Allergen specific immunotherapy

Recent topic asked in MD/DCH/DNB Pediatrics exam.
Covers information on specific immunotherapy

1. Allergen Specific Immunotherapy Dr. Himanshu S Dave Department of Pediatrics NRCH, New Delhi

2. Allergen specific immunotherapy (SIT) : Defined as a gradual immunizing process in which increasing doses of antigens responsible for causing allergic symptoms are administered to a patient to induce increased tolerance to the allergen when natural exposure occurs. Known as hypo sensitization or desensitization

3. The benefit of specific immunotherapy is dependent on both the dose and the route of administration . Mechanism : Not fully understood . The current consensus is that specific immunotherapy works by inducing allergen-specific T regulatory cells that reduce the late-phase response to the allergen. It was introduced by Noon in 1911 by inoculating pollen extracts in cases of hay fever

4. During a period of years, specific immuno therapy typically induces an allergen-specific IgG response. In the past, this type of antibody was called blocking antibody , although there is no evidence that it actually blocks the allergic response or has any physiologic role.

5. Immunotherapy is effective in : Allergic rhinitis A llergic asthma Insect stinging insect sensitivity Whereas it is not effective in eczema., Food allergy, latex allergy and urticaria .

6. Goals of immunotherapy : Complete disappearance of symptoms with use of medications less or in low doses with no significant side effects or symptoms should be at a tolerable level even after completion of immunotherapy.

7. Indications for Immunotherapy

8. Insufficient response to pharmacotherapy. Insufficient response to environmental control. Significant side-effects to medical therapy. Patients who have perennial disease. Poor compliance to medical regimen. Possible prevention of asthma from allergic rhinitis.

9. Contraindications for Immunotherapy

10. Severe asthma – FEV1 < 70% with active Rx . Contraindications for epinephrine (Beta-blocker ). Immunodeficiency/auto immune diseases. Pregnancy . Malignancy . Psychological . Mentally impaired patients. Short expected life span < 5 years. Non-compliant patient.

11. Safety and Efficacy of Immunotherapy

12. When properly administered to an appropriate candidate, it is a safe, effective form of therapy capable not only of reducing or preventing symptoms, but of potentially altering the natural history of the disease by minimizing disease duration and preventing disease progression. The use of standardized extracts is advised to get optimal results

13. Success of immunotherapy depends on: Optimal means of allergy testing Quality of allergen extract Correct initial dose of immunotherapy Follow-up with maintenance dose.

14. Failure of immunotherapy is mainly due to: Inadequate environmental control . Missed diagnosis (non-allergic rhinitis ) Failure to include allergen in SIT Exposure to unknown allergen Inadequate dose of allergen injection Noncompliance of schedule Development of new allergic sensitivities, unrealistic patient expectations for cure and some patients may not responded favorably to SIT itself

15. Adverse Reaction

16. Systemic reactions to immunotherapy: O ccur within one hour Usually scattered hives Rarely severe anaphylaxis, Whereas local reactions : Occur up to 24 hours . Incidences of fatal anaphylaxis is 1 per 2 million injections .

17. Common local reactions are wheals, indurations or both mainly due to poor injection technique. Patient should be under observation for 30 minutes to monitor allergic reactions. Patient education is essential especially for delayed reactions

18. At the first sign of a systemic reaction, a tourniquet may be applied above the injection site and epinephrine administered at a weight appropriate dose preferably by the intramuscular route.

19. Schedule of Immunotherapy

20. Schedules of allergen administration are selected based on the sensitivity of the patient to the allergens in the extract . Dose ranges from 4-12 ug administered subcutaneously. Despite the established efficacy of subcutaneous injections of causal allergens, the therapy did not gain popularity due to risk of systemic reactions.

21. Primary Immunotherapy : To start with low doses are administered Can be stepped up gradually in dosage and frequency until maintenance dose is reached . It has to be given for 3-5 months.

22. Maintenance Immunotherapy : After attaining adequate control with twice dose, it can be changed over to once a month dose. To get adequate response one year of treatment is compulsory . If there is no response it can be discontinued. Progressive improvement occurs by 2-3 years . Maintenance immunotherapy is given for a period of 3-5 years. Prediction of response is difficult. Extracts are stored at 2-8°C in the refrigerator for optimal efficacy.

23. Alternative Routes

24. Nasal Immunotherapy is administered as spray allergen solution into the nose in a phased manner but lack of significant immunologic response led to discontinuation of this route. Sublingual immunotherapy is administered as drops of high dose allergen solution underneath the tongue which is then swallowed. It may be started at the full maintenance dose, without the gradual increase in dose

25. The common side effect of sublingual immunotherapy is local irritation in the mouth and under the tongue (47 to 52 %). But it is usually transient and does not progress to anaphylaxis . It has the added advantage of ease of administration, home based therapy and avoidance of painful injections. So it can be advocated for children.

26. Intrabronchial administration : Out of general usage due to untoward side effects . Future strategies Alum depot preparations which act as adjuvants Allergoids which are chemically modified allergens Peptide immunotherapy which uses allergen derived T-cell peptide epitope , recombinant allergens and anti- IgE antibodies

27. Rush Immunotherapy

28. The process of inducing adequate immunological response in an accelerated pace , where in all the doses could be given within a period of few days is termed as Rush Immunotherapy. Here the doses are spaced out in 2-6 hourly intervals so that maintenance dose is reached within few days.

29. The risk of Systemic Allergic reactions is high. It has to be undertaken where facilities for intensive care and monitoring are available . Patients should be pretreated with antihistamines and corticosteroids.

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