Cellular and molecular immunological mechanisms in eosinophilic esophagitis: an updated overview of their clinical implications

References

• Lucendo AJ, Sanchez-Cazalilla M. Adult versus pediatric eosinophilic esophagitis: important differences and similarities for the clinician to understand. Expert Rev Clin Immunol 2012;8:733-45
   PubMed Web of Science ®Google Scholar
• Straumann A, Aceves SS, Blanchard C, et al. Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy 2012;67:477-90
   PubMed Web of Science ®Google Scholar
• Soon IS, Butzner JD, Kaplan GG, Debruyn JC. Incidence and prevalence of eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr 2013;57:72-80
   PubMed Web of Science ®Google Scholar
• Dellon ES, Jensen ET, Martin CF, et al. The Prevalence of Eosinophilic Esophagitis in the United States. Clin Gastroenterol Hepatol 2014;12(4):589-96. e1
   PubMed Web of Science ®Google Scholar
• Arias A, Lucendo AJ. Prevalence of eosinophilic oesophagitis in adult patients in a central region of Spain. Eur J Gastroenterol Hepatol 2013;25:208-12
   PubMed Web of Science ®Google Scholar
• Hruz P, Straumann A, Bussmann C, et al. Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol 2011;128:1349-50
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, Friginal-Ruiz AB, Rodriguez B. Boerhaave’s syndrome as the primary manifestation of adult eosinophilic esophagitis. Two case reports and a review of the literature. Dis Esophagus 2011;24:E11-15
   PubMed Web of Science ®Google Scholar
• Miller SM, Goldstein JL, Gerson LB. Cost-effectiveness model of endoscopic biopsy for eosinophilic esophagitis in patients with refractory GERD. Am J Gastroenterol 2011;106(8):1439-45
   PubMed Web of Science ®Google Scholar
• Kelly KJ, Lazenby AJ, Rowe PC, et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology 1995;109:1503-12
   PubMed Web of Science ®Google Scholar
• Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011;128:3-20
   PubMed Web of Science ®Google Scholar
• Arias Á, Lucendo AJ. Dietary therapies for eosinophilic esophagitis. Expert Rev Clin Immunol 2014;10:133-42
   PubMed Web of Science ®Google Scholar
• Schoepfer AM. Safroneeva, Bussmann C, et al. Delay in Diagnosis of Eosinophilic Esophagitis Increases Risk for Stricture Formation, in a Time-Dependent Manner. Gastroenterology 2013;145(6):1230-6. e1-2
   PubMed Web of Science ®Google Scholar
• Gonzalez-Castillo S, Arias A, Lucendo AJ. Treatment of eosinophilic esophagitis: how should we manage the disease? J Clin Gastroenterol 2010;44:663-71
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, Arias A, Molina-Infante J, et al. Diagnostic and therapeutic management of eosinophilic oesophagitis in children and adults: results from a Spanish registry of clinical practice. Dig Liver Dis 2013;45:562-8
   PubMedGoogle Scholar
• Svensson-Frej M. Immunobiology of intestinal eosinophils - a dogma in the changing? J Innate Immun 2011;3:565-76
   PubMed Web of Science ®Google Scholar
• Johnsson M, Bove M, Bergquist H, et al. Distinctive blood eosinophilic phenotypes and cytokine patterns in eosinophilic esophagitis, inflammatory bowel disease and airway allergy. J Innate Immun 2011;3:594-604
   PubMed Web of Science ®Google Scholar
• Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol 2004;113:11-28
   PubMed Web of Science ®Google Scholar
• Rothenberg ME. Eosinophilia. N Engl J Med 1998;338:1592-600
   PubMed Web of Science ®Google Scholar
• Gleich GJ, Kita H. Bronchial astma: lessions from murine models. Proc Natt Acad Sci USA 1997;94:2101-2
   PubMed Web of Science ®Google Scholar
• Cieslewicz G, Tomkinson A, Adler A, et al. The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration. J Clin Invest 1999;104:301-8
   PubMed Web of Science ®Google Scholar
• Gharaee-Kermani M, McGarry B, Lukacs N, et al. The role of IL-5 in bleomycin-induced pulmonary fibrosis. J Leukoc Biol 1998;64:657-66
   PubMed Web of Science ®Google Scholar
• 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;169:4604-12
