Gastroenterology
Volume 137, Issue 4 , Pages 1238-1249 , October 2009

Biology and Treatment of Eosinophilic Esophagitis

  • Marc E. Rothenberg

      Affiliations

    • Corresponding Author InformationReprint requests Address requests for reprints to: Marc E. Rothenberg, MD, PhD, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229. fax: (513) 636-3310

Received 26 May 2009 ,Accepted 1 July 2009.

References 

  1. Mishra A, Hogan SP, Lee JJ, et al. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest. 1999;103:1719–1727
  2. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol. 2004;113:11–28
  3. Balatsinou C, Milano A, Caldarella MP, et al. Eosinophilic esophagitis is a component of the anticonvulsant hypersensitivity syndrome: description of two cases. Dig Liver Dis. 2008;40:145–148
  4. Noble C, Francis L, Withers GW, et al. Audit of eosinophilic oesophagitis in children post-liver transplant. Pediatr Transplant. 2008 Nov 1;[Epub ahead of print]
  5. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133:1342–1363
  6. Noble A, Drouin E, Faure C. Eosinophilic esophagitis and gastritis in Rubinstein-Taybi syndrome. J Pediatr Gastroenterol Nutr. 2007;44:498–500
  7. Kagalwalla AF, Shah A, Ritz S, et al. Cow's milk protein-induced eosinophilic esophagitis in a child with gluten-sensitive enteropathy. J Pediatr Gastroenterol Nutr. 2007;44:386–388
  8. Quaglietta L, Coccorullo P, Miele E, et al. Eosinophilic oesophagitis and coeliac disease: is there an association?. Aliment Pharmacol Ther. 2007;26:487–493
  9. Verzegnassi F, Bua J, De Angelis P, et al. Eosinophilic oesophagitis and coeliac disease: is it just a casual association?. Gut. 2007;56:1029–1030
  10. Heine RG. Eosinophilic esophagitis in children with celiac disease: new diagnostic and therapeutic dilemmas. J Gastroenterol Hepatol. 2008;23:993–994
  11. Ooi CY, Day AS, Jackson R, et al. Eosinophilic esophagitis in children with celiac disease. J Gastroenterol Hepatol. 2008;23:1144–1148
  12. 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
  13. Hue S, Mention JJ, Monteiro RC, et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity. 2004;21:367–377
  14. van Heel DA. Interleukin 15: its role in intestinal inflammation. Gut. 2006;55:444–445
  15. Caillat-Zucman S. How NKG2D ligands trigger autoimmunity?. Hum Immunol. 2006;67:204–207
  16. Koning F, Gilissen L, Wijmenga C. Gluten: a two-edged sword (Immunopathogenesis of celiac disease). Springer Semin Immunopathol. 2005;27:217–232
  17. Stepniak D, Koning F. Celiac disease—sandwiched between innate and adaptive immunity. Hum Immunol. 2006;67:460–468
  18. van Heel DA, Franke L, Hunt KA, et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet. 2007;39:827–829
  19. Hunt KA, Zhernakova A, Turner G, et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet. 2008;40:395–402
  20. Gudbjartsson DF, Bjornsdottir US, Halapi E, et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet. 2009;41:342–347
  21. 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
  22. Walsh SV, Antonioli DA, Goldman H, et al. Allergic esophagitis in children: a clinicopathological entity. Am J Surg Pathol. 1999;23:390–396
  23. Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005;3:1198–1206
  24. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004;351:940–941
  25. Noel RJ, Rothenberg ME. Eosinophilic esophagitis. Curr Opin Pediatr. 2005;17:690–694
  26. Desai TK, Stecevic V, Chang CH, et al. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc. 2005;61:795–801
  27. Mackenzie SH, Go M, Chadwick B, et al. Eosinophilic oesophagitis in patients presenting with dysphagia—a prospective analysis. Aliment Pharmacol Ther. 2008;28:1140–1146
  28. Bassett J, Maydonovitch C, Perry J, et al. Prevalence of esophageal dysmotility in a cohort of patients with esophageal biopsies consistent with eosinophilic esophagitis. Dis Esophagus. 2009;6:543–548
