Allergy desensitization, allergen immunotherapy (AIT), or hypo-sensitization was first introduced by Leonard Noon in 1911, who proposed that people with hay fever were sensitive to grass pollen toxins. Desensitization is "a method, to develop a temporary state of tolerance to an agent responsible for an allergic or hypersensitivity reaction." It is a disease-modifying treatment and lasts longer even after stopping the treatment, which then provides prophylactic effects.
Immunotherapy is the treatment of allergic disease by promoting or suppressing immunity. Allergen immunotherapy is a group of therapies that seek to promote immune tolerance to allergens. Hyposensitization is a term formerly used as synonymous with allergen immunotherapy because complete desensitization is rare with immunotherapy.
Types of Allergic or Hypersensitivity Disorders
Respiratory tract disorders include allergic rhinitis, allergic aspergillus rhinosinusitis, allergic bronchopulmonary aspergillosis (ABPA), or allergic asthma. Ocular disorders include allergic conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis.  Skin and mucous membranes disorders include allergic contact urticaria, oral allergy syndrome, acute urticaria due to IgE-mediated allergy, and atopic eczema. Drug hypersensitivity includes exanthematous drug eruption, drug-induced urticaria, angioedema and anaphylaxis, and Samter's syndrome. Food hypersensitivity includes food-induced urticaria, angioedema anaphylaxis, IgE-mediated food-induced gastrointestinal hypersensitivity, and oral allergy syndrome. Insect hypersensitivity or allergies include anaphylaxis, cutaneous reactions or local reaction to Hymenoptera venom.
Several cellular and molecular mechanisms explain the beneficial effects of immunotherapy including allergic specific suppression of inducible CD4(+), CD 25+, forkhead box p3+ T-regulatory cells, and IL-10 secreting T-regulatory cells; preventing their increase in peripheral blood. Other mechanisms include suppression of eosinophils, mast cells, and basophils, and antibody switch from IgE to IgG4.
Required Equipment and Procedures
The prescribing physician should select allergen extracts. The physician should consider several important factors including the quality of allergen extracts, cross-reactivity, and degradation of allergens and immunotherapy doses, for example, the starting dose will be lower than the maintenance dose.
Allergenic proteins from pollen, dander, dust mites, insects, mold, among others are the main ingredient of allergen extract. However, the final product is a mixture of diluents or solvents and preservatives. Different extracts including aqueous, glycerinated, lyophilized, acetone precipitated, alum-precipitated are available. Diluents will keep the allergen in liquid form; commonly used agents are glycerin, phenol saline, and HSA. The staff should use measures that include good personal hygiene, hand washing, and antiseptics to clean working areas. These include a water-based disinfectant followed by the application of alcohol on working surfaces for preparing allergen extracts. Alcohol kills organisms by dehydration. Sanitization will prevent bacterial contamination.
Complications include systemic reactions like anaphylaxis and a local reaction at the injection site.
Management of Complications
The physician should re-visit the benefit versus risk of continuing immunotherapy after systemic reactions.
Allergen immunotherapy can reduce short-term symptoms in allergic asthma; however, there is a moderate increase in the risk of systemic and local reactions based on meta-analysis. A 3-year course of either sublingual or subcutaneous immunotherapy prevents asthma for up to 2 years in children and adolescents with grass/birch pollen that triggers moderate to severe allergic rhinitis; However, this still requires further research.
Allergen immunotherapy has been found to be beneficial in improving rhino-conjunctivitis symptoms. Some evidence suggests that there is a maintenance effect on reducing symptoms after discontinuation of immunotherapy.
Current and Future Trends in Allergen Immunotherapy
There are different approaches to providing safety and overcoming the risk of severe adverse allergic reactions during immunotherapy. The data from the meta-analysis suggest new allergen preparations available are allergoids, recombinant allergens (recA) and modified-recombinant allergens (recA). Studies on virus-like-particles and CpG-motifs, adjuvants like MPL and aluminum hydroxide have been shown to increase immunological response and can improve safety and efficacy. The latest approaches to allergen immunotherapy include the application of extract patches on the skin and/or inguinal lymph node injection. Recombinant technology or chemicals may alter allergen molecules that make them less reactive; this may be due to suppression of Th2 responses or stimulation of toll-like receptor (approval is pending). The new advances in allergy immunotherapy not only provide disease-modifying treatments but are also cost-effective and improve the quality of life. The major allergen Bet v 1 involved in birch pollen allergy may be the future of allergen immunotherapy for rhino conjunctivitis.
Doses, Delivery, and Application of Immunotherapy