Abstract
Allergologie select, Vol. 5/2021 (51-56)
Occupational rhinitis
Sebastian Kotz1, Lisa Pechtold1,2, Rudolf A. Jörres3, Dennis Nowak3, and Adam M. Chaker1,2
1Department of Otolaryngology – Head and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, 2Center of Allergy and Environment (ZAUM) of the Technical University of Munich (TUM) and the Helmholtz Zentrum München (HMGU), and 3Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Clinical Center of the Ludwig Maximilian University Munich, Germany, Comprehensive Pneumology Center (CPC) Munich, German Center for Lung Research (DZL)
Occupational rhinitis (OR) has so far received little attention even though it shares common pathophysiological features and trigger factors and is closely associated with occupational asthma (OA). Work-related exposure to certain substances, such as animal dander, is considered to be the main factor for the development of OR. The new EAACI definition of OR stresses the causal relationship between workplace exposure and onset of rhinitis symptoms as opposed to previous definitions that mainly focused on a temporal relationship between workplace exposure and occurrence of nasal symptoms. Also, it has been suggested to use the term “work-related rhinitis” for classifying the different forms of rhinitis associated with the workplace. These forms can be subdivided into allergic or non-allergic OR, which is due to causes and conditions related to a particular work environment, as well as work-exacerbated rhinitis, which is defined as a pre-existing rhinitis exacerbated by exposure at the workplace. Even though taking a detailed patient history is especially important when it comes to diagnosing OR, the gold standard for confirming the diagnosis is nasal provocation testing. Best possible symptomatic relief and prevention of development of OA constitute the main therapeutic objectives in OR. Treatment options consist of total avoidance of trigger substances (main goal), reduction of exposure to certain substances, and pharmacotherapy. Furthermore, it is important to note that allergic OR is an occupational disease in Germany (Berufskrankheit No 4301) and needs to be reported to health authorities.Correspondence to:
Sebastian Kotz, Department of Otolaryngology – Head and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
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]
Abstract
Allergologie select, Vol. 8/2024 (26-39)
Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?
Ludger Klimek1, Ulrike Förster-Ruhrmann2, Heidi Olze2, Achim G. Beule3,4, Adam M. Chaker5,6, Jan Hagemann7, Tilman Huppertz7, Thomas K. Hoffmann8, Stefan Dazert9, Thomas Deitmer10, Sebastian Strieth11, Holger Wrede12, Wolfgang W. Schlenter13, Hans-Jürgen Welkoborsky14, Barbara Wollenberg5, Sven Becker15, Fredericke Bärhold15, Felix Klimek1, Ingrid Casper1, Jaron Zuberbier2, Claudia Rudack3, Mandy Cuevas16, Constantin A. Hintschich17, Orlando Guntinas-Lichius18, Timo Stöver19, Christoph Bergmann20, Pascal Werminghaus21, Oliver Pfaar22, Jan Gosepath23, Moritz Gröger24, Caroline Beutner25, Martin Laudien26, Rainer K. Weber27, Tanja Hildenbrand28, Anna S. Hoffmann29, and Claus Bachert30
1Center for Rhinology and Allergology, Wiesbaden, 2HNO-University Clinic Charité, Berlin, 3Clinic for Otorhinolaryngology, Münster University Hospital, 4Clinic for Otorhinolaryngology, Head and Neck Surgery at Greifswald University Medical Center, 5Department of Otolaryngology - Head and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, 6Center of Allergy and Environment (ZAUM) of the Technical University of Munich, 7Clinic and Polyclinic for Otolaryngology, University Medical Center Mainz, Mainz, 8Department of Otorhinolaryngology, Head and Neck Surgery, University of Ulm, Ulm, 9Clinic for Otorhinolaryngology, Head and Neck Surgery, Ruhr University Bochum, St. Elisabeth Hospital, 10German Society for Otorhinolaryngology, Head and Neck Surgery, Bonn, 11Clinic and Polyclinic for Otorhinolaryngology, University Hospital Bonn, 12Ear, nose and throat specialist, Herford, 13Medical Association of German Allergists, Wiesbaden, 14Clinic for Ear, Nose and Throat Medicine, Head and Neck Surgery, Nordstadt Clinic of the KRH, Hannover, 15HNO-University Clinic Tübingen, 16K Clinic and Polyclinic for Otolaryngology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, 17Clinic and Polyclinic for Ear, Nose and Throat Medicine, University Hospital Regensburg, Regensburg, 18Clinic for Otorhinolaryngology, Jena University Hospital, 19Otorhinolaryngology University Clinic Frankfurt am Main, 20HNO RKM740 Interdisciplinary Specialist Clinic, Düsseldorf, Germany, 21Praxis für Hals-, Nasen-, Ohrenheilkunde und Allergologie, Düsseldorf, 22Kl Clinic for Ear, Nose and Throat Medicine, University Hospital Giessen and Marburg GmbH, Marburg site, Philipps University Marburg, Marburg, 23Clinic for Otorhinolaryngology, HSK Wiesbaden, 24Clinic and Polyclinic for Otorhinolaryngology, University Hospital LMU Munich, 25K Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Germany Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen, 26Department of Otorhinolaryngology, Head and Neck Surgery, Kiel University, University Medical Centre Schleswig-Holstein, Kiel, 27Clinic for Otorhinolaryngology, Karlsruhe Municipal Hospital, 28Department of Ear, Nose and Throat Medicine, Freiburg University Medical Center, 29Clinic for Ear, Nose and Throat Medicine, University Medical Center Hamburg-Eppendorf, 30Kli Upper Airways Research Laboratory and Department of Oto-Rhino-Laryngology, Ghent University and Ghent, University Hospital, Ghent, Belgien
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. Materials and methods: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. Results: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. Conclusion: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.Correspondence to:
Professor Dr. med. L. Klimek, Zentrum für Rhinologie und Allergologie Wiesbaden, An den Quellen 10, 65183 Wiesbaden, Germany
Email: [email protected]
