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Eosinophilic Esophagitis

November 2005



Eosinophilic Esophagitis (EE): Questions and Answers



What is an Eosinophil?

Eosinophils, a type of white blood cell, are an important part of the immune system, helping us fight off certain types of infections, such as parasites. Many different problems can cause high numbers of eosinophils in the blood including allergies (food and environmental), parasite infection, eosinophil associated gastrointestinal disorders, leukemia, and other problems. When eosinophils occur in higher than normal numbers in the body, without a known cause, an eosinophilic disorder may be present.

Eosinophilic disorders are further defined by the area affected. For instance, eosinophilic esophagitis means abnormal numbers of eosinophils in the esophagus. Separate files are available for individual disorders: Eosinophilic esophagitis, Eosinophil-associated gastrointestinal disorders, and Hypereosinophilic syndrome.





Image 1: Eosinophil, Courtesy of Dr. Margaret Collins



What is EE?

Eosinophilic esophagitis is characterized by the infiltration of a large number of eosinophils, a type of white blood cell, in the esophagus (the tube connecting the mouth to the stomach). Eosinophils are an important part of the immune system, helping us fight off certain types of infections, such as parasites. A variety of stimuli may trigger this abnormal production and accumulation of eosinophils, including certain foods. Eosinophilic esophagitis means eosinophils infiltrating the esophagus, –itis means swelling. People with EE commonly have other allergic diseases such as asthma or eczema. EE affects people of all ages, gender and ethnic backgrounds. In certain families, there may be an inherited (genetic) tendency.




Image 2: Upper gastrointestinal tract



Eosinophils are not normally present in the esophagus, although they may be found in small numbers in other areas of the gastrointestinal tract. Diseases other than EE can cause eosinophils in the esophagus including gastroesophageal reflux diseases (GERD), food allergy, and inflammatory bowel disease. EE cannot be accurately diagnosed without first treating for reflux with acid blocking medicines, such as proton pump inhibitors.

What are the symptoms of EE?

Symptoms vary from one individual to the next and may differ depending on age. Vomiting may occur more commonly in young children and difficulty swallowing in older individuals. Common symptoms include:

  • Reflux that does not respond to usual therapy (which includes proton pump inhibitors, a medicine which stops acid production in the stomach)

  • Difficulty swallowing (dysphagia)

  • Food impactions (food gets stuck in the throat)

  • Nausea and Vomiting

  • Failure to thrive (poor growth or weight loss)

  • Abdominal or chest pain

  • Poor appetite

  • Malnutrition

  • Difficulty sleeping


How is EE diagnosed?

In individuals with symptoms consistent with EE, an upper endoscopy with biopsies is needed for the diagnosis. The endoscopy is often performed after treatment with reflux medications have failed to relieve the symptoms. Medications for reflux include proton pump inhibitors or histamine-2 blockers.

During an upper endoscopy, the gastroenterologist looks at the esophagus, stomach and duodenum (first part of the small bowel) through an endoscope (small tube inserted through the mouth) and takes multiple small tissue samples (biopsies) which the pathologist reviews under the microscope. Even if the esophagus appears normal, the biopsies may show EE. A high number of eosinophils (counted per high power field) suggest the diagnosis of EE. GERD also causes eosinophils in the esophagus, but typically far fewer. The pathologist will also look for tissue injury, swelling and thickening of the esophageal layers. With EE, the eosinophils are limited to the esophagus and not found in other areas. Once the diagnosis of EE is confirmed, food allergy testing is typically recommended to guide treatment. Skin prick testing to different foods is the most common type of allergy testing.

Treatment

  • Dietary

  • Medications


Most children and adults with EE respond favorably to dietary treatments. The dietary restrictions are guided by food allergy testing and ‘fine-tuned’ with food trials once the symptoms have resolved.

Elimination diets, in which all ‘positive’ foods on allergy testing are removed from the diet, are one type of dietary treatment. An elimination diet may be the only treatment needed for some individuals with eosinophilic esophagitis.

