Evidence-Based Treatment of Canine Atopic Dermatitis: 2010 Practice Guidelines - The WSAVA Hills Excellence in Veterinary Healthcare Award
Department of Clinical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
Atopic dermatitis (AD) is a common, chronic, relapsing pruritic skin disease of dogs, for which treatment has varied over time. Recent high-quality randomized controlled trials and systematic reviews have established which drugs are likely to offer consistent benefit. In 2010, the International Task Force for Canine AD published guidelines recommending a multifaceted approach to treat dogs with AD. Treatment recommendations vary depending on whether one is dealing with acute flares or chronic AD, and whether skin lesions are localized or extensive.
Treatment of Acute Flares of Atopic Dermatitis
Identification and Avoidance of Flare Factors
Identification and Removal of Allergenic Causes of Flares
When an exacerbation of signs occurs in a dog that previously had a disease in remission, one must look for, and eliminate, if at all feasible, the cause of such flares. Currently recognized sources of flares of canine AD include fleas, food and environmental (e.g., house dust mites, pollens) allergens.
Evaluation of Use of Antimicrobial Therapy
Skin and ear infections are common reasons why lesions and pruritus acutely worsen in dogs with AD. If bacterial or yeast infections are identified with some combination of clinical signs, cytology and/or culture, antimicrobial therapy is indicated, normally using topical with or without oral medications.
Improvement of Skin and Coat Hygiene and Care
Bathing with a Non-irritating Shampoo
Bathing dogs with AD might reduce their pruritus (itch) manifestations. This benefit appears to lie in the mechanical action of washing the pet. Outside of a lipid-containing shampoo (Allermyl, Virbac), there is currently no evidence of benefit of other shampoos or conditioners containing ingredients such as oatmeal, pramoxine, antihistamine, lipids or glucocorticoids.
Reduction of Pruritus and Skin Lesions with Pharmacological Agents
Short-term Treatment with a Topical Glucocorticoid
To reduce skin lesions and pruritus of canine AD, there is evidence for the high efficacy of two medium-potency glucocorticoid sprays: triamcinolone (Genesis, Virbac) and hydrocortisone aceponate (CortavanceTM, Virbac). These sprays are especially suitable for localized skin lesions and for short durations. Clinicians must tailor the frequency and duration of application to the severity of clinical signs. Caution is advised with long-term use, as adverse effects, such as skin thinning, are likely to occur.
Short Course of Oral Glucocorticoids
If signs are too severe or extensive to be controlled with topical formulations, then oral glucocorticoids are recommended. Prednisone, prednisolone or methylprednisolone can be given at 0.5 mg/kg once to twice daily until clinical remission occurs. Side effects of oral glucocorticoids are usually proportional to drug potency, dosage and duration of administration.
Interventions Likely To Be of Little or No Benefit to Treat Acute Flares of Canine AD
Antihistamines: when examined as a group, there is no conclusive evidence of efficacy of oral type 1 antihistamines for treatment of active AD in dogs.
Essential fatty acid supplements: as their mode of action necessitates several weeks of treatment, essential fatty acids (EFA) are unlikely to be of any benefit for acute flares of AD in dogs.
Tacrolimus and ciclosporin: because of their slow onset of treatment effect, topical tacrolimus and oral ciclosporin are unlikely to offer any benefit for treatment of acute flares of canine AD.
Treatment Options for Chronic Canine AD
Identification and Avoidance of Flare Factors
Performance of Dietary Restriction-Provocation Trials in Dogs with Nonseasonal AD
Food allergens can cause flares of AD in dogs hypersensitive to such allergens. As a result, one or more restriction-provocation dietary trials must be performed in all dogs with nonseasonal AD to determine whether food allergens contribute to clinical signs in these patients.
Implementation of an Effective Flea Control Regimen
There is evidence that the atopic status predisposes dogs to develop hypersensitivity to flea saliva if exposed repeatedly to flea bites. As a result, where flea infestation is endemic, all dogs with AD should be treated with year-round flea adulticides combined with relevant environmental measures.
Performance of Allergen-Specific Intradermal and/or IgE Serological Tests to Identify Possible Environmental Allergen Flare Factors
Environmental allergens, such as house dust mites, have been shown to cause flares of AD in dogs hypersensitive to these allergens. The performance of allergen-specific intradermal testing (IDT) and/or IgE serological tests is helpful to identify hypersensitivity to environmental allergens in dogs with AD. Importantly, positive immediate IDT reactions and IgE serologies to environmental allergens are also common in dogs without signs of AD. As a result, these tests cannot be used to differentiate dogs with AD from normal dogs.
Evaluation of Use of Antimicrobial Therapy
The skin and ears of dogs with AD are commonly infected or colonized with Staphylococcus and Malassezia species. It is suspected that these microorganisms might contribute to the severity of AD outside of "classical" superficial infections (e.g., bacterial folliculitis). The systematic prescription of antibiotics and antifungal drugs to every dog with AD is not recommended; however, as such, routine use of antimicrobial drugs is likely to increase the prevalence of drug-resistant microbes.
Improvement of Skin and Coat Hygiene and Care
Bathing with a Non-irritating Shampoo
Weekly bathing with a mild, non-irritating shampoo and lukewarm water is likely to be beneficial for a direct soothing effect to the skin, the physical removal of surface allergens and microbes and an increase in skin hydration. At this time, there is no evidence of superiority of any particular shampoo or protocol to achieve these goals.
Dietary Supplementation with EFA
In normal dogs, dietary supplementation with EFA, or the feeding of EFA-rich diets (especially those rich in the omega-6 EFA linoleic acid) usually results in improvement in coat quality and gloss. Not all EFA-rich diets appear to have such coat improvement effect. At this time, there is no evidence of superiority of any particular EFA combination, dosage, ratio or formulation (including enriched diets) to improve skin and coat quality in dogs with AD, but, in general, EFA-enriched diets provide higher amounts of EFA than oral supplements. The benefit of EFA, if any, might not be seen before two months of supplementation.
Reduction of Pruritus and Skin Lesions with Pharmacological Agents
Treatment with Topical Glucocorticoids or Tacrolimus
As discussed above, there is good evidence supporting the efficacy of topical glucocorticoids for treatment of AD in dogs. Clinicians must tailor the frequency and duration of application of topical glucocorticoids to the severity of clinical signs. Such formulations are best suited for focal (e.g., foot) or multifocal lesions and for relatively short durations (e.g., less than two months).
As an alternative to topical glucocorticoids, 0.1% tacrolimus ointment (Protopic, Astellas) has been shown to be effective, especially in dogs with localized AD. The efficacy of tacrolimus ointment appears highest when used twice daily for one week with later reduced frequency of application as needed to control signs. Signs suggesting mild irritation might follow the application of tacrolimus.
Treatment with Oral Glucocorticoids or Ciclosporin
There is strong evidence of the efficacy of oral glucocorticoids and ciclosporin for treatment of AD in dogs. Such oral medications are especially suited for dogs with generalized AD, and when other flare factors have been identified and eliminated. The onset of clinical benefit arises earlier with glucocorticoids than with ciclosporin. Details on dosages and modalities of use of oral glucocorticoids and ciclosporin can be found in the online publication downloadable for free.
Treatment with Subcutaneous Interferons
There are studies providing evidence of the efficacy of injections of recombinant canine gamma-interferon (InterdogTM, Toray) and feline omega interferon (Virbagen Omega, Virbac) to treat dogs with AD. Details on treatment protocols are available in the online paper.
Interventions Likely To Be of Little or No Benefit To Treat Chronic Canine AD
Results from clinical trials suggest that, as a group, first- (i.e., sedating) and second- (i.e., lower sedation) generation oral type 1 antihistamines are unlikely to be beneficial in dogs with chronic AD skin lesions. If veterinarians wish to use type 1 antihistamines, they should limit their prescription to those drugs with demonstrable antihistamine effect in dogs (e.g., hydroxyzine at 2 mg/kg twice daily or cetirizine 0.5–1.0 mg/kg once daily). Finally, antihistamines should be given as a preventative, which is every single day at the recommended dosage, to keep blocking histamine receptors before histamine is released. The main side effect of most antihistamines is sedation.
A systematic review of clinical trials provides evidence that EFA supplements, EFA-enriched diets and nutritional or herbal supplements are unlikely to provide meaningful benefit if given alone for relief of inflammation and/or pruritus. As discussed above, EFA might be useful to improve coat quality and ameliorate dry skin, but, at this time, there is no evidence of superiority of any particular EFA combination, dosage, ratio or formulation (including enriched diets) to achieve skin barrier, coat quality or antiallergic effect.
There is some evidence of antiallergic efficacy of oral pentoxifylline, misoprostol and tepoxalin, but because of their modest benefit, potentially high costs and adverse effects, these medications should probably not be used as first-line medications to treat dogs with AD.
Implement Strategies to Prevent Recurrence of Signs
Avoidance of Flare Factors
Avoidance of known flare factors is the strategy most optimal to prevent recurrence of signs in patients with AD. As discussed in the sections above, the maintenance of the dog on a diet not containing ingredients to which it is hypersensitive, the implementation of an effective flea control and a reduction of contact with provocative environmental or microbial allergens would be ideal, wherever and whenever possible.
Implementation of Proactive (Preventive) Pharmacotherapy
In humans with AD, there is evidence of high benefit, low cost and low risk of proactive intermittent applications of topical glucocorticoids and tacrolimus to skin areas repeatedly affected during flares of AD. Whether or not a similar strategy would be equally effective in dogs with AD has not been established at this time, but because of the possible benefit, low risk and low cost, such interventions are worth considering in dogs with recurrent moderate or severe AD.
Implementation of Allergen-Specific Immunotherapy
Allergen-specific immunotherapy (ASIT) is the practice of administering gradually increasing quantities of an allergen extract to an allergic subject to ameliorate the symptoms associated with subsequent exposure to the causative allergen. Subcutaneous ASIT appeared effective and safe to reduce signs of AD in dogs. It should be considered in any dog in which intradermal test or IgE serology have permitted the identification of allergens likely to contribute to the disease and in whom allergen contact is unavoidable. The dog's owners should be able to afford the time, expense and technical aspects of this regimen. In addition, when symptomatic antiinflammatory therapy is ineffective, or associated with unacceptable or potentially unacceptable side effects (e.g., glucocorticoids), or is impractical to maintain for an extended period of time, then ASIT is indicated, even in dogs with seasonal disease of short duration. Finally, due to its unique mode of action, ASIT is the only intervention that has the potential to prevent the development of signs and alter the long-term course of the disease.
It is expected that between approximately 50 and 80% of dogs with AD that have been treated with ASIT for six to twelve months will exhibit an improvement in signs and/or a decrease in antiinflammatory or antipruritic medication use. At this time, there appears to exist no clear advantage of a particular ASIT protocol (traditional, rush or low-dose). Most importantly, injection frequencies and amounts injected must be tailored to each patient depending upon the clinical improvement observed and the presence of adverse events (e.g., increases in pruritus after each injection). Because of the delay in ASIT effect, antiinflammatory drugs should be given temporarily, as needed to maintain good quality of life until ASIT might offer clinical benefit. Immunotherapy must be continued for at least one year before dismissing it as ineffective.
Note: this is a short summary of an extensive article (Olivry T, et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Vet Dermatol. 2010;21(3):233–248) that can be downloaded freely, in English and in 18 other languages at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3164.2010.00889.x/pdf (VIN editor: link was updated on 1/30/13)