Skip to main content

Advertisement

Log in

Classification of patients with esophageal eosinophilia by patterns of sensitization revealed by a diagnostic assay for multiple allergen-specific IgEs

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Eosinophilic esophagitis (EoE) is considered to be an immunoglobulin E (IgE)-mediated allergic disorder. Our goal was to examine IgE-mediated allergic sensitization patterns in patients with esophageal eosinophilia (EE).

Methods

We enrolled subjects with EE who underwent evaluation with a diagnostic panel to document multiple allergen-specific IgEs. Statistically significant groups were identified by cluster analysis. We also defined allergens based on their characteristics including outdoor, indoor, plant, and animal allergens.

Results

We classified patients with EE into 3 distinct groups, including cluster 1 (n = 62) who were minimally sensitized to most allergens except pollen and house dust, cluster 2 (n = 30) who were hypersensitized to outdoor and plant allergens, and cluster 3 (n = 15) who were hypersensitized to most allergens, most notably to indoor and animal allergens. Dysphagia reported among those in clusters 1, 2, and 3 at 35.5%, 46.7%, and 73.3%, respectively, (p = 0.028) and EoE endoscopic reference scores (EREFS) at 3.0, 6.0, and 8.0, respectively, (p < 0.001) differed significantly between the 3 clusters. Those in cluster 3 had a significantly higher prevalence of dysphagia (35.5% vs. 73.3%, p = 0.030), and higher EREFS with respect to rings (0.3 vs. 0.9, p = 0.003) and strictures (0.0 vs. 0.13, p = 0.011) compared to those in cluster 1.

Conclusions

IgE-mediated allergic sensitization patterns are associated with clinical features of patients with EE. Use of a diagnostic panel that detects multiple allergen-specific IgEs can help to explain the heterogeneous phenotype of this patient cohort.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

BMI:

Body mass index

EE:

Esophageal eosinophilia

EoE:

Eosinophilic esophagitis

EPZ:

Esomeprazole

EREFS:

Eosinophilic esophagitis endoscopic reference score

HPF:

High-power field

IgE:

Immunoglobulin E

LPZ:

Lansoprazole

P-CAB:

Potassium-competitive acid blocker

PPI:

Proton pump inhibitor

RPZ:

Rabeprazole

Th2:

T helper type 2

TSLP:

Thymic stromal lymphopoietin

VPZ:

Vonoprazan

WBC:

Peripheral white blood cell count

References

  1. 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.

    PubMed  Google Scholar 

  2. Straumann A, Aceves SS, Blanchard C, et al. Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy. 2012;67:477–90.

    CAS  PubMed  Google Scholar 

  3. Lucendo AJ, Molina-Infante J, Arias A, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. Eur Gastroenterol J. 2017;5:335–58.

    Google Scholar 

  4. Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116:536–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Noti M, Wojno ED, Kim BS, et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med. 2013;19:1005–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Rothenberg ME, Spergel JM, Sherrill JD, et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet. 2010;42:289–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Doherty TA, Baum R, Newbury RO, et al. Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis. J Allergy Clin Immunol. 2015;136(792–4):e3.

    Google Scholar 

  8. Iwakura N, Fujiwara Y, Tanaka F, et al. Basophil infiltration in eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia. Aliment Pharmacol Ther. 2015;41:776–84.

    CAS  PubMed  Google Scholar 

  9. Merves J, Muir A, Modayur Chandramouleeswaran P, et al. Eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2014;112:397–403.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Hirano I, Aceves SS. Clinical implications and pathogenesis of esophageal remodeling in eosinophilic esophagitis. Gastroenterol Clin North Am. 2014;43:297–316.

    PubMed  PubMed Central  Google Scholar 

  11. Straumann A, Bauer M, Fischer B, et al. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. J Allergy Clin Immunol. 2001;108:954–61.

    CAS  PubMed  Google Scholar 

  12. Blanchard C, Mingler MK, Vicario M, et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007;120:1292–300.

    CAS  PubMed  Google Scholar 

  13. Ko E, Chehade M. Biological therapies for eosinophilic esophagitis: where do we stand? Clin Rev Allergy Immunol. 2018;55:205–16.

    CAS  PubMed  Google Scholar 

  14. Simon D, Cianferoni A, Spergel JM, et al. Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity. Allergy. 2016;71:611–20.

    CAS  PubMed  Google Scholar 

  15. Blanchard C, Simon D, Schoepfer A, et al. Eosinophilic esophagitis: unclear roles of IgE and eosinophils. J Intern Med. 2017;281:448–57.

    CAS  PubMed  Google Scholar 

  16. Hill DA, Dudley JW, Spergel JM. The prevalence of eosinophilic esophagitis in pediatric patients with IgE-mediated food allergy. J Allergy Clin Immunol Pract. 2017;5:369–75.

    PubMed  Google Scholar 

  17. Simpson A, Lazic N, Belgrave DC, Johnson P, Bishop C, Mills C, et al. Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years. J Allergy Clin Immunol. 2015;136:1224–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Yamana Y, Fukuda K, Ko R, Uchio E. Local allergic conjunctivitis: a phenotype of allergic conjunctivitis. Int Ophthalmol. 2019;39:2539–44.

    PubMed  Google Scholar 

  19. Hata T, Furusawa-Horie T, Arai Y, et al. Studies of royal jelly and associated cross-reactive allergens in atopic dermatitis patients. PLoS ONE. 2020;15:e0233707.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Kuwabara K, Hirose M, Kato K, et al. Serological analysis of sensitization in allergic bronchopulmonary aspergillosis: a study on allergen components and interspecies relationships. J Asthma. 2020;57:610–7.

    CAS  PubMed  Google Scholar 

  21. Hirano I, Moy N, Heckman MG, et al. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut. 2013;62:489–95.

    PubMed  Google Scholar 

  22. Shoda T, Wen T, Aceves SS, et al. Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study. Lancet Gastroenterol Hepatol. 2018;3:477–88.

    PubMed  PubMed Central  Google Scholar 

  23. Punj G, Stewart DW. Cluster analysis in marketing research: review and suggestions for application. J Mark Res. 1983;20:134–48.

    Google Scholar 

  24. Kuzumoto T, Tanaka F, Sawada A, et al. Vonoprazan shows efficacy similar to that of proton pump inhibitors with respect to symptomatic, endoscopic, and histological responses in patients with eosinophilic esophagitis. Esophagus. 2020. https://doi.org/10.1007/s10388-020-00783-0.

    Article  PubMed  Google Scholar 

  25. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    CAS  Google Scholar 

  26. Atkins D, Furuta GT, Liacouras CA, Spergel JM. Eosinophilic esophagitis phenotypes: ready for prime time? Pediatr Allergy Immunol. 2017;28:312–9.

    PubMed  PubMed Central  Google Scholar 

  27. Aceves SS. Remodeling and fibrosis in chronic eosinophil inflammation. Dig Dis. 2014;32:15–21.

    PubMed  PubMed Central  Google Scholar 

  28. Chen JW, Pandolfino JE, Lin Z, et al. Severity of endoscopically identified esophageal rings correlates with reduced esophageal distensibility in eosinophilic esophagitis. Endoscopy. 2016;48:794–801.

    PubMed  PubMed Central  Google Scholar 

  29. Bohm M, Richter JE, Kelsen S, et al. Esophageal dilation: simple and effective treatment for adults with eosinophilic esophagitis and esophageal rings and narrowing. Dis Esophagus. 2010;23:377–85.

    CAS  PubMed  Google Scholar 

  30. Rawson R, Anilkumar A, Newbury RO, et al. The TGFβ1 promoter SNP C-509T and food sensitization promote esophageal remodeling in pediatric eosinophilic esophagitis. PLoS ONE. 2015;10:e0144651.

    PubMed  PubMed Central  Google Scholar 

  31. Boyce JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-Sponsored Expert Panel Report. J Allergy Clin Immunol. 2010;126:1105–18.

    PubMed  PubMed Central  Google Scholar 

  32. Markowitz JE, Spergel JM, Ruchelli E, et al. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003;98:777–82.

    CAS  PubMed  Google Scholar 

  33. Kagalwalla AF, Wechsler JB, Amsden K, et al. Efficacy of a 4-food elimination diet for children with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2017;15(1698–707):e7.

    Google Scholar 

  34. Molina-Infante J, Arias A, Alcedo J, et al. Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: the 2-4-6 study. J Allergy Clin Immunol. 2018;141:1365–72.

    PubMed  Google Scholar 

  35. Spergel JM, Brown-Whitehorn TF, Cianferoni A, et al. Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allergy Clin Immunol. 2012;130(461–7):e5.

    Google Scholar 

  36. Henderson CJ, Abonia JP, King EC, et al. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012;129:1570–8.

    PubMed  PubMed Central  Google Scholar 

  37. Gonsalves N, Yang GY, Doerfler B, et al. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142(1451–9):e1.

    Google Scholar 

  38. 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;4:1097–102.

    PubMed  Google Scholar 

  39. Wolf WA, Jerath MR, Sperry SL, et al. Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2014;12:1272–9.

    PubMed  PubMed Central  Google Scholar 

  40. Wechsler JB, Schwartz S, Amsden K, et al. Elimination diets in the management of eosinophilic esophagitis. J Asthma Allergy. 2014;7:85–94.

    PubMed  PubMed Central  Google Scholar 

  41. Niranjan R, Rayapudi M, Mishra A, et al. Pathogenesis of allergen-induced eosinophilic esophagitis is independent of interleukin (IL)-13. Immunol Cell Biol. 2013;91:408–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Spergel J, Aceves SS. Allergic components of eosinophilic esophagitis. J Allergy Clin Immunol. 2018;142:1–8.

    PubMed  PubMed Central  Google Scholar 

  43. Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. J Allergy Clin Immunol. 2003;112:796–7.

    PubMed  Google Scholar 

  44. Wolf WA, Jerath MR, Dellon ES. De-novo onset of eosinophilic esophagitis after large volume allergen exposures. J Gastrointestin Liver Dis. 2013;22:205–8.

    PubMed  PubMed Central  Google Scholar 

  45. Williamson P, Aceves S. Allergies and eosinophilic esophagitis-current updates for the pediatric gastroenterologist. Curr Gastroenterol Rep. 2019;21:56.

    PubMed  PubMed Central  Google Scholar 

  46. Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014;134(1016–25):e43.

    Google Scholar 

  47. Skypala IJ, Bull S, Deegan K, et al. The prevalence of PFS and prevalence and characteristics of reported food allergy; a survey of UK adults aged 18–75 incorporating a validated PFS diagnostic questionnaire. Clin Exp Allergy. 2013;43:928–40.

    CAS  PubMed  Google Scholar 

  48. Egger M, Mutschlechner S, Wopfner N, et al. Pollen-food syndromes associated with weed pollinosis: an update from the molecular point of view. Allergy. 2006;61:461–76.

    CAS  PubMed  Google Scholar 

  49. Bohle B. The impact of pollen-related food allergens on pollen allergy. Allergy. 2007;62:3–10.

    CAS  PubMed  Google Scholar 

  50. van Rhijn BD, van Ree R, Versteeg SA, et al. Birch pollen sensitization with cross-reactivity to food allergens predominates in adults with eosinophilic esophagitis. Allergy. 2013;68:1475–81.

    PubMed  Google Scholar 

  51. Melioli G, Spenser C, Reggiardo G, et al. Allergenius, an expert system for the interpretation of allergen microarray results. World Allergy Organ J. 2014;7:15.

    PubMed  PubMed Central  Google Scholar 

  52. Canonica GW, Ansotegui IJ, Pawankar R, et al. A WAO–ARIA–GA(2)LEN consensus document on molecular-based allergy diagnostics. World Allergy Organ J. 2013;6:17.

    PubMed  PubMed Central  Google Scholar 

  53. Lopata AL, Lehrer SB. New insights into seafood allergy. Curr Opin Allergy Clin Immunol. 2009;9:270–7.

    CAS  PubMed  Google Scholar 

  54. Savi E, Rossi A, Incorvaia C. Cat-pork syndrome: a case report with a there years follow-up. Eur Ann Allergy Clin Immunol. 2006;38:366–8.

    CAS  PubMed  Google Scholar 

  55. Clayton F, Fang JC, Gleich GJ, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology. 2014;147:602–9.

    CAS  PubMed  Google Scholar 

  56. Kim HP, Vance RB, Shaheen NJ, et al. The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10(988–96):e5.

    Google Scholar 

  57. Kinoshita Y, Furuta K, Ishimaura N, et al. Clinical characteristics of Japanese patients with eosinophilic esophagitis and eosinophilic gastroenteritis. J Gastroenterol. 2013;48:333–9.

    PubMed  Google Scholar 

  58. Shimura S, Ishimura N, Tanimura T, et al. Reliability of symptoms and endoscopic findings for diagnosis of esophageal eosinophilia in a Japanese population. Digestion. 2014;90:49–57.

    PubMed  Google Scholar 

  59. Sato H, Honma T, Nozawa Y, et al. Eosinophilic esophagitis in Japanese patients: A mild and slow-progressing disorder. PLoS ONE. 2018;13:e0206621.

    PubMed  PubMed Central  Google Scholar 

  60. Ishimura N, Sumi S, Okada M, et al. Is asymptomatic esophageal eosinophilia the same disease entity as eosinophilic esophagitis? Clin Gastroenterol Hepatol. 2019;17:1405–7.

    PubMed  Google Scholar 

  61. Philpott H, Nandurkar S, Royce SG, et al. Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities. Aliment Pharmacol Ther. 2016;44:223–33.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fumio Tanaka.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 26 KB)

Supplementary file2 (PDF 305 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakata, A., Tanaka, F., Nadatani, Y. et al. Classification of patients with esophageal eosinophilia by patterns of sensitization revealed by a diagnostic assay for multiple allergen-specific IgEs. J Gastroenterol 56, 422–433 (2021). https://doi.org/10.1007/s00535-021-01766-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-021-01766-3

Keywords

Navigation