  29. Korsapati HR, Babaei A, Bhargava V, et al. Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic esophagitis. Gut. 2009;58:1056–1062
  30. Lucendo AJ, Castillo P, Martin-Chavarri S, et al. Manometric findings in adult eosinophilic oesophagitis: a study of 12 cases. Eur J Gastroenterol Hepatol. 2007;19:417–424
  31. Nurko S, Rosen R. Esophageal dysmotility in patients who have eosinophilic esophagitis. Gastrointest Endosc Clin North Am. 2008;18:73–89ix
  32. Roy-Ghanta S, Larosa DF, Katzka DA. Atopic characteristics of adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2008;6:531–535
  33. Assa'ad AH, Putnam PE, Collins MH, et al. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol. 2007;119:731–738
  34. Kapel RC, Miller JK, Torres C, et al. Eosinophilic esophagitis: a prevalent disease in the United States that affects all age groups. Gastroenterology. 2008;134:1316–1321
  35. Spergel JM, Brown-Whitehorn TF, Beausoleil JL, et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr. 2009;48:30–36
  36. Almansa C, Krishna M, Buchner AM, et al. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol. 2009;104:828–833
  37. Croese J, Fairley SK, Masson JW, et al. Clinical and endoscopic features of eosinophilic esophagitis in adults. Gastrointest Endosc. 2003;58:516–522
  38. Cherian S, Smith NM, Forbes DA. Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch Dis Child. 2006;91:1000–1004
  39. Cury EK, Schraibman V, Faintuch S. Eosinophilic infiltration of the esophagus: gastroesophageal reflux versus eosinophilic esophagitis in children—discussion on daily practice. J Pediatr Surg. 2004;39:e4–e7
  40. Attwood SE, Smyrk TC, Demeester TR, et al. Esophageal eosinophilia with dysphagia (A distinct clinicopathologic syndrome). Dig Dis Sci. 1993;38:109–116
  41. Cantu P, Velio P, Prada A, et al. Ringed oesophagus and idiopathic eosinophilic oesophagitis in adults: an association in two cases. Dig Liver Dis. 2005;37:129–134
  42. Shitrit AB, Reinus C, Zeides S, et al. Eosinophilic esophagitis. Isr Med Assoc J. 2006;8:587
  43. Fujiwara H, Morita A, Kobayashi H, et al. Infiltrating eosinophils and eotaxin: their association with idiopathic eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2002;89:429–432
  44. Munitiz V, Martinez de Haro LF, Ortiz A, et al. Primary eosinophilic esophagitis. Dis Esophagus. 2003;16:165–168
  45. Lucendo Villarin AJ, Carrion Alonso G, Navarro Sanchez M, et al. Eosinophilic esophagitis in adults, an emerging cause of dysphagia (Description of 9 cases). Rev Esp Enferm Dig. 2005;97:229–239
  46. Straumann A, Spichtin HP, Bucher KA, et al. Eosinophilic esophagitis: red on microscopy, white on endoscopy. Digestion. 2004;70:109–116
  47. Molina-Infante J, Hernandez-Alonso M, Perez-Gallardo B, et al. The first Asian case report of eosinophilic esophagitis in an asymptomatic adult: what about a proton pump inhibitor trial?. J Chin Med Assoc. 2009;72:166–167
  48. Ruchelli E, Wenner W, Voytek T, et al. Severity of esophageal eosinophilia predicts response to conventional gastroesophageal reflux therapy. Pediatr Dev Pathol. 1999;2:15–18
  49. Markowitz JE, Liacouras CA. Eosinophilic esophagitis. Gastroenterol Clin North Am. 2003;32:949–966
  50. Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointest Endosc. 2002;56:260–270
  51. Straumann A, Simon HU. Eosinophilic esophagitis: escalating epidemiology?. J Allergy Clin Immunol. 2005;115:418–419
  52. Ronkainen J, Talley NJ, Aro P, et al. Prevalence of eosinophilia and eosinophilic esophagitis in adults in the community: a random population based study (Kalixanda) (abstr). Gastroenterology. 2006;130:A575
  53. 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;7:420–426426 e1–2
  54. Bousvaros A, Morley-Fletcher A, Pensabene L, et al. Research and clinical challenges in paediatric inflammatory bowel disease. Dig Liver Dis. 2008;40:32–38
  55. Catassi C, Fasano A. Celiac disease. Curr Opin Gastroenterol. 2008;24:687–691
