Sublingual Immunotherapy (SLIT): What it is and How it Works
Sublingual immunotherapy is a method of treating allergies by desensitizing individuals to allergens over time, in many cases with the goal that they
be cured of their allergies. Sublingual immunotherapy (SLIT) is similar to subcutaneous immunotherapy (SCIT), commonly known as allergy shots. In
principle, patients are given small doses of allergens in order to train the body not to react to them. Unlike allergy shots, SLIT,
is a solution
of allergen extracts, often called allergy drops, that is placed under the tongue.
The antigen in the solution interacts with the immune system to decrease the allergic individuals sensitivity over time. Although the full course
of treatment can last years, many patients report improvement in their symptoms after just a few months.
On a more scientific level, SLIT takes advantage of the tolerance of the oral mucosa, the mucous membrane of the mouth, to non-pathogenic antigens.
When antigens are placed under the tongue, immune cells, called dendritic cells, move them to lymphoid tissues and an immune response occurs. By creating
immune tolerance to these antigens, the process alters the allergic response.
One of the benefits of SLIT is that the sublingual mucosa, the membrane lining under the tongue, where the antigen is placed, has few pro-inflammatory
cells, making an allergic reaction far less likely than when the allergen is encountered in the environment or even through injections. Early in treatment,
sublingual dendritic cells secrete IL-10, which causes T-cells to inhibit the inflammatory response. Over time, sublingual immunotherapy decreases IgE
production and the overall allergic response.
SLIT in the United States
Mostly due to the fact that the FDA has not yet approved the existing antigen extract for sublingual immunotherapy use, there are some hurdles to
obtaining SLIT. First, although it is well within a doctor's rights to use medications and products outside of the bounds of what they were tested to
do (a practice that is very often put into use), many physicians are uncomfortable prescribing the treatment for their patients until the FDA gives its
stamp of approval.
One such allergist is Dr. Spencer Atwater, Jr. of Allergy Partners of Western North Carolina. When asked for an allergist's perspective on SLIT, he
responded that SLIT represents a new and exciting treatment for people with allergic disease, but added that he has concerns for patients who are interested
in the therapy now.
Insurance does not reimburse for the treatment, and it can cost anywhere from thirty to one hundred fifty dollars a month. In addition, Dr. Atwater
points out that most of the European studies were conducted with a single allergen and that when multiple allergens are mixed together the response is
not always as effective. "Before I would treat patients with SLIT, I would want to be sure that the treatment is both cost effective and medically effective."
He adds that of the fifty-nine allergists in his group, not one currently offers SLIT, though they have discussed the possibility.
Not all allergists share Dr. Atwater's view, however. Dr. Kingsley Chin of Atlanta's Piedmont Ear, Nose, Throat & Related Allergy, which offers
SLIT, has a lot of good things to say about the treatment. The real advantage of SLIT is that it is more convenient than traditional allergy shots, easy
to do, safer, and most of the time cheaper.
History of SLIT
Although it may seem to be a fairly new treatment option to many allergy sufferers in the United States, sublingual immunotherapy has actually been
practiced for almost a century. As early as 1900, New York physician H.H. Curtis relieved his patients' hay fever by placing pollen antigen drops in their
mouths. In 1911, British allergists Drs. Leonard Noon and John Freeman published an account of allergy desensitization through subcutaneous injections of
pollen extract until reactions to the allergen were drastically reduced or entirely eliminated.
Although Noon and Freeman's administration was under the skin and not sublingual, their demonstration of treating allergies through desensitization
caused the theory to become a predominant principle in clinical allergy research during the following decades. Clinical attempts to scientifically
determine the ideal route of allergy therapy increased dramatically in the 1920s and 30s.
One physician who advanced the therapy was Dr. French Hansel, who experimented with sublingual allergy drops for dust mite allergy when he was a
Mayo Clinic Fellow. He published his results in 1936 and was the first physician to say definitively that placing antigen drops under the tongue
specifically led to more rapid and effective desensitization than when administered in any other place in the mouth. He said that, It is not
unreasonable to assume that this highly absorptive sublingual area has definite immunologic function. Through this route practically all the
injectables, many of which are not well tolerated, can be introduced without apparent injury to or reaction in the local tissues."
