Skip to main content

Epicutaneous Immunotherapy

  • Chapter
  • First Online:
Pediatric Food Allergy

Abstract

There are currently no FDA-approved forms of immunotherapy for the treatment of IgE-mediated food allergy. Existing treatment includes avoidance of the food(s) to which a patient is allergic and being prepared to treat allergic reactions due to accidental exposures with epinephrine. Epicutaneous immunotherapy (EPIT) is an emerging treatment for IgE-mediated food allergy, and Phase II and III clinical studies have shown that treatment with EPIT results in a moderate increase in the amount of food tolerated after treatment with EPIT for 1 year, notably with a high safety profile. Further treatment with EPIT for 2–3 years has shown ongoing benefit, with recent data demonstrating sustained unresponsiveness after discontinuing therapy in a subset of patients. This chapter aims to review human studies that have shown efficacy of EPIT in peanut and cow’s milk allergic patients. EPIT treatment regimens and clinical pearls for patients and medical providers are also discussed, in addition to comparison of EPIT with other emerging treatments for food allergy, including oral and sublingual immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126(6 Suppl):S1–58.

    PubMed  PubMed Central  Google Scholar 

  2. Gupta RS, Warren CM, Smith BM, Jiang J, Blumenstock JA, Davis MM, et al. Prevalence and severity of food allergies among US adults. JAMA Netw Open. 2019;2(1):e185630.

    PubMed  PubMed Central  Google Scholar 

  3. Branum AM, Lukacs SL. Food allergy among children in the United States. Pediatrics. 2009;124(6):1549–55.

    PubMed  Google Scholar 

  4. 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. 2018;142(6). pii: e20181235.

    Google Scholar 

  5. Scurlock AM, Jones SM. Advances in the approach to the patient with food allergy. J Allergy Clin Immunol. 2018;141(6):2002–14.

    PubMed  Google Scholar 

  6. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Food and Nutrition Board; Committee on Food Allergies: Global Burden, Causes, Treatment, Prevention, and Public Policy. In: Oria MP, Stallings VA, editors. Finding a path to safety in food allergy: assessment of the global burden, causes, prevention, management, and public policy. Washington, DC: National Academics Press; 2016.

    Google Scholar 

  7. Walkner M, Warren C, Gupta RS. Quality of life in food allergy patients and their families. Pediatr Clin N Am. 2015;62(6):1453–61.

    Google Scholar 

  8. Clark S, Espinola J, Rudders SA, Banerji A, Camargo CA Jr. Frequency of US emergency department visits for food-related acute allergic reactions. J Allergy Clin Immunol. 2011;127(3):682–3.

    PubMed  Google Scholar 

  9. Fleischer DM, Perry TT, Atkins D, Wood RA, Burks AW, Jones SM, et al. Allergic reactions to foods in preschool-aged children in a prospective observational food allergy study. Pediatrics. 2012;130(1):e25–32.

    PubMed  PubMed Central  Google Scholar 

  10. Pautrizel R, Cabanieu G, Bricaud H, Broustet P. Allergenic group specificity & therapeutic consequences in asthma; specific desensitization method by epicutaneous route. La semaine des hopitaux: organe fonde par l’Association d’enseignement medical des hopitaux de Paris. 1957;33(22):1394–403.

    CAS  Google Scholar 

  11. 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. J Immunol (Baltimore, Md:1950). 2011;186(10):5629–37.

    CAS  Google Scholar 

  12. Jones SM, Sicherer SH, Burks AW, Leung DY, Lindblad RW, Dawson P, et al. Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults. J Allergy Clin Immunol. 2017;139(4):1242–52.e9.

    CAS  PubMed  Google Scholar 

  13. Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH. Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol. 2010;125(5):1165–7.

    CAS  PubMed  Google Scholar 

  14. Rutault K, Agbotounou W, Peillon A, Thébault C, Vincent F, Martin L, et al. Safety of Viaskin milk epicutaneous immunotherapy (EPIT) in IgE-mediated cow’s milk allergy (CMA) in children (MILES study). J Allergy Clin Immunol. 2016;137(2):AB132.