  56. Whitney-Miller CL, Katzka D, Furth EE. Eosinophilic esophagitis: a retrospective review of esophageal biopsy specimens from 1992 to 2004 at an adult academic medical center. Am J Clin Pathol. 2009;131:788–792
  57. Rothenberg ME, Mishra A, Collins MH, et al. Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin Immunol. 2001;108:891–894
  58. Shah A, Kagalwalla AF, Gonsalves N, et al. Histopathologic variability in children with eosinophilic esophagitis. Am J Gastroenterol. 2009;104:716–721
  59. Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointest Endosc Clin North Am. 2008;18:59–71viii–ix
  60. Noel RJ, Putnam PE, Collins MH, et al. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2004;2:568–575
  61. Steiner SJ, Kernek KM, Fitzgerald JF. Severity of basal cell hyperplasia differs in reflux versus eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2006;42:506–509
  62. Lewis CJ, Lamb CA, Kanakala V, et al. Is the etiology of eosinophilic esophagitis in adults a response to allergy or reflux injury? (Study of cellular proliferation markers). Dis Esophagus. 2009;22:249–255
  63. Parfitt JR, Gregor JC, Suskin NG, et al. Eosinophilic esophagitis in adults: distinguishing features from gastroesophageal reflux disease: a study of 41 patients. Mod Pathol. 2006;19:90–96
  64. Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology. 2002;122:1216–1225
  65. Konikoff MR, Noel RJ, Blanchard C, et al. A randomized double-blind-placebo controlled trial of fluticasone proprionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131:1381–1391
  66. Lucendo AJ, Navarro M, Comas C, et al. Immunophenotypic characterization and quantification of the epithelial inflammatory infiltrate in eosinophilic esophagitis through stereology: an analysis of the cellular mechanisms of the disease and the immunologic capacity of the esophagus. Am J Surg Pathol. 2007;31:598–606
  67. Protheroe C, Woodruff SA, Depetris G, et al. A novel histological scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2009;7:749–755.e11
  68. Fox VL, Nurko S, Teitelbaum JE, et al. High-resolution EUS in children with eosinophilic “allergic” esophagitis. Gastrointest Endosc. 2003;57:30–36
  69. Dahshan A, Rabah R. Correlation of endoscopy and histology in the gastroesophageal mucosa in children: are routine biopsies justified?. J Clin Gastroenterol. 2000;31:213–216
  70. Spergel JM, Andrews T, Brown-Whitehorn TF, et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol. 2005;95:336–343
  71. Spergel JM. Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients. Curr Opin Allergy Clin Immunol. 2007;7:274–278
  72. 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;4:1097–1102
  73. Mishra A, Hogan SP, Brandt EB, et al. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001;107:83–90
  74. Mishra A, Hogan SP, Brandt EB, et al. Interleukin-5 promotes eosinophil trafficking to the esophagus. J Immunol. 2002;168:2464–2469
  75. Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology. 2003;125:1419–1427
  76. Blanchard C, Mishra A, Saito-Akei H, et al. Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy. 2005;35:1096–1103
  77. Akei HS, Mishra A, Blanchard C, et al. Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology. 2005;129:985–994
  78. Onbasi K, Sin AZ, Doganavsargil B, et al. Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season. Clin Exp Allergy. 2005;35:1423–1431
  79. 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;120:204–214
  80. Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol. 2006;118:1054–1059
  81. Collins MH, Blanchard C, Abonia JP, et al. Clinical, pathologic, and molecular characterization of familial eosinophilic esophagitis compared with sporadic cases. Clin Gastroenterol Hepatol. 2008;6:621–629
  82. Bhattacharya B, Carlsten J, Sabo E, et al. Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease. Hum Pathol. 2007;38:1744–1753
