Global Atlas oF ALLERGY

Published by the European Academy of Allergy and Clinical Immunology

www.eaaci.org Allergy - Mechanisms

Epidemiology and risk factors

Allergy diagnosis tlas Major Allergic Diseases

Other hypersensitivity diseases

Special considerations

Management of allergic

oF ALL ERGY diseases Global A

Towards a comprehensive global strategy for the management of allergic diseases Global Atlas oF ALLERGY

Editors Cezmi A. Akdis Ioana Agache

Editorial Board Pascal Demoly Peter Hellings Antonella Muraro Nikolaos G.Papadopoulos Ronald van Ree

Published by the European Academy of Allergy and Clinical Immunology 2014 Global Atlas of ALLERGY

EAACI Executive Committee

BOARD OF OFFICERS Nikos Papadopoulos, President Antonella Muraro, Secretary General Peter Hellings, Treasurer Ioana Agache, Vice-President Communication and Membership Pascal Demoly, Vice-President Education and Specialty Ronald Van Ree, Vice-President Congresses Cezmi A. Akdis, Past President

SECTION CHAIRPERSONS Leif Bjermer, Asthma Carsten Bindslev-Jensen, Dermatology Cemal Cingi, ENT Carsten Schmidt-Weber, Immunology Susanne Lau, Pediatrics Alexandra Santos, Junior Members and Affiliates

INTEREST GROUP REPRESENTATIVES Moises Calderon Karin Hoffmann-Sommergruber

MEMBERS AT LARGE Lars K. Poulsen Tomas Chivato Thomas Werfel Beatrice M. Bilo Graham Roberts Musa Khaitov

CHAIR EAACI PATIENT ORGANIZATION COMMITTEE Frans Timmermans

ADJUNCT MEMBERS Fulvio Braido, CME Committee Chairperson Jan de Monchy, Specialty Committee Chairperson Jacques Gayraud, Ethics Committee Secretary Peter Schmid-Grendelmeier, Exam Committee Chairperson Marek Jutel, SPC Co-ordinator Angel Mazon, Web Editor Olympia Tsilochristou, Web Editor Michael Walker, Executive Director

II EAACI Executive Committee Global Atlas of ALLERGY

contributors

Azza Abdel-Gadir, PhD Zürich, Switzerland Montpellier, France Division of Immunology, Boston Mark Ballow, MD Onur Boyman, MD Children’s Hospital. Department Division of Allergy and Immunology, Department of Clinical Immunology, of Pediatrics, Harvard Medical University of South Florida University Hospital Zurich, Zurich, School. Morsani School of Medicine, All Switzerland. Ioana Agache, MD Children’s Hospital, St Petersburg Gert Jan Braunstahl, MD Dept, of Allergy and Clinical USA St. Franciscus Gasthuis Rotterdam, Immunology, Transylvania Nuray Bayar Muluk, MD The Netherlands University of Brasov, Faculty of Dept Otorhinolaryngology,-Kırıkkale Medicine Heimo Breiteneder, PhD University, Turkey Department of Pathophysiology Cezmi A. Akdis, MD Thomas Bieber, MD, PhD, MDRA and Allergy Research, Medical Swiss Institute of Allergy and Asthma Department of Dermatology and University of Vienna, Austria Research (SIAF), University of Allergy, University Medical Center, Zurich, Davos, Switzerland Knut Brockow, MD Friedrich-Wilhelms University of Christine Kühne – Center for Allergy Department of Dermatology Bonn, Germany Research and Education (CK- and AllergologyBiederstein, CARE), Davos, Switzerland M. Beatrice Bilò, MD TechnischeUniversitätMünchen, Germany. Medical Faculty, University of Zurich Allergy Unit - Department of Internal Medicine – University Hospital Mübeccel Akdis, MD, PhD A. Wesley Burks, MD Ospedali Riuniti di Ancona - Italy Department of Pediatrics, University Swiss Institute of Allergy and Asthma Research (SIAF), University of Carsten Bindslev-Jensen, MD of North Carolina at Chapel Hill, Zurich, Davos, Switzerland Odense Research Center for Chapel Hill ,USA Anaphylaxis, Odense Denmark Walter J. Ammann, PhD Robert K. Bush, MD Odense University Hospital, Odense Global Risk Forum (GRF) Davos, University of Wisconsin-Madison, Switzerland Denmark U.S.A Abena S. Amoah, MD Leif Bjemer, MD Jeroen Buters, PhD Department of Parasitology, Leiden Lund University, Department Center for Allergy & Environment University Medical Center, Leiden, of Respiratory Medicine and (ZAUM), Technische Universität The Netherlands Allergology, Sweden München and Helmholtzzentrum Department of Parasitology, Noguchi Barbara Bohle, PhD München, Germany Memorial Institute for Medical Department of Pathophysiology EAACI Interest Group Aerobiology Research, Accra, Ghana and Allergy Research and and Air Pollution Evangelos Andreakos, PhD Christian Doppler Laboratory Moisés A. Calderón, MD Biomedical Research Foundation, for Immunomodulation, Division Section of Allergy and Clinical Academy of Athens, Greece of Cellular Allergology, Medical Immunology, Imperial College University of Vienna, Vienna, London, NHLI, Royal Brompton Isabella Annesi-Maesano, MD Austria French Institute of Health and Hospital, London, UK. Medical Research, Epidemiology Matteo Bonini, MD Victòria Cardona, MD, PhD of Allergic and Respiratory Department of Public Health and Allergy Section, Department of Diseases (EPAR), France Infectious Diseases “Sapienza” Internal Medicine. Hospital University of Rome, Italy Claus Bachert, MD UniversitariValld’Hebron, Upper Airways Research Laboratory, Sergio Bonini, MD Barcelona, Spain University of Ghent, Ghent, Department of Internal Medicine, Kai-Håkon Carlsen, MD Belgium; Second University of Naples, Italy (Paediatric respiratory medicine and Division of ENT Diseases, CLINTEC, Jean Bousquet, MD allergology), University of Oslo, Karolinska Institutet Stockholm, University of Montpellier,France Institute for Clinical Medicine Sweden WHO Global Alliance Against and Oslo University Hospital, Barbara Ballmer-Weber, MD Chronic Respiratory Diseases Department of Paediatrics, Oslo, Department of Dermatology, (GARD) Norway University Hospital Zürich, Director of the WHO Collaborating Jean-Christoph Caubet, MD Switzerland University Hospital Centre for Asthma and Rhinitis in Department of Child and Adolescent,

