When Food Keeps Getting Stuck: Recognizing and Understanding Eosinophilic Esophagitis in Children

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1 When Food Keeps Getting Stuck: Recognizing and Understanding Eosinophilic Esophagitis in Children Jenifer R. Lightdale, MD, MPH, FASGE Division Chief, Pediatric Gastroenterology UMass Memorial Children s Medical Center

2 Disclosures A. I have the following financial relationships with the manufacturers of commercial products and/or providers of commercial services: Mead Johnson Honorarium Perrigo Paid Consultant Medtronic Paid Consultant Norgine Paid Consultant B. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation

3 Eosinophilic Esophagitis Chronic, immune/antigen mediated esophageal disease characterized Clinically by symptoms related to esophageal dysfunction AND Histologically by eosinophil predominant inflammation >1 biopsy showing 15+ eos/high power field Exclusion of other causes PPI REE Dellon, AJG, 2013

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5 Learning Objectives Recognize clinical symptoms in children associated with EoE Understand the diagnostic approach to children with EoE Discuss guidelines for appropriately treating EoE, as a chronic condition in children

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9 Natural History of EoE Not completely understood Chronic inflammation leads to Esophageal wall remodeling Fibrostenosis Stricture formation EoE accounts for 80% of food impactions in adults

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12 Liacouras, J Allergy Clin Immun, 2011

13 Typical Patient with EoE Male (3:1) Thin body habitus Atopic Asthma History of food allergy Family history of allergic and/or atopic disorders Peripheral eosinophilia on CBC

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15 Typical Patient with EoE Complain of persistent reflux symptoms, Vomiting, dysphagia, food impaction Slow eater Last at the table Chews carefully, cuts food into small pieces Gagging, food refusal, feels food going down

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17 EoE Overlap with GERD Symptoms/Heartburn Studies of EoE % of EoE study sample who c/o GERD (n) Alexander JA et al, % of 21 Gonsalves N et al, % of 50 Spergel J et al, % of 169 Iwanczak B et al, % of 74 Assa d et al, % of 149

18 Endoscopic Features of EoE Esophageal rings Linear Furrows Edema White plaques/exudates Can occur in isolation or combination

19 Endoscopic Features of EoE

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23 Histological Features of EoE Prominent eosinophilic infiltrate (H&E staining) Eosinophilic degranulation Eosinophilic microabscesses Basal layer hyperplasia Dilated intracellular spaces May be a transmural process

24 Histological Features of EoE

25 2013 Diagnostic Criteria for EoE from the American College of Gastroenterology (ACG) 1. Clinical symptoms of esophageal dysfunction 2. Pathological findings isolated to the esophagus >1 biopsy of an eosinophil predominant inflammation (15+ eosinophils/hpf) 3. Exclusion of other causes (i.e. PPI REE) Lack of response to high dose PPI

26 PPI Responsive Esophageal Eosinophilia Condition in which esophageal eosinophilia is highly responsive to treatment with PPI PPI REE currently considered distinct from EoE Mechanism remains unclear Gastroesophageal reflux responsive to acid suppression? Evidence of anti inflammatory effect of PPI? Combination of GERD and EoE?

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28 2013 American College of Gastroenterology Guidelines All patients with suspected EoE should receive a two month course of PPI, followed by endoscopy with biopsies [as a repeat procedure if necessary] to exclude PPI REE Dellon, AJG, 2013

29 Initial Steps in Evaluation Refer to GI for endoscopy Start PPI Consider UGI imaging

30 Small Caliber Esophagus

31 Ringed Esophagus

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33 Options for Clinical Management Dietary exclusions Elemental diet 6 food elimination Pharmacologic PPI Steroids (Topical, Systemic) Endoscopic dilation

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37 Six food elimination diet (SFED) Milk, soy, egg, wheat, beef, fish 6 weeks Clinicopathological remission with SFED Eosinophilia returns when diet liberalized Gonsalves et al, Gastroenterology 2012

38 Fast Forward to 2016 EoE is a chronic immune mediated inflammatory condition with no current curative therapy At risk for fibrostenosis and stricture development Current palliative approaches Elimination diet PPI Topical steroids Treatments used alone or in combination To minimize disease risks, while preserving quality of life

39 Eosinophils Th2 cells Mast Cells Basophils Immune Cells in EoE

40 Potential Therapeutic Targets Immune therapy directed at IL 13 and eotaxin Prostaglandin D2 inhibitor CRTH2 Other FDA approved Phase I trials ongoing

41 Current Pharmacologic Therapy PPI may be effective adjunct Topical glucocorticoids Fluticasone (220mcg inhaler) Budesonide (1 2mg daily) Lead to decrease in eosinophil counts Recurrence of symptoms when discontinued Associated with candidal esophagitis Systemic steroids effective, but NOT for maintenance

42 Budesonide Oral viscous budesonide (2mg slurry) Randomized placebo controlled study OVB=15, placebo 9 Significant reduction in symptoms and eosinophilia Dohil 2010

43 Treatment End Points Ideal = Complete resolution of symptoms, inflammation and remodeling Reality = EoE is currently a chronic disease with no curative treatment High likelihood of symptom recurrence after discontinuing treatment

44 Treatment End Points Reasonable = A balance Use treatment options to minimize symptoms and prevent disease complications Preserve quality of life Limit adverse effects of treatment

45 Changes You May Want to Make in Your Practice Recognize the presenting symptoms of EoE Chronic inflammatory disease Immune mediated, food allergen induced Highly associated with atopy Relatively common worldwide Understand there is no current curative therapy

46 Take Home Points Diagnosis of EoE is clinicopathologic Consider other ee s Particularly PPI REE Tailor therapies to minimize disease associated inflammation and fibrostenosis Treatment should minimize disease risks, while preserving quality of life

47 Thank you!