Publications by authors named "Gunter Sturm"

51 Publications

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Regional Ministry of Health of Andalusia, Seville, Spain.

Older adults, especially men and/or those with diabetes, hypertension and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritised to receive COVID-19 vaccines due to high risk of death. In very rare instances,the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society)Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
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http://dx.doi.org/10.1111/all.14838DOI Listing
April 2021

β-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

Allergy 2021 Feb 19. Epub 2021 Feb 19.

Department of Internal Diseases, Pulmonology and Allergology, Medical University of Wroclaw, Wroclaw, Poland.

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT).

Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment.

Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI.

Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).
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http://dx.doi.org/10.1111/all.14785DOI Listing
February 2021

Healthcare provision for insect venom allergy patients during the COVID-19 pandemic.

Allergo J Int 2020 8;29(8):257-261. Epub 2020 Dec 8.

Department and Outpatient Clinic for Dermatology and Allergology, University Hospital Munich, Munich, Germany.

The population prevalence of insect venom allergy ranges between 3-5%, and it can lead to potentially life-threatening allergic reactions. Patients who have experienced a systemic allergic reaction following an insect sting should be referred to an allergy specialist for diagnosis and treatment. Due to the widespread reduction in outpatient and inpatient care capacities in recent months as a result of the COVID-19 pandemic, the various allergy specialized centers in Germany, Austria, and Switzerland have taken different measures to ensure that patients with insect venom allergy will continue to receive optimal allergy care. A recent data analysis from the various centers revealed that there has been a major reduction in newly initiated insect venom immunotherapy (a 48.5% decline from March-June 2019 compared to March-June 2020: data from various centers in Germany, Austria, and Switzerland). The present article proposes defined organizational measures (e.g., telephone and video appointments, rearranging waiting areas and implementing hygiene measures and social distancing rules at stable patient numbers) and medical measures (collaboration with practice-based physicians with regard to primary diagnostics, rapid COVID-19 testing, continuing already-initiated insect venom immunotherapy in the outpatient setting by making use of the maximal permitted injection intervals, prompt initiation of insect venom immunotherapy during the summer season, and, where necessary, using outpatient regimens particularly out of season) for the care of insect venom allergy patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s40629-020-00157-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722411PMC
December 2020

EAACI Allergen Immunotherapy User's Guide.

Pediatr Allergy Immunol 2020 05;31 Suppl 25:1-101

Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.
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http://dx.doi.org/10.1111/pai.13189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317851PMC
May 2020

Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.

Allergy 2021 03;76(3):629-647

Department of Respiratory Medicine, Royal Sussex County Hospital, University of Sussex and University of Brighton, Brighton, UK.

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.
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http://dx.doi.org/10.1111/all.14331DOI Listing
March 2021

Large local reactions and systemic reactions to insect stings: Similarities and differences.

PLoS One 2020 16;15(4):e0231747. Epub 2020 Apr 16.

Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.

Background: Large local reactions (LLR) to Hymenoptera stings were considered as IgE-mediated late-phase inflammatory reactions. However, in older studies, most patients with LLR were skin test positive, but only around 50% had detectable sIgE determined by the RAST system.

Methods: Data of 620 patients were evaluated retrospectively: 310 patients who suffered from LLR and 310 patients with previous systemic sting reactions (SSR). We aimed to clarify if sIgE can generally be detected by the CAP system in patients with LLR; sIgE levels and clinical parameters were compared between patients with LLR and SSR.

Results: Positive sIgE levels were detected in 80.7% of patients with LLR, and in 95.2% of patients with SSR (p<0.001). Of the 310 patients with LLR, 80.6% had a LLR with a size of 10-20cm, whereas 19.4% had swellings >20cm, with a mean duration of seven days. In only 2.9% of patients, LLRs occurred after stings on the trunk, while 14.8% of SSR resulted from stings on this site (p<0.001). Similarly, LLR were also less frequent on the capillitium compared to SSR (8.1% versus 26.2%; p = 0.035).

Conclusions: LLR usually persisted over seven days and about one fifth of patients had swellings greater than 20cm. Contrary to SSR, LLR were less frequently observed on the capillitium and on the trunk. In most patients with LLR, sIgE could be detected. However, total IgE and sIgE levels to bee or vespid venom did not differ between patients with LLR and SSR.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231747PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162517PMC
August 2020

Perspectives in allergen immunotherapy: 2019 and beyond.

