Publications by authors named "Katja Nemat"

23 Publications

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Severe allergic reactions after COVID-19 vaccination with the Pfizer/BioNTech vaccine in Great Britain and USA: Position statement of the German Allergy Societies: Medical Association of German Allergologists (AeDA), German Society for Allergology and Clinical Immunology (DGAKI) and Society for Pediatric Allergology and Environmental Medicine (GPA).

Allergo J Int 2021 24;30(2):51-55. Epub 2021 Feb 24.

Allergologie und Immunologie, Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.

Two employees of the National Health Service (NHS) in England developed severe allergic reactions following administration of BNT162b2 vaccine against COVID-19 (coronavirus disease 2019). The British SmPC for the BNT162b2 vaccine already includes reference to a contraindication for use in individuals who have had an allergic reaction to the vaccine or any of its components. As a precautionary measure, the Medicines and Healthcare products Regulatory Agency (MHRA) has issued interim guidance to the NHS not to vaccinate in principle in "patients with severe allergies". Allergic reactions to vaccines are very rare, but vaccine components are known to cause allergic reactions. BNT162b2 is a vaccine based on an mRNA embedded in lipid nanoparticles and blended with other substances to enable its transport into the cells. In the pivotal phase III clinical trial, the BNT162b2 vaccine was generally well tolerated, but this large clinical trial, used to support vaccine approval by the MHRA and US Food and Drug Administration, excluded individuals with a "history of a severe adverse reaction related to the vaccine and/or a severe allergic reaction (e.g., anaphylaxis) to a component of the study medication". Vaccines are recognized as one of the most effective public health interventions. This repeated administration of a foreign protein (antigen) necessitates a careful allergological history before each application and diagnostic clarification and a risk-benefit assessment before each injection. Severe allergic reactions to vaccines are rare but can be life-threatening, and it is prudent to raise awareness of this hazard among vaccination teams and to take adequate precautions while more experience is gained with this new vaccine.
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http://dx.doi.org/10.1007/s40629-020-00160-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903024PMC
February 2021

Update "Systemic treatment of atopic dermatitis" of the S2k-guideline on atopic dermatitis.

J Dtsch Dermatol Ges 2021 Jan;19(1):151-168

Fachbereich Pädiatrische Dermatologie und Allergologie, Kinder- und Jugendkrankenhaus Auf der Bult, Hannover.

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.
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http://dx.doi.org/10.1111/ddg.14371DOI Listing
January 2021

Peanut induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry.

Allergy 2020 Dec 3. Epub 2020 Dec 3.

Division of Allergy and Immunology, Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents.

Methods: Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre.

Results: 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004).

Conclusions: The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.
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http://dx.doi.org/10.1111/all.14683DOI Listing
December 2020

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI), Österreichische Gesellschaft für Pneumologie (ÖGP) in co-operation with the German, Austrian, and Swiss ARIA groups, and the European Academy of Allergy and Clinical Immunology (EAACI).

