Non-IgE Mediated Food Allergy

Antonella       Cianferoni
Abstract

Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in western countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody– mediated immune responses, there is an increasing recognition of cell-mediated disorders, such as eosinophilic esophagitis and food protein–induced enterocolitis. Non-IgE-Mediated gastrointestinal food allergies are a heterogeneous group of food allergies in which there is an immune reaction against food but the primary pathogenesis is not a production of IgE and activation of mast cells and basophils.
Those diseases tend to affect mainly the gastrointestinal tract and can present as acute (FPIES) or chronic reaction, such as Eosinophilic Esophagitis (EoE), Food Protein-Induced Allergic Proctocolitis (FPIAP). The role of food allergy in Non-EoE gastrointestinal Eosinophilic disorders (Non- EoE EGID) is poorly understood.
In some diseases like EoE, T cell seems to play a major role in initiating the immunological reaction against food, however, in FPIES and FPIAP, the mechanism of sensitization is not clear.
Diagnosis requires food challenges and/or endoscopies in most of the patients, as there are no validated biomarkers that can be used for monitoring or diagnosis of Non-IgE mediated food allergies.
The treatment of Non-IgE food allergy is dependent on diet (FPIES, and EoE) and/or use of drugs (i.e. steroids, PPI) in EoE and Non-EoE EGID.
Non-IgE mediated food allergies are being being investigated.
Keywords: Food Allergy, IgE, non-IgE, immune, eosinophilic, diagnosis, mediated.
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Graphical Abstract

[1] 
Sampson HA. Food allergy. Part 1: immunopathogenesis and clinical disorders. J Allergy Clin Immunol  1999; 103(5 Pt 1): 717-28.
[http://dx.doi.org/10.1016/S0091-6749(99)70411-2] [PMID:  10329801] 
[2] 
Cianferoni A, Spergel JM. Food allergy: review, classification and diagnosis. Allergol Int  2009; 58(4): 457-66.
[http://dx.doi.org/10.2332/allergolint.09-RAI-0138] [PMID:  19847094] 
[3] 
Sampson HA. Food allergy. Part 2: diagnosis and management. J Allergy Clin Immunol  1999; 103(6): 981-9.
[http://dx.doi.org/10.1016/S0091-6749(99)70167-3] [PMID:  10359874] 
[4] 
Nowak-Wegrzyn A, Sampson HA. Adverse reactions to foods. Med Clin North Am  2006; 90(1): 97-127.
[http://dx.doi.org/10.1016/j.mcna.2005.08.012] [PMID:  16310526] 
[5] 
Lee LA, Burks AW. Food allergies: prevalence, molecular characterization, and treatment/prevention strategies. Annu Rev Nutr  2006; 26: 539-65.
[http://dx.doi.org/10.1146/annurev.nutr.26.061505.111211] [PMID:  16602930] 
[6] 
Sheikh A, Hippisley-Cox J, Newton J, Fenty J. Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England. J R Soc Med  2008; 101(3): 139-43.
[http://dx.doi.org/10.1258/jrsm.2008.070306] [PMID:  18344471] 
[7] 
Turner PJ, Gowland MH, Sharma V, et al. Increase in anaphylaxisrelated
	hospitalizations but no in-crease in fatalities: An analysis of
	United Kingdom national anaphylaxis data, 1992-2012 J Allergy
 Clin Immunol 2015; 135: 956-963e1.. 
[8] 
Cianferoni A, Muraro A. Food-induced anaphylaxis. Immunol Allergy Clin North Am  2012; 32(1): 165-95.
[http://dx.doi.org/10.1016/j.iac.2011.10.002] [PMID:  22244239] 
[9] 
Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA. American College of Gastroenterology. 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.
[http://dx.doi.org/10.1038/ajg.2013.71] [PMID:  23567357] 
[10] 
Cianferoni A, Spergel J. Eosinophilic esophagitis: A comprehensive review. Clin Rev Allergy Immunol  2016; 50(2): 159-74.
[http://dx.doi.org/10.1007/s12016-015-8501-z] [PMID:  26194940] 
[11] 
Goswami R, Blazquez AB, Kosoy R, Rahman A, Nowak-Wegrzyn A, Berin MC. Systemic innate immune activation in food protein
	duced enterocolitis sindrome. J Allergy Clin Immunol 2017; 139:
	1885-1896 e9.. 
[12] 
Dellon ES, Jensen ET, Martin CF, Shaheen NJ, Kappelman MD. Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol Hepatol  2014; 12(4): 589-96.e1.
[PMID:  24035773] 
[13] 
Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol  2011; 128(1): 3-20.e6.
[http://dx.doi.org/10.1016/j.jaci.2011.02.040] [PMID:  21477849] 
[14] 
Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol  2003; 98(4): 777-82.
[http://dx.doi.org/10.1111/j.1572-0241.2003.07390.x] [PMID:  12738455] 
[15] 
Peterson KA, Byrne KR, Vinson LA, et al. Elemental diet induces histologic response in adult eosinophilic esophagitis. Am J Gastroenterol  2013; 108(5): 759-66.
