Atopic dermatitis phenotypes and the need for personalized medicine

Abstract

Purpose of review: To describe recent developments in therapies which target the molecular mechanisms in atopic dermatitis.

Recent findings: Current advances in the understanding of the molecular basis of atopic dermatitis are leading to the stratification of different atopic dermatitis phenotypes. New therapies offer the option to target-specific molecules involved in the pathophysiology of atopic dermatitis. Current new therapies under investigation aim to modulate specific inflammatory pathways associated with distinctive atopic dermatitis phenotypes, which would potentially translate into the development of personalized, targeted-specific treatments of atopic dermatitis.

Summary: Despite the unmet need for well tolerated, effective, and personalized treatment of atopic dermatitis, the current standard treatments of atopic dermatitis do not focus on the individual pathogenesis of the disease. The development of targeted, phenotype-specific therapies has the potential to open a new promising era of individualized treatment of atopic dermatitis.

Box 1

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FIGURE 1

AD immunopathology and mechanisms of action of targeted therapies. AD immunopathology (central picture): damage in the skin barrier promotes the penetration of allergens into the skin and facilitate the entrance of microbial products. Antigens are taken up by LC and IDEC, initiating the sensitization and T-cell driven immune response. In the acute phase, Th2 and Th22 responses are augmented with contribution of Th17. The proinflammatory mediators produced in this phase further contribute to the impairment of the skin barrier and to the activation of different cell types that enhance the skin inflammation. Progression into chronicity involves an increased role of the Th1 pathway, but with important contributions of other T-cell subpopulations. Targeted therapies (external pictures, counter-clockwise from top left). Mechanism of action of nemolizumab (anti-IL-31 receptor antibody); omalizumab (anti-IgE antibody); JAK inhibitors; dupilumab (anti-IL-4/IL-13 receptors antibody); PDE4 inhibitors; and ustekinumab (anti-IL-12/-23p40 antibody). AD, atopic dermatitis; B, basophil; DC, dendritic cell; E, eosinophil. IDEC, inflammatory dendritic epidermal cells; ILC, innate lymphoid cell; LC, Langerhans cells; MC, mast cell; PDE, phosphodiesterase; Th, T-helper.