Cover
Title Page
Preface
Section I: Pathogenesis and Clinical Features
1. 1 Epidemiology and Pathogenesis
  1. Epidemiology
  2. Pathogenesis
  3. Case Studies and Multiple Choice Questions
  4. References
  5. Answers to Questions
2. 2 Clinical Features and Diagnosis of Crohn’s Disease
  1. Clinical Features
  2. Disease Course and Natural History
  3. Diagnosis
  4. Case Studies and Multiple Choice Questions
  5. References
  6. Answers to Questions
3. 3 Clinical Features and Diagnosis of Ulcerative Colitis
  1. Clinical Features
  2. Disease Course and Natural History
  3. Diagnosis
  4. Differential Diagnosis (UC and CD)
  5. Case Studies and Multiple Choice Questions
  6. References
  7. Answers to Questions
4. 4 Extraintestinal Manifestations of Inflammatory Bowel Diseases
  1. Arthritis and Arthropathy
  2. Metabolic Bone Disease
  3. Cutaneous Manifestations
  4. Hepatobiliary Manifestations
  5. Ophthalmologic Manifestations
  6. Renal Complications
  7. Thromboembolic and Cardiovascular Complications
  8. Case Studies and Multiple Choice Questions
  9. References
  10. Answers to Questions
Section II: Therapeutic Agents
1. 5 Aminosalicylates
  1. Efficacy in Ulcerative Colitis
  2. Efficacy in Crohn’s Disease
  3. Safety
  4. Multiple Choice Questions
  5. References
  6. Answers to Questions
2. 6 Corticosteroids
  1. Efficacy in Ulcerative Colitis
  2. Efficacy in Crohn’s Disease
  3. Safety
  4. Case Studies and Multiple Choice Questions
  5. References
  6. Answers to Questions
3. 7 Immunomodulators
  1. Thiopurines
  2. Methotrexate
  3. Calcineurin Inhibitors
  4. Case Studies and Multiple Choice Questions
  5. References
  6. Answers to Questions
4. 8 Biologic Therapies
  1. Infliximab
  2. Adalimumab
  3. Certolizumab Pegol
  4. Golimumab
  5. Natalizumab
  6. Vedolizumab
  7. Newer Therapies
  8. Case Studies and Multiple Choice Questions
  9. References
  10. Answers to Questions
5. 9 Antibiotics
  1. Efficacy in Ulcerative Colitis
  2. Efficacy in Crohn’s Disease
  3. Other Microbial Modification Methods – Probiotics and Fecal Microbiota Transplantation
  4. Multiple Choice Questions
  5. References
  6. Answers to Questions
Section III: Management
1. 10 Medical Management of Ulcerative Colitis
  1. Assessment of Extent, Activity, and Severity
  2. Limited Colitis – Proctitis, Proctosigmoiditis, and Left‐sided Colitis
  3. Pancolitis
  4. Case Studies and Multiple Choice Questions
  5. References
  6. Answers to Questions
2. 11 Medical Management of Crohn’s Disease
  1. Mild to Moderate Disease
  2. Moderate to Severe Disease
  3. Case Studies and Multiple Choice Questions
  4. References
  5. Answers to Questions
3. 12 Surgical Management of Inflammatory Bowel Diseases
  1. Surgery for Ulcerative Colitis
  2. Surgery for Crohn’s Disease
  3. Case Studies and Multiple Choice Questions
  4. References
  5. Recommended Reading
  6. Answers to Questions
4. 13 Complications of Inflammatory Bowel Diseases
  1. Complications of Ulcerative Colitis
  2. Complications of Crohn’s Disease
  3. Case Studies and Multiple Choice Questions
  4. References
  5. Answers to Questions
Section IV: Special Considerations
1. 14 Nutrition in Inflammatory Bowel Diseases
  1. Malnutrition and Micronutrient Deficiencies
  2. Dietary Therapies for Inflammatory Bowel Diseases
  3. Case Studies and Multiple Choice Questions
  4. References
  5. Answers to Questions
2. 15 Pregnancy, Conception, and Childbirth
  1. Fertility
  2. Effect of Pregnancy on Disease
  3. Effect of Disease on Pregnancy
  4. Maternal Medication Use During Pregnancy
  5. Paternal Medication Use
  6. Inheritance
  7. Case Studies and Multiple Choice Questions
  8. References
  9. Answers to Questions
3. 16 Inflammatory Bowel Disease During Childhood and Adolescence
  1. Epidemiology and Clinical Features
  2. Treatment of Pediatric Inflammatory Bowel Disease
  3. Very Early‐onset Inflammatory Bowel Disease
  4. Transition of Care in Pediatric Crohn’s Disease
  5. Case Studies and Multiple Choice Questions
  6. References
  7. Answers to Questions
Index
End User License Agreement

List of Tables

Chapter 01
1. Table 1.1 Effect of environmental risk factors on risk of development of Crohn’s disease or ulcerative colitis.
Chapter 02
1. Table 2.1 Clinical, endoscopic, and histologic findings differentiating Crohn’s disease from ulcerative colitis.
2. Table 2.2 The Montreal classification of disease location and behavior in Crohn’s disease.
3. Table 2.3 The Crohn’s disease activity index (CDAI): a CDAI <150 indicates remission, 150–220 indicates mild disease, 220–450 indicates moderate disease, and >450 indicates severe disease.
4. Table 2.4 Table for calculation of Crohn’s disease endoscopic index of severity (CDEIS).
5. Table 2.5 Rutgeerts classification of post‐operative recurrence in Crohn’s disease.
Chapter 03
1. Table 3.1 Montreal classification of extent and severity of ulcerative colitis.
2. Table 3.2 Truelove–Witts classification of severity of ulcerative colitis.
3. Table 3.3 Ulcerative colitis endoscopic index of severity.
4. Table 3.4 Histologic findings in ulcerative colitis and acute self‐limited colitides.
Chapter 04
1. Table 4.1 Major extraintestinal manifestations of inflammatory bowel diseases.
2. Table 4.2 Recommendations for screening and treatment of osteoporosis in patients with inflammatory bowel diseases.
Chapter 05
1. Table 5.1 Preparations of 5‐aminosalicylic acid derivatives in the United States.
Chapter 06
1. Table 6.1 Side effects of systemic corticosteroids.
Chapter 08
1. Table 8.1 Dose and route of administration of biologic agents in Crohn’s disease and ulcerative colitis.
Chapter 10
1. Table 10.1 Components of the Mayo clinical and endoscopic scoring system in ulcerative colitis.
2. Table 10.2 Stepwise management of acute severe colitis.
Chapter 12
1. Table 12.1 Classification of ileal pouch disorders and associated complications.
Chapter 13
1. Table 13.1 Risk factors for colorectal neoplasia in patients with inflammatory bowel disease.
Chapter 14
1. Table 14.1 Common micronutrient deficiency in inflammatory bowel diseases: causes and treatment.
Chapter 15
1. Table 15.1 Medication categories and safety during pregnancy and breastfeeding.
Chapter 16
1. Table 16.1 Barriers to successful transition of care of adolescents with inflammatory bowel disease.

List of Illustrations

Chapter 01
1. Figure 1.1 Geographic variation in incidence of Crohn’s disease and ulcerative colitis.
2. Figure 1.2 Inflammatory bowel disease develops as a result of a complex interplay between genetics, the microbiome, immunologic dysregulation, and the external environment.
Chapter 02
1. Figure 2.1 Clinical image of perianal Crohn’s disease demonstrating multiple perineal fistulae.
2. Figure 2.2 Natural history of Crohn’s disease is characterized by progression with an increasing proportion of penetrating and stricturing complications.
3. Figure 2.3 Endoscopic appearance of colonic Crohn’s disease with wide ulcerations, edema, and intervening areas of normal mucosa.
4. Figure 2.4 Histologic appearance of the small bowel in Crohn’s disease demonstrating a single discrete non‐necrotizing granuloma.
5. Figure 2.5 Active terminal ileal Crohn’s disease on CTE demonstrating wall thickening, mucosal hyperenhancement, and mesenteric inflammation.
Chapter 03
1. Figure 3.1 Mayo endoscopic score for assessment of disease activity in ulcerative colitis.
2. Figure 3.2 Biopsy from an individual with ulcerative colitis. Colonic mucosa with histologic evidence of chronic colitis. Note the marked crypt architectural distortion including crypt branching. An increased number of lymphocytes and plasma cells are present throughout the lamina propria.
3. Figure 3.3 Approach to new diagnosis of ulcerative colitis.
Chapter 04
1. Figure 4.1 Plain radiograph of right sacroiliac joint in a patient with ulcerative colitis and sacroileitis.
2. Figure 4.2 Image of a patient with erythema nodosum.
3. Figure 4.3 Pyoderma gangrenosum in a patient with inflammatory bowel disease.
4. Figure 4.4 Endoscopic retrograde cholangiographic image of a patient with PSC demonstrating beading and dilation of the intrahepatic ducts.
5. Figure 4.5 Uveitis in a patient with inflammatory bowel disease.
Chapter 05
1. Figure 5.1 Dose response to delayed release oral mesalamine (4.8 g per day compared with 2.4 g per day) in mild to ‐moderate ulcerative colitis.
Chapter 06
1. Figure 6.1 One‐year outcomes after initiation of systemic corticosteroid therapy in Crohn’s disease and ulcerative colitis. CS, corticosteroid.
Chapter 07
1. Figure 7.1 Metabolism of thiopurines.
2. Figure 7.2 Algorithm for management of loss of response to thiopurines.
Chapter 08
1. Figure 8.1 Efficacy of infliximab maintenance in ulcerative colitis: proportion of patients with a sustained clinical response (a) and in sustained clinical remission (b) in ACT 1 and ACT 2.
2. Figure 8.2 Efficacy of infliximab in Crohn’s disease: clinical response and clinical remission for week‐2 responders in the ACCENT I randomized trial. Groups I, II, and III indicate patients randomized to placebo, 5 mg kg^–1, and 10 mg kg^–1 maintenance regimens, respectively.
3. Figure 8.3 Algorithm for management of loss of response to infliximab. CRP, C‐reactive protein; NSAIDs, non‐steroidal anti‐inflammatory drugs; IFX, infliximab; ATI, antibodies to inlfiximab; anti‐TNF, monoclonal antibodies to TNF‐α; IMM, immunomodulator.
4. Figure 8.4 Comparative effectiveness of infliximab, azathioprine, and combination therapy: corticosteroid‐free clinical remission (a) and mucosal healing (b) at week 26 in the SONIC trial.
5. Figure 8.5 Efficacy of adalimumab maintenance therapy in Crohn’s disease. Clinical remission at weeks 26 and 56 (a) and clinical remission over time (b) in randomized responder population (week 4 responders) in the CHARM trial.
6. Figure 8.6 Efficacy of vedolizumab in ulcerative colitis: the GEMINI trial demonstrating improvement in partial Mayo score with placebo and vedolizumab every 4 weeks and every 8 weeks in patients with ulcerative colitis.
Chapter 10
1. Figure 10.1 Algorithm for management of limited distal ulcerative colitis. 5‐ASA, 5‐aminosalicylates.
2. Figure 10.2 Algorithm for management of mild‐to‐moderate pancolitis. 5‐ASA, 5‐aminosalicylates; anti‐TNF, monoclonal antibodies to tumor necrosis factor alpha; VDZ, vedolizumab.
3. Figure 10.3 Algorithm for management of moderate to severe UC. Anti‐TNF, monoclonal antibodies to tumor necrosis factor alpha; VDZ, vedolizumab; IMM, immunomodulators.
Chapter 11
1. Figure 11.1 Algorithm for management of mild‐to‐moderate CD. Anti‐TNF, monoclonal antibodies to tumor necrosis factor alpha; VDZ, vedolizumab; NAT, natalizumab; IMM, immunomodulator.
2. Figure 11.2 Algorithm for management of moderate‐to severe CD. Anti‐TNF, monoclonal antibodies to tumor necrosis factor alpha; IMM, immunomodulator.
Chapter 12
1. Figure 12.1 Three‐stage surgery for surgery for ulcerative colitis – total proctocolectomy with an ileal pouch–anal anastomosis (IPAA).
2. Figure 12.2 Algorithm for management of pouchitis. Anti‐TNF, monoclonal antibodies to tumor necrosis factor alpha; 5‐ASA, 5‐aminosalicylates.
3. Figure 12.3 Algorithm for postoperative prophylaxis to prevent recurrence in Crohn’s disease. Anti‐TNF, monoclonal antibodies to tumor necrosis factor alpha; 5‐ASA, 5‐aminosalicylates; i0–i4, Rutgeerts postoperative classification.
Chapter 13
1. Figure 13.1 Computed tomography images of toxic megacolon in a patient with severe ulcerative colitis.
2. Figure 13.2 Magnetic resonance enterography image of terminal ileal stricture and high‐grade small‐bowel obstruction in a patient with Crohn’s disease.
3. Figure 13.3 Algorithm for management of intra‐abdominal abscess. Anti‐TNF, monoclonal antibodies to tumor necrosis factor alpha; IMM, immunomodulator.
4. Figure 13.4 Types of perianal fistulae in Crohn’s disease.
5. Figure 13.5 An axial T2 fat‐suppressed image showing a trans‐sphincteric fistula with a horseshoe abscess and also an additional abscess extending posteriorly into the left ischioanal fossa.

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Library of Congress Cataloging‐in‐Publication Data

Names: Ananthakrishnan, Ashwin N., author. | Xavier, Ramnik J., author. | Podolsky, Daniel Kalman, author.
Title: Inflammatory bowel diseases : a clinician’s guide / Ashwin N. Ananthakrishnan, Ramnik J. Xavier, Daniel K. Podolsky.
Description: Chichester, West Sussex, UK ; Hoboken, NJ : John Wiley & Sons, Inc., 2017. | Includes bibliographical references and index.
Identifiers: LCCN 2017001705 (print) | LCCN 2017002995 (ebook) | ISBN 9781119077602 (cloth) | ISBN 9781119077619 (pdf) | ISBN 9781119077626 (epub)
Subjects: | MESH: Inflammatory Bowel Diseases
Classification: LCC RC862.I53 (print) | LCC RC862.I53 (ebook) | NLM WI 420 | DDC 616.3/44–dc23
LC record available at https://lccn.loc.gov/2017001705

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover images: The image fifth from the left (inset) is reproduced with permission of Vikram Deshpande MD. (See the caption for figure 2.4 for more details.) All other images are courtesy of the authors.

Preface

Inflammatory bowel diseases (IBDs), comprising Crohn’s disease (CD) and ulcerative colitis (UC), are complex diseases that often have their onset during young adulthood. They have a protracted course characterized by periods of remission and relapse, and frequently result in hospitalization, surgery, and continued morbidity. Importantly, they also exert a significant impact on the individuals’ health‐related quality of life and work productivity. Physicians caring for patients with IBD encounter varied and often complex challenges. The importance of optimal decision‐making for the welfare of the patient cannot be overstated.

This book was developed to serve as a resource for practicing physicians, allied healthcare providers, and trainees who care for patients with Crohn’s disease and ulcerative colitis. Although exhaustive textbooks are available, this new handbook aims to provide a concise understanding of these disorders and practical guidance on approaches to diagnosis and treatment. Care of patients with IBD is integral to the practice of gastroenterology and frequently also encountered by internists, surgeons, pediatricians, and other physicians, in addition to nurses and other caregivers.

The past two decades have witnessed a significant revolution both in our understanding of the pathogenesis behind these complex diseases and in the availability of therapeutic options that have enhanced the ability to achieve clinical and endoscopic remission. Facilitated by advances in sequencing tools and analytic methods, we now recognize that these diseases arise as a result of a dysregulated immune response to intestinal microflora in a genetically susceptible individual. Over 150 genes have been identified that contribute to the pathogenesis of these disease, influencing innate and adaptive immune responses and integrity of the intestinal barrier. The intestinal microflora demonstrate a dysbiotic pattern with reduced diversity and altered abundance of pro‐ and anti‐inflammatory bacterial species. Therapeutic paradigms have evolved with our understanding of the benefit of effective treatment early in the course of disease and the role of combination therapy to reduce immunogenicity and increase the likelihood of sustained response. Whereas therapy for IBD was initially restricted to broad, non‐selective immunosuppressive therapy, emerging treatments increasingly target specific inflammatory pathways such as tumor necrosis factor α, adhesion molecules, and the IL‐23 pathway. Yet this scientific and therapeutic revolution has made the management of these diseases more complex than ever before.

Part I describes the epidemiology and pathogenesis of IBD, including the role of genetics, the environment, and the gut microbiome. We discuss the clinical features and procedures that aid in establishing a diagnosis of Crohn’s disease and ulcerative colitis. We also discuss the various manifestations of IBD that occur outside the intestine and are a source of morbidity to a significant fraction of patients. We discuss the evolution of these diseases towards more complicated behavior and identify relevant risk factors.

Part II discusses each of the classes of therapeutic agents used for the management of IBD, and systematically examines the efficacy of each class in the treatment of patients with ulcerative colitis or Crohn’s disease. We also discuss the safety of each category and review newer therapeutic modalities such as those aimed at the microbiome.

Part III presents practical algorithms for the medical and surgical management of ulcerative colitis and Crohn’s disease, stratifying by severity and extent of involvement. We also review the disease‐specific complications for each IBD subtype and the management of these complications.

Part IV reviews some special clinical considerations in the management of these diseases, including the role of nutrition and dietary therapies, and two commonly encountered clinical scenarios – the management of IBD during pregnancy and in children – ending with a discussion of transition of care.

Throughout this book, learning is facilitated by practical take‐home points in each chapter and patient‐centered questions reviewing the material covered in each chapter. Overall, we hope that this guide will enable clinicians to provide the best help to their patients with IBD through the many challenges that they may face.

Inflammatory Bowel Diseases

A Clinician’s Guide

Preface

Section I
Pathogenesis and Clinical Features