Allergy 2019 12;74 Suppl 108:3-25

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Zurich, Switzerland.

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future.
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http://dx.doi.org/10.1111/all.14077DOI Listing
December 2019

Apolipoprotein A-IV acts as an endogenous anti-inflammatory protein and is reduced in treatment-naïve allergic patients and allergen-challenged mice.

Allergy 2020 02 10;75(2):392-402. Epub 2019 Sep 10.

Division of Pharmacology, Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.

Background: Recent studies pointed to a crucial role for apolipoproteins in the pathogenesis of inflammatory diseases. However, the role of apolipoprotein-IV (ApoA-IV) in allergic inflammation has not been addressed thoroughly thus far.

Objective: Here, we explored the anti-inflammatory effects and underlying signaling pathways of ApoA-IV on eosinophil effector function in vitro and in vivo.

Methods: Migratory responsiveness, Ca -flux and apoptosis of human peripheral blood eosinophils were assessed in vitro. Allergen-driven airway inflammation was assessed in a mouse model of acute house dust mite-induced asthma. ApoA-IV serum levels were determined by ELISA.

Results: Recombinant ApoA-IV potently inhibited eosinophil responsiveness in vitro as measured by Ca -flux, shape change, integrin (CD11b) expression, and chemotaxis. The underlying molecular mechanism involved the activation of Rev-ErbA-α and induced a PI3K/PDK1/PKA-dependent signaling cascade. Systemic application of ApoA-IV prevented airway hyperresponsiveness (AHR) and airway eosinophilia in mice following allergen challenge. ApoA-IV levels were decreased in serum from allergic patients compared to healthy controls.

Conclusion: Our data suggest that ApoA-IV is an endogenous anti-inflammatory protein that potently suppresses effector cell functions in eosinophils. Thus, exogenously applied ApoA-IV may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophil-driven disorders.
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http://dx.doi.org/10.1111/all.14022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065107PMC
February 2020

Coadministration of Sublingual Immunotherapy Tablets and Management of Potential Adverse Effects: Austrian, German, and Swiss Expert Recommendations.

Clin Ther 2019 09 25;41(9):1880-1888. Epub 2019 Jul 25.

Allergy & Asthma Center Westend, Berlin, Germany.

Sublingual immunotherapy (SLIT) is currently available as liquid drops and tablets for treatment of allergic patients. Because several allergens are available and many patients are polyallergic, it is possible to treat patients with multiple clinically relevant allergies by >1 SLIT product. Austrian, German, and Swiss medical experts discussed the available data on allergen uptake at the oral mucosa and recently published data on coadministration of a grass and a ragweed tablet. The experts agreed on a schedule considering data from a North American trial on sequential administration of 2 SLIT-tablets with different allergens and their own experiences made during initiation of treatment with >1 SLIT-tablet in their clinics and subsequent self-administration by the patient and discussed the handling and management of potential adverse drug reactions (ADRs). According to the medical experts' opinion, tolerability at each phase of administration and patient preference should be taken into consideration to ensure a high level of adherence to treatment. Local ADRs that are uncomfortable for the patient may be alleviated by a 2- to 4-week course of antihistamine pretreatment. ADRs with severe swelling and/or systemic ADRs need the physician's particular attention and a decision together with the patient on continuation of treatment with SLIT or possible alternative routes of administration.
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http://dx.doi.org/10.1016/j.clinthera.2019.07.005DOI Listing
September 2019

Possible utility of basophil activation test in dual honeybee and vespid sensitization.

J Allergy Clin Immunol Pract 2020 01 22;8(1):392-394.e5. Epub 2019 Jun 22.

Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria; Allergy Outpatient Clinic Reumannplatz, Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2019.06.008DOI Listing
January 2020

Risk factors and indicators of severe systemic insect sting reactions.

Allergy 2020 03 16;75(3):535-545. Epub 2019 Jul 16.

Department of Dermatology, Venereology and Allergy & Allergy Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.

Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.
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http://dx.doi.org/10.1111/all.13945DOI Listing
March 2020

Allergic rhinitis is associated with complex alterations in high-density lipoprotein composition and function.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 10 8;1864(10):1280-1292. Epub 2019 Jun 8.

Division of Pharmacology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.; BioTechMed Graz, Mozartgasse 12/II, 8010 Graz, Austria. Electronic address:

Despite strong evidence that high-density lipoproteins (HDLs) modulate the immune response, the role of HDL in allergies is still poorly understood. Many patients with allergic rhinitis (AR) develop a late-phase response, characterized by infiltration of monocytes and eosinophils into the nasal submucosa. Functional impairment of HDL in AR-patients may insufficiently suppress inflammation and cell infiltration, but the effect of AR on the composition and function of HDL is not understood. We used apolipoprotein (apo) B-depleted serum as well as isolated HDL from AR-patients (n = 43) and non-allergic healthy controls (n = 20) for detailed compositional and functional characterization of HDL. Both AR-HDL and apoB-depleted serum of AR-patients showed decreased anti-oxidative capacity and impaired ability to suppress monocyte nuclear factor-κB expression and pro-inflammatory cytokine secretion, such as interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor alpha and IL-1 beta. Sera of AR-patients showed decreased paraoxonase and cholesteryl-ester transfer protein activities, increased lipoprotein-associated phospholipase A2 activity, while lecithin-cholesterol acyltransferase activity and cholesterol efflux capacity were not altered. Surprisingly, apoB-depleted serum and HDL from AR-patients showed an increased ability to suppress eosinophil effector responses upon eotaxin-2/CCL24 stimulation. Mass spectrometry and biochemical analyses showed reduced levels of apoA-I and phosphatidylcholine, but increased levels of apoA-II, triglycerides and lyso-phosphatidylcholine in AR-HDL. The changes in AR-HDL composition were associated with altered functional properties. In conclusion, AR alters HDL composition linked to decreased anti-oxidative and anti-inflammatory properties but improves the ability of HDL to suppress eosinophil effector responses.
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http://dx.doi.org/10.1016/j.bbalip.2019.06.007DOI Listing
October 2019

EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma.

Allergy 2019 05;74(5):855-873

Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland.

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence).
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http://dx.doi.org/10.1111/all.13749DOI Listing
May 2019

Medical Algorithms: Diagnosis and treatment of Hymenoptera venom allergy.

Allergy 2019 10 2;74(10):2016-2018. Epub 2019 Jun 2.

Mozartpraxis, Paediatric Respiratory and Allergy Outpatient Practice, Graz, Austria.

Diagnosis of Hymenoptera venom allergy (HVA) is straightforward in the majority of patients, but can be challenging in double positive and test negative patients. Test results sometimes can be confusing as patients with high skin test reactivity and high specific IgE (sIgE) levels are not at risk for severe systemic sting reactions (SSR), and conversely, patients with weakly positive or even negative tests can experience severe SSR. Venom immunotherapy (VIT) is safe, highly effective, and recommended in patients with moderate to severe SSR and in patients with SSR confined to generalized skin symptoms if quality of life is impaired.
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http://dx.doi.org/10.1111/all.13817DOI Listing
October 2019

2019 ARIA Care pathways for allergen immunotherapy.

Allergy 2019 11 15;74(11):2087-2102. Epub 2019 Jul 15.

Unité de pneumo-allergologie de l'enfant, pôle pédiatrique, CHU de Clermont-Ferrand-Estaing, Clermont-Ferrand, France.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.
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http://dx.doi.org/10.1111/all.13805DOI Listing
November 2019

Univ.- Prof. Dr. Werner Aberer in den Ruhestand verabschiedet.

Authors:
Gunter Sturm

J Dtsch Dermatol Ges 2019 Jan;17(1):107-108

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http://dx.doi.org/10.1111/ddg.13725DOI Listing
January 2019

New trends in anaphylaxis.

Allergo J Int 2017 15;26(8):295-300. Epub 2017 Nov 15.

Department of Dermatology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

This review presents the current trends in anaphylaxis management discussed at the fourth International Network for Online-Registration of Anaphylaxis (NORA) conference held in Berlin in April 2017. Current data from the anaphylaxis registry show that Hymenoptera venom, foods, and pharmaceutical drugs are still among the most frequent triggers of anaphylaxis. Rare triggers include chicory, cardamom, asparagus, and goji berries. A meta-analysis on recent trends in insect venom anaphylaxis demonstrated for the first time that, although data on the efficacy of insect venom immunotherapy is limited, the occurrence of severe reactions upon repeated sting events can be prevented and patients' quality of life improved. Molecular diagnostics of insect venom anaphylaxis have significantly improved diagnostic sensitivity and specificity. Self-treatment of anaphylaxis is of great importance. Recent data from the anaphylaxis registry show an increase (from 23% in 2012 to 29% in 2016) in the use of adrenaline as recommended in the guidelines. A survey on the implementation of guidelines conducted among the centers reporting to the anaphylaxis registry highlights the extent to which the guideline has been perceived and implemented. Reports on a variety of cases in the anaphylaxis registry illustrate the diversity of this potentially life-threatening reaction. Component-resolved diagnostics can help to specify sensitization profiles in anaphylaxis, particularly in terms of the risk for severe reactions. Recent studies on anaphylaxis awareness show that training methods are effective; nevertheless, target groups and learning methods need to undergo further scientific investigation in coming years.
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http://dx.doi.org/10.1007/s40629-017-0042-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705757PMC
November 2017

EAACI guidelines on allergen immunotherapy: Prevention of allergy.

Pediatr Allergy Immunol 2017 Dec 27;28(8):728-745. Epub 2017 Oct 27.

Food Allergy Referral Centre Veneto Region, Department of Woman and Child Health, Padua University Hospital.

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 the 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 multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer-review of draft recommendations. Our key recommendation is that a 3-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 2 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 2 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 the prevention of allergic comorbidities 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.
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http://dx.doi.org/10.1111/pai.12807DOI Listing
December 2017

Reply.

J Allergy Clin Immunol 2017 03 4;139(3):1067-1068. Epub 2017 Jan 4.

Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.

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http://dx.doi.org/10.1016/j.jaci.2016.09.059DOI Listing
March 2017

Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

Clin Transl Allergy 2015 16;6. Epub 2016 Feb 16.

Allergy and Respiratory Research Group, The University of Edinburgh, Edinburgh, UK.

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy.

Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised.

Discussion: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT.
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http://dx.doi.org/10.1186/s13601-016-0095-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754882PMC
February 2016

Sensitivity and specificity of Hymenoptera allergen components depend on the diagnostic assay employed.

J Allergy Clin Immunol 2016 05 5;137(5):1603-5. Epub 2016 Jan 5.

Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria; Allergy Outpatient Clinic Reumannplatz, Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2015.10.041DOI Listing
May 2016

Phosphoinositide-dependent protein kinase 1 (PDK1) mediates potent inhibitory effects on eosinophils.

Eur J Immunol 2015 May 27;45(5):1548-59. Epub 2015 Feb 27.

Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.

Prostaglandin E2 (PGE2 ) protects against allergic responses via binding to prostanoid receptor EP4, which inhibits eosinophil migration in a PI3K/PKC-dependent fashion. The phosphoinositide-dependent protein kinase 1 (PDK1) is known to act as a downstream effector in PI3K signaling and has been implicated in the regulation of neutrophil migration. Thus, here we elucidate whether PDK1 mediates inhibitory effects of E-type prostanoid receptor 4 (EP4) receptors on eosinophil function. Therefore, eosinophils were isolated from human peripheral blood or differentiated from mouse BM. PDK1 signaling was investigated in shape change, chemotaxis, CD11b, respiratory burst, and Ca(2+) mobilization assays. The specific PDK1 inhibitors BX-912 and GSK2334470 prevented the inhibition by prostaglandin E2 and the EP4 agonist ONO-AE1-329. Depending on the cellular function, PDK1 seemed to act through PI3K-dependent or PI3K-independent mechanisms. Stimulation of EP4 receptors caused PDK1 phosphorylation at Ser396 and induced PI3K-dependent nuclear translocation of PDK1. EP4-induced inhibition of shape change and chemotaxis was effectively reversed by the Akt inhibitor triciribine. In support of this finding, ONO-AE1-329 induced a PI3K/PDK1-dependent increase in Akt phosphorylation. In conclusion, our data illustrate a critical role for PDK1 in transducing inhibitory signals on eosinophil effector function. Thus, our results suggest that PDK1 might serve as a novel therapeutic target in diseases involving eosinophilic inflammation.
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http://dx.doi.org/10.1002/eji.201445196DOI Listing
May 2015

Unusual reactions to hymenoptera stings: what should we keep in mind?

