Immunologic Research

, Volume 56, Issue 2–3, pp 249–260 | Cite as

Eosinophilic esophagitis: an immune-mediated esophageal disease

  • Jenny Weinbrand-Goichberg
  • Idit Segal
  • Adi Ovadia
  • Arie Levine
  • Ilan Dalal
Etio Pathogenesis of Autoimmunity

Abstract

Eosinophilic esophagitis (EoE) is an emerging disease defined by esophageal dysfunction, by typical endoscopic findings and by abnormal eosinophilic inflammation within the esophagus. Eosinophilic accumulation in the esophagus occurs as a result of esophageal overexpression of pro-inflammatory mediators, including T cells and mast cells, cytokines such as interleukin (IL)-13, IL-5 and IL-15, as well as chemoattractants (eotaxin and transforming growth factor-β1, fibroblast growth factor and the newly characterized gene—thymic stromal lymphopoietin, which is a key regulator of allergic sensitization initiation). The role of allergy, particularly food allergy in EoE is indisputable, as elimination diet is a proven commonly used treatment for the disease. However, unlike classical immediate IgE-mediated reaction to allergen, EoE is associated with an altered immune response, characterized by a combination of IgE-mediated and non-IgE-mediated mechanisms. In this review, we aim to discuss the many typical aspects of EoE as opposed to other entities involving the esophagus, with focusing on the aberrant immune-mediated key players contributing to the pathogenesis of this unique disease.

Keywords

Esophagitis Eosinophilic inflammation Mix IgE and non-IgE mediated Food allergy Elimination diet Eotaxin-3 

Notes

Conflict of interest

None.

References

  1. 1.
    Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol. 2006;118:1054–9.PubMedGoogle Scholar
  2. 2.
    Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, Burks AW, Chehade M, Collins MH, Dellon ES, Dohil R, Falk GW, Gonsalves N, Gupta SK, Katzka DA, Lucendo AJ, Markowitz JE, Noel RJ, Odze RD, Putnam PE, Richter JE, Romero Y, Ruchelli E, Sampson HA, Schoepfer A, Shaheen NJ, Sicherer SH, Spechler S, Spergel JM, Straumann A, Wershil BK, Rothenberg ME, Aceves SS. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128:3–20.e6; quiz 21–2.Google Scholar
  3. 3.
    Aceves SS, Newbury RO, Dohil R, Schwimmer J, Bastian JF. Distinguishing eosinophilic esophagitis in pediatric patients: clinical, endoscopic, and histologic features of an emerging disorder. J Clin Gastroenterol. 2007;41:252–6.PubMedGoogle Scholar
  4. 4.
    Steiner SJ, Kernek KM, Fitzgerald JF. Severity of basal cell hyperplasia differs in reflux versus eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2006;42:506–9.PubMedGoogle Scholar
  5. 5.
    Spergel JM, Andrews T, Brown-Whitehorn TF, Beausoleil JL, Liacouras CA. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol. 2005;95:336–43.PubMedGoogle Scholar
  6. 6.
    Helou EF, Simonson J, Arora AS. 3-yr-follow-up of topical corticosteroid treatment for eosinophilic esophagitis in adults. Am J Gastroenterol. 2008;103:2194–9.PubMedGoogle Scholar
  7. 7.
    Dohil R, Newbury R, Fox L, Bastian J, Aceves S. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology. 2010;139:418–29.PubMedGoogle Scholar
  8. 8.
    Abu-Sultaneh SM, Durst P, Maynard V, Elitsur Y. Fluticasone and food allergen elimination reverse sub-epithelial fibrosis in children with eosinophilic esophagitis. Dig Dis Sci. 2011;56:97–102.PubMedGoogle Scholar
  9. 9.
    Mukkada VA, Haas A, Maune NC, Capocelli KE, Henry M, Gilman N, Petersburg S, Moore W, Lovell MA, Fleischer DM, Furuta GT, Atkins D. Feeding dysfunction in children with eosinophilic gastrointestinal diseases. Pediatrics. 2010;126:e672–7.PubMedGoogle Scholar
  10. 10.
    Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004;351:940–1.PubMedGoogle Scholar
  11. 11.
