Individual sol-gel microencapsulation of benzoyl peroxide and tretinoin enables controlled release onto the skin.

A combination of benzoyl peroxide (BPO) and tretinoin is recommended for treating acne; however, concurrent administration can be irritating, and coformulation is prevented by BPO-mediated oxidation of tretinoin. In rosacea, benzoyl peroxide has been shown to be efficacious; however, its use has been limited by poor tolerability. To overcome these limitations, the active ingredients can be encapsulated within silica microcapsules. The US Food and Drug Administration has approved 2 products using this technology, a combination of encapsulated benzoyl peroxide and encapsulated tretinoin product for acne vulgaris and encapsulated benzoyl peroxide to treat inflammatory lesions in rosacea. The active ingredients are released through small channels in the silica shell, gradually releasing the active ingredients to the skin. This study describes the stability and release profiles of encapsulated tretinoin and encapsulated benzoyl peroxide from the silica shell in physiologically relevant conditions and provides differentiation from traditional formulations.

Elevated Specific Pro-Inflammatory Cytokines in Peripheral Circulation Indicate an Increased Risk of Anxiety and Depression in Rosacea.

Objective: Pro-inflammatory cytokines mediate the course of rosacea, anxiety, and depression through various means such as immunity and inflammation. This study aims to further explore the relationship between rosacea, anxiety, and depression through changes in the levels of pro-inflammatory cytokines. Methods: 280 rosacea patients were included in the rosacea group, divided into: rosacea without mental disorders, rosacea with anxiety, rosacea with depression, and rosacea with combined anxiety and depression. The mental control group included 210 anxiety and depression patients, divided into: anxiety, depression, and combined anxiety and depression. The healthy control group consisted of 70 healthy individuals. Serum specimens were collected and ELISA was used to detect major pro-inflammatory cytokines. CEA, IGA, GFSS, RosaQoL, HAMA, and HAMD-24 were used for the diagnosis and severity assessment of rosacea and anxiety and depression. Results: This study primarily used the Chi-Square test, Kruskal-Wallis H-test, generalized linear model, and binary logistic regression to evaluate the data. IL-1ß, IL-17, and IL-8 levels in rosacea patients and anxiety/depression patients were higher than those in the healthy population (P<0.001), and TNF-α levels in rosacea patients were higher than those in the healthy population (P<0.001). There was an interaction between rosacea, anxiety, and depression in terms of IL-1ß, IL-17, and IL-8 levels (P<0.001). Elevated levels of IL-1ß, IL-17, and IL-8 are positively correlated with anxiety and depression in rosacea (all P<=0.05). Conclusion: It was confirmed that the elevated levels of IL-1ß, IL-17, and IL-8 are positively correlated with the onset of anxiety and depression in rosacea. The interaction of the above inflammatory factors suggests a possible common inflammatory mechanism in the coexistence of rosacea and mental disorders. TNF-α only increased in patients with rosacea, combined with the skin-to-mental irreversible phenomenon, indicating that this cytokine may be a key and potential therapeutic target for the onset of rosacea.

Beyond the Surface: Understanding Demodex and Its Link to Blepharitis and Facial Dermatoses.

Demodex represents the most frequent ectoparasite found in humans. Although Demodex mites are considered commensals of human pilosebaceous units, an abnormally high mite density can cause several ocular and cutaneous symptoms and signs, sometimes to a severe degree. Both Demodex spp. (folliculorum and brevis) play a significant part in eye pathology and facial dermatoses. These mites have been related to blepharitis, ocular rosacea, meibomian gland dysfunction and various skin diseases, including rosacea, demodicosis and seborrheic dermatitis. Understanding the importance of Demodex in both eye and skin conditions is crucial for accurate diagnosis and appropriate management strategies, which may involve targeted treatments to control the mite population and reduce associated symptoms.

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.

Fabrication and efficacy assessment of combination of brimonidine and ivermectin for treatment of papulopustular rosacea.