[http://dx.doi.org/10.1038/ajg.2012.468] [PMID:  23381017] 
[16] 
Warners MJ, Vlieg-Boerstra BJ, Verheij J, et al. Esophageal and small intestinal mucosal integrity in eosinophilic esophagitis and response to an elemental diet. Am J Gastroenterol  2017; 112(7): 1061-71.
[http://dx.doi.org/10.1038/ajg.2017.107] [PMID:  28417991] 
[17] 
Warners MJ, Vlieg-Boerstra BJ, Verheij J, et al. Elemental diet decreases inflammation and improves symptoms in adult eosinophilic oesophagitis patients. Aliment Pharmacol Ther  2017; 45(6): 777-87.
[http://dx.doi.org/10.1111/apt.13953] [PMID:  28112427] 
[18] 
Spergel JM, Andrews T, Brown-Whitehorn TF, Beausoleil JL, Liacouras CA. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol  2005; 95(4): 336-43.
[http://dx.doi.org/10.1016/S1081-1206(10)61151-9] [PMID:  16279563] 
[19] 
Spergel JM, Brown-Whitehorn TF, Beausoleil JL, et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr  2009; 48(1): 30-6.
[http://dx.doi.org/10.1097/MPG.0b013e3181788282] [PMID:  19172120] 
[20] 
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med  2004; 351(9): 940-1.
[http://dx.doi.org/10.1056/NEJM200408263510924] [PMID:  15329438] 
[21] 
Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut  2013; 62(4): 489-95.
[PMID:  22619364] 
[22] 
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointest Endosc Clin N Am  2008; 18(1): 59-71. [viii-ix.
[23] 
Collins MH, Martin LJ, Alexander ES, et al. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus  2017; 30(3): 1-8.
[PMID:  26857345] 
[24] 
Tringali A, Thomson M, Dumonceau JM, et al. Pediatric gastrointestinal endoscopy: European society of gastrointestinal endoscopy (ESGE) and European society for paediatric gastroenterology hepatology and nutrition (ESPGHAN) guideline executive summary. Endoscopy  2017; 49(1): 83-91.
[PMID:  27617420] 
[25] 
Gonsalves N, Policarpio-Nicolas M, Zhang Q, Rao MS, Hirano I. Histopathologic variability and endoscopic correlates in adults with eosinophilic esophagitis. Gastrointest Endosc  2006; 64(3): 313-9.
[http://dx.doi.org/10.1016/j.gie.2006.04.037] [PMID:  16923475] 
[26] 
Schaefer ET, Fitzgerald JF, Molleston JP, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol  2008; 6(2): 165-73.
[http://dx.doi.org/10.1016/j.cgh.2007.11.008] [PMID:  18237866] 
[27] 
Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol  2011; 128(1): 3-20.e6.
[http://dx.doi.org/10.1016/j.jaci.2011.02.040] [PMID:  21477849] 
[28] 
Furuta GT, Liacouras CA, Collins MH, et al. First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology  2007; 133(4): 1342-63.
[http://dx.doi.org/10.1053/j.gastro.2007.08.017] [PMID:  17919504] 
[29] 
Cianferoni A, Spergel JM. From genetics to treatment of eosinophilic esophagitis. Curr Opin Allergy Clin Immunol  2015; 15(5): 417-25.
[http://dx.doi.org/10.1097/ACI.0000000000000200] [PMID:  26258919] 
[30] 
Lebowitz MD, Barbee R, Burrows B. Family concordance of IgE, atopy, and disease. J Allergy Clin Immunol  1984; 73(2): 259-64.
[http://dx.doi.org/10.1016/S0091-6749(84)80017-2] [PMID:  6699309] 
[31] 
Aceves S, Hirano I, Furuta GT, Collins MH. Eosinophilic gastrointestinal diseases--clinically diverse and histopathologically confounding. Semin Immunopathol  2012; 34(5): 715-31.
[http://dx.doi.org/10.1007/s00281-012-0324-x] [PMID:  22842863] 
[32] 
Aceves SS, Ackerman SJ. Relationships between eosinophilic inflammation, tissue remodeling, and fibrosis in eosinophilic esophagitis. Immunol Allergy Clin North Am  2009; 29(1): 197-211. [xiii-xiv
[33] 
Aceves SS, Broide DH. Airway fibrosis and angiogenesis due to eosinophil trafficking in chronic asthma. Curr Mol Med  2008; 8(5): 350-8.
[http://dx.doi.org/10.2174/156652408785161023] [PMID:  18691061] 
[34] 
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(2): 536-47.
[http://dx.doi.org/10.1172/JCI26679] [PMID:  16453027] 
[35] 
Ávila-Castellano R, García-Lozano JR, Cimbollek S, Lucendo AJ, Bozada JM, Quiralte J. Genetic variations in the TLR3 locus are associated with eosinophilic esophagitis. United European Gastroenterol J  2018; 6(3): 349-57.
[http://dx.doi.org/10.1177/2050640617732643] [PMID:  29774148] 
[36] 
Sleiman PM, Wang ML, Cianferoni A, et al. GWAS identifies four novel eosinophilic esophagitis loci. Nat Commun  2014; 5: 5593.
