European Journal of Pediatrics

, Volume 177, Issue 5, pp 649–663 | Cite as

Treatment of eosinophilic esophagitis in the pediatric patient: an evidence-based approach

  • Mery Munoz-Persy
  • Alfredo J. Lucendo


Eosinophilic esophagitis (EoE) is a unique form of non-IgE-mediated food allergy characterized by esophageal eosinophilic infiltration that commonly causes dysphagia and food impaction in children and adolescents. Assessing the efficacy of dietary restrictions or drug therapies to achieve clinical and histologic resolution of EoE through randomized controlled trials and meta-analyses has resulted in new evidence-based guidelines. Avoiding food triggers is the only therapy targeting the cause of the disease. None of the currently available food allergy tests adequately predict food triggers for EoE. Exclusively feeding with an amino acid-based elemental diet and empiric six-food elimination diet (avoiding the six foods most commonly related with food allergy) has consistently provided the best cure rates, but their high level of restriction and need for multiple endoscopies are deterrents for implementation. Simpler and less restrictive empirical methods, like a four-food (milk, gluten-containing cereals, egg, legumes) or a two-food (milk and gluten) elimination diet, show encouraging results. Proton pump inhibitors are currently a first-line treatment, achieving histological remission and improvement of symptoms in 54.1 and 64.9% of pediatric EoE patients, respectively. The efficacy of topical corticosteroids in EoE assessed in several trials and summarized in meta-analyses indicates that budesonide and fluticasone propionate are significantly superior to placebos, both in decreasing eosinophil mucosal infiltration and in relieving symptoms. Owing to differences in drug delivery, viscous budesonide formulas seem to be the best pharmacological therapy for EoE.

Conclusion: Applying evidence-based therapies and a practical management algorithm provide an effective control of EoE.

What is Known:

Eosinophilic esophagitis (EoE) now constitutes the main cause of dysphagia and food impaction in children, adolescents, and young adults.

Its chronic course and frequent progression to subepithelial fibrosis leading to strictures and narrow-caliber esophagus indicate the need for treatment.

What is New:

Therapeutic goals in children with EoE include resolution of esophageal symptoms, to cure esophageal inflammation (mucosal healing) and restore a proper esophageal caliber in case of fibrostenotic endoscopic findings. Avoiding iatrogenic drug effects and nutritional deficiencies, as well as maintaining an adequate quality of life, is also essential.

Novel evidence-based guidelines, endorsed by several European scientific societies, incorporate recent advances in knowledge from several randomized controlled trials and systematic reviews to provide the best standard of care to pediatric patients, by following simple management algorithms.


Eosinophilic esophagitis Diet therapy Drug therapy Dilation Glucocorticoids Proton pump inhibitors Disease management 



American Gastroenterological Association


Dysphagia Symptom Questionnaire


Eosinophilic Esophagitis Activity Index


Eosinophilic esophagitis


Four-food elimination diet


Gastroesophageal reflux disease


Grading of Recommendations Assessment, Development and Evaluation


High-powered field


North American Society of Gastroenterology, Hepatology and Pediatric Nutrition


Pediatric Eosinophilic Esophagitis Symptom Score


Randomized controlled trial


Six-food elimination diet


Two-food elimination diet


Authors’ Contributions

MM-P and AJL contributed equally to write the paper. All authors have read and approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Ahmet A, Benchimol EI, Goldbloom EB, Barkey JL (2016) Adrenal suppression in children treated with swallowed fluticasone and oral viscous budesonide for eosinophilic esophagitis. Allergy Asthma Clin Immunol 12:49PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Alexander JA, Jung KW, Arora AS, Enders F, Katzka DA, Kephardt GM, Kita H, Kryzer LA, Romero Y, Smyrk TC, Talley NJ (2012) Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol 10:742–749PubMedCrossRefGoogle Scholar
  3. 3.
    Alexander JA, Ravi K, Enders FT, Geno DM, Kryzer LA, Mara KC, Smyrk TC, Katzka DA (2017) Montelukast does not maintain symptom remission after topical steroid therapy for eosinophilic esophagitis. Clin Gastroenterol Hepatol 15:214–221PubMedCrossRefGoogle Scholar
  4. 4.
    Andreae DA, Hanna MG, Magid MS, Malerba S, Andreae MH, Bagiella E, Chehade M (2016) Swallowed fluticasone propionate is an effective long-term maintenance therapy for children with eosinophilic esophagitis. Am J Gastroenterol 111:1187–1197PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Arias A, Lucendo AJ (2014) Dietary therapies for eosinophilic esophagitis. Expert Rev Clin Immunol 10:133–142PubMedCrossRefGoogle Scholar
  6. 6.
    Arias A, Gonzalez-Cervera J, Tenias JM, Lucendo AJ (2014) Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology 146:1639–1648PubMedCrossRefGoogle Scholar
  7. 7.
    Arias A, Pérez-Martínez I, Tenías JM, Lucendo AJ (2016) Systematic review with meta-analysis: the incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther 43:3–15PubMedCrossRefGoogle Scholar
  8. 8.
    Assa’ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, Perschy TL et al (2011) An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology 141:1593–1604PubMedCrossRefGoogle Scholar
  9. 9.
    Assiri AM, Saeed A (2014) Incidence and diagnostic features of eosinophilic esophagitis in a group of children with dysphagia and gastroesophageal reflux disease. Saudi Med J 35:292–297PubMedGoogle Scholar
  10. 10.
    Attwood SE, Smyrk TC, Demeester TR, Jones JB (1993) Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 38:109–116PubMedCrossRefGoogle Scholar
  11. 11.
    Attwood SE, Ell C, Galmiche JP, Fiocca R, Hatlebakk JG, Hasselgren B, Långström G, Jahreskog M, Eklund S, Lind T, Lundell L (2015) Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies. Aliment Pharmacol Ther 41:1162–1174PubMedCrossRefGoogle Scholar
  12. 12.
    Binkovitz LA, Lorenz EA, Di Lorenzo C, Kahwash S (2010) Pediatric eosinophilic esophagitis: radiologic findings with pathologic correlation. Pediatr Radiol 40:714–719PubMedCrossRefGoogle Scholar
  13. 13.
    Butz BK, Wen T, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot C, Jackson WD, O’Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME (2014) Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology 147:324–333PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Chehade M, Sher E (2017) Medical therapy versus dietary avoidance in eosinophilic esophagitis: which approach is better? Allergy Asthma Proc 38:170–176PubMedCrossRefGoogle Scholar
  15. 15.
    Chuang M-YA, Chinnaratha MA, Hancock DG, Woodman R, Wong GR, Cock C, Fraser RJ (2015) Topical steroid therapy for the treatment of eosinophilic esophagitis (EoE): a systematic review and meta-analysis. Clin Transl Gastroenterol 6:e82PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Clayton F, Fang JC, Gleich GJ, Lucendo AJ, Olalla JM, Vinson LA, Lowichik A, Chen X, Emerson L, Cox K, O’Gorman MA, Peterson KA (2014) Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology 147:602–609PubMedCrossRefGoogle Scholar
  17. 17.
    Constantine G, Seth N, Chokshi N, Minard CG, Guffey D, Olive AP, Davis CM (2017) Combination steroid and test-based food elimination for eosinophilic esophagitis: a retrospective analysis. J Pediatr Gastroenterol Nutr 64:933–938PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Cury EK, Schraibman V, Faintuch S (2004) Eosinophilic infiltration of the esophagus: gastroesophageal reflux versus eosinophilic esophagitis in children—discussion on daily practice. J Pediatr Surg 39:e4-e7CrossRefGoogle Scholar
  19. 19.
    De la Cruz-Patiño E, Ruíz Juárez I, Meixueiro Daza A, Grube Pagola P, Roesch-Dietlen F, Remes-Troche JM (2015) Eosinophilic esophagitis prevalence in an adult population undergoing upper endoscopy in southeastern Mexico. Dis Esophagus 28:524–529PubMedCrossRefGoogle Scholar
  20. 20.
    Delaney AL, Arvedson JC (2008) Development of swallowing and feeding: prenatal through first year of life. Dev Disabil Res Rev 14:105–117PubMedCrossRefGoogle Scholar
  21. 21.
    Dellon ES, Sheikh A, Speck O, Woodward K, Whitlow AB, Hores JM, Ivanovic M, Chau A, Woosley JT, Madanick RD, Orlando RC, Shaheen NJ (2012) Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis. Gastroenterology 143:321–324PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA (2013) ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 108:679–692PubMedCrossRefGoogle Scholar
  23. 23.
    Dellon ES, Irani A-M, Hill MR, Hirano I (2013) Development and field testing of a novel patient-reported outcome measure of dysphagia in patients with eosinophilic esophagitis. Aliment Pharmacol Ther 38:634–642PubMedCrossRefGoogle Scholar
  24. 24.
    Dellon ES, Kim HP, Sperry SLW, Rybnicek DA, Woosley JT, Shaheen NJ (2014) A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc 79:577–585PubMedCrossRefGoogle Scholar
  25. 25.
    Dellon ES, Speck O, Woodward K, Covey S, Rusin S, Shaheen NJ, Woosley JT et al (2015) Distribution and variability of esophageal eosinophilia in patients undergoing upper endoscopy. Mod Pathol 28:383–390PubMedCrossRefGoogle Scholar
  26. 26.
    Dohil R, Newbury RO, Aceves S (2012) Transient PPI responsive esophageal eosinophilia may be a clinical sub-phenotype of pediatric eosinophilic esophagitis. Dig Dis Sci 57:1413–1419PubMedCrossRefGoogle Scholar
  27. 27.
    Eckmann JD, Ravi K, Katzka DA, Davis DR, See JA, Geno DR, Kryzer LA et al (2016) Efficacy of atopy patch testing in directed dietary therapy of eosinophilic esophagitis: a pilot study. Dig Dis Sci 63:694–702CrossRefGoogle Scholar
  28. 28.
    Faubion WA, Perrault J, Burgart LJ, Zein NN, Clawson M, Freese DK (1998) Treatment of eosinophilic esophagitis with inhaled corticosteroids. J Pediatr Gastroenterol Nutr 27:90–93PubMedCrossRefGoogle Scholar
  29. 29.
    Franciosi JP, Hommel KA, DeBrosse CW, Greenberg AB, Greenler AJ, Abonia JP, Rothenberg ME et al (2011) Development of a validated patient-reported symptom metric for pediatric eosinophilic esophagitis: qualitative methods. BMC Gastroenterol 11:126PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Francis DL, Foxx-Orenstein A, Arora AS, Smyrk TC, Jensen K, Nord SL, Alexander JA, Romero Y, Katzka DA (2012) Results of ambulatory pH monitoring do not reliably predict response to therapy in patients with eosinophilic oesophagitis. Aliment Pharmacol Ther 35:300–307PubMedCrossRefGoogle Scholar
  31. 31.
    Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME, First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees (2007) Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 133:1342–1363PubMedCrossRefGoogle Scholar
  32. 32.
    Golekoh MC, Hornung LN, Mukkada VA, Khoury JC, Putnam PE, Backeljauw PF (2016) Adrenal insufficiency after chronic swallowed glucocorticoid therapy for eosinophilic esophagitis. J Pediatr 170:240–245PubMedCrossRefGoogle Scholar
  33. 33.
    Gómez-Torrijos E, García-Rodríguez R, Castro-Jiménez A, Rodríguez-Sanchez J, Méndez Díaz Y, Molina-Infante J (2016) The efficacy of step-down therapy in adult patients with proton pump inhibitor-responsive oesophageal eosinophilia. Aliment Pharmacol Ther 43:534–540PubMedCrossRefGoogle Scholar
  34. 34.
    Gonsalves N, Yang G-Y, Doerfler B, Ritz S, Ditto AM, Hirano I (2012) Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology 142:1451–1459PubMedCrossRefGoogle Scholar
  35. 35.
    Gutiérrez-Junquera C, Fernández-Fernández S, Cilleruelo ML, Rayo A, Echeverría L, Quevedo S, Bracamonte T, Román E (2016) High prevalence of response to proton-pump inhibitor treatment in children with esophageal eosinophilia. J Pediatr Gastroenterol Nutr 62:704–710PubMedCrossRefGoogle Scholar
  36. 36.
    Harel S, Hursh BE, Chan ES, Avinashi V, Panagiotopoulos C (2015) Adrenal suppression in children treated with oral viscous budesonide for eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 61:190–193PubMedCrossRefGoogle Scholar
