BackgroundRosacea, a chronic inflammatory skin disorder etiologically associated with immune cells and the antibacterial peptide cathelicidin LL-37, can be effectively treated by oral carvedilol administration.ObjectiveTo investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment.MethodsSkin samples of patients with rosacea were subjected to histopathological (hematoxylin and eosin) and immunohistochemical (CD68, Toll-like receptor 2 (TLR2), kallikrein 5, cathelicidin, TNF-α, and IL-1β) evaluation. An in vivo murine rosacea-like inflammation model was established by LL-37 intradermal injection with or without carvedilol gavage-based pretreatment. Erythema proportion (Image J) and skin redness (L*a*b colorimetry) were quantified. Murine skin samples underwent pathological examination for inflammatory status and immunofluorescence staining. Murine skin and lipopolysaccharide-stimulated RAW 264.7 cells with or without carvedilol pretreatment were evaluated by quantitative reverse transcription-polymerase chain reaction and western blotting. Clinical facial images of patients were obtained using the VISIA skin analysis system before, 4, and 6 months following oral carvedilol administration.ResultsRosacea skin lesions exhibited more pronounced inflammatory cell infiltration than peripheral areas, with profound macrophage infiltration and inflammatory cytokines (TLR2, kallikrein 5, cathelicidin, TNF-α, and IL-1β). In vivo, carvedilol alleviated inflammation in LL-37 mice, down-regulating TLR2, KLK5, and cathelicidin expression. In vitro, carvedilol decreased TLR2 expression in RAW 264.7 cells, further reducing KLK5 secretion and LL-37 expression and ultimately inhibiting rosacea-like inflammatory reactions. Clinical manifestations and facial redness obviously improved during 6-month follow-up with systemic carvedilol administration.ConclusionCarvedilol is effective against rosacea, with inhibition of macrophage TLR2 expression as a novel anti-inflammatory mechanism.

Background Rosacea and cardiovascular diseases (CVD) are chronic inflammatory disorders. While CVD is the leading cause of mortality globally, increasing evidence indicates that CVD prevalence could be higher among patients with rosacea. Aims This review aimed to determine the association between the prevalence of CVD and rosacea. Patients/Methods A systematic review of observational studies with controls available in MEDLINE, EMBASE, PubMed, Cochrane, and Web of Science databases was conducted. We performed a pooled meta‐analysis using random‐effects weighting. Overall, 11 studies met the inclusion criteria, which indicated increased odds for at least one risk factor of CVD, including diabetes, high blood pressure, or dyslipidemia. Results The pooled meta‐analysis indicated an association of rosacea with higher odds of insulin resistance or diabetes (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.97‐1.45), high systolic blood pressure (OR, 1.96; 95% CI, 1.35‐2.84), dyslipidemia (OR, 1.50; 95% CI, 1.19‐1.88), and CVD (OR, 6.65; 95% CI, 2.80‐15.76). No publication bias was detected. The effect of confounding factors due to overlapping symptoms and lack of individual‐level data were limitations of this review. Conclusion Patients with rosacea have a high risk of CVD. However, further studies are warranted to confirm the association between rosacea and CVD.

Background: Rosacea, a chronic in ammatory disorder of the facial skin, is effectively treated by intense pulsed light (IPL).Objective: To explore the potential molecular mechanism underlying the photobiomodulation effect of IPL for rosacea treatment.Methods: Skin samples from patients with rosacea were subjected to histological and immunohistological staining. Ten patients were followed up after IPL treatment using the VISIA ® skin analysis system, and the severity was assessed. In vivo, skin changes in mice with rosacea-like in ammation induced by intradermal injection of 320 μM LL-37 with or without IPL treatment were evaluated using L*a*b colorimetry as well as histological and immunological staining. In vitro, LL-37stimulated mast cells (MCs) with or without IPL treatment were evaluated for protein expression of matrix metalloproteinase (MMP)-9, kallikrein-related peptidase 5 (KLK5), and cathelicidin using western blotting and qRT-PCR.Results: Profound in ltration of in ammatory cells and evident MC degranulation were found in rosacea skin lesions. The expression of rosacea-related biomarkers and in ammatory cytokines was higher in lesion areas than in non-lesional areas, as demonstrated via immunochemical staining. In all patients, rosacea severity reduced after IPL therapy. In vivo, IPL alleviated in ammation in mice with rosacea-like in ammation, as demonstrated by the signi cantly decreased MMP-9, KLK5, and cathelicidin expression and reduced percentage of degranulating MCs. In vitro, IPL decreased MMP-9, KLK5, and cathelicidin expression in P815 cells, reducing the release of in ammatory cytokines and inhibiting rosacea-like in ammatory reactions. Conclusion:The photobiomodulation effect of IPL for rosacea treatment may inhibit MC degranulation and alleviate in ammatory reactions.