Contributors III Global Atlas of ALLERGY

University Hospitals of Geneva Imperial College London, United Philippe Gevaert, MD, PhD and Medical School of the Kingdom. Dept Otorhinolaryngology, Ghent University of Geneva, Geneva, EAACI Patient Organisation University Hospital Switzerland Committee, Stefanie Gilles, PhD Yih-Chih Chan, MD Philippe Eigenmann, MD Institute for environmental medicine, King’s College London, London, University Hospitals of Geneva, UNIKA-T, TechnischeUniversität United Kingdom Geneva, Switzerland Munich, Germany Talal Chatila, MD Veit Erpenbeck, PhD Christine Kühne Center for Allergy Division of Immunology, Boston Novartis Institutes for Biomedical Research and Education (CK- Children’s Hospital/ Department Research, Basel, Switzerland Care), Davos, Switzerland of Pediatrics, Harvard Medical Claude Favrot, Dr .Vet. Hannah Gould, PhD School. Dermatology Service, Clinic for Division of Cell and Molecular R. Sharon Chinthrajah, MD Small Animal Internal Medicine, Biophysics and Division of Allergy, Division of Immunology and Allergy, Vetsuisse Faculty, University of Asthma and Lung Biology, Allergy Department of Pediatrics, Zurich, Zurich, Switzerland and Asthma Group in the Division Stanford University, Stanford, Fatima Ferreira, PhD of Cell and Molecular Biophysics USA Department of Molecular Biology, King’s College London, London, Tomás Chivato Pérez, MD Christian Doppler Laboratory for United Kingdom University CEU San Pablo, Madrid, Allergy Diagnosis and Therapy, Clive E. Grattan, MD Spain Saltzburg, Austria Norfolk and Norwich University Cemal Cingi, MD Michael B. Foggs, MD Hospital, UK Dept Otorhinolaryngology, Eskisehir President American College of Hans Grönlund, PhD Osmangazi University, Turkey Allergy, Asthma & Immunology Karolinska Institutet, Therapeutic Linda Cox, MD Dept of Allergy and Immunology, Immune Design Unit, Department Allergy and Asthma Center, Fort Advocate Health Care, Chicago, of Clinical Neuroscience, Center Lauderdale, Florida, USA United States for Molecular Medicine Reto Crameri, PhD Remo Frei, PhD Karolinska University Hospital Swiss Institute of Allergy and Asthma Swiss Institute of Allergy and Asthma Tari Haahtela, MD Research (SIAF), University of Research (SIAF), University of Skin and Allergy Hospital, Helsinki Zürich, Davos, Switzerland Zurich, Davos, Switzerland University Hospital, Finland Adnan Custovic, MD, PhD Christine Kühne-Center for Allergy Viktor Hafner, PhD University of Manchester, UK Research and Education, Davos Landesgeschäftsstelle Wien, Öster- Janet Davies, PhD Anthony J. Frew, MD reichische Apothekerkammer, Lung and Allergy Research Department of Respiratory Medicine, Austria Centre, School of Medicine, Royal Sussex County Hospital, Susanne Halken, MD, DMSci The University of Queensland, Brighton, UK Hans Christian Andersen Children’s Translational Research Institute, Gabriele Gadermaier, MD Hospital, Odense University Woolloongabba, Queensland, Department of Molecular Biology, Hospital, Denmark Australia Christian Doppler Laboratory for Firdaus Hamid, MD Jan G. R. de Monchy, MD Allergy Diagnosis and Therapy, Department of Parasitology, Leiden University of Groningen, University University of Salzburg, Austria University Medical Center, Leiden, Medical Center Groningen, The Stephen J. Galli, MD The Netherlands Netherlands Stanford Center for Genomics and Department of Microbiology, Pascal Demoly, MD Personalized Medicine Faculty of Medicine, Hasanuddin University Hospital of Montpellier, Professor Stanford University, USA, University, Makassar, Indonesia France Chair, Department of Pathology Catherine M. Hawrylowicz, PhD Günnur Deniz, PhD James Gardner, RN Dip MRC and Asthma UK Centre for Istanbul University, Experimental Department of Child Health, Royal Allergic Mechanisms in Asthma, Asthma Research Institute, Free Hospital, London, UK Division of Asthma, Allergy and Lung Istanbul, Turkey Jacques Gayraud, MD Biology, Guy’s Hospital, King’s Anthony E.J. Dubois, MD Polyclinique de l’Ormeau, Tarbes, College London, London, United Dept. of Pediatric Allergy, University France Kingdom of Groningen, The Netherlands Julia Katharina Genser, MD Enrico Heffler, MD, PhD Stephen R. Durham, MD Allergy Unit, Dept of Dermatology, Department of Medical Sciences, Allergy and Clinical Immunology, University Hospital of Zürich, Allergy and Clinical Immunology, National Heart and Lung Institute, Switzerland University of Torino, Italy

