Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Gastroenterology Reports
Published in: Current Gastroenterology Reports 9/2015

01-09-2015 | Esophagus (JO Clarke, Section Editor)

Do We Know What Causes Eosinophilic Esophagitis? A Mechanistic Update

Authors: Thomas M. Runge, Evan S. Dellon

Published in: Current Gastroenterology Reports | Issue 9/2015

Login to get access

Abstract

The mechanisms underlying eosinophilic esophagitis (EoE) have been intensely investigated, and significant advances have been made in understanding the pathogenesis of EoE. EoE is defined as a chronic immune/antigen-mediated disease, characterized clinically by symptoms of esophageal dysfunction and histologically by an esophageal eosinophilic infiltrate. In this paper, we will review the current knowledge of EoE pathophysiology based on both animal and human data and discuss possible etiologic mechanisms from the genetic and environmental perspectives. EoE is a Th2-predominant inflammatory process triggered by allergens. Proinflammatory cytokines and chemokines recruit eosinophils and other effector cells, such as mast cells, into the esophageal epithelium, where they cause direct damage and promote esophageal remodeling. The genetic expression profile of EoE has been described, and several single nucleotide polymorphisms have been identified and associated with EoE. While this genetic contribution is important, it is difficult to postulate that EoE is primarily a genetic disease. Given the rapid epidemiologic changes in the incidence and prevalence of EoE over the past two decades, environmental factors may be the driving force. While it is not known what causes EoE in an individual patient at a specific time, the current hypothesis is that there is a complex interaction between genetic factors and environmental exposures that remains to be elucidated.
Literature
1.
Liacouras CA. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128(1):3–20. e6.PubMedCrossRef
2.
Furuta GT et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment: sponsored by the American Gastroenterological Association (AGA) Institute and North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Gastroenterology. 2007;133(4):1342–63.PubMedCrossRef
3.•
Dellon ES. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013;108(5):679–92. The most recent updated clinical guidelines for diagnosis and management of esophageal eosinophilia and EoE.PubMedCrossRef
4.
5.
Collins MH et al. Clinical, pathologic, and molecular characterization of familial eosinophilic esophagitis compared with sporadic cases. Clin Gastroenterol Hepatol. 2008;6(6):621–9.PubMedPubMedCentralCrossRef
6.
Hurrell JM, Genta RM, Melton SD. Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract. Adv Anat Pathol. 2011;18(5):335–48.PubMedCrossRef
7.
Aceves SS. Eosinophilic esophagitis. Immunol Allergy Clin N Am. 2015;35:145–59.CrossRef
8.
Spergel JM et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr. 2009;48(1):30–6.PubMedCrossRef
9.
Kapel RC et al. Eosinophilic esophagitis: a prevalent disease in the United States that affects all age groups. Gastroenterology. 2008;134(5):1316–21.PubMedCrossRef
10.
Dellon ES et al. Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review. Am J Gastroenterol. 2007;102(10):2300–13.PubMedCrossRef
11.
Dellon ES et al. Clinical, endoscopic, and histologic findings distinguish eosinophilic esophagitis from gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2009;7(12):1305–13.PubMedPubMedCentralCrossRef
12.
Prasad GA et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County. Minnesota Clin Gastroenterol Hepatol. 2009;7(10):1055–61.PubMedCrossRef
13.
14.
Mackenzie S et al. Eosinophilic oesophagitis in patients presenting with dysphagia—a prospective analysis. Aliment Pharmacol Ther. 2008;28(9):1140–6.PubMedCrossRef
15.
Veerappan GR et al. Prevalence of eosinophilic esophagitis in an adult population undergoing upper endoscopy: a prospective study. Clin Gastroenterol Hepatol. 2009;7(4):420–6. e2.PubMedCrossRef
16.
Franciosi JP et al. A case-control study of sociodemographic and geographic characteristics of 335 children with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2009;7(4):415–9.PubMedCrossRef
17.
18.
Dellon ES. Epidemiology of eosinophilic esophagitis. Gastroenterol Clin N Am. 2014;43(2):201–18.CrossRef
19.
20.
Hruz P et al. Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol. 2011;128(6):1349–50. e5.PubMedCrossRef
21.
