Food Allergy Testing in Eosinophilic Esophagitis: What the Gastroenterologist Needs to Know
2013; Elsevier BV; Volume: 12; Issue: 8 Linguagem: Inglês
10.1016/j.cgh.2013.09.007
ISSN1542-7714
Autores Tópico(s)Eosinophilic Disorders and Syndromes
ResumoEosinophilic 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. 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. See similar article on page 1272 in this issue of Clinical Gastroenterology and Hepatology. Eosinophilic esophagitis (EoE) is a clinicopathologic entity of increasing worldwide prevalence that affects both children and adults.1Liacouras C.A. Furuta G.T. Hirano I. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-22Abstract Full Text Full Text PDF PubMed Scopus (1559) Google Scholar, 2Dellon E.S. Diagnosis and management of eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2012; 10: 1066-1078Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar EoE is a chronic, immune, antigen-mediated disorder with a pathogenesis akin to other allergic diseases such as asthma and eczema in which an antigen induces a cascade of Th2 interleukins (ILs) and chemokines in addition to inflammatory cell infiltration.1Liacouras C.A. Furuta G.T. Hirano I. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-22Abstract Full Text Full Text PDF PubMed Scopus (1559) Google Scholar, 3Blanchard 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: 1292-1300Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar, 4Blanchard 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: 536-547Crossref PubMed Scopus (698) Google Scholar The diagnosis of EoE relies on the presence of robust esophageal eosinophilia of ≥15 eosinophils per high-power field that persists after a proton pump inhibitor trial.1Liacouras C.A. Furuta G.T. Hirano I. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-22Abstract Full Text Full Text PDF PubMed Scopus (1559) Google Scholar The process is frequently pan-esophageal and accompanied by histologic remodeling inclusive of submucosal fibrosis and angiogenesis, which translates clinically into esophageal rigidity and dysmotility and symptoms of dysphagia.5Aceves S.S. Newbury R.O. Dohil R. et al.Esophageal remodeling in pediatric eosinophilic esophagitis.J Allergy Clin Immunol. 2007; 119: 206-212Abstract Full Text Full Text PDF PubMed Scopus (371) Google Scholar, 6Rubinstein 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: 409-416Crossref PubMed Scopus (67) Google Scholar, 7Kwiatek M.A. Hirano I. Kahrilas P.J. et al.Mechanical properties of the esophagus in eosinophilic esophagitis.Gastroenterology. 2011; 140: 82-90Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar, 8Straumann A. The natural history and complications of eosinophilic esophagitis.Gastrointest Endosc Clin N Am. 2008; 18: 99-118Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 9Persad 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: 251-260Crossref PubMed Scopus (36) Google Scholar, 10Nurko S. Rosen R. Furuta G.T. Esophageal dysmotility in children with eosinophilic esophagitis: a study using prolonged esophageal manometry.Am J Gastroenterol. 2009; 104: 3050-3057Crossref PubMed Scopus (77) Google Scholar Important molecular factors for eosinophilia and remodeling include IL-5, IL-13, eotaxin-3, and transforming growth factorβ-1.3Blanchard 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: 1292-1300Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar, 4Blanchard 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: 536-547Crossref PubMed Scopus (698) Google Scholar, 5Aceves S.S. Newbury R.O. Dohil R. et al.Esophageal remodeling in pediatric eosinophilic esophagitis.J Allergy Clin Immunol. 2007; 119: 206-212Abstract Full Text Full Text PDF PubMed Scopus (371) Google Scholar, 11Straumann 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: 954-961Abstract Full Text Full Text PDF PubMed Scopus (476) Google Scholar, 12Mishra A. Hogan S.P. Brandt E.B. et al.IL-5 promotes eosinophil trafficking to the esophagus.J Immunol. 2002; 168: 2464-2469Crossref PubMed Scopus (287) Google Scholar, 13Straumann A. Conus S. Degen L. et al.Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis.Gastroenterology. 2010; 139: 1526-1537Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar, 14Aceves 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: 1198-1204Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar Food antigens clearly function as antigenic triggers for EoE induction and exacerbation in pediatric and adult populations.15Gonsalves N. Yang G.Y. Doerfler B. et al.Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.Gastroenterology. 