Sublingual Immunotherapy

Seasonal allergies, including allergic rhinitis, are thought to affect up to 20% of the population.^[1] Allergy is a major cause of absenteeism and restricted activity in both children and adults. Allergy prevalence begins in infancy, peaking in childhood and adolescence, continuing in adulthood, and decreasing in the elderly.^[1] Seasonal allergy includes typical symptoms such as sneezing, itching, nasal congestion, runny nose (also known as allergic rhinitis), coughing, itchy watery eyes, dark circles under the eyes, and itchy throat, as well as fatigue, headache, and malaise; comorbidities can include asthma, sinusitis, and ear infections.^[2] Since allergy symptoms result from a chain of immune responses ending in histamine release, many people depend on antihistamine medications to control their symptoms. In this article, we will first discuss the cause of allergies, common treatments, and then introduce our readers to a novel, natural immune therapy called sublingual immunotherapy (SLIT).

Allergy is a condition of immune hyperresponsiveness to environmental triggers. The body recognizes the allergen as a bacteria or virus and initiates an immune response against it. Once initial sensitization has occurred, subsequent exposures to the allergen results in the activation of IgE-coated mast cells.^[2] These mast cells infiltrate and accumulate in the mucosal layer, where they bind the allergen, and “degranulate”; this means that they release packages of chemicals including histamine, tryptase, kininogenase, and other enzymes, and produce proinflammatory mediators including prostaglandin D2, and leukotrienes LTC4, LTD4, and LTE2.^[2] These chemicals are responsible for changes such as increased permeability of blood vessels, leading to swelling, edema, and water discharges for the eyes and nose. There is also increased production of mucus, leading to congestion and difficulty breathing. This can also contribute to sinusitis. Stimulation of local nerve endings results in itching and reflexes such as sneezing. Within hours, there is also infiltration of the mucosa with other immune cells, including macrophages, eosinophils, neutrophils, basophils, and T cells.^[2] With continued exposure to the allergen, the threshold exposure required to trigger a reaction decreases, leading to increased susceptibility to this and other allergens.

Common strategies for managing allergy include identifying the causative agent(s) and limiting exposure accordingly, use of antihistamine medications, as well as use of “allergy shots.”

Dealing with Pollens

Common environmental allergens include pollens from grasses, trees, and weeds, as well as pet dander (cat, dog), dust, mold, and mites. According to Skoner, about 40% of allergy sufferers are afflicted with perennial allergies, that is allergies to other allergens such as dust, mites, and mold, that continue to elicit symptoms year-round.^[2] About 40% of sufferers have a mixed form of allergy, responding both to perennial triggers as well as pollens in the spring. About 20% of sufferers are predominantly affected by pollens in the spring and/or summer. Depending on the precise trigger, symptoms worsen at specific times of the year: for instance, mid-March to mid-June are often worst for those with tree allergies, while mid-May to end of July are worst for those with grass allergies; finally, August until first frost is the season for ragweed.^[3] Despite these demarcations, it is not unusual for allergy sufferers to be reactive to one or more of these types of triggers, and many suffer throughout the spring and summer as a result. Pollen counts are one indicator available to allergy sufferers that provide an estimate of how much pollen is circulating in the air on a particular day. Pollen counts are available from various weather reporting sites, including the Weather Network website,^[4] which offers projected three-day pollen counts for centers across Canada, at http://www.theweathernetwork.com/outdoors/pollen/list. Knowing pollen counts can help allergy sufferers plan their outdoor activities accordingly.

According to the Allergy Asthma & Immunology Association of Ontario, some lifestyle tips that may help alleviate allergy symptoms include:

• Keep your windows in the house and the car closed during pollen season.
• Air conditioning will help control the outdoor air coming in and perhaps relieve your symptoms.
• Minimize early morning activities when pollen is commonly released (between 5:00 and 10:00 a.m.)
• Stay indoors when the pollen count is high, and on windy days when dust and pollen are distributed.
• Exercise indoors when pollen counts are high.
• Days that are rainy, cloudy, and without wind will help to alleviate symptoms as pollen is not being circulated: hot, dry, and windy weather will cause allergic symptoms to return.
• Do not allow your dog or cat to run at large, as it can become a carrier of pollen.
• Avoid contact with animals, and never allow pets in the bedroom.
• Regular washing of cats may lessen their allergic potential.
• Do not cut the grass yourself or spend time around freshly cut grass, and do not rake leaves — these activities will stir up pollens and mold.
• Remove indoor plants, which will cause mold to grow.
• Remove all carpets from the sleeping area.
• Cover mattresses and pillows with mite-proof casings to reduce house dust mites.^[3

It is not possible, however, for most people to completely avoid allergen exposure. Indeed, even if one were to live in virtual hibernation and isolation, this would hardly be feasible, nor healthy. Lifestyle adaptations such as those listed above can help minimize the severity of symptoms, but for most, it will not result in allergy eradication. Most allergy sufferers need to resort to some form of pharmacological strategy to control their allergy symptoms.

Common Medications

Antihistamines such as Reactine or Claritin are over-the-counter medications that suppress the primary culprit end-product of the immune cascade: release of histamine. Depending on the severity of allergy, some individuals use antihistamines to curb peak symptoms, while others are dependent on continuous antihistamine use throughout allergy season. Other medications may include decongestant nasal sprays, and even corticosteroid nasal sprays such as Nasonex. Side effects from these medications can include drowsiness, dizziness, nausea, blurred vision, and restlessness or moodiness in children.^[5] Repeated use of corticosteroids can reduce immunity against infectious agents, cause nosebleeds or changes to the nasal mucosa, and slowed growth in children.^[6] Apart from the inconvenience of use, dependency, and risk of side effects, antihistamines, corticosteroids, and decongestant medications have the distinct disadvantage that they manage symptoms only. These medications do not address the underlying problem, which is inappropriate immune responsiveness. For many individuals, allergy symptoms get worse from year to year despite reliance on medication.

A strategy that circumvents the problem of symptomatic management is allergen immunotherapy, a method of allergy desensitization, modifying the actual immunologic response. The traditional method for allergy desensitization is by injection, popularly known as “allergy shots”.^[7] Because it involves injections, this therapy is typically reserved for those who do not respond adequately to other medications. There are two phases of treatment, the buildup phase and the maintenance phase.^[7] During the buildup phase, minute doses of allergen are injected once to twice weekly, for between three and six months. During this phase, the amount of allergen injected is gradually increased. Once the effective dose is achieved, the maintenance phase begins. During this phase, the time between treatments is typically two to four weeks. Given in this fashion, exposure to small amounts of allergen is used to induce immune tolerance. Basically, over time and continued treatment, the immune response against the allergen diminishes and in some people results in lasting long-term relief. An obvious disadvantage of this strategy is that it consists of a series of injections, which can be a serious deterrent for adults and children alike.

A novel route for this type of therapy is sublingual immunotherapy (SLIT). This therapy is already in widespread use in Europe, but is only making inroads in North America recently. SLIT represents a new, convenient method of allergy desensitization.

Evidence on Sublingual Immunotherapy

Sublingual immunotherapy first became available commercially about twenty years ago, in the 1990s.^[8] The first randomized, double-blind, placebo-controlled trial of SLIT was published in 1986.^[8] Since then, a wealth of clinical data has accumulated on the use of SLIT therapy for the treatment of allergy and asthma. Today, a search of the PubMed database of peer-reviewed medical journals reveals almost 300 clinical trials evaluating SLIT. Sublingual immunotherapy is, as the name implies, a form of very low–dose allergen exposure that is administered by drops or tablets placed under the tongue. Administration may be short-term for relief of acute allergy symptoms, but is more commonly used over a period of several months to years for allergy desensitization. Based on the triggers identified for a particular person, an individualized formula of low-dose allergen is compounded. The ease of use of this method of desensitization, combined with a well-established evidence base showing effectiveness and superior safety compared to allergy injections,^[8] make it an attractive option for allergy sufferers.

There are several meta-analyses in existence on SLIT. These studies combine the data of many clinical trials into one comprehensive result. A 2013 meta-analysis compared the efficacy of sublingual compared to subcutaneous (injection) immunotherapy for seasonal allergy.^[9] Including data from 170 randomized trials, the study concluded that there was “clear evidence of effectiveness of both SCIT and SLIT, [however] superiority of one mode of administration over the other could not be consistently demonstrated”,^[9] suggesting equivalent effectiveness of sublingual compared to injection immunotherapy. A Cochrane review assessed the effectiveness of SLIT in reducing symptoms of allergic conjunctivitis (eye symptoms).^[10] The study included data from 42 trials. Compared to placebo, SLIT resulted in significant reductions of total ocular symptom scores (60% reduction) as well as between 60% and 70% reduction in individual symptoms such as itchy eyes, eye redness, watery eyes, or swelling eyes. There was also an increase in the threshold allergen exposure for conjunctival immediate allergen sensitivity. A study evaluating SLIT in children with allergic asthma and rhinitis found that patients treated with SLIT over a period of three years experienced significant improvements in rhinitis symptoms and asthma symptoms compared to children who did not receive immunotherapy and only used symptom management drugs.^[11] Importantly, there were no incidents of serious adverse reactions.

Another study investigated the effect of SLIT in children with grass-pollen allergic rhinitis.^[12] A total of 207 children were treated with SLIT therapy or placebo for one allergy season. The SLIT group demonstrated a significant reduction in medication use, as well as reduced symptoms of rhinoconjunctivitis (eye and nose allergy symptoms). There was also a decrease in levels of allergen-specific antibodies, IgG and IgE, indicating a change in immune responsiveness. Authors concluded that SLIT “showed significant effects on allergen-specific antibodies, was well tolerated, and appeared to be a valid therapeutic option in children allergic to grass pollen”.^[12]

Readers who are interested in further information on or who would like to be assessed for sublingual immunotherapy are encouraged to contact a licensed naturopathic doctor in their area.