Allergen Immunotherapy and Atopic Dermatitis: the Good, the Bad, and the Unknown

  • Patrick Rizk
  • Mario Rodenas
  • Anna De BenedettoEmail author
Allergic Skin Diseases (L Fonacier and A Wollenberg, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Allergic Skin Diseases


Purpose of Review

In light of the recent advancements in atopic dermatitis treatment, this review aims to summarize the utility and efficacy of allergy immunotherapy in atopic dermatitis patients. We examine its mechanism, pathophysiology, cost-efficacy, and current guidelines for clinical practice.

Recent Findings

The literature supports the use of allergy immunotherapy in atopic conditions such as allergic rhinitis and asthma but insufficient evidence exists to suggest its efficacy in atopic dermatitis. The use of allergy immunotherapy has been shown to provide long-term cost savings in both the USA and the European Union in certain populations but differences in prescribing patterns and manufacturing make it difficult to study its impact on a larger, generalizable scale.


Conflicting meta-analyses data and conclusions highlight the need for better, higher quality research to better understand allergy immunotherapy utility in atopic dermatitis.


Atopic dermatitis Allergy immunotherapy AIT efficacy Treatment 



Allergy immunotherapy


Atopic dermatitis


Allergic rhinitis


Eczema Area and Severity Index




Quality adjusted life years


Subcutaneous immunotherapy


Sublingual immunotherapy


SCORing Atopic Dermatitis


Compliance with Ethics Guidelines

Conflict of Interest

Dr. De Benedetto has served on advisory board for Regeneron & Sanofi and Allakos. She has been an investigator for Novartis, Kiniksa, Alchem, Regeneron and Sanofi. Drs. Rizk and Rodenas declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Leung DYM, Bieber T. Atopic dermatitis. Lancet. 2003;361(9352):151–60. Scholar
  2. 2.
    •• Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138(2):336–49. Excellent paper summarizing the immunological mechanisms in AD pathogenesis. CrossRefPubMedGoogle Scholar
  3. 3.
    Novak N, Bieber T. Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol. 2003;112(2):252–62.CrossRefGoogle Scholar
  4. 4.
    Werfel T, Breuer K, Rueff F, Przybilla B, Worm M, Grewe M, et al. Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose–response study. Allergy. 2006;61(2):202–5.CrossRefGoogle Scholar
  5. 5.
    Frischmeyer-Guerrerio PA, Rasooly M, Gu WJ, Levin S, Jhamnani RD, Milner JD et al. IgE testing can predict food allergy status in patients with moderate to severe atopic dermatitis. Ann Allergy Asthma Immunol. 2019;122(4):393-+. doi:10.1016/j.anai.2019.01.001.CrossRefGoogle Scholar
  6. 6.
    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(4):578–83.e1.CrossRefGoogle Scholar
  7. 7.
    Ring J, Zink A, Arents BWM, Seitz IA, Mensing U, Schielein MC, et al. Atopic eczema: burden of disease and individual suffering - results from a large EU study in adults. J Eur Acad Dermatol Venereol. 2019;33(7):1331–40. Scholar
  8. 8.
    Williams H, Robertson C, Stewart A, Ait-Khaled N, Anabwani G, Anderson R, et al. Worldwide variations in the prevalence of symptoms of atopic eczema in the international study of asthma and allergies in childhood. J Allergy Clin Immunol. 1999;103(1):125–38. Scholar
  9. 9.
    Silverberg JI, Simpson EL. Association between severe eczema in children and multiple comorbid conditions and increased healthcare utilization. Pediatr Allergy Immunol. 2013;24(5):476–86. Scholar
  10. 10.
    Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483–94. Scholar
  11. 11.
    Lee HH, Patel KR, Singam V, Rastogi S, Silverberg JI. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-+. Scholar
  12. 12.
    Hanifin JM, Tofte SJ. Update on therapy of atopic dermatitis. J Allergy Clin Immunol. 1999;104(3):S123–S5. Scholar
  13. 13.
    Paller AS, Kabashima K, Bieber T. Therapeutic pipeline for atopic dermatitis: end of the drought? J Allergy Clin Immunol. 2017;140(3):633–43. Scholar
  14. 14.
    Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J Eur Acad Dermatol Venereol. 2018;32(6):850–78.CrossRefGoogle Scholar
  15. 15.
    Andersen YM, Egeberg A, Ban L, Gran S, Williams HC, Francis NA, et al. Association between topical corticosteroid use and type 2 diabetes in two European population-based adult cohorts. Diabetes Care. 2019;42(6):1095–103.CrossRefGoogle Scholar
  16. 16.
    Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365(14):1315–27. Scholar
