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Sublingual Immunotherapy

Mark E. Reiber, MD, FACS, FAAOA
"Allergy Drops"

As complex as treating nasal allergies can be, it still can be simplified into three steps: avoidance measures, medications, and desensitization vaccines or immunotherapy. Prescription and over the counter medications are the most utilized, but environmental control measures can be very effective. When these two methods are insufficient, immunotherapy is necessary. 

Immunotherapy was first reported in 1911 and involved repeated injections to induce tolerance. Each allergen must be treated individually, except for instances of  cross-reactivity where one is similar enough to another to induce tolerance for that antigen. Minor modifications to subcutanceous (injection) immunotherapy (SCIT) have been made over the years, but it has been the dominant form of therapy in the United States for over a century.

Unfortunately, SCIT is not without risks and disadvantages. Years of weekly injections can be inconvenient, and local skin reactions with itching, shortness or breath, and even serious anaphylactic reactions can occur. Very rarely death has been reported, usually in asthmatics. Current recommendations include a 20 minute observation following injections given only in a physician's office. Given these limitations, researchers have looked for alternative methods of desensitization.

sublingual immunotherapyAs early as 1913, nasal and oral immunotherapies showed the greatest promise. Oral therapy includes direct swallow and sublingual (under the tongue) methods (SLIT). In 1998 the World Health Organization approved both sublingual and nasal methods as viable alternatives to injections. Nasal immunotherapy has subsequently proven to be difficult and less well-received. Oral immunotherapy with immediate swallowing is less effective than SLIT in most studies.;

Immunotherapy by any method is thought to work primarily through three mechanisms:

  1. antibody action (blocking antibodies),
  2. inflammatory chemicals, and
  3. cellular inflammatory responses (white blood cells).

SLIT may use different mechanisms than SCIT (injections).

The effectiveness of SLIT seems to relate to duration of contact with the immune cells in the floor of the mouth. Minimal absorption occurs, but there is persistence of antigen in the mouth for long periods. Antigen that is swallowed is minimally absorbed and completely degraded in the intestines. We feel it is critical to watch the clock with SLIT to ensure a 2 minute exposure.

The effectiveness of SLIT has been based on patient reports of symptom decrease and reduced dependency on medications. Treatment duration of at least two years appears necessary, but we recommend 3-5 years as with injections. Pollens seem to be most effective with dust mite and pet danders requiring longer durations of treatment. We see effects begin in less than six months in many cases.

Sublingual immunotherapy is made from the same antigen extracts as injections. This is an "off-label" use. Off-label use of medications is very common, with between 25%-40% of all medications used for indications not approved by the Food and Drug Administration (FDA).

There have been only mild reactions noted such as oral itching, headache, runny nose, hives, constipation or other gastrointerstinal side effects. To date, only a few episodes of anaphylaxis associated with SLIT have been reported. Two of these were with food allergy SLIT and one with Latex SLIT. No reports have been with inhalant allergens and there have been no deaths.

We follow the American Academy of Otolaryngic Allergy recommendations. For patients responding to therapy, it is continued for 3-5 years before trying to terminate. After 5 years a small percentage of patients will not develop lasting tolerance and may require longer therapy.

In 2005, the Asthma and Allergy Foundation of America performed a survey of allergy patients that asked for the important features of an allergy medication. These were the features that were important to 50% or more of the respondants, and how these features relate to SLIT.

1. Long lasting symptom relief Immunotherapy is the only lasting allergy treatment
2. Rapid relief of symptoms Generally 6 months or less
3. Minimal side effects Fewer effects than allergy shots
Minimal risk for anaphylaxis
Rare tingling in mouth
4. No sedation/drowsiness None
5. Covered by insurance No, but cost may be compareable with insurance copays
6. Inexpensive Affordable, convenient and time saver
7. Safe with other medications Yes, except for "Beta Blockers"
8. Easy to take Home based, once per day, self-administered
9. Non-habit forming Not addictive
10. Dosing flexible (as needed) Best if used regularly
11. Targets specific symptoms Targets all symptoms of allergy
12. Steroid-free Yes

October, 2010