The causal relationship between blood metabolites and rosacea: A Mendelian randomization.

BACKGROUND: An increasing amount of research demonstrates that metabolic disorders are related to rosacea. However, the correlations and causal relationships among them remain unknown. METHODS: We conducted not only forward 2-sample MR (Mendelian randomization) analyses but also reverse MR analyses which showed positive results in the forward MR analysis. In the forward MR analyses, inverse-variance weighted (IVW) and MR-Egger were performed as MR analyses. Cochran's Q test and the MR-Egger Intercept were used for sensitivity analyses. Concerning reverse MR analyses, IVW, MR-Egger, weighted median, simple mode, and weighted mode were applied. Cochran's Q test, MR-Egger Intercept, and MR pleiotropy residual sum and outlier (MR-PRESSO) outlier test were applied as sensitivity analyses. RESULTS: A total of 24 metabolites and 1 metabolite ratio were shown to have a causal effect on rosacea. N-lactoyl phenylalanine (N-Lac-Phe) was estimated as statistically significant by Bonferroni correction. Interestingly, we found three metabolites that were negatively associated with rosacea, especially caffeine, which are in line with the results of a large cohort study of females. For reverse MR analysis, we revealed that rosacea could potentially decrease the generation of two metabolites: octadecenedioate (C18:1-DC) and methyl vanillate sulfate. CONCLUSION: This study identified blood metabolites that may be associated with the development of rosacea. However, the exact mechanism by which these positive metabolites influence rosacea remains uncertain due to the paucity of experimental investigations. The combination of genetics and metabolomics offers novel viewpoints on the research of underlying mechanisms of rosacea and has significant value in screening and prevention of rosacea.

Randomised, split-face study of a dermocosmetic cream containing Sphingobioma xenophaga extract and Neurosensine® in subjects with rosacea associated with erythema and sensitive skin.

INTRODUCTION: Rosacea is a chronic inflammatory skin condition associated with erythema, inflammation and skin sensitivity. OBJECTIVES: To assess the benefit of a dermocosmetic cream (DC cream) containing Sphingobioma xenophaga extract and soothing agent in adult females with rosacea-associated erythema and sensitive skin. MATERIALS AND METHODS: During phase 1, DC was applied twice daily on the randomized half-face and compared to usual-skincare (USC) for 28 days. During phase 2, DC was applied on the full face twice daily for 56 days. Clinical, instrumental and skin sensitivity assessments were performed at all visits; demodex density (standardized skin surface biopsy (SSSB) method) was performed at baseline and D28, quality of life (QoL) was assessed using the stigmatization questionnaire (SQ), Rosacea Quality of Life index (ROSAQoL) and Dermatology Life Quality Index (DLQI) at baseline and D84. RESULTS: At D28, a significant benefit of DC over USC was observed for erythema, tightness, burning and stinging (all p ≤ 0.05), erythema measured by chromameter (p < 0.01), corneometry and transepidermal water loss (p < 0.0001 and p < 0.05, respectively), skin sensitivity (p < 0.001) and significant reduction of mean demodex density (p < 0.05) on the DC side. At D84, DC significantly (all p < 0.05) improved clinical signs and symptoms on both sides of the face compared to baseline; SQ, ROSAQoL and DLQI scores improved by 40.4%, 25.0% and 55.7%, respectively compared to baseline. Tolerance was excellent. CONCLUSION: DC significantly improved erythema, skin sensitivity, demodex count, QoL and feeling of stigmatization of subjects with rosacea and is very well tolerated.

Rosacea: Common Questions and Answers.

Rosacea is a chronic inflammatory skin disease of the central face, affecting 5% of the population. The exact etiology is unknown. A diagnosis is made based on the updated 2017 National Rosacea Society Expert Committee guidelines, including fixed erythema, phymatous changes of skin thickening due to sebaceous gland hyperplasia and fibrosis, papules, pustules, telangiectasia, and flushing. Delays in an accurate diagnosis and treatment may occur in skin of color due to difficulty visualizing erythema and telangiectasia. The daily use of sunscreen, moisturizers, and mild skin cleansers and avoidance of triggers are essential aspects of maintenance treatment. Effective topical treatment options include alpha-adrenergic receptor agonists for flushing and ivermectin, metronidazole, and azelaic acid for papules and pustules. Systemic treatments include nonselective beta blockers for flushing, low-dose doxycycline, and isotretinoin for papules and pustules. Rosacea can significantly affect a patient's emotional health and quality of life. A referral for care is recommended for fixed phymatous changes and ocular rosacea. (Am Fam Physician. 2024;109(6):533-542.

