Skip to main content

Advertisement

SpringerLink
Log in

The Role of the Environment in Eosinophilic Esophagitis

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease with incompletely understood pathogenesis. Though disease manifestations were initially ascribed to a delayed reaction to food allergens, emerging evidence suggests that modifiable host factors and environmental allergen exposure may also play critical roles in the pathogenesis and ongoing manifestations of EoE. As with other atopic diseases, lack of early-life exposure to microbial pathogens leads to an immune tolerance defect and reprograms the commensal gut microflora toward a type 2 T helper (Th2) phenotype; the esophageal microbiota, a rich environment consisting of diverse bacterial species, is greatly altered by inflammation. Although multiple early life microbiome-altering factors are associated with EoE development, no causative, direct relationships have been identified. Interestingly, large, cross-sectional analyses of several populations identify an inverse relationship between Helicobacter pylori presence and EoE, likely via virulence factors that downregulate Th2 inflammation, though causality has not been proven. In regard to environmental allergens, some studies support seasonal variation in EoE diagnosis and flares, and EoE can be generated after a large, identifiable aeroallergen exposure. Examples include mouse models of intranasal Aspergillus dosing and following initiation of oral immunotherapy to foods or environmental allergens. Conversely, treatment of allergic rhinoconjunctivitis may improve EoE symptoms, though data is limited to case reports and small series. Unfortunately, biologic therapies for atopic conditions have failed to improve EoE symptoms despite improvement in esophageal eosinophil count, though dupilumab shows promise in ongoing studies. Overall, this chapter shows that EoE pathogenesis is likely multifactorial, and the environment is a key component in our understanding of EoE.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA, American College of Gastroenterology (2013) ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 108(5):679–692. https://doi.org/10.1038/ajg.2013.71

    Article  PubMed  Google Scholar 

  2. 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(5):1503–1512

    Article  CAS  Google Scholar 

  3. Moawad FJ (2018) Eosinophilic esophagitis: incidence and prevalence. Gastrointest Endosc Clin N Am 28(1):15–25. https://doi.org/10.1016/j.giec.2017.07.001

    Article  PubMed  Google Scholar 

  4. Heine RG (2015) Insights into the emerging epidemic of eosinophilic oesophagitis. Best Pract Res Clin Gastroenterol 29(5):731–737. https://doi.org/10.1016/j.bpg.2015.09.004

    Article  PubMed  Google Scholar 

  5. Arias Á, 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(1):3–15. https://doi.org/10.1111/apt.13441

    Article  CAS  PubMed  Google Scholar 

  6. Stiemsma LT, Turvey SE (2017) Asthma and the microbiome: defining the critical window in early life. Allergy Asthma Clin Immunol 13:3. https://doi.org/10.1186/s13223-016-0173-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Clausen ML, Agner T, Lilje B, Edslev SM, Johannesen TB, Andersen PS (2018) Association of Disease Severity with Skin Microbiome and Filaggrin Gene Mutations in adult atopic dermatitis. JAMA Dermatol 154:293–300. https://doi.org/10.1001/jamadermatol.2017.5440

    Article  PubMed  PubMed Central  Google Scholar 

  8. García-Compeán D, González-González JA, González-Moreno EI, Maldonado-Garza HJ (2017) Eosinophilic esophagitis. The north against the south? A bio-economic-social mechanistic approach and clinical implications. Rev Gastroenterol Mex 82(4):328–336. https://doi.org/10.1016/j.rgmx.2017.02.007

    Article  PubMed  Google Scholar 

  9. Jensen ET, Kuhl JT, Martin LJ, Langefeld CD, Dellon ES, Rothenberg ME (2017) Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol 141:632–637.e5. https://doi.org/10.1016/j.jaci.2017.07.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jensen ET, Kuhl JT, Martin LJ, Rothenberg ME, Dellon ES (2017) Prenatal, intrapartum, and postnatal factors are associated with pediatric eosinophilic esophagitis. J Allergy Clin Immunol 141:214–222. https://doi.org/10.1016/j.jaci.2017.05.018

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jensen ET, Dellon ES (2017) Household dust, innate immunity, and the Amish: lessons for eosinophilic esophagitis? Gastroenterology 152(8):2070–2072. https://doi.org/10.1053/j.gastro.2017.04.038

