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Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 1, pp 70–87 | Cite as

Dietary Therapy for Eosinophilic Esophagitis: Elimination and Reintroduction

  • Kara L. Kliewer
  • Alison M. Cassin
  • Carina Venter
Article

Abstract

Eosinophilic esophagitis (EoE) is a food antigen-mediated disorder of the esophagus characterized by eosinophil predominant inflammation and symptoms of esophageal dysfunction. Dietary antigen elimination induces clinical and histological remission in patients with EoE. The most restrictive of elimination diets (the elemental diet) removes all possible food antigens while empiric elimination diets remove all (or a subset) of food antigens most commonly reported to cause esophageal eosinophilia and food allergies (milk, egg, wheat, soy, peanuts, tree nuts, fish, or legumes). Elimination diets are effective treatments for EoE but pose psychosocial and financial challenges to patients and consequently may impair quality of life. Foods that are commonly eliminated, especially milk, are also nutrient-dense and therefore their elimination may result in inadequate nutrient intake or deficiencies without careful diet planning to include nutritionally comparable and safe food substitutes. After remission is achieved with elimination diets, foods can be reintroduced sequentially to identify specific food triggers, but this reintroduction is not standardized. Food elimination and food reintroductions should consider the patient’s lifestyle, nutrition needs, and skills and ideally be managed by a team with knowledge of eosinophilic gastrointestinal disorders and nutrition.

Keywords

Eosinophilic esophagitis Elimination diet Food reintroduction Nutrition 

Notes

Funding

There is no funding source for this review.

Compliance with Ethical Standards

Conflict of Interest

KK declares no conflicts of interest. AC has received honoraria from Nutricia and Abbott Nutrition. CV has received honoraria from Danone, Nestle, Mead Johnson, and DBV Technologies.

Ethical Approval and Informed Consent

This article does not contain any studies with human participants or animals performed by any of the authors. The present article is a review; therefore, no informed consent was required.

