Clinical Reviews in Allergy & Immunology

, Volume 50, Issue 2, pp 159–174 | Cite as

Eosinophilic Esophagitis: A Comprehensive Review

  • Antonella Cianferoni
  • Jonathan Spergel


Eosinophilic esophagitis (EoE) is an emerging chronic atopic clinical-pathologic disease with an estimated prevalence of 1/1000 similar to the one of Crohn’s diseases. Usually, EoE is firstly suspected due to symptoms that are caused by esophageal dysfunction and/or fibrosis. EoE diagnosis is confirmed if the esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf) as a peak value in one or more of at least four specimens obtained randomly from the esophagus. Most of the patients affected by EoE have other atopic diseases such as allergic rhinitis, asthma, IgE-mediated food allergies, and/or atopic dermatitis. The local inflammation is a T helper type 2 (Th2) flogosis, which most likely is driven by a mixed IgE and non-IgE-mediated reaction to food and/or environmental allergens. Recently published genetic studies showed also that EoE is associated with single nucleotide polymorphism (SNP) on genes which are important in atopic inflammation such as thymic stromal lymphopoietin (TSLP) located close to the Th2 cytokine cluster (IL-4, IL-5, IL-13) on chromosome 5q22. When the EoE diagnosis is made, it is imperative to control the local eosinophilic inflammation not only to give symptomatic relief to the patient but also to prevent complications such as esophageal stricture and food impaction. EoE is treated like many other atopic diseases with a combination of topical steroids and/or food antigen avoidance.


Eosinophilic esophagitis Genome-wide association study Th2 inflammation 



Antigen-presenting cells


The Children’s Hospital of Philadelphia


Dendritic cells


Center for Applied Genomics


Chemoattractant receptor expressed on Th2 cells




Esophago-gastroduodenal endoscopy


Eosinophilic esophagitis




Gastro-esophageal reflux


High power field


Inflammatory bowel disease




Invariant-natural killer cells


Langerhans cells


Prostaglandin D2


Proton pump inhibitors




A small nuclear polymorphism


Tumor necrosis factor alpha


Transforming growth factor beta


T helper type 2


Thymic stromal lymphopoietin



Institutional Support from The Department of Pediatrics, The Children’s Hospital of Philadelphia, and Joint Center for Gastroenterology and Nutrition of CHOP-HUP, and The CHOP Food Allergy Family Research Fund

