Winner of the BMA Medical Book Award for Gastroenterology, 2006
Canadian Journal of Gastroenterology about Fast Facts: Inflammatory Bowel Disease, Second edition
Fast Facts: Inflammatory Bowel Disease 7
Etiopathogenesis
24
Clinical features and complications
39
Diagnosis
53
Drug treatment
81
Medical management of ulcerative colitis
102
Medical management of Crohn’s disease
124
Surgery
133
IBD in pregnancy and childhood
136
Prognosis
138
Future trends
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Fast Facts
Fast Facts:
Inflammatory Bowel Disease David S Rampton and Fergus Shanahan Third edition
Third edition
ISBN 978-1-905832-46-0
Fast Facts Inflammatory Bowel Disease
‘Ideal for the non-specialist, particularly for the use of the family physician and medical residents, nurses, stoma specialists, dieticians, psychologists, counsellors and social workers’
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© 2008 Health Press Ltd www.fastfacts.com
Fast Facts
Fast Facts: Inflammatory Bowel Disease Third edition David S Rampton DPhil FRCP Gastroenterology Clinical Academic Unit Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry Queen Mary, University of London London, UK
Fergus Shanahan MD Alimentary Pharmabiotic Centre Department of Medicine University College Cork National University of Ireland and Cork University Hospital Cork, Ireland
Declaration of Independence This book is as balanced and as practical as we can make it. Ideas for improvement are always welcome:
[email protected]
© 2008 Health Press Ltd www.fastfacts.com
Fast Facts: Inflammatory Bowel Disease First published 2000; second edition 2006 Third edition September 2008 Text © 2008 David S Rampton, Fergus Shanahan © 2008 in this edition Health Press Limited Health Press Limited, Elizabeth House, Queen Street, Abingdon, Oxford OX14 3LN, UK Tel: +44 (0)1235 523233 Fax: +44 (0)1235 523238 Book orders can be placed by telephone or via the website. For regional distributors or to order via the website, please go to: www.fastfacts.com For telephone orders, please call +44 (0)1752 202301 (UK and Europe), 1 800 247 6553 (USA, toll free), +1 419 281 1802 (Americas) or +61 (0)2 9351 6173 (Asia–Pacific). Fast Facts is a trademark of Health Press Limited. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the express permission of the publisher. The rights of David S Rampton and Fergus Shanahan to be identified as the authors of this work have been asserted in accordance with the Copyright, Designs & Patents Act 1988 Sections 77 and 78. The publisher and the authors have made every effort to ensure the accuracy of this book, but cannot accept responsibility for any errors or omissions. For all drugs, please consult the product labeling approved in your country for prescribing information. Registered names, trademarks, etc. used in this book, even when not marked as such, are not to be considered unprotected by law. A CIP record for this title is available from the British Library. ISBN 978-1-905832-46-0 Rampton DS (David) Fast Facts: Inflammatory Bowel Disease/ David S Rampton, Fergus Shanahan Medical illustrations by Dee McLean, London, UK. Typesetting and page layout by Zed, Oxford, UK. Printed by Latimer Trend & Company Limited, Plymouth, UK. Printed with vegetable inks on biodegradable and recyclable paper manufactured from sustainable forests. © 2008 Health Press Ltd www.fastfacts.com
Low chlorine
Sustainable forests
Glossary of abbreviations
4
Introduction
5
Etiopathogenesis
7
Clinical features and complications
24
Diagnosis
39
Drug treatment
53
Medical management of ulcerative colitis
81
Medical management of Crohn’s disease
102
Surgery
124
IBD in pregnancy and childhood
133
Prognosis
136
Future trends
138
Useful resources
140
Index
142
© 2008 Health Press Ltd www.fastfacts.com
Glossary of abbreviations 5-ASA: 5-aminosalicylate