Syed A et al. The rising incidence of eosinophilic oesophagitis is associated with increasing biopsy rates: a population‐based study. Aliment Pharmacol Ther. 2012;36(10):950–8.PubMedCrossRef
22.
Prasad GA et al. Prevalence and predictive factors of eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. Am J Gastroenterol. 2007;102(12):2627–32.PubMedCrossRef
23.
Ricker J. et al. Routine screening for eosinophilic esophagitis in patients presenting with dysphagia. Therapeutic Adv Gastroenterol, 2010: p. 1756283X10384172.
24.
Dellon E.S., 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.
25.
Desai TK et al. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc. 2005;61(7):795–801.PubMedCrossRef
26.
Hurtado CW, Furuta GT, Kramer RE. Etiology of esophageal food impactions in children. J Pediatr Gastroenterol Nutr. 2011;52(1):43–6.PubMedCrossRef
27.
Kerlin P et al. Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus. J Clin Gastroenterol. 2007;41(4):356–61.PubMedCrossRef
28.
Sperry SL et al. Esophageal foreign-body impactions: epidemiology, time trends, and the impact of the increasing prevalence of eosinophilic esophagitis. Gastrointest Endosc. 2011;74(5):985–91.PubMedPubMedCentralCrossRef
29.
30.
Dellon ES et al. S1972 increasing incidence of eosinophilic esophagitis: a persistent trend after accounting for procedure indication and biopsy rate. Gastroenterology. 2008;134(4):A-289.
31.
Dellon E, Erichsen R, Baron J. The increasing incidence and prevalence of eosinophilic esophagitis outpaces changes in endoscopic and biopsy practice: National population-based estimates from Denmark (abstr Mo1829). Gastroenterology. 2014;146 suppl 1:665.
32.
33.
Straumann A et al. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. J Allergy Clin Immunol. 2001;108(6):954–61.PubMedCrossRef
34.
35.
Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology. 2003;125(5):1419–27.PubMedCrossRef
36.
Akei HS et al. Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology. 2005;129(3):985–94.PubMedCrossRef
37.
38.
Mishra A et al. Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2007;81(4):916–24.PubMedCrossRef
39.
Mishra A et al. IL-5 promotes eosinophil trafficking to the esophagus. J Immunol. 2002;168(5):2464–9.PubMedCrossRef
40.•
Masterson JC et al. Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. Gut. 2014;63(1):43–53. This paper describes development and features of a novel murine model of EoE. PubMedCrossRef
41.
Rayapudi M et al. Invariant natural killer T cell neutralization is a possible novel therapy for human eosinophilic esophagitis. Clin Translat Immunol. 2014;3(1):e9.CrossRef
42.••
Noti M et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med. 2013;19(8):1005–13. An important invesigation of potential mechanisms of TSLP involvement in EoE pathogenesis, and one of the first reports about the possible role of basophil responses in EoE. PubMedPubMedCentralCrossRef
43.
Straumann A, Simon H-U. Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol. 2005;115(2):418–9.PubMedCrossRef
44.
Jyonouchi S, Brown-Whitehorn TA, Spergel JM. Association of eosinophilic gastrointestinal disorders with other atopic disorders. Immunol Allergy Clin N Am. 2009;29(1):85–97.CrossRef
45.
Assa’ad AH et al. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol. 2007;119(3):731–8.PubMedCrossRef
46.
Simon D et al. Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway diseases. J Allergy Clin Immunol. 2005;115(5):1090–2.PubMedCrossRef
47.
Assa’ad A. Eosinophilic esophagitis: association with allergic disorders. Gastrointest Endosc Clin N Am. 2008;18(1):119–32.PubMedCrossRef
48.
Penfield JD et al. The role of allergy evaluation in adults with eosinophilic esophagitis. J Clin Gastroenterol. 2010;44(1):22–7.PubMedCrossRef
49.
Roy–Ghanta S, Larosa DF, Katzka DA. Atopic characteristics of adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2008;6(5):531–5.PubMedCrossRef
50.
Rhijn B et al. Birch pollen sensitization with cross‐reactivity to food allergens predominates in adults with eosinophilic esophagitis. Allergy. 2013;68(11):1475–81.PubMedCrossRef
51.
