Date Published: November 10, 2011
Publisher: BioMed Central
Author(s): William Moote, Harold Kim.
Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.
Allergen-specific immunotherapy (also known as allergy shots) is an effective treatment used by allergists and immunologists for common allergic conditions, particularly allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity [1-4]. This form of therapy typically involves the subcutaneous administration of gradually increasing quantities of the patient’s relevant allergens until a dose is reached that is effective in inducing immunologic tolerance to the allergens. The primary objectives of allergen-specific immunotherapy are to decrease the symptoms triggered by allergens and to prevent recurrence of the disease in the long-term. Currently, it is the only identified disease-modifying intervention for allergic disease [5,6].
Immunologic changes that occur during allergen-specific immunotherapy are complex and not completely understood. However, successful immunotherapy has been associated with a shift from T helper cell type-2 (Th2) immune responses, which are associated with the development of atopic conditions, to Th1 immune responses. It is also associated with the production of T regulatory cells that produce the anti-inflammatory cytokine, interleukin 10 (IL-10), amongst others such as transforming growth factor (TGF)-beta. IL-10 has been shown to reduce levels of allergen-specific immunoglobulin E (IgE) antibodies, increase levels of immunoglobulin G (IgG) (blocking) antibodies that play a role in secondary immune responses, and reduce the release of pro-inflammatory cytokines from mast cells, eosinophils and T cells. Allergen-specific immunotherapy has also been found to decrease the recruitment of mast cells, basophils, and eosinophils to the skin, nose, eye, and bronchial mucosa after exposure to allergens, and reduce the release of mediators, such as histamine, from basophils and mast cells [5,7]. Research surrounding the mechanisms of immunotherapy is still ongoing and will help further elucidate how this form of therapy exerts its beneficial effects in allergic diseases.
Allergen-specific immunotherapy is indicated in patients with allergic rhinitis/conjunctivitis and/or allergic asthma who have evidence of specific IgE antibodies to clinically relevant allergens (see Table 1). Skin prick testing (SPT) is the preferred method of testing for specific IgE antibodies. Allergen-specific IgE testing which provides an in vitro measure of a patient’s specific IgE levels against particular allergens is a reasonable alternative to SPT. However, SPTs are generally considered to be more sensitive and cost effective than allergen-specific IgE tests [5-7]. Patients with allergic rhinitis/conjunctivitis or allergic asthma who may be good candidates for immunotherapy include those who: have symptoms that are not well controlled by pharmacological therapy or avoidance measures; require high doses of medication, multiple medications, or both to maintain control of their disease; experience adverse effects of medications; or wish to avoid the long-term use of pharmacological therapy .
Allergen-specific immunotherapy is contraindicated in patients with medical conditions that increase the patient’s risk of dying from treatment-related systemic reactions, such as those with severe or poorly controlled asthma or significant cardiovascular diseases (e.g., unstable angina, recent myocardial infarction, significant arrhythmia, and uncontrolled hypertension) (see Table 1). Immunotherapy is also contraindicated in patients using beta-blockers since these agents can amplify the severity of the reaction and make the treatment of systemic reactions more difficult. Immunotherapy should be considered, however, in patients with life-threatening stinging insect hypersensitivity, even if they also require beta-blocker medications, because the fatal risk associated with an insect sting is greater than the risk of an immunotherapy-related systemic reaction [6,7].
Special consideration should be given to the use of allergen-specific immunotherapy in children under 6 years of age, pregnant women, the elderly, and patients with malignancy, or immunodeficiency/autoimmune diseases (see Table 1). Immunotherapy is effective in children and is often well tolerated. However, children less than 6 years of age may have difficulty cooperating with the immunotherapy regimen and injections and, therefore, physicians need to weigh the risks and benefits of therapy in this patient population. Immunotherapy is generally not initiated in pregnant women; however, it can be safely continued in women who have been on treatment prior to becoming pregnant. Special consideration must also be given to the use of immunotherapy in the elderly since these patients often have comorbid medical conditions that may increase the risk of experiencing immunotherapy-associated adverse events. Finally, some physicians feel uncomfortable about manipulating the immune system in patients with autoimmune disorders, immunodeficiency syndromes, or malignant disease. However, there is no solid evidence that allergen-specific immunotherapy is actually harmful to these patients, provided the risks and benefits of therapy in these patients have been considered .
The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, and the adverse effects of pharmacological treatment .
Allergen-specific immunotherapy carries the risk of anaphylactic reactions (serious allergic reactions that are rapid in onset and may cause death) and, therefore, should only be prescribed by physicians who are adequately trained in the treatment of allergy and the use of immunotherapy (such as allergists and immunologists). The injections must be given where a physician is present, and in clinics that are equipped to manage possible life-threatening reactions.
Allergen-specific immunotherapy is generally safe and well-tolerated when used in appropriately selected patients. However, local and systemic reactions may occur. Local reactions, such as redness or itching at the injection site, can generally be managed with local treatment (e.g., cool compresses or topical corticosteroids) or oral antihistamines. Systemic reactions occur in approximately 1-4% of patients on allergen immunotherapy  and can be mild to severe. The most severe reaction is anaphylaxis. Fatal anaphylactic reactions are rare, occurring in an estimated 1 in every 8 million doses of immunotherapy administered .
Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. Although it is still unclear exactly how this form of therapy works, immunotherapy has been associated with a shift from Th2 to Th1 immune responses, and the production of T regulatory cells that dampen the immune response to relevant allergens. When used in appropriately-selected patients, allergen-specific immunotherapy is extremely safe. This form of therapy, however, does carry the risk of anaphylactic reactions and, therefore, should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, immunotherapy should be administered only by physicians who are equipped to manage life-threatening anaphylaxis.
• Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity.
Dr. William Moote has received consulting fees or honoraria for continuing education from AstraZeneca, Merck and Amgen.