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Mark E. Reiber, MD, FACS, FAAOA

History of Immunotherapy

Immunotherapy was first reported in 1911 as repeated injections with pollens to induce tolerance, a “vaccine for allergy”. In general, each allergen to which a person is allergic must be treated individually and a mix is created based on testing. The exception is some antigens are so similar in structure to others that they can elicit tolerance for each other allowing smaller numbers of allergens to be used.

Allergy “Shots” are Accepted

Minor modifications to subcutaneous immunotherapy (SCIT, or allergy shots) have occurred, but it has been the dominant form of therapy for a century. It’s proven effective for pollens, molds, cats, dogs, dust mites and cockroach antigens for asthma and allergic rhinitis.

How SCIT Works

Ten weekly doses are given, increasing the amount each week. Then a five times stronger mixture is made and the process starts again.  This continues until a maximum concentration is reached or the patient experiences reactions preventing further advancement. It may take a year to reach this point.

Once maintenance is reached, weekly injections are given for 3-5 years. If symptom relief is maintained, shots are tapered and discontinued. A majority of patients develop lasting effects, but a small percentage needs to continue shots beyond the five year point.

The Downsides to Allergy Shots

SCIT is not without small risks and disadvantages. Weekly office visits, with a 20 minute wait following injection, can become inconvenient and difficult to maintain. Rare reactions include local skin reactions, shortness of breath, and even shock. Very rarely, death has been reported, usually in asthmatics. These factors motivated research to find alternative forms of immunotherapy.

Looking for Alternatives: SLIT is Born

As early as 1913, alternatives such as nasal and oral routes were proposed. Oral therapy includes direct swallow and sublingual (under the tongue) methods (SLIT). In 1998 the World Health Organization approved both the sublingual and nasal methods as viable alternatives to SCIT. Nasal delivery proved to be difficult and less accepted. Oral immunotherapy with immediate swallowing is less effective than SLIT (held under the tongue).

SLIT- the basics

At ENT Carolina, we offer SLIT and follow the American Academy of Otolaryngic Allergy dosing recommendations. Patients start at a standard concentration and advance over twelve weeks to a maximum strength for one year. If satisfactory response is not seen by a year, therapy is stopped but for the great majority of patients who respond, continue for 3-5 years. At the end of 5 years, a small percentage require longer therapy, but most develop persistent symptom relief.

How SLIT works

It appears the effectiveness of SLIT correlates with the duration of contact with the mouth’s lining. There may be a critical interaction between the immune cells of the floor of the mouth and this effectiveness. It is important to watch the clock to ensure 2 minutes of exposure time. Dosing is performed once daily.

Effectiveness of SLIT has been based on reports of symptom decrease and reduced dependency on medications. Duration of at least three years appears necessary but we recommend 4-5 years. Pollen therapy appears most effective with dust mite and pets requiring longer times. We generally see effects beginning in about six months or less.

The downsides to SLIT:

Only occasional mild reactions such as oral itching, headache, runny nose, hives, constipation or other gastrointestinal side effects are  seen. To date there have been only a few episodes of anaphylaxis world-wide, and no deaths, associated with SLIT. These reports were all in non-inhalant allergens that we do not use.

Sublingual immunotherapy is prepared from the same FDA approved antigen extracts used for subcutaneous therapy; however, the FDA has not approved sublingual administration. This is an "off-label" use. Off-label use of medications is very common with estimates of 25-50% of all prescriptions being for off-label indications. The studies and review needed to obtain FDA approval are underway at this time.  Experience in Europe for over 30 years has demonstrated safety and efficacy but American data is just beginning to become available.

In 2005, the Asthma and Allergy Foundation of America performed a survey of allergy patients asking about the important features of an allergy medication. These features were important to 50% or more of respondent. I have shown how these features relate to SLIT.



SLIT- drops

Long lasting symptom relief



Rapid relief of symptoms

No (months)

No (months)

Minimal side effects

Yes, but more than SLIT


No sedation/ Drowsiness



Covered by insurance




Depends on insurance benefits

Less than $20/week

Safe with other medications

Yes, except Beta Blockers

Yes, except Beta Blockers

Easy to take

Requires office visits

Home based, 2 min/day

Non-habit forming

Yes, but must use weekly

Yes, but must use daily

Dosing flexibility (as needed)

No, must use weekly

Somewhat, but should use daily

Targets specific symptoms

No, works on all

No, works on all

Steroid free



So why would someone choose one form over another? Subcutaneous immunotherapy is time tested for over a century. In addition, insurance companies have generally provided better benefits for SCIT than SLIT.  Sublingual immunotherapy is newer, but has in over a decade of my experience had very positive results. European studies show efficacy similar to subcutaneous therapy for several antigens. There is the obvious benefit to a home-based, self administered, needleless therapy. The safety and side effect profiles of SLIT appear superior to SCIT. For many patients, there is not a significant cost difference even with insurance coverage, so they would just prefer the ease and convenience of allergy drops.