Immunotherapy for allergic diseases

Author: Dr Beth Wright, Core Medical Trainee, Bristol, United Kingdom; Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, December 2014.


What is immunotherapy?

Immunotherapy is a medical treatment that alters the immune system by causing induction, enhancement or suppression of an immune response.

In allergic disease, an untoward immune response is mounted towards an allergen that causes the allergic symptoms. Immunotherapy is used to modulate this response. The treatment is also called desensitisation.

How does immunotherapy work in the management of allergic diseases?

The patient undergoing immunotherapy is administered gradually increasing amounts of their allergen.

The protective immunological changes are complex, and not fully understood. There are three important components.

1. Altered bisphasic allergic response

Patients who are exposed to an allergen demonstrate a biphasic response, consisting of an early phase of symptoms that occur within minutes of exposure, and often a delayed phase that occurs hours later.

During the early phase, mediators are released from local tissue mast cells and circulating basophils. These include histamine, prostaglandin D2, kinins, cysteinyl leukotrienes, cytokines, and chemokines. Some of these mediators stimulate cells to recruit more inflammatory cells to the area that is challenged by the allergen, including T lymphocytes, eosinophils, and additional basophils. These cells release specific inflammatory mediators contributing to persistent allergic symptoms (the delayed phase).

Following immunotherapy, the early response is dampened (although rarely eliminated) and the delayed phase response is reduced even more [1].

2. Change in humoral immunity

Immunotherapy also causes complex changes in humoral immunity and allergen specific antibodies:

  • IgE is initially increased, then reduces
  • IgG levels increase and remain elevated
  • IgA levels increase in serum and secretions

3. Change in cellular immunity

Several changes in T-cell responses to allergen occur and may contribute to developing tolerance to an allergen by several overlapping and complex mechanisms.

Over time, if successful, these immunological changes result in desensitisation to the allergen, meaning the patient suffers fewer symptoms when next exposed to it.

How is it immunotherapy administered?

Immunotherapy for the allergen to which the patient is sensitive is administered at regular intervals by an allergy specialist. The concentration of the allergen in the formulation is gradually increased as part of the schedule. The allergen can be administered by subcutaneous injection or sublingually. The patient is observed for up to an hour following administration, in case of adverse reaction including anaphylaxis.

Subcutaneous injection immunotherapy (SCIT)

Subcutaneous injection is the most established form of immunotherapy for the treatment of allergies. An injection containing the allergen is injected just below the skin.

Sublingual immunotherapy (SLIT)

In sublingual immunotherapy, the allergen is applied to the oral mucosa or under the tongue in a solution or dissolvable tablet. This is typically held in the mouth for a few minutes and then swallowed. Once a patient is established and ‘safe’ on treatment, medication can be taken at home, however strict compliance with instructions is important otherwise therapy may not work.

Few studies have directly compared SCIT and SLIT. Different immunologic therapies and routes of administration are areas of ongoing research and development.

Immunotherapy for bee and wasp stings – venom immunotherapy (VIT)

Immunotherapy for venom allergy is highly effective and can be life saving for those who suffer a severe systemic response to allergies, including anaphylaxis.

In patients who have suffered severe allergic reactions to bee and wasp stings, and have evidence of venom specific IgE, the risk of systemic reaction to a further sting is up to 60% in adults [2] and this can be reduced to less than 5% following VIT [3].

The way in which VIT works is not fully understood. It is believed to be result of several immunologic changes, including the production of venom-specific immunoglobulin G (IgG) antibodies. These interfere with the immunoglobulin E (IgE)-mediated allergic mechanism described above.

A patient may be suitable for VIT if they give a history of systemic reaction to one or more previous stings, AND elevated levels of venom-specific IgE is present on in-vitro testing. Both of these criteria must be met if they are to be considered a suitable candidate.

Immunotherapy for atopic dermatitis

Allergen specific immunotherapy (SIT) is not standard treatment for eczema. However, it may be considered in patients with proven sensitisation to inhalant allergens (such as dust mite or pollens shown by prick tests or specific IgE antibody blood tests) and that have severe eczema that is not controlled with conventional eczema treatment.

A small number of studies have looked at SIT administered sublingually and subcutaneously, with dust mite extract [4-6], birch and grass pollen [7]. These have suggested some benefit and clinical improvement in atopic dermatitis, if the patient is sensitised to these inhalant allergens. There are also studies that negate this [8]. Currently overall the strength of recommendation is weak and higher quality evidence is needed [9].

Immunotherapy for chronic urticaria

Immunotherapy may be considered in selected patients that suffer with chronic urticaria and have identifiable antibodies. Effectiveness has been demonstrated in some patients with chronic urticaria due to autoimmune or allergic disease, rather than being purely idiopathic in origin [10,11]. Further evidence is needed, as there have been few studies that evaluate the use of immunotherapy in chronic urticaria.

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References:

  1. Iliopoulos O, Proud D, Adkinson NF Jr, et al. Effects of immunotherapy on the early, late, and rechallenge nasal reaction to provocation with allergen: changes in inflammatory mediators and cells. J Allergy Clin Immunol. 1991 Apr;87(4):855-66. PubMed PMID: 2013680.
  2. van der Linden PW, Hack CE, Struyvenberg A, van der Zwan JK. Insect-sting challenge in 324 subjects with a previous anaphylactic reaction: current criteria for insect-venom hypersensitivity do not predict the occurrence and the severity of anaphylaxis. J Allergy Clin Immunol. 1994 Aug;94(2 Pt 1):151-9. PubMed PMID: 8064067.
  3. Carballada F, Boquete M, Núñez R, Lombardero M, de la Torre F. Follow-up of venom immunotherapy (VIT) based on conventional techniques and monitoring of immunoglobulin E to individual venom allergens. J Investig Allergol Clin Immunol. 2010;20(6):506-13. PubMed PMID: 21243935.
  4. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011 Jan;127(1 Suppl):S1-55. doi: 10.1016/j.jaci.2010.09.034. Epub 2010 Dec 3. Erratum in: J Allergy Clin Immunol. 2011 Mar;127(3):840. PubMed PMID: 21122901.
  5. Bussmann C, Maintz L, Hart J et al. Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcutaneous immunotherapy with a house dust mite allergoid: a pilot study. Clin Exp Allergy. 2007 Sep;37(9):1277-85. PubMed PMID: 17845407.
  6. Werfel T, Breuer K, Ruéff F et al. Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Allergy. 2006 Feb;61(2):202-5. PubMed PMID: 16409197.
  7. Darsow U. Allergen-specific immunotherapy for atopic eczema: updated. Curr Opin Allergy Clin Immunol. 2012 Dec;12(6):665-9. doi: 10.1097/ACI.0b013e3283588cf4. Review. PubMed PMID: 22918221.
  8. Glover MT, Atherton DJ. A double-blind controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with atopic eczema. Clin Exp Allergy. 1992 Apr;22(4):440-6. PubMed PMID: 1611544.
  9. Gendelman SR, Lang DM. Specific immunotherapy in the treatment of atopic dermatitis: a systematic review using the GRADE system. Ann Allergy Asthma Immunol. 2013 Dec;111(6):555-61. doi: 10.1016/j.anai.2013.08.020. Epub 2013 Sep 21. Review. PubMed PMID: 24267368.
  10. Greaves MW. Chronic idiopathic urticaria. Curr Opin Allergy Clin Immunol. 2003 Oct;3(5):363-8. Review. PubMed PMID: 14501436.
  11. Song, Z. Q., et al. Effect of specific immunotherapy in chronic urticaria patients with IgE antibody against house-dust mite. J Clin Dermatol 37 (2008): 809-811.

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