, Volume 79, Issue 13, pp 1419–1434 | Cite as

Pharmacotherapies for the Treatment of Eosinophilic Esophagitis: State of the Art Review

  • Willemijn E. de Rooij
  • Evan S. Dellon
  • Claire E. Parker
  • Brian G. Feagan
  • Vipul Jairath
  • Christopher Ma
  • Albert J. BredenoordEmail author
Review Article


Eosinophilic esophagitis (EoE), a chronic allergic disorder of the esophagus, is characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. The incidence of EoE has increased substantially over the past two decades, coinciding with the so-called allergy epidemic. Current treatment options consist of dietary intervention, endoscopic dilatation, and pharmacotherapy. Given that EoE is a chronic progressive disease that is prone to relapse after cessation of therapy, these treatment options are suboptimal for long-term management. Persistent, uncontrolled esophageal inflammation is associated with esophageal remodeling and stricture formation, thus, the creation and/or discovery of alternative treatments is of paramount importance. The pathogenesis of EoE is currently under intense investigation, and recent insights concerning cellular and molecular etiology have led to the development of therapies that target specific pathophysiological pathways. This article provides an overview of established EoE pharmacotherapies, which include proton pump inhibitors and swallowed topical steroids. Additionally, anti-allergic targets, immunosuppressives, and monoclonal antibodies (such as mepolizumab, reslizumab, QAX576, RPC4046, dupilumab, omalizumab, and infliximab) that have been evaluated as treatments for EoE are summarized. Finally, several promising therapeutic agents (e.g., sialic acid-binding immunoglobulin-like lectin 8 antibodies, the transforming growth factor-β1 signal blocker losartan, CC chemokine receptor type 3 antagonists, thymic stromal lymphopoietin antibodies, antibodies targeting the α4β7 integrin, anti-interleukin-9 antibodies, and anti-interleukin-15 antibodies) that target specific molecules or cells implicated in the pathogenesis of EoE are proposed.


Compliance with Ethical Standards


No sources of funding were used to conduct this study or prepare this manuscript.

Conflicts of interest

WEdR has no conflicts of interest that are directly relevant to the content of this article. ESD has received research funding from Adare, Allakos, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos, Regeneron, and Shire; consulting fees from Adare, Alivio, Allakos, AstraZeneca, Banner, Calypso, Enumeral, EsoCap, Celgene/Receptos, GSK, Regeneron, Robarts and Shire; and educational grants from Allakos, Banner, and Holoclara. CEP is an employee of Robarts Clinical Trials Inc. BGF has received grant/research support from AbbVie Inc., Amgen Inc., AstraZeneca/MedImmune Ltd., Atlantic Pharmaceuticals Ltd., Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann-La Roche Ltd., Gilead Sciences Inc., GlaxoSmithKline (GSK), Janssen Research & Development LLC., Pfizer Inc., Receptos Inc./Celgene International, Sanofi, Santarus Inc., Takeda Development Center Americas Inc., Tillotts Pharma AG, and UCB; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport Inc., Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD Inc, JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., and Zyngenia; speakers bureaux fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; and is the Senior Scientific Officer of Robarts Clinical Trials Inc. CM has received consulting fees from Robarts Clinical Trials Inc. VJ has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials Inc, Topivert, and Celltrion; and speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, and Pfizer. AJB has received research funding from Nutricia, Norgine, and Bayer; and speaker and/or consulting fees from Laborie, EsoCap, Diversatek, Medtronic, DrFalk, Calypso, Thelial, Regeneron, Celgene, Bayer, Norgine, AstraZeneca, Almirall, and Allergan.


  1. 1.
    Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128(1):3.e6–20.e6. (quiz 1-2).CrossRefGoogle Scholar
  2. 2.
    Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342–63. Scholar
  3. 3.
    Warners MJ, de Rooij W, van Rhijn BD, Verheij J, Bruggink AH, Smout A, et al. Incidence of eosinophilic esophagitis in the Netherlands continues to rise: 20-year results from a nationwide pathology database. Neurogastroenterol Motil. 2018;30(1):1. Scholar
  4. 4.
    Dellon ES, Erichsen R, Baron JA, Shaheen NJ, Vyberg M, Sorensen HT, et al. The increasing incidence and prevalence of eosinophilic oesophagitis outpaces changes in endoscopic and biopsy practice: national population-based estimates from Denmark. Aliment Pharmacol Ther. 2015;41(7):662–70. Scholar
  5. 5.
