Addressing epidermal barrier function in canine atopic dermatitis

Research and treatment modalities are evolving for atopic dermatitis, a chronic pruritic skin disease in dogs. Dogs with atopic dermatitis have seasonal to nonseasonal pruritus that is often accompanied by secondary bacterial and yeast infections. Lesions (erythema, alopecia, pustules, papules, and crusts) are usually worse on the face, feet, skin folds, and flexural surfaces and in areas of friction (Figure 1).

1. An 8-year-old neutered male French bulldog with atopic dermatitis. Note the erythema of the ears, face, feet, and inguinal region. A few papules are present on the inguinal region as well.

Classically, atopic dermatitis 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 genetic defects in skin lipids and proteins create a barrier defect that lets allergens into the body, stimulating an immune response.1 The study of skin barrier function in dogs is the subject of a lot of research, and measuring transepidermal water loss is commonly used to estimate barrier function. New topical treatments geared toward improving the skin barrier are emerging and may be useful additions to the classic atopic dermatitis treatment protocol.

TRANSEPIDERMAL WATER LOSS

To understand skin barrier defect research, a brief review of transepidermal water loss is necessary. A machine called an evaporimeter measures the amount of water evaporating from the skin. The evaporimeter can have an open or closed chamber, and a debate exists about which type is superior.2 Transepidermal water loss measurement is noninvasive and has been shown to be a good estimate of barrier function in dogs and people.

All animals lose a small amount of water through the skin, called perspiratio insensibilis.3 But atopic dogs lose higher amounts of water than normal dogs do.4,5 It is thought that the higher water loss dries out and irritates the skin, but more important, it signifies that the skin barrier is not working properly. If water is leaking out, allergens may be penetrating the barrier.

THE EPIDERMAL BARRIER

Most canine epithelial barrier research can be divided into two categories: research to determine the chemical content of skin and research with electron microscopy to determine the physical architecture of skin. Canine skin can be described as bricks and mortar, with epithelial cells making up the bricks and extracellular lipids and proteins making up the mortar.

The stratum granulosum of the epithelium produces lamellar bodies, which contain necessary lipids and enzymes needed for differentiation and desquamation of epithelial cells.1 The lamellar bodies are extruded into the extracellular space and form organized 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 atopic dermatitis have a skin deficiency of ceramides,5,6 and their lamellae are arranged in a disorderly manner.1

TRADITIONAL TREATMENT

Treating canine atopic dermatitis usually involves a combination of therapeutic modalities. The mainstay of treatment is allergen-specific immunotherapy (allergy vaccines) (Figure 2), cyclosporine (Atopica—Novartis Animal Health), and low-dose alternate-day oral glucocorticoids. Adjunctive treatment includes antibiotics and antifungals to eliminate infection, strict flea control, diet trials, antihistamines, shampoos, and fatty acid supplementation.7

2. An intradermal skin test in a dog with positive test results. These results are used to guide the formulation of allergen-specific immunotherapy.

NEW TOPICAL THERAPIES

Some new topical therapies have been developed with the goal of improving epidermal barrier function. The theory is that topically applying lipids to the skin stimulates it to produce its own lipids, leading to barrier repair. These therapies are different from supplementing fatty acids because they are administered directly onto the skin and because many of them provide ceramides, the most important lipid component of the skin barrier. It has been shown that the skin barrier cannot be disrupted unless ceramides are removed.6

Allerderm Spot-On (Virbac Animal Health; $20 to $30 for a six-pack), a ceramide and fatty acid-containing liquid, is applied to the skin in a similar manner to monthly flea control products (Figure 3). The instructions for this product are to apply one pipette a week for four weeks and then one pipette a month for maintenance. A small study that evaluated skin biopsy samples with electron microscopy showed that after repeated application of this product, atopic dogs had higher concentrations of lamellar lipids in the stratum corneum compared with pretreatment concentrations.8

3. Allerderm Spot-On (Virbac Animal Health), a ceramide and fatty acid-containing liquid, has been shown to increase the concentration of lamellar lipids in the stratum corneum of atopic dogs.

Dermoscent Essential 6 spot-on (Laboratoire De Dermo-Cosmetique Animale, Castres, France; $15 to $20 for a four-pack) contains essential oils and fatty acids (Figure 4). The instructions for this product are to apply one pipette a week for eight weeks and then one pipette every two weeks for maintenance. In a small study, seven atopic dogs were treated with this product for eight weeks and had their canine atopic dermatitis extent and severity index (CADESI) scores measured before and after treatment.9 They had statistically significant improvement (P = 0.0043) in severity of disease, though there was not a control group.

4. Dermoscent Essential 6 spot-on (Laboratoire De Dermo-Cosmetique Animale, Castres, France) has been shown to decrease the severity of atopic dermatitis, pruritus, and transepidermal water loss in atopic dogs.

Sogeval Laboratories makes a line of products containing phytosphingosine, a precursor to ceramides (Figure 5). Douxo Seborrhea Shampoo (Sogeval Laboratories; $50 to $65 for a 25-pack) can be used one or two times a week along with the Douxo Seborrhea Micro-emulsion Spray (Sogeval Laboratories). Duoxo Seborrhea Spot-on (Sogeval Laboratories) can be used alone or in combination with the shampoo or spray and should be applied once weekly for four weeks and then twice monthly for maintenance.

5. (Left to right) Douxo Seborrhea Shampoo, Seborrhea Micro-emulsion Spray, and Seborrhea Spot-on (Sogeval Laboratories) are a line of phytosphingosine-containing products.

CONCLUSION

More research is needed to determine the efficacy of these new barrier-repair topicals. For years, dermatologists have emphasized grooming, coat hygiene, and bathing as adjunct treatments. The barrier-repair products take that idea one step further. In our opinion, lipid-containing topicals can be added to almost any atopic dermatitis case without causing harm. They may be more beneficial when skin infections are under control, since twice weekly bathing could remove the product. It does not seem likely that they will completely replace conventional therapies, but they may be a useful addition to the atopic dermatitis treatment arsenal if they can improve the efficacy of allergen-specific immunotherapy and allow for lower doses of glucocorticoids and cyclosporine.

Jacqueline Gimmler, DVM

Jenise Daigle, DVM, DACVD

Central Texas Veterinary Specialty Hospital

301 Chisholm Trail

Round Rock, TX 78664

REFERENCES

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3. Forslind B, Engstrom S, Engblom J, et al. A novel approach to the understanding of human skin barrier function. J Dermatol Sci 1997;14:115-125.

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8. Piekutowska A, Pin D, Reme CA, et al. Effects of a topically applied preparation of epidermal lipids on the stratum corneum barrier of atopic dogs. J Comp Pathol 2008;138;197-203.

9. Tretter S, Mueller RS. The influence of topical unsaturated fatty acids and essential oils on normal and atopic dogs-a pilot study. NAVDF 2010 Abstracts. Vet Dermatol 2010;21:311-328.