Ralf S. Mueller, DACVD, DECVD, FACVSc
Canine atopic dermatitis (CAD) is a common skin disease in small animal practice. The primary clinical presentation of atopic dermatitis is pruritus. Secondary skin lesions result from self-trauma and include alopecia, crusting and lichenification. The most commonly affected areas are the face, feet, ventral abdomen/inguinal region, axillae, flexor surface of the tarsal joint/extensor surface of the carpal joint, pinnae and external ear canals. When the pinnae and external ear canals are affected, otitis externa is a common complication. Secondary infections with yeast or bacteria are frequently seen. Breed predispositions are reported, but may vary from location to location. However, German shepherd dogs, Golden and Labrador retrievers, as well as West Highland White terriers, are predisposed in most reports.
In practice, atopic dermatitis is commonly diagnosed based on the clinical presentation and either a good response to glucocorticoid therapy or a positive intradermal test or serum test for allergen specific IgE. Unfortunately, glucocorticoid therapy leads at least to temporary improvement in many skin diseases and positive skin or serum test results are commonly found in normal animals or patients affected with skin diseases other than allergies. Thus, rather than confirming a suspicion of the disease with one or several laboratory test results, the clinician has to rule out all differential diagnoses for that particular case to make the diagnosis. This requires the intellectual, emotional and financial dedication of the owner and a thorough understanding of a logical work-up by the attending clinician. In some patients, due to owner constraints, the clinician will have to resort to guessing the most likely diagnosis and perform trial therapy. There is nothing wrong with that approach as long as clinician and owner are aware of the limitations and risks involved in such an approach.
If, however, an owner is interested in the best long-term strategy, only a proper diagnosis will allow an efficient and efficacious treatment of the pet's skin condition and a diagnostic work-up needs to be recommended. Each differential diagnosis needs to be excluded with appropriate procedures and tests/treatments. The diagnosis is atopic dermatitis if all other diagnoses have been ruled out. Skin or serum testing are not suitable for the diagnosis, but are used after the disease has been confirmed to determine allergens involved and to formulate an allergen extract for specific immunotherapy. For most dogs with atopic dermatitis, food adverse reaction is a possible differential diagnosis. The only reliable way of identifying these patients at this point in time is an elimination diet. If the pruritus is of sudden onset and focused more on the trunk and head and less on the paws, canine scabies needs to be considered. Similarly, flea bite hypersensitivity may lead to pruritus of the trunk and thighs. If there is only the slightest suspicion of mite or flea involvement, an ectoparasitic treatment trial must be performed even without evidence of fleas or flea dirt and with negative superficial skin scrapings. Canine demodicosis may be associated with alopecia, erythema, papules and crusting on the face and feet and may mimic atopic dermatitis. Typically, demodicosis, in the early stages and without a significant secondary infection, is not associated with severe pruritus. However, any dog with pododermatitis and any dog with lesional pruritus should undergo deep skin scrapings to rule out demodicosis. Secondary infections are common and cytology is an important tool to identify organisms involved in suspected infections. A logical work-up will confirm or exclude the diagnosis of canine atopic dermatitis in most patients and allow us to choose the best long-term management for that particular patient. However, owner constraints are an unfortunate but regular feature of practice. If owners refuse the diagnostic work-up offered despite the clinician's efforts to explain the limits of educated guesses, one will have to rely on our clinical experience and a good guess in those patients.
A number of drugs have been reported as successful treatment for this disease in human and veterinary medicine, and glucocorticoids, calcineurin inhibitors, antihistamines, fatty acids, allergen-specific immunotherapy (ASIT) and topical therapy for canine atopic dermatitis will be discussed in more detail.
There is good evidence for high efficacy of oral and topical glucocorticoids and low harm of short-term treatment. Topical triamcinolone acetonide is available in the USA and topical hydrocortisone aceponate in Europe. Oral glucocorticoids were typically evaluated as standard-of-care controls in randomized controlled trials (RCT) for comparison with other interventions and methylprednisolone, prednisone and prednisolone at 0.4-1 mg/kg/day were most commonly used.1 At the end of 4-16 weeks of treatment, lesion scores were reduced from 45-83% and pruritus by 33-81%. Adverse effects included polyphagia, PU/PD, weight gain and/or intermittent GI signs. The benefit of long-term treatment with glucocorticoids must be weighed against the risk of adverse drug effects impacting on health and quality of life.
Oral cyclosporine is a thoroughly evaluated drug for the treatment of canine atopic dermatitis. At a dose of 5 mg/kg/day, it was found to be equally effective as prednisolone and methylprednisolone. After six weeks of treatment, the reduction of clinician-graded lesion scores was 52-67%. Similarly, decrease of owner-assessed pruritus was 36-100%. Vomiting and diarrhoea were the most commonly seen adverse effects, seen in 14-42% of cases, but were mostly mild to moderate and a reason for cessation of therapy in less than 1% of the patients.2 Papillomatous eruptions and gingival hyperplasia were also seen occasionally. The trials provided good evidence for high efficacy of oral cyclosporine in canine atopic dermatitis and are documented in a recent meta-analysis. However, the long-term safety of cyclosporine in dogs is not known beyond the safety studies of cyclosporine treatment for one year in beagle dogs.
The topical calcineurin inhibitor tacrolimus was evaluated in several studies. At a concentration of 0.1%, it decreased clinician-assessed lesion scores and owner-assessed pruritus scores of localized atopic dermatitis by 60-63% and 58% respectively after 4-6 weeks of once- to twice-daily therapy. The only adverse effect seen in the studies using tacrolimus was mild and transient irritation at the site of application. These trials provide good evidence for medium efficacy of 1% tacrolimus in CAD.1
Studies evaluating antihistamines provide conflicting evidence of benefit for chlorpheniramine, clemastine, diphenhydramine, hydroxyzine, promethazine and trimeprazine for treatment of CAD.1 However, adverse effects are rare and consist most commonly of drowsiness.1 One blinded RCT provided fair evidence of medium efficacy of a combination of hydroxyzine (25-100 mg/dog/day) and chlorpheniramine (1-4 mg/kg/day).3 An improvement of more than 50% in lesional scores was seen in 18% and of pruritus scores in 30% of the dogs, investigators judged the treatment satisfactory in 24% of the dogs. This combination product is the first choice treatment with type 1 histamine receptor antagonists in our clinic. Second generation low-sedation type-1 histamine receptor antagonists such as loratidine and astemizole did not show efficacy in several studies, whilst terfenadine showed conflicting results.1 Both terfenadine and astemizole can induce cardiac arrhythmias in dogs. Considering the concurrently demonstrated lack of efficacy, these antihistamines should be used cautiously for the therapy of CAD. Oxatomide at 1-2 mg/kg/day did show medium efficacy in several trials with 20-50% of patients exhibiting a satisfactory control of pruritus. Adverse effects were only mild and transient and consisted most commonly of increased appetite. These trials provide fair evidence of no or low efficacy of the first-generation sedating type-1 histamine receptor antagonists chlorpheniramine, pheniramine, diphenhydramine, hydroxyzine, promethazine and trimeprazine for treatment of CAD, fair evidence of medium efficacy of treatment of CAD with oxatomide and with a combination of chlorpheniramine and hydroxyzine. As a group, there is conflictual evidence of the benefit of type-1 histamine receptor antagonists for treatment of CAD.
There are a number of studies evaluating polyunsaturated fatty acids for the treatment of canine atopic dermatitis. Omega-6, omega-3 fatty acids, or a combination thereof, were evaluated. In double-blinded, placebo-controlled studies, the difference between placebo and PUFA (polyunsaturated fatty acids) supplementation was typically significant, between 25 and 40% of patients responded favorably in the treatment groups.4 There is also evidence that concurrent administration of PUFAs decreases the requirements for glucocorticoids in atopic patients5 and that a combination of antihistamines and PUFAs is more effective than either therapy alone.6 Adverse effects of PUFA therapy were mild and typically consisted of diarrhoea. There is good evidence for moderate efficacy of PUFA therapy in canine atopic dermatitis.
Although there are a number of studies evaluating the effect of ASIT (allergen-specific immunotherapy) on canine atopic dermatitis, most studies were retrospective and thus neither blinded nor controlled. In addition, in many studies follow-up times were short. Most of these studies report excellent efficacy in approximately 20% of the patients and good response in an additional 25-45%. The first prospective double-blinded, placebo-controlled study of ASIT in veterinary medicine reported 59% of 27 patients with significant improvement7, but improvement was not evaluated with detailed clinical and pruritus scores used in more recent studies evaluating therapies for canine atopic dermatitis. Two years ago, a double-blinded RCT comparing conventional with 'rush' immunotherapy found significant improvement in pruritus, medication and clinical scores after 12 months of immunotherapy, there was no significant improvement with conventional immunotherapy.8 As ASIT is a long-term therapy and many patients are in need of additional medication, and as each patient has its unique set of allergens as well as possibly a unique protocol of administration, to maximize success rate, scientific evaluation of ASIT is difficult. However, at this point, the numerous studies can be considered fair evidence for moderate efficacy of ASIT in the treatment of CAD.
An open four-week trial evaluated two commercially available formulations of pramoxine-containing cream rinses. Overall, a good reduction (51-75%) in pruritus for 48 hours was assessed subjectively by the owners for seven dogs (41%).1 This provides limited evidence of medium efficacy of pramoxine.
Another RCT compared the efficacy of whirlpool therapy with an antipruritic shampoo, conventional shampoo therapy and whirlpooling in water.9 Dogs improved significantly more with conventional shampooing and with shampoo therapy in the whirlpool compared to the control group, but there was no difference between the two modes of therapy. More dogs improved by 50% and 90% respectively in the whirlpool group compared with the conventional shampoo treatment, but the difference was not statistically significant.
1. Olivry T, Mueller RS. Evidence-based veterinary dermatology: A systematic review on the pharmacotherapy of canine atopic dermatitis. Vet Der 2003; 14: 121-146.
2. Steffan J, Favrot C, Mueller RS. A systematic review and meta-analysis of the efficacy of cyclosporine for the treatment of canine atopic dermatitis. 2006; 17: 3-16.
3. Ewert G, Daems T. Treatment of canine atopic dermatitis by a fatty acid copolymer: comparative double blind study. Prat Med Chir Anim Comp 2001; 36: 401-408.
4. Mueller RS, Fieseler KV, Fettman M, et al. Effect of omega-3 fatty acids on canine atopic dermatitis. J Sm Anim Pract 2004; 45: 293-297.
5. Bond R, Lloyd DH. Combined treatment with concentrated essential fatty acids and prednisone in the management of canine atopy. Vet Rec 1994; 134: 30.
6. Paterson S. Additive benefits of EFAs in dogs with atopic dermatitis after partial response to antihistamine therapy. J Small Anim Pract 1995; 36: 389.
7. Willemse A, et al. Effect of hyposensitization on atopic dermatitis in dogs. J Am Vet Med Assoc 1984; 184: 277.
8. Mueller RS, Fieseler KV, Zabel S, Rosychuk RAW. Conventional and rush immunotherapy in canine atopic dermatitis. Advances in Veterinary Dermatology V, 2005, 60-69.
9. Loeflath A, von Voigts-Rhetz A, Jaeger K, Mueller RS. The use of a whirlpool in topical antipruritic therapy--a double-blinded, randomized, cross-over study. North American Veterinary Dermatology Forum 2006: 175.