References

  1. 1.
    Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA et al (2011) Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 128(1):3–20 e6; quiz 1-2PubMedCrossRefGoogle Scholar
  2. 2.
    Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA (1995) Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology 109(5):1503–1512PubMedCrossRefGoogle Scholar
  3. 3.
    Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM et al (2006) Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol 4(9):1097–1102PubMedCrossRefGoogle Scholar
  4. 4.
    Arias A, Gonzalez-Cervera J, Tenias JM, Lucendo AJ (2014) Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology 146(7):1639–1648PubMedCrossRefGoogle Scholar
  5. 5.
    Peterson KA, Byrne KR, Vinson LA, Ying J, Boynton KK, Fang JC, Gleich GJ, Adler DG, Clayton F (2013) Elemental diet induces histologic response in adult eosinophilic esophagitis. Am J Gastroenterol 108(5):759–766.  https://doi.org/10.1038/ajg.2012.468 PubMedCrossRefGoogle Scholar
  6. 6.
    Warners MJ, Vlieg-Boerstra BJ, Verheij J, van Rhijn BD, Van Ampting MT, Harthoorn LF et al (2017) Elemental diet decreases inflammation and improves symptoms in adult eosinophilic oesophagitis patients. Aliment Pharmacol Ther 45(6):777–787.  https://doi.org/10.1111/apt.13953 PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Henderson CJ, Abonia JP, King EC, Putnam PE, Collins MH, Franciosi JP, Rothenberg ME (2012) Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol 129(6):1570–1578.  https://doi.org/10.1016/j.jaci.2012.03.023 PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Al-Hussaini A, Al-Idressi E, Al-Zahrani M (2013) The role of allergy evaluation in children with eosinophilic esophagitis. J Gastroenterol 48(11):1205–1212PubMedCrossRefGoogle Scholar
  9. 9.
    De Agustin JC, Sanz N, Canals MJ, Alvarez E, Morales JL, Soler J et al (2002) Successful medical treatment of two patients with eosinophilic oesophagitis. J Pediatr Surg 37(2):207–213PubMedCrossRefGoogle Scholar
  10. 10.
    Kagalwalla AF, Amsden K, Shah A, Ritz S, Manuel-Rubio M, Dunne K, Nelson SP, Wershil BK, Melin-Aldana H (2012) Cow’s milk elimination: a novel dietary approach to treat eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 55(6):711–716.  https://doi.org/10.1097/MPG.0b013e318268da40 PubMedCrossRefGoogle Scholar
  11. 11.
    Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, Flick J, Kelly J, Brown–Whitehorn T, Mamula P, Markowitz JE (2005) Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 3(12):1198–1206.  https://doi.org/10.1016/S1542-3565(05)00885-2 PubMedCrossRefGoogle Scholar
  12. 12.
    Lucendo AJ, Arias A, Gonzalez-Cervera J, Yague-Compadre JL, Guagnozzi D, Angueira T et al (2013) 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 131(3):797–804.  https://doi.org/10.1016/j.jaci.2012.12.664 PubMedCrossRefGoogle Scholar
  13. 13.
    Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I (2012) Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology 142(7):1451–9 e1 quiz e14–5PubMedCrossRefGoogle Scholar
  14. 14.
    Wolf WA, Jerath MR, Sperry SL, Shaheen NJ, Dellon ES (2014) Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol 12(8):1272–1279.  https://doi.org/10.1016/j.cgh.2013.12.034 PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Rodriguez-Sanchez J, Gomez Torrijos E, Lopez Viedma B, de la Santa Belda E, Martin Davila F, Garcia Rodriguez C et al (2014) Efficacy of IgE-targeted vs empiric six-food elimination diets for adult eosinophilic oesophagitis. Allergy 69(7):936–942.  https://doi.org/10.1111/all.12420 PubMedCrossRefGoogle Scholar
  16. 16.
    Philpott H, Nandurkar S, Royce SG, Thien F, Gibson PR (2016) A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis. Aliment Pharmacol Ther 43(9):985–993.  https://doi.org/10.1111/apt.13576 PubMedCrossRefGoogle Scholar
  17. 17.
    Kagalwalla AF, Shah A, Li BU, Sentongo TA, Ritz S, Manuel-Rubio M et al (2011) Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr 53(2):145–149.  https://doi.org/10.1097/MPG.0b013e31821cf503 PubMedCrossRefGoogle Scholar
  18. 18.
    Molina-Infante J, Arias A, Barrio J, Rodriguez-Sanchez J, Sanchez-Cazalilla M, Lucendo AJ (2014) Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study. J Allergy Clin Immunol 134(5):1093–1099 e1PubMedCrossRefGoogle Scholar
  19. 19.
    Kagalwalla AF, Wechsler JB, Amsden K, Schwartz S, Makhija M, Olive A, Davis CM, Manuel-Rubio M, Marcus S, Shaykin R, Sulkowski M, Johnson K, Ross JN, Riffle ME, Groetch M, Melin-Aldana H, Schady D, Palac H, Kim KYA, Wershil BK, Collins MH, Chehade M (2017) Efficacy of a 4-food elimination diet for children with eosinophilic esophagitis. Clin Gastroenterol Hepatol 15(11):1698–1707.e7.  https://doi.org/10.1016/j.cgh.2017.05.048 PubMedCrossRefGoogle Scholar
  20. 20.
    Molina-Infante J, Arias A, Alcedo J, Garcia-Romero R, Casabona-Frances S, Prieto-Garcia A, Modolell I, Gonzalez-Cordero PL, Perez-Martinez I, Martin-Lorente JL, Guarner-Argente C, Masiques ML, Vila-Miravet V, Garcia-Puig R, Savarino E, Sanchez-Vegazo CT, Santander C, Lucendo AJ (2017) Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: the 2-4-6 study. J Allergy Clin Immunol.  https://doi.org/10.1016/j.jaci.2017.08.038