Elemental diets, in which all sources of protein are removed from the diet, are another dietary therapy. The elemental diet includes only an amino acid formula (building blocks of protein), no whole or partial proteins. Simple sugars, salt and oils are permitted on an elemental diet.

Food trials involve adding back one ingredient at a time to determine specific foods causing a reaction. Food trials begin after symptoms resolve and eosinophils have cleared.

Medications for EE most commonly include steroids to control inflammation and suppress the eosinophils. Steroids are used if dietary measures do not resolve the symptoms. Steroids can be taken orally, intravenously or topically (swallowed from an asthma inhaler).

Patients with EE may require additional endoscopies to assess how the esophagus is responding to specific treatment.

The initial diagnosis of EE can be overwhelming and often affects the entire family. A positive attitude and a focus on non-food activities go a long way in learning to live with EE. With proper treatment, individuals with EE can lead a normal life.



Copyright © 2005, American Partnership for Eosinophilic Disorders (APFED), all rights reserved. Reprinted with permission.

About APFED:
American Partnership for Eosinophilic Disorders (APFED) is a non-profit organization dedicated to patients and their families coping with eosinophilic disorders. APFED's mission is Education, Awareness, Support and Research. All medical information is reviewed for accuracy by its medical advisory board.


References:
Updated 5-5-05, Wendy Book, mail@apfed.org

  1. Liacouras CA, Ruchelli E. Eosinophilic esophagitis. Curr Opin Pediatr. 2004 Oct;16(5):560-6.

  2. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004 Aug 26;351(9):940-1.

  3. Dahms BB. Reflux esophagitis: sequelae and differential diagnosis in infants and children including eosinophilic esophagitis. Pediatr Dev Pathol. 2004 Jan-Feb;7(1):5-16. Review

  4. Arora AS, Yamazaki K. Eosinophilic esophagitis: asthma of the esophagus? Clin Gastroenterol Hepatol. 2004 Jul;2(7):523-30. Review.

  5. Ahmad M, Soetikno R, Ahmed A. The differential diagnosis of eosinophilic esophagitis. J Allergy Clin Immunol 2004;30(3):242-244

  6. Fox V, Nurko S, Furuta G. Eosinophilic Esophagitis: It’s not just kid’s stuffGastrointestinal Endoscopy 260-270, Vol 56, No 2, 2002

  7. Furuta GT, Nurko S, Bousvaros A, et al. The spectrum of pediatric gastroesophageal reflux. JAMA 2000;284(24)

  8. Liacouras CA. Eosinophilic esophagitis in children and adults. J Pediatr Gastroenterol Nutr. 2003 Nov-Dec;37 Suppl 1:S23-8

  9. Liacouras C, Markowitz JE. Eosinophilic Esophagitis: A Subset of Eosinophilic Gastroenteritis. Current Gastroenterology Reports, 1999 1:253-258

  10. Markowitz JE and Liacouras CA. Eosinophilic Esophagitis. Gastroenterology Clinics of NA. Sept 2003

  11. Orenstein S, Shalaby T, DiLorenzo C, Putnam PE. The Spectrum of Pediatric Eosinophilic Esophagitis Beyond Infancy: A Clinical Series of 30 Children. American Journal of Gastroenterology 2000; 95:1422-1430

  12. Sampson HA. Food Allergy. J Allergy Clin Immunol. 2003;111:S540-547

  13. Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology. 2003 Dec;125(6):1660-9

  14. Walsh SV, Antonioli DA, Goldmann H, Fox VL, Bousvaros A, Leichtner AM, and Furuta GT. Allergic Esophagitis in Children. A Clinicopathological Entity. American Journal of Surgical Pathology1999, 23(4):390-396

Clinical Features
  1. Sant'Anna AM, Rolland S, Fournet JC, Yazbeck S, Drouin E. Eosinophilic Esophagitis in Children: Symptoms, Histology and pH Probe Results. J Pediatr Gastroenterol Nutr. 2004 Oct;39(4):373-377

  2. Lim JR, Gupta SK, Croffie JM, Pfefferkorn MD, Molleston JP, Corkins MR, Davis MM, Faught PP, Steiner SJ, Fitzgerald JF. . White specks in the esophageal mucosa: An endoscopic manifestation of non-reflux eosinophilic esophagitis in children. Gastrointest Endosc. 2004 Jun;59(7):835-8.