  17. 17.
    Yang H, Wang J, Zhang X, Zhang Y, Qin ZL, Wang H, et al. Application of topical phosphodiesterase 4 inhibitors in mild to moderate atopic dermatitis a systematic review and meta-analysis. Jama Dermatol. 2019;155(5):585–93. Scholar
  18. 18.
    Bäumer W, Hoppmann J, Rundfeldt C, Kietzmann M. Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007;6(1):17–26.CrossRefGoogle Scholar
  19. 19.
    Dastidar SG, Rajagopal D, Ray A. Therapeutic benefit of PDE4 inhibitors in inflammatory diseases. Curr Opin Investig Drugs. 2007;8(5):364–72.PubMedGoogle Scholar
  20. 20.
    Jimenez JL, Punzón C, Navarro J, Muñoz-Fernández MA, Fresno M. Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation. J Pharmacol Exp Ther. 2001;299(2):753–9.PubMedGoogle Scholar
  21. 21.
    Hamilton JD, Ungar B, Guttman-Yassky E. Drug evaluation review: dupilumab in atopic dermatitis. Immunotherapy. 2015;7(10):1043–58. Scholar
  22. 22.
    Holm JG, Thomsen SF. Omalizumab for atopic dermatitis: evidence for and against its use. G Ital Dermatol Venereol. 2019;154(4):480–7. Scholar
  23. 23.
    Kupczyk M. Future directions of application and development of allergen immunotherapy. Alergol Polska-Polish J Allergol. 2018;5(2):80–4. Scholar
  24. 24.
    Hotze M, Baurecht H, Rodríguez E, Chapman-Rothe N, Ollert M, Fölster-Holst R, et al. Increased efficacy of omalizumab in atopic dermatitis patients with wild-type filaggrin status and higher serum levels of phosphatidylcholines. Allergy. 2014;69(1):132–5.CrossRefGoogle Scholar
  25. 25.
    • Owens S, Liu H, Sun K, Venturanza M, Kuligowski M, Howell M, editors. Ruxolitinib cream significantly modulates inflammatory profiles of atopic dermatitis patients. J Investig Dermatol; 2019: ELSEVIER SCIENCE INC STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA. Study showing the efficacy of ruxolitinib in reducing itch, reveling novel mechanism involved in itch. Google Scholar
  26. 26.
    Uermosi C, Zabel F, Manolova V, Bauer M, Beerli RR, Senti G. IgG-mediated down-regulation of IgE bound to mast cells: a potential novel mechanism of allergen-specific desensitization (vol 69, pg 338, 2014). Allergy. 2014;69(8):1118. Scholar
  27. 27.
    •• Larche M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6(10):761–71. Detailed overview of mechanisms of allergy immunotherapy in atopic disorders. CrossRefPubMedGoogle Scholar
  28. 28.
    Stanic B, van de Veen W, Wirz OF, Ruckert B, Morita H, Sollner S, et al. IL-10-overexpressing B cells regulate innate and adaptive immune responses. J Allergy Clin Immunol. 2015;135(3):771–U299. Scholar
  29. 29.
    Frankland A. High and low dosage pollen extract treatment in summer hay fever and asthma. Allergy. 1955;9(3):183–7.CrossRefGoogle Scholar
  30. 30.
    Patel P, Salapatek AMF. Pollinex((R)) Quattro: a novel and well-tolerated, ultra short-course allergy vaccine. Expert Rev Vaccines. 2006;5(5):617–29. Scholar
  31. 31.
    Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, et al. Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials. Ann Allergy Asthma Immunol. 2006;97(2):141–8. Scholar
  32. 32.
    Pajno GB, Caminiti L, Vita D, Barberio G, Salzano G, Lombardo F, et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol. 2007;120(1):164–70. Scholar
  33. 33.
    Cox LS, Hankin C, Lockey R. Allergy immunotherapy adherence and delivery route: location does not matter. J Allergy Clin Immunol. 2014;2(2):156–60.e2.CrossRefGoogle Scholar
  34. 34.
    Sade K, Berkun Y, Dolev Z, Shalit M, Kivity S. Knowledge and expectations of patients receiving aeroallergen immunotherapy. Ann Allergy Asthma Immunol. 2003;91(5):444–8.CrossRefGoogle Scholar
  35. 35.
    Abramowicz M, Kruszewski J, Chcialowski A. Evaluation of the placebo effect in the trials of allergen immunotherapy effectiveness: meta-analysis of randomized and placebo-controlled trials. Postepy Dermatologii I Alergologii. 2018;35(6):620–5. Scholar
  36. 36.
    Incorvaia C, Berto P, Ariano R, Elia R, Frati F. Cost-effectiveness of allergen immunotherapy. J Aller Ther S. 2012;6:2.Google Scholar
  37. 37.
    Petersen KD, Gyrd-Hansen D, Dahl R. Health-economic analyses of subcutaneous specific immunotherapy for grass pollen and mite allergy. Allergol Immunopathol. 2005;33(6):296–302.CrossRefGoogle Scholar
  38. 38.
    Hankin CS, Cox L, Lang D, Levin A, Gross G, Eavy G, et al. Allergy immunotherapy among Medicaid-enrolled children with allergic rhinitis: patterns of care, resource use, and costs. J Allergy Clin Immunol. 2008;121(1):227–32.CrossRefGoogle Scholar
