Unravelling the skin barrier: a new paradigm for atopic dermatitis and house dust mites

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease caused by complex interactions between genetics and environmental factors. In human beings, impairment of the skin barrier is demonstrated and thought to be responsible for enhanced penetration of allergens and increased risk for allergic sensitization. Once inflammation is triggered, further impairment of the skin barrier occurs, leading to self-perpetuating cycles of sensitizations. Canine AD appears to share many similarities with the human counterpart, clinically and immunologically. It is hypothesized that a primary defect of skin barrier function also exists in subsets of atopic dogs (e.g. in an experimental model using high IgE-producing beagles), particularly in young dogs, and in sites predisposed to the development of lesions. This impairment is present in clinically normal skin, worsens with development of lesions and can be quantified by measurement of transepidermal water loss. Therefore, the distribution of lesions in AD may be linked to a primary skin barrier defect in those sites and not simply due to contact with allergens, and increased susceptibility to penetration of allergen may exist early in life. Ultrastructurally, transmission electron microscopy reveals that clinically normal skin in atopic dogs has abnormalities in lamellar body secretion and extracellular lamellar bilayer structure when compared with normal dogs. Development of lesions worsens these changes (e.g. widening of intercellular spaces, release of lamellar bodies, and disorganization of lipid lamellae). It is proposed that the paradigm of canine AD as primarily due to immunologic aberration ('inside/outside') should be shifted to include a primary defect in barrier function ('outside/inside').