Clin Rev Allergy Immunol 2014 Aug;47(1):91-9

Department of Allergology and Clinical Immunology, "Mother Theresa" School of Medicine, Tirana, Albania,

This review includes a variety of extremely rare and unusual hymenoptera sting (HS) circumstances with regard to sting localization, geographic region, massivity of multiple stings, and particularly related to clinical symptoms. Such reactions occur in a temporal relationship to HS (s), differ from typical allergic symptomatology, and sometimes need follow-up during many months. With respect to pathogenesis, the major mechanisms involved are toxic, autoimmune, and other delayed immunological ones. While delayed inflammatory symptoms of the nervous system are considered as delayed hypersensitization or autoimmune entities, generalized rhabdomyolysis and consecutive acute kidney injury is considered a toxic reaction, mostly induced by massive envenomation to wasps or "Africanized" bees. Hemorrhagic episodes of targeted organ (s) could be additional potential risk for acute kidney injury, while the bee venom-induced hemorrhage is proposed to be a nonimmune-mediated anaphylactic symptom. The hemodynamic involvement of vital organs and systems with hypoxia and hypovolemia together with simultaneous immunoglobulin E (IgE) sensitization are considered potential indications for venom immunotherapy. In contrast, patients who have experienced various complications with unknown or nonallergic mechanisms should be informed about the importance of epinephrine's use and additional measures on future sting avoidance. In conclusion, although unusual reactions are extremely rare, it is important to keep them in mind.
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http://dx.doi.org/10.1007/s12016-014-8434-yDOI Listing
August 2014

Specificity of conventional and Ves v 5-spiked venom decreases with increasing total IgE.

J Allergy Clin Immunol 2014 Sep 13;134(3):739-41. Epub 2014 May 13.

Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2014.03.038DOI Listing
September 2014

Sensitization to Hymenoptera venoms is common, but systemic sting reactions are rare.

J Allergy Clin Immunol 2014 Jun 22;133(6):1635-43.e1. Epub 2013 Dec 22.

Department of Dermatology, Division of Environmental Dermatology and Venerology, Medical University of Graz, Graz, Austria.

Background: Sensitization to Hymenoptera venom without systemic sting reactions (SSRs) is commonly observed in the general population. Clinical relevance for a future sting has not yet been investigated.

Objective: We aimed to evaluate the effect of these debatable sensitizations with deliberate sting challenges and to monitor serologic changes for up to 2 years.

Methods: One hundred thirty-one challenges with bees and wasps were performed in 94 subjects with a hitherto irrelevant sensitization. The clinical outcome was recorded, and results of specific IgE (sIgE) determinations, skin tests, and basophil activation tests were correlated to the sting reaction. sIgE levels were monitored in reactors and nonreactors after 3 hours, 1 week, 4 weeks, and 1 year.

Results: Only 5 (5.3%) patients had SSRs, but 41 (43.6%) had large local reactions (LLRs) after the sting. Compared with the general population, there was a 9.5-fold higher risk for LLRs but not for SSRs. Three hours after the sting, sIgE levels slightly decreased, but none of the 94 subjects' results turned negative. After 1 week, sIgE levels already increased, increasing up to 3.5-fold (range, 0.2- to 34.0-fold) baseline levels after 4 weeks. To assess the clinical relevance of this increase, we randomly selected 18 patients for a re-sting. Again, 50% had an LLR, but none had an SSR.

Conclusion: Although sensitization to Hymenoptera venoms was common, the risk of SSRs in sensitized subjects was low in our study. The sIgE level increase after the sting was not an indicator for conversion into symptomatic sensitization. Currently available tests were not able to distinguish between asymptomatic sensitization, LLRs, and SSRs.
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http://dx.doi.org/10.1016/j.jaci.2013.10.046DOI Listing
June 2014