BACKGROUND & AIM: Rosacea is a chronic inflammatory, multifactorial disease for which combination therapy could be an effective treatment. In this study, we evaluate the effect of the combination therapy of brimonidine 0.33% and ivermectin 1% as a single cream for the treatment of papulopustular rosacea. METHOD: A stable and appropriate formulation was prepared by adding the aqueous phase to the lipid phase while being stirred. The stability and physicochemical properties of the formulation were evaluated under accelerated conditions. Twelve patients (36-60 years) with mild to moderate papulopustular rosacea and a Demodex count of five or more were treated with the combination of brimonidine 0.33% and ivermectin 1% cream. Clinician's Erythema Assessment (CEA), Patients Self-Assessment (PSA), skin erythema (ΔE) and lightness (ΔL), and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, pH, and sebum content, as well as erythema and melanin index and ultrasound parameters, were measured before treatment and 4 and 8 weeks after. Adverse drug reactions were also recorded. RESULTS: CEA and PSA decreased significantly from 3 to 2 after 8 weeks, respectively (p-value = 0.014 for CEA and 0.010 for PSA). ΔE and ΔL, as well as skin erythema index and TEWL improved after 8 weeks of treatment (p < 0.05). Two patients withdrew from the study in the first week because of local adverse effects; one developed flushing following treatment and left the investigation after 4 weeks and another patient withdrew from the study after 4 weeks due to deciding to become pregnant. CONCLUSION: Eight-week treatment with the combination of brimonidine 0.33% and ivermectin 1% was shown to be effective for improvement of erythema and inflammatory lesions in mild to moderate papulopustular rosacea.

A two-center randomized controlled trial of a repairing mask as an adjunctive treatment for mild to moderate rosacea.

OBJECTIVE: To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea. METHODS: Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score. RESULTS: A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants. CONCLUSION: The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use.

Evaluation of Delayed Contact Hypersensitivity in Patients with Rosacea.

Introduction: Rosacea is a common chronic inflammatory dermatosis characterized by erythema, telangiectasia, papules, and pustules on the central face. The frequency of contact sensitization complicating rosacea and its therapy is unknown, with only few studies published in the literature. In the present study, we aimed to evaluate contact sensitivity in patients with rosacea. Methods: A total of 50 rosacea patients and 50 age- and sex-matched healthy controls were enrolled. Both groups were patch tested with the European Baseline Series. Results: A positive reaction to at least one allergen of the European Baseline Series was observed in 15 (30%) of rosacea patients and 10 (20%) of the healthy controls. Although the rate of positive reaction in the rosacea group was higher than in the controls, no statistically significant difference was documented. In addition, the total number of positive reactions to allergens in the rosacea group was higher than the control group, namely, 26 versus 17. Conclusion: Contact hypersensitivity may coexist with rosacea. Its identification holds significant clinical relevance, influencing the long-term management and justifying the application of patch testing in rosacea patients.

Challenges and real-world solutions for adoption of holistic skincare routine (cleansing, treatment, moisturization, and photoprotection) in acne, rosacea, atopic dermatitis, and sensitive skin: An expert consensus.

BACKGROUND: While treatment is a definitive therapeutic component in the management of inflammatory skin conditions, adjunctive skin care comprising of appropriate cleansing, moisturization, and photoprotection are just as important. Cleansing, treatment, moisturization, and photoprotection (CTMP) constitute the four major components of holistic skincare routine for dermatological conditions. However, inadequate patient understanding of the condition, limited resources for physicians, and insufficient time for patient education during busy dermatological consultations are the main obstacles to establishing a holistic skincare routine in the real world. AIMS: This study aimed to identify key challenges in the implementation of a holistic skincare routine, and offer practical guidance to physicians to improve adoption in the management of acne, atopic dermatitis, rosacea, and sensitive skin syndrome. METHODS: An expert panel comprising of nine dermatologists from Australia, China, Hong Kong, Taiwan, India, Philippines, Singapore, South Korea, and Thailand convened to develop consensus statements to stimulate real-world adoption of holistic skincare routine in acne, rosacea, atopic dermatitis, and sensitive skin syndrome using the Delphi approach. RESULTS: Consensus was defined as ≥80% of panel rating statement as ≥8 or median rating of ≥8. The final statements were collated to develop consensus recommendations to encourage adoption of holistic skincare routine. CONCLUSION: Promoting patient education on the skin condition, training support staff in patient counseling, and offering physician training opportunities are the key strategies to encourage real-world adoption of CTMP as a holistic skincare routine. The consensus recommendations presented here should be considered in all dermatology patients to accomplish the ultimate goals of improved treatment outcomes and patient satisfaction.

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.

Targeting the STAT3/IL-36G signaling pathway can be a promising approach to treat rosacea.

