European Journal of Pediatrics

, Volume 170, Issue 2, pp 137–148

Clinical practice

Allergen-specific immunotherapy in children: facts and FAQs
  • Zsolt Szépfalusi
  • Saskia Gruber
  • Thomas Eiwegger
  • Eleonora Dehlink


Allergen-specific immunotherapy (SIT) in its various application forms represents the main treatment approach of IgE-mediated allergic diseases in adults and children. Despite this clear recommendation, many particularities of products, patient characteristics, and product availability in different countries hamper the use of allergen-specific immunotherapy in particular in children. The frequently asked questions by parents, patients, and physicians are the backbone of this review. Thus, the potentials and limitations of allergen-specific immunotherapy in children and adolescents will be highlighted. IgE-mediated allergic diseases are affecting about 20% of the population. They manifest commonly early in life, and hence, the use of SIT should be considered also early in the course of the disease.


Allergen-specific immunotherapy SIT SCIT SLIT Immunotherapy Allergen IgE-mediated allergy Allergy 



Allergen-specific immunotherapy


Sublingual allergen-specific immunotherapy


Subcutaneous allergen-specific immunotherapy


Chemically modified allergen extracts


  1. 1.
    Abramson MJ, Puy RM, Weiner JM (2010) Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev (8):CD001186Google Scholar
  2. 2.
    Abramson MJ, Puy RM, Weiner JM (2003) Allergen immunotherapy for asthma. Cochrane Database Syst Rev (4):CD001186Google Scholar
  3. 3.
    Akdis CA, Blesken T, Akdis M et al (1998) Role of interleukin 10 in specific immunotherapy. J Clin Invest 102:98–106PubMedGoogle Scholar
  4. 4.
    Akdis M (2009) Immune tolerance in allergy. Curr Opin Immunol 21:700–707PubMedGoogle Scholar
  5. 5.
    Akdis M, Akdis CA (2007) Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 119:780–791PubMedGoogle Scholar
  6. 6.
    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 199:1567–1575PubMedGoogle Scholar
  7. 7.
    Ariano R, Kroon AM, Augeri G et al (1999) Long-term treatment with allergoid immunotherapy with Parietaria. Clinical and immunologic effects in a randomized, controlled trial. Allergy 54:313–319PubMedGoogle Scholar
  8. 8.
    Asher MI, Montefort S, Bjorksten B et al (2006) Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 368:733–743PubMedGoogle Scholar
  9. 9.
    Bahceciler NN, Isik U, Barlan IB, Basaran MM (2001) Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double-blind, placebo-controlled study. Pediatr Pulmonol 32:49–55PubMedGoogle Scholar
  10. 10.
    Bellinghausen I, Metz G, Enk AH et al (1997) Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects. Eur J Immunol 27:1131–1139PubMedGoogle Scholar
  11. 11.
    Bernardini R, Campodonico P, Burastero S et al (2006) Sublingual immunotherapy with a latex extract in paediatric patients: a double-blind, placebo-controlled study. Curr Med Res Opin 22:1515–1522PubMedGoogle Scholar
  12. 12.
    Bernardini R, Pecora S, Milani M, Burastero SE (2008) Natural rubber latex allergy in children: clinical and immunological effects of 3-years sublingual immunotherapy. Eur Ann Allergy Clin Immunol 40:142–147PubMedGoogle Scholar
  13. 13.
    Beyer K, Wahn U (2008) Oral immunotherapy for food allergy in children. Curr Opin Allergy Clin Immunol 8:553–556PubMedGoogle Scholar
  14. 14.
    Bohle B (2007) The impact of pollen-related food allergens on pollen allergy. Allergy 62:3–10PubMedGoogle Scholar
  15. 15.
    Bordignon V, Parmiani S (2003) Variation of the skin end-point in patients treated with sublingual specific immunotherapy. J Investig Allergol Clin Immunol 13:170–176PubMedGoogle Scholar
  16. 16.
    Bousquet J, Lockey R, Malling HJ (1998) Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 102:558–562PubMedGoogle Scholar
  17. 17.
    Bousquet J, Lockey R, Malling HJ et al (1998) Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American Academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 81:401–405PubMedGoogle Scholar
  18. 18.
    Bousquet J, Van Cauwenberge P, Khaltaev N (2001) Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 108:S147–S334PubMedGoogle Scholar
  19. 19.
    Brewczynski PZ, Kroon AM (1999) Wirksamkeit und Verträglichkeit einer Immuntherapie mit modifizierten Gräserpollenallergenen. Allergologie 22:411–420Google Scholar
  20. 20.
    Bufe A, Eberle P, Franke-Beckmann E et al (2009) Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol 123(167–173):e167Google Scholar
  21. 21.
    Bufe A, Ziegler-Kirbach E, Stoeckmann E et al (2004) Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study. Allergy 59:498–504PubMedGoogle Scholar
  22. 22.
    Businco L, Zannino L, Cantani A et al (1995) Systemic reactions to specific immunotherapy in children with respiratory allergy: a prospective study. Pediatr Allergy Immunol 6:44–47PubMedGoogle Scholar
  23. 23.
    Cadario G, Galluccio AG, Pezza M et al (2007) Sublingual immunotherapy efficacy in patients with atopic dermatitis and house dust mites sensitivity: a prospective pilot study. Curr Med Res Opin 23:2503–2506PubMedGoogle Scholar
  24. 24.
    Cady CT, Powell MS, Harbeck RJ et al (2010) IgG antibodies produced during subcutaneous allergen immunotherapy mediate inhibition of basophil activation via a mechanism involving both FcgammaRIIA and FcgammaRIIB. Immunol Lett 130:57–65PubMedGoogle Scholar
  25. 25.
    Calderon MA, Alves B, Jacobson M et al (2007) Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev (1):CD001936Google Scholar
  26. 26.
    Caminiti L, Passalacqua G, Barberi S et al (2009) A new protocol for specific oral tolerance induction in children with IgE-mediated cow’s milk allergy. Allergy Asthma Proc 30:443–448PubMedGoogle Scholar
  27. 27.
    Canonica GW, Baena-Cagnani CE, Bousquet J et al (2007) Recommendations for standardization of clinical trials with allergen specific immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce. Allergy 62:317–324PubMedGoogle Scholar
  28. 28.
    Clark AT, Islam S, King Y et al (2009) Successful oral tolerance induction in severe peanut allergy. Allergy 64:1218–1220PubMedGoogle Scholar
  29. 29.
    Clavel R, Bousquet J, Andre C (1998) Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, placebo-controlled trial of a standardized five-grass-pollen extract in rhinitis. Allergy 53:493–498PubMedGoogle Scholar
  30. 30.
    Coifman RE, Cox LS (2007) 2006 American Academy of Allergy, Asthma & Immunology member immunotherapy practice patterns and concerns. J Allergy Clin Immunol 119:1012–1013PubMedGoogle Scholar
  31. 31.
    Compalati E, Penagos M, Tarantini F et al (2009) Specific immunotherapy for respiratory allergy: state of the art according to current meta-analyses. Ann Allergy Asthma Immunol 102:22–28PubMedGoogle Scholar
  32. 32.
    de Blay F, Barnig C, Kanny G et al (2007) Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a double-blind, placebo-controlled study. Ann Allergy Asthma Immunol 99:453–461PubMedGoogle Scholar
  33. 33.
    de Groot H, Mulder W (2010) Clinical practice: drug desensitization in children. Eur J Pediatr 169:1305–1309PubMedGoogle Scholar
  34. 34.
    Des Roches A, Paradis L, Menardo JL 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 99:450–453PubMedGoogle Scholar
  35. 35.
    Di Rienzo V, Marcucci F, Puccinelli P et al (2003) Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study. Clin Exp Allergy 33:206–210PubMedGoogle Scholar
  36. 36.
    Dolz I, Martinez-Cocera C, Bartolome JM, Cimarra M (1996) A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy. Allergy 51:489–500PubMedGoogle Scholar
  37. 37.
    Drachenberg KJ, Heinzkill M, Urban E, Woroniecki SR (2003) Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MLP) for children and adolescents. Allergol Immunopathol 31:270–277Google Scholar
  38. 38.
    Drachenberg KJ, Pfeiffer P, Urban E (2001) Sublinguale Immuntherapie. Ergebnisse einer randomisierten, doppelblinden, plazebokontrollierten Multicenterstudie mit einem standardisierten Birken- und Gräser-/Roggenpollenextrakt. Allergologie 24:525–534Google Scholar
  39. 39.
    Dreborg S, Agrell B, Foucard T et al (1986) A double-blind, multicenter immunotherapy trial in children, using a purified and standardized Cladosporium herbarum preparation. I. Clinical results. Allergy 41:131–140PubMedGoogle Scholar
  40. 40.
    Eifan AO, Akkoc T, Yildiz A et al (2010) Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy 40:922–932PubMedGoogle Scholar
  41. 41.
    Eng PA, Borer-Reinhold M, Heijnen IA, Gnehm HP (2006) Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood. Allergy 61:198–201PubMedGoogle Scholar
  42. 42.
    Eng PA, Reinhold M, Gnehm HP (2002) Long-term efficacy of preseasonal grass pollen immunotherapy in children. Allergy 57:306–312PubMedGoogle Scholar
  43. 43.
    Evans R, Pence H, Kaplan H, Rocklin RE (1976) The effect of immunotherapy on humoral and cellular responses in ragweed hayfever. J Clin Invest 57:1378–1385PubMedGoogle Scholar
  44. 44.
    Faith A, Richards DF, Verhoef A et al (2003) Impaired secretion of interleukin-4 and interleukin-13 by allergen-specific T cells correlates with defective nuclear expression of NF-AT2 and jun B: relevance to immunotherapy. Clin Exp Allergy 33:1209–1215PubMedGoogle Scholar
  45. 45.
    Feliziani V, Lattuada G, Parmiani S, Dall'Aglio PP (1995) Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. A double blind study. Allergol Immunopathol Madr 23:224–230PubMedGoogle Scholar
  46. 46.
    Fontana V, Holt LJ, Mainland D (1966) Effectiveness of hyposensitization therapy in ragweed hay-fever in children. JAMA 195:985–992PubMedGoogle Scholar
  47. 47.
    Francis JN, Till SJ, Durham SR (2003) Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol 111:1255–1261PubMedGoogle Scholar
  48. 48.
    Gafvelin G, Thunberg S, Kronqvist M et al (2005) Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1. Int Arch Allergy Immunol 138:59–66PubMedGoogle Scholar
  49. 49.
    Gillissen A, Bergmann KC, Kleine-Tebbe J et al (2003) Specific immunotherapy in allergic asthma. Dtsch Med Wochenschr 128:204–209PubMedGoogle Scholar
  50. 50.
    Gleich GJ, Zimmermann EM, Henderson LL, Yunginger JW (1982) Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study. J Allergy Clin Immunol 70:261–271PubMedGoogle Scholar
  51. 51.
    Glover MT, Atherton DJ (1992) A double-blind controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with atopic eczema. Clin Exp Allergy 22:440–446PubMedGoogle Scholar
  52. 52.
    Golden DB (2006) Insect allergy in children. Curr Opin Allergy Clin Immunol 6:289–293PubMedGoogle Scholar
  53. 53.
    Golden DB, Kagey-Sobotka A, Norman PS et al (2004) Outcomes of allergy to insect stings in children, with and without venom immunotherapy. N Engl J Med 351:668–674PubMedGoogle Scholar
  54. 54.
    Gotzsche PC, Johansen HK (2008) House dust mite control measures for asthma: systematic review. Allergy 63:646–659PubMedGoogle Scholar
  55. 55.
    Grosclaude M, Bouillot P, Alt R et al (2002) Safety of various dosage regimens during induction of sublingual immunotherapy. A preliminary study. Int Arch Allergy Immunol 129:248–253PubMedGoogle Scholar
  56. 56.
    Hedlin G, Heilborn H, Lilja G et al (1995) Long-term follow-up of patients treated with a three-year course of cat or dog immunotherapy. J Allergy Clin Immunol 96:879–885PubMedGoogle Scholar
  57. 57.
    Hofmann AM, Scurlock AM, Jones SM et al (2009) Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol 124:286–291, 291 e281–286PubMedGoogle Scholar
  58. 58.
    Horst M, Hejjaoui A, Horst V et al (1990) Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract. J Allergy Clin Immunol 85:460–472PubMedGoogle Scholar
  59. 59.
    Inal A, Altintas DU, Yilmaz M et al (2007) Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite. J Investig Allergol Clin Immunol 17:85–91PubMedGoogle Scholar
  60. 60.
    Ippoliti F, De Santis W, Volterrani A et al (2003) Immunomodulation during sublingual therapy in allergic children. Pediatr Allergy Immunol 14:216–221PubMedGoogle Scholar
  61. 61.
    Itoh N, Itagaki Y, Kurihara K (2010) Rush specific oral tolerance induction in school-age children with severe egg allergy: one year follow up. Allergol Int 59:43–51PubMedGoogle Scholar
  62. 62.
    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 62:943–948PubMedGoogle Scholar
  63. 63.
    Johansen P, Haffner AC, Koch F et al (2005) Direct intralymphatic injection of peptide vaccines enhances immunogenicity. Eur J Immunol 35:568–574PubMedGoogle Scholar
  64. 64.
    Jones SM, Pons L, Roberts JL et al (2009) Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 124:292–300, 300 e291–297PubMedGoogle Scholar
  65. 65.
    Jutel M, Akdis M, Budak F et al (2003) IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33:1205–1214PubMedGoogle Scholar
  66. 66.
    Jutel M, Pichler WJ, 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 154:4187–4194PubMedGoogle Scholar
  67. 67.
    Keskin O, Tuncer A, Adalioglu G et al (2006) The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis. Pediatr Allergy Immunol 17:396–407PubMedGoogle Scholar
  68. 68.
    Kinaciyan T, Jahn-Schmid B, Radakovics A et al (2007) Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. J Allergy Clin Immunol 119:937–943PubMedGoogle Scholar
  69. 69.
    Kleine-Tebbe J, Bergmann KC, Friedrichs F et al (2006) Die spezifische Immuntherapie (Hyposensibilisierung) bei IgE-vermittelten allergischen Erkrankungen. Allergo J 15:56–74Google Scholar
  70. 70.
    Kleine-Tebbe J, Bufe A, Ebner C et al (2009) Die spezifische Immuntherapie (Hyposensibilisierung) bei IgE-vermittelten allergischen Erkrankungen. Allergo J 18:508–537Google Scholar
  71. 71.
    Kleine-Tebbe J, Fuchs T, Klimek L et al (2001) Allergen immunotherapy—a position paper of the German society for allergology and clinical immunology. Pneumologie 55:438–444PubMedGoogle Scholar
  72. 72.
    Kopp MV, Niggemann B, Forster J (2009) House dust mite allergy: complete removal of the provoking allergen is a primary therapeutic approach. Allergy 64:1402–1403, author reply 1405PubMedGoogle Scholar
  73. 73.
    La Rosa M, Ranno C, Andre C et al (1999) Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 104:425–432PubMedGoogle Scholar
  74. 74.
    Larche M, Akdis CA, Valenta R (2006) Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 6:761–771PubMedGoogle Scholar
  75. 75.
    Laurent J, Smiejan JM, Bloch-Morot E, Herman D (1997) Safety of Hymenoptera venom rush immunotherapy. Allergy 52:94–96PubMedGoogle Scholar
  76. 76.
    Leroy B, Lachapelle JM, Jacquemin MG, Saint-Remy JM (1993) Immunotherapy of atopic dermatitis by injections of antigen–antibody complexes. Dermatology 186:276–277PubMedGoogle Scholar
  77. 77.
    Leynadier F, Herman D, Vervloet D, Andre C (2000) Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. J Allergy Clin Immunol 106:585–590PubMedGoogle Scholar
  78. 78.
    Ling EM, Smith T, Nguyen XD et al (2004) Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 363:608–615PubMedGoogle Scholar
  79. 79.
    Longo G, Barbi E, Berti I et al (2008) Specific oral tolerance induction in children with very severe cow’s milk-induced reactions. J Allergy Clin Immunol 121:343–347PubMedGoogle Scholar
  80. 80.
    Löwer J, Becker W-M, Vieths S (2003) Regulatory control and standardization of allergenic extracts. Druck- und Verlagshaus Sperlich Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe, Frankfurt am Main, pp 65–115Google Scholar
  81. 81.
    Lüderitz-Püchel U, Keller-Stanislawski B, Haustein D (2001) Neubewertung des Risikos von Test- und Therapieallergenen. Eine Analyse der UAW-Meldungen von 1991 bis 2000. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 44:709–718Google Scholar
  82. 82.
    Madonini E, Agostinis F, Barra R et al (2003) Long-term and preventive effects of sublingual allergen-specific immunotherapy: a retrospective, multicentric study. Int J Immunopathol Pharmacol 16:73–79PubMedGoogle Scholar
  83. 83.
    Madsen F (2007) EAACI ‘Standards for practical allergen-specific immunotherapy’. Allergy 62:332PubMedGoogle Scholar
  84. 84.
    Malling HJ (1999) WHO position paper (summary)—allergen-immunotherapy: therapeutic vaccines for allergic diseases. Wien Med Wochenschr 149:410–414PubMedGoogle Scholar
  85. 85.
    Malling HJ (2000) Minimising the risks of allergen-specific injection immunotherapy. Drug Saf 23:323–332PubMedGoogle Scholar
  86. 86.
    Marcotte GV, Braun CM, Norman PS et al (1998) Effects of peptide therapy on ex vivo T-cell responses. J Allergy Clin Immunol 101:506–513PubMedGoogle Scholar
  87. 87.
    Marcucci F, Sensi L, Di Cara G et al (2005) Dose dependence of immunological response to sublingual immunotherapy. Allergy 60:952–956PubMedGoogle Scholar
  88. 88.
    Marcucci F, Sensi L, Frati F et al (2003) Effects on inflammation parameters of a double-blind, placebo controlled one-year course of SLIT in children monosensitized to mites. Allergy 58:657–662PubMedGoogle Scholar
  89. 89.
    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 28:54–62PubMedGoogle Scholar
  90. 90.
    Menardo JL, Bousquet J, Ville G, Michel FB (1983) Desensitisation with hymenoptera venom in children. Arch Fr Pédiatr 40:543–547PubMedGoogle Scholar
  91. 91.
    Moller C, Dreborg S, Ferdousi HA et al (2002) Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 109:251–256PubMedGoogle Scholar
  92. 92.
    Mortemousque B, Bertel F, De Casamayor J et al (2003) House-dust mite sublingual-swallow immunotherapy in perennial conjunctivitis: a double-blind, placebo-controlled study. Clin Exp Allergy 33:464–469PubMedGoogle Scholar
  93. 93.
    Muller U, Akdis CA, 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 101:747–754PubMedGoogle Scholar
  94. 94.
    Niggemann B, Beyer K (2007) Pitfalls in double-blind, placebo-controlled oral food challenges. Allergy 62:729–732PubMedGoogle Scholar
  95. 95.
    Nouri-Aria KT, Wachholz PA, Francis JN et al (2004) Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172:3252–3259PubMedGoogle Scholar
  96. 96.
    Novembre E, Galli E, Landi F et al (2004) Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 114:851–857PubMedGoogle Scholar
  97. 97.
    Pajno GB, Barberio G, De Luca F et al (2001) Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. Clin Exp Allergy 31:1392–1397PubMedGoogle Scholar
  98. 98.
    Pajno GB, Caminiti L, Vita D et al (2007) Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol 120:164–170PubMedGoogle Scholar
  99. 99.
    Pajno GB, Peroni DG, Barberio G, Boner AL (2003) Efficacy of sublingual immunotherapy in asthma and eczema. Chem Immunol Allergy 82:77–88PubMedGoogle Scholar
  100. 100.
    Passalacqua G, Durham SR (2007) Allergic rhinitis and its impact on asthma update: allergen immunotherapy. J Allergy Clin Immunol 119:881–891PubMedGoogle Scholar
  101. 101.
    Pauli G, Larsen TH, Rak S et al (2008) Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J Allergy Clin Immunol 122:951–960PubMedGoogle Scholar
  102. 102.
    Pauli G, Purohit A, Oster JP et al (2000) Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population. Clin Exp Allergy 30:1076–1084PubMedGoogle Scholar
  103. 103.
    Piconi S, Trabattoni D, Saresella M et al (2007) Effects of specific immunotherapy on the B7 family of costimulatory molecules in allergic inflammation. J Immunol 178:1931–1937PubMedGoogle Scholar
  104. 104.
    Plewako H, Wosinska K, Arvidsson M et al (2006) Production of interleukin-12 by monocytes and interferon-gamma by natural killer cells in allergic patients during rush immunotherapy. Ann Allergy Asthma Immunol 97:464–468PubMedGoogle Scholar
  105. 105.
    Pradalier A, Basset D, Claudel A et al (1999) Sublingual-swallow immunotherapy (SLIT) with a standardized five-grass-pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis. Allergy 54:819–828PubMedGoogle Scholar
  106. 106.
    Przybilla B, Rueff F (1999) Desensitization of allergy to hymenoptera venoms. Wien Med Wochenschr 149:421–428PubMedGoogle Scholar
  107. 107.
    Purello-D'Ambrosio F, Gangemi S, Merendino RA et al (2001) Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study. Clin Exp Allergy 31:1295–1302PubMedGoogle Scholar
  108. 108.
    Purohit A, Niederberger V, Kronqvist M et al (2008) Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Clin Exp Allergy 38:1514–1525PubMedGoogle Scholar
  109. 109.
    Regulation of (EC) No 1901/2006 the European Parliament and of the Council of December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004. http://eceuropaeu/enterprise/pharmaceuticals/eudralex/vol1/reg_2006_1901/reg_2006_1901_enpdf
  110. 110.
    Reha CM, Ebru A (2007) Specific immunotherapy is effective in the prevention of new sensitivities. Allergol Immunopathol Madr 35:44–51PubMedGoogle Scholar
  111. 111.
    Rienzo VD, Minelli M, Musarra A et al (2005) Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years. Clin Exp Allergy 35:560–564PubMedGoogle Scholar
  112. 112.
    Ring J (1982) Successful hyposensitization treatment in atopic eczema: results of a trial in monozygotic twins. Br J Dermatol 107:597–602PubMedGoogle Scholar
  113. 113.
    Roder E, Berger MY, de Groot H, Gerth van Wijk R (2008) Sublingual immunotherapy in youngsters: adherence in a randomized clinical trial. Clin Exp Allergy 38:1659–1667PubMedGoogle Scholar
  114. 114.
    Rodriguez F, Boquete M, Ibanez MD et al (2006) Once daily sublingual immunotherapy without updosing—a new treatment schedule. Int Arch Allergy Immunol 140:321–326PubMedGoogle Scholar
  115. 115.
    Rolinck-Werninghaus C, Hamelmann E, Keil T et al (2004) The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children. Allergy 59:973–979PubMedGoogle Scholar
  116. 116.
    Rolinck-Werninghaus C, Staden U, Mehl A et al (2005) Specific oral tolerance induction with food in children: transient or persistent effect on food allergy? Allergy 60:1320–1322PubMedGoogle Scholar
  117. 117.
    Rolinck-Werninghaus C, Wolf H, Liebke C et al (2004) A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen. Allergy 59:1285–1293PubMedGoogle Scholar
  118. 118.
    Rueff F, Przybilla B (2004) Venom immunotherapy: adverse reactions and treatment failure. Curr Opin Allergy Clin Immunol 4:307–311PubMedGoogle Scholar
  119. 119.
    Rueff F, Wenderoth A, Przybilla B (2001) Patients still reacting to a sting challenge while receiving conventional Hymenoptera venom immunotherapy are protected by increased venom doses. J Allergy Clin Immunol 108:1027–1032PubMedGoogle Scholar
  120. 120.
    Sabbah A, Hassoun S, Le Sellin J et al (1994) A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen extract. Allergy 49:309–313PubMedGoogle Scholar
  121. 121.
    Sampson HA, Munoz-Furlong A, Bock SA et al (2005) Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol 115:584–591PubMedGoogle Scholar
  122. 122.
    Savolainen J, Jacobsen L, Valovirta E (2006) Sublingual immunotherapy in children modulates allergen-induced in vitro expression of cytokine mRNA in PBMC. Allergy 61:1184–1190PubMedGoogle Scholar
  123. 123.
    Schafer T, Ring J (1997) Epidemiology of allergic diseases. Allergy 52:14–22, discussion 35–16PubMedGoogle Scholar
  124. 124.
    Schuetze GE, Forster J, Hauk PJ et al (2002) Bee-venom allergy in children: long-term predictive value of standardized challenge tests. Pediatr Allergy Immunol 13:18–23PubMedGoogle Scholar
  125. 125.
    Secrist H, Chelen CJ, Wen Y et al (1993) Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med 178:2123–2130PubMedGoogle Scholar
  126. 126.
    Sheikh A, Shehata YA, Brown SG, Simons FE (2009) Adrenaline for the treatment of anaphylaxis: Cochrane systematic review. Allergy 64:204–212PubMedGoogle Scholar
  127. 127.
    Sicherer SH, Sampson HA (2007) Peanut allergy: emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol 120:491–503, quiz 504–495PubMedGoogle Scholar
  128. 128.
    Simons FE (2003) H1-Antihistamines: more relevant than ever in the treatment of allergic disorders. J Allergy Clin Immunol 112:S42–S52PubMedGoogle Scholar
  129. 129.
    Simons FE (2004) First-aid treatment of anaphylaxis to food: focus on epinephrine. J Allergy Clin Immunol 113:837–844PubMedGoogle Scholar
  130. 130.
    Simons FE, Gu X, Johnston LM, Simons KJ (2000) Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis? Pediatrics 106:1040–1044PubMedGoogle Scholar
  131. 131.
    Sopo SM, Onesimo R, Giorgio V, Fundaro C (2010) Specific oral tolerance induction (SOTI) in pediatric age: clinical research or just routine practice? Pediatr Allergy Immunol 21:e446–e449PubMedGoogle Scholar
  132. 132.
    Staden U, Rolinck-Werninghaus C, Brewe F et al (2007) Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 62:1261–1269PubMedGoogle Scholar
  133. 133.
    Steiss JO, Jodicke B, Lindemann H (2006) A modified ultrarush insect venom immunotherapy protocol for children. Allergy Asthma Proc 27:148–150PubMedGoogle Scholar
  134. 134.
    Stelmach I, Kaczmarek-Wozniak J, Majak P et al (2009) Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen. Clin Exp Allergy 39:401–408PubMedGoogle Scholar
  135. 135.
    Stewart GE 2nd, Lockey RF (1992) Systemic reactions from allergen immunotherapy. J Allergy Clin Immunol 90:567–578PubMedGoogle Scholar
  136. 136.
    Szepfalusi Z, Emminger W, Eitelberger F et al (2009) Allergen-specific immunotherapy for children and adolescents—a review on available products in Austria. Wien Klin Wochenschr 121:648–660PubMedGoogle Scholar
  137. 137.
    Tabar AI, Anda M, Bonifazi F et al (2006) Specific immunotherapy with standardized latex extract versus placebo in latex-allergic patients. Int Arch Allergy Immunol 141:369–376PubMedGoogle Scholar
  138. 138.
    Tabar AI, Lizaso MT, Garcia BE et al (2008) Double-blind, placebo-controlled study of Alternaria alternata immunotherapy: clinical efficacy and safety. Pediatr Allergy Immunol 19:67–75PubMedGoogle Scholar
  139. 139.
    Tari MG, Mancino M, Monti G (1990) Efficacy of sublingual immunotherapy in patients with rhinitis and asthma due to house dust mite. A double-blind study. Allergol Immunopathol Madr 18:277–284PubMedGoogle Scholar
  140. 140.
    Thalhamer T, Dobias H, Stepanoska T et al (2010) Designing hypoallergenic derivatives for allergy treatment by means of in silico mutation and screening. J Allergy Clin Immunol 125:926–934.e910PubMedGoogle Scholar
  141. 141.
    Till S, Walker S, Dickason R et al (1997) IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis. Clin Exp Immunol 110:114–121PubMedGoogle Scholar
  142. 142.
    Tonnel AB, Scherpereel A, Douay B et al (2004) Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy. Allergy 59:491–497PubMedGoogle Scholar
  143. 143.
    Ullrich D, Thum-Oltimer S, Mussler S, Jaeschke B (2007) Successful specific subcutaneous immunotherapy (SCIT) with non-modified semi-depot pollen and mite preparations. Allergo J 16:193–198Google Scholar
  144. 144.
    Urbanek R, Forster J, Kuhn W, Ziupa J (1985) Discontinuation of bee venom immunotherapy in children and adolescents. J Pediatr 107:367–371PubMedGoogle Scholar
  145. 145.
    Valenta R, Vrtala S, Focke-Tejkl M et al (2002) Synthetic and genetically engineered allergen derivatives for specific immunotherapy of type I allergy. Clin Allergy Immunol 16:495–517PubMedGoogle Scholar
  146. 146.
    Valentine MD, Schuberth KC, Kagey-Sobotka A et al (1990) The value of immunotherapy with venom in children with allergy to insect stings. N Engl J Med 323:1601–1603PubMedGoogle Scholar
  147. 147.
    Valovirta E, Jacobsen L, Ljorring C et al (2006) Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children. Allergy 61:1177–1183PubMedGoogle Scholar
  148. 148.
    van Neerven RJ, Arvidsson M, Ipsen H et al (2004) A double-blind, placebo-controlled birch allergy vaccination study: inhibition of CD23-mediated serum-immunoglobulin E-facilitated allergen presentation. Clin Exp Allergy 34:420–428PubMedGoogle Scholar
  149. 149.
    Vourdas D, Syrigou E, Potamianou P et al (1998) Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization. Allergy 53:662–672PubMedGoogle Scholar
  150. 150.
    Wachholz PA, Nouri-Aria KT, Wilson DR et al (2002) Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios. Immunology 105:56–62PubMedGoogle Scholar
  151. 151.
    Wachholz PA, Soni NK, Till SJ, Durham SR (2003) Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 112:915–922PubMedGoogle Scholar
  152. 152.
    Wahn U, Tabar A, Kuna P et al (2009) Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis. J Allergy Clin Immunol 123(160–166):e163Google Scholar
  153. 153.
    Warner JO, Price JF, Soothill JF, Hey EN (1978) Controlled trial of hyposensitisation to Dermatophagoides pteronyssinus in children with asthma. Lancet 2:912–915PubMedGoogle Scholar
  154. 154.
    Weisnagel J (1979) Nouvel agent hyposensibilisant dans le traitement de la rhinite allergique saisonniere (fievre des foins) a l´herbe a poux chez lnfant: le MRTA (modified ragweed tyrosine adsorbate). Unión Méd Can 108:685–690PubMedGoogle Scholar
  155. 155.
    Wenzel J, Meissner-Kraemer M, Bauer R et al (2003) Safety of rush insect venom immunotherapy. The results of a retrospective study in 178 patients. Allergy 58:1176–1179PubMedGoogle Scholar
  156. 156.
    Werfel T, Aberer W, Augustin M et al (2008) Leitlinien: Neurodermitis. AWMW onlineGoogle Scholar
  157. 157.
    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 multi-centre, randomized, dose–response study. Allergy 61:202–205PubMedGoogle Scholar
  158. 158.
    Wilson DR, Lima MT, Durham SR (2005) Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy 60:4–12PubMedGoogle Scholar
  159. 159.
    Zielen S, Metz D, Sommer E, Scherf H-P (2007) Kurzzeit-Immuntherapie mit Allergoiden und dem Adjuvans Monophosphoryl-Lipid-A. Allergologie 30:S1–S8Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Zsolt Szépfalusi
    • 1
  • Saskia Gruber
    • 1
  • Thomas Eiwegger
    • 1
  • Eleonora Dehlink
    • 1
  1. 1.Division of Pediatric Pneumology, Allergology and Endocrinology, Department of PediatricsMedical University of ViennaViennaAustria

Personalised recommendations