  21. 21.
    Kruszewski PG, Russo JM, Franciosi JP, Varni JW, Platts-Mills TA, Erwin EA (2016) Prospective, comparative effectiveness trial of cow’s milk elimination and swallowed fluticasone for pediatric eosinophilic esophagitis. Dis Esophagus 29(4):377–384.  https://doi.org/10.1111/dote.12339 PubMedCrossRefGoogle Scholar
  22. 22.
    Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA (2002) The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol 109(2):363–368.  https://doi.org/10.1067/mai.2002.121458 PubMedCrossRefGoogle Scholar
  23. 23.
    Simon D, Cianferoni A, Spergel JM, Aceves S, Holbreich M, Venter C, Rothenberg ME, Terreehorst I, Muraro A, Lucendo AJ, Schoepfer A, Straumann A, Simon HU (2016) Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity. Allergy 71(5):611–620.  https://doi.org/10.1111/all.12846 PubMedCrossRefGoogle Scholar
  24. 24.
    van Rhijn BD, Vlieg-Boerstra BJ, Versteeg SA, Akkerdaas JH, van Ree R, Terreehorst I, Sprikkelman AB, Verheij J, Smout AJPM, Bredenoord AJ (2015) Evaluation of allergen-microarray-guided dietary intervention as treatment of eosinophilic esophagitis. J Allergy Clin Immunol 136(4):1095–1097 e3.  https://doi.org/10.1016/j.jaci.2015.02.038 PubMedCrossRefGoogle Scholar
  25. 25.
    Clayton F, Fang JC, Gleich GJ, Lucendo AJ, Olalla JM, Vinson LA, Lowichik A, Chen X, Emerson L, Cox K, O’Gorman MA, Peterson KA (2014) Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology 147(3):602–609.  https://doi.org/10.1053/j.gastro.2014.05.036 PubMedCrossRefGoogle Scholar
  26. 26.
    Wilson JM, Schuyler AJ, Tripathi A, Erwin EA, Commins SP, Platts-Mills TAE (2016) IgG4 component allergens are preferentially increased in eosinophilic esophagitis as compared to patients with milk anaphylaxis or galactose-alpha-1,3-galactose allergy. J Allergy Clin Immunol. Presented AAAAI 2016Google Scholar
  27. 27.
    Venter C, Fleischer DM (2016) Diets for diagnosis and management of food allergy: the role of the dietitian in eosinophilic esophagitis in adults and children. Ann Allergy Asthma Immunol 117(5):468–471.  https://doi.org/10.1016/j.anai.2016.08.003 PubMedCrossRefGoogle Scholar
  28. 28.
    Liacouras CA, Wenner WJ, Brown K, Ruchelli E (1998) Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr 26(4):380–385PubMedCrossRefGoogle Scholar
  29. 29.
    Aceves SS, Dohil R, Newbury RO, Bastian JF (2005) Topical viscous budesonide suspension for treatment of eosinophilic esophagitis. J Allergy Clin Immunol 116(3):705–706PubMedCrossRefGoogle Scholar
  30. 30.
    Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, Akers R, Cohen MB, Collins MH, Assa’ad AH, Aceves SS, Putnam PE, Rothenberg ME (2006) A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology 131(5):1381–1391.  https://doi.org/10.1053/j.gastro.2006.08.033 PubMedCrossRefGoogle Scholar
  31. 31.
    Ahmet A, Benchimol EI, Goldbloom EB, Barkey JL (2016) Adrenal suppression in children treated with swallowed fluticasone and oral viscous budesonide for eosinophilic esophagitis. Allergy Asthma Clin Immunol 12:49PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Golekoh MC, Hornung LN, Mukkada VA, Khoury JC, Putnam PE, Backeljauw PF (2016) Adrenal insufficiency after chronic swallowed glucocorticoid therapy for eosinophilic esophagitis. J Pediatr 170:240–245.  https://doi.org/10.1016/j.jpeds.2015.11.026 PubMedCrossRefGoogle Scholar
  33. 33.
    Turpeinen M, Pelkonen AS, Nikander K, Sorva R, Selroos O, Juntunen-Backman K, Haahtela T (2010) Bone mineral density in children treated with daily or periodical inhaled budesonide: the Helsinki early intervention childhood asthma study. Pediatr Res 68(2):169–173.  https://doi.org/10.1203/PDR.0b013e3181e69e36 PubMedCrossRefGoogle Scholar
  34. 34.
    Pedersen S (2006) Clinical safety of inhaled corticosteroids for asthma in children: an update of long-term trials. Drug Saf 29(7):599–612PubMedCrossRefGoogle Scholar
  35. 35.
    Wolf WA, Cotton CC, Green DJ, Hughes JT, Woosley JT, Shaheen NJ, Dellon ES (2015) Predictors of response to steroid therapy for eosinophilic esophagitis and treatment of steroid-refractory patients. Clin Gastroenterol Hepatol 13(3):452–458.  https://doi.org/10.1016/j.cgh.2014.07.034 PubMedCrossRefGoogle Scholar
  36. 36.
    Leung J, Hundal NV, Katz AJ, Shreffler WG, Yuan Q, Butterworth CA et al (2013) Tolerance of baked milk in patients with cow’s milk-mediated eosinophilic esophagitis. J Allergy Clin Immunol 132(5):1215–1216 e1PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Groetch M, Henry M, Feuling MB, Kim J (2013) Guidance for the nutrition management of gastrointestinal allergy in pediatrics. J Allergy Clin Immunol Pract 1(4):323–331.  https://doi.org/10.1016/j.jaip.2013.05.002 PubMedCrossRefGoogle Scholar
  38. 38.
    Burks AW, Jones SM, Boyce JA, Sicherer SH, Wood RA, Assa’ad A et al (2011) NIAID-sponsored 2010 guidelines for managing food allergy: applications in the pediatric population. Pediatrics 128(5):955–965PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Singhal S, Baker RD, Baker SS (2017) A comparison of the nutritional value of cow’s milk and nondairy beverages. J Pediatr Gastroenterol Nutr 64(5):799–805.  https://doi.org/10.1097/MPG.0000000000001380 PubMedCrossRefGoogle Scholar
