Title: Understanding the atopic dermatitis-psoriasis phenotypic switch through a mechanistic epidemiology approach

AbstractAtopic Dermatitis (AD) and psoriasis (PsO) are two frequent dermatologic conditions that may co-occur in a cluster of patients, yet current understanding of how these two conditions relate to one-another remains poorly understood. One way to better understand their relationship is through a process called phenotypic switching, where AD and PsO can turn into one another. We utilized a pharmacovigilance-based epidemiological approach to better understand this phenomenon. By generating adverse event-related disproportionality signals for various therapies and therapeutic classes used in AD and PsO, several potential mechanisms for the AD-PsO phenotypic switch were uncovered. This includes mechanisms involving TH2 and TH22 repolarization, TH17 and TH22 repolarization, and immune shifting between TH1, TH17, and TH2 cells. Clinically and immunologically related conditions were also analyzed to gain a clearer understanding of the specificity of the switch from PsO to an eczematous phenotype. Together, these findings provide mechanistic insight into the underpinnings behind the AD-PsO phenotypic switch through a novel approach, adding evidence to the fluid nature of immune phenotypes in common medical conditions. One Sentence SummaryThe atopic dermatitis-psoriasis phenotypic switch creates an overlap phenotype that is likely TH22-driven.