Immunotherapy in Allergic Skin Disease

  • Hao Cheng
Part of the Advanced Topics in Science and Technology in China book series (ATSTC)


Allergic skin diseases, such as atopic dermatitis (AD) and urticaria are common diseases with increasing incidence in recent decades that are responsible for a serious burden on patients and their families, highlighting the need for devising effective therapeutic and preventive strategies. During the past few years, there have been significant advances in our understanding of the cellular and immunologic mechanisms underlying allergic skin diseases. Allergen-specific immunotherapy (SIT) that involves the administration of increasing concentrations of crude allergen extracts over a period of time, in an attempt to switch the indi- vidual’s allergic response to that of a non-allergic individual, is widely recognized as an effective treatment in asthma and allergic rhinitis, while its efficacy in most common allergic skin diseases, AD has been a matter of debate for a long time??Some novel immunotherapeutic approaches including monoclonal antibodies, CpG DNA, peptides, and recombinant allergen vaccines has significantly increased our treatment options. In this review, we provide some of the recent advances in our understanding of the immunotherapy in allergic skin disease AD.


Atopic Dermatitis Allergic Skin Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abramson, M.J., Puy, R.M., Weiner, J.M. (2003). Allergen immunotherapy for asthma. Cochrane Database Syst Rev, (4), CD001186.Google Scholar
  2. Abramson, M.J., Puy, R.M., Weiner, J.M. (1995). Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials. Am J Respir Crit Care Med, 151, 969–974.PubMedGoogle Scholar
  3. Akdis, M., Akdis, C.A. (2007). Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol, 119(4), 780–791.PubMedCrossRefGoogle Scholar
  4. Akdis, C., Akdis, A., Blesken, M. et al., (1996). Epitope-specific T-cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J Clin Invest, 98(7), 1676–1683.PubMedCrossRefGoogle Scholar
  5. Akdis, M., Verhagen, J., Taylor, A. et al. (2004). Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med, 199(11), 1567–1575.PubMedCrossRefGoogle Scholar
  6. Ali, F.R., Larché, M. (2005). Peptide-based immunotherapy: A novel strategy for allergic disease. Expert Rev Vaccines, 4(6), 881–889.PubMedCrossRefGoogle Scholar
  7. Álvarez-Cuesta, E., Bousquet, J., Canonica, G.W., et al. (2006). Standards for practical allergen-specific immunotherapy. Allergy, 61 (Suppl 82), 1–20.PubMedCrossRefGoogle Scholar
  8. Bauer, R., Scheiblhofer, S., Kern, K., et al. (2006). Generation of hypoallergenic DNA vaccines by forced ubiquitination: preventive and therapeutic effects in a mouse model of allergy. J Allergy Clin Immunol, 118, 269–276.PubMedCrossRefGoogle Scholar
  9. Bousquet, J., Demoly, P., Michel, F. (2001). Specific immunotherapy in rhinitis and asthma. J Allergy Clin Immunol, 87(1), 38–42.Google Scholar
  10. Beck, L. A., Marcotte, G. V., MacGlashan, D., et al. (2004). Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J Allergy Clin Immunol, 114(3), 527–530.PubMedCrossRefGoogle Scholar
  11. Boguniewicz, M., Leung, D.Y. (2006). Atopic dermatitis. J Allergy Clin Immunol, 117, S475–S480.PubMedCrossRefGoogle Scholar
  12. Bohle, B., Kinaciyan, T., Gerstmayr, M., et al. (2007). Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen specific T-cell tolerance, and immune deviation. J Allergy Clin Immunol, 120(3), 707–713.PubMedCrossRefGoogle Scholar