    Pentiuk SP, Miller CK, Kaul A. Eosinophilic esophagitis in infants and toddlers. Dysphagia. 2007;22:44–8.PubMedGoogle Scholar
  12. 12.
    Straumann A, Aceves SS, Blanchard C, Collins MH, Furuta GT, Hirano I, Schoepfer AM, Simon D, Simon HU. Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy. 2012;67:477–90.PubMedGoogle Scholar
  13. 13.
    Walsh SV, Antonioli DA, Goldman H, Fox VL, Bousvaros A, Leichtner AM, Furuta GT. Allergic esophagitis in children: a clinicopathological entity. Am J Surg Pathol. 1999;23:390–6.PubMedGoogle Scholar
  14. 14.
    Blanchard C, Mingler MK, McBride M, Putnam PE, Collins MH, Chang G, Stringer K, Abonia JP, Molkentin JD, Rothenberg ME. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses. Mucosal Immunol. 2008;1:289–96.PubMedGoogle Scholar
  15. 15.
    Kerlin P, Jones D, Remedios M, Campbell C. Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus. J Clin Gastroenterol. 2007;41:356–61.PubMedGoogle Scholar
  16. 16.
    Collins MH, Blanchard C, Abonia JP, Kirby C, Akers R, Wang N, Putnam PE, Jameson SC, Assa’ad AH, Konikoff MR, Stringer KF, Rothenberg ME. Clinical, pathologic, and molecular characterization of familial eosinophilic esophagitis compared with sporadic cases. Clin Gastroenterol Hepatol. 2008;6:621–9.PubMedGoogle Scholar
  17. 17.
    Ober C. Perspectives on the past decade of asthma genetics. J Allergy Clin Immunol. 2005;116:274–8.PubMedGoogle Scholar
  18. 18.
    Cherian S, Smith NM, Forbes DA. Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch Dis Child. 2006;91(12):1000–4.PubMedGoogle Scholar
  19. 19.
    Straumann A, Simon HU. Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol. 2005;115(2):418–9.PubMedGoogle Scholar
  20. 20.
    Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, Flick J, Kelly J, Brown-Whitehorn T, Mamula P, Markowitz JE. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005;3:1198–206.PubMedGoogle Scholar
  21. 21.
    Hruz P, Straumann A, Bussmann C, et al. Swiss EoE study group. Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol. 2011;128(6):1349–50.PubMedGoogle Scholar
  22. 22.
    Weller PF. The immunobiology of eosinophils. N Engl J Med. 1991;324:1110–8.PubMedGoogle Scholar
  23. 23.
    Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME. First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees: eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133:1342–63.PubMedGoogle Scholar
  24. 24.
    Spergel JM, Brown-Whitehorn TF, Beausoleil JL, Franciosi J, Shuker M, Verma R, Liacouras CA. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr. 2009;48:30–6.PubMedGoogle Scholar
  25. 25.
    Zink DA, Amin M, Gebara S, Desai TK. Familial dysphagia and eosinophilia. Gastrointest Endosc. 2007;65:330–4.PubMedGoogle Scholar
  26. 26.
    Patel SM, Falchuk KR. Three brothers with dysphagia caused by eosinophilic esophagitis. Gastrointest Endosc. 2005;61:165–7.PubMedGoogle Scholar
  27. 27.
    Meyer GW. Eosinophilic esophagitis in a father and a daughter. Gastrointest Endosc. 2005;61:932.PubMedGoogle Scholar
  28. 28.
    Penrose LS. The genetical background of common diseases. Acta Genet Stat Med. 1953;4:257–65.PubMedGoogle Scholar
  29. 29.
    Wang FY, Gupta SK, Fitzgerald JF. Is there a seasonal variation in the incidence or intensity of allergic eosinophilic esophagitis in newly diagnosed children? J Clin Gastroenterol. 2007;41:451–3.PubMedGoogle Scholar
  30. 30.
    Malerba G, Lauciello MC, Scherpbier T, Trabetti E, Galavotti R, Cusin V, Pescollderungg L, Zanoni G, Martinati LC, Boner AL, Levitt RC, Pignatti PF. Linkage analysis of chromosome 12 markers in Italian families with atopic asthmatic children. Am J Respir Crit Care Med. 2000;162:1587–90.PubMedGoogle Scholar
  31. 31.