Conflict of Interest



  1. 1.
    Furuta GT, Liacouras CA, Collins MH et al (2007) Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 133:1342–1363PubMedCrossRefGoogle Scholar
  2. 2.
    Liacouras CA, Furuta GT, Hirano I (2011) Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 128:3–20, e26PubMedCrossRefGoogle Scholar
  3. 3.
    Prasad GA, Alexander JA, Schleck CD et al (2009) Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol 7:1055–1061PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Noel RJ, Putnam PE, Rothenberg ME (2004) Eosinophilic esophagitis. N Engl J Med 351:940–941PubMedCrossRefGoogle Scholar
  5. 5.
    Straumann A, Simon HU (2005) Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol 115:418–419PubMedCrossRefGoogle Scholar
  6. 6.
    Hruz P, Straumann A, Bussmann C et al (2011) Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol 128(1349–1350):e1345Google Scholar
  7. 7.
    Cherian S, Smith NM, Forbes DA (2006) Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch Dis Child 91:1000–1004PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    van Rhijn BD., Verheij J., Smout AJ. and Bredenoord AJ. (2012) Rapidly increasing incidence of eosinophilic esophagitis in a large cohort. Neurogastroenterol MotilGoogle Scholar
  9. 9.
    Spergel JM, Brown-Whitehorn TF, Beausoleil JL et al (2009) 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr 48:30–36PubMedCrossRefGoogle Scholar
  10. 10.
    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(461–467):e465Google Scholar
  11. 11.
    Orenstein SR, Shalaby TM, Di Lorenzo C et al (2000) The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical series of 30 children. Am J Gastroenterol 95:1422–1430PubMedCrossRefGoogle Scholar
  12. 12.
    Blanchard C, Wang N, Rothenberg ME (2006) Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol 118:1054–1059PubMedCrossRefGoogle Scholar
  13. 13.
    Blanchard C, Wang N, Stringer KF et al (2006) Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest 116:536–547PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Gupta SK, Fitzgerald JF, Kondratyuk T, HogenEsch H (2006) Cytokine expression in normal and inflamed esophageal mucosa: a study into the pathogenesis of allergic eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 42:22–26PubMedCrossRefGoogle Scholar
  15. 15.
    Straumann A, Bauer M, Fischer B, Blaser K, Simon HU (2001) Idiopathic eosinophilic esophagitis is associated with a T (H)2-type allergic inflammatory response. J Allergy Clin Immunol 108:954–961PubMedCrossRefGoogle Scholar
  16. 16.
    Straumann A, Kristl J, Conus S et al (2005) Cytokine expression in healthy and inflamed mucosa: probing the role of eosinophils in the digestive tract. Inflamm Bowel Dis 11:720–726PubMedCrossRefGoogle Scholar
  17. 17.
    Blanchard C, Mingler MK, Vicario M et al (2007) IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol 120:1292–1300PubMedCrossRefGoogle Scholar
  18. 18.
    Blanchard C, Mishra A, Saito-Akei H, Monk P, Anderson I, Rothenberg ME (2005) Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy 35:1096–1103PubMedCrossRefGoogle Scholar
  19. 19.
    Blanchard C, Stucke EM, Burwinkel K et al (2010) Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol 184:4033–4041PubMedCrossRefGoogle Scholar
  20. 20.
    Mishra A, Hogan SP, Brandt EB, Rothenberg ME (2002) IL-5 promotes eosinophil trafficking to the esophagus. J Immunol 168:2464–2469PubMedCrossRefGoogle Scholar
  21. 21.
    Mishra A, Rothenberg ME (2003) Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology 125:1419–1427PubMedCrossRefGoogle Scholar
  22. 22.
    Schmid-Grendelmeier P, Altznauer F, Fischer B et al (2002) Eosinophils express functional IL-13 in eosinophilic inflammatory diseases. J Immunol 169:1021–1027PubMedCrossRefGoogle Scholar
  23. 23.
    Levin M, Motala C (2011) Eosinophilic esophagitis in Cape Town, South Africa. Clin Translat Allerg 1:p26CrossRefGoogle Scholar
  24. 24.
    Dellon ES, Jensen ET, Martin CF, Shaheen NJ. and Kappelman MD. (2013) Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol HepatolGoogle Scholar
  25. 25.
