Allergen-Specific Immunotherapy

Chapter 93

Allergen-Specific Immunotherapy

Allergen-specific immunotherapy (ASIT) is a treatment for atopic dermatitis (AD) in dogs and cats in which allergenic substances to which the patient is sensitive are administered in gradually increasing amounts to lessen the hypersensitivity state. It is the only proven treatment for allergies that reverses the underlying immunopathogenesis of the disease instead of covering up clinical signs, as with antiinflammatory therapies. ASIT is nearly free of serious adverse effects in the great majority of dogs and cats, and can produce substantial, long-lasting relief in many patients. In human beings, ASIT is recommended as early as possible in the course of the disease because it may prevent development of additional sensitivities as well as progression of disease severity. These factors have not been studied in animals, but nevertheless, the potential lifelong benefits of ASIT make it a preferred treatment for AD that should be discussed with owners earlier rather than later in the management process.

The mechanisms of action of ASIT still are not completely understood but likely include downregulation of effector cells (mast cells, basophils, eosinophils), immune deviation of lymphocytes away from a proallergic response, production of immunoglobulin G (IgG) blocking antibodies, and induction of immunologic tolerance or nonreactivity.

Allergen Selection and Formulation

Most effects of ASIT are known to be allergen specific, and thus accurate testing to identify the offending allergens is of paramount importance. In general practice, serologic tests are often used as a basis for ASIT. The results of such tests should be interpreted in light of the individual patient’s clinical history; if the results do not fit the clinical picture (e.g., positive results are obtained for only a few seasonal allergens in a dog with year-round disease), then referral for an intradermal test should be considered.

Choosing which allergens to include in a treatment mixture is part art and part science. Effective ASIT is dose dependent; thus it is generally recommended that no more than 10 to 12 allergens be included in a single treatment set. This recommendation is controversial, and some clinicians routinely include more than this number in their formulations. When a large number of test reactions are positive in a given animal, selection of allergens for inclusion in the treatment set is based on known allergen cross-reactivities, botanical relationships of allergenic plants, exposure history, and strength of the test reaction. In practical terms, these decisions are facilitated by the company performing the serologic testing.

Conventional ASIT for animals in the United States has typically involved administration of aqueous extracts via subcutaneous injection. Extracts contain a phenol preservative and require refrigeration to maintain potency. Proteases in a treatment solution may degrade the allergens; it is well established that mold extracts contain proteases and, if mixed with pollen extracts in the same vial, accelerate degradation of the pollen allergens. Thus, if there is notable mold allergy, mold extracts should be formulated in a separate vial and administered by separate injection.

Treatment solutions for injection are provided as a series of two or three vials of gradually increasing concentration. The concentration of the vial is expressed in units that are somewhat archaic and unique to allergen extracts. The most common is protein nitrogen units per milliliter (PNU/ml; 100,000 PNU = 1 mg protein and therefore a solution of 20,000 PNU/ml contains 0.2 mg/ml of allergen protein). Alternatively, the strength may be expressed as weight/volume (w/v; a solution of 1/10 w/v simply means that 1 g of starting material was extracted with 10 ml of buffer to produce the solution).

Protocols and Injection Schedules

The treatment set manufacturer will provide an injection schedule, and no particular schedule has been shown to be superior to another. An initial buildup or escalation phase (in which injections are given every 2 to 7 days, gradually increasing in volume and concentration over a period of several weeks) is followed by a prolonged maintenance phase (in which a uniform dose is given less frequently, e.g., every 7 to 30 days, with gradual tapering of frequency as response occurs). (Examples of typical schedules can be found in Chapter 92 of the previous edition of Current Veterinary Therapy.) Protocols are similar for dogs and cats.

Injections are administered using 1-ml syringes and fine-gauge (e.g., 27-gauge) needles, which cause negligible injection pain to the pet. After proper instruction, most owners are able to give the injections at home with relative ease. An office visit should be scheduled at which the injection schedule and technique are explained to the owner (Box 93-1).

Box 93-1   Important Elements of Client Education Regarding Allergen-Specific Immunotherapy (ASIT)

Discuss each of the following points with the client, and ideally provide a printed explanatory handout for the client’s later reference:

• Explain that ASIT is only part of an overall management plan.

    Emphasize the lifelong nature of atopic dermatitis and the necessity of developing a long-term management plan that will be based on ASIT but also may include periodic use of concurrent medications, avoidance strategies, topical therapies, infection prevention strategies, and other measures as appropriate to the patient.

• Explain the administration schedule.

    Outline the specific injection or oral administration schedule and progression through escalating vial series. Emphasize the importance of consistent administration. Stress that, even if benefits occur quite rapidly, for lasting benefit a full therapy course of several years will be necessary and that some patients require lifetime maintenance treatment.

• Provide proper instruction on administration technique.

    For injections, describe the need for refrigerated storage and the way to fill and measure with syringes, and make the client practice injection in the office. For sublingual ASIT, demonstrate the use of the dispenser and administration; remind the client that the solution cannot be mixed with food.

• Explain the necessity and schedule for follow-up examinations.

    Plan routine follow-up examinations for 3 months, 6 months, and 12 months after starting therapy. Emphasize the importance of rechecks to adjust the injection schedule, adjust concurrent medication use, and identify flare factors such as infections before they become severe.

• Explain possible adverse effects of ASIT and how to recognize them.

    Advise the client to watch for mild localized or transient reactions and report them if concerned. Describe signs associated with systemic anaphylaxis and note that these typically occur within an hour or so after administration.

• Explain the response that is expected to occur.

    Clarify that the expected response is a gradual diminution of itch, episodes of infections, and other clinical signs. Instruct the client to be patient—response occurs gradually over a period of months, and it may take 6 to 12 months or more for the treatment to reach maximum benefit.

• Explain when to call for advice.

    Advise an initial call after 4 weeks of treatment to report grade of itching, any problems with administration, and any possible mild reactions. Instruct the client always to call immediately in the case of suspected anaphylactic reaction. Communicate that the overall management plan should result in a comfortable, minimally symptomatic pet.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Allergen-Specific Immunotherapy

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