Clinical Performance Enhancing Program 1-2 (CPEP 1-2) : Update on the pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is a common, but chronic, pruritic, inflammatory skin condition. However, its pathogenesis is not completely understood, which is complex & heterogeneous, including skin barrier dysfunctions, allergy/immunology, and pruritus We can easily observe the barrier dysfunctions in patients with AD. Among various molecules that involve in the skin barrier composition, filaggrin and tight junction (tJ) molecules are the main stream of interests. Barrier dysfunction in line with filaggrin deficiency will lead to Th2 skewing conditions, which may play an important role in the development of AD. The role of TJs in AD remains unknown. A knockout study of claudin-1, a TJ-specific integral membrane protein, demonstrated that TJs function as paracellular diffusion barriers in the epidermis. In the terms of Immunology and allergy, Th2 deviation has been regarded as primary reason for the disease. But recently, immune changes beyond the initial Th2 concept were defined in AD, with a role for specialized dendritic cells as well as newly identified Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self-antigens. Another main component of AD pathogensis is pruritus. There are so many mediatiors which are able to induce or aggravate itching sense including Histamine 4 receptor agonist, IL-31, Nerve growth factor (NGF) and they can interplay between pruritus and skin barrier, allergy/immunology In short, Patients with AD have genetically determined risk factors that affect their skin barrier function and immune responses and interact with environmental triggers. Clinically, this results in intensely pruritic, inflamed skin that allows the penetration of irritants and allergens and predisposes patients to colonization and infection by microbial organisms. Insights into the complex relationship between skin barrier, immune abnormalities and pruritus should lead to more understanding of AD and to more appropriate therapy for AD.