Endophenotypic Variations of Atopic Dermatitis by Age, Race, and Ethnicity

Abstract

Atopic dermatitis (AD) is a heterogeneous disease with unique clinical manifestations across age groups and race/ethnicities. Characteristic molecular mechanisms, known as endotypes, including IgE level, status of epidermal barrier genes, and differential cytokine axes activation in the background of T_H2 upregulation, are also implicated. In adults, the T_H22, T_H17, and T_H1 pathways are involved, and a weakened epidermal barrier is characteristic. In contrast, pediatric patients exhibit less T_H1 activation, and defects in epidermal lipid metabolism contribute to their barrier defect. European American patients are characterized by higher differential T_H2/T_H22 activation, lower expression of the T_H1/T_H17 axes, and suppression of filaggrin (FLG) and loricrin gene expressions. Asian patients have accentuated polarity of the T_H22/T_H17 pathways, and also exhibit epidermal barrier defects despite relative maintenance of FLG and loricrin expression. African American patients do not exhibit FLG mutations and have distinct attenuation of T_H17/T_H1 axes activation. Dissecting the molecular basis of AD endotypes has provided an important framework upon which targeted therapeutics are being developed. An increased understanding of these subtypes and the alteration of biomarkers that correlate with disease can ultimately push AD treatment in an era of personalized medicine.

Keywords: Age; Atopic dermatitis; Dupilumab; Endotypes; Ethnicity; Genetics; Phenotypes; Precision medicine; Race.