Why Does Sublingual Immunotherapy Work?

Drops under the tongue? How is that is going to help my allergies? I used to hear this daily from my patients and now there seems to be a seismic shift in what patients know about sublingual immunotherapy, or allergy drops, and their success in allergy treatment.

Sublingual immunotherapy involves more than the gradual increasing doses of allergen placed under the tongue to build tolerance. Tolerance is the most accurate term used to describe the permanent change to the allergic immune response induced by sublingual immunotherapy.

We have found that that delivering immunotherapy under the tongue balances the best of safety and efficacy. This area under the tongue is rich in dendritic cells — cells which help induce tolerance, and it’s poor in mast and other effector cells such as basophils and eosinophils which can trigger allergic reactions. “…The mucosal surface has to deal with regular exposure to a wide range of innocuous material and its default response is set to nonresponse.”6 The sublingual area also has the highest permeability compared to any other easily accessible mucosal surface — which explains why fast-acting medications and highly effective vaccines have used this oral mucosal route for over a century, and not surprisingly, is increasingly becoming a popular route to deliver therapies today.

Titrated Dosing

We are also often asked how we dose and why. Dosing starts off with testing (either blood testing or skin testing), then incremental dosing for sublingual immunotherapy is determined by intradermal 5-fold dilutional testing in order to define a level of tolerance. Sublingual immunotherapy begins at the highest dilution that produced a near-negative skin test. This starts the immunotherapy at a low level and proceeds with increased doses as skin reactivity declines or clinical improvements are noted through blood testing. This gradual build up minimizes systemic and local reactions in patients.

Not all patients with a given allergy are equally reactive to the allergen(s) in question nor are allergen batches produced by the same manufacturer equal to each other, therefore we use titrated dosing for more accurate results. Likewise, custom dosing based on the specific patient’s reactivity eliminates the need for unnecessarily high doses that can increase both risk of reaction and cost without providing incremental benefit to the patient.

Frequent Administration

“Allergen persistence in the oral mucosa may be a far more relevant factor for gaining efficacy than allergen concentration.”3 A number of studies have shown that allergen administration to the sublingual mucosa is retained for a period of up to 48 hours.4,5 Multiple daily doses provide continuous, uninterrupted allergen exposure. While a higher concentration of antigen may stay on the sublingual mucosa longer, the capacity of the mucosa to take up antigens at any one time is limited. Antigen that is not taken up for presentation may contribute to side effects. Given this restriction, studies suggest, and our clinical experience corroborates, that there is a greater advantage to increasing the frequency to two or three times a day rather than increasing the dose by two or three times. Additionally, lower-dose antigen administered two or three times a day provides a greater margin of safety for our patients. Frequent administration may prove conducive to effector cell conditioning and may be the reason sublingual immunotherapy allergy drops, titrated against skin test/blood reactivity, has fewer side effects than SCIT2.

An additional benefit of the La Crosse Method is the metered dosing system that contains the drops. We use easy pump bottles for consistent metered delivery of customized dosing for each patient.  Patients are prescribed one vial at a time containing a 90-day supply of their customized allergen prescription drops. Patients can easily take them in the comfort of their home, work or when traveling, making adherence and ultimately long-term benefit more achievable.

Sublingual immunotherapy has been an effective tool for La Crosse Method providers for 45 years, with great success in both inhalant and food allergies. Our experience and research has demonstrated that customized sublingual immunotherapy allergy drops is a safe and effective allergy treatment.

This is part 2 of a 3 part series on the Key Tenets of the La Crosse Method Practice Protocol.

Author: Mary Morris, MD, ABIM


  1. Passalaqua, G., Compalati, E., Canonica, G.W. Sublingual Immunotherapy: Clinical Indications in the WAO-SLIT Position Paper. World Allergy Organization Journal 2010 Jul;3(7):216-219.
  2. Theodoropoulos, D., Morris, M., Morris, D. Emerging Concepts of Sublingual Immunotherapy for Allergy. Drugs of Today 2009, 45(10):737-750.
  3. Bordignon V, Burastero SE. Multiple daily administrations of low-dose sublingual immunotherapy in allergic rhinoconjunctivitis. Annals of Allergy, Asthma & Immunology 2006, 97:158-163.
  4. Bagnasco, M., Mariani, G., Passalacqua, G., et al. Absorption and distribution kinetics of the major Paretaria judaica allergen(Par j 1) administered by noninjectable routes in healthy human beings. Journal of Allergy and Clinical Immunology 1997 July;100(1):122-129.
  5. Cox, L., Li, J.T., Nelson, H., et al. Allergen Immunotherapy: a practice parameter second update. Journal of Allergy & Clinical Immunology. 2007 Sep;120(3Suppl):S25-85.
  6. Frew, AJ, Smith, HE. Sublingual immunotherapy. Journal of Allergy & Clinical Immunotherapy. 2001 March;170(3):441-444.