[http://dx.doi.org/10.1038/ncomms6593] [PMID:  25407941] 
[37] 
Kottyan LC, Davis BP, Sherrill JD, 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.
[http://dx.doi.org/10.1038/ng.3033] [PMID:  25017104] 
[38] 
Sherrill JD, Gao PS, Stucke EM, et al. Variants of thymic stromal
lymphopoietin and its receptor as-sociate with eosinophilic esophagitis.	J Allergy Clin Immunol 2010; 126: 160-165 e3.. 
[39] 
Rothenberg ME, Spergel JM, Sherrill JD, et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet  2010; 42(4): 289-91.
[http://dx.doi.org/10.1038/ng.547] [PMID:  20208534] 
[40] 
Abonia JP, Wen T, Stucke EM, et al. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. J Allergy Clin Immunol  2013; 132(2): 378-86.
[http://dx.doi.org/10.1016/j.jaci.2013.02.030] [PMID:  23608731] 
[41] 
Arora M, Bagi P, Strongin A, et al. Gastrointestinal Manifestations of STAT3-Deficient Hyper-IgE Syndrome. J Clin Immunol  2017; 37(7): 695-700.
[http://dx.doi.org/10.1007/s10875-017-0429-z] [PMID:  28803389] 
[42] 
Paluel-Marmont C, Bellon N, Barbet P, et al. Eosinophilic esophagitis and colonic mucosal eosinophilia in Netherton syndrome. J Allergy Clin Immunol  2017; 139(6): 2003-2005.e1.
[http://dx.doi.org/10.1016/j.jaci.2016.10.045] [PMID:  28025013] 
[43] 
Henderson CJ, Ngeow J, Collins MH, et al. Increased prevalence of eosinophilic gastrointestinal disorders in pediatric PTEN hamartoma tumor syndromes. J Pediatr Gastroenterol Nutr  2014; 58(5): 553-60.
[http://dx.doi.org/10.1097/MPG.0000000000000253] [PMID:  24345843] 
[44] 
Sherrill JD, Kc K, Wang X, et al. Whole-exome sequencing uncovers oxidoreductases DHTKD1 and OGDHL as linkers between mitochondrial dysfunction and eosinophilic esophagitis. JCI Insight  2018; 3(8): 3.
[http://dx.doi.org/10.1172/jci.insight.99922] [PMID:  29669943] 
[45] 
Jensen ET, Kuhl JT, Martin LJ, Langefeld CD, Dellon ES, Rothenberg ME. Early-life environmental exposures interact with genetic
	sus-ceptibility variants in pediatric patients with eosinophilic esophagitis.
	J Allergy Clin Immunol 2018; 141: 632-637 e5.. 
[46] 
Radano MC, Yuan Q, Katz A, et al. Cesarean section and antibiotic
	use found to be associated with eosinophilic esophagitis. J Allergy
	Clin Immunol Pract 2014; 2: 475-477 e1.. 
[47] 
Slae M, Persad R, Leung AJ, Gabr R, Brocks D, Huynh HQ. Role of Environmental Factors in the Development of Pediatric Eosinophilic Esophagitis. Dig Dis Sci  2015; 60(11): 3364-72.
[http://dx.doi.org/10.1007/s10620-015-3740-7] [PMID:  26062820] 
[48] 
Cianferoni A, Ruffner MA, Guzek R, et al. Elevated expression of activated TH2 cells and milk-specific TH2 cells in milk-induced eosinophilic esophagitis Ann Allergy Asthma Immunol 2018; 120:
207	177-183 e2.. 
[49] 
Cianferoni A, Spergel J. The importance of TSLP in allergic disease and its role as a potential therapeutic target. Expert Rev Clin Immunol  2014; 10(11): 1463-74.
[http://dx.doi.org/10.1586/1744666X.2014.967684] [PMID:  25340427] 
[50] 
Ruffner MA, Kennedy K, Cianferoni A. Pathophysiology of eosinophilic esophagitis: recent advances and their clinical implications. Expert Rev Clin Immunol  2018; 1-13.
[PMID:  30394139] 
[51] 
Spergel JM, Aceves SS, Kliewer K, et al. New developments in patients with eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERS Symposium at the 2018 American Academy of Allergy, Asthma & Immunology Meeting. J Allergy Clin Immunol  2018; 142(1): 48-53.
[http://dx.doi.org/10.1016/j.jaci.2018.05.005] [PMID:  29803797] 
[52] 
Simon D, Cianferoni A, Spergel JM, et al. Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity. Allergy  2016; 71(5): 611-20.
[http://dx.doi.org/10.1111/all.12846] [PMID:  26799684] 
[53] 
Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults;
	food reintroduction identifies causative factors. Gastroenterology
	2012; 142: 1451-1459 e1.. 
[54] 
Lucendo AJ. Meta-Analysis-Based Guidance for Dietary Management in Eosinophilic Esophagitis. Curr Gastroenterol Rep  2015; 17(10): 464.
[http://dx.doi.org/10.1007/s11894-015-0464-y] [PMID:  26292666] 
[55] 
Petroni D, Spergel JM. Eosinophilic esophagitis and symptoms possibly related to eosinophilic esophagitis in oral immunotherapy Ann Allergy Asthma Immunol 2018; 120: 237-240 e4.. 
[http://dx.doi.org/10.1016/j.anai.2017.11.016] 
[56] 
Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol  2014; 113(6): 624-9.
[http://dx.doi.org/10.1016/j.anai.2014.08.004] [PMID:  25216976] 
[57] 
Maggadottir SM, Hill DA, Ruymann K, et al. Resolution of acute IgE-mediated allergy with development of eosinophilic esophagitis
	triggered by the same food. J Allergy Clin Immunol 2014; 133:
	1487-1489 e1.. 
[58] 
Ridolo E, De Angelis GL, Dall’aglio P. Eosinophilic esophagitis after specific oral tolerance induction for egg protein. Ann Allergy Asthma Immunol  2011; 106(1): 73-4.
[http://dx.doi.org/10.1016/j.anai.2010.10.010] [PMID:  21195949] 
[59] 
Kasagi Y, Dods K, Wang JX, et al. Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-alpha. J Allergy Clin Immunol  2019; 144(1): 171-82.
[PMID:  30578874] 
[60] 
Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. 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.
[http://dx.doi.org/10.1053/j.gastro.2003.09.024] [PMID:  14724818] 
[61] 
Spechler SJ, Konda V, Souza R. Can Eosinophilic Esophagitis Cause Achalasia and Other Esophageal Motility Disorders? Am J Gastroenterol  2018; 113(11): 1594-9.
[http://dx.doi.org/10.1038/s41395-018-0240-3] [PMID:  30315308] 
[62] 
Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol  2011; 128(1): 3-20.e6.
[http://dx.doi.org/10.1016/j.jaci.2011.02.040] [PMID:  21477849] 
[63] 
Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis. Gastroenterology  2018; 155(4): 1022-1033.e10.
[64] 
Spergel JM, Dellon ES, Liacouras CA, et al. participants of AGREE. Summary of the updated international consensus diagnostic criteria for eosinophilic esophagitis: AGREE conference. Ann Allergy Asthma Immunol  2018; 121(3): 281-4.
[http://dx.doi.org/10.1016/j.anai.2018.05.035] [PMID:  30030146] 
[65] 
Lucendo AJ, Arias A, Molina-Infante J. Efficacy of proton pump inhibitor drugs for inducing clinical and histologic remission in patients with symptomatic esophageal eosinophilia: A systematic review and meta-analysis Clin Gastroenterol Hepatol 2016; 14: 13-
	22 e1.. 
[http://dx.doi.org/10.1016/j.cgh.2015.07.041] 
[66] 
Wen T, Dellon ES, Moawad FJ, Furuta GT, Aceves SS, Rothenberg ME. Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation. J Allergy Clin Immunol  2015; 135(1): 187-97.
[http://dx.doi.org/10.1016/j.jaci.2014.08.043] [PMID:  25441638] 
[67] 
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(11)e50037
[http://dx.doi.org/10.1371/journal.pone.0050037] [PMID:  23185525] 
[68] 
Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol  2005; 3(12): 1198-206.
[http://dx.doi.org/10.1016/S1542-3565(05)00885-2] [PMID:  16361045] 
[69] 
Caldwell JM, Blanchard C, Collins MH, et al. .Glucocorticoidregulated
	genes in eosinophilic esophagitis: a role for FKBP51. J
	Allergy Clin Immunol 2010; 125: 879-888 e8.. 
[70] 
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(10): 2271-9.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01379.x] [PMID:  17581266] 
[71] 
Dohil R, Newbury R, Fox L, Bastian J, Aceves S. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology  2010; 139(2): 418-29.
[http://dx.doi.org/10.1053/j.gastro.2010.05.001] [PMID:  20457157] 
[72] 
Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology  2006; 131(5): 1381-91.
[http://dx.doi.org/10.1053/j.gastro.2006.08.033] [PMID:  17101314] 
[73] 
Noel RJ, Putnam PE, Collins MH, et al. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol  2004; 2(7): 568-75.
[http://dx.doi.org/10.1016/S1542-3565(04)00240-X] [PMID:  15224281] 
[74] 
Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology  2002; 122(5): 1216-25.
[http://dx.doi.org/10.1053/gast.2002.32998] [PMID:  11984507] 
[75] 
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 e1.. 
[http://dx.doi.org/10.1053/j.gastro.2010.07.048] 
[76] 
Dellon ES, Sheikh A, Speck O, et al. Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis Gastroenterology 2012; 143: 321-324 e1.. 
[http://dx.doi.org/10.1053/j.gastro.2012.04.049] 
[77] 
Aceves SS, Newbury RO, Chen D, et al. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy  2010; 65(1): 109-16.
[http://dx.doi.org/10.1111/j.1398-9995.2009.02142.x] [PMID:  19796194] 
[78] 
Lucendo AJ, Miehlke S, Schlag C, et al. International EOS-1 study group. Efficacy of budesonide orodispersible tablets as induction therapy for eosinophilic esophagitis in a randomized placebo-controlled trial. Gastroenterology  2019; 157(1): 74-86.e15.
