Treatment of Eosinophilic Esophagitis: Diet, Drugs, or Dilation?

Abstract

See “Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors,” by Gonsalves N, Yang G–Y, Doerfler B, et al, on page 1451. See “Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors,” by Gonsalves N, Yang G–Y, Doerfler B, et al, on page 1451. Eosinophilic esophagitis (EoE) is a chronic, inflammatory, immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction, and histologically, by an eosinophil-predominant inflammation.1Furuta G.T. Liacouras C. Collins M.H. et al.Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment.Gastroenterology. 2007; 133: 1342-1363Abstract Full Text Full Text PDF PubMed Scopus (1334) Google Scholar, 2Liacouras C.A. Furuta G.T. Hirano I. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-20Abstract Full Text Full Text PDF PubMed Scopus (1526) Google Scholar EoE currently affects up to 1 individual among 2500 inhabitants in the United States and Europe.3Prasad G.A. Alexander J.A. Schleck C.D. et al.Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota.Clin Gastroenterol Hepatol. 2009; 7: 1055-1061Abstract Full Text Full Text PDF PubMed Scopus (373) Google Scholar, 4Hruz P. Straumann A. Bussmann C.h. et al.Escalating incidence of eosinophilic esophagitis: a 20 year prospective, population-based study in Olten County Switzerland.J Allergy Clin Immunol. 2011; 128: 1349-1350Abstract Full Text Full Text PDF PubMed Scopus (269) Google Scholar Of note, EoE has a strong gender predilection, concordantly confirmed in clinical, epidemiologic, endoscopic, and pathologic studies, demonstrating that between 70% and 80% of all cases diagnosed are males.1Furuta G.T. Liacouras C. Collins M.H. et al.Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment.Gastroenterology. 2007; 133: 1342-1363Abstract Full Text Full Text PDF PubMed Scopus (1334) Google Scholar, 2Liacouras C.A. Furuta G.T. Hirano I. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-20Abstract Full Text Full Text PDF PubMed Scopus (1526) Google Scholar Adult patients often cope for years with their swallowing difficulties and do not seek medical attention until they experience a long-lasting food impaction requiring emergency endoscopic intervention.5Straumann A. Bussmann C. Zuber M. et al.Eosinophilic esophagitis: analysis of food impaction and perforation in 251 adolescent and adult patients.Clin Gastroenterol Hepatol. 2008; 6: 598-600Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar Nevertheless, there are at least three good reasons to treat patients with clinically and histologically active EoE before this risky complication occurs: First, to enhance the quality of life because dysphagia, with its ongoing risk of food impaction, exerts a marked negative impact on the patient's daily life6Straumann A. Spichtin H.P. Grize L. et al.Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years.Gastroenterology. 2003; 125: 1660-1669Abstract Full Text Full Text PDF PubMed Scopus (632) Google Scholar; second, to reduce the risk of severe esophageal injury by preventing long-lasting food impactions, an incident occurring almost exclusively in untreated EoE5Straumann A. Bussmann C. Zuber M. et al.Eosinophilic esophagitis: analysis of food impaction and perforation in 251 adolescent and adult patients.Clin Gastroenterol Hepatol. 2008; 6: 598-600Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar; and third, to prevent esophageal damage and dysfunction caused by tissue remodeling due to unbridled eosinophilic inflammation.7Mishra A. Wang M. Pemmaraju V.R. et al.Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia.Gastroenterology. 2008; 134: 204-214Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar, 8Aceves S.S. Newbury R.O. Chen D. et al.Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids.Allergy. 2010; 65: 109-116Crossref PubMed Scopus (236) Google Scholar, 9Lucendo A.J. Arias A. De Rezende L.C. et al.Subepithelial collagen deposition, profibrogenic cytokine gene expression, and changes after prolonged fluticasone propionate treatment in adult eosinophilic esophagitis: a prospective study.J Allergy Clin Immunol. 2011; 128: 1037-1046Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar Currently, the treatment modalities for EoE include the 3 Ds: Dilation, drugs, and diet. Dilation was used by gastroenterologists for “dysphagia of unknown origin” in adults even before EoE was first recognized as a distinct entity by Attwood et al in 1993.10Attwood S.E. Smyrk T.C. Demeester T.R. et al.Esophageal eosinophilia with dysphagia, a distinct clinicopathologic syndrome.Dig Dis Sci. 1993; 38: 109-116Crossref PubMed Scopus (629) Google Scholar It has since become clear that dilation improves symptoms, but does not influence the underlying inflammatory process and today, this option is considered a second-line treatment when drugs or diets fail to control the disease.11Schoepfer A.M. Gonsalves N. Bussmann C.H. et al.Esophageal dilation in eosinophilic esophagitis: effectiveness, safety and impact on the underlying inflammation.Am J Gastroenterol. 