The role of allergen-specific immunotherapy in the treatment of canine atopic dermatitis: Part 2 Sarah Warren BVetMed MSc(ClinOnc) CertVD MRCVS Regional Veterinary Dermatologist CVS UK, Southern Region MILDMAY VETERINARY CENTRE, EASTON LANE, WINCHESTER, HAMPSHIRE. SO23 7RU ABSTRACT: 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 antiinflammatory 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. DOI: 10.1111/j.2044-3862.2012.00262.x INTRODUCTION 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. Fig. 2. In many cases, improvement is not seen until six-tonine 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. Figs. 1 and 2: Response to immunotherapy: atopic Weimeraner before immunotherapy and, Fig. 2, nine months after starting allergen-specific immunotherapy. Note generalised erythema and self-induced alopecia, especially over periorbital regions, muzzle, ventral neck, ventral chest and feet, before treatment, and marked improvement in coat condition nine months after starting therapy. 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. Companion Animal Vol 18 January 2013 27
Figs. 3 and 4: Same patient as in Figs. 1 and 2. Note erythema and alopecia over dorsal aspects of the feet before treatment, and, in Fig. 4, marked improvement after nine months of therapy. ADVERSE EFFECTS 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. Fig. 4. 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. Treatment of anaphylaxis l intravenous adrenaline 0.5-1.0 ml diluted 1:1000 (according to effect - inject slowly) l ensure airway open and supply oxygen through an endotracheal tube if dyspnoea is present l intravenous injection of rapidly-acting glucocorticoid such as hydrocortisone sodium succinate 2-4 mg/kg l intravenous or intramuscular injection of anti-histamine such as diphenhydramine hydrochloride 1-2 mg/kg l 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? 28 Companion Animal Vol 18 January 2013
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. FURTHER READING BOUSQUET, J., LOCKEY, R., MALLING, H. J., et al. (1998) Allergen immunotherapy; therapeutic vaccines for allergic diseases. World Health Organisation. American Academy of Allergy, Asthma and Immunology. Annals of Allergy, Asthma and Immunology 81: 401-5. DEBOER, D. J. and HILLIER, A. (2001) The ACVD task force on canine atopic dermatitis (XVI): laboratory evaluation of dogs with atopic dermatitis with serum-based allergy tests. Veterinary Immunology and Immunopathology 81: 277-87. GOLDMAN, C., ROSSER, E., PETERSON, A. and HAUPTMAN, J. (2010) Investigation on the effects of ciclosporin (Atopica) on intradermal test reactivity and allergen-specific immunoglobulin IgE serology in atopic dogs. Veterinary Dermatology 21: 393-399
GRIFFIN, C. E. and HILLIER, A. (2001) The ACVD task force on canine atopic dermatitis (XXIV): allergen specific immunotherapy. Veterinary Immunology and Immunopathology. 81: 363-83. HILLIER, A. and DEBOER, D. J. (2001) The ACVD task force on canine atopic dermatitis (XVII): Intradermal testing. Veterinary Immunology and Immunopathology 81: 289-304. LEE, K. W., BLANKENSHIP, Z. M., MCCURRY, M., ESCH, R. E., DEBOER, D. J. and MARSELLA, R. (2009) Performance characteristics of a monoclonal antibody cocktail-based ELISA for detection of allergen-specific IgE in dogs and comparison with a high affinity IgE receptor-based ELISA. Veterinary Dermatology 20: 157-164. LOWENSTEIN, C. and MULLER, R. S. (2008) A review of allergenspecific immunotherapy in human and veterinary medicine. Veterinary Dermatology 20:84-98. MUELLER, R. S., FIESELER, K. V., ROSYCHUK, R. A. and GREENWALT, T. (2005) Intradermal testing with the storage mite Tyrophagus putrescentiae in normal dogs and dogs with atopic dermatitis in Colorado. Veterinary Dermatology 16: 27-31. NUTTALL, T. J., THODAY, K. L., VAN DEN BROEK, A. et al. (1998) Retrospective survey of allergen specific immunotherapy in canine atopy. Veterinary Record 143: 139-42. OLIVRY, T. (2010) New diagnostic criteria for canine atopic dermatitis (Letter to the editor) Veterinary Dermatology 21: 124-7. OLIVRY, T., DEBOER, D. J., FAVROT., C., JACKSON, H. A., MUELLER, R. S., NUTTAL, T. and PRELAUD, P. (2010) ACDV task force on canine atopic dermatitis: Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Veterinary Dermatology 21: 233-248 ROQUE., J. B., O LEARY, C., KYAW-TANNER, M., et al. (2011) High allergen-specific serum immunoglobulin E levels in non-atopic West Highland white terriers. Veterinary Dermatology 22: 257-66. ROSENBAUM, M. R., ESCH, R. E. and SCHWARTZMAN, R. M. (1996) Effects of mould proteases on the biological activity of allergenic pollen extracts. American Journal of Veterinary Research 57: 1447-52. SCHNABL, B., BETTENAY, S. V., DOW, K. and MUELLER, R. S. (2006) Results of allergen-specific immunotherapy in 117 dogs with atopic dermatitis. Veterinary Record 158: 81-85. ADDENDUM 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 TM 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 TM 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. The effective approach to allergy in dogs and cats starts with the Artuvetrin Serum Test. The outcome of this test, combined with our technical support and advice, will help you to fi ght the cause of allergies. ALK-Abelló Ltd - 1 Manor Park, Manor Farm Road, Reading RG2 0NA, United Kingdom. Tel: +44-(0)118 9037 940. Fax: +44-(0)118 9037 941. artuvetrin@alk.net
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. REFERENCE ADDITIONS D. J. DeBOER, M. VERBRUGGE and M. MORRIS. 2010. Pilot trial of sublingual immunotherapy (SLIT) in mite-sensitive atopic dogs. Veterinary Dermatology 21:325. D. J. DeBOER, M. MORRIS. 2012. Multicentre Open Trial Demonstrates Efficacy of Sublingual Immunotherapy in Canine Atopic Dermatitis. Veterinary Dermatology 23 (Supplement 1), 65. NEWSREVIEW THE POSITIVE EXTERNALITIES OF PET OWNERSHIP OR PETS ARE GOOD FOR GOVERNMENT The benefits of pet ownership also extend to the Chancellor as the Autumn statement approaches. The Pet Advisory Committee (PAC) using the government s own figures estimates that pet lovers spent almost 6 billion in 2010 and contributed more than 2 billion a year to the nation s coffers in taxes. Additionally there are other less visible benefits that help balance the Chancellor s books. Independent studies indicate that the health benefits of pet ownership (and around of half of UK households do) effectively save the NHS as much as 1.5 billion a year. As the Euro crisis deepens, other Finance Ministers in the EU should also take note. Throughout the EU in 2010, owners spent 29 billion on their pets (equating to 12 billion in tax revenues) and social scientists studying the health benefits of pet ownership in Germany estimated savings of 5.5 billion annually. The Pet Advisory Committee points out that not everything can be reduced to hard cash as chair Tracey Crouch MP says What this research shows is the positive contribution pets and their owners make to the economy and towards a healthy society. While the contribution to the economy is easier to identify, the companionship, interaction and exercise pets can give to their owners, in particular the elderly, and the effect this has on their well-being is of equal worth to individuals and society as a whole. 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 www.ukvet.co.uk, and find many more multiple choice questions to test your understanding. 1. Which 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-tothree days following the injections. 2. True 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. True b. False 3. In many cases, how long may it take before the benefits of immunotherapy are seen: a. Two years b. Six-to-nine months c. One-to-two months d. Five years e. One-to-two weeks Answers to the above questions appear on page 47 of the print version, and as supporting information in the online version of this article at: www.wileyonlinelibrary.com/journal/coan Are you a subscriber? Then more MCQS are available online at www.ukvet.co.uk. If answering these and the additional MCQs through www.ukvet.co.uk, then answers will be provided as part of the marking and submission process to achieve a Certificate of Completion, which you can print off and keep as part of your Professional Development Portfolio. If you would like to submit an article for publication contact the editorial panel at ukvet@ukvet.co.uk Companion Animal Vol 18 January 2013 31