  39. 39.
    Berto P, Bassi M, Incorvaia C, Frati F, Puccinelli P, Giaquinto C, et al. Cost effectiveness of sublingual immunotherapy in children with allergic rhinitis and asthma. Eur Ann Allergy Clin Immunol. 2005;37(8):303–8.PubMedGoogle Scholar
  40. 40.
    Pearson SD, Rawlins MD. Quality, innovation, and value for money: NICE and the British National Health Service. Jama. 2005;294(20):2618–22.CrossRefGoogle Scholar
  41. 41.
    Bachert C, Vestenbaek U, Christensen J, Griffiths UK, Poulsen PB. Cost-effectiveness of grass allergen tablet (GRAZAX (R)) for the prevention of seasonal grass pollen induced rhinoconjunctivitis - a Northern European perspective. Clin Exp Allergy. 2007;37(5):772–9. Scholar
  42. 42.
    Canonica GW, Poulsen PB, Vestenbaek U. Cost-effectiveness of GRAZAX (R) for prevention of grass pollen induced rhinoconjunctivitis in Southern Europe. Respir Med. 2007;101(9):1885–94. Scholar
  43. 43.
    Hankin CS, Cox L. Allergy immunotherapy: what is the evidence for cost saving? Curr Opin Allergy Clin Immunol. 2014;14(4):363–70. Scholar
  44. 44.
    •• Mahler V, Esch RE, Kleine-Tebbe J, Lavery WJ, Plunkett G, Vieths S, et al. Understanding differences in allergen immunotherapy products and practices in North America and Europe. J Allergy Clin Immunol. 2019;143(3):813–30. Provides an in-depth discussion of AIT in US vs. EU regulations, diagnostics, and practice patterns. CrossRefPubMedGoogle Scholar
  45. 45.
    Slater JE, Menzies SL, Bridgewater J, Mosquera A, Zinderman CE, Ou AC, et al. The US Food and Drug Administration review of the safety and effectiveness of nonstandardized allergen extracts. J Allergy Clin Immunol. 2012;129(4):1014–9.CrossRefGoogle Scholar
  46. 46.
    Golden DB, Demain J, Freeman T, Graft D, Tankersley M, Tracy J, et al. Stinging insect hypersensitivity: a practice parameter update 2016. Ann Allergy Asthma Immunol. 2017;118(1):28–54.CrossRefGoogle Scholar
  47. 47.
    Roberts G, Pfaar O, Akdis C, Ansotegui I, Durham S, Gerth van Wijk R, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy. 2018;73(4):765–98.CrossRefGoogle Scholar
  48. 48.
    Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, et al. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases. Allergo J Int. 2014;23(8):282–319.CrossRefGoogle Scholar
  49. 49.
    Virchow JC, Backer V, Kuna P, Prieto L, Nolte H, Villesen HH, et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. Jama. 2016;315(16):1715–25.CrossRefGoogle Scholar
  50. 50.
    Sánchez Caraballo JM, Cardona VR. Clinical and immunological changes of immunotherapy in patients with atopic dermatitis: randomized controlled trial. ISRN Allergy. 2012;2012.Google Scholar
  51. 51.
    • Tam HH, Calderon MA, Manikam L, Nankervis H, Núñez IG, Williams HC, et al. Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review. Allergy. 2016;71(9):1345–56. Recent meta-analysis on AIT efficacy in AD.CrossRefPubMedGoogle Scholar
  52. 52.
    Bae JM, Choi YY, Park CO, Chung KY, Lee KH. Efficacy of allergen-specific immunotherapy for atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol. 2013;132(1):110–7.CrossRefGoogle Scholar
  53. 53.
    •• Ridolo E, Martignago I, Riario-Sforza GG, Incorvaia C. Allergen immunotherapy in atopic dermatitis. Expert Rev Clin Immunol. 2018;14(1):61–8 Great source of updated guidelines and recommendations for AIT. CrossRefGoogle Scholar
  54. 54.
    • Boguniewicz M, Fonacier L, Guttman-Yassky E, Ong PY, Silverberg J, Farrar JR. Atopic dermatitis yardstick: Practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120(1):10–22.e2. Updates on AD management with practical information based on disease severity and impact on quality of life. CrossRefPubMedGoogle Scholar
  55. 55.
    Eichenfield LF, Ahluwalia J, Waldman A, Borok J, Udkoff J, Boguniewicz M. Current guidelines for the evaluation and management of atopic dermatitis–a comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology Guidelines. Alergol Polska-Polish J Allergol. 2017;4(4):158–68.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Patrick Rizk
    • 1
  • Mario Rodenas
    • 2
  • Anna De Benedetto
    • 1
    Email author
  1. 1.Department of DermatologyCollege of Medicine University of FloridaGainesvilleUSA
  2. 2.Section of Allergy and Clinical Immunology, Division of Rheumatology, Department of MedicineCollege of Medicine University of FloridaGainesvilleUSA

Personalised recommendations