Flushing New Light on Rosacea

Abstract

The study "Integrated omics reveal the molecular characterization and pathogenic mechanism of rosacea" (Zhang et al, 2023) presents the first multiomics integrative analysis comparing proteomic and transcriptomic signatures of lesional and nonlesional rosacea skin (in contrast to healthy and psoriatic skin), leading to the identification of novel disease drivers. The findings of Li's group confirm earlier reports of immune disturbances driving rosacea, demonstrating a unique inflammatory microenvironment (Buhl et al, 2015; Steinhoff et al, 2011). However, the identification of novel mediators likely implicated in the formation of the unique nerve-hypersensitive microenvironment, in particular, forms one of the main achievements of this research study. The group identified an increased expression of axon extension DPYSL2 and DBNL regulators, which may explain the increased nerve fiber network observed in the (facial) skin of patients with rosacea (Schwab et al, 2011). Prior research has well established that genetic predisposition (Deng et al, 2023) plus trigger factors (Steinhoff et al, 2013) activate hypersensitive sensory nerve endings in rosacea skin, resulting in neuroinflammation and thus vasodilation (erythema), plasma extravasation (edema), and leukocyte infiltration (inflammation) as well as pain (Steinhoff et al, 2011). We can elaborate on this vicious phenomenon of nerval sensitization in patients with rosacea with this study, a novel putative mechanistic foundation, providing potential glimpses into mediators that might lead to changes in the nerve fiber network of patients with rosacea. However, a strong limitation of this study is the missing functional examination linking DPYSL2 and DBNL to nerval branching, producing a rosacea-like phenotype when challenged with triggers associated with rosacea.