The Twenty-Seven Year Itch of Canine Atopic Dermatitis

Atopic dermatitis is the most common chronic inflammatory and pruritic skin disease in dogs. The characteristic clinical features and pathogenesis are comparable with those in human atopic dermatitis (hAD). In the last three decades, much has been unraveled regarding the pathogenesis in both species. Consequently, various therapeutic strategies have been proposed of which some have proven their effectiveness in dogs. However, nowadays canine atopic dermatitis (cAD) is still considered a challenging disease to manage. The reason for this matter lies beneath the fact that this skin condition is a multifaceted disease with a diverse nature.

Many cells play an important role in the pathogenesis of cAD. Skin-infiltrating cells of lesional skin are constituted of T-lymphocytes, antigen-presenting cells (APC) as Langerhans` cells (LH) and dermal dendritic cells, mast cells, low numbers of eosinophils and neutrophils, and rare B-lymphocytes. At the onset of the disease, allergens from epidermal exposure become bound to epidermal LH cells and are presented to T-cells in the regional lymph node. The activated T-cells are mainly T-helper 2 cells (Th2). These cells produce cytokines (IL-4, IL-5, IL-13) responsible for the activation of allergen-specific IgE production by B-cells. Infiltration of the Th2 cells from the peripheral blood into the skin in the acute phase can be regulated by specific chemokines and their receptors. Chemokine receptor 4 (CCR4) is expressed on Th2 cells. Additionally, expression of thymus and activation- regulated chemokine (TARC), a functional ligand of CCR4 which is produced by keratinocytes, was found to be specific for cAD lesions. When allergens cross-link IgE antibodies bound to the high-affinity receptor (FcεRI) on the surface of mast cells, mediators as histamine, leukotrienes, and substance P are released upon mast cell degranulation. It is this cascade of reactions that is involved in the production of pruritus and development of inflammation. In chronic lesional skin cytokines as IFN-γ and IL-12 produced by Th1 cells exert their effects. Several studies have reported indications for a mixed Th cell responsiveness in chronic lesional skin. At this moment, it is unknown if other specialized T-helper subsets as Th17 and Th22 may also be involved in the pathogenesis of cAD. Another subset is formed by the regulatory T-cells (Tregs)which play an important role in the regulation of normal immune responses. Targets of these cells include B cells, mast cells and both Th1 and Th2 cells. The Tregs are able to suppress their target cells by producing the regulatory cytokines IL-10 and TGF-β. It is likely that in dogs TGF-β and IL-10 are associated with tolerance to allergens. However, whether or not Tregs play a role in the pathogenesis of cAD is currently unclear.

In previous years, cAD has been found to be associated most commonly with IgE antibodies to environmental allergens as house dust mites, storage mites and various pollens. Both genetic and environmental factors play a role in this IgE production. However, in some dogs fulfilling the clinical criteria for AD, a negative intradermal test and allergen-specific IgE serology is seen. In humans, a non-IgE associated form of AD, or intrinsic AD, exists. It is currently believed that this also occurs in a small proportion of dogs.  [...]