Facial Rosacea Research Articles

Doxycycline monohydrate and azelaic acid Co-loaded nanoemulgel for the treatment of facial rosacea: In vitro and In vivo evaluation

Nanoemulgel have gained importance as topical delivery systems because of their potential to incorporate hydrophilic and lipophilic drugs simultaneously like emulsions and improved stability and spreadability like gels. Therefore, the current research was aimed to prepare, optimize, and evaluate the combined therapeutic efficacy of doxycycline monohydrate (DOX.H2O) and azelaic acid (AZL) loaded into a nanoemulgel (NE) against facial rosacea. The nanoemulsion was prepared via phase inversion low energy emulsification method by solubilizing DOX.H2O in peppermint oil and AZL in deionized water. The formulation was optimized using Design Expert 13. The optimized nanoemulsion has a particle size of 210.6 nm, a PDI of 0.234 and a zeta potential of −15.1 mV. SEM observations revealed the spherical morphology of oil globules, whereas FTIR results confirmed that no chemical interaction among the ingredients took place. The in vitro release study showed the burst release of 82.1 % AZL and 48.1 % release of DOX.H2O from the optimized DOX-AZL co-loaded NE in 6 h. The ex vivo permeation profile showed a minimum permeation of DOX.H2O and AZL across rat skin. Croton oil induced inflammation in mice ear confirmed the therapeutic efficacy of the prepared NE against facial rosacea. Considering the results obtained herein, the developed NE could enhance the safety and efficacy of the combination therapy against facial rosacea.

Therapeutic effects of mesoderm introduction of compound glycyrrhizin injection on the treatment of rosacea.

This study aims to introduce compound glycyrrhizin injection for the treatment of rosacea by mesoderm therapy, and further analyze the therapeutic and aesthetic effects of this treatment method and its impact on the dermatological quality of life index, which provides new ideas and methods for cosmetic dermatology treatment of rosacea. The recruited rosacea patients were divided into Control group (n=58) and observation group (n=58) according to the random number table. The control group was treated with topical metronidazole clindamycin liniment, and the study group was additionally used mesoderm introduction of compound glycyrrhizin injection. The transepidermal water loss (TEWL), water content in corneum, and dermatology life quality index (DLQI) in rosacea patients were evaluated. Our results showed that the scores of erythema, flushing, telangiectasia, and papulopustule were significantly reduced in the observation group. In addition, the observation group significantly decreased TEWL and increased the water content of the stratum corneum. Furthermore, the observation group significantly reduced the DLQI of rosacea patients compared to the control group. The use of mesoderm therapy combined with compound glycyrrhizic acid has a therapeutic effect on facial rosacea and improves patient satisfaction.

Effectiveness of VISIA system in evaluating the severity of rosacea.

Rosacea is a facial chronic inflammatory skin disease with almost 5.5% prevalence. Although there are various scales of rosacea, they are objective and discordant among different dermatologists. Noninvasive objective measurements such as VISIA system might play essential roles in the diagnosis and evaluation of rosacea. Here, we intended to reveal the effectiveness of VISIA system in rosacea. A number of 563 participants diagnosed with facial rosacea were enrolled in study. They all received both full-face image-shoot by VISIA system with quantitative analysis software and physician's assessment via five different scales, including investigator global assessment (IGA), clinician erythema assessment (CEA), numerical score, the National Rosacea Society (NRS) grading system and telangiectasis. Absolute score and percentile of red area had significant correlations with IGA and CEA, whereas red area had no significant correlation with numerical score, NRS and telangiectasis. Red area in erythematotelangiectatic rosacea patients demonstrated the highest correlation with IGA and CEA, especially in those aged between 51 and 60. Besides red area, pigmentation parameters in VISIA system (brown spot) also showed significant correlation with IGA and CEA. VISIA system might be an effective measurement in the assessment of rosacea severity.