BACKGROUND: Rosacea is an inflammatory skin disorder characterized by the release of inflammatory mediators from keratinocytes, which are thought to play a crucial role in its pathogenesis. Despite an incidence of approximately 5.5%, rosacea is associated with a poor quality of life. However, as the pathogenesis of rosacea remains enigmatic, treatment options are limited. OBJECTIVES: To investigate the pathogenesis of rosacea and explore new therapeutic strategies. METHODS: Transcriptome data from rosacea patients combined with immunohistochemical staining were used to investigate the activation of STAT3 in rosacea. The role of STAT3 activation in rosacea was subsequently explored by inhibiting STAT3 activation both in vivo and in vitro. The key molecules downstream of STAT3 activation were identified through data analysis and experiments. Dual-luciferase assay and ChIP-qPCR analysis were used to validate the direct binding of STAT3 to the IL-36G promoter. DARTS, in combination with experimental screening, was employed to identify effective drugs targeting STAT3 for rosacea treatment. RESULTS: STAT3 signaling was hyperactivated in rosacea and served as a promoter of the keratinocyte-driven inflammatory response. Mechanistically, activated STAT3 directly bind to the IL-36G promoter region to amplify downstream inflammatory signals by promoting IL-36G transcription, and treatment with a neutralizing antibody (α-IL36γ) could mitigate rosacea-like inflammation. Notably, a natural plant extract (pogostone), which can interact with STAT3 directly to inhibit its activation and affect the STAT3/IL36G signaling pathway, was screened as a promising topical medication for rosacea treatment. CONCLUSIONS: Our study revealed a pivotal role for STAT3/IL36G signaling in the development of rosacea, suggesting that targeting this pathway might be a potential strategy for rosacea treatment.

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.

Efficacy of fractional radiofrequency in the treatment of erythematous capillary rosacea: A split-face study.

OBJECTIVE: To assess the effectiveness and safety of treating erythematotelangiectatic rosacea using fractional radiofrequency (FRF). METHODS: Twenty patients with a confirmed diagnosis of erythema capillaris rosacea were selected, and one side of each patient's face was randomly assigned to receive FRF treatments for three to six times, with an interval of 2 weeks between each treatment. VISIA, dermoscopy, and the Clinician's Erythema Evaluation Scale (CEA) were applied to evaluate the efficacy of the treatment before and after the treatment, to record the VAS scores and adverse reactions, and to conduct a patient satisfaction survey. RESULTS: The characteristic counts and scores of red zone and porphyrin as assessed by VISIA test were significantly decreased, and the difference between the treated side and the pretreatment side was statistically significant (p < 0.05), and the efficacy of the treatment was statistically insignificant compared with the control side, except for the red zone and porphyrin which were statistically significant before and after the treatment (p > 0.05). By CEA score, the difference between the treated side after treatment and the control side was statistically significant (p < 0.05), and the difference between the treated side before and after treatment was statistically significant (p < 0.05); the difference between the control side before and after treatment was not statistically significant (p > 0.05). Dermatoscopic observation showed reduction in pore size, reduction of yellowish-white and black horn plugs within the pores, lightening of the red background and thinning and blurring of the capillary structure on the treated side of the skin compared to the control side, and the skin on the treated side showed the above mentioned changes before and after the treatment as well. The mean pain score of the subjects was obtained by VAS score 3.67 ± 0.90. Adverse effects included mild edema, erythema, and microscopic crusting; no long-term adverse effects were seen in all patients. The efficacy of FRF treatment was evaluated 1 month after the final treatment, and 85% of the subjects rated it as satisfactory, very satisfactory, and very satisfactory. CONCLUSION: FRF for the treatment of erythematous capillary dilatation rosacea is effective, safe, and suitable for clinical promotion.

Potential Role of Tranexamic Acid in Rosacea Treatment: conquering Flushing Beyond Melasma.

Rosacea is a chronic inflammatory skin disease that affects a patient's appearance and quality of life. It mainly affects the midface region and presents as erythema, flushing, telangiectasia, papules, pustules, and rhinophyma. Despite its prevalence, the precise pathophysiology of rosacea remains unknown, and novel pharmacological therapies are currently under investigation. Tranexamic acid (TA) is a synthetic, lysine-like compound that competitively inhibits fibrinogen production by synthesizing fibrinolytic enzymes. In addition to its popular application in hemorrhage treatment, TA has been used to manage a number of skin conditions, including melasma, chronic urticaria, and angioedema. TA is a better option for melasma treatment. However, the role of TA in treating rosacea has not yet been systematically elucidated. In this study, we reviewed all available literature on the use of TA for rosacea treatment. The included articles examined the therapeutic effects of TA in patients with rosacea, including traditional methods such as oral and topical administration and more novel approaches such as intradermal injections, microneedling, and laser-assisted delivery. Several recent clinical studies demonstrated that TA alleviates rosacea symptoms by restoring the permeability barrier, ameliorating the immune reaction, and inhibiting angiogenesis. In this review, we summarized the function and potential application of TA in rosacea treatment, aiming to facilitate the implementation of clinical applications.

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.

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.