    Prasad GA, Talley NJ, Romero Y, Arora AS, Kryzer LA, Smyrk TC, Alexander JA. Prevalence and predictive factors of eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. Am J Gastroenterol. 2007;102:2627–32.PubMedGoogle Scholar
  32. 32.
    Shah A, Kagalwalla AF, Gonsalves N, Melin-Aldana H, Li BU, Hirano I. Histopathologic variability in children with eosinophilic esophagitis. Am J Gastroenterol. 2009;104(3):716–21.PubMedGoogle Scholar
  33. 33.
    Krarup AL, Villadsen GE, Mejlgaard E, Olesen SS, Drewes AM, Funch-Jensen P. Acid hypersensitivity in patients with eosinophilic oesophagitis. Scand J Gastroenterol. 2010;45:273–81.PubMedGoogle Scholar
  34. 34.
    Mueller S, Neureiter D, Aigner T, Stolte M. Comparison of histological parameters for the diagnosis of eosinophilic oesophagitis versus gastro-oesophageal reflux disease on oesophageal biopsy material. Histopathology. 2008;53:676–84.PubMedGoogle Scholar
  35. 35.
    Kephart GM, Alexander JA, Arora AS, Romero Y, Smyrk TC, Talley NJ, Kita H. Marked deposition of eosinophil-derived neurotoxin in adult patients with eosinophilic esophagitis. Am J Gastroenterol. 2010;105:298–307.PubMedGoogle Scholar
  36. 36.
    Chehade M, Sampson HA, Morotti RA, Magid MS. Esophageal subepithelial fibrosis in children with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007;45:319–28.PubMedGoogle Scholar
  37. 37.
    Straumann A, Conus S, Degen L, Felder S, Kummer M, Engel H, Bussmann C, Beglinger C, Schoepfer A, Simon HU. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology. 2010;139:1526–37, 1537.e1.Google Scholar
  38. 38.
    Aceves SS, Newbury RO, Chen D, Mueller J, Dohil R, Hoffman H, Bastian JF, Broide DH. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy. 2010;65:109–16.PubMedGoogle Scholar
  39. 39.
    Baxi S, Gupta SK, Swigonski N, Fitzgerald JF. Clinical presentation of patients with eosinophilic inflammation of the esophagus. Gastrointest Endosc. 2006;64:473–8.PubMedGoogle Scholar
  40. 40.
    Kapel RC, Miller JK, Torres C, Aksoy S, Lash R, Katzka DA. Eosinophilic esophagitis: a prevalent disease in the United States that affects all age groups. Gastroenterology. 2008;134:1316–21.PubMedGoogle Scholar
  41. 41.
    Pentiuk S, Putnam PE, Collins MH, Rothenberg ME. Dissociation between symptoms and histological severity in pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2009;48:152–60.PubMedGoogle Scholar
  42. 42.
    Korsapati H, Babaei A, Bhargava V, Dohil R, Quin A, Mittal RK. Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis. Gut. 2009;58:1056–62.PubMedGoogle Scholar
  43. 43.
    Assa’ad A. Eosinophilic esophagitis: association with allergic disorders. Gastrointest Endosc Clin N Am. 2008;18:119–32; x.Google Scholar
  44. 44.
    Moawad FJ, Veerappan GR, Lake JM, Maydonovitch CL, Haymore BR, Kosisky SE, Wong RK. Correlation between eosinophilic oesophagitis and aeroallergens. Aliment Pharmacol Ther. 2010;31:509–15.PubMedGoogle Scholar
  45. 45.
    Penfield JD, Lang DM, Goldblum JR, Lopez R, Falk GW. The role of allergy evaluation in adults with eosinophilic esophagitis. J Clin Gastroenterol. 2010;44:22–7.PubMedGoogle Scholar
  46. 46.
    Roy-Ghanta S, Larosa DF, Katzka DA. Atopic characteristics of adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2008;6:531–5.PubMedGoogle Scholar
  47. 47.
