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]
Abstract
Allergologie select, Vol. 7/2023 (154-190)
Diagnosis and treatment of Hymenoptera venom allergy
Franziska Ruëff1, Andrea Bauer2, Sven Becker3, Randolf Brehler4, Knut Brockow5, Adam M. Chaker6, Ulf Darsow5, Jörg Fischer7, Thomas Fuchs8, Michael Gerstlauer9, Sunhild Gernert10, Eckard Hamelmann11, Wolfram Hötzenecker12, Ludger Klimek13, Lars Lange10, Hans Merk14, Norbert K. Mülleneisen15, Irena Neustädter16, Wolfgang Pfützner17, Wolfgang Sieber18, Helmut Sitter19, Christoph Skudlik20, Regina Treudler21, Bettina Wedi22, Stefan Wöhrl23, Margitta Worm24 and Thilo Jakob25
1Department of Dermatology and Allergy, LMU University Hospital, Munich, 2Department of Dermatology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, 3Department of Otorhinolaryngology, Head and Neck Surgery, University of Tuebingen, Tübingen, 4Department of Dermatology, Münster University Hospital, Münster, 5Department of Dermatology and Allergology Biederstein, Faculty of Medicine, Technical University of Munich, Munich, 6Department of Otorhinolaryngology Klinikum rechts der Isar, Faculty of Medicine, Technical University of Munich, Munich, 7University Hospital for Dermatology and Allergology, Clinic Oldenburg, Oldenburg, 8Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, 9Clinic for Children and Adolescents, University Hospital Augsburg, Augsburg, 10Pediatric Clinic, Marienhospital Bonn, GFO Kliniken, Bonn, 11Children’s Center Bethel, University Hospital OWL, Bielefeld University, Bielefeld, Germany, 12Department of Dermatology, Kepler University Hospital, Medical Faculty of University Linz, Linz, Austria, 13Center for Rhinology and Allergology, Wiesbaden, 14Department of Dermatology and Allergology, University Hospital of RWTH Aachen University, Aachen, 15Center for Asthma and Allergy, Leverkusen, 16Cnopfsche Paediatric Clinic, Nuremberg, 17Department of Dermatology and Allergology, University Hospital Marburg, Philipps-Universität Marburg, Marburg, 18Hospital Wörth an der Donau, Wörth an der Donau, 19Institute for Theoretical Surgery, Philipps-University Marburg, Marburg, 20Institute for Interdisciplinary Dermatological Prevention and Rehabilitation (iDerm) at the University of Osnabrueck, Osnabrueck, and BG Clinic Hamburg, Hamburg, 21University Leipzig Medical Faculty, Leipzig, 22Comprehensive Allergy, Department of Dermatology and Allergy, Hannover Medical School, Hanover, Germany, 23Floridsdorf Allergy Center (FAZ), Vienna, Austria, 24Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, and 25Department of Dermatology and Allergology, University Hospital Giessen, Justus Liebig University Gießen, Gießen, Germany
Hymenoptera venom (HV) is injected into the skin during a sting by Hymenoptera such as bees or wasps. Some components of HV are potential allergens and can cause large local and/or systemic allergic reactions (SAR) in sensitized individuals. During their lifetime, ~ 3% of the general population will develop SAR following a Hymenoptera sting. This guideline presents the diagnostic and therapeutic approach to SAR following Hymenoptera stings. Symptomatic therapy is usually required after a severe local reaction, but specific diagnosis or allergen immunotherapy (AIT) with HV (VIT) is not necessary. When taking a patient’s medical history after SAR, clinicians should discuss possible risk factors for more frequent stings and more severe anaphylactic reactions. The most important risk factors for more severe SAR are mast cell disease and, especially in children, uncontrolled asthma. Therefore, if the SAR extends beyond the skin (according to the Ring and Messmer classification: grade > I), the baseline serum tryptase concentration shall be measured and the skin shall be examined for possible mastocytosis. The medical history should also include questions specific to asthma symptoms. To demonstrate sensitization to HV, allergists shall determine concentrations of specific IgE antibodies (sIgE) to bee and/or vespid venoms, their constituents and other venoms as appropriate. If the results are negative less than 2 weeks after the sting, the tests shall be repeated (at least 4 – 6 weeks after the sting). If only sIgE to the total venom extracts have been determined, if there is double sensitization, or if the results are implausible, allergists shall determine sIgE to the different venom components. Skin testing may be omitted if in-vitro methods have provided a definitive diagnosis. If neither laboratory diagnosis nor skin testing has led to conclusive results, additional cellular testing can be