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Mishra A, Hogan SP, Brandt EB, Rothenberg ME. IL-5 promotes eosinophil trafficking to the esophagus. J Immunol 2002;168:2464-9
   PubMed Web of Science ®Google Scholar
• Akei H S, Mishra A, Blanchard C, Rothenberg ME. Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology 2005;129:985-94
   PubMed Web of Science ®Google Scholar
• Yamazaki K, Murray JA, Arora AS, et al. Allergen-specific in vitro cytokine production in adult patients with eosinophilic esophagitis. Dig Dis Sci 2006;51:1934-41
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Spergel JM, Rothenberg ME, Collins MH, 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
   PubMed Web of Science ®Google Scholar
• Assa′ad AH, Gupta SK, Collins MH, et al. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology 2011;141:1593-604
   PubMed Web of Science ®Google Scholar
• Straumann A, Hoesli S, Bussmann C, et al. Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy 2013;68:375-85
   PubMed Web of Science ®Google Scholar
• Montalvillo E, Garrote JA, Bernardo D, Arranz E. Innate lymphoid cells and natural killer T cells in the immune system of the gastrointestinal tract. Rev Esp Enfer Dig 2014; In press
   PubMed Web of Science ®Google Scholar
• Rescigno M. The intestinal epithelial barrier in the control of homeostasis and immunity. Trends Immunol 2011;32:256-64
   PubMed Web of Science ®Google Scholar
• Goto Y, Ivanov II. Intestinal epithelial cells as mediators of the commensal-host immune crosstalk. Immunol Cell Biol 2013;91:204-14
   PubMed Web of Science ®Google Scholar
• Lucendo A J, 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
   PubMed Web of Science ®Google Scholar
• Fillon S, Robinson ZD, Colgan SP, Furuta GT. Epithelial function in EGID. Immunol Allergy Clin N Am 2009;29:171-8
   PubMed Web of Science ®Google Scholar
• Gutierrez Ramos JC, Lloyd C, Gonzalo JA. Eotaxin: from an eosinophilic chemokine to a major regulator of allergic reactions. Immunol Today 1999;20:500-4
   PubMedGoogle Scholar
• Mishra A, Hogan SP, Lee JJ, et al. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest 1999;103:1719-27
   PubMed Web of Science ®Google Scholar
• García-Zepeda EA, Rothenberg ME, Ownbey RT, et al. Human eotaxin is a specific chemoattractant for eosinophils cells and provides a new mechanism to explain tissue eosinophilia. Nat Med 1996;2:449-56
   PubMed Web of Science ®Google Scholar
• Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest 2006;116:536-47
   PubMed Web of Science ®Google Scholar
• Blanchard C, Mingler MK, Vicario M, et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol 2007;120:1292-300
   PubMed Web of Science ®Google Scholar
• Schmid-Grendelmeier P, Altznauer F, Fischer B, et al. Eosinophils express functional IL-13 in eosinophilic inflammatory diseases. J Immunol 2002;169:1021-7
   PubMed Web of Science ®Google Scholar
• Neilsen CV, Bryce PJ. Interleukin-13 directly promotes oesophagus production of CCL11 and CCL24 and the migration of eosinophils. Clin Exp Allergy 2010;40:427-34
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Blanchard C, Stucke EM, Burwinkel K, et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol 2010;184:4033-41
   PubMed Web of Science ®Google Scholar
• Sherrill JD, Kc K, Wu D, et al. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol 2013. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Ravelli AM, Villanacci V, Ruzzenenti N, et al. Dilated intercellular spaces: a major morphological feature of esophagitis. J Pediatr Gastroenterol Nutr 2006;42:510-15
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, Lucendo B. An update on the immunopathogenesis of eosinophilic esophagitis. Expert Rev Gastroenterol Hepatol 2010;4:141-8
   PubMed Web of Science ®Google Scholar
• Jovani M, Fiorino G, Danese S. Anti-IL-13 in inflammatory bowel disease: from the bench to the bedside. Curr Drug Targets 2013;14:1444-52
   PubMed Web of Science ®Google Scholar
• Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011;365:1088-98
