The pathogenesis of canine atopic dermatitis is complex, and our understanding of it continues to change and advance. For years we have been moving away from the concept of inhaled allergies being the main cause of atopic dermatitis, instead recognizing that atopic dermatitis is predominantly a cutaneous reaction to allergens that directly interact with the skin. Multiple research projects have shown that the main, most likely route of sensitization is through the skin.
Sensitization and development of allergy involves much more than IgE production and stimulation of mast cells. The role of the skin's immune system, with activation of Langerhans cells and T cells, became an important target of interest and research and this did advance our knowledge. Eosinophils, once believed to be unimportant, are involved in the inflammatory reaction and are significantly increased in the dermis though histopathology does not typically reveal eosinophilic perivascular dermatitis. Even the keratinocyte, a cell originally believed to offer little more than structural protection, is an active component of the skin's immune system capable of producing cytokines that may be very important in the development of allergic reactions.
Now we are moving in a new direction and may be discovering abnormalities that predispose to the development of atopic dermatitis. Dry skin has been described for many years in atopic dermatitis in people and the presence of abnormalities in skin barrier function have been demonstrated. The stratum corneum has a lipid bilayer present between the corneocytes, which acts as a barrier to water loss from the skin and to penetration of external material in the skin. (See Figure 1) Classically, the function of this structure can be assessed by measuring transepidermal water loss (TEWL), a technique that has been evaluated in dogs and has been shown to correlate with experimentally-induced abnormal barrier function. Older dogs develop increased TEWL, and it has been speculated this may be associated with increased incidence of disease. We now know that atopic dogs also have abnormal TEWL and that the abnormality is present prior to the development of atopic dermatitis. The abnormal TEWL of atopic dogs also is associated with decreases in ceramides major constituents of the lipid epidermal barrier that has been associated with normal function.
Another important component of the epidermal barrier function is filaggrin, a protein derived from keratohyalin granules in the skin. In people with atopic dermatitis, genetically programmed filaggrin synthesis abnormalities are associated with development and severity of atopic dermatitis, but not atopic asthma. Recent work in the beagle model of atopic dermatitis in dogs has shown filaggrin abnormalities are present in these dogs as well. Genetic studies have shown that atopic dogs have genetic differences from normal dogs and that some of these genes are located in regions believed to be important with innate immune function and epidermal barrier function. These observations showing abnormal TEWL and filaggrin and epidermal barrier function, along with the fact that some of these are present prior to development of atopic dermatitis, has led to a new concept about how the disease develops. It has been proposed that the barrier abnormalities may allow absorption of allergens, and it is this abnormal absorption and presentation of allergen that leads to the development of atopic dermatitis.
Figure 1: This drawing of the skin shows the epidermis with the lipid bilayer between corneocytes. The purple dots represent the extrusion of the lamellar granules into the intercellular space between the keratinocytes. The brown lines are the development of the lipid bilayer and the green represents the emulsion contributed to the skin surface from the sebaceous and apocrine glands.
These new insights into the pathogenesis of atopic dermatitis may lead to new treatments or even methods of preventing the development of disease in genetically prone animals if the barrier function can be normalized. Though research has not been done to show this in atopic dogs, it is known that the TEWL can be improved with a combination dietary supplements (pantothenate, choline, nicotinamide, histidine, and inositol) at least in normal animals. This new and exciting research is currently stimulating new approaches to studying and managing atopic dermatitis in dogs.