1. Eosinophilic Esophagitis (EoE), an Evolving Disease 12
1.1. Evolving in the sense of "new onset" 12
1.2. Evolving in the sense of "global dissemination" 12
1.3. Evolving in the sense of "presence in the medical and scientific community" 12
1.4. Evolving in the sense of "exploration of a new disease" 13
1.5. References cited in text and further specialist articles 13
2. Epidemiology of Eosinophilic Esophagitis 15
2.1. Prevalence of esophageal eosinophilia 15
2.2. Incidence and prevalence of EoE 15
2.3. Incidence and prevalence of EoE in geographically confined regions 16
2.4. Demographic profile of EoE patients 17
2.4.1. Age, gender and social parameters 17
2.4.2. Symptoms of esophageal dysfunction 18
2.4.3. Allergic predisposition 18
2.4.4. EoE and celiac disease 19
2.5. EoE and seasonal distribution 19
2.6. References cited in text and further specialist articles 20
3. Clinical Presentation of Eosinophilic Esophagitis in Children 24
3.1. Clinical features 24
3.2. Investigations 25
3.3. Endoscopy 25
3.4. Treatment 26
3.5. Quality of Life and transition to adulthood 28
3.6. References cited in text and further specialist articles 28
4. Clinical Presentation of Eosinophilic Esophagitis in Adults 32
4.1. Clinical symptoms in EoE 32
4.2. Atopic diseases in EoE patients 33
4.3. Upper endoscopy and biopsies 34
4.4. References cited in text and further specialist articles 35
5. Interplay between Eosinophilic Esophagitis and Gastroesophageal Reflux
Disease 37
5.1. Characteristics of EoE 38
5.2. Characteristics of GERD 38
5.3. PPI responsive EoE 38
5.4. Interplay between GERD and EoE 39
5.5. The role of esophageal epithelial barrier 39
5.6. Can GERD trigger a TH2 immune response similar to that seen in EoE? 40
5.7. Anti-inflammatory effects of PPI therapy 40
5.8. References cited in text and further specialist articles 40
6. Pathology of Eosinophilic Esophagitis 42
6.1. Diagnosis 42
6.2. Focal appearance 42
6.3. Histology 42
6.4. Immunoglobulin G4 (IgG4) 47
6.5. Histology scoring system and activity of inflammation 47
6.6. Cytology 47
6.7. Differential diagnosis of esophageal eosinophilia 47
6.8. Therapeutic effects 47
6.9. References cited in text and further specialist articles 49
7. Molecular Pathogenesis of Eosinophilic Esophagitis 50
7.1. Familial inheritance in EoE 50
7.2. Molecular pathogenesis of a complex disease 50
7.3. Association with other diseases and single nucleotide variant 52
7.4. Genome-wide association study and missing heritability 52
7.5. Perspective and epigenetics 53
7.6. References cited in text and further specialist articles 54
8. Immunologic Background of Eosinophilic Esophagitis 56
8.1. Cells and cytokines 56
8.2. Tissue damage and remodeling 57
8.3. References cited in text and further specialist articles 57
9. Role of Allergies in Eosinophilic Esophagitis 59
9.1. EoE peaks in pollen season 59
9.2. The allergen pattern in adolescents and adults with EoE 59
9.3. The allergen pattern in children with EoE 59
9.4. Sensitization to Candida albicans 60
9.5. Diagnostic work-up of EoE patients 60
9.6. Unmet needs 62
9.7. References cited in text and further specialist articles 62
10. Assessment of Eosinophilic Esophagitis Disease Severity and Therapeutic
Principles 64
10.1. How to measure disease activity of EoE 64
10.2. Development of PRO instruments: current overview 65
10.3. Development of biologic scores: current overview 65
10.4. Clinically relevant outcomes, unmet needs, and outlook 66
10.5. References cited in text and further specialist articles 66
11. Treatment of Eosinophilic Esophagitis with Corticosteroids 68
11.1. Reasons for treating EoE 68
11.1.1. Improvement of Quality of Life 68
11.1.2. Prevention of food impaction 68
11.1.3. Prevention of remodeling of the esophagus 69
11.2. Treatment of EoE with corticosteroids 69
11.3. Efficacy of topical corticosteroids 69
11.3.1. Topical corticosteroids (tCS) 69
11.4. Side effects of topical corticosteroids 73
11.5. Treatment schedule 73
11.6. Corticosteroid-refractory EoE 73
11.7. References cited in text and further specialist articles 74
12. Treatment of Eosinophilic Esophagitis with Diets 76
12.1. Introduction 76
12.2. Dietary treatment options for EoE 77
12.3. Elemental diets for EoE 77
12.3.1. Elemental diets in children with EoE 78
12.3.2. Elemental diets in adults with EoE 78
12.3.3. Effectiveness of elemental diets in patients with EoE 79
12.3.4. Disadvantages and limitations of elemental diets in EoE 79
12.4. Elimination diets directed by skin allergy testing 79
12.4.1. Skin allergy testing-directed food exclusion in pediatric EoE 79
12.4.2. Skin allergy testing-based food elimination in adult EoE 80
12.4.3. Effectiveness of skin allergy testing-based targeted diet in EoE 81
12.4.4. Novel allergy testing in EoE 81
12.4.5. The significance of skin allergy testing in identifying EoE food triggers 81
12.5. Empiric dietary elimination 82
12.5.1. Six-food elimination diet in pediatric EoE 82
12.5.2. Empiric six-food elimination diet in adult patients 83
12.5.3. Effectiveness of six-food elimination diet in patients with EoE 83
12.5.4. Reducing the level of restriction: the four-food elimination diet 83
12.5.5. Minimal elimination diet: the one-food elimination diet 84
12.5.6. Putting elimination diet for eosinophilic esophagitis upside down: the 2-4-6 step-up diet 84
12.6. Identification of food triggers for EoE 85
12.7. Long term efficacy and safety of dietary therapy in EoE 85
12.8. How can we succeed in the dietary management of EoE patients? 86
12.8.1. Discussing therapeutic options to patients is the first step to achieving success 86
12.8.2. Select the appropriate dietary strategy for each patient 86
12.8.3. Coping with the avoidance of common foods 86
12.8.4. Response to a dietary intervention and subsequent food reintroduction 88
12.9. Unsolved aspects and suggestion for further research 88
12.10. References cited in text and further specialist articles 88
13. Emerging Treatments and Future Perspectives 91
13.1. Recent developments in medical therapy 91
13.1.1. Anti-allergic drugs 91
13.1.2. Immunomodulators and biologics 91
13.2. Recent developments in diagnosis and disease monitoring 91
13.2.1. Endoscopic classification of EoE 91
13.2.2. Minimal invasive biomarkers 92
13.3. Summary and guidelines 92
13.4. References cited in text and further specialist articles 93
14. Abbreviations 95
Index 96