  13. Bussmann, C., Bockenhoff, A., Henke, H., et al. (2006). Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis? J Allergy Clin Immunol, 118(6), 1292–1298.PubMedCrossRefGoogle Scholar
  14. Bussmann, C., Maintz, L., Hart, J. (2007). Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcutaneous immuno-therapy with a house dust mite allergoid: A pilot study. Clin Exp Allergy, 37(9), 1277–1285.PubMedCrossRefGoogle Scholar
  15. Cadario, G., Galluccio, A.G., Pezza, M. (2007). Sublingual immunotherapy efficacy in patients with atopic dermatitis and house dust mites sensitivity: A prospective pilot study. Curr Med Res Opin, 23(10), 2503–2506.PubMedCrossRefGoogle Scholar
  16. Calamita, Z., Saconato, H., Pela, A.B. (2006). Efficacy of sublingual immunetherapy in asthma: Systematic review of randomized-clinical trials using the Cochrane collaboration method. Allergy, 61(10), 1162–1172.PubMedCrossRefGoogle Scholar
  17. Calderon, M.A., Alves, B., Jacobson, M. (2007). Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev, 24 (1), CD001936.Google Scholar
  18. Canonica, G.W., Passalacqua, G. (2003). Noninjection routes for immunetherapy. Review J Allergy Clin Immunol, 111 (3), 437–448.CrossRefGoogle Scholar
  19. Cho, J.Y., Miller, M., Baek, K.J., et al. (2004). Inhibition of airway remodeling in IL-5-deficient mice. J Clin Invest, 113, 551–560.PubMedGoogle Scholar
  20. Cooke, R.A., Barnard, J.H., Hebald, S., Stull, A. (1935). Serological evidence of immunity with coexisting sensitization in a type of human allergy (hay fever). J Exp Med, 62, 733–751.PubMedCrossRefGoogle Scholar
  21. Cosmi, L., Santarlasci, V., Angeli, R., et al. (2006). Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-gamma-and interleukin-10-production. Clin Exp Allergy, 36(3), 261–272.PubMedCrossRefGoogle Scholar
  22. Cox, L.S., Linnemann, DL., Nolte, H., et al. (2006). Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol, 117(5), 1021–1035.PubMedCrossRefGoogle Scholar
  23. Crameri, R., Flückiger, S., Daigle, I, et al. (2007) Design, engineering and in vitro evaluation of MHC class-II targeting allergy vaccines. Allergy, 62(2), 197–206.PubMedCrossRefGoogle Scholar
  24. Creticos, P.S., Schroeder, J.T., Hamilton, R.G., et al. (2006). Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med, 355(14), 1445–1455.PubMedCrossRefGoogle Scholar
  25. Czarnecka-Operacz, M., Silny, W. (2006). Specific immunotherapy in atopic dermatitis-four-year treatment in different age and airborne allergy type subgroups. Acta Dermatovenerol Croat, 14(4), 230–240.PubMedGoogle Scholar
  26. Des Roches, A., Paradis, L., Menardo, J.L., et al. (1997). Immunotherapy with a standardized dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol, 99 (4), 450–453.PubMedCrossRefGoogle Scholar
  27. Drew, A.C., Eusebius, N.P., Kenins, L., et al. (2004). Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity. J Immunol, 173(9), 5872–5879.PubMedGoogle Scholar
  28. Durham, S.R., Walker, S.M., Varga, E.M., et al. (1999). Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med, 341(7), 468–475.PubMedCrossRefGoogle Scholar
  29. Durham, S.R., Ying, S., Varney, V.A., et al. (1996). Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4+ T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-gamma. J Allergy Clin Immunol, 97(6), 1356–1365.PubMedCrossRefGoogle Scholar
  30. Finegold, I. (2001). Immunotherapy historical perspective. Annals of Allergy, Asthma & Immunology, 87(1), 3–4.CrossRefGoogle Scholar