performed. Therapy for HV allergy includes prophylaxis of reexposure, patient self treatment measures (including use of rescue medication) in the event of re-stings, and VIT. Following a grade I SAR and in the absence of other risk factors for repeated sting exposure or more severe anaphylaxis, it is not necessary to prescribe an adrenaline auto-injector (AAI) or to administer VIT. Under certain conditions, VIT can be administered even in the presence of previous grade I anaphylaxis, e.g., if there are additional risk factors or if quality of life would be reduced without VIT. Physicians should be aware of the contraindications to VIT, although they can be overridden in justified individual cases after weighing benefits and risks. The use of β-blockers and ACE inhibitors is not a contraindication to VIT. Patients should be informed about possible interactions. For VIT, the venom extract shall be used that, according to the patient’s history and the results of the allergy diagnostics, was the trigger of the disease. If, in the case of double sensitization and an unclear history regarding the trigger, it is not possible to determine the culprit venom even with additional diagnostic procedures, VIT shall be performed with both venom extracts. The standard maintenance dose of VIT is 100 µg HV. In adult patients with bee venom allergy and an increased risk of sting exposure or particularly severe anaphylaxis, a maintenance dose of 200 µg can be considered from the start of VIT. Administration of a non-sedating H1-blocking antihistamine can be considered to reduce side effects. The maintenance dose should be given at 4-weekly intervals during the first year and, following the manufacturer’s instructions, every 5 – 6 weeks from the second year, depending on the preparation used; if a depot preparation is used, the interval can be extended to 8 weeks from the third year onwards. If significant recurrent systemic reactions occur during VIT, clinicians shall identify and as possible eliminate co-factors that promote these reactions. If this is not possible or if there are no such co-factors, if prophylactic administration of an H1-blocking antihistamine is not effective, and if a higher dose of VIT has not led to tolerability of VIT, physicians should should consider additional treatment with an anti IgE antibody such as omalizumab as off lable use. For practical reasons, only a small number of patients are able to undergo sting challenge tests to check the success of the therapy, which requires in-hospital monitoring and emergency standby. To perform such a provocation test, patients must have tolerated VIT at the planned maintenance dose. In the event of treatment failure while on treatment with an ACE inhibitor, physicians should consider discontinuing the ACE inhibitor. In the absence of tolerance induction, physicians shall increase the maintenance dose (200 µg to a maximum of 400 µg in adults, maximum of 200 µg HV in children). If increasing the maintenance dose does not provide adequate protection and there are risk factors for a severe anaphylactic reaction, physicians should consider a co-medication based on an anti-IgE antibody (omalizumab; off-label use) during the insect flight season. In patients without specific risk factors, VIT can be discontinued after 3 – 5 years if maintenance therapy has been tolerated without recurrent anaphylactic events. Prolonged or permanent VIT can be considered in patients with mastocytosis, a history of cardiovascular or respiratory arrest due to Hymenoptera sting (severity grade IV), or other specific constellations associated with an increased individual risk of recurrent and/or severe SAR (e.g., hereditary α-tryptasemia). In cases of strongly increased, unavoidable insect exposure, adults may receive VIT until the end of intense contact. The prescription of an AAI can be omitted in patients with a history of SAR grade I and II when the maintenance dose of VIT has been reached and tolerated, provided that there are no additional risk factors. The same holds true once the VIT has been terminated after the regular treatment period. Patients with a history of SAR grade ≥ III reaction, or grade II reaction combined with additional factors that increase the risk of non response or repeated severe sting reactions, should carry an emergency kit, including an AAI, during VIT and after regular termination of the VIT.Correspondence to:
Prof. Dr. med. Franziska Ruëff, Klinik und Poliklinik für Dermatologie, und Allergologie, Klinikum der Universität München, Frauenlobstraße 9-11, 80337 Munich, Germany,
Email: [email protected]