    Franciosi JP, Tam V, Liacouras CA, Spergel JM (2009) A case–control study of sociodemographic and geographic characteristics of 335 children with eosinophilic esophagitis. Clin Gastroenterol Hepatol 7:415–419PubMedCrossRefGoogle Scholar
  26. 26.
    Spergel JM, Andrews T, Brown-Whitehorn TF, Beausoleil JL, Liacouras CA (2005) Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol 95:336–343PubMedCrossRefGoogle Scholar
  27. 27.
    Collins MH (2008) Histopathologic features of eosinophilic esophagitis. Gastrointest Endosc Clin N Am 18:59–71, viii-ixPubMedCrossRefGoogle Scholar
  28. 28.
    Dellon ES, Gonsalves N, Hirano I et al (2013) ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 108:679–692, quiz 693PubMedCrossRefGoogle Scholar
  29. 29.
    Rothenberg ME, Spergel JM, Sherrill JD et al (2010) Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet 42:289–291PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Sherrill JD, Gao PS, Stucke EM et al (2010) Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol 126(160–165):e163Google Scholar
  31. 31.
    Blanchard C, Stucke EM, Rodriguez-Jimenez B (2011) A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol 127:208–217, 217 e201-207PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kinoshita Y, Furuta K, Ishimura N, Ishihara S (2012) Elevated plasma cytokines in Japanese patients with eosinophilic esophagitis and gastroenteritis. Digestion 86:238–243PubMedCrossRefGoogle Scholar
  33. 33.
    Akei HS, Mishra A, Blanchard C, Rothenberg ME (2005) Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology 129:985–994PubMedCrossRefGoogle Scholar
  34. 34.
    Merves J, Muir A., Modayur Chandramouleeswaran P, Cianferoni A., Wang ML. and Spergel JM. (2014) Eosinophilic esophagitis. Ann Allergy Asthma ImmunolGoogle Scholar
  35. 35.
    Muir AB, Lim DM, Benitez AJ et al (2013) Esophageal epithelial and mesenchymal cross-talk leads to features of epithelial to mesenchymal transition in vitro. Exp Cell Res 319:850–859PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Wenzel SE, Schwartz LB, Langmack EL et al (1999) Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med 160:1001–1008PubMedCrossRefGoogle Scholar
  37. 37.
    Mishra A, Wang M, Pemmaraju VR et al (2008) Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology 134:204–214PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Pope SM, Brandt EB, Mishra A et al (2001) IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism. J Allergy Clin Immunol 108:594–601PubMedCrossRefGoogle Scholar
  39. 39.
    Mishra A, Hogan SP, Brandt EB et al (2002) Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. J Biol Chem 277:4406–4412PubMedCrossRefGoogle Scholar
  40. 40.
    Spergel JM, Rothenberg ME, Collins MH (2012) Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 129:456–463, 463 e451-453PubMedCrossRefGoogle Scholar
  41. 41.
    Assa’ad AH, Gupta SK, Collins MH et al (2011) An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology 141:1593–1604PubMedCrossRefGoogle Scholar
  42. 42.
    Li M, Hener P, Zhang Z, Ganti KP, Metzger D, Chambon P (2009) Induction of thymic stromal lymphopoietin expression in keratinocytes is necessary for generating an atopic dermatitis upon application of the active vitamin D3 analogue MC903 on mouse skin. J Invest Dermatol 129:498–502PubMedCrossRefGoogle Scholar
  43. 43.
    Soumelis V, Reche PA, Kanzler H et al (2002) Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 3:673–680PubMedCrossRefGoogle Scholar
  44. 44.
    Noti M., Wojno ED., Kim BS., et al. (2013) Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat MedGoogle Scholar
  45. 45.
    Siracusa MC, Kim BS, Spergel JM, Artis D (2013) Basophils and allergic inflammation. J Allergy Clin Immunol 132:789–801, quiz 788PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Siracusa MC, Saenz SA, Hill DA et al (2011) TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477:229–233PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Wojno EDT, Noti M, Kim BS et al (2013) TSLP-elicited basophil responses mediate the pathogenesis of eosinophilic esophagitis. Cytokine 63:310–310CrossRefGoogle Scholar
