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.

Association between rosacea and helicobacter pylori infection: A meta-analysis.

BACKGROUND AND OBJECTIVES: The potential association between rosacea and a heightened prevalence of Helicobacter pylori (HP) infection has been previously suggested. However, existing studies offer inconsistent results. This systematic review and meta-analysis aimed to elucidate the relationship between rosacea and HP infection. METHODS: We conducted comprehensive searches of PubMed, Embase, and Web of Science databases to identify relevant observational studies for our investigation. We utilized the random-effects model to aggregate the data to address the potential influence of heterogeneity among the studies on the outcome. RESULTS: Our analysis incorporated twenty-five datasets from 23 case-control and cross-sectional studies, encompassing 51,054 rosacea patients and 4,709,074 controls without skin disease. The pooled results revealed a significantly higher prevalence of HP infection in individuals with rosacea compared to controls (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.17-1.95, p<0.001; I2 = 79%). Subgroup analysis indicated an increased prevalence of HP infection in rosacea studies that utilized one (OR: 1.72, 95% CI: 1.11-2.66, p = 0.02; I2 = 76%) or more tests for HP infection (OR: 2.26, 95% CI: 1.29-3.98, p = 0.005; I2 = 56%). However, this association was not observed in population-based studies that determined HP infection based on prescription records for HP eradication drugs (OR: 0.90, 95% CI: 0.76-1.07, p = 0.024; I2 = 54%). CONCLUSION: Rosacea may be significantly associated with a higher prevalence of HP infection. High-quality prospective studies with delicately controlled confounding factors are needed to determine if HP infection is a risk factor for rosacea.

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.

Clinical characteristics of the well-defined upper eyelid vascular network pattern in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin disease. The diagnosis is based on the symptoms and physical signs, which still lacks objective laboratory tests or imaging tests. OBJECTIVES: To propose and evaluate the upper eyelid network pattern in rosacea. METHODS: Participants included patients diagnosed with rosacea, other facial erythematous skin diseases, and normal controls, all of whom underwent full-face imaging utilizing the VISIA® system software. According to these images, researchers evaluated the condition of the upper eyelid vascular network, developed the grading scale and then compared the difference of distribution in the three groups. RESULTS: The occurrence rate of upper eyelid vascular network in rosacea was significantly higher than that in other facial erythematous skin diseases (84.3 vs. 32.0%, P < 0.001) and normal controls (84.3 vs. 28.0%, P < 0.001). The upper eyelid vascular network pattern was proposed (none [no clearly reticular vessels], mild [10-50% area of reticular vessels], moderate-to-severe [>50% area of reticular vessels]). Moderate-to-severe grade was defined as well-defined upper eyelid vascular network pattern, which was specific to patients with rosacea (rosacea vs. other facial erythematous skin diseases, adjusted odds ratio [aOR] = 5.814, 95% confidence interval [CI]: 3.899-8.670) (rosacea vs. heathy controls, aOR = 12.628, 95% CI: 8.334-19.112). The severity of the well-defined pattern had no significant association with age, duration, and phenotypes of rosacea (P > 0.05). CONCLUSION: The well-defined upper eyelid vascular network pattern specifically appeared in patients with rosacea, which could be a possible clue to the diagnosis of rosacea.

Treating rosacea with botulism toxin: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rosacea is a chronic inflammatory disease usually associated with persistent erythema and periodic flushing. This disease is difficult to treat, and the outcomes are often unsatisfactory and prone to recurrence. In recent years, botulinum toxin has been used as a new treatment for rosacea; however, its efficacy and safety remain under discussion. Although a systematic review of the effectiveness and safety of botulinum toxin has been previously conducted by other researchers, our systematic review and meta-analysis evaluate the efficacy of botulinum toxin from a more comprehensive and detailed perspective to provide evidence for clinicians. METHODS: Any study using botulinum toxin for the treatment of rosacea was considered for the analysis. RESULTS: A total of 22 studies were included, 9 of which were randomized controlled trials involving 720 subjects. After treatment, all studies showed varying degrees of improvement in patient signs and symptoms along with reduced Clinician's Erythema Assessment (CEA) scores. The improvement was maintained for several months, and the adverse effects were mild and self-limiting. CONCLUSION: Botulinum toxin may be an effective treatment for patients with rosacea; however, further clinical evidence is needed to confirm its long-term efficacy and side effects. The study was preregistered with Prospero (CRD42022358911).

