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Eosinophilic gastrointestinal disorders (part II)

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Eosinophilic Gastrointestinal disorders (Part II)

Presented by Yoavanit Srivaro, MD.

April10, 2015

Published in: Health & Medicine
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Eosinophilic gastrointestinal disorders (part II)

  1. 1. Eosinophilic Gastrointestinal disorders (Part II) Yoavanit Srivaro M.D.
  2. 2. Outline • Eosinophilic Gastritis and Gastroenteritis • Eosinophilic Colitis
  3. 3. Eosinophilic Gastritis and Gastroenteritis
  4. 4. Eosinophilic Gastritis and Gastroenteritis • Definition • Classification • Epidemiology • Etiology • Clinical Presentation • Diagnostic evaluation • Treatment
  5. 5. Definition • characterized by selective infiltration of eosinophils in • stomach, small intestine, or both with variable involvement of esophagus, large intestine, or both. Simon D, Wardlaw A, Rothenberg ME. Organ-specific eosinophilic disorders of the skin, lung, and gastrointestinal tract. The Journal of allergy and clinical immunology. 2010;126(1):3-13.
  6. 6. Classification Primary subtypes • Atopic • Nonatopic • Familial primary subtypes Secondary subtypes Eosinophilic disorders • Hypereosinophilic syndrome Noneosinophilic disorders • Celiac disease • Connective tissue disease (scleroderma) • Iatrogenic • Infection • Inflammatory bowel disease • Vasculitis (Churg-Strauss syndrome) Mucosal, Muscularis,Serosal Simon D, Wardlaw A, Rothenberg ME. Organ-specific eosinophilic disorders of the skin, lung, and gastrointestinal tract. The Journal of allergy and clinical immunology. 2010;126(1):3-13.
  7. 7. Epidemiology • Wide age range Infancy Seventh decades • Most commonly Third Fifth decades Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6. Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27.
  8. 8. Epidemiology • An electronic survey sent to North American Allergists and Pediatric Gastroenterologists indicate prevalence for EGE of 22 to 28 per 100,000 persons Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27. Spergel JM, Book WM, Mays E, Song L, Shah SS, Talley NJ, et al. Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States. Journal of pediatric gastroenterology and nutrition. 2011;52(3):300-6.
  9. 9. Etiology • Idiopathic • Allergic mechanism 1. Increased total IgE and Food specific IgE levels 2.Increased T helper 2 associated cytokines Simon D, Wardlaw A, Rothenberg ME. Organ-specific eosinophilic disorders of the skin, lung, and gastrointestinal tract. The Journal of allergy and clinical immunology. 2010;126(1):3-13.
  10. 10. Etiology • Data from clinical studies suggest that patients with eosinophilic gastroenteritis have increased secretion of IL-4 and IL-5 by peripheral blood T cells. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  11. 11. Etiology • T cells derived from the lamina propria of the duodenum of patients with EGID preferentially secrete Th2 cytokines (especially IL-13) when stimulated with milk proteins Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  12. 12. Etiology • Mast cells are also increased in EGID. • Recent murine model of oral allergen–induced diarrhea has indicated that mast cells have a critical role in the pathogenesis of allergic diarrhea in EGID. Brandt EB, Strait RT, Hershko D, et al. Mast cells are required for experimental oral allergen-induced diarrhea. J Clin Invest 2003;112:1666-77.
  13. 13. Hogan SP, Mishra A, Brandt EB, Foster PS, Rothenberg ME. A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(12):6681-6. Allergen sensitized mice Challange with Oral allergen •Marked allergen-specific IgG1 and IgE, Th2-type (IL-4 and IL-5) cytokine production •Eosinophil accumulation in the blood and small intestine Genetic absence of eotaxin mice (se (sensitized mice) Challange with Oral allergen •Eosinophil recruitment into small intestine was ablated •Enhanced eosinophil accumulation in the blood compared with wild-type mice. Genetic absence of IL-5 mice (sensitized mice) Challange with Oral allergen • Partial eosinophil accumulation small intestine •Decline in circulating eosinophil levels
  14. 14. Hogan SP, Mishra A, Brandt EB, Foster PS, Rothenberg ME. A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(12):6681-6. Allergen sensitized mice Challange with Oral allergen •Marked allergen-specific IgG1 and IgE, Th2-type (IL-4 and IL-5) cytokine production •Eosinophil accumulation in the blood and small intestine Challange with Oral allergen •Eosinophil recruitment into small intestine was ablated •Enhanced eosinophil accumulation in the blood compared with wild-type mice. Challange with Oral allergen • Partial eosinophil accumulation small intestine •Decline in circulating eosinophil levels These results establish that the accumulation of gastrointestinal eosinophils is antigen induced, can occur independent of IL-5. Genetic absence of eotaxin mice (se (sensitized mice) Genetic absence of IL-5 mice (sensitized mice)
  15. 15. Eotaxin CC Chemokine Original name Chemokine receptor Major function CCL 11 Eotaxin CCR3 Eosinophil, Basophil,TH2 recruitment CCL 24 Eotaxin-2 CCR3 Eosinophil, Basophil,TH2 recruitment CCL 26 Eotaxin-3 CCR3 Eosinophil, Basophil,TH2
  16. 16. Hogan SP, Mishra A, Brandt EB, Royalty MP, Pope SM, Zimmermann N, et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nature immunology. 2001;2(4):353-60. •(OVA)-alum–sensitized mice were challenged with 2 doses of oral OVA in the form of enteric-coated beads •Mice developed eosinophil-associated GI dysfunction, including gastromegaly, delayed food transit, and weight loss, all strongly dependent on the chemokine eotaxin-1
  17. 17. Hogan SP, Mishra A, Brandt EB, Royalty MP, Pope SM, Zimmermann N, et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nature immunology. 2001;2(4):353-60. •(OVA)-alum–sensitized mice were challenged with 2 doses of oral OVA in the form of enteric-coated beads •Mice developed eosinophil- associated GI dysfunction, including gastromegaly, delayed food transit, and weight loss, all strongly dependent on the chemokine eotaxin-1 Placebo
  18. 18. Clinical Presentation • Approximately 80% have symptoms for several years • Occasionally, the disease may manifest itself as an acute abdomen or bowel obstruction Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  19. 19. Clinical Presentation Children & Adolescent • Growth retardation • Failure to thrive • Delayed puberty or amenorrhea. Adults • Abdominal pain • Diarrhea • Dysphagia Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  20. 20. Clinical Presentation • Present with a constellation of symptoms that are related to the degree and area of the GI tract affected 1. Mucosal layer 2. Muscularis layer 3. Serosal layer Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  21. 21. Clinical Presentation Mucosal disease • Vomiting • Abdominal pain • Diarrhea • Blood loss in stools • Iron deficiency anemia • Malabsorption • Protein-losing enteropathy • Failure to thrive Chehade M, Magid MS, Mofidi S, Nowak-Wegrzyn A, Sampson HA, Sicherer SH. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow- up. Journal of pediatric gastroenterology and nutrition. 2006;42(5):516-21.
  22. 22. Clinical Presentation Muscle layer disease Bowel wall thickening & Intestinal obstruction Cramping & abdominal pain associated with nausea and vomiting Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  23. 23. Clinical Presentation Subserosal disease • Eosinophilic exudate ascites • Abundant peripheral eosinophilia • Serosal and visceral peritoneal inflammation leads to leakage of fluids Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  24. 24. Clinical Presentation • EGE can occasionally involve the hepatobiliary tree. : Pancreatitis : Cholangitis Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27.
  25. 25. Diagnostic evaluation • Laboratory • Allergic evaluation • Radiographic evaluation • Endoscopic and Pathology Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  26. 26. Laboratory • Complete blood count • Serum albumin • Fecal protein • Stool examination Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  27. 27. Complete Blood Count Peripheral blood eosinophilia Iron deficeicy anemia Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  28. 28. Complete Blood Count Peripheral blood eosinophilia Layer Average count eosinophil/microltr Mucosal 2,000 Muscular 1,000 Serosa 8,000 • Found in 20%-80% of cases Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  29. 29. Fecal protein • Alpha1-antitrypsin in a 24-h feces collection • Identify the inability to digest and absorb proteins in GI tract. • The normal value is 0-54 mg/dL. • Patients with eosinophilic gastroenteritis have elevated alpha1- antitrypsin in their feces. Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  30. 30. Stool examination Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6. •Should be performed to rule out parasitic infestation. •Mild-to-moderate steatorrhea is present approximately 30% of patients.
