Reintroduction of excluded food triggers as a crucial step in managing patients with food allergies

Introduction. Despite active research into the mechanisms of food allergies (FA), the main approach to managing patients with this condition remains the complete exclusion of causative allergens from the diet for a certain period. At the same time, the question of timely reintroduction of excluded food triggers into the diet is frequently raised, which is important both for maintaining oral tolerance and reducing the negative effects of long-term elimination diets, such as nutritional and eating behavior disorders, as well as financial burdens on families. However, clear recommendations on the reintroduction of previously excluded foods have not existed until recently. Regarding cow’s milk protein allergy (CMPA), such recommendations were provided in 2023 in the consensus document of the World Allergy Organization (WAO) — DRACMA.

Aim. The aim of this review is to present current approaches to the reintroduction of food allergens into the diets of patients with food allergies and to evaluate various reintroduction protocols, including those used for cow’s milk protein allergy (CMPA).

Material and methods. This review provides a concise summary of current approaches to reintroducing food allergens into the diet, covering both IgE-mediated and non-IgE-mediated forms of food allergy. The advantages of different patient management protocols are discussed, with special attention given to CMPA as one of the most common manifestations of FA in children.

Results. An analysis of modern approaches has demonstrated that modern recommendations regarding the reintroduction of allergens, including those presented in the document of the World Allergological Organization — DRACMA for allergy to cow’s milk proteins, allow for a more personalized and safe approach to the reintroduction of allergens, which helps reduce risks and maintain food tolerance.

Conclusions. The introduction of new guidelines for the reintroduction of food allergens is an important step in managing patients with food allergies. These recommendations provide a more personalized approach to treating food-allergic patients, including those with cow’s milk protein allergy, reducing the risks associated with reintroducing allergens into the diet. They also help to mitigate the negative effects of elimination diets and maintain oral tolerance in patients, which is particularly important for children with FA.

1. Burney P.G., Potts J., Kummeling I., et al. The prevalence and distribution of food sensitization in European adults. Allergy. 2014; 69 (3): 365–371. https://doi.org/10.1111/all.12341.

2. Muraro A., Roberts G., Worm M., et al. Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy. 2014; 69 (8): 1026–1045. https://doi.org/10.1111/all.12437.

3. Clinical guidelines. Food allergy [internet]. 2021. (In Russ.)

4. Makarova S.G., Balabolkin I.I., Fisenko A.P. Food allergy in children and adolescents: monograph. Moscow: FGAU “NMIC of Children’s Health” of the Ministry of Health of Russia; 2021. 288 p. (Informational materials) (In Russ.)

5. Dambacher W.M., de Kort E.H., Blom W.M., Houben G.F., de Vries E. Double-blind placebo-controlled food challenges in children with alleged cow’s milk allergy: prevention of unnecessary elimination diets and determination of eliciting doses. Nutr J. 2013; 12 (1): 12–22. https://doi.org/10.1186/1475-2891-12-22.

6. Miceli Sopo S., Monaco S., Greco M., Onesimo R. Prevalence of adverse reactions following a passed oral food challenge and factors affecting successful re-introduction of foods. A retrospective study of a cohort of 199 children. Allergol Immunopathol (Madr). 2016; 44 (1): 54–58. https://doi.org/10.1016/j.aller.2015.04.010.

7. van der Valk J.P., Gerth van Wijk R., Dubois A.E., de Groot H., de Jong N.W. Failure of introduction of cashew nut after a negative oral food challenge test in children. Pediatr Allergy Immunol. 2016; 27 (6): 654–658. https://doi.org/10.1111/pai.12591.

8. Oole-Groen C.J., Brand P.L. Double-blind food challenges in children in general paediatric practice: useful and safe, but not without pitfalls. Allergol Immunopathol (Madr). 2014; 42 (4): 269–274. https://doi.org/10.1016/j.aller.2013.06.005.

9. Strinnholm A., Winberg A., Hedman L., Ronmark E., Lindh V. Reintroduction failure is common among adolescents after dou-ble-blind placebo-controlled food challenges. Acta Paediatr. 2017; 106 (2): 282–287. https://doi.org/10.1111/apa.13673.

10. Meyer R., Venter C., Bognanni A., et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update - VII - Milk elimination and reintroduction in the diagnostic process of cow’s milk allergy. World Allergy Organ J. 2023; 16 (7): 100785. https://doi.org/10.1016/j.waojou.2023.100785.

11. Gau J., Wang J. Rate of food introduction after a negative oral food challenge in the pediatric population. J Allergy Clin Immunol Pract. 2017; 5 (2): 475–476. https://doi.org/10.1016/j.jaip.2016.06.027.

12. Fiocchi A., Bognanni A., Brożek J., Ebisawa M., Schünemann H.; WAO DRACMA guideline group. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines update - I - Plan and definitions. World Allergy Organ J. 2022; 15 (1): 100609. https://doi.org/10.1016/j.waojou.2021.100609.

13. Wambre E., Jeong D., Tordesillas L., Berin M.C. Oral Tolerance Development and Maintenance. Immunol Allergy Clin North Am. 2018; 38 (1): 27–37. https://doi.org/10.1016/j.iac.2017.09.003.

14. Satitsuksanoa P., Jansen K., Głobińska A., et al. Regulatory immune mechanisms in tolerance to food allergy. Front Immunol. 2018; 9: 2939. https://doi.org/10.3389/fimmu.2018.02939.

15. Ho H.E., Bunyavanich S. Role of the microbiome in food allergy. Curr Allergy Asthma Rep. 2018; 18 (4): 27. doi:10.1007/s11882018-0780-z.

