Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver.

Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.

[2022 Update of the Austrian Society for Rheumatology and Rehabilitation nutrition and lifestyle recommendations for patients with gout and hyperuricemia]. / Empfehlungen der Österreichischen Gesellschaft für Rheumatologie und Rehabilitation zu Ernährung und Lebensstil bei Gicht und Hyperurikämie ­ Update 2022.

BACKGROUND: Gout is the most frequent inflammatory joint disease in the western world and has a proven genetic background. Additionally, lifestyle factors, such as increasing life expectation and standard of living, sufficient or excess nutrition and a growing prevalence of obesity in the population as well as e.g. alcohol consumption, contribute to the rising incidence of hyperuricemia and gout. Apart from an adequate medication, medical consultation on nutrition and lifestyle is an essential part of the management of gout patients, who have a high risk of internal comorbidities. OBJECTIVE: In 2015 the Austrian Society for Rheumatology and Rehabilitation (ÖGR) working group for osteoarthritis and crystal arthropathies published nutrition and lifestyle recommendations for patients with gout and hyperuricemia. Since then, a multitude of studies have been published addressing this topic, which necessitated an update. METHODS: First, the authors performed a hierarchical literature search to screen for the literature published since 2015. Considering references given in the first publication, the relevant literature was selected and the recommendations from 2015 were either kept as published, reformulated or recreated. Finally, the evidence level and the level of agreement for each recommendation were added by the authors. RESULTS: Based on this process, 10 recommendations were generated instead of the initial 9. As in the original publication, a graphical presentation with symbols was constructed to complement the written text. CONCLUSION: The ÖGR recommendations on nutrition and lifestyle for patients with gout and hyperuricemia were updated in accordance with the most recent relevant literature. These are supposed to serve as information and education material for patients and updated information for physicians.

Laser produced soft x-ray source diagnostics with temporal, spectral, and spatial resolution.

We demonstrate the use of three diagnostic tools which simultaneously view the target from nearly the same direction, and their results are combined to provide temporally, spectrally, and spatially resolved absolutely calibrated target emission information. To demonstrate this capability, Au targets were irradiated by 1.8 kJ, 3 ns laser pulses to produce broadband soft x-ray emission in the 0.1-3.5 keV spectral range. Target diagnostics included a time-resolved x-ray diode array, each measured a partial spectral band, time-integrated spectrally resolved absolutely calibrated transmission grating spectrometer, and static and time-resolved soft x-ray imagers coupled to a charge-coupled device camera and to a streak camera, respectively, measuring spatially and temporally resolved radiation at the main Au target emission bands. The combined temporally, spectrally, and spatially resolved absolutely calibrated target emission result can be compared to simulations and be used to design and analyze experiments in which the source emission is used as a drive for various physical processes.

[Sexual and reproductive health of adolescents living with HIV in pediatric care programs in Abidjan : Structured provision of care and perceptions of health care workers in 2019]. / Santé sexuelle et reproductive des adolescent(e)s vivant avec le VIH dans les programmes de prise en charge pédiatrique à Abidjan : offre de services des structures et perceptions des professionnels de santé en 2019.

INTRODUCTION: The majority of adolescents living with HIV (ALHIV) reside in sub-Saharan Africa, with sexual and reproductive health (SRH) needs to be met. The health care facilities and professionals involved have a major role to assume in the quality of SRH services offered to these teenagers. OBJECTIVE: To investigate the SRH services offered to ALHIV subjects in pediatric facilities in Abidjan, Ivory-Coast. METHODS: In 2019 we conducted an exploratory cross-sectional study using qualitative and quantitative methods in three pediatric facilities caring for ALHIV subjects (CIRBA, CTAP and CePReF) and participating in the IeDEA (International epidemiologic databases to Evaluate AIDS project) in Abidjan, Ivory Coast. This study included: (1) an inventory of SRH services, using a questionnaire and direct observation, describing their adaptation to the teenagers' needs and their inclusion in provision of care; (2 an assessment by means of semi-structured interviews of 14 health professionals' perceptions of the SRH needs of the ALHIV subjects with whom they worked. Quantitative data were expressed in percentages and qualitative data from the interviews were analyzed through inductive thematic analysis. RESULTS: The care provided in the three facilities was poorly adapted to the teenagers' needs. Few SRH services were effectively provided to the ALHIV subjects in the different centers. The services essentially consisted in condom distribution and organization of SRH-based focus groups. Exceptionally, hormonal contraception was offered to teenage girls. Barriers to the services were largely due to poorly equipped facilities, particularly in terms of SRH offer, health professionals' experience, and support provided for ALHIV subjects and their parents. The health professionals were desirous of SRH skill-building programs enabling them to deliver optimal, adequately contextualized SRH services to the teenagers. CONCLUSIONS: In pediatric programs addressed to ALHIV subjects in three Abidjan facilities, the teenagers' SRH needs remain unmet. It is urgently necessary to strengthen the health facilities by means of improved equipment, enhanced awareness of teenagers' needs, and training programs enabling the health professionals to provide more adapted sexual and reproductive health services.