  40. 40.
    Fiocchi A, Schunemann HJ, Brozek J, Restani P, Beyer K, Troncone R et al (2010) Diagnosis and Rationale for Action Against Cow’s Milk Allergy (DRACMA): a summary report. J Allergy Clin Immunol 126(6):1119–1128 e12PubMedCrossRefGoogle Scholar
  41. 41.
    Carvalho NF, Kenney RD, Carrington PH, Hall DE (2001) Severe nutritional deficiencies in toddlers resulting from health food milk alternatives. Pediatrics 107(4):E46PubMedCrossRefGoogle Scholar
  42. 42.
    Kliewer KL, Venter C, Cassin AM, Abonia JP, Aceves SS, Bonis PA et al (2016) Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet? J Allergy Clin Immunol 137(4):1011–1014PubMedCrossRefGoogle Scholar
  43. 43.
    Doerfler B, Bryce P, Hirano I, Gonsalves N (2015) Practical approach to implementing dietary therapy in adults with eosinophilic esophagitis: the Chicago experience. Dis Esophagus 28(1):42–58PubMedCrossRefGoogle Scholar
  44. 44.
    Hernando A, Mujico JR, Mena MC, Lombardia M, Mendez E (2008) Measurement of wheat gluten and barley hordeins in contaminated oats from Europe, the United States and Canada by Sandwich R5 ELISA. Eur J Gastroenterol Hepatol 20(6):545–554.  https://doi.org/10.1097/MEG.0b013e3282f46597 PubMedCrossRefGoogle Scholar
  45. 45.
    Marketsandmarkets.com. Gluten-free products market by type, sales channel and geography: global trends and forecasts to 2018. Available at http://www.marketsandmarkets.com/MarketReports/gluten-free-products-market-738.html2013
  46. 46.
    Awazuhara H, Kawai H, Baba M, Matsui T, Komiyama A (1998) Antigenicity of the proteins in soy lecithin and soy oil in soybean allergy. Clin Exp Allergy 28(12):1559–1564.  https://doi.org/10.1046/j.1365-2222.1998.00431.x PubMedCrossRefGoogle Scholar
  47. 47.
    Groetch M, Venter C, Skypala I, Vlieg-Boerstra B, Grimshaw K, Durban R, Cassin A, Henry M, Kliewer K, Kabbash L, Atkins D, Nowak-Węgrzyn A, Holbreich M, Chehade M, Eosinophilic Gastrointestinal Disorders Committee of the American Academy of Allergy, Asthma and Immunology (2017) Dietary therapy and nutrition management of eosinophilic esophagitis: a work group report of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol Pract 5(2):312–324 e29.  https://doi.org/10.1016/j.jaip.2016.12.026 PubMedCrossRefGoogle Scholar
  48. 48.
    Borneo R, Aguirre A, Leon AE (2010) Chia (Salvia hispanica L) gel can be used as egg or oil replacer in cake formulations. J Am Diet Assoc 110(6):946–949PubMedCrossRefGoogle Scholar
  49. 49.
    Leonard SA, Nowak-Wegrzyn AH (2016) Baked milk and egg diets for milk and egg allergy management. Immunol Allergy Clin N Am 36(1):147–159.  https://doi.org/10.1016/j.iac.2015.08.013 CrossRefGoogle Scholar
  50. 50.
    Assa'ad AH, Putnam PE, Collins MH, Akers RM, Jameson SC, Kirby CL et al (2007) Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol 119(3):731–738PubMedCrossRefGoogle Scholar
  51. 51.
    Teuber SS, Brown RL, Haapanen LA (1997) Allergenicity of gourmet nut oils processed by different methods. J Allergy Clin Immunol 99(4):502–507PubMedCrossRefGoogle Scholar
  52. 52.
    Stutius LM, Sheehan WJ, Rangsithienchai P, Bharmanee A, Scott JE, Young MC, Dioun AF, Schneider LC, Phipatanakul W (2010) Characterizing the relationship between sesame, coconut, and nut allergy in children. Pediatr Allergy Immunol 21(8):1114–1118.  https://doi.org/10.1111/j.1399-3038.2010.00997.x PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Fiocchi A, Bouygue GR, Sarratud T, Terracciano L, Martelli A, Restani P (2004) Clinical tolerance of processed foods. Ann Allergy Asthma Immunol 93(5 Suppl 3):S38–S46.  https://doi.org/10.1016/S1081-1206(10)61731-0 PubMedCrossRefGoogle Scholar
  54. 54.
    United States Food and Drug Administration CfFSaAN. Food Allergen Labeling and Consumer Protection Act of 2004 (Title II of Public Law 108e282). August 2004 ed2004Google Scholar
  55. 55.
    Allen KJ, Turner PJ, Pawankar R, Taylor S, Sicherer S, Lack G, Rosario N, Ebisawa M, Wong G, Mills EN, Beyer K, Fiocchi A, Sampson HA (2014) Precautionary labelling of foods for allergen content: are we ready for a global framework? World Allergy Organ J 7(1):10.  https://doi.org/10.1186/1939-4551-7-10 PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Turner PJ, Kemp AS, Campbell DE (2011) Advisory food labels: consumers with allergies need more than “traces” of information. BMJ 343(oct13 2):d6180.  https://doi.org/10.1136/bmj.d6180 PubMedCrossRefGoogle Scholar
  57. 57.
    Ford LS, Taylor SL, Pacenza R, Niemann LM, Lambrecht DM, Sicherer SH (2010) Food allergen advisory labeling and product contamination with egg, milk, and peanut. J Allergy Clin Immunol 126(2):384–385.  https://doi.org/10.1016/j.jaci.2010.05.034 PubMedCrossRefGoogle Scholar
  58. 58.
    Taft TH, Ballou S, Keefer L (2012) Preliminary evaluation of maternal caregiver stress in pediatric eosinophilic gastrointestinal disorders. J Pediatr Psychol 37(5):523–532PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Menard-Katcher C, Henry M, Furuta GT, Atkins D, Maune NC, Haas AM (2014) Significance of feeding dysfunction in eosinophilic esophagitis. World J Gastroenterol 20(31):11019–11022PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Haas AM, Maune NC (2009) Clinical presentation of feeding dysfunction in children with eosinophilic gastrointestinal disease. Immunol Allergy Clin N Am 29(1):65–75 ixCrossRefGoogle Scholar