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study.

INTRODUCTION: Prior research has explored the relationship between inflammatory skin disorders and breast cancer (BC), yet the causality of this association remains uncertain. METHODS: Utilizing a bidirectional two-sample Mendelian randomization (MR) approach, this study aimed to elucidate the causal dynamics between various inflammatory skin conditions-namely acne, atopic dermatitis, psoriasis vulgaris, urticaria, and rosacea-and BC. Genetic variants implicated in these disorders were sourced from comprehensive genome-wide association studies representative of European ancestry. In the forward MR, BC was posited as the exposure, while the reverse MR treated each inflammatory skin disease as the exposure. A suite of analytical methodologies, including random effects inverse variance weighted (IVW), weighted median (WME), and MR-Egger, were employed to probe the causative links between inflammatory skin diseases and BC. Sensitivity analyses, alongside evaluations for heterogeneity and pleiotropy, were conducted to substantiate the findings. RESULTS: The MR analysis revealed an increased risk of acne associated with BC (IVW: OR = 1.063, 95% CI = 1.011-1.117, p = 0.016), while noting a decreased risk of atopic dermatitis (AD) in BC patients (IVW: OR = 0.941, 95% CI = 0.886-0.999, p = 0.047). No significant associations were observed between BC and psoriasis vulgaris, urticaria, or rosacea. Conversely, reverse MR analyses detected no effect of BC on the incidence of inflammatory skin diseases. The absence of pleiotropy and the consistency of these outcomes strengthen the study's conclusions. CONCLUSION: Findings indicate an elevated incidence of acne and a reduced incidence of AD in individuals with BC within the European population.

Health-related Quality of Life of Patients with Rosacea: A Systematic Review and Meta-analysis of Real-world Data.

Patients with rosacea commonly experience stigmatization, which induces stress and thereby exacerbates their symptoms. Given the strong effects of rosacea on health-related quality of life (HRQoL), addressing the physical and psychosocial aspects of rosacea is essential. To examine the effects of rosacea on HRQoL, we conducted a systematic review and meta-analysis involving real-world data. PubMed, EMBASE, and the Cochrane Library were searched, and randomized controlled trials (RCTs), cross-sectional studies, and case series evaluating the HRQoL of patients with rosacea were included. HRQoL assessment tools such as the Dermatology Life Quality Index (DLQI) and Rosacea-Specific Quality-of-Life Questionnaire (RosaQoL) were used. Data on 13,453 patients were retrieved from 52 eligible studies: 4 RCTs, 15 case series, and 33 cross-sectional studies. Compared with healthy controls, patients with rosacea had significantly lower DLQI scores (standardized mean difference [SMD] = -1.09, 95% confidence interval [CI] = -0.81 to -1.37). The DLQI scores after treatment were higher than those before treatment (SMD = -1.451, 95% CI = -1.091 to -1.810). The pooled estimates for the overall DLQI and RosaQoL scores were 8.61 and 3.06, respectively. In conclusion, patients with rosacea have lower HRQoL compared with healthy individuals, and treatment for rosacea improves their HRQoL.

Efficacy and safety comparison between pulsed dye laser and intense pulsed light configured with different wavelength bands in treating erythematotelangiectatic rosacea.

Previous clinical studies have shown that pulsed dye laser (PDL) and intense pulsed light (IPL) are effective for treating erythematotelangiectatic rosacea(ETR). This article aims to compare the efficacy and safety of PDL and IPL at three different wavelength bands (broad-band, single-narrow-band, and dual-narrow-band) in treating ETR. Sixty subjects with ETR were randomly categorized into four groups and received one of the following laser treatments: PDL (595 nm), IPL with Delicate Pulse Light (DPL, 500-600 nm), IPL with M22 590 (590-1200 nm), or IPL with M22 vascular filter (530-650 nm and 900-1200 nm). Four treatment sessions were administered at 4-week intervals, with one follow-up session 4 weeks after the final treatment. The efficacy of the four lasers was evaluated by comparing the clinical symptom score, total effective rate, VISIA red area absolute score, and RosaQoL score before and after treatment. The safety was evaluated by comparing adverse reactions such as pain, purpura, erythematous edema, and blister. All 60 subjects completed the study. Within-group effects showed that the clinical symptom score, VISIA red area absolute score, and RosaQoL score of all four groups were significantly reduced compared to before treatment (p < 0.001). Between-group effects showed no statistically significant difference among the four laser groups. Safety analysis showed that all four lasers were safe, but the incidence of blister was higher in the M22 vascular group. Nonpurpurogenic PDL, DPL, M22 590, and M22 vascular were equally effective in treating ETR and were well-tolerated. ClinicalTrial.gov Identifier: NCT05360251.

Correlation between cigarette smoking and alcohol consumption and Rosacea: A two-sample Mendelian randomization study.

BACKGROUND: Controversy persists regarding the causal relationship between Cigarette smoking, alcohol consumption, and Rosacea. This paper employs the Mendelian randomization (MR) method to elucidate the correlation between Cigarette smoking, alcohol consumption, and Rosacea. The aim is to contribute valuable insights to aid in the prevention and early treatment of Rosacea. METHOD: Summary datasets for cigarette smoking parameters (Cigarettes smoked per day, Smoking status: Previous, smoking status: Current) and alcohol consumption (Alcoholic drinks per week) were selected alongside data for Rosacea from genome-wide association studies (GWAS). The Two-sample MR method was employed to analyze the correlation between cigarette smoking, alcohol consumption, and Rosacea. Various MR analysis methods, including inverse variance weighting (IVW), MR-Egger, Simple Mode, Weighted Mode, and Weighted Median, were chosen. IVW served as the primary analysis method. RESULTS: The results indicate a significant negative association between Cigarettes smoked per day and Rosacea. Moreover, a significant positive correlation was observed between Smoking status: Previous and Rosacea. However, no significant associations were found between Smoking status: Current, Alcoholic drinks per week, and Rosacea. CONCLUSION: This study provides further clarity on the association between cigarette smoking, drinking, and Rosacea through a two-sample MR analysis. Notably, the number of cigarettes smoked per day appears to be associated with a reduced incidence of Rosacea, while cigarette smoking cessation may increase the risk. Surprisingly, alcohol consumption does not emerge as a significant risk factor for Rosacea. These findings contribute to a nuanced understanding of the complex relationship between lifestyle factors and the occurrence of Rosacea, offering potential insights for preventive measures and early intervention.

Which factors influence Demodex mite density in standardized superficial skin biopsy in patients with rosacea? A prospective cross-sectional analysis.

Rosacea is a chronic cutaneous disease that manifests with facial erythema, telangiectasia, papules and pustules on the central face. Although the pathogenesis is not well established, rosacea appears to have a close relationship with Demodex mites. The aim of the study was to elucidate the factors influencing Demodex mite density by standardized superficial skin biopsy (SSSB) in patients with rosacea. This prospective, cross-sectional study included 200 patients with rosacea. Clinical characteristics of the patients were recorded and SSSB was used to measure Demodex density (Dd). If Dd was < 5 D/cm2 in the first SSSB, SSSB was repeated 4 more times to avoid false negative results. Of 200 patients, 152 (76%) were females and 48 (24%) males with a mean age of 43.47 ± 11.87 years. Ninety-nine patients (49.5%) had erythematotelangiectatic (ETR) and 101 patients (50.5%) had papulopustular (PPR) subtype of rosacea. Among 200 patients, the ratio of cumulative positive results of the consecutive SSSBs were as follows: 1st SSSB = 125 (62.5%), 2nd SSSB = 155 (77.5%), 3rd SSSB = 170 (85%), 4th SSSB = 173 (86.5%) and 5th SSSB = 174 (87%). The ratio of detecting Demodex infestation in the first SSSB was significantly lower in patients with PPR (55/101, 54.5%) than in patients with ETR (70/99, 70.7%). Median total Demodex mite density and D. folliculorum density were significantly higher in the ETR group than in the PPR group. There was a statistically significant relationship between density of Demodex tails in dermoscopy and positive/negative results of Demodex infestation in SSSB. As a conclusion, Demodex mite density by SSSB was influenced by various factors such as subtypes of rosacea, types of Demodex species, and dermoscopic findings.

Rosacea is strongly associated with melanoma in Caucasians.

Rosacea is often considered a cosmetic problem but is known to be associated with a variety of comorbidities. To identify such risks, we generated two age- and sex-matched real-world cohorts of 122,444 patients each with and without rosacea. In contrast to earlier studies, we found significant associations with malignant melanoma (OR 6.02, 95% CI 5.76-6.32). This association does not exist for an Asian sub-cohort, which could explain previous inconclusive or conflicting reports. Several strongly associated comorbidities like visual disturbances (ICD-10: H53-H54; OR 4.80, 4.68-4.92), metabolic disorders (E73-E79; OR 3.17, 3.11-3.22), joint problems (M25; OR 4.16, 4.08-4.25) and type 2 diabetes (E11; OR 1.62, 1.58-1.65) should be watched as a risk for rosacea patients. Rosacea is associated with some comorbidities and ethnicity may be a risk factor in melanoma development. The retrospective nature of this study and the sole use of ICD-10 code based filtering calls for future validation of our findings. Additionally, confounding factors such as skin type and previous UV exposure should be included in future studies.

The role of vitamins and nutrients in rosacea.

Rosacea is a common inflammatory skin condition displaying symptoms like flushing, erythema, papules, and pustules. Oral antibiotics, despite long-term adverse effects, are often used due to topical treatment limitations, underscoring the need for cost-effective choices like dietary modifications. Our review investigates the role of vitamins and minerals in rosacea, and provides evidence-based recommendations for supplementation and topical treatment of these nutrients for rosacea. An online search was performed on PubMed, Web of Science, Science Direct, Google Scholar, and ClinicalTrials.gov from 1998 to 2023. Included studies were summarized and assessed for quality and relevance in rosacea management. Varied outcomes emerged concerning the impact of essential vitamins and minerals on rosacea treatment. Vitamin A derivatives, specifically oral isotretinoin, demonstrated significant efficacy, with a 90% reduction in lesions, complete remission in 24% of patients, and marked improvement in 57% of patients. Vitamin B3 derivatives, such as topical 1-methylnicotinamide 0.25% and NADH 1%, improved symptoms in 76.4% (26/34) and 80% of patients, respectively. Outcomes for vitamin D, vitamin C, and zinc supplementation varied across studies. However, zinc sulfate solution 5% significantly reduced acne rosacea severity for patients with 40% and 60% exhibiting a moderate or good response, respectively. Omega-3 fatty acids showed significant improvement in alleviating xerophthalmia in 64% of patients with ocular rosacea. Vitamins and minerals hold potential in managing rosacea symptoms, offering a safe and cost-effective alternative or adjunctive treatment option. Currently, there are no established recommendations regarding their supplementation for rosacea. Studies assessing serum levels of vitamins and minerals in relation to rosacea are warranted, as this avenue holds potential for future advancements in the field.

Novel insights into rosacea's role in cancer risk: A Mendelian randomization approach.

BACKGROUND: Chronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long-term inflammatory skin condition and had been reported to link with increased risk for several types of malignancies, but evidence for causality is lacking. OBJECTIVES: To systematically estimate the causal relationship between rosacea and several types of cancer, including cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), actinic keratosis (AK), thyroid cancer, breast cancer, glioma and hepatic cancer, as well as explore the potential underlying pathogenesis. METHODS: We conducted a bidirectional two-sample Mendelian randomization study to probe the potential causal relationships between rosacea and several types of cancer. Instrumental variables were established using genome-wide significant single nucleotide polymorphisms associated with rosacea and cancers. The assessment of causality was carried out through multiple methods, and the robustness of the results was evaluated via sensitivity analyses. RESULTS: There was no significant indication of causal effects of rosacea on CMM (pivw = 0.71), cSCC (pivw = 0.45), BCC (pivw = 0.90), AK (pivw = 0.73), thyroid cancer (pivw = 0.59), glioma (pivw = 0.15), and hepatic cancer (pivw = 0.07), but the genetic risk of rosacea was associated with an increased susceptibility to human epidermal growth factor receptor (HER)-negative malignant neoplasm of breast (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18; pivw = 0.01). TANK (TRAF family member associated nuclear factor kappa B (NFKB) activator) was identified as a common protective gene for both rosacea (OR, 0.90; 95% CI, 0.82-0.99; pivw = 0.048) and HER-negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75-0.98; pivw = 0.032), which was primarily enriched in the negative regulation of NF-κB signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer. CONCLUSIONS: Our findings provide suggestive evidence for causal links between rosacea and HER-negative malignant neoplasm of the breast risk.

Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea: A Nonrandomized Controlled Trial.

Importance: Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease. Objective: To examine the effectiveness, tolerability, and safety of erenumab, an anti-CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing. Design, Setting, and Participants: This single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021. Eligible participants included adults with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. No concomitant rosacea treatment was allowed throughout the study period. Visits took place at the Danish Headache Center, Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark. Participants received 140 mg of erenumab subcutaneously every 4 weeks for 12 weeks. A safety follow-up visit was performed at week 20. Data analysis occurred from January 2023 to January 2024. Intervention: 140 mg of erenumab every 4 weeks for 12 weeks. Main Outcomes and Measures: The primary outcome was mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The mean change in number of days with moderate to severe erythema was a secondary outcome. Adverse events were recorded for participants who received at least 1 dose of erenumab. Differences in means were calculated with a paired t test. Results: A total of 30 participants (mean [SD] age, 38.8 [13.1] years; 23 female [77%]; 7 male [23%]) were included, of whom 27 completed the 12-week study. The mean (SD) number of days with moderate to extreme flushing was reduced by -6.9 days (95% CI, -10.4 to -3.4 days; P < .001) from 23.6 (5.8) days at baseline. The mean (SD) number of days with moderate to severe erythema was reduced by -8.1 days (95% CI, -12.5 to -3.7 days; P < .001) from 15.2 (9.1) days at baseline. Adverse events included transient mild to moderate constipation (10 participants [33%]), transient worsening of flushing (4 participants [13%]), bloating (3 participants [10%]), and upper respiratory tract infections (3 participants [10%]), consistent with previous data. One participant discontinued the study due to a serious adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time. Conclusions and Relevance: These findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding. Trial Registration: ClinicalTrials.gov Identifier: NCT04419259.

Rosacea treatment with 532 nm KTP versus 595 nm pulsed dye laser-A prospective, controlled study.

BACKGROUND: Pulsed-dye lasers (PDL) are one of the standard therapies for rosacea, but alternatives are needed. AIMS: To compare the efficacy and safety of the variable-sequenced, large-spot 532 nm KTP laser to the 595 nm PDL in treating rosacea. MATERIALS AND METHODS: A prospective, controlled, evaluator-blinded study. Patients were treated with either a KTP or PDL with 1-3 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled on Week 6 post-treatment. Clinical outcome was assessed by computer-assisted analysis and by patients and two blinded dermatologists. Pain intensity during treatment and adverse events were documented. RESULTS: Forty-five patients (mean age 51 years) were allocated in a 2:1 ratio to either the KTP or PDL. Erythema in both treatment arms decreased significantly (p < 0.01). Clinical evaluation revealed high improvement. Mean pain intensity was significantly lower with the KTP (2.5/10) than with the PDL (4.1/10). Both lasers showed a good safety profile. Relevant purpura was only seen in the PDL group. CONCLUSIONS: Both the variable-sequenced, large-spot KTP and the PDL demonstrated comparable efficacy in treatment of rosacea. Regarding safety, the KTP exhibited fewer post-treatment reactions. The KTP might serve as a potential alternative to PDL in the treatment of rosacea.

Quercetin attenuates inflammation in rosacea by directly targeting p65 and ICAM-1.

AIMS: Rosacea is an inflammatory skin disease with immune and vascular dysfunction. Although there are multiple treatment strategies for rosacea, the clinical outcomes are unsatisfactory. MAIN METHODS: Combining transcriptome data and the Connectivity Map database quercetin was identified as a novel candidate for rosacea. Next, the therapeutic efficacy of quercetin was substantiated through proteomic analyses, in vivo experiments, and in vitro assays. Additionally, the utilization of DARTS, molecular docking and experimental verification revealed the therapeutic mechanisms of quercetin. KEY FINDINGS: Treatment with quercetin resulted in the following effects: (i) it effectively ameliorated rosacea-like features by reducing immune infiltration and angiogenesis; (ii) it suppressed the expression of inflammatory mediators in HaCaT cells and HDMECs; (iii) it interacted with p65 and ICAM-1 directly, and this interaction resulted in the repression of NF-κB signal and ICAM-1 expression in rosacea. SIGNIFICANCE: We show for the first time that quercetin interacted with p65 and ICAM-1 directly to alleviated inflammatory and vascular dysfunction, suggesting quercetin is a novel, promising therapeutic candidate for rosacea.