People having allergy develop a special type of antibody called Immunoglobulin E (IgE) which can react with environmental substances in harmful way. These substances are called allergens. The most common allergens are house dust mite, animal dander, pollen, moulds and foodstuffs. Children spend maximum time at home hence they are more likely to be exposed to indoor allergens.

For curative treatment, it is essential that allergen responsible for the symptoms be accurately identified. There are different ways to arrive at a diagnosis. The history is extremely important in all allergological investigations. Allergy testing procedures are employed to identify allergens responsible for the symptoms. There are two methods of allergy testing:

1. In-vitro testing : In-vitro method involves the measurement of serum IgE by using various techniques such as RAST, PRIST, ELIZA, Immunocap etc.
2. In-vivo testing : The skin testing covers three modes of testing; Prick test, Intradermal test and Patch test.

Among skin allergy testing procedures, modified skin prick test method is more precise, widely used and can be recommended for children in all age group.1

Management of Allergic Disorders in Paediatric Age Group.
There are basically three types of treatment available to manage allergic ailments : (a) Avoidance measures, (b) Pharmacological management, (c) specific allergen immunotherapy.

Avoidance therapy is the least expensive and is the simplest way to avoid allergens. However, avoidance of allergens is often not practical. Pharmacological management is the treatment of allergic diseases through medication. Unfortunately, some of the allergic conditions do not respond to drug treatment. Further more, there are always some side effects of drugs.

Specific Allergen Immunotherapy
Allergen immunotherapy is the choice of treatment in cases where drug treatment is not responding and avoidance is not feasible. Controlled studies have shown that allergen immunotherapy is effective for patients with allergic rhinitis or conjunctivitis, allergic asthma and stinging insect hypersensitivity.1 Allergen immunotherapy is the only treatment which alters the natural course of the disease (WHO position paper 1998).3

Allergen immunotherapy enjoyed widespread use before the first control studies showing efficacy in allergic rhinitis and allergic asthma were published (Lowell and Franklin, 1963).8 Allergen immunotherapy is based on administration of allergen extracts in incremental pattern to achieve a safe and effective maintenance dose.

Route of Administration

Subcutaneous
Subcutaneous route of allergens administration is widely used and well documented. Despite of the established efficacy of subcutaneous injections of causal allergens, the therapy did not gain popularity due to risk of systemic reactions especially in children. Further, the initial treatment (build-up phase) requires 30-40 injections, each of which involves time and cost to the patient.

In order to minimize untoward reactions, there has been increasing interest in non-injection routes of administration of immunotherapy especially in Europe.

Local and Nasal
The rationale of giving the allergen orally is that the gastrointestinal tract has an abundant mucosal immune system (so called gut associated lymphoid tissue). Therefore, an effective antigen representation can be expected.

Local and Nasal administration of allergen extracts have been tried by spraying specified dose of allergen extracts into nasal cavity at specified time interval. Though, the efficacy has been reported; the side effects like nasal pruritus, congestion, sneezing are intolerable and inconvenient to children, hence this route is not yet recommended in this age group.

Oral/sublingual
The original rationale for administering immunotherapy sublingually was that of achieving a prompt and rapid absorption of the vaccine to avoid possible gastrointestinal degradation. Although, it was recently demonstrated that no relevant direct absorption through the sublingual mucosa occurs, the sublingual immunotherapy proved effective in a great number of trials; therefore, it is presently the most widely used non-injection route of immunotherapy in Europe.5

There have been a number of studies from Europe, particularly from Germany, indicating that the oral route is effective in desensitizing hay fever patients. Recent claims have been made that sublingual immunotherapy may be a viable alternative to injection immunotherapy.2 In the year, 1998 a panel of experts of WHO, on the basis of an extensive review of the literature, concluded that both sublingual and local/nasal immunotherapy are variable alternatives to the injection route and that their use in practice in adults is justified.3

Efficacy and Safety
The main rationale of sublingual immunotherapy is to minimize the risk of adversed events. The most frequently reported side effect in oral/sublingual immunotherapy is itching after ingestion of the dose, however, it is mild and self-resolving. An other important side effect is gastrointestinal complaints; sporadically headache, rhinorrhoea, constipation and urticaria are reported. Andre et al4 reported only mild side effects but no severe systemic adverse events.