    Sampson HA. Food allergy. Part 1: immunopathogenesis and clinical disorders. J Allergy Clin Immunol. 1999;103:717–28.PubMedGoogle Scholar
  48. 48.
    Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol. 2002;109:363–8.PubMedGoogle Scholar
  49. 49.
    Ooi CY, Day AS, Jackson R, Bohane TD, Tobias V, Lemberg DA. Eosinophilic esophagitis in children with celiac disease. J Gastroenterol Hepatol. 2008;23:1144–8.PubMedGoogle Scholar
  50. 50.
    Arora AA, Weiler CR, Katzka DA. Eosinophilic esophagitis: allergic contribution, testing, and management. Curr Gastroenterol Rep. 2012;14:206–15.PubMedGoogle Scholar
  51. 51.
    Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it’s not just kid’s stuff. Gastrointest Endosc. 2002;56:260–70.PubMedGoogle Scholar
  52. 52.
    Prasad GA, Alexander JA, Schleck CD, Zinsmeister AR, Smyrk TC, Elias RM, Locke GR 3rd. Talley NJ: epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol. 2009;7:1055–61.PubMedGoogle Scholar
  53. 53.
    Almansa C, Krishna M, Buchner AM, Ghabril MS, Talley N, DeVault KR, Wolfsen H, Raimondo M, Guarderas JC, Achem SR. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol. 2009;104:828–33.PubMedGoogle Scholar
  54. 54.
    Erwin EA, James HR, Gutekunst HM, Russo JM, Kelleher KJ, Platts-Mills TA. Serum IgE measurement and detection of food allergy in pediatric patients with eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2010;104:496–502.PubMedGoogle Scholar
  55. 55.
    Rothenberg ME, Mishra A, Brandt EB, Hogan SP. Gastrointestinal eosinophils. Immunol Rev. 2001;179:139–55.PubMedGoogle Scholar
  56. 56.
    Spergel JM. Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients. Curr Opin Allergy Clin Immunol. 2007;7:274–8.PubMedGoogle Scholar
  57. 57.
    Sugnanam KK, Collins JT, Smith PK, Connor F, Lewindon P, Cleghorn G, Withers G. Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis. Allergy. 2007;62:1257–60.PubMedGoogle Scholar
  58. 58.
    Mishra A, Hogan SP, Brandt EB, Rothenberg ME. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001;107:83–90.PubMedGoogle Scholar
  59. 59.
    Mishra A, Hogan SP, Lee JJ, Foster PS, Rothenberg ME. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest. 1999;103:1719–27.PubMedGoogle Scholar
  60. 60.
    Mishra A, Schlotman J, Wang M, Rothenberg ME. Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2007;81:916–24.PubMedGoogle Scholar
  61. 61.
    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;108:954–61.PubMedGoogle Scholar
  62. 62.
    Vicario M, Blanchard C, Stringer KF, Collins MH, Mingler MK, Ahrens A, Putnam PE, Abonia JP, Santos J, Rothenberg ME. Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis. Gut. 2010;59:12–20.PubMedGoogle Scholar
  63. 63.
    Yen EH, Hornick JL, Dehlink E, Dokter M, Baker A, Fiebiger E, Nurko S. Comparative analysis of FcepsilonRI expression patterns in patients with eosinophilic and reflux esophagitis. J Pediatr Gastroenterol Nutr. 2010;51:584–92.PubMedGoogle Scholar
  64. 64.
    Abonia JP, Blanchard C, Butz BB, Rainey HF, Collins MH, Stringer K, Putnam PE, Rothenberg ME. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol. 2010;126:140–9.PubMedGoogle Scholar
  65. 65.
    Aceves SS, Newbury RO, Dohil R, Bastian JF, Broide DH. Esophageal remodeling in pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119:206–12.PubMedGoogle Scholar
  66. 66.
    Gleich GJ, Adolphson CR. The eosinophilic leukocyte: structure and function. Adv Immunol. 1986;39:177–253.PubMedGoogle Scholar
  67. 67.
    Uhm TG, Kim BS, Chung IY. Eosinophil development, regulation of eosinophil-specific genes, and role of eosinophils in the pathogenesis of asthma. Allergy Asthma Immunol Res. 2012;4:68–79.PubMedGoogle Scholar
  68. 68.
    Abu-Ghazaleh RI, Dunnette SL, Loegering DA, Checkel JL, Kita H, Thomas LL, Gleich GJ. Eosinophil granule proteins in peripheral blood granulocytes. J Leukoc Biol. 1992;52:611–8.PubMedGoogle Scholar
  69. 69.
    Gleich GJ, Frigas E, Loegering DA, Wassom DL, Steinmuller D. Cytotoxic properties of the eosinophil major basic protein. J Immunol. 1979;123:2925–7.PubMedGoogle Scholar
  70. 70.
    Mueller S, Aigner T, Neureiter D, Stolte M. Eosinophil infiltration and degranulation in oesophageal mucosa from adult patients with eosinophilic oesophagitis: a retrospective and comparative study on pathological biopsy. J Clin Pathol. 2006;59:1175–80.PubMedGoogle Scholar
  71. 71.
    Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol. 2004;113:11–28; quiz 29.Google Scholar
  72. 72.
    Lukacs NW, Oliveira SH, Hogaboam CM. Chemokines and asthma: redundancy of function or a coordinated effort? J Clin Invest. 1999;104:995–9.PubMedGoogle Scholar
  73. 73.
    Nickel R, Beck LA, Stellato C, Schleimer RP. Chemokines and allergic disease. J Allergy Clin Immunol. 1999;104:723.PubMedGoogle Scholar
  74. 74.
    Rothenberg ME. Eosinophilia. N Engl J Med. 1998;338:1592–600.PubMedGoogle Scholar
  75. 75.
    Gleich GJ. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol. 2000;105:651–63.PubMedGoogle Scholar
  76. 76.
    Mishra A, Hogan SP, Brandt EB, Rothenberg ME. IL-5 promotes eosinophil trafficking to the esophagus. J Immunol. 2002;168:2464–9.PubMedGoogle Scholar
  77. 77.
    Mishra A, Wang M, Pemmaraju VR, Collins MH, Fulkerson PC, Abonia JP, Blanchard C, Putnam PE, Rothenberg ME. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology. 2008;134:204–14.PubMedGoogle Scholar
  78. 78.
    Bhattacharya B, Carlsten J, Sabo E, Kethu S, Meitner P, Tavares R, Jakate S, Mangray S, Aswad B, Resnick MB. Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease. Hum Pathol. 2007;38:1744–53.PubMedGoogle Scholar
  79. 79.
    Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood. 1992;79:3101–9.PubMedGoogle Scholar
  80. 80.
    Zimmermann N, Hershey GK, Foster PS, Rothenberg ME. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol. 2003;111:227.PubMedGoogle Scholar
  81. 81.
    Stein ML, Villanueva JM, Buckmeier BK, Yamada Y, Filipovich AH, Assa’ad AH, Rothenberg ME. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008;121:1473–83, 1483.e1–4.Google Scholar
  82. 82.
    Hogan SP, Mishra A, Brandt EB, Foster PS, Rothenberg ME. A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy. Proc Natl Acad Sci USA. 2000;97:6681–6.PubMedGoogle Scholar
  83. 83.
    Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, Jameson SC, Kirby C, Konikoff MR, Collins MH, Cohen MB, Akers R, Hogan SP, Assa’ad AH, Putnam PE, Aronow BJ, Rothenberg ME. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116:536–47.PubMedGoogle Scholar
  84. 84.
    Blanchard C, Mishra A, Saito-Akei H, Monk P, Anderson I, Rothenberg ME. Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy. 2005;35:1096–103.PubMedGoogle Scholar
  85. 85.
    Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology. 2003;125:1419–27.PubMedGoogle Scholar
  86. 86.
    Blanchard C, Mingler MK, Vicario M, Abonia JP, Wu YY, Lu TX, Collins MH, Putnam PE, Wells SI, Rothenberg ME. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007;120:1292–300.PubMedGoogle Scholar
  87. 87.
    Zuo L, et al. IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha 2-inhibited pathway. J Immunol. 2010;185:660–9.PubMedGoogle Scholar
  88. 88.
    Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev. 1997;77:1033–79.PubMedGoogle Scholar
  89. 89.
    Gupta SK, Fitzgerald JF, Kondratyuk T, HogenEsch H. Cytokine expression in normal and inflamed esophageal mucosa: a study into the pathogenesis of allergic eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2006;42:22–6.PubMedGoogle Scholar
  90. 90.
    Rothenberg ME, Aceves S, Bonis PA, Collins MH, Gonsalves N, Gupta SK, Hirano I, Liacouras CA, Putnam PE, Spergel JM, Straumann A, Wershil BK, Furuta GT. Working with the US Food and Drug Administration: progress and timelines in understanding and treating patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2012;130:617–9.PubMedGoogle Scholar
  91. 91.
    Gharaee-Kermani M, Phan SH. The role of eosinophils in pulmonary fibrosis (Review). Int J Mol Med. 1998;1:43–53.PubMedGoogle Scholar
  92. 92.
    Desreumaux P, Bloget F, Seguy D, Capron M, Cortot A, Colombel JF, Janin A. Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis. Gastroenterology. 1996;110:768–74.PubMedGoogle Scholar
  93. 93.
    Phipps S, Ying S, Wangoo A, Ong YE, Levi-Schaffer F, Kay AB. The relationship between allergen-induced tissue eosinophilia and markers of repair and remodeling in human atopic skin. J Immunol. 2002;169:4604–12.PubMedGoogle Scholar
  94. 94.
    Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol. 2001;2(3):REVIEWS3005. doi: 10.1186/gb-2001-2-3-reviews3005.PubMedGoogle Scholar
  95. 95.
    Karsan A, Yee E, Poirier GG, Zhou R, Craig JM. Harlan. Fibroblast growth factor-2 inhibits endothelial cell apoptosis by Bcl-2-dependent and independent mechanisms. Am J Pathol. 1997;151(6):1775–84.PubMedGoogle Scholar
  96. 96.
    Burton JD, Bamford RN, Peters C, et al. A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci USA. 1994;91:4935–9.PubMedGoogle Scholar
  97. 97.
    Grabstein KH, Eisenman J, Shanebeck K, et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science. 1994;264:965–8.PubMedGoogle Scholar
  98. 98.
    Zhu X, Wang M, Mavi P, Rayapudi M, Pandey AK, Kaul A, Putnam PE, Rothenberg ME, Mishra A. Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice. Gastroenterology. 2010;139(1):182–93.e7.Google Scholar
  99. 99.
    Sherrill JD, Rothenberg ME. Genetic dissection of eosinophilic esophagitis provides insight into disease pathogenesis and treatment strategies. J Allergy Clin Immunol. 2011;128:23–32; quiz 33–4.Google Scholar
  100. 100.
    Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology. 2009;137:1238–49.PubMedGoogle Scholar
  101. 101.
    Blanchard C, Stucke EM, Burwinkel K, Caldwell JM, Collins MH, Ahrens A, Buckmeier BK, Jameson SC, Greenberg A, Kaul A, Franciosi JP, Kushner JP, Martin LJ, Putnam PE, Abonia JP, Wells SI, Rothenberg ME. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010;184:4033–41.PubMedGoogle Scholar
  102. 102.
    O’Regan GM, Sandilands A, McLean WH, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2009;124:R2–6.PubMedGoogle Scholar
  103. 103.
    Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, Gober L, Kim C, Glessner J, Frackelton E, Thomas K, Blanchard C, Liacouras C, Verma R, Aceves S, Collins MH, Brown-Whitehorn T, Putnam PE, Franciosi JP, Chiavacci RM, Grant SF, Abonia JP, Sleiman PM, Hakonarson H. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet. 2010;42:289–91.PubMedGoogle Scholar
  104. 104.
    Ziegler SF. The role of thymic stromal lymphopoietin (TSLP) in allergic disorders. Curr Opin Immunol. 2010;22:795–9.PubMedGoogle Scholar
  105. 105.
    Sherrill JD, Gao PS, Stucke EM, Blanchard C, Collins MH, Putnam PE, Franciosi JP, Kushner JP, Abonia JP, Assa’ad AH, Kovacic MB, Biagini Myers JM, Bochner BS, He H, Hershey GK, Martin LJ, Rothenberg ME. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol. 2010;126(160):5.e3.Google Scholar
  106. 106.
    DeBrosse CW, Franciosi JP, King EC, Butz BK, Greenberg AB, Collins MH, Abonia JP, Assa’ad A, Putnam PE, Rothenberg ME. Long-term outcomes in pediatric-onset esophageal eosinophilia. J Allergy Clin Immunol. 2011;128:132–8.PubMedGoogle Scholar
  107. 107.
    Francalanci P, De Angelis P, Minnei F, Diomedi Camassei F, Torroni F, Dall’Oglio L, Callea F. Eosinophilic esophagitis and Barrett’s esophagus: an occasional association or an overlap disease? Esophageal ‘double trouble’ in two children. Digestion. 2008;77:16–9.PubMedGoogle Scholar
  108. 108.
    Wolfsen HC, Hemminger LL, Achem SR. Eosinophilic esophagitis and Barrett’s esophagus with dysplasia. Clin Gastroenterol Hepatol. 2007;5:A18.PubMedGoogle Scholar
  109. 109.
    Furuta GT, Straumann A. Review article: the pathogenesis and management of eosinophilic oesophagitis. Aliment Pharmacol Ther. 2006;24:173–82.PubMedGoogle Scholar
  110. 110.
    Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, Melin-Aldana H, Li BU. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006;4:1097–102.PubMedGoogle Scholar
  111. 111.
    Kagalwalla AF, Shah A, Li BU, Sentongo TA, Ritz S, Manuel-Rubio M, Jacques K, Wang D, Melin-Aldana H, Nelson SP. Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr. 2011;53:145–9.PubMedGoogle Scholar
  112. 112.
    Schaefer ET, Fitzgerald JF, Molleston JP, Croffie JM, Pfefferkorn MD, Corkins MR, Lim JD, Steiner SJ, Gupta SK. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol. 2008;6:165–73.PubMedGoogle Scholar
  113. 113.
    Dohil R, Newbury R, et al. Oral viscous budesonide is effective in children with eosinophilic esophagitisin a randomized placebo controlled trial. Gastro. 2010;139:418–29.Google Scholar
  114. 114.
    Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr. 1998;26:380–5.PubMedGoogle Scholar
  115. 115.
    Lucendo AJ, De Rezende LC, Jimenez-Contreras S, Yague-Compadre JL, Gonzalez-Cervera J, Mota-Huertas T, Guagnozzi D, Angueira T, Gonzalez-Castillo S, Arias A. Montelukast was inefficient in maintaining steroid-induced remission in adult eosinophilic esophagitis. Dig Dis Sci. 2011;56:3551–8.PubMedGoogle Scholar
  116. 116.
    Stein ML, Collins MH, Villanueva JM, Kushner JP, Putnam PE, Buckmeier BK, Filipovich AH, Assa’ad AH, Rothenberg ME. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118:1312–9.PubMedGoogle Scholar
  117. 117.
    Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, Beglinger C, Smith DA, Patel J, Byrne M, Simon HU. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59:21–30.PubMedGoogle Scholar
  118. 118.
    Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, Beck LA, Boyce JA, Filipovich AH, Villanueva JM, Sutton SA, Assa’ad AH, Rothenberg ME. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004;113:115–9.PubMedGoogle Scholar
  119. 119.
    Assa’ad AH, Putnam PE, Collins MH, Akers RM, Jameson SC, Kirby CL, Buckmeier BK, Bullock JZ, Collier AR, Konikoff MR, Noel RJ, Guajardo JR, Rothenberg ME. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol. 2007;119:731–8.PubMedGoogle Scholar
  120. 120.
    Spergel JM, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129:456–63.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jenny Weinbrand-Goichberg
    • 1
  • Idit Segal
    • 2
  • Adi Ovadia
    • 1
  • Arie Levine
    • 2
    • 4
  • Ilan Dalal
    • 3
    • 4
  1. 1.Pediatric DepartmentE. Wolfson Medical CenterHolonIsrael
  2. 2.Pediatric Gastroenterology and Nutrition UnitE. Wolfson Medical CenterHolonIsrael
  3. 3.Pediatric Allergy and Immunology UnitE. Wolfson Medical CenterHolonIsrael
  4. 4.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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