IV Contributors Global Atlas of ALLERGY

Peter W. Hellings, MD Marek Jutel, MD Medicine, McMaster University, Department of Otorhinolaryngology, Department of Clinical Immunology, Hamilton, ON, Canada Head and Neck Surgery, University Wroclaw Medical University Désirée Larenas Linnemann, MD Hospitals Leuven, Belgium ALL-MED Medical Research Institute, Hospital Médica Sur, Mexico city, Department of Otorhinolaryngology, Wroclaw , Poland Mexico Academic Medical Center, Ömer Kalayci, MD Susanne Lau , MD Amsterdam, The Netherlands Pediatric Allergy and Asthma Unit, Charité Medical University Berlin, Christoph Heusser, PhD Hacettepe University School of Germany Novartis Institutes for Biomedical Medicine, Ankara, Turkey Roger Lauener, MD Research, Basel, Switzerland Hajime Karasuyama, MD, PhD Children’s Hospital of Eastern Hans Jürgen Hoffmann, PhD Department of Immune Regulation, Switzerland, St. Gallen, Department of Respiratory Medicine Graduate School of Medical and Switzerland and Allergology, Aarhus University Dental Sciences, Tokyo Medical Christine Kühne-Center for Allergy Hospital and Dental University (TMDU), Research and Education, Davos Department of Clinical Medicine, Tokyo, Japan Dennis K. Ledford, MD Aarhus University, Denmark Constance H. Katelaris, MB BS Morsani College of Medicine, Karin Hoffmann-Sommergruber, PhD FRACP University of South Florida and MD, PhD Immunology & Allergy, University James A. Haley V.A. Hospital, Tampa, Dept. of Pathophysiology and Allergy of Western Sydney and Florida, USA Research, Medical University of Campbelltown Hospital, Sydney, Robert F. Lemanske Jr., MD Vienna,Vienna, Austria Australia. University of Wisconsin, Madison, Stephen T Holgate, MD, DSc, Musa R. Khaitov, MD Wisconsin FMedSci NRC Institute of Immunology FMBA Donald Y. M. Leung, MD, PhD Clinical and Experimental Sciences, Russia Department of Pediatrics, National Faculty of Medicine, University of Rakhim M. Khaitov, MD Jewish Health, Denver, USA Southampton,UK. NRC Institute of Immunology FMBA James T. Li, MD PhD Patrick G. Holt, MD, PhD Russia Mayo Clinic, Rochester, Minnesota, Division of Cell Biology, Telethon Jörg Kleine-Tebbe, MD USA Institute for Child Health Allergy & Asthma Center Westend, Maximin Liebl, PhD Research, The University Outpatient Clinic Hanf, Ackermann Pharmaceutical Group of the of Western Australia and & Kleine-Tebbe, Berlin, Germany European Union, Bolzano, Bozen, Queensland Children’s Medical Edward F. Knol, PhD Italy Research Institute, The University Dept. Immunology and Dermatology/ of Queensland, Australia Richard F. Lockey, MD Allergology; University Medical Joy McCann Culverhouse Airway Friedrich Horak, PhD Center Utrecht, Utrecht, The Disease Research Center, Division Research Consult GmbH, Dpt. Netherlands of Allergy and Immunology, Vienna Challenge Chamber (VCC), Marek L. Kowalski, MD Department of Internal Medicine, Vienna, Austria Medical University of Lodz, Poland University of South Florida Arne Høst, MD Thomas M. Kündig, MD Morsani College of Medicine; Head of Hans Christian Andersen Department of Dermatology, James A. Haley Veterans’ Hospital, Children’s Hospital, Odense University Hospital Zurich, Zurich, Tampa, FL, USA University Hospital Denmark Switzerland Karin C. Lødrup Carlsen, MD Natalia I. Ilyna, MD Gideon Lack, MD Head of Research, University of Oslo, NRC Institute of Immunology FMBA MRC Asthma UK Centre in Allergic Institute for Clinical Medicine Russia Mechanisms of Asthma, King’s and Oslo University Hospital, Kenji Izuhara, MD, PhD College London, Guy’s and St Department of Paediatrics, Oslo, Saga Medical School, Saga, Japan Thomas’ NHS Foundation Trust, Norway Jan Lötval, MD Children’s Allergies Department, Lyudmila V. Luss, MD Krefting Research Center, University St Thomas’ Hospital, London, UK NRC Institute of Immunology FMBA of Gothenburg, Göteborg, Sweden Bart N. Lambrecht, MD, PhD Russia S.G.O. Johansson, MD, PhD VIB Inflammation Research Center, Adriano Mari, MD Department of Medicine, Allergy Gent University, Belgium Associated Centers for Molecular and Clinical Immunology Unit, Mark Larché, PhD Allergology, Rome, Italy Karolinska Institute, Stockholm, Division of Allergy & Clinical Gianni Marone, MD, PhD Sweden Immunology, Department of Department of Translational Medical

