Epicutaneous immunotherapy for peanut allergy treatment in pediatrics: A literature review
Main Article Content
Keywords
Peanut Allergy, Pediatric Allergy, Epicutaneous Immunotherapy
Abstract
Peanut allergy in children is a growing public health concern that significantly affects patients' quality of life. Although oral immunotherapy (OIT) has shown effectiveness in desensitizing allergic reactions, it is associated with a threefold increased risk of anaphylaxis compared to strict avoidance. As an alternative, epicutaneous immunotherapy (EPIT) has emerged as a promising therapy due to its favorable safety profile, ease of administration, and non-invasive nature. However, despite increasing interest in EPIT, there is still limited evidence assessing its efficacy and safety in pediatric populations. This literature review aims to summarize current findings on the mechanism of desensitization, clinical efficacy, safety, and impact on quality of life associated with EPIT in managing peanut allergy in children. Relevant articles were identified through database searches in PubMed, Cochrane, Science Direct, Scopus, and Google Scholar using Medical Subject Headings (MeSH) and keyword combinations such as "Epicutaneous Immunotherapy", "Peanut Allergy", and "Pediatric Allergy". EPIT works by delivering peanut allergens through a patch applied to intact skin. The allergen is taken up by Langerhans cells and presented to the immune system, triggering regulatory T-cell (Treg) responses that reduce allergic sensitivity. Viaskin© is the most clinically advanced EPIT delivery system currently available. Findings from clinical studies indicate that EPIT is effective in inducing desensitization, with a lower risk of systemic reactions compared to OIT. Furthermore, EPIT contributes to improved quality of life in children with peanut allergy. These results support EPIT as a promising therapeutic option for pediatric peanut allergy management.
References
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34. Greenhawt M, Sindher SB, Wang J, O’Sullivan M, du Toit G, Kim EH, et al. Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy. New England Journal of Medicine. 2023 May 11;388(19):1755–66.
35. Fleischer DM, Greenhawt M, Sussman G, Bégin P, Nowak-Wegrzyn A, Petroni D, et al. Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy. JAMA. 2019 Mar 12;321(10):946.
36. Jones SM, Burks AW, Dupont C. State of the art on food allergen immunotherapy: Oral, sublingual, and epicutaneous. Journal of Allergy and Clinical Immunology. 2014 Feb;133(2):318–23.
37. Jones SM, Agbotounou WK, Fleischer DM, Burks AW, Pesek RD, Harris MW, et al. Safety of epicutaneous immunotherapy for the treatment of peanut allergy: A phase 1 study using the Viaskin patch. Journal of Allergy and Clinical Immunology. 2016;137(4):1258-1261.e10.
38. Pongracic JA, Gagnon R, Sussman G, Siri D, Oriel RC, Brown-Whitehorn TF, et al. Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results. Journal of Allergy and Clinical Immunology: In Practice. 2022;10(7):1864-1873.e10.
39. Walkner M, Warren C, Gupta RS. Quality of Life in Food Allergy Patients and Their Families. Pediatr Clin North Am [Internet]. 2015 Dec;62(6):1453–61. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0031395515001133
40. Gupta RS, Warren CM, Smith BM, Blumenstock JA, Jiang J, Davis MM, et al. The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States. Pediatrics [Internet]. 2018 Dec 1;142(6). Available from: https://publications.aap.org/pediatrics/article/142/6/e20181235/76867/The-Public-Health-Impact-of-Parent-Reported
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43. Stensgaard A, Bindslev‐Jensen C, Nielsen D, Munch M, DunnGalvin A. Quality of life in childhood, adolescence and adult food allergy: Patient and parent perspectives. Clinical & Experimental Allergy [Internet]. 2017 Apr 14;47(4):530–9. Available from: https://onlinelibrary.wiley.com/doi/10.1111/cea.12849
44. Galvin AD, Vereda A, Rodríguez del Río P, Muraro A, Jones C, Ryan R, et al. Children and caregiver proxy quality of life from peanut oral immunotherapy trials. Clin Transl Allergy. 2022 Dec 19;12(12).
45. Leung N, Virkud Y, Steele PH, Kamilaris JS, Kim E, Vickery BP, et al. Quality Of Life With Sublingual Immunotherapy For Peanut. Journal of Allergy and Clinical Immunology [Internet]. 2014 Feb 1;133(2):AB103. Available from: https://doi.org/10.1016/j.jaci.2013.12.383
2. Lieberman JA, Gupta RS, Knibb RC, Haselkorn T, Tilles S, Mack DP, et al. The global burden of illness of peanut allergy: A comprehensive literature review. Allergy. 2021 May 16;76(5):1367–84.
3. Sicherer SH, Sampson HA. Food allergy. Journal of Allergy and Clinical Immunology. 2010 Feb;125(2):S116–25.
4. Abrams EM, Chan ES, Sicherer S. Peanut Allergy: New Advances and Ongoing Controversies. Pediatrics. 2020 May 1;145(5).
