1. EOSINOPHILIC ESOPHAGITIS AND OTHER EOSINOPHILIC DISORDERS OF GI TRACT Saransh jain Preceptor Dr Anoop saraya

2. Outline  Introduction  Eosinophilic esophagitis  Pathophysiology  Clinical features  Endoscopic findings  Histopathology  Differential diagnosis  Management  Other EGID  Eosinophilic gastroenteritis  FPIEC  Eosinophilic proctitis

3. Classification of EGID

5. Definition  Chronic immune/ antigen-mediated clinicopathological condition diagnosed based on  Symptoms of esophageal dysfunction  HPE at least 15 eosinophill / HPF  Exclusion of other competing causes of eosinophilia including PPI-REE

6. Eosinophilic esophagitis Epidemiology  Prevalence 0.5 to 1 case / 1000 persons (general population) 1  12-22% (in person symptomatic with dysphagia) 2  46-63% (food impaction )3  Incidence 10/10000 person/year  Prevalence increasing  No reported cohorts in India and Africa  All ages but peak children and adults < 40 yrs  3-4 X male > female  White > non white Dellon ESet al. Prevalence of eosinophilic esophagitis in the United States. CGH2013 Mackenzie SH et al. Clinical trial: eosinophilic esophagitis in patients presenting with dysphagia: a prospective analysis. Desai TK et al. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc 2005;

7. Pathogenesis

9. Clinical presentation  Children  Nonspecific  Vomiting  Regurgitation  Abdominal pain  Decreased appetite  Fever / weight loss  Atopy  50-75% allergic rhinitis  30-50 % asthma

10. Clinical presentation  Adults  Solid food dysphagia 60 – 100% Difficulty swallowing Dietary modification Lubricating foods  Heartburn 30 – 60%  Non cardiac chest pain 8- 44 %  Atopy (allergic rhinitis, asthma)  Abdominal pain, diarrhea, weight loss Dellon ES, Gibbs WB, Fritchie KJ, Rubinas TC, Wilson LA, Woosley JT, Shaheen NJ. Clinical, endoscopic, and histologic findings distinguish eosinophilic esophagitis from gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2009;7:1305-1313.

11. Mechanism of differential presentation

12. Endoscopic findings Concentric rings Transient - felinization Longitudinal furrows

13. White exudateDecreased vascularity

14. Crepe paper mucosa

15. Endoscopic finding : salient features  Finding may occur in isolation or together  Children normal / edema / plaque  Adult rings / strictures  However 7-10 % cases normal esophagus on luminal imaging  Therefore the need for obtaining tissue diagnosis  EoE endoscopic reference score (EREFS)  Exudates,rings, edema,furrows, strictures Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut 2013;62:489-95.

16. Histopathology

19. Distal esophagus Proximal esophagus

21.  At least 15 eosinophils/hpf must be present to consider a diagnosis of EoE (peak count)  Other findings  Eosinophilic degranulation  Eosinophil micro-abscesses  Basal layer hyperplasia  Elongation of the rete pegs  Dilated intracellular spaces or spongiosis  Lamina propria fibrosis  None of these findings are pathognomonic for EoE, and histopathologic findings alone cannot diagnose EoE  Changes are patchy

22. Histopathological criteria  Greater than or equal to 15 intraepithelial eosinophils per HPF in at least one esophageal site  Additional sections should be obtained from nondiagnostic but highly suggestive biopsies, and fewer eosinophils than the recommended threshold value may not eliminate the diagnosis in patients who otherwise would qualify for the diagnosis  Altered eosinophil character manifest as surface layering and abscesses.  Epithelial changes such as basal layer hyperplasia, dilated intercellular spaces.  Thickened lamina propria fibers.

23. Diagnostic criteria  Diagnosis based on  Symptoms of esophageal dysfunction  HPE at least 15 eosionophil / HPF  Peak count  Size of HPF described  2-4 biopsy separate location (distal and mid /proximal)  Exclusion of other competing causes of eosinophilia including PPI-REE

24. Differential diagnosis  GERD  PPI-REE  Secondary eosinophilia  HES  CTD  Eosinophillic gastroentritis  Crohn’s disease

25. EoE Vs. PPI-REE  Patients suspected of having EoE  Symptoms  Endoscopic findings  ≥ 15 eosinophils/hpf in esophageal biopsies  Undergo clinical and histologic resolution following PPI therapy (2 weeks)

26. EoE Vs. GERD  Symptoms overlap esp. heartburn  GERD much more prevalent  HPE in GERD can have eosinophil infiltration(< 15 cells /HPF)  Presence of GERD does not preclude a diagnosis of EoE  Determine contribution of of reflux towards patients symptoms GERD Eosinophilic esophagitis Impaired esophageal clearance of physiologic reflux Reflux leads to a leaky epithelial barrier

27. Management  Pharmcological therapy  Steroids  Non pharmacological therapy  Diet elimination therapy  Endoscopic dilatation  Maintenance therapy  Need  Options  NONE FDA approved

28. Steroids  Topical corticosteroids  Fluticasone MDI swallow no spacer  Dose 88-1760 µg/day  Budesonide OVB (slurry mixed with sucralose)  Dose 2 mg/day 3-5 gm of sucralose per 2 ml of aqueous solution  Proper technique important  MDI end expiration during breath hold  After meals  Do not eat /drink anything for 60 min after swallowing

29.  Side effects of local steroids  No reports of adrenal axis suppression after 8-12 weeks course  No long term follow-up study  Avoid grape fruit (- CYP3A )  Oral candidiasis uncommon  Esophagial candidiasis 15-20%

33. Diet elimination therapy  Principle -Removal of allergens  Amino acid based  Directed elimination diets based on allergy test results  Non directed elimination diets

35. Elemental diet  Remission 85-95%  Absence of complication  Issues  Palatablity  Need for enteral feeding tubes  Patient complaince  Cost Baseline Introduce diet 4-6 week Reintroduce group A 2-3 mon Endoscopy Reintroduce group B and so on

37. Elimination diet  Directed based on  Skin prick test not effective  Atopy patch test effective  Remission 35-56%  Empiric elimination diet  6 food elimination diet  Cow milk protein, soy, egg, peanut and fish  Remission 66-78%  Allows variety of foods

38. Endoscopic dilatation  Treats symptoms not inflammation  Done via balloons or wire guided bougie  Goal- mucosal tear (NOT a complication)  Symptoms improve 50% symptom free after 1 session for 1 year  S/E 75% chest pain (expect it )  Perforation  Previous series as high as 8 %  Recent data 0.3%1 Egan JV, Baron TH, Adler DG, Davila R, Faigel DO, Gan SL, Hirota WK, Leighton JA, RD. Esophageal dilation. Gastrointest Endosc 2006;63:755-60.

40. Eosinophilic gastroenteritis  Rare prevalence 22-28/100000 persons  20- 60 years M=F rare children  Atopy 40-50%  Symptoms protean vary by site and depth of involvement  small intestine > stomach  Mucosal abdominal pain vomiting diarrhea  Muscular GOO intestinal obstruction (but stricture RARE)  Serosal 10% ascites protracted course

41.  Management : mainly case series  Systemic corticosteroids 0.5 to 1 mg/ kg induction  Budesonide 9 mg/day solubilized OD HS  Dietary therapy elemental and 6 food elimination diet  anti IgE, monteleukast, cromolyn Na not effective

42. Food protein induced enterocolitis  Presents in Infancy, 1st few weeks of life  Trigger cow milk protein based formula  Profuse bloody mucoid diarhoea wieght loss  Rx elimination of causal milk and soy proteins  90% can tolerate milk by 3 years of age

43. Eosinophilic proctitis  Children younger than 2 years  Bloody stool, lack any systematic symptoms  Endoscopy focal rectal erythma, erosions  HPE eosinophil in mucosa minimum 6 eosinophils /HPF and /or eosinophils invading crypts or muscularis mucosae  Rx elimination diet

44. Summary and take home points  Over the past ten years, EoE has become a major cause of GI symptoms,including dysphagia and food impaction in adolescents and adults, and feeding intolerance, failure-to-thrive, regurgitation, heartburn, and vomiting in children.  EoE is a clinicopathologic condition, so the entire clinical and histologic picture must to be considered in order to make a diagnosis; no single feature is diagnostic on its own.  EoE is now diagnosed based on consensus guidelines requiring symptoms of esophageal dysfunction, at least 15 eosinophils per high- power microscopy field on esophageal biopsy, and eosinophilia limited to the esophagus with other causes of esophageal eosinophilia (including proton pump inhibitor responsive esophageal eosinophilia) excluded.  Effective first line treatment strategies include topical steroids, such as swallowed fluticasone or budesonide, or dietary therapy with either an elemental formula, a six-food elimination diet, or a targeted elimination diet.

45. THANK YOU

51. Maintenance therapy  Chronic disease  Long standing disease higher risk of stictures  Elemental diet and Local steroids prevent fibrosis  Options diet / local steroids  Unanswered questions  Duration  Side effects