Esophageal Dysphagia prior to 1995: Structural Etiologies. Eosinophilic Esophagitis. Eosinophilic Esophagitis Eosinophilic Esophagitis (EoE)
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1 Case sentation 42 year old male presents with 12 years of intermittent dysphagia for solids that localizes to his mid sternum. Symptoms have been progressive; now occurring on a daily basis. He has had repeated food impactions after eating meat or bread that last up to 1 hour. He was seen in the ER on 2 occasions for endoscopic disimpaction. It takes the patient over an hour to complete his meals. He is afraid to talk while eating and embarrassed when he needs to leave the table during meals to vomit. The patient was previously diagnosed with GERD and then esophageal spasm. He has mild heartburn a few times a year. PPI trials have not relieved his symptoms. History of childhood asthma and allergic rhinitis. localized to neck, nasal regurgitation, aspiration, associated ENT symptoms Oropharyngeal Solid & Liquid Propulsive localized to chest or neck, food impaction Esophageal Solid Structural Esophageal prior to 1995: Structural Etiologies Schatzki ring Peptic stricture Esophageal neoplasm Esophageal diverticula Esophageal web Iatrogenic (radiation,surgery) Congenital esophageal stenosis Eosinophilic Esophagitis Ikuo Hirano, MD Gastroenterology Division Northwestern University Medical School What is and how common is it? What are the clinical features of? What are the complications of? What is the best treatment for? Eosinophilic Esophagitis 2011 is a clinicopathologic disease Clinically, is characterized by symptoms related to esophageal dysfunction Pathologically, 1 or more biopsy specimens must show eosinophil-predominant inflammation. With few exceptions, 15 eos/hpf is considered a minimum threshold for the diagnosis of The disease is isolated to the esophagus, and other causes of esophageal eosinophilia should be excluded Liacouras et al. Eosinophilic Esophagitis Updated Consensus Recommendation. J Allergy Clin Immunol
2 valence per 100,000 Historical Notes valence of Eosinophilic Esophagitis in Children and Adults =GERD Winter 1982, Brown 1984 as food allergy Kelly Sampson case reports of in adults Dobbins 1977, Landres 1978, Picus case series of in adults Attwood 1993, Straumann Noel, Rothenberg N Engl J Med 351;9 2005, Straumann J Allergy Clin Immunol. 115(2) Epidemiology of in US Health insurance database of 11.5 million; valence based on ICD9 (530.13) 57/100,000 What is and is it really new? What are the clinical features of? What are the complications of? What is the best treatment for? Dellon Clin Gastro Hep 2014; 12 (4): 589 Clinical Features in Adults Age (yrs) 37 (14-81) Male 72% Mean Duration 5 yrs Atopic History 74% Food Allergy History 19% 82% Frequency 1x/week Food Impaction 76% Heartburn 29% Chest pain 8% (n=387) sentation of in Children is Distinct from Adults % Adult p < 0.05 Children Gonsalves. Gastroenterol 2005;128(4)S2:A7. 2
3 Etiology of Retrospective Study 1371 Adults Undergoing EGD for dysphagia Histology in : Increased Esophageal Eosinophils (>15 Eos/hpf) GERD GERD Kidambi, Toto, Hirano World J Gastro 2012 Role of Endoscopy in Classify and grade severity of characteristic findings of Edema, Rings, Exudates, Furrows, Strictures (EREFS) Classification and grading of endoscopically detected esophageal features in Endoscopic Reference Score (EREFS) NORMAL Edema (pallor) Rings ( trachealization ) Exudates (plaques) Furrows (vertical lines) Stricture Normal Eosinophilic Esophagitis Mucosal fragility Narrow caliber esophagus Hirano Moy Heckman Thomas Gonsalves Achem. Gut Hirano Moy Heckman Thomas Gonsalves Achem. Gut Classification and grading of endoscopically detected esophageal features in Endoscopic Reference Score (EREFS) Inflammatory NORMAL Edema (pallor) Rings ( trachealization ) Exudates (plaques) Furrows (vertical lines) Stricture Fibrostenotic Mucosal fragility Narrow caliber esophagus Hirano Moy Heckman Thomas GonsalvesAchem. Gut Endoscopic Reference Score (EREFS) Grade 0 Grade 1 Grade 2 Grade 3 Edema (loss vascular markings) Grade 0: Distinct vascularity Grade 1: Decreased Grade 2: Absent Rings (trachealization) Grade 0: None Grade 1: Mild (ridges) Grade 2: Moderate (distinct rings) Grade 3: Severe (not pass scope) Exudate (white plaques) Grade 0: None Grade 1: Mild (<10% surface area) Grade 2: Severe (>10% surface area) Furrows (vertical lines) Grade 0: None Grade 1: Mild Grade 2: Severe (depth) Stricture Grade 0: Absent Grade 1: sent Hirano Gut
4 Endoscopic Reference Score (EREFS) Inter and intraobserver agreement validated in both US and European studies (Hirano, Gut 2013; 62(4):489-95, van Rhijn, Endoscopy 2014; 46(12): ) Endoscopic severity as measured by EREFS is a major determinant of physician assessment of disease activity (Schoepfer, Am J Gastro 2015; 110(3):402-14) EREFS severity associated with food impaction outcomes as well as symptom severity (Nicodeme, Clin Gastro Hep 2013; 11: , Schoepfer Gastroenterology 2014; 147(6): ) GERD vs Eosinophilic Esophagitis (): circa 2005 GERD 15 PPI Responsive Esophageal Eosinophilia Prospective Study, 712 adults with EGD; 35 pts with > 15 eos/hpf; Rabeprazole 20 mg BID x 2 mos; PPI response < 5 eos/hpf Prospective studies have demonstrated a 33-50% histologic response in adults with suspected Peterson Fang Dig Dis Sci 2009; Molina-Infante, Gonzalez-Nunez Clin Gastro Hep 2011; Moawad Wong Am J Gastro 2013 GERD PPI vs Response PPI responsive = GERD?? PPI responsive esophageal eosinophilia (PPIREE) Molina-Infante, Gonzalez-Nunez Clin Gastro Hep 2011 What is and how common is it? What are the clinical features of? What are the complications of? What is the best treatment for? Complications of in Adults Impaired quality of life Food impaction Esophageal stricture Esophageal perforation Malnutrition No reports of progression to cancer or eosinophilic gastroenteritis 4
5 is One of the Most Common Causes of Food Impaction identified in 11-55% of adults with food impaction Complications of : Narrow caliber esophagus Desai Furuta GastrointestEndosc 2005;61: Gonsalves Sanger Zhang Hirano Am J Gastro 2006;101, S66 Kerlin Jones Remedios Campbell J Clin Gastro 2007;41: Byrne Peterson Fang Dig Dis Sci 2007; 52: Hirano Aceves Gastro Clin North Am 2014;43(2): Fibrostenotic Complications of Eosinophilic Esophagitis : A Conceptual Model of Clinical Subtypes Based On Inflammation and Tissue Remodeling Normal inflammation inflammation + Fibrosis Fibrosis EGD.. Histo Risk of esophageal stricture doubled with each decade of untreated disease Slide courtesy of Alain Schoepfer MD Schoepfer AM, Safroneeva E, et al, Gastroenterology 2013 Children Adults Hirano Aceves Gastro Clin North Am 2014;43(2): What is and how common is it? What are the clinical features of? What are the complications of? What is the best treatment for? Increasing Incidence of Eosinophilic Esophagitis: Hygiene Hypothesis? Bach JF. New Engl J Med
6 Treatment Options for Endoscopic Therapy Medical Therapy Topical steroids Systemic steroids Leukotriene antagonists (montelukast) Mast cell stabilizers (cromolyn sodium) Immunomodulators (CRTH2 antagonist, azathioprine) Biologics (anti IL5, anti IL13, anti TNF, anti IgE) Dietary Therapy Empiric elimination diet Allergy testing directed elimination diet Elemental diet Topical steroids Swallowed - not inhaled Fluticasone 220 mcg 2-4 puffs BID Budesonide mg BID Ciclesonide (aerosolized) mcg BID Liquid formulations are mixed with substance (sucralose, honey, syrup) to increase viscosity Patients instructed to fast for 30 minutes after administration Topical steroids significantly improve histopathology in : Meta-analysis