Spergel JM et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann AllerG, Asthma Immunol. 2005;95(4):336–43.CrossRef
52.
Spergel JM. Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients. Curr Opin Allergy Clin Immunol. 2007;7(3):274–8.PubMedCrossRef
53.
Kelly KJ et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology. 1995;109(5):1503–12.PubMedCrossRef
54.
Markowitz JE et al. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003;98(4):777–82.PubMedCrossRef
55.
Kagalwalla AF et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006;4(9):1097–102.PubMedCrossRef
56.
Liacouras CA et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005;3(12):1198–206.PubMedCrossRef
57.
Peterson KA et al. Elemental diet induces histologic response in adult eosinophilic esophagitis. Am J Gastroenterol. 2013;108(5):759–66.PubMedCrossRef
58.
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 Allerg, Asthma Immunol. 2005;95(4):309–11.CrossRef
59.
Henderson CJ et al. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012;129(6):1570–8.PubMedPubMedCentralCrossRef
60.
Wolf W.A., et al. Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis. Clini Gastroenterol Hepatol 2014.
61.••
Arias Á et al. Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology. 2014;146(7):1639–48. A comprehensive meta-analysis of dietary elimination therapy in EoE, highlighting that the repsonse to removal of food triggers supports the allergic hypothesis of EoE etiology. PubMedCrossRef
62.
Gonsalves N et al. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142(7):1451–9. e1.PubMedCrossRef
63.
Lucendo AJ 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(3):797–804.PubMedCrossRef
64.
Molina-Infante J et al. Selective elimination diet based on skin testing has suboptimal efficacy for adult eosinophilic esophagitis. J Allergy Clin Immunol. 2012;130(5):1200–2.PubMedCrossRef
65.
Wolf WA, Jerath MR, Dellon ES. De-novo onset of eosinophilic esophagitis after large volume allergen exposures. J Gastrointestin Liver Dis: JGLD. 2013;22(2):205.PubMedPubMedCentral
66.
Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. J Allergy Clin Immunol. 2003;112(4):796–7.PubMedCrossRef
67.
Moawad F et al. Correlation between eosinophilic oesophagitis and aeroallergens. Aliment Pharmacol Ther. 2010;31(4):509–15.PubMedCrossRef
68.
Almansa C et al. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol. 2009;104(4):828–33.PubMedCrossRef
69.
Wang FY, Gupta SK, Fitzgerald JF. Is there a seasonal variation in the incidence or intensity of allergic eosinophilic esophagitis in newly diagnosed children? J Clin Gastroenterol. 2007;41(5):451–3.PubMedCrossRef
70.
Simon D et al. Frequent sensitization to Candida albicans and profilins in adult eosinophilic esophagitis. Allergy. 2013;68(7):945–8.PubMedCrossRef
71.
Uzzaman A. and S.H. Cho. Classification of hypersensitivity reactions. In allergy and asthma proceedings. 2012. OceanSide Publications, Inc.
72.
Bryce PJ et al. Immune sensitization in the skin is enhanced by antigen-independent effects of IgE. Immunity. 2004;20(4):381–92.PubMedCrossRef
73.
Rocha R et al. Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Eur J Pediatr. 2011;170(11):1471–4.PubMedCrossRef
74.••
Clayton F., et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology, 2014. 146(7). This study not only presents the results of a randomized trial of an anti-IgE antibody, but investigates why this medication did not work and identified for the first time the potential role of IgG4 in the pathogenesis of EoE.
75.
Chetty R, Gatter K. CD3: structure, function, and role of immunostaining in clinical practice. J Pathol. 1994;173(4):303–7.PubMedCrossRef
76.
Grunow R et al. Masking of pan-T-cell markers in patients with autoimmune diseases. Dermatologische Monatschrift. 1986;173(7):390–9.
77.
Syrbe U., J. Siveke and A. Hamann. Th1/Th2 subsets: distinct differences in homing and chemokine receptor expression? in Springer seminars in immunopathology. 1999. Springer.
78.