16. Du Toit G., Sampson H.A., Plaut M., Burks A.W., Akdis C.A., Lack G. Food allergy: Update on prevention and tolerance. J Allergy Clin Immunol. 2018; 141 (1): 30–40. https://doi.org/10.1016/j.jaci.2017.11.010.

17. Ditlof C., Hummel R., Wong S., Alexanian-Farr M., et al. Food reintroduction after passing an oral food challenge: A cross-sectional structured interview-based assessment of barriers, challenges, and impact on quality of life. J Allergy Clin Immunol. 2021; 147 (2 Suppl). https://doi.org/10.1016/j.jaci.2020.12.057.

18. Vandenplas Y., Broekaert I., Domellöf M., et al. An ESPGHAN position paper on the diagnosis, management and prevention of cow’s milk allergy. J Pediatr Gastroenterol Nutr. Published online July 26, 2023. https://doi.org/10.1097/MPG.0000000000003897.

19. Aguirre C.P.M., Vasconcelos P.D.S.P., Caldas J.P.S., Lomazi E.A., Bellomo-Brandão M.A. Induced proctocolitis - oral food challenge should be done to confirm the diagnosis of cow’s milk allergy in neonates? Arq Gastroenterol. 2022; 59 (3): 365–369. https://doi.org/10.1590/S0004-2803.202203000-66.

20. Martin V.M., Virkud Y.V., Phadke N.A., Su K.W., Seay H., Atkins M.R., Keet C., Shreffler W.G., Yuan Q. Increased IgE-mediated food allergy with food protein-induced allergic proctocolitis. Pediatrics. 2020; 146 (3). https://doi.org/10.1542/peds.2020-0202.

21. Emelyashenkov E.E., Makarova S.G., Murashkin N.N., Galimova A.A., Pronina I.Y., Yasakov D.S. Influence of an elimination diet on the quality of life and eating behavior of children with severe atopic dermatitis and food allergies. Med Al’fab. 2023; (8): 69–74. https://doi.org/10.33667/2078-5631-2023-8-69-74. (In Russ.)

22. Athanasopoulou P., Deligianni E., Dean T., Dewey A., Venter C. Use of baked milk challenges and milk ladders in clinical practice: a worldwide survey of healthcare professionals. Clin Exp Allergy. 2017; 47 (3): 430–434. https://doi.org/10.1111/cea.12890.

23. Nowak-Wegrzyn A., Bloom K.A., Sicherer S.H., Shreffler W.G., Noone S., Wanich N., Sampson H.A. Tolerance to extensively heated milk in children with cow’s milk allergy. J Allergy Clin Immunol. 2008; 122 (2): 342–347.e2. https://doi.org/10.1016/j.jaci.2008.05.043.

24. Monaco S., Russo G., Romano A., et al. Yogurt is tolerated by the majority of children with IgE-mediated cow’s milk allergy. Allergol Immunopathol. 2019; 47: 322–327. https://doi.org/10.1016/j.aller.2018.10.005.

25. Ayats-Vidal R., Valdesoiro-Navarrete L., García-González M., Asensio-De la Cruz O., Larramona-Carrera H., Bosque-García M. Predictors of a positive oral food challenge to cow’s milk in children sensitized to cow’s milk. Allergol Immunopathol (Madr). 2020; 48 (6): 568–575. https://doi.org/10.1016/j.aller.2020.03.007.

26. Ogata M., Yoshida T., Kido J., et al. Safety of oral food challenge for individuals with low egg white and ovomucoid-specific IgE antibodies. Int Arch Allergy Immunol. 2024; 185 (1): 33–42. https://doi.org/10.1159/000531955.

27. Kabil N., Stokes J. Cracking the Egg: Predictors of Baked Egg Oral Food Challenge Outcomes. Ann Allergy Asthma Immunol. 2018; 121 (5 Suppl).

28. Venter C., Meyer R., Ebisawa M., Athanasopoulou P., Mack D.P. Food allergen ladders: A need for standardization. Pediatr Allergy Immunol. 2022; 33 (1). https://doi.org/10.1111/pai.13714.

29. Meyer R., De Koker C., Dziubak R., Godwin H., Reeve K., Chebar-Lozinsky A., Foong R.-X., Skrapac A.-K., Ellmer M., Shah N. The Challenge of Home Allergen Reintroductions Using the Ladder Approach in Children With Non-IgE Mediated Gastrointestinal Food Allergy. Front Allergy. 2021; 2: 721686. https://doi.org/10.3389/falgy.2021.721686.

30. Ye L., Wong T., Lavine E., Cook V.E., Erdle S.C. Using the Canadian egg ladder in children with food protein-induced enterocolitis syndrome: a case series. Allergy Asthma Clin Immunol. 2023; 19 (1): 87. https://doi.org/10.1186/s13223-023-00843-x.

31. Bognanni A., Chu D.K., Firmino R.T., et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) guideline update - XIII - Oral immunotherapy for CMA — Systematic review. World Allergy Organ J. 2022; 15 (9): 100682. https://doi.org/10.1016/j.waojou.2022.100682.

32. Pajno G.B., Fernandez-Rivas M., Arasi S., et al. EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy. Allergy. 2018; 73 (4): 799–815. https://doi.org/10.1111/all.13319.

33. Guillaume P., Guillaume L. Oral immunotherapy for food allergy: Translation from studies to clinical practice? World Allergy Organ J. 2023; 16 (2): 100747. doi:10.1016/j.waojou.2023.100747.

34. Brozek J.L., Firmino R.T., Bognanni A., et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update - XIV — Recommendations on CMA immunotherapy. World Allergy Organ J. 2022; 15 (4): 100646. https://doi.org/10.1016/j.waojou.2022.100646.