  48. 48.
    Noti M, Wojno ED, Kim BS et al (2013) Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med 19:1005–1013PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Blanchard C, Durual S, Estienne M, Emami S, Vasseur S, Cuber JC (2005) Eotaxin-3/CCL26 gene expression in intestinal epithelial cells is up-regulated by interleukin-4 and interleukin-13 via the signal transducer and activator of transcription 6. Int J Biochem Cell Biol 37:2559–2573PubMedCrossRefGoogle Scholar
  50. 50.
    Cheng E, Zhang X, Huo X et al (2013) Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut 62:824–832PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Johnsson M, Bove M, Bergquist H et al (2011) Distinctive blood eosinophilic phenotypes and cytokine patterns in eosinophilic esophagitis, inflammatory bowel disease and airway allergy. J Innate Immun 3:594–604PubMedCrossRefGoogle Scholar
  52. 52.
    Sherrill J. D., Kc K., Wu D., et al. (2013) Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal ImmunolGoogle Scholar
  53. 53.
    Wen T, Stucke EM, Grotjan TM et al (2013) Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology 145:1289–1299PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Yen EH, Hornick JL, Dehlink E et al (2010) Comparative analysis of FcepsilonRI expression patterns in patients with eosinophilic and reflux esophagitis. J Pediatr Gastroenterol Nutr 51:584–592PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Lim DM, Narasimhan S, Michaylira CZ, Wang ML (2009) TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol 297:G1172–G1180PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Mulder DJ, Lobo D, Mak N, Justinich CJ (2012) Expression of toll-like receptors 2 and 3 on esophageal epithelial cell lines and on eosinophils during esophagitis. Dig Dis Sci 57:630–642PubMedCrossRefGoogle Scholar
  57. 57.
    Jyonouchi S., Smith CL., Saretta F., et al. (2013) Invariant natural killer T cells in children with eosinophilic esophagitis. Clin Exp AllergyGoogle Scholar
  58. 58.
    Mulder DJ, Pooni A, Mak N, Hurlbut DJ, Basta S, Justinich CJ (2011) Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis. Am J Pathol 178:744–753PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Straumann A, Conus S, Grzonka P et al (2010) Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 59:21–30PubMedCrossRefGoogle Scholar
  60. 60.
    Spergel JM, Rothenberg ME, Collins MH (2012) Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 129:456–463, 463 e451-453PubMedCrossRefGoogle Scholar
  61. 61.
    Rajavelu P, Rayapudi M, Moffitt M, Mishra A, Mishra A (2012) Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 302:G645–G654PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Mishra A, Schlotman J, Wang M, Rothenberg ME (2007) Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J Leukoc Biol 81:916–924PubMedCrossRefGoogle Scholar
  63. 63.
    Yamazaki K, Murray JA, Arora AS et al (2006) Allergen-specific in vitro cytokine production in adult patients with eosinophilic esophagitis. Dig Dis Sci 51:1934–1941PubMedCrossRefGoogle Scholar
  64. 64.
    Abonia JP, Blanchard C, Butz BB et al (2010) Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol 126:140–149PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Crockett SD, Sperry SL, Miller CB, Shaheen NJ, Dellon ES (2013) Emergency care of esophageal foreign body impactions: timing, treatment modalities, and resource utilization. Dis Esophagus 26:105–112PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Desai TK, Stecevic V, Chang CH, Goldstein NS, Badizadegan K, Furuta GT (2005) Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc 61:795–801PubMedCrossRefGoogle Scholar
  67. 67.
    Aceves SS, Ackerman SJ (2009) Relationships between eosinophilic inflammation, tissue remodeling, and fibrosis in eosinophilic esophagitis. Immunol Allergy Clin North Am 29:197–211, xiii-xivPubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA (2002) Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3:349–363PubMedCrossRefGoogle Scholar
  69. 69.
    Kagalwalla AF, Akhtar N, Woodruff SA et al (2012) Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment. J Allergy Clin Immunol 129(1387–1396):e1387CrossRefGoogle Scholar
  70. 70.
    Aceves SS, Newbury RO, Chen D et al (2010) Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy 65:109–116PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Aceves SS, Newbury RO, Dohil R, Bastian JF, Broide DH (2007) Esophageal remodeling in pediatric eosinophilic esophagitis. J Allergy Clin Immunol 119:206–212PubMedCrossRefGoogle Scholar
  72. 72.
    Kottyan LC, Davis BP, Sherrill JD et al (2014) Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet 46:895–900PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Lal G, Bromberg JS (2009) Epigenetic mechanisms of regulation of Foxp3 expression. Blood 114:3727–3735PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Schmidl C, Hansmann L, Lassmann T et al (2014) The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations. Blood 123:e68–e78PubMedCrossRefGoogle Scholar
  75. 75.
    He H, Ni B, Tian Y et al (2014) Histone methylation mediates plasticity of human FOXP3(+) regulatory T cells by modulating signature gene expressions. Immunology 141:362–376PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Tian Y, Jia Z, Wang J et al (2011) Global mapping of H3K4me1 and H3K4me3 reveals the chromatin state-based cell type-specific gene regulation in human Treg cells. PLoS One 6:e27770PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Lim EJ, Lu TX, Blanchard C, Rothenberg ME (2011) Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation. J Biol Chem 286:13193–13204PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Zhang X, Cheng E, Huo X et al (2012) Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PLoS One 7:e50037PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Lim E, Rothenberg ME (2014) Demethylation of the human eotaxin-3 gene promoter leads to the elevated expression of eotaxin-3. J Immunol 192:466–474PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Lu TX, Rothenberg ME (2013) Diagnostic, functional, and therapeutic roles of microRNA in allergic diseases. J Allergy Clin Immunol 132:3–13PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    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 109:1503–1512PubMedCrossRefGoogle Scholar
  82. 82.
    Kagalwalla AF, Sentongo TA, Ritz S et al (2006) Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol 4:1097–1102PubMedCrossRefGoogle Scholar
  83. 83.
    Gonsalves N (2007) Food allergies and eosinophilic gastrointestinal illness. Gastroenterol Clin North Am 36(75–91):viGoogle Scholar
  84. 84.
    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 53:145–149PubMedCrossRefGoogle Scholar
  85. 85.
    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 41:451–453PubMedCrossRefGoogle Scholar
  86. 86.
    Sugnanam KK, Collins JT, Smith PK et al (2007) Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis. Allergy 62:1257–1260PubMedCrossRefGoogle Scholar
  87. 87.
    Rocha R, Vitor AB, Trindade E et al (2011) Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Euro J Pediatr 170:1471–1474CrossRefGoogle Scholar
  88. 88.
    Maggadottir SM, Hill DA, Ruymann K (2014) Resolution of acute IgE-mediated allergy with development of eosinophilic esophagitis triggered by the same food. J Allergy Clin Immunol 133:1487–1489, 1489 e1481PubMedCrossRefGoogle Scholar
  89. 89.
    Ridolo E, De Angelis GL, Dall’aglio P (2011) Eosinophilic esophagitis after specific oral tolerance induction for egg protein. Ann Allergy Asthma Immunol 106:73–74PubMedCrossRefGoogle Scholar
  90. 90.
    Liacouras CA, Furuta GT, Hirano I et al (2011) Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 128(3–20):e26, quiz 21–22Google Scholar
  91. 91.
    Rothenberg ME, Aceves S, Bonis PA et al (2012) Working with the US Food and Drug Administration: progress and timelines in understanding and treating patients with eosinophilic esophagitis. J Allergy Clin Immunol 130:617–619PubMedCrossRefGoogle Scholar
  92. 92.
    Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I (2012) Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology 142:1451–1459, e1451; quiz e1414-1455PubMedCrossRefGoogle Scholar