[http://dx.doi.org/10.1053/j.gastro.2019.03.025] [PMID:  30922997] 
[79] 
Kelly HW, Sternberg AL, Lescher R, et al. CAMP Research Group. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med  2012; 367(10): 904-12.
[http://dx.doi.org/10.1056/NEJMoa1203229] [PMID:  22938716] 
[80] 
Turpeinen M, Pelkonen AS, Nikander K, et al. Bone mineral density in children treated with daily or periodical inhaled budesonide: the Helsinki Early Intervention Childhood Asthma study. Pediatr Res  2010; 68(2): 169-73.
[http://dx.doi.org/10.1203/PDR.0b013e3181e69e36] [PMID:  20485203] 
[81] 
Hsu S, Wood C, Pan Z, et al. Adrenal insufficiency in pediatric eosinophilic esophagitis patients treated with swallowed topical steroids. Pediatr Allergy Immunol Pulmonol  2017; 30(3): 135-40.
[http://dx.doi.org/10.1089/ped.2017.0779] [PMID:  29062584] 
[82] 
Spergel JM, Brown-Whitehorn TF, 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 e5.. 
[83] 
Kagalwalla AF, Sentongo TA, Ritz S, et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol  2006; 4(9): 1097-102.
[http://dx.doi.org/10.1016/j.cgh.2006.05.026] [PMID:  16860614] 
[84] 
Lucendo AJ, Arias Á, González-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(3): 797-804.
[http://dx.doi.org/10.1016/j.jaci.2012.12.664] [PMID:  23375693] 
[85] 
Molina-Infante J, Arias Á, Alcedo J, et al. Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study. J Allergy Clin Immunol  2018; 141(4): 1365-72.
[http://dx.doi.org/10.1016/j.jaci.2017.08.038] [PMID:  29074457] 
[86] 
Molina-Infante J, Arias A, Barrio J, Rodriguez-Sanchez J, Sanchez-Cazalilla M, Lucendo AJ. Four-food group elimination diet
	for adult eosinophilic esophagitis: A prospective multicenter study.
	J Allergy Clin Immunol 2014; 134: 1093-1099 e1. 
[87] 
Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology  1995; 109(5): 1503-12.
[http://dx.doi.org/10.1016/0016-5085(95)90637-1] [PMID:  7557132] 
[88] 
Cianferoni A, Shuker M, Brown-Whitehorn T, Hunter H, Venter C, Spergel JM. Food avoidance strategies in eosinophilic oesophagitis. Clin Exp Allergy  2019; 49(3): 269-84.
[http://dx.doi.org/10.1111/cea.13360] [PMID:  30714219] 
[89] 
Spergel J, Aceves SS. Allergic components of eosinophilic esophagitis. J Allergy Clin Immunol  2018; 142(1): 1-8.
[http://dx.doi.org/10.1016/j.jaci.2018.05.001] [PMID:  29980277] 
[90] 
Clayton F, Fang JC, Gleich GJ, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology  2014; 147(3): 602-9.
[http://dx.doi.org/10.1053/j.gastro.2014.05.036] [PMID:  24907494] 
[91] 
Conus S, Straumann A, Bettler E, Simon HU. Mepolizumab does not alter levels of eosinophils, T cells, and mast cells in the duodenal mucosa in eosinophilic esophagitis. J Allergy Clin Immunol  2010; 126(1): 175-7.
[http://dx.doi.org/10.1016/j.jaci.2010.04.029] [PMID:  20542323] 
[92] 
Straumann A, Conus S, Grzonka P, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut  2010; 59(1): 21-30.
[http://dx.doi.org/10.1136/gut.2009.178558] [PMID:  19828470] 
[93] 
Conus S, Straumann A, Simon HU. Anti-IL-5 (mepolizumab) therapy does not alter IL-5 receptor alpha levels in patients with eosinophilic esophagitis. J Allergy Clin Immunol  2009; 123(1): 269.
[http://dx.doi.org/10.1016/j.jaci.2008.09.031] [PMID:  18951621] 
[94] 
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: 456-463 e1-3.. 
[95] 
Straumann A, Hoesli S, Bussmann Ch, et al. Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy  2013; 68(3): 375-85.
[http://dx.doi.org/10.1111/all.12096] [PMID:  23379537] 
[96] 
Sastre J, Dávila I. Dupilumab: A new paradigm for the treatment of allergic diseases. J Investig Allergol Clin Immunol  2018; 28(3): 139-50.
[http://dx.doi.org/10.18176/jiaci.0254] [PMID:  29939132] 
[97] 
Hirano I, Collins MH, Assouline-Dayan Y, et al. RPC4046, a Monoclonal
	Antibody Against IL13, Reduces histologic and endoscopic
	activity in patients with eosino-philic esophagitis. Gastroenterology
	2019; 156: 592-603 e10.. 
[98] 
Straumann A. Idiopathic eosinophilic gastrointestinal diseases in adults. Best Pract Res Clin Gastroenterol  2008; 22(3): 481-96.