Contributors V Global Atlas of ALLERGY

Sciences and Center for Basic and Allergy and Immunology, Johannes Ring, MD, PhD Clinical Immunology Research Jaffe Food Allergy Institute, Department Dermatology and (CISI), University of Naples Department of Pediatrics, Division Allergology Biederstein, Federico II, School of Medicine, of Allergy and Immunology, Kravis Technische Universität München Naples, Italy Children’s Hospital, Icahn School Christine Kühne-Center for Allergy Paolo Maria Matricardi, MD of Medicine at Mount Sinai, New Research and Education (CK- Dept. of Paediatric Pneumology and York, NY, USA CARE) Davos Immunology, Charité Medical Liam O’Mahony, PhD Graham Roberts, MD University, Berlin, Germany Swiss Institute of Allergy and Asthma David Hide Asthma and Allergy Marcus Maurer, MD Research (SIAF), University of Research Centre, St Mary’s Department of Dermatology Zurich, Davos, Switzerland Hospital, Newport, Isle of Wight and Allergy, Charité – Christine Kühne-Center for Allergy NIHR Southampton Respiratory Universitätsmedizin Berlin Research and Education, Davos Biomedical Research Unit, Angel Mazon, MD Markus Ollert, MD University Hospital Southampton Children’s Hospital La Fe, Valencia, Technische Universität München NHS Foundation Trust Spain (TUM), Munich, Germany Faculty of Medicine, Human Development and Health and Shanthi Mendis, MD, PhD Nikolaos G. Papadopoulos, MD Clinical Experimental Sciences WHO Dept of Allergy & Pediatric Allergy, University of Manchester, UK, Academic Units, University of Department of Management of Southampton, Southampton, UK Noncommunicable Diseases, University of Athens, Greece, World Health Organisation, EAACI President Caroline Roduit, MD Geneva, Switzerland Zurich University Children’s Hospital, Ruby Pawankar, MD, PhD Zurich, Switzerland Past President, World Allergy Dean D. Metcalfe, MD Children’s Hospital of Eastern Organization National Institute of Allergy and Switzerland, St. Gallen, Infectious Diseases, National Dept. of Pediatrics, Nippon Medical Switzerland Institutes of Health, Bethesda, School,Tokyo, Japan. Maryland, United States Lanny J. Rosenwasser, MD Oliver Pfaar, MD President, World Allergy Antonella Muraro, MD, PhD Center for Rhinology and Allergology Organization Food Allergy Referral Centre Veneto Wiesbaden, Department of Allergy-Immunology Division, Region Department of Women Otorhinolaryngology, Head and Children’s Mercy Hospital, Kansas and Child Health , Padua General Neck Surgery, University Hospital, City University Hospital Mannheim, Mannheim, Germany University of Missouri-Kansas City Dept of Pediatric Allergology, Werner J Pichler, MD School of Medicine University of Padua, Italy Clinic for Rheumatology and Frederick J. Rubner, MD Erika von Mutius, MD Clinical Immunology/Allergology, University of Wisconsin, Madison, Dr. von Hauner Children’s Hospital, University Hospital of Bern, Bern, Wisconsin Ludwig-Maximilians-University Switzerland Munich, Germany Thomas A.E Platts-Mills, MD, Franziska Ruëff, MD Department of Dermatology and Kari C Nadeau, MD, PhD PhD, FRS Allergology, Ludwig-Maximilian Division of Immunology and Allergy, Asthma and Allergic Disease University, Munich, Germany Department of Pediatrics, Center, University of Virginia, Stanford University, Stanford, Charlottesville, USA Dermot Ryan, Dr. USA GP Woodbrook Medical Centre, Lars K. Poulsen, PhD Loughborough Honorary Clinical Jennifer A. Namazy, MD National University Hospital, Allergy Research Fellow Allergy and Scripps Clinic, San Diego, California, Clinic, Copenhagen, Denmark Respiratory Research Group, USA Susan L. Prescott, MD Centre for Population Health Andrew Nickels, MD School of Paediatrics and Child Sciences, University of Edinburgh, Dept. of Allergy and Immunology Health (SPACH), University of Medical School Fellow, Mayo Clinic, Rochester, Western Australia, Australia Hirohisa Saito, MD, PhD Minnesota Santiago Quirce, MD, PhD National Research Institute for Child Verena Niederberger, PhD Department of Allergy, Hospital La Health & Development, Tokyo, Department of Otorhinolaryngology, Paz Institute for Health Research Japan Medical University of Vienna, (IdiPAZ), Madrid, Spain. Boleslaw Samolinski, MD Austria Harald Renz, MD Department of Prevention of Anna Nowak-Węgrzyn, MD Philipps- University of Marburg, Environmental Hazards and Associate Professor Pediatrics, Institute of Laboratory Medicine Allergology, Medical University of

