Skip to main content

Update on Allergen Immunotherapy for Allergic Rhinitis: Drops, Tablets, or Shots?


Purpose of Review

Allergen immunotherapy (AIT) is the only disease-modifying treatment available for allergic rhinitis (AR). Dosing considerations, efficacy, and safety of subcutaneous (SCIT), sublingual (SLIT), and intralymphatic (ILIT) immunotherapy are discussed.

Recent Findings

Patients with AR who cannot tolerate or do not wish to continue indefinite pharmacotherapy may be candidates for AIT. SCIT is the gold standard formulation but requires repeat injections over several years and may place the patient at risk for systemic allergic reactions such as anaphylaxis. SLIT has been developed as an alternative formulation by which the patient can avoid multiple injections and physician visits as it is dosed at home. SLIT has been proven to be very safe but still requires prolonged treatment, and efficacy compared to SCIT has been questioned. ILIT is currently being developed with the goal of shortening length of treatment while maintaining the efficacy and safety of SCIT and SLIT.


SCIT and SLIT are current options for patients wishing to undergo AIT. Further studies are required to determine if ILIT may become an effective option for patients who do not wish to undergo long-term treatments.

This is a preview of subscription content, access via your institution.


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

  1. 1.

    Dykewicz MS, Fineman S, Skoner DP, Nicklas R, Lee R, Blessing-Moore J, et al. Diagnosis and management of rhinitis: complete guidelines of the joint task force on practice parameters in allergy, asthma and immunology. American Academy of allergy, asthma, and immunology. Ann Allergy Asthma Immunol (Internet). 1998;81(5 Pt 2):478–518. Accessed 30 May 2017

    CAS  Article  Google Scholar 

  2. 2.

    Wright AL, Holberg CJ, Martinez FD, Halonen M, Morgan W, Taussig LM. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics (Internet). 1994;94(6 Pt 1):895–901. Accessed 30 May 2017

    CAS  Google Scholar 

  3. 3.

    Meltzer EO, Bukstein DA. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy, Asthma Immunol (Internet). 2011;106(2):S12–6. Accessed 30 May 2017

    Article  Google Scholar 

  4. 4.

    Blaiss MS. Allergic rhinitis: direct and indirect costs. Allergy Asthma Proc (Internet). 2010;31(5):375–80. Accessed 2017 May 30

    Article  Google Scholar 

  5. 5.

    Reisman RE, Mauriello PM, Davis GB, Georgitis JW, DeMasi JM. A double-blind study of the effectiveness of a high-efficiency particulate air (HEPA) filter in the treatment of patients with perennial allergic rhinitis and asthma. J Allergy Clin Immunol (Internet). 1990;85(6):1050–7. 30 May 2017

    CAS  Article  Google Scholar 

  6. 6.

    Nurmatov U, van Schayck CP, Hurwitz B, Sheikh A. House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review. Allergy (Internet). 2012;67(2):158–65. Accessed 30 May 2017

    CAS  Article  Google Scholar 

  7. 7.

    Seidman MD, Gurgel RK, Lin SY, Schwartz SR, Baroody FM, Bonner JR, et al. Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg (Internet). 2015;152(1 Suppl):S1–43. Accessed 2017 May 30

    Google Scholar 

  8. 8.

    Lin SY. Sublingual immunotherapy: current concepts for the U.S. practitioner. Int Forum Allergy Rhinol. 2014;4(Suppl. 2):55–9.

    Article  Google Scholar 

  9. 9.

    Senti G, Kündig TM. Intralymphatic immunotherapy. World Allergy Organ J (Internet). 2015;8(1):9. Accessed 30 May 2017

    Google Scholar 

  10. 10.

    Roche AM, Wise SK. Subcutaneous immunotherapy. Int Forum Allergy Rhinol (Internet). 2014;4(S2):S51–4. Accessed 2017 Jun 8

    Article  Google Scholar 

  11. 11.

    Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Calderon MA, editor. Cochrane database Syst Rev (Internet). 2007;(1):CD001936. doi:/10.1002/14651858.CD001936.pub2. Accessed 8 Jun 2017.

  12. 12.

    Matricardi PM, Kuna P, Panetta V, Wahn U, Narkus A. Subcutaneous immunotherapy and pharmacotherapy in seasonal allergic rhinitis: a comparison based on meta-analyses. J Allergy Clin Immunol (Internet). 2011;128(4):791–799.e6. Accessed 8 Jun 2017

    Article  Google Scholar 

  13. 13.

    Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Chelladurai Y, Segal JB, et al. Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review. Laryngoscope. 2014;124(3):616–27.

    Article  PubMed  Google Scholar 

  14. 14.

    •• Dhami S, Nurmatov U, Arasi S, Khan T, Asaria M, Zaman H, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis. Allergy (Internet). 2017; Accessed 7 Jun 2017. Largest systematic review to date, assessing 61 SCIT and 71 SLIT trials. The authors conclude that both forms of immunotherapy improved symptom, medication, and combined symptom and medication scores in the short term. There was modest evidence for improvement of symptom scores after discontinuation of therapy for both SCIT and SLIT.

  15. 15.

    Bernstein DI, Wanner M, Borish L, Liss GM, Immunotherapy Committee, American Academy of Allergy, Asthma and Immunology. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol (Internet). 2004;113(6):1129–36. Accessed 8 Jun 2017

    Article  Google Scholar 

  16. 16.

    Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. Risk factors for fatal and nonfatal reactions to subcutaneous immunotherapy. Ann Allergy, Asthma Immunol (Internet). 2016;116(4):354–359.e2. Accessed 8 Jun 2017

    Article  Google Scholar 

  17. 17.

    Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol (Internet). 2011;127(1):S1–55. Accessed 2017 Jun 8.

    Article  Google Scholar 

  18. 18.

    Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. AAAAI and ACAAI surveillance study of subcutaneous immunotherapy, year 3: what practices modify the risk of systemic reactions? Ann Allergy, Asthma Immunol (Internet). 2013;110(4):274–278.e1. Accessed 2017 Jun 8

    Article  Google Scholar 

  19. 19.

    James C, Bernstein DI. Allergen immunotherapy. Curr Opin Allergy Clin Immunol (Internet). 2017;17(1):55–9.

    CAS  Article  Google Scholar 

  20. 20.

    Kannan JA, Epstein TG. Immunotherapy safety: what have we learned from surveillance surveys? Curr Allergy Asthma Rep (Internet). 2013;13(4):381–8. Accessed 8 Jun 2017

    CAS  Article  Google Scholar 

  21. 21.

    Ryan MW, Marple BF, Leatherman B, Mims JW, Fornadley J, Veling M, et al. Current practice trends in allergy: results of a united states survey of otolaryngologists, allergist-immunologists, and primary care physicians. Int Forum Allergy Rhinol (Internet). 2014;4(10):789–95. doi:10.1002/alr.21359. Accessed 30 May 2017

    Article  Google Scholar 

  22. 22.

    Sambugaro R, Puccinelli P, Burastero SE, Di Rienzo V. The efficacy of sublingual immunotherapy for respiratory allergy is not affected by different dosage regimens in the induction phase. Allergol Immunopathol (Madr) (Internet). 31(6):329–37. Accessed 30 May 2017

  23. 23.

    Highlights of Prescribing Information (Internet). Prescribing Information-Med Guide.pdf. Accessed 30 May 2017.

  24. 24.

    Marogna M, Spadolini I, Massolo A, Canonica GW, Passalacqua G. Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study. J Allergy Clin Immunol (Internet). 2010;126(5):969–75. Accessed 2017 May 30

    Article  Google Scholar 

  25. 25.

    • Scadding GW, Calderon MA, Shamji MH, Eifan AO, Penagos M, Dumitru F, et al. Effect of 2 years of treatment with sublingual grass pollen immunotherapy on nasal response to allergen challenge at 3 years among patients with moderate to severe seasonal allergic rhinitis. Jama (Internet). 2017;317(6):615. doi:10.1001/jama.2016.21040. This is a randomized controlled prospective study that suggests that a short course of sublingual immunotherapy is not as effective as a longer course for management of AR.

    CAS  Article  Google Scholar 

  26. 26.

    Wilson DR, Torres LI, Durham SR. Sublingual immunotherapy for allergic rhinitis. Wilson D, editor. Cochrane database Syst Rev (Internet). 2003;(2):CD002893. doi: 10.1002/14651858.CD002893. Accessed 7 Jun 2017.

  27. 27.

    •• Lin SY, Erekosima N, Kim JM, Ramanathan M, Suarez-Cuervo C, Chelladurai Y, et al. Sublingual immunotherapy for the treatment of allergic Rhinoconjunctivitis and asthma a systematic review. Jama-Journal Am Med Assoc. 2013;309(12):1278–88. Large systematic review assessing management of both asthma and AR with sublingual immunotherapy. The authors concluded that there is moderate evidence supporting the effectiveness of SLIT, and that there were no life-threatening adverse events associated with SLIT.

    CAS  Article  Google Scholar 

  28. 28.

    Compalati E, Passalacqua G, Bonini M, Canonica GW. The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis. Allergy (Internet). 2009;64(11):1570–9. doi:10.1111/j.1398-9995.2009.02129.x. Accessed 7 Jun 2017

    CAS  Article  Google Scholar 

  29. 29.

    Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di Lorenzo G. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol (Internet). 2010;126(3):558–66. Accessed 7 Jun 2017

    Article  Google Scholar 

  30. 30.

    Radulovic S, Wilson D, Calderon M, Durham S. Systematic reviews of sublingual immunotherapy (SLIT). Allergy (Internet). 2011;66(6):740–52. Accessed 5 Jul 2017

    CAS  Article  Google Scholar 

  31. 31.

    Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy (Internet). 2012;67(3):302–11. doi:10.1111/j.1398-9995.2011.02761.x. Accessed 30 May 2017

    Article  Google Scholar 

  32. 32.

    Wasan A, Nanda A. Systemic reaction to timothy grass pollen sublingual immunotherapy. Ann Allergy Asthma Immunol (Internet). 2017; Accessed 30 May 2017.

  33. 33.

    Vissers JLM, van Esch BCAM, Hofman GA, Kapsenberg ML, Weller FR, van Oosterhout AJM. Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model. J Allergy Clin Immunol (Internet). 2004;113(6):1204–10. Accessed 2017 May 31

    CAS  Article  Google Scholar 

  34. 34.

    Pierson-Mullany LK, Jackola D, Blumenthal M, Rosenberg A. Altered allergen binding capacities of Amb a 1-specific IgE and IgG4 from ragweed-sensitive patients receiving immunotherapy. Ann Allergy Asthma Immunol (Internet). 2000;84(2):241–3. Available from: Accessed 31 May 2017

    CAS  Article  Google Scholar 

  35. 35.

    Zinkernagel RM. Localization dose and time of antigens determine immune reactivity. Semin Immunol (Internet). 2000;12(3):163–171-344. Accessed 31 May 2017.

  36. 36.

    Hylander T, Larsson O, Petersson-westin U, Eriksson M, Georén SK, Winqvist O, et al. Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial. Respir Res. 2016:1–9. doi:10.1186/s12931-016-0324-9.

  37. 37.

    Lee SP, Choi SJ, Joe E, Lee SM, Lee MW, Shim JW, et al. A pilot study of Intralymphatic immunotherapy for house dust mite, cat, and dog allergies 2017;9(3):272–277.

  38. 38.

    Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, et al. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci (Internet). 2008;105(46):17908–12. Accessed 31 May 2017

    CAS  Article  Google Scholar 

  39. 39.

    Witten M, Malling H-J, Blom L, Poulsen BC, Poulsen LK. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013;132(5):1248–1252.e5. Accessed 1 Jun 2017

    Article  PubMed  Google Scholar 

  40. 40.

    Leader BA, Rotella M, Stillman L, DelGaudio JM, Patel ZM, Wise SK. Immunotherapy compliance: comparison of subcutaneous versus sublingual immunotherapy. Int Forum Allergy Rhinol. 2016;6(5):460–4. Accessed 8 Jun 2017

    Article  PubMed  Google Scholar 

  41. 41.

    Musa F, Al-Ahmad M, Arifhodzic N, Al-Herz W. Compliance with allergen immunotherapy and factors affecting compliance among patients with respiratory allergies. Hum Vaccin Immunother. 2017;13(3):514–7. Accessed 8 Jun 2017

    Article  PubMed  Google Scholar 

  42. 42.

    Meadows A, Kaambwa B, Novielli N, Huissoon A, Fry-Smith A, Meads C, et al. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis. Heal Technol Assess. 2013;17(27):1–322. vi, xi–xiv. Accessed 8 Jun 2017.

    Google Scholar 

  43. 43.

    Chelladurai Y, Lin SY. Effectiveness of subcutaneous versus sublingual immunotherapy for allergic rhinitis. Curr Opin Otolaryngol Head Neck Surg. 2014;22(3):211–5.

    Article  PubMed  Google Scholar 

  44. 44.

    Dretzke J, Meadows A, Novielli N, Huissoon A, Fry-Smith A, Meads C. Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison. J Allergy Clin Immunol. 2013;131(5):1361–6. Accessed 8 Jun 2017

    Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Sandra Y. Lin.

Ethics declarations

Conflict of Interest

Dr. Christopher R. Roxbury and Dr. Sandra Y. Lin declare that they have no conflicts of interest.

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.

Additional information

This article is part of the Topical Collection on Special Topics In Otorhinolaryngology: Otolaryngic Allergy

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Roxbury, C.R., Lin, S.Y. Update on Allergen Immunotherapy for Allergic Rhinitis: Drops, Tablets, or Shots?. Curr Otorhinolaryngol Rep 5, 181–186 (2017).

Download citation


  • Allergic rhinitis
  • Allergen-specific immunotherapy
  • Sublingual immunotherapy
  • Subcutaneous immunotherapy
  • Intralymphatic immunotherapy