Main Article Content
food allergy, pathogenesis, diagnosis, prevention, management, children
Food allergy (FA) is an adverse immunologic response triggered by normally innocuous food protein antigens. FA can be broadly classified into those that are IgE mediated, those that are mediated by both IgE-dependent and IgE-independent pathways (mixed), and those that are not IgE mediated Immunoglobulin E. (IgE)-mediated reaction is characterized by rapid onset of symptoms involving respiratory, gastrointestinal, dermatologic and cardiovascular systems; mixed and non-IgE-mediated has a longer onset and manifests primary in the gastrointestinal tract and skin. The diagnosis of food allergy is based on clinical history, diagnostic testing (skin prick test and allergen-specific IgE levels in the serum), elimination diet and, oral food challenge. In recent years the diagnosis and treatment of pediatric FA have notably improved. In the diagnostic pathway of FA an important recent innovation is the CRD introduction. This resulted in the possibility of improving diagnostic accuracy through FA prediction severity and prognosis and thereby decreasing the OCF necessity. Recent studies emphasize the possibility of preventing FA through early introduction of food (peanuts and egg) to high-risk infants. FA management is based on avoidance of offending food and prompt treatment of allergic reaction. Currently under study are recently developed treatment approaches for FA management including specific OIT.
2. Burks AW, TangM, Sicherer S, et al. ICON: food alllergy. J Allergy Clin Immunol 2012;129:906-20.
3. Sicherer SH, Sampson HA. Food Allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol 2018;141:41-58.
4. Branum AM, Lukacs SL. Food allergy among children in the United States. Pediatrics 2009;124:1549-55.
5. Gupta RS, Springston EE, Warrier MR, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics 2011,128:e9-e17.
6. Koplin JJ, Peters RL, Ponsonby AL, et al. Increased risk of peanut allergy in infants Asian-born parents compared to those of Australian-born parents. Allergy 2014;69:1639-47.
7. Renz H, Allen KJ, Sicherer SH, et al. Food Allergy. Nat Rev Dis Primers 2018;4:17098.
8. Chehade M, Mayer L. Oral tolerance and its relation to food hypersensitivities. J Allergy Clin Immunol 2005;115:3-12.
9. Tordesillas L, Berin MC. Mechanisms of oral tolerance. Clin Rev Allergy Immunol 2018;55:107-17.
10. Noval Rivas M, Burton OT, Wise P, et al. A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis. J Allergy Clin Immunol 2013;131:201-12.
11. Stefka AT, Feehley T, Tripathi P, et al. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci USA 2014;111:13145-50.
12. Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY. Retinoic acid imprints gut-homing specificity on T cells. Immunity 2004;21:527-38.
13. Frossard CP, Hauser C, Eigenmann PA. Antigen-specific secretory IgA antibodies in the gut are decreased in a mouse model of food allergy. J Allergy Clin Immunol 2004,114:377-82.
14. Defrance T, Vanbervliet B, Briere f, Durand I, Rousset F, Banchereau J. Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activate naïve human B cells to secrete immunoglobulin A. J Exp Med 1992;175:671-82.
15. Barni S, Liccioli G, Sarti L, Giovannini M, Novembre E, Mori F. Immunoglobulin E (IgE)-mediated food allergy in children: epidemiology, pathogenesis, diagnosis, prevention, and management. Medicina (Kaunas) 2020;56:111.
16. Wambre E, Bajzik V, DeLong JH, et al. A phenotypically and functionally distinct human TH2 cell subpopulation is associated with allergic disrders. Sci Transl Med 2017;9.
17. Schmiechen ZC, Weissler KA, Frischmeyer-Guerrerio PA. Recent developments in understsnding the mechanisms of food allergy. Curr Opin Pediatr 2019;31:807-14.
18. Johnston LK, Chien KB, Bryce PJ. The Immunology of food allergy. J Immunol 2014;192:2529-34.
19. Meiler F, Klunker S, Zimmermann M, Rückert B, Akdis CA, Akdis M. Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy 2008;63:1455-63.
20. Strachan DP. Hay fever, hygiene, and household size. Br Med J 1989;299:1259-60.
21. Koplin JJ, Dharmage SC, Ponsonby AL, et al. Environmental and demographic risk factors for egg allergy in a population-based study of infants. Allergy 2012;67:1415-22.
22. Marrs T, Bruce KD, Logan K, et al. Is there an association between microbial exposure and food allergy? A systematic review. Pediatr Allergy Immunol 2013;24:311-20.