[http://dx.doi.org/10.1016/j.bpg.2007.09.001] [PMID:  18492567] 
[99] 
Furuta GT, Forbes D, Boey C, et al. Eosinophilic Gastrointestinal Diseases Working Group. Eosinophilic gastrointestinal diseases (EGIDs). J Pediatr Gastroenterol Nutr  2008; 47(2): 234-8.
[http://dx.doi.org/10.1097/MPG.0b013e318181b1c3] [PMID:  18664881] 
[100] 
Mukkada VA, Furuta GT. Idiopathic eosinophilic disorders of the gastrointestinal tract in children. Best Pract Res Clin Gastroenterol  2008; 22(3): 497-509.
[http://dx.doi.org/10.1016/j.bpg.2007.09.002] [PMID:  18492568] 
[101] 
Pineton de Chambrun G, Gonzalez F, Canva JY, et al. Natural history of eosinophilic gastroenteritis Clin Gastroenterol Hepatol
	2011; 9: 950-956 e1.. 
[http://dx.doi.org/10.1016/j.cgh.2011.07.017] 
[102] 
Ko HM, Morotti RA, Yershov O, Chehade M. Eosinophilic gastritis in children: clinicopathological correlation, disease course, and response to therapy. Am J Gastroenterol  2014; 109(8): 1277-85.
[http://dx.doi.org/10.1038/ajg.2014.166] [PMID:  24957155] 
[103] 
Caldwell JM, Collins MH, Stucke EM, et al. Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome. J Allergy Clin Immunol  2014; 134(5): 1114-24.
[http://dx.doi.org/10.1016/j.jaci.2014.07.026] [PMID:  25234644] 
[104] 
Reed C, Woosley JT, Dellon ES. Clinical characteristics, treatment outcomes, and resource utilization in children and adults with eosinophilic gastroenteritis. Dig Liver Dis  2015; 47(3): 197-201.
[http://dx.doi.org/10.1016/j.dld.2014.11.009] [PMID:  25547198] 
[105] 
Lucendo AJ, Serrano-Montalban B, Arias A, Redondo O, Tenias JM. Systematic Review: The efficacy of dietary treatment for inducing disease remission in eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr  2015; 61(1): 56-64.
[http://dx.doi.org/10.1097/MPG.0000000000000766] 
[106] 
Chen MJ, Chu CH, Lin SC, Shih SC, Wang TE. Eosinophilic gastroenteritis: clinical experience with 15 patients. World J Gastroenterol  2003; 9(12): 2813-6.
[http://dx.doi.org/10.3748/wjg.v9.i12.2813] [PMID:  14669340] 
[107] 
Lombardi C, Salmi A, Passalacqua G. An adult case of eosinophilic pyloric stenosis maintained on remission with oral budesonide. Eur Ann Allergy Clin Immunol  2011; 43(1): 29-30.
[PMID: 21409859] 
[108] 
Lombardi C, Salmi A, Savio A, Passalacqua G. Localized eosinophilic ileitis with mastocytosis successfully treated with oral budesonide. Allergy  2007; 62(11): 1343-5.
[http://dx.doi.org/10.1111/j.1398-9995.2007.01461.x] [PMID:  17919149] 
[109] 
Elsing C, Placke J, Gross-Weege W. Budesonide for the treatment of obstructive eosinophilic jejunitis. Z Gastroenterol  2007; 45(2): 187-9.
[http://dx.doi.org/10.1055/s-2006-927138] [PMID:  17304405] 
[110] 
Siewert E, Lammert F, Koppitz P, Schmidt T, Matern S. Eosinophilic gastroenteritis with severe protein-losing enteropathy: successful treatment with budesonide  Digestive and liver disease : Official
journal of the Italian So-ciety of Gastroenterology and the
	Italian Association for the Study of the Liver 2006; 38: 55-9.. 
[http://dx.doi.org/10.1016/j.dld.2005.06.013] 
[111] 
Tan AC, Kruimel JW, Naber TH. Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets. Eur J Gastroenterol Hepatol  2001; 13(4): 425-7.
[http://dx.doi.org/10.1097/00042737-200104000-00021] [PMID:  11338074] 
[112] 
Kennedy K, Muir AB, Grossman A, et al. Modified oral enteric-coated budesonide regimens to treat pediatric eosinophilic gastroenteritis, a single center experience. J Allergy Clin Immunol Pract  2019; 7(6): 2059-61.
[http://dx.doi.org/10.1016/j.jaip.2019.01.053] [PMID:  30763733] 
[113] 
Sherrill JD, Rothenberg ME. Genetic and epigenetic underpinnings of eosinophilic esophagitis. Gastroenterol Clin North Am  2014; 43(2): 269-80.
[http://dx.doi.org/10.1016/j.gtc.2014.02.003] [PMID:  24813515] 
[114] 
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(5): 441-4.
[http://dx.doi.org/10.1016/S0025-6196(12)61640-1] [PMID:  8170195] 
[115] 
Chang JY, Choung RS, Lee RM, et al. A shift in the clinical spectrum of eosinophilic gastroenteritis toward the mucosal disease type. Clin Gastroenterol Hepatol  2010; 8(8): 669-75.
[http://dx.doi.org/10.1016/j.cgh.2010.04.022] [PMID:  20451664] 
[116] 
Wechsler JB, Hirano I. Biological therapies for eosinophilic gastrointestinal
	diseases. J Allergy Clin Immunol 2018; 142: 24-31
	e2.. 
[117] 
Powell GK. Milk- and soy-induced enterocolitis of infancy. Clinical features and standardization of challenge. J Pediatr  1978; 93(4): 553-60.
[http://dx.doi.org/10.1016/S0022-3476(78)80887-7] [PMID:  568171] 
[118] 
Powell GK. Food protein-induced enterocolitis of infancy: differential diagnosis and management. Compr Ther  1986; 12(2): 28-37.
[PMID:  3956146] 
[119] 
Nowak-Wegrzyn A, Chehade M, Groetch ME, et al. International
	consensus guidelines for the diagnosis and man-agement of food
	protein-induced enterocolitis syndrome: Ex-ecutive summary-
	Workgroup Report of the Adverse Reac-tions to Foods Committee,
	American Academy of Allergy, Asthma & Immunology. The
	Journal of allergy and clinical immunology 2017; 139: 1111-1126
	e4.. 
[120] 
Katz Y, Goldberg MR, Rajuan N, Cohen A, Leshno M. The prevalence
	and natural course of food protein-induced enterocolitis
	syndrome to cow’s milk: a large-scale, prospec-tive populationbased
	study. J Allergy Clin Immunol 2011; 127(3): 647-53.--> e1,
	3.. 
[121] 
Alonso SB, Ezquiaga JG, Berzal PT, et al. Food protein-induced enterocolitis syndrome: Increased prevalence of this great unknown-results of the PREVALE study. J Allergy Clin Immunol 2018.
[PMID:  30244024] 
[122] 
Nowak-Wegrzyn A, Warren CM, Brown-Whitehorn T, Cianferoni A, Schultz-Matney F, Gupta RS. Food protein-induced enterocolitis syndrome in the US popu-lation-based study J Allergy Clin Immunol 2019.S0091-6749(19): 30899-1.. 
[123] 
Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH. Food protein-induced enterocolitis syndrome caused by solid food proteins. Pediatrics  2003; 111(4 Pt 1): 829-35.
[http://dx.doi.org/10.1542/peds.111.4.829] [PMID:  12671120] 
[124] 
Hwang JB, Sohn SM, Kim AS. Prospective follow-up oral food challenge in food protein-induced enterocolitis syndrome. Arch Dis Child  2009; 94(6): 425-8.
[http://dx.doi.org/10.1136/adc.2008.143289] [PMID:  18829623] 
[125] 
Mehr S, Kakakios A, Frith K, Kemp AS. Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics  2009; 123(3): e459-64.
[http://dx.doi.org/10.1542/peds.2008-2029] [PMID:  19188266] 
[126] 
Sopo SM, Giorgio V, Dello Iacono I, Novembre E, Mori F, Onesimo R. A multicentre retrospective study of 66 Italian children with
	food protein-induced enterocolitis syndrome: different management
	for different phenotypes. Clinical and experimental allergy
	: journal of the British Socie-ty for Allergy and Clinical Immunology
	2012; 42: 1257-65.. 
[127] 
Ruffner MA, Ruymann K, Barni S, Cianferoni A, Brown-Whitehorn T, Spergel JM. Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract  2013; 1(4): 343-9.
[http://dx.doi.org/10.1016/j.jaip.2013.05.011] [PMID:  24565539] 
[128] 
Nomura I, Morita H, Ohya Y, Saito H, Matsumoto K. Non-IgE-mediated gastrointestinal food allergies: distinct differences in clinical phenotype between Western countries and Japan. Curr Allergy Asthma Rep  2012; 12(4): 297-303.
[http://dx.doi.org/10.1007/s11882-012-0272-5] [PMID:  22644865] 
[129] 
Ntoumpara M, Sotiriadou F, Fotoulaki M. Acute-on-chronic food protein-induced enterocolitis syndrome in an exclusively breast-fed infant. Clin Case Rep  2018; 7(1): 71-3.
[http://dx.doi.org/10.1002/ccr3.1905] [PMID:  30656011] 
[130] 
Joshi SR, Bird JA. Cow’s milk-associated chronic food protein-induced enterocolitis syndrome exacerbated by extensively hydrolyzed formula. Ann Allergy Asthma Immunol  2018; 120(5): 532-3.
[http://dx.doi.org/10.1016/j.anai.2018.02.025] [PMID:  29481888] 
[131] 
Weinberger T, Feuille E, Thompson C, Nowak-Węgrzyn A. Chronic food protein-induced enterocolitis syndrome: Characterization of clinical phenotype and literature review. Ann Allergy Asthma Immunol  2016; 117(3): 227-33.
