Molecular Mechanisms in the Etiopathology of Rosacea—Systematic Review

Rosacea is a chronic inflammatory skin disorder of multifactorial pathogenesis, in which dysregulated innate immunity, neurovascular dysfunction, oxidative stress, and microbiome imbalance are central contributors. Recent molecular studies have revealed altered cytokine expression (e.g., IL-1β, IL-6, IL-36 family), aberrant activation of signaling pathways (STAT3, NF-κB, MAPKs), and enhanced expression of innate immune receptors such as TLR2,b TLR4, and TLR7, all of which promote chronic inflammation, angiogenesis, and barrier dysfunction. This systematic review was performed according to PRISMA guidelines. A total of 1425 records were retrieved from PubMed, Scopus, and Web of Science, and 14 studies met the inclusion criteria. The included studies comprised both clinical cohorts and translational experimental investigations using human samples. Reported findings consistently confirmed systemic and tissue-specific inflammatory activity, with elevated circulating monocytes, indoleamine 2,3-dioxygenase, and inflammatory indices, as well as tissue expression of STAT3, NF-κB, MAPKs, and cathelicidin fragments. Oxidative stress markers (TOS, OSI, AOPP, MMP-9) and hypoxia-related molecules (HIF-1α) were significantly increased in patients, correlating with disease severity and vascular manifestations. Taken together, these results highlight that rosacea involves both cutaneous and systemic molecular alterations. The evidence identifies multiple biomarkers with diagnostic potential and provides mechanistic insights into immune, vascular, and metabolic dysregulation. Future research should aim to validate these findings in larger cohorts, establish standardized biomarker panels, and explore novel therapeutic strategies targeting key molecular pathways.