VI Contributors Global Atlas of ALLERGY

Warsaw, Warsaw, Poland London, UK Research, Western Australia Marek Sanak, MD Helen Smith, MD Claudia Traidl-Hoffmann, MD Department of Medicine, Jagiellonian Brighton & Sussex Medical School, Institute of environmental medicine University Medical College, UK UNIKA-T, Technische Universität, Kraków, Poland Hermelijn H. Smits, PhD Munich, Germany Alexandra Santos, MD Department of Parasitology, Leiden Christine Kühne Center for Allergy King’s College, Paediatric Allergy, University Medical Center, Leiden, Research and Education (CK- London, UK The Netherlands Care), Davos, Switzerland Georg Schäppi, MD François Spertini, MD Massimo Triggiani, MD aha! Swiss Allergy Centre Division of Immunology and Allergy, Division of Allergy and Clinical Christine Kühne – Center for Allergy Centre Hospitalier Universitaire Immunology, University of Research and Education (CK- Vaudois, Lausanne, Switzerland Salerno, Italy CARE), Davos, Switzerland Otto Spranger, MD Rudolf Valenta, PhD Michael Schatz, MD, MS Österreichische Lungenunion, Wien, Department of Pathophysiology Department of Allergy, Kaiser Austria and Allergy Research, Medical University of Vienna, Austria Permanente Medical Center, San Cristiana Stellato, MD Diego, California, USA Department of Medicine and Surgery, Willem van de Veen, PhD Peter Schmid-Grendelmeier, MD University of Salerno, Italy, Swiss Institute of Allergy and Asthma Research (SIAF), University of Head of the Allergy Unit, University Division of Allergy and Clinical Zurich,Davos, Switzerland Hospital Zurich, Dept of Immunology, Johns Hopkins Dermatology, Zürich, Switzerland University, Baltimore, Ronald van Ree, PhD Carsten B. Schmidt-Weber, PhD Alex Straumann, MD Professor, Department of Experimental Immunology, Center for Allergy & Environment Chairman Swiss EoE Research Academic Medical (ZAUM), Technische Universität Network Center, Amsterdam, The München and Helmholtzzentrum Department of Gastroenterology, Netherlands, Department of München University Hospital Basel, Basel, Otorhinolaryngology, Academic Switzerland Gabriela Senti, MD Medical Center, Amsterdam, The Clinical Trials Center, University Stanley J. Szefler, MD Netherlands Hospital Zurich, Zurich, Pediatric Asthma Research Program, Roy Gert van Wijk, MD Switzerland Section of Pediatric Pulmonary Dept of Internal Medicine, Erasmus Saira Z Sheikh, MD Medicine, Breathing Institute, Medical Center Rotterdam, Division of Rheumatology, Allergy Department of Pediatrics, Netherlands Children’s Hospital Colorado; & Immunology, Department of Gilda Varricchi, MD University of Colorado Denver School Medicine and Thurston Arthritis Department of Translational Medical of Medicine, Aurora, Colorado Research Center, University of Sciences and Center for Basic and North Carolina at Chapel Hill, Morvarid Tavassoli, MD Clinical Immunology Research Chapel Hill ,USA Division of Immunology and Allergy, (CISI), University of Naples Scott H. Sicherer, MD Department of Pediatrics, Federico II, School of Medicine, The Elliot and Roslyn Jaffe Food Stanford University, Stanford, Naples, Italy Allergy Institute, Kravis Children’s USA J. Christian Virchow, MD Hospital, Division of Allergy Michael N. Teng, MD Universitätsmedizin Rostock, and Immunology, Department Joy McCann Culverhouse Airway Germany of Pediatrics, Icahn School of Disease Research Center, Division Department of Pneumology/ Medicine at Mount Sinai, New of Allergy and Immunology, Intensive Care Medicine, Clinic 1, York, NY, USA Department of Internal Medicine, Center of Internal Medicine University of South Florida Hans-Uwe Simon, Berber Vlieg-Boerstra, PhD RD Morsani College of Medicine Institute of Pharmacology, University Department of Pediatric Respiratory of Bern, Switzerland Ingrid Terreehorst, MD Medicine and Allergy, Emma F. Estelle R. Simons, MD Department of ENT & Pediatrics, Children’s Hospital, Academic Department of Pediatrics & Academic Medical Center, Medical Center, University of Child Health, Department of Amsterdam, The Netherlands Amsterdam, The Netherlands Immunology , Faculty of Medicine Wayne R. Thomas, PhD Kimberly Vu, MD University of Manitoba, Canada Centre for Child Health Research, Division of Immunology and Allergy, Isabel Skypala, PhD University of Western Australia, Department of Pediatrics, Royal Brompton&Harefield NHS Perth, Australia Stanford University, Stanford, Foundation Trust, Sydney Street, Telethon Institute for Child Health USA