Prospective evaluation of intense pulsed light treatment for meibomian gland dysfunction and blepharitis due to ocular rosacea

Ocular rosacea is a common skin condition leading to dry eye that is difficult to manage. To estimate the efficacy and safety of a new intense pulsed light device, Thermaeye Plus, for meibomian gland dysfunction and blepharitis due to ocular rosacea. This prospective, longitudinal study included 74 eyes of 37 consecutive patients with ocular rosacea, with mean age of 45.6±11.7 years. Four consecutive sessions were undertaken, including14 flashes with 10 J/cm²on the periocular area and facial cheeks on Day 1, 14, 28, and 49. Clinical evaluation was based on: ocular surface disease index (OSDI) and symptom score questionnaires, quality of live and facial severity degree, non-invasive tear meniscus height, non-invasive tear break up time, corneal fluorescein staining and eyelid margin and meibomian gland assessment. Adverse effects on the eye and periocular area, and systemic complications were evaluated. The OSDI questionnaire showed a decrease in symptoms, achieving normal values in 91.9% of patients. The symptom score showed amelioration, with the most significant changes relating to dryness, foreign body sensation, light sensitivity, and pain. Longitudinal analysis showed the most significant improvement between baseline at Day 1 and 49. All eyelid signs improved, most significantly for telangiectasia/vascularity and blepharitis, leading to a 78% clearance of facial rosacea and 81.1% reduction of flushing. In total, 100% of the patients reported an improvement in their quality of life after treatment and 94.6% a very significant improvement (p<0.001). These results demonstrate that Thermaeye Plus is an effective and safe treatment for ocular rosacea.

Oral antibiotics for chronic blepharitis.

Oral antibiotics for chronic blepharitis.

Evaluation of the Effectiveness of Neodymium Laser Therapies for Rosacea of the Face

Objectives: The study aimed at assessing the efficacy of neodymium laser therapies and Accutane (isotretinoin) systemic therapy for patients with rosacea. Materials and Methods: A total of 64 patients with rosacea were selected for the study for the treatment of facial rosacea; the study was conducted from 2016 to 2020. All patients underwent a thorough clinical examination according to the generally accepted scheme. Patients received neodymium laser therapies and Accutane (isotretinoin) systemic therapy. Investigator Global Assessment (IGA) scale, Laser Doppler Fluorometry (LDF), and Dermatology Life Quality Index (DLQI) questionnaire were used to assess outcome treatments, resulting in the rosacea of the scene before and after neodymium therapy and Accutane (isotretinoin) systemic therapy. Results: A multitargeted therapy effectiveness rosacea neodymium is ideal for the management of the signs and symptoms of rosacea and it results in reductions in the mean acne lesion counts after 7 seans therapy, with persistent reduction at the 12-month follow-up, indicating significant long-term remission. The average rosacea IGA scale decreased from 4.2 at baseline to 0.6 after treatment. The average indicators of DLQI before and after laser treatment were 17.3 and 2, 4 respectively. Laser Doppler imaging showed that the mean value of the facial area was 151 units, before treatment; after the treatment, the values decreased, and the mean was 129 units. Conclusion: Neodymium laser therapy exposure has been effective in treatment therapies for rosacea. Our results indicate that the use of neodymium monotherapy represents an option to consider when dealing with treatment rosacea, being effective, well tolerated, and free of side effects, as confirmed by clinical and instrumental evaluation. The condition improved from baseline in 92.3% of subjects.

Systemic Conditions Associated with Severity of Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management Study

Certain systemic conditions are reported to be risk factors for dry eye disease (DED), but their associations with DED severity are not well studied. We evaluated whether systemic conditions reported to be DED risk factors are associated with severity of DED signs and symptoms. Secondary analysis of data from the Dry Eye Assessment and Management Study, a large-scale multicenter randomized clinical trial of patients with moderate to severe DED. Five hundred thirty-five adult patients with moderate to severe DED from 27 United States centers. Patients reported their medical history at baseline. They underwent ocular surface examinations and symptom evaluation using standardized protocols at baseline, 6 months, and 12 months. We analyzed the associations of systemic conditions (a systemic disease or smoking history) reported as potential DED risk factors with the severity of DED signs and symptoms using generalized linear regression models adjusted by age, gender, race, and visit. Dry eye disease symptoms assessed using the Ocular Surface Disease Index (OSDI), 6 DED signs (tear film break-up time, anesthetized Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, tear osmolarity, and meibomian gland dysfunction), and a composite signs severity score from 0 to 1 (1= most severe). The mean age was 58 years; 81% were women. More severe DED signs were associated significantly with Sjögren syndrome (mean composite signs severity score 0.52 with disease vs. 0.43 without disease; P < 0.001), facial rosacea (0.47 vs. 0.43; P= 0.002), rheumatoid arthritis (0.47 vs. 0.42; P= 0.002), peripheral artery disease (0.50 vs. 0.43; P < 0.001), and daily smoking history (0.45 vs. 0.43; P= 0.047). Thyroid dysfunction, osteoarthritis, diabetes, irritable bowel syndrome, hypercholesterolemia, hypertension, and hypertriglyceridemia were not associated significantly with DED signs. No conditions were associated significantly with OSDI. In this large, well-characterized cohort of patients with DED assessed under standardized procedures, patients with certain systemic diseases and smoking history showed more severe DED signs compared with patients without the conditions. The profile of significant DED signs varied by systemic condition, reflecting different DED causes. Understanding the systemic conditions and underlying causes that predispose some patients to severe DED can improve management.

17800 Open-label extension study evaluating the long-term safety, efficacy, and tolerability of FMX103 1.5% topical minocycline foam in the treatment of moderate to severe facial papulopustular rosacea

17800 Open-label extension study evaluating the long-term safety, efficacy, and tolerability of FMX103 1.5% topical minocycline foam in the treatment of moderate to severe facial papulopustular rosacea

Clinical translation of choline and geranic acid deep eutectic solvent.

Choline geranate deep eutectic solvent/ionic liquid (CAGE) has shown several desirable therapeutic properties including antimicrobial activity and ability to deliver drugs transdermally in research laboratories. Here, we describe the first report of clinical translation of CAGE from the lab into the clinic for the treatment of rosacea, a common chronic inflammatory skin disorder that affects the face. We describe the seven steps of clinical translation including (a) scale‐up, (b) characterization, (c) stability analysis, (d) mechanism of action, (e) dose determination, (f) GLP toxicity study, and (g) human clinical study. We describe the challenges and outcomes in these steps, especially those that uniquely arise from the deep eutectic nature of CAGE. Our translational efforts led to a 12‐week open‐label phase 1b cosmetic study with CAGE1:2 gel (CGB400) in mild–moderate facial rosacea in 26 patients where CGB400 exhibited a marked reduction in the number of inflammatory lesions. These results demonstrate the therapeutic potential of CGB400 for treating rosacea as well as it provides insights into the translational journey of deep eutectic solvents, in particular CAGE, for dermatological applications.

Open-Label Extension Study Evaluating the Long-Term Safety, Efficacy, and Tolerability of FMX103 1.5% Topical Minocycline Foam in the Treatment of Moderate-to-Severe Facial Papulopustular Rosacea

Abstract not available.

Open-Label Extension Study Evaluating the Long-Term Safety, Efficacy, and Tolerability of FMX103 1.5% Topical Minocycline Foam in the Treatment of Moderate-to-Severe Facial Papulopustular Rosacea

Abstract Not Available.

Ocular rosacea: The insight

Rosacea is a chronic cutaneous disorder with non specific and variable ocular manifestations. Ocular rosacea is often underdiagnosed, despite the potential for serious sight threatening sequelae. The study was designed to determine the incidence of ocular disease among the population of rosacea patients along with evaluating the presence of eye dryness in both the patients and controls using Schirmer 1 test. It correlated the severity of ocular disease with the severity of cutaneous rosacea. A total of 72 patients with facial rosacea were enrolled and evaluated with thorough history, physical and ophthalmological examination for ocular rosacea. Schirmer’s test was performed on all patients with ocular rosacea and controls. Out of 72 patients with facial rosacea, 30 (41.62%) were diagnosed with ocular rosacea. On the Schirmer test, ocular rosacea patients had statistically significant lower value than the control group. There was also a statistically significant difference between mean Schirmer test values of male patients and controls and female patients and controls. Symptoms of ocular rosacea are not always specific hence underdiagnosed. Ocular features of rosacea in patients presenting with mere cutaneous findings should not be overlooked.

Bioequivalence Study of Ivermectin Cream 1% in Treatment of Moderate to Severe Facial Rosacea

Bioequivalence Study of Ivermectin Cream 1% in Treatment of Moderate to Severe Facial Rosacea

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

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. To give insight into available noninvasive imaging techniques and biophysical methods in rosacea by performing a systematic review. 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. 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. 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.

A Case Report of Fulminant Type 1 Diabetes Mellitus Caused by Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Complicated by Iodine-Induced Thyrotoxicosis.

A 46-year-old woman presented with rash, fever, lymphadenopathy, eosinophilia and liver dysfunction. She had been treated with ornidazole for facial rosacea 2 months previously. Two weeks following presentation, she developed diabetic ketoacidosis with exhausted beta islets (2 h postprandial laboratory values: glucose 22.0 mmol/L, C-peptide < 0.017 nmol/L, proinsulin < 0.23 pmol/L) and negative autoantibodies. Several days thereafter, after having undergone an enhanced computed tomography examination to screen for malignancy, the patient developed thyrotoxicosis with a low iodine absorption rate and super-high urine and serum levels of iodine. The patient was ultimately diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), a hypersensitivity reaction to drugs. Studies have shown that immune dysregulation during DRESS renders patients susceptible to new diseases. Here we report a patient who recovered from DRESS but developed fulminant type 1 diabetes complicated with iodine-induced thyrotoxicosis. This case report sheds light on the pathogenesis of DRESS and its sequelae and illustrates that patients with DRESS require long-term care and follow-up.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-0607-5) contains supplementary material, which is available to authorized users.

Effect of recombinant bovine basic fibroblast growth factor gel on repair of rosacea skin lesions: A randomized, single-blind and vehicle-controlled study.

The aim of the present study was to assess the effect of topical use of recombinant bovine basic fibroblast growth factor (rbFGF) gel on the repair of facial skin lesions in patients with rosacea. In the present single-blind study, a total of 1,287 patients with Demodex mite-induced rosacea who received treatment with ornidazole tablets were randomized to rbFGF gel treatment group (n=651) or control group (n=636) without revealing the group identity. Patients in the treatment group were treated with topical application of rbFGF gel over the skin lesions (0.2 g/cm2) for up to 8 weeks, whereas patients in the control group received gel vehicle treatment unless ulceration occurred. Skin lesions of all patients were scored prior to and following treatment with rbFGF gel and subjected to histological analysis. All patients were followed up for 6 months. Significant improvement in the total effective rates for erythema, papules, desquamation and dryness were observed in the rbFGF treatment group. At the end of the 2, 4 and 6 months of follow-up, the total effective rates for patients in the treatment group were significantly higher than those in the control group (81.67 vs. 28.84%; 85.11 vs. 40.81%, and 96.56 vs. 55.82%, respectively). Following treatment for 6 months, none of the patients in the rbFGF group exhibited ulceration or scar formation. In the control group, 61% of patients experienced exacerbation of skin lesions, of which, 12% exhibited ulceration and were treated with rbFGF gel to prevent scar formation. Histological analysis revealed gradual reduction in epidermal hyperplasia and resolution of dermal edema in skin lesions treated with rbFGF gel. In conclusion, rbFGF gel may improve the repair of facial rosacea skin lesions in patients treated with anti-Demodex.

An empirically generated responder definition for rosacea treatment.

ObjectiveThe aim of this study was to empirically generate a responder definition for the treatment of papulopustular rosacea.MethodsA total of 8 multicenter clinical studies on patients with papulopustular facial rosacea were analyzed. All patients were treated with azelaic acid and/or comparator treatments. The severity of rosacea was described by the Investigator Global Assessment (IGA) and the number of lesions. Patients with the IGA score of “clear/minimal” were considered as responders, and those staying in the range of IGA “mild to severe” as nonresponders. The respective number of lesions was determined.ResultsA total of 2,748 patients providing 12,410 measurements were included. After treatment, responders showed 2.23±2.48 lesions (median 2 lesions [0–3]), and nonresponders showed 13.74±10.40 lesions (median 12 lesions [6–18]). The optimal cutoff point between both groups was 5.69 lesions.ConclusionThe calculated cutoff point of 5.69 lesions allows discrimination of responders (5 or less remaining lesions) and nonresponders (6 or more remaining lesions) of therapeutic interventions in rosacea.

Ocular Rosacea: Treatment with Rifaximin, a Non-Systemic Antibiotic

Background: Rosacea is associated with Crohn’s disease, liver disease, chronic pancreatitis, achlorhydria, Helicobacter pylori and recently with idiopathic small intestinal bacterial overgrowth (SIBO). Two publications demonstrated that rifaximin, a non-absorbed, gut-directed antibiotic for SIBO led to improvement in facial rosacea. Ocular manifestations occur in up to 58% of rosacea patients and include dry eyes, foreign body sensation, photosensitivity, eyelid inflammation, neovascularization and corneal ulcers. Methods: Patients who had been diagnosed with ocular rosacea by four ophthalmologists were referred for SIBO testing using the lactulose breath test (LBT). All were refractory to rosacea therapy. An open-label, IRBapproved trial of rifaximin 550 mg/3x/day for 10-14 days was performed in LBT-positive subjects. Ten and twenty days after ending rifaximin, subjects were queried if their eye symptoms had marked, moderate or mild improvement or if they were unchanged. Results: Twenty four patients (21F/3M), mean age 59 with facial involvement in 4 were tested. The LBT was positive in 9/24 (38%). LBT-positive subjects had chronic gastrointestinal symptoms in 63% vs., 33% in LBTnegative subjects. Rifaximin was prescribed to 9 LBT-positive subjects. Insurance denied the prescription in one subject. One subject was lost was to follow up. Improvement in ocular rosacea symptoms was marked (4), moderate (1) and mild (2). Conclusions: Rifaximin therapy led to improvement in ocular rosacea in the setting of SIBO. Dysregulation of the innate immune system as a result of gastrointestinal inflammation could lead to an increase in systemic cytokines and microbial antigens/antibodies in the skin and eyelids leading to activation of rosacea.

Reflectance confocal microscopy for monitoring the density of Demodex mites in patients with rosacea before and after treatment.

Demodex mites seem to serve as a pathogenic trigger in many Demodex-associated diseases such as rosacea. In facial skin of patients with rosacea significantly higher numbers of Demodex mites have been shown compared with healthy controls. Reflectance confocal microscopy (RCM) allows the detection and quantification of Demodex mites in vivo noninvasively. It is hypothesized that a reduction of Demodex mites under rosacea therapy can be monitored by RCM. To use RCM to monitor the density of Demodex mites in patients with rosacea before and after treatment. In 25 patients with facial rosacea RCM was performed before and after therapy. Mosaics of 5 × 5 mm(2) and 8 × 8 mm(2) were scanned, and the total numbers of mites per follicle and per area were counted, along with the number of follicles per area. In all patients Demodex folliculorum could be detected and quantified using RCM. RCM showed significant differences pre- and post-treatment (P = 0.0053 for 5 × 5 mm(2) and P < 0.001 for 8 × 8 mm(2)). The mean numbers of mites per follicle were 0.63 (range 0.16-2.28) per 8 × 8 mm(2) area and 0.70 (range 0.11-2.20) per 5 × 5 mm(2) area before treatment, and 0.41 (range 0.074-1.75) and 0.51 (range 0.094-1.70), respectively, after treatment. The corresponding mean numbers of mites were 155 (range 45-446) and 86.2 (range 12-286), respectively, before treatment and 96.2 (range 18-363) and 58.5 (range 12-230), respectively, after treatment. By RCM, a reduction in the density of Demodex mites in facial skin of patients with rosacea under therapy, correlating to clinical improvement, can be quantified and monitored noninvasively. Possible reasons for this therapeutic effect are discussed.

Facial Dystonias and Rosacea: Is There an Association?

Purpose: Benign essential blepharospasm (BEB) and hemifacial spasm (HFS) belong to a spectrum of focal movement disorders that cause involuntary, spasmodic contractions of the eyelid and facial muscles. In our clinical experience, we have observed an increased prevalence of rosacea in patients who present with BEB and HFS. We investigate our clinical findings with a review of disease pathophysiology and treatment.Methods: Retrospective study approved by the Ochsner Institutional Review Board and literature review. A total of 140 charts dated from 1990 to 2013 were reviewed, including 87 patients with BEB and 53 patients with HFS. Rosacea, BEB, and HFS were defined by standard diagnostic criteria.Results: Within our BEB and HFS patient cohort, approximately 15% of patients presented with rosacea, compared to the general American population prevalence rate of 1.34% (p < 0.001). Of the 140 patients reviewed, a total of 21 patients (13 with BEB and 8 with HFS) exhibited rosacea (p = 0.995).Conclusions: Dry eye and tear instability often co-exist in patients with facial dystonias and rosacea, which may provide the initial drive towards tonic eyelid contractions and simultaneously exacerbate rosacea. Studies suggest that neurogenic inflammation and altered vasoregulation jointly contribute to the pathogenesis of rosacea. From our preliminary observations, we suggest the possibility of shared immune-inflammatory pathways involved in both facial dystonias and rosacea. Identification of common inflammatory mediators involved in both disease processes may facilitate a more targeted approach in drug treatment. Further biochemical analysis will likely be necessary to elucidate this potential association.