This is a review of the author’s experience with Sublingual Immunotherapy in a private office setting. Sublingual Immunotherapy should be considered by any allergy practitioner as a useful tool. Sublingual Immunotherapy is safe while at the same time it is effective. It enables the practitioner to treat asthmatics and young children without the concerns implicit with allergy injections.
Sublingual Immunotherapy (SLIT) has been used in the US since the late 19th century. The earliest description dates back to the year 1900 [
Safety is one of the striking features of SLIT. It is a well-known fact that Subcutaneous Injection Immunotherapy (SCIT) can elicit reactions as either local arm reactions or systemic reactions, ranging from mild to severe [
SLIT is not problem free. There are reactions after SLIT administration, usually known as Adverse Events (AEs). Published literature commonly describes these reactions as mild and sometimes as self-resolving [
Reports of SLIT using few or several allergens are infrequent [
The author will summarize his experience with SLIT, which was successfully incorporated into a private practice setting in 2003. The author was trained at the American Academy of Otolaryngic Allergy (AAOA) where he learned to use the intradermal test with multiple serial dilutions (Intradermal Dilutional Test or IDT) [
The author developed a protocol for SLIT administration based on 1 : 5 dilutions [
The author has performed a series of studies in the setting of his private practice. These studies do not meet the same standards of a study from an academic institution. Their objective was to prove over time that the protocol being used was mostly in agreement with existing published literature on SLIT. Through those studies it was possible to establish that the treatment results obtained on patients treated using this protocol were positive, proving the technique effective and in agreement with data from the European literature. In other words, the clinical impression that the protocol provided effective and safe treatment was documented, and patients in a private office setting were able to benefit from a treatment modality often found only in clinics.
The first evaluation included a group of patients that received SLIT, but roughly half of those patients had been previously treated with SCIT and for a variety of reasons changed into SLIT [
The second evaluation was a head-to-head comparison between SCIT and SLIT [
While a severe reaction never occurred after administration of SLIT with this protocol, AEs during SLIT administration are not uncommon. The AEs usually reported in the literature include labial or buccolingual edema, itching in oral cavity or other parts of the face, throat irritation, rhinoconjunctivitis, and gastrointestinal (GI) symptoms [
In the author’s experience [
There is still no universally accepted system to grade and classify AEs. It has been proposed to classify AEs according to site of origin as local versus systemic [
Local reactions are reported as occurring frequently; systemic reactions are reported as occurring rarely. There is no uniform criterion for inclusion of symptoms. For example, local reactions are reported as oral itching and/or swelling and as GI complaints (nausea, stomach pain, vomiting, abdominal pain, and diarrhea) but also as altered taste perception, itching of lips, swelling of lips, itching of oral mucosa, swelling of oral mucosa, swelling of tongue, glossodynia, mouth or tongue ulceration, throat irritation, or uvular edema [
Systemic reactions are reported as cutaneous symptoms (urticaria and itching), ocular symptoms (redness, itching, and tearing), nasal symptoms (itching, sneezing, rhinorrhea, and obstruction), asthma symptoms (cough, wheezing, shortness of breath, and chest tightness) [
AEs usually occur during the induction phase and with low doses of allergen [
AE management usually involves dose adjustment or symptomatic treatment [
The author collected all the AEs that occurred in his practice during a 5-year period [
To further assess this finding, an additional 100 charts of SLIT patients were randomly evaluated and it was found that there was a discontinuation rate, not necessarily related to AEs, of 27%–34%. When comparing the data from the group with AEs (85.5% discontinuation) versus the group with spontaneous discontinuation of treatment not necessarily related to an AE (27%–34%), the importance of the AE as a factor to determine treatment discontinuation becomes clear.
In the same study [
SLIT literature generally analyzes what percentage of treated patients get AEs and what the AEs are. If the information we found could be confirmed, then it is to be expected that any patient who develops an AE during SLIT administration would be likely to quit treatment, even more so if the AE involved the GI system. This is an important piece of information for the practitioner in private practice. By anticipating the probable outcome of a patient that develops an AE during SLIT administration, the treating physician can intervene before the patient quits.
AEs involving the GI system are reported rather frequently and they are considered by some researchers as local reactions [
Reports regarding the use of sublingual tablets describe many AEs but GI symptoms are not usually reported [
In support of this contention the author observed the following: When patients had AEs not related to the GI system, the AEs would abate by diluting the treatment bottle, but this would not happen when the AE involved the GI system. The dilution process implies administering a lesser amount of allergen (less concentrated) but the diluent concentration (glycerin) remains the same. The GI AE would often get worse with continued administration of SLIT. This observation has also been suggested in the literature, as GI AEs are reported to be dose related. In other words, they occur more frequently with higher doses [ Diluting the bottle in saline sometimes led to a resolution of the GI complaint. We observed that this only worked for diluted allergens at the beginning of the treatment. As the dose advanced and the concentration of the allergens increased, so did the content of glycerin and the AE would reappear.
As SLIT is effective and extremely safe it can be considered the ideal modality for home-based immunotherapy. It can be used when patients are not good candidates for SCIT as is the case with young children, very old patients, and high-risk patients. There is a subgroup of patients, not necessarily children, who are scared of needles. For these patients oral vaccines are ideal.
