Proton pump inhibitor-responsive oesophageal eosinophilia and eosinophilic oesophagitis: More similarities than differences

Current Opinion in Gastroenterology

Volumn 31, Issue 4, 2015, Pages 309-315

  Eluri, Swathi ^a   Dellon, Evan S ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Eosinophilic oesophagitis; Gastroesophageal reflux disease; Proton pump inhibitor responsive oesophageal eosinophilia

Indexed keywords

EOTAXIN 3; INTERLEUKIN 13; INTERLEUKIN 5; MAJOR BASIC PROTEIN; PROTON PUMP INHIBITOR;

ANTIINFLAMMATORY ACTIVITY; ARTICLE; CLINICAL FEATURE; DRUG MECHANISM; EOSINOPHILIA; EOSINOPHILIC ESOPHAGITIS; ESOPHAGEAL EOSINOPHILIA; ESOPHAGUS DISEASE; ESOPHAGUS FUNCTION; GASTROESOPHAGEAL REFLUX; GENE EXPRESSION; HISTOPATHOLOGY; HUMAN; META ANALYSIS; PH; REMISSION; TREATMENT RESPONSE; DRUG EFFECTS; ESOPHAGEAL PH MONITORING; ESOPHAGOSCOPY; GENE EXPRESSION REGULATION; GENETICS; PROCEDURES; PROGNOSIS;

EOSINOPHILIC ESOPHAGITIS; ESOPHAGEAL PH MONITORING; ESOPHAGOSCOPY; GASTROESOPHAGEAL REFLUX; GENE EXPRESSION REGULATION; HUMANS; PROGNOSIS; PROTON PUMP INHIBITORS;

EID: 84942597450     PISSN: 02671379     EISSN: 15317056     Source Type: Journal    
DOI: 10.1097/MOG.0000000000000185     Document Type: Article

References (63)

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.
2. 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. This is the first guideline differentiating oesophageal eosinophilia and PPI-REE as distinct entities from EoE. The article also provides a diagnostic algorithm for EoE and mechanisms of pathogenesis that are not entirely acid mediated.
3. Rodrigo S, Abboud G, Oh D, et al. High intraepithelial eosinophil counts in esophageal squamous epithelium are not specific for eosinophilic esophagitis in adults. Am J Gastroenterol 2008;103:435-442.
4. Dellon ES, Liacouras CA. Advances in clinical management of eosinophilic esophagitis. Gastroenterology 2014;147:1238-1254.
5. 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;101:1666-1670.
6. Dellon ES, Speck O, Woodward K, et al. Clinical and endoscopic characteristics do not reliably differentiate PPI-responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study. Am J Gastroenterol 2013;108:1854-1860. This is one of the first studies that investigated the clinical, endoscopic, and histologic features of PPI-REE in a prospective fashion at a single centre in the United States, and found that none of these features could independently distinguish PPI-REE from EoE prior to a PPI trial.
7. Molina-Infante J, Ferrando-Lamana L, Ripoll C, et al. Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol 2011;9:110-117.
8. Dranove JE, Horn DS, Davis MA, et al. Predictors of response to proton pump inhibitor therapy among children with significant esophageal eosinophilia. J Pediatr 2009;154:96-100.
9. Sayej WN, Patel R, Baker RD, et al. Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2009;49:393-399.
10. Dohil R, Newbury RO, Aceves S. Transient PPI responsive esophageal eosinophilia may be a clinical sub-phenotype of pediatric eosinophilic esophagitis. Dig Dis Sci 2012;57:1413-1419.
11. Francis DL, Foxx-Orenstein A, Arora AS, et al. Results of ambulatory pH monitoring do not reliably predict response to therapy in patients with eosinophilic oesophagitis. Aliment Pharmacol Ther 2012;35:300-307.
12. Vazquez-Elizondo G, Ngamruengphong S, Khrisna M, et al. The outcome of patients with oesophageal eosinophilic infiltration after an eight-week trial of a proton pump inhibitor. Aliment Pharmacol Ther 2013;38:1312-1319.
13. 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.
14. Fujiwara Y, Sugawa T, Tanaka F, et al. A multicenter study on the prevalence of eosinophilic esophagitis and PPI-responsive esophageal eosinophilic infiltration. Intern Med (Tokyo, Japan) 2012;51:3235-3239.
15. Schroeder S, Capocelli KE, Masterson JC, et al. Effect of proton pump inhibitor on esophageal eosinophilia. J Pediatr Gastroenterol Nutr 2013;56:166-172.
16. Dellon ES, Farrell TM, Bozymski EM, Shaheen NJ. Diagnosis of eosinophilic esophagitis after fundoplication for 'refractory reflux': implications for preoperative evaluation. Dis Esophagus 2010;23:191-195.
17. Spechler SJ, Genta RM, Souza RF. Thoughts on the complex relationship between gastroesophageal reflux disease and eosinophilic esophagitis. Am J Gastroenterol 2007;102:1301-1306.
18. Souza RF, Huo X, Mittal V, et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology 2009;137:1776-1784.
19. Cheng E, Zhang X, Huo X, et al. Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut 2013;62:824-832. This is the first experimental study that showed that GERD and EoE cells express Th2 cytokines-stimulated eotaxin-3, and also showed that omeprazole blocked eotaxin-3 expression in both GERD and EoE patients, suggesting an anti-inflammatory PPI effect.
20. Moawad FJ, Schoepfer AM, Safroneeva E, et al. Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings. Aliment Pharmacol Ther 2014;39:603-608. This retrospective study with patients from the United States and Switzerland added to the existing literature that EoE and PPI-REE are indistinguishable clinically, endoscopically, and histologically without a PPI trial.
21. Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005;3:1198-1206.
22. Orenstein SR, Shalaby TM, Di Lorenzo C, et al. The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical series of 30 children. Am J Gastroenterol 2000;95:1422-1430.
23. Schoepfer AM, Safroneeva E, Bussmann C, et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a timedependent manner. Gastroenterology 2013;145:1230-1236.
24. Gonsalves N, Policarpio-Nicolas M, Zhang Q, et al. Histopathologic variability and endoscopic correlates in adults with eosinophilic esophagitis. Gastrointest Endosc 2006;64:313-319.
25. Veerappan GR, Perry JL, Duncan TJ, et al. Prevalence of eosinophilic esophagitis in an adult population undergoing upper endoscopy: a prospective study. Clin Gastroenterol Hepatol 2009;7:420-426.
26. Dellon ES, Gibbs WB, Fritchie KJ, et al. Clinical, endoscopic, and histologic findings distinguish eosinophilic esophagitis from gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2009;7:1305-1313.
27. Dellon ES, Kim HP, Sperry SL, et al. A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc 2014;79:577-585.
28. Molina-Infante J, Katzka DA, Gisbert JP. Review article: proton pump inhibitor therapy for suspected eosinophilic oesophagitis. Aliment Pharmacol Ther 2013;37:1157-1164.
29. Kim HP, Vance RB, Shaheen NJ, Dellon ES. The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis. Clin Gastroenterol Hepatol 2012;10:988-996.
30. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment: sponsored by the American Gastroenterological Association (AGA) Institute and North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Gastroenterology 2007;133:1342-1363.
31. Winter HS, Madara JL, Stafford RJ, et al. Intraepithelial eosinophils: a new diagnostic criterion for reflux esophagitis. Gastroenterology 1982;83:818-823.
32. 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.
33. Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology 2009;137:1238-1249.
34. Blanchard C, Stucke EM, Rodriguez-Jimenez B, et al. A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol 2011;127:208-217.
35. Neilsen C, Bryce P. Interleukin - 13 directly promotes oesophagus production of CCL11 and CCL24 and the migration of eosinophils. Clin Exp Allergy 2010;40:427-434.
36. Weinbrand-Goichberg J, Segal I, Ovadia A, et al. Eosinophilic esophagitis: an immune-mediated esophageal disease. Immunol Res 2013;56:249-260.
37. Zafra MP, Cancelliere N, Rodriguez Del Rio P, et al. Misregulation of suppressors of cytokine signaling in eosinophilic esophagitis. J Gastroenterol 2013;48:910-920.
38. Noti M, Wojno ED, Kim BS, et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med 2013;19:1005-1013.
39. Blanchard C, Stucke EM, Burwinkel K, et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol 2010;184:4033-4041.
40. Rothenberg ME, Hogan SP. The eosinophil. Ann Rev Immunol 2006;24:147-174.
41. Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest 2006;116:536-547.
42. Gupta SK, Peters-Golden M, Fitzgerald JF, et al. Cysteinyl leukotriene levels in esophageal mucosal biopsies of children with eosinophilic inflammation: are they all the same? Am J Gastroenterol 2006;101:1125-1128.
43. Attwood SE, Lewis CJ, Bronder CS, et al. Eosinophilic oesophagitis: a novel treatment using Montelukast. Gut 2003;52:181-185.
44. Dellon ES, Chen X, Miller CR, et al. Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. Am J Gastroenterol 2012;107:1503-1511.
45. Dellon ES, Speck O, Woodward K, et al. Markers of eosinophilic inflammation for diagnosis of eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia: a prospective study. Clin Gastroenterol Hepatol 2014;12:2015-2022. This prospective study utilized cell staining for MBP, eotaxin-3, and tryptase in an assay that could identify EoE with an accuracy of 100% but could not differentiate between EoE and PPI-REE, pointing to a possible shared pathogenesis between these two conditions.
46. Dellon ES, Chen X, Miller CR, et al. Tryptase staining of mast cells may differentiate eosinophilic esophagitis from gastroesophageal reflux disease. Am J Gastroenterol 2011;106:264-271.
47. Molina-Infante J, Rivas MD, Hernandez-Alonso M, et al. Proton pump inhibitorresponsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression. Aliment Pharmacol Ther 2014;40:955-965. This is the first study to show that the baseline eotaxin-3 and Th2 cytokine expression in PPI-REE and EoE were similar before PPI treatment, but the PPI treatment significantly downregulated the cytokine expression only in the PPI-REE group and not in EoE. EoE patients had a similar downregulation of cytokines when treated with steroids.
48. Wen T, Stucke EM, Grotjan TM, et al. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology 2013;145:1289-1299.
49. Wen T, Dellon ES, Moawad FJ, et al. Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitorreversible allergic inflammation. J Allergy Clin Immunol 2015;135:187-197. This study provides definitive evidence that PPI-REE has a gene expression signature that has significant overlap with EoE, and that this signature completely reverses with PPI therapy. This provides novel insights into the shared mechanisms of pathogenesis between EoE and PPI-REE.
50. 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;120:1292-1300.
51. + channels. Am J Physiol Cell Physiol 2004;286:C495-C506.
52. + channels'. Am J Physiol Cell Physiol 2004;286:C478-C479.
53. Van Rhijn BD, Weijenborg PW, Verheij J, 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;12:1815-1823. This is the first study to assess oesophageal mucosal integrity in PPI-REE and EoE. PPI therapy partially restored mucosal integrity in PPI-REE, but not in EoE patients, suggesting increased permeability of the oesophageal mucosa as a possible mechanism for the pathogenesis of PPI-REE.
54. Farre R, Fornari F, Blondeau K, et al. Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal nonexposed human oesophagus. Gut 2010;59:164-169.
55. Caviglia R, Ribolsi M, Gentile M, et al. Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with nonerosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2007;25:629-636.
56. Kedika RR, Souza RF, Spechler SJ. Potential anti-inflammatory effects of proton pump inhibitors: a review and discussion of the clinical implications. Dig Dis Sci 2009;54:2312-2317.
57. Zhang X, Cheng E, Huo X, et al. Omeprazoleb locks STAT6b in ding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PLoS One 2012;7:e50037.
58. Cortes JR, Rivas MD, Molina-Infante J, et al. Omeprazole inhibits IL-4 and IL-13 signaling signal transducer and activator of transcription 6 activation and reduces lung inflammation in murine asthma. J Allergy Clin Immunol 2009;124:607-610.
59. Park JY, Zhang X, Nguyen N, et al. Proton pump inhibitors decrease eotaxin-3 expression in the proximal esophagus of children with esophageal eosinophilia. PLoS One 2014;9:e101391.
60. Cheng EZX, Zhang Q, et al. TH2 cytokines stimulate eotaxin-3 secretion by esophageal fibroblasts: an effect that is not blocked by omeprazole. Gastroenterology 2013;144(Suppl 1):S79-S80. This study shows that Th2-stimulated eotaxin-3 that is secreted from fibroblasts is not blocked by omeprazole, which blocks eotaxin-3 from epithelial cells, suggesting that there are alternate paths of pathogenesis of PPI-REE and EoE that need further investigation.
61. Molina-Infante J, Martinek J, Martinez-Alcala C, et al. Long-term efficacy of PPI therapy in patients with PPI-responsive esophageal eosinophilia: an international multicenter study. Gastroenterology 2014;146:S-17. This is the first study that introduces the idea of differential PPI metabolism as a mechanism of explaining PPI response in PPI-REE, and is supported by a rapid PPI metabolism phenotype in those patients who had disease relapse after a decrease in PPI dosing.
62. Hirano I. Editorial: should patients with suspected eosinophilic esophagitis undergo a therapeutic trial of proton pump inhibition? Am J Gastroenterol 2013;108:373-375.
63. Molina-Infante J, Katzka DA, Dellon ES. Proton pump inhibitor-responsive esophageal eosinophilia: a historical perspective on a novel and evolving entity. Rev Esp Enferm Dig 2015;107:29-36.