In a study of 60 children with allergic asthma and rhinitis due to mite, 25 children underwent 4-5 years course of sublingual immunotherapy with standardized extract showed significant difference verses base line for the presence of asthma and use of asthma medications even 5 years after discontinuation of sublingual immunotherapy.4

In recent paediatric studies, the occurrence of side effect was reported negligible and they were not troublesome. Noticeably, no severe systemic events were reported in the literature during a period of 15 years.9

Sublingual immunotherapy can be administered without any side effect as co-seasonal immunotherapy whereas pre-seasonal immunotherapy is recommended in case of pollinosis (subcutaneous immunotherapy) which should be discontinued during the peak pollen season in order to avoid adverse reactions.

Long Term Benefit
Traditional subcutaneous immunotherapy (SIT) is usually given for 3 years with symptoms benefits at least for 4-5 years thereafter. Di Rienzo et al7 conducted an open study with sublingual immunotherapy and advocated clinical benefits for 5 years after 4-5 years of course.

Clinical use of sublingual immunotherapy has reviewed in several official position papers but, none of these reviews addressed lasting benefit compared with subcutaneous immunotherapy except simple symptoms control.

Cost Effectiveness
Concerning the costs, it is true that cumulative dose of allergen given by sublingual route is 20-300 times the usual dose of injection immunotherapy, therefore, cost of the vaccine is expected to be higher. This higher cost is balanced by the reduced need of medical supervision, as it can be self-administrated.

Allergen Extracts for Immunotherapy
Standardized allergenic extracts should be used. These allergens have a definite potency and are labelled with common unit. Non-standardized allergens are labelled by w/v units, but this does not reflect the potency of the product, hence there is increased risk of adverse reactions. Standardized allergens are generally available at a comparatively higher concentration. They are prepared as aqueous glycerinated formulations and are compatible for mixing with non standardized products. Theoretically, there is less risk of adverse reaction with a standardized allergens because of greater predictability about their potency.

However, glycerinated aqueous extract are used in sublingual immunotherapy. The allergen extract suspended in extracting fluid containing 50% glycerol is provided three different concentrations i.e. 0.01% (strength - 1), 0.01% (strength - 2) and 1% (strength - 3) for initial treatment course. The maintenance therapy is recommended with strength - 3.

Recommended Dosage and Procedures

• Dosage is administrated always individually according to individual sensitization.
• Care should be taken while increasing the dose.
• If the treatment is interrupted by more than two weeks, therapy should be continued, for safety reason, with half of the dose last given. In the event of interruption of more than 4 weeks, the therapy should resumed from the start.
• Sublingual drops should be taken preferably on empty stomach (2 hours before meal or after meal).
• If parallel therapy with two oral extracts is indicated, they should be given one in morning and the other in evening.
• Treatment can be initiated with one drop of the weakest concentration (strength - 1). This drop is increased by one drop every day till top tolerable dose is reached. Strength 2 is followed in the same manner.
• Maintenance therapy is resumed by 2 drops of strength 3. This dose is increased by one drop every day until top tolerable dose is reached.
• Drops should be taken at the same time each day.

Conclusion
Sublingual immunotherapy has a degree of efficacy and significant advantages over controversial subcutaneous immunotherapy in terms of patients acceptability and safety. Sublingual immunotherapy has been proved safe and effective in numerous double blind trials. Sublingual allergen immunotherapy could be a noble treatment for allergic rhinitis, conjunctivitis, and allergic asthma in paediatric age group.

References

1. Nelson HS. Advances in upper airway diseases and allergen immunotherapy. J Allergy Clinic Immunol 2004; 113 (4) : 635-42.
2. Frew AJ, Smith HE. Sublingual immunotherapy. J Allergy Clinic Immunol 2001; Rostrum : 441-4.
3. Bousqueet J, Lockey R, Malling HJ (Eds.). World Health Organization position paper; Allergen Immunotherapy - therapeutical vaccines for allergic disease. Allergy 1998; 53 (suppl).
4. Andre C, Vatrinet C, Galvain S, Carat F, Sicard H. Safety of sublingual swallow immunotherapy in children and adults. Int Arch Allergy Immunol 2000;121:229-34.
5. Canonica GW, Passalacqua G. Non injection routes of immunotherapy. J Allergy Clinic Immunol 2003; 111 : 437-48.
6. Pajno GB, Morabito L, Barberio G, Parmiani S. Clinical and immunological effect of long term sublingual immunotherapy in asthmatic children sensitized to mite : a double blind study. Allergy 2000; 55 : 1142-7.
7. Di Rienzo V, Pagani A, Parmiani S, Passalacqua G, Canonica GW. Post marketing surveillance study on the safety of sublingual immunotherapy in children. Allergy 1999; 54 : 1110-3.
8. Loweel HC, Franklin WA. A double blind study of treatment with aqueous allergen extracts. Allergy 1963; 34 : 165-71.