THIS series will look first at the skin barrier and global management of atopic dermatitis; later articles will discuss the management of Malassezia dermatitis; pruritus; the role of steroids; and shampoo therapy.
Skin barrier in atopic dermatitis
The pathogenesis of atopic dermatitis (AD) is considered multifaceted due to the action of genetic and environmental factors. Classically, AD is thought to be caused by a genetic defect in the immune system, leading to a hypersensitivity to normal environmental allergens. Newer theories propose that a defect in the skin barrier has an important role in the pathogenesis. In healthy individuals skin offers an effective barrier function against bacteria, viruses, parasites and allergens, such as house dust mites, forage mites and pollens. Genetic defects in skin lipids and proteins create a barrier defect, causing increased entry of the allergens into the body, stimulating an immune response.
Building blocks
The skin can be described as a bricks and mortar structure, with epithelial cells making up the bricks and extracellular lipids and proteins making up the mortar. Both human and canine patients
with AD have been shown to have abnormalities and deficiencies in the intercellular lipid barrier, showing in particular difference in the way the lipids are formed and organised. Lipids are produced by the epithelial cells into structures called lamellar bodies. The lamellar bodies are extruded into the extracellular space and form organised stacks called lamellae, which help prevent water loss and allergen penetration. Ceramides are a type of lipid that makes up a large portion of the lamellae. Dogs with AD have a skin deficiency of ceramides and their lamellae are arranged in a disorderly manner. Additionally, in human atopic patients, a mutation in the gene encoding for filaggrin (filament aggregating protein) have been identified. In the canine counterpart the presence and role of filaggrin mutation has not been clearly elucidated. Although more research is clearly needed, there is increasing, albeit preliminary evidence, to support a role for skin barrier dysfunction in canine AD.
Global management of atopic dermatitis
Management of canine AD usually involves a combination of therapeutic modalities. In a recent paper, the options were divided into two categories: treating acute manifestations and treating chronic cases. Currently recognised causes of flares of canine AD include fleas, food and environmental (e.g. house dust mites, pollens) allergens; other ectoparasites, such as Cheyletiella or Sarcoptes, can also contribute to increase pruritus. In addition to addressing these factors, where infections are present, it is recommended that they are treated topically or systemically, according to the clinical signs. When pruritus is not complicated
by infections, glucocorticoids should be used, including topical (e.g. hydrocorticosne aceponate spray) or systemic (prednisone or
methylprednisolone at antiinflammatory doses) formulations, according to the clinical signs and lesions’ distribution. Medications that are not suitable for management of acute flares include antihistamines (they would not have had the time to block
histamine receptors before their occupation by histamine released in early allergic reactions), essential fatty acids (they take too long to be incorporated into the cells’ membrane) and ciclosporin (due to its delayed therapeutic benefit). n the management of chronic cases, the mainstay of treatment is allergen-specific immunotherapy, topical, systemic (low-dose alternateday
oral) glucocorticoids, and ciclosporin. Adjunctive treatment includes antibiotics and antifungals, strict flea control, diet trials, antihistamines, shampoos, and fatty acid supplementation.
Intradermal and serological tests are both recommended as useful to identify environmental triggers in view of pursuing allergen specific immunotherapy. Interestingly, there is no evidence that anti-inflammatory therapy interferes with allergen specific immunotherapy; therefore this can be used during the induction phase, before any improvement is seen from the vaccine. Control of localised pruritus can be successfully achieved by use of topical glucocorticoids and tacrolimus and more generalised inifestations
benefit from systemic glucocorticoids, to be started as for acute flare, with the aim of achieving a low-dose alternate-day dosage, and with ciclosporin. This should be started on a daily basis and then, upon clinical signs, reduced gradually. Essential fatty acids, Chinese herbs and antihistamines are recognised as useful steroids, sparing drugs in the long term. Bathing with non-irritating, anti-seborrheic or antimicrobial shampoos is also believed to be beneficial, albeit not recommendable as a sole therapy. It is tempting to speculate that addressing the skin barrier defects could produce a beneficial effect. In one human study, the application of a topical moisturiser containing ceramides produced dramatic improvement in clinical scores after three and six weeks of treatment. In dogs with AD, topical application of a lipid preparation was shown to be effective in reestablishing a normal skin structure. In atopic dogs it is difficult to demonstrate the clinical efficacy of this skin lipid complex spot-on treatment in clinical practice, because topical lipid applications are not used as monotherapy. These formulations are intended to be used as adjunct therapies in combination with other antiinflammatory
drugs, antimicrobial drugs, and immunotherapy as part of the global approach to the management of canine AD. In a recent study, conducted on eight dogs already on treatment with allergen-specific immunotherapy and/or pentoxyfilline, during a 12- week treatment period, their canine atopic dermatitis extent and severity index (CADESI) scores were measured before and after treatment, and the total clinical score progressively decreased, in association with an improvement in clinical signs. The change in the scores for excoriations and erythema was the
most dramatic. Because the only change in treatment over the 12 weeks was the addition of the topical spot-on therapy, these results may suggest that topical lipids may play a role in the reduction of inflammation. Repair of epidermal barrier function
presumably leads to the reduction in inflammation seen in this study. These findings are encouraging, but double-blinded placebo-controlled or cross-over studies are needed for further confirmation.
References
Shimada, K., Yoon, J. S., Yoshihara, T. J. S., Iwasaki, T. and Nishifuji, K. (2009) Increased transepidermal water loss and decreased ceramide content in lesional and non-lesional skin of dogs with atopic dermatitis. Veterinary Dermatology 20 (5-6): 541-546. Marsella, R., Olivry, T. and Carlotti, D. N. (2011) International Task Force on Canine Atopic Dermatitis: Current evidence of skin barrier dysfunction in human and canine atopic dermatitis. Veterinary Dermatology 22 (3): 239-248. Olivry, T., DeBoer, D., Favrot, C. et al (2010) Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Veterinary Dermatology 21 (3): 233-248. Piekutowska, A., Pin, D., Rème, C. A., Gatto, H. and Haftek, M. (2008) Effects of a topically applied preparation of epidermal lipids on the stratum corneum barrier of atopic dogs. Journal of Comparative Pathology 138 (4): 197-203. Fujimura, M., Nakatsuji, Y., Fujiwara, S., Rème, C. A. and Gatto, H. (2011) Spot-on skin lipid complex as an adjunct therapy in dogs with atopic dermatitis: an open pilot study. Veterinary Medicine International 281846. E-pub 2011 Sept 29.