Contributors VII Global Atlas of ALLERGY

Ulrich Wahn, MD Stephan Weidinger, MD Maria Yazdanbakhsh, PhD Department of Pediatric Pneumology Department of Dermatology and Department of Parasitology, Leiden and Immunology, Charité, Berlin, Allergy, University Hospital University Medical Center, Leiden, Germany Schleswig-Holstein, Kiel, Germany The Netherlands Michael Wallner, MD Thomas Werfel, MD M Osman Yusuf, MD University of Salzburg, Department Division of Immunodermatology and of Molecular Biology, Christian Allergy Research, Department of The Allergy & Asthma Institute, Doppler Laboratory for Allergy Dermatology, Hannover Medical Pakistan. Diagnosis and Therapy, Saltzburg, School, Hannover, Germany The International Primary Care Austria Marsha Wills-Karp, PhD Respiratory Group Canonica G. Walter, MD Department of Environmental Quaid e Azam University, Islamabad, Dept of Allergy & Respiratory Health Sciences, Johns Hopkins Pakistan. Diseases Clinic, University of Bloomberg School of Public Genova, Genova- Italy Health, Baltomore, USA Torsten Zuberbier, MD Dept. of Dermatology and Allergy, Richard Weber, MD Margitta Worm, MD Department of Medicine, National Charité-Universitätsmedizin, Klinik Charité, Berlin Jewish Medical & Research für Dermatologie, Venerologie Global Allergy and Asthma European Center, Denver, US und Allergologie, Berlin, Germany Network (GA2LEN)

VIII Contributors Global Atlas of ALLERGY

Contents

Section A Allergy - Mechanisms

2 What is allergy 60 T cells Johannes Ring Carsten B. Schmidt-Weber 4 The discovery of IgE 62 B cells S.G.O. Johansson Azza Abdel-Gadir, Talal Chatila 6 Allergens – structure and function 64 Immunoglobulin E and other antibodies in Ronald van Ree allergy 9 Mechanisms of allergenicity of allergens Hannah Gould, Yih-Chih Chan Heimo Breiteneder 67 Role of superantigens in allergic diseases 11 Allergens and cross-reactivity Donald Y. M. Leung Barbara Bohle 13 House dust mite allergens 69 Cytokines in allergy Wayne R. Thomas Lars K. Poulsen 15 Pet allergens 71 Cell migration and chemokines Hans Grönlund Cristiana Stellato, Gilda Varricchi, Gianni Marone 18 Tree pollen allergens 76 Complement-mediated regulation of the Fatima Ferreira, Gabriele Gadermaier, Michael Wall- allergic response ner Marsha Wills-Karp 22 Grass pollen allergens 79 Lipid mediators of hypersensitivity and Jörg Kleine-Tebbe, Janet Davies inflammation 27 Weed pollen allergens Marek Sanak Richard W. Weber 81 Lipid mediators in resolution of allergic 29 Food allergens Barbara Ballmer-Weber inflammation Evangelos Andreakos 32 Venom allergens Franziska Ruëff 84 Allergy and the epithelial barriers 34 Emerging allergens Stephen T. Holgate Karin Hoffmann-Sommergruber 88 Epithelial proteases and allergic diseases 36 Pollen allergens and geographical factors Ömer Kalayci Jeroen Buters 90 Mechanisms of immune regulation in allergy 39 The underlying mechanisms in allergy Willem van de Veen, Mübeccel Akdis Cezmi A. Akdis 92 Neuro-immune regulation of allergic 43 Innate immune response in allergy inflammation Michael N. Teng, Richard F. Lockey Harald Renz 45 Dendritic cells 95 United airways and immune regulation Bart N. Lambrecht Claus Bachert 48 Natural killer cells and natural killer-T cells Günnur Deniz 98 Genetics of allergy Stephan Weidinger 50 Innate lymphoid cells Hirohisa Saito 101 Epigenetics of Allergy 53 Mast cells R. Sharon Chinthrajah, Kimberly Vu, Morvarid Tavas- Stephen J. Galli soli, Kari C Nadeau, 56 Basophils 104 Endotypes of allergic diseases Hajime Karasuyama Ioana Agache, Cezmi A. Akdis 58 Eosinophils 108 Animal models of allergic disease Hans-Uwe Simon Remo Frei, Liam O’Mahony

Contents IX Global Atlas of ALLERGY

Section B Epidemiology and risk factors 112 The allergy epidemic 133 Environmental risk factors for allergy: working Paolo Maria Matricardi environment 115 Natural history of allergy Roy Gert van Wijk Susanne Lau 135 Risk factors for childhood asthma: viral 119 Birth cohorts infection and allergic sensitization Adnan Custovic Frederick J. Rubner, Robert F. Lemanske Jr. 121 Environmental risk factors for allergy: outdoor/ 138 Environmental risk factors for allergy: helminth indoor pollution and climate change infections Stefanie Gilles, Claudia Traidl-Hoffmann Abena S. Amoah, Firdaus Hamid, Hermelijn H. Smits, 124 Measuring exposure to environmental airborne Maria Yazdanbakhsh allergens 141 Perinatal immune development and its role in Isabella Annesi-Maesano atopy development 127 Environmental risk factors for allergy: food Patrick G. Holt Scott H. Sicherer 143 Perinatal risk and protective factors for allergic 130 Environmental risk factors for allergy: home diseases environment Arne Høst Thomas A.E. Platts-Mills 146 The role of microbiome Erika von Mutius

Section C Allergy diagnosis 150 In vivo allergy diagnosis - skin tests 163 The allergen challenge chamber Julia Katharina Genser, Peter Schmid-Grendelmeier Friedrich Horak 153 In vivo allergy diagnosis‑ nasal and bronchial 166 In vitro allergy diagnosis – Allergen- specific provocation tests IgE Gert Jan Braunstahl Reto Crameri 156 In-vivo allergy diagnosis‑ food provocation 168 In vitro allergy diagnosis – molecules and tests component-resolved diagnosis Philippe Eigenmann Markus Ollert, Adriano Mari 158 In vivo diagnosis of NSAID hypersensitivity 171 In vitro allergy diagnosis - cellular allergy Marek L. Kowalski testing 161 In vivo allergy diagnosis - drug provocation test Hans Jürgen Hoffmann Knut Brockow 173 Biomarkers for allergy diagnosis and treatment Kenji Izuhara

Section D Major Allergic Diseases 178 Allergic rhinitis 191 Anaphylaxis Peter W. Hellings F. Estelle R. Simons 180 Chronic rhinosinusitis and nasal polyposis 197 Drug allergy Cemal Cingi, Philippe Gevaert , Nuray Bayar Muluk Pascal Demoly 184 Ocular allergy 199 Food allergy Constance H. Katelaris Susanne Halken, Antonella Muraro 186 Pediatric Asthma 203 Atopic dermatitis Stanley J. Szefler Thomas Bieber 188 Adult asthma 206 Urticaria Leif Bjermer Carsten Bindslev-Jensen

X Contents Global Atlas of ALLERGY

209 EAACI - GA2LEN - EDF - WAO Guideline on 217 Latex allergy Urticaria Clive E. Grattan Torsten Zuberbier, Marcus Maurer 219 Insect sting allergy 212 Angioedema M. Beatrice Bilò Massimo Triggiani 221 Occupational allergy 215 Allergic contact dermatitis Santiago Quirce Thomas Werfel

Section E Other hypersensitivity diseases 226 Eosinophilic esophagitis 236 Allergic bronchopulmonary aspergillosis Alex Straumann J. Christian Virchow 228 Food protein-induced enterocolitis syndrome 239 Hypersensivity pneumonitis Anna Nowak-Węgrzyn Ioana Agache 232 Reactions to food and drug additives 242 Mastocytosis Margitta Worm Dean D. Metcalfe 234 Adverse reactions to vaccines for infectious 245 Hypersensitivity vasculitis diseases Marcus Maurer, Torsten Zuberbier Jean-Christoph Caubet , Ingrid Terreehorst

Section F Special considerations 248 Primary immunodeficiency diseases 259 Allergic diseases in adolescents Mark Ballow Graham Roberts 251 Allergic disease in the elderly 261 Adherence to the management plan Robert K. Bush Andrew Nickels, James T. Li 253 Allergic diseases in pregnancy 264 Allergic diseases and quality of life Jennifer A. Namazy, Michael Schatz Anthony E.J. Dubois 256 Allergic diseases and sports 266 Allergic diseases in animals Matteo Bonini, Sergio Bonini Claude Favrot

Section G Management of allergic diseases 270 Overview: avoidance, treatment, induction of 285 Anti IgE treatment for allergic disease tolerance Christoph Heusser, Veit Erpenbeck Anthony J. Frew 287 Biological agents for the treatment of allergic 273 Avoidance measures in the management of disorders allergic diseases – focus on environment Onur Boyman, François Spertini Ulrich Wahn 290 Biosimilars and allergy treatment 276 Avoidance measures - focus on diet G. Walter Canonica Alexandra F. Santos, Gideon Lack 292 Targeting basophils and mast cells for novel 278 Perinatal risk factors and strategies for allergy treatment approaches prevention Edward F. Knol Susan L. Prescott 295 Tolerance induction: principle and modalities 281 Pharmacological treatment of allergic disease Catherine M. Hawrylowicz Dennis K. Ledford 297 Allergen immunotherapy‑ overview Linda Cox

Contents XI Global Atlas of ALLERGY

300 Mechanisms of allergen immunotherapy Thomas M. Kündig, Gabriela Senti Marek Jutel 319 Measuring clinical outcomes in allergen 303 Subcutaneous allergen immunotherapy immunotherapy Désirée Larenas Linnemann Stephen R. Durham, Oliver Pfaar 306 Sublingual allergen immunotherapy 323 Implementing a healthy life style Moisés A. Calderón Caroline Roduit, Roger Lauener 309 Oral allergen Immunotherapy for foods 326 Psychological support in the management of Saira Z Sheikh, A. Wesley Burks allergic patients 311 Recombinant allergens for allergen Helen Smith immunotherapy 329 Pharmacogenetics and pharmacogenomics of Rudolf Valenta, Verena Niederberger allergic diseases 313 Peptide immunotherapy for allergic disease Lanny J. Rosenwasser Mark Larché 331 Pharmacoeconomics of allergic diseases 316 New routes for allergen immunotherapy Linda Cox

Section H Towards a comprehensive global strategy for the management of allergic diseases

336 Contribution of allergy to the burden of Tomás Chivato Pérez non‑communicable diseases 362 Best buys for allergy prevention and control Shanthi Mendis Tari Haahtela 338 Allergic diseases on the political agenda 365 Dealing with the implementation gap for Nikolaos G. Papadopoulos allergy prevention and control 340 Policies and strategies to facilitate access to Victòria Cardona diagnosis and treatment for allergic diseases 367 Generating resources for allergy prevention Michael B. Foggs and control 342 Policies and strategies to reduce risk factors for Kai-Håkon Carlsen, Karin C. Lødrup Carlsen allergic diseases 369 Strengthening the speciality of Allergology and Ruby Pawankar Clinical Immunology 344 The role of primary care in the management of Jan G. R. de Monchy, Jaques Gayraud allergic diseases 371 EAACI-UEMS Exam in Allergology/Clinical Dermot Ryan, M. Osman Yusuf Immunology 346 The role of allied health in the management of Werner J. Pichler , Peter Schmid-Grendelmeier allergic diseases 374 Managing allergic diseases in developing Berber Vlieg-Boerstra, James Gardner,Isabel Skypala countries 348 The role of patient organisations in the Musa R. Khaitov, Lyudmila V. Luss, Natalia I. Ilyna, management of allergic diseases Rakhim M. Khaitov EAACI Patient Organisation Committee 377 The “One Health” concept and allergic diseases 352 The role of pharmacists in managing allergic Walter J. Ammann diseases 379 Allergy and active and healthy ageing Maximin Liebl, Viktor Hafner, Otto Sprange Jean Bousquet, Boleslaw Samolinski 354 The role of schools in managing allergic 381 Allergy in internet diseases Enrico Heffler Angel Mazon 383 iCAALL: International Collaboration in Asthma, 357 Comprehensive allergy management plan. Allergy and Immunology Towards a patient-centered attitude Jan Lötval, Denis Ledford, Cezmi A. Akdis, iCAALL Georg Schäppi Chairs 359 Social mobilization for management of allergic 385 Vision and roadmap to fight with allergies diseases Cezmi A. Akdis

XII Contents Global Atlas of ALLERGY

preface

Allergic diseases are affecting the lives of more than one billion people worldwide. With an epidemic rise during the last 60 years, their prevalence is expected to reach up to 4 billion in 2050s. Because of immense numbers of affected individuals, the general public confronts huge direct and indirect costs with major effects on macroeconomics due to health-care, loss of productivity and absenteeism of patients. Unfortunately, high number of unmet needs due to missing scientific knowledge in disease mechanisms, prevention, patient care, and social determinants remain to be resolved. To tackle this huge global health problem, we as the EAACI decided to develop the “Global Atlas of Al- lergy” as a follow up of our “Global Atlas of Asthma” which was launched last year. With this Atlas, we aimed to gather evidence to call attention to the burden of allergic diseases; to warrant their recog- nition as a main concern in national health strategies; to reveal their priority for research; to describe environmental factors; to evaluate the best ways to prevent and control allergies; to provide guidance on how to overcome barriers; to alert the political bodies to ensure global management approaches. The EAACI Global Atlas of Allergy contains 139 chapters written by 183 authors with 274 illustra- tions and 100 tables. It is developed as a desktop reference for multisectoral usage covering all as- pects of allergic diseases from allergens, epidemiology, risk factors and molecular and cellular mecha- nisms to their management, major current problems in allergies and associated diseases, prevention and control of allergic diseases. In addition, the Atlas will offer an educational tool and a desktop reference for medical students, allied health workers, primary care physicians, medical industry, pol- icy makers, patient organizations and specialists dealing with allergies and co-morbid diseases. We would like to thank all of the authors for their contributions.

Cezmi A. Akdis Ioana Agache Editors

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