    Attwood SEA, Smyrk TC, Demeester TR, Jones JB. Esophageal eosinophilia with dysphagia. Dig Dis Sci. 1993;38(1):109–16. Scholar
  6. 6.
    Arias A, Perez-Martinez I, Tenias JM, Lucendo AJ. Systematic review with meta-analysis: the incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther. 2016;43(1):3–15. Scholar
  7. 7.
    Dellon ES, Hirano I. Epidemiology and natural history of eosinophilic esophagitis. Gastroenterology. 2018;154(2):319.e3–332.e3. Scholar
  8. 8.
    Dellon ES, Jensen ET, Martin CF, Shaheen NJ, Kappelman MD. Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol Hepatol. 2014;12(4):589.e1–596.e1. Scholar
  9. 9.
    Giriens B, Yan P, Safroneeva E, Zwahlen M, Reinhard A, Nydegger A, et al. Escalating incidence of eosinophilic esophagitis in Canton of Vaud, Switzerland, 1993–2013: a population-based study. Allergy. 2015;70(12):1633–9. Scholar
  10. 10.
    Hruz P, Straumann A, Bussmann C, Heer P, Simon HU, Zwahlen M, et al. Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol. 2011;128(6):1349.e5–1350.e5. Scholar
  11. 11.
    Mansoor E, Cooper GS. The 2010–2015 prevalence of eosinophilic esophagitis in the USA: a population-based study. Dig Dis Sci. 2016;61(10):2928–34. Scholar
  12. 12.
    Prasad GA, Alexander JA, Schleck CD, Zinsmeister AR, Smyrk TC, Elias RM, et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol. 2009;7(10):1055–61. Scholar
  13. 13.
    Schoepfer A, Blanchard C, Dawson H, Lucendo A, Mauro A, Ribi C, et al. Eosinophilic esophagitis: latest insights from diagnosis to therapy. Ann N Y Acad Sci. 2018;1434(1):84–93. Scholar
  14. 14.
    Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46.e42–54.e42. (quiz e30).CrossRefGoogle Scholar
  15. 15.
    DeBrosse CW, Collins MH, Buckmeier Butz BK, Allen CL, King EC, Assa’ad AH, et al. Identification, epidemiology, and chronicity of pediatric esophageal eosinophilia, 1982–1999. J Allergy Clin Immunol. 2010;126(1):112–9. Scholar
  16. 16.
    Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006;355(21):2226–35. Scholar
  17. 17.
    Dellon ES. Epidemiology of eosinophilic esophagitis. Gastroenterol Clin North Am. 2014;43(2):201–18. Scholar
  18. 18.
    Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004;351(9):940–1. Scholar
  19. 19.
    Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology. 2018;155(4):1022.e10–1033.e10. Scholar
  20. 20.
    Prasad GA, Talley NJ, Romero Y, Arora AS, Kryzer LA, Smyrk TC, et al. Prevalence and predictive factors of eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. Am J Gastroenterol. 2007;102(12):2627–32. Scholar
  21. 21.
    Lucendo AJ, Molina-Infante J, Arias A, von Arnim U, Bredenoord AJ, Bussmann C, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United Eur Gastroenterol J. 2017;5(3):335–58. Scholar
  22. 22.
    Schoepfer AM, Safroneeva E, Bussmann C, Kuchen T, Portmann S, Simon HU, et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology. 2013;145(6):1230.e1-2–1236.e1-2. Scholar
  23. 23.
    Straumann A, Bussmann C, Zuber M, Vannini S, Simon HU, Schoepfer A. Eosinophilic esophagitis: analysis of food impaction and perforation in 251 adolescent and adult patients. Clin Gastroenterol Hepatol. 2008;6(5):598–600. Scholar
  24. 24.
    Warners MJ, Oude Nijhuis RAB, de Wijkerslooth LRH, Smout A, Bredenoord AJ. The natural course of eosinophilic esophagitis and long-term consequences of undiagnosed disease in a large cohort. Am J Gastroenterol. 2018;113(6):836–44. Scholar
  25. 25.
    Greuter T, Bussmann C, Safroneeva E, Schoepfer AM, Biedermann L, Vavricka SR, et al. Long-term treatment of eosinophilic esophagitis with swallowed topical corticosteroids: development and evaluation of a therapeutic concept. Am J Gastroenterol. 2017;112(10):1527–35. Scholar
  26. 26.
    Schaefer ET, Fitzgerald JF, Molleston JP, Croffie JM, Pfefferkorn MD, Corkins MR, 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(2):165–73. Scholar
  27. 27.
