Atopic dermatitis in dogs_novel insights into mechanisms of disease

    Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)


    Atopic dermatitis in dogs Novel insights into mechanisms of disease Atopic dermatitis in dogs is the most important canine pruritic disorder, described for the first time in 1971. It is defined as a genetically-predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features, associated with IgE antibodies specific for environmental allergens such as house dust mites and grass pollen. Atopic dermatitis in dogs harbors many similarities with its human counterpart such as the young age of onset, the clinical presentation and the genetic predisposition to develop the disease. Atopic dermatitis in human and dogs has been largely viewed as a disease of immunologic etiology. Key roles are played by dendritic cell signaling, the Th1/T2 cell dysregulation, IgE production, and mast cell hyperreactivity in the development of the pruritic inflammatory dermatosis. However, more recently it has been proposed that an intrinsic defect in the epithelial cell leads to a dysfunction in the epidermal barrier followed by immune system activation. In this thesis major research questions addressed, concern the role of fatty acids and their metabolic enzymes in the inflammation in canine atopic dermatitis and their possible modulatory effect. In addition, we have characterized the immunologic phenotype of atopic skin, particularly at the level of mRNA expression. It is concluded that spontaneous atopic dogs show a mixed Th1/Th2 inflammatory pattern which is consistent with human findings. In addition, it was found that lesional skin of atopic dogs contains a significant higher amount of arachidonic acid, which metabolism results primarily in inflammatory metabolites, the 2-series prostaglandins and the 4-series leukotrienes. This likely contributes to the inflammatory reaction seen in lesional skin. A question for future research is how the arachidonic content in lesional skin becomes this high. Several explanations for this high arachidonic acid content are discussed, whereas one of these have been addressed in this thesis and concern the cell infiltrates in lesional atopic skin. As atopic skin inhabits increased amounts of inflammatory cells and as arachidonic acid is the main fatty acid in the membranes of these cells, this might explain our finding of the high amount of AA in lesional skin. It is further reasoned that these cell infiltrates in lesional (and non-lesional) skin explain the high levels found for 5-lipoxygenase, 5-lipoxygenase-activating protein, leukotriene A4 hydrolase and microsomal prostaglandin-E synthase. These observations support future therapies with anti-leukotriene drugs in atopic dogs. It is very likely that in dogs, as in human, an epidermal barrier dysfunction together with an immunologic disturbance leads to atopic dermatitis; however it is not yet known which of these two systems initiate disease development. Based on the currently known similarities between human and canine atopic dermatitis now supplemented with our findings, there is strong evidence that the dog might serve as a good model for further research into human atopic dermatitis as well.
    Original languageUndefined/Unknown
    QualificationDoctor of Philosophy
    Awarding Institution
    • Utrecht University
    • Willemse, Ton, Primary supervisor
    • Bruijnzeel - Koomen, C.A.F.M., Supervisor, External person
    • Rutten, Victor, Supervisor
    • Knol, E.F., Co-supervisor, External person
    Award date9 Dec 2009
    Print ISBNs978-94-90122-93-5
    Publication statusPublished - 9 Dec 2009

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