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Eosinophilic Gastrointestinal disorders (Part I)

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Eosinophilic Gastrointestinal disorders (Part I)

Presented by Yoavanit Srivaro, MD.

February 2015

Published in: Health & Medicine
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Eosinophilic Gastrointestinal disorders (Part I)

  1. 1. Eosinophilic Gastrointestinal disorders (Part I) Yoavanit Srivaro M.D.
  2. 2. Outline • Introduction • Epidemiology • Classification • Gastrointestinal Eosinophils Under Homeostatic Healthy States • Clinical Evaluation • Eosinophilic Esophagitis
  3. 3. Eosinophilic Esophagitis Outline • Definition • Etiology • Pathogenesis • Clinical feature • Diagnostic studies • Treatment • Prognosis
  4. 4. Introduction • Disorders that selectively affect GI tract • Eosinophil-rich inflammation in the absence of known causes for eosinophilia Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  5. 5. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  6. 6. Epidemiology(1) • EoE is a global health problem now reported in - Australia - Japan - Brazil - Spain - England - Switzerland - Italy - Israel Shitrit AB, Reinus C, Zeides S, et al. Eosinophilic esophagitis. Isr Med Assoc J 2006;8:587.
  7. 7. Epidemiology(4) Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. The New England journal of medicine. 2004;351(9):940-1.
  8. 8. Epidemiology(3) • 0.4% (~4 : 1000) prevalence of EoE in a random sample of Swedish adults. • EoE occurred in about 1 : 1000 children in the Cincinnati metropolitan area over a 10-year period. Ronkainen J, Talley NJ, Aro P, et al. Prevalence of eosinophilia and eosinophilic esophagitis in adults in the community: a random population based study (Kalixanda). Gastroenterology 2006;130:A575 Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med 2004;351:940-1.
  9. 9. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  10. 10. Gastrointestinal Eosinophils Under Homeostatic Healthy States • Eosinophils are present at low levels in numerous tissues • In biopsy and autopsy specimens, organs that normally demonstrate tissue eosinophils at substantial levels are - GI tract - Lymph nodes - Spleen - Thymus DeBrosse CW, Case JW, Putnam PE, Collins MH, Rothenberg ME. Quantity and distribution of eosinophils in the gastrointestinal tract of children. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2006;9(3):210-8.
  11. 11. Gastrointestinal Eosinophils Under Homeostatic Healthy States • Eosinophils throughout the GI tract of conventional healthy mice : normally present in the lamina propria of the stomach, small intestine, cecum, and colon. • Eosinophils are not normally present in Peyer patches or intraepithelial locations. • Eosinophils are frequently infiltrate in Peyer patches regions in EGID. Mishra A, Hogan SP, Lee JJ, et al. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest 1999;103: 1719-27 Rothenberg ME, Mishra A, Collins MH, et al. Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin Immunol 2001;108:891-4.
  12. 12. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  13. 13. DeBrosse CW, Case JW, Putnam PE, Collins MH, Rothenberg ME. Quantity and distribution of eosinophils in the gastrointestinal tract of children. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2006;9(3):210-8.
  14. 14. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279 PROINFLAMMATORY ROLE OF EOSINOPHILS
  15. 15. Date of download: 12/28/2014 Copyright © 2014 McGraw-Hill Education. All rights reserved. Transmission electron micrograph (×10,000) of an eosinophil showing the characteristic binucleate cell with specific granules containing an electron dense core. The major contents of the cell are listed. (Courtesy of Dr. A. Dewar, National Heart and Lung Institute.) CLC, Charcot Leyden crystal; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EPO, eosinophil peroxidase; GF, growth factor; GM-CSF, granulocyte-monocyte colony-stimulating growth factor; HETE, hydroxyeicosatetraenoic acid; LT, leukotriene; MBP, major basic protein; PAF, platelet-activating factor; PDGF, platelet-derived growth factor; PG, prostaglandin; PSGL, P-selectin glycoprotein ligand; TBX, Legend: From: Chapter 62. Eosinophils and Their Disorders Williams Hematology, 8e, 2010
  16. 16. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
  17. 17. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
  18. 18. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279 MBP, EPX, and ECP have cytotoxic effects on epithelium at concentrations similar to those in biologic fluids from patients with eosinophilia
  19. 19. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279 MBP triggers degranulation of mast cells and basophils.
  20. 20. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279 Eosinophil-mediated damage is caused by • Toxic hydrogen peroxide and halide acids generated by EPX • Superoxide generated by the respiratory burst oxidase enzyme pathway in eosinophils
  21. 21. Proinflammatory Role of Eosinophils • Triggering of eosinophils by engagement of receptors for cytokines, immunoglobulins, and complement can lead to the generation of a wide range of inflammatory cytokines Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nature medicine. 2008;14(9):949-53.
  22. 22. Proinflammatory Role of Eosinophils • TGF-β is linked with epithelial growth, fibrosis, and tissue remodeling. • Eosinophils express MHC class II molecules and relevant costimulatory molecules (CD28, CD40, CD80 [B7-1], CD86 • Eosinophils secrete cytokines capable of promoting lymphocyte proliferation , activation &Th1 or Th2 polarization (IL-2, -4, - 6, -12, -10). Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  23. 23. Clinical Evaluation • Pts with EGID present with a variety of clinical problems, most often -Failure to Thrive -Abdominal pain -Irritability -Gastric dysmotility -Vomiting -Diarrhea -Dysphagia -Microcytic anemia -Hypoproteinemia Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  24. 24. Clinical Evaluation Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  25. 25. Clinical Evaluation Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  26. 26. Clinical Evaluation Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106 •Blood eosinophil counts are generally in the normal range in most pts • Above-normal levels can distinguish pts with active versus inactive EoE
  27. 27. Evaluation for Hypereosinophilic syndrome Diagnostic criteria for HES established by Chusid and colleagues,1975 1.Peripheral blood eosinophilia (>1,500 cells/microliter) for longer than 6 months 2.Evidence of eosinophil-related target organ damage 3.Exclusion of all other etiologies for eosinophilia Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine. 1975;54(1):1-27.
  28. 28. Evaluation for Hypereosinophilic syndrome Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes 1. Hypereosinophilia-absolute eosinophil count >1,500 cells/microlitr for 1 mo,checked on 2 occasions* 2. Evidence of eosinophil-mediated target organ damage 3. Exclusion of all other potential causes of hypereosinophilia Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
  29. 29. Evaluation for Hypereosinophilic syndrome *Tissue hypereosinophilia can be identified in addition to an elevated absolute eosinophil count with tissue hypereosinophilia, defined as: 1. Eosinophils >20% of nucleated cells in bone marrow 2. Extensive tissue infiltration of target organ by histologic analysis 3. Histologic evidence of eosinophil degranulation in a target tissue in the absence of eosinophils in that target tissue Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
  30. 30. HE-related organ damage Organ dysfunction With Marked tissue eosinophil infiltrates And/Or Extensive deposition of eosinophil-derived proteins In the presence or absence of marked tissue eosinophils (1) Fibrosis (lung, heart, digestive tract, skin, and others) (2) Thrombosis with or without thromboembolism (3) Cutaneous (including mucosal) erythema, edema/angioedema, ulceration, pruritus, and eczema (4) Peripheral or central neuropathy with chronic or recurrent neurologic deficit And 1 or more of the following Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
  31. 31. Evaluation for Hypereosinophilic syndrome • Pts with EGID, the diagnosis of HES should always be considered, especially if they develop extra-GI manifestations . • Thus, additional diagnostic testing for HES should be considered. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  32. 32. Evaluation for Hypereosinophilic syndrome • Pts with marked eosinophilia are at risk for the development of cardiac disease. • Routine surveillance of the cardiorespiratory system is warranted. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  33. 33. Eosinophilic Esophagitis
  34. 34. Eosinophilic Esophagitis Outline • Defnition • Etiology • Pathogenesis • Clinical feature • Diagnostic studies • Treatment • Prognosis
  35. 35. Definition • “Eosinophilic esophagitis represents a chronic, immune/antigen mediated, esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation” Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. The Journal of allergy and clinical immunology. 2011;128(1):3-20.e6; quiz 1-2.
  36. 36. Etiology • Food allergen and aeroallergen sensitization • Genetics • Cytokine (IL-5) , Chemokine(Eotaxin-3) • Immune dysregulation
  37. 37. Etiology • Food allergen and aeroallergen sensitization
  38. 38. Esophageal eosinophilic inflammation is mechanistically linked to pulmonary inflammation, on the basis of the induction of experimental EoE by repeated delivery of specific allergens to the lung of mice. Mishra A, Hogan SP, Brandt EB, et al. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest 2001; 107:83-90.
  39. 39. Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. The Journal of allergy and clinical immunology. 2003;112(4):796-7.
  40. 40. Etiology • Food allergen and aeroallergen sensitization • Genetics
  41. 41. Genetics • 3 Basic approach 1) Mendelian disorder 2) Candidate gene identification 3) Genome wide association study
  42. 42. Thymic stromal lymphopoeitin (TSLP) protein • GWAS, genotyping 351 patients with EoE and 3104 healthy controls and evaluating 550,000 common variants. • On chromosome 5q22, a single locus spanning the TSLP and WD repeat domain 36 (WDR36) genes showed a significant association with EoE. Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nature genetics. 2010;42(4):289-91.
  43. 43. Thymic stromal lymphopoeitin (TSLP) protein • TSLP has a known role in processes germane to EoE 1. Polarization of Th2 immunity 2. Induction of eotaxins Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  44. 44. Etiology • Food allergen and aeroallergen sensitization • Genetics • Cytokine (IL-5) , Chemokine(Eotaxin-3)
  45. 45. Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene expression profile in eosinophilic esophagitis. J Clin Invest 2006;116:536-47.
  46. 46. Pathogenesis • Activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]). Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
  47. 47. Pathogenesis • Activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]). • Impaired barrier function (mediated by loss of desmoglein-1). Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
  48. 48. Pathogenesis • Activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]). • Impaired barrier function (mediated by loss of desmoglein-1). • Increased production and/or activity of transforming growth factor-b. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
  49. 49. Pathogenesis • Activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]). • Impaired barrier function (mediated by loss of desmoglein-1). • Increased production and/or activity of transforming growth factor-b. • Induction of allergic inflammation by eosinophils and mast cells. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
  50. 50. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
  51. 51. Clinical feature(1) Yan BM, Shaffer EA. Eosinophilic esophagitis: a newly established cause of dysphagia. World journal of gastroenterology : WJG. 2006;12(15):2328-34.
  52. 52. Clinical feature(2) Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  53. 53. Clinical feature(2) Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. The New England journal of medicine. 2004;351(9):940-1.
  54. 54. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to treatment with fluticasone propionate. Gastrointestinal endoscopy. 2006;63(1):3-12.
  55. 55. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to treatment with fluticasone propionate. Gastrointestinal endoscopy. 2006;63(1):3-12. Study of 26 adult patients with EoE, all had dysphagia, 11 had food impaction.
  56. 56. Diagnostic Studies • Esophageal ultrasound • Radiographic and Endoscopic Studies • Histology • Allergy Evaluation
  57. 57. Esophageal ultrasound • Dysfunctional muscularis mucosa. • Providing a possible explanation for the impaired esophageal dysmotility. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  58. 58. Esophageal ultrasound C. Endosonographic image (20 MHz catheter probe) showing thick-wall esophagus with prominent mucosa/submucosa layer and narrow lumen. Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointestinal endoscopy. 2002;56(2):260-70.
  59. 59. Radiographic and Endoscopic Studies • Strictures • Mucosal rings • Ulcerations • Whitish papules • Polyps Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  60. 60. Radiographic studies Figure 2. Radiographic and endoscopic studies from an 18-year-old female with history of asthma, eczema, and long- standing obstructive dysphagia beginning in early childhood. A.Barium esophagram showing a small caliber esophagus Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointestinal endoscopy. 2002;56(2):260-70.
  61. 61. Endoscopic Studies Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointestinal endoscopy. 2002;56(2):260-70.
  62. 62. Endoscopic Studies Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America. 2008;18(1):45-57; viii.
  63. 63. Endoscopic Studies Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America. 2008;18(1):45-57; viii.
  64. 64. Endoscopic Studies Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America. 2008;18(1):45-57; viii.
  65. 65. Endoscopic Studies A) mucosal edema, concentric ring, linear furrow B) linear furrow, white exudates C) corrugated appearance, linear shearing Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America. 2008;18(1):45-57; viii.
  66. 66. Endoscopic Studies Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  67. 67. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  68. 68. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  69. 69. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  70. 70. Histology Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
  71. 71. Histology Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
  72. 72. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  73. 73. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  74. 74. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  75. 75. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  76. 76. Histology Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North America. 2008;18(1):59-71; viii-ix.
  77. 77. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  78. 78. Allergy Evaluation • Peripheral blood eosinophil count • Food allergen and Aeroallergen sensitization - Skin-prick tests - Allergen-specific IgE in serum - Delayed skin patch testing : Food protein sensitization Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  79. 79. Allergy Evaluation • Peripheral blood eosinophil count - There was a significant amount of variability in the defining level for “peripheral eosinophilia” -Range of eosinophils reported as abnormal ranged from greater than 350 eosinophils per mm3 to greater than 800 eosinophils per mm3). Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
  80. 80. Allergy Evaluation • Peripheral blood eosinophil count • One study demonstrated that persistent blood eosinophilia correlated with persistent dysphagia. • In another study, the degree of elevation of serum eosinophils correlated with the severity of Eosinophilic esophagitis Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
  81. 81. Allergy Evaluation • Peripheral blood eosinophil count • Food allergen and Aeroallergen sensitization - - Skin-prick tests - Allergen-specific IgE in serum - Delayed skin patch testing : Food protein sensitization Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  82. 82. Allergy Evaluation
  83. 83. 26 Pts with EoE Identify by BX SPT+ Milk&Egg Patch+Wheat SPT & Patch test Avoid food Resolution 18 Pts Partial improve 6 Pts Loss F/U 2 Pts Overall, after intervention, esophageal eosinophil counts improved from 55.8 to 8.4 eosinophils/HPF Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic
  84. 84. Treatment • A trial of specific food allergen and aeroallergen avoidance • Systemic or topical glucocorticoids • Anti–IL-5 monoclonal antibody • Anti– human IL-13 antibody • Siglec-F • PPI Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  85. 85. Specific food allergen and aeroallergen avoidance • Indicated for patients with atopic EoE • If results are unsatisfactory or avoidance is difficult for practical reasons - A diet consisting of an elemental (amino acid–based) formula - Avoidance of the most common allergic foods (cow’s milk, soy, wheat, egg, peanut/tree nuts, seafood/shellfish) Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  86. 86. Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2006;4(9):1097-102.
  87. 87. 60 Pts with EoE ELED 25 Pts SFED 35 Pts 6 weeks later Esophageal Bx Specimen was obtained SFED gr. Improve Esophageal inflammation 26 Pts(74%) ELED gr improve Esophageal inflammation 22 Pts (88%) Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2006;4(9):1097-102.
  88. 88. Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2006;4(9):1097-102.
  89. 89. Systemic or topical glucocorticoids • Systemic glucocorticoids are used for acute exacerbations • Topical glucocorticoids are used to provide long-term control Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  90. 90. Systemic or topical glucocorticoids Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. The Journal of allergy and clinical immunology. 2011;128(1):3-20.e6; quiz 1-2.
  91. 91. Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131(5):1381-91.
  92. 92. Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131(5):1381-91.
  93. 93. 36 Pts with EoE 880 g of FP 21 Pts Placebo 15 Pts 3 mnths later Esophageal Bx Specimen was obtained 50% of FP Pts Improve 9% of Placebo Pts Improve Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131(5):1381-91.
  94. 94. Result • FP decreased esophageal eosinophil levels, with a more pronounced effect in nonallergic individuals Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131(5):1381-91. Eo/HPF In Proximal Esophagus Eo/HPF In Distal Esophagus P (Value) FP 65.9 +/- 25.3 84.6+/-19.7 .03 Placebo 1.4+/-1.1 19.6+/- 12.9 .04
  95. 95. Anti–IL-5 monoclonal antibody Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
  96. 96. Anti–IL-5 monoclonal antibody Straumann et al. Gut. 2010;59:21–30.
  97. 97. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
  98. 98. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
  99. 99. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3. 227 Pts with EoE Reslizumab 1 mg/kg 56 Pts Reslizumab 3 mg/kg 57 Pts Reslizumab 2 mg/kg 57 Pts Placebo % Reduction Eo 59 % % Reduction Eo 67 % % Reduction Eo 64 % % Reduction Eo 24 %
  100. 100. Siglec-F Rubinstein E, Cho JY, Rosenthal P, Chao J, Miller M, Pham A, et al. Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis. Journal of pediatric gastroenterology and nutrition. 2011;53(4):409-16. • New approach is to target the sialic acid–binding immunoglobulin-like lectin F (Siglec-F) • An inhibitory receptor expressed on eosinophils • Siglec-F inhibition was useful in a mouse model of EoE.
  101. 101. Proton Pump Inhihitor • PPI are useful 1. Eliminate GERD as a cause of esophageal eosinophilia. 2. GERD is a comorbid disease 3. PPI-responsive esophageal eosinophilia • Mechanism of PPI 1. Primarily involve acid blockade 2. Other mechanisms Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. The Journal of allergy and clinical immunology. 2011;128(1):3-20.e6; quiz 1-2.
  102. 102. Proton Pump Inhihitor • Recommended PPI dose that should be used to eliminate PPI-responsive esophageal eosinophilia - Adults 20-40 mg, once or twice daily for 8 to 12 weeks - Children 1 mg/kg per dose, twice daily for 8 to 12 weeks Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. The Journal of allergy and clinical immunology. 2011;128(1):3-20.e6; quiz 1-2.
  103. 103. Prognosis • EoE requires prolonged treatment, similar to allergic asthma. • Natural history of EoE has not been fully delineated. • Results of a 15-year follow up study of esophageal eosinophilia indicate that Vast majority of patients have ongoing symptoms from childhood into adulthood. DeBrosse CW, Franciosi JP, King EC, Butz BK, Greenberg AB, Collins MH, et al. Long-term outcomes in pediatric-onset esophageal eosinophilia. The Journal of allergy and clinical immunology. 2011;128(1):132-8.
  104. 104. Prognosis • If left untreated, chronic EoE will likely develop into progressive esophageal scarring & dysfunction -> consideration of esophageal dilation • The risk for developing Barrett esophagitis, especially in pts with coexisting EoE and GERD • Pts with EoE are at increased risk for developing other forms of EGID -> routine surveillance of the entire GI tract by endoscopy Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
  105. 105. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
  106. 106. Thank You

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