  31. Flood-Page, P.T., Menzies-Gow, A.N., Kay, A.B., et al. (2003). Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med, 167, 199–204.PubMedCrossRefGoogle Scholar
  32. Frew, A.J. (2008). Sublingual immunotherapy. N Engl J Med, 358(21), 2259–2264.PubMedCrossRefGoogle Scholar
  33. Gafvelin, G., Parmley, S., Neimert-Andersson, T., Blank, U., Eriksson, T.L.J., van Hage, M., Punnonen, J. (2007). Hypoallergens for Allergen-specific Immunotherapy by Directed Molecular Evolution of Mite Group 2 Allergens. J Bio Chem, 282, 3778–3787.CrossRefGoogle Scholar
  34. Gardner, L.M., O’Hehir, R.E., Rolland, J.M. (2004a). High dose allergen stimulation of T cells from house dust mite-allergic subjects induces expansion of IFN gamma+T cells, apoptosis of CD4+IL-4+ T-cells and T-cell anergy. Int Arch Allergy Immunol, 133(1), 1–13.PubMedCrossRefGoogle Scholar
  35. Gardner, L.M., Thien, F.C., Douglass, J.A., et al. (2004c). Induction of T “regulatory” cells by standardized house dust mite immunotherapy: An increase in CD4+ CD25+ interleukin-10+ T-cells expressing peripheral tissue trafficking markers. Clin Exp Allergy, 34(8), 1209–1219.PubMedCrossRefGoogle Scholar
  36. Garrett, J.K., Jameson, S.C., Thomson, B., et al. (2004). Anti-Interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol, 113, 115–119.PubMedCrossRefGoogle Scholar
  37. Gerstmayr, M., Ilk, N., Schabussova, I., et al. (2007). A novel approach to specific allergy treatment: The recombinant allergen-Slayer fusion protein rSbsC-Bet v 1 matures dendritic cells that prime Th0/Th1 and IL-10-producing regulatory T-cells. J Immunol, 179(11), 7270–7275.PubMedGoogle Scholar
  38. Gidaro, G.B., Marcucci, F., Sensi, L., et al. (2005). The safety of sublingualswallow immunotherapy: an analysis of published studies. Clin Exp Allergy, 35(5), 565–571.PubMedCrossRefGoogle Scholar
  39. Gleich, G.J., Zimmermann, E.M., Henderson, L.L., et al. (1982). Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: A six-year prospective study. J Allergy Clin Immunol, 70(4), 261–271.PubMedCrossRefGoogle Scholar
  40. Gordon, B.R. (1995). Immunotherapy basics. Otolaryngology-Head and Neck Surgery, 113,597–602.PubMedGoogle Scholar
  41. Guerra, F., Carracedo, J., Solana-Lara, R., et al. (2001). TH2 lymphocytes from atopic patients treated with immunotherapy undergo rapid apoptosis after culture with specific allergens. J Allergy Clin Immunol, 107(4), 647–653.PubMedCrossRefGoogle Scholar
  42. Incorvaia, C., Pravettoni, C., Mauro, M., et al. (2008). Yacoub MR, Tarantini F, Riario-Sforza GG. Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis. Monaldi Arch Chest Dis, 69(2), 78–80.PubMedGoogle Scholar
  43. Inoue, J., Yotsumoto, S., Sakamoto, T., et al. (2005). Changes in immune responses to antigen applied to tape-stripped skin with CpG oligodeoxynucleotide in NC/Nga mice. Pharm Res, 22, 1627–1633.PubMedCrossRefGoogle Scholar
  44. Inoue, J., Aramaki, Y. (2007). Suppression of skin lesions by transdermal application of CpG-oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis. J Immunol, 178, 584–591.PubMedGoogle Scholar
  45. Jacobsen, L., Niggemann, B., Dreborg, S., et al. (2007). Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy, 62(8), 943–948.PubMedCrossRefGoogle Scholar
  46. James, L.K., Durham, S.R. (2008). Update on mechanisms of allergen injection immunotherapy. Clin Exp Allergy, 38(7), 1074–1088.PubMedCrossRefGoogle Scholar
