Front Cover

Handbook of Systemic Autoimmune Diseases, Volume 13: The Digestive Involvement in Systemic Autoimmune Diseases

Handbook of Systemic Autoimmune Diseases

Handbook of Systemic Autoimmune Diseases, Volume 13: The Digestive Involvementin Systemic AutoimmuneDiseases

Copyright

Dedication

Contents

List of Contributors

Preface

I Introduction

1 - Digestive System and Autoimmunity

1. THE DIGESTIVE SYSTEM AND GUT-ASSOCIATED IMMUNITY

2. SELF-TOLERANCE AND AUTOIMMUNITY

3. TOLERANCE MECHANISMS FOR AUTOREACTIVE B CELLS IN THE BONE MARROW

4. TOLERANCE MECHANISMS FOR AUTOREACTIVE T CELLS IN THE THYMUS

5. CLONAL ANERGY AND TUNING

6. EXTRINSIC CONTROLS OF SELF-REACTIVE LYMPHOCYTES

7. LIMITATION OF COSTIMULI

8. REGULATION OF SELF-REACTIVE LYMPHOCYTES IN FOLLICLES

9. TOLERANCE AT THE EFFECTOR PHASE

10. CONCLUSIONS

REFERENCES

2 - Immunopathogenesis of Autoimmune Liver Damage

1. INTRODUCTION

2. ANTIGENS AND ANTIGEN RESPONSES

2.1 Target Antigen(s)

2.2 Molecular Mimicry

2.3 Promiscuous Lymphocyte Targeting

3. MOLECULAR MECHANISMS OF LIVER CELL INJURY

3.1 Chemokines and Cell Trafficking

3.2 Pro- and Antiinflammatory Cytokines

3.3 Apoptotic Activity

3.4 Hepatocyte Necrosis

3.5 Oxidative Stress

3.6 Nitrosative Stress

4. CELLULAR MEDIATORS OF LIVER CELL INJURY

4.1 Innate and Adaptive Immune Responses

4.2 Natural Killer T Cells

4.3 Gamma Delta Lymphocytes

4.4 Regulatory T Cells

5. GENETIC PREDISPOSITIONS

5.1 Associations Within the Major Histocompatibility Complex

5.2 Associations Outside the Major Histocompatibility Complex

REFERENCES

3 - Autoantibodies in Gastrointestinal Autoimmune Diseases

1. ANTIBODIES IN INFLAMMATORY BOWEL DISEASES

1.1 The Antibodies

1.2 Genetics

1.3 Pathogenic Role

1.4 Sensitivity and Specificity of Anti–Saccharomyces cerevisiae Antibodies

1.5 Clinical Practice

2. ANTIBODIES IN CELIAC DISEASE

2.1 The Antibodies

2.2 Pathogenic Role

2.3 Genetics

2.4 Sensitivity and Specificity

2.5 Clinical Practice

3. ANTIBODIES IN AUTOIMMUNE LIVER DISEASES

3.1 The Antibodies

3.1.1 Antinuclear Antibodies

3.1.2 Smooth Muscle Antibodies

3.1.3 Antibodies to Liver–Kidney Microsome

3.1.4 Antimitochondrial Antibodies

3.1.5 Atypical Perinuclear Antineutrophil Cytoplasmic Antibodies

3.1.6 Antibodies to Liver Cytosol Type 1

3.1.7 Antibodies to Soluble Liver Antigen/Liver Pancreas Antigen

3.1.8 Antibodies to Asialoglycoprotein Receptor

3.1.9 Antibodies to Nuclear Pore Complex Antigens

3.2 Genetics

3.3 Pathogenic Role

4. CLINICAL PRACTICE

REFERENCES

4 - Imaging Techniques in Digestive Diseases

1. INTRODUCTION

2. IMAGING MODALITIES

2.1 Plain Abdominal Film and Barium Studies

2.2 Ultrasound or Ultrasonography

2.3 Computed Tomography

2.4 Magnetic Resonance

2.4.1 Magnetic Resonance Technique

2.4.2 Contrast Agents

2.4.3 Indications and Limitations

2.5 Positron Emission Tomography

3. FUTURE PROSPECTS

REFERENCES

II - Autoimmune Liver Diseases

5 - Primary Biliary Cholangitisa

1. INTRODUCTION

2. EPIDEMIOLOGICAL HIGHLIGHTS

3. PATHOPHYSIOLOGICAL INSIGHTS

4. CLINICAL PRESENTATIONS

5. NATURAL HISTORY AND PROGNOSTIC CONSIDERATIONS

6. TREATMENT CONSIDERATIONS

7. CONCLUSION

8. FIVE-YEAR UPDATE

8.1 Changing Nomenclature

8.2 Autoantibodies

8.3 Bile Acid–Based New Therapies

8.4 Biological Therapies

8.5 Antifibrotic Agents

8.6 Targeting Multiple Etiopathogenic Pathways

REFERENCES

6 - Autoimmune Hepatitis

1. INTRODUCTION

2. HISTORY AND EPIDEMIOLOGY

3. CLINICAL FEATURES [7]

4. DIAGNOSIS AND LABORATORY FINDINGS

5. PATHOPHYSIOLOGY

5.1 Genetics

5.2 Immune Mechanisms [20]

5.2.1 Regulatory T Cells [21]

5.2.2 Autoreactive T Cells

6. MANAGEMENT AND PROGNOSIS

7. AUTOIMMUNE HEPATITIS AND LIVER TRANSPLANT

7.1 Recurrence of Autoimmune Hepatitis After Transplant

7.2 De Novo Autoimmune Hepatitis After Transplant

8. CONCLUSION

REFERENCES

7 - Primary Sclerosing Cholangitis

1. INTRODUCTION

2. EPIDEMIOLOGY

3. ETIOPATHOGENESIS

3.1 Genetic Factors

3.2 Other Proposed Mechanisms

4. CLINICAL FEATURES

4.1 Symptoms and Signs

4.2 Serology

5. DIAGNOSIS

5.1 Laboratory Investigations

5.2 Radiological Features

5.3 Liver Histology

6. SPECIAL PATIENT POPULATIONS

6.1 Secondary Sclerosing Cholangitis

6.2 Small Duct Primary Sclerosing Cholangitis

6.3 Autoimmune Hepatitis Overlap

6.4 IgG4-Related Sclerosing Cholangitis

6.5 High Serum IgG4 Levels in Primary Sclerosing Cholangitis

7. INFLAMMATORY BOWEL DISEASE IN PRIMARY SCLEROSING CHOLANGITIS

8. PRIMARY SCLEROSING CHOLANGITIS AND MALIGNANCY

8.1 Colorectal Cancer

8.2 Cholangiocarcinoma

8.3 Gallbladder, Pancreatic Cancer, and Hepatoma

9. NONMALIGNANT COMPLICATIONS

9.1 Dominant Strictures

9.2 Metabolic Bone Disease

10. NATURAL HISTORY OF DISEASE

10.1 Prognosis

10.2 Prognostic Models

11. TREATMENT

11.1 Treatment of Complications

11.2 Specific Medical Treatment

11.3 Liver Transplantation

12. CONCLUSION

REFERENCES

III Autoimmune Manifestations of Viral Hepatitis

8 - Systemic and Autoimmune Manifestations of Hepatitis B Virus Infection

1. INTRODUCTION

2. HEPATITIS B VIRUS INFECTION

2.1 Main Viral Characteristics

2.2 Hepatitis B Virus Infection and Diagnosis

3. EXTRAHEPATIC MANIFESTATIONS OF HEPATITIS B VIRUS INFECTION

3.1 Prodromal Preicteric Syndrome

3.2 Hepatitis B Virus–Associated Vasculitis

3.2.1 Epidemiology

3.2.2 Pathogenesis

3.2.3 Histology

3.2.4 Clinical Manifestations and Diagnosis

3.2.5 Treatment

3.2.6 Outcome

3.3 Hepatitis B Virus–Related Glomerulonephritis

3.4 Gianotti–Crosti Syndrome

3.5 Porphyria Cutanea Tarda

3.6 Diabetes Mellitus

3.7 Metabolic Syndrome

3.8 Thyroid Manifestations

3.9 Autoimmune Manifestations

3.9.1 Antiphospholipid Syndrome

3.9.2 Other Autoantibodies

3.10 Miscellaneous

KEY POINTS

REFERENCES

9 - Extrahepatic Manifestations in Patients With Chronic Hepatitis C Virus Infection

1. INTRODUCTION

2. AUTOANTIBODIES AND HEPATITIS C VIRUS

3. ORGAN-SPECIFIC AUTOIMMUNE DISEASES AND HEPATITIS C VIRUS

3.1 Thyroiditis

3.2 Diabetes Mellitus and Steatosis

4. SYSTEMIC AUTOIMMUNE DISEASES AND HEPATITIS C VIRUS

4.1 Sjögren Syndrome

4.2 Rheumatoid Arthritis

4.3 Systemic Lupus Erythematosus

4.4 Antiphospholipid Syndrome

4.5 Cryoglobulinemic Vasculitis

4.6 Sarcoidosis

4.6.1 Sarcoidosis Triggered by Antiviral Therapy

4.6.2 Sarcoidosis in Treatment-Naïve Patients

4.7 Noncryoglobulinemic Systemic Vasculitis

4.8 Inflammatory Myopathies

4.9 Other Systemic Autoimmune Diseases

5. HEMATOLOGICAL DISEASES AND HEPATITIS C VIRUS

5.1 Autoimmune Cytopenias

5.2 Lymphoproliferative Diseases

REFERENCES

10 - New Antivirals for Extrahepatic Manifestations of Hepatitis C Virus: The Model of Mixed Cryoglobulinemia Vascu ...

1. INTRODUCTION

2. TREATMENT OF HEPATITIS C VIRUS–MIXED CRYOGLOBULINEMIA VASCULITIS

2.1 Antiviral Agents

2.2 Other Nonvirological Treatments

2.3 Therapeutic Guidelines

REFERENCES

IV - Gastrointestinal Involvement of Systemic Diseases

11 - Systemic Lupus Erythematosus

1. INTRODUCTION

2. OVERVIEW OF GASTROINTESTINAL MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

3. ORAL CAVITY, ESOPHAGUS, AND GASTROINTESTINAL ABNORMALITIES

4. MAIN IDENTIFIABLE LUPUS-RELATED GASTROINTESTINAL SYNDROMES

4.1 Lupus Mesenteric Vasculitis

4.2 Intestinal Pseudoobstruction

4.3 Protein-Losing Enteropathy

5. LUPUS-ASSOCIATED PANCREATITIS

6. OTHER SYSTEMIC LUPUS ERYTHEMATOSUS–RELATED GASTROINTESTINAL PROBLEMS

REFERENCES

12 - Digestive Involvement in the Antiphospholipid Syndrome

1. INTRODUCTION

2. GASTROINTESTINAL INVOLVEMENT

2.1 Ischemic Gastrointestinal Involvement

2.1.1 Esophageal Involvement

2.1.2 Gastric Involvement

2.1.3 Intestinal Involvement

2.1.3.1 Venous Mesenteric Bowel Disease

2.1.3.2 Acute Ischemic Bowel Disease

2.1.3.3 Chronic Mesenteric Arterial Ischemia

2.1.3.4 Colon Ischemic Disease

2.2 Inflammatory Bowel Disease and Antiphospholipid Syndrome

3. HEPATIC INVOLVEMENT

3.1 Vascular Liver Disease

3.1.1 Budd–Chiari Syndrome

3.1.2 Sinusoidal Obstruction Syndrome

3.1.3 Hepatic Thrombosis and Infarction

3.2 Autoimmune Liver Disease

3.2.1 Nodular Regenerative Hyperplasia of the Liver

3.2.2 Autoimmune Hepatitis

3.2.3 Primary Biliary Cholangitis

3.2.4 Primary Sclerosing Cholangitis

3.3 Liver Cirrhosis

3.4 Liver Transplant

4. SPLENIC INVOLVEMENT

4.1 Splenic Ischemic Disease

4.2 Autosplenectomy or Functional Asplenia

5. PANCREATIC INVOLVEMENT

REFERENCES

13 - Gastrointestinal Involvement in Systemic Sclerosis

1. INTRODUCTION

2. PATHOGENESIS OF GASTROINTESTINAL TRACT DYSMOTILITY

3. ESOPHAGUS

3.1 Esophageal Dysmotility

3.2 Gastroesophageal Reflux Disease

3.3 Barrett Esophagus

4. STOMACH

4.1 Gastroparesis

4.2 Gastric Antral Vascular Ectasia

5. SMALL INTESTINE

5.1 Intestinal Pseudoobstruction

5.2 Small Intestinal Bacterial Overgrowth

5.3 Pneumatosis Cystoides Intestinalis

5.4 Malnutrition

6. COLON AND ANORECTAL DISORDERS

6.1 Colon Involvement

6.2 Anorectal Dysfunction

7. PATIENT-REPORTED OUTCOME MEASURES

8. CONCLUSION

REFERENCES

14 - Gastrointestinal Involvement in Inflammatory Myositis

1. INTRODUCTION

2. DYSPHAGIA

3. GASTRIC INVOLVEMENT

4. GASTROINTESTINAL VASCULITIS AND INFLAMMATION

5. PNEUMATOSIS CYSTOIDES INTESTINALIS

6. OVERLAP WITH INFLAMMATORY BOWEL DISEASE

7. OVERLAP WITH COELIAC DISEASE

8. ASSOCIATION WITH CHRONIC VIRAL INFECTIONS

9. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

10. THERAPEUTIC MANAGEMENT

REFERENCES

15 - Digestive Involvement in Primary Sjögren's Syndrome

1. INTRODUCTION

2. ESOPHAGEAL INVOLVEMENT

2.1 Dysphagia

2.2 Gastroesophageal Reflux

3. GASTRIC INVOLVEMENT

3.1 Chronic Gastritis

3.2 Helicobacter pylori Infection

3.2.1 Prevalence and Clinical Significance

3.2.2 Association With Gastric Lymphoma

4. INTESTINAL INVOLVEMENT

4.1 Association With Celiac Disease

4.2 Gastrointestinal Vasculitis

4.3 Protein-Losing Gastroenteropathy

5. PANCREATIC INVOLVEMENT

6. LIVER INVOLVEMENT

6.1 Chronic Hepatitis C Virus Infection

6.2 Chronic Hepatitis B Virus

6.3 Primary Biliary Cholangitis

6.3.1 Prevalence of Antimitochondrial Antibodies in Primary Sjögren's syndrome

6.3.2 Prevalence of SS in Patients With Primary Biliary Cirrhosis

6.4 Autoimmune Hepatitis

6.4.1 Type-1 Autoimmune Hepatitis

6.4.2 Type-2 Autoimmune Hepatitis

6.5 Other Autoimmune Liver Diseases

6.5.1 Sclerosing Cholangitis

6.6 Evaluation of Altered Liver Profile in Patients With Sjögren's Syndrome

REFERENCES

16 - Gastrointestinal Involvement in Systemic Vasculitis

1. INTRODUCTION

2. LARGE-VESSEL VASCULITIS

2.1 Takayasu Arteritis

2.2 Giant Cell Arteritis

2.3 Chronic Periaortitis

3. MEDIUM-SIZED VESSEL VASCULITIS

3.1 Polyarteritis Nodosa

3.2 Kawasaki's Disease

4. SMALL-SIZED VESSELS VASCULITIS

4.1 Henoch–Schönlein Purpura and Leukocytoclastic Vasculitis

4.2 ANCA-Associated Small-Vessel Vasculitis

4.3 Mixed Cryoglobulinemia, Hepatitis C Virus Infection, and Gastrointestinal Involvement

REFERENCES

17 - Mixed Connective Tissue Disease

1. INTRODUCTION

2. ARE GASTROINTESTINAL FEATURES A COMMON MANIFESTATION OF MIXED CONNECTIVE TISSUE DISEASE?

3. ORAL MANIFESTATIONS

4. ESOPHAGEAL DYSFUNCTION

5. BOWEL MANIFESTATIONS

6. OTHER CONDITIONS

7. THERAPEUTIC CONSIDERATIONS

8. CONCLUSION

REFERENCES

18 - Gastrointestinal Manifestations of Rheumatoid Arthritis

1. INTRODUCTION

2. MANIFESTATIONS DIRECTLY DUE TO RHEUMATOID ARTHRITIS

3. GASTROINTESTINAL DISEASE RESULTING FROM RHEUMATOID ARTHRITIS THERAPEUTICS

4. MIMICS OF GASTROINTESTINAL DISEASE IN RHEUMATOID ARTHRITIS

5. CONCLUSION

REFERENCES

19 - Spondyloarthritis and Gastrointestinal Involvement

1. INTRODUCTION

2. PREVALENCE AND EPIDEMIOLOGY

3. ETIOLOGY/PATHOGENESIS

4. CLINICAL MANIFESTATIONS

5. DIAGNOSTIC INVESTIGATIONS

5.1 Radiological

5.2 Functional Tests

5.3 Biochemistry/Serology/Immunology

6. DIFFERENTIAL DIAGNOSIS

7. TREATMENT

REFERENCES

20 - Intestinal Behçet's Disease

1. INTRODUCTION

2. EPIDEMIOLOGY

3. CLINICAL FEATURES

4. DIFFERENTIAL DIAGNOSIS

5. PATHOGENESIS

6. DIAGNOSIS

6.1 Skin Pathergy Reaction

6.2 Inflammatory Markers

6.3 Imaging

6.4 Histopathology

7. ASSESSMENT OF SEVERITY

8. MANAGEMENT

8.1 Corticosteroids

8.2 Azathioprine

8.3 Anti-Tumor Necrosis Factor

8.4 Thalidomide

8.5 Surgical Treatment

9. PROGNOSIS

REFERENCES

21 - Gastrointestinal Involvement of Sarcoidosis

1. INTRODUCTION

2. SARCOIDOSIS OF UPPER GASTROINTESTINAL TRACT

3. SARCOIDOSIS OF LOWER GASTROINTESTINAL TRACT

4. HEPATIC AND SPLENIC SARCOIDOSIS

4.1 Histopathology and Pathogenesis

4.2 Clinical Features

4.3 Diagnosis

4.4 Differential Diagnosis

4.5 Treatment

4.5.1 First-Line Treatment

4.5.2 Second-Line Treatments

4.5.3 Management of Refractory Cases

4.5.4 Management of Pruritus

5. CONCLUSION

REFERENCES

22 - IgG4-Related Disease: Gastrointestinal Involvement

1. INTRODUCTION

2. CLINICAL SPECTRUM OF IGG4-GASTROINTESTINAL DISEASE

2.1 Sclerosing Sialadenitis

2.2 Esophageal Involvement

2.3 Gastric Involvement

2.4 Involvement of the Small Intestine

2.5 Involvement of the Large Intestine

2.6 Liver Involvement

2.7 Sclerosing Cholangitis

2.8 Cholecystitis

2.9 Autoimmune Pancreatitis

2.10 Intraabdominal Lymphadenopathy

3. DIAGNOSTIC APPROACH

3.1 Imaging Studies

3.2 Laboratory Abnormalities

3.3 Histopathological Studies

3.4 Diagnostic Criteria

4. THERAPEUTIC APPROACH

ACKNOWLEDGMENTS

REFERENCES

23 - Gastrointestinal Complications of Antirheumatic Drugs

1. INTRODUCTION

2. THE CLINICAL SETTING

2.1 Populations With Musculoskeletal Pain

2.2 Burdens of Analgesic and Antiinflammatory Medication Use

3. GASTROINTESTINAL REACTIONS IN AUTOIMMUNE ARTHROPATHIES

3.1 Multiple Origins of Gastrointestinal Reactions

3.2 Variation in Ulcerogenicity of NSAIDs

3.3 Mechanisms of Action of the NSAIDs

4. GASTROINTESTINAL REACTIONS IN AUTOIMMUNE ARTHROPATHIES

4.1 Multiple Origins of Gastrointestinal Reactions

4.2 Variation in Ulcerogenicity of NSAIDs

5. COXIBS VERSUS NONSELECTIVE NSAIDS

5.1 Pharmacological Rationale for Development of Coxibs

5.2 Potential for Impact of Arthritic Disease

5.3 Gastrointestinal Symptomatic Adverse Drug Reactions

5.4 Enter the Second-Generation Coxibs

6. STRATEGIES TO MINIMIZE OR ELIMINATE GASTROINTESTINAL COMPLICATIONS

6.1 Effects of NSAIDs and Helicobacter pylori on Acid Secretion

6.2 Acid Secretion and Gastrin Production in Rheumatic Patients

6.3 Why Give Antisecretory Agents to Rheumatic Patients?

6.4 Risk Factors

6.5 Agents Used to Control Acid

6.5.1 Antacids

6.5.2 H2-Receptor Antagonists

6.5.3 Misoprostol

6.5.4 Proton-Pump Inhibitors

6.5.5 Evaluation of Relative Benefits of Antisecretory Therapies

7. MODIFICATION OF ANALGESICS TO PREVENT GASTRIC COMPLICATIONS

8. CONCLUSION

REFERENCES

FURTHER READING

Index

A

B

C

D

E

F

G

H

I

J

K

L

M

N

O

P

R

S

T

U

V

W

X

Y

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