    Article  PubMed  Google Scholar 

  12. Jensen ET, Kappelman MD, Kim HP, Ringel-Kulka T, Dellon ES (2013) Early life exposures as risk factors for pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 57(1):67–71. https://doi.org/10.1097/MPG.0b013e318290d15a

    Article  PubMed  Google Scholar 

  13. Radano MC, Yuan Q, Katz A et al (2014) Cesarean section and antibiotic use found to be associated with eosinophilic esophagitis. J Allergy Clin Immunol Pract 2(4):475–77.e1. https://doi.org/10.1016/j.jaip.2014.02.018

    Article  PubMed  Google Scholar 

  14. Kottyan LC, Davis BP, Sherrill JD, Liu K, Rochman M, Kaufman K, Weirauch MT, Vaughn S, Lazaro S, Rupert AM, Kohram M, Stucke EM, Kemme KA, Magnusen A, He H, Dexheimer P, Chehade M, Wood RA, Pesek RD, Vickery BP, Fleischer DM, Lindbad R, Sampson HA, Mukkada VA, Putnam PE, Abonia JP, Martin LJ, Harley JB, Rothenberg ME (2014) Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet 46(8):895–900. https://doi.org/10.1038/ng.3033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, Kambayashi T, LaRosa DF, Renner ED, Orange JS, Bushman FD, Artis D (2012) Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18(4):538–546. https://doi.org/10.1038/nm.2657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Stefka AT, Feehley T, Tripathi P, Qiu J, McCoy K, Mazmanian SK, Tjota MY, Seo GY, Cao S, Theriault BR, Antonopoulos DA, Zhou L, Chang EB, Fu YX, Nagler CR (2014) Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci U S A 111(36):13145–13150. https://doi.org/10.1073/pnas.1412008111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. O'Shea KM, Aceves SS, Dellon ES et al (2017) Pathophysiology of eosinophilic esophagitis. Gastroenterology 154:333–345. https://doi.org/10.1053/j.gastro.2017.06.065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Furuta K, Adachi K, Aimi M, Ishimura N, Sato S, Ishihara S, Kinoshita Y (2013) Case-control study of association of eosinophilic gastrointestinal disorders with helicobacter pylori infection in Japan. J Clin Biochem Nutr 53(1):60–62. https://doi.org/10.3164/jcbn.13-15

    Article  PubMed  PubMed Central  Google Scholar 

  19. Amedei A, Cappon A, Codolo G, Cabrelle A, Polenghi A, Benagiano M, Tasca E, Azzurri A, D'Elios MM, del Prete G, de Bernard M (2006) The neutrophil-activating protein of helicobacter pylori promotes Th1 immune responses. J Clin Invest 116(4):1092–1101. https://doi.org/10.1172/JCI27177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shi Y, Liu XF, Zhuang Y, Zhang JY, Liu T, Yin Z, Wu C, Mao XH, Jia KR, Wang FJ, Guo H, Flavell RA, Zhao Z, Liu KY, Xiao B, Guo Y, Zhang WJ, Zhou WY, Guo G, Zou QM (2010) Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice. J Immunol 184(9):5121–5129. https://doi.org/10.4049/jimmunol.0901115

    Article  CAS  PubMed  Google Scholar 

  21. Oertli M, Sundquist M, Hitzler I, Engler DB, Arnold IC, Reuter S, Maxeiner J, Hansson M, Taube C, Quiding-Järbrink M, Müller A (2012) DC-derived IL-18 drives Treg differentiation, murine helicobacter pylori-specific immune tolerance, and asthma protection. J Clin Invest 122(3):1082–1096. https://doi.org/10.1172/JCI61029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Arnold IC, Dehzad N, Reuter S, Martin H, Becher B, Taube C, Müller A (2011) Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J Clin Invest 121(8):3088–3093. https://doi.org/10.1172/JCI45041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Muir AB, Benitez AJ, Dods K, Spergel JM, Fillon SA (2016) Microbiome and its impact on gastrointestinal atopy. Allergy 71(9):1256–1263. https://doi.org/10.1111/all.12943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yang L, Lu X, Nossa CW, Francois F, Peek RM, Pei Z (2009) Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology 137(2):588–597. https://doi.org/10.1053/j.gastro.2009.04.046

    Article  PubMed  PubMed Central  Google Scholar 

  25. Benitez AJ, Hoffmann C, Muir AB, Dods KK, Spergel JM, Bushman FD, Wang ML (2015) Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome 3:23. https://doi.org/10.1186/s40168-015-0085-6