Eosinophilic Esophagitis: Dietary Treatment Elemental diet: Amino acid, carbohydrate, lipid, vitamin/mineral based formula (Kelly Sampson Gastroenterology 1995) Directed elimination diet: Exclusion of specific food allergens based on the results of allergy testing (skin prick & patch) (Spergel, Liacouras Ann Allergy Asthma Immunol 2005) Non-directed elimination diet: Empiric exclusion of common food allergens (Kagalwalla, Li Clin Gastro Hep 2006) Sawas et al Aliment Pharm Ther 2015 Six Food Elimination Diet (SFED) Prospective Study in Adults (n=50) 6 wk elimination (milk, soy, nuts, eggs, wheat, seafood/shellfish) Before Diet After Diet Gonsalves, Ritz, Yang, Ditto, Hirano. Gastroenterology 2012 Effect of duction of Foods on Esophageal Eosinophilia Proximal Esophagus Distal Esophagus Eos/ hpf P <0.01 Gonsalves. Gastroenterology 2012; 142(7):
7 Effect of duction of Foods on Esophageal Eosinophilia Proximal Esophagus Distal Esophagus SFED: Not Just for Kids Anymore 73% response in children; 72% response in adults Eos/ hpf Food triggers identified by reintroduction: Wheat (60%), milk(50%), soy (10%), egg (5%) 15% of patients with more than one food trigger SPT accurately predicted 13% of food triggers. 67% of patients with food trigger had negative SPT P <0.01 Gonsalves. Gastroenterology 2012; 142(7): Arias Diet Interventions for : Systematic review and meta-analysis. Gastroenterology 2014 Emerging Pharmaceutical Therapies for Compound Company Mechanism_ TOPICAL STEROID Budesonide tablet Falk Corticosteroid Budesonide liquid Shire (Meritage) Corticosteroid BIOLOGIC Mepolizumab Glaxo Smith Kline Anti-IL-5 Rezlizumab Teva Anti-IL-5 Omalizumab Novartis Anti-IgE QAX576 Novartis Anti-IL-13 RPC4046 Receptos Anti-IL-13 Dupilumab Regeneron Anti-IL-4/IL-13 MISCELLANEOUS Cromolyn sodium Investigator initiated Mast cell stabilizer OC Oxagen CRTH2 antagonist Montelukast Merck Leukotriene recept antag Losartan Investigator initiated ACE inhibitor Sulcralfate Investigator initiated Mucosal protectant Updated from Kern Hirano Expert Opinion Emerging Drugs 2013 Suggested Algorithm for Management Of Eosinophilic Esophagitis Symptom relief & Normal histology PPI Responsive Esophageal Eosinophilia ( vs GERD) Suspected PPI x 8 wks EGD with Bx Persistent Symptoms and Pathology Elimination diet Dose topical Systemic steroid Biologic therapy? Persistent dysphagia with stricture Esophageal dilation > 15 Eos/hpf EGD with Bx Topical steroid Dietary therapy Symptom relief & Normal histology Consider Maintenance Therapy Hirano. Eosinophilic Esophagitis (Liacouras Ed) : Interdisciplinary Approach Gastroenterology Nirmala Gonsalves MD, Ikuo Hirano MD, Peter Kahrilas MD, John Pandolfino MD, Christine Ebert BS, Angelika Zalewski BS Allergy & Immunology Paul Bryce PhD, Bruce Bochner MD, Anne Ditto MD, Carol Saltoun MD, Anju Peters MD, Paul Greenberger MD, Robert Schleimer PhD Pathology Guang-Yu Yang MD, Sam Rao MD Nutrition Bethany Doerfler RD, Sally Ritz RD Behavioral Medicine Laurie Keefer PhD, Tiffany Taft PhD Collaborators TIGERS, CEGIR, Alex Straumann MD (Bern), Alain Schoepfer MD (Lucerne), Sami Achem MD (Mayo), David Katzka (Mayo), Steve Ackerman PhD (Univ Colorado), Glenn Furuta (Denver), Amir Kagalwalla MD & Barry Wershil MD (Lurie Childrens) Research Support: ASGE, FDA, NIH, RDCRN Medical students, residents, GI fellows Patients What is? A recently identified chronic, immune/antigen driven esophageal disease. Affects 5-10/10,000. What are the clinical features of? esp. in younger males with h/o atopy; PPI responsive esophageal eosinophilia: GERD vs What are the complications of? Esophageal stricture, food impaction, perforation What is the best treatment for? Topical steroids and elimination diet are highly effective; Esophageal dilation for strictures 7
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