Allergen immunotherapy (AIT), also known as allergy shots, have been around for over 100 years. This treatment not only creates a long-term tolerance for a specific allergen, but can stop both the development of new sensitivities and the allergic march.

"If you can catch it early, allergy shots put up a wall against allergic rhinitis progressing into allergic asthma," says Carol Smith, MD, allergist with Birmingham Allergy & Asthma. "I don't think a lot of people know that's possible, because they don't think of asthma as being related to their allergies."

AIT is also the only treatment to alter the immune mechanism of the allergic disease on a long-term basis. "It works by decreasing the response to common things that the body sees as foreign," Smith says. "It decreases the T-helper 2 (Th2) response and stimulates IL-10 and TGF-β expression cells, while increasing the blocking antibodies, particularly the immunoglobin IgG4.

"This may block the interaction between allergen and IgE, creating an inhibitory effect. We always assumed that there was some sort of antibody that blocked the allergy response, but we didn't know until the last ten years. Now we know it's IgG4."

Smith says that confirmation did not necessarily change things in AIT, but it did open the door to looking at new things including the administration route for the allergens. "We've had allergy shots since the beginning, but now we have sublingual tablets," she says.

The tablets, held under the tongue until dissolved, began receiving FDA approval for various airborne allergens in 2014. The advantage is that treatment with sublingual tablets has a lower chance of anaphylaxis compared to allergy shots, and they do not require an office visit. "The tablet is felt to be almost as effective as subcutaneous shots, but it has a drawback," Smith says. "They only have tablets for grasses, dust mite and ragweed. So if you have pollen sensitivities, you're better off taking allergy shots."

More recently, clinicians have used skin patches to administer the needed dosing. "Epicutaneous patches don't work well for aeroallergens, but do show promise for food allergies" Smith says. The mechanisms for altering the immune system differ for each allergen designation. But in food allergies, the patch could be ideal, because the treatment must be continuous. "You're developing a sustained tolerance to the food. You can't ever stop your treatment," Smith says. "If you stop, you lose all desensitization."

For the patches, their time may soon come. A review of the literature in 2018, published in the Journal of Translational Medicine, found eight placebo-controlled, double-blind patch trials, covering grass pollen rhinoconjunctivitis, cow's milk allergy, and peanut allergy. The studies showed high safety and adherence to the patch.

The peanut allergy patch may even hit the market soon. Last fall, the FDA nixed the first patch to treat peanut allergies for children, because it lacked "sufficient detail regarding data on manufacturing procedures and quality controls." But the maker, DBV Technologies, has stated that because the FDA's concerns did not pertain to the safety or efficacy of the patch, they will be able to gather the needed data and resubmit their application this fall.

Another new way to administer allergens is currently in clinical trials. It utilizes the traditional shots but places them into the lymph nodes. "It would probably be painful, but it would give you the benefit a whole lot faster--like days versus years," Smith says. Because the lymph nodes are the source for both IgE, which causes the reactions, and the IgG that blocks the reaction, injecting the lymph nodes creates a faster, purer route for the allergen.

A different protocol using the traditional subcutaneous injections can also shorten the initial part of the treatment span. Called rush, the typical weekly doses are condensed into one day by being delivered every 30 minutes. The allergist generally administers extra medication prior to the allergy shot treatment, such as an antihistamine and steroid. "This is to block all these receptors," Smith says. "That's what allergists do is push people to the edge of their tolerance. That's why the expertise of an allergist is needed."

That one-day treatment equals about the first four months of weekly visits, followed by the usual allergy shot regime. "After the single-day treatment, patients come weekly for another 15 to 20 weeks until they hit their goal dose, after which they come monthly for three to five years," Smith says. "Then they can stop."

The Rush protocol is for people who need to get their allergic reactions under control faster or who don't have time to come in weekly. "People who work outdoors who have anaphylactic reactions to stings benefit from the Rush protocol. It can also be helpful for someone who has terrible spring allergies and wants to build up some tolerance before spring comes," Smith says.

"The point is that allergen immunotherapy works well," Smith says. Plus research and applications are now on the horizon for easier and shorter administration. "AIT may have been around forever," she says, "but it is still the only therapy we have available to alter the immune mechanism of allergic disease long-term."