    Article  PubMed  PubMed Central  Google Scholar 

  26. Harris JK, Fang R, Wagner BD, Choe HN, Kelly CJ, Schroeder S, Moore W, Stevens MJ, Yeckes A, Amsden K, Kagalwalla AF, Zalewski A, Hirano I, Gonsalves N, Henry LN, Masterson JC, Robertson CE, Leung DY, Pace NR, Ackerman SJ, Furuta GT, Fillon SA (2015) Esophageal microbiome in eosinophilic esophagitis. PLoS One 10(5):e0128346. https://doi.org/10.1371/journal.pone.0128346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Spergel JM, Brown-Whitehorn TF, Cianferoni A et al (2012) Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allergy Clin Immunol 130(2):461–7.e5. https://doi.org/10.1016/j.jaci.2012.05.021

    Article  PubMed  Google Scholar 

  28. Kagalwalla AF, Shah A, Li BU et al (2011) Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr 53(2):145–149. https://doi.org/10.1097/MPG.0b013e31821cf503

    Article  CAS  PubMed  Google Scholar 

  29. Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, Melin–Aldana H, Li BUK (2006) Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol 4(9):1097–1102. https://doi.org/10.1016/j.cgh.2006.05.026

    Article  PubMed  Google Scholar 

  30. 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(2):363–368

    Article  Google Scholar 

  31. Walsh SV, Antonioli DA, Goldman H, Fox VL, Bousvaros A, Leichtner AM, Furuta GT (1999) Allergic esophagitis in children: a clinicopathological entity. Am J Surg Pathol 23(4):390–396

    Article  CAS  Google Scholar 

  32. Onbasi K, Sin AZ, Doganavsargil B, Onder GF, Bor S, Sebik F (2005) Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season. Clin Exp Allergy 35(11):1423–1431. https://doi.org/10.1111/j.1365-2222.2005.02351.x

    Article  CAS  PubMed  Google Scholar 

  33. Fogg MI, Ruchelli E, Spergel JM (2003) Pollen and eosinophilic esophagitis. J Allergy Clin Immunol 112(4):796–797

    Article  Google Scholar 

  34. Prasad GA, Alexander JA, Schleck CD, Zinsmeister AR, Smyrk TC, Elias RM, Locke GR III, Talley NJ (2009) Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol 7(10):1055–1061. https://doi.org/10.1016/j.cgh.2009.06.023

    Article  PubMed  PubMed Central  Google Scholar 

  35. Moawad FJ, Veerappan GR, Lake JM et al (2010) Correlation between eosinophilic oesophagitis and aeroallergens. Aliment Pharmacol Ther 31(4):509–515. https://doi.org/10.1111/j.1365-2036.2009.04199.x

    Article  CAS  PubMed  Google Scholar 

  36. Wang FY, Gupta SK, Fitzgerald JF (2007) Is there a seasonal variation in the incidence or intensity of allergic eosinophilic esophagitis in newly diagnosed children? J Clin Gastroenterol 41(5):451–453. https://doi.org/10.1097/01.mcg.0000248019.16139.67

    Article  PubMed  Google Scholar 

  37. Almansa C, Krishna M, Buchner AM, Ghabril MS, Talley N, DeVault KR, Wolfsen H, Raimondo M, Guarderas JC, Achem SR (2009) Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol 104(4):828–833. https://doi.org/10.1038/ajg.2008.169

    Article  PubMed  Google Scholar 

  38. Elitsur Y, Aswani R, Lund V, Dementieva Y (2013) Seasonal distribution and eosinophilic esophagitis: the experience in children living in rural communities. J Clin Gastroenterol 47(3):287–288. https://doi.org/10.1097/MCG.0b013e31826df861

    Article  PubMed  Google Scholar 

  39. Sorser SA, Barawi M, Hagglund K, Almojaned M, Lyons H (2013) Eosinophilic esophagitis in children and adolescents: epidemiology, clinical presentation and seasonal variation. J Gastroenterol 48(1):81–85. https://doi.org/10.1007/s00535-012-0608-x

    Article  PubMed  Google Scholar 

  40. Schlegel CR, Quintanilla NM, Olive AP, Minard CG, Davis CM (2014) Relationship of pediatric eosinophilic esophagitis diagnosis to pollen and mold counts. Ann Allergy Asthma Immunol 113(3):321–322. https://doi.org/10.1016/j.anai.2014.06.007

    Article  PubMed  Google Scholar 

  41. Philpott HL, Nandurkar S, Thien F, Bloom S, Lin E, Goldberg R, Boyapati R, Finch A, Royce SG, Gibson PR (2015) Seasonal recurrence of food bolus obstruction in eosinophilic esophagitis. Intern Med J 45(9):939–943. https://doi.org/10.1111/imj.12790

    Article  CAS  PubMed  Google Scholar 

  42. Lucendo AJ, Arias Á, Redondo-González O, González-Cervera J (2015) Seasonal distribution of initial diagnosis and clinical recrudescence of eosinophilic esophagitis: a systematic review and meta-analysis. Allergy 70(12):1640–1650. https://doi.org/10.1111/all.12767

    Article  CAS  PubMed  Google Scholar 

  43. Guajardo JR, Zegarra-Bustamante MA, Brooks EG (2018) Does aeroallergen sensitization cause or contribute to eosinophilic esophagitis? Clin Rev Allergy Immunol 55:65–69. https://doi.org/10.1007/s12016-018-8671-6

    Article  CAS  PubMed  Google Scholar 

  44. Morais Silva P, Antunes J, Chambel M, Prates S, Leiria PP (2014) Diagnosis of eosinophilic esophagitis in an infant undergoing milk oral immunotherapy - a case report. Eur Ann Allergy Clin Immunol 46(4):154–156

    CAS  PubMed  Google Scholar 

  45. Lucendo AJ, Arias A, Tenias JM (2014) Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol 113(6):624–629. https://doi.org/10.1016/j.anai.2014.08.004

    Article  PubMed  Google Scholar 

  46. Petroni D, Spergel JM (2018) Eosinophilic esophagitis and symptoms possibly related to eosinophilic esophagitis in oral immunotherapy. Ann Allergy Asthma Immunol 120:237–240.e4. https://doi.org/10.1016/j.anai.2017.11.016

    Article  PubMed  Google Scholar 

  47. Miehlke S, Alpan O, Schröder S, Straumann A (2013) Induction of eosinophilic esophagitis by sublingual pollen immunotherapy. Case Rep Gastroenterol 7(3):363–368. https://doi.org/10.1159/000355161

    Article  PubMed  PubMed Central  Google Scholar 

  48. Patel C, Menon P (2016) A complication of eosinophilic esophagitis from sublingual immunotherapy. J Allergy Clin Immunol 137(2):Supp AB62

    Article  Google Scholar 

  49. Béné J, Ley D, Roboubi R, Gottrand F, Gautier S (2016) Eosinophilic esophagitis after desensitization to dust mites with sublingual immunotherapy. Ann Allergy Asthma Immunol 116(6):583–584. https://doi.org/10.1016/j.anai.2016.03.017

    Article  PubMed  Google Scholar 

  50. Akdis CA, Barlan IB, Bahceciler N, Akdis M (2006) Immunological mechanisms of sublingual immunotherapy. Allergy 61(Suppl 81):11–14. https://doi.org/10.1111/j.1398-9995.2006.01159.x

    Article  PubMed  Google Scholar 

  51. Geroldinger-Simic M, Kinaciyan T, Nagl B, Baumgartner-Durchschlag U, Huber H, Ebner C, Lidholm J, Bartel D, Vieths S, Jahn-Schmid B, Bohle B (2013) Oral exposure to mal d 1 affects the immune response in patients with birch pollen allergy. J Allergy Clin Immunol 131(1):94–102. https://doi.org/10.1016/j.jaci.2012.06.039

    Article  CAS  PubMed  Google Scholar 

  52. Wolf WA, Jerath MR, Dellon ES (2013) De-novo onset of eosinophilic esophagitis after large volume allergen exposures. J Gastrointestin Liver Dis 22(2):205–208

    PubMed  PubMed Central  Google Scholar 

  53. Mishra A, Hogan SP, Brandt EB, Rothenberg ME (2001) An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest 107(1):83–90. https://doi.org/10.1172/JCI10224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Akei HS, Mishra A, Blanchard C, Rothenberg ME (2005) Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology 129(3):985–994. https://doi.org/10.1053/j.gastro.2005.06.027

    Article  CAS  PubMed  Google Scholar 

  55. Mavi P, Rajavelu P, Rayapudi M, Paul RJ, Mishra A (2012) Esophageal functional impairments in experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 302(11):G1347–G1355. https://doi.org/10.1152/ajpgi.00013.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chapman MD, Wünschmann S, Pomés A (2007) Proteases as Th2 adjuvants. Curr Allergy Asthma Rep 7(5):363–367