MRI: magnetic resonance imaging
ASCA: anti-Saccharomyces cerevisiae antibody
NF: nuclear transcription factor
ATI: antibodies to infliximab BMI: body mass index CARD15: caspase-activiting recruitment domain, member 15 (also known as NOD2) CDAI: Crohn’s Disease Activity Index CMV: cytomegalovirus COX: cyclo-oxygenase
NF-κB: nuclear [transcription] factor κB NOD2: other name for CARD15 NSAIDs: non-steroidal antiinflammatory drugs pANCA: perinuclear antineutrophil cytoplasmic antibody PPAR: peroxisome proliferator-activated receptor
CUTE: colitis of uncertain type or etiology
PPD: purified protein derivatives (prepared from Mycobacterium tuberculosis for the Mantoux test, which indicates past or present exposure to tuberculosis)
ERCP: endoscopic retrograde cholangiopancreatography
SeHCAT: 75selenium-labeled homocholic acid taurine
ESR: erythrocyte sedimentation rate
TB: tuberculosis
HACA: human antichimeric antibodies, now known as ATI
99
HLA: human leukocyte antigen
TGF: transforming growth factor
IBD: inflammatory bowel disease
Th: T helper cell
IFN: interferon
TNF: tumor necrosis factor
IL: interleukin
TPMT: thiopurine methyltransferase
MAP: mitogen-activated protein
Treg: regulatory T cells
CT: computed tomography
Tc-HMPAO: 99technetium-labeled hexamethylpropyleneamine oxime
MDP: muramyl dipeptide MHC: major histocompatibility complex MP: mercaptopurine
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Introduction Inflammatory bowel disease (IBD) comprises two idiopathic chronic relapsing and remitting inflammatory disorders of the gastrointestinal tract: ulcerative colitis and Crohn’s disease. Ulcerative colitis affects only the colon and rectum, while Crohn’s disease may involve any part of the digestive tract from mouth to anus. Over recent decades, the incidence of IBD, particularly Crohn’s disease, has been steadily increasing; it now affects almost 1 in 250 people in Europe and the USA. Onset is most common in early adulthood, and the chronic waxing and waning nature of ulcerative colitis and Crohn’s disease means that together they represent a substantial burden of sickness, not only in hospitals, but also in the community. Because of the wide-ranging effects of IBD, multidisciplinary care of affected patients, both within and outside hospital, is essential. This third edition of Fast Facts: Inflammatory Bowel Disease encompasses recent developments relating to the cause, investigation and management of IBD. We have aimed the book at non-specialist doctors (particularly primary care providers and hospital doctors in training), nurses, stoma therapists, dieticians, psychologists, counselors, social workers and other professionals involved in the care of patients with IBD. Medical students should also find it helpful. We hope too that patients with IBD may benefit from reading this overview of their chronic illness.
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1
Etiopathogenesis
The cause of IBD remains unknown, but increasing evidence suggests that these conditions, like many other chronic inflammatory disorders, involve immune-mediated tissue damage due to a variable interaction amongst genetic susceptibility factors and environmental triggers or modifiers (Figure 1.1). Different mechanisms may account for subsets of disease. For example, various genetic polymorphisms of proteins which sense, or otherwise interact with, the microbial environment in the gut have been shown to predispose to Crohn’s disease. This seems to be consistent with the proposal that the disease results, at least in some individuals, from an inappropriate immunologic response to the normal commensal microbiota. However, molecular analysis of the gut microbiota has raised the possibility that a subset of patients with Crohn’s disease or ulcerative colitis have an abnormal or altered microbial composition in the gut.
Genetic predisposition
Environmental factors
Immunologic dysfunction
Chronic inflammation
Ulcerative colitis
Crohn’s disease
Figure 1.1 Overview of the etiopathogenesis of IBD. © 2008 Health Press Ltd www.fastfacts.com
7
Fast Facts: Inflammatory bowel disease
While it remains possible that a specific IBD-causing pathogen is waiting to be discovered, work from several research groups has linked Crohn’s disease with a virulent form of enteroadherent Escherichia coli. Furthermore, there is intriguing evidence linking defective innate immunity with an altered microbiota. Finally, the complexity of host–microbe interactions in the gut is shown by the finding that some microbial products are protective against pathogenic inflammation whereas others represent an essential ingredient for the pathogenesis of intestinal inflammation in animal models.
Epidemiology Incidence and prevalence figures for ulcerative colitis and Crohn’s disease are shown in Table 1.1. Both diseases are more common in the Western world than in Africa, Asia or South America. However, the incidence of IBD seems to increase in developing countries as they become more westernized. A consistent pattern has been the appearance of ulcerative colitis first, followed by the emergence of Crohn’s disease. Studies of migrant populations from low- to high-prevalence areas confirm the influence of environmental and lifestyle factors, and suggest that their impact is greatest at the earliest stages of life, perhaps while the immune system is still developing. This phenomenon may be due to a variety of factors which may alter the commensal microbiota or influence immune development: these include enhanced sanitation, exposure to antibiotics, vaccination and altered age at exposure to enteric infections. In the West, the incidence of Crohn’s disease in particular has risen over the last 40 years, though it may now have leveled off in some countries. TABLE 1.1
Incidence and prevalence of IBD in the Western world Incidence (new cases/100 000 population/year)
Prevalence (cases/100 000 population)
Ulcerative colitis
10
150
Crohn’s disease
7
100
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3
Diagnosis
The differential diagnosis of common presentations of IBD is shown in Tables 3.1–3.4. In younger patients (under 50 years) the main differential diagnoses, depending on presentation, include infection and irritable bowel syndrome. In older people (over 50 years), neoplasia, diverticular disease and ischemia require special consideration. TABLE 3.1
Causes of bloody diarrhea Cause
Disease
Inflammatory
Ulcerative colitis Crohn’s colitis Behçet’s colitis
Infective colitis
Campylobacter Salmonella Shigella Clostridium difficile Yersinia Tuberculosis Enterohemorrhagic Escherichia coli (VTEC/0157:H7) Amebiasis Schistosomiasis Cytomegalovirus* Herpes simplex*
Neoplastic
Colorectal cancer
Vascular
Ischemia
Iatrogenic
NSAIDs Antibiotics Irradiation
*Particularly in immunocompromised patients. NSAIDs, non-steroidal anti-inflammatory drugs. 39 © 2008 Health Press Ltd www.fastfacts.com
Fast Facts: Inflammatory bowel disease
TABLE 3.2
Causes of rectal bleeding Cause
Disease
Inflammatory
Proctitis Crohn’s disease
Sexually transmitted
Gonococcus Cytomegalovirus Herpes simplex Atypical mycobacterium Chlamydia Kaposi’s sarcoma
Neoplasia
Colorectal polyps Colorectal cancer Anal cancer
Vascular
Ischemia Angiodysplasia
Iatrogenic
NSAIDs (oral or suppositories) Irradiation
Other
Benign solitary rectal ulcer Diverticulosis (acute bleeds only) Severe upper gastrointestinal bleeding
NSAIDs, non-steroidal anti-inflammatory drugs.
The aims of investigation (Tables 3.5 and 3.6) are to establish the diagnosis, its site, extent and activity, and to check for complications of the disease and its treatment.
Blood tests
40
Hematology. In patients presenting with abdominal pain and/or diarrhea, test results revealing anemia, raised platelet count and raised erythrocyte sedimentation rate (ESR) may suggest active IBD, but they are not diagnostic. Those with extensive chronic terminal ileal Crohn’s disease may have low serum B12, while a low red-cell folate may indicate active chronic inflammation, reduced intake or malabsorption. Iron deficiency is common, although again it is not diagnostic of IBD. © 2008 Health Press Ltd www.fastfacts.com
