Atopic Dermatitis

Initial cutaneous sensitization in atopic dermatitis occurs when antigens such as allergens (pollen), viruses, or bacteria come into contact with the epidermis and penetrate the epidermal barrier. Antigens are processed by dendritic cells, causing priming of T helper 2 cells (antigen presentation) and inflammation. In atopic individuals, a mixture of factors can be associated with inflammatory flares. As part of the changes associated with eczematous flares, Th2 cells are activated and produce cytokines such as IL-4 and IL-13 which perpetuate an inflammatory response. Additionally, non-specific responses such as itch can lead to localized inflammation. Atopic dermatitis is a Th2 driven process. Activated T cells produce IL-4 and IL-13. This causes vasodilation (redness of skin) and infiltration of immune cells (macrophages, neutrophils, b cells). Skin inflammation and an enhanced immune response contribute to the pathophysiology of AD. cAMP is the main second messenger involved in regulating immune responses. Activation of cellular receptors on T cells leads to conversion of cAMP to AMP by the intracellular enzyme PDE4, which perpetuates an immune response, release of cytokines, and inflammation. Inhibition of PDE4 enhances the effects of cAMP, thereby suppressing Th2 immune responses and reducing inflammation. IL-31 is released from T cells as part of the immune response in atopic dermatitis. IL-31 binds to its receptor on neurons. IL-31 receptor activation leads to intracellular signaling and propagation of neuronal transmission. Propagation of a nerve signal results in the sensation of itch.