Authors:
Ludger Klimek Oliver Pfaar Margitta Worm Thomas Eiwegger Jan Hagemann Markus Ollert Eva Untersmayr Karin Hoffmann-Sommergruber Alessandra Vultaggio Ioana Agache Sevim Bavbek Apostolos Bossios Ingrid Casper Susan Chan Alexia Chatzipetrou Christian Vogelberg Davide Firinu Paula Kauppi Antonios Kolios Akash Kothari Andrea Matucci Oscar Palomares Zsolt Szépfalusi Wolfgang Pohl Wolfram Hötzenecker Alexander R Rosenkranz Karl-Christian Bergmann Thomas Bieber Roland Buhl Jeroen Buters Ulf Darsow Thomas Keil Jörg Kleine-Tebbe Susanne Lau Marcus Maurer Hans Merk Ralph Mösges Joachim Saloga Petra Staubach Uta Jappe Klaus F Rabe Uta Rabe Claus Vogelmeier Tilo Biedermann Kirsten Jung Wolfgang Schlenter Johannes Ring Adam Chaker Wolfgang Wehrmann Sven Becker Laura Freudelsperger Norbert Mülleneisen Katja Nemat Wolfgang Czech Holger Wrede Randolf Brehler Thomas Fuchs Peter-Valentin Tomazic Werner Aberer Antje-Henriette Fink-Wagner Fritz Horak Stefan Wöhrl Verena Niederberger-Leppin Isabella Pali-Schöll Wolfgang Pohl Regina Roller-Wirnsberger Otto Spranger Rudolf Valenta Mübecell Akdis Paolo M Matricardi François Spertini Nicolai Khaltaev Jean-Pierre Michel Larent Nicod Peter Schmid-Grendelmeier Marco Idzko Eckard Hamelmann Thilo Jakob Thomas Werfel Martin Wagenmann Christian Taube Erika Jensen-Jarolim Stephanie Korn Francois Hentges Jürgen Schwarze Liam O Mahony Edward F Knol Stefano Del Giacco Tomás Chivato Pérez Jean Bousquet Anna Bedbrook Torsten Zuberbier Cezmi Akdis Marek Jutel

Allergol Select 2020 7;4:53-68. Epub 2020 Sep 7.

European Academy of Allergy and Clinical Immunology (EAACI).

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials And Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
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http://dx.doi.org/10.5414/ALX02166EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480069PMC
September 2020

Allergen immunotherapy in the current COVID-19 pandemic: A position paper of AeDA, ARIA, EAACI, DGAKI and GPA: Position paper of the German ARIA Group in cooperation with the Austrian ARIA Group, the Swiss ARIA Group, German Society for Applied Allergology (AEDA), German Society for Allergology and Clinical Immunology (DGAKI), Society for Pediatric Allergology (GPA) in cooperation with AG Clinical Immunology, Allergology and Environmental Medicine of the DGHNO-KHC and the European Academy of Allergy and Clinical Immunology (EAACI).

Allergol Select 2020 28;4:44-52. Epub 2020 May 28.

German ARIA Group.

No abstract available.
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http://dx.doi.org/10.5414/ALX02147EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304289PMC
May 2020

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Zentrum für Rhinologie & Allergologie, An den Quellen 10, 65183 Wiesbaden, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

Peanut oral immunotherapy protects patients from accidental allergic reactions to peanut.

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2437-2441.e3. Epub 2020 Apr 15.

Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1016/j.jaip.2020.03.043DOI Listing
April 2020

ARIA guideline 2019: treatment of allergic rhinitis in the German health system.

Allergol Select 2019 30;3(1):22-50. Epub 2019 Dec 30.

Department of Dermatology and Allergy, Allergie-Centrum - Charité, Charité - Universitätsmedizin, Berlin, Berlin, Germany.

Background: The number of patients affected by allergies is increasing worldwide. The resulting allergic diseases are leading to significant costs for health care and social systems. Integrated care pathways are needed to enable comprehensive care within the national health systems. The ARIA (Allergic Rhinitis and its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases.

Methods: ARIA serves to improve the care of patients with allergies and chronic respiratory diseases. In collaboration with other international initiatives, national associations and patient organizations in the field of allergies and respiratory diseases, real-life integrated care pathways have been developed for a digitally assisted, integrative, individualized treatment of allergic rhinitis (AR) with comorbid asthma. In the present work, these integrated care pathways have been adapted to the German situation and health system.

Results: The present ICP (integrated care pathway) guideline covers key areas of the care of AR patients with and without asthma. It includes the views of patients and other healthcare providers.

Discussion: A comprehensive ICP guideline can reflect real-life care better than traditional guideline models.
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http://dx.doi.org/10.5414/ALX02120EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066682PMC
December 2019

Efficacy, Safety, and Quality of Life in a Multicenter, Randomized, Placebo-Controlled Trial of Low-Dose Peanut Oral Immunotherapy in Children with Peanut Allergy.

J Allergy Clin Immunol Pract 2019 02 10;7(2):479-491.e10. Epub 2018 Nov 10.

Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: Only 2 small placebo-controlled trials on peanut oral immunotherapy (OIT) have been published.

Objective: We examined the efficacy, safety, immunologic parameters, quality of life (QOL), and burden of treatment (BOT) of low-dose peanut OIT in a multicenter, double-blind, randomized placebo-controlled trial.

Methods: A total of 62 children aged 3 to 17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo. The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge (OFC) after 16 months of OIT. We measured the occurrence of adverse events (AEs), immunologic changes, and QOL before and after OIT and BOT during OIT.

Results: Twenty-three of 31 (74.2%) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 (16.1%) in the placebo group (P < .001). Thirteen of 31 (41.9%) children of the active versus 1 of 31 (3.2%) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC (P < .001). There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number, severity, and treatment of objective AEs. In the peanut-OIT group, we noted a significant reduction in peanut-specific IL-4, IL-5, IL-10, and IL-2 production by PBMCs compared with the placebo group, as well as a significant increase in peanut-specific IgG levels and a significant improvement in QOL; 86% of children evaluated the BOT positively.

Discussion: Low-dose OIT is a promising, effective, and safe treatment option for peanut-allergic children, leading to improvement in QOL, a low BOT, and immunologic changes showing tolerance development.
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http://dx.doi.org/10.1016/j.jaip.2018.10.048DOI Listing
February 2019

S2k guideline on diagnosis and treatment of atopic dermatitis - short version.

Allergo J Int 2016;25:82-95. Epub 2016 May 2.

Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité - UniversitÄtsmedizin, Berlin, Deutschland.

Atopic dermatitis (AD) represents a pruritic, non-contagious, chronic or chronically relapsing, inflammatory skin disease. The course of the disease may be complicated by bacterial or viral superinfections. The first manifestation of the disease and further flare-ups are due to genetic predisposition and also to a variety of further trigger factors. The therapy regimen should be adapted to disease symptoms that are actually present and consider individual features of the disease as reported by the patients or their parents. This short version of the German guideline on AD provides an overview of evidence-based diagnostic and treatment options. All recommendations made here are the result of a consensus of the scientific medical societies, working groups and support groups based on scientific data published to date. Abstracts and details of the studies cited are provided in the long version of this guideline (see: www.awmf.org).
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http://dx.doi.org/10.1007/s40629-016-0110-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861742PMC
May 2016

Anaphylaxis in children and adolescents: The European Anaphylaxis Registry.

J Allergy Clin Immunol 2016 Apr 21;137(4):1128-1137.e1. Epub 2016 Jan 21.

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Background: Anaphylaxis in children and adolescents is a potentially life-threatening condition. Its heterogeneous clinical presentation and sudden occurrence in virtually any setting without warning have impeded a comprehensive description.

Objective: We sought to characterize severe allergic reactions in terms of elicitors, symptoms, emergency treatment, and long-term management in European children and adolescents.

Methods: The European Anaphylaxis Registry recorded details of anaphylaxis after referral for in-depth diagnosis and counseling to 1 of 90 tertiary allergy centers in 10 European countries, aiming to oversample the most severe reactions. Data were retrieved from medical records by using a multilanguage online form.

Results: Between July 2007 and March 2015, anaphylaxis was identified in 1970 patients younger than 18 years. Most incidents occurred in private homes (46%) and outdoors (19%). One third of the patients had experienced anaphylaxis previously. Food items were the most frequent trigger (66%), followed by insect venom (19%). Cow's milk and hen's egg were prevalent elicitors in the first 2 years, hazelnut and cashew in preschool-aged children, and peanut at all ages. There was a continuous shift from food- to insect venom- and drug-induced anaphylaxis up to age 10 years, and there were few changes thereafter. Vomiting and cough were prevalent symptoms in the first decade of life, and subjective symptoms (nausea, throat tightness, and dizziness) were prevalent later in life. Thirty percent of cases were lay treated, of which 10% were treated with an epinephrine autoinjector. The fraction of intramuscular epinephrine in professional emergency treatment increased from 12% in 2011 to 25% in 2014. Twenty-six (1.3%) patients were either admitted to the intensive care unit or had grade IV/fatal reactions.

