Canine atopic dermatitis (CAD) is the name given to describe a genetically predisposed inflammatory and pruritic skin disease with characteristic clinical signs, driven by an IgE/antibody-associated reaction (Canine Atopic Task Force 2006). The pathogenesis is much more complex than this as dogs with the same set of clinical signs exist but with no demonstrable allergen-specific IgE, giving rise to the term atopic-like dermatitis by Halliwell (2006), (intrinsic atopic dermatitis in the human literature). Human AD is considered a polyfactorial disease characterised by pruritus, immunodysregulation, disrupted epidermal barrier function and IgE-mediated sensitisation to food and environmental allergens (Misery 2011).

A similar polyfactorial pathogenesis appears to be operating in canine atopic dermatitis, and this explains why a "one size fits all" recipe approach is unsuitable and inadequate to achieve effective long-term control of the disease.

Pathogenesis

IgE-Mediated Response

The dogma for many years was a Type I hypersensitivity triggered production of allergen-specific IgE antibodies. Re-exposure to the allergen would cause mast cell and basophil degranulation releasing range of inflammatory cytokines causing erythema and pruritus.

The current proposed pathogenesis is more complex: The major route of allergen exposure is percutaneous absorption with barrier dysfunction allowing increased allergen entry. Once the allergen enters, it is presented to naïve T cells in the draining lymph nodes. This leads to Th2 differentiation/polarisation and these Th2 lymphocytes release cytokines that stimulate IgE production. Re-exposure to allergens causes mast cell degranulation, cutaneous inflammation, erythema and pruritus (Marsella et al. 2012). However, it has become clear that in addition to this (more complex) immune response, both epidermal barrier dysfunction and infections play an important and interrelated role in the pathogenesis and severity of disease.

Barrier Function

There is increasing evidence that animals with CAD have abnormalities in their barrier function and that these changes contribute significantly to the disease severity (although it is not yet clear if this is primary [i.e., genetic] or secondary [to atopic inflammation]). The consequence of this impaired barrier function is an increase in the transepidermal water loss along with increased allergen penetration into the skin, stimulation of the skin immune system and increased risk of cutaneous infections.

Role of Infections

For a variety of reasons, atopics have a greater incidence of infections. Bacterial exotoxins can act as superantigens and augment the inflammatory response and worsen pruritus. In dogs, hypersensitivity to Malassezia spp. has also been recognised in recent years. All this leads to more severe pruritus and skin trauma.

In addition to this, bacteria can produce ceramidases and proteases that lead to further reduction in the stratum corneum, creating a self-perpetuating cycle of disruption in barrier function and inflammation.

The ongoing debate regarding the pathogenesis of AD is whether it is an "inside-outside" process (primary immune defect leading to inflammation), "outside-inside" (primary barrier dysfunction leading to inflammation) or "inside-outside-inside" (genetic barrier defect leads to atopic cutaneous inflammation that leads to further barrier dysfunction).

From a practical/clinical point, this means that all of the potential components that contribute to the pathogenesis (immune dysfunction, infection, epidermal barrier disruption) need to be identified and considered in the diagnosis and eventual treatment plan for successful control.

Clinical Signs and Diagnosis

No clinical sign is pathopneumonic; as a consequence, there have been a number of sets of diagnostic criteria proposed that can be used once other causes of pruritus have been eliminated.

The first was by Willemse that called for 3 major and 3 minor clinical signs to be present.

The latest has been proposed by Favrot et al. (2010)

The sensitivity and specificity varied depending on which set was used and how many criteria were included in the diagnosis:

When the sensitivity and specificity is examined, it can be seen that an incorrect diagnosis could be made in every fifth pruritic dog and so these criteria must only be used after a complete and thorough elimination of all other causes of pruritus. As the signs of CAD are clinically indistinguishable from cutaneous adverse food reaction, a food elimination should be performed to rule this out before a diagnosis of CAD is made.

Treatment

It is beyond the scope of these notes to detail the treatment of CAD, so the reader is directed to 2010 treatment guidelines produced by International Task Force on canine atopic dermatitis (free to download). However, the following are some of my thoughts on the treatment of this complex disease.

Due to the complex pathogenesis of the disease, there cannot be a simple "recipe" that will be effective in all cases. The treatment must identify the relative importance of the three fundamental elements of the disease, namely immune dysfunction, epidermal barrier disruption and infections. The presence and relative importance of each may also vary over time and this must be taken into consideration as well.