5. Al-Muhsen S, Clarke AE, Kagan RS. Peanut allergy: an overview. CMAJ. 2003 May 13;168(10):1279–85.
6. Patel R, Koterba AP. Peanut Allergy. StatPearls. 2023.
7. Remington BC, Baumert JL. Risk Reduction in Peanut Immunotherapy. Immunol Allergy Clin North Am. 2020 Feb;40(1):187–200.
8. FDA approves first drug for treatment of peanut allergy for children [Internet]. 2020. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treatment-peanut-allergy-children
9. Jones SM, Kim EH, Nadeau KC, Nowak-Wegrzyn A, Wood RA, Sampson HA, et al. Efficacy and safety of oral immunotherapy in children aged 1–3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. The Lancet. 2022 Jan;399(10322):359–71.
10. Hamad A, Burks WA. Emerging Approaches to Food Desensitization in Children. Curr Allergy Asthma Rep. 2017 May 20;17(5):32.
11. Chong KW, Turner PJ. Food allergy desensitisation: a hard nut to crack? Arch Dis Child. 2019 Nov;104(11):1021–2.
12. Chong KW, Turner PJ. Peanut Allergy – No Longer a Life Sentence. Acta Med Acad. 2020 Nov 11;49(2):198.
13. Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, Gorelik M, Schroeder J, Hamilton RG, et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. Journal of Allergy and Clinical Immunology. 2015 May;135(5):1275-1282.e6.
14. Langlois A, Graham F, Bégin P. Epicutaneous peanut patch device for the treatment of peanut allergy. Expert Rev Clin Immunol. 2019 May 4;15(5):449–60.
15. Dunlop JH. Oral Immunotherapy for Treatment of Peanut Allergy. Journal of Investigative Medicine. 2020 Aug 5;68(6):1152–5.
16. Chinthrajah RS, Cao S, Dunham T, Sampath V, Chandra S, Chen M, et al. Oral immunotherapy for peanut allergy: The pro argument. World Allergy Organization Journal. 2020 Aug;13(8):100455.
17. Fiocchi A, Artesani MC, Fierro V, Riccardi C, Dahdah L, Mennini M. Oral immunotherapy for peanut allergy: The con argument. World Allergy Organization Journal. 2020 Aug;13(8):100445.
18. Whitsel RM, Bjelac JA, Subramanian A, Hoyt AEW, Hong SJ. Oral immunotherapy: The answer to peanut allergy? Cleve Clin J Med. 2021 Feb;88(2):104–9.
19. Tirumalasetty J, Barshow S, Kost L, Morales L, Sharma R, Lazarte C, et al. Peanut allergy: risk factors, immune mechanisms, and best practices for oral immunotherapy success. Expert Rev Clin Immunol. 2023 Jul 3;19(7):785–95.
20. Harrison FC, Giovannini M, Kalaichandran A, Santos AF. Food Allergy. In: Encyclopedia of Life Sciences. Wiley; 2020. p. 1–12.
21. Muraro A, Tropeano A, Giovannini M. Allergen immunotherapy for food allergy: Evidence and outlook. Allergol Select. 2022 Jan 1;6(01):285–92.
22. Anagnostou A. A Practical, Stepwise Approach to Peanut Oral Immunotherapy in Clinical Practice: Benefits and Risks. J Asthma Allergy. 2021 Mar;Volume 14:277–85.
23. Kim EH, Yang L, Ye P, Guo R, Li Q, Kulis MD, et al. Long-term sublingual immunotherapy for peanut allergy in children: Clinical and immunologic evidence of desensitization. Journal of Allergy and Clinical Immunology. 2019 Nov;144(5):1320-1326.e1.
24. Kim EH, Keet CA, Virkud Y V., Chin S, Ye P, Penumarti A, et al. Open-label study of the efficacy, safety, and durability of peanut sublingual immunotherapy in peanut-allergic children. Journal of Allergy and Clinical Immunology. 2023 Jun;151(6):1558-1565.e6.
25. Bird JA, Sánchez-Borges M, Ansotegui IJ, Ebisawa M, Ortega Martell JA. Skin as an immune organ and clinical applications of skin-based immunotherapy. World Allergy Organization Journal [Internet]. 2018;11:38. Available from: https://linkinghub.elsevier.com/retrieve/pii/S193945511930095X
26. Senti G, von Moos S, Kündig TM. Epicutaneous Immunotherapy for Aeroallergen and Food Allergy. Curr Treat Options Allergy [Internet]. 2014 Mar 17;1(1):68–78. Available from: http://link.springer.com/10.1007/s40521-013-0003-8
27. Mondoulet L, Dioszeghy V, Thébault C, Benhamou PH, Dupont C. Epicutaneous immunotherapy for food allergy as a novel pathway for oral tolerance induction. Immunotherapy [Internet]. 2015 Dec;7(12):1293–305. Available from: https://www.futuremedicine.com/doi/10.2217/imt.15.86
28. Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Benhamou PH, et al. Epicutaneous Immunotherapy Results in Rapid Allergen Uptake by Dendritic Cells through Intact Skin and Downregulates the Allergen-Specific Response in Sensitized Mice. The Journal of Immunology. 2011 May 15;186(10):5629–37.
29. Wang Z, Wu L, Wang W. Innovative delivery systems for epicutaneous immunotherapy. Front Immunol. 2023 Aug 22;14.
30. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. Role of Treg in immune regulation of allergic diseases. Eur J Immunol. 2010 May 29;40(5):1232–40.
31. Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, et al. The regulatory
32. Mondoulet L, Dioszeghy V, Puteaux E, Ligouis M, Dhelft V, Letourneur F, et al. Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice. Clin Transl Allergy [Internet]. 2012 Jan 12;2(1). Available from: https://onlinelibrary.wiley.com/doi/10.1186/2045-7022-2-22
33. Fleischer DM, Shreffler WG, Campbell DE, Green TD, Anvari S, Assa’ad A, et al. Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results. Journal of Allergy and Clinical Immunology. 2020 Oct;146(4):863–74.
34. Greenhawt M, Sindher SB, Wang J, O’Sullivan M, du Toit G, Kim EH, et al. Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy. New England Journal of Medicine. 2023 May 11;388(19):1755–66.
35. Fleischer DM, Greenhawt M, Sussman G, Bégin P, Nowak-Wegrzyn A, Petroni D, et al. Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy. JAMA. 2019 Mar 12;321(10):946.
36. Jones SM, Burks AW, Dupont C. State of the art on food allergen immunotherapy: Oral, sublingual, and epicutaneous. Journal of Allergy and Clinical Immunology. 2014 Feb;133(2):318–23.
37. Jones SM, Agbotounou WK, Fleischer DM, Burks AW, Pesek RD, Harris MW, et al. Safety of epicutaneous immunotherapy for the treatment of peanut allergy: A phase 1 study using the Viaskin patch. Journal of Allergy and Clinical Immunology. 2016;137(4):1258-1261.e10.
38. Pongracic JA, Gagnon R, Sussman G, Siri D, Oriel RC, Brown-Whitehorn TF, et al. Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results. Journal of Allergy and Clinical Immunology: In Practice. 2022;10(7):1864-1873.e10.
39. Walkner M, Warren C, Gupta RS. Quality of Life in Food Allergy Patients and Their Families. Pediatr Clin North Am [Internet]. 2015 Dec;62(6):1453–61. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0031395515001133
40. Gupta RS, Warren CM, Smith BM, Blumenstock JA, Jiang J, Davis MM, et al. The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States. Pediatrics [Internet]. 2018 Dec 1;142(6). Available from: https://publications.aap.org/pediatrics/article/142/6/e20181235/76867/The-Public-Health-Impact-of-Parent-Reported
41. Parlaman JP, Oron AP, Uspal NG, DeJong KN, Tieder JS. Emergency and Hospital Care for Food-Related Anaphylaxis in Children. Hosp Pediatr [Internet]. 2016 May 1;6(5):269–74. Available from: https://publications.aap.org/hospitalpediatrics/article/6/5/269/26352/Emergency-and-Hospital-Care-for-Food-Related
42. DunnGalvin A, Fleischer DM, Campbell DE, O’B Hourihane J, Green TD, Sampson HA, et al. Improvements in Quality of Life in Children Following Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in the PEPITES and PEOPLE Studies. J Allergy Clin Immunol Pract [Internet]. 2021 Jan;9(1):216-224.e1. Available from: https://linkinghub.elsevier.com/retrieve/pii/S221321982030831X
43. Stensgaard A, Bindslev‐Jensen C, Nielsen D, Munch M, DunnGalvin A. Quality of life in childhood, adolescence and adult food allergy: Patient and parent perspectives. Clinical & Experimental Allergy [Internet]. 2017 Apr 14;47(4):530–9. Available from: https://onlinelibrary.wiley.com/doi/10.1111/cea.12849
44. Galvin AD, Vereda A, Rodríguez del Río P, Muraro A, Jones C, Ryan R, et al. Children and caregiver proxy quality of life from peanut oral immunotherapy trials. Clin Transl Allergy. 2022 Dec 19;12(12).
45. Leung N, Virkud Y, Steele PH, Kamilaris JS, Kim E, Vickery BP, et al. Quality Of Life With Sublingual Immunotherapy For Peanut. Journal of Allergy and Clinical Immunology [Internet]. 2014 Feb 1;133(2):AB103. Available from: https://doi.org/10.1016/j.jaci.2013.12.383