  47. Jutel, M., Akdis, M., Blaser, K., et al. (2006). Mechanisms of allergen specific immunotherapy-T-cell tolerance and more. Allergy, 61(7), 796–807.PubMedCrossRefGoogle Scholar
  48. Jutel, M., Pichler, W.J., Skrbic, D., et al. (1995). Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures. J Immunol, 154(8), 4187–4194.PubMedGoogle Scholar
  49. Kim, E., Kim, S.H., Kim, S., et al. (2006). The novel cytokine p43 induces IL-12 production in macrophages via NF-kB activation, leading to enhance IFN-g production in CD4t T cells. J Immunol, 176, 256–264.PubMedGoogle Scholar
  50. Kim, E., Kim, S.H., Kim, S., et al. (2008). AIMP1/p43 protein induces the maturation of bone marrow-derived dendritic cells with T helper type 1-polarizing ability. J Immunol, 180, 2894–2902.PubMedGoogle Scholar
  51. Kleine-Tebbe, J., Ribel, M., Herold, D.A. (2006). Safety of a SQ-standardized grass allergen tablet for sublingual immunotherapy: A randomized, placebo-controlled trial. Allergy, 61(2), 181–184.PubMedCrossRefGoogle Scholar
  52. Kline, J.N. (2007). Eat dirt: CpG DNA and immunomodulation of asthma. Proc Am Thorac, 4(3), 283–288.CrossRefGoogle Scholar
  53. Klinman, D.M. (2004). Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol, 4, 249–258.PubMedCrossRefGoogle Scholar
  54. Larche, M. (2007). Peptide immunotherapy for allergic diseases. Allergy, 62(3), 325–331.PubMedCrossRefGoogle Scholar
  55. Leckie, M., Brinke, A., Khan, J., et al. (2000). Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsìveness, and the late asthmatic response. Lancet, 356, 2144–2148.PubMedCrossRefGoogle Scholar
  56. Leung, D.Y., Boguniewicz, M., Howell, M.D., et al. (2004). New insights into atopic dermatitis. J Clin Invest, 113, 651–657.PubMedGoogle Scholar
  57. Linhart, B., Valenta, R. (2005). Molecular design of allergy vaccines. Current Opinion in Immunology, 17, 646–655.PubMedCrossRefGoogle Scholar
  58. Lopez, A.F., Sanderson, C.J., Gamble, J.R., et al. (1998). Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med, 167, 219–224.CrossRefGoogle Scholar
  59. Maintz, L., Novak, N. (2007). Getting more and more complex: the pathophysiology of atopic eczema. Eur J Dermatol, 17, 267–283.PubMedGoogle Scholar
  60. Mauro, M., Russello, M., Incorvaia, C., et al. (2007). Comparison of efficacy, safety and immunologic effects of subcutaneous and sublingual immunotherapy in birch pollinosis: A randomized study. Eur Ann Allergy Clin Immunol, 39(4), 119–122.PubMedGoogle Scholar
  61. Mastrandrea, F., Serio, G., Minelli, M., et al. (2000). Specific sublingual immunotherapy in atopic dermatitis. Results of a 6-year follow-up of 35 consecutive patients. Allergol Immunopathol (Madr), 28(2), 54–62.Google Scholar
  62. Mellerup, M.T., Hahn, G.W., Poulsen, L.K. et al. (2000). Safety of allergen-specific immunotherapy. Relation between dosage regimen, allergen extract, disease and systemic side-effects during induction treatment. Clin Exp Allergy, 30(10), 1423–1429.PubMedCrossRefGoogle Scholar
  63. Moingeon, P., Batard, T., Fadel, R., et al. (2006). Immune mechanisms of allergen-specific sublingual immunotherapy. Allergy, 61(2), 151–165.PubMedCrossRefGoogle Scholar
  64. Möller C., Dreborg, S., Ferdousi, H.A., et al. (2002). Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol, 109(2), 251–256.PubMedCrossRefGoogle Scholar
  65. Mori, H., Yamanaka, K., Matsuo, K., et al. (2009). Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing regulatory T-cells. Arch Dermatol Res, 301,151–157.PubMedCrossRefGoogle Scholar
