Dual response to dietary/topical steroid and proton pump inhibitor therapy in adult patients with eosinophilic esophagitis
2015; Elsevier BV; Volume: 137; Issue: 3 Linguagem: Inglês
10.1016/j.jaci.2015.07.033
ISSN1097-6825
AutoresAlfredo J. Lucendo, Ángel Arias, Jesús González‐Cervera, José María Olalla, Javier Molina‐Infante,
Tópico(s)Eosinophilic Disorders and Syndromes
ResumoEosinophilic esophagitis (EoE) is a common cause of chronic esophageal symptoms characterized by an eosinophil-rich inflammatory infiltrate limited to the esophagus.1Liacouras C.A. Furuta G.T. Hirano I. Atkins D. Attwood S.E. Bonis P.A. 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 (1578) Google Scholar Despite being first categorized as a distinct clinicopathological disorder 2 decades ago,2Attwood S.E. Smyrk T.C. Demeester T.R. Jones J.B. Esophageal eosinophilia with dysphagia: a distinct clinicopathologic syndrome.Dig Dis Sci. 1993; 38: 109-116Crossref PubMed Scopus (652) Google Scholar, 3Straumann A. Spichtin H.P. Bernoulli R. Loosli J. Vögtlin J. Idiopathic eosinophilic esophagitis: a frequently overlooked disease with typical clinical aspects and discrete endoscopic findings [in German].Schweiz Med Wochenschr. 1994; 124: 1419-1429PubMed Google Scholar EoE has rapidly become recognized in recent years as the most prevalent cause of chronic dysphagia among children and young adults in Western countries.4Hruz P. Straumann A. Bussmann C. Heer P. Simon H.U. Zwahlen M. et al.Swiss Study GroupEscalating 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 (278) Google Scholar, 5Arias A. Lucendo A.J. Prevalence of eosinophilic oesophagitis in adult patients in a central region of Spain.Eur J Gastroenterol Hepatol. 2013; 25: 208-212Crossref PubMed Scopus (70) Google Scholar, 6Dellon E.S. Jensen E.T. Martin C.F. Shaheen N.J. Kappelman M.D. Prevalence of eosinophilic esophagitis in the United States.Clin Gastroenterol Hepatol. 2014; 12: 589-596Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar Increasing knowledge of the disease has led to gradual changes in interpreting the eosinophilic infiltration within the esophageal mucosa, and these changes are reflected in the differing guidelines categorizing EoE since 2007.1Liacouras C.A. Furuta G.T. Hirano I. Atkins D. Attwood S.E. Bonis P.A. 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 (1578) Google Scholar, 7Furuta G.T. Liacouras C.A. Collins M.H. Gupta S.K. Justinich C. Putnam P.E. et al.First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. 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 (1371) Google Scholar, 8Dellon E.S. Gonsalves N. Hirano I. Furuta G.T. Liacouras C.A. Katzka D.A. American College of Gastroenterology. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE).Am J Gastroenterol. 2013; 108: 679-692Crossref PubMed Scopus (798) Google Scholar, 9Papadopoulou A. Koletzko S. Heuschkel R. Dias J.A. Allen K.J. Murch S.H. et al.ESPGHAN Eosinophilic Esophagitis Working Group and the Gastroenterology Committee. Management guidelines of eosinophilic esophagitis in childhood.J Pediatr Gastroenterol Nutr. 2014; 58: 107-118Crossref PubMed Scopus (216) Google Scholar Until the early 1990s, a dense esophageal eosinophilia was mostly associated with gastroesophageal reflux disease (GERD).E1Winter H.S. Madara J.L. Stafford R.J. Grand R.J. Quinlan J.E. Goldman H. Intraepitelial eosinophils: a new diagnostic criterion for reflux esophagitis.Gastroenterology. 1982; 83: 818-823Abstract Full Text PDF PubMed Scopus (391) Google Scholar, E2Brown L.F. Goldman H. Antonioli D.A. Intraepitelial eosinophils in endoscopic biopsies of adults with reflux esophagitis.Am J Surg Pathol. 1984; 8: 899-905Crossref PubMed Scopus (159) Google Scholar The ineffectiveness of antireflux therapies in patients with characteristic EoE profile, however, led to the recognition of EoE as a new entity.E3Kelly K.J. Lazenby A.J. Rowe P.C. Yardley J.H. Perman J.A. Sampson H.A. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula.Gastroenterology. 1995; 109: 1503-1512Abstract Full Text PDF PubMed Scopus (880) Google Scholar, 2Attwood S.E. Smyrk T.C. Demeester T.R. Jones J.B. Esophageal eosinophilia with dysphagia: a distinct clinicopathologic syndrome.Dig Dis Sci. 1993; 38: 109-116Crossref PubMed Scopus (652) Google Scholar, 3Straumann A. Spichtin H.P. Bernoulli R. Loosli J. Vögtlin J. Idiopathic eosinophilic esophagitis: a frequently overlooked disease with typical clinical aspects and discrete endoscopic findings [in German].Schweiz Med Wochenschr. 1994; 124: 1419-1429PubMed Google Scholar Consensus guidelines published in 2007 rigidly separated EoE from GERD7Furuta G.T. Liacouras C.A. Collins M.H. Gupta S.K. Justinich C. Putnam P.E. et al.First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. 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 (1371) Google Scholar: EoE was defined by either clinical and/or histologic unresponsiveness to proton pump inhibitor (PPI) therapy or a normal esophageal pH, whereas GERD was defined by either complete remission on PPI therapy or a pathological esophageal pH. Soon after this distinction was made, a few retrospective studies suggested the existence of pediatric patients with clinicopathological features of EoE who fully responded to PPI therapy.E4Ngo P. Furuta G. Antonioli D. Fox V. Eosinophils in the esophagus—peptic or allergic eosinophilic esophagitis? Case series of three patients with esophageal eosinophilia.Am J Gastroenterol. 2006; 101: 1666-1670Crossref PubMed Scopus (275) Google Scholar, E5Sayej W.N. Patel R. Baker R.D. Tron E. Baker S.S. Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis.J Pediatr Gastroenterol Nutr. 2009; 49: 393-399Crossref PubMed Scopus (114) Google Scholar, E6Dranove J.E. Horn D.S. Davis M.A. Kernek K.M. Gupta S.K. Predictors of response to proton pump inhibitor therapy among children with significant esophageal eosinophilia.J Pediatr. 2009; 154: 96-100Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar A large prospective adult series published in 2011 corroborated this finding, showing that PPIs effectively induced remission of both esophageal inflammation and accompanying symptoms in 50% of the patients with a presumptive diagnosis of EoE.E7Molina-Infante J. Ferrando-Lamana L. Ripoll C. Hernandez-Alonso M. Mateos J.M. Fernandez-Bermejo M. et al.Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults.Clin Gastroenterol Hepatol. 2011; 9: 110-117Abstract Full Text Full Text PDF PubMed Scopus (314) Google Scholar Notably, most of these patients presented with an associated atopic background as well as symptoms of dysphagia and food impaction instead of heartburn. Furthermore, PPI responsiveness was independent of pH-monitoring results. These observations gave rise to the new "PPI-responsive esophageal eosinophilia (PPI-REE)" concept, which referred to patients who not only appeared to have EoE clinically but also achieved complete remission after PPI therapy. This novel phenotype was recognized in the 2011 updated consensus recommendations on EoE1Liacouras C.A. Furuta G.T. Hirano I. Atkins D. Attwood S.E. Bonis P.A. 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 (1578) Google Scholar and endorsed in all subsequent guidelines.8Dellon E.S. Gonsalves N. Hirano I. Furuta G.T. Liacouras C.A. Katzka D.A. American College of Gastroenterology. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE).Am J Gastroenterol. 