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.

Validity and reliability of the Rosacea Area and Severity Index: A novel scoring system for clinical assessment of rosacea severity.

BACKGROUND: Rosacea is a common chronic inflammatory facial skin disorder. Standardized evaluation of the severity and extent of rosacea is important for baseline assessment and treatment effect. The currently used Investigator's Global Assessment (IGA) is unspecific and fails to consider subtypes/phenotypes of rosacea and area involvement. The Rosacea Area and Severity Index (RASI) was developed to give a more nuanced evaluation of rosacea features in four facial skin areas adjusted to the relative importance of each area of the face to obtain an overall severity score. OBJECTIVES: To validate RASI against the IGA and to assess the inter- and intraobserver reliability for RASI. METHODS: Sixteen dermatologists evaluated photographs of 60 adult patients with rosacea (3 photographs per patient, one from the front and one from each side). IGA and RASI scores were performed for interobserver reliability assessment. To determine intraobserver reliability, 14 dermatologists evaluated 10 other patients twice with at least 1 week interval. RESULTS: The IGA and RASI correlated well (Spearman correlation coefficient (SCC) = 0.75, 95% confidence interval (CI) = 0.72-0.78). Interobserver reliability was moderate for RASI and poor to moderate for IGA. Reliability was strongest for rhinophyma, followed by papules/pustules and erythema, and rather weak for telangiectasia. For area scores, interobserver reliability was strongest for cheeks, followed by nose, chin and forehead. We found a moderate-to-strong intraobserver agreement both for IGA and RASI. CONCLUSIONS: We have designed a new practical tool to examine clinical severity of rosacea. RASI proved simple and reliable in scoring clinical severity of rosacea with an agreement comparable to the currently used IGA although RASI will provide a more nuanced view of the current rosacea extent and severity. We suggest that RASI is used in the daily clinical setting as well as in clinical studies assessing the efficacy of rosacea therapies.

Assessment of hearing loss in patients with rosacea.

OBJECTIVES/AIMS: Rosacea is not only a skin condition but a systemic inflammatory disease that includes chronic inflammation, vascular alterations, and autoimmunity in pathogenesis. We aimed to evaluate the presence of a sensorineural hearing loss in the patients with rosacea in comparison with the healthy control group and, also to compare the audiometric results according to the severity of disease among the patient group. METHODS: Fifty-three patients with erythematelangiectatic or papulopustular type of rosacea and 105 age- and sex-matched healthy controls were included. Each participant had audiometric measurements after a complete ear-nose-throat examination by the same otorhinolaryngologist. RESULTS: The results of air and bone conduction thresholds showed statistically significant differences in particularly high frequencies between the groups in both the right and left ear (for all p < 0.05), but there was no correlation between audiometric measurements and the severity or the type of rosacea (p > 0.05). CONCLUSIONS: Regardless of disease severity or type, rosacea patients are likely to have sensorineural hearing loss, and it is important to refer these patients in the early period.

Assessment of Frequency of Rosacea Subtypes in Patients With Rosacea: A Systematic Review and Meta-analysis.