  61. 61.
    Mukkada VA, Haas A, Maune NC, Capocelli KE, Henry M, Gilman N et al (2010) Feeding dysfunction in children with eosinophilic gastrointestinal diseases. Pediatrics 126(3):e672–e677PubMedCrossRefGoogle Scholar
  62. 62.
    Pentiuk S, Putnam PE, Collins MH, Rothenberg ME (2009) Dissociation between symptoms and histological severity in pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 48(2):152–160.  https://doi.org/10.1097/MPG.0b013e31817f0197 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    van Rhijn BD, van Ree R, Versteeg SA, Vlieg-Boerstra BJ, Sprikkelman AB, Terreehorst I, Smout AJPM, Bredenoord AJ (2013) Birch pollen sensitization with cross-reactivity to food allergens predominates in adults with eosinophilic esophagitis. Allergy 68(11):1475–1481.  https://doi.org/10.1111/all.12257 PubMedCrossRefGoogle Scholar
  64. 64.
    Mahdavinia M, Bishehsari F, Hayat W, Elhassan A, Tobin MC, Ditto AM (2017) Association of eosinophilic esophagitis and food pollen allergy syndrome. Ann Allergy Asthma Immunol 118(1):116–117.  https://doi.org/10.1016/j.anai.2016.10.012 PubMedCrossRefGoogle Scholar
  65. 65.
    Ram G, Lee J, Ott M, Brown-Whitehorn TF, Cianferoni A, Shuker M, Wang ML, Verma R, Liacouras CA, Spergel JM (2015) Seasonal exacerbation of esophageal eosinophilia in children with eosinophilic esophagitis and allergic rhinitis. Ann Allergy Asthma Immunol 115(3):224–228 e1.  https://doi.org/10.1016/j.anai.2015.07.004 PubMedCrossRefGoogle Scholar
  66. 66.
    Broussard JL, Devkota S (2016) The changing microbial landscape of Western society: diet, dwellings and discordance. Mol Metab 5(9):737–742.  https://doi.org/10.1016/j.molmet.2016.07.007 PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Tamburini S, Shen N, HC W, Clemente JC (2016) The microbiome in early life: implications for health outcomes. Nat Med 22(7):713–722PubMedCrossRefGoogle Scholar
  68. 68.
    Jensen ET, Kuhl JT, Martin LJ, Rothenberg ME, Dellon ES (2017) Prenatal, intrapartum, and postnatal factors are associated with pediatric eosinophilic esophagitis. J Allergy Clin ImmunolGoogle Scholar
  69. 69.
    Benitez AJ, Hoffmann C, Muir AB, Dods KK, Spergel JM, Bushman FD, Wang ML (2015) Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome 3(1):23.  https://doi.org/10.1186/s40168-015-0085-6 PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Harris JK, Fang R, Wagner BD, Choe HN, Kelly CJ, Schroeder S, Moore W, Stevens MJ, Yeckes A, Amsden K, Kagalwalla AF, Zalewski A, Hirano I, Gonsalves N, Henry LN, Masterson JC, Robertson CE, Leung DY, Pace NR, Ackerman SJ, Furuta GT, Fillon SA (2015) Esophageal microbiome in eosinophilic esophagitis. PLoS One 10(5):e0128346.  https://doi.org/10.1371/journal.pone.0128346 PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA (2003) Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol 98(4):777–782PubMedCrossRefGoogle Scholar
  72. 72.
    Wechsler JB, Schwartz S, Amsden K, Kagalwalla AF (2014) Elimination diets in the management of eosinophilic esophagitis. J Asthma Allergy 7:85–94.  https://doi.org/10.2147/JAA.S47243 PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Miles MV, Putnam PE, Miles L, Tang PH, DeGrauw AJ, Wong BL, Horn PS, Foote HL, Rothenberg ME (2011) Acquired coenzyme Q10 deficiency in children with recurrent food intolerance and allergies. Mitochondrion 11(1):127–135.  https://doi.org/10.1016/j.mito.2010.08.010 PubMedCrossRefGoogle Scholar
  74. 74.
    Lucendo AJ, Arias A, Gonzalez-Cervera J, Mota-Huertas T, Yague-Compadre JL (2013) Tolerance of a cow’s milk-based hydrolyzed formula in patients with eosinophilic esophagitis triggered by milk. Allergy 68(8):1065–1072PubMedCrossRefGoogle Scholar
  75. 75.
    Delaney AL, Arvedson JC (2008) Development of swallowing and feeding: prenatal through first year of life. Dev Disabil Res Rev 14(2):105–117.  https://doi.org/10.1002/ddrr.16 PubMedCrossRefGoogle Scholar
  76. 76.
    Davis BP, Rothenberg ME (2013) Emerging concepts of dietary therapy for pediatric and adult eosinophilic esophagitis. Expert Rev Clin Immunol 9(4):285–287PubMedCrossRefGoogle Scholar
  77. 77.
    Pelz BJ, Wechsler JB, Amsden K, Johnson K, Singh AM, Wershil BK, Kagalwalla AF, Bryce PJ (2016) IgE-associated food allergy alters the presentation of paediatric eosinophilic esophagitis. Clin Exp Allergy 46(11):1431–1440.  https://doi.org/10.1111/cea.12776 PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Colson D, Kalach N, Soulaines P, Vannerom Y, Campeotto F, Talbotec C, Chatenoud L, Hankard R, Dupont C (2014) The impact of dietary therapy on clinical and biologic parameters of pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol Pract 2(5):587–593.  https://doi.org/10.1016/j.jaip.2014.05.012 PubMedCrossRefGoogle Scholar
  79. 79.
    Berry MJ, Adams J, Voutilainen H, Feustel PJ, Celestin J, Jarvinen KM (2015) Impact of elimination diets on growth and nutritional status in children with multiple food allergies. Pediatr Allergy Immunol 26(2):133–138PubMedCrossRefGoogle Scholar
