Rosacea through the lens of the exposome: From triggers to systems biology

The dermatologic exposome encompasses the full spectrum of environmental and lifestyle exposures that interact with an individual's genome and immune system to influence skin biology. Originally introduced within environmental and molecular epidemiology, the exposome framework has been increasingly applied in dermatology to explain complex, multifactorial conditions. While it has been most extensively studied in atopic dermatitis, its relevance to other chronic inflammatory dermatoses is becoming increasingly apparent.1 Rosacea has long been recognized as a chronic inflammatory facial dermatosis most commonly presenting with centrofacial erythema and/or papulopustular lesions. Beneath these visible manifestations lies a biologically nuanced condition shaped by an individual's lived environment. In their comprehensive review, Grafanaki et al.2 bring this broader reality into focus by integrating molecular insights with the emerging science of the exposome, offering a framework that is both timely and urgently needed by clinicians and researchers. The strength of their work is twofold. First, the authors synthesize decades of fragmented evidence into a cohesive narrative that acknowledges rosacea as more than a dermatologic trait. They delineate the convergence of genetic predisposition, neurovascular instability, and immune dysregulation, while assigning equal importance to extrinsic triggers such as airborne pollutants, diet, and cosmetic practices. Second, they link these mechanistic insights to the real-world experiences of patients, including psychosocial burden, diagnostic disparities in skin of colour and the growing influence of social media misinformation. This dual emphasis addresses a longstanding gap in the field. Perhaps the most paradigm-shifting contribution of the review is its emphasis on fibroblasts as central orchestrators of rosacea pathology. Recent single-cell RNA sequencing studies identifying aberrant fibroblast subsets and prostaglandin D2 synthase-driven vasodilation challenge long-standing keratinocyte- and mast cell-centric models of disease. Rather than serving merely structural roles, fibroblasts emerge as integrative regulators of immune and neurovascular signalling. This conceptual shift reframes rosacea as a disorder of stromal-immune crosstalk and highlights a previously overlooked therapeutic target. The authors further reinforce a systems-level view of rosacea through their discussion of its genetic and epigenetic architecture. Genome-wide association studies demonstrate overlap between rosacea susceptibility loci and those implicated in autoimmune disease, while variants affecting VEGF signalling and oxidative stress pathways point to vascular instability and impaired antioxidant defences. In parallel, mounting evidence over the past decade has established non-coding RNAs as key orchestrators of epigenetic gene regulation across health and disease3 and potential drivers of various cutaneous pathologies.4 Within the field of rosacea research, emerging data on lncRNAs, miRNAs and m6A-modified transcripts underscore RNA-mediated control of angiogenesis and inflammation, opening new avenues for molecular classification and targeted intervention. Lastly, the review underscores an unresolved tension in rosacea research: causality versus correlation. Mendelian randomization studies linking rosacea with inflammatory bowel disease, metabolic traits and smoking behaviours strengthen the argument for shared inflammatory architectures, but they do not yet explain directionality at the tissue level. Integrating exposome data with longitudinal multi-omics data—ideally before disease onset—will be essential to distinguish causal drivers from downstream consequences. By integrating exposomal science with molecular dermatology and patient experience, this review reframes rosacea as more than a chronic inflammatory facial skin disorder; it becomes a model for exposome-driven inflammatory disease. The challenge now is translation. Future progress will depend on exposome-informed clinical trials, biomarker-guided patient stratification and therapeutic strategies that move beyond suppressing visible clinical findings to addressing upstream environmental and systemic drivers. In this regard, Grafanaki et al. provide not only a synthesis of current knowledge, but also a compelling roadmap for where the field must go next. None to be disclosed. Not applicable. Not applicable. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.