Infection Control

There are very commonly either bacterial infections (predominantly Staphylococcus spp.) Malassezia infections or both present. If there are lesions that are consistent with a bacterial or increased numbers of bacteria on cytology, appropriate systemic antibiotics need to be given. Generally the duration of treatment is 3 weeks (time to cure plus 7–10 days). Shorter treatment course will commonly see a relapse in infection as soon as the antibiotics are stopped.

In addition, topical antiseptics (chlorhexidine, benzyl peroxide, iodine) can be used. These can be applied whilst the antibiotics are administered and then continued on a weekly basis to try and prevent infection relapse.

Malassezia: If the cytology shows increased numbers of organisms, then treatment should be initiated. In cases of marked lichenification systemic medication (itraconazole 5 mg/kg q24 or terbinafine 20 mg/kg q12h) may be started and used for the first 2–3 weeks and then topicals (miconazole, ketoconazole, enilconazole) applied to prevent relapse.

Barrier Dysfunction

Whilst there are only limited studies to document the benefits of trying to correct barrier disruption, I will try and correct it in affected individuals and feel that it is a very important component of the overall treatment plan. The affect is variable and the same treatment will produce different responses. It is also important to note that the application of topical barrier repair products has been shown to lead to increased disruption in some. So, if the owner reports deterioration following treatment, the product should be discontinued and changed.

Oral essential fatty acid supplementation (omega 3 and 6 oils) is used - either as a supplement to the existing diet or contained within a commercial "skin support" diet of which there are several alternatives. I will also occasionally use topical EFA application in animals that are fussy eaters.

There is a range of topical barrier repair products available but most share the same active ingredients and so there is no need to stock multiple products with the same ingredients.

I tend to recommend weekly application of a product, although this can be increased in more severe cases.

Immune Dysregulation

The treatment of this aspect of the disease falls into 2 broad categories, namely pharmacotherapy or immunotherapy.

Olivry and Mueller (2003) published an evidence-based review of the various therapies that have been proposed and came to the following conclusions:

Most recently, oclacitinib, a selective Janus kinase inhibitor, has been released. This has been shown to inhibit the pruritogenic effects of IL-31 in dogs.

Allergen-Specific Immunotherapy (ASIT)

For successful treatment outcomes, there must be good patient selection, good owner compliance, identification and control of other contributing factors and appropriate allergen selection. Reported efficacy varies (52–100%), but in our hands we find response in 60–70% of cases. The time to improvement varies, but generally see improvement by 6–8 weeks (corresponds to the end of initial build up phase). Rush induction protocols significantly reduce this lag phase. If the treatment has been successful, vaccine is continued for at least 2 years. At that point, some animals are able to stop and remain well controlled, whilst most need to remain on immunotherapy to maintain control.

References

1.  Olivry T, Mueller RS, International Task Force on Canine Atopic Dermatitis. Evidence-based veterinary dermatology: a systemic review of the pharmacology of canine atopic dermatitis. Vet Dermatol. 2003;14:121–146.

2.  Olivery T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Vet Dermatol. 2010;21:233–248.

3.  Olivry T. Is the skin barrier abnormal in dogs with atopic dermatitis? Vet Immunol Immunopathol. 2011;144:11–16.

4.  Willemse T. Atopic dermatitis: a review and reconsideration of diagnostic criteria. J Small Anim Pract. 1986;27:771–778.

5.  Favrot C, Steffan J, Seewald W, Picco F. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Vet Dermatol. 2010;21:23–30.

6.  Halliwell R. Revised nomenclature for veterinary allergy. Vet Immunol Immunopathol. 2006;114:207–208.

7.  Marsella R, Sousa CA, Gonzales AJ, Fadok FA. Current understanding of the pathophysiologic mechanisms of canine atopic dermatitis. J Am Vet Med Assoc. 2012;241(2):194–207.

8.  Marsella R, Olivry T, Carlotti D. Current evidence of sin barrier dysfunction in human and canine atopic dermatitis. Vet Dermatol. 2011;22:239–248.

9.  Misery L. Atopic dermatitis: new trends and perspectives. Clin Rev Allergy Immunol. 2011;41:296–297.