2013; 108: 679-692Crossref PubMed Scopus (798) Google Scholar, 9Papadopoulou A. Koletzko S. Heuschkel R. Dias J.A. Allen K.J. Murch S.H. et al.ESPGHAN Eosinophilic Esophagitis Working Group and the Gastroenterology Committee. Management guidelines of eosinophilic esophagitis in childhood.J Pediatr Gastroenterol Nutr. 2014; 58: 107-118Crossref PubMed Scopus (216) Google Scholar Currently, several retrospective and prospective studies in both children and adults consistently show that at least one-third of the patients with suspected EoE eventually receive a PPI-REE diagnosis.E8Molina-Infante J. Katzka D.A. Dellon E.S. Proton pump inhibitor-responsive esophageal eosinophilia: a historical perspective on a novel and evolving entity.Rev Esp Enferm Dig. 2015; 107: 29-36PubMed Google Scholar Interestingly, PPI-REE and EoE remain indistinguishable based on clinical, endoscopic,E10Warners M.J. van Rhijn B.D. Curvers W.L. Smout A.J. Bredenoord A.J. PPI-responsive esophageal eosinophilia cannot be distinguished from eosinophilic esophagitis by endoscopic signs.Eur J Gastroenterol Hepatol. 2015; 27: 506-511Crossref PubMed Scopus (27) Google Scholar, E9Dellon E.S. Speck O. Woodward K. Gebhart J.H. Madanick R.D. Levinson S. et al.Clinical and endoscopic characteristics do not reliably differentiate PPI-responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study.Am J Gastroenterol. 2013; 108: 1854-1860Crossref PubMed Scopus (192) Google Scholar and histologic findingsE11Moawad F.J. Schoepfer A.M. Safroneeva E. Ally M.R. Chen Y.J. Maydonovitch C.L. et al.Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings.Aliment Pharmacol Ther. 2014; 39: 603-608Crossref PubMed Scopus (94) Google Scholar; pH monitoringE17Lucendo A.J. Arias A. Gonzalez-Cervera J. Yagüe-Compadre J.L. Guagnozzi D. Angueira T. et al.Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease.J Allergy Clin Immunol. 2013; 131: 797-804Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar; and the measurement of tissue markers,E12Iwakura N. Fujiwara Y. Tanaka F. Tanigawa T. Yamagami H. Shiba M. et al.Basophil infiltration in eosinophilic oesophagitis and proton-pump inhibitor responsive oesophageal eosinophilia.Aliment Pharmacol Ther. 2015; 41: 776-784Crossref PubMed Scopus (30) Google Scholar, E13Moawad F.J. Wells J.M. Johnson R.L. Reinhardt B.J. Maydonovitch C.L. Baker T.P. Comparison of eotaxin-3 biomarker in patients with eosinophilic oesophagitis, proton pump inhibitor-responsive oesophageal eosinophilia and gastro-oesophageal reflux disease.Aliment Pharmacol Ther. 2015; 42: 231-238Crossref PubMed Scopus (31) Google Scholar cytokines related to eosinophilic inflammation,E14Molina-Infante J. Dueñas-Sadornil C. Rivas M.D. Vinagre-Rodríguez G. Mateos-Rodríguez J.M. Dueñas-Sadornil C. et al.Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression.Aliment Pharmacol Ther. 2014; 40: 955-965Crossref PubMed Scopus (111) Google Scholar, E15van Rhijn B.D. Weijenborg P.W. Verheij J. van den Bergh Weerman M.A. Verseijden C. van den Wijngaard R.M. et al.Proton pump inhibitors partially restore mucosal integrity in patients with proton pump inhibitor-responsive esophageal eosinophilia but not eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2014; 12: 1815-1823Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar and esophageal gene transcripts from esophageal tissue.E16Wen T. Dellon E.S. Moawad F.J. Furuta G.T. Aceves S.S. Rothenberg M.E. Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation.J Allergy Clin Immunol. 2015; 135: 187-197Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar In addition, PPI monotherapy completely reverses cytokineE14Molina-Infante J. Dueñas-Sadornil C. Rivas M.D. Vinagre-Rodríguez G. Mateos-Rodríguez J.M. Dueñas-Sadornil C. et al.Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression.Aliment Pharmacol Ther. 2014; 40: 955-965Crossref PubMed Scopus (111) Google Scholar, E15van Rhijn B.D. Weijenborg P.W. Verheij J. van den Bergh Weerman M.A. Verseijden C. van den Wijngaard R.M. et al.Proton pump inhibitors partially restore mucosal integrity in patients with proton pump inhibitor-responsive esophageal eosinophilia but not eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2014; 12: 1815-1823Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar and esophageal gene transcriptE16Wen T. Dellon E.S. Moawad F.J. Furuta G.T. Aceves S.S. Rothenberg M.E. Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation.J Allergy Clin Immunol. 2015; 135: 187-197Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar levels in patients with PPI-REE, similar to the way that topical steroids do in EoE. Collectively, these data support the idea that PPI-REE may constitute a subphenotype of EoE rather than a distinct disease entity and that PPIs may be considered a therapeutic option to effectively manage a high proportion of patients with EoE. Here, we provide additional evidence to support that PPI-REE and EoE should be considered within the spectrum of the same disease by showing that patients with PPI-REE also respond to dietary/topical steroid treatment and that some patients with EoE respond to PPI therapy. Databases containing information on patients with an EoE diagnosis who had prospectively attended 2 Spanish reference centers for EoE (Tomelloso General Hospital and San Pedro de Alcántara Hospital) between January 2014 and April 2015 were retrospectively analyzed to identify those who responded to both dietary/topical steroid treatment and PPI therapy. Nine patients (7 males, 2 females) were identified (Table I), and all presented with an atopic background. (Of note, despite this atopic background, the esophageal eosinophilia diagnosis or the documentation of its remission in esophageal biopsy samples was not made more frequently in the spring or summer months when environmental allergens peak [see Table E1 in this article's Online Repository available at www.jacionline.org].)Table IClinical, demographic, and therapeutic characteristics of our series of patients with EoE who presented dual response to dietary/topical steroid and PPI therapyPatientAge (y)SexAtopy backgroundFamilial history of atopy (relative)Ph monitoringBaseline peak eosinophil density (eosinophils/hpf) (proximal; distal)Initial therapy (year instituted)Posttreatment peak eosinophil density (eosinophils/hpf) (proximal; distal)Secondary therapyPosttreatment peak eosinophil density (eosinophils/hpf) (proximal; distal)Identified EoE food triggers (by individual food reintroduction)Maintenance therapy136MaleSeasonal allergic rhinitisNoNormal50; 50Six-food elimination diet (2008)0; 5Omeprazole 20 mg twice a day3; 0Wheat.Food reintroduction protocol abandonedOmeprazole 20 mg twice a day245MaleSeasonal rhinoconjunctivitisRhinoconjunctivitis (brother)Normal56; 60Six-food elimination diet (2009)0; 4Omeprazole 20 mg twice a day0; 0Egg, fish, and legumesOmeprazole 40 mg every day341MaleSeasonal bronchial asthma and rhinoconjunctivitisNoNormal10; 20Six-food elimination diet (2009)1; 2Esomeprazole 20 mg twice a day0; 0Milk, eggEsomeprazole 20 mg twice a day410MaleOral allergy syndrome with fruitsNoNormal30; 60Six-food elimination diet (2010)5; 10Omeprazole 20 mg twice a day1; 5Milk, wheat, and legumesOmeprazole 20 mg twice a day536MaleSeasonal rhinoconjunctivitisFish- and seafood-induced anaphylaxis (mother)Not done100; 45Esomeprazole 40 mg twice a day (2013)0; 0Four-food elimination diet0; 3Milk and wheatMilk and wheat exclusion from the diet628FemaleSeasonal bronchial asthma and rhinoconjunctuvitisBronchial asthma (brother)Not done15; 30Omeprazole 40 mg twice a day (2013)2; 8Four-food elimination diet10; 10WheatOngoingfood reintroduction protocol732FemaleSeasonal rhinoconjunctivitisSeasonal rhinoconjunctivitis (mother and sister)Not done76; 92Omeprazole 40 mg twice a day (2013)0; 4Four-food elimination diet2; 6Milk, legumesMilk and legumes exclusion from the diet829MaleSeasonal bronchial asthma and rhinoconjunctivitisNoNot done25; 34Omeprazole 40 mg twice a day (2013)0; 