    Gomez-Torrijos E, Garcia-Rodriguez R, Castro-Jimenez A, Rodriguez-Sanchez J, Mendez Diaz Y, Molina-Infante J. The efficacy of step-down therapy in adult patients with proton pump inhibitor-responsive oesophageal eosinophilia. Aliment Pharmacol Ther. 2016;43(4):534–40. Scholar
  28. 28.
    Gutierrez-Junquera C, Fernandez-Fernandez S, Cilleruelo ML, Rayo A, Echeverria L, Borrell B, et al. Long-term treatment with proton pump inhibitors Is effective in children with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2018;67(2):210–6. Scholar
  29. 29.
    Molina-Infante J, Rodriguez-Sanchez J, Martinek J, van Rhijn BD, Krajciova J, Rivas MD, et al. Long-term loss of response in proton pump inhibitor-responsive esophageal eosinophilia is uncommon and influenced by CYP2C19 genotype and rhinoconjunctivitis. Am J Gastroenterol. 2015;110(11):1567–75. Scholar
  30. 30.
    Moledina DG, Perazella MA. PPIs and kidney disease: from AIN to CKD. J Nephrol. 2016;29(5):611–6. Scholar
  31. 31.
    Ye X, Liu H, Wu C, Qin Y, Zang J, Gao Q, et al. Proton pump inhibitors therapy and risk of hip fracture: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2011;23(9):794–800. Scholar
  32. 32.
    Eluri S, Runge TM, Hansen J, Kochar B, Reed CC, Robey BS, et al. Diminishing effectiveness of long-term maintenance topical steroid therapy in PPI non-responsive eosinophilic esophagitis. Clin Transl Gastroenterol. 2017;8(6):e97. Scholar
  33. 33.
    Rajan J, Newbury RO, Anilkumar A, Dohil R, Broide DH, Aceves SS. Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids. J Allergy Clin Immunol. 2016;137(1):147.e8–156.e8. Scholar
  34. 34.
    Straumann A, Conus S, Degen L, Frei C, Bussmann C, Beglinger C, et al. Long-term budesonide maintenance treatment is partially effective for patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2011;9(5):400.e1–409.e1. Scholar
  35. 35.
    Andreae DA, Hanna MG, Magid MS, Malerba S, Andreae MH, Bagiella E, et al. Swallowed fluticasone propionate is an effective long-term maintenance therapy for children with eosinophilic esophagitis. Am J Gastroenterol. 2016;111(8):1187–97. Scholar
  36. 36.
    Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005;3(12):1198–206.CrossRefGoogle Scholar
  37. 37.
    Noel RJ, Putnam PE, Collins MH, Assa’ad AH, Guajardo JR, Jameson SC, et al. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2004;2(7):568–75.CrossRefGoogle Scholar
  38. 38.
    Falcoz C, Oliver R, McDowall JE, Ventresca P, Bye A, Daley-Yates PT. Bioavailability of orally administered micronised fluticasone propionate. Clin Pharmacokinet. 2000;39(Suppl 1):9–15. Scholar
  39. 39.
    Eluri S, Runge T, Hansen J, Kochar B, Reed CC, Robey B, et al. Mo1175 Diminishing effectiveness of maintenance topical steroid therapy on long-term endoscopic and histologic outcomes in eosinophilic esophagitis. Gastroenterology. 2016;150(4):S658–9. Scholar
  40. 40.
    Straumann A, Bauer M, Fischer B, Blaser K, Simon HU. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. J Allergy Clin Immunol. 2001;108(6):954–61. Scholar
  41. 41.
    Blanchard C, Stucke EM, Rodriguez-Jimenez B, Burwinkel K, Collins MH, Ahrens A, et al. A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol. 2011;127(1):208–317. Scholar
  42. 42.
    Blanchard C, Mingler MK, Vicario M, Abonia JP, Wu YY, Lu TX, et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007;120(6):1292–300. Scholar
  43. 43.
    Aceves SS, Newbury RO, Dohil R, Bastian JF, Broide DH. Esophageal remodeling in pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119(1):206–12. Scholar
  44. 44.
    Tkachenko E, Rawson R, La E, Doherty TA, Baum R, Cavagnero K, et al. Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression. J Allergy Clin Immunol. 2016;137(4):1270.e1–1272.e1. Scholar
  45. 45.
    Chehade M, Sher E. Medical therapy versus dietary avoidance in eosinophilic esophagitis: Which approach is better? Allergy Asthma Proc. 2017;38(3):170–6. Scholar
  46. 46.
