Oral food challenge in IgE mediated food allergy in eastern Mediterranean children

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Hilal Unsal
Gokce Ozyilmaz Bozat
Melike Ocak
Aysegul Akarsu
Umit Murat Sahiner
Ozge Soyer
Bülent Enis Şekerel


Anaphylaxis, children, food allergy, IgE, oral food challenge, positive reaction


Background: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks.
Objective: Documentation of the rate, spectrum, and predictors of positive reactions is instructive.
Methods: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed.
Results: A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly consid-ered food groups were cow’s milk (31.8%), hen’s egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow’s milk, 4.9% with hen’s egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03–14.90]), wheat (OR: 3.80, [CI: 1.64–8.84]), and tree nuts (OR: 2.78, [CI: 1.83–4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27–10.28]) was more likely to elicit anaphylaxis.
Conclusion: In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC.

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1. Savage J, Johns CB. Food allergy: Epidemiology and natural history. Immunol Allergy Clin. 2015;35:45–59. https://doi.org/10.1016/j.iac.2014.09.004
2. Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128:e9–e17. https://doi.org/10.1542/peds.2011-0204
3. Kahveci M, Koken G, Şahiner ÜM, Soyer Ö, Şekerel BE. Immunoglobulin e-mediated food allergies differ in east Mediterranean children aged 0–2 years. Int Arch Allergy Immunol. 2020;181:365–74. https://doi.org/10.1159/000505996
4. Greiwe J. Oral food challenges in infants and toddlers. Immunol Allergy Clin. 2019;39:481–93. https://doi.org/10.1016/ j.iac.2019.07.003
5. Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol. 2010;125:S116–25. https://doi.org/10.1016/j.jaci.2009.08.028
6. Cox AL, Nowak-Wegrzyn A. Innovation in food challenge tests for food allergy. Curr Allergy Asthma Rep. 2018;18:74. https://doi.org/10.1007/s11882-018-0825-3
7. 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. https://doi.org/10.1016/j.jaci.2017.11.003
8. Niggemann B, Rolinck-Werninghaus C, Mehl A, Binder C, Ziegert M, Beyer K. Controlled oral food challenges in children– when indicated, when superfluous? Allergy. 2005;60:865–70. https://doi.org/10.1111/j.1398-9995.2005.00828.x
9. Sampson HA, Ho DG. Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. J Allergy Clin Immunol. 1997;100:444– 51. https://doi.org/10.1016/S0091-6749(97)70133-7
10. Mankad VS, Williams LW, Lee LA, LaBelle GS, Anstrom KJ, Burks AW. Safety of open food challenges in the office setting. Ann Allergy Asthma Immunol. 2008;100:469–74. https://doi. org/10.1016/S1081-1206(10)60473-5
11. Noone S, Ross J, Sampson HA, Wang J. Epinephrine use in positive oral food challenges performed as a screening test for food allergy therapy trials. J Allergy Clin Immunol In Pract. 2015;3:424–8. https://doi.org/10.1016/j.jaip.2014.10.008
12. Sampson HA, Van Wijk RG, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, et al. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology–European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012;130:1260–74.
13. Niggemann B. When is an oral food challenge positive? Allergy. 2010;65:2–6. https://doi.org/10.1111/j.1398-9995.2009.02170.x
14. Perry TT, Matsui EC, Conover-Walker MK, Wood RA. Risk of oral food challenges. J Allergy Clin Immunol. 2004;114:1164–8. https://doi.org/10.1016/j.jaci.2004.07.063
15. Bindslev-Jensen C, Ballmer-Weber B, Bengtsson U, Blanco C, Ebner C, Hourihane J, et al. Standardization of food chal-lenges in patients with immediate reactions to foods– position paper from the European Academy of Allergology and Clinical Immunology. Allergy. 2004;59:690–7. https://doi.org/10.1111/j.1398-9995.2004.00466.x
16. Fleischer DM, Bock SA, Spears GC, Wilson CG, Miyazawa NK, Gleason MC, et al. Oral food challenges in children with a diagnosis of food allergy. J Pediatr. 2011;158:578–83. e571. https://doi.org/10.1016/j.jpeds.2010.09.027
17. Cianferoni A, Garrett JP, Naimi DR, Khullar K, Spergel JM. Predictive values for food challenge-induced severe reactions: Development of a simple food challenge score. Sat. 2012;11:20.
