Food Allergy Testing in Eosinophilic Esophagitis: What the Gastroenterologist Needs to Know

  • Seema S. Aceves
    Reprint requests Address requests for reprints to: Seema S. Aceves, MD, PhD, Division of Allergy and Immunology, 9500 Gilman Drive, MC-0635, La Jolla, California 92093; fax: (858) 966-6791.
    Division of Allergy and Immunology, Departments of Pediatrics and Medicine, University of California, San Diego, Rady Children's Hospital, San Diego, La Jolla, California
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Published:September 13, 2013DOI:
      Eosinophilic esophagitis (EoE) is a clinicopathologic disease of increasing prevalence in children and adults. The triggering antigen in EoE is often a food that initiates a cascade of Th2-associated interleukins such as interleukin-5 and interleukin-13 and chemokines such as eotaxin-3 as well as esophageal eosinophilia and mastocytosis. Amino acid–based formulas have high efficacy rates in EoE and constitute the first evidence for food-triggered esophageal eosinophilia. Animal models have demonstrated the sufficiency of food antigens in triggering both the inflammatory and remodeling complications of EoE. Food elimination diets that are followed by single food introduction with repeat biopsy have proven the efficacy of empiric and allergy testing based elimination diets in children and adults. Although the ideal allergy test for identifying food antigens in EoE remains to be elucidated, the utility of food skin prick combined with atopy patch testing has been shown in large pediatric cohorts. By comparison, smaller, non-U.S. adult cohorts have not had similar results. Currently, a positive test on food allergy evaluation suggests a food trigger for EoE but does not substitute for biopsy-based tissue evaluation after food removal and reintroduction. The higher rates of food anaphylaxis in children with EoE, potential loss of tolerance to immunoglobulin E–positive foods that can occur with food avoidance, and the high rates of other atopic diatheses in EoE subjects all support the evaluation of EoE subject by an allergist, consideration for allergy testing, and an integrated approach by allergists, gastroenterologists, and pathologists in EoE management.


      Abbreviations used in this paper:

      APT (atopy patch testing), EoE (eosinophilic esophagitis), Ig (immunoglobulin), IL (interleukin), SPT (skin prick testing)
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        • Liacouras C.A.
        • Furuta G.T.
        • Hirano I.
        • et al.
        Eosinophilic esophagitis: updated consensus recommendations for children and adults.
        J Allergy Clin Immunol. 2011; 128: 3-22
        • Dellon E.S.
        Diagnosis and management of eosinophilic esophagitis.
        Clin Gastroenterol Hepatol. 2012; 10: 1066-1078
        • Blanchard C.
        • Mingler M.K.
        • Vicario M.
        • et al.
        IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids.
        J Allergy Clin Immunol. 2007; 120: 1292-1300
        • Blanchard C.
        • Wang N.
        • Stringer K.F.
        • et al.
        Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis.
        J Clin Invest. 2006; 116: 536-547
        • Aceves S.S.
        • Newbury R.O.
        • Dohil R.
        • et al.
        Esophageal remodeling in pediatric eosinophilic esophagitis.
        J Allergy Clin Immunol. 2007; 119: 206-212
        • Rubinstein E.
        • Cho J.Y.
        • Rosenthal P.
        • et al.
        Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis.
        J Pediatr Gastroenterol Nutr. 2011; 53: 409-416
        • Kwiatek M.A.
        • Hirano I.
        • Kahrilas P.J.
        • et al.
        Mechanical properties of the esophagus in eosinophilic esophagitis.
        Gastroenterology. 2011; 140: 82-90
        • Straumann A.
        The natural history and complications of eosinophilic esophagitis.
        Gastrointest Endosc Clin N Am. 2008; 18: 99-118
        • Persad R.
        • Huynh H.Q.
        • 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: 251-260
        • Nurko S.
        • Rosen R.
        • Furuta G.T.
        Esophageal dysmotility in children with eosinophilic esophagitis: a study using prolonged esophageal manometry.
        Am J Gastroenterol. 2009; 104: 3050-3057
        • 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: 954-961
        • Mishra A.
        • Hogan S.P.
        • Brandt E.B.
        • et al.
        IL-5 promotes eosinophil trafficking to the esophagus.
        J Immunol. 2002; 168: 2464-2469
        • Straumann A.
        • Conus S.
        • Degen L.
        • et al.
        Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis.
        Gastroenterology. 2010; 139: 1526-1537
        • Aceves S.S.
        • Chen D.
        • Newbury R.O.
        • 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: 1198-1204
        • Gonsalves N.
        • Yang G.Y.
        • Doerfler B.
        • et al.
        Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.
        Gastroenterology. 2012; 142: 1451-1459
        • Kagalwalla A.F.
        • Sentongo T.A.
        • Ritz S.
        • et al.
        Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis.
        Clin Gastroenterol Hepatol. 2006; 4: 1097-1102
        • Kelly K.J.
        • Lazenby A.J.
        • Rowe P.C.
        • et al.
        Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula.
        Gastroenterology. 1995; 109: 1503-1512
        • Henderson C.J.
        • Abonia J.P.
        • King E.C.
        • et al.
        Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis.
        J Allergy Clin Immunol. 2012; 129: 1570-1578
        • Gonzalez-Cervera J
        • Angueira T
        • Rodriguez-Dominguez B
        • et al.
        Successful food elimination therapy in adult eosinophilic esophagitis: not all patients are the same.
        J Clin Gastroenterol. 2012; 46: 855-858
        • Markowitz J.E.
        • Spergel J.M.
        • Ruchelli E.
        • et al.
        Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents.
        Am J Gastroenterol. 2003; 98: 777-782
        • Spergel J.M.
        • Brown-Whitehorn T.F.
        • Cianferoni A.
        • et al.
        Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet.
        J Allergy Clin Immunol. 2012; 130: 461-467
        • Peterson K.A.
        • Byrne K.R.
        • Vinson L.A.
        • et al.
        Elemental diet induces histologic response in adult eosinophilic esophagitis.
        Am J Gastroenterol. 2013; 108: 759-766
        • Kagalwalla AF
        • Amsden K
        • Shah A
        • et al.
        Cow's milk elimination: a novel dietary approach to treat eosinophilic esophagitis.
        J Pediatr Gastroenterol Nutr. 2012; 55: 711-716
        • Kagalwalla A.F.
        • Shah A.
        • Li B.U.
        • et al.
        Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet.
        J Pediatr Gastroenterol Nutr. 2011; 53: 145-149
        • Gonzalez-Castillo S.
        • Arias A.
        • Lucendo A.J.
        Treatment of eosinophilic esophagitis: how should we manage the disease?.
        J Clin Gastroenterol. 2010; 44: 663-671
        • Lieberman J.A.
        • Morotti R.A.
        • Konstantinou G.N.
        • et al.
        Dietary therapy can reverse esophageal subepithelial fibrosis in patients with eosinophilic esophagitis: a historical cohort.
        Allergy. 2012; 67: 1299-1307
        • 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-G654
        • Boyce J.A.
        • Assa'ad A.
        • Burks A.W.
        • et al.
        Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-Sponsored Expert Panel Report.
        J Allergy Clin Immunol. 2010; 126: 1105-1118
        • Fleischer D.M.
        • Conover-Walker M.K.
        • Christie L.
        • et al.
        Peanut allergy: recurrence and its management.
        J Allergy Clin Immunol. 2004; 114: 1195-1201
        • Boyce J.A.
        • Assa'a A.
        • Burks A.W.
        • et al.
        Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-Sponsored Expert Panel Report.
        Nutrition. 2011; 27: 253-267
        • Niggemann B.
        • Reibel S.
        • Wahn U.
        The atopy patch test (APT): a useful tool for the diagnosis of food allergy in children with atopic dermatitis.
        Allergy. 2000; 55: 281-285
        • Mehl A.
        • Rolinck-Werninghaus C.
        • Staden U.
        • et al.
        The atopy patch test in the diagnostic workup of suspected food-related symptoms in children.
        J Allergy Clin Immunol. 2006; 118: 923-929
        • Devillers A.C.
        • de Waard-van der Spek F.B.
        • Mulder P.G.
        • et al.
        Delayed- and immediate-type reactions in the atopy patch test with food allergens in young children with atopic dermatitis.
        Pediatr Allergy Immunol. 2009; 20: 53-58
        • Giusti F.
        • Seidenari S.
        Patch testing with egg represents a useful integration to diagnosis of egg allergy in children with atopic dermatitis.
        Pediatr Dermatol. 2005; 22: 109-111
        • Heine R.G.
        • Verstege A.
        • Mehl A.
        • Staden U.
        • et al.
        Proposal for a standardized interpretation of the atopy patch test in children with atopic dermatitis and suspected food allergy.
        Pediatr Allergy Immunol. 2006; 17: 213-217
        • Vicario M.
        • Blanchard C.
        • Stringer K.F.
        • et al.
        Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis.
        Gut. 2010; 59: 12-20
        • Yen E.H.
        • Hornick J.L.
        • Dehlink E.
        • et al.
        Comparative analysis of FcepsilonRI expression patterns in patients with eosinophilic and reflux esophagitis.
        J Pediatr Gastroenterol Nutr. 2010; 51: 584-592
        • Mishra A.
        • Schlotman J.
        • Wang M.
        • et al.
        Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice.
        J Leukoc Biol. 2007; 81: 916-924
        • Noti M.
        • Wojno E.D.
        • Kim B.S.
        • et al.
        Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.
        Nat Med. 2013; 19: 1005-1013
        • Ridolo E.
        • De Angelis G.L.
        • Dall'aglio P.
        Eosinophilic esophagitis after specific oral tolerance induction for egg protein.
        Ann Allergy Asthma Immunol. 2011; 106: 73-74
        • 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: 1155-1157
        • Penfield J.D.
        • Lang D.M.
        • Goldblum J.R.
        • et al.
        The role of allergy evaluation in adults with eosinophilic esophagitis.
        J Clin Gastroenterol. 2010; 44: 22-27
        • Castellano Mdel R.
        • Cimbollek S.
        • Quiralte J.
        Defining the role of food allergy in a population of adult patients with eosinophilic esophagitis.
        Inflamm Allergy Drug Targets. 2010; 9: 257-262
        • Molina-Infante J.
        • Martin-Noguerol E.
        • Alvarado-Arenas M.
        • et al.
        Selective elimination diet based on skin testing has suboptimal efficacy for adult eosinophilic esophagitis.
        J Allergy Clin Immunol. 2012; 130: 1200-1202
        • Erwin E.A.
        • James H.R.
        • Gutekunst H.M.
        • et al.
        Serum IgE measurement and detection of food allergy in pediatric patients with eosinophilic esophagitis.
        Ann Allergy Asthma Immunol. 2010; 104: 496-502
        • Sugnanam K.K.
        • Collins J.T.
        • Smith P.K.
        • et al.
        Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis.
        Allergy. 2007; 62: 1257-1260
        • Paquet B.
        • Begin P.
        • Paradis L.
        • et al.
        Variable yield of allergy patch testing in children with eosinophilic esophagitis.
        J Allergy Clin Immunol. 2013; 131: 613
        • Astier C.
        • Morisset M.
        • Roitel O.
        • et al.
        Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy.
        J Allergy Clin Immunol. 2006; 118: 250-256
        • Asero R.
        • Mistrello G.
        • Roncarolo D.
        • et al.
        Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion.
        Int Arch Allergy Immunol. 2001; 124: 67-69
        • Ocmant A.
        • Mulier S.
        • Hanssens L.
        • et al.
        Basophil activation tests for the diagnosis of food allergy in children.
        Clin Exp Allergy. 2009; 39: 1234-1245
        • Shreffler W.G.
        Evaluation of basophil activation in food allergy: present and future applications.
        Curr Opin Allergy Clin Immunol. 2006; 6: 226-233
        • Siracusa M.C.
        • Saenz S.A.
        • Hill D.A.
        • et al.
        TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation.
        Nature. 2011; 477: 229-233
        • Konikoff M.R.
        • Blanchard C.
        • Kirby C.
        • et al.
        Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis.
        Clin Gastroenterol Hepatol. 2006; 4: 1328-1336
        • Protheroe C.
        • Woodruff S.A.
        • de Petris G.
        • et al.
        A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis.
        Clin Gastroenterol Hepatol. 2009; 7: 749-755
        • Prussin C.
        • Lee J.
        • Foster B.
        Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5(-) T(H)2 responses.
        J Allergy Clin Immunol. 2009; 124: 1326-1332
        • Upadhyaya B.
        • Yin Y.
        • Hill B.J.
        • et al.
        Hierarchical IL-5 expression defines a subpopulation of highly differentiated human Th2 cells.
        J Immunol. 2011; 187: 3111-3120
        • Nowak-Wegrzyn A.
        • Assa'ad A.H.
        • Bahna S.L.
        • et al.
        Work group report: oral food challenge testing.
        J Allergy Clin Immunol. 2009; 123: S365-S383
        • Spergel J.M.
        • Brown-Whitehorn T.F.
        • Beausoleil J.L.
        • et al.
        14 years of eosinophilic esophagitis: clinical features and prognosis.
        J Pediatr Gastroenterol Nutr. 2009; 48: 30-36
        • Sears M.R.
        • Greene J.M.
        • Willan A.R.
        • et al.
        A longitudinal, population-based, cohort study of childhood asthma followed to adulthood.
        N Engl J Med. 2003; 349: 1414-1422
        • Platts-Mills T.A.
        • Tovey E.R.
        • Mitchell E.B.
        • et al.
        Reduction of bronchial hyperreactivity during prolonged allergen avoidance.
        Lancet. 1982; 2: 675-678
        • Onbasi K.
        • Sin A.Z.
        • Doganavsargil B.
        • et al.
        Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season.
        Clin Exp Allergy. 2005; 35: 1423-1431
        • Mishra A.
        • Hogan S.P.
        • Brandt E.B.
        • et al.
        An etiological role for aeroallergens and eosinophils in experimental esophagitis.
        J Clin Invest. 2001; 107: 83-90
        • Rayapudi M.
        • Mavi P.
        • Zhu X.
        • et al.
        Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice.
        J Leukoc Biol. 2010; 88: 337-346
        • Ramirez R.M.
        • Jacobs R.L.
        Eosinophilic esophagitis treated with immunotherapy to dust mites.
        J Allergy Clin Immunol. 2013; 132: 503-504
        • Fogg M.I.
        • Ruchelli E.
        • Spergel J.M.
        Pollen and eosinophilic esophagitis.
        J Allergy Clin Immunol. 2003; 112: 796-797

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