23. Papathoma E, Triga M, Fouzas S, Dimitriou G. Cesarian section delivery and development of food allergy and atopic dermatitis in early childhood. Pediatr Allergy Immunol 2016;27:419-24.
24. Caffarelli C, Di Mauro D, Mastrorilli C, Bottau P, Cipriani F, Ricci G. Solid food introduction and the development of food allergies. Nutrients 2018;10:1790.
25. Suaini NHA, Zhang Y, Vuillermin PJ, Allen KJ, Harrison LC. Immune modulation by vitamin D and its relevance to food allergy. Nutrients 2015,7:6088-108.
26. Allen KJ, Koplin JJ, Ponsonby AL, et al. Vitamin D insufficiency is associated with challenge-proven food allergy in infants. J Allergy Clin Immunol 2013;131:1109-16.
27. Molloy J, Ponsonby AL, Allen KJ, et al. Is low vitamin D status a risk factor for food allergy? Current evidence and future directions. Min Rev Med Chem 2015; 15:944-52.
28. Julia V, Macia L, Dombrowicz D. The impact of diet on asthma and allergic diseases. Nat Rev Immunol 2015;15:308-22.
29. Kongsbak M, von Essen MR, Boding L, et al. Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells. PLoS One 2014; 9:e96695.
30. Wittke A, Weaver V, Mahon BD, August A, Cantorna MT. Vitamin D receptor-deficient mice fail to develop experimental allergic asthma. J Immunol 2004;173:3432-6.
31. De Martinis M, Sifuro MM, Suppa M, Ginaldi L. New prospective in food allergy. Int J Mol Sci 2020;21:1474.
32. Mastrorilli C, Caffarelli C, Hoffmann-Sommergruber K. Food allergy and atopic dermatitis: Prediction, progression, and prevention. Pediatr Allergy Immunol 2017;28:831-840.
33. Smith PK, Masilamani M, Li XM, Sampson HA. The false alarm hypothesis: Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins. J Allergy Clin Immunol 2017;139:429-37.
34. Keet CA, Allen KJ. Advances in food allergy in 2017. J Allergy Clin Immunol 2018;142:1719-29.
35. Sicherer AH: Determinants of systemic manifestations of food allergy J Allergy Clin Immunol 2000; 106: s251-7
36. Commins SP, Jerath MR, Cox K, Erickeson LD, Platts Mills T: Delayed anaphylaxis to alpha-gal, an oligosaccharide in mammalian meat. Allergol Int 2016;65:16-20.
37. Muraro A, Werfel T, Hoffmann-Sommergruber K, et al. EAACI food allergy and anaphylaxis guidelines: Diagnosis and management of food allegy. Allergy 2014;69:1008–25.
38. Caubet J-C, Szajewska H, Shamir R, Nowak-Wezgrzyn A. Non-IgE-mediated gastrointestinal food allergies in children. Pediatr Allergy Immunol 2017;28:6–17.
39. LIghtdale JR, Gremse DA, Lightdale JR, Gremse DA; Section on Gastroenterology, Hepatology, and Nutrition. Gastroesophageal reflux: management guidance for the pediatrician. Pediatrics 2013;131:e1684–e1695.
40. Simons FE, Ardusso LRF, Bilò MB, et a. International consensus on (ICON) anaphylaxis. World Allergy Organ J 2014;7: 1-19.
41. Poowuttikul P, Seth D. Anaphylaxis in children and adolescents. Pediatr Clin N Am 2019;66:995-1005.
42. LoVerde D, Iweala OI, Eginli A, Krishnaswamy G. Anaphylaxis. Chest 2018; 153:528-43.
43. Grabenhenrich LB, Dölle S, Moneret-Vautrin A, et al. Anaphylaxis in children and adolescents. The European anaphylaxis registry. J Allergy Clin Immunol 2016;137:1128-37.
44. Rancè F, Deschildre A, Villard-Truc F, et al. SFAIC and SP2A Workgroup on OFC in children. Oral food challenge in children: an expert review. Eur Ann Allergy Clin Immunol 2009;41:35-49.
45. Nowak-Wegrzyn A, Assa’ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS. Adverse Reactions to Food Committee of American Academy of Allergy, Asthma & Immunology. Work Group report: oral food challenge testing. J Allergy Clin Immunol 2009;123(Suppl 6): S365-83.
46. Calvani M, Bianchi A, Reginelli C, Peresso M, Testa A: Oral Food challenge. Medicina (Kaunas) 2019; 55:651
47. Greenhawt M. Oral food challenges in children: review and future perspectives. Curr Allergy Asthma Rep 2011;11:465-72.
48. Calvani M, Arasi S, Bianchi A, et al. Is it possible to make a diagnosis of raw, heated and baked egg allergy in children using cut-offs? A systematic review. Pediatr Allergy Immunol 2015;26:509–21.
49. Cuomo B, Indirli GC, Bianchi A, et al. Specific IgE and skin prick tests to diagnose allergy to fresh and baked cow’s milk according to age: A systematic review. Ital J Pediatr 2017;43:1-10.
50. Sporik R, Hill D.J, Hosking CS. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy 2000;30:1540–46.
51. Saarinen KM, Suomalainen H, Savilahti E. Diagnostic value of skin-prick and patch tests and serum eosinophil cationic protein and cow’s milk-specific IgE in infants with cow’s milk allergy. Clin Exp Allergy 2001;31:423–29.
52. Onesimo R, Monaco S, Greco M, et al. Predictive value of MP4 (Milk Prick Four), a panel of skin prick test for the diagnosis of pediatric immediate cow’s milk allergy. Eur Ann Allergy Clin Immunol 2013;45:201–8.
53. Keskin O, Tuncer A, Adalioglu G, Sekerel BE, Sackesen C, Kalayci O. Evaluation of the utility of atopy patch testing, skin prick testing, and total and specific IgE assays in the diagnosis of cow’s milk allergy. Ann Allergy Asthma Immunol 2005;94:553–60.
54. Peters RL, Allen KJ, Dharmage SC, et al. Health Nuts Study. Skin prick test responses and allergen specific IgE levels as predictors of peanut, egg, and sesame allergy in infants. J Allergy Clin Immunol 2013;132:874–80.
55. Vazquez-Ortiz M, Pascal M, Jimenez-Feijoo R. Ovalbumin-specific IgE/IgG4 ratio might improve the prediction of cooked and uncooked egg tolerance development in egg allergic children. Clin Exp Allergy 2014; 44:579–88.
56. Mehl A, Rolinck-Werninghaus C, Staden U. The atopy patch test in the diagnostic workup of suspected food-related symptoms in children. J Allergy Clin Immunol 2006;118:923–29.
57. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001; 107:891–96.
58. Ando H, Moverare, R, Kondo Y. Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol 2008;122:583–88.
59. Garcia-Ara C. Boyano-Martinez T, Diaz-Pena JM, Martin-Muñoz F, Reche-Frutos M, Martin-Esteban M: Specific IgE levels in the diagnosis of immediate hypersensitivity to cow’s milk protein in the infant. J. Allergy Clin Immunol 2001, 107, 185–190.
60. Nowak-Wegrzyn A, Assa'ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS, Work Group report: oral food challenge testing. Adverse reactions to food committee of American academy of allergy, asthma & immunology. J Allergy Clin Immunol 2009;123(6 Suppl): S365–83.
61. Miceli Sopo S, Greco M, Monaco S, et al. Matrix effect on baked milk tolerance in children with IgE cow milk allergy. Allergol Immunopathol (Madr) 2016;44:517–23.
62. Levy Y, Broides A, Segal N, Danon YL. Peanut and tree nut allergy in children: role of peanut snacks in Israel? Allergy 2003;58:1206-7.
63. Eigenmann PA, Sicherer SH, Borkowski TA, Cohen BA, Sampson HA. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics 1998;101:e8.
64. Du Toit G, Robert G, Sayre P, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 2015;372:803-13.
65. Perkin MR, Logan K, Tseng A, et al. EAT Study Team. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med 2016;374:1733-43.
66. Togias A, Cooper SF, Acebal ML. et al. Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. Ann Allergy Asthma Immunol. 2017;139:29–44.
67. Natsume O, Kabashima S, Nakasato J, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;389:276-86
68. Palmer DJ, Metcalf J, Makrides M, et al. Early regular egg exposure in infants with eczema: a randomized controlled trial. J Allergy Clin Immunol 2013;132:387-92.
69. Palmer DJ, Sullivan TR, Gold MS, Prescott SL, Makrides M. Randomized controlled trial of early regular egg intake to prevent egg allergy. J Allergy Clin Immunol 2017;139:1600-07.
70. Wei-Liang Tan J, Valerio C, Barnes EH, et al . A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy. J Allergy Clin Immunol 2017;139:1621-8.
71. Bellach J, Schwarz V, Ahrens B, et al. Randomized placebocontrolled trial of hen’s egg consumption for primary prevention in infants. J Allergy Clin Immunol 2017;139:1591-9.