  83. Blanchard C, Mingler MK, McBride M, et al. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses. Mucosal Immunol. 2008;1:289–296
  84. O'Regan GM, Sandilands A, McLean WH, et al. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008;122:689–693
  85. Fallon PG, Sasaki T, Sandilands A, et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet. 2009;41:602–608
  86. Howell MD, Fairchild HR, Kim BE, et al. Th2 cytokines act on S100/A11 to downregulate keratinocyte differentiation. J Invest Dermatol. 2008;128:2248–2258
  87. Vicario M, Blanchard C, Stringer KF, et al. Local B cells and IgE production in the esophageal mucosa in eosinophilic esophagitis. Gut. 2009 Jun 14;[Epub ahead of print]
  88. Mishra A, Schlotman J, Wang M, et al. Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2007;81:916–924
  89. Mishra A, Wang M, Pemmaraju VR, et al. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology. 2008;134:204–214
  90. Bullock JZ, Villanueva JM, Blanchard C, et al. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007;45:22–31
  91. Yamazaki K, Murray JA, Arora AS, et al. Allergen-specific in vitro cytokine production in adult patients with eosinophilic esophagitis. Dig Dis Sci. 2006;51:1934–1941
  92. Garrett JK, Jameson SC, Thomson B, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004;113:115–119
  93. Stein ML, Collins MH, Villanueva JM, et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118:1312–1319
  94. Stein ML, Villanueva JM, Buckmeier BK, et al. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008;121:1473–14831483 e1–4
  95. Straumann A, Conus S, Kita H, et al. Mepolizumab, a humanized monoclonal antibody to IL-5, for severe eosinophilic esophagitis in adults: a randomized placebo-controlled double-blind trial. J Allergy Clin Immunol. 2008;121:S44
  96. Zink DA, Amin M, Gebara S, et al. Familial dysphagia and eosinophilia. Gastrointest Endosc. 2007;65:330–334
  97. Patel SM, Falchuk KR. Three brothers with dysphagia caused by eosinophilic esophagitis. Gastrointest Endosc. 2005;61:165–167
  98. Penrose LS. The genetic background of common diseases. Acta Genet Stat Med. 1953;257–265
  99. Malerba G, Lauciello MC, Scherpbier T, et al. Linkage analysis of chromosome 12 markers in Italian families with atopic asthmatic children. Am J Respir Crit Care Med. 2000;162:1587–1590
  100. Mueller S, Aigner T, Neureiter D, et al. Eosinophil infiltration and degranulation in esophageal mucosa from adult patients with eosinophilic esophagitis (EE) (A retrospective comparative pathologic biopsy study). J Clin Pathol. 2006;59:1175–1180
  101. Gleich GJ, Frigas E, Loegering DA, et al. The cytotoxic properties of the eosinophil major basic protein. J Immunol. 1979;123:2925
  102. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147–174
  103. Slifman NR, Loegering DA, McKean DJ, et al. Ribonuclease activity associated with human eosinophil-derived neurotoxin and eosinophil cationic protein. J Immunol. 1986;137:2913–2917
  104. Rosenberg HF. Recombinant human eosinophil cationic protein: ribonuclease activity not essential for cytotoxicity. J Biol Chem. 1995;270:7876–7881
  105. Yang D, Chen Q, Su SB, et al. Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. J Exp Med. 2008;205:79–90
  106. Young JD, Peterson CG, Venge P, et al. Mechanism of membrane damage mediated by human eosinophil cationic protein. Nature. 1986;321:613–616
  107. Jacoby DB, Gleich GJ, Fryer AD. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest. 1993;91:1314–1318
  108. Mulder DJ, Pacheco I, Hurlbut DJ, et al. FGF9-induced proliferative response to eosinophilic inflammation in oesophagitis. Gut. 2009;58:166–173
  109. Jacobsen EA, Taranova AG, Lee NA, et al. Eosinophils: singularly destructive effector cells or purveyors of immunoregulation?. J Allergy Clin Immunol. 2007;119:1313–1320
  110. Phipps S, Ying S, Wangoo A, et al. The relationship between allergen-induced tissue eosinophilia and markers of repair and remodeling in human atopic skin. J Immunol. 2002;169:4604–4612