Conclusions: The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hen's egg, cow's milk, and nuts. Reactions to insect venom were seen more in young adulthood. Intensive care unit admissions and grade IV/fatal reactions were rare. The registry will serve as a systematic foundation for a continuous description of this multiform condition.
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http://dx.doi.org/10.1016/j.jaci.2015.11.015DOI Listing
April 2016

S2k guideline on diagnosis and treatment of atopic dermatitis--short version.

J Dtsch Dermatol Ges 2016 Jan;14(1):92-106

Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Berlin.

Atopic dermatitis (AD) represents a pruritic, non-contagious, chronic or chronically relapsing, inflammatory skin disease. The course of the disease may be complicated by bacterial or viral superinfections. The first manifestation of the disease and further flare-ups are due to genetic predisposition and also to a variety of further trigger factors. The therapy regimen should be adapted to disease symptoms that are actually present and consider individual features of the disease as reported by the patients or their parents. This short version of the German guideline on AD provides an overview of evidence-based diagnostic and treatment options. All recommendations made here are the result of a consensus of the scientific medical societies, working groups and support groups based on scientific data published to date. Abstracts and details of the studies cited are provided in the long version of this guideline (see: www.awmf.org).
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http://dx.doi.org/10.1111/ddg.12871DOI Listing
January 2016

Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance.

PLoS Genet 2015 Mar 10;11(3):e1005076. Epub 2015 Mar 10.

Max-Delbrück-Centrum (MDC) for Molecular Medicine, Berlin, Germany; Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.

Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring's susceptibility to a common human disease.
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http://dx.doi.org/10.1371/journal.pgen.1005076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355615PMC
March 2015

Triggers and treatment of anaphylaxis: an analysis of 4,000 cases from Germany, Austria and Switzerland.

Dtsch Arztebl Int 2014 May;111(21):367-75

Allergy Center Charité, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, ADAC Air Rescue Service Senftenberg, Department of Dermatology and Venereology, Medical University of Graz, Austria, Department of Pediatrics, Pneumonology and Immunology, Charité - Universitätsmedizin Berlin, Allergy Clinic, Department of Dermatology, SALK, Paracelsus Medical University, Salzburg, Austria, Pediatric Allergology, University Children's Hospital Zurich, Zurich, Switzerland, Department of Dermatology, University Hospital Erlangen-Nürnberg, Department of Pediatric Pneumology and Allergology at the KID Center, Dresden-Friedrichstadt, Department of Dermatology, Venerology and Allergy at the Saarland University, Homburg/Saar, Department of Allergology, Johanniter-Krankenhaus im Fläming Treuenbrietzen GmbH, Treuenbrietzen, Department of Internal Medicine I: Pneumology & Allergology/Immunology, Friedrich Schiller University Jena, Department of Pediatric Pulmonology and Allergology, Children's Hospital of the University of Cologne, Allergy Unit, Department of Dermatology, University Hospital Basel, Basel, Schweiz, Department of Dermatology, Venereology and Allergology, University of Leipzig, Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Margitta Worm and Oliver Eckermann have equally contributed to the manuscript.

Background: Anaphylaxis is the most severe manifestation of a mast cell-dependent immediate reaction and may be fatal. According to data from the Berlin region, its incidence is 2-3 cases per 100 000 persons per year.

Method: We evaluated data from the anaphylaxis registry of the German-speaking countries for 2006-2013 and data from the protocols of the ADAC air rescue service for 2010-2011 to study the triggers, clinical manifestations, and treatment of anaphylaxis.

Results: The registry contained data on 4141 patients, and the ADAC air rescue protocols concerned 1123 patients. In the registry, the most common triggers for anaphylaxis were insect venom (n = 2074; 50.1%), foods (n = 1039; 25.1%), and drugs (n = 627; 15.1%). Within these groups, the most common triggers were wasp (n = 1460) and bee stings (n = 412), legumes (n = 241), animal proteins (n = 225), and analgesic drugs (n = 277). Food anaphylaxis was most frequently induced by peanuts, cow milk, and hen's egg in children and by wheat and shellfish in adults. An analysis of the medical emergency cases revealed that epinephrine was given for grade 3 or 4 anaphylaxis to 14.5% and 43.9% (respectively) of the patients in the anaphylaxis registry and to 19% and 78% of the patients in the air rescue protocols.

Conclusion: Wasp and bee venom, legumes, animal proteins, and analgesic drugs were the commonest triggers of anaphylaxis. Their relative frequency was age-dependent. Epinephrine was given too rarely, as it is recommended in the guidelines for all cases of grade 2 and above.
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http://dx.doi.org/10.3238/arztebl.2014.0367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075276PMC
May 2014

Modified oral food challenge used with sensitization biomarkers provides more real-life clinical thresholds for peanut allergy.

J Allergy Clin Immunol 2014 Aug 13;134(2):390-8. Epub 2014 May 13.

Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: Threshold levels for peanut allergy determined by using oral challenges are important for the food industry with regard to allergen labeling. Moreover, the utility of biological markers in predicting threshold levels is uncertain.

Objective: We sought to use a modified oral food challenge regimen that might determine threshold levels for peanut allergy mimicking a more real-life exposure and to correlate the eliciting dose (ED) and severity of clinical reaction in children with peanut allergy with B-cell, T-cell, and effector cell markers.

Methods: A modified food challenge procedure with doses scheduled 2 hours apart was used in 63 children with peanut allergy. All children received a maximum of 8 semi-log increasing titration steps of roasted peanuts ranging from 3 to 4500 mg of peanut protein until objective allergic reactions occurred. Severity of symptoms was graded from I to V. Biological markers were measured before challenge.

Results: Forty-five of 63 patients showed objective symptoms after greater than 30 minutes, with a median latency of clinical reaction of 55 minutes. By using a log-normal dose-distribution model, the ED5 was calculated to be 1.95 mg of peanut protein. The ED was significantly and inversely correlated with peanut- and Ara h 2-specific IgE levels, skin prick test responses, basophil activation, and TH2 cytokine production by PBMCs. Symptom severity did not correlate with any of the markers or the ED.

Conclusion: This modified food challenge procedure might better reflect threshold levels for peanut allergy than the standard procedure because most of the patients reacted at a time interval of greater than 30 minutes. By using this model, threshold levels, but not severity, could be correlated with biological markers.
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http://dx.doi.org/10.1016/j.jaci.2014.03.035DOI Listing
August 2014

A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis.

J Allergy Clin Immunol 2013 Aug 9;132(2):371-7. Epub 2013 Apr 9.

Pediatric Allergology, Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: Atopic dermatitis (AD) is a common inflammatory skin disease. Previous studies have revealed shared genetic determinants among different inflammatory disorders, suggesting that markers associated with immune-related traits might also play a role in AD.

Objective: We sought to identify novel genetic risk factors for AD.

Methods: We examined the results of all genome-wide association studies from a public repository and selected 318 genetic markers that were significantly associated with any inflammatory trait. These markers were considered candidates and tested for association with AD in a 3-step approach including 7 study populations with 7130 patients with AD and 9253 control subjects.

Results: A functional amino acid change in the IL-6 receptor (IL-6R Asp358Ala; rs2228145) was significantly associated with AD (odds ratio [OR], 1.15; P = 5 × 10(-9)). Interestingly, investigation of 2 independent population-based birth cohorts showed that IL-6R 358Ala specifically predisposes to the persistent form of AD (ORpersistent AD = 1.22, P = .0008; ORtransient AD = 1.04, P = .54). This variant determines the balance between the classical membrane-bound versus soluble IL-6R signaling pathways. Carriers of 358Ala had increased serum levels of soluble IL-6R (P = 4 × 10(-14)), with homozygote carriers showing a 2-fold increase. Moreover, we demonstrate that soluble IL-6R levels were higher in patients with AD than in control subjects (46.0 vs 37.8 ng/mL, P = .001). Additional AD risk variants were identified in RAD50, RUNX3, and ERBB3.

Conclusion: Our study supports the importance of genetic variants influencing inflammation in the etiology of AD. Moreover, we identified a functional genetic variant in IL6R influencing disease prognosis and specifically predisposing to persistent AD.
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http://dx.doi.org/10.1016/j.jaci.2013.01.057DOI Listing
August 2013

Implementation of anaphylaxis management guidelines: a register-based study.

PLoS One 2012 10;7(5):e35778. Epub 2012 May 10.

Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Centre Berlin, Berlin, Germany.

Background: Anaphylaxis management guidelines recommend the use of intramuscular adrenaline in severe reactions, complemented by antihistamines and corticoids; secondary prevention includes allergen avoidance and provision of self-applicable first aid drugs. Gaps between recommendations and their implementation have been reported, but only in confined settings. Hence, we analysed nation-wide data on the management of anaphylaxis, evaluating the implementation of guidelines.

Methods: Within the anaphylaxis registry, allergy referral centres across Germany, Austria and Switzerland provided data on severe anaphylaxis cases. Based on patient records, details on reaction circumstances, diagnostic workup and treatment were collected via online questionnaire. Report of anaphylaxis through emergency physicians allowed for validation of registry data.

Results: 2114 severe anaphylaxis patients from 58 centres were included. 8% received adrenaline intravenously, 4% intramuscularly; 50% antihistamines, and 51% corticoids. Validation data indicated moderate underreporting of first aid drugs in the Registry. 20% received specific instructions at the time of the reaction; 81% were provided with prophylactic first aid drugs at any time.

Conclusion: There is a distinct discrepancy between current anaphylaxis management guidelines and their implementation. To improve patient care, a revised approach for medical education and training on the management of severe anaphylaxis is warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035778PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349675PMC
September 2012

Provoking allergens and treatment of anaphylaxis in children and adolescents--data from the anaphylaxis registry of German-speaking countries.

Pediatr Allergy Immunol 2011 Sep 16;22(6):568-74. Epub 2011 Mar 16.

Department of Dermatology and Allergy, University Hospital Charité Berlin, Germany.

Anaphylaxis is the most severe reaction of an IgE-mediated hypersensitivity. Data about affected patients may help to improve our knowledge of anaphylaxis and its medical care. We analysed data from the anaphylaxis registry of German speaking countries with regard to the provoking allergens and treatment modalities of anaphylaxis in children and adolescents. Inclusion criteria were severe systemic allergic reactions with concomitant pulmonary and/or cardiovascular symptoms. The data are collected by a password-controlled online-questionnaire. For this analysis, data of 197 reported anaphylactic reactions from children and adolescents registered between 2006 and 2009 were included. The data show that within the registered cases the most frequently affected organ systems for children and adolescents were the skin (89%) and the respiratory tract (87%) followed by symptoms of the cardiovascular system (47%) and the gastrointestinal tract (43%). The most frequent elicitors were food allergens accounting for 58% of cases, followed by insect venom (24%) and drugs (8%). The most frequent food allergens were peanuts followed by tree nuts and animal related food products. In 18% aggravating factors such as physical exercise were noted by the clinicians. 26% of the analysed patients had experienced more than one reaction. The data regarding the emergency treatment show that antihistamines (87%) and corticosteroids (85%) were often used but that adrenaline was rarely used (22% of the registered cases). Taken together these data show that the analysis of anaphylaxis by registration of affected individuals can provide data about provoking allergens and treatment measures but also suggest the impact of aggravating factors on anaphylactic reactions. The under-represented usage of adrenaline indicates the need of educational measures for patients and their physicians.
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http://dx.doi.org/10.1111/j.1399-3038.2011.01154.xDOI Listing
September 2011