0Fluticasone propionate 800 μg twice a day0; 0—Swallowed fluticasone propionate 400 μg twice a day918MaleSeasonal bronchial asthma and rhinoconjunctivitisFish-induced anaphylaxisOral allergy syndrome with nuts and fruitsSeasonal bronchial asthma and rhinoconjunctivitis (brother)Not done114; 87Fluticasone propionate, 800 μg twice a day (2011)0; 0Omeprazole 40 mg twice a day2; 3—Omeprazole 40 mg every day Open table in a new tab Patients 1 to 4 had esophageal eosinophilia and were diagnosed with EoE after ruling out pathologic reflux by pH monitoring; no PPI trial was performed because exclusion of PPI-REE was not required before 2011. These patients showed disease remission after undergoing a 6-food elimination diet. Although patient 1 prematurely abandoned food reintroduction, specific food triggers were identified in the other 3 patients by a previously described sequential food reintroduction protocol,E17Lucendo A.J. Arias A. Gonzalez-Cervera J. Yagüe-Compadre J.L. Guagnozzi D. Angueira T. et al.Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease.J Allergy Clin Immunol. 2013; 131: 797-804Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar and food avoidance maintained disease remission for more than 3 years. Remarkably, 2 or more foods were involved in the origin of disease in these patients, hampering complete adherence to the diet. A 2-month-long PPI trial was thus offered to all the 4 patients, and a free diet was allowed up until the moment that new esophageal endoscopic biopsies were obtained. These patients were considered PPI responders because esophageal eosinophilia did not recur, and all preferred receiving PPI while on a liberalized diet. However, patients 5 to 7 were first diagnosed with esophageal eosinophilia in 2013 and then subsequently diagnosed with PPI-REE after their esophageal inflammation remitted after a 2-month-long PPI course. Because all patients expressed concerns regarding long-term PPI consumption, we offered them further dietary therapy. After discontinuing PPIs, disease remission was achieved with a 4-food elimination diet, and specific food triggers were identified by subsequent food challenge.E18Molina-Infante J. Arias A. Barrio J. Rodríguez-Sánchez J. Sanchez-Cazalilla M. Lucendo A.J. Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study.J Allergy Clin Immunol. 2014; 134: 1093-1099.e1Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar Patient 8 was diagnosed with PPI-REE and maintained full remission with long-term omeprazole treatment (40 mg/d). After 15 months of follow-up, the patient suddenly developed tinnitus, and PPIs were withdrawn at the request of the otorhinolaryngologist. Esophageal symptoms relapsed 6 weeks after discontinuation of PPI therapy. Topical steroid therapy was then prescribed, leading again to clinical and histologic remission of the disease. Patient 9, an 18-year-old man with a severe atopic background, was diagnosed with esophageal eosinophilia attributed to EoE in 2011 (without a PPI trial) and achieved clinicohistologic remission after immediately starting topical steroid therapy. In 2014, the patient voiced concerns about long-term intake of corticosteroids, and topical steroid therapy was discontinued. Clinical and histologic remission was redocumented after a 2-month-long PPI trial (omeprazole 40 mg twice a day), which was maintained as long-term treatment. We report here the first series of patients with EoE exhibiting a complete response to either PPI therapy or dietary/topical steroid therapy. Our clinical observation emphasizes the similar nature of EoE and PPI-REE because they are indistinguishable entities not only in the genetic and phenotypic sense but also in the therapeutic sense, which we show here for the first time. As has recently been pointed out,E18Molina-Infante J. Arias A. Barrio J. Rodríguez-Sánchez J. Sanchez-Cazalilla M. Lucendo A.J. Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study.J Allergy Clin Immunol. 2014; 134: 1093-1099.e1Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar defining a disease (eg, PPI-REE) by its responsiveness to a specific therapy (eg, PPI therapy) instead of its clinical and mechanistic characteristics (eg, indistinguishable from EoE) is counterintuitive. Our data are especially important for patients with EoE who did not undergo a PPI trial before receiving an EoE diagnosis because the opportunity to treat with a safe, effective, and convenient therapeutic asset may have been missed. Evolving evidence points toward reclassifying patients with PPI-REE as PPI-responsive patients with EoE.E19Katzka D.A. Eosinophilic esophagitis and proton pump-responsive esophageal eosinophilia: what is in a name?.Clin Gastroenterol Hepatol. 2014; 12: 2023-2025Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Moreover, PPIs should now be considered as the first step in the treatment algorithm for patients with EoE so as to rule out patient responsiveness to PPI therapy rather than to just rule out GERD. This novel concept was foretold in a visionary review article in 2007E20Spechler S.J. Genta R.M. Souza R.F. Thoughts on the complex relationship between gastroesophageal reflux disease and eosinophilic esophagitis.Am J Gastroenterol. 2007; 102: 1301-1306Crossref PubMed Scopus (290) Google Scholar in which the authors suggested that "a PPI trial should be recommended even when the diagnosis of EoE seems clear-cut" and "a favorable response to PPI therapy does not preclude a diagnosis of EoE." Some aspects related to PPI responsiveness in patients with EoE require further understanding and clarification, including the following: 1) the ultimate underlying mechanisms explaining a distinct response among patients who share apparently identical characteristics; 2) whether both variants of the disease share an identical natural history with fibrostenotic progression; and 3) the potential ability of PPIs to reverse esophageal fibrous remodeling. Nevertheless, we believe that there is enough evidence at present to consider abandoning the PPI-REE concept in favor of reclassifying patients with PPI-REE as having EoE that responds to PPI therapy. Table E1Histologic and therapeutic characteristics and month each endoscopic examination was carried out in our series of patients with EoE who presented dual response to dietary/topical steroid and PPI therapyPatientBaseline peak eosinophil density (eosinophils/hpf)(proximal; distal)(month)Patient on PPIs at the moment of baseline endoscopyInitial therapy (year instituted)Posttreatment peak eosinophil density(eosinophils/hpf)(proximal; distal)(month)Secondary therapyPosttreatment peak eosinophil density(eosinophils/hpf)(proximal; distal)(month)150; 50(July)NoSix-food elimination diet (2008)0; 5(September)Omeprazole 20 mg twice a day3; 0(February)256; 60(January)NoSix-food elimination diet (2009)0; 4(March)Omeprazole 20 mg twice a day0; 0(November)310; 20(March)NoSix-food elimination diet (2009)1; 2(April)Esomeprazole 20 mg twice a day0; 0(May)430; 60(October)NoSix-food elimination diet (2010)5; 10(December)Omeprazole 20 mg twice a day1; 5(July)5100; 45(March)NoEsomeprazole 40 mg twice a day (2013)0; 0(May)Four-food elimination diet0; 3(January)615; 30(June)NoOmeprazole 40 mg twice a day (2013)2; 8(August)Four-food elimination diet10; 10(November)776; 92(February)NoOmeprazole 40 mg twice a day (2013)0; 4(April)Four-food elimination diet2; 6(March)825; 34(November)NoOmeprazole 40 mg twice a day (2013)0; 0(January)Fluticasone propionate 800 μg twice a day0; 0(April)9114; 87(November)NoFluticasone propionate, 800 μg twice a day (2011)0; 0(February)Omeprazole 40 mg twice a day2; 3(February) Open table in a new tab
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