    Google Scholar 

  15. DBV technologies announces results from PHASE II study of Viaskin milk in milk- allergic patients [2018 press release]. 2/26/2018.

    Google Scholar 

  16. Dupont C, Bourrier T, de Blay F, Guénard-Bilbault L, Sauvage C, Cousin M-O, et al. Peanut epicutaneous immunotherapy (EPIT) in peanut-allergic children: 18 months treatment in the Arachild study. J Allergy Clin Immunol. 2014;133(2):AB102.

    Google Scholar 

  17. Sampson HA, Agbotounou W, Thébault C, Charles R, Martin L, Yang WH, et al. Epicutaneous immunotherapy (EPIT) is effective and safe to treat peanut allergy: a multi-national double-blind placebo-controlled randomized Phase IIb trial. J Allergy Clin Immunol. 2015;135(2):AB390.

    Google Scholar 

  18. Sampson HA, Shreffler WG, Yang WH, Sussman GL, Brown-Whitehorn TF, Nadeau KC, et al. Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: a randomized clinical trial. JAMA. 2017;318(18):1798–809.

    PubMed  PubMed Central  Google Scholar 

  19. Sampson HA, Gerth van Wijk R, 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(6):1260–74.

    PubMed  Google Scholar 

  20. Sampson HA, Agbotounou W, Thébault C, Ruban C, Martin L, Sussman GL, et al. Enhanced efficacy and confirmed safety of a two-year epicutaneous immunotherapy (EPIT) treatment of peanut allergy with Viaskin® peanut: the continuation of the Vipes Phase IIb randomized controlled trial (RCT). J Allergy Clin Immunol. 2016;137(2):AB408.

    Google Scholar 

  21. Brown-Whitehorn T, Sampson H. Sustained unresponsiveness following long-term epicutaneous immunotherapy (EPIT) with VIASKIN peanut: results of the OLFUS-VIPES Phase IIb study. EAACI congress 2018, Munich, 26–30 May 2018, 2018.

    Google Scholar 

  22. DBV technologies announces initiation of the Phase III study of Viaskin peanut for the treatment of peanut allergy children [2015 press release]. www.dbv-technologies.com, 12/7/2015.

  23. DBV technologies announces topline results of Phase III clinical trial in peanut-allergic patients four to 11 years of age [2017 press release]. www.dbv-technologies.com, 10/20/2017.

  24. DBV technologies announces completion of enrollment in Phase III extension study of Viaskin peanut [2017 press release]. www.dbv-technologies.com, 8/29/2017.

  25. DBV technologies announces expansion of clinical program of Viaskin peanut for the treatment of peanut allergy [2016 press release]. www.dbv-technologies.com, 8/1/2016.

  26. DBV technologies announces completion of blinded period in REALISE study of Viaskin peanut [2017 press release]. www.dbv-technologies.com, 10/12/2017.

  27. DBV technologies announces positive topline safety results from REALISE Phase III trial of Viaskin peanut for the treatment of peanut-allergic patients [2017 press release]. www.dbv-technologies.com, 11/20/2017.

  28. 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. J Allergy Clin Immunol. 2016;137(4):1258–61.e10.

    PubMed  Google Scholar 

  29. DBV technologies initiates Phase III study of Viaskin peanut in peanut-allergic patients one to three years of age [2017 press release]. www.dbv-technologies.com, 8/2/2017.

  30. Turjanmaa K, Darsow U, Niggemann B, Rance F, Vanto T, Werfel T. EAACI/GA2LEN position paper: present status of the atopy patch test. Allergy. 2006;61(12):1377–84.

    CAS  PubMed  Google Scholar 

  31. Sampson HA. Anaphylaxis and emergency treatment. Pediatrics. 2003;111(6 Pt 3):1601–8.

    PubMed  Google Scholar 

  32. Hofmann AM, Scurlock AM, Jones SM, Palmer KP, Lokhnygina Y, Steele PH, et al. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol. 2009;124(2):286–91.e1–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Anagnostou K, Islam S, King Y, Foley L, Pasea L, Bond S, et al. Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. Lancet. 2014;383(9925):1297–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol. 2008;122(6):1154–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Narisety SD, Skripak JM, Steele P, Hamilton RG, Matsui EC, Burks AW, et al. Open-label maintenance after milk oral immunotherapy for IgE-mediated cow’s milk allergy. J Allergy Clin Immunol. 2009;124(3):610–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Wood RA. Food allergen immunotherapy: current status and prospects for the future. J Allergy Clin Immunol. 2016;137(4):973–82.

    CAS  PubMed  Google Scholar 

  37. Begin P, Winterroth LC, Dominguez T, Wilson SP, Bacal L, Mehrotra A, et al. Safety and feasibility of oral immunotherapy to multiple allergens for food allergy. Allergy Asthma Clin Immunol. 2014;10(1):1.

    PubMed  PubMed Central  Google Scholar 

  38. Wood RA. Oral immunotherapy for food allergy. J Investig Allergol Clin Immunol. 2017;27(3):151–9.

    CAS  PubMed  Google Scholar 

  39. Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128(1):3–20.e6; quiz 1–2.

    PubMed  Google Scholar 

  40. Petroni D, Spergel JM. Eosinophilic esophagitis and symptoms possibly related to eosinophilic esophagitis in oral immunotherapy. Ann Allergy Asthma Immunol. 2018;120(3):237–40.e4.

    PubMed  Google Scholar 

  41. Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2014;113(6):624–9.

    PubMed  Google Scholar 

  42. Echeverria-Zudaire LA, Fernandez-Fernandez S, Rayo-Fernandez A, Munoz-Archidona C, Checa-Rodriguez R. Primary eosinophilic gastrointestinal disorders in children who have received food oral immunotherapy. Allergol Immunopathol (Madr). 2016;44(6):531–6.

    CAS  Google Scholar 

  43. Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367(3):233–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kim EH, Bird JA, Kulis M, Laubach S, Pons L, Shreffler W, et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J Allergy Clin Immunol. 2011;127(3):640–6.e1.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Fleischer DM, Burks AW, Vickery BP, Scurlock AM, Wood RA, Jones SM, et al. Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial. J Allergy Clin Immunol. 2013;131(1):119–27.e1–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Burks AW, Wood RA, Jones SM, Sicherer SH, Fleischer DM, Scurlock AM, et al. Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial. J Allergy Clin Immunol. 2015;135(5):1240–8.e1–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Taylor SL, Baumert JL. Cross-contamination of foods and implications for food allergic patients. Curr Allergy Asthma Rep. 2010;10(4):265–70.

    PubMed  Google Scholar 

  48. Baumert JL, Taylor SL, Koppelman SJ. Quantitative assessment of the safety benefits associated with increasing clinical peanut thresholds through immunotherapy. J Allergy Clin Immunol Pract. 2018;6(2):457–65.e4.

    PubMed  Google Scholar 

  49. Mondoulet L, Kalach N, Dhelft V, Larcher T, Delayre-Orthez C, Benhamou PH, et al. Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts. Clin Exp Allergy. 2017;47(12):1640–7.

    CAS  PubMed  Google Scholar 

  50. Mondoulet L, Dioszeghy V, Larcher T, Ligouis M, Dhelft V, Puteaux E, et al. Epicutaneous immunotherapy (EPIT) blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice. PLoS One. 2012;7(2):e31967.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. ClinicalTrials.Gov. Milk patch for eosinophilic esophagitis (SMILEE) 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT02579876?term=SMILEE&rank=1

  52. Gavillet BM, Mondoulet L, Dhelft V, Eberhardt CS, Auderset F, Pham HT, et al. Needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: preclinical proof of concept. Vaccine. 2015;33(30):3450–5.

    PubMed  Google Scholar 

  53. DBV Technologies. Pipeline – diagnostics. Available from: https://www.dbv-technologies.com/pipeline/

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Allison G. Hicks .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hicks, A.G., Fleischer, D.M. (2020). Epicutaneous Immunotherapy. In: Gupta, R. (eds) Pediatric Food Allergy . Springer, Cham. https://doi.org/10.1007/978-3-030-33292-1_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-33292-1_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-33291-4

  • Online ISBN: 978-3-030-33292-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics