Safety of Allergen Immunotherapy
Safety of Allergen Immunotherapy
From the first allergen immunotherapy proposed in the early 1900s to the present day, numerous studies have proven the efficacy of allergen immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity. The major risk, however small, with allergen immunotherapy is anaphylaxis. There has been considerable interest and debate regarding risk factors for immunotherapy reactions (local and systemic) and interventions to reduce the occurrence of these reactions. One of these interventions that is especially debated regards dose adjustment for various reasons, but in particular for local reactions. In this review, we discuss the safety of immunotherapy and provide a comprehensive review of the literature regarding immunotherapy schedules and doses.
From the first allergen injections proposed in the early 1900s to the present day, numerous studies have proven the efficacy of allergen immunotherapy (AIT) for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity. This treatment modality should be considered for patients who have symptoms of allergic rhinitis, conjunctivitis or asthma with natural exposure to allergens, and who demonstrate specific IgE antibodies to a relevant allergen or allergens. Immunotherapy is also recommended for patients with a history of systemic reaction to Hymenoptera stings who demonstrate the presence of Hymenoptera-specific IgE antibodies in vivo (skin test) or in vitro.
AIT is the only antigen-specific immunomodulatory treatment in routine clinical use that alters the natural history of allergic disease. It results in immunologic tolerance, which is manifested by a relative decrease in antigen-specific responsiveness that might be accompanied by immune deviation, T-cell anergy and/or T-cell apoptosis. There exists an allergen-specific immune deviation from Th2 to Th1 responses and a clonal deletion of sensitized cells that reduces the hyper-reactivity of the recipient to those allergens. When immunotherapy is initiated in children with sensitivity to a single allergen, the number of new sensitivities that subsequently develop over time is reduced. It has also been shown to be effective in reducing the development of asthma in children with pre-existing allergic rhinitis. Venom immunotherapy is highly effective in reducing the risk of anaphylaxis when administered to adults and children with a history of systemic reaction(s) to Hymenoptera stings, including both flying insects and imported fire ants.
A patient receiving subcutaneous AIT would ideally receive increasing doses during build-up, without interruption, until reaching and continuing the maintenance dose in order to achieve the earliest maximum clinical benefit. The ultimate duration of AIT injections is largely related to preservation of the clinical improvement gained in the first 1–2 years of treatment. Although the majority of patients receive a full course of AIT without any serious clinical complications, there are several scenarios where practicing allergists will recommend dose adjustment for immediate or delayed local reactions at the injection site, missed injections, newly mixed vials and after systemic reactions. In each case, the concern is that administration of nondose-adjusted injections may deliver an allergen concentration greater than that which the patient can safely tolerate. The main intention of dose adjustment, although not proven in previous studies, is to reduce the risk of systemic reactions. There may also be other perceived benefits, such as reducing patient discomfort and increasing patient adherence to the immunotherapy treatment. However, the practice of dose adjustment is largely anecdotal with elements of tradition and is not evidence based.
Abstract and Introduction
Abstract
From the first allergen immunotherapy proposed in the early 1900s to the present day, numerous studies have proven the efficacy of allergen immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity. The major risk, however small, with allergen immunotherapy is anaphylaxis. There has been considerable interest and debate regarding risk factors for immunotherapy reactions (local and systemic) and interventions to reduce the occurrence of these reactions. One of these interventions that is especially debated regards dose adjustment for various reasons, but in particular for local reactions. In this review, we discuss the safety of immunotherapy and provide a comprehensive review of the literature regarding immunotherapy schedules and doses.
Introduction
From the first allergen injections proposed in the early 1900s to the present day, numerous studies have proven the efficacy of allergen immunotherapy (AIT) for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity. This treatment modality should be considered for patients who have symptoms of allergic rhinitis, conjunctivitis or asthma with natural exposure to allergens, and who demonstrate specific IgE antibodies to a relevant allergen or allergens. Immunotherapy is also recommended for patients with a history of systemic reaction to Hymenoptera stings who demonstrate the presence of Hymenoptera-specific IgE antibodies in vivo (skin test) or in vitro.
AIT is the only antigen-specific immunomodulatory treatment in routine clinical use that alters the natural history of allergic disease. It results in immunologic tolerance, which is manifested by a relative decrease in antigen-specific responsiveness that might be accompanied by immune deviation, T-cell anergy and/or T-cell apoptosis. There exists an allergen-specific immune deviation from Th2 to Th1 responses and a clonal deletion of sensitized cells that reduces the hyper-reactivity of the recipient to those allergens. When immunotherapy is initiated in children with sensitivity to a single allergen, the number of new sensitivities that subsequently develop over time is reduced. It has also been shown to be effective in reducing the development of asthma in children with pre-existing allergic rhinitis. Venom immunotherapy is highly effective in reducing the risk of anaphylaxis when administered to adults and children with a history of systemic reaction(s) to Hymenoptera stings, including both flying insects and imported fire ants.
A patient receiving subcutaneous AIT would ideally receive increasing doses during build-up, without interruption, until reaching and continuing the maintenance dose in order to achieve the earliest maximum clinical benefit. The ultimate duration of AIT injections is largely related to preservation of the clinical improvement gained in the first 1–2 years of treatment. Although the majority of patients receive a full course of AIT without any serious clinical complications, there are several scenarios where practicing allergists will recommend dose adjustment for immediate or delayed local reactions at the injection site, missed injections, newly mixed vials and after systemic reactions. In each case, the concern is that administration of nondose-adjusted injections may deliver an allergen concentration greater than that which the patient can safely tolerate. The main intention of dose adjustment, although not proven in previous studies, is to reduce the risk of systemic reactions. There may also be other perceived benefits, such as reducing patient discomfort and increasing patient adherence to the immunotherapy treatment. However, the practice of dose adjustment is largely anecdotal with elements of tradition and is not evidence based.