    Gonsalves N. Steroids versus dietary therapy for the treatment of eosinophilic esophagitis. Curr Opin Gastroenterol. 2014;30(4):396–401. Scholar
  47. 47.
    Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142(7):1451.e1–1459.e1. Scholar
  48. 48.
    Runge TM, Eluri S, Woosley JT, Shaheen NJ, Dellon ES. Control of inflammation decreases the need for subsequent esophageal dilation in patients with eosinophilic esophagitis. Dis Esophagus. 2017;30(7):1–7. Scholar
  49. 49.
    Lucendo AJ, Arias A, De Rezende LC, Yague-Compadre JL, Mota-Huertas T, Gonzalez-Castillo S, 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(5):1037–46. Scholar
  50. 50.
    Rieder F, Nonevski I, Ma J, Ouyang Z, West G, Protheroe C, et al. T-helper 2 cytokines, transforming growth factor beta1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis. Gastroenterology. 2014;146(5):1266.e1-9–1277.e1-9. Scholar
  51. 51.
    Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013;108(5):679–92. Scholar
  52. 52.
    Spechler SJ, Genta RM, Souza RF. Thoughts on the complex relationship between gastroesophageal reflux disease and eosinophilic esophagitis. Am J Gastroenterol. 2007;102(6):1301–6. Scholar
  53. 53.
    Molina-Infante J, van Rhijn BD. Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis. Best Pract Res Clin Gastroenterol. 2015;29(5):749–58. Scholar
  54. 54.
    Krarup AL, Villadsen GE, Mejlgaard E, Olesen SS, Drewes AM, Funch-Jensen P. Acid hypersensitivity in patients with eosinophilic oesophagitis. Scand J Gastroenterol. 2010;45(3):273–81. Scholar
  55. 55.
    Desai TK, Stecevic V, Chang CH, Goldstein NS, Badizadegan K, Furuta GT. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc. 2005;61(7):795–801.CrossRefGoogle Scholar
  56. 56.
    Dranove JE, Horn DS, Davis MA, Kernek KM, Gupta SK. Predictors of response to proton pump inhibitor therapy among children with significant esophageal eosinophilia. J Pediatr. 2009;154(1):96–100. Scholar
  57. 57.
    Molina-Infante J, Ferrando-Lamana L, Ripoll C, Hernandez-Alonso M, Mateos JM, Fernandez-Bermejo M, et al. Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol. 2011;9(2):110–7. Scholar
  58. 58.
    Ngo P, Furuta GT, Antonioli DA, Fox VL. Eosinophils in the esophagus–peptic or allergic eosinophilic esophagitis? Case series of three patients with esophageal eosinophilia. Am J Gastroenterol. 2006;101(7):1666–70. Scholar
  59. 59.
    Lucendo AJ, Arias A, Molina-Infante J. 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. 2016;14(1):13.e1–22.e1. Scholar
  60. 60.
    van Rhijn BD, Weijenborg PW, Verheij J, van den Bergh Weerman MA, Verseijden C, van den Wijngaard RM, 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(11):1815.e2–1823.e2. Scholar
  61. 61.
    Ishimura N, Ishihara S, Kinoshita Y. Sustained acid suppression by potassium-competitive acid blocker (P-CAB) may be an attractive treatment candidate for patients with eosinophilic esophagitis. Am J Gastroenterol. 2016;111:1203. Scholar
  62. 62.
    Cheng E, Zhang X, Huo X, Yu C, Zhang Q, Wang DH, et al. Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut. 2013;62(6):824–32. Scholar
  63. 63.
    Weinstein MLSM, Adams EL. Omeprazole attenuates oxygen-derived free radical production from human neutrophils. Free Radic Biol Med. 1996;21(5):727–31.CrossRefGoogle Scholar
  64. 64.
    Zhang X, Cheng E, Huo X, Yu C, Zhang Q, Pham TH, et al. Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PloS One. 2012;7(11):e50037. Scholar
  65. 65.
    Sasaki T, Yamaya M, Yasuda H, Inoue D, Yamada M, Kubo H, et al. The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured human tracheal epithelial cells. Eur J Pharmacol. 2005;509(2–3):201–10. Scholar
  66. 66.
    Cheng E, Zhang X, Wilson KS, Wang DH, Park JY, Huo X, et al. JAK-STAT6 pathway inhibitors block eotaxin-3 secretion by epithelial cells and fibroblasts from esophageal eosinophilia patients: promising agents to improve inflammation and prevent fibrosis in EoE. PloS One. 2016;11(6):e0157376. Scholar
  67. 67.
