Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Managing dry skin in patients with comorbidities or with advanced age: unmet needs and roles for products containing potential emollient-plus ingredients.

In dry skin (DS), skin-barrier function is easily disturbed and moisturizing factors in the stratum corneum are reduced. Despite being a common condition, DS is often overlooked in patients with advanced age or comorbid diseases. In September 2022, specialists in dermatology and skin care met to discuss unmet needs and management of patients with DS with existing medical conditions or DS induced by ongoing pharmacological treatments. There was consensus about the need to improve the current understanding and management of DS in patients with comorbidities, including type 2 diabetes, chronic kidney disease, radiodermatitis, and photodamaged skin. Clinical guidance related to optimal treatment of DS in patients with advanced age or comorbid diseases is needed. Dexpanthenol-containing emollients have been shown to provide rapid relief from the symptoms and clinical signs of skin inflammation and are well-tolerated and effective in terms of moisturizing and soothing DS and maintaining skin-barrier function. Thus, dexpanthenol-containing emollients may play an important role in future management of DS. Further research is needed to elucidate the efficacy of dexpanthenol across the spectrum of DS, irrespective of comorbidity status or age.

A Randomized, Controlled Clinical Trial of a Dermocosmetic Containing Vichy Volcanic Mineralizing Water and Probiotic Fractions in Subjects with Rosacea Associated with Erythema and Sensitive Skin and Wearing Protective Masks.

Purpose: Rosacea is a common facial dermatosis, with flares induced by exposome factors. M89PF containing Vichy mineralizing water, probiotic fractions, hyaluronic acid, niacinamide and tocopherol repairs the skin barrier and reinforces skin defences against exposome factors. This study assessed the benefit of M89PF in subjects with rosacea associated with erythema and sensitive skin during the Covid-19 pandemic using protective face masks. Methods: M89PF was compared to usual skin care in a randomized, split-face study, for 30 days in subjects with rosacea associated with erythema and sensitive skin. Clinical evaluations included erythema, desquamation, skin tightness, dryness, burning sensation, itching, stinging, stinging test, and local tolerability. Instrument evaluations included erythema, skin hydration and TEWL. Subject satisfaction was also assessed. Results: Erythema significantly improved with M89PF at both time points (p<0.01 at D15, and p<0.001 at D30). Skin sensitivity assessed by the skin stinging test improved significantly (p<0.01) with M89PF at D30, compared to baseline and usual skin care. Skin erythema, tightness, dryness, hydration and TEWL significantly improved (p≤0.05) with M89PF at D15 and D30, versus baseline and the untreated side. Subjects were highly satisfied with M89PF at D15 and D30. Tolerance was very good in all subjects. Conclusion: In subjects with rosacea, M89PF significantly reduces erythema, skin tightness, dryness and TEWL, and improves skin hydration and skin sensitivity, even when using protective masks. M89PF is well tolerated and received high satisfaction ratings. ClinicalTrialsgov No: NCT05562661.

Vitamin E supplementation in inflammatory skin diseases.

Vitamin E is a powerful lipophilic antioxidant that protects membranes from lipid peroxidation, and consequently, oxidative damage. Oxidative stress plays a role in the development of neurodegenerative diseases. Vitamin E supplementation is recommended in patients with vitamin E deficiency due to fat malabsorption. The addition of vitamin E to the diet slows Alzheimer's disease progression and protects older patients against respiratory infections. Recent studies also point to the involvement of oxidative stress in the pathology of immune-mediated skin diseases, such as atopic dermatitis and psoriasis. We reviewed the available clinical trials that investigated the role of vitamin E supplementation in preventing and treating atopic dermatitis and psoriasis. Data from these studies point to a positive role of vitamin E supplementation in these diseases. Still, due to limitations in study design, further evidence is needed to reach a definite conclusion.

Effects of food supplements and a topical solution containing nanosilicon on skin hydration, barrier function, and elasticity.

BACKGROUND: Silicon is an abundant element in the human body and plays an important role in the skin, taking part in the synthesis of collagen and glycosaminoglycans. The use of nanotechnology methods, which processes materials at an atomic and molecular scale, has allowed the development of nanosilicons. AIMS: The study evaluates the effectiveness of a food supplement and a topical solution containing nanosilicon in improving skin hydration and elasticity. METHODS: A total of 30 female subjects were randomized to receive the placebo (n = 15) and the active compound (n = 15). All enrolled subjects took the food supplement twice a day for 20 days and then once a day for the next 20 days, and they also had to apply the nanosilicon solution on the right forearm four times a day. Evaluation of several parameters was performed after 20 and 40 days through the use of non-invasive instrumental methods (Corneometer® CM 825, Cutometer® MPA 580, Visioscan® VC, Tewameter® TM 200). RESULTS: Both treatment groups showed a statistically significant improvement in barrier function and in skin hydration on the right forearm after 20 days; increase in skin elasticity was observed only in the group taking the active compound. CONCLUSIONS: The study showed that the administration of a food supplement and a topical solution, both containing nanosilicon, improves hydration, elasticity, and skin barrier function.

Assessment of the skin efficacy and acceptability of a cosmetic product in the treatment of the forearm hypertrichosis in female patients.

BACKGROUND: Treatment of unwanted body hair is a challenging area in cosmetic dermatology. Topical soy isoflavones and derivatives or eflornithine have been utilized in dermatocosmetology for their estrogenic and antiandrogenic activity. AIMS: To evaluate the efficacy of a formulation containing capryloyl glycine 4% in decreasing hair growth on the forearms after topical application for 120 days vs placebo. METHODS: A total of 69 female patients entered the study (age 37 ± 6). Hair growth was quantified using TrichoScan software on both forearms at 20-fold magnification (analyzed area 0.651 cm2). Hair density (number of hairs/cm2 ), density vellus hair, density terminal hair, and median length of hairs were evaluated. The data were analyzed using ANOVA for repeated measures to evaluate changes during the treatment (T0, T60, and T120) and Student's t test (placebo vs active). RESULTS: There was a significant decrease on hair density, median, and terminal hair at the end of the treatment in the active-treated site (P < .001) as measured by TrichoScan software. Direct comparison between active and placebo-treated sites showed no significant differences at T0, but highly significant differences at T120 (P < .001). CONCLUSIONS: The study shows that a cosmetic formulation based on capryloyl glycine 4% is highly effective in reducing several parameters related to hair growth and hair thickness vs placebo, thus showing efficacy in the treatment of hypertrichosis.

A Split-Face Study Assessing the Clinical Benefit, Tolerability and Subject Satisfaction of a Dermocosmetic in Subjects with Rosacea Associated with Erythema and Sensitive Skin.

OBJECTIVE: This study assessed the efficacy and tolerability of M89 in patients with rosacea associated with erythema and sensitive skin. METHODS: Intra-individual study in a split-face design comparing after 30 days M89 twice daily and usual skin care in 20 adult subjects with rosacea and sensitive skin. M89 contains 89% Vichy volcanic mineralizing water (VVMW) and 0.4% hyaluronic acid. It is hypoallergenic and contains no perfume and this convenes in rosacea. Contained minerals reinforce the natural defences of the skin in restoring the natural skin barrier, stimulating antioxidant activity and reducing inflammation, commonly observed in subjects with rosacea. Clinical evaluations included assessment of erythema, desquamation, papules and pustules, skin tightness, dryness, burning sensation, itching, stinging and stinging test as well as local tolerability. Instrumental evaluations included skin hydration and TEWL. Subject satisfaction was assessed at Days 15 and 30. Demodex density was assessed at Day 30. RESULTS: A significant superiority of M89 over the standard skin care was observed for erythema, skin tightness and dryness (all P≤0.05) as early as Day 15, the skin stinging test was significantly in favour of M89 (P<0.05 at Day 15 and P<0.01 at Day 30) and for skin hydration (P<0.0001) at Day 15 and 30 with no difference in mean Demodex density between M89 and usual skin care after 30 days. Tolerance was excellent and subject satisfaction very high. CONCLUSION: Study results concerning M89 are encouraging for its use either alone or as an adjuvant daily skin care to topical medication in patients with persistent centrofacial erythema of rosacea with no more than 3 papules and pustules.

Clinical and noninvasive instrumental evaluation of the efficacy of a nonsteroidal anti-inflammatory 8-beta glycyrrhetinic acid cream for the treatment of erythema in rosacea.

Rosacea is a very common chronic facial dermatosis characterized by a multiphase evolution. Inflammation is an important reaction in rosacea not only due to inflammatory reactions to cutaneous microorganisms, such as Demodex follicolorum, but also to ultraviolet damage that generates reactive oxygen species. This study evaluated the efficacy and tolerability of a nonsteroidal anti-inflammatory 18-beta glycyrrhetinic acid cream for the treatment of mild rosacea by means of noninvasive methods. A total of 24 subjects suffering from erythemato-telangiectatic or mild papulo-pustular rosacea were recruited in the trial. Twelve patients applied an anti-inflammatory cream with 18-beta glycyrrhetinic acid twice daily for 20 days and 12 patients, recruited as control, applied the same formulation without 18-beta glycyrrhetinic acid. After 10 days of treatment, a significant reduction of erythema was recorded in the patient sample who applied the 18-beta glycyrrhetinic acid cream, the mean change from baseline showed an increase in hydration level of the skin surface but it was not statistically significant. The use of 18-beta glycyrrhetinic acid cream can be helpful in managing symptoms and condition of rosacea skin, especially in the management of erythema.

Non-invasive assessment of urea efficacy: A review.

Urea is an emollient widely used in clinical dermatology to moisturise and protect the skin. Non-invasive techniques can be useful in evaluating and quantifying the moisturising and hydrating properties of topically applied urea. Amongst these, transepidermal water loss, skin conductance and capacitance are the most widely used. Dynamic tests and mapping of skin moisturisation are additional features that can be used to evaluate the dynamics of water into the stratum corneum. Ultrasound and mechanical properties can be used to investigate the effects on skin smoothness and tone. In conclusion, urea is a fundamental ingredient of cosmetic and dermatological formulations and can have several positive effects on skin function. These can be easily investigated and monitored using non-invasive techniques measuring the stratum corneum function.

Dry skin management: practical approach in light of latest research on skin structure and function.

Dry skin is a common condition that is attributed to a lack of water in the stratum corneum. With the availability of new technologies, light has been shed on the pathophysiology of dry skin at the molecular level. With the aim to discuss implications of this latest research for the optimal formulation of emollients designed to treat dry skin, five specialists met in November 2017. Research on three topics thereby provided particularly detailed new insights on how to manage dry skin: research on the lipid composition and organization of the stratum corneum, research on natural moisturizing factors, and research on the peripheral nervous system. There was consensus that latest research expands the rationale to include physiological lipids in an emollient used for dry skin, as they were found to be essential for an adequate composition and organization in the stratum corneum but are reduced in dry skin. Latest findings also confirmed the incorporation of carefully selected humectants into a topical emollient for dry skin, given the reduced activity of enzymes involved in the synthesis of moisturizing factors when skin is dry. Overall, the group of specialists concluded that the previous concept of the five components for an ideal emollient for dry skin is well in accordance with latest research.

Effectiveness of a new cosmetic treatment for melasma.

BACKGROUND: Melasma treatment is difficult due to extended treatment periods, suboptimal adherence, inconsistent results, and frequent relapses. Kojic acid has been shown to be effective in reducing melasma severity and is now increasingly used in cosmetic treatments. AIMS: The purpose of the present study was to evaluate the effectiveness of a new cosmetic treatment for melasma at 45 and 90 days. METHODS: Multicenter prospective study across 20 dermatology clinics/ambulatories. One hundred patients with mild-to-moderate melasma were evaluated. The primary endpoints were changes in mean modified melasma area and severity index (mMASI) score and patient-reported satisfaction at 45 and 90 days. RESULTS: The mean age of patients was 45.19 ± 11.5 years. Most patients were female and Caucasian. Patients presented mixed (65%), epidermal (26%), and dermal (4%) types of melasma. Triggering factors were hormonal contraception (33%), pregnancy (31%), and pharmacological treatment (11%); mean disease duration was 6.7 ± 6.8 years. Overall, a statistically significant decrease in mean mMASI scores was seen at 45 (2.19 ± 0.182 vs 3.29 ± 0.267, P < .0001) and 90 days (1.27 ± 0.128 vs 3.29 ± 0.267, P < .00001). The highest reduction in mMASI scores was observed in patients with dermal melasma. IGA scores showed a statistically significant improvement in pigmentation at 90 days (P < .00001). CONCLUSION: The novel cosmetic treatment was associated with the improvement of melasma, as assessed by mMASI.

Lichen sclerosus: the role of oxidative stress in the pathogenesis of the disease and its possible transformation into carcinoma.

Lichen sclerosus (LS) is an autoimmune chronic inflammatory disease usually involving the anogenital skin of both sexes; more rarely LS exclusively involves extragenital areas. As a chronic inflammatory disease, in most cases, LS evolves and progresses causing scleroatrophy of the skin or scars which may cause stenosis in the affected areas. A few LS patients are at risk of developing squamous cell carcinoma in their lifetime, but appropriate long-term treatment diminishes the possibility of a malignant evolution. Oxidative stress (OS) has been proven to play a role not only in the pathogenesis of LS, but also in the development and progression of the disease. OS, by causing DNA damage and lipid peroxidation, contributes directly to the possible malignant transformation of LS. Moreover, the increase in oxidative DNA damage is associated with mutations in tumor suppressor genes. Considering the role that OS plays in LS, therapeutic use of antioxidants appears to be rational and possible, in association with other treatments. Antioxidants would counteract the oxidative DNA damage, which is the most important factor for the progression of LS and its malignant transformation.

Biotin: overview of the treatment of diseases of cutaneous appendages and of hyperseborrhea.

One of the most common micronutrient deficiencies with cutaneous findings is the vitamin B, also known as biotin, deficiency. Biotin deficiency may be due to congenital lack of biotinidase, or acquired following some conditions that interfere with its absorption, such as inflammatory bowel disorders, a diet too rich in avidin, magnesium deficiency, smoking habit and treatment with broad-spectrum antibiotics, anticonvulsants and sulfonamides. This review highlights the role of biotin in the most common skin disorders such associated with biotin deficiency and an approach to their treatment. Biotin administration may improve the treatment of hair loss when deficiency is detected on the basis of a careful patient history, clinical examination and the determination of serum biotin levels. The use of biotin is rationale in seborrheic dermatitis as the vitamin intercepts the main metabolic pathways underlying the pathogenesis of the disease. Treatment with biotin could also be useful in comedonal acne characterized by a high rate of seborrhea, and may be helpful for acne treated with topical retinoids, contributing to the control of flaking and irritation. The tolerability of biotin is excellent and there is no risk of hypervitaminosis even in the case of high doses. It is important that administration is controlled by physicians and follows a medical diagnosis and prescription. Correct doses used in dermatological conditions are safe and are not at risk of interference with laboratory tests.

Intrinsic and Extrinsic Factors Affecting Skin Surface pH.

The body skin pH can usually vary from 4.0 to 7.0 depending on location. The presence of natural acidic compounds on the skin surface helps maintain the skin's physicochemical properties as well as its protective functions. Since the slightly acidic pH of the skin is extremely important for the skin's protective function, the skin is widely known as "acid mantel." Factors such as age, race, gender, body sites, biochemical differences, and even washing affect the pH of the stratum corneum. Recent clinical studies using an emollient-base finish product using the traditional way of measuring skin pH produced results that indicated an apparent increase in skin pH. The apparent pH increase with these products is most probably an artifact of the skin pH measurement technique. Our findings show that certain petrolatum-based emollients and components could create a protective barrier and help maintain the healthy acidity of the skin. Our work provides new evidence of emollients helping to stabilize skin pH in its natural balanced state rather than affecting it. This new learning should be taken into consideration by other researchers in the area of skin pH as well as in clinical studies to avoid misleading results.

pH and Microbial Infections.

Maintenance of an acidic stratum corneum pH is a major component of the skin's protective system and creates a hostile environment for colonization with pathogenic microorganisms. This barrier can however be overcome on healthy and in particular on compromised skin. Mycosis, diaper/incontinence dermatitis and wound healing are examples of cases where microbial infection is promoted by the altered skin conditions or environment. Fungi have a complex system that senses ambient pH that leads to metabolic responses allowing adhesion, growth and invasion, as microbial metabolites further increase skin pH resulting in a clinically manifest infection (mycosis). Diabetic patients with a higher pH in intertriginous areas are particularly vulnerable to candidiasis. In diaper and incontinence dermatitis, the increase in skin pH and damage to the skin barrier function is triggered by the contact with urine and faeces with or without occlusion and maintained by host and microbial enzymes and metabolites. This leads to the reduction of the protective resident microflora and fungal overgrowth, mostly with Candida albicans. Skin care with slightly acidic products may help to prevent and treat this kind of dermatitis. Wound healing is a complex sequence of biologic events correlated with ambient pH, which influences the different phases of the healing process. The pH determines the appropriate activity of immune cells and key enzymes as well as biofilm formation. Chronic wounds emerging from the disruption of the healing process are characterized by a neutral to slightly alkaline pH and may benefit from wound pH monitoring and therapeutic acidification.

The revised EEMCO guidance for the in vivo measurement of water in the skin.

BACKGROUND: Noninvasive quantification of stratum corneum water content is widely used in skin research and topical product development. METHODS: The original EEMCO guidelines on measurements of skin hydration by electrical methods and transepidermal water loss (TEWL) by evaporimeter published in 1997 and 2001 have been revisited and updated with the incorporation of recently available technologies. RESULTS: Electrical methods and open-chamber evaporimeters for measurement of TEWL are still the preferred techniques to measure the water balance in the stratum corneum. The background technology and biophysics of these instruments remain relevant and valid. However, new methods that can image surface hydration and measure depth profiles of dermal water content now available. Open-chamber measurement of TEWL has been supplemented with semiopen and closed chamber probes, which are more robust to environmental influence and therefore convenient to use and more applicable to field studies. However, closed chamber methods interfere with the evaporation of water, and the methods cannot be used for continuous monitoring. Validation of methods with respect to intra- and inter-instrument variation remains challenging. No validation standard or test phantom is available. RESULTS AND CONCLUSIONS: The established methods for measurement of epidermal water content and TEWL have been supplemented with important new technologies including methods that allow imaging of epidermal water distribution and water depth profiles. A much more complete and sophisticated characterization of the various aspects of the dermal water barrier has been accomplished by means of today's noninvasive techniques; however, instrument standardization and validation remain a challenge.

Efficacy of a shower cream and a lotion with skin-identical lipids in healthy subjects with atopic dry skin.

BACKGROUND: Atopic dermatitis is a chronic, pruritic inflammatory skin disease that adversely affects quality of life. AIMS: The current study evaluates the efficacy of a shower cream and a lotion, each with skin-identical lipids and emollients, in the treatment of atopic dry skin of subjects with a history of atopic condition. METHODS: In all, 40 healthy females with clinically dry skin on the lower legs were enrolled in the study and underwent 4 weeks of daily use of the shower cream and 2 additional weeks of both the shower cream and the body lotion. Subjects were evaluated at day 0, week 4, and week 6. Skin barrier function was assessed by Tewameter® , skin hydration by Corneometer® , smoothness and desquamation by Visioscan® , and stratum corneum architecture by reflectance confocal microscopy (RCM). The investigator assessed the degree of dryness, roughness, redness, cracks, tingling and itch, and subjective self-assessment evaluated the perception of skin soothing, smoothness, and softness. RESULTS: Skin barrier function and skin moisture maintenance were significantly improved using the shower cream. The lotion with physiological lipids, together with the shower cream, also improved skin barrier function and moisture. Both the shower cream and the body lotion reduced clinical dryness, roughness, redness, cracks, tingling and itch, according to the dermatologist, and increased soothing, smoothness, and softness, according to the subjects of the study. CONCLUSION: The combination of a shower cream and a lotion with physiological lipids efficiently restores skin barrier function and increases skin hydration, becoming an effective skin-care option for patients with atopic dry skin.

Comparative instrumental evaluation of efficacy and safety between a binary and a ternary system in chemexfoliation.

OBJECTIVE: To instrumentally evaluate the efficacy and the safety of a new ternary system chemo exfoliating formulation (water-dimethyl isosorbide-acid) vs traditional binary systems (water and acid) where the acid is maintained in both the systems at the same concentration. METHODS: Different peelings (binary system pyruvic acid and trichloroacetic acid-TCA, and ternary system pyruvic acid and TCA) were tested on the volar forearm of 20 volunteers of both sexes between 28 and 50 years old. The outcomes were evaluated at the baseline, 10 minutes, 24 hours, and 1 week after the peeling by means of noninvasive skin diagnosis techniques. In vivo reflectance confocal microscopy was used for stratum corneum evaluation, transepidermal waterloss, and Corneometry for skin barrier and hydration, Laser Doppler velocimetry in association with colorimetry for irritation and erythema analysis. RESULTS: The instrumental data obtained showed that the efficacy and safety of the new ternary system peel compounds were significantly higher compared with the binary system formulations tested. The new formulation peels improved chemexfoliation and reduced complications such as irritation, redness, and postinflammatory pigmentation compared to the traditional aqueous solutions. CONCLUSION: The study showed that ternary system chemexfoliation, using a controlled delivery technology, was able to provide the same clinical effects in term of stratum corneum reduction with a significantly reduced barrier alteration, water loss, and irritation/erythema compared to traditional binary system peels.

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey.

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti-TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1; 95% CI: 4.2-15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6-16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 2.3; 95% CI: 1.4-3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1-4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti-TNF agents for the treatment of PsO and PsA patients.