  66. Mothes, N., Heinzkill, M., Drachenberg, K.J., et al. (2003). Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: Reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Clin Exp Allergy, 33 (9), 1198–1208.PubMedCrossRefGoogle Scholar
  67. Muller, U., Akdis, C.A., Fricker, M., et al. (1998). Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol, 101, 747–754.PubMedCrossRefGoogle Scholar
  68. Noon, L. (1911). Prophylactic inoculation against hayfever. Lancet, 1, 1572–1573.CrossRefGoogle Scholar
  69. O’Brien, R.M., Byron, K.A., Varigos, G.A., et al. (1997). House dust mite immunotherapy results in a decrease in Der p 2-specific IFN-gamma and IL-4 expression by circulating T lymphocytes. Clin Exp Allergy, 27, 46–51.CrossRefGoogle Scholar
  70. O’Hehir, R.E., Sandrini, A., Anderson, G.P., et al. (2007). Sublingual allergen immunotherapy: Immunological mechanisms and prospects for refined vaccine preparation. Curr Med Chem, 14(21), 2235–2244.CrossRefGoogle Scholar
  71. Oldhoff, J.M., Darsow, U., Werfel, T., et al. (2005). Anti-IL-5 recombinant humanized monoclonal antibody (Mepolizumab) for the treatment of atopic dermatitis. Allergy, 60, 693–696.PubMedCrossRefGoogle Scholar
  72. Ozdemir, C. (2009). An immunological overview of allergen specific immunotherapy — subcutaneous and sublingual routes. Ther Adv Respir Dis, 3, 253–262.PubMedCrossRefGoogle Scholar
  73. Pajno, G.B., Caminiti, L., Vita, B., et al. (2007). Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol, 120, 164–170.PubMedCrossRefGoogle Scholar
  74. Patriarca, G., Schiavino, D., Pecora, V., et al. (2009). Food allergy and food intolerance: Diagnosis and treatment. Intern Emerg Med, 4, 11–24.PubMedCrossRefGoogle Scholar
  75. Pene, J., Desroches, A., Paradis, L. (1998). Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T-cells of patients allergic to cats. J Allergy Clin Immunol, 102, 571–578.PubMedCrossRefGoogle Scholar
  76. Rhyner, C., Kundig, T., Akdis, C.A., et al. (2007). Targeting the MHC II presentation pathway in allergy vaccine development. Biochemical Society Transactions, 35(4), 833–834.PubMedCrossRefGoogle Scholar
  77. Rolland, J.M., O’Hehir, R.E. (2008). Latex allergy: A model for therapy. Clin Exp Allergy, 38(6), 898–912.PubMedCrossRefGoogle Scholar
  78. Scadding, K., Brostoff, J. (1986). Low dose sublingual therapy in patients with allergic rhinitis due to dust mite. Clin Exp Allergy, 16, 483–491.CrossRefGoogle Scholar
  79. Sheinkopf, L.E., Rafi, A.W., Do, L.T. (2008). Efficacy of omalizumab in the treatment of atopic dermatitis: A pilot study. Allergy Asthma Proc, 29(5), 530–537.PubMedCrossRefGoogle Scholar
  80. Simons, F.E., Imada, M., Li, Y., et al. (1996). Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. Int Immunol, 8, 1937–1945.PubMedCrossRefGoogle Scholar
  81. Takatsu, K., Kariyone, A. (2003). The immunogenic peptide for Th1 development. Int Immunopharmacol, 3, 783–800.PubMedCrossRefGoogle Scholar
  82. Valenta, R., Niederberger, V. (2007). Recombinant allergens for immunothe-rapy. J Allergy Clin Immunol, 119(4), 826–830.PubMedCrossRefGoogle Scholar
  83. Werfel, T., Breuer, K., Rueff, F., et al. (2006). Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: A multicentre, randomized, dose-response study. Allergy, 61, 202–205.PubMedCrossRefGoogle Scholar

Copyright information

© Zhejiang University Press, Hangzhou and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Hao Cheng
    • 1
  1. 1.Department of Dermatology, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina

Personalised recommendations