Zhang Z, Sferra TJ, Eroglu Y. T cell co-stimulatory molecules: a co-conspirator in the pathogenesis of eosinophilic esophagitis? Dig Dis Sci. 2013;58(6):1497–506.PubMedCrossRef
79.
Straumann A et al. Cytokine expression in healthy and inflamed mucosa: probing the role of eosinophils in the digestive tract. Inflamm Bowel Dis. 2005;11(8):720–6.PubMedCrossRef
80.
Blanchard C et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007;120(6):1292–300.PubMedCrossRef
81.
Blanchard C et al. A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol. 2011;127(1):208–17. e7.PubMedPubMedCentralCrossRef
82.
Lucendo AJ 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(4):598–606.PubMedCrossRef
83.
Blanchard C et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010;184(7):4033–41.PubMedCrossRef
84.
Sherrill J et al. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol. 2014;7(3):718–29.PubMedPubMedCentralCrossRef
85.
Blanchard C et al. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses. Mucosal Immunol. 2008;1(4):289–96.PubMedPubMedCentralCrossRef
86.•
Cheng E., et al. Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut, 2012: p. gutjnl-2012-302250. This article presents a novel anti-inflammatory/anti-eosinophilic and acid-independent effect of omperazole, a proton pump inhibitor.
87.
Straumann A., et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomized, placebo-controlled, double-blind trial. Gut, 2009: p. gut. 2009.178558.
88.
Spergel JM et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129(2):456–63. e3.PubMedCrossRef
89.
Stein ML et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118(6):1312–9.PubMedCrossRef
90.
Assa’ad AH et al. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011;141(5):1593–604.PubMedCrossRef
91.
Otani IM 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(6):1576–82. e2.PubMedPubMedCentralCrossRef
92.•
Rothenberg, M.E., et al., Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. J Allerg Clin Immunol, 2014. A proof-of-principle study of a new medication class for treatment of EoE.
93.
Johnsson M et al. Distinctive blood eosinophilic phenotypes and cytokine patterns in eosinophilic esophagitis, inflammatory bowel disease and airway allergy. J innate Immun. 2011;3(6):594–604.PubMedCrossRef
94.
Lingblom C., et al., Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells. Inflammation, 2014: p. 1–13.
95.
Bullock JZ et al. Interplay of adaptive th2 immunity with eotaxin-3/cC chemokine receptor 3 in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007;45(1):22–31.PubMedCrossRef
96.
97.•
Furuta, G.T., et al., The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut, 2012. A novel and minimally invasive technique that could have application for diagnosis and monitoring of EoE in the future.
98.
Moqbel R et al. Identification of messenger RNA for IL-4 in human eosinophils with granule localization and release of the translated product. J Immunol. 1995;155(10):4939–47.PubMed
99.
Möller G et al. Immunolocalization of interleukin-4 in eosinophils in the bronchial mucosa of atopic asthmatics. Am J Respir Cell Mol Biol. 1996;14(5):439–43.PubMedCrossRef
100.
101.
Saffari H et al. Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2014;133(6):1728–34. e1.PubMedCrossRef
102.
Jacoby D, Gleich G, Fryer A. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Investig. 1993;91(4):1314.PubMedPubMedCentralCrossRef
103.
Aceves SS et al. Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-β1, and increase esophageal smooth muscle contraction. J Allergy Clin Immunol. 2010;126(6):1198–204. e4.PubMedCrossRef
104.
Young JD-E et al. Mechanism of membrane damage mediated by human eosinophil cationic protein. Nature. 1986;321(6070):613–6.PubMedCrossRef
105.
O’Donnell MC et al. Activation of basophil and mast cell histamine release by eosinophil granule major basic protein. J Experiment Med. 1983;157(6):1981–91.CrossRef
106.
Aceves SS et al. Esophageal remodeling in pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119(1):206–12.PubMedCrossRef
107.
Kagalwalla AF et al. Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment. J Allergy Clin Immunol. 2012;129(5):1387–96. e67.PubMedPubMedCentralCrossRef
108.
Lucendo AJ 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(5):1037–46.PubMedCrossRef
109.
Cheng E, Souza RF, Spechler SJ. Tissue remodeling in eosinophilic esophagitis. Am J Physiol-Gastrointestin Liver Physiol. 2012;303(11):G1175–87.CrossRef
110.