18. Abrams EM, Becker AB. Oral food challenge outcomes in a pediatric tertiary care center. Allergy Asthma Clin Immunol. 2017;13:43.
19. Itazawa T, Adachi Y, Takahashi Y, Miura K, Uehara Y, Kameda M, et al. The severity of reaction after food challenges depends on the indication: A prospective multicenter study. Pediatr Allergy Immunol. 2020;31:167–74. https://doi.org/10.1111/pai.13140
20. Rolinck-Werninghaus C, Niggemann B, Grabenhenrich L, Wahn U, Beyer K. Outcome of oral food challenges in children in relation to symptom-eliciting allergen dose and allergen-specific I g E. Allergy. 2012;67:951–7. https://doi.org/10.1111/j.13989995.2012.02838.x
21. Sporik R, Hill D, Hosking C. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy. 2000;30:1541–6. https://doi.org/10.1046/j.1365-2222.2000.00928.x
22. Niggemann B, Sielaff B, Beyer K, Binder C, Wahn U. Outcome of double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis. Clin Exp Allergy. 1999;29:91– 6. https://doi.org/10.1046/j.1365-2222.1999.00454.x
23. Du Toit G, Santos A, Roberts G, Fox A, Smith P, Lack G. The diagnosis of IgE-mediated food allergy in childhood. Pediatr Allergy Immunol. 2009;20:309–19. https://doi.org/10.1111/j.1399-3038.2009.00887.x
24. Sampson HA. Food allergy. Part 2: Diagnosis and manage-ment. J Allergy Clin Immunol. 1999;103:981–9. https://doi.org/10.1016/S0091-6749(99)70167-3
25. Wood RA, Sicherer SH, Vickery BP, Jones SM, Liu AH, Fleischer DM, et al. The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol. 2013;131:805–12. e804. https://doi.org/10.1016/j.jaci.2012.10.060
26. Sicherer SH, Wood RA, Vickery BP, Jones SM, Liu AH, Fleischer DM, et al. The natural history of egg allergy in an obser-vational cohort. Journal of allergy and clinical immunology. 2014;133:492–9. e498. https://doi.org/10.1016/j.jaci.2013. 12.1041
27. Peters RL, Allen KJ, Dharmage SC, Koplin JJ, Dang T, Tilbrook KP, et al. Natural history of peanut allergy and predictors of resolution in the first 4 years of life: A population-based assessment. J Allergy Clin Immunol. 2015;135:1257–66. e1252. https://doi.org/10.1016/j.jaci.2014.12.1902
28. Verstege A, Mehl A, Rolinck-Werninghaus C, Staden U, Nocon M, Beyer K, et al. The predictive value of the skin prick test weal size for the outcome of oral food challenges. Clin Exp Allergy. 2005;35:1220–6. https://doi.org/10.1111/j.1365-2222.2005.2324.x
29. Eigenmann PA, Sampson HA. Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol. 1998;9:186–91. https://doi.org/10.1111/j.13993038.1998.tb00371.x
30. Osborne NJ, Koplin JJ, Martin PE, Gurrin LC, Lowe AJ, Matheson MC, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol. 2011;127:668–76. e662. https://doi.org/10.1016/j. jaci.2011.01.039
31. Isolauri E, Turjanmaa K. Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis. J Allergy Clin Immunol. 1996;97:9–15. https://doi.org/10.1016/S0091-6749(96)70277-4
32. Nowak-Węgrzyn A, Assa’ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS. Work Group report: Oral food challenge testing. J Allergy Clin Immunol. 2009;123:S365–83. https://doi.org/10.1016/j.jaci.2009.03.042
33. Niggemann B, Beyer K. Pitfalls in double-blind, placebo-controlled oral food challenges. Allergy. 2007;62:729–32. https://doi.org/10.1111/j.1398-9995.2007.01396.x
34. Perry TT, Matsui EC, Conover-Walker MK, Wood RA. The rela-tionship of allergen-specific IgE levels and oral food challenge outcome. J Allergy Clin Immunol. 2004;114:144–9. https://doi.org/10.1016/j.jaci.2004.04.009
35. Dang AT, Chundi PK, Mousa NA, Beyer AI, Chansakulporn S, Venter C, et al. The effect of age, sex, race/ethnicity, health insurance, and food specific serum immunoglobulin E on outcomes of oral food challenges. World Allergy Organ J. 2020;13:100100. https://doi.org/10.1016/j.waojou.2020.100100
36. Hossny E, Ebisawa M, El-Gamal Y, Arasi S, Dahdah L, Owaidy RE, et al. Challenges of managing food allergy in the developing world. World Allergy Organ J. 2019;12:100089. https://doi.org/10.1016/j.waojou.2019.100089
37. Woods RK, Thien F, Raven J, Walters EH, Abramson M. Prevalence of food allergies in young adults and their relationship to asthma, nasal allergies, and eczema. Ann Allergy Asthma Immunol. 2002;88:183–9. https://doi.org/10.1016/S1081-1206(10)61994-1
38. Lee AJ, Thalayasingam M, Lee BW. Food allergy in Asia: How does it compare? Asia Pac Allergy. 2013;3:3–14. https://doi.org/10.5415/apallergy.2013.3.1.3
39. Cetinkaya PG, Buyuktiryaki B, Soyer O, Sahiner UM, Sackesen C, Sekerel BE. Phenotypical characterization of tree nuts and peanut allergies in east Mediterranean children. Allergol Immunopathol. 2020;48:316–22. https://doi.org/10.1016/j.aller.2019.07.005
40. Celik-Bilgili S, Mehl A, Verstege A, Staden U, Nocon M, Beyer K, et al. The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges. Clin Exp Allergy. 2005;35:268–73. https://doi.org/10.1111/j.13652222.2005.02150.x
41. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI food allergy and anaphylaxis guidelines: Diagnosis and management of food allergy. Allergy. 2014;69:1008–25. https://doi.org/10.1111/all.12429
42. Sindher S, Long AJ, Purington N, Chollet M, Slatkin S, Andorf S, et al. Analysis of a large standardized food challenge data set to determine predictors of positive outcome across multiple allergens. Front Immunol. 2018;9:2689. https://doi.org/10.3389/fimmu.2018.02689
43. Simberloff T, Parambi R, Bartnikas LM, Broyles AD, Hamel V, Timmons KG, et al. Implementation of a standardized clini-cal assessment and management plan (SCAMP) for food challenges. J Allergy Clin Immunol In Pract. 2017;5:335–344. e333.
44. Zijlstra WT, Flinterman AE, Soeters L, Knulst AC, Sinnema G, L’Hoir MP, et al. Parental anxiety before and after food challenges in children with suspected peanut and hazelnut allergy. Pediatr Allergy Immunol. 2010;21:e439–45. https://doi.org/10.1111/j.13993038.2009.00929.x
45. Kemp AS, Allen CW, Campbell DE. Parental perceptions in egg allergy: Does egg challenge make a difference? Pediatr Allergy Immunol. 2009;20:648–53. https://doi.org/10.1111/j.1399-3038.2009.00859.x
46. DunnGalvin A, Cullinane C, Daly D, Flokstra-de Blok B, Dubois A, Hourihane JOB. Longitudinal validity and respon-siveness of the Food Allergy Quality of Life Questionnaire–Parent Form in children 0–12 years following positive and negative food challenges. Clin Exp Allergy. 2010;40:476–85. https://doi.org/10.1111/j.13652222.2010.03454.x