    Aceves SS, Newbury RO, Chen D, Mueller J, Dohil R, Hoffman H, et al. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy. 2010;65(1):109–16. Scholar
  68. 68.
    van Rhijn BD, Verheij J, van den Bergh Weerman MA, Verseijden C, van den Wijngaard RM, de Jonge WJ, 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(9):1289–97. Scholar
  69. 69.
    Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr. 1998;26(4):380–5.CrossRefGoogle Scholar
  70. 70.
    Dellon ES, Sheikh A, Speck O, Woodward K, Whitlow AB, Hores JM, et al. Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis. Gastroenterology. 2012;143(2):321.e1–324.e1. Scholar
  71. 71.
    Miehlke S, Hruz P, Vieth M, Bussmann C, von Arnim U, Bajbouj M, et al. A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut. 2016;65(3):390–9. Scholar
  72. 72.
    Lucendo AJ, Miehlke S, Schlag C, Vieth M, von Arnim U, Molina-Infante J, et al. Efficacy of Budesonide orodispersible tablets as induction therapy for eosinophilic esophagitis in a randomized placebo-controlled trial. Gastroenterology. 2019. (e-pub ahead of print).CrossRefPubMedGoogle Scholar
  73. 73.
    European Medicines Agency. New medicine for rare inflammatory condition of the oesophagus: Jorveza approved under accelerated assessment. Accessed 2 Jan 2 2018.
  74. 74.
    Lieberman JA, Zhang J, Whitworth J, Cavender C. A randomized, double-blinded, placebo-controlled study of the use of viscous oral cromolyn sodium for the treatment of eosinophilic esophagitis. Ann Allergy Asthma. 2018;120(5):527–31. Scholar
  75. 75.
    Langlois A, Ferland C, Tremblay GM, Laviolette M. Montelukast regulates eosinophil protease activity through a leukotriene-independent mechanism. J Allergy Clin Immunol. 2006;118(1):113–9. Scholar
  76. 76.
    Stumphy J, Al-Zubeidi D, Rahhal R, Mitros F, Guerin L. Observations on use of montelukast in pediatric eosinophilic esophagitis: insights for the future. Dis Esophagus. 2011;24(4):229–34. Scholar
  77. 77.
    Alexander JA, Ravi K, Enders FT, Geno DM, Kryzer LA, Mara KC, et al. Montelukast does not maintain symptom remission after topical steroid therapy for eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2017;15(2):214.e2–221.e2. Scholar
  78. 78.
    Lucendo AJ, De Rezende LC, Jimenez-Contreras S, Yague-Compadre JL, Gonzalez-Cervera J, Mota-Huertas T, et al. Montelukast was inefficient in maintaining steroid-induced remission in adult eosinophilic esophagitis. Dig Dis Sci. 2011;56(12):3551–8. Scholar
  79. 79.
    Peinhaupt M, Sturm EM, Heinemann A. Prostaglandins and their receptors in eosinophil function and as therapeutic targets. Front Med (Lausanne). 2017;4:104. Scholar
  80. 80.
    Pettipher R. The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. Br J Pharmacol. 2008;153(Suppl 1):S191–9. Scholar
  81. 81.
    Straumann A, Hoesli S, Bussmann C, Stuck M, Perkins M, Collins LP, et al. Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy. 2013;68(3):375–85. Scholar
  82. 82.
    Netzer P, Gschossmann JM, Straumann A, Sendensky A, Weimann R, Schoepfer AM. Corticosteroid-dependent eosinophilic oesophagitis: azathioprine and 6-mercaptopurine can induce and maintain long-term remission. Eur J Gastroenterol Hepatol. 2007;19(10):865–9. Scholar
  83. 83.
    Molina-Infante J, Schoepfer AM, Lucendo AJ, Dellon ES. Eosinophilic esophagitis: what can we learn from Crohn’s disease? United Eur Gastroenterol J. 2017;5(6):762–72. Scholar
  84. 84.
    Mishra A, Hogan SP, Brandt EB, Rothenberg ME. IL-5 promotes eosinophil trafficking to the esophagus. J Immunol. 2002;168(5):2464–9.CrossRefGoogle Scholar
  85. 85.
    O’Byrne PM, Inman MD, Parameswaran K. The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol. 2001;108(4):503–8. Scholar
  86. 86.
    Rothenberg ME. Eosinophilia. N Eng J Med. 1998;338(22):1592–600. Scholar
  87. 87.
    Masterson JC, McNamee EN, Hosford L, Capocelli KE, Ruybal J, Fillon SA, et al. Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. Gut. 2014;63(1):43–53. Scholar
  88. 88.
    Antoniu SA. Mepolizumab for difficult-to-control asthma with persistent sputum eosinophilia. Expert Opin Investig Drugs. 2009;18(6):869–71. Scholar
  89. 89.
    Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T, Acke F, et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011;128(5):989.e1-8–995.e1-8. Scholar
  90. 90.
    Plotz SG, Simon HU, Darsow U, Simon D, Vassina E, Yousefi S, et al. Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with eosinophilic dermatitis. N Engl J Med. 2003;349(24):2334–9. Scholar
  91. 91.
    Stein ML, Collins MH, Villanueva JM, Kushner JP, Putnam PE, Buckmeier BK, et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118(6):1312–9. Scholar
  92. 92.
    Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59(1):21–30. Scholar
  93. 93.
    Assa’ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, et al. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011;141(5):1593–604. Scholar
  94. 94.
    Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129(2):456.e1-3–463.e1-3. Scholar
  95. 95.
    Markowitz JE, Jobe L, Miller M, Frost C, Laney Z, Eke R. Safety and efficacy of reslizumab for children and adolescents with eosinophilic esophagitis treated for 9 years. J Pediatr Gastroenterol Nutr. 2018;66(6):893–7. Scholar
  96. 96.
    Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448–58. Scholar
  97. 97.
    Matera MG, Rogliani P, Calzetta L, Canonica GW, Cazzola M. Benralizumab for the treatment of asthma. Drugs Today (Barc). 2017;53(12):633–45. Scholar
  98. 98.
    FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–41. Scholar
  99. 99.
    Blanchard C, Mingler MK, McBride M, Putnam PE, Collins MH, Chang G, et al. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses. Mucosal Immunol. 2008;1(4):289–96. Scholar
  100. 100.
    Blanchard C, Stucke EM, Burwinkel K, Caldwell JM, Collins MH, Ahrens A, et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010;184(7):4033–41. Scholar
  101. 101.
    Sherrill JD, Kc K, Wu D, Djukic Z, Caldwell JM, Stucke EM, et al. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol. 2014;7(3):718–29. Scholar
  102. 102.
    Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology. 2003;125(5):1419–27.CrossRefGoogle Scholar
  103. 103.
    Rothenberg ME, Wen T, Greenberg A, Alpan O, Enav B, Hirano I, et al. Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. J Allergy Clin Immunol. 2015;135(2):500–7. Scholar
  104. 104.
    Hirano I, Collins MH, Assouline-Dayan Y, Evans L, Gupta S, Schoepfer AM, et al. RPC4046, a monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients with eosinophilic esophagitis. Gastroenterology. 2018. Scholar
  105. 105.
    Collins MH, Martin LJ, Alexander ES, Boyd JT, Sheridan R, He H, et al. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus. 2017;30(3):1–8. Scholar
  106. 106.
    Dellon ES, Collins MH, Assouline-Dayan Y, Evans L, Gupta S, Schoepfer A, et al. Long-term efficacy and safety of RPC4046, an anti-interleukin-13 monoclonal antibody, in patients with eosinophilic esophagitis: results from the open-label extension of the HEROES study. J Allergy Clin Immunol. 2019;143(2):AB208. Scholar
  107. 107.
    Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088–98. Scholar
  108. 108.
    Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41(2):330–8. Scholar
  109. 109.
    Simpson EL, Flohr C, Eichenfield LF, Bieber T, Sofen H, Taieb A, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78(5):863.e11–871.e11. Scholar
  110. 110.
    Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2019;143(1):135–41. Scholar
  111. 111.
    Abonia JP, Blanchard C, Butz BB, Rainey HF, Collins MH, Stringer K, et al. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol. 2010;126(1):140–9. Scholar
  112. 112.
    Mulder DJ, Mak N, Hurlbut DJ, Justinich CJ. Atopic and non-atopic eosinophilic oesophagitis are distinguished by immunoglobulin E-bearing intraepithelial mast cells. Histopathology. 2012;61(5):810–22. Scholar
  113. 113.
    Vicario M, Blanchard C, Stringer KF, Collins MH, Mingler MK, Ahrens A, et al. Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis. Gut. 2010;59(1):12–20. Scholar
  114. 114.
    Arasi S, Costa S, Magazzù G, Ieni A, Crisafulli G, Caminiti L, et al. Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis. Ital J Pediatr. 2016;42:32. Scholar
  115. 115.
    Rocha R, Vitor AB, Trindade E, Lima R, Tavares M, Lopes J, et al. Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Eur J Pediatr. 2011;170(11):1471–4. Scholar
  116. 116.
    Clayton F, Fang JC, Gleich GJ, Lucendo AJ, Olalla JM, Vinson LA, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology. 2014;147(3):602–9. Scholar
  117. 117.
    Loizou D, Enav B, Komlodi-Pasztor E, Hider P, Kim-Chang J, Noonan L, et al. A pilot study of omalizumab in eosinophilic esophagitis. PloS One. 2015;10(3):e0113483. Scholar
  118. 118.
    Kagami S, Saeki H, Komine M, Kakinuma T, Tsunemi Y, Nakamura K, et al. Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells. Clin Exp Immunol. 2005;141(3):459–66. Scholar
  119. 119.
    Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 study group. N Engl J Med. 1997;337(15):1029–35.CrossRefGoogle Scholar
  120. 120.
    Straumann A, Bussmann C, Conus S, Beglinger C, Simon HU. Anti-TNF-alpha (infliximab) therapy for severe adult eosinophilic esophagitis. J Allergy Clin Immunol. 2008;122(2):425–7. Scholar
  121. 121.
    Radonjic-Hoesli S, Valent P, Klion AD, Wechsler ME, Simon H-U. Novel targeted therapies for eosinophil-associated diseases and allergy. Annu Rev Pharmacol Toxicol. 2015;55(1):633–56. Scholar
  122. 122.
    Rubinstein E, Cho JY, Rosenthal P, Chao J, Miller M, Pham A, et al. Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2011;53(4):409–16. Scholar
  123. 123.
    Youngblood B, Brock EC, Leung J, Bebbington C, Tomasevic N. Anti-Siglec-8 antibody reduces eosinophil and mast cell infiltration in a mouse model of eosinophilic gastritis: a novel therapeutic approach for eosinophilic gastrointestinal diseases. Gastroenterology. 2018;154(6):S1358. Scholar
  124. 124.
    Lavoie P, Robitaille G, Agharazii M, Ledbetter S, Lebel M, Lariviere R. Neutralization of transforming growth factor-beta attenuates hypertension and prevents renal injury in uremic rats. J Hypertens. 2005;23(10):1895–903.CrossRefGoogle Scholar
  125. 125.
    Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science (New York, NY). 2006;312(5770):117–21. Scholar
  126. 126.
    Dietz HC. TGF-beta in the pathogenesis and prevention of disease: a matter of aneurysmic proportions. J Clin Investig. 2010;120(2):403–7. Scholar
  127. 127.
    Cohn RD, van Erp C, Habashi JP, Soleimani AA, Klein EC, Lisi MT, et al. Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states. Nat Med. 2007;13(2):204–10. Scholar
  128. 128.
    Chamberlain JS. ACE inhibitor bulks up muscle. Nat Med. 2007;13(2):125–6. Scholar
  129. 129.
    Takeda N, Yagi H, Hara H, Fujiwara T, Fujita D, Nawata K, et al. Pathophysiology and management of cardiovascular manifestations in Marfan and Loeys-Dietz syndromes. Int Heart J. 2016;57(3):271–7. Scholar
  130. 130.
    Neighbour H, Boulet LP, Lemiere C, Sehmi R, Leigh R, Sousa AR, et al. Safety and efficacy of an oral CCR130 antagonist in patients with asthma and eosinophilic bronchitis: a randomized, placebo-controlled clinical trial. Clin Exp Allergy. 2014;44(4):508–16. Scholar
  131. 131.
    Noti M, Wojno ED, Kim BS, Siracusa MC, Giacomin PR, Nair MG, et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med. 2013;19(8):1005–13. Scholar
  132. 132.
    Gauvreau GM, O’Byrne PM, Boulet LP, Wang Y, Cockcroft D, Bigler J, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med. 2014;370(22):2102–10. Scholar
  133. 133.
    Simpson EL, Parnes JR, She D, Crouch S, Rees W, Mo M, et al. Tezepelumab, an anti-TSLP monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: a randomized phase 2a clinical trial. J Am Acad Dermatol. 2018. Scholar
  134. 134.
    Caldwell JM, Collins MH, Kemme KA, Sherrill JD, Wen T, Rochman M, et al. Cadherin 26 is an alpha integrin-binding epithelial receptor regulated during allergic inflammation. Mucosal Immunol. 2017;10(5):1190–201. Scholar
  135. 135.
    Nhu QM, Chiao H, Moawad FJ, Bao F, Konijeti GG. The anti-alpha4beta7 integrin therapeutic antibody for inflammatory bowel disease, vedolizumab, ameliorates eosinophilic esophagitis: a novel clinical observation. Am J Gastroenterol. 2018;113(8):1261–3. Scholar
  136. 136.
    Kim HP, Reed CC, Herfarth HH, Dellon ES. Vedolizumab treatment may reduce steroid burden and improve histology in patients with eosinophilic gastroenteritis. Clin Gastroenterol Hepatol. 2018;16(12):1992–4. Scholar
  137. 137.
    Otani IM, Anilkumar AA, Newbury RO, Bhagat M, Beppu LY, Dohil R, et al. Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2013;131(6):1576–82. Scholar
  138. 138.
    Aceves SS, Chen D, Newbury RO, Dohil R, Bastian JF, Broide DH. Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-beta1, and increase esophageal smooth muscle contraction. J Allergy Clin Immunol. 2010;126(6):1198.e4–1204.e4. Scholar
  139. 139.
    Chen CY, Lee JB, Liu B, Ohta S, Wang PY, Kartashov AV, et al. Induction of interleukin-9-producing mucosal mast cells promotes susceptibility to IgE-mediated experimental food allergy. Immunity. 2015;43(4):788–802. Scholar
  140. 140.
    Oh CK, Leigh R, McLaurin KK, Kim K, Hultquist M, Molfino NA. A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma. Respir Res. 2013;14:93. Scholar
  141. 141.
    Doshi A, Khamishon R, Rawson R, Duong L, Dohil L, Myers SJ, et al. Interleukin 9 alters epithelial barrier and E-cadherin in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2019;68(2):225–31. Scholar
  142. 142.
    Hoontrakoon R, Chu HW, Gardai SJ, Wenzel SE, McDonald P, Fadok VA, et al. Interleukin-15 inhibits spontaneous apoptosis in human eosinophils via autocrine production of granulocyte macrophage-colony stimulating factor and nuclear factor-kappaB activation. Am J Respir Cell Mol Biol. 2002;26(4):404–12. Scholar
  143. 143.
    Mori A, Suko M, Kaminuma O, Inoue S, Ohmura T, Nishizaki Y, et al. IL-15 promotes cytokine production of human T helper cells. J Immunol. 1996;156(7):2400–5.PubMedGoogle Scholar
  144. 144.
    Rayapudi M, Rajavelu P, Zhu X, Kaul A, Niranjan R, Dynda S, et al. Invariant natural killer T-cell neutralization is a possible novel therapy for human eosinophilic esophagitis. Clin Transl Immunology. 2014;3(1):e9. Scholar
  145. 145.
    Zhu X, Wang M, Mavi P, Rayapudi M, Pandey AK, Kaul A, et al. Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice. Gastroenterology. 2010;139(1):182.e7–193.e7. Scholar
  146. 146.
    Vicari AP, Schoepfer AM, Meresse B, Goffin L, Leger O, Josserand S, et al. Discovery and characterization of a novel humanized anti-IL-15 antibody and its relevance for the treatment of refractory celiac disease and eosinophilic esophagitis. MAbs. 2017;9(6):927–44. Scholar
  147. 147.
    Dellon ES, Woosley JT, Arrington A, McGee SJ, Covington J, Moist SE, et al. Efficacy of budesonide vs fluticasone for initial treatment of eosinophilic esophagitis in a randomized controlled trial. Gastroenterology. 2019;15791:65–73. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Willemijn E. de Rooij
    • 1
  • Evan S. Dellon
    • 2
  • Claire E. Parker
    • 3
  • Brian G. Feagan
    • 3
    • 4
    • 5
  • Vipul Jairath
    • 3
    • 4
    • 5
  • Christopher Ma
    • 3
    • 6
  • Albert J. Bredenoord
    • 1
    Email author
  1. 1.Department of Gastroenterology and HepatologyAcademic Medical CentreAmsterdamThe Netherlands
  2. 2.Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and SwallowingUniversity of North Carolina School of MedicineChapel HillUSA
  3. 3.Robarts Clinical Trials IncLondonCanada
  4. 4.Department of MedicineUniversity of Western OntarioLondonCanada
  5. 5.Department of Epidemiology and BiostatisticsUniversity of Western OntarioLondonCanada
  6. 6.Division of Gastroenterology and HepatologyUniversity of CalgaryCalgaryCanada

Personalised recommendations