  93. 93.
    Liacouras CA, Spergel JM, Ruchelli E et al (2005) Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 3:1198–1206PubMedCrossRefGoogle Scholar
  94. 94.
    Konikoff MR, Noel RJ, Blanchard C et al (2006) A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology 131:1381–1391PubMedCrossRefGoogle Scholar
  95. 95.
    Noel RJ, Putnam PE, Collins MH et al (2004) Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol 2:568–575PubMedCrossRefGoogle Scholar
  96. 96.
    Teitelbaum JE, Fox VL, Twarog FJ et al (2002) Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology 122:1216–1225PubMedCrossRefGoogle Scholar
  97. 97.
    Caldwell JM, Blanchard C, Collins MH et al (2010) Glucocorticoid-regulated genes in eosinophilic esophagitis: a role for FKBP51. J Allergy Clin Immunol 125(879–888):e878Google Scholar
  98. 98.
    Aceves SS, Bastian JF, Newbury RO, Dohil R (2007) Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children. Am J Gastroenterol 102:2271–2279, quiz 2280PubMedCrossRefGoogle Scholar
  99. 99.
    Dohil R, Newbury R, Fox L, Bastian J, Aceves S (2010) Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology 139:418–429PubMedCrossRefGoogle Scholar
  100. 100.
    Schaefer ET, Fitzgerald JF, Molleston JP et al (2008) Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol 6:165–173PubMedCrossRefGoogle Scholar
  101. 101.
    Alexander JA, Jung KW, Arora AS et al (2012) Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol 10(742–749):e741Google Scholar
  102. 102.
    Straumann A, Conus S, Degen L (2010) Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology 139:1526–1537, 1537 e1521PubMedCrossRefGoogle Scholar
  103. 103.
    Dellon ES, Sheikh A, Speck O et al (2012) Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis. Gastroenterology 143(321–324):e321CrossRefGoogle Scholar
  104. 104.
    Lucendo AJ, Arias A, De Rezende LC et al (2011) Subepithelial collagen deposition, profibrogenic cytokine gene expression, and changes after prolonged fluticasone propionate treatment in adult eosinophilic esophagitis: a prospective study. J Allergy Clin Immunol 128:1037–1046PubMedCrossRefGoogle Scholar
  105. 105.
    Kelly HW, Sternberg AL, Lescher R et al (2012) Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med 367:904–912PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Turpeinen M, Pelkonen AS, Nikander K et al (2010) Bone mineral density in children treated with daily or periodical inhaled budesonide: the Helsinki Early Intervention Childhood Asthma study. Pediatr Res 68:169–173PubMedCrossRefGoogle Scholar
  107. 107.
    Spergel JM (2007) Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients. Curr Opin Allergy Clin Immunol 7:274–278PubMedCrossRefGoogle Scholar
  108. 108.
    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 109:363–368PubMedCrossRefGoogle Scholar
  109. 109.
    Spergel JM, Brown-Whitehorn T (2005) The use of patch testing in the diagnosis of food allergy. Curr Allerg Asthma Rep 5:86–90CrossRefGoogle Scholar
  110. 110.
    Simon D, Marti H, Heer P, Simon HU, Braathen LR, Straumann A (2005) Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway diseases. J Allergy Clin Immunol 115:1090–1092PubMedCrossRefGoogle Scholar
  111. 111.
    Spergel JM, Brown-Whitehorn T, Beausoleil JL, Shuker M, Liacouras CA (2007) Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol 119:509–511PubMedCrossRefGoogle Scholar
  112. 112.
    Kalach N, Soulaines P, de Boissieu D, Dupont C (2005) A pilot study of the usefulness and safety of a ready-to-use atopy patch test (Diallertest) versus a comparator (Finn Chamber) during cow’s milk allergy in children. J Allergy Clin Immunol 116:1321–1326PubMedCrossRefGoogle Scholar
  113. 113.
    Isolauri E, Turjanmaa K (1996) Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis. J Allergy Clin Immunol 97:9–15PubMedCrossRefGoogle Scholar
  114. 114.
    Kekki OM, Turjanmaa K, Isolauri E (1997) Differences in skin-prick and patch-test reactivity are related to the heterogeneity of atopic eczema in infants. Allergy 52:755–759PubMedCrossRefGoogle Scholar
  115. 115.
    Rance F (2004) What is the optimal occlusion time for the atopy patch test in the diagnosis of food allergies in children with atopic dermatitis? Pediatr Allergy Immunol 15:93–96PubMedCrossRefGoogle Scholar
  116. 116.
    Greenhawt MJ, Aceves S, Spergel JM, Rothenberg ME (2013) The management of eosinophilic esophagitis. J Allergy Clin Immunol: In Practice 1:332–340CrossRefGoogle Scholar
  117. 117.
    Spergel JM, Shuker M (2008) Nutritional management of eosinophilic esophagitis. Gastrointest Endosc Clin N Am 18:179–194, xiPubMedCrossRefGoogle Scholar
  118. 118.
    Hart TK, Cook RM, Zia-Amirhosseini P et al (2001) Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J Allergy Clin Immunol 108:250–257PubMedCrossRefGoogle Scholar
  119. 119.
    Egan RW, Athwal D, Bodmer MW et al (1999) Effect of Sch 55700, a humanized monoclonal antibody to human interleukin-5, on eosinophilic responses and bronchial hyperreactivity. Arzneimittelforschung 49:779–790PubMedGoogle Scholar
  120. 120.
    Conus S, Straumann A, Bettler E, Simon HU (2010) Mepolizumab does not alter levels of eosinophils, T cells, and mast cells in the duodenal mucosa in eosinophilic esophagitis. J Allergy Clin Immunol 126:175–177PubMedCrossRefGoogle Scholar
  121. 121.
    Straumann A, Bussmann C, Conus S, Beglinger C, Simon HU (2008) Anti-TNF-alpha (infliximab) therapy for severe adult eosinophilic esophagitis. J Allergy Clin Immunol 122:425–427PubMedCrossRefGoogle Scholar
  122. 122.
    Rocha R, Vitor AB, Trindade E et al (2011) Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Eur J Pediatr 170:1471–1474PubMedCrossRefGoogle Scholar
  123. 123.
    Straumann A, Hoesli S, Bussmann C et al (2013) Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy 68:375–385PubMedCrossRefGoogle Scholar
  124. 124.
    Nelson HS, Lahr J, Rule R, Bock A, Leung D (1997) Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol 99:744–751PubMedCrossRefGoogle Scholar
  125. 125.
    Nowak-Wegrzyn A, Sampson HA (2011) Future therapies for food allergies. J Allergy Clin Immunol 127:558–573, quiz 574–555PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Jones SM, Pons L, Roberts JL (2009) Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 124:292–300, 300 e291-297PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Buchanan AD, Green TD, Jones SM et al (2007) Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol 119:199–205PubMedCrossRefGoogle Scholar
  128. 128.
    Patriarca G, Nucera E, Pollastrini E et al (2007) Oral specific desensitization in food-allergic children. Dig Dis Sci 52:1662–1672PubMedCrossRefGoogle Scholar
  129. 129.
    Patriarca G, Schiavino D, Nucera E, Schinco G, Milani A, Gasbarrini GB (1998) Food allergy in children: results of a standardized protocol for oral desensitization. Hepatogastroenterology 45:52–58PubMedGoogle Scholar
  130. 130.
    Skripak JM, Nash SD, Rowley H et al (2008) A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol 122:1154–1160PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Hofmann AM, Scurlock AM, Jones SM (2009) Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol 124:286–291, 291 e281-286PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Narisety SD, Skripak JM, Steele P et al (2009) Open-label maintenance after milk oral immunotherapy for IgE-mediated cow’s milk allergy. J Allergy Clin Immunol 124:610–612PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Sanchez-Garcia S, Rodriguez Del Rio P, Escudero C, Martinez-Gomez MJ, Ibanez MD (2012) Possible eosinophilic esophagitis induced by milk oral immunotherapy. J Allergy Clin Immunol 129:1155–1157PubMedCrossRefGoogle Scholar
  134. 134.
    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 35:1423–1431PubMedCrossRefGoogle Scholar
  135. 135.
    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(600–602):e601–e603Google Scholar
  136. 136.
    Ramirez R. M. and Jacobs RL. (2013) Eosinophilic esophagitis treated with immunotherapy to dust mites. J Allergy Clin ImmunolGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Division of Allergy and ImmunologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations