Official reprint from UpToDate®
www.uptodate.com ©2015 UpToDate®

Subcutaneous immunotherapy for allergic disease: Indications and efficacy

Peter S Creticos, MD
Section Editor
Jonathan Corren, MD
Deputy Editor
Anna M Feldweg, MD


Immunotherapy for allergic disease involves the gradual administration of increasing amounts of allergen to which the patient is sensitive, for the purpose of modulating the untoward immune response to that allergen and alleviating allergic symptoms. Immunotherapy is the only treatment that alters the abnormal immune response underlying allergic disease.

Subcutaneous injection immunotherapy (SCIT) is the established form of this treatment. Oral forms of immunotherapy are not discussed in this topic review. The indications and efficacy for SCIT will be reviewed here. The therapeutic mechanisms of SCIT and the preparation of allergen extracts are discussed elsewhere. (See "Subcutaneous immunotherapy for allergic disease: Therapeutic mechanisms" and "Allergen extracts: Composition, manufacture, and labeling".)


The indications for SCIT with aeroallergens (ie, inhaled allergens, such as pollens, animal danders, etc) will be reviewed here. There are several questions that should be addressed to determine if SCIT is appropriate for a specific patient. The indications for venom immunotherapy for treatment of stinging insect hypersensitivity are discussed separately. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action" and "Stings of imported fire ants: Clinical manifestations, diagnosis, and treatment", section on 'Venom immunotherapy'.)

Does the patient have a disorder that responds to immunotherapy? — SCIT using preparations of aeroallergens may be indicated in the management of the following disorders:

Allergic rhinitis, with or without conjunctivitis, including:


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Oct 2015. | This topic last updated: Jul 16, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2015 UpToDate, Inc.
  1. Omnes LF, Bousquet J, Scheinmann P, et al. Pharmacoeconomic assessment of specific immunotherapy versus current symptomatic treatment for allergic rhinitis and asthma in France. Eur Ann Allergy Clin Immunol 2007; 39:148.
  2. Ramirez NC, Ledford DK. Immunotherapy for allergic asthma. Med Clin North Am 2002; 86:1091.
  3. Petersen KD, Gyrd-Hansen D, Dahl R. Health-economic analyses of subcutaneous specific immunotherapy for grass pollen and mite allergy. Allergol Immunopathol (Madr) 2005; 33:296.
  4. Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127:S1.
  5. Bussmann C, Maintz L, Hart J, et al. Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcutaneous immunotherapy with a house dust mite allergoid: a pilot study. Clin Exp Allergy 2007; 37:1277.
  6. Werfel T, Breuer K, Ruéff F, 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; 61:202.
  7. Glover MT, Atherton DJ. A double-blind controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with atopic eczema. Clin Exp Allergy 1992; 22:440.
  8. Dreborg S, Lee TH, Kay AB, Durham SR. Immunotherapy is allergen-specific: a double-blind trial of mite or timothy extract in mite and grass dual-allergic patients. Int Arch Allergy Immunol 2012; 158:63.
  9. Norman PS, Lichtenstein LM. The clinical and immunologic specificity of immunotherapy. J Allergy Clin Immunol 1978; 61:370.
  10. Lack G, Nelson HS, Amran D, et al. Rush immunotherapy results in allergen-specific alterations in lymphocyte function and interferon-gamma production in CD4+ T cells. J Allergy Clin Immunol 1997; 99:530.
  11. Nelson HS. Multiallergen immunotherapy for allergic rhinitis and asthma. J Allergy Clin Immunol 2009; 123:763.
  12. Calderón MA, Cox L, Casale TB, et al. Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: looking at the published evidence. J Allergy Clin Immunol 2012; 129:929.
  13. Norman PS. Immunotherapy: 1999-2004. J Allergy Clin Immunol 2004; 113:1013.
  14. Bousquet J, Lockey R, Malling HJ, et al. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 1998; 81:401.
  15. Nelson HS. Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol 2004; 113:635.
  16. Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 1999; 341:468.
  17. Walker SM, Pajno GB, Lima MT, et al. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. J Allergy Clin Immunol 2001; 107:87.
  18. Hedlin G, Silber G, Naclerio R, et al. Comparison of the in-vivo and in-vitro response to ragweed immunotherapy in children and adults with ragweed-induced rhinitis. Clin Exp Allergy 1990; 20:491.
  19. Durham SR, Ying S, Varney VA, et al. 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 1996; 97:1356.
  20. Li JT. Immunotherapy for allergic rhinitis. Immunol Allergy Clin North Am 2000; 20:383.
  21. Leynadier F, Banoun L, Dollois B, et al. Immunotherapy with a calcium phosphate-adsorbed five-grass-pollen extract in seasonal rhinoconjunctivitis: a double-blind, placebo-controlled study. Clin Exp Allergy 2001; 31:988.
  22. Schmidt BM, Kusma M, Feuring M, et al. The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis. J Allergy Clin Immunol 2001; 108:530.
  23. Ewbank PA, Murray J, Sanders K, et al. A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract. J Allergy Clin Immunol 2003; 111:155.
  24. Nanda A, O'connor M, Anand M, et al. Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract. J Allergy Clin Immunol 2004; 114:1339.
  25. Ross RN, Nelson HS, Finegold I. Effectiveness of specific immunotherapy in the treatment of allergic rhinitis: an analysis of randomized, prospective, single- or double-blind, placebo-controlled studies. Clin Ther 2000; 22:342.
  26. Lowell FC, Franklin W. A double-blind study of the effectiveness and specificity of injecton therapy in ragweed hay fever. N Engl J Med 1965; 273:675.
  27. Alvarez-Cuesta E, Aragoneses-Gilsanz E, Martín-Garcia C, et al. Immunotherapy with depigmented glutaraldehyde-polymerized extracts: changes in quality of life. Clin Exp Allergy 2005; 35:572.
  28. Calderon MA, Alves B, Jacobson M, et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev 2007; :CD001936.
  29. Rak S, Heinrich C, Jacobsen L, et al. A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. J Allergy Clin Immunol 2001; 108:921.
  30. Bielory L, Mongia A. Current opinion of immunotherapy for ocular allergy. Curr Opin Allergy Clin Immunol 2002; 2:447.
  31. Bousquet J, Calvayrac P, Guérin B, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. I. In vivo and in vitro parameters after a short course of treatment. J Allergy Clin Immunol 1985; 76:734.
  32. Creticos PS, Reed CE, Norman PS, et al. Ragweed immunotherapy in adult asthma. N Engl J Med 1996; 334:501.
  33. Abramson MJ, Puy RM, Weiner JM. Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials. Am J Respir Crit Care Med 1995; 151:969.
  34. Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2003; :CD001186.
