Maintenance effect of a once-weekly regimen of a Selenium Disulfide-based shampoo in moderate-to-severe scalp seborrheic dermatitis after initial treatment with topical corticosteroid/salicylic acid.

INTRODUCTION: Seborrheic dermatitis (SD) is a chronic, relapsing, inflammatory disorder of the head and trunk. OBJECTIVES: To explore the potential of a 1% Selenium disulphide (SeS2)-based shampoo to prevent relapses of scalp SD (SSD) following corticosteroid/salicylic acid (TCS/SA) treatment. MATERIALS & METHODS: After a 2-week treatment with TCS/SA, adult patients with moderate-to-severe SSD received either the SeS2-based shampoo or its vehicle for eight weeks in a randomized, double-blinded fashion. Visits took place at baseline, weeks 2, 6 and 10. SSD severity was assessed based on erythema, flakes and pruritus; patients assessed the severity of pruritus. Global investigator and patient satisfaction were assessed at week 10. RESULTS: Forty-eight adults were included. After four and eight weeks of post TCS/SA maintenance regimen, 8.1% and 16.7% in the SeS2, and 41.7% and 54.2% in the vehicle group relapsed, respectively. First median time-to-relapse in the vehicle group was 56 days; this was not reached for SeS2. After two weeks of TCS/SA, the prevalence of patients with no pruritus was 29.2% in the SeS2 group, and 41.7% in the vehicle group; it increased to 76.2% with SeS2 and to 57.1% with the vehicle at the end of the study. The clinical benefit of treatment with TCS/SCA was maintained in the SeS2 group only. Investigators and patients were highly satisfied with the efficacy of SeS2. Tolerance to SeS2 was excellent, with no reported adverse events. CONCLUSION: The SeS2-based shampoo significantly reduces the time-to-relapse of moderate-to-severe SSD flares. Its tolerance was excellent, with no reported adverse events.

The Effects of a Non-crossed-linked Hyaluronic Acid Gel on the Aging Signs of the Face versus Normal Saline: A Randomized, Double-blind, Placebo-controlled, Split-faced Study.

Background: Skin bio-revitalization improves skin quality globally; it permits the rejuvenation of the skin by increasing hydration and by reconstructing an optimal physiological environment for the skin cells together with a micro-filling effect. Objective: To assess the comparative efficacy of a non-cross-linked hyaluronic acid (NCHA) preparation (M-HA®10, FILLMED Laboratories, France) on fine lines reduction and on skin hydration, radiance and mechanical properties, after three sessions of multiple intradermal injections, active versus placebo, on the face of subjects presenting aging signs. Methods: Thirty healthy subjects received filler injections on one side and a control solution (saline) on the contralateral side of the face. Fine lines depth, skin hydration, and mechanical properties were evaluated using instrumental methods. Skin radiance, cheek fold and crow's feet were scored clinically. In addition, Investigator and subject satisfaction rates were evaluated by the Global Aesthetic Improvement Scale and a subject self-assessment questionnaire. Results: Ten days after the last multi-injection session, the following significant results were observed compared to the control: a reduction of both crow's feet wrinkle depth (in the 110 to 1000µm range, -10% for NCHA and +7% for control) and clinical scoring of cheek wrinkles, and increases in skin radiance and hydration (+35%) and also skin firmness (+27%). The Investigator found that NCHA either improved or much improved the aesthetic aspect on 82% of subjects whereas no improvement was found on the saline side. Subjects found that NCHA significantly reduced wrinkles and increased both skin firmness and elasticity. Conclusion: Intradermal injection of NCHA can improve the quality of facial skin with aging signs by reducing fine wrinkles and improving hydration, firmness and radiance.

Prevention of Polymorphic Light Eruption Afforded by a Very High Broad-Spectrum Protection Sunscreen Containing Ectoin.

INTRODUCTION: Polymorphic light eruption (PLE) is the most common idiopathic, acquired photodermatosis. The pathophysiology of PLE is not yet fully understood but seems to involve immunological mechanisms, UVA-induced oxidative stress, and the subsequent elicitation of a cellular stress response affecting keratinocyte gene expression and skin immune function. In the present study, a high broad-spectrum sunscreen medical device (MD), containing a very high protection complex of UVB and UVA filters and ectoin, was investigated for its ability to protect against UVA-induced PLE. METHODS: The study was carried out as a monocentric, double-blinded, randomized, untreated controlled design. The test MD was applied (2 mg/cm2) on one side of the chest according to a randomization list of 15 patients with a typical history of PLE, and the contralateral area remained untreated. After product application, the test areas were exposed daily to increasing doses of UVA radiation (from 40 to 60 J/cm2) until a PLE reaction was detected or for a maximum of five consecutive days. Evaluations of induced PLE included clinical scoring and chromametry for erythema and pigmentation. RESULTS: Overall, no positive PLE reaction was observed on the side of the chest treated by the test MD, whereas positive PLE reactions were triggered on the untreated side of 13 subjects. Subjective sensations were very rare on the MD-treated side but were numerous and more severe on the untreated side. Chromametry and clinical visual inspection indicated that the skin color was unchanged on the MD-protected side, whereas high increased values of erythema and pigmentation were observed on the untreated chest side. CONCLUSION: This MD sunscreen based on a complex of UVA-UVB filters and 1% of ectoin may be effective in preventing UVA-induced PLE. New studies comparing this MD sunscreen versus the same product without ectoin should be conducted. CLINICALTRIALS: gov identifier: NCT05320315 (retrospectively registered 09/17/2021).

A method to assess the protective efficacy of sunscreens against visible light-induced pigmentation.

BACKGROUND: Until now, photoprotection of human skin has involved the development of sunscreens effective in the ultraviolet (UV) domain. During the last ten years, several studies have shown that besides the well-known damaging effects of UV, visible (400-700 nm) and even infrared light (> 700 nm) can induce damage which contributes to photoaging. Furthermore, many photodermatoses are also known to be triggered by visible light (VL). OBJECTIVE/METHOD: An in vivo method is proposed to assess the protective efficacy of sunscreens in the VL domain. This method is based on the intensity of pigmentation induced by four repeated daily doses of VL, each equivalent to about one hour of midday sun. Exposures are performed using a solar simulator (xenon lamp) equipped with appropriate filters, and pigmentation is measured both clinically and by chromametry. Three commercially available sunscreens designed to protect in the visible range were evaluated. RESULTS: The results indicate that the VL-induced pigmentation was already significantly detectable visually and by chromametry 24 hours after the first exposure on the unprotected zone. Two products with moderate protective activity could be differentiated from the untreated zone from Day 3 to Day 5 and were also significantly less effective than a third tested product within the same study period. CONCLUSION: The method is simple, based on a clinical end point of VL-induced skin pigmentation, and can be performed within a 5-day period. It allows discrimination between products of different protective capacities. VL protection factor is also discussed.

Efficacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam Compared with Betamethasone 17-Valerate-Medicated Plaster for the Treatment of Psoriasis.

BACKGROUND: Fixed combination calcipotriol as hydrate (Cal) 50 µg/g plus betamethasone as dipropionate (BD) 0.5 mg/g aerosol foam is an alcohol-free treatment for psoriasis. Betamethasone 17-valerate 2.25 mg (BV)-medicated plasters are recommended for treating psoriasis plaques localized in difficult-to-treat (DTT; elbow, knee, anterior face of the tibia) areas. OBJECTIVE: The aim of this study was to compare the efficacy of Cal/BD foam with BV-medicated plaster in patients with plaque psoriasis. METHODS: In this phase IIa, randomized, single-center, investigator-blinded, 4-week study, both Cal/BD foam and BV-medicated plaster were applied once daily to six test sites (three for each treatment). The primary efficacy endpoint was absolute change in total clinical score (TCS; sum of erythema, scaling, and infiltration); secondary endpoints were changes from baseline in each individual clinical score, ultrasonographic changes (total skin and echo-poor band thickness), and safety; and post hoc analysis was change from baseline in TCS on DTT areas. RESULTS: Thirty-five patients were included. Least-squares mean change in TCS from baseline was significantly greater for Cal/BD foam (-5.8) than BV-medicated plaster (-3.7; difference -2.2; 95% confidence interval -2.6 to -1.8; p < 0.001); greater changes for Cal/BD foam were observed from day 8 for each clinical sign. Absolute total skin and echo-poor band thickness change was significantly greater for Cal/BD foam than for BV-medicated plaster (both p < 0.001). Post hoc analyses showed that Cal/BD foam was significantly more effective than BV-medicated plaster on DTT areas after 4 weeks (p < 0.001), and both treatments were well tolerated. CONCLUSION: Cal/BD foam demonstrated superior efficacy versus BV-medicated plasters, including on DTT areas, in patients with plaque psoriasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT02518048.

An 18-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Moderate Nasolabial Folds.

BACKGROUND: Hyaluronic acid (HA) filler injection is a popular nonsurgical aesthetic procedure. OBJECTIVE: To compare the effectiveness and safety of 2 hyaluronic acid fillers (HAEC and HARES) for treatment of moderate nasolabial folds (NLFs). MATERIALS AND METHODS: This was an evaluator- and subject-blinded split-face study. HAEC or HARES was randomly assigned to the left or right NLF at baseline. Retreatment was performed after 9 months; follow-up extended to 18 months after baseline (9 months after retreatment). Effectiveness assessments included the Wrinkle Severity Rating Scale (WSRS) and subject preference. Safety assessments included adverse events (AEs) and local tolerability symptoms recorded by subjects during 3 weeks after treatment. RESULTS: HAEC was noninferior to HARES measured as mean change from baseline in WSRS score at 6 months. Mean WSRS score change from baseline was similar between products up to 18 months. A majority of subjects (>70%) were still responders at 18 months (after retreatment at 9 months). The volume required at retreatment was approximately two-thirds of that at baseline. There was no difference in subject preference between products. Both fillers were well tolerated and associated with few treatment-related AEs. CONCLUSION: HAEC and HARES were effective and well tolerated for treatment of moderate NLFs.

Efficacy of an innovative aerosol foam formulation of fixed combination calcipotriol plus betamethasone dipropionate in patients with psoriasis vulgaris.

BACKGROUND AND OBJECTIVE: The antipsoriatic effect of an innovative aerosol foam formulation of fixed combination calcipotriol 50 µg/g (as hydrate; Cal) and betamethasone 0.5 mg/g (as dipropionate; BD) was explored in order to compare the effect with that of the first-line treatment Cal/BD ointment. METHODS: This was a Phase IIa, single-centre, investigator-blinded, exploratory study, with intra-individual comparison using a modified psoriasis plaque test. Patients were treated once daily (6 days/week) for 4 weeks with Cal/BD foam, Cal/BD ointment, BD foam and Cal/BD foam vehicle, randomized to four plaque test sites (5 cm(2) each). The primary efficacy endpoint was change in total clinical score (TCS; sum of erythema, scaling and lesional thickness). Secondary endpoints included ultrasonographic changes in total skin thickness and echo-poor band thickness, and adverse events. RESULTS: Twenty-four patients, median age 52.5 years (range 21-75), completed this study. At week 4, test sites treated with Cal/BD foam had a significantly greater decrease in mean (±SD) TCS (-6.00 ± 1.27) versus those treated with Cal/BD ointment (-5.25 ± 1.78; difference -0.75; 95 % CI -1.46 to -0.04; p = 0.038), BD foam (-4.96 ± 1.85; difference -1.04; 95 % CI -1.75 to -0.33; p = 0.005) or foam vehicle (-1.88 ± 1.12; difference -4.13; 95 % CI -4.83 to -3.42; p < 0.001). Total skin thickness and echo-poor band thickness of Cal/BD foam-treated sites were reduced to a greater extent than those treated with comparators. Eleven patients reported 17 adverse events, the most frequent being headache (five patients). There were no lesional/perilesional adverse events or adverse drug-related events. CONCLUSIONS: Cal/BD foam demonstrated a significant improvement in antipsoriatic effect over Cal/BD ointment, BD foam and foam vehicle alone.

Differences in visible light-induced pigmentation according to wavelengths: a clinical and histological study in comparison with UVB exposure.

The visible light spectrum is wide, and it can be hypothesized that all the wavelengths between 400-700 nm do not induce the same photobiological effects on pigmentation. We assessed the potential pro-pigmenting effects of two single wavelengths located at both extremities of the visible spectrum: the blue/violet line (λ = 415 nm) and the red line (λ = 630 nm). We made colorimetric, clinical, and histological assessments with increasing doses of those lights on healthy volunteers. Then, we compared these irradiations to non-exposed and UVB-exposed skin. Colorimetric and clinical assessments showed a clear dose effect with the 415-nm irradiation, in both skin type III and IV subjects, whereas the 630 nm did not induce hyperpigmentation. When compared to UVB irradiation, the blue-violet light induced a significantly more pronounced hyperpigmentation that lasted up to 3 months. Histological examination showed a significant increase of keratinocyte necrosis and p53 with UVB, as compared to 415- and 630-nm exposures.

Phase 1 clinical trial of stereotactic body radiation therapy concomitant with neoadjuvant chemotherapy for breast cancer.

PURPOSE: Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer. METHODS AND MATERIALS: To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate. RESULTS: Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported. CONCLUSIONS: This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial.

Use of a psoriasis plaque test in the development of a gel formulation of calcipotriol and betamethasone dipropionate for scalp psoriasis.

BACKGROUND: The efficacy and safety of calcipotriol plus betamethasone dipropionate ointment in the treatment of psoriasis vulgaris has consistently been demonstrated in several clinical trials. For treatment of scalp psoriasis, more convenient formulations are required. Therefore, new lipophilic alcohol-free gel formulations containing calcipotriol (50 µg/g) and betamethasone (0.5 mg/g; as dipropionate) (two-compound gels) for treatment of scalp psoriasis were developed. OBJECTIVE: To identify the optimal gel formulation by evaluating the antipsoriatic effect in a psoriasis plaque test model. METHOD: The use of a psoriasis plaque test enables investigation of the antipsoriatic effect of several formulations and compounds in a limited number of patients, and is a useful method for predicting treatment efficacy in psoriasis vulgaris. Five different gel vehicles were investigated in two plaque test studies. RESULTS AND CONCLUSION: The optimised two-compound gels showed superior antipsoriatic effect over marketed betamethasone dipropionate solution. The results suggest that use of the psoriasis plaque test early in the development process can improve the development of topical formulations for dermatological use and can be a beneficial tool for selecting the most promising formulations for further clinical studies in psoriasis vulgaris.

Comparison of the antipsoriatic effect and tolerability of calcipotriol-containing products in the treatment of psoriasis vulgaris using a modified psoriasis plaque test.

BACKGROUND AND OBJECTIVE: In 1972, Dumas and Scholtz developed the psoriasis plaque test to evaluate the potency of local corticosteroids. Through further modification of this method, the efficacy between antipsoriatic products can be differentiated. This method allowed for the simultaneous application of several products to different test sites in the same psoriasis patient. The objective of this current study was to compare the antipsoriatic effect of six topical products using a modified version of the original psoriasis plaque test with emphasis on the predictive capacity of this model. Validation of the use of immunohistochemical and histological scoring of biopsy material, in conjunction with clinical scoring, in the prediction of antipsoriatic effects was an additional objective. METHODS: This study was a single-centre, investigator-blinded, within-subject randomized, active- and vehicle-controlled, intraindividual comparison of six topical products in patients with psoriasis vulgaris. The products evaluated were calcipotriol ointment (50 µg/g); calcipotriol cream (50 µg/g); two-compound ointment (calcipotriol 50 µg/g; betamethasone dipropionate 0.5 mg/g); two-compound gel (calcipotriol 50 µg/g; betamethasone dipropionate 0.5 mg/g) [all in their marketed formulations]; an investigational ointment (calcipotriol 25 µg/g; hydrocortisone 10 mg/g); and a vehicle control. Psoriasis patients (≥18 years of age; n = 24) received simultaneous topical application of each of the products 6 days a week for a period of 21 days, at different test sites located on psoriasis plaques. Clinical assessment of the test sites was completed twice a week. Test site biopsies were taken at the final visit for histological analysis. The primary endpoint was the absolute change in total clinical score (TCS; erythema, scaling and infiltration) from baseline. RESULTS: For all products, the change in TCS correlated well with changes in histological and immunohistochemical values. The two-compound ointment and the two-compound gel both resulted in a large and significant reduction in TCS. Calcipotriol ointment and the calcipotriol/hydrocortisone ointment were less effective, although they were still more effective than the calcipotriol cream and the ointment vehicle. CONCLUSION: This study has demonstrated that the modified psoriasis plaque test can provide a relatively quick and effective method to evaluate the antipsoriatic effect of several topical treatments in small cohorts and that, by combining clinical scoring and histological assessment, a more accurate prediction of the antipsoriatic effect can be made. The two-compound formulations (ointment and gel) had a comparable antipsoriatic effect, which was superior to the other products tested. Furthermore, these data indicate that the gel formulation could provide an alternative effective treatment option to the well established two-compound ointment for psoriasis patients. CLINICAL TRIAL REGISTRATION: Registered as EudraCT no: 2007-005463-10.

Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL).

Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.

Efficacy and safety of a new hyaluronic acid dermal filler in the treatment of moderate nasolabial folds: 6-month interim results of a randomized, evaluator-blinded, intra-individual comparison study.

BACKGROUND: Hyaluronic acid (HA) fillers such as Restylane(®) are frequently used for the correction of facial soft tissue defects. OBJECTIVE: To compare the efficacy and safety of a novel HA filler, Emervel(®) Classic, with those of Restylane in the treatment of moderate nasolabial folds. METHODS: This was a split-face, randomized and evaluator-blinded comparison study. Subjects were randomized to receive an injection of Emervel Classic or Restylane on their left or right side. Efficacy was evaluated based on the change in Wrinkle Severity Rating Score (WSRS) from baseline. Local tolerability was assessed based on subject diary, which recorded the severity of erythema, oedema/swelling, bruising, pain/tenderness and pruritus during the first 3 weeks after injection. RESULTS: The interim results 6 months after injection are reported. At week 24, the mean improvement in WSRS from baseline was 0.83 ± 0.51 for Emervel Classic, similar to that for Restylane (0.90 ± 0.57). A similar volume of both fillers was injected. Most local tolerability events were mild and transient. Erythema, oedema/swelling and pain/tenderness were significantly less severe and disappeared faster with Emervel Classic than with Restylane (at least p < 0.05). CONCLUSION: Emervel Classic provides similar efficacy and better overall local tolerability compared with Restylane 6 months after treatment of moderate nasolabial folds.

Assessment of the clinical efficacy of a hyaluronic acid-based deep wrinkle filler using new instrumental methods.

BACKGROUND: The efficacy of numerous hyaluronic acid (HA)-based fillers has been demonstrated by semi-quantitative and qualitative methods, useful in clinical practice, but poorly reliable. OBJECTIVE: To objectively evaluate the efficacy of a HA gel in treating nasolabial folds (NLFs) over a 9-12-month follow-up period. METHODS: A total of 47 adult patients with moderate to severe NLFs received one or two injections of HA gel. Efficacy was assessed by measuring NLF depth at time intervals up to 12 months subjectively by blind and open clinical scoring using the Lemperle scale, and objectively using skin replicas and in vivo 3D imaging methods. Tissue characterization and dermal thickness were also assessed using radiofrequency ultrasonography and high-resolution ultrasound imaging, respectively. RESULTS: The filler injection highly significantly decreased the depth of NLFs (p < 0.0001) at all time points, with an improvement of at least 1 grade in the Lemperle score in 77% and 89% of the subjects at 9 and 12 months, respectively. NLF volume measured on replicas and 3D images significantly decreased after injection and this improvement was maintained over 12 months. CONCLUSION: This HA gel is well tolerated and provides a significant and long-lasting correction of moderate to severe NLFs, as objectively demonstrated by instrumental methods.

3% diclofenac in 2.5% hyaluronic acid (Solaraze) does not induce photosensitivity or phototoxicity alone or in combination with sunscreens.

Topical treatment with 3% diclofenac in 2.5% hyaluronic acid (Solaraze) has been extensively documented for the treatment of actinic keratoses (AK). Since sun protection is a vital part of AK management, two Phase IV studies were carried out to investigate the phototoxicity and photosensitisation potential of 3% diclofenac in 2.5% hyaluronic acid in combination with sunscreens. Patches of 3% diclofenac in 2.5% hyaluronic acid and control were applied under occlusion to the backs of healthy volunteers aged 18-65. In the phototoxicity study (n = 32), a single application followed by administration of the sunscreens and exposition with ultraviolet (UV) were done, whereas in the photosensitisation study, application was repeated twice weekly for three weeks, then once after a two-week rest phase. The erythema reaction was recorded, together with other local skin reactions. In both analyses, areas treated with 3% diclofenac in 2.5% hyaluronic acid in combination with sunscreens had the lowest incidence of erythema reactions, indicating that it was well tolerated when used in conjunction with sunscreen products, and with exposure to UV irradiation. The results showed that no phototoxic or photosensitisation reactions occurred with 3% diclofenac in 2.5% hyaluronic acid, either alone or in combination with sunscreens.