2012; 142: 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (474) Google Scholar, 16Kagalwalla 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: 1097-1102Abstract Full Text Full Text PDF PubMed Scopus (573) Google Scholar, 17Kelly 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: 1503-1512Abstract Full Text PDF PubMed Scopus (874) Google Scholar, 18Henderson 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: 1570-1578Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar, 19Gonzalez-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: 855-858Crossref PubMed Scopus (26) Google Scholar In 1995, Kelley et al17Kelly 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: 1503-1512Abstract Full Text PDF PubMed Scopus (874) Google Scholar postulated that acid-resistant esophageal eosinophilia could be due to food antigen exposure in children. On the basis of this hypothesis, these investigators treated children with gastrointestinal symptoms and esophageal eosinophilia with amino acid formula. After a minimum of 6 weeks of treatment, all of the children experienced resolution or improvement of symptoms, with significant reductions in esophageal eosinophilia. Since then, these data have been validated at multiple centers. Indeed, amino acid formulas are one of the most effective EoE therapies, with resolution rates often higher than 96% in children.16Kagalwalla 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: 1097-1102Abstract Full Text Full Text PDF PubMed Scopus (573) Google Scholar, 18Henderson 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: 1570-1578Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar, 20Markowitz 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: 777-782Crossref PubMed Scopus (495) Google Scholar, 21Spergel 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: 461-467Abstract Full Text Full Text PDF PubMed Scopus (293) Google Scholar The removal of all food antigens from the adult diet is also effective in resolving EoE, with improvements in endoscopic and histologic features in 72% of subjects after 4 weeks of treatment.22Peterson K.A. Byrne K.R. Vinson L.A. et al.Elemental diet induces histologic response in adult eosinophilic esophagitis.Am J Gastroenterol. 2013; 108: 759-766Crossref PubMed Scopus (183) Google Scholar A second line of evidence in support of food antigens in the pathogenesis of EoE is the clinicopathologic response to specific food elimination in the form of empiric elimination diets.15Gonsalves N. Yang G.Y. Doerfler B. et al.Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.Gastroenterology. 2012; 142: 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (474) Google Scholar, 16Kagalwalla 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: 1097-1102Abstract Full Text Full Text PDF PubMed Scopus (573) Google Scholar, 23Kagalwalla 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: 711-716Crossref PubMed Scopus (114) Google Scholar, 24Kagalwalla 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: 145-149Crossref PubMed Scopus (210) Google Scholar Empiric elimination of specific food groups (milk, egg, soy, wheat, peanuts/tree nuts, fish/shellfish) is highly effective in controlling EoE-associated symptoms, endoscopic abnormalities, and eosinophilia. In children and adults, the empiric elimination diet resolves EoE in more than 60% of subjects.15Gonsalves N. Yang G.Y. Doerfler B. et al.Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.Gastroenterology. 2012; 142: 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (474) Google Scholar, 16Kagalwalla 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: 1097-1102Abstract Full Text Full Text PDF PubMed Scopus (573) Google Scholar, 18Henderson 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: 1570-1578Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar, 25Gonzalez-Castillo S. Arias A. Lucendo A.J. Treatment of eosinophilic esophagitis: how should we manage the disease?.J Clin Gastroenterol. 2010; 44: 663-671Crossref PubMed Scopus (21) Google Scholar Food antigen elimination can also resolve fibrosis, at least in children.26Lieberman 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: 1299-1307Crossref PubMed Scopus (73) Google Scholar As such, this food elimination diet not only provides a therapeutic remedy in EoE but also provides proof of concept that food antigens are EoE instigators. Further evidence for the sufficiency of food antigens in initiating EoE comes from experimental models in which both peanut and egg exposure can cause the accumulation of eosinophils in the murine esophagus.6Rubinstein 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: 409-416Crossref PubMed Scopus (67) Google Scholar, 27Rajavelu 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-G654Crossref PubMed Scopus (62) Google Scholar In these animal model systems, food antigen exposure induces many features of EoE inclusive of basal cell proliferation, esophageal eosinophilia and mastocytosis, and lamina propria remodeling with fibrosis.6Rubinstein 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: 409-416Crossref PubMed Scopus (67) Google Scholar, 27Rajavelu 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-G654Crossref PubMed Scopus (62) Google Scholar Allergy testing is generally aimed at elucidating 2 distinct mechanisms of hypersensitivity. Immediate reactions are gauged by the presence of immunoglobulin E (IgE) in the context of clinical history and the presence of food-specific IgE. Clinically meaningful, immediate food hypersensitivity reactions are defined as the presence of food-specific IgE and a reproducible clinical reaction occurring within minutes to a few hours (up to about 4 hours) after ingestion of the instigating food. Food allergy in general, however, is defined as “an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food.”28Boyce 