    Article  CAS  Google Scholar 

  57. Rayapudi M, Mavi P, Zhu X, Pandey AK, Abonia JP, Rothenberg ME, Mishra A (2010) Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice. J Leukoc Biol 88(2):337–346. https://doi.org/10.1189/jlb.0110025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Pesek RD, Rettiganti M, O'Brien E, Beckwith S, Daniel C, Luo C, Scurlock AM, Chandler P, Levy RA, Perry TT, Kennedy JL, Chervinskiy S, Vonlanthen M, Casteel H, Fiedorek SC, Gibbons T, Jones SM (2017) Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis. Ann Allergy Asthma Immunol 119(2):177–183. https://doi.org/10.1016/j.anai.2017.06.006

    Article  PubMed  PubMed Central  Google Scholar 

  59. Kliegman R, Stanton B, StGeme J, Schor N (2016) Nelson textbook of pediatrics. Elsevier, Philadelphia

    Google Scholar 

  60. Kaplan M, Mutlu EA, Jakate S, Bruninga K, Losurdo J, Keshavarzian A (2003) Endoscopy in eosinophilic esophagitis: "feline" esophagus and perforation risk. Clin Gastroenterol Hepatol 1(6):433–437

    Article  Google Scholar 

  61. Merves J, Chandramouleeswaran PM, Benitez AJ, Muir AB, Lee AJ, Lim DM, Dods K, Mehta I, Ruchelli ED, Nakagawa H, Spergel JM, Wang ML (2015) Altered esophageal histamine receptor expression in eosinophilic esophagitis (EoE): implications on disease pathogenesis. PLoS One 10(2):e0114831. https://doi.org/10.1371/journal.pone.0114831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 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(12):1198–1206

    Article  Google Scholar 

  63. Lucendo AJ, De Rezende LC, Jiménez-Contreras S et al (2011) Montelukast was inefficient in maintaining steroid-induced remission in adult eosinophilic esophagitis. Dig Dis Sci 56(12):3551–3558. https://doi.org/10.1007/s10620-011-1775-y

    Article  CAS  PubMed  Google Scholar 

  64. 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(4):229–234. https://doi.org/10.1111/j.1442-2050.2010.01134.x

    Article  CAS  PubMed  Google Scholar 

  65. Alexander JA, Ravi K, Enders FT et al (2017) Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 15(2):214–21.e2. https://doi.org/10.1016/j.cgh.2016.09.013

    Article  CAS  PubMed  Google Scholar 

  66. Straumann A, Hoesli S, Bussmann C, Stuck M, Perkins M, Collins LP, Payton M, Pettipher R, Hunter M, Steiner J, Simon HU (2013) Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy 68(3):375–385. https://doi.org/10.1111/all.12096

    Article  CAS  PubMed  Google Scholar 

  67. De Swert L, Veereman G, Bublin M et al (2013) Eosinophilic gastrointestinal disease suggestive of pathogenesis-related class 10 (PR-10) protein allergy resolved after immunotherapy. J Allergy Clin Immunol 131(2):600–2.e1–3. https://doi.org/10.1016/j.jaci.2012.10.057

    Article  PubMed  Google Scholar 

  68. Ramirez RM, Jacobs RL (2013) Eosinophilic esophagitis treated with immunotherapy to dust mites. J Allergy Clin Immunol 132(2):503–504. https://doi.org/10.1016/j.jaci.2013.04.053

    Article  PubMed  Google Scholar 

  69. Assa'ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, Perschy TL, Jurgensen CH, Ortega HG, Aceves SS (2011) An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology 141(5):1593–1604. https://doi.org/10.1053/j.gastro.2011.07.044

    Article  CAS  PubMed  Google Scholar 

  70. 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(1):21–30. https://doi.org/10.1136/gut.2009.178558

    Article  CAS  PubMed  Google Scholar 

  71. Spergel JM, Rothenberg ME, Collins MH 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(2):456–463, 63.e1–3. https://doi.org/10.1016/j.jaci.2011.11.044

    Article  CAS  PubMed  Google Scholar 

  72. Markowitz JE, Jobe L, Miller M, Frost C, Laney Z, Eke R (2017) Safety and efficacy of Reslizumab for children and adolescents with eosinophilic esophagitis treated over nine years. J Pediatr Gastroenterol Nutr 66:893–897. https://doi.org/10.1097/MPG.0000000000001840

