Sublingual Immunotherapy: An Effective Approach to Environmental Allergy

LAURIE MENK OTTO, ND, MPH

Allergy is a leading chronic health condition throughout the world and is especially prevalent in westernized societies. The prevalence of allergic rhinitis and asthma in the US population is 7-8% for all ages.^1,2 Allergy accounts for upwards of $20 billion per year in healthcare expenses in the United States alone,³ leading world expenditures for this condition. Environmental allergy is characterized by rhinorrhea, persistent sneezing, nasal obstruction, conjunctivitis, and itching, and symptoms range from mild to severe and debilitating. Technically speaking, allergy is an erroneous reaction to non-harmful environmental elements involving multiple cell types, with the resultant inflammation dominated by Th2-driven IgE antibodies, eosinophils, and mast cells.^4-6 Reactivity is induced by environmental exposures and is strongly genetically determined, with a 30% or 80% increased prevalence in children of 1 or 2 affected parents, respectively.⁷  

Significance of Environmental Allergy 

To fully appreciate the significance of allergic disease, the burden of conditions associated with allergy – such as asthma (for which 75% cases have an allergic trigger), chronic sinusitis and bronchitis, nasal polyposis, allergic conjunctivitis, urticaria, eczema, otitis media, sleep-disordered breathing, and others – must be considered as well. The total annual US health care costs associated with diagnosed and treated allergy, eczema, and asthma approach and likely exceed $100 billion. These conditions cause significant morbidity among sufferers.^8-11  

Allergy-related illness is responsible for 3.5 million and 2 million lost work days and school days, respectively, in the United States each year.¹² These trends are expected to accelerate due to the impact of human-driven climate change, which is the driving factor behind consistently increasing pollen counts (21% increase from 1990 to 2020) and a longer high-pollen season (20 additional days in 2020 compared to 1990); it has also led to increasing allergic sensitization and allergy and asthma expression among all age groups.¹³ The significant debility and cost of care, along with environmental factors driving reactivity, underscore the significance of allergy and allergic disease, as well as the need for targeted therapies to reduce the overall burden and suffering of allergic disease. It is important that naturopathic doctors understand the tools available to treat, rather than palliate, allergy. Addressing underlying causes of inflammation (Tolle causam) helps to prevent acceleration of immune reactivity, as well as the development of secondary effects such as infection and chronic inflammation. This article focuses treatment on immunotherapy, as it is expected that naturopathic doctors have proficiency in addressing the modifiable factors listed below. 

Treatment Considerations 

The Allergic Load 

Choosing the appropriate treatment of allergy requires understanding modifiable and nonmodifiable factors contributing to inflammatory burden.¹⁴ Nonmodifiable factors include genetic predisposition. Modifiable factors may influence allergy directly (environmental exposures) or indirectly (biome, food sensitivity, nutrition, hormones, stress, and exposure to environmental chemicals), and collectively constitute “allergic load.”¹⁴ My approach to allergy and atopic disease includes taking a detailed history and developing clinical suspicion regarding important allergens, individually assessing relevant modifiable factors suspected to be driving inflammation (the allergic load), avoidance of known triggers,⁷ and most often by treating allergy directly using immunotherapy.  

Immunotherapy 

Immunotherapy is a disease-modifying treatment that consists of strategic introduction of a known allergen in order to induce tolerance. Immunotherapy for inhalant allergy, specifically, can be in the form of sublingual immunotherapy drops (referred to as “allergy drops” in this article), subcutaneous immunotherapy (“allergy shots”), and sublingual immunotherapy tablets developed by pharmaceutical companies. Allergy drops and allergy shots offer the benefit of treating multiple allergens simultaneously, whereas sublingual immunotherapy tablets treat only 1 or 2 allergens (eg, dust, grass). To date, allergy drops are the safest and most convenient form of immunotherapy for inhalant allergies, when compared to allergy shots and tablets. It’s a common recommendation to transition to allergy drops if allergy shots were not tolerated, or if a patient experienced systemic side effects, including anaphylaxis. 

Sublingual Immunotherapy 

Mechanism of Action 

Sublingual immunotherapy consists of the introduction of known allergens to the mucosal tissues of the mouth. Because the oral cavity is generally predisposed towards tolerance, this route is utilized for its favorable immunological environment. Following introduction, antigens are processed by antigen-presenting dendritic cells of the superficial mucosal tissues, thereby avoiding the Th2 inflammation-inducing eosinophils and mast cells of the submucosal tissues.⁶ Following capture, antigens are brought to cervical draining lymph nodes, resulting in a tolerogenic immune profile specific to the antigens introduced.¹⁵ Specifically, interferon-gamma (IFNγ) and interleukin-10 expression lead to induction of tolerance by naïve T cells, deviation from Th2 towards Th1, and/or apoptosis of Th2 cells specific to antigen triggers.^6,15-18 The outcomes of consistent, long-term administration include decreased eosinophil activation and IgE production upon exposure to seasonal allergens, persistent increase in blocking IgG4 antibody activity, and likely prevention of new sensitization. Arguably, this is the most direct root-cause allergy treatment available.   

Risks inherent to any type of immunotherapy include anaphylaxis and local reactions such as oral swelling reactions, mouth and throat itching, and increased allergy symptoms. For these reasons, it is important to work with someone specifically trained in immunotherapy administration as well as knowledgeable in risk assessment and dose adjustment. 

Treatment Course 

A typical course of sublingual immunotherapy using allergy drops lasts 2 or more years, with steady improvements and symptom reduction noted over time. The duration of the therapy is key, due to the fact that desensitization results from consistent immune priming. Time to improvement is variable. Some patients may note immediate improvement in symptoms, while others will continue with treatment for multiple years or with consistent use throughout their lives. Treating pre-seasonally, starting 3 months prior to onset of the most problematic season, is an option for patients who have a history of seasonal symptoms after using immunotherapy for an initial extended period. Typically, immunotherapy treatment does have durability of effect, and patients will notice improvements in allergy symptoms for months to years after discontinuing treatment. Again, addressing relevant elements of the allergic load is important in patients in whom non-allergic sources of inflammation are suspected, in patients for whom immunotherapy has been incompletely helpful, or if treatment response has plateaued. Importantly, immunotherapy is the only disease-modifying treatment available that addresses the underlying genetic predisposition towards allergy by shifting immune deviation towards tolerance of specific triggering allergens. This, in addition to basic lifestyle and personal care controls, can have profound effects on quality of life and can decrease inflammatory burden as well as the burden of associated conditions. 

References: 

1. Summary Health Statistics: National Health Interview Survey, 2018. Table C-2a. Last reviewed November 5, 2019. Available at: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2018_SHS_Table_C-2.pdf. Accessed February 22, 2021. 

2. Summary Health Statistics: National Health Interview Survey, 2018. Table A-2a. Last reviewed November 5, 2019. Available at: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2018_SHS_Table_A-2.pdf. Accessed February 22, 2021. 

3. Pawankar R. Allergic diseases and asthma: a global public health concern and a call to action. World Allergy Organ J. 2014;7(1):12.  

4. Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008;454(7203):445-454.  

5. Holgate ST. The epidemic of allergy and asthma. Nature. 1999;402(6760):2-4.  

6. Tam HH, Calderon MA, Manikam L, et al. Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review. Allergy. 2016;71(9):1345-1356.  

7. Chad Z. Allergies in children. Paediatr Child Health. 2001;6(8):555-566. 

8. Ellis CN, Drake LA, Prendergast MM, et al. Cost of atopic dermatitis and eczema in the United States. J Am Acad Dermatol. 2002;46(3):361-370. 

9. Centers for Disease Control and Prevention. Allergens and Pollen. Last reviewed August 21, 2020. CDC Web site. https://www.cdc.gov/climateandhealth/effects/allergen.htm. Accessed February 27, 2021. 

10. Nurmagambetov T, Kuwahara R, Garbe P. The Economic Burden of Asthma in the United States, 2008–2013. Ann Am Thorac Soc. 2018;15(3):348-356. 

11. Centers for Disease Control and Prevention. Asthma in the US. CDC Vital Signs. Last reviewed May 3, 2011. CDC Web site. https://www.cdc.gov/vitalsigns/asthma/index.html. Accessed February 27, 2021. 

12. Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(1):3-9.  

13. Anderegg WRL, Abatzoglou JT, Anderegg LDL, et al. Anthropogenic climate change is worsening North American pollen seasons. Proc Natl Acad Sci U S A. 2021;118(7):e2013284118.  

14. Laurie Menk Otto, ND, MPH. Comprehensive allergy treatment and the “allergic load” –what does it mean? [Blog post] February 22, 2021. Available at: https://drlauriemenkottopdx.com/blog-posts/. 

15. Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy. 2009;64 Suppl 91:1-59.  

16. Calderón MA, Simons FE, Malling HJ, et al. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy. 2012;67(3):302-311.  

17. Moingeon P. Update on immune mechanisms associated with sublingual immunotherapy: practical implications for the clinician. J Allergy Clin Immunol Pract. 2013;1(3):228-241.  

18. Moingeon P, Mascarell L. Induction of tolerance via the sublingual route: mechanisms and applications. Clin Dev Immunol. 2012;2012:623474.  

Laurie Menk Otto, ND, MPH is a naturopathic doctor in private practice in Portland, OR. Her practice focuses on the treatment of asthma, allergy, concussion recovery (CCMI certified), and digestive issues. She offers allergy evaluation, skin testing, and treatment including sublingual immunotherapy. Her approach to treatment is informed by a strong background in research and public health. After graduating from the National College of Natural Medicine in 2007, she completed a 3-year NIH-NCCAM-sponsored clinical research fellowship and completed a Master of Public Health degree from the University of Arizona. She can be found at drlauriemenkottopdx.com and reconstructedwellness.com.