72. Ierodiakonou D, Garcia-Larsen V, Logan A, et al. Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease. a systematic review and meta-analysis. JAMA 2016;316:1181-92.
73. Fewtrell M, Bronsky J, Campoy C, et al. Complementary feeding: a position paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) committee on nutrition. J Pediatr Gastroenterol Nutr 2017;64:119–32.
74. BSACI; https://www.bsaci.org/about/early-feedingguidance).
75. Verduci E, Bianchi A, Brambilla M, Calvani M. Egg introduction during complementary feeding according to allergic risk: not just for peanuts! Ital J Pediatrics 2018;44:77.
76. Verduci E, Bianchi A, Atzeri F, Brindisi G, Cuomo B, Ferrara F, Romano G, Calvani M: Alimentazione complementare e prevenzione delle allergie alimentari: revisione della letteratura. Riv Allergol Immunol Ped 2017; 3: 1-10.
77. Kvenshagen BK, Carlsen KH, Mowinckel P, Berents TL, Carlsen KC. Can early skin care normalise dry skin and possibly prevent atopic eczema? A pilot study in young infants. Allergol Immunopathol (Madr) 2014;42:539–43.
78. Horimukai K, Morita K, Narita M, et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol 2014; 134: 824–30.e6.
79. Lowe A, Su J, Tang M, et al. PEBBLES study protocol: a randomised controlled trial to prevent atopic dermatitis, food allergy and sensitisation in infants with a family history of allergic disease using a skin barrier improvement strategy. BMJ Open 2019;9: e024594.
80. Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. J Clin Immunol 2014;134:1016-25.
81. Licari A, Manti S, Marseglia A, et al. Food Allergies: current and future treatments. Medicina (Kaunas) 2019;55(5):120.
82. Hefle Sl, Furlong TJ, Niemann L, Lemon-Mule H, Sicherer S, Taylor SL. Consumer attitudes and risks associated with packaged foods having advisory labeling regarding the presence of peanuts. J Allergy Clin Immunol 2007;120:171-6.
83. Hobbs CB, Skinner AC, Burks AW, Vickery BP. Food allergies affect growth in children. J Allergy Clin immunol Pract 2015;3:133-4.
84. Metha H, Ramesh M, Feuille E, et al. Growth comparison in children with and without food allergies in 2 different demographic populations. J Pediatr 2014;165:842-8.
85. Warren CM, Gupta RS,Sohn M-W, et al.Differences empowerment and quality of life among parents of children with food allergy. Ann Allergy Asthma Immunol 2015;114:117-25.
86. Gupta R, Holdford D, Bilaver L, Dyer A, Holl JL, Meltzer D. The economic impact of childhood allergy in the United States. JAMA pediatr 2013;167:1026-31.
87. Wright BL, Walkner M, Vickery BP, Gupta RS. Clinical management of food allergy. Pediatr Clin N Am 2015;62:1409-24.
88. Simons FER. First aid treatmenr of anaphylaxis to food: focus on epinephrine [published correction appears in J Allergy Clin Immunol J 2004:113:837-44.
89. Simons FER. Anaphylaxis, killer allergy: long-term management in the community. J Allergy Clin Immunol 2006;117:367-77.
90. Arasi S, Castagnoli R, Pajno GB. Oral immunotherapy in pediatrics. Pediatr Allergy Immunol 2020;31 Suppl 24:51-53.
91. Pajno GB, Castagnoli R, Muraro A, et al. Allergen immunotherapy for IgE-mediated food allergy: There is a measure in everything to a proper proportion of therapy. Pediatr Allergy Immunol 2019;30:415-422.
92. Nurmatov U, Dhami S, Arasi S, et al. Allergen immunotherapy for IgEmediated food allergy: a systematic review and meta-analysis. Allergy. 2017;72:1133-47.
93. Romantsik O, Tosca MA, Zappettini S, Calevo MG. Oral and sublingual immunotherapy for egg allergy. Cochrane Database Syst Rev 2018;4:CD010638.
94. Pajno GB, Fernandez-Rivas M, Arasi S, et al. EAACI guidelines on allergen immunotherapy: IgE mediated food allergy. Allergy 2018;73:799-815.
95. Burks AW, Sampson HA, Plaut M, Lack G, Akdis CA. Treatment for food allergy. J Allergy Clin Immunol 2018;141:1-9.
96. Chu DK, Wood RA, French S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. Lancet 2019;393:2222-32.