2010; 105: 1062-1070Crossref PubMed Scopus (240) Google Scholar With respect to drugs, it is almost exclusively the systemic12Liacouras C.A. Spergel J.M. Ruchelli E. et al.Eosinophilic esophagitis: a 10-year experience in 381 children.Clin Gastroenterol Hepatol. 2005; 3: 1198-1206Abstract Full Text Full Text PDF PubMed Scopus (706) Google Scholar, 13Schaefer E.T. Fitzgerald J.F. Molleston J.P. et al.Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.Clin Gastroenterol Hepatol. 2008; 6: 165-173Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar and topically administered corticosteroids12Liacouras C.A. Spergel J.M. Ruchelli E. et al.Eosinophilic esophagitis: a 10-year experience in 381 children.Clin Gastroenterol Hepatol. 2005; 3: 1198-1206Abstract Full Text Full Text PDF PubMed Scopus (706) Google Scholar, 13Schaefer E.T. Fitzgerald J.F. Molleston J.P. et al.Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.Clin Gastroenterol Hepatol. 2008; 6: 165-173Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar, 14Konikoff M.R. Noel R.J. Blanchard C. et al.A randomized, double-blind, placebo-controlled Trial of Fluticasone Propionate for pediatric Eosinophilic Esophagitis.Gastroenterology. 2006; 131: 1381-1391Abstract Full Text Full Text PDF PubMed Scopus (509) Google Scholar, 15Dohil R. Newbury R. Fox L. et al.Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial.Gastroenterology. 2010; 139: 418-429Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar, 16Straumann A. Conus S. Degen L. et al.Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis.Gastroenterology. 2010; 139: 1526-1537Abstract Full Text Full Text PDF PubMed Scopus (421) Google Scholar that have proven their efficacy in resolving symptoms and signs of EoE. A comparison of topical with systemic corticosteroid application showed that, for efficacy, there is no significant difference between the 2.13Schaefer E.T. Fitzgerald J.F. Molleston J.P. et al.Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.Clin Gastroenterol Hepatol. 2008; 6: 165-173Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar However, topical steroids have far fewer side effects13Schaefer E.T. Fitzgerald J.F. Molleston J.P. et al.Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.Clin Gastroenterol Hepatol. 2008; 6: 165-173Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar and are therefore recommended as a first-line medication.2Liacouras C.A. Furuta G.T. Hirano I. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-20Abstract Full Text Full Text PDF PubMed Scopus (1526) Google Scholar Unfortunately, when topical or systemic corticosteroids are discontinued, the disease generally reappears rather directly, with reports citing recurrence within 3 months.13Schaefer E.T. Fitzgerald J.F. Molleston J.P. et al.Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.Clin Gastroenterol Hepatol. 2008; 6: 165-173Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar, 17Straumann A. Conus S. Degen L. et al.Long-term Budesonide maintenance treatment is partially effective for patients with eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2011; 9: 400-409Abstract Full Text Full Text PDF PubMed Scopus (311) Google Scholar Diets were first used by pediatricians based on the assumption that EoE is a new manifestation of food allergy.18Kelly K.J. Lazenby A.J. Rowe P.C. et al.Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula.Gastroenterology. 1995; 109: 1503-1512Abstract Full Text PDF PubMed Scopus (863) Google Scholar Both elemental diets with amino acid formulations18Kelly K.J. Lazenby A.J. Rowe P.C. et al.Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula.Gastroenterology. 1995; 109: 1503-1512Abstract Full Text PDF PubMed Scopus (863) Google Scholar and skin-testing based, individually tailored elimination diets19Spergel J.M. Beausoleil J.L. Mascarenhas M. et al.The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis.J Allergy Clin Immunol. 2002; 109: 363-368Abstract Full Text Full Text PDF PubMed Scopus (466) Google Scholar have shown efficacy. Independent of the patient's sensitization status, a so-called 6-food elimination diet (6-FED), an empiric concept of avoiding the 6 most common food allergens—cow's milk, soy, egg, wheat, peanuts/walnuts, and shellfish/fish—has shown in pediatric EoE patients results comparable with the other dietary approaches.20Kagalwalla A.F. Sentongo T.A. Ritz S. et al.Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2006; 4: 1097-1102Abstract Full Text Full Text PDF PubMed Scopus (560) Google Scholar The study reported by Gonsalves et al21Gonsalves N. Yang G.–Y. Doerfler B. et al.Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.Gastroenterology. 