Synonyms: desensitisation, allergen immunotherapy

During hyposensitisation the aim is to expose a patient with sensitivity to a known allergen, to progressively larger doses of the allergen so that the severity of their hypersensitive response is reduced or even abolished.

Various appraisal methods have been devised to measure efficacy.¹

The most common allergens administered worldwide

• House dust mite.
• Grass and tree pollen.
• Animal dander (cat or dog).
• Wasp and bee venom.

Indications

Points to note regarding the use of allergen immunotherapy

• There is inadequate evidence of the benefit from desensitisation to other allergens such as house dust, house dust mite, animal danders and foods and these are thus not recommended at present.
• Allergen immunotherapy is not effective in the treatment of atopic dermatitis, urticaria, or headaches and is potentially dangerous if used for food or antibiotic allergies.

Method³

• Allergen immunotherapy (also called allergy vaccine therapy) involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure.
• Progressive exposure to the allergen leads to IgG production rather than the IgE production which occurs in type 1 allergic responses.
• Safe administration of allergen immunotherapy requires the immediate availability of a healthcare professional capable of recognising and treating anaphylaxis, and the presence of cardiopulmonary resuscitation facilities.
• An observation period of one hour after injection is mandatory. If the patient develops any symptoms, even if mild, they need to be observed until these completely resolve.
• One study found that the use of an ultra-short course (four doses) of grass modified allergen tyrosine adsorbate monophosphoryl lipid A (MATA MPLA®) was effective.⁴
• Patients should not be taking beta-adrenergic blocking agents or angiotensin-converting enzyme (ACE) inhibitors when receiving immunotherapy because these drugs may mask early signs and symptoms of anaphylaxis and may make the treatment of anaphylaxis more difficult.⁵

Investigations⁶

Patients need to be referred to a specialist in immunotherapy. Diagnostic skin tests alone are unreliable and should only be used in conjunction with a detailed history of allergen exposure.

Benefits and risks

• Hyposensitisation may be effective in allergic rhinitis if sensitisation to a particular allergen can be proven.
• The benefit of hyposensitisation needs to be balanced against the significant risk of anaphylaxis, particularly in patients with asthma.
• An Australian review estimated the risk of mild effects at 1 in 1,500 injections; near-fatal anaphylaxis one per million injections and death at one in 2.5 million injections.⁷

Contra-indications

Adverse reactions

These mostly relate to the site of injection - for example:

• Itchiness
• Swelling
• Redness

Administration

• The allergen is given subcutaneously
• Recent studies have investigated the effects of sublingual allergen administration.

Sublingual allergen administration

There have been a number of studies that have observed the effects of sublingual grass pollen. For example, a randomised, double-blind, placebo-controlled trial testing sublingual grass pollen was associated with a significant decrease in symptoms and reduced the frequency of other treatment usage, e.g. steroids.⁸ There were no significant adverse events associated with this product.

A preparation called Grazax® to use in immunotherapy for grass pollen allergy is now licensed in the UK.⁹ The first dose is usually administered in clinic and can then continue unsupervised. It is taken for three to four months before the pollen season and therapy should continue (for up to three years). Adverse effects have been described and include oral itching and mild swelling.¹⁰ Other sublingual preparations are undergoing further research in hay fever¹¹ and food allergies.¹²

One study reported that oral immunotherapy was preferred by patients and improved compliance.¹³ Another found significant improvement in quality of life outcomes.¹⁴

Document references

1. Grouin JM, Vicaut E, Jean-Alphonse S, et al; The average Adjusted Symptom Score, a new primary efficacy end-point for specific Clin Exp Allergy. 2011 Mar 7. doi: 10.1111/j.1365-2222.2011.03700.x. [abstract]
2. British National Formulary
3. Srivastava D, Arora N, Singh BP; Current immunological approaches for management of allergic rhinitis and Inflamm Res. 2009 Sep;58(9):523-36. Epub 2009 Mar 31. [abstract]
4. Dubuske L, Frew A, Horak F, et al; Ultrashort-specific immunotherapy successfully treats seasonal allergic Allergy Asthma Proc. 2011 Apr 29. [abstract]
5. Saltoun C, Avila PC; Advances in upper airway diseases and allergen immunotherapy in 2007. J Allergy Clin Immunol. 2008 Sep;122(3):481-7. Epub 2008 Aug 9. [abstract]
6. Douglass JA, O'Hehir RE; 1. Diagnosis, treatment and prevention of allergic disease: the basics. Med J Aust. 2006 Aug 21;185(4):228-33. [abstract]
7. Weiner JM; Allergen injection immunotherapy. Med J Aust. 2006 Aug 21;185(4):234.
8. Dahl R, Kapp A, Colombo G, et al; Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J Allergy Clin Immunol. 2008 Feb;121(2):512-518.e2. Epub 2007 Dec 26. [abstract]
9. Summary of Product Characteristics, Grazax®, ALK-Abello Ltd, electronic Medicines Compendium. Dated November 2010
10. Bonnin AJ, Zacharias DM; Sublingual immunotherapy. N Engl J Med. 2008 Aug 21;359(8):869-70; author reply 870.
11. Frati F, Scurati S, Puccinelli P, et al; Development of a sublingual allergy vaccine for grass pollinosis. Drug Des Devel Ther. 2010 Jul 21;4:99-105. [abstract]
12. Burks AW, Laubach S, Jones SM; Oral tolerance, food allergy, and immunotherapy: implications for future treatment. J Allergy Clin Immunol. 2008 Jun;121(6):1344-50. Epub 2008 Apr 14. [abstract]
13. Sieber J, De Geest S, Shah-Hosseini K, et al; Medication persistence with long-term, specific grass pollen immunotherapy Curr Med Res Opin. 2011 Apr;27(4):855-61. Epub 2011 Feb 16. [abstract]
14. Wise SK, Woody J, Koepp S, et al; Quality of life outcomes with sublingual immunotherapy. Am J Otolaryngol. 2009 Sep-Oct;30(5):305-11. Epub 2009 Feb 6. [abstract]

Internet and further reading

• Broide DH; Immunomodulation of allergic disease. Annu Rev Med. 2009;60:279-91. [abstract]
• Rank MA, Li JT; Allergen immunotherapy. Mayo Clin Proc. 2007 Sep;82(9):1119-23. [abstract]