Integrative concepts of rosacea pathophysiology, clinical presentation, and new therapeutics

Abstract

Rosacea is a chronic relapsing inflammatory skin disease with high prevalence world-wide. Recent research suggests that dysregulation of innate and adaptive immune pathways as well as neuro-vascular changes are present, with different degrees of importance in the various subtypes. Neither the etiology, genetics, nor pathophysiological basis of the vascular, inflammatory or fibrotic changes are well understood. The clinical spectrum comprises a huge variability from erythema (vasodilation) to papules/pustules (inflammatory infiltrate) to phymata (fibrosis, glandular hyperplasia) making it a valuable human disease model to understand the interplay between the neurovascular and immune systems as well as the progression from chronic inflammation to fibrosis in skin. The lack of appropriate animal models emphasizes the importance of further translational research validating observed molecular pathways under disease conditions.

A wide spectrum of physical (UV, temperature), biological (microbiota, food) and endogenous (genetic, stress) stimuli have been discussed as 'trigger factors' of rosacea. Novel findings implicate keratinocytes, smooth muscle cells, endothelial cells, macrophages, mast cells, fibroblasts, Th1/Th17 cells, antibody-producing B cells, and neurons in the pathobiology of rosacea. So far, pattern recognition receptors like TLR2, transient receptor potential ion channels (TRPV1, TRPA1), cytokines, chemokines, and proteases have been implicated as critical receptors/mediators. However, our understanding of the interactive networks on the molecular level is very limited. Identification of critical molecular components of the inflammatory cascade including antimicrobial peptides, the IL-1β inflammasome, TNF, IFNγ, proteases, and neuropeptides may provide the basis for novel pathomechanism-based therapeutic approaches for this frequent and bothersome skin disease.

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