  35. Zielen S, Kardos P, Madonini E. Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: a randomized controlled trial. J Allergy Clin Immunol 2010; 126:942.
  36. National Asthma Education and Prevention Program: Expert Panel Report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD. National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051). www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (Accessed on April 23, 2009).
  37. Bousquet J, Hejjaoui A, Clauzel AM, et al. Specific immunotherapy with a standardized Dermatophagoides pteronyssinus extract. II. Prediction of efficacy of immunotherapy. J Allergy Clin Immunol 1988; 82:971.
  38. Creticos PS. The consideration of immunotherapy in the treatment of allergic asthma. J Allergy Clin Immunol 2000; 105:S559.
  39. Ortolani C, Pastorello E, Moss RB, et al. Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis. J Allergy Clin Immunol 1984; 73:283.
  40. Kang BC, Johnson J, Morgan C, Chang JL. The role of immunotherapy in cockroach asthma. J Asthma 1988; 25:205.
  41. Des Roches A, Paradis L, Menardo JL, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol 1997; 99:450.
  42. Abramson M, Puy R, Weiner J. Immunotherapy in asthma: an updated systematic review. Allergy 1999; 54:1022.
  43. Polosa R, Al-Delaimy WK, Russo C, et al. Greater risk of incident asthma cases in adults with allergic rhinitis and effect of allergen immunotherapy: a retrospective cohort study. Respir Res 2005; 6:153.
  44. Corren J. The connection between allergic rhinitis and bronchial asthma. Curr Opin Pulm Med 2007; 13:13.
  45. Jacobsen L, Niggemann B, Dreborg S, et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 2007; 62:943.
  46. Jacobsen L, Valovirta E. How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Curr Opin Allergy Clin Immunol 2007; 7:556.
  47. Amin HS, Liss GM, Bernstein DI. Evaluation of near-fatal reactions to allergen immunotherapy injections. J Allergy Clin Immunol 2006; 117:169.
  48. Reid MJ, Lockey RF, Turkeltaub PC, Platts-Mills TA. Survey of fatalities from skin testing and immunotherapy 1985-1989. J Allergy Clin Immunol 1993; 92:6.
  49. Kopp MV, Hamelmann E, Zielen S, et al. Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma. Clin Exp Allergy 2009; 39:271.
  50. Massanari M, Nelson H, Casale T, et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol 2010; 125:383.
  51. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol 2007; 120:S25.
  52. van Wijk RG. When to initiate immunotherapy in children with allergic disease? Lessons from the paediatric studies. Curr Opin Allergy Clin Immunol 2008; 8:565.
  53. Asero R. Efficacy of injection immunotherapy with ragweed and birch pollen in elderly patients. Int Arch Allergy Immunol 2004; 135:332.
  54. Schädlich PK, Brecht JG. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics 2000; 17:37.
  55. Incorvaia C, Agostinis F, Amoroso S, et al. Pharmacoeconomics of subcutaneous allergen immunotherapy. Eur Ann Allergy Clin Immunol 2007; 39 Spec No:17.
  56. Hankin CS, Cox L, Lang D, et al. Allergen immunotherapy and health care cost benefits for children with allergic rhinitis: a large-scale, retrospective, matched cohort study. Ann Allergy Asthma Immunol 2010; 104:79.
  57. Hankin CS, Cox L, Lang D, et al. Allergy immunotherapy among Medicaid-enrolled children with allergic rhinitis: patterns of care, resource use, and costs. J Allergy Clin Immunol 2008; 121:227.
  58. Brüggenjürgen B, Reinhold T, Brehler R, et al. Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma. Ann Allergy Asthma Immunol 2008; 101:316.
  59. Simoens S. The cost-effectiveness of immunotherapy for respiratory allergy: a review. Allergy 2012; 67:1087.
  60. Hankin CS, Cox L, Bronstone A, Wang Z. Allergy immunotherapy: reduced health care costs in adults and children with allergic rhinitis. J Allergy Clin Immunol 2013; 131:1084.
  61. Li JT, Lockey RF, Bernstien IL, et al. Allergen immunotherapy: a practice parameter. Ann Allergy Asthma Immunol 2003; 90:S1.
  62. Des Roches A, Paradis L, Knani J, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. V. Duration of the efficacy of immunotherapy after its cessation. Allergy 1996; 51:430.
  63. Tabar AI, Arroabarren E, Echechipía S, et al. Three years of specific immunotherapy may be sufficient in house dust mite respiratory allergy. J Allergy Clin Immunol 2011; 127:57.
  64. Platts-Mills TA, von Maur RK, Ishizaka K, et al. IgA and IgG anti-ragweed antibodies in nasal secretions. Quantitative measurements of antibodies and correlation with inhibition of histamine release. J Clin Invest 1976; 57:1041.
  65. Jacobsen L, Nũchel Petersen B, Wihl JA, et al. Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long-term (6-year) follow-up. Allergy 1997; 52:914.
  66. Naclerio RM, Proud D, Moylan B, et al. A double-blind study of the discontinuation of ragweed immunotherapy. J Allergy Clin Immunol 1997; 100:293.
  67. Mosbech H, Osterballe O. Does the effect of immunotherapy last after termination of treatment? Follow-up study in patients with grass pollen rhinitis. Allergy 1988; 43:523.