2012; 142: 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (459) Google Scholar in this issue of Gastroenterology is the first clinical trial that evaluates the efficacy of a 6-FED in adults with EoE. Fifty patients with active EoE were educated by a dietician specifically trained in allergy diet restriction. In addition to endoscopic and histologic examinations, patients underwent at baseline an allergy work-up that included history and skin prick testing. Patients were then treated for 6 weeks with 6-FED. After achieving a remission, in 20 of these 50 patients, a controlled, stepwise reintroduction process was instituted, with follow-up endoscopies and biopsies to identify specific food triggers. The 6-week dietary course led to an impressive response observed in the eosinophilic inflammation throughout the entire esophagus: Proximally, the mean peak eosinophilic density declined significantly from 34 to 8 eosinophils per high-power field, and distally, from 48 to 13. Noteworthy, at the end of the diet period, 64% of the patients showed complete histologic remission with <5 eosinophils per high-power field. Parallel to this, symptom scores decreased in 94% of the patients under the influence of the 6-FED, with a significant reduction in the median scores, from 12 to 3.5, and endoscopic abnormalities improved as well. During the reintroduction process, all patients had clinical, endoscopic, and histologic recurrence after exposure to the causal agent with a median time to symptom recurrence of 3 days. Wheat (60%) and cow's milk (50%) were identified as the leading causative agents. Of note, skin prick tests predicted only 13% of the causal agents, and 67% of the patients who had a food trigger identified by the reintroduction process had negative skin prick tests to all foods. The message of this study is important for the following 3 reasons. First, it offers a new therapeutic modality for bringing adults with active EoE into remission. This might be important in the care of patients who either respond inadequately to medical therapy or for those who refuse corticosteroids. Second, it provides new insights in the pathogenetic mechanisms of EoE, demonstrating that adult EoE is likely a food-driven disease, with wheat and milk as the leading causative agents. Third, this study indicates that adult and pediatric EoE have comparable response patterns. This adds further support to the argument that adult and pediatric EoE together represent a single entity, despite their different clinical manifestations. Nevertheless, this study clearly elucidates several weaknesses and limitations inherent to all dietary concepts: Diets are not able to cure EoE and remissions generally last not much longer than the time the dietary restriction is followed. Hypoallergenic diets currently available are not feasible as a long-term treatment when more than one staple food must be excluded. They impair substantially the quality of life and harbor the risk of nutritional deficiencies. Of note, the dietary approach in EoE cannot be compared with those in classical food allergies. In the latter, a targeted exclusion of few causative foods, based on the determination of an individual sensitization pattern, generally provides a reliable control of the symptoms. Finally, this study shows that skin prick testing might not identify the actual problem food and therefore has limited value in discovering causative agents. Nonetheless, the knowledge that wheat and cow's milk are critical food compounds in inducing and sustaining a deleterious inflammation in the esophagus is an important message. It might stimulate further investigations focusing on the ultrastructural and molecular characterization of these 2 food categories, with the purpose of developing either a practical and reasonable elimination diet or even an immunotherapy. Elimination Diet Effectively Treats Eosinophilic Esophagitis in Adults; Food Reintroduction Identifies Causative FactorsGastroenterologyVol. 142Issue 7PreviewAdults with eosinophilic esophagitis (EoE) typically present with dysphagia and food impaction. A 6-food elimination diet (SFED) is effective in children with EoE. We assessed the effects of the SFED followed by food reintroduction on the histologic response, symptoms, and quality of life in adults with EoE. Full-Text PDF Covering the CoverGastroenterologyVol. 142Issue 7PreviewEosinophilic esophagitis in adults commonly presents as dysphagia, food impaction, chest pain, reflux symptoms, or abdominal pain. The most common presentation is dysphagia to solid foods. It may also present as chest pain or reflux symptoms that are refractory to antacid therapy. In patients presenting with consistent symptoms, endoscopy establishes the diagnosis, which grossly may include linear furrowing, strictures, stacked circular rings, or whitish papules that represent eosinophilic microabscesses. Full-Text PDF