With SLIT there is no need for treatment interruption for vacations or relocations. If SLIT treatment is interrupted it is very easy to restart. Glycerin is a potent protein stabilizer. When glycerin is used as the diluent for mixing SLIT, potency of the allergens is maintained for a long time; therefore these drops do not need refrigeration.
SLIT implies a noninjectable route; therefore local arm reactions are nonexistent. These are sometimes painful and often interfere with injectable dose advancement.
SLIT may offer an economical advantage: patients with no medical insurance coverage or those that have insurance but with high copays can easily be treated with SLIT instead of SCIT. The patient also saves time as there is no need to come to the office, obviating the need to wait 30 minutes after injections.
These factors imply a potential for more compliance. At least one report suggests that adherence to SLIT could be more than 90% [
The asthmatic patient and the very young patient are difficult to manage with specific immunotherapy, even more so if the patient is an asthmatic child. These difficult-to-treat patients can safely receive SLIT [
Guidelines for the administration of injectable immunotherapy do not advise treating patients younger than 5 years, as reactions, if they were to occur, are more difficult to manage [
Young children are routinely seen at the author’s office. A brief review of treatment results in a small group of 10 children with nasal allergies and asthma was done [
In our office, the treatment results are evaluated using a symptom-scoring sheet that is filled out by nursing personnel every time a new vial for SCIT or a bottle for SLIT is started. The scoring sheet includes symptoms, information on medication use, and an objective evaluation consisting of the use of a Peak Flow Meter to assess the value of the PF [
From the analysis of the scoring sheets it was realized that patients often deny having asthma despite having one or more of the symptoms characteristic of lower airway inflammation or even if using an inhaler prescribed by their primary care doctor. This is an important concept as severe reactions following allergen injections for testing or treatment are more common in asthmatics [
The treatment of the pregnant patient is problematic. Present guidelines do not suggest advancing the injectable dose in a pregnant patient. There is not much information about the administration of SLIT during pregnancy but a retrospective chart review and a prospective report suggested that it was safe to administer SLIT during pregnancy even though the numbers in those papers were small for definite conclusions [
The success of the treatment protocol is strongly based on it being safe and effective. It is also important in order to increase compliance that the protocol is easy for the patient to follow as this is a home-based therapy. Many protocols advocate leaving the drops under the tongue for several minutes. The author advises the patients to keep the drops under the tongue for 20–30 seconds before swallowing them. This is based on evidence from pharmacokinetic studies that upon a brief contact with the sublingual mucosa the allergen attaches to it and the attachment lasts for hours [
It is common in a private practice setting that the patient on immunotherapy leaves for a long vacation, changes jobs, moves far from the office, or loses insurance coverage. In all these circumstances it may be necessary to change treatment modalities “back and forth” from SCIT into SLIT or vice versa. Because of SLIT’s safety it is very easy to change from SCIT into SLIT, which is very important in order to keep the patient treated while circumstances change. Changing from SLIT into SCIT may not be safe. The author decreases the administered dose often “going back” to the initial formulation when changing from SLIT into SCIT.
SLIT in the US is not approved by the FDA. Its use implies an off-label use of the allergenic extracts. Still there is a growing interest in this treatment modality and yearly courses on SLIT are offered by the main allergy academies. The situation is different in Europe, where an estimated 45% to 80% of all immunotherapy is administered as SLIT [
The author anticipates that the use of SLIT in the US for the private setting will only increase in the near future for 2 reasons: Present day medical insurances are becoming very expensive, with high deductibles and high copays. For this reason, many patients will not be able to afford the lengthy allergy treatment with weekly injections. Although SLIT is an out-of-pocket expense it is becoming a more viable option in those circumstances. It also saves the patient time and transportation costs. From the practical point of view it is observed that there are patients that find the cost of the noncovered service (SLIT) preferable to the covered service (SCIT). Prevalence of asthma (and allergic rhinitis) has shown a worldwide increase over the last two to three decades [ After severe storms affected the author’s geographical area it was observed that the patient population consulting at the author’s office for allergic conditions appeared to be younger, more sensitive, and more reactive [
In 2014 the FDA approved allergy tablets for use in the US, for the treatment of pollen-induced allergic rhinitis with or without conjunctivitis [
In this case, the allergen(s) is (are) delivered to the oral mucosa in a rapidly dissolving tablet. The patient is treated with a preset dose of the allergen(s) without an updosing schedule. Because ultimately the allergens are delivered to the oral mucosa in a similar way as with SLIT it could be speculated that FDA approval for these tablets will eventually ease the approval of the same allergens in a liquid form, mixed at doctors’ offices.
SLIT is a versatile treatment modality. Its safety makes it ideal for handling the difficult-to-treat patient like the asthmatic and the child. If SLIT were reimbursed by insurance companies it would potentially be the treatment of choice for those difficult-to-manage circumstances. It could also be more convenient in many other cases like when there are recurrent local arm reactions, the patient has time management problems that prevent coming to the office for shots, or the patient lives far away or has physical difficulties getting to and from the office.
The author declares that he has no competing interests.