   PubMed Web of Science ®Google Scholar
• Noonan M, Korenblat P, Mosesova S, et al. Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids. J Allergy Clin Immunol 2013;132:576-4
   Web of Science ®Google Scholar
• 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;35:1096-103
   PubMed Web of Science ®Google Scholar
• Efficacy and Safety of QAX576 in Patients With Eosinophilic Esophagitis. ClinicalTrial.gov (internet). Available from: http://clinicaltrials.gov/ct2/show/study/NCT01022970?term=%22eosinophilic+esophagitis%22&rank=22 [Last accessed 26 September 2013]
   Google Scholar
• Cuvelier SL, Patel KD. Shear-dependent eosinophil transmigration on interleukin 4-stimulated endothelial cells: a role for endothelium-associated eotaxin-3. J Exp Med 2001;194:1699-709
   PubMed Web of Science ®Google Scholar
• Abonyo BO, Alexander MS, Heiman AS. Autoregulation of CCL26 synthesis and secretion in A549 cells: a possible mechanism by which alveolar epithelial cells modulate airway inflammation. Am J Physiol Lung Cell Mol Physiol 2005;289:L478-88
   PubMed Web of Science ®Google Scholar
• Simon D, Marti H, Heer P, et al. Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway diseases. J Allergy Clin Immunol 2005;115:1090-2
   PubMed Web of Science ®Google Scholar
• Arias A, González-Cervera J, Tenias JM, Lucendo AJ. Efficacy of dietary interventions in inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology 2014. [Epub ahead of print]
   Web of Science ®Google Scholar
• Lucendo AJ, Arias A, Gonzalez-Cervera J, et al. Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease. J Allergy Clin Immunol 2013;131:797-804
   PubMed Web of Science ®Google Scholar
• Almansa C, Krishna M, Buchner AM, et al. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol 2009;104:828-33
   PubMed Web of Science ®Google Scholar
• Moawad FJ, Veerappan GR, Lake JM, et al. Correlation between eosinophilic oesophagitis and aeroallergens. Aliment Pharmacol Ther 2010;31:509-15
   PubMed Web of Science ®Google Scholar
• Garn H, Renz H. Epidemiological and immunological evidence for the hygiene hypothesis. Immunobiology 2007;212:441-52
   PubMed Web of Science ®Google Scholar
• Lexmond WS, Neves JF, Nurko S, et al. Involvement of the iNKT Cell Pathway Is Associated With Early-Onset Eosinophilic Esophagitis and Response to Allergen Avoidance Therapy. Am J Gastroenterol 2014. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Bernardo D. Human intestinal dendritic cells as controllers of mucosal immunity. Rev Esp Enferm Dig 2013;105:279-90
   PubMed Web of Science ®Google Scholar
• Berin MC, Shreffler WG. T(H)2 adjuvants: implications for food allergy. J Allergy Clin Immunol 2008;121:1311-20
   PubMed Web of Science ®Google Scholar
• Blanchard C, Rothenberg ME. Basic pathogenesis of eosinophilic esophagitis. Gastrointest Endosc Clin N Am 2008;18:133-43
   PubMedGoogle Scholar
• Lucendo AJ, De Rezende L, Comas C, et al. Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis. Am J Gastroenterol 2008;103:2184-93
   PubMed Web of Science ®Google Scholar
• Straumann A, Bauer M, Fischer B, et al. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. J Allergy Clin Immunol 2001;108:954-61
   PubMed Web of Science ®Google Scholar
• Bendelac A, Hunziker RD, Lantz O. Increased interleukin 4 and immunoglobulin E production in transgenic mice overexpressing NK1 T cells. J Exp Med 1996;184:1285-93
   PubMed Web of Science ®Google Scholar
• Kim JO, Kim DH, Chang WS, et al. Asthma is induced by intranasal coadministration of allergen and natural killer T-cell ligand in a mouse model. J Allergy Clin Immunol 2004;114:1332-8
   PubMed Web of Science ®Google Scholar
• Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 2012;336:489-93
   PubMed Web of Science ®Google Scholar
• Jensen ET, Kappelman MD, Kim HP, et al. Early life exposures as risk factors forpediatric eosinophilic esophagitis: a pilot and feasibility study. J Pediatr Gastroenterol Nutr 2013;57:67-71
   PubMed Web of Science ®Google Scholar
