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Improving management with immunotherapy

What are the benefits of allergen-specific immunotherapy in the management of canine atopic dermatitis?

06 March 2019, at 1:58p.m.

Atopic dermatitis is a lifelong pruritic skin condition that has no cure and requires long-term management. The most obvious management tool is allergen avoidance, which on its own is not enough to manage the pruritus and subsequent progression of skin lesions. The alternative is a multimodal approach with allergen-specific immunotherapy and/or symptomatic treatment using various drugs, which are either anti-inflammatory or immunomodulating.

Allergen-specific immunotherapy (ASIT) is a prophylactic treatment for the management of canine atopic dermatitis that has to be tailored to the individual. It involves administering gradually increasing doses of those allergens to which the individual is allergic in order to increase the tolerance to these allergens, with the intention of reducing the clinical signs associated with the disease.

The success of immunotherapy is dependant on an accurate diagnosis of atopic dermatitis, which is based on the history and clinical signs (Figures 1 and 2). Only then should the selection of allergens be made, based on the results of an intradermal allergy test (Figure 3) and/or serum allergy testing which have been correlated with the history of the disease in the patient.

Mechanism of immunotherapy

Although the mechanism(s) involved in ameliorating the clinical signs are not fully understood, there are a number of studies supporting various changes in the immune responses in dogs on ASIT when compared to normal dogs. ASIT affects T-cell and B-cell responses, antibody production and the response of effector cells such as the eosinophils. ASIT significantly increases T-regulatory cells and IL-10 concentrations and other cytokines. A shift in the immune response from Th2 to Th1 cytokine profiles and blocking antibodies are also involved.

Immunotherapy formulation and administration

Injectable immunotherapy

Two types of allergen extracts, aqueous or alum precipitated, are available in the UK (once a special import certificate has been obtained from the VMD, as both are unlicensed preparations in the UK). The aqueous extracts require more frequent administration as they are more easily absorbed, whereas the alum precipitated extracts are absorbed more slowly and therefore the interval between injections can be extended.

Most formulations limit the total number of allergens to 8 to 10 per 10ml vial. When multiple allergens are involved it may be necessary to have two or three vials for an optimal result, even though the therapy then becomes more cumbersome to administer. If this is not possible due to costs, the most relevant allergens should be chosen for the ASIT.

In dogs, the immunotherapy injections are administered subcutaneously. The frequency of administration is usually based on whether the aqueous or alum precipitated extracts are used for the therapy. Most protocols will have an induction phase followed by a maintenance phase. The protocols for induction can be slow (gradually increased concentration over days) or rushed (increased concentration over hours). Rushed immunotherapy should be performed in a hospital where the animal can be intensively monitored by experienced clinicians. A maintenance dose will then be administered, typically every four weeks. Commercially prepared immunotherapies will be supplied with a dosage and frequency schedule.

The frequency of the maintenance doses can be tailored to individual needs, depending on the patient’s response to treatment and seasonal allergen loads.

It is best to monitor the patient for any adverse effects in the induction phase of the injections. The more serious adverse effects (see below under adverse effects) are more immediate. Best practice is to ask the owner to wait in the surgery for about 30 minutes after each injection during the induction phase so that, should the animal require urgent treatment for urticaria, angioedema or anaphylaxis, it is in the right place to receive it.

Sublingual immunotherapy

For oral administration, the allergen extracts are mixed with glycerol to improve stability and absorption in the oral cavity. It is administered twice daily using a pump. The treatment can be carried out at home by the owner.

In the author’s experience, many owners prefer to give the dog a monthly injection as opposed to the twice daily treatment needed with sublingual formulations.

Efficacy

The efficacy of treatment is variable and is demonstrated either by a marked reduction in the clinical signs (including complete remission), or a reduction in the usage of symptomatic medication.

The rate of response varies between individuals and most animals that are going to benefit from ASIT tend to do so within the first 12 months of treatment. It is best to warn the owner at the outset of the slowness of response in some cases and to complete at least the first 10 to 12 months of treatment before discarding it as a potential long-term management option.

Several factors influence the clinical efficacy of ASIT. They include the selection and concentration of allergens, the age of the animal and the severity of the disease.

Adverse effects

Serious adverse reactions to ASIT are uncommon to rare, but clinicians administering the therapy should be aware of the potential adverse effects. Systemic reactions range from serious urticarial reactions, angioedema and anaphylaxis, to lethargy, gastrointestinal disturbances, weakness and changes in behaviour.

An increase in pruritus following immunotherapy (generally during the induction phase) is the most common adverse effect. In the author’s experience, it generally lasts for 24 to 48 hours post-injection. Usually pretreatment with antihistamine for two to three days (the day prior to, the day of and the day after administration) overcomes the problem. Injection site reactions such as localised swelling may occur in some individuals.

One of the most frequent dilemmas is whether concurrent medication should be used to alleviate the pruritus. Because of the slow response to ASIT in some individuals and for welfare reasons, they should be used. Success of immunotherapy in many cases depends on concurrent management of secondary infections caused by bacteria and yeasts.

If pruritus is localised, topical corticosteroids such as hydrocortisone aceponate spray can be added to the management protocol, provided the individual has no infections.

Summary

Allergen-specific immunotherapy is a specific tailored treatment for canine atopic dermatitis. It does not offer a cure, but it is an effective modality as a prophylactic measure in ameliorating the clinical signs associated with atopic dermatitis. In the author’s experience, about two thirds of dogs benefit from it and it is a safe, lifelong treatment. It is especially worth trying as it has negligible side effects and remains efficacious, even after years of treatment.

Successful outcome depends on the early recognition of flare factors and dealing with them appropriately before the disease becomes chronic. In future, the focus of immunotherapy is likely to be on recombinant peptide therapies providing a more targeted approach, based on the relevant allergenic peptides of each allergen.