Contraindications to immunotherapy: a global approach.

BACKGROUND: Recommendations on contraindications to allergen immunotherapy (AIT) have been independently developed by National and International Societies/Academies. AIT contraindications are mainly based on case reports, case-series, or experts' opinion, while evidence-based information is limited. The aim of the present review was to describe existing guidelines on contraindications to AIT and to highlight differences between them. MAIN BODY: An extended review of the literature regarding contraindications to AIT for respiratory allergy and venom hypersensitivity was performed. Furthermore, Societies and Academies registered in the World Allergy Organization and EAACI databases, were asked for additional information. Only AIT guidelines published under official auspicies were included. A large heterogeneity among the various recommendations on contraindications was registered. Common contraindications to most of the guidelines were: lack of adherence, pregnancy before the start of AIT, the use of beta-blockers, certain age groups, uncontrolled asthma, autoimmune diseases and malignancies. CONCLUSION: As new data arise, revisions might soon be needed allowing AIT in the cases of patients treated with ACE inhibitors and beta-blockers, in elderly patients and in patients with concomitant autoimmune diseases and neoplasias in remission. The decision to prescribe AIT is always tailor-made, balancing risk vs benefit. Creating globally accepted guidelines would help Allergologists in their decision making.

[HIV Disclosure to the Child/Adolescent in Central and West Francophone Africa]. / Annonce à l'enfant et à l'adolescent de son statut VIH en Afrique francophone centrale et de l'Ouest.

We report the attitudes and practices of health care workers involved in the disclosure process to adolescents living with HIV (ALHIV) in a network including West and Central African French-speaking countries, and the experiences of young living with HIV (YLHIV). During a three-day workshop in Abidjan, Côte d'Ivoire, caregivers (doctors, psychologists, social workers) from 19 pediatric HIV treatment sites shared their practices and difficulties, and four YPLHIV their own disclosure experience. Thirty five participants from eight West/Central African countries (Benin, Burkina Faso, Ivory Coast, Cameroon, Mali, Democratic Republic of Congo, Senegal, Togo) contributed: 14 doctors, eight psychologists, six counselors, three social workers. The experience of the centers was variable, but the age at disclosure was late: 34% of 1296 adolescents between 10 and 12 years of age knew their status. The median age at disclosure was 13 years (range: 11-15 years). The practice of the disclosure was often complex, because of multiple factors (fear of the parents of the breaking of the secrecy, lack of communication between professionals). The individual disclosure was the main practice. Four centers practiced HIV disclosure in group sessions to facilitate mirror support, and one used peer-to-peer support. YPLHIV have advocated for an earlier disclosure, from 10 years. In West and Central Africa, the process of HIV disclosure remains complex for parents and caregivers, and occurs too late. The development of a good practice guideline for HIV disclosing adapted to socio-cultural contexts should help to improve this process.