  3. Straumann A, Spichtin HP, Bucher KA, Heer P, Simon HU. Eosinophilic esophagitis: red on microscopy, white on endoscopy. Digestion. 2004;70(2):109-16. Epub 2004 Sep 20.

  4. Steiner SJ, Gupta SK, Croffie JM, Fitzgerald JF. Correlation between number of eosinophils and reflux index on same day esophageal biopsy and 24 hour esophageal pH monitoring. Am J Gastroenterol. 2004 May;99(5):801-5.

  5. Attwood SEA, Smyrk TC, Demeester TR, Jones JB. Esophageal Eosinophilia with Dysphagia. A Distinct Clinicopathologic Syndrome. Digestive Disease Science, 1993, 38: 109-116

  6. Brown LF, Goldman H, Antonioli DA. Intraepithelial Eosinophils in Endoscopic Biopsies of Adults with Reflux Esophagitis. American Journal of Pathology, 1984 8:899-905

  7. Cheung KM, Oliver MR, Cameron DJ, Catto-Smith AG, Chow CW. Esophageal eosinophilia in children with dysphagia. J Pediatr Gastroenterol Nutr. 2003 Oct;37(4):498-503

  8. Croese J, Fairley SK, Masson JW, Chong AK, Whitaker DA, Kanowski PA, Walker NI. Clinical and endoscopic features of eosinophilic esophagitis in adults. Gastrointestinal Endosc. 2003 Oct;58(4):516-22

  9. Cury EK, Schraibman V, Faintuch S. Eosinophilic infiltration of the esophagus: gastroesophageal reflux versus eosinophilic esophagitis in children--discussion on daily practice. J Pediatr Surg. 2004 Feb;39(2):e4-7

  10. Desai T, Goldstein N, Stecevic V, Badizadegan K, Furuta GT. Esophageal Eosinophilia is Common among Adults with Esophageal Food Impaction. Gastroenterology, 2002; 122:M1723

  11. Khan S, Orenstein SR, DiLorenzo C, Kocoshis SA, Putnam PE, Sigurdsson L, Shalaby TM. Eosinophilic esophagitis: strictures, impactions, dysphagia. Dig Dis Sci. 2003 Jan;48(1):22-9

  12. Potter JW, Saeian K, Staff D, Massey BT, Komorowski RA, Shaker R, Hogan WJ. Eosinophilic esophagitis in adults: An emerging problem with unique esophageal features. Gastrointestinal Endosc. 2004 Mar;59(3):355-61

  13. Rothenberg ME, Mishra A, Collins MH, Putnam PE. Pathogenesis and Clinical Features of Eosinophilic Gastroenteritis. Journal of Allergy and Clinical Immunology, 2001, 108:891-894

  14. Straumann A, Rossi L, Simon HU, Heer P, Spichtin HP, Beglinger C.. Fragility of the esophageal mucosa: a pathognomonic endoscopic sign of primary eosinophilic esophagitis? Gastrointestinal Endosc 2003 Mar;57(3:407-12

  15. Vasilopoulos S, Murphy P, Auerbach A, Massey BT, Shaker R, Stewart E. et al. The Small-Caliber Esophagus: An Unappreciated Cause of Dysphagia for Solids in Patients with Eosinophilic Esophagitis. Gastrointestinal Endoscopy, 2002, 55:99-106

Etiology
  1. Braun-Fahrlander C, Rieldler J, Herz U, et al. Environmental exposure to endotoxin and its relation to asthma in school –age children. N Engl J Med 2002;347(12):869-876

  2. Cury EK, Schraibman V, Faintuch S. Eosinophilic infiltration of the esophagus: gastroesophageal reflux versus eosinophilic esophagitis inchildren--discussion on daily practice. J Pediatr Surg. 2004 Feb;39(2):e4-7.

  3. Fogg, Rachelli, and Spergel. Pollen and Eosinophilic Esophagitis. Jounal of Allergy and Clinical Immunology. 2003 Oct;112(4):796-7.