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: 1105-1118Abstract Full Text Full Text PDF PubMed Scopus (1159) Google Scholar Food-specific IgE can be detected either by skin prick testing (SPT) or by serum IgE testing. SPT assesses both the presence and the function of mast cell–bound IgE, whereas serum IgE documents the presence and quantity of food-specific IgE. SPT can be done by using commercially available food extracts or fresh foods. The more common testing reagents in food allergy are commercially prepared food extracts. IgE food allergy testing is standardized and validated in the context of immediate reactions such as hives, eczema flares, angioedema, and symptoms of anaphylaxis. However, food-specific IgE is detectable in some individuals even in the absence of clinical reactions to the particular food. The clinical state of having IgE to a food is referred to as sensitization.28Boyce 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: 1105-1118Abstract Full Text Full Text PDF PubMed Scopus (1159) Google Scholar When this is coupled with a predictable and repeatable clinical reaction on food ingestion, it is termed an allergy. Subjects who eat a food and have no detectable clinical reaction are tolerant. It can be difficult to accurately predict if a sensitized person who has never consumed the food to which he/she is sensitized will have a reaction on consumption of that food. However, predicting the likelihood of a response is usually based on the level of serum-specific IgE and/or on the size of the wheal on SPT. In addition, the loss of food tolerance can occur when a food-sensitized subject begins to avoid the food to which they carry IgE. This loss of tolerance can occur relatively rapidly, in weeks to months, and is manifested by the onset of clinical immediate hypersensitivity reactions such as hives, angioedema, and/or respiratory distress on ingestion of the previously tolerated food. Current data suggest that continued consumption of a food once desensitization has occurred is likely an essential component for the maintenance of tolerance.29Fleischer D.M. Conover-Walker M.K. Christie L. et al.Peanut allergy: recurrence and its management.J Allergy Clin Immunol. 2004; 114: 1195-1201Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar Serum IgE is done by a number of laboratories. However, the literature for predictive tests for serum IgE testing in pediatric subjects with immediate food hypersensitivity is based on the Phadia ImmunoCAP system (ImmunoDiagnostics, Uppsala, Sweden). A study assessing this system in comparison with other serum IgE food tests (Turbo-MP and Immunlite) found that values were significantly different for milk, egg, and peanut.30Boyce 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: 253-267Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar As such, the results obtained from different tests are not comparable. Testing, which was previously done by radioactivity and known as RAST (radioimmunoassay), has been entirely replaced by non-radioactive enzyme-linked immunosorbent assay testing. Unlike IgG testing, which is entirely unwarranted in food allergy with the exception of IgG4 for research purposes, IgE testing requires the detection of nanogram quantities of antibody. This is due to the fact that the majority of IgE is bound to tissue cells such as mast cells and basophils. The pre-bound nature of IgE to its receptor is pivotal for the rapid time course of immediate hypersensitivity because the cell is essentially “primed” for its allergic response. In addition, the predictive values for reactions based on serum food IgE are specific to the food and the age of the subject such that younger children can have immediate reactions at lower food-specific serum IgE levels than older children. Because of the complexity of food allergy testing and evaluation, referral to an allergist is warranted when there are concerns for immediate hypersensitivity. The second type of food allergy testing is atopy patch testing (APT), which is used to assess the presence of non-IgE, cell-mediated food reactions. The histologic recrudescence of EoE after food reintroduction is relatively rapid, within 3–7 days.15Gonsalves N. Yang G.Y. Doerfler B. et al.Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.Gastroenterology. 2012; 142: 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (474) Google Scholar, 22Peterson K.A. Byrne K.R. Vinson L.A. et al.Elemental diet induces histologic response in adult eosinophilic esophagitis.Am J Gastroenterol. 