[http://dx.doi.org/10.1016/j.anai.2016.03.004] [PMID:  27613454] 
[132] 
Miceli Sopo S, Monaco S, Greco M, Scala G. Chronic food protein-induced enterocolitis syndrome caused by cow’s milk proteins passed through breast milk. Int Arch Allergy Immunol  2014; 164(3): 207-9.
[http://dx.doi.org/10.1159/000365104] [PMID:  25034379] 
[133] 
Blackman AC, Anvari S, Davis CM, Anagnostou A. Emerging triggers of food protein-induced enterocolitis syndrome: Lessons from a pediatric cohort of 74 children in the United States. Ann Allergy Asthma Immunol  2019; 122(4): 407-11.
[http://dx.doi.org/10.1016/j.anai.2019.01.022] [PMID:  30742916] 
[134] 
Caubet JC, Ford LS, Sickles L, et al. Clinical features and resolution of food protein-induced enterocolitis syndrome: 10-year experience. J Allergy Clin Immunol  2014; 134(2): 382-9.
[http://dx.doi.org/10.1016/j.jaci.2014.04.008] [PMID:  24880634] 
[135] 
Barasche J, Stollar F, Bergmann MM, Caubet JC. Severely altered-consciousness status and profuse vomiting in infants: Food protein-induced enterocolitis syndrome (FPIES), a challenging diagnosis. Pediatr Emerg Care  2018; 34(10): e187-9.
[PMID:  27741073] 
[136] 
Wang KY, Lee J, Cianferoni A, et al. food protein-induced enterocolitis syndrome food challenges: experience from a large referral center. J Allergy Clin Immunol Pract  2019; 7(2): 444-50.
[http://dx.doi.org/10.1016/j.jaip.2018.09.009] [PMID:  30243880] 
[137] 
Nowak-Węgrzyn A, Katz Y, Mehr SS, Koletzko S. Non-IgE-mediated gastrointestinal food allergy. J Allergy Clin Immunol  2015; 135(5): 1114-24.
[http://dx.doi.org/10.1016/j.jaci.2015.03.025] [PMID:  25956013] 
[138] 
Caglayan Sozmen S, Povesi Dascola C, Gioia E, Mastrorilli C, Rizzuti L, Caffarelli C. Diagnostic accuracy of patch test in children with food allergy. Pediatr Allergy Immunol  2015; 26(5): 416-22.
[http://dx.doi.org/10.1111/pai.12377] [PMID:  25808316] 
[139] 
Caffarelli C, Dondi A, Povesi Dascola C, Ricci G. Skin prick test to foods in childhood atopic eczema: pros and cons. Ital J Pediatr  2013; 39: 48.
[http://dx.doi.org/10.1186/1824-7288-39-48] [PMID:  23902622] 
[140] 
Miceli Sopo S, Monaco S, Bersani G, Romano A, Fantacci C. Proposal for management of the infant with suspected food protein-induced allergic proctocolitis. Pediatr Allergy Immunol  2018; 29(2): 215-8.
[http://dx.doi.org/10.1111/pai.12844] [PMID:  29197125] 
[141] 
Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol  2001; 107(5): 891-6.
[http://dx.doi.org/10.1067/mai.2001.114708] [PMID:  11344358] 
[142] 
Verstege A, Mehl A, Rolinck-Werninghaus C, et al. The predictive value of the skin prick test weal size for the outcome of oral food challenges. Clin Exp Allergy  2005; 35(9): 1220-6.
[http://dx.doi.org/10.1111/j.1365-2222.2005.2324.x] [PMID:  16164451] 
[143] 
Boyano Martínez T, García-Ara C, Díaz-Pena JM, Muñoz FM, García Sánchez G, Esteban MM. Validity of specific IgE antibodies in children with egg allergy. Clin Exp Allergy  2001; 31(9): 1464-9.
[http://dx.doi.org/10.1046/j.1365-2222.2001.01175.x] [PMID:  11591198] 
[144] 
Monti G, Muratore MC, Peltran A, et al. High incidence of adverse reactions to egg challenge on first known exposure in young atopic dermatitis children: predictive value of skin prick test and radioallergosorbent test to egg proteins. Clin Exp Allergy  2002; 32(10): 1515-9.
[http://dx.doi.org/10.1046/j.1365-2745.2002.01454.x] [PMID:  12372134] 
[145] 
Roberts G, Lack G. Diagnosing peanut allergy with skin prick and specific IgE testing. J Allergy Clin Immunol  2005; 115(6): 1291-6.
[http://dx.doi.org/10.1016/j.jaci.2005.02.038] [PMID:  15940149] 
[146] 
Sporik R, Hill DJ, Hosking CS. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy  2000; 30(11): 1540-6.
[http://dx.doi.org/10.1046/j.1365-2222.2000.00928.x] [PMID:  11069561] 
[147] 
Celik-Bilgili S, Mehl A, Verstege A, et al. The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges. Clin Exp Allergy  2005; 35(3): 268-73.
[http://dx.doi.org/10.1111/j.1365-2222.2005.02150.x] [PMID:  15784102] 
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DOI https://dx.doi.org/10.2174/1573396315666191031103714	Print ISSN 1573-3963
Publisher Name Bentham Science Publisher	Online ISSN 1875-6336
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