The three basic treatments for allergy are avoidance therapy, pharmacologic therapy, and immunotherapy. Complete avoidance of the allergen responsible for inducing the signs and symptoms of the allergy is the most effective treatment for any allergic condition. When avoidance of a specific allergen such as house dust, molds, or pollens is impossible, pharmacologic therapy is initiated (e.g., antihistamines, adrenergic agonists, anticholinergics, beta-adrenergic agonists, corticosteroids, cromolyn sodium, methylxanthines). When known allergens are unavoidable and not effectively controlled with pharmacologic agents, allergy immunotherapy may be necessary.
Allergy (or allergen) immunotherapy or subcutaneous immunotherapy (SCIT) is the repeated administration of specific allergens to an individual with immune globulin E (IgE)--mediated conditions, to provide long-lasting protection against the allergic symptoms and inflammatory reactions associated with exposure to these allergens. In an individual with allergy, allergen challenge leads to a cascade of biological events resulting in clinical manifestation of allergy. For example, immune effector cells such as mast cells and basophils release chemical mediators (e.g., histamine) that are responsible for symptoms of allergy such as itching and sneezing. Administration of allergy immunotherapy yields a decrease in mast cell and basophil activity and degranulation, as well as the generation of specific regulatory T and B cells, suppression of allergen-specific effector T cells, decrease in tissue granulocytes, and other important systemic changes. The effect is a gradual lessening of the immune response upon subsequent allergen challenge.
Allergy (or allergen) immunotherapy has been shown in clinical studies to be effective for individuals with allergic rhinitis or conjunctivitis, allergic asthma, and stinging insect hypersensitivity. Aeroallergen immunotherapy is indicated for individuals with inhalant allergen sensitivities due to seasonal pollinosis caused by trees, grasses, and weeds, and in the treatment of mold-, dust-, and mite-induced rhinitis. According to American Academy of Allergy, Asthma & Immunology (AAAAI), five years of age is the youngest recommended age to start immunotherapy; however, there is no upper age limit for receiving immunotherapy.
Venom immunotherapy is indicated for individuals who have a severe systemic anaphylactic reaction after an insect sting and a positive skin test or other documented IgE sensitivity to a specific insect venom. Individuals with delayed systemic reactions with symptoms of anaphylaxis or serum sickness and with a positive skin test or presence of venom-specific IgE by in vitro testing are also recommended for treatment.
Animal dander sensitivity (epidermal) may respond to immunotherapy, but immunotherapy is not routinely recommended to replace removal of the offending allergen. Individuals who have unavoidable occupational exposures (e.g., veterinarians or laboratory workers) may require a trial of immunotherapy.
There are usually two phases of immunotherapy: a build-up phase and a maintenance phase.
The build-up phase involves an individual receiving therapy injections with increasing small amounts of an antigen. The duration of the build-up phase generally ranges from three to six months and depends on the frequency of the injections, which is progressively increased as tolerated to every four to six weeks. The injections are administered once or twice per week, at least two days apart. The goal of administering a slowly increasing quantity of antigen is to gradually increase the individual's immunity to the offending allergen and to help the individual develop a degree of tolerance to the antigen. This treatment regimen leads to a lessening of the individual's symptoms and medication requirements.
The maintenance phase begins when the therapeutic dose is reached. The effective maintenance dose is different for each individual, depending on the level of allergen sensitivity and response to the immunotherapy build-up phase. The intervals between injections will be longer and generally range from every two to four weeks, as determined by the allergist or immunologist. Individuals should be evaluated every six to 12 months while on immunotherapy. Clinical improvement is usually attainable within one year. Once the maintenance dose is reached, immunotherapy should continue for three to five years.
Cluster immunotherapy involves the administration of two or more injections per visit to achieve a maintenance dose more rapidly than is achieved with conventional schedules. It is a type of rush immunotherapy characterized by giving several allergen injections on the same day.
Rush immunotherapy involves incremental doses of an allergen administered at intervals varying from 15 to 30 minutes and 24 hours, until the optimal effect is achieved. Very sensitive individuals may experience various degrees of systemic reaction during this procedure. Physicians frequently premedicate individuals with an antihistamine or corticosteroid to minimize the risk of systemic reaction. A modified rush method involves subcutaneous allergen injections administered 24 hours apart, and may or may not require a premedication.
Allergy or allergen immunotherapy is different from desensitization. Desensitization is a process by which effector cells are rendered less reactive or nonreactive to IgE-mediated immune responses by the rapid administration of incremental doses of an allergenic substance. By contrast, allergy immunotherapy is often thought to describe a state of incomplete desensitization, as complete desensitization is rarely accomplished with allergy immunotherapy. Rapid desensitization may be used in cases of allergy to insulin, penicillin, and horse serum. In addition, it can be effective for allergies to sulfonamides, cephalosporins, and other commonly used drugs. Desensitization is performed when an individual requires the use of an allergic substance; therefore, physician supervision is required in a hospital setting to monitor the individual's reactions and response to treatment. In some cases, the skin test response to the agent is reduced or is negative after desensitization.
According to the parameters developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology: "Immunotherapy is effective for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma, and stinging insect hypersensitivity. Therefore immunotherapy merits consideration in patients with these disorders as a possible treatment option."
HOME-BASED SUBCUTANEOUS ALLERGY IMMUNOTHERAPY
According to guidelines from the American Academy of Asthma, Allergy and Immunotherapy (AAAAI), subcutaneous allergen immunotherapy should be administered in a medical facility with trained staff and medical equipment capable of recognizing and treating anaphylaxis. Under rare circumstances, when the benefit of allergen immunotherapy clearly outweighs the risk of withholding immunotherapy (e.g., individuals with a history of venom-induced anaphylaxis living in a remote region), at-home administration of allergen immunotherapy should be considered on an individual basis. Furthermore, AAAAI emphasizes that frequent or routine prescription of home immunotherapy is not appropriate under any circumstances.
There are a limited number of studies of home-based allergy immunotherapy. The largest is a prospective study by Hurst, et al. (1999). A major limitation of the study is that it was limited to otolaryngic allergy practices; the generalizability of the results to primary care practices is uncertain.
PREPARATION AND PROVISION OF ANTIGENS FOR SUBCUTANEOUS ALLERGY IMMUNOTHERAPY
The preparation of antigens for allergy injections, but not the injection itself, is billed under Current Procedural Terminology (CPT) code 95165. CPT Code 95165, (with the narrative: Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy; single or multiple antigens [specify number of doses]),represents preparation of vials of non-venom antigens. As in the case of venoms, some non-venom antigens cannot be mixed together, i.e., they must be prepared in separate vials. An example of this is mold and pollen. Therefore, some individuals will be injected at one time from one vial – containing in one mixture all of the appropriate antigens – while other individuals will be injected at one time from more than one vial. In establishing the practice expense component for mixing a multidose vial of antigens, Medicare, as reported in a detailed publication entitled Medicare Antigen Preparation, by the Office of Inspector General (Department of Health and Human Services), observed that the most common practice was to prepare a 10 cubic centimeter (cc) vial. Medicare also observed that the most common use was to remove aliquots with a volume of 1 cc. As explained in Medicare Claims Processing Manual, Chapter 12, Medicare based its practice expense (PE) computations for CPT code 95165 on the aforementioned factors. Therefore, per Medicare, a provider’s removing 10 1-cc aliquot captures the entire PE component for the services represented by CPT code 95165, since practice expense payable for the preparation of a vial remains the same regardless of the size or number of aliquots removed from it.
PROFESSIONAL SERVICE FOR INJECTION ADMINISTRATION FOR ALLERGY IMMUNOTHERAPY
According to ACAAI, for a majority of individuals in clinical need of allergy immunotherapy, an injection may be given once a week for about 30 weeks, after which injections can be administered every two weeks. Eventually, injections can be given every four weeks. The duration of therapy may be three to five years.
Standardized allergen extracts can also be administered under the tongue to allow absorption through the mucosa. This method is known as sublingual immunotherapy. Several types of allergen preparations have been studied in sublingual immunotherapy (SLIT), including sublingual allergen tablets (SLIT-tablets) and sublingual aqueous or glycerinated liquid allergen extracts, which are referred to as SLIT-drops. In April 2014, the U.S. Food and Drug Administration (FDA) approved the first sublingual allergen extract tablets for treatment of pollen-induced allergic rhinitis with or without conjunctivitis. However, the other main SLIT preparation, drop constructs, are being studied in United States clinical trials. In the United States, phase I studies on safety and tolerability have been carried out with ragweed, grass, house dust mite, and cat glycerinated extracts. There are several fundamental issues with SLIT-drops that require further study before clinicians can be confident that SLIT-drops using available products represent an effective alternative to subcutaneous immunotherapy (SCIT). Of primary importance is the question of effective dose. At this time, there is a lack of scientific evidence in the published peer-reviewed medical literature to support the safety and effectiveness of SLIT-drops.
Clinical studies do not show support for the use of allergy immunotherapy for food hypersensitivity (gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens in food), chronic urticaria (persistent itchy hives for six weeks or more, usually without a known cause), and/or angioedema (the sudden development of painful, itchy swelling or welts that can occur around the eyes and lips or on the hands, feet, and throat).