2013; 108: 759-766Crossref PubMed Scopus (183) Google Scholar This time course supports a delayed-type hypersensitivity/cell-mediated mechanism. In contrast, there is no clinical evidence for reactions that are as rapid as those seen in subjects with food-induced anaphylaxis, that is, within minutes of food consumption, or that food impactions are due to sudden esophageal spasm caused by allergen exposure. APT is the most studied delayed allergy testing. The most rigorously investigated APT has been in the context of chemical and environmental contact dermatitis. In this context, both the specific chemical components and the best vehicle for solubilizing the chemical have been standardized. Results of food APT have been most closely evaluated in eczema.31Niggemann 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: 281-285Crossref PubMed Scopus (257) Google Scholar, 32Mehl 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: 923-929Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar, 33Devillers 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: 53-58Crossref PubMed Scopus (30) Google Scholar, 34Giusti 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: 109-111Crossref PubMed Scopus (16) Google Scholar APT is done by placing fresh or rehydrated foods in metal Finn chambers, applying the chambers to the back for 48 hours, and reading the results at 72 hours by using European guidelines for the analysis of food patch testing.35Heine 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: 213-217Crossref PubMed Scopus (83) Google Scholar For food APT in EoE, there have been no studies that have incorporated skin biopsies to verify the presence of an immunologic infiltrate at the cutaneous site of a positive patch test. Both cell-mediated and IgE-mediated mechanisms may be at work in the EoE esophagus. Immunologic class switch machinery is present at elevated levels in the EoE esophagus as are B cells, IgE/IgE receptor–positive cells, and ILs such as IL-13 that promote class switch to IgE.3Blanchard 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: 1292-1300Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar, 36Vicario M. Blanchard C. Stringer K.F. et al.Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis.Gut. 2010; 59: 12-20Crossref PubMed Scopus (155) Google Scholar, 37Yen 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: 584-592Crossref PubMed Scopus (35) Google Scholar As such, there is a precedent for in situ esophageal-specific IgE production. Animal models of allergen-induced experimental EoE show a dependence on T cells, recombination, and basophils but not on B cells or mast cells for disease induction.38Mishra 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: 916-924Crossref PubMed Scopus (135) Google Scholar, 39Noti M. Wojno E.D. Kim B.S. et al.Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.Nat Med. 2013; 19: 1005-1013Crossref PubMed Scopus (276) Google Scholar In addition, animal models deficient in IgE have EoE induction, suggesting that IgE plays a role in sustaining or exacerbating but not in inciting EoE.38Mishra 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: 916-924Crossref PubMed Scopus (135) Google Scholar, 39Noti M. Wojno E.D. Kim B.S. et al.Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.Nat Med. 2013; 19: 1005-1013Crossref PubMed Scopus (276) Google Scholar Interestingly, there have been reports of EoE onset during oral desensitization trials for egg and milk.40Ridolo E. De Angelis G.L. Dall'aglio P. Eosinophilic esophagitis after specific oral tolerance induction for egg protein.Ann Allergy Asthma Immunol. 2011; 106: 73-74Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar, 41Sanchez-Garcia S. Rodriguez Del Rio P. Escudero C. et al.Possible eosinophilic esophagitis induced by milk oral immunotherapy.J Allergy Clin Immunol. 2012; 129: 1155-1157Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar This clearly suggests that the mechanism of food allergy in EoE is not through IgE but, instead, through a cellular process. The current data for allergy testing to elucidate food triggers in EoE support a number of conclusions. First, allergy testing for foods may be more useful in the pediatric than the adult population. In this context, it is important to keep the natural history of the atopic march in mind. Young children tend to have food sensitization and allergic responses, whereas older children and adults have aeroallergen allergies. Second, the negative predictive values for foods generally tend to be superior to the positive predictive values. If SPT is negative for a food allergen, there is a greater than 90% chance that the patient will not have an IgE-mediated reaction. An exception to the negative predictive value of food testing in EoE is milk.21Spergel 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: 461-467Abstract Full Text Full Text PDF PubMed Scopus (293) Google Scholar Third, the presence of food-specific IgE can be due to cross-reactivity with environmental allergens. For example, a patient may have wheat-specific IgE that is due to a grass allergy. Fourth, the current data do not support a role for serum IgE–based dietary elimination and also do not support the use of serum food allergy panels. Last, although positive SPT and/or APT to foods may reveal a food EoE trigger, the testing does not provide an alternative to endoscopic and biopsy evaluation after food elimination and reintroduction (Figure 1). Generally, EoE subjects are highly atopic and tend to have polysensitization to both food and aeroallergens, with children having more food sensitization and adults having more aeroallergen sensitization, consistent with the natural history of allergy. Both SPT and APT in EoE have been more rigorously studied in the pediatric population. Currently, IgE food testing has been most rigorously studied via SPT. The exact extent that s
Referência(s)