Position Paper
Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic
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, and Marek Jutel
Volume 4 (2020) p. 53 - 68
Abstract
Allergologie select, Volume 4/2020 (53-68)
Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic
Ludger Klimek1, Oliver Pfaar2, Margitta Worm3, Thomas Eiwegger4,5,6, Jan Hagemann7, Markus Ollert8,9, Eva Untersmayr10, Karin Hoffmann-Sommergruber10, Alessandra Vultaggio11, Ioana Agache12, Sevim Bavbek13, Apostolos Bossios14,15, Ingrid Casper1,16,17, Susan Chan18, Alexia Chatzipetrou19, Christian Vogelberg20, Davide Firinu21, Paula Kauppi22, Antonios Kolios16,23, Akash Kothari4, Andrea Matucci11, Oscar Palomares24, Zsolt Szépfalusi25, Wolfgang Pohl26, Wolfram Hötzenecker27, Alexander R. Rosenkranz28, Karl-Christian Bergmann3, Thomas Bieber29, Roland Buhl30, Jeroen Buters31, Ulf Darsow32, Thomas Keil33, Jörg Kleine-Tebbe34, Susanne Lau35, Marcus Maurer98, Hans Merk36, Ralph Mösges37,38,39, Joachim Saloga40, Petra Staubach40, Uta Jappe41, Klaus F. Rabe42, Uta Rabe42, Claus Vogelmeier44, Tilo Biedermann32,45, Kirsten Jung46, Wolfgang Schlenter47, Johannes Ring48,49, Adam Chaker50,51, Wolfgang Wehrmann52, Sven Becker53, Laura Freudelsperger7, Norbert Mülleneisen54, Katja Nemat55, Wolfgang Czech56, Holger Wrede57, Randolf Brehler58, Thomas Fuchs59, Peter-Valentin Tomazic60, Werner Aberer61, Antje-Henriette Fink-Wagner62, Fritz Horak63, Stefan Wöhrl64, Verena Niederberger-Leppin65, Isabella Pali-Schöll10,66,67, Wolfgang Pohl68, Regina Roller-Wirnsberger69, Otto Spranger70, Rudolf Valenta71,94,95,96, Mübecell Akdis72, Paolo M. Matricardi73, François Spertini74, Nicolai Khaltaev75, Jean-Pierre Michel76, Larent Nicod77, Peter Schmid-Grendelmeier78, Marco Idzko79, Eckard Hamelmann80, Thilo Jakob81, Thomas Werfel82, Martin Wagenmann83, Christian Taube84, Erika Jensen-Jarolim10,66, Stephanie Korn30, Francois Hentges85, Jürgen Schwarze86, Liam O´Mahony87, Edward F. Knol88, Stefano del Giacco89, Tomás Chivato Pérez90, Jean Bousquet91,92,93,94,95, Anna Bedbrook91, Torsten Zuberbier3, Cezmi Akdis72, and Marek Jutel96,97
1Zentrum für Rhinologie und Allergologie, Wiesbaden, 2HNO-Universitätsklinik Marburg, Sektion Rhinologie und Allergologie, Medizinische Fakultät Marburg, Philipps-Universität Marburg, 3Comprehensive Allergy Centre Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin, Germany, 4Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Ontario, Canada, 5Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Hospital for Sick Children, Toronto, Ontario, Canada, 6Department of Immunology, University of Toronto, Toronto, Ontario, Canada, 7Hals-, Nasen-, Ohrenklinik und Poliklinik, Universitätsmedizin Mainz, Germany 8Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxemburg, 9Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark, 10Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medizinische Fakultät der Universität Wien, Vienna, Austria, 11Immunoallergology Unit, Careggi University Hospital, Florence, Italy, 12Transylvania University, Brasov, Romania, 13Ankara University, School of Medicine, Department of Chest Disease, Division of, Immunology and Allergy, Ankara, Turkey, 14Abteilung für Atemwegsmedizin und Allergie, Karolinska University Hospital, Huddinge und Abteilung für Medizin, Huddinge, Karolinska Institutet, Stockholm, Sweden, 15Zentrum für Allergieforschung, Karolinska Institutet, Stockholm, Sweden, 16Department of Immunology, University Hospital Zürich, Zürich, Switzerland, 17Faculty of Medicine, University of Zürich, Zürich, Switzerland, 18Guy’s and St. Thomas’ NHS Foundation Trust, Westminster Bridge Road, London, United Kingdom, King’s College London School of Life Course Sciences & School of Immunology & Microbial Sciences, King’s Health Partners, United Kingdom, 19Allergy Unit 2nd Department of Dermatology and Venereology, National University of Athens, Medical School, University General Hospital „ATTIKON“, Athen, Greece, 20Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Kinder- und Jugendmedizin, Fachbereich Kinderpneumologie/Allergologie, Dresden, Germany 21Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy, 22Abteilung für Allergie, Entzündungszentrum, Universitätsklinikum Helsinki, Helsinki, Finland, 23Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA, 24Department of Biochemistry and Molecular Biology, Chemistry School, Complutense University of Madrid, Spain, 25Abteilung für Pädiatrische Pulmologie, Allergologie und Endokrinologie, Universitätsklinik für Kinder- und Jugendheilkunde, Comprehensive Center for Pediatrics, Medizinische Universität Wien, Vienna, Austria, 26Abteilung für Atmungs- und Lungenerkrankungen, Krankenhaus Hietzing, Vienna, Austria, 27Abteilung für Dermatologie und Venerologie, Kepler Universitätsklinikum, Linz, Austria, 28Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Austria, 29Klinik für Dermatologie und Allergologie, Universität Bonn, Bonn, 30Schwerpunkt Pneumologie, III. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, 31Zentrum Allergie und Umwelt (ZAUM) Technische Universität und Helmholtz Zentrum München, 32Klinik und Poliklinik für Dermatologie und Allergologie der Technischen Universität München, 33Institut für Klinische Epidemiologie und Biometrie, Universität Würzburg, 34Allergie- und Asthma-Zentrum Westend, Berlin, 35Klinik für Pädiatrie m.S. Pneumologie, Immunologie und Intensivmedizin, Charité – Universitätsmedizin Berlin, 36Abteilung Dermatologie und Allergologie, RWTH Universität, Aachen, 37Medizinische Fakultät der Universität zu Köln, Cologne 38CRI – Clinical Research International Ltd., Hamburg, 39ClinCompetence Cologne GmbH, Köln, Cologne 40Hautklinik und Poliklinik, Universitätsmedizin Mainz, 41Forschungsgruppe Klinische und Molekulare Allergologie des Forschungszentrums Borstel, Airway Research Center North (ARCN), Mitglied des Deutschen Zentrums für Lungenforschung (DZL); Interdisziplinäre Allergie-Ambulanz, Medizinische Klinik III, Universität zu Lübeck, 42LungenClinic Grosshansdorf, Großhansdorf, 43Klinik für Allergologie, Johanniter-Krankenhaus im Fläming Treuenbrietzen GmbH, Treuenbrietzen, 44Klinik für Innere Medizin Schwerpunkt Pneumologie, Philipps-Universität Marburg, 45Einheit für Klinische Allergologie (EKA), Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, 46Praxis für Dermatologie, Immunologie und Allergologie, Erfurt, 47Ärzteverband Deutscher Allergologen, Dreieich, 48Haut- und Laserzentrum an der Oper, München, Munich, 49Academia München, 50HNO-Klinik, Universitätsklinik TUM, München, 51ZAUM, Helmholtz Zentrum München, Munich 52Praxis für Dermatologie und Allergologie, Münster, 53Klinik für Hals-, Nasen- und Ohrenheilkunde, Universität Tübingen, 54Asthma und Allergiezentrum Leverkusen, 55Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Dresden; Praxis für Kinderpenumologie/Allergologie am Kinderzentrum Dresden (Kid), Dresden, 56Praxis und Klinik für Dermatologie/Allergologie am Schwarzwald-Baar Klinikum, Villingen-Schwenningen, 57Hals-, Nasen- und Ohrenarzt, Nordrhein-Westfalen, 58Universitätsklinikum Münster, Klinik für Hautkrankheiten, Ambulanz für Allergologie, Berufsdermatologie und Umweltmedizin, Münster, 59Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum, Georg-August-Universität, Göttingen, Germany 60Klinische Abteilung für allgemeine HNO, Medizinische Universität Graz, Austria, 61Universitätsklinik für Dermatologie und Venerologie, Medizinische Universität Graz, Austria, 62Global Allergy and Airways Patient Platform GAAPP, Vienna, Austria, 63Allergiezentrum Wien West, Vienna, Austria, 64Floridsdorfer Allergiezentrum, Vienna, Austria, 65Universitätsklinik für Hals-, Nasen- und Ohrenkrankheiten, Medizinische Universität Vienna, Austria, 66Komperative Medizin, Interdisziplinäres Messerli Forschungsinstitut, Veterinärmedizinische Universität Wien, Medizinische Universität Wien, 67Institut für Pathophysiologie und Allergieforschung, Medizinische Universität Wien, 68Abteilung für Atmungs- und Lungenerkrankungen, Krankenhaus Hietzing, Vienna, Austria, 69Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Austria, 70Österreichische Lungenunion, Vienna, Austria, 71Immunopathologie, Abteilung für Pathophysiologie und Allergieforschung, Zentrum für Pathophysiologie, Infektiologie und Immunologie, Medizinische Universität Wien, Austria, 72Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland, 73Charité – Universitätsmedizin Berlin, 74Division of Allergy and Immunology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 75GARD Chairman, Genf, Switzerland, 76Department of Rehabilitation and Geriatrics, University of Geneva, Genf, Switzerland, 77Clinic Cecil of Hirslanden Group of Lausanne; Centre Hôpitalier Universitaire du canton de Vaud Lausanne, Switzerland, 78Allergiestation, Dermatologische Klinik, Universitätsspital Zürich, Switzerland, 79Klinische Abteilung für Pneumologie, Universitätsklinik für Innere Medizin II, Medizinische Universität Wien, Austria, 80Kinderzentrum Bethel, Evangelisches Klinikum Bethel, Universitätsmedizin OWL der Universität Bielefeld, 81Klinik für Dermatologie und Allergologie, Universitätsklinikum Gießen, UKGM, Justus-Liebig-Universität, Gießen, 82Klinik für Dermatologie, Allergologie und Venerologie Medizinische Hochschule Hannover, 83HNO-Klinik, Universitätsklinikum Düsseldorf, 84Universitätsklinikum Essen (AöR), Germany 85Service Immunologie-Allergologie Centre Hospitalier de Luxembourg, Luxemburg, 86Kinderleben und Gesundheit, Universität von Edinburgh, United Kingdom, 87Medicine and Microbiology, APC Microbiome Ireland, National University of Ireland, Cork, Irland, 88Departments of Immunology, Dermatology and Allergology, University Medical Center Utrecht, the Netherlands, 89Università degli Studi di Cagliari, Cagliari, Italy, 90University Foundation San Pablo CEU, Madrid, Spain, 91MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France, 92INSERM U 1168, VIMA: Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, France, 93Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France, 94Euforea, Brussels, Belgium, 95Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Germany 96Department of Clinical Immunology, Wrocław Medical University, Wrocław, Poland, 97ALL-MED Medical Research Institute, Wrocław, Poland, and 98Dermatologische Allergologie, Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin, Germany
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.Correspondence to:
Prof. Dr. Ludger Klimek, Zentrum für Rhinologie und Allergologie, An den Quellen 10, 65183 Wiesbaden
Email: [email protected]
Review
Biologics for atopic diseases: Indication, side effect management, and new developments
Uta Jappe, Hendrik Beckert, Karl-Christian Bergmann, Askin Gülsen, Ludger Klimek, Sandra Philipp, Julia Pickert, Michèle M. Rauber-Ellinghaus, Harald Renz, Christian Taube, Regina Treudler, Martin Wagenmann, Thomas Werfel, Margita Worm, and Torsten Zuberbier
Volume 5 (2021) p. 1 - 25
Abstract
Allergologie select, Vol. 5/2021 (1-25)
Biologics for atopic diseases: Indication, side effect management, and new developments
Uta Jappe1,2, Hendrik Beckert3, Karl-Christian Bergmann4, Askin Gülsen2, Ludger Klimek5, Sandra Philipp6, Julia Pickert7, Michèle M. Rauber-Ellinghaus8, Harald Renz9, Christian Taube3, Regina Treudler10, Martin Wagenmann11, Thomas Werfel12, Margita Worm13, and Torsten Zuberbier14
1Research Group Clinical and Molecular Allergology of the Research Center Borstel, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 2Interdisciplinary Allergy Outpatient Clinic, Medical Clinic III, University of Lübeck, 3Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Essen, 4Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 5Center for Rhinology and Allergology, Wiesbaden, 6Dermatology practice Dr. Markus Friedrich/Dr. Sandra Philipp, Oranienburg, 7Department of Dermatology and Allergology, University Hospital Gießen and Marburg, Marburg site, 8Experimental Dermatology and Allergology, Justus Liebig University Giessen, 9Department of Medicine, Institute of Laboratory Medicine and Pathobiochemistry – Molecular Diagnostics, Member of the German Centre for Lung Research (DZL), Philipps-University, Marburg, 10Leipzig Comprehensive Allergy Center LICA-CAC, Department of Dermatology, Venereology and Allergology, University of Leipzig, 11Department of Otorhinolaryngology, HNO-Klinik, Universitätsklinikum Düsseldorf, Düsseldorf, 12Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, 13Dermatology, Venerology and Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 14Department of Dermatology and Allergy, Charité Universitätsmedizin, Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Berlin, Germany
With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodermatitis, and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic viral and bacterial infections and, if necessary, the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.Correspondence to:
Prof. Dr. med. Uta Jappe, Research Center Borstel, Leibniz Lung Center, Parkallee 35, 23845 Borstel
Email: [email protected]
Case Report
Omalizumab ensures compatibility to bee venom immunotherapy (VIT) after VIT-induced anaphylaxis in a patient with systemic mastocytosis
Askin Gülsen, Franziska Ruëff, and Uta Jappe
Volume 5 (2021) p. 128 - 132
Abstract
Allergologie select, Vol. 5/2021 (128-132)
Omalizumab ensures compatibility to bee venom immunotherapy (VIT) after VIT-induced anaphylaxis in a patient with systemic mastocytosis
Askin Gülsen1, Franziska Ruëff2, and Uta Jappe1,3
1Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck, 2Department of Dermatology and Allergology, Klinikum der Ludwig-Maximilians-Universität, Munich, and 3Division of Clinical and Molecular Allergology, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany
Background: Systemic reactions and anaphylaxis due to Hymenoptera venoms occur in up to 7.5% of the European population. Fatal sting reactions are very rare. Serum tryptase levels should be measured in all patients with a history of severe reactions in order to detect mastocytosis and to determine the risk of severe reactions to venom immunotherapy (VIT). The risk to experience severe or even fatal anaphylaxis due to insect stings is quite high in patients with mastocytosis. Therefore, lifelong VIT is recommended in these highly threatened patients. Multicenter studies involving a large population report that up to 20% of patients undergoing VIT have intolerance and systemic reactions to immunotherapy. Some of these side effects occur repeatedly and cannot be managed by standard treatment. A pre-treatment with the anti-IgE antibody omalizumab was useful in many cases. However, omalizumab is not approved for the indication anaphylaxis. Therefore, there is still no defined protocol for omalizumab pre-treatment, and the optimal duration, dosage as well as long-time benefits are still unclear. Case report: We present a 60-year-old female patient with mastocytosis who developed a severe anaphylactic reaction during initiation of bee VIT. Serum tryptase was elevated, and a KIT mutation D816V was subsequently confirmed. Component-resolved diagnostic tests revealed specific IgE antibodies to recombinant Api m 1 only. The patient was treated with 150 mg omalizumab, administered subcutaneously 5 weeks, 3 weeks, and 1 week prior to re-start of immunotherapy and for 2 months in parallel to VIT. Updosing was done by a 7-day rush schedule. During this period, no anaphylactic reaction developed, and the bee VIT was well tolerated with up to 200 µg bee venom. The patient is currently in the 3rd year of treatment and tolerates the treatment very well. Conclusion: Omalizumab may be used as a premedication in patients with mastocytosis who do not tolerate VIT. Although there is no consensus on the treatment protocol, treatment for 2 – 6 months is considered adequate. The long-term benefits of such treatment require further research.Correspondence to:
Prof. Dr. Uta Jappe, FG Klinische und Molekulare Allergologie, Forschungszentrum Borstel, Leibniz, Lungenzentrum, Parkallee 1 – 40, 23845 Borstel
Email: [email protected]
Guideline
Update of the S2k guideline on the management of IgE-mediated food allergies
Margitta Worm, Imke Reese, Barbara Ballmer-Weber, Kirsten Beyer, Stephan C. Bischoff, Barbara Bohle, Knut Brockow, Martin Claßen, Peter J. Fischer, Eckard Hamelmann, Uta Jappe, Jörg Kleine-Tebbe, Ludger Klimek, Berthold Koletzko, Lars Lange, Susanne Lau, Ute Lepp, Vera Mahler, Katja Nemat, Martin Raithel, Joachim Saloga, Christiane Schäfer, Sabine Schnadt, Jens Schreiber, Zsolt Szépfalusi, Regina Treudler, Martin Wagenmann, Thomas Werfel, and Torsten Zuberbier
Volume 5 (2021) p. 195 - 243
Abstract
Allergologie select, Vol. 5/2021 (195-243)
Update of the S2k guideline on the management of IgE-mediated food allergies
Margitta Worm1, Imke Reese2, Barbara Ballmer-Weber3, Kirsten Beyer4, Stephan C. Bischoff5, Barbara Bohle6, Knut Brockow7, Martin Claßen8, Peter J. Fischer9, Eckard Hamelmann10, Uta Jappe11#12, Jörg Kleine-Tebbe13, Ludger Klimek14, Berthold Koletzko15, Lars Lange16, Susanne Lau4, Ute Lepp17, Vera Mahler18, Katja Nemat19, Martin Raithel20, Joachim Saloga21, Christiane Schäfer22, Sabine Schnadt23, Jens Schreiber24, Zsolt Szépfalusi25, Regina Treudler26, Martin Wagenmann27, Thomas Werfel28, and Torsten Zuberbier29
1Allergology and Immunology, Department of Dermatology, Venereology, and Allergology, Charité – Universitätsmedizin Berlin, Germany, 2Nutritional Counseling and Therapy, Focus on Allergology, Munich, Germany, 3University Hospital Zurich, Department of Dermatology, Zurich, Switzerland, and Cantonal Hospital St. Gallen, Department of Dermatology and Allergology, St. Gallen, Switzerland, 4Clinic of Pediatrics m. S. Pneumology, Immunology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Germany, 5Institute of Nutritional Medicine and Prevention, University of Hohenheim, Stuttgart, Germany, 6Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria, 7Department of Dermatology and Allergology, Biederstein, Klinikum rechts der Isar, Technical University of Munich, Germany, 8Klinik für Kinder und Jugendmedizin/Päd. Intensivmedizin, Eltern-Kind-Zentrum Prof. Hess Klinikum Bremen-Mitte, 9Practice for Pediatric and Adolescent Medicine m. S. Allergology and Pediatric Pneumology, Schwäbisch Gmünd, 10University Clinic for Pediatric and Adolescent Medicine, Evangelisches Klinikum Bethel gGmbH, Bielefeld, 11Research Group Clinical and Molecular Allergology, Research Center Borstel, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Borstel, 12Interdisciplinary Allergy Outpatient Clinic, Medical Clinic III, University Hospital Schleswig-Holstein, Lübeck, 13Allergy and Asthma Center Westend, Berlin, 14Center for Rhinology and Allergology, Wiesbaden, 15Pediatric Clinic and Pediatric Polyclinic, Dr. von Haunersches Kinderspital, Department of Metabolic and Nutritional Medicine, Ludwig-Maximilians-University, Munich, 16Pediatric and Adolescent Medicine, St.- Marien-Hospital, Bonn, 17Practice for Pulmonary Medicine and Allergology, Buxtehude, 18Paul-Ehrlich-Institut, Langen, 19Practice for Pediatric Pneumology/Allergology at the Children’s Center Dresden (Kid), Dresen, 20Medical Clinic II, Malteser Waldkrankenhaus, Erlangen, 21Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, 22Nutritional Therapy, Focus on Allergology and Gastroenterology, Schwarzenbek, Germany, 23German Allergy and Asthma Association, Mönchengladbach, Germany, 24Pneumology, University Hospital of Otto von Guericke University, Magdeburg, Germany, 25University Hospital for Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria, 26Clinic of Dermatology, Venereology and Allergology, University Medical Center Leipzig, Germany, 27Nose and Throat Clinic, University Hospital Düsseldorf, Germany, 28Clinic of Dermatology, Allergology and Venerology, Hannover Medical School, Germany, and 29Department of Dermatology, Venerology and Allergology, Charité – Universitätsmedizin Berlin
Correspondence to:
Univ.-Prof. Dr. med. Margitta Worm, Allergologie und Immunologie, Klinik für Dermatologie, Venerologie, und Allergologie, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin
Email: [email protected]
Position Paper
Vegan diets from an allergy point of view – Position paper of the DGAKI working group on food allergy
Imke Reese, Christiane Schäfer, Barbara Ballmer-Weber, Kirsten Beyer, Sabine Dölle-Bierke, Suzanne van Dullemen, Uta Jappe, Sabine Müller, Sabine Schnadt, Regina Treudler, and Margitta Worm
Volume 7 (2023) p. 57 - 83
Abstract
Allergologie select, Vol. 7/2023 (57-83)
Vegan diets from an allergy point of view – Position paper of the DGAKI working group on food allergy
Imke Reese1, Christiane Schäfer2, Barbara Ballmer-Weber3,4, Kirsten Beyer5, Sabine Dölle-Bierke6, Suzanne van Dullemen7, Uta Jappe8,9, Sabine Müller10, Sabine Schnadt11, Regina Treudler12, and Margitta Worm6
1Nutrition Therapy, Munich, 2NutritionTherapy, Schwarzenbek, Germany, 3Clinic for Dermatology and Allergology, Cantonal Hospital St. Gallen, St. Gallen, 4Department of Dermatology, University Hospital Zürich, Switzerland, 5Clinic for Pediatrics with focus on Pneumology and Immunology, Charité-Universitätsmedizin – Campus Virchow-Klinikum, 6Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, 7University Clinic Frankfurt, Clinic for Pediatrics, Frankfurt, 8Division of Clinical and Molecular Allergology, Research Center Borstel, German Center for Lung Research (DZL) Airway Research Center North (ARCN), Borstel, 9Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Lübeck, Lübeck, 10Department of Dermatology and Venereology, University Clinic Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 11German Allergy and Asthma Association (DAAB), Mönchengladbach, and 12Department of Dermatology, Venereology and Allergology, Leipzig University Medical Center, Leipzig, Germany
Vegan diets are currently attracting a great deal of attention. However, avoiding animal-based foods restricts the diet and is associated with risks, the extent and medical implications of which are at present not sufficiently understood. Elimination diets represent the usual therapeutic long-term management in the presence of food allergy. In order to understand the risks of vegan diets and to discuss these critically from the perspective of food allergies, the expertise of a nutritionist/dietitian with expertise in this area is indispensable. This position paper deals with the incentives behind and the benefits of a plant-based diet. The knowledge required to cover macro- and micronutrient dietary requirements is presented. Using the avoidance of cow’s milk as an example, the challenges of adequately meeting nutritional needs are identified and (so-called) milk alternatives are evaluated from an allergy and nutritional point of view. Finally, other plant-based (substitute) products are evaluated from the same perspective, as significant protein sources in vegan diets (e.g., legumes, nuts, and seeds) are at the same time potential and potent triggers of allergic reactions. However, the allergic potential of many substitute products cannot be fully assessed at present due to gaps in research. Wheat as the most important trigger for anaphylaxis in adults is also evaluated. Finally, the increase in ultra-processed products in the (vegan) food sector and their potential consequences for the immune system are discussed.
Please notice: There is an erratum to this article, which can be found at: https://www.dustri.com/nc/de/article-response-page.html?artId=191243&doi=10.5414%2FALX02400ECorr.Correspondence to:
Dr. Imke Reese, Ernährungsberatung und -therapie, Schwerpunkt Allergologie, Ansprengerstr. 19, 80803 Munich, Germany
Email: [email protected]
Review
Biologics in allergology and clinical immunology: Update on therapies for atopic diseases, urticaria, and angioedema and on safety aspects focusing on hypersensitivity reactions
Uta Jappe, Karl-Christian Bergmann, Folke Brinkmann, Valentina Faihs, Askin Gülsen, Ludger Klimek, Harald Renz, Sebastian Seurig, Christian Taube, Stephan Traidl, Regina Treudler, Martin Wagenmann, Thomas Werfel, Margitta Worm, and Torsten Zuberbier
Volume 8 (2024) p. 365 - 406
Abstract
Allergologie select, Vol. 8/2024 (365-406)
Biologics in allergology and clinical immunology: Update on therapies for atopic diseases, urticaria, and angioedema and on safety aspects focusing on hypersensitivity reactions
Uta Jappe1#2, Karl-Christian Bergmann3, Folke Brinkmann4, Valentina Faihs5, Askin Gülsen6, Ludger Klimek7, Harald Renz8, Sebastian Seurig9, Christian Taube10, Stephan Traidl11, Regina Treudler12, Martin Wagenmann13, Thomas Werfel11, Margitta Worm14, and Torsten Zuberbier3
1Division Clinical and Molecular Allergology, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, 2Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University Medical Center Schleswig-Holstein, Campus Lübeck, University of Lübeck, 3Institute of Allergology, Charité Universitätsmedizin Berlin und Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, 4Division of Pediatric Pulmonology and Allergology, University Children’s Hospital, German Center for Lung Research (ARCN, DZL), Lübeck, 5Department of Dermatology and Allergy Biederstein, Klinikum rechts der Isar, Technical University of Munich, 6Division of Cardiology, Pulmonary Diseases, Vascular Medicine, University Hospital Duesseldorf, 7Center for Rhinology and Allergology, Wiesbaden, 8Institute of Laboratory Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Philipps Universität Marburg, Member of the German Center for Lung Research (DZL) Marburg, 9Interdisciplinary Allergy Center Nuremberg (NIZA), Department of Internal Medicine 3, Pneumology, Nuremberg Hospital, Nuremberg, 10Department of Pulmonary Medicine, University Hospital Essen-Ruhrlandklinik, Essen, 11Department of Dermatology and Allergy, Hannover Medical School, Hannover, 12Institute of Allergology IFA, Charité Universitätsmedizin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, 13Department of Otorhinolaryngology, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, 14Division of Allergy and Immunology, Department of Dermatology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
The development of targeted therapies for atopic diseases, urticaria, and angioedema with biologics is progressing rapidly: New “targets” of clinical-therapeutic relevance have been identified, the corresponding targeted antibodies developed, tested in clinical trials, and approved for therapy. These include the anti-IgE antibody omalizumab (also effective and approved for the treatment of urticaria), the anti-IL-4/13 receptor-specific antibody dupilumab, the two anti-IL-13 antibodies lebrikizumab and tralokinumab, the anti-TSLP antibody tezepelumab, the two anti-IL-5 antibodies mepolizumab and reslizumab, and the anti-IL5 receptor-specific antibody benralizumab for the treatment of atopic diseases. For the treatment of hereditary angioedema, C1 inhibitor and the antibody lanadelumab (directed against kallikrein) have also long been approved as biologics in addition to low-molecular substances. Other therapeutic antibodies are in various stages of development. Furthermore, the range of indications for some very effective biologics has been successfully expanded to include additional diseases. In this context, the first results on biologic therapy of food allergy and eosinophilic esophagitis are interesting. Biologics that address different target structures are also increasingly being administered in combination, either simultaneously or sequentially, in order to achieve optimal efficacy. A developing area is the use of biologics in children and the observation of immunological and non-immunological side effects. In some cases, new unexpected side effects and hypersensitivity reactions have emerged, which in turn raise pathomechanistic questions, such as conjunctivitis with dupilumab therapy, which only appears to occur in the treatment of atopic dermatitis but not in the treatment of other atopic diseases. In dermatology, paradoxical reactions have been described under therapy with some biologics. And immune reactions of type alpha to epsilon to biologics (hypersensitivity reactions) continue to be a clinically relevant problem, whereby the selection of an alternative therapeutic agent is a challenge and the diagnostics that support this have not yet been sufficiently incorporated into routine work.Correspondence to:
Prof. Dr. med. Uta Jappe, Division Clinical and Molecular Allergology, Research Center Borstel, Leibniz Lung Center, Parkallee 35, 23845 Borstel, Germany
Email: [email protected]
Position Paper
Occupational anaphylaxis: A Position Paper of the German Society of Allergology and Clinical Immunology (DGAKI)
Regina Treudler, Margitta Worm, Andrea Bauer, Heinrich Dickel, Guido Heine, Uta Jappe, Ludger Klimek, Monika Raulf, Bettina Wedi, Dorothea Wieczorek, Wojciech Francuzik, Thilo Jakob, Oliver Pfaar, Johannes Ring, Franziska Rueff, Sabine Schnadt, Thomas Werfel, Gerda Wurpts, Julia Zarnowski, Torsten Zuberbier, and Knut Brockow
Volume 8 (2024) p. 407 - 424
Abstract
Allergologie select, Vol. 8/2024 (407-424)
Occupational anaphylaxis: A Position Paper of the German Society of Allergology and Clinical Immunology (DGAKI)
Regina Treudler1, Margitta Worm2, Andrea Bauer3, Heinrich Dickel4, Guido Heine5, Uta Jappe6, Ludger Klimek7, Monika Raulf8, Bettina Wedi9, Dorothea Wieczorek9, Wojciech Francuzik2, Thilo Jakob10, Oliver Pfaar11, Johannes Ring12, Franziska Rueff13, Sabine Schnadt14, Thomas Werfel9, Gerda Wurpts15, Julia Zarnowski16, Torsten Zuberbier1,17, and Knut Brockow12
1Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, 2Department of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, 3Department of Dermatology, University AllergyCenter, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, 4Department of Dermatology, Venereology and Allergology, St. Josef Hospital, University Medical Center, Ruhr University Bochum, Bochum, 5Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, 6Division of Clinical and Molecular Allergology, Research Center Borstel, Airway Research, Center North (ARCN), Member of the German Center for Lung Research, Borstel, Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck, 7Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz and Center for Rhinology and Allergology, Wiesbaden, 8Department of Allergology/Immunology; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bochum, Germany, 9Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover, 10Department of Dermatology and Allergology, University Medical Center Giessen (UKGM), Justus-Liebig-University Giessen, Giessen, 11Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, 12Department of Dermatology and Allergy Biederstein, School of Medicine and Health, Technical University of Munich TUM), 13Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, 14German Allergy and Asthma Association (DAAB), Mönchengladbach, 15Clinic for Dermatology and Allergology, Aachen Comprehensive Allergy Center (ACAC), University Hospital of RWTH Aachen University, Aachen, 16Department of Dermatology, Venerology and Allergology, University of Leipzig Medical Center, Leipzig, and 17Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany
Background: Anaphylaxis is a systemic allergic reaction that is potentially life-threatening. Occupational anaphylaxis is an anaphylaxis that occurs in an occupational context. In this position paper, we propose diagnostic criteria for occupational anaphylaxis and provide an overview of the current state of knowledge in terms of prevalence, triggers, prevention, and management. Results: The most common triggers of occupational anaphylaxis include Hymenoptera venoms, followed by food and drugs. Chemicals, bites or contact with animals (mammals/snakes/insects) and natural rubber latex are far less common. Occupations at risk for occupational anaphylaxis are therefore beekeepers, outdoor workers, or those who handle food as well as healthcare workers. The route of contact, intensity, and frequency of exposure, type of allergen, and the simultaneous occurrence of co-factors determine the clinical manifestation. A detailed medical history is required to confirm the diagnosis of anaphylaxis and to identify the trigger. Both skin tests and the determination of specific IgE are recommended, but only very few commercially available and quality-tested allergens are available that can be examined using both test methods. Preventive measures are based on avoiding further exposure or, if necessary, replacing a working substance. A written emergency plan and the prescription of an adrenaline autoinjector as well as instructions for its use are mandatory. Allergen immunotherapy is recommended for systemic Hymenoptera venom allergy. Depending on the national healthcare systems, patients with occupational anaphylaxis must be reported to the accident insurance. Conclusion: Occupational anaphylaxis is very rare. We recommend educational measures and generally standardized recording of occupational anaphylaxis for occupations with an increased risk of anaphylaxis.Correspondence to:
Prof. Dr. Regina Treudler, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Institute of Allergology, Hindenburgdamm 30, 12203 Berlin, Germany
Email: [email protected]
Response
Response to Letter to the Editor from Christian Koeder
Imke Reese, Christiane Schäfer, Barbara Ballmer-Weber, Kirsten Beyer, Sabine Dölle-Bierke, Suzanne van Dullemen, Uta Jappe, Sabine Schnadt, and Regina Treudler
Volume 9 (2025) p. 18 - 20
Abstract
Allergologie select, Vol. 9/2025 (18-20)
Response to Letter to the Editor from Christian Koeder
Imke Reese1, Christiane Schäfer2, Barbara Ballmer-Weber3,4, Kirsten Beyer5, Sabine Dölle-Bierke6, Suzanne van Dullemen7, Uta Jappe8,9, Sabine Schnadt10, and Regina Treudler11
1Nutrition Therapy, Munich, 2NutritionTherapy, Schwarzenbek, Germany, 3Clinic for Dermatology and Allergology, Cantonal Hospital St. Gallen, St. Gallen, 4Department of Dermatology, University Hospital Zürich, Switzerland, 5Clinic for Pediatrics with focus on Pneumology and Immunology, Charité-Universitätsmedizin – Campus, Virchow-Klinikum, 6Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, 7University Clinic Frankfurt, Clinic for Pediatrics, Frankfurt/Main, 8Division of Clinical and Molecular Allergology, Research, Center Borstel, German Center for Lung Research (DZL) Airway Research Center North (ARCN), Borstel, 9Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Lübeck, Lübeck, 10German Allergy and Asthma Association (DAAB), Mönchengladbach, and 11Department of Dermatology, Venereology and Allergology, Leipzig University Medical Center, Leipzig, Germany
Correspondence to:
Dr. Imke Reese, Ernährungsberatung und -therapie, Schwerpunkt Allergologie, Ansprengerstr. 19, 80803 Munich, Germany
Email: [email protected]
Review
Allergens from plant-based food allergen sources and their clinical and diagnostic relevance
Eva-Maria Rick, Melanie Plum, Marua Abu Risha, and Uta Jappe
Volume 10 (2026) p. 170 - 191
Abstract
Allergologie select, Vol. 10/2026 (170-191)
Allergens from plant-based food allergen sources and their clinical and diagnostic relevance
Eva-Maria Rick1, Melanie Plum1, Marua Abu Risha1, and Uta Jappe1,2
1Division of Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, and 2Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, UKSH and University of Lübeck, Lübeck, Germany
Lately, a rise of plant-related food allergies could be observed following the increase of plant-based food consumption. This narrative review provides an overview of important plant allergens from the most common allergen sources including the “Big 9”, and those gaining more clinical significance such as legumes (other than peanuts) or fruits. Both commercially available and unavailable allergens for in vitro (i.e., specific IgE) and ex vivo (e.g., basophil activation test) diagnostics described in the literature to date are included in this work. In addition, gaps in the commercially available test panels (e.g., oleosins) as well as a lack of knowledge about the clinical relevance of some allergens are highlighted using the latest publications. Furthermore, practical applications are provided in exemplary case reports. In conclusion, molecular allergology provides important tools to advance precision diagnostics of allergic diseases and consequently, patient care.Correspondence to:
Prof. Uta Jappe, Division of Clinical and Molecular Allergology, Research Center Borstel, Leibniz Lung Center, Parkallee 35, 23845 Borstel, Germany
Email: [email protected]
