Sublingual immunotherapy

Sublingual Immunotherapy is method of allergy treatment that uses an allergen solution given under the tongue, which over the course of treatment, reduces sensitivity to allergens. Sublingual immunotherapy, or SLIT, has a very good safety profile and is given at home in adults and children. [cite journal |author=Gidaro G, Marcucci F, Sensi L, Incorvaia C, Frati F, Ciprandi G |title=The safety of sublingual-swallow immunotherapy: an analysis of published studies |journal=Clin Exp Allergy |volume=35 |issue=5 |pages=565–71 |year=2005 |pmid=15898976 |doi=10.1111/j.1365-2222.2005.02240.x]

As more patients are treated with SLIT, additional side effects are being studied. A serious anaphylactic reaction occurred in a patient being treated with multiple allergens prepared from commercially available US extracts. [cite journal |author=Dunsky EH |title=Anaphylaxis to sublingual immunotherapy |journal= Allergy |volume=61 |pages=1235 |year=2006 |pmid=16942576 |doi=10.1111/j.1398-9995.2006.01137.x]

The basis of sublingual immunotherapy is treatment of the underlying allergic sensitivity. Allergic symptoms improve as the allergic sensitivity improves. As a safe and effective method of treating the underlying disease, sublingual immunotherapy is capable of modifying the natural progression of allergic disease which can begin with allergic food sensitivities and eczema in young children and progress through allergic rhinitis and asthma in older children and adults.Fact|date=January 2007

A recent study, published in Allergy 2007: 62: 943–948, showed that a 3-year course of Sub-cutaneous immunotherapy had long-term clinical effects, by significantly reducing the development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment. In a recent review of ALL studies on SLIT by the American Academy of Allergy, Asthma and Immunology published in Journal of Allergy and Clinical Immunology, 2007: 6: 1466-1468, 35% of studies resulted in significant reductions in medications and symptom scores but 38% of studies found no significant benefit from SLIT. When SLIT did work, it was typically less effective than with conventional subcutaneous injection immunotherapy and sometimes SLIT took two years to show significant clinical benefit.


Sublingual immunotherapy is taken as drops or tablets, placed under the tongue, containing a specific allergen which interacts with the immune system to decrease allergic sensitivity. Commonly the medication is taken once a day. The antigen persists on the mucosal surface and is taken up by dendritic cells which interact with T lymphocytes (T-cells).

Sublingual immunotherapy takes advantage of immunologic tolerance of the oral mucosa to non-pathogenic antigens such as foods and resident bacteria. Consider the vast number of antigens we are exposed to every day which do not elicit an allergic response. Dendritic cells in the oral mucosa act as antigen presenting cells (APC) to T-cells in the cervical lymph nodes. This system modulates the allergic response by creating immune tolerance to antigens. The sublingual mucosa has few pro-inflammatory cells, such as mast cells, which would provoke an allergic reaction. This explains in part the safety margin of sublingual therapy.

Early in treatment, sublingual dendritic cells secrete interleukin 10 (IL-10) which induces regulatory T cells to inhibit the inflammatory response. cite journal |author=Moingeon P, Batard T, Fadel R, Frati F, Sieber J, Van Overtvelt L |title=Immune mechanisms of allergen-specific sublingual immunotherapy |journal=Allergy |volume=61 |issue=2 |pages=151–65 |year=2006 |pmid=16409190 |doi=10.1111/j.1398-9995.2006.01002.x ] Long term changes that occur with immunotherapy include a decrease in mast cell sensitivity and a decrease in IgE production by B-cells. With sublingual immunotherapy there is a decrease in the IgE/IgG4 and a decrease in the TH1/TH2 ratio.

The effect of sublingual immunotherapy is to treat the allergic sensitivity by short term and long term mechanisms. Allergic symptoms improve as the underlying basis of the allergic disease improves.


Specific immunotherapy has been practiced for almost 100 years. Classical immunotherapy by subcutaneous injection was demonstrated by Noon [cite journal |author=NOON L |title=Prophylactic inoculation against hay fever |journal=Int Arch Allergy Appl Immunol |volume=4 |issue=4 |pages=285–8 |year=1953 |pmid=13096152] and Freeman in 1911. The oral route of immunotherapy was suggested earlier in 1900 [Curtis HH. (1900) The immunizing cure of hayfever. Med News (NY);77:16-8.] . Clinical attempts to determine the best dose and route for allergy therapy increased dramatically in the 1920s and 1930s. [Black JH. (1927) The oral administration of pollen. J Lab Clin Med;12:1156 ] Clinical use of sublingual immunotherapy for foods was described in 1969 by David Morris [cite journal |author=Morris D |title=Use of sublingual antigen in diagnosis and treatment of food allergy |journal=Ann Allergy |volume=27 |issue=6 |pages=289–94 |year=1969 |pmid=5785921] and in 1970 for inhalant allergens. [cite journal |author=Morris D |title=Treatment of respiratory disease with ultra-small doses of antigens |journal=Ann Allergy |volume=28 |issue=10 |pages=494–500 |year=1970 |pmid=5521180] Although patients treated for food, pollen, pet dander and mold allergy by sublingual immunotherapy improved, the mechanism of why it was effective was not apparent and few studies were published in peer reviewed journals. The practice of sublingual immunotherapy remained an alternative therapy until controlled clinical trials and advances immunology showed the validity of this method.

While the practice of sublingual immunotherapy has been more available in Europe than in the United States, it was not until concerns regarding the risks of injection immunotherapy including deaths from anaphylaxis [cite journal |author=Reid M, Lockey R, Turkeltaub P, Platts-Mills T |title=Survey of fatalities from skin testing and immunotherapy 1985-1989 |journal=J Allergy Clin Immunol |volume=92 |issue=1 Pt 1 |pages=6–15 |year=1993 |pmid=8335856 |doi=10.1016/0091-6749(93)90030-J.] were published in the 1980’s that formal research into alternatives to injection therapy was supported. Pioneering studies in Europe demonstrating the safety and effectiveness of sublingual immunotherapy and fostered international acceptance of the method. In 1998 the World Health Organization concluded that sublingual immunotherapy was a viable alternative to the injection route and that its use in clinical practice is justified. [ cite journal |author=Bousquet J, Lockey R, Malling H |title=Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper |journal=J Allergy Clin Immunol |volume=102 |issue=4 Pt 1 |pages=558–62 |year=1998 |pmid=9802362 |doi=10.1016/S0091-6749(98)70271-4] Public acceptance facilitated the publication of new research. Between 1990 and 2005 more than 40 controlled trials with non-injection routes were published in peer-reviewed journals. [cite journal |author=Canonica G, Passalacqua G |title=Noninjection routes for immunotherapy |journal=J Allergy Clin Immunol |volume=111 |issue=3 |pages=437–48; quiz 449 |year=2003 |pmid=12642818 |doi=10.1067/mai.2003.129] Today in Europe, sublingual immunotherapy accounts for 40 percent of allergy treatment. In the United States, sublingual immunotherapy is gaining support among traditional allergists and is endorsed by otolarygologists who practice allergy treatment.

Comparison to other allergy management regimens

Options for managing allergy include avoiding what you're allergic to, such as not eating a food you have a known problem with, avoiding pets, etc. Many allergens are unavoidable due to the widespread nature of dust, molds, pollens, weeds, and various food elements in packaged and processed foods. A limitation of avoidance is that low levels of exposure to antigens allows the immune system to modulate the allergic sensitivity through T regulatory cells which are short lived. The allergic sensitivity persists much longer so that intermittent exposure is more problematic than frequent low level exposure.

Symptomatic treatment options for allergies include over the counter medications such as antihistamines, prescription oral medication, nasal sprays and short-term prednisone. Biologics such as anti-IgE anti-bodies have been used in severe cases. While there is a role for all of these options, Allergy immunotherapy is the only treatment directed at resolving the underlying cause of allergy symptoms.

Currently, immunotherapy is offered via allergy injections (allergy shots) for inhalation allergies although not for foods. Sublingual immunotherapy (allergy drops and tablets) is offered for inhalation allergies and foods. Like injection therapy, sublingual immunotherapy directly changes the body’s ability to react with allergens. Following successful treatment with immunotherapy, allergy symptoms are less apparent or at least less problematic.

ide Effects

Sublingual drops are considered safe to use at home. Some local sensitivities have been reported (minor oral itching) during initial treatment. cite journal |author=Passalacqua G, Guerra L, Pasquali M, Lonbardi C, Canonica G |title= Efficacy and safety of sublingual immunotherapy |journal=Annals of Allergy, Asthma & Immunology |volume=93 | pages=3–12 |year=2004 |pmid=16409190 ]


External links

* [ Sublingual Immunotherapy (SLIT)] Australasian Society of Clinical Immunology & Allergy (ASCIA).
* [ Sublingual Immunotherapy] McLean Hospital (Belmont, MA, USA).
* [ Allergy Drops (Sublingual Immunotherapy or SLIT): FAQ] Fauquier ENT Consultants.
* [ Article on Sublingual Immunotherapy]
* [ Sublingual Immunotherapy Research]

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