    Article  Google Scholar 

  73. 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(11):1471–1474. https://doi.org/10.1007/s00431-011-1540-4

    Article  CAS  PubMed  Google Scholar 

  74. Loizou D, Enav B, Komlodi-Pasztor E, Hider P, Kim-Chang J, Noonan L, Taber T, Kaushal S, Limgala R, Brown M, Gupta R, Balba N, Goker-Alpan O, Khojah A, Alpan O (2015) A pilot study of omalizumab in eosinophilic esophagitis. PLoS One 10(3):e0113483. https://doi.org/10.1371/journal.pone.0113483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 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(2):500–507. https://doi.org/10.1016/j.jaci.2014.07.049

    Article  CAS  PubMed  Google Scholar 

  76. Dellon E, Collins M, Assouline-Dayan Y et al (2016) A randomized, double-blind, placebo-controlled trial of a novel recombinant, humanized,anti-interleukin-13 monoclonal antibody (RPC4046) in patients with active eosinophilic esophagitis: results of the HEROES study. American College of Gastroenterology ACG, Las Vegas

    Book  Google Scholar 

  77. Hirano I, Dellon E, Hamilton J et al (2017) Dupilumab efficacy and safety in adult patients with active eosinophilic esophagitis: a randomized, double blind, placebo controlled phase 2 trial. World Congress of Gastroenterology at ACG, Orlando

    Google Scholar 

  78. Peinhaupt M, Sturm EM, Heinemann A (2017) Prostaglandins and their receptors in eosinophil function and as therapeutic targets. Front Med (Lausanne) 4:104. https://doi.org/10.3389/fmed.2017.00104

    Article  Google Scholar 

  79. Fahey L, Robinson G, Weinberger K, Giambrone AE, Solomon AB (2017) Correlation between aeroallergen levels and new diagnosis of eosinophilic esophagitis in new York City. J Pediatr Gastroenterol Nutr 64(1):22–25. https://doi.org/10.1097/MPG.0000000000001245

    Article  PubMed  PubMed Central  Google Scholar 

  80. Furuta GT, Atkins FD, Lee NA, Lee JJ (2014) Changing roles of eosinophils in health and disease. Ann Allergy Asthma Immunol 113(1):3–8. https://doi.org/10.1016/j.anai.2014.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Leung J, Beukema KR, Shen AH (2015) Allergic mechanisms of eosinophilic oesophagitis. Best Pract Res Clin Gastroenterol 29(5):709–720. https://doi.org/10.1016/j.bpg.2015.09.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Masterson JC, McNamee EN, Hosford L et al (2014) Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. Gut 63(1):43–53. https://doi.org/10.1136/gutjnl-2012-303631

    Article  CAS  PubMed  Google Scholar 

  83. Blanchard C, Mingler MK, Vicario M, Abonia JP, Wu YY, Lu TX, Collins MH, Putnam PE, Wells SI, Rothenberg ME (2007) IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol 120(6):1292–1300. https://doi.org/10.1016/j.jaci.2007.10.024

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This review article was not funded.

Author information

Authors and Affiliations

  1. Division of Allergy and Immunology, Children’s Mercy Hospital Kansas City, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Paul J. Dowling

  2. Department of Graduate Medical Education, Children’s Mercy Hospital Kansas City, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Hannah Neuhaus

  3. Division of Pediatric Allergy, Immunology, and Pulmonary Medicine, Washington University in St. Louis School of Medicine, One Children’s Place, Campus Box 8116, Saint Louis, MO, 63110, USA

    Brooke I. Polk

Authors
  1. Paul J. Dowling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hannah Neuhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brooke I. Polk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brooke I. Polk.

Ethics declarations

Conflicts of Interest

Authors Hannah Neuhaus and Brooke Polk declare no conflicts of interest. Author Paul Dowling reports performing clinical research for Aimmune, DBV, Regeneron, and Sanofi, and belonging to the Advisory Committee for FARE and the ACGME Residency Review Committee.

Ethical Approval and Informed Consent

This review article did not involve animal or human subjects.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dowling, P.J., Neuhaus, H. & Polk, B.I. The Role of the Environment in Eosinophilic Esophagitis. Clinic Rev Allerg Immunol 57, 330–339 (2019). https://doi.org/10.1007/s12016-018-8697-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-018-8697-9

Keywords

Search

Navigation