When things go awry with the stratum corneuma bricks-and-mortar structure of corneocytes and lipidsatopic dermatitis may be a result. Researchers are trying to fit the pieces together.
Chris Rose/stock.adobe.com; Trifonenko Ivan/stock.adobe.comThe barrier function of the skin has become a hot topic in our understanding of the pathogenesis of skin disease, especially atopic dermatitis in dogs. Specifically, a better understanding of the role of the skin barrier could lead to more targeted therapies for skin dysfunction in atopic dermatitis.
The outer layer of the skin is the anatomical and physiological barrier between the environment-including the microflora of the skin-and the body's immune system. The outermost layer, called the stratum corneum, provides the barrier function for the epidermis. This barrier is composed of “bricks” (flattened, protein-enriched corneocytes) and “mortar” (intercellular lipid-enriched layers). As a result of this “bricks-and-mortar” structure, the stratum corneum in mammalian skin is essential to normal skin health because it retains water and solutes essential for physiological homeostasis and provides protection from physical, chemical and biological stress.
The epidermal barrier is created by epidermal cornification, the endpoint of epidermal differentiation. An effective epidermal barrier requires intricate organization and formation of the keratin intermediate filaments and the intercellular lipids, together with tight regulation of desquamation. The stratum corneum consists of a sheet of corneocytes embedded in an intercellular lipid matrix and is the primary barrier against pathogen entry. It's also largely responsible for the regulation of water loss from the body (transepidermal water loss [TEWL]).
Multiple studies confirm that dogs with atopic dermatitis have high TEWL values in both nonlesional and lesional skin, along with structural abnormalities of lipid lamellae and abnormal filaggrin expression. Allergen challenge increases TEWL in commonly affected skin sites and worsens lipid lamellae and architecture of the stratum corneum, resulting in altered expression of the upper epidermal structure and adhesion proteins in sensitized dogs. Ceramide reduction and structural abnormalities of the epidermis further increase TEWL.
Clinical remission of atopic dermatitis is associated with normalization of TEWL values, ceramide levels and epidermal structural defects. Despite these findings, there is still no conclusive evidence of a primary genetic barrier defect in atopic dermatitis.
In dogs, the skin barrier is often assessed by TEWL measurements, although this methodology is unreliable. A relationship between ceramide deficiency and increased TEWL has been described, while a relationship between disease severity and skin barrier dysfunction measured by TEWL has yet to be proven in dogs. While it's reasonable to speculate that restoration of lipid deficiency should improve skin barrier function, it's still not clear whether skin barrier repair directly translates to improvement of clinical signs in affected dogs.
There are multiple commercial topical therapies (shampoos, spray and mousses) containing ceramides, ceramide complexes and phytosphingosines designed to improve and potentially normalize the physical aspects of the skin barrier. Both oral and topical supplementation of essential and omega-six fatty acids may also result in improvement of the skin barrier.
Current evidence suggests, however, that reducing inflammation and attaining clinical remission of atopic dermatitis is the most promising route to normalizing barrier structure and function. While barrier products can certainly be associated with symptomatic improvement of the skin and hair coat, addressing the primary disease should be the veterinarian's major focus. This is accomplished through symptomatic management of inflammation and pruritus along with altering the underlying immunologic abnormalities using allergen-specific immunotherapy.
Dr. Rusty Muse is a veterinary dermatologist at the Animal Dermatology Clinic in Tustin and Long Beach, California.
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