Allergy PDF
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A L L E R G Y Commissioning Editor: Sue Hodgson Development Editor: Sharon Nash Project Manager: Sukanthi Sukumar Designer: Kirsteen Wright Illustration Manager: Merlyn Harvey Illustrators: Robert Britton (4e), Martin Woodward (3e) Marketing Manager(s) (UK/USA): Gaynor Jones/Helena Mutak 4 th EDITION A L L E R G Y Stephen T Holgate David H Broide CBE BSc MB BS MB ChB MD DSc CSci FRCP FRCP(Edin) FRCPath Professor of Medicine FSB FIBMS FMedSci University of California, San Diego La Jolla, CA, USA MRC Clinical Professor of Immunopharmacology School of Medicine Fernando D Martinez MD Infection, Inflammation and Immunity Division University of Southampton Regents’ Professor Southampton General Hospital Director, BIO5 Institute Southampton, UK Director, Arizona Respiratory Center Swift-McNear Professor of Pediatrics The University of Arizona Martin K Church MPharm PhD DSc Tucson, AZ, USA FAAAAI Professor of Immunopharmacology Department of Dermatology and Allergy Allergy Centre Charitè Charitè Universitätsmedizin Berlin, Germany Emeritus Professor of Immunopharmacology University of Southampton Southampton, UK Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2012 SAUNDERS an imprint of Elsevier Limited © 2012, Elsevier Limited. All rights reserved. First edition 1993 Second edition 2001 Third edition 2006 The right of Stephen T. Holgate, Martin K. Church, David H. Broide, and Fernando D. Martinez to be identified as authors of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act 1988. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. British Library Cataloguing in Publication Data Allergy. – 4th ed. 1. Allergy. I. Holgate, S. T. 616.9′7–dc22 ISBN-13: 9780723436584 The Working together to grow publisher’s libraries in developing countries policy is to use paper manufactured from sustainable forests www.elsevier.com | www.bookaid.org | www.sabre.org Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 preface In 1992, we published the first edition of an entirely new text on allergic diseases and their mechanisms based on specifically designed, clear and informative dia- grams. This allowed us to produce a text that found a unique niche between the more heavily referenced books and the more superficial guides. In this edition, the reader was introduced to the individual cells and mediators that participate in the allergic response and this information was then built on to describe the histopathological features, diagnoses and treatment of allergic responses occurring in all major organs. When preparing the second edition, we took note of the feedback of many clinicians who asked us if we could put primary emphasis on the clinical mani- festations of allergy and augment this with a solid scientific background. We kept this format for the third edition. This format has appeared to be very successful with our readers, so much so that it was awarded ‘Book of the Year’ prize by the British Medical Association. Now, 19 years after the original Allergy we are at the fourth edition with two new editors. Dr Lawrence Lichtenstein has retired and we welcome Dr David Broide and Dr Fernando Martinez to the editorial team. We have also updated the format slightly by emphasising the clinical aspects while reducing the cellular science to a single chapter introducing mechanisms of allergic disease. Further- more, two new chapters have been added, one on eosinophilia, including eosi- nophilic oesophagitis and the other on systemic mastocytosis. One thing that has not changed is our policy of inviting international authorities, often two or more authors from different countries, to work together to produce their sections. Although this approach is not without its logistical problems, we believe it has produced a more authoritative text and we thank all the authors for their forbearance. Indeed, we owe a great debt of gratitude to the many experts who have contributed such informative chapters. As readers, we hope that you will appreciate the fourth edition of Allergy and that you find its content enjoyable and educative to read. As we requested in the first three editions, please give us your feedback on the book so that we can refine it even further in the future. STH, MKC, DHB, FDM 2012 vii list of contributors Mitsuru Adachi MD PhD David H Broide MB ChB Adnan Custovic DM MD PhD FRCP Professor of Medicine Professor of Medicine Professor of Allergy Division of Allergology and Respiratory University of California, San Diego Head, Respiratory Research Group Medicine La Jolla, CA University of Manchester School of Medicine USA Education and Research Centre Showa University University Hospital of South Manchester William W Busse MD Tokyo, Japan Manchester, UK Professor of Medicine Sarah Austin MS Allergy, Pulmonary and Critical Care Charles W DeBrosse MD MS Scientific Operations Manager Medicine Allergy and Immunology Fellow Laboratory of Allergic Diseases Department of Medicine Cincinnati Children’s Hospital Medical National Institute of Allergy and Infectious University of Wisconsin School of Center Diseases Medicine and Public Health Cincinnati, OH National Institutes of Health Madison, WI USA Bethesda, MD USA Pascal Demoly MD PhD USA Virginia L Calder PhD Professor and Head Leonard Bielory MD Senior Lecturer in Immunology Allergy Department Director Department of Genetics Maladies Respiratoires – Hôpital Arnaud STARx Allergy and Asthma Research UCL Institute of Ophthalmology de Villeneuve Center London, UK University Hospital of Montpellier Springfield, NJ Montpellier, France Thomas B Casale MD Rutgers University Professor of Medicine Stephen R Durham MA MD FRCP Center for Environmental Prediction Chief, Division of Allergy/Immunology Professor of Allergy and Respiratory New Brunswick, NJ Creighton University Medicine Professor Omaha, NE Head, Allergy and Clinical Immunology Medicine, Pediatrics, Ophthalmology and USA National Heart and Lung Institute Visual Sciences Imperial College and Royal Brompton New Jersey Medical School Martin K Church MPharm PhD DSc Hospital Newark, NJ FAAAAI London, UK USA Professor of Immunopharmacology Stephan C Bischoff MD Department of Dermatology and Allergy Mark S Dykewicz MD Professor of Medicine Allergy Centre Charitè Professor of Internal Medicine Department of Clinical Nutrition and Charitè Universitätsmedizin Director, Allergy and Immunology Prevention Berlin, Germany Section on Pulmonary, Critical Care, University of Hohenheim Emeritus Professor of Allergy and Immunologic Diseases Stuttgart, Germany Immunopharmacology Allergy and Immunology Fellowship University of Southampton Program Director Attilio L Boner MD Southampton, UK Wake Forest University School of Medicine Professor of Pediatrics Center for Human Genomics and Pediatric Department Jonathan Corren MD Personalized Medicine Research University of Verona Associate Clinical Professor of Medicine Winston-Salem, NC Verona, Italy Division of Pulmonary and Critical Care USA Medicine Larry Borish MD Section of Clinical Immunology and Allergy Pamela W Ewan CBE FRCP FRCPath Professor of Medicine University of California Consultant Allergist and Associate Lecturer Asthma and Allergic Disease Center Los Angeles, CA Head, Allergy Department University of Virginia USA Cambridge University Hospitals Charlottesville, VA National Health Service Foundation Trust USA Peter S Creticos MD Cambridge, UK Associate Professor of Medicine Piera Boschetto MD PhD Medical Director Clive EH Grattan MA MD FRCP Associate Professor of Occupational Asthma and Allergic Diseases Consultant Dermatologist Medicine Division of Allergy and Clinical Immunology Dermatology Centre Department of Clinical and Experimental Johns Hopkins University Norfolk and Norwich University Hospital Medicine Baltimore, MD Norwich, UK University of Ferrara USA Ferrara, Italy viii list of contributors Rebecca S Gruchalla MD PhD Martha Ludwig PhD David B Peden MD MS Professor of Internal Medicine and Associate Professor Professor of Pediatrics, Medicine and Pediatrics School of Biomedical, Biomolecular and Microbiology/Immunology Section Chief, Division of Allergy and Chemical Sciences Chief, Division of Pediatric Allergy, Immunology The University of Western Australia Immunology, Rheumatology and Infectious UT Southwestern Medical Center Perth, WA, Australia Diseases Dallas, TX Director, Center for Environmental Piero Maestrelli MD USA Medicine, Asthma and Lung Biology Professor of Occupational Medicine Deputy Director for Child Health, Melanie Hingorani MA MBBS Department of Environmental Medicine NC Translational & Clinical Sciences FRCOphth MD and Public Health Institute (CTSA) School of Medicine Consultant Ophthalmologist University of Padova The University of North Carolina at Chapel Ophthalmology Department Padova, Italy Hill Hinchingbrooke Hospital Hans-Jorgen Malling MD DMSci Chapel Hill, NC Huntingdon, Cambridgeshire USA Associate Professor Richard Desmond Children’s Eye Centre Moorfields Eye Hospital Allergy Clinic R Stokes Peebles MD Gentofte University Hospital London, UK Professor of Medicine Copenhagen, Denmark Division of Allergy, Pulmonary, and Critical Stephen T Holgate CBE BSc MB BS Fernando D Martinez MD Care Medicine MD DSc CSci FRCP FRCP(Edin) Vanderbilt University School of Medicine Regents’ Professor FRCPath FSB FIBMS FMedSci Nashville, TN Director, BIO5 Institute MRC Clinical Professor of USA Director, Arizona Respiratory Center Immunopharmacology Swift-McNear Professor of Pediatrics Thomas AE Platts-Mills MD PhD FRS School of Medicine The University of Arizona Infection, Inflammation and Immunity Department of Medicine Tucson, AZ Division Division of Allergy and Immunology USA University of Southampton University of Virginia Southampton General Hospital Marcus Maurer MD Charlottesville, VA Southampton, UK Professor of Dermatology and Allergy USA John W Holloway PhD Director of Research Susan Prescott BMedSci(Hons) Department of Dermatology and Allergy Professor of Allergy and Respiratory MBBS PhD FRACP Allergie-Centrum-Charité/ECARF Genetics, Human Development & Health Winthrop Professor Charité – Universitätsmedizin Berlin Faculty of Medicine School of Paediatrics and Child Health Berlin, Germany University of Southampton University of Western Australia Southampton, UK Dean D Metcalfe MD Paediatric Allergist and Immunologist Chief, Laboratory of Allergic Diseases Princess Margaret Hospital for Children Patrick G Holt DSc FRCPath FAA National Institute of Allergy and Infectious Perth, WA, Australia Head, Division of Cell Biology Diseases Telethon Institute for Child Health Marc E Rothenberg MD PhD National Institutes of Health Research and Centre for Child Health Professor of Pediatrics Bethesda, MD Research Director, Division of Allergy and USA University of Western Australia Immunology Perth, WA, Australia Dean J Naisbitt PhD Director, Cincinnati Center for Eosinophilic Senior Lecturer Disorders Alexander Kapp MD PhD MRC Centre for Drug Safety Science Cincinnati Children’s Hospital Medical Professor of Dermatology and Allergy Department of Pharmacology Center Chairman and Director University of Liverpool University of Cincinnati College of Department of Dermatology and Allergy Liverpool, UK Medicine Hannover Medical School Cincinnati, OH Hannover, Germany Hans Oettgen MD PhD USA Associate Chief Phil Lieberman MD Division of Immunology Hugh A Sampson MD Clinical Professor of Medicine and Children’s Hospital Dean for Translational Biomedical Pediatrics Associate Professor of Pediatrics Sciences University of Tennessee College of Harvard Medical School Kurt Hirschhorn Professor of Pediatrics Medicine Boston, MA Department of Pediatrics and Immunology Memphis, TN USA The Mount Sinai School of Medicine USA The Jaffe Food Allergy Institute B Kevin Park PhD New York, NY Susan Lightman PhD FRCP Professor, Translational Medicine USA FRCOphth FMedSci MRC Centre for Drug Safety Science Professor of Clinical Ophthalmology Department of Pharmacology UCL/Institute of Ophthalmology University of Liverpool Moorfields Eye Hospital Liverpool, UK London, UK ix list of contributors Glenis K Scadding MA MD FRCP Philip J Thompson MBBS FRACP Erika von Mutius MD MSc Hon. Consultant Allergist and Rhinologist MRACMA FCCP Professor of Pediatrics Royal National Throat, Nose and Ear Director, Lung Institute of Western Dr. von Haunersche Children’s Hospital Hospital Australia Inc Ludwig Maximilian University London, UK Winthrop Professor of Respiratory Munich, Germany Medicine Peter D Sly MBBS MD DSc FRACP John O Warner MD FRCP FRCPCH Director, Centre for Asthma, Allergy and Senior Clinical Research Fellow FMedSci Respiratory Research Queensland Children’s Medical Research Professor of Paediatrics and University of Western Australia Institute Head of Department Clinical Professor University of Queensland Imperial College Curtin University Brisbane, Australia Honorary Consultant Paediatrician Consultant Respiratory Physician Imperial College Healthcare NHS Trust Geoffrey A Stewart PhD Sir Charles Gairdner Hospital London, UK Winthrop Professor Western Australia School of Biomedical, Biomolecular and Perth, WA, Australia Thomas Werfel MD Chemical Sciences Peter Valent MD Professor of Medicine The University of Western Australia Department of Dermatology and Associate Professor of Internal Medicine Perth, WA, Australia Allergology Division of Hematology and Hannover Medical School Hemostaseology Hannover, Germany Department of Internal Medicine I and Ludwig Boltzmann Cluster Oncology Bruce L Zuraw MD Medical University of Vienna Professor of Medicine Vienna, Austria University of California, San Diego and San Diego VA Healthcare System La Jolla, CA USA x 1 Introduction to mechanisms of allergic disease Hans Oettgen and David H Broide DEFINITION An improved understanding of Introduction to the immune response the mechanisms mediating allergic inflammation provides The immune system has evolved to play a pivotal role in host defence against a rationale for the infection as without a functioning immune system individuals would be development of targeted predisposed to develop a variety of infections from viruses, bacteria, therapies to prevent and treat fungi, protozoa, and multicellular parasites. The key components of a well- allergic disorders. functioning immune system include the ability to generate both innate and adaptive immune responses (Fig. 1.1). The innate immune system comprises cellular elements that are both resident in tissues (i.e. epithelium, macro- phages, mast cells) for a rapid response and circulating leukocytes that are recruited from the blood stream (neutrophils, eosinophils, basophils, mono- nuclear cells, natural killer (NK) cells, and NK T cells). In addition to the cellular response the innate immune system has humoral elements (comple- ment, antimicrobial peptides, mannose-binding lectin), which provides a mechanism for an immediate response to infection that is not antigen specific and does not have immunological memory. In contrast, the adaptive immune response generated by its component T and B cells is slower to respond to infections (taking days) but has the advantage of exhibiting antigen specificity and immunological memory. A malfunctioning immune system may lead not only to immunodeficiency with recurrent infections, but also to autoimmu- nity and allergic diseases. In this chapter, we focus on the cellular and molecular mechanisms through which an aberrant immune response to low levels of otherwise innocuous and ubiquitous environmental exposures such as airborne grass pollens or ingested foods may trigger a range of allergic responses from chronic symptoms affecting quality of life to acute severe allergic reactions that are life threatening. Overview of the allergic immune response Allergic diseases such as allergic rhinitis, asthma, and food allergy are char- acterized by the ability to make an IgE antibody response to an environmental allergen. There is both a strong genetic (see Ch. 2) as well as environmental contribution to the development of allergic disease (see Chs 3 and 4). Immu- noglobulin E (IgE)-mediated allergic responses most frequently occur on mucosal (nose, conjunctiva, airway, gastrointestinal tract) or skin surfaces as these anatomical sites contain high levels of mast cells to which IgE is affixed. © 2012 Elsevier Ltd DOI: 10.1016/B978-0-7234-3658-4.00005-6 11 1 Introduction to mechanisms of allergic disease Anatomical and Innate immunity Adaptive immunity physiological barriers Natural Neutrophils killer cells Natural Eosinophils Cellular killer T cells Cellular Intact skin Macrophages Mast cells B cells T cells Dendritic cells Ciliary clearance Mannose binding Complement lectin Low Humoral Humoral stomach pH LPS binding protein Antimicrobial peptides Lysozyme Antibodies C-reactive protein in tears and saliva Fig. 1.1 Innate and adaptive immune response. The human microbial defence system can be simplistically viewed as consisting of three levels: (1) anatomical and physiological barriers; (2) innate immunity; and (3) adaptive immunity. In common with many classification systems, some elements are difficult to categorize. For example, NK T cells and dendritic cells could be classified as being on the cusp of innate and adaptive immunity rather than being firmly in one camp. (Adapted from: Figure 2 in Turvey SE, Broide DH. J Allergy Clin Immunol. 2010; 125:S24–32.) Initial exposure of a genetically predisposed individual to immune and inflammatory responses contribute to aller- low levels of allergens such as grass pollens results in gic inflammation. In this chapter we explore these mech- uptake of the pollen allergen by antigen-presenting cells anisms in greater detail to gain insight into the cellular (APCs), intracellular digestion of the allergen into peptide and molecular events that contribute to the development fragments, and display of the allergen peptide fragments of the allergic inflammatory response. Such important in an human leukocyte antigen (HLA) groove on the APC insights provide the rationale for the development of surface (Fig. 1.2). When circulating T cells (expressing novel therapies for the targeted treatment of allergic an antigen cell surface receptor specific for the allergen disease, as well as the potential development of biomark- peptide) interact with the APC, the interaction activates ers to assess allergic disease severity, progression, or the T cell to express cytokines characterized by a helper response to therapy. T cell type 2 (Th2) cytokine profile (Fig. 1.3). Th2 cytokines (Table 1.1) play an important role in inducing Central role of IgE and B cells to switch class and express IgE (e.g. interleukin-4, IL-4), induce eosinophil proliferation in the bone marrow mast cells (i.e. induced by IL-5), and up-regulate adhesion mole- cules on blood vessels to promote tissue infiltration of Atopy, the tendency to produce IgE antibodies specific circulating inflammatory cells associated with allergic for environmental allergens, affects 30–40% of the popu- inflammation such as eosinophils and basophils. The aller- lation of developed nations. The production of IgE results gen specific IgE (induced by initial exposure to allergen) in a range of hypersensitivity disorders including, anaphy- binds to high-affinity IgE receptors on mast cells and laxis, allergic rhinitis, atopic dermatitis and asthma. IgE basophils. These IgE sensitized mast cells upon re-exposure antibodies, IgE receptors, and several lineages of effector to specific allergen are activated to release histamine and cells activated by IgE have persisted through vertebrate many other proinflammatory mediators that contribute evolution implicating this antibody isotype in important to the allergic inflammatory response (Fig. 1.4). Although physiological immune functions. IgE probably serves to this induction of a Th2 response is characteristic of aller- eliminate helminthic parasites during primary infection gic inflammation, it is increasingly evident that additional and in parasite endemic regions to protect previously 2
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