Importance: Four distinct rosacea subtypes have traditionally been recognized, but the frequency of these subtypes among patients with rosacea remains unknown. Objective: To assess the frequency of 4 rosacea subtypes. Data Sources: This systemic review and meta-analysis included a search of 2 databases, PubMed and Embase, from inception of the databases to November 2, 2021. The search was filtered to include only studies of human participants published in English, French, and German. Study Selection: Studies were screened independently by 2 of the authors and were included if they were original with a sample size of 25 or more patients and reported absolute numbers or frequency of patients affected by rosacea subtypes. Studies that did not report sufficient data to calculate the proportions of subtypes were excluded. Data Extraction and Synthesis: Data extraction was performed independently and in duplicate by 2 of the authors, using the search term rosacea, according to the Preferred Reporting items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search term, objectives, and study protocol methods were defined before the study was initiated. A total of 292 studies were included for full-text assessment. Owing to the heterogeneity of the included studies, a random-effects model was used. Main Outcome and Measures: The main outcome was the proportion of patients with rosacea in each of the 4 major subtype groups defined by the 2002 National Rosacea Society classification system. Measures were absolute numbers or frequency of patients affected by each of the 4 rosacea subtypes. Results: A total of 39 studies examining 9190 patients with rosacea were included. The pooled proportion of erythematotelangiectatic rosacea was 56.7% (95% CI, 51.4%-62.0%), of papulopustular rosacea was 43.2% (95% CI, 38.8%-47.6%), of phymatous rosacea was 7.4% (95% CI, 6.1%-8.9%), and of ocular rosacea was 11.1% (95% CI, 6.7%-16.3%). Subtype distribution occurred equally among men and women except for phymatous rosacea, which was more prevalent in men. Studies from Africa showed the lowest proportion of erythematotelangiectatic rosacea. Differences in frequency of subtypes were observed when stratification by publication year was performed. Conclusion and Relevance: In this systematic review and meta-analysis, differences were found in rosacea subtypes by patient sex and by continent of origin and publication year of included studies. Erythematotelangiectatic and papulopustular rosacea were the most prevalent subtypes, but data should be interpreted with caution. Future studies should use the phenotype-based rosacea approach.

Inter-observer evaluation of erythema-directed photography for the assessment of erythema and telangiectasias in rosacea.

BACKGROUND: Persistent centrofacial erythema associated with telangiectasias is one of the most common phenotypes of rosacea in clinical practice, and the assessment of each component is crucial as each of them may require a different approach. The aim of this study was to evaluate the inter-observer reliability of standard photography vs erythema-directed photography for the assessment of erythema and telangiectasias in rosacea. MATERIALS AND METHODS: One hundred full-face images of 50 rosacea patients (50 standard photographs and 50 erythema-directed digital photographs) were evaluated by 8 independent experienced dermatologists using a 5-item score for erythema and telangiectasias, respectively. Inter-rater reliability, by comparing erythema and telangiectasias scores and calculating the percentage of agreement between evaluators, was assessed and the strength of agreement using the Cohen's Kappa values (95% CI) was calculated. RESULTS: Poor and fair strength of agreement for erythema and telangiectasias using standard photography vs moderate and good strength of agreement using erythema-directed digital photography was found. CONCLUSION: Erythema-directed digital photography may provide a better strength of agreement and higher reliability among independent observers compared to standard photography in the assessment of erythema and telangiectasias in rosacea, thus suggesting new horizons for digital appraisal of skin diseases.

Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel.

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.

Noninvasive objective skin measurement methods for rosacea assessment: a systematic review.

BACKGROUND: Rosacea assessment and therapy monitoring can be challenging to standardize, as most clinical evaluation systems are prone to interobserver variability and not always validated. Therefore, objective, reliable and preferably noninvasive measurement tools are needed. OBJECTIVES: To give insight into available noninvasive imaging techniques and biophysical methods in rosacea by performing a systematic review. METHODS: PubMed, Embase, Cochrane and Web of Science databases were searched until 1 September 2018 in accordance with PRISMA guidelines, to identify studies providing original data about objective noninvasive imaging and/or biophysical skin measurement techniques for diagnosis, assessing severity or therapy monitoring of adult patients with cutaneous facial rosacea. Risk of bias of included articles was assessed with the Cochrane Risk of Bias tool, Quality in Prognosis Studies tool, and the Newcastle-Ottawa Scale. RESULTS: A total of 78 studies were included, describing 14 imaging and biophysical methods. Widespread information about (sub)surface cutaneous morphology and functionality was obtained. Methodological study quality was relatively low and interstudy outcome variability was large. Several tools show promising value in research settings: for treatment follow-up Demodex mites are countable with reflectance confocal microscopy, spectrometry can quantify erythema, and rosacea severity could be objectified with skin hydration- and transepidermal water loss measurements. CONCLUSIONS: This systematic review describes the spectrum of noninvasive imaging and biophysical methods in rosacea assessment, giving multifaceted information about structure and properties of rosacea skin, especially useful for research purposes. Larger studies with good methodological quality are needed to create validated protocols for further implementation into research. What's already known about this topic? Rosacea is a chronic inflammatory skin disease with a variety of clinical manifestations. Most clinical evaluation systems are subjective, not always validated, and subsurface skin processes remain unnoticed. Currently, different types of noninvasive measurement tools are available for rosacea assessment and therapy monitoring, but a comprehensive overview is lacking. What does this study add? Seventy-eight publications were included, describing 14 imaging and biophysical tools, providing a wide range of information about rosacea skin morphology and functionality. Reflectance confocal microscopy and spectrometry are especially promising in therapy monitoring and skin barrier measurements for rosacea severity assessment. Larger studies with better methodological quality are needed to create validated protocols for implementation into research.

Patient-focused Solutions in Rosacea Management: Treatment Challenges in Special Patient Groups

Rosacea is among the most common facial skin conditions diagnosed by dermatologists. Typical clinical features include erythema, flushing, telangiectasia, papules, and pustules distributed on the central face. While the prevalence of rosacea is highest among white populations of Northern European descent, recent reports have found that rosacea frequently occurs in people from a broad range of racial/ethnic backgrounds and skin types. When rosacea presents in darker skin types, the diagnosis is often more challenging due to masking of features by increased epidermal melanin. As such, under-diagnosis and underreporting may contribute to misconceptions about the prevalence of rosacea in populations with skin of color. Recognizing the unique presentations and complications associated with darker skin types is necessary to reduce the disparities in rosacea treatment, especially as the American population continues to become increasingly heterogeneous. Although rosacea is most common in middle-aged females, patients of other demographics may have more negative impacts on quality of life due to their disease. In this article, we review rosacea management with a focus on special patient groups: people with skin of color, and less common forms of rosacea, in order to diminish the physical and psychosocial burden of rosacea in all patient groups. Due to the variability inherent to rosacea, we advocate for an individualized, patient-centered approach to disease management.

Assessment of Tear Functions in Patients with Acne Rosacea without Meibomian Gland Dysfunction.

Purpose: To evaluate the results of tear functions in acne rosacea. Methods: This prospective study includes 64 eyes of 32 acne rosacea patients without blepharitis and meibomian gland dysfunction and 90 eyes of 45 patients as control group. Tear functions of all were evaluated with ocular surface disease index (OSDI) questionnaire, and measurements of tear osmolarity were performed by using TearLab, Schirmer I tests without anesthesia and fluorescein tear break-up time (TBUT). Results: The mean Schirmer test result was 12.53 ± 6.54 in study group and 16.21 + 7.52 mm/5 min in control group (p = 0.28). The mean TBUT in study group was 8.21 ± 4.01 and in control group was 18.03 ± 6.45 s (p = 0.02). Mean tear osmolarity in study group was 304.77 ± 15.59and in control group was 275.23 + 28.52 mOsms/L (p = 0.03). Mean OSDI score in study group was 27.51 ± 16.73 and was 18.15 ± 7.05 in control group (p = 0.38). Conclusions: Our study demonstrated lower dry eye tests before the appearance of clinical signs of meibomian gland disease in acne rosacea.

Validity and Reliability of a Rosacea Self-Assessment Tool.

The lack of validated rosacea assessment tools is a hurdle in assessing rosacea severity. This article discusses a valid and reliable rosacea severity self-assessment tool (RSAT) to measure rosacea severity. To determine test-retest validity, participants completed the self-assessment twice. A blinded physician graded the participant's disease severity with the Investigator Global Severity (IGS) score. Pearson correlations were used to assess the relationship between the self-assessment measure and the IGS. Test-retest RSAT measurements were correlated. The RSAT represents a valid and reliable tool. This tool may facilitate determination of rosacea severity in survey research studies.

Incidence and prevalence of rosacea: a systematic review and meta-analysis.

BACKGROUND: The exact prevalence and incidence of rosacea remain unknown, although it is a common condition associated with severe noncutaneous diseases. OBJECTIVES: To perform a systematic review of the published literature to examine the global incidence and prevalence of rosacea. METHODS: A systematic review of population-based and dermatological outpatient studies reporting the incidence and/or prevalence of rosacea was performed using three electronic medical databases: PubMed, Embase and Web of Science. Data were extracted and a proportion meta-analysis was performed to obtain pooled proportions. RESULTS: In total 32 studies were included examining a total of 41 populations with 26 519 836 individuals. Twenty-two populations were from Europe, three from Africa, four from Asia, nine from North America and three from South America. The pooled proportion of individuals with rosacea was 5·46% [95% confidence interval (CI) 4·91-6·04] in the general population and 2·39% (95% CI 1·56-3·39) among dermatological outpatients. Self-reported rosacea gave higher prevalence estimates than rosacea diagnosed by clinical examination, suggesting a low specificity of questionnaires based on symptoms. Rosacea affected both women (5·41%, 95% CI 3·85-7·23) and men (3·90%, 95% CI 3·04-4·87), and mostly those aged 45-60 years. CONCLUSIONS: We estimated the global prevalence of rosacea based on published data and found that 5·46% of the adult population is affected. However, the prevalence of rosacea depended on the diagnostic method, with higher estimates in questionnaire studies of rosacea symptoms and lower estimates in health registries with International Classification of Diseases codes.

Cross-Sectional Survey of the Burden of Illness of Rosacea by Erythema Severity.

Rosacea is a chronic skin condition characterized by persistent central facial erythema. To explore the burden of illness of rosacea in US adults, a cross-sectional web-based survey was conducted. Participants answered questions on sociodemographics, clinical characteristics, bothersome symptoms, coping and avoidance behaviors, self-perceptions, and health care resource utilization, and completed 2 quality of life instruments, the 21-item rosacea-specific quality of life questionnaire (RosaQoL) and the 36-item Short Form Health Survey (SF-36). This paper reports the data from the 409 respondents with erythematotelangiectatic rosacea (ETR), analyzed by erythema severity. Mean age was 53.1 years; mild, moderate, or severe erythema was reported by 63.6%, 32.0%, and 4.4% of participants, respectively. Blushing/flushing and bumps/pustules were the most bothersome symptoms across severity subgroups. Participants in all subgroups coped with rosacea by applying make-up and managing their stress and anxiety, and tried to prevent rosacea flares by avoiding sun exposure, specific skin care products, and other triggers. Self-perceptions differed by severity subgroup: satisfaction with facial appearance significantly decreased, and worrying about how people will react and feelings of unattractiveness to others significantly increased, with greater erythema severity (all P less than 0.01). Treatment or assessment of rosacea was sought by 20% of participants in the past 3 months, most commonly from a dermatologist. Metronidazole was the most frequently prescribed topical product across severity subgroups, whereas doxycycline and other oral antibiotics were prescribed most frequently in the severe erythema subgroup. RosaQoL emotional domain scores increased with erythema severity (P equals 0.0035), but none of the SF-36 domain scores differed significantly by erythema severity. These results demonstrate that rosacea is associated with a substantial burden of illness that spans all levels of erythema severity in patients with ETR. Feelings of unattractiveness and the adverse impact of rosacea on emotional quality of life increased with erythema severity. J Drugs Dermatol. 2018;17(2):150-158.

Cost of diagnosing psoriasis and rosacea for dermatologists versus primary care physicians.

Growing incentives to control health care costs may cause accountable care organizations (ACOs) to reconsider how skin disease is best managed. Limited data have suggested that disease management by a primary care physician (PCP) may be less costly than seeing a specialist, though it is not clear if the same is true for the management of skin disease. This study assessed the cost of seeing a dermatologist versus a PCP for diagnosis of psoriasis and rosacea.

Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

Clinical assessment of rosacea severity: oriental score vs. quantitative assessment method with imaging and biomedical tools.

BACKGROUND: Rosacea is a common chronic inflammatory disorder affecting facial skin. Currently, no accurate and objective method is available for assessing the severity of rosacea. Most studies use the National Rosacea Society Standard (NRSS) grading method, which lacks objectivity and yields varying results. METHODS: Eighteen patients with rosacea were included. Clinical severity was assessed on the basis of the NRSS grade, Investigators' Global Assessment, Patients' Global Assessment, and Dermatology Quality of Life Index. A skin color analysis system was used to measure the facial area showing erythema, and biophysical parameters of facial skin (transepidermal water loss and skin surface hydration) were examined. To find statistical significant in classification severity of the rosacea, statistical analysis was performed with all parameters. RESULTS: A significant correlation (P < 0.05) was found between the NRSS grade, facial area showing erythema, and biophysical parameters. The latter two factors differed significantly among patients with rosacea of different levels of severity (mild, moderate, severe; P < 0.05). CONCLUSION: Color imaging systems can be useful and reliable for evaluating the severity of rosacea, in addition to biophysical parameter assessment. The combination of these two analytical methods enabled objective and quantitative evaluation of the severity of rosacea.

Canadian Clinical Practice Guidelines for Rosacea.

Rosacea is a chronic facial inflammatory dermatosis characterized by background facial erythema and flushing and may be accompanied by inflammatory papules and pustules, cutaneous fibrosis and hyperplasia known as phyma, and ocular involvement. These features can have adverse impact on quality of life, and ocular involvement can lead to visual dysfunction. The past decade has witnessed increased research into pathogenic pathways involved in rosacea and the introduction of novel treatment innovations. The objective of these guidelines is to offer evidence-based recommendations to assist Canadian health care providers in the diagnosis and management of rosacea. These guidelines were developed by an expert panel of Canadian dermatologists taking into consideration the balance of desirable and undesirable outcomes, the quality of supporting evidence, the values and preferences of patients, and the costs of treatment. The 2015 Cochrane review "Interventions in Rosacea" was used as a source of clinical trial evidence on which to base the recommendations.

Assessment of rosacea severity: A review of evaluation methods used in clinical trials.

BACKGROUND: Novel rosacea treatments are needed. Assessment methodologies for clinical trials of rosacea treatments are not standardized and are relatively inadequate. To determine the efficacy of new treatments, a valid and reliable assessment methodology is needed. OBJECTIVE: We sought to determine the assessment methodologies used in clinical trials for rosacea treatments, to demonstrate the need for a valid and reliable assessment tool, and to describe the relevant properties of such a tool. METHODS: PubMed and MEDLINE were searched for clinical trials of rosacea treatments since January 1, 1985. RESULTS: In all, 32 clinical trials met inclusion criteria. Assessment methodologies were highly variable, and standardized assessment methodologies were used in only 3 studies. The various manifestations of rosacea were assessed inconsistently. LIMITATIONS: Eighteen articles could not be included as a result of lack of access to the full text. CONCLUSIONS: The diverse methodologies make the assessment of novel treatments and comparison of treatments difficult. A valid and reliable assessment tool is needed to properly assess novel treatments to improve the management of rosacea.

Reliability of Clinician Erythema Assessment grading scale.

BACKGROUND: Facial erythema is a clinical hallmark of rosacea and often causes social and psychological distress. Although facial erythema assessments are a common endpoint in rosacea clinical trials, their reliability has not been evaluated. OBJECTIVE: The objective of this study was to evaluate the inter- and intrarater reliability of the Clinician's Erythema Assessment (CEA), a 5-point grading scale of facial erythema severity. METHODS: Twelve board-certified dermatologists, previously trained on use of the scale, rated erythema of 28 rosacea subjects twice on the same day. Interrater and intrarater agreement was assessed with the intraclass correlation and κ statistic. RESULTS: The CEA had high interrater reliability and good intrarater reliability with an overall intraclass correlation coefficient (ICC) for session 1 and session 2 of 0.601 and 0.576, respectively; the overall weighted κ statistic for session 1 and session 2 was 0.692. LIMITATIONS: Raters were experienced dermatologists and there may be a risk of recall bias. CONCLUSION: When used by trained raters, CEA is a reliable scale for measuring the facial erythema of rosacea.