Nous rapportons les attitudes et pratiques des soignants en Afrique francophone concernant l'annonce du statut VIH aux adolescents, et les témoignages de jeunes vivant avec le VIH (jvVIH). Lors d'un atelier de trois jours à Abidjan, Côte d'Ivoire, en novembre 2016, les soignants (médecins, psychologues, travailleurs sociaux) de 19 sites de prise en charge pédiatrique du VIH ont partagé leurs pratiques et difficultés et 4 jvVIH leur vécu de l'annonce. Au total, 35 participants de 8 pays d'Afrique de l'Ouest/centrale (Bénin, Burkina Faso, Côte d'Ivoire, Cameroun, Mali, République démocratique du Congo, Sénégal, Togo) ont contribué : 14 médecins, 8 psychologues, 6 conseillers, 3 travailleurs sociaux. L'expérience des centres était variable, mais l'âge à l'annonce restait tardif : 34 % des 1 296 adolescents âgés entre 10 et 12 ans connaissaient leur statut. L'âge médian à l'annonce était de 13 ans (étendue : 11-15 ans). La pratique de l'annonce s'avérait complexe, en raison de multiples facteurs (crainte des parents de la rupture du secret, manque de communication entre professionnels). L'annonce individuelle était la pratique majoritairement adoptée. Quatre centres pratiquaient une annonce en séances de groupe pour faciliter le soutien en miroir, et un avait recours à l'appui de pairs-adolescents. Les jvVIH ont plaidé pour une annonce plus précoce, dès 10 ans. En Afrique de l'Ouest/centrale francophone, le processus de l'annonce reste complexe pour parents et soignants, et l'annonce trop tardive. L'élaboration d'un guide de bonnes pratiques de l'annonce du VIH, adapté aux contextes socio-culturels devrait permettre d'améliorer ce processus.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

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.

EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

PURPOSE: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. METHODS: We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. RESULTS: The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. CONCLUSIONS: Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

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.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

Immunological differences between insect venom-allergic patients with and without immunotherapy and asymptomatically sensitized subjects.

BACKGROUND: Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings. METHODS: We included 77 asymptomatically sensitized subjects, 85 allergic patients with acute systemic sting reactions, and 61 allergic patients currently treated with VIT. Levels of sIgE and sIgG4 to bee and vespid venom, rApi m 1, and rVes v 5 were measured immediately after allergic sting reactions or before sting challenges and 4 weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT inhibition and ELIFAB assay. RESULTS: Median sIgG4 levels were 96-fold higher in VIT patients (P < .001) while sIgE/sIgG4 ratios were consistently lower (P < .001). The ELIFAB assay was paralleled by low sIgE/sIgG4 ratios in VIT patients, showing markedly higher allergen-blocking capacity (P < .001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG4 levels were increased in allergic and asymptomatically sensitized patients, but not in VIT patients. CONCLUSION: Immunological responses after stings varied in bee and vespid venom-allergic patients. In patients under VIT, sIgE and sIgG4 remained completely stable after sting challenges. Monitoring VIT efficacy was only possible in vespid venom allergy, and the sIgG4 threshold for rVes v 5 had the highest sensitivity to confirm tolerance. The BAT inhibition test was the most reliable tool to confirm tolerance on an individual basis.

Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Questionable diagnostic benefit of the commercially available panel of bee venom components.

For many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV-allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double-sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross-reacting allergens.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. RESULTS: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. CONCLUSIONS: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.

Hymenoptera stings in the head region induce impressive, but not severe sting reactions.

Stings in the head region are considered to be a risk factor for severe systemic reactions to hymenoptera stings. We supposed that stings in skin areas, which are well supplied with blood, lead to more severe reactions and tested our hypothesis in 847 patients with confirmed hymenoptera venom allergy. However, symptom severity was independent from sting site: only 16.3% of patients with severe reactions were stung on the head (P = 0.017). But we confirmed age > 40 years (P < 0.001) as well as elevated basal tryptase levels (P = 0.001) as risk factors. Taking antihypertensive drugs seemed to have an influence: 41.7% of patients taking antihypertensive drugs experienced a severe reaction compared to 29.5% of patients, not taking such drugs (P = 0.019). However, considering patients' age in regression analysis, taking antihypertensive drugs had no effect on symptom severity (P = 0.342). Importantly, in most patients with severe reactions, cutaneous signs were absent (P < 0.001).

Self-medication of anaphylactic reactions due to Hymenoptera stings-an EAACI Task Force Consensus Statement.

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self-medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self-management of sting reactions, to propose indications for the prescription of an adrenaline auto-injector (AAI), and to discuss other forms of medication. First-line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom-allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.