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Hymenoptera venom allergy is a central thematic in allergology. The recent limitation in the obtention of certain venom products has forced Swiss centers to adapt their diagnostic and therapeutical approaches. In this review, we will discuss diagnostics tools using recombinants serologies, recent recommendations for the screening of indolent systemic mastocytosis and the different immunotherapy protocols available for venom desensitization using aqueous and aluminum hydroxide-adsorbed purified venoms.

International audience; The European Academy of Allergy and Clinical Immunology (EAACI) supports three journals: "Allergy," "Pediatric Allergy and Immunology (PAI)," and "Clinical and Translational Allergy (CTA)." One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. This paper summarizes the achievements of 2018 in anaphylaxis, and food and drug allergy. Main topics that have been focused are anaphylaxis, mechanisms of food allergy (FA), epidemiology of FA, food allergens, diagnosis of FA, prevention and control of FA, FA immunotherapy, drug allergy, and political agenda.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for prevention of i) development of allergic comorbidities in those with established allergic diseases, ii) development of first allergic condition and iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multi-disciplinary expert working group, a systematic review of the underpinning evidence and external peer-review of draft recommendations. Our key recommendation is that a three year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate to severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to two years post-AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than two years post AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease or for prevention of allergic co-morbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease modifying treatment exists but there is an urgent need for more high-quality clinical trials. This article is protected by copyright. All rights reserved.

BACKGROUND: Desensitization is a method for inducing temporary tolerance to allergen. The mechanism underlying desensitization is yet to be established.METHODS: Basophil granulocytes in whole blood from grass pollen allergic subjects were desensitized ex vivo by sequential addition of increasing allergen concentrations. At each step basophil activation (CD193(+) CD63(+) ) was monitored with and without (background activation) allergen challenge at optimal concentration. The sequential desensitization protocol was compared to a single-dose desensitization protocols with threshold and subthreshold allergen concentrations. Incubation intervals and allergen concentrations were varied in order to optimise the protocol.RESULTS: Sequential desensitization effectively reduced basophil response. The single-dose subthreshold protocol and single-dose threshold protocols did not reduce basophil activation with optimal allergen challenge from a mean 57.1 (95% CI 32.7-81.5) to 50.4% (95% CI 16.3-84.4; n=5; p=0.43) and 45.0% (95% CI 23.1-66.9; p=0.14) respectively, while the sequential desensitization protocol reduced activation to a mean 37.2% (95% CI 16.3-58.1; p=0.018). Reducing incubation time from 10 to 5 minutes increased mean background activation from 22.4 (95% CI 11.7-33.1) to 30.0% (95% CI 19.7-40.3; n=5; p=0.026). Increasing time intervals from 10 to 20 minutes reduced background activation from 30.9 (95% CI 22.8-39.0) to 21.9% (95% CI 16.0-27.7; n=5; p=0.020). Increasing allergen concentrations intervals from 2-fold to 5- and 10-fold did not have significant effect on basophil activation.CONCLUSIONS: Sequential desensitization ex vivo effectively attenuates the basophil response to allergen. Increasing the time spent at each step improves desensitization. This protocol could be valuable for investigation of the mechanism of desensitization. This article is protected by copyright. All rights reserved.

BACKGROUND:The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy.METHODS:We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses.RESULTS:We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses.CONCLUSIONS:AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. In order to inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitis METHODS: We searched 15 international biomedical databases for published, in progress and unpublished evidence. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. RESULTS: We identified 5932 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95%CI -0.63, -0.42), medication (SMD -0.37, 95%CI -0.49, -0.26) and combined symptom and medication (SMD -0.49, 95%CI -0.69, -0.30) scores whilst on treatment that were robust to pre-specified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, this suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is effective in improving symptom, medication and combined symptom and medication scores in patients with allergic rhinoconjunctivitis whilst on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy. This article is protected by copyright. All rights reserved.

Background: Intranasal administration of high amount of allergen was shown to induce tolerance and to reverse the allergic phenotype. However, mechanisms of tolerance induction via the mucosal route are still unclear. Objectives: To characterize the therapeutic effects of intranasal application of ovalbumin (OVA) in a mouse model of bronchial inflammation as well as the cellular and molecular mechanisms leading to protection upon re-exposure to allergen. Methods: After induction of bronchial inflammation, mice were treated intranasally with OVA and re-exposed to OVA aerosols 10 days later. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined. The respective role of CD4(+)CD25(+) and CD4(+)CD25(-) T cells in the induction of tolerance was analysed. Results: Intranasal treatment with OVA drastically reduced inflammatory cell recruitment into BALF and bronchial hyperresponsiveness upon re-exposure to allergen. Both OVA- specific-proliferation of T cells, T(h)1 and T(h)2 cytokine production from lung and bronchial lymph nodes were inhibited. Transfer of CD4(+)CD25(-) T cells, which strongly expressed membrane-bound transforming growth factor beta (mTGF beta), from tolerized mice protected asthmatic recipient mice from subsequent aerosol challenges. The presence of CD4(+)CD25(+)(Foxp3(+)) T cells during the process of tolerization was indispensable to CD4(+)CD25(-) T cells to acquire regulatory properties. Whereas the presence of IL-10 appeared dispensable in this model, the suppression of CD4(+)CD25(-)mTGF beta(+) T cells in transfer experiments significantly impaired the down-regulation of airways inflammation. Conclusion: Nasal application of OVA in established asthma led to the induction of CD4(+)CD25(-)mTGF beta(+) T cells with regulatory properties, able to confer protection upon allergen re-exposure.

Sublingual immunotherapy (SLIT) has been recognized as a viable alternative to subcutaneous immunotherapy for respiratory allergies both in adults and children, but clinical documentation about safety and efficacy in children is still poor. The purpose of this study was to assess the efficacy and tolerance of SLIT in children who are sensitized to grass pollen.Children with a clinical history of intermittent rhinoconjunctivitis, with or without mild asthma and positive skin prick tests to grass pollen, were selected to participate in a 2-year double-blind, placebo-controlled study with SLIT, using a grass extract (ALK-Abellò).22 children were analyzed at the end of the study. No relevant side effects occurred in the active group. A statistically significant difference (p = 0.05; Mann-Whitney test) in favor of the active group (n = 10) could be shown for drug consumption during the second year, as well as a significant improvement as compared to the first year of SLIT (p = 0.05; Wilcoxon test).Despite the small number of patients, our data suggest that SLIT with a grass pollen extract is well tolerated in children and is able to significantly reduce drug consumption during the second year of treatment. Studies in larger groups of children sensitized to both grass and tree pollens are needed to definitively assess the role of SLIT in intermittent, seasonal rhinitis and pollen asthma.