Allergen-specific immunotherapy is considered an effective therapy for the management of canine atopic dermatitis when relevant allergens have been identified through either intradermal or serological testing. It is an extremely safe form of treatment and serious adverse effects are uncommon. Additional anti-inflammatory or symptomatic therapy during the induction phase of immunotherapy is often needed, depending on the severity of clinical signs in the individual. The long-term success of immunotherapy can be measured by the ability to taper or even withdraw these supportive therapies.
The indications for canine immunotherapy were discussed in Part 1 of this review, along with the types of therapy available and protocols for their administration. In Part 2, response to treatment, concurrent therapies, possible side-effects and some common questions will be considered.
TREATMENT RESPONSE TO ALLERGEN-SPECIFIC IMMUNOTHERAPY
Allergen-specific immunotherapy is considered an effective therapy for the management of canine atopic dermatitis when relevant allergens have been identified through either intradermal or serological testing.
In many cases, improvement is not seen until six-to-nine months after therapy has begun, and it is recommended that at least twelve months of treatment are undertaken before discarding immunotherapy as a potential long-term management option (Figs. 1–4). If immunotherapy is shown to be successful, it should, in principle, be continued for the life of the animal in order that the signs of disease are controlled, and in order for any acquired benefits to be maintained.
ADDITIONAL SYMPTOMATIC THERAPY AND IMMUNOTHERAPY
Additional anti-inflammatory or symptomatic therapy during the induction phase of immunotherapy is often needed and will depend on the severity of clinical signs in the individual. This may range from the use of essential fatty acid supplementation, colloidal oatmeal shampoo and antihistamines in mild cases, to topical corticosteroids such as hydrocortisone aceponate (Cortavance; Virbac) in moderate cases and glucocorticoids or ciclosporin (Atopica; Novartis) in more severe cases.
If glucocorticoids or other immunosuppressive therapies are used, it is recommended that the dose be tapered, if possible, two weeks prior to starting induction of immunotherapy. As well as potentially affecting the mechanism of immunotherapy, these drugs may also interfere with detecting clinical responses to immunotherapy so that indications for altering the regime may be masked. If a steroid-free starting point is not possible, however, the lowest effective, alternate-day dose of prednisolone can be used.
Anti-microbial drugs, antihistamines and essential fatty acids are considered to have no effect on responses to immunotherapy. The long-term success of immunotherapy can be measured by the ability to taper or even withdraw these supportive therapies. In some cases, however, it is not possible to withdraw other therapies completely, but immunotherapy may at least have a dose-sparing effect.
Allergen-specific immunotherapy is an extremely safe form of treatment and serious adverse effects are uncommon. Practitioners should, however, be aware of the potential adverse effects so that these can be recognised and treated appropriately.
An increase in pruritus in the days following injection is the most common adverse effect and usually lasts for two-to-three days. Pre-treatment with antihistamine for two-to-three days until the day after administration usually overcomes the problem. Hydrocortisone aceponate spray (Cortavance; Virbac) may also be useful if pruritus is localised. If pruritus is seen consistently following injection, the dose of immunotherapy should be reduced. Injection-site reactions such as localised swelling may occur in some individuals but usually requires no treatment.
More serious reactions may include: urticaria, angioedema, gastrointestinal disturbances, behavioural changes, weakness, lethargy or collapse. Anaphylaxis is of greatest concern although the risk is low (around 1%). Dogs should be kept in the practice for 30 minutes following administration of the first few doses of immunotherapy to permit prompt treatment should anaphylaxis occur.
Treatment of anaphylaxis
• intravenous adrenaline 0.5–1.0 ml diluted 1:1000 (according to effect – inject slowly)
• ensure airway open and supply oxygen through an endotracheal tube if dyspnoea is present • intravenous injection of rapidly-acting glucocorticoid such as hydrocortisone sodium succinate 2–4 mg/kg
• intravenous or intramuscular injection of anti-histamine such as diphenhydramine hydrochloride 1–2 mg/kg
• hospitalisation, intravenous fluid therapy, supportive intensive therapy if required.
FREQUENTLY ASKED QUESTIONS
Can immunotherapy be given during pregnancy and lactation?
Dogs diagnosed with atopic dermatitis should not be used for breeding, so these situations should not arise. No safety studies have been performed, however, so immunotherapy cannot be recommended during pregnancy and lactation.
Can immunotherapy be given to animals with concurrent diseases?
Immunotherapy is contraindicated in diseases that affect the immune system, including immunodeficiency, malignant disease and autoimmune disease. It is also contraindicated in patients with renal disease.
Can immunotherapy and routine vaccination be given together?
These should not be given at the same time. A minimum one-to-two week period between injections is recommended.
Can immunotherapy be administered if an animal is unwell?
The injection should be postponed if the animal is unwell or pyrexic.
What happens if the immunotherapy vial has been left out of the fridge or delayed in the post?
It is possible that the allergen extracts could be ineffective in these situations and the vial should be replaced. Vials should be stored at 2–8°C in a refrigerator in the original packaging.
What if the vial has been frozen inadvertently?
Freezing will denature the allergens so the vial should be replaced
What to do if an immunotherapy vial has gone out of date?
The vial should not be used past the expiry date.
If the immunotherapy has become discoloured, can it still be used?
Discolouration is possible over time and some allergen extracts are naturally darker than others. This is not associated with loss of potency. If brown precipitates develop, however, the vial should be discarded.
A patient has missed an injection, when should the next one be given?
During induction, if only one dose has been missed over a short time period, it may be possible to restart with the missed dose and continue with the protocol. If a longer time period has elapsed, it may be advisable to return to a lower dose initially. The protocols provided are a guide only – it is not vital to follow this to the day, e.g. if a dose falls on a weekend when the owners are away, choosing the nearest day will suffice.
The owner has discontinued therapy for some time and now symptoms have recurred – can we restart therapy where we left off?
The longer the time since the last injection was given, the lower the dose should be on restarting therapy. In some cases it may be safer to restart the induction protocol.
In Part 1 of this series (UKVet Vol 17.9) sub-lingual immunotherapy (SLIT) was discussed as a new alternative route of administration of allergens for immunotherapy, and until now has only been commercially available in the USA. In November of this year, Axiom Veterinary Laboratories Ltd started distributing ACTT Allergy™ Drops (Bio-Medical Services). This product does not possess a UK licence as yet, but is available upon application for a Special Treatment Certificate (STC).
ACTT Allergy™ Drops are prepared in a palatable glycerine solution and are administered twice daily to the sub-lingual mucosa via a simple pump dispenser applied under the dog's tongue or inside the lip or cheek. Food and water can interfere with the absorption of the therapy therefore the drops should be given at least 10 minutes before either.
Each initial treatment set begins with a three-bottle series with increasing concentration of allergen in each. The initial induction protocol is rapid and allows the dog to reach therapeutic dosage in four weeks. Maintenance is then continued using a twice daily regime and tailored to the individuals' response. Although further studies are needed to fully evaluate this route of immunotherapy, the pilot studies have shown encouraging results with approximately 70% of dogs showing improvement in their symptoms. Furthermore, SLIT is extremely safe with systemic adverse events virtually unreported in the literature; it may also be effective in patients who have previously failed subcutaneously immunotherapy and safe in patients who have experienced serious systemic effects with previously administered subcutaneous immunotherapy. Mild reactions can include facial pruritus, pruritus, GI upset or lethargy. Sub-lingual immunotherapy provides an alternative route of administration of allergens for immunotherapy and may be useful for those owners or dogs who are needle adverse, who have a history of intolerance to subcutaneous immunotherapy and may even increase compliance in those owners happy to administer an oral medication twice daily.
CONTINUING PROFESSIONAL DEVELOPMENT
In order to test your understanding of this article, answer these multiple choice questions, or if you are a subscriber, go online at http://www.ukvet.co.uk, and find many more multiple choice questions to test your understanding.
1Which one(s) of these statements is true:a. Allergen-specific immunotherapy should be used as a sole treatment for canine atopic dermatitis.b. It is not possible to use other therapies alongside allergen-specific immunotherapy.c. The dosage and frequency of injections should be maintained at the same volume every four weeks whatever the circumstances.d. Allergen-specific immunotherapy is 100% effective.e. There may be a slight increase in pruritus two-to-three days following the injections.
2True or false: It is possible for individuals to acquire further allergies following initial allergy testing, especially if tested in the early stages of their disease.a. Trueb. False
3In many cases, how long may it take before the benefits of immunotherapy are seen:a. Two yearsb. Six-to-nine monthsc. One-to-two monthsd. Five yearse. One-to-two weeks