industrial scale an NRL extract from. freshly collected NRL and to evaluate, calibrate, and standardize the extract by both in vivo and in vitro testing. The source material latex of the rubber tree, Hevea brasiliensis (clone RRIM 600), was frozen immediately after collection in Malaysia and shipped in dry ice to Stallergènes SA, France. Protein and allergen profiles were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, isoelectric focusing (IEF), crossed immunoelectrophoresis (CIE), and crossed radioimmunoelectrophoresis (CRIE). Allergen quantification was effected by RAST inhibition. The capacity of the preparation to elicit immediate hypersensitivity reactions in vivo was measured by skin prick testing in 46 latex-allergic patients and 76 nonallergic control subjects. SDS-PAGE and immunoblot profiles of the extract and an NRL standard (E8) provided by the US Food and Drug Administration were almost identical, disclosing several distinct IgE-binding proteins with apparent molecular weights of 14, 20, 27, 30, and 45 kDa, conforming to reported molecular weights of several significant NRL allergens. An arbitrary index of reactivity (IR) of 100 was assigned to the extract at 1 : 200 dilution (w/v) having a protein content of 22 μg/ml. Skin puck testing of latex-allergic patients and controls using the extract at 100 IR revealed 93% sensitivity, 100% specificity, 100% negative predictive value, and 96% positive predictive value. In conclusion, a skin prick test reagent was diagnosis of type I NRL allergy was successfully standardized. The reagent was demonstrated to contain most, if not all, of the currently known clinically significant NRL allergens, and it showed high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate venom-related and venom-non-related immunological reactions in patients stung by bee or wasp. Sixteen consecutive patients (7 with local and 9 with systemic reactions) were tested with skin tests, RAST and basophil histamine release (BHR) test immediately after the insect sting and 2, 4, and 16 weeks later. No test was useful immediately after the insect sting, the "anergic period". In agreement with earlier findings, the SPT was the only allergy test that showed statistically significant differences between patients with local and systemic reactions, although a great overlap was found. Release of histamine from basophils after incubation with anti-IgE also showed statistically significant differences between local and systemic reactions. Further studies are needed, especially measurement of BHR after incubation with anti-IgE before insect stings. [ABSTRACT FROM AUTHOR]

The growth in popularity of flying ultralight aircraft and paragliding has been associated with an increased involvement of Emergency Medical Services because of various types of trauma suffered from both inexperienced and skilled individuals. This case presentation reports on a paraglider pilot, who was seen spinning 'unusually' rapidly toward the ground, without visible attempts to regain control of the aircraft. Besides the bilateral mydriasis and the absence of any ECG activity, there was a significant swelling of face, lips, neck, and tongue. Upon opening the mouth, a dead bee was found over the tongue, underneath the palate. A fatal anaphylactic shock was the likely cause of death of the pilot while still 'in mid-air.' This case is certainly different from the commonly reported accidents during paragliding. An updated review of the medical literature shows no reported cases of fatal anaphylactic shock during the practice of paragliding. [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]

The article presents the case of a 36-year old women with eosinophilic panniculitis. She had allergic reaction due to bee sting. She had symptoms consisting of urticaria, angio-oedema, hypotension, anaphylaxis, dyspnea and nausea-vomiting. The diagnosis of venom allergy was confirmed by positive prick and intradermal testing using Apis mellifera antigen.

The article presents a case of a 30-year-old patient suffering from anaphylaxis caused by a snakebite in Brazil. The patient is presented at the Vital Brazil Hospital after he was bitten by a lance-headed viper. The common symptoms of anaphylaxis include dyspnoea, cough, pain and bleeding. The patient is treated with several anti-agent treatments including adrenaline, hydrocortisone and antihistamine.

The article discusses the discovery of alternative therapy methods for bee and wasp allergy in Turkey. The study reveals that the systemic reactions are only 1-4% of the whole insect allergy. The Ministry of Agriculture and Rural Affairs describes Turkey as the world's fourth country with honey production growth. The primary purpose of the study is to discover the alternative therapy method in treating insect allergies.

The article presents a case report concerning a 15-year-old son of a beekeeper who experienced a systematic allergic reaction with urticaria and a slight cough after a bee sting in May 2004. He was treated with adrenalin and corticosteroids and then referred to an outpatient clinic. The physicians performed a Prick test to examine the venom level and was addressed to ultra rush specific immunotherapy (SIT) covered by omalizumab. After the treatment, the boy recovered without any side-effects.

The article cites a case of anoxic encephalopathy after stopping venom immunotherapy (VIT). The patient was stung by a yellow-jacket. This case is the first report of near fatal insect sting reaction with ischemic encephalopathy in a young healthy patient after stopping VIT. Researchers conclude that the risk of the re-occurrence of a systemic reaction after stopping VIT is elevated in adult age.

Interleukin-5 is a T-celi-, mast-cell-, and eosinophil-derived cyt okine with selective effect on cells of the eosinophil lineage. Its role is debatable in experimental models of bronchial hyperresponsiveness, where it is linked to induction of 1gB responses in mice, as well as in human asthma. CD8 + lymphocytes exerting Th2-like activity on B-cell production of IgE have been reported. The unexpected and still unreported finding in this patient was the increased presence of a subpopulation of double-negative.