Topical ivermectin 1.0% cream in the treatment of ocular demodicosis.

PURPOSE: Ocular demodicosis can cause debilitating ocular surface disease. As ivermectin is effective at reducing Demodex proliferation in rosacea, this study investigated the efficacy of topical ivermectin 1.0% cream in treating ocular demodicosis. METHODS: This retrospective single-centre clinical practice chart analysis involved the off-label treatment of patients who had ocular demodicosis with topical ivermectin 1.0 % cream (Soolantra, Galderma Ltd, UK) applied nightly to the lid margins of both eyes for 3 months. Ocular surface health was assessed at baseline when the treatment was prescribed and followed up at 3 and 12 months after baseline. Slit lamp biomicroscopy was used to take digital images of the upper eyelid lashes. Manual image analysis with ImageJ was conducted by a masked assessor to quantify signs of ocular demodicosis including the number of lashes with collarettes, with visible Demodex tails and with follicle pouting. RESULTS: Data from a total of 75 patients with ocular demodicosis were analysed for this study (mean age 66.6 ± 13.9 years, 44 female). The numbers of lashes with collarettes (Median [Interquartile range]: 8 [4-13] at baseline to 0 [0-2] at the final visit, p < 0.001) and lashes with follicle pouting (3 [1-5] at baseline to 0 [0-1.8] at the final visit, p < 0.001) decreased with treatment. Any sign of lashes with visible tails was eliminated by the final visit (p < 0.007). Fluorescein staining severity score also improved, particularly from baseline (1 [0-2]) to the second visit (0 [0-1], p < 0.001). CONCLUSIONS: The findings of this study show evidence for the efficacy of a 3-month course of topical ivermectin 1.0% cream in treating ocular demodicosis as indicated by reduction in collarettes, follicle pouting and visible Demodex tails. More research is warranted to improve the diagnosis, management and monitoring of this condition which is often overlooked or misdiagnosed.

Association of Rosacea with Depressive and Anxiety Symptoms: A General Population Study.

BACKGROUND: The association between rosacea and psychiatric comorbidity has been reported previously. However, there is a lack of general population studies about this subject area. OBJECTIVES: The aim of this study was to the association between rosacea with depressive and anxiety symptoms at the population level. METHODS: A clinical whole-body examination was performed by dermatologists for 1,932 subjects belonging to the Northern Finland Birth Cohort 1966 Study during the 46-year follow-up survey. The presence of depressive and anxiety symptoms was gathered by using validated Hopkins Symptom Checklist-25 (HSCL-25) included in the self-administered questionnaires. Binary logistic regression analysis was used to identify associations between rosacea and psychological symptoms. RESULTS: Rosacea was found in dermatological evaluation in 15.1% of the study subjects (n = 292). In logistic regression analyses, after adjusting for confounding factors, those with rosacea had 1.6-fold (OR 1.55, 95% CI: 1.02-2.32) risk for psychiatric symptoms according to HSCL-25 when compared with controls. In separate analyses of the HSCL-25 depression subscale, the risk was increased, especially for depressive symptoms (OR 1.56, 95% CI: 1.10-2.18). CONCLUSIONS: Patients with rosacea seem to have increased risk for depressive and anxiety symptoms in general population. Physicians treating patients with rosacea should pay more attention to the psychosocial health of patients.

Evidence for the Clinical Association between Demodex and Rosacea: A Review.

BACKGROUND: Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. SUMMARY: As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following the Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes.

Increased risk of sleep disturbances in patients with rosacea: A nationwide population-based cohort study.

Rosacea is a chronic inflammatory skin disorder linked to various mental disorders, but little is known about the impact of rosacea on sleep disorders. The aim of this study is to confirm the association of rosacea with sleep disorders using a large administrative data set. This nationwide population-based retrospective cohort study enrolled 1129 individuals with rosacea and 11 017 age- and sex-matched controls without rosacea from the Korean National Health Insurance System database from 2002 to 2015. The prevalence of sleep disorder (7.8%) was significantly higher in patients with rosacea than in controls (5.81%; p < 0.001). Rosacea was associated with an increased risk of sleep disorder (adjusted odds ratio [aOR], 1.287 [95% confidence interval (CI), 1.022-1.623]). Among a variety of sleep disorders, patients with rosacea were likely to have an increased risk of insomnia (aOR, 1.318 [95% CI, 1.002-1.743]). In subgroup analysis, female patients with rosacea (aOR, 1.297 [95% CI, 1.010-1.722]) and those with rosacea and dyslipidemia (aOR, 1.417 [95% CI, 1.062-1.891]) were at a higher risk of having a sleep disorder. Rosacea is associated with an increased risk of having sleep disorders. The management of modifiable risk factors is important for managing sleep disorders in patients with rosacea.

Associations of serum gamma-linolenic acid levels with erythema severity and anxiety/depression status in patients with rosacea.

BACKGROUND: The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. OBJECTIVE AND LIMITATIONS OF THE STUDY: The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. METHODS: A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. RESULTS: Lower levels of serum GLA in rosacea patients were observed (p<0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. CONCLUSION: The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.

Wound excision and closure by secondary intention and growth factor application in the management of rosacea complicated by giant rhinophyma.

BACKGROUND: Rosacea is a significant problem, affecting 5.5% of the world population. Currently used treatment techniques such as transfer flaps and implants are insufficient to meet the needs of many patients, which suggests that alternative approaches are needed. CASE REPORT: This report describes a case of rosacea complicated by giant rhinophyma treated with excision and closure by secondary intention and growth factor application. The patient was admitted to the Department of Dermatology at The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, in July 2021, and underwent excision of the external nasal redundancy under general anesthesia. The postoperative wound was left open. The patient's wounds healed completely 2 months after surgery, and there was no recurrence at 6-month follow-up. The wounds recovered well, with only slight scarring. CONCLUSION: The positive outcomes for this patient suggest that wound excision and closure by secondary intention and growth factor application may be beneficial for patients with rosacea complicated by giant rhinophyma.

Evaluation of Ocular and Systemic Oxidative Stress Markers in Ocular Rosacea Patients.

Purpose: To investigate oxidative stress markers in tears and serum of patients with ocular rosacea and to examine their association with both ocular surface parameters and cutaneous rosacea subtypes. Methods: This prospective study includes rosacea patients with ocular involvement and healthy controls. We performed ophthalmological examination of all participants and collected tear breakup time (TBUT), Schirmer, Meibomian gland dysfunction (MGD) and Ocular Surface Disease Index (OSDI) scores. We quantified the total antioxidant status (TAS), total oxidant status (TOS), and arylesterase (ARE) levels from tear and serum samples, and calculated the oxidative stress index (OSI). We also classified patients into phymatous, erythematotelangiectatic, papulopustular subtypes. Results: We included 90 ocular rosacea patients and 30 healthy controls. Oxidative stress (TOS, OSI) levels were significantly higher (P < 0.01) and antioxidant levels (TAS, ARE) were significantly lower (P < 0.01) in both tear and serum samples of ocular rosacea patients as compared to controls. We found a significant positive correlation between the tear and serum values regarding oxidative stress parameters (P < 0.05). Besides, OSI was negatively correlated with TBUT and positively correlated with MGD score (meiboscore) and OSDI (P < 0.05). The Schirmer score was not correlated with OSI. No difference was found between the cutaneous subtypes with respect to TAS, TOS, ARE, and OSI results. Conclusions: In this study, we identified oxidative stress markers in the serum and tears of ocular rosacea patients and showed their correlation with clinical signs of MGD, suggesting that oxidative stress contributes to ocular rosacea pathogenesis and that oxidative stress could be an indicator of MGD severity.

Cross-Sectional Study of Psoriasis, Atopic Dermatitis, Rosacea, and Alopecia Areata Suggests Association With Cardiovascular Diseases.

BACKGROUND: A growing body of evidence suggests that several inflammatory skin diseases (ISDs) are associated with systemic inflammation and cardiovascular disease (CVDs). METHODS: We used the TriNetX analytics platform to conduct a retrospective, cross-sectional, single-center study in the Mount Sinai Health System network. Cases (all patients ≥18 years of age with a diagnosis of 1 of the 4 ISDs studied) were compared with matched controls (no history of any of these ISDs) to evaluate odds ratios for being diagnosed with CVD. RESULTS: We identified a total of 70,090 patients with ISDs, including 35,160 patients with atopic dermatitis, 19,490 with psoriasis, 12,470 with rosacea, and 2,970 with alopecia areata, and 70,090 propensity score-matched controls without any of these ISDs. Patients with atopic dermatitis and psoriasis had significantly increased odds of all CVD diagnoses analyzed compared to controls (P<0.001 for all comparisons). Patients with rosacea had significantly increased odds of being diagnosed with all diseases of the circulatory system (P<0.001), hypertensive diseases (P<0.001), cerebrovascular diseases (P=0.037), and arterial disease (P<0.001) compared to controls. Patients with alopecia areata had increased odds for all diseases of the circulatory system (P<0.001), hypertensive diseases (P<0.001), and arterial disease (P<0.001). The prevalence of patients with elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels was significantly greater in all ISD groups compared to controls. CONCLUSION: This study identified significant associations between ISDs and several CVD diagnoses. Furthermore, CRP and ESR were elevated in all ISD groups compared to controls. Pagan AD, Jung S, Caldas S, et al. Cross-sectional study of psoriasis, atopic dermatitis, rosacea, and alopecia areata suggests association with cardiovascular diseases. J Drugs Dermatol. 2023;22(6):576-581. doi:10.36849/JDD.7424.

Reduction of Erythema in Moderate-Severe Rosacea by a Low Molecular Weight Heparan Sulfate Analog (HSA).

Rosacea changes are a result of an immune mediated response and the angiogenic properties of the LL-37 peptide. This peptide induces an inflammatory signal that activates the NLRP3-mediated inflammasome, triggering rosacea pathogenesis. Research findings show that LL-37 peptide is inhibited by binding to a cell surface glycosaminoglycan, heparan sulfate. Heparan Sulfate Analog (HSA) is a proprietary low molecular weight analog of heparan sulfate that has been formulated into a Dermal Repair Cream (DRC), specifically to aid in such immune mediated responses. Herein, in vitro studies using human epidermal keratinocytes showed an increase in HSA decreased LL-37 toxicity and IL-8 cytokine release. A single-center, randomized double-blind trial included 16 subjects (Fitzpatrick skin types I-IV) with a clinical diagnosis of type 1 rosacea and moderate to severe facial erythema, who were undergoing Pulsed Dye Laser (PDL) treatment. The clinical improvements of their facial erythema were assessed at baseline, 2 weeks, 4 weeks, and 8 weeks. Results revealed that low molecular weight HSA significantly improves the clinical signs of rosacea during the 8 weeks of use likely resulting from inhibition of LL-37 induced IL-8 cytokine release. These findings support the use of DRC in rosacea topical treatment regimens as it demonstrates visible skin benefits and improves tolerability of PDL therapy in a shorter duration of time as compared with PDL alone.George R, Gallo RL, Cohen JL, et al. Reduction of erythema in moderate-severe rosacea by a low molecular weight Heparan Sulfate Analog (HSA). J Drugs Dermatol. 2023;22(6):546-553. doi:10.36849/JDD.7494.

Idiopathic facial aseptic granuloma in children: Management and long-term follow-up.

AIMS: The primary objective was to study long-term outcomes in children with idiopathic facial aseptic granuloma (IFAG). The secondary objectives were to describe the clinical polymorphism of this entity, the different therapeutic options, and the occurrence of rosacea in this population. METHODS: We selected patients with a clinical diagnosis of IFAG seen in two different hospitals in Normandy between March 2016 and February 2021, and we collected clinical and therapeutic data from computerized medical records. A remote consultation based on recent photographs was performed to collect new data, and the children's parents were asked to complete a questionnaire between February and August 2021. RESULTS: Ten children were included in this study. Nine patients presented with a single red to purplish nodule. One patient presented multiple papulopustular plaques. IFAG healed spontaneously without major sequelae, and this outcome was not influenced by any treatments. During follow-up, two patients developed childhood rosacea. CONCLUSION: Although some clinical heterogeneity exists, early diagnosis and follow-up of IFAG is necessary to avoid unnecessary topical or systemic antibiotic treatments that do not shorten the disease course. IFAG appears to be a possible mode of entry for infantile rosacea.

Diagnosing Disorders of Facial Erythema.

Identification of specific patterns, shades, and intensity of erythema in the skin has always been critical and fundamental to diagnostic accuracy in dermatology. Erythema is often less noticeable in darker skin types. The interplay of inflammation and variance of skin tone contributes to appreciable differences in the clinical appearance of cutaneous disease in darker complexions. In this article, we discuss common disorders that present with facial erythema in skin of color and offer distinguishing features of each disorder to assist the clinician with diagnosing these conditions in the presence of deeply pigmented skin.