  4. Fox V, Nurko S, Teitelbaum JE, Badizadegan K, Furuta G. High resolution EUS in Children with Eosinophilic “Allergic” Esophagitis Gastrointestinal Endoscopy, 30-36, Vol. 57, No. 1 2003

  5. Jean-Francois B. Mechanisms of disease - The effect of infections on susceptibility to autoimmune and allergic diseases N Engl J Med 2002;347(12):911-918

  6. Latcham F, Merino F, Lang A, et al. A consistence pattern of immunodeficiency and subtle enteropathy in children with multiple food allergy. Journal of Pediatrics 2003;143(1)

  7. Spergel JM, Beausoleil JL, Mascarenhas M, et al. The use of Skin Prick Tests and Patch Tests to identify causative foods in Eosinophilic Esophagitis. Journal of ClinicalImmunology 2002, 109:363-368

  8. Straumann A, Bauer M, Fischer B, Blaser K, Simon HU. Idiopathic Eosinophilic Esophagitis is Associated with a Th2-type Allergic Inflammatory Response. Journal of Allergy and Clinical Immunology 2001: 108:954-961

  9. Straumann A, Simon H.-U. The physiological and pathophysiological roles of eosinophils in the gastointestinal tract. Allergy 2004;59:15-25

  10. Weiss ST. Eat Dirt- The hygiene hypothesis and allergic diseases. N Engl J Med 2002;347(12)

Formula, Corticosteroids and other treatment

  1. Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Elemental Diet is an Effective Treatment for Eosinophilic Esophagitis in Children and Adolescents. American Journal of Gastroenterology, 2003 Vol 98 No. 4, 777-782

  2. Kelly K, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic Esophagitis Attributed to Gastroesophageal Reflux: Improvement with an Amino Acid-Based Formula. Gastroenterology, 1995, 1503-1512

  3. Gawrieh S, Shaker R. Treatment options for eosinophilic esophagitis: montelukast. Curr Gastroenterol Rep. 2004 Jun;6(3):189

  4. Attwood SE, Lewis CJ, Bronder CS, Morris CD, Armstrong GR, Whittam J. Eosinophilic oesophagitis: a novel treatment using Montelukast. Gut. 2003 Feb;52(2):181-5.

  5. Elkon KB, Sher R, Seftel HC. Immunological studies of eosinophilic gastro-enteritis and treatment with disodium cromoglycate and beclomethasone dipropionate. S Afr Med J. 1977 Nov 12;52(21):838-41.

  6. Friesen CA, Kearns GL, Andre L, et al. Clinical efficacy and pharmacokinetics of montelukast in Dyspeptic children with duodenal eosinophilia. Journal of Ped Gastr and Nutr. 2004;38:343-351

  7. Heine RG. Pathophysiology, diagnosis and treatment of food protein-induced gastrointestinal diseases. Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):221-9.

  8. Khan S, Henderson WA. Treatment of Eosinophilic Esophagitis in Children. Curr Treat Options Gastroenterol. 2002 Oct;5(5):367-376

  9. Khan S, Orenstein SR. Eosinophilic gastroenteritis: epidemiology, diagnosis and management. Paediatr Drugs. 2002;4(9:563-70. Review.

  10. Kukuruzovic R, Elliott E, O'Loughlin E, Markowitz J. Non-surgical interventions for eosinophilic oesophagitis. Cochrane Database Sys Rev 2004;3:CD004065

  11. Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary Eosinophilic Esophagitis in Children: Successful Treatment with Oral Corticosteroids. Journal of Pediatric Gastroenterology and Nutriion. 1998, 26:380-385

  12. Ruchelli E, Wenner W, Voytek T, Brown K, Liacouras C. Severity of Esophageal Eosinophilia Predicts Response to Conventional Gastroesophageal Reflux Therapy.Pediatric and Developmental Pathology, 1999. 2, 15-18.

Topical Steroid Therapy and EE
  1. Noel RJ, Putnam PE, Collins MH, Assa'ad AH, Guajardo JR, Jameson SC, Rothenberg ME. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2004 Jul;2(7):568-75.

  2. Arora AS, Perrault J, Smyrk TC. Topical corticosteroid treatment of dysphagia due to eosinophilic esophagitis. Mayo Clinic Proc.2003 Jul;78(7);830-5

  3. Teitelbaum JE, Fox VL, Twarog FJ, Nurko S, Antonioli D, Gleich G, Badizadegan K, and Furuta GT. Eosinophilic Esophagitis in Children: Immunopathological Analysis and Response to Fluticasone Propionate. Gastroenterology 2002. 122:1216-1225

  4. Cave A, Arlett P, Lee E. Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects. Pharmacol Ther. 1999;83(3):153-79

  5. Drake AJ, Howells RJ, Shield JPH, et al. Symptomatic adrenal insufficiency presenting with hypoglycemia in children with asthma receiving high dose inhaled fluticasone proprionate. British Medical Journal 2002;324(7345):1081-1082

  6. Eid N, Morton R, Olds B, et al. Decreased morning serum cortisol levels in children with asthma treated with inhaled fluticasone proprionate. Pediatrics 2002;110(5):1030-1

  7. England RW, Nugent JS, Grathwohl KW, et al. High-dose inhaled fluticasone and delayed hypersensitivity skin testing. Chest 2003;123(4):1014-1017

  8. Falcoz C, Oliver R, McDowall JE, et al. Bioavailability of orally administerd micronised fluticasone proprionate. Clin Pharmacokinet 2002;39 Suppl 1:9-15

  9. Faubion, Jr. WA, Perrault J, Burgart LJ, Zein NN, Clawson M, Freese DK. Treatment of Eosinophilic Esophagitis with Inhaled Corticosteroids. Journal of Pediatric Gastroenterology and Nutriion 27:90-93, July 1998

  10. Harrison TW. Systemic availability of inhaled budesonide and fluticasone proprionate: healthy versus asthmatic lungs. Bio Drugs 2001;15(6):405-11

  11. Howland WC 3rd. Fluticasone proprionate: topical or systemic effects? Clin Exp 1996;26 Suppl 3:18-22

  12. Kemp JP, Osur S, Shrewsbury SB, et al. Potential effects of fluticasone proprionate on bone mineral density in patients with asthma: A 2-year randomized, double –blind, placebo-controlled trial. Mayo Clinic Proc. 2004;79:458-466

  13. Krishnaswami S, Hochhaus G, Derendorf H. An interactive algorithm for the cumulative cortisol suppression during inhaled corticosteroid therapy. AAPS PharmSci. 2002;2(3):E22

  14. Mohammed A. Adrenal insufficiency after treatment with fluticasone: Dose-response curve should have been highlighted. Briish Medical Journal 2002;325(7368):837

  15. Nguyen KL, Lauver D, Kim I, et al. The effect of a steroid "burst" and long-term, inhaled fluticasone proprionate on adrenal reserve. Ann Allergy Asthma Immunol. 2003;9(1):38-43

  16. Noel RJ, Putnam PE, Collins MH, et al. A subset of children with refractory allergic eosinophilic esophagitis are resistant to swallowed fluticasone proprionate. Pediatric Gastroenterol Nutr 2002;35(3): 447-456

  17. Patel L, Clayton P. Adrenal insufficiency after treatment with fluticasone: Lowest possible dose of Glucocorticoids should be given. British Medical Journal 2002;325(7368):837-838

  18. Thorsson L, Dahlstrom K, Edsbacker S, et al. Pharmacokinetics and systemic effects of inhaled fluticasone proprionate in healthy subjects. Br. Journ Clin Pharmacol 1997;43(2):155-61


Food Allergies
  1. Sampson HA. Food Allergies. J Allergy Clin Immunol 2004;113:805-819.

  2. Heine RG. Pathophysiology, diagnosis and treatment of food protein-induced gastrointestinal diseases. Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):221-9.

  3. Munoz-Furlong A. Daily Coping Strategies for Patients and their Families. Pediatrics 2002;111:1654-






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