Gupta SK et al. Cytokine expression in normal and inflamed esophageal mucosa: a study into the pathogenesis of allergic eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2006;42(1):22–6.PubMedCrossRef
111.
Kirsch R et al. Activated mucosal mast cells differentiate eosinophilic (allergic) esophagitis from gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2007;44(1):20–6.PubMedCrossRef
112.
Mueller S et al. Comparison of histological parameters for the diagnosis of eosinophilic oesophagitis versus gastro‐oesophageal reflux disease on oesophageal biopsy material. Histopathology. 2008;53(6):676–84.PubMedCrossRef
113.
Dellon ES et al. Tryptase staining of mast cells may differentiate eosinophilic esophagitis from gastroesophageal reflux disease. Am J Gastroenterol. 2010;106(2):264–71.PubMedPubMedCentralCrossRef
114.
115.
Dellon ES et al. Markers of eosinophilic inflammation for diagnosis of eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia: a prospective study. Clin Gastroenterol Hepatol. 2014;12(12):2015–22.PubMedPubMedCentralCrossRef
116.
Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol. 2006;118(5):1054–9.PubMedCrossRef
117.
Adamko D, Lacy P, Moqbel R. Mechanisms of eosinophil recruitment and activation. Curr Allerg Asthma Rep. 2002;2(2):107–16.CrossRef
118.
Denburg JA et al. Systemic aspects of allergic disease: bone marrow responses. J Allergy Clin Immunol. 2000;106(5):S242–6.PubMedCrossRef
119.
Sehmi R et al. Increased levels of CD34+ hemopoietic progenitor cells in atopic subjects. Am J Respir Cell Mol Biol. 1996;15(5):645–55.PubMedCrossRef
120.
Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol. 2005;26:877–900.CrossRef
121.
Brennan PJ, Brigl M, Brenner MB. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol. 2013;13(2):101–17.PubMedCrossRef
122.
Lexmond WS 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;109(5):646–57.PubMedPubMedCentralCrossRef
123.
Rajavelu P et al. Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis. Am J Physiol-Gastrointestin Liver Physiol. 2012;302(7):G645–54.CrossRef
124.
Orlando RC. The integrity of the esophageal mucosa. Balance between offensive and defensive mechanisms. Best Pract Res Clin Gastroenterol. 2010;24(6):873–82.PubMedPubMedCentralCrossRef
125.
126.
Rubinstein E et al. Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2011;53(4):409.PubMedPubMedCentralCrossRef
127.
Zuo L et al. IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13Rα2-inhibited pathway. J Immunol. 2010;185(1):660–9.PubMedPubMedCentralCrossRef
128.
129.
Hirano I, Aceves SS. Clinical implications and pathogenesis of esophageal remodeling in eosinophilic esophagitis. Gastroenterol Clin N Am. 2014;43(2):297–316.CrossRef
130.
Fontillón 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(11):1762.PubMedCrossRef
131.
Kwiatek MA et al. Esophagogastric junction distensibility assessed with an endoscopic functional luminal imaging probe (EndoFLIP). Gastrointest Endosc. 2010;72(2):272–8.PubMedPubMedCentralCrossRef
132.
133.•
Nicodème F et al. Esophageal distensibility as a measure of disease severity in patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2013;11(9):1101–1107 e1. This study shows that esophageal compliance can be used to predict treatment outcomes in EoE, and emphasizes the important role that esophageal remodeling plays in the clinical picture of EoE. PubMedPubMedCentralCrossRef
134.
Malerba G et al. Linkage analysis of chromosome 12 markers in Italian families with atopic asthmatic children. Am J Respir Crit Care Med. 2000;162(4):1587–90.PubMedCrossRef
135.
Straumann A et al. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology. 2003;125(6):1660–9.PubMedCrossRef
136.
Patel SM, Falchuk KR. Three brothers with dysphagia caused by eosinophilic esophagitis. Gastrointest Endosc. 2005;61(1):165–7.PubMedCrossRef
137.
138.••
Alexander ES et al. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis. J Allergy Clin Immunol. 2014;134(5):1084–1092 e1. A comprehensive assessment of the roles of heritability and environment in EoE. PubMedPubMedCentralCrossRef
139.
140.
Blanchard C et al. Eotaxin-3/CCL26 gene expression in intestinal epithelial cells is upregulated by interleukin-4 and interleukin-13 via the signal transducer and activator of transcription 6. Int J Biochem Cell Biol. 2005;37(12):2559–73.PubMedCrossRef
141.
Bhattacharya B et al. Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease. Hum Pathol. 2007;38(12):1744–53.PubMedCrossRef
142.
Lucendo AJ 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(9):2184–93.PubMedCrossRef
143.•
Sherrill J et al. Analysis and expansion of the eosinophilic esophagitis transcriptome by RNA sequencing. Genes Immun. 2014;15(6):361–9. This study expands the known EoE transcriptome, identifying numberous new targets for future pathogenic investigations. PubMedPubMedCentralCrossRef
144.
145.
146.••
Kottyan LC et al. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet. 2014;46(8):895–900. One of three GWAS studies of EoE to date, which identified a novel gene locus, CAPN14, as a potential explanation for esophageal specificity in EoE. PubMedPubMedCentralCrossRef
147.
Sleiman P.M., et al. GWAS identifies four novel eosinophilic esophagitis loci. Nature communications, 2014. 5.
148.
Larsson H, Bergquist H, Bove M. The incidence of esophageal bolus impaction is there a seasonal variation? Otolaryngol Head Neck Surg. 2011;144(2):186–90.PubMedCrossRef
149.
Hurrell JM, Genta RM, Dellon ES. Prevalence of esophageal eosinophilia varies by climate zone in the United States. Am J Gastroenterol. 2012;107(5):698–706.PubMedPubMedCentralCrossRef
150.
Jensen, E., et al. Esophageal eosinophilia and eosinophilic esophagitis are increased in rural areas with low population density: results from a national pathology database. in American Journal Of gastroenterology. 2013. Nature publishing group 75 varick st, 9th flr, New York, NY 10013–1917 USA.
151.
Elitsur Y et al. Seasonal distribution and eosinophilic esophagitis: the experience in children living in rural communities. J Clin Gastroenterol. 2013;47(3):287–8.PubMedCrossRef
152.
Spergel JM et al. Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States. J Pediatr Gastroenterol Nutr. 2011;52(3):300–6.PubMedPubMedCentralCrossRef
153.
Bonis PA. Putting the puzzle together: epidemiological and clinical clues in the etiology of eosinophilic esophagitis. Immunol Allergy Clin N Am. 2009;29(1):41–52.CrossRef
154.
155.
Dellon ES et al. Inverse association of esophageal eosinophilia with Helicobacter pylori based on analysis of a US pathology database. Gastroenterology. 2011;141(5):1586–92.PubMedPubMedCentralCrossRef
156.
Ronkainen J et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study. Gut. 2007;56(5):615–20.PubMedPubMedCentralCrossRef
157.
Furuta K et al. Case-control study of association of eosinophilic gastrointestinal disorders with Helicobacter pylori infection in Japan. J Clin Biochem Nutr. 2013;53(1):60.PubMedPubMedCentralCrossRef
158.
Elitsur,Y., et al. Does helicobacter pylori protect against eosinophilic esophagitis in children? Helicobacter, 2014.
159.
Yamazaki K et al. Allergen-specific in vitro cytokine production in adult patients with eosinophilic esophagitis. Dig Dis Sci. 2006;51(11):1934–41.PubMedCrossRef
160.•
Jensen ET et al. Early life exposures as risk factors for pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2013;57(1):67–71. The first study showing that selected early life exposures, such as antibiotic use during infancy, can increase the risk of pediatric development of EoE. PubMedCrossRef
Metadata
Title
Do We Know What Causes Eosinophilic Esophagitis? A Mechanistic Update
Authors
Thomas M. Runge
Evan S. Dellon
Publication date
01-09-2015
Publisher
Springer US
Published in
Current Gastroenterology Reports / Issue 9/2015
Print ISSN: 1522-8037
Electronic ISSN: 1534-312X
DOI
https://doi.org/10.1007/s11894-015-0458-9
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits