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. 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.

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. It is hoped that ongoing studies using the sublingual route, will show similar benefits.

Mechanism
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 illicit 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. 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.

History
Specific immunotherapy has been practiced for almost 100 years. Classical immunotherapy by subcutaneous injection was demonstrated by Noon and Freeman in 1911. The oral route of immunotherapy was suggested earlier in 1900. Clinical attempts to determine the best dose and route for allergy therapy increased dramatically in the 1920s and 1930s. Clinical use of sublingual immunotherapy for foods was described in 1969 by David Morris and in 1970 for inhalant allergens. 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 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. 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. 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 intermittant 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.

Side Effects
Sublingual drops are considered safe to use at home. Some local sensitivities have been reported (minor oral itching) during initial treatment.