Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach PDF
Preview Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach
Daniel C. Baumgart Editor Crohn’s Disease and Ulcerative Colitis From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach Second Edition 1 3 Crohn’s Disease and Ulcerative Colitis Daniel C. Baumgart Editor Crohn’s Disease and Ulcerative Colitis From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach Second Edition Editor Daniel C. Baumgart Inflammatory Bowel Disease Center Department of Gastroenterology and Hepatology Charité Medical School—Humboldt-University of Berlin Berlin, Germany ISBN 978-3-319-33701-2 ISBN 978-3-319-33703-6 (eBook) DOI 10.1007/978-3-319-33703-6 Library of Congress Control Number: 2016959449 © Springer International Publishing AG 2017 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustra-tions, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Foreword The clinical features of the major forms of Inflammatory Bowel Disease, Crohn’s disease and ulcerative colitis, have been generally well known for decades. After a long period in which advances in our understanding of the causation and pathogenesis of inflammatory bowel dis- eases remained painfully slow and, in parallel, improvements in management were at best incremental, the momentum of progress has accelerated over the past several years, making a textbook that draws together the full continuum of these advances timely. The recent pace of progress in understanding the underlying pathogenesis has been espe- cially remarkable. This has been possible because of more powerful methodological approaches as well as a growing community of investigators focused on these disorders and the basic processes associated with them. Progress in recent years has been rapid along a number of fronts, and a general paradigm has emerged to suggest that these disorders result from altera- tions in the host response to the microflora present within the GI tract. These host responses comprise the collective functional integrity of the mucosal epithelium and the complex set of innate and adaptive immune responses. While many details remain to be fleshed out, molecular pathways intrinsic to the interactions and functional regulation of these responses have been identified and it is clear that for many the “set point” is determined by the genotypic variations at dozens of susceptibility genes. Undoubtedly surprises remain. History suggests the skeptic of any entrenched dogma has a good likelihood of eventually being proven right. However, this paradigm or model has proven a powerful context to ask better questions that should eventuate in more complete answers about the causation and pathogenesis of inflammatory bowel dis- eases. Progress in understanding of the basic processes underlying the development of inflam- matory bowel diseases should be an engine for still more effective therapies as well as diagnostic tools to facilitate management. On the clinical front, the global epidemiology of inflammatory bowel diseases continues to evolve. While incidence and prevalence plateaued after a long period of steady rise in those regions that remain highest, Europe and North America, other areas of the world are seeing a characteristic pattern of increases in the frequency of ulcerative colitis followed pari passu by increases in Crohn’s disease. Clinicians caring for these patients cannot be complacent. There is more information that needs to be incorporated into management decisions and, most impor- tantly, much more to offer patients. Improvements in management include evolving surgical approaches and, in some instances, alternative interventions via endoscopy offering efficacy with less morbidity. Advances in nonsurgical medical therapy have had an even greater impact on treatment of IBD patients. These include categorically new agents, which have been devel- oped on the basis of advances in our understanding of mechanisms relevant to the pathogenesis of these disorders. As exemplified by anti-TNF agents, the age of biologics has arrived. Given that understanding of pathogenesis is still progressing rapidly, one can anticipate that more and more effective agents will yet be forthcoming. These advances have resulted in greater complexity in good decision-making. Those caring for these patients should welcome this complexity in so far as it reflects the possibility of find- ing management strategies better tailored to the specific needs of an individual patient. The opportunities to make more confident management decisions, if not initial diagnosis as well, have also become both more complicated and more promising with the advent of new imaging v vi Foreword modalities (both “radiologic” and “endoscopic”) as well as various biomarkers. While it is not yet clear how specific susceptibility genotypes might be best used clinically there is, in con- cept, the possibility of more definitive diagnosis after decades in which diagnosis has remained, in the final analysis, an empiric process. In these general reflections on recent progress are clear indications of the timeliness for a textbook that endeavors to bring these new advances into better focus. The editors have embraced this ambitious goal and assembled an outstanding group of authors who have been at the forefront of much of this progress. This volume provides both the clinician and the scientist with an understanding of the most recent advances as well as the context for each of them to be pursuing their mission of caring for patients and advancing our knowledge, respec- tively. However, these general reflections also come with an embedded caution. Clinicians will recognize that even with this progress, unmet needs persist and there remain many patients for whom current approaches are simply not good enough. The scientist will recog- nize how still incomplete our understanding of these diseases remains. So, this textbook pro- vides a powerful tool to ensure that clinicians can provide today’s best care and scientists can pose today’s best questions. One can only hope that within a few years the next volume will be ready to be written. Professor of Medicine Daniel K. Podolsky President of the University of Texas Southwestern Medical Center Dallas, TX, USA Preface to the Second Edition Crohn’s disease and ulcerative colitis—two chronic inflammatory diseases (IBD) on the rise— result from an inappropriate immune response, in genetically susceptible individuals, to micro- bial antigens of commensal microorganisms. This inappropriate response is promoted by certain environmental factors including Western life style, explaining their globally increasing incidence. As a systemic disorder of the immune system, IBD manifest itself primarily in the gastrointestinal tract but can affect all of the organ systems of the human body. Thus, not only gastroenterologist, but many other clinicians are confronted with IBD. On the other hand IBD is an excellent example of how the exponential growth of knowledge in biomedical science can make a remarkable impact on clinical practice and patient’s quality of life. The number of novel and targeted treatments is growing rapidly. They are continuously being refined to treat not only the two original conditions of the gut but also the variety of asso- ciated immune disorders. New therapies are sometimes complex and associated with important risks requiring a deeper understanding of their molecular principles from clinicians. This book continues to serve as a unique combined resource for physicians and scientists addressing the needs of both groups. It is meant to help stimulate exchange and collaboration, shorten the path between discovery and clinical application, and also help clinicians under- stand new therapeutic concepts from their origins. The great success of the first edition confirms our concept. It encouraged us to not only bring all chapters up to date but also include new scientific and clinical trends in new chapters. I’m grateful to my colleagues from all over the world who took out time out of their busy days to contribute new and updated chapters in their respective fields of expertise to make accomplishing the goals of this book possible. Berlin, Germany Daniel C. Baumgart vii Preface Crohn’s disease and ulcerative colitis—two chronic inflammatory diseases (IBD) on the rise— result from an inappropriate immune response, in genetically susceptible individuals, to micro- bial antigens of commensal microorganisms. This inappropriate response is promoted by certain environmental factors including Western life style, explaining their globally increasing incidence. As a systemic disorder of the immune system, IBD manifest itself primarily in the gastrointestinal tract but can affect all of the organ systems of the human body. Thus, not only gastroenterologist, but many other clinicians are confronted with IBD. On the other hand IBD is an excellent example of how the exponential growth of knowledge in biomedical science can make a remarkable impact on clinical practice and patient’s quality of life. It has led to the development of a number of novel targeted and tailored treatments. These are continuously being refined to treat not only the two original conditions in the gut but also the variety of associated immune disorders. New therapies are sometimes complex and associated with important risks requiring a deeper understanding of their molecular principles from clinicians. This book is intended to serve as a unique combined resource for physicians and scientists addressing the needs of both groups. It is meant to help stimulate exchange and collaboration and shorten the path between discovery and application of new knowledge and also help clini- cians understand new therapeutic concepts from their origins. I’m grateful to my colleagues from all over the world who contributed chapters in their respective fields of expertise and made accomplishing the goals of this book possible. Berlin, Germany Daniel C. Baumgart ix Contents Part I Epidemiology 1 Environmental Factors in the Epidemiology of Inflammatory Bowel Disease ........................................................................................................... 3 Morten H. Vatn Part II Immunobiology 2 Role of the Intestinal Immune System in Health .................................................. 23 Per Brandtzaeg 3 Understanding the Epithelial Barrier in IBD ........................................................ 57 Matthew A. Odenwald and Jerrold R. Turner 4 Intestinal Microbiology and Ecology in Crohn’s Disease and Ulcerative Colitis............................................................................................... 67 Ludovica F. Buttó and Dirk Haller 5 The Immune System in IBD: Antimicrobial Peptides .......................................... 75 Charles L. Bevins 6 Vascular Responses to Intestinal Inflammation .................................................... 87 D. Neil Granger and Norman R. Harris 7 Immunobiology of Human Dendritic Cells in Inflammatory Bowel Disease ..... 93 Daniel C. Baumgart 8 Immunobiology of T-cells in Inflammatory Bowel Disease .................................. 101 S. Snapper, D. Nguyen, and A. Biswas 9 Immunobiology of B Cells in Inflammatory Bowel Disease ................................. 111 Atsushi Mizoguchi and Atul K. Bhan 10 Immune Cells: Monocytes and Macrophages ....................................................... 119 Gerhard Rogler 11 Immune Functions of Epithelial Cells in Inflammatory Bowel Disease ............. 123 Eric L. Campbell and Sean P. Colgan 12 Autophagy and Endoplasmic Reticulum Stress .................................................... 131 Arthur Kaser 13 Matrix Metalloproteinases ...................................................................................... 135 Paolo Biancheri and Thomas T. MacDonald 14 Paradigm of T Cell Differentiation in IBD ............................................................ 141 Takashi Nagaishi and Mamoru Watanabe xi xii Contents 15 Mouse Models of Chronic Intestinal Inflammation: Characterization and Use in Pharmacological Intervention Studies .................. 149 Cynthia Reinoso Webb and Matthew B. Grisham 16 Stem Cells and Organoids to Study Epithelial Cell Biology in IBD .................... 167 Jorge O. Munera and James M. Wells Part III Diagnostic Approach 17 Enhanced Endoscopy ............................................................................................... 175 R. Kiesslich 18 Magnetic Resonance Enterography ....................................................................... 185 Patrik Rogalla and Luís Guimarães 19 Computed Tomography Enterography and Inflammatory Bowel Disease ........ 205 J.G. Fletcher 20 Ultrasound in Inflammatory Bowel Disease .......................................................... 217 A. Potthoff, C. Agne, and M. Gebel 21 Laboratory Evaluation, Including Novel Diagnostic Markers ............................ 233 M. Flamant and X. Roblin 22 Pathology of Inflammatory Bowel Disease ............................................................ 243 Nora E. Joseph and Christopher R. Weber 23 Objective Assessment of Clinical Disease Activity ................................................ 259 Edouard Louis, Catherine Van Kemseke, and Catherine Reenaers 24 Objective Assessment of Endoscopic Disease Activity and Mucosal Healing .... 267 Britt Christensen and David T. Rubin 25 Evaluation of Quality of Life in Crohn’s Disease and Ulcerative Colitis: What Is Health-Related Quality of Life? ............................................................... 279 Katrine Carlsen, Pia Munkholm, and Johan Burisch 26 Evaluation of Health Economics in Inflammatory Bowel Disease ...................... 291 Reena Khanna and Brian G. Feagan Part IV Therapy: Crohn’s Disease 27 The Natural History of Inflammatory Bowel Disease .......................................... 301 Charles N. Bernstein 28 Conventional Medical Management of Crohn’s Disease: Sulfasalazine ............. 311 Miquel A. Gassull and Eduard Cabré 29 Steroid Therapy for Crohn’s Disease ..................................................................... 315 A. Hillary Steinhart 30 Thiopurines in Crohn’s Disease .............................................................................. 321 Adi Lahat and Rami Eliakim 31 Conventional Medical Management of Crohn’s Disease: Methotrexate ............ 333 Grace Harkin and Laurence Egan 32 Adalimumab for the Treatment of Crohn’s Disease ............................................. 343 Remo Panaccione
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