• Jyonouchi S, Smith CL, Saretta F, et al. Invariant natural killer T cells in children with eosinophilic esophagitis. Clin Exp Allergy 2014;44:58-68
   PubMed Web of Science ®Google Scholar
• Kinjo Y, Wu D, Kim G, et al. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 2005;434:520-5
   PubMed Web of Science ®Google Scholar
• Wieland Brown LC, Penaranda C, Kashyap PC, et al. Production of -galactosylceramide by a prominent member of the human gut microbiota. PLoS Biol 2013;11:e1001610
   PubMed Web of Science ®Google Scholar
• Sampson HA. Update in food allergy. J Allergy Clin Immunol 2004;113:813-19
   Web of Science ®Google Scholar
• Rajavelu P, Rayapudi M, Moffitt M, et al. Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 2012;302:G645-54
   PubMed Web of Science ®Google Scholar
• Aceves SS, Bastian JF, Newbury RO, Dohil R. Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children. Am J Gastroenterol 2007;102:2271-9
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, Molina-Infante J. Emerging therapeutic strategies for eosinophilic esophagitis. Curr Treat Options Gastroenterol 2014;12:1-17
   PubMedGoogle Scholar
• Blanchard C, Mingler MK, Vicario M, et al. IL-13 involvement in eosinophilic esophagitis: trasncriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol 2007;120:1292-300
   PubMed Web of Science ®Google Scholar
• Caldwell JM, Blanchard C, Collins MH, et al. Glucocorticoid-regulated genes in eosinophilic esophagitis: a role for FKBP51. J Allergy Clin Immunol 2010;125:879-88
   PubMed Web of Science ®Google Scholar
• Allergy immunotherapy in the management ofEosinophilic esophagitis (AIMEE). Available from http://clinicaltrials.gov/ct2/show/NCT01685034?term=allergy+immunotherapy+and+eosinophilic+esophagitis&rank=1 [Last accessed 25 September 2013]
   Google Scholar
• Krishnaswamy G, Ajitawi O, Chi DS. The human mast cell: an overview. Methods Mol Biol 2006;315:13-34
   PubMedGoogle Scholar
• Kirsch R, Bokhary R, Marcon M A, Cutz E. Activated mucosal mast cells differentiate eosinophilic (allergic) esophagitis from gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr 2007;44:20-6
   PubMed Web of Science ®Google Scholar
• Lucendo A J, Bellon T, Lucendo B. The role of mast cells in eosinophilic esophagitis. Pediatr Allergy Immunol 2009;20:512-18
   PubMed Web of Science ®Google Scholar
• Hsu Blatman KS, Gonsalves N, Hirano I, Bryce PJ. Expression of mast cell-associated genes is upregulated in adult eosinophilic esophagitis and responds to steroid or dietary therapy. J Allergy Clin Immunol 2011;127:1307-8
   PubMed Web of Science ®Google Scholar
• Aceves SS, Chen D, Newbury RO, et al. Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-beta1, and increase esophageal smooth muscle contraction. J Allergy Clin Immunol 2010;126:1198-204
   PubMed Web of Science ®Google Scholar
• Otani I M, Anilkumar AA, Newbury RO, et al. Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol 2013;131:1576-82
   PubMed Web of Science ®Google Scholar
• Abonia JP, Blanchard C, Butz BB, et al. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol 2010;126:140-9
   PubMed Web of Science ®Google Scholar
• Niranjan R, Mavi P, Rayapudi M, et al. Pathogenic role of mast cells in experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 2013;304:G1087-94
   PubMed Web of Science ®Google Scholar
• Holgate ST. The role of mast cells and basophils in inflammation. Clin Exp Allergy 2000;30(Suppl 1):28-32
   PubMed Web of Science ®Google Scholar
• Mulder DJ, Justinich CJ. B cells, IgE and mechanisms of type I hypersensitivity in eosinophilic oesophagitis. Gut 2010;59:6-7
   PubMed Web of Science ®Google Scholar
• Vicario M, Blanchard C, Stringer KF, et al. Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis. Gut 2010;59:12-20
   PubMed Web of Science ®Google Scholar
• Gonsalves N, Yang GY, Doerfler B, et al. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology 2012;142:1451-9
   PubMed Web of Science ®Google Scholar
• Molina-Infante J, Martin-Noguerol E, Varado-Arenas M, et al. Selective elimination diet based on skin testing has suboptimal efficacy for adult eosinophilic esophagitis. J Allergy Clin Immunol 2012;130:1200-2
   PubMed Web of Science ®Google Scholar
• Ryan JJ, Huff TF. Biology of mast cells. In: Middletown's allergy, principles and practice. Mosby; Philadelphia, PA, USA: 2003. p. 333-46
   Google Scholar
• Schwartz LB. Mast cells and basophils. Clin Allergy Immunol 2002;16:3-42
   PubMedGoogle Scholar
• Austen KF, Boyce JA. Mast cell lineage development and phenotypic regulation. Leuk Res 2001;25:511-18
   PubMed Web of Science ®Google Scholar
• Barclay RL, Dinda PK, Morris GP, Paterson WG. Morphological evidence of mast cell degranulation in an animal model of acid-induced esophageal mucosal injury. Dig Dis Sci 1995;40:1651-8
   PubMed Web of Science ®Google Scholar
• Feldman MJ, Morris GP, Dinda PK, Paterson WG. Mast cells mediate acid-induced augmentation of opossum esophageal blood flow via histamine and nitric oxide. Gastroenterology 1996;110:121-8
   PubMed Web of Science ®Google Scholar
• Quist RG, Ton-Nu HT, Lillienau J, et al. Activation of mast cells by bile acids. Gastroenterology 1991;101:446-56
   PubMed Web of Science ®Google Scholar
• Pérez-Millán A, Martín-Lorente JL, López-Morante A, et al. Subserosal eosinophilic gastroenteritis treated efficaciously with sodium cromoglicate. Dig Dis Sci 1997;42:342-4
   PubMed Web of Science ®Google Scholar
• Suzuki J, Kawasaki Y, Nozawa R, et al. Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy. Asian Pac J Allergy Immunol 2003;21:193-7
   PubMed Web of Science ®Google Scholar
• Van Dellen RG, Lewis JC. Oral administration of cromolyn in a patient with protein-losing enteropathy, food allergy, and eosinophilic gastroenteritis. Mayo Clin Proc 1994;69:441-4
   PubMed Web of Science ®Google Scholar
• Moots RJ, Prouse P, Gumpel JM. Near fatal eosinophilic gastroenteritis responding to oral sodium chromoglycate. Gut 1988;29:1282-5
   PubMed Web of Science ®Google Scholar
• Di Gioacchino M, Pizzicannella G, Fini N, et al. Sodium cromoglycate in the treatment of eosinophilic gastroenteritis. Allergy 1990;45:161-6
   PubMed Web of Science ®Google Scholar
• Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005;3:1198-206
   PubMed Web of Science ®Google Scholar
• Fang JC, Hilden K, Gleich GJ, et al. A pilot study of the treatment of eosinophilic esophagitis with omalizumab. Gastroenterology 2011;5:140
   Google Scholar
• Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med 2004;351:940-1
   PubMed Web of Science ®Google Scholar
• 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;6:621-9
   PubMed Web of Science ®Google Scholar
• Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol 2006;118:1054-9
   PubMed Web of Science ®Google Scholar
• Holvoet S, Blanchard C. Genetic and molecular mechanisms leading to eosinophilic esophagitis. Rev Esp Enferm Dig 2014; In press
   PubMed Web of Science ®Google Scholar
• Ober C. Perspectives on the past decade of asthma genetics. J Allergy Clin Immunol 2005;116:274-8
   PubMed Web of Science ®Google Scholar
• Spergel JM. New genetic links in eosinophilic esophagitis. Genome Med 2010;2:60
   PubMed Web of Science ®Google Scholar
• Lu TX, Sherrill JD, Wen T, et al. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol 2012;129:1064-75
   PubMed Web of Science ®Google Scholar
• Franciosi JP, Tam V, Liacouras CA, Spergel JM. A case-control study of sociodemographic and geographic characteristics of 335 children with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2009;7:415-19
   PubMed Web of Science ®Google Scholar
• Sherrill J D, Gao PS, Stucke EM, et al. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol 2010;126:160-5
   PubMed Web of Science ®Google Scholar
• Rothenberg ME, Spergel JM, Sherrill JD, et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet 2010;42:289-91
   PubMed Web of Science ®Google Scholar
• Liu YJ. TSLP in epithelial cell and dendritic cell cross talk. Adv Immunol 2009;101:1-25
   PubMed Web of Science ®Google Scholar
• Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001;413:732-8
   PubMed Web of Science ®Google Scholar
• Wen T, Stucke EM, Grotjan TM, et al. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology 2013;145:1289-99
   PubMed Web of Science ®Google Scholar
• Rodríguez-Sánchez J, Gómez Torrijos E, de la Santa Belda E, et al. Serological markers of activity in eosinophilic esophagitis. Is this possible? Rev Esp Enferm Dig 2013;105:462-88
   PubMed Web of Science ®Google Scholar
• Landres RT, Kuster GG, Strum WB. Eosinophilic esophagitis in a patient with vigorous achalasia. Gastroenterology 1978;74:1298-301
   PubMed Web of Science ®Google Scholar
• Picus D, Frank PH. Eosinophilic esophagitis. AJR Am J Roentgenol 1981;136:1001-3
   PubMed Web of Science ®Google Scholar
• Winter HS, Madara JL, Stafford RJ, et al. Intraepitelial eosinophils: a new diagnostic criterion for reflux esophagitis. Gastroenterology 1982;83:818-23
   PubMed Web of Science ®Google Scholar
• Brown LF, Goldman H, Antonioli DA. Intraepitelial eosinophils in endoscopic biopsies of adults with reflux esophagitis. Am J Surg Pathol 1984;8:899-905
   PubMed Web of Science ®Google Scholar
• Lee RG. Marked eosinophilia in esophageal mucosal biopsies. Am J Surg Pathol 1985;9:475-9
   PubMed Web of Science ®Google Scholar
• Feczko PJ, Halpert RD, Zonca M. Radiographic abnormalities in eosinophilic esophagitis. Gastrointest Radiol 1985;10:321-4
   PubMedGoogle Scholar
• Vitellas KM, Bennet WF, Bova JG, et al. Idiopathic eosinophilic esophagitis. Radiology 1993;186:789-93
   PubMed Web of Science ®Google Scholar
• Attwood SE, Smyrk TC, Demeester TR, Jones JB. Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 1993;38:109-16
   PubMed Web of Science ®Google Scholar
• Straumann A, Spichtin H P, Bernoulli R, et al. Idiopathic eosinophilic esophagitis: a frequently overlooked disease with typical clinical aspects and discrete endoscopic findings. Schweiz Med Wochenschr 1994;124:1419-29
   PubMedGoogle Scholar
• 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;9:110-17
   PubMed Web of Science ®Google Scholar
• Molina-Infante J, Katzka DA, Gisbert JP. Review article: proton pump inhibitor therapy for suspected eosinophilic oesophagitis. Aliment Pharmacol Ther 2013;37:1157-64
   PubMed Web of Science ®Google Scholar
• 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;62:824-32
   PubMed Web of Science ®Google Scholar
• Zhang X, Cheng E, Huo X, et al. Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PLoS ONE 2012;7:e50037
   PubMed Web of Science ®Google Scholar
• 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;108:1854-60
   PubMed Web of Science ®Google Scholar
• Molina-Infante J, Rivas MD, Vinagre Rodrígez G, et al. Remission in proton pump inhibitors-responsive esophageal eosinophilia correlates with downregulation of eotaxin-3 and TH2 cytokines, similarly to eosinophilic esophagitis after steroids. Gastroenterology 2013;144(Suppl 1):S-484
   Google Scholar
• Peterson KA, Thomas KL, Hilden K, et al. Comparison of esomeprazole to aerosolized, swallowed fluticasone for eosinophilic esophagitis. Dig Dis Sci 2010;55:1313-19
   PubMed Web of Science ®Google Scholar
• Moawad FJ, Veerappan GR, Dias JA, et al. Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia. Am J Gastroenterol 2013;108:366-72
   PubMed Web of Science ®Google Scholar
• 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;57:1413-19
   PubMed Web of Science ®Google Scholar
• Sobrino-Cossío S, López-Alvarenga JC, Remes-Troche JM, et al. Proton pump inhibitors in gastroesophageal reflux disease: “a custom-tailored therapeutic regimen”. Rev Esp Enferm Dig 2012;104:367-78
   PubMed Web of Science ®Google Scholar
• Aceves SS, Ackerman SJ. Relationships between eosinophilic inflammation, tissue remodeling, and fibrosis in eosinophilic esophagitis. Immunol Allergy Clin North Am 2009;29:197-xiv
   PubMed Web of Science ®Google Scholar
• Aceves SS, Broide DH. Airway fibrosis and angiogenesis due to eosinophil trafficking in chronic asthma. Curr Mol Med 2008;8:350-8
   PubMed Web of Science ®Google Scholar
• Dellon ES, Kim HP, Sperry SL, et al. A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc 2014;79(4):577-585.e4
   PubMed Web of Science ®Google Scholar
• Fontillon M, Lucendo AJ. Transmural eosinophilic infiltration and fibrosis in a patient with non-traumatic Boerhaave’s syndrome due to eosinophilic esophagitis. Am J Gastroenterol 2012;107:1762
   PubMed Web of Science ®Google Scholar
• Siafakas CG, Ryan CK, Brown MR, Miller TL. Multiple esophageal rings: an association with eosinophilic esophagitis: case report and review of the literature. Am J Gastroenterol 2000;95:1572-5
   PubMed Web of Science ®Google Scholar
• Chehade M, Sampson HA, Morotti RA, Magid MS. Esophageal subepithelial fibrosis in children with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2007;45:319-28
   PubMed Web of Science ®Google Scholar
• Aceves SS, Newbury RO, Dohil R, et al. Esophageal remodeling in pediatric eosinophilic esophagitis. J Allergy Clin Immunol 2007;119:206-12
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, Arias A, De Rezende LC, et al. 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 2011;128:1037-46
   PubMed Web of Science ®Google Scholar
• Straumann A, Conus S, Degen L, et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology 2010;139:1526-37
   PubMed Web of Science ®Google Scholar
• Schoepfer AM, Safroneeva E, Bussmann C, et al. Delay in diagnosis. of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 2013;145:1230-6
   PubMed Web of Science ®Google Scholar
• Mishra A, Wang M, Pemmaraju VR, et al. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology 2008;134:204-14
   PubMed Web of Science ®Google Scholar
• Rieder F, Nonevski I, Ma J, et al. T-helper 2 cytokines, transforming growth factor 1, and Eosinophil products induce fibrogenesis and alter muscle motility in patients with Eosinophilic esophagitis. Gastroenterology 2014. [Epub ahead of print]
   PubMedGoogle Scholar
• Persad R, Huynh HQ, Hao L, et al. Angiogenic remodeling in pediatric EoE is associated with increased levels of VEGF-A, angiogenin, IL-8, and activation of the TNF-alpha-NFkappaB pathway. J Pediatr Gastroenterol Nutr 2012;55:251-60
   PubMed Web of Science ®Google Scholar
• Mulder DJ, Pacheco I, Hurlbut DJ, et al. FGF9-induced proliferative response to eosinophilic inflammation in oesophagitis. Gut 2009;58:166-73
   PubMed Web of Science ®Google Scholar
• Cheng E, Souza RF, Spechler SJ. Tissue remodeling in eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 2012;303:G1175-87
   PubMed Web of Science ®Google Scholar
• Kagalwalla AF, Akhtar N, Woodruff SA, et al. Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment. J Allergy Clin Immunol 2012;129:1387-96
   PubMed Web of Science ®Google Scholar
• Roman S, Hirano I, Kwiatek M A, et al. Manometric features of eosinophilic esophagitis in esophageal pressure topography. Neurogastroenterol Motil 2011;23:208-14
   PubMed Web of Science ®Google Scholar
• Hoeck J, Woisetschlager M. Activation of eotaxin-3/CCLl26 gene expression in human dermal fibroblasts is mediated by STAT6. J Immunol 2001;167:3216-22
   PubMed Web of Science ®Google Scholar
• Hoeck J, Woisetschlager M. STAT6 mediates eotaxin-1 expression in IL-4 or TNF-alpha-induced fibroblasts. J Immunol 2001;166:4507-15
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, Castillo P, Martín-Chávarri S, et al. Manometric findings in adult eosinophilic oesophagitis: a study of 12 cases. Eur J Gastroenterol Hepatol 2007;19:417-24
   PubMed Web of Science ®Google Scholar
• Fox VL, Nurko S, Teitelbaum JE, et al. High-resolution EUS in children with eosinophilic “allergic” esophagitis. Gastrointest Endosc 2003;57:30-6
   PubMed Web of Science ®Google Scholar
• Nurko S, Fox V, Fortunato C, et al. Esophageal motor abnormalities in patients with allergic esophagitis. a study with prolonged esophageal ph/manometry (abstract). J Pediatr Gastroenterol Nutr 2001;33:417-18
   Google Scholar
• Lucendo AJ. Motor disturbances participate in the pathogenesis of eosinophilic oesophagitis, beyond the fibrous remodelling of the oesophagus. Aliment Pharmacol Ther 2006;24:1264-7
   PubMed Web of Science ®Google Scholar
• Martin-Munoz MF, Lucendo AJ, Navarro M, et al. Food allergies and eosinophilic esophagitis--two case studies. Digestion 2006;74:49-54
   PubMed Web of Science ®Google Scholar
• Monnerat MM, Lemme EM. Eosinophilic esophagitis: manometric and pHmetric findings. Arq Gastroenterol 2012;49:113-17
   PubMedGoogle Scholar
• Nicodeme F, Hirano I, Chen J, et al. Esophageal Distensibility as a Measure of Disease Severity in Patients With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2013;11:1101-7
   PubMed Web of Science ®Google Scholar
• Aceves SS, Newbury RO, Chen D, et al. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy 2010;65:109-16
   PubMed Web of Science ®Google Scholar
• Lieberman JA, Morotti RA, Konstantinou GN, et al. Dietary therapy can reverse esophageal subepithelial fibrosis in patients with eosinophilic esophagitis: a historical cohort. Allergy 2012;67:1299-307
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, Jiménez-Contreras S. Endoscopic aspects of eosinophilic esophagitis: from diagnosis to therapy. In: Pascu O, editor. Gastrointestinal endoscopy. In Tech; Rijeka, Croatia: 2011. p. 63-78
   Google Scholar
• Ally MR, Dias J, Veerappan GR, et al. Safety of dilation in adults with eosinophilic esophagitis. Dis Esophagus 2013;26:241-5
   PubMed Web of Science ®Google Scholar
• Lucendo AJ, De Rezende L. Endoscopic dilation in eosinophilic esophagitis: a treatment strategy associated with a high risk of perforation. Endoscopy 2007;39:376
   PubMed Web of Science ®Google Scholar
• Schoepfer AM, Gonsalves N, Bussmann C, et al. Esophageal dilation in eosinophilic esophagitis: effectiveness, safety, and impact on the underlying inflammation. Am J Gastroenterol 2010;105:1062-70
   PubMed Web of Science ®Google Scholar
• Dellon ES, Gibbs WB, Rubinas TC, et al. Esophageal dilation in eosinophilic esophagitis: safety and predictors of clinical response and complications. Gastrointest Endosc 2010;71:706-12
   PubMed Web of Science ®Google Scholar
• Ally MR, Dias J, Veerappan GR, et al. Safety of dilation in adults with eosinophilic esophagitis. Dis Esophagus 2013;26:241-5
   PubMed Web of Science ®Google Scholar
• Cohen MS, Kaufman AB, Palazzo JP, et al. An audit of endoscopic complications in adult eosinophilic esophagitis. Clin Gastroenterol Hepatol 2007;5:1149-53
   PubMed Web of Science ®Google Scholar
• Testing effectiveness of losartan in patients with EoE with or without a CTD. ClinicalTrials.gov (internet). http://clinicaltrials.gov/ct2/show/record/NCT01808196?term=%22eosinophilic+esophagitis%22&rank=39 [Last accessed 26 September 2013]
   Google Scholar
• Sanchez-Garcia S, Rodriguez Del Rio P, Escudero C, et al. Possible eosinophilic esophagitis induced by milk oral immunotherapy. J Allergy Clin Immunol 2012;129:1155-7
   PubMed Web of Science ®Google Scholar
• Ridolo E, De Angelis GL, Dall’aglio P. Eosinophilic esophagitis after specific oral tolerance induction for egg protein. Ann Allergy Asthma Immunol 2011;106:73-4
   PubMed Web of Science ®Google Scholar
• Miehlke S, Alpan O, Schröder S, Straumann A. Induction of eosinophilic esophagitis by sublingual pollen immunotherapy. Case Rep Gastroenterol 2013;7:363-8
   PubMedGoogle Scholar
• Gupta SK, Fitzgerald JF, Roudratynk 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
   PubMed Web of Science ®Google Scholar
• Straumann A, Bussmann C, Conus S, et al. Anti-TNF-alpha (infliximab) therapy for severe adult eosinophilic esophagitis. Gastroenterology 2008;122:425-7
   Google Scholar
• Furuta GT, Kagalwalla AF, Lee JJ, et al. The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut 2013;62:1395-405
   PubMed Web of Science ®Google Scholar
• Al-Hassi HO, Mann ER, Sanchez B, et al. Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp. Mol Nutr Food Res 2013. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar