Skip to main content
Log in

Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Topical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE).

Aims

We aimed to summarize published manuscripts that report outcomes of these therapies for EoE.

Methods

We performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis.

Results

Systematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2–96.0%] for fluticasone, 76.8% (95% PL 36.1–95.1%) for budesonide, and 69.0% (95% PL 31.9–91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0–56.7), 62.5 (95% PL 125.6 to −0.67, and 44.6 (95% PL 26.5–62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1–91.1%), 87.9% (95% PL 42.7–98.6%), and 87.3% (95% PL 64.5–96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations’ baseline eosinophil count and age.

Conclusions

The literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Dellon ES, Gonsalves N, Hirano I, et al. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013;108:679–692; quiz 693.

  2. Jensen ET, Kappelman MD, Martin CF, Dellon ES. Health-care utilization, costs, and the burden of disease related to eosinophilic esophagitis in the United States. Am J Gastroenterol. 2015;110:626–632.

    Article  PubMed  Google Scholar 

  3. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128:3–20 e26; quiz 21–22.

  4. Shah NA, Albert DM, Hall NM, Moawad FJ. Managing eosinophilic esophagitis: challenges and solutions. Clin Exp Gastroenterol. 2016;9:281–290.

    PubMed  PubMed Central  Google Scholar 

  5. Schroeder S, Fleischer DM, Masterson JC, et al. Successful treatment of eosinophilic esophagitis with ciclesonide. J Allergy Clin Immunol. 2012;129:1419–1421.

    Article  CAS  PubMed  Google Scholar 

  6. Arias A, Gonzalez-Cervera J, Tenias JM, Lucendo AJ. Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology. 2014;146:1639–1648.

    Article  PubMed  Google Scholar 

  7. Bahgat M, Dawe N, Flood L. Eosinophilic oesophagitis: a systematic review for otolaryngologists. J Laryngol Otol. 2015;129:1156–1166.

    Article  CAS  PubMed  Google Scholar 

  8. Chuang MY, Chinnaratha MA, Hancock DG, et al. Topical steroid therapy for the treatment of eosinophilic esophagitis (EoE): a systematic review and meta-analysis. Clin Transl Gastroenterol. 2015;6:e82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lipka S, Kumar A, Miladinovic B, Richter JE. 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. 2016;43:663–673.

    Article  CAS  PubMed  Google Scholar 

  10. Lucendo AJ. Meta-analysis-based guidance for dietary management in eosinophilic esophagitis. Curr Gastroenterol Rep. 2015;17:464.

    Article  PubMed  Google Scholar 

  11. Murali AR, Gupta A, Attar BM, Ravi V, Koduru P. Topical steroids in eosinophilic esophagitis: systematic review and meta-analysis of placebo controlled randomized clinical trials. J Gastroenterol Hepatol. 2015;31:1111–1119.

    Article  Google Scholar 

  12. Sawas T, Dhalla S, Sayyar M, Pasricha PJ, Hernaez R. Systematic review with meta-analysis: pharmacological interventions for eosinophilic oesophagitis. Aliment Pharmacol Ther. 2015;41:797–806.

    Article  CAS  PubMed  Google Scholar 

  13. Tan ND, Xiao YL, Chen MH. Steroids therapy for eosinophilic esophagitis: systematic review and meta-analysis. J Dig Dis. 2015;16:431–442.

    Article  CAS  PubMed  Google Scholar 

  14. Poole C, Greenland S. Random-effects meta-analyses are not always conservative. Am J Epidemiol. 1999;150:469–475.

    Article  CAS  PubMed  Google Scholar 

  15. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Higgins JP, Thompson SG. Controlling the risk of spurious findings from meta-regression. Stat Med. 2004;23:1663–1682.

    Article  PubMed  Google Scholar 

  17. Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta-analyses. BMJ. 2011;342:d549.

    Article  PubMed  Google Scholar 

  18. R Core Team. R: a language and environment for statistical computing. City; R Foundation for Statistical Computing; 2015.

  19. Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.

    Article  Google Scholar 

  20. Abe Y, Iijima K, Ohara S, et al. A Japanese case series of 12 patients with esophageal eosinophilia. J Gastroenterol. 2011;46:25–30.

    Article  PubMed  Google Scholar 

  21. Abu-Sultaneh SM, Durst P, Maynard V, Elitsur Y. Fluticasone and food allergen elimination reverse sub-epithelial fibrosis in children with eosinophilic esophagitis. Dig Dis Sci. 2011;56:97–102.

    Article  CAS  PubMed  Google Scholar 

  22. Alexander JA, Jung KW, Arora AS, et al. Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis Clin Gastroenterol Hepatol. 2012;10:742–749 e741.

  23. Arora AS, Perrault J, Smyrk TC. Topical corticosteroid treatment of dysphagia due to eosinophilic esophagitis in adults. Mayo Clin Proc. 2003;78:830–835.

    Article  CAS  PubMed  Google Scholar 

  24. Assa’ad AH, Putnam PE, Collins MH, et al. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol. 2007;119:731–738.

    Article  PubMed  Google Scholar 

  25. Butz BK, Wen T, Gleich GJ, et al. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014;147:324–333 e325.

  26. Czaja-Bulsa G, Jakubik M. Primary eosinophilic esophagitis in children of West Pomerania. Pediatr Wspolczesna. 2012;14:5–9.

    Google Scholar 

  27. Enns R, Kazemi P, Chung W, Lee M. Eosinophilic esophagitis: clinical features, endoscopic findings and response to treatment. Can J Gastroenterol. 2010;24:547–551.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Golekoh MC, Hornung LN, Mukkada VA, et al. Adrenal insufficiency after chronic swallowed glucocorticoid therapy for eosinophilic esophagitis. J Pediatr. 2016;170:240–245.

    Article  CAS  PubMed  Google Scholar 

  29. Helou EF, Simonson J, Arora AS. 3-yr-follow-up of topical corticosteroid treatment for eosinophilic esophagitis in adults. Am J Gastroenterol. 2008;103:2194–2199.

    Article  PubMed  Google Scholar 

  30. Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131:1381–1391.

    Article  CAS  PubMed  Google Scholar 

  31. Kruszewski PG, Russo JM, Franciosi JP, et al. Prospective, comparative effectiveness trial of cow’s milk elimination and swallowed fluticasone for pediatric eosinophilic esophagitis. Dis Esophagus. 2016;29:377–384.

    Article  CAS  PubMed  Google Scholar 

  32. Kuchen T, Straumann A, Safroneeva E, et al. Swallowed topical corticosteroids reduce the risk for long-lasting bolus impactions in eosinophilic esophagitis. Allergy. 2014;69:1248–1254.

    Article  CAS  PubMed  Google Scholar 

  33. Lee J, Huprich J, Kujath C, et al. Esophageal diameter is decreased in some patients with eosinophilic esophagitis and might increase with topical corticosteroid therapy. Clin Gastroenterol Hepatol. 2012;10:481–486.

    Article  CAS  PubMed  Google Scholar 

  34. Leung J, Mehrzad R, Hundal NV, et al. Longitudinal perspective on managing refractory eosinophilic esophagitis. J Allergy Clin Immunol Pract. 2015;3:951–956.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Li N, Green B, Sideridis K. Efficacy of combined treatment on eosinophilic esophagitis in adults: case study. J Gastroenterol Hepatol Res. 2012;1:153–156.

    Google Scholar 

  36. Lieberman JA, Morotti RA, Konstantinou GN, Yershov O, Chehade M. Dietary therapy can reverse esophageal subepithelial fibrosis in patients with eosinophilic esophagitis: a historical cohort. Allergy. 2012;67:1299–1307.

    Article  CAS  PubMed  Google Scholar 

  37. Lucendo AJ, Arias A, DeRezende LC, 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;128:1037–1046.

    Article  CAS  PubMed  Google Scholar 

  38. Lucendo AJ, Pascual-Turrion JM, Navarro M, et al. Endoscopic, bioptic, and manometric findings in eosinophilic esophagitis before and after steroid therapy: a case series. Endoscopy. 2007;39:765–771.

    Article  CAS  PubMed  Google Scholar 

  39. Lucendo Villarín AJ, Carrión Alonso G, Navarro Sánchez M, et al. Eosinophilic esophagitis in adults, an emerging cause of dysphagia. Description of 9 cases. Rev Esp Enferm Dig. 2005;97:229–239.

    PubMed  Google Scholar 

  40. Noel RJ, Putnam PE, Collins MH, et al. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2004;2:568–575.

    Article  CAS  PubMed  Google Scholar 

  41. Pasha SF, DiBaise JK, Kim HJ, et al. Patient characteristics, clinical, endoscopic, and histologic findings in adult eosinophilic esophagitis: a case series and systematic review of the medical literature. Dis Esophagus. 2007;20:311–319.

    Article  CAS  PubMed  Google Scholar 

  42. Pentiuk S, Putnam PE, Collins MH, Rothenberg ME. Dissociation between symptoms and histological severity in pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2009;48:152–160.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Peterson KA, Thomas KL, Hilden K, et al. Comparison of esomeprazole to aerosolized, swallowed fluticasone for eosinophilic esophagitis. Dig Dis Sci. 2010;55:1313–1319.

    Article  PubMed  Google Scholar 

  44. Philla KQ, Min SB, Hefner JN, et al. Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function. J Pediatr Endocrinol Metab. 2015;28:1101–1106.

    Article  CAS  PubMed  Google Scholar 

  45. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to treatment with fluticasone propionate. Gastrointest Endosc. 2006;63:3–12.

    Article  PubMed  Google Scholar 

  46. Sayej WN, Patel R, Baker RD, Tron E, Baker SS. Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2009;49:393–399.

    Article  CAS  PubMed  Google Scholar 

  47. Schaefer ET, Fitzgerald JF, Molleston JP, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol. 2008;6:165–173.

    Article  CAS  PubMed  Google Scholar 

  48. Schlag C, Pfefferkorn S, Brockow K, et al. Serum eosinophil cationic protein is superior to mast cell Tryptase as marker for response to topical corticosteroid therapy in eosinophilic esophagitis. J Clin Gastroenterol. 2014;48:600–606.

    Article  CAS  PubMed  Google Scholar 

  49. Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology. 2002;122:1216–1225.

    Article  CAS  PubMed  Google Scholar 

  50. van Rhijn BD, Verheij J, van den Bergh Weerman MA, et al. Histological response to fluticasone propionate in patients with eosinophilic esophagitis is associated with improved functional esophageal mucosal integrity. Am J Gastroenterol. 2015;110:1289–1297.

    Article  PubMed  Google Scholar 

  51. Wolf WA, Cotton CC, Green DJ, et al. Predictors of response to steroid therapy for eosinophilic esophagitis and treatment of steroid-refractory patients. Clin Gastroenterol Hepatol. 2015;13:452–458.

    Article  PubMed  Google Scholar 

  52. Moawad FJ, Veerappan GR, Dias JA, et al. Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia. Am J Gastroenterol. 2013;108:366–372.

    Article  CAS  PubMed  Google Scholar 

  53. Aceves SS, Bastian JF, Newbury RO, Dohil R. Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children Am J Gastroenterol. 2007;102:2271–2279; quiz 2280.

  54. Aceves SS, Newbury RO, Chen D, et al. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy. 2010;65:109–116.

    Article  CAS  PubMed  Google Scholar 

  55. Dellon ES, Sheikh A, Speck O, et al. Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis. Gastroenterology. 2012;143:321–324 e321.

  56. Dohil R, Newbury R, Fox L, Bastian J, Aceves S. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology. 2010;139:418–429.

    Article  CAS  PubMed  Google Scholar 

  57. Gupta SK, Vitanza JM, Collins MH. Efficacy and safety of oral budesonide suspension in pediatric patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2015;13:66–76 e63.

  58. Harel S, Hursh BE, Chan ES, Avinashi V, Panagiotopoulos C. Adrenal suppression in children treated with oral viscous budesonide for eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2015;61:190–193.

    Article  CAS  PubMed  Google Scholar 

  59. Miehlke S, Hruz P, Vieth M, et al. A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut. 2016;65:390–399.

    Article  CAS  PubMed  Google Scholar 

  60. Philpott H, Nandurkar S, Royce SG, Thien F, Gibson PR. A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis. Aliment Pharmacol Ther. 2016;43:985–993.

    Article  CAS  PubMed  Google Scholar 

  61. Rubinstein E, Lee JJ, Fried A, et al. Comparison of 2 delivery vehicles for viscous budesonide to treat eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr. 2014;59:317–320.

    Article  CAS  PubMed  Google Scholar 

  62. Straumann A, Conus S, Degen L, et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology. 2010;139:1526–1537, 1537 e1521.

  63. Arias A, Lucendo AJ, Martinez-Fernandez P, et al. Dietary treatment modulates mast cell phenotype, density, and activity in adult eosinophilic oesophagitis. Clin Exp Allergy. 2016;46:78–91.

    Article  CAS  PubMed  Google Scholar 

  64. Colson D, Kalach N, Soulaines P, et al. The impact of dietary therapy on clinical and biologic parameters of pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol Pract. 2014;2:587–593.

    Article  PubMed  Google Scholar 

  65. Gonsalves N, Yang GY, Doerfler B, et al. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142:1451–1459 e1451; quiz e1414–1455.

  66. Henderson CJ, Abonia JP, King EC, et al. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012;129:1570–1578.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Kagalwalla AF, Sentongo TA, Ritz S, et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006;4:1097–1102.

    Article  PubMed  Google Scholar 

  68. Lucendo AJ, Arias A, Gonzalez-Cervera J, 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;131:797–804.

    Article  PubMed  Google Scholar 

  69. Rodriguez-Sanchez J, Gomez Torrijos E, Lopez Viedma B, et al. Efficacy of IgE-targeted vs empiric six-food elimination diets for adult eosinophilic oesophagitis. Allergy. 2014;69:936–942.

    Article  CAS  PubMed  Google Scholar 

  70. Wolf WA, Jerath MR, Sperry SL, Shaheen NJ, Dellon ES. Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2014;12:1272–1279.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Rajan J, Newbury RO, Anilkumar A, et al. Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids J Allergy Clin Immunol. 2016;137:147–156 e148.

  72. Andreae DA, Hanna MG, Magid MS, et al. Swallowed fluticasone propionate is an effective long-term maintenance therapy for children with eosinophilic esophagitis. Am J Gastroenterol. 2016;111:1187–1197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Dellon ES, Liacouras CA. Advances in clinical management of eosinophilic esophagitis. Gastroenterology. 2014;147:1238–1254.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Wolf WA, Huang KZ, Durban R, et al. The six-food elimination diet for eosinophilic esophagitis increases grocery shopping cost and complexity. Dysphagia. 2016;31:765–770.

    Article  Google Scholar 

  75. Wolf WA, Cotton CC, Green DJ, et al. Evaluation of histologic cutpoints for treatment response in eosinophilic esophagitis. J Gastroenterol Hepatol Res. 2015;4:1780–1787.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Franciosi JP, Hommel KA, Bendo CB, et al. PedsQL eosinophilic esophagitis module: feasibility, reliability, and validity. J Pediatr Gastroenterol Nutr. 2013;57:57–66.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Taft TH, Kern E, Kwiatek MA, et al. The adult eosinophilic oesophagitis quality of life questionnaire: a new measure of health-related quality of life. Aliment Pharmacol Ther. 2011;34:790–798.

    Article  CAS  PubMed  Google Scholar 

  78. Dellon ES, Cotton CC, Gebhart JH, et al. Accuracy of the eosinophilic esophagitis endoscopic reference score in diagnosis and determining response to treatment. Clin Gastroenterol Hepatol. 2016;14:31–39.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This research was funded by NIH Awards T32 DK007634 (CCC, SE, WAW), and R01DK101856 (ESD).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evan S. Dellon.

Ethics declarations

Conflict of interest

Dr. Dellon is consultant for Adare, Alivio, Banner, Receptos/Celgene, Regeneron, and Shire, has received grant funding from Meritage, Miraca, Nutricia, Receptos/Celegene, Regeneron, and Shire, and has received an educational grant: Banner. The other authors have no potential conflicts related to this manuscript to report.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cotton, C.C., Eluri, S., Wolf, W.A. et al. Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression. Dig Dis Sci 62, 2408–2420 (2017). https://doi.org/10.1007/s10620-017-4642-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-017-4642-7

Keywords

Navigation