  37. 37.
    Henderson CJ, Abonia JP, King EC, Putnam PE, Collins MH, Franciosi JP, Rothenberg ME (2012) Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol 129:1570–1578PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hsu S, Wood C, Pan Z, Rahat H, Zeitler P, Fleischer D, Menard-Katcher C, Furuta GT, Atkins D (2017) Adrenal insufficiency in pediatric eosinophilic esophagitis patients treated with swallowed topical steroids. Pediatr Allergy Immunol Pulmunol 30:135–140CrossRefGoogle Scholar
  39. 39.
    Hunter SS, Helmy DO, Zayed NA, El-Tayeb TM, El-Serafy MA (2014) Eosinophilic esophagitis in Egyptian adult patients presenting with upper gastrointestinal symptoms. Open J Gastroenterol 4:88–95CrossRefGoogle Scholar
  40. 40.
    Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, Melin-Aldana H et al (2006) Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol 4:1097–1102PubMedCrossRefGoogle Scholar
  41. 41.
    Kagalwalla AF, Shah A, Li BUK, Sentongo TA, Ritz S, Manuel-Rubio M, Jacques K, Wang D, Melin-Aldana H, Nelson SP (2011) Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr 53:145–149PubMedCrossRefGoogle Scholar
  42. 42.
    Kagalwalla AF, Wechsler JB, Amsden K, Schwartz S, Makhija M, Olive A, Davis CM, Manuel-Rubio M, Marcus S, Shaykin R, Sulkowski M, Johnson K, Ross JN, Riffle ME, Groetch M, Melin-Aldana H, Schady D, Palac H, Kim KYA, Wershil BK, Collins MH, Chehade M (2017) Efficacy of a 4-food elimination diet for children with eosinophilic esophagitis. Clin Gastroenterol Hepatol 15:1698–1707PubMedCrossRefGoogle Scholar
  43. 43.
    Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA (1995) Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology 109:1503–1512PubMedCrossRefGoogle Scholar
  44. 44.
    Kinoshita Y, Ishimura N, Oshima N, Ishihara S (2015) Systematic review: eosinophilic esophagitis in Asian countries. World J Gastroenterol 21:8433–8440PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Kruszewski PG, Russo JM, Franciosi JP, Varni JW, Platts-Mills TA, Erwin EA (2016) Prospective, comparative effectiveness trial of cow’s milk elimination and swallowed fluticasone for pediatric eosinophilic esophagitis. Dis Esophagus 29:377–384PubMedCrossRefGoogle Scholar
  46. 46.
    Liacouras CA (1997) Failed Nissen fundoplication in two patients who had persistent vomiting and eosinophilic esophagitis. J Pediatr Surg 32:1504–1506PubMedCrossRefGoogle Scholar
  47. 47.
    Liacouras CA, Wenner WJ, Brown K, Ruchelli E (1998) Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr 26:380–385PubMedCrossRefGoogle Scholar
  48. 48.
    Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, Flick J, Kelly J, Brown-Whitehorn T, Mamula P, Markowitz JE (2005) Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 3:1198–1206PubMedCrossRefGoogle Scholar
  49. 49.
    Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, Burks AW, Chehade M, Collins MH, Dellon ES, Dohil R, Falk GW, Gonsalves N, Gupta SK, Katzka DA, Lucendo AJ, Markowitz JE, Noel RJ, Odze RD, Putnam PE, Richter JE, Romero Y, Ruchelli E, Sampson HA, Schoepfer A, Shaheen NJ, Sicherer SH, Spechler S, Spergel JM, Straumann A, Wershil BK, Rothenberg ME, Aceves SS (2011) Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 128:3–20PubMedCrossRefGoogle Scholar
  50. 50.
    Lipka S, Kumar A, Richter JE (2016) Impact of diagnostic delay and other risk factors on eosinophilic esophagitis phenotype and esophageal diameter. J Clin Gastroenterol 50:134–140PubMedCrossRefGoogle Scholar
  51. 51.
    Lipka S, Kumar A, Miladinovic B, Richter JE (2016) Systematic review with network meta-analysis: comparative effectiveness of topical steroids vs. PPIs for the treatment of the spectrum of eosinophilic oesophagitis. Aliment Pharmacol Ther 43:663–673PubMedCrossRefGoogle Scholar
  52. 52.
    Lucendo AJ (2015) Meta-analysis-based guidance for dietary management in eosinophilic esophagitis. Curr Gastroenterol Rep 17:464PubMedCrossRefGoogle Scholar
  53. 53.
    Lucendo AJ, Molina-Infante J (2016) Limitation of symptoms as predictors of remission in eosinophilic esophagitis: the need to go beyond endoscopy and histology. Gastroenterology 150:547–549PubMedCrossRefGoogle Scholar
  54. 54.
    Lucendo AJ, Sanchez-Cazalilla M (2012) Adult versus pediatric eosinophilic esophagitis: important differences and similarities for the clinician to understand. Expert Rev Clin Immunol 8:733–745PubMedCrossRefGoogle Scholar
  55. 55.
    Lucendo AJ, De Rezende LC, Jimenez-Contreras S, Yague-Compadre JL, Gonzalez-Cervera J, Mota-Huertas T, Guagnozzi D et al (2011) Montelukast was inefficient in maintaining steroid-induced remission in adult eosinophilic esophagitis. Dig Dis Sci 56:3551–3558PubMedCrossRefGoogle Scholar
  56. 56.
    Lucendo AJ, Arias A, Gonzalez-Cervera J, Yague-Compadre JL, Guagnozzi D, Angueira T, Jiménez-Contreras S et al (2013) 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 131:797–804PubMedCrossRefGoogle Scholar
  57. 57.
    Lucendo AJ, Arias A, Molina-Infante J (2016) Efficacy of proton pump inhibitor drugs for inducing clinical and histologic remission in patients with symptomatic esophageal eosinophilia: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 14:13–22PubMedCrossRefGoogle Scholar
  58. 58.
    Lucendo AJ, Arias A, Gonzalez-Cervera J, Olalla JM, Molina-Infante J (2016) Dual response to dietary/topical steroid and proton pump inhibitor therapy in adult patients with eosinophilic esophagitis. J Allergy Clin Immunol 137:931–934PubMedCrossRefGoogle Scholar
  59. 59.
    Lucendo AJ, Molina-Infante J, Arias A, von Arnim U, Bredenoord AJ, Bussmann C, Amil Dias J, Bove M, González-Cervera J, Larsson H, Miehlke S, Papadopoulou A, Rodríguez-Sánchez J, Ravelli A, Ronkainen J, Santander C, Schoepfer AM, Storr MA, Terreehorst I, Straumann A, Attwood SE (2017) Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United Eur Gastroenterol J 5:335–358CrossRefGoogle Scholar
  60. 60.
    Lucendo AJ, Arias-González L, Molina-Infante J, Arias Á (2017) Systematic review: health-related quality of life in children and adults with eosinophilic oesophagitis—measure instruments and determinant factors. Aliment Pharmacol Ther 46:401–409PubMedCrossRefGoogle Scholar
  61. 61.
    Lucendo AJ, Arias A, Redondo-Gonzalez O, Molina-Infante J (2017) Quality assessment of clinical practice guidelines for eosinophilic esophagitis using the AGREE II instrument. Expert Rev Gastroenterol Hepatol 11:383–390PubMedCrossRefGoogle Scholar
  62. 62.
    Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA (2003) Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol 98:777–782PubMedCrossRefGoogle Scholar
  63. 63.
    Martin LJ, Franciosi JP, Collins MH, Abonia JP, Lee JJ, Hommel KA, Varni JW, Grotjan JT, Eby M, He H, Marsolo K, Putnam PE, Garza JM, Kaul A, Wen T, Rothenberg ME (2015) Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease. J Allergy Clin Immunol 135:1519–1528PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Menard-Katcher C, Swerdlow MP, Mehta P, Furuta GT, Fenton LZ (2015) Contribution of esophagram to the evaluation of complicated pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 61:541–546PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Menard-Katcher C, Furuta GT, Kramer RE (2017) Dilation of pediatric eosinophilic esophagitis: adverse events and short-term outcomes. J Pediatr Gastroenterol Nutr 64:701–706PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Miehlke S, Hruz P, Vieth M, Bussmann C, Von Arnim U, Bajbouj M, Schlag C et al (2016) A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut 65:390–399PubMedCrossRefGoogle Scholar
  67. 67.
    Moawad FJ, Schoepfer AM, Safroneeva E, Ally MR, Chen Y-J, Maydonovitch CL, Wong RK (2014) Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings. Aliment Pharmacol Ther 39:603–608PubMedCrossRefGoogle Scholar
  68. 68.
    Moawad FJ, Molina-Infante J, Lucendo AJ, Cantrell SE, Tmanova L, Douglas K (2017) Systematic review with meta-analysis: endoscopic dilation is highly effective and safe in children and adults with eosinophilic oesophagitis. Aliment Pharmacol Ther 46:96–105PubMedCrossRefGoogle Scholar
  69. 69.
    Molina-Infante J, Lucendo AJ (2014) Eosinophilic esophagitis: a practical approach to diagnosis and management. Expert Rev Gastroenterol Hepatol 8:925–934PubMedCrossRefGoogle Scholar
  70. 70.
    Molina-Infante J, Lucendo AJ (2015) Update on topical steroid therapy for eosinophilic esophagitis. Gastroenterol Hepatol 38:388–397PubMedCrossRefGoogle Scholar
  71. 71.
    Molina-Infante J, Lucendo AJ (2016) Combining different therapeutic interventions in eosinophilic esophagitis may lead to unreplicable and misleading results. Dis Esophagus 29:1172PubMedCrossRefGoogle Scholar
  72. 72.
    Molina-Infante J, Ferrando-Lamana L, Ripoll C, Hernandez-Alonso M, Mateos JM, Fernandez-Bermejo M, Dueñas C et al (2011) Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol 9:110–117PubMedCrossRefGoogle Scholar
  73. 73.
    Molina-Infante J, Martin-Noguerol E, Alvarado-Arenas M, Porcel-Carreño SL, Jimenez-Timon S, Hernandez-Arbeiza FJ (2012) Selective elimination diet based on skin testing has suboptimal efficacy for adult eosinophilic esophagitis. J Allergy Clin Immunol 130:1200–1202PubMedCrossRefGoogle Scholar
  74. 74.
    Molina-Infante J, Arias A, Barrio J, Rodriguez-Sanchez J, Sanchez-Cazalilla M, Lucendo AJ (2014) Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study. J Allergy Clin Immunol 134:1093–1099PubMedCrossRefGoogle Scholar
  75. 75.
    Molina-Infante J, Rivas MD, Hernandez-Alonso M, Vinagre-Rodríguez G, Mateos-Rodríguez JM, Dueñas-Sadornil C, Perez-Gallardo B, Ferrando-Lamana L, Fernandez-Gonzalez N, Bañares R, Zamorano J (2014) Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression. Aliment Pharmacol Ther 40:955–965PubMedCrossRefGoogle Scholar
  76. 76.
    Molina-Infante J, Rodriguez-Sanchez J, Martinek J, van Rhijn BD, Krajciova J, Rivas MD, Barrio J, Moawad FJ, Martinez-Alcalá C, Bredenoord AJ, Zamorano J, Dellon ES (2015) Long-term loss of response in proton pump inhibitor-responsive esophageal eosinophilia is uncommon and influenced by CYP2C19 genotype and rhinoconjunctivitis. Am J Gastroenterol 110:1567–1575PubMedCrossRefGoogle Scholar
  77. 77.
    Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, Hirano I et al (2016) Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. Gut 65:521–531CrossRefGoogle Scholar
  78. 78.
    Molina-Infante J, Gonzalez-Cordero PL, Arias A, Lucendo AJ (2017) Update on dietary therapy for eosinophilic esophagitis in children and adults. Expert Rev Gastroenterol Hepatol 11:115–123PubMedCrossRefGoogle Scholar
  79. 79.
    Molina-Infante J, Schoepfer AM, Lucendo AJ, Dellon ES (2017) Eosinophilic esophagitis: what can we learn from Crohn’s disease? United Eur Gastroenterol J 5:762–772CrossRefGoogle Scholar
  80. 80.
    Molina-Infante J, Arias Á, Alcedo J, Garcia-Romero R, Casabona-Frances S, Prieto-Garcia A, Modolell I, Gonzalez-Cordero PL, Perez-Martinez I, Martin-Lorente JL, Guarner-Argente C, Masiques ML, Vila-Miravet V, Garcia-Puig R, Savarino E, Sanchez-Vegazo CT, Santander C, Lucendo AJ (2017) Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: the 2-4-6 study. J Allergy Clin Immunol.
  81. 81.
    Molina-Infante J, Gonzalez-Cordero PL, Ferreira-Nossa HC, Mata-Romero P, Lucendo AJ, Arias A (2018) Rising incidence and prevalence of adult eosinophilic esophagitis in midwestern Spain (2007–2016). United Eur Gastroenterol J 6:29–37CrossRefGoogle Scholar
  82. 82.
    Mukkada VA, Furuta GT (2014) Management of refractory eosinophilic esophagitis. Dig Dis 32:134–138PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Murali AR, Gupta A, Attar BM, Ravi V, Koduru P (2016) Topical steroids in eosinophilic esophagitis: systematic review and meta-analysis of placebo-controlled randomized clinical trials. J Gastroenterol Hepatol 31:1111–1119PubMedCrossRefGoogle Scholar
  84. 84.
    Netzer P, Gschossmann JM, Straumann A, Sendensky A, Weimann R, Schoepfer AM (2007) Corticosteroid-dependent eosinophilic oesophagitis: azathioprine and 6-mercaptopurine can induce and maintain long-term remission. Eur J Gastroenterol Hepatol 19:865–869PubMedCrossRefGoogle Scholar
  85. 85.
    Ngo P, Furuta GT, Antonioli DA, Fox VL (2006) Eosinophils in the esophagus—peptic or allergic eosinophilic esophagitis? Case series of three patients with esophageal eosinophilia. Am J Gastroenterol 101:1666–1670PubMedCrossRefGoogle Scholar
  86. 86.
    Nurko S, Teitelbaum JE, Husain K, Buonomo C, Fox VL, Antonioli D, Fortunato C, Badizadegan K, Furuta GT (2004) Association of Schatzki ring with eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr 38:436–441PubMedCrossRefGoogle Scholar
  87. 87.
    Papadopoulou A, Koletzko S, Heuschkel R, Dias JA, Allen KJ, Murch SH, Chong S, Gottrand F, Husby S, Lionetti P, Mearin ML, Ruemmele FM, Schäppi MG, Staiano A, Wilschanski M, Vandenplas Y, ESPGHAN Eosinophilic Esophagitis Working Group and the Gastroenterology Committee (2014) Management guidelines of eosinophilic esophagitis in childhood. J Pediatr Gastroenterol Nutr 58:107–118PubMedCrossRefGoogle Scholar
  88. 88.
    Peters RL, Gurrin LC, Allen KJ (2012) The predictive value of skin prick testing for challenge-proven food allergy: a systematic review. Pediatr Allergy Immunol 23:347–352PubMedCrossRefGoogle Scholar
  89. 89.
    Peterson KA, Byrne KR, Vinson LA, Ying J, Boynton KK, Fang JC, Gleich GJ, Adler DG, Clayton F (2013) Elemental diet induces histologic response in adult eosinophilic esophagitis. Am J Gastroenterol 108:759–766PubMedCrossRefGoogle Scholar
  90. 90.
    Philla KQ, Min SB, Hefner JN, Howard RS, Reinhardt BJ, Nazareno LG, Vogt KS (2015) Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function. J Pediatr Endocrinol Metab 28:1101–1106PubMedCrossRefGoogle Scholar
  91. 91.
    Philpott H, Nandurkar S, Royce SG, Thien F, Gibson PR (2016) Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities. Aliment Pharmacol Ther 44:223–233PubMedCrossRefGoogle Scholar
  92. 92.
    Reed CC, Wolf WA, Cotton CC, Rusin S, Perjar I, Hollyfield J, Woosley JT, Shaheen NJ, Dellon ES (2018) Optimal histologic cutpoints for treatment response in patients with eosinophilic esophagitis: analysis of data from a prospective cohort study. Clin Gastroenterol Hepatol 16:226–233PubMedCrossRefGoogle Scholar
  93. 93.
    Robles-Medranda C, Villard F, le Gall C, Lukashok H, Rivet C, Bouvier R, Dumortier J, Lachaux A (2010) Severe dysphagia in children with eosinophilic esophagitis and esophageal stricture: an indication for balloon dilation? J Pediatr Gastroenterol Nutr 50:516–520PubMedGoogle Scholar
  94. 94.
    Rocha R, Vitor AB, Trindade E, Lima R, Tavares M, Lopes J, Dias JA (2011) Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Eur J Pediatr 170:1471–1474PubMedCrossRefGoogle Scholar
  95. 95.
    Rodrigues M, D’Amico MFM, Patino FRA, Barbieri D, Damiao AOMC, Sipahi AM (2013) Clinical manifestations, treatment, and outcomes of children and adolescents with eosinophilic esophagitis. J Pediatr 89:197–203CrossRefGoogle Scholar
  96. 96.
    Rothenberg ME, Wen T, Greenberg A, Alpan O, Enav B, Hirano I, Nadeau K, Kaiser S, Peters T, Perez A, Jones I, Arm JP, Strieter RM, Sabo R, Gunawardena KA (2015) Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. J Allergy Clin Immunol 135:500–507PubMedCrossRefGoogle Scholar
  97. 97.
    Safroneeva E, Straumann A, Coslovsky M, Zwahlen M, Kuehni CE, Panczak R, Haas NA, Alexander JA, Dellon ES, Gonsalves N, Hirano I, Leung J, Bussmann C, Collins MH, Newbury RO, de Petris G, Smyrk TC, Woosley JT, Yan P, Yang GY, Romero Y, Katzka DA, Furuta GT, Gupta SK, Aceves SS, Chehade M, Spergel JM, Schoepfer AM, Achem SR, Arora AS, Alpan O, Armstrong D, Attwood SE, Butterfield JH, Crowell MD, DeVault KR, Drouin E, Enav B, Enders FT, Fleischer DE, Foxx-Orenstein A, Francis DL, Guyatt GH, Harris LA, Kagalwalla AF, Kita H, Krishna M, Lee JJ, Lewis JC, Lim K, Locke GR III, Murray JA, Nguyen CC, Orbelo DM, Pasha SF, Ramirez FC, Sheikh J, Umar SB, Weiler CR, Wo JM, Wu TT, Yost KJ (2016) Symptoms have modest accuracy in detecting endoscopic and histologic remission in adults with eosinophilic esophagitis. Gastroenterology 150:581–590PubMedCrossRefGoogle Scholar
  98. 98.
    Sawas T, Dhalla S, Sayyar M, Pasricha PJ, Hernaez R (2015) Systematic review with meta-analysis: pharmacological interventions for eosinophilic oesophagitis. Aliment Pharmacol Ther 41:797–806PubMedCrossRefGoogle Scholar
  99. 99.
    Sayej WN, Patel R, Baker RD, Tron E, Baker SS (2009) Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis. J Pediatr Gastroenterol Nutr 49:393–399PubMedCrossRefGoogle Scholar
  100. 100.
    Schaefer ET, Fitzgerald JF, Molleston JP, Croffie JM, Pfefferkorn MD, Corkins MR, Lim JD, Steiner SJ, Gupta SK (2008) Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol 6:165–173PubMedCrossRefGoogle Scholar
  101. 101.
    Schoelwer MJ, Nebesio TD (2016) Diagnosis of adrenal insufficiency in eosinophilic esophagitis: the importance of timing of cortisol measurements in interpreting low-dose adrenocorticotropic hormone stimulation testing. J Pediatr 174:282PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Schoepfer AM, Safroneeva E, Bussmann C, Kuchen T, Portmann S, Simon H-U, Straumann A (2013) Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 145:1230–1236PubMedCrossRefGoogle Scholar
  103. 103.
    Schoepfer AM, Straumann A, Panczak R, Coslovsky M, Kuehni CE, Maurer E, Haas NA, Romero Y, Hirano I, Alexander JA, Gonsalves N, Furuta GT, Dellon ES, Leung J, Collins MH, Bussmann C, Netzer P, Gupta SK, Aceves SS, Chehade M, Moawad FJ, Enders FT, Yost KJ, Taft TH, Kern E, Zwahlen M, Safroneeva E, International Eosinophilic Esophagitis Activity Index Study Group (2014) Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis. Gastroenterology 147:1255–1266PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Schoepfer AM, Panczak R, Zwahlen M, Kuehni CE, Coslovsky M, Maurer E, Alexander JA et al (2015) How do gastroenterologists assess overall activity of eosinophilic esophagitis in adult patients? Am J Gastroenterol 110:402–414PubMedCrossRefGoogle Scholar
  105. 105.
    Schroeder S, Capocelli KE, Masterson JC, Harris R, Protheroe C, Lee JJ, Furuta GT (2013) Effect of proton pump inhibitor on esophageal eosinophilia. J Pediatr Gastroenterol Nutr 56:166–172PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Simon D, Cianferoni A, Spergel JM, Aceves S, Holbreich M, Venter C, Rothenberg ME, Terreehorst I, Muraro A, Lucendo AJ, Schoepfer A, Straumann A, Simon HU (2016) Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity. Allergy 71:611–620PubMedCrossRefGoogle Scholar
  107. 107.
    Slae M, Persad R, Leung AJ-T, Gabr R, Brocks D, Huynh HQ (2015) Role of environmental factors in the development of pediatric eosinophilic esophagitis. Dig Dis Sci 60:3364–3372PubMedCrossRefGoogle Scholar
  108. 108.
    Sodikoff J, Hirano I (2016) Proton pump inhibitor-responsive esophageal eosinophilia does not preclude food-responsive eosinophilic esophagitis. J Allergy Clin Immunol 137:631–633PubMedCrossRefGoogle Scholar
  109. 109.
    Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA (2002) The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol 109:363–368PubMedCrossRefGoogle Scholar
  110. 110.
    Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, O’Gorman MA et al (2012) Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 129:456–463PubMedCrossRefGoogle Scholar
  111. 111.
    Spergel JM, Brown-Whitehorn TF, Cianferoni A, Shuker M, Wang M-L, Verma R, Liacouras CA (2012) Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allergy Clin Immunol 130:461–467PubMedCrossRefGoogle Scholar
  112. 112.
    Straumann A, Bussmann C, Conus S, Beglinger C, Simon H-U (2008) Anti-TNF-alpha (infliximab) therapy for severe adult eosinophilic esophagitis. J Allergy Clin Immunol 122:425–427PubMedCrossRefGoogle Scholar
  113. 113.
    Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, Beglinger C, Smith DA, Patel J, Byrne M, Simon HU (2010) Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 59:21–30PubMedCrossRefGoogle Scholar
  114. 114.
    Straumann A, Conus S, Degen L, Frei C, Bussmann C, Beglinger C, Schoepfer A, Simon H-U (2011) Long-term budesonide maintenance treatment is partially effective for patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 9:400–409PubMedCrossRefGoogle Scholar
  115. 115.
    Stumphy J, Al-Zubeidi D, Guerin L, Mitros F, Rahhal R (2011) Observations on use of montelukast in pediatric eosinophilic esophagitis: insights for the future. Dis Esophagus 24:229–234PubMedCrossRefGoogle Scholar
  116. 116.
    Tan ND, Xiao YL, Chen MH (2015) Steroids therapy for eosinophilic esophagitis: systematic review and meta-analysis. J Dig Dis 16:431–442PubMedCrossRefGoogle Scholar
  117. 117.
    Tjon JA, Pe M, Soscia J, Mahant S (2013) Efficacy and safety of proton pump inhibitors in the management of pediatric gastroesophageal reflux disease. Pharmacotherapy 33:956–971PubMedCrossRefGoogle Scholar
  118. 118.
    van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA (2011) Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics 127:925–935PubMedCrossRefGoogle Scholar
  119. 119.
    van Rhijn BD, Vlieg-Boerstra BJ, Versteeg SA, Akkerdaas JH, van Ree R, Terreehorst I, Sprikkelman AB, Verheij J, Smout AJPM, Bredenoord AJ (2015) Evaluation of allergen-microarray-guided dietary intervention as treatment of eosinophilic esophagitis. J Allergy Clin Immunol 136(4):1095–1097PubMedCrossRefGoogle Scholar
  120. 120.
    Vazquez-Elizondo G, Ngamruengphong S, Khrisna M, Devault KR, Talley NJ, Achem SR (2013) The outcome of patients with oesophageal eosinophilic infiltration after an eight-week trial of a proton pump inhibitor. Aliment Pharmacol Ther 38:1312–1319PubMedCrossRefGoogle Scholar
  121. 121.
    Warners MJ, Vlieg-Boerstra BJ, Verheij J, van Rhijn BD, Van Ampting MTJ, Harthoorn LF, de Jonge WJ et al (2017) Elemental diet decreases inflammation and improves symptoms in adult eosinophilic oesophagitis patients. Aliment Pharmacol Ther 45:777–787PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Wen T, Dellon ES, Moawad FJ, Furuta GT, Aceves SS, Rothenberg ME (2015) Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation. J Allergy Clin Immunol 135:187–197PubMedCrossRefGoogle Scholar
  123. 123.
    Wolf WA, Jerath MR, Sperry SLW, Shaheen NJ, Dellon ES (2014) Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol 12:1272–1279PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PediatricsHospital General de TomellosoTomellosoSpain
  2. 2.Department of GastroenterologyHospital General de TomellosoCiudad RealSpain
  3. 3.Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain

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