In 1960s and 70s, Dr. David Morris continued to make advances. Dr. Morris, whose family medicine practice was located in the rural Midwest,
became increasingly interested in allergy treatments when he began seeing many farmers with mold allergies. Initially he treated them with allergy
shots, but many of his patients had adverse reactions to them and he began looking for alternatives. At a medical conference in 1966, Dr. Morris
became particularly interested in SLIT, and started giving his patients the option of allergy drops. He was the first to prescribe allergy drops
for mold allergy, and also went on to treat patients with SLIT for allergies to food, pollen, pet dander, and more.
The 1980s saw another jump in formal research for SLIT. When concerns were published regarding the risks of subcutaneous immunotherapy, including
anaphylaxis, pioneering studies in Europe demonstrated the safety and effectiveness of SLIT. In 1998, the World Health Organization (WHO) concluded
that SLIT was a viable, safe, and effective alternative to allergy shots and that its use in clinical practice was justified.
Today, SLIT accounts for approximately 40 percent of allergy treatment in Europe. However, despite over 40 controlled trials with non-injection
routes published in peer-reviewed journals since 1990, SLIT still does not have FDA approval in the United States.
Why Choose SLIT
With several allergy treatment options out there, why would someone choose sublingual immunotherapy? First of all, in contrast to methods like
medication and allergen avoidance, which offer patients better quality of life by preventing symptoms, immunotherapy aims to get to the root of the
problem and actually alter the immune systems response.
Proponents of sublingual immunotherapy cite various reasons for using SLIT instead of allergy shots, including the following:
- Convenience - Allergy drops are less intrusive than allergy shots and are therefore more tolerable, especially for children. It is
important that children's allergies are treated when they are young in order to help halt what's known as the Atopic March, the natural progression
of allergic disease in which individuals become sensitive to an increasing number of allergens and may even develop asthma. Indeed, a recent Pediatric
Asthma Treatment study found that the incidence of asthma decreased dramatically in children who underwent immunotherapy.
Furthermore, allergy shots require weekly visits, which are oftentimes difficult for patients to maintain. Allergy drops require follow-up visits
every few months, but most of the treatment can be done at home. Since consistency is imperative to any type of immunotherapy treatment, the easy
compliance that SLIT offers has a clear advantage.
- Customization - SLIT can be highly customized to meet each patients unique needs. Dr. Mary Morris of Allergy Associates of La Crosse, one
of the foremost clinics specializing in SLIT, describes aspects of the La Crosse Method of SLIT, which helps physicians treat each person based on
their individual allergic profile and sensitivity.
Unlike with subcutaneous immunotherapy, which starts each individual out on the same dose of the antigen, SLIT in general and the La Crosse Method
specifically, allows physicians both to start highly allergenic substances out at very weak doses and to start out other less allergenic substances at
a higher dose.
Respectively, this capability enables increased safety for the patient and quicker results. As Dr. Morris puts it, the La Crosse Method, born
through clinical trials on thousands of patients, allows for specific dosing based on sensitivity protocol.
- Safety - Particularly with protocols like the La Crosse Method mentioned above, SLIT offers patients increased safety. Unlike with
allergy shots, there have been no reported fatalities from SLIT. While side effects like allergic reactions and anaphylaxis can occur, they are
less likely with SLIT than SCIT.
In addition, patients sensitivity improvement is regularly monitored and physicians know when and how much more antigen can be administered. In
this way, very sensitive patients as well as those with multiple allergies or unstable asthma can be treated. Dr. Morris points out that, though antigen
extracts have not been approved by the FDA for sublingual use, the La Crosse Method entails a level of physician involvement in dosage and supervision
that does not exist with subcutaneous immunotherapy. Sublingual immunotherapy is specifically fine-tuned based on an individuals response to treatment
and follow-up testing.
A Typical Patients Experience of SLIT with the La Crosse Method
Doctors at Allergy Associates of La Crosse have developed a treatment protocol called the La Crosse Method, which was obtained through clinical
experience with tens of thousands of patients over many years. SLIT pioneer Dr. David Morris began offering his patients sublingual immunotherapy
after many of the mold allergic farmers he saw could not tolerate allergy shots.
Since then, over one hundred thousand patients have been treated by the clinic. With several doctors collaborating based on their
patients results, treatment protocol was fine-tuned. Through clinical observation and serial testing, Dr. Morris and his staff learned how to
measure how much of an immune response their patients had experienced and how to tell when they could be more aggressive about treating a particular allergy.
Dr. Mary Morris, daughter of Dr. David Morris, describes a typical patients experience of undergoing sublingual immunotherapy: When a patient
first comes in, we test them to see what they are allergic to and start them on the appropriate drops. Patients come back after about three to four
months for follow-up testing with key allergens. After that, patients usually come in about every six months. The average total length of treatment
is four to five years. The weaker you have to start with the antigen [if the allergy is severe], the longer the treatment takes. However, patients
typically report symptom improvement within two to three months.
SLIT and FDA Approval
The antigens used in SLIT are the same as those used in SCIT; they are just administered differently. The FDA has approved the antigens
for subcutaneous injections, but not for oral administration. However, it is well within a physician's jurisdiction to use the antigen sublingually
in what's called off-label use.
However, the lack of FDA approval does pose logistical problems regarding availability. Many physicians will not offer SLIT as an option
for their patients until the FDA gives its approval. Furthermore, compounding labs who make the antigens are prohibited from promoting their
products for SLIT until the therapy has FDA approval.
There are a couple of reasons that might be holding up the FDA approval for sublingual immunotherapy. First, since the product itself has
been tested and approved, there is not as much of a push to retest it for another therapy because the product is already on the market.
The second issue relates to the mechanisms of the treatment itself. Subcutaneous injections involve shots in pre-specified dosages; with SLIT,
antigens are combined into tailor-made doses that fit an individuals personal allergy profile as well as their level of sensitivity to various
allergens. Thousands of antigen combinations are possible and its virtually impossible to test and approve every possible combination and dosage.
In addition to its more widespread use of the therapy, Europe is ahead of the United States in terms of gaining official approval for SLIT
treatment. Denmarks ALK-Abello and France-based Stallergenes are in the process of producing an under-tongue tablet for treating grass allergies,
which affect about 50 to 60 percent of the allergic population.
FDA approval for sublingual immunotherapy products in the United States may be on the horizon as well. According to Derek Constable, Ph.D. of
Hollistier-Stier Laboratories, a company that manufactures immunotherapy products, some laboratories are looking at getting approval for SLIT
extracts for grass, pollen, ragweed, and cat dander.
Dr. Constable describes the position of immunotherapy products from the vantage of immunotherapy product manufacturing: Using extracts for
sublingual immunotherapy is all off-label use at this point. We cant expect to see many new products on the market because allergy extracts are a
small niche and the cost of trying to develop new products wouldnt be returned. Trying alternative uses for existing products as in the case of
SLIT is the biggest thing happening now within the extract field and should be coming through in the near future. He predicts that the earliest
we could see SLIT products on the market with FDA approval is twelve to eighteen months.
The Future of SLIT
Sublingual immunotherapy is exciting because it does offer the prospect of a cure for allergies, both food allergies and environmental ones.
Current immunotherapy treatment for food allergies aims at decreasing the risk if a person is accidently exposed to the food they're allergic to;
but research goals point toward curing food allergic patients to the level that they could not eat the food they're allergic to and then eat it and
still be fine.
Allergy sufferers of non-life threatening allergies report an improvement in their symptoms in as little as a few months. The appeal of
immunotherapy for many people is the prospect of curing allergies once and for all rather than just controlling symptoms, which they'd have
to do for the rest of their lives. And the benefits of curbing allergic disease early in
children's lives is far-reaching, including the
possibility of preventing increasing allergies, eczema, sinus infections, and even asthma.
SLIT makes these ideas not only possible, but accessible. Although the absence of FDA approval and the shortage of public awareness and
acceptance of the treatment has prevented SLIT from becoming a predominant allergy treatment, sublingual immunotherapy is positioned to become
the next treatment of choice for allergy sufferers the world over.
By Shifrah Combiths