  80. 80.
    Meyer R, De Koker C, Dziubak R, Venter C, Dominguez-Ortega G, Cutts R, Yerlett N, Skrapak AK, Fox AT, Shah N (2014) Malnutrition in children with food allergies in the UK. J Hum Nutr Diet 27(3):227–235.  https://doi.org/10.1111/jhn.12149 PubMedCrossRefGoogle Scholar
  81. 81.
    Flammarion S, Santos C, Guimber D, Jouannic L, Thumerelle C, Gottrand F et al (2011) Diet and nutritional status of children with food allergies. Pediatr Allergy Immunol 22(2):161–165PubMedCrossRefGoogle Scholar
  82. 82.
    Thomassen RA, Kvammen JA, Eskerud MB, Juliusson PB, Henriksen C, Rugtveit J (2017) Iodine status and growth in 0-2-year-old infants with cow’s milk protein allergy. J Pediatr Gastroenterol Nutr 64(5):806–811.  https://doi.org/10.1097/MPG.0000000000001434 PubMedCrossRefGoogle Scholar
  83. 83.
    Tuokkola J, Luukkainen P, Nevalainen J, Ahonen S, Toppari J, Ilonen J, Veijola R, Knip M, Virtanen SM, Kaila M (2017) Eliminating cows' milk, but not wheat, barley or rye, increases the risk of growth deceleration and nutritional inadequacies. Acta Paediatr 106(7):1142–1149.  https://doi.org/10.1111/apa.13846 PubMedCrossRefGoogle Scholar
  84. 84.
    Berni Canani R, Leone L, D'Auria E, Riva E, Nocerino R, Ruotolo S et al (2014) The effects of dietary counseling on children with food allergy: a prospective, multicenter intervention study. J Acad Nutr Diet 114(9):1432–1439PubMedCrossRefGoogle Scholar
  85. 85.
    Robbins KA, Wood RA, Keet CA (2014) Milk allergy is associated with decreased growth in US children. J Allergy Clin Immunol 134(6):1466–1468 e6.  https://doi.org/10.1016/j.jaci.2014.08.037 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Christie L, Hine RJ, Parker JG, Burks W (2002) Food allergies in children affect nutrient intake and growth. J Am Diet Assoc 102(11):1648–1651PubMedCrossRefGoogle Scholar
  87. 87.
    Jarvinen KM, Konstantinou GN, Pilapil M, Arrieta MC, Noone S, Sampson HA et al (2013) Intestinal permeability in children with food allergy on specific elimination diets. Pediatr Allergy Immunol 24(6):589–595.  https://doi.org/10.1111/pai.12106 PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Sova C, Feuling MB, Baumler M, Gleason L, Tam JS, Zafra H et al (2013) Systematic review of nutrient intake and growth in children with multiple IgE-mediated food allergies. Nutr Clin Pract 28(6):669–675PubMedCrossRefGoogle Scholar
  89. 89.
    Kabbani TA, Goldberg A, Kelly CP, Pallav K, Tariq S, Peer A et al (2012) Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet. Aliment Pharmacol Ther 35(6):723–729PubMedCrossRefGoogle Scholar
  90. 90.
    Ohlund K, Olsson C, Hernell O, Ohlund I (2010) Dietary shortcomings in children on a gluten-free diet. J Hum Nutr Diet 23(3):294–300.  https://doi.org/10.1111/j.1365-277X.2010.01060.x PubMedCrossRefGoogle Scholar
  91. 91.
    Wild D, Robins GG, Burley VJ, Howdle PD (2010) Evidence of high sugar intake, and low fibre and mineral intake, in the gluten-free diet. Aliment Pharmacol Ther 32(4):573–581.  https://doi.org/10.1111/j.1365-2036.2010.04386.x PubMedCrossRefGoogle Scholar
  92. 92.
    Murray JA, Watson T, Clearman B, Mitros F (2004) Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. Am J Clin Nutr 79(4):669–673PubMedCrossRefGoogle Scholar
  93. 93.
    Innis SM (2008) Dietary omega 3 fatty acids and the developing brain. Brain Res 1237:35–43PubMedCrossRefGoogle Scholar
  94. 94.
    De Caterina R (2011) N-3 fatty acids in cardiovascular disease. N Engl J Med 364(25):2439–2450.  https://doi.org/10.1056/NEJMra1008153 PubMedCrossRefGoogle Scholar
  95. 95.
    Aldamiz-Echevarria L, Bilbao A, Andrade F, Elorz J, Prieto JA, Rodriguez-Soriano J (2008) Fatty acid deficiency profile in children with food allergy managed with elimination diets. Acta Paediatr 97(11):1572–1576PubMedCrossRefGoogle Scholar
  96. 96.
    Kim SH, Lee JH, Ly SY (2016) Children with atopic dermatitis in Daejeon, Korea: individualized nutrition intervention for disease severity and nutritional status. Asia Pac J Clin Nutr 25(4):716–728.  https://doi.org/10.6133/apjcn.092015.31 PubMedCrossRefGoogle Scholar
  97. 97.
    Paassilta M, Kuusela E, Korppi M, Lemponen R, Kaila M, Nikkari ST (2014) Food allergy in small children carries a risk of essential fatty acid deficiency, as detected by elevated serum mead acid proportion of total fatty acids. Lipids Health Dis 13(1):180.  https://doi.org/10.1186/1476-511X-13-180 PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Meyer R, De Koker C, Dziubak R, Godwin H, Dominguez-Ortega G, Chebar Lozinsky A, Skrapac AK, Gholmie Y, Reeve K, Shah N (2016) The impact of the elimination diet on growth and nutrient intake in children with food protein induced gastrointestinal allergies. Clin Transl Allergy. 6(1):25.  https://doi.org/10.1186/s13601-016-0115-x PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Pasiakos SM, Agarwal S, Lieberman HR, Fulgoni VL 3rd (2015) Sources and amounts of animal, dairy, and plant protein intake of US adults in 2007-2010. Nutrients 7(8):7058–7069PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    van Vliet S, Burd NA, van Loon LJ (2015) The skeletal muscle anabolic response to plant- versus animal-based protein consumption. J Nutr 145(9):1981–1991PubMedCrossRefGoogle Scholar
  101. 101.
    Dietary protein quality evaluation in human nutrition (2013). Report of an FAQ Expert Consultation. FAO Food Nutr Pap 92:1–66Google Scholar
  102. 102.
    Saturni L, Ferretti G, Bacchetti T (2010) The gluten-free diet: safety and nutritional quality. Nutrients 2(1):16–34PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Pellegrini N, Agostoni C (2015) Nutritional aspects of gluten-free products. J Sci Food Agric 95(12):2380–2385.  https://doi.org/10.1002/jsfa.7101 PubMedCrossRefGoogle Scholar
  104. 104.
    Martin J, Geisel T, Maresch C, Krieger K, Stein J (2013) Inadequate nutrient intake in patients with celiac disease: results from a German dietary survey. Digestion 87(4):240–246PubMedCrossRefGoogle Scholar
  105. 105.
    Missbach B, Schwingshackl L, Billmann A, Mystek A, Hickelsberger M, Bauer G, König J (2015) Gluten-free food database: the nutritional quality and cost of packaged gluten-free foods. PeerJ 3:e1337.  https://doi.org/10.7717/peerj.1337 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    JH W, Neal B, Trevena H, Crino M, Stuart-Smith W, Faulkner-Hogg K et al (2015) Are gluten-free foods healthier than non-gluten-free foods? An evaluation of supermarket products in Australia. Br J Nutr 114(3):448–454CrossRefGoogle Scholar
  107. 107.
    Miranda J, Lasa A, Bustamante MA, Churruca I, Simon E (2014) Nutritional differences between a gluten-free diet and a diet containing equivalent products with gluten. Plant Foods Hum Nutr 69(2):182–187.  https://doi.org/10.1007/s11130-014-0410-4 PubMedCrossRefGoogle Scholar
  108. 108.
    Anderson JW, Baird P, Davis RH Jr, Ferreri S, Knudtson M, Koraym A et al (2009) Health benefits of dietary fiber. Nutr Rev 67(4):188–205.  https://doi.org/10.1111/j.1753-4887.2009.00189.x PubMedCrossRefGoogle Scholar
  109. 109.
    Golden NH, Abrams SA (2014) Committee on N. Optimizing bone health in children and adolescents. Pediatrics 134(4):e1229–e1243.  https://doi.org/10.1542/peds.2014-2173 PubMedCrossRefGoogle Scholar
  110. 110.
    Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, Shoenfeld Y, Lerchbaum E, Llewellyn DJ, Kienreich K, Soni M (2013) Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence. Autoimmun Rev 12(10):976–989.  https://doi.org/10.1016/j.autrev.2013.02.004 PubMedCrossRefGoogle Scholar
  111. 111.
    Prasad AS (2008) Zinc in human health: effect of zinc on immune cells. Mol Med 14(5–6):353–357.  https://doi.org/10.2119/2008-00033.Prasad PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Prado EL, Dewey KG (2014) Nutrition and brain development in early life. Nutr Rev 72(4):267–284.  https://doi.org/10.1111/nure.12102 PubMedCrossRefGoogle Scholar
  113. 113.
    Kim J, Kwon J, Noh G, Lee SS (2013) The effects of elimination diet on nutritional status in subjects with atopic dermatitis. Nutr Res Pract 7(6):488–494.  https://doi.org/10.4162/nrp.2013.7.6.488 PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Meyer R, De Koker C, Dziubak R, Skrapac AK, Godwin H, Reeve K, Chebar-Lozinsky A, Shah N (2015) A practical approach to vitamin and mineral supplementation in food allergic children. Clin Transl Allergy 5(1):11.  https://doi.org/10.1186/s13601-015-0054-y PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Meyer R, De Koker C, Dziubak R, Godwin H, Dominguez-Ortega G, Shah N (2014) Dietary elimination of children with food protein induced gastrointestinal allergy—micronutrient adequacy with and without a hypoallergenic formula? Clin Transl Allergy 4(1):31PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Moore CE, Radcliffe JD, Liu Y, Vitamin D (2014) Intakes of children differ by race/ethnicity, sex, age, and income in the United States, 2007 to 2010. Nutr Res 34(6):499–506.  https://doi.org/10.1016/j.nutres.2014.06.002 PubMedCrossRefGoogle Scholar
  117. 117.
    Bailey RL, Dodd KW, Goldman JA, Gahche JJ, Dwyer JT, Moshfegh AJ, Sempos CT, Picciano MF (2010) Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr 140(4):817–822.  https://doi.org/10.3945/jn.109.118539 PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Molina-Infante J, Katzka DA, Gisbert JP (2013) Review article: proton pump inhibitor therapy for suspected eosinophilic oesophagitis. Aliment Pharmacol Ther 37(12):1157–1164PubMedCrossRefGoogle Scholar
  119. 119.
    Jung SB, Nagaraja V, Kapur A, Eslick GD (2015) Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis. Intern Med J 45(4):409–416PubMedCrossRefGoogle Scholar
  120. 120.
    Freedberg DE, Kim LS, Yang YX (2017) The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology 152(4):706–715.  https://doi.org/10.1053/j.gastro.2017.01.031 PubMedCrossRefGoogle Scholar
  121. 121.
    do Nascimento AB, Fiates GM, Dos Anjos A, Teixeira E (2013) Analysis of ingredient lists of commercially available gluten-free and gluten-containing food products using the text mining technique. Int J Food Sci Nutr 64(2):217–222.  https://doi.org/10.3109/09637486.2012.718744 PubMedCrossRefGoogle Scholar
  122. 122.