  111. Gharaee-Kermani M, Phan SH. The role of eosinophils in pulmonary fibrosis. Int J Mol Med. 1998;1:43–53
  112. Aceves SS, Newbury RO, Dohil R, et al. Esophageal remodeling in pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119:206–212
  113. Yousefi S, Gold JA, Andina N, et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med. 2008;14:949–953
  114. Nizet V, Rothenberg ME. Mitochondrial missile defense. Nat Med. 2008;14:910–912
  115. Jacobsen EA, Ochkur SI, Pero RS, et al. Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells. J Exp Med. 2008;205:699–710
  116. Walsh ER, Sahu N, Kearley J, et al. Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma. J Exp Med. 2008;205:1285–1292
  117. Justinich CJ, Ricci A, Kalafus DA, et al. Activated eosinophils in esophagitis in children: a transmission electron microscopic study. J Pediatr Gastroenterol Nutr. 1997;25:194–198
  118. Hogan SP, Mishra A, Brandt EB, et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2001;2:353–360
  119. Lee GS, Craig PI, Freiman JS, et al. Intermittent dysphagia for solids associated with a multiringed esophagus: clinical features and response to dilatation. Dysphagia. 2007;22:55–62
  120. Spergel JM, Beausoleil JL, Mascarenhas M, et al. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol. 2002;109:363–368
  121. Spergel JM, Brown-Whitehorn T, Beausoleil JL, et al. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119:509–511
  122. Assa'ad A. Detection of causative foods by skin prick and atopy patch tests in patients with eosinophilic esophagitis: things are not what they seem. Ann Allergy Asthma Immunol. 2005;95:309–311
  123. Aceves SS, Dohil R, Newbury RO, et al. Topical viscous budesonide suspension for treatment of eosinophilic esophagitis. J Allergy Clin Immunol. 2005;116:705–706
  124. Schaefer ET, Fitzgerald JF, Molleston JP, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol. 2008;6:165–173
  125. Attwood SE, Lewis CJ, Bronder CS, et al. Eosinophilic oesophagitis: a novel treatment using montelukast. Gut. 2003;52:181–185
  126. Straumann A, Bussmann C, Conus S, et al. Anti-TNF-alpha (infliximab) therapy for severe adult eosinophilic esophagitis. J Allergy Clin Immunol. 2008;122:425–427
  127. Netzer P, Gschossmann JM, Straumann A, et al. Corticosteroid-dependent eosinophilic oesophagitis: azathioprine and 6-mercaptopurine can induce and maintain long-term remission. Eur J Gastroenterol Hepatol. 2007;19:865–869
  128. Stone KD, Prussin C. Immunomodulatory therapy of eosinophil-associated gastrointestinal diseases. Clin Exp Allergy. 2008;38:1858–1865
  129. Ober C. Perspectives on the past decade of asthma genetics. J Allergy Clin Immunol. 2005;116:274–278
  130. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360:790–800
  131. Bischoff S, Crowe SE. Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives. Gastroenterology. 2005;128:1089–1113
  132. Lack G. Clinical practice (Food allergy). N Engl J Med. 2008;359:1252–1260
  133. Milner JD, Ward JM, Keane-Myers A, et al. Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease. Proc Natl Acad Sci U S A. 2007;104:576–581
  134. Burks AW, Laubach S, Jones SM. Oral tolerance, food allergy, and immunotherapy: implications for future treatment. J Allergy Clin Immunol. 2008;121:1344–1350

 Conflicts of interest The author discloses the following: Dr Rothenberg is a paid consultant for Centocor, Ception Therapeutics, Merck & Co, Novartis, and Nycomed.

 Funding Supported by National Institutes of Health grants R01 AI45898, R01 DK067255, U19 AI070235, R01 DK076893, R01 AI057803, and P30 DK078392; the Campaign Urging Research for Eosinophilic Disorders; the Food Allergy and Anaphylaxis Network; the Food Allergy Project; and the Buckeye Foundation.

PII: S0016-5085(09)01156-1

doi: 10.1053/j.gastro.2009.07.007

Gastroenterology
Volume 137, Issue 4 , Pages 1238-1249 , October 2009