  31. 31. Allergic evaluation • Skin prick test • Specific IgE antibody to inhaled & oral allergen • Atopic patch testing • Diagnostic trials of therapy with 1. Elimination 2. Oligoantigenic diets 3. Elemental (amino-acid based) diets Khan S. Eosinophilic gastroenteritis. Best practice & research Clinical gastroenterology. 2005;19(2):177-98.
  32. 32. Radiographic evaluation Chen MJ, Chu CH, Lin SC, Shih SC, Wang TE. Eosinophilic gastroenteritis: Clinical experience with 15 patients. World JGastroenterol 2003; 9(12): 2813-2816
  33. 33. Endoscopic and Pathology Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  34. 34. Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27.
  35. 35. Histology of The Stomach higheredbcs.wiley.com
  36. 36. Histology of The Stomach Pathologyoutlines.com Submucosa Mucosa Lamina propia
  37. 37. Histology of The Intestine
  38. 38. Histology of The Intestine The organized tissues of the Peyer's patches and mesenteric lymph nodes (MLNs) are involved in the induction of immunity and tolerance, whereas the effector sites are scattered throughout the lamina propria and epithelium of the mucosa. Both the Peyer's patches and villus lamina propria are drained by afferent lymphatics that go to the MLNs. SED, subepithelial dome; TDA, thymus-dependent area.
  39. 39. 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.
  40. 40. 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.
  41. 41. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  42. 42. 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.
  43. 43. Histology of The Intestine Normal Duodenum histology Pathologyoutlines.com
  44. 44. Histology of The Intestine Normal Colon histology Pathologyoutlines.com
  45. 45. Histology of The Intestine Normal Colon histology Embryology.med.unsw.ed
  46. 46. Endoscopic and Pathology Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6. Dense eosinophilic infiltrates in the lamina propria and mucosae
  47. 47. Endoscopic and Pathology Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6. Dense eosinophilic infiltrates in the lamina propria and mucosae
  48. 48. Endoscopic and Pathology Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6. Dense eosinophilic infiltrates in the lamina propria and mucosae
  49. 49. Dense eosinophilic infiltrates in the lamina propria and mucosae
  50. 50. No standards exist for diagnosis The following findings support the diagnosis 1.Presence of elevated eosinophils in biopsy specimens from the GI tract wall 2. Infiltration of eosinophils within intestinal crypts and gastric glands 3. Lack of involvement of other organs 4. Exclusion of other causes of eosinophilia Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  51. 51. g •Gross Endoscoopic finding are often normal •Endoscopic bx should be obtained from 5-6 site of afffected organ •In stomach eosinophil levels>30 eo/HPF differrentiate eosinophilic gastritis from normal adult control Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106 Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27.
  52. 52. No standards exist for diagnosis Four criteria are required for the diagnosis 1. Presence of gastrointestinal symptoms 2. Eosinophilic infiltration of gastrointestinal tract 3. Exclusion of parasitic disease 4. Absence of other systemic involvement Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology : WJG. 2013;19(31):5061-6.
  53. 53. Treatment • Eliminating the dietary intake of foods implicated by skin-prick tests • Drugs Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  54. 54. Chehade M, Magid MS, Mofidi S, Nowak-Wegrzyn A, Sampson HA, Sicherer SH. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow-up. Journal of pediatric gastroenterology and nutrition. 2006;42(5):516-21. 6 6 Pts with AEG with PLE 6 Pts with AEG 5 Pts with Abd S/S with Bx -ve Medical records of patients were reviewed for clinical history, physical ,laboratory values.
  55. 55. Chehade M, Magid MS, Mofidi S, Nowak-Wegrzyn A, Sampson HA, Sicherer SH. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow- up. Journal of pediatric gastroenterology and nutrition. 2006;42(5):516-21.
  56. 56. Chehade M, Magid MS, Mofidi S, Nowak-Wegrzyn A, Sampson HA, Sicherer SH. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow- up. Journal of pediatric gastroenterology and nutrition. 2006;42(5):516-21.
  57. 57. Chehade M, Magid MS, Mofidi S, Nowak-Wegrzyn A, Sampson HA, Sicherer SH. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow- up. Journal of pediatric gastroenterology and nutrition. 2006;42(5):516-21. 6 Pts with AEG with PLE •Pts had excellent response to therapy with amino acid based formula and tolerated gradual introduction of some foods with time.
  58. 58. Eliminating the dietary intake of foods Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106 Dietary modification Disease remission Specific food groups are slowly reintroduced, at about 3-week intervals for each food group Endoscopy is performed every 3 months to identify either sustained remission or disease flare-up
  59. 59. Treatment • Cromoglycate • Montelukast • Ketotifen • Suplatast tosilate • Mycophenolate mofetil (inosine monophosphate dehydrogenase inhibitor) • Alternative Chinese medicines Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  60. 60. Treatment • Cromoglycate • Montelukast • Ketotifen • Suplatast tosilate • Mycophenolate mofetil (inosine monophosphate dehydrogenase inhibitor) • Alternative Chinese medicines Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106 Generally unsuccessful
  61. 61. Treatment • Suplatast tosilate :Anti-Th2 drug :Inhibits the expression of Th2 cytokines, such as IL-5. :Successful treatment of EGE with suplatast has been described in 2 single patient case reports. Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27.
  62. 62. Treatment • Anti-inflammatory drugs :Systemic steroids :Topical steroids • Anti–IL-5 • Anti-IgE • Azathioprine or 6-mercaptopurine Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  63. 63. Antiinflammatory drugs • If diet restriction is not feasible or has failed to improve the disease. • As with treatment for asthma, topical steroids have a better benefit-to-risk effect than systemic steroids. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  64. 64. Anti-inflammatory drugs • Systemic steroid therapy : A course of 2 to 6 weeks with relatively low doses seems to work better than a 7-day course of burst glucocorticoids. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  65. 65. Anti-inflammatory drugs • Topical glucocorticoids :Budesonide tablets (Entocort EC) are designed to deliver the drug to the ileum and proximal colon. :As with treatment for asthma, topical steroids have a better benefit-to-risk effect than systemic steroids. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  66. 66. Patient profile: A 32-year-old Caucasian woman Present illness: Admitted to hospital with complaints of recurrent cramping pain in the upper abdomen associated with nausea and non-bloody diarrhoea. She had lost 4 kg in weight. Past history : No history of food intolerance, allergy, travel to tropical areas, or prior medication Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. European journal of gastroenterology & hepatology. 2001;13(4):425-7.
  67. 67. Physical examination: Slightly enlarged belly with normal bowel sounds. Laboratory data: Hb 8.1 mmol/l WBC 29x109/l Eosinophil 69%. Total serum protein 67.3 g/l. Immunoglobulins:normal. Echography : ascitic fuid. Upper gastrointestinal endoscopy (biopsies):normal Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. European journal of gastroenterology & hepatology. 2001;13(4):425-7.
  68. 68. Problem list: Eosinophilia and Ascitic fuid Strong suspicious :Eosinophilic gastroenteritis of the serosal type Treatment: Prednisolone 40 mg/day was initiated Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. European journal of gastroenterology & hepatology. 2001;13(4):425-7.
  69. 69. Clinical course: - A rapid dissolution of complaints and a decrease in the eosinophilic count. - After tapering and eventually stopping the prednisone medication, the patient remained without complaints for over 1 year. - Then she experienced more complaints of diarrhoea and ascites. Total eosinophilic count was markedly increased Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. European journal of gastroenterology & hepatology. 2001;13(4):425-7.
  70. 70. Clinical course: - To ascertain the diagnosis of eosinophilic gastroenteritis - A full-thickness surgical antrum biopsy was taken. - Histology revealed eosinophilic granulocytic infiltration in the muscular mucosa . - In the ascitic fuid, an inflammatory response with eosinophilic granulocytes Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. European journal of gastroenterology & hepatology. 2001;13(4):425-7.
  71. 71. Clinical course: -Prednisone was started at a dose of 25 mg, with rapid dissolution of complaints and peripheral eosinophilia. -When the prednisone dose was tapered to 5 mg/day, the patient complained of crampy abdominal pain and diarrhoea. Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. European journal of gastroenterology & hepatology. 2001;13(4):425-7.
  72. 72. Clinical course: -We gave budesonide tablets, normally used for the preparation of the budesonide clysma. -Starting dose was 4 mg daily, with a good clinical effect. - With this treatment regimen, the patient has been in remission for more than 2 years. Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. European journal of gastroenterology & hepatology. 2001;13(4):425-7.
  73. 73. Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27. Initiated using prednisone at 0.4 to 0.8 mg/kg each morning + Solubilized budesonide is begun at 9 mg orally daily, taken at bedtime on an empty stomach Prednisone is tapered over the next 2 or more weeks clinical symptoms are controlled •One to 2 months after the prednisone has been stopped •Budesonide dose is slowly tapered over an additional 2 to 4 months to the minimum required dose. clinical symptoms are controlled
  74. 74. Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27. Initiated using prednisone at 0.4 to 0.8 mg/kg each morning + Solubilized budesonide is begun at 9mg orally daily, taken at bedtime on an empty stomach Prednisone is tapered over the next 2 or more weeksclinical symptoms are controlled •One to 2 months after the prednisone has been stopped •Budesonide dose is slowly tapered over an additional 2 to 4 months to the minimum required dose. clinical symptoms are controlled
  75. 75. Foroughi S, Foster B, Kim N, Bernardino LB, Scott LM, Hamilton RG, et al. Anti-IgE treatment of eosinophil-associated gastrointestinal disorders. The Journal of allergy and clinical immunology. 2007;120(3):594-601. Nine EGE pts 3 wks pre Omalizumab baseline screen 16 wks Omalizumab q 2 wks Repeat all baseline study
  76. 76. Foroughi S, Foster B, Kim N, Bernardino LB, Scott LM, Hamilton RG, et al. Anti-IgE treatment of eosinophil-associated gastrointestinal disorders. The Journal of allergy and clinical immunology. 2007;120(3):594-601. Omalizumab was associated with decrease in absolute eosinophil count :at week 16 (34%, P = 0.004) : combined weeks 12 to 16 (42%, P = 0.012)
  77. 77. Foroughi S, Foster B, Kim N, Bernardino LB, Scott LM, Hamilton RG, et al. Anti-IgE treatment of eosinophil-associated gastrointestinal disorders. The Journal of allergy and clinical immunology. 2007;120(3):594-601. Tissue eosinophils decreased in the duodenum (59%) and gastric antrum (69%) but did not reach statistical significance (P 0.074 and 0.098, respectively).
  78. 78. Foroughi S, Foster B, Kim N, Bernardino LB, Scott LM, Hamilton RG, et al. Anti-IgE treatment of eosinophil-associated gastrointestinal disorders. The Journal of allergy and clinical immunology. 2007;120(3):594-601. Symptom scores were decreased at both the midstudy (63%) and end of study (70%) time points (P < .005 for both)
  79. 79. Anti–IL-5 Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterology clinics of North America. 2014;43(2):317-27. Reslizumab • an open-label clinical trial of reslizumab (SCH55700) was undertaken in 4 subjects with EGE. • Reslizumab suppressed blood eosinophilia in a significant manner. • tissue eosinophilia was only modestly suppressed •EGE symptoms were minimally affected.
  80. 80. Eosinophilic Colitis
  81. 81. Eosinophilic Colitis • Introduction • Classification • Epidemiology • Etiology • Clinical Presentation • Diagnostic evaluation • Treatment
  82. 82. Introduction • Eosinophils accumulate in the colon of patients with a variety of disorders : Eosinophilic gastroenteritis : Allergic colitis of infancy : Infections (e.g., pinworms, dog hookworms) : Drug reactions : Vasculitis (e.g., Churg-Strauss syndrome) : IBD Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  83. 83. Classification Primary subtypes • Atopic • Nonatopic Secondary subtypes Eosinophilic disorders • Hypereosinophilic syndrome Noneosinophilic disorders • Celiac disease • Connective tissue disease (scleroderma) • Iatrogenic • Infection • Inflammatory bowel disease • Vasculitis (Churg-Strauss syndrome) Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  84. 84. Allergic colitis in infancy • Cow’s milk and soy proteins are the foods most frequently implicated in allergic colitis of infancy • This condition may occur more often in infants exclusively breastfed and can even occur in infants fed with protein hydrolysate formulas Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  85. 85. Allergic colitis in infancy • Dietary protein– induced proctocolitis of infancy syndrome • Most common cause of bloody stools in the first year of life • An early expression of protein-induced enteropathy or protein-induced enterocolitis syndrome. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  86. 86. Etiology • A non- IgE–associated disease • Some studies point to a T lymphocyte– mediated process. • Exact immunologic mechanisms responsible for this condition have not been identified. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  87. 87. Clinical Presentation • Bimodal age distribution :Infantile :Early adolescent and Adulthood Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  88. 88. Clinical Presentation • Diarrhea • Abdominal pain • Weight loss • Anorexia Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  89. 89. Differential diagnosis of EC Okpara N, Aswad B, Baffy G. Eosinophilic colitis. World journal of gastroenterology : WJG. 2009;15(24):2975-9.
  90. 90. Diagnostic evaluation • No single test is the “gold standard” for diagnosis • Peripheral blood eosinophilia or eosinophils in the stool suggests eosinophilic colitis. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  91. 91. Endoscopic and Pathology Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28. • Patchy erythema • Loss of vascularity, • Lymphonodular hyperplasia mostly localized to the rectum but might extend to the entire colon Gastroenterol Res Pract. 2011
  92. 92. Endoscopic and Pathology Okpara N, Aswad B, Baffy G. Eosinophilic colitis. World journal of gastroenterology : WJG. 2009;15(24):2975-9. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28. • Patchy erythema • Loss of vascularity, • Lymphonodular hyperplasia mostly localized to the rectum but might extend to the entire colon
  93. 93. Histology of The Intestine Normal Colon histology
  94. 94. Endoscopic and Pathology Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28. • Overall architecture of the mucosa is well preserved • Focal aggregates of eosinophils in the lamina propria, crypt epithelium, and muscularis mucosa, • Multinucleated giant cells are occasionally present in the submucosa. Okpara N, Aswad B, Baffy G. Eosinophilic colitis. World journal of gastroenterology : WJG. 2009;15(24):2975-9.
  95. 95. Endoscopic and Pathology Gastroenterol Res Pract. 2011 Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28. • Overall architecture of the mucosa is well preserved • Focal aggregates of eosinophils in the lamina propria, crypt epithelium, and muscularis mucos., • Multinucleated giant cells are occasionally present in the submucosa.
  96. 96. Treatment • Eosinophilic colitis of infancy :Benign disease :Withdrawal of the offending protein trigger from the diet -->the gross blood in the stools usually resolves within 72 hours --> occult blood loss may persist longer Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  97. 97. Treatment • Eosinophilic colitis of older :Usually requires medical management because IgE associated triggers are rarely identified. Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  98. 98. Treatment • Eosinophilic colitis of older : Cromoglycate ,Montelukast,Histamine receptor antagonists : generally unsuccessful :Aminosalicylates and systemic or topical glucocorticoids :typically used and appear to be efficacious :Azathioprine or 6-mercaptopurine: in severe cases Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
  99. 99. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  100. 100. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  101. 101. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28. EGID are generally tissue- specific problems HES tends to involve the heart, lungs, and skin
  102. 102. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28. Eosinophilic esophagitis (EoE), a disease mechanistically linked with eosinophilic airway inflammation (asthma).
  103. 103. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28. Eosinophilic gastroenteritis, specific regions of the GI tract may be selectively involved
  104. 104. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  105. 105. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  106. 106. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  107. 107. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  108. 108. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004;113(1):11-28.
  109. 109. Thank You

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