    deCastro BR, Caldwell KL, Jones RL, Blount BC, Pan Y, Ward C, Mortensen ME (2014) Dietary sources of methylated arsenic species in urine of the United States population, NHANES 2003-2010. PLoS One 9(9):e108098.  https://doi.org/10.1371/journal.pone.0108098 PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Bulka CM, Davis MA, Karagas MR, Ahsan H, Argos M (2017) The unintended consequences of a gluten-free diet. Epidemiology 28(3):e24–ee5.  https://doi.org/10.1097/EDE.0000000000000640 PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Raehsler SL, Choung RS, Marietta EV, Murray JA (2017) Accumulation of heavy metals in people on a gluten-free diet. Clin Gastroenterol Hepatol.  https://doi.org/10.1016/j.cgh.2017.01.034
  125. 125.
    Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ (2012) Heavy metal toxicity and the environment. EXS 101:133–164.  https://doi.org/10.1007/978-3-7643-8340-4_6 PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    De Geest S, Sabate E (2003) Adherence to long-term therapies: evidence for action. Eur J Cardiovasc Nurs 2(4):323.  https://doi.org/10.1016/S1474-5151(03)00091-4 PubMedCrossRefGoogle Scholar
  127. 127.
    Hommel KA, Franciosi JP, Hente EA, Ahrens A, Rothenberg ME (2012) Treatment adherence in pediatric eosinophilic gastrointestinal disorders. J Pediatr Psychol 37(5):533–542PubMedCrossRefGoogle Scholar
  128. 128.
    Franciosi JP, Hommel KA, Greenberg AB, DeBrosse CW, Greenler AJ, Abonia JP, Rothenberg ME, Varni JW (2012) Development of the pediatric quality of life inventory eosinophilic esophagitis module items: qualitative methods. BMC Gastroenterol 12(1):135.  https://doi.org/10.1186/1471-230X-12-135 PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Leffler DA, Edwards-George J, Dennis M, Schuppan D, Cook F, Franko DL et al (2008) Factors that influence adherence to a gluten-free diet in adults with celiac disease. Dig Dis Sci 53(6):1573–1581PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    MacCulloch K, Rashid M (2014) Factors affecting adherence to a gluten-free diet in children with celiac disease. Paediatr Child Health 19(6):305–309.  https://doi.org/10.1093/pch/19.6.305 PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Singh J, Whelan K (2011) Limited availability and higher cost of gluten-free foods. J Hum Nutr Diet 24(5):479–486.  https://doi.org/10.1111/j.1365-277X.2011.01160.x PubMedCrossRefGoogle Scholar
  132. 132.
    McMahon EJ, Campbell KL, Mudge DW, Bauer JD (2012) Achieving salt restriction in chronic kidney disease. Int J Nephrol 2012:720429PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Whitaker JK, West J, Holmes GK, Logan RF (2009) Patient perceptions of the burden of coeliac disease and its treatment in the UK. Aliment Pharmacol Ther 29(10):1131–1136.  https://doi.org/10.1111/j.1365-2036.2009.03983.x PubMedCrossRefGoogle Scholar
  134. 134.
    Schulman-Green D, Jaser SS, Park C, Whittemore R (2016) A metasynthesis of factors affecting self-management of chronic illness. J Adv Nurs 72(7):1469–1489PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Wang R, Hirano I, Doerfler B, Zalewski A, Gonsalves N, Taft T (2017) Assessing adherence and barriers to long term dietary elimination therapy in patients with eosinophilic esophagitis (EOE). Gastroenterology 152(5):S864CrossRefGoogle Scholar
  136. 136.
    Asher Wolf W, Huang KZ, Durban R, Iqbal ZJ, Robey BS, Khalid FJ et al (2016) The six-food elimination diet for eosinophilic esophagitis increases grocery shopping cost and complexity. Dysphagia 31(6):765–770PubMedCrossRefGoogle Scholar
  137. 137.
    Roma E, Roubani A, Kolia E, Panayiotou J, Zellos A, Syriopoulou VP (2010) Dietary compliance and life style of children with coeliac disease. J Hum Nutr Diet 23(2):176–182.  https://doi.org/10.1111/j.1365-277X.2009.01036.x PubMedCrossRefGoogle Scholar
  138. 138.
    Giovannini M, D'Auria E, Caffarelli C, Verduci E, Barberi S, Indinnimeo L, Iacono I, Martelli A, Riva E, Bernardini R (2014) Nutritional management and follow up of infants and children with food allergy: Italian Society of Pediatric Nutrition/Italian Society of Pediatric Allergy and Immunology Task Force Position Statement. Ital J Pediatr 40(1):1.  https://doi.org/10.1186/1824-7288-40-1 PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Harris RF, Menard-Katcher C, Atkins D, Furuta GT, Klinnert MD (2013) Psychosocial dysfunction in children and adolescents with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 57(4):500–505.  https://doi.org/10.1097/MPG.0b013e31829ce5ad PubMedCrossRefGoogle Scholar
  140. 140.
    Webb D, Byrd-Bredbenner C (2015) Overcoming consumer inertia to dietary guidance. Adv Nutr 6(4):391–396PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Henry ML, Atkins D, Fleischer D, Pan Z, Ruybal J, Furuta GT (2012) Factors contributing to adherence to dietary treatment of eosinophilic gastrointestinal diseases. J Pediatr Gastroenterol Nutr 54(3):430–432.  https://doi.org/10.1097/MPG.0b013e3182407aee PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Division of Allergy and ImmunologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Division of Nutrition TherapyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Section of Allergy and ImmunologyUniversity of Colorado Denver School of Medicine, Colorado Children’s HospitalAuroraUSA

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