Long-Term Use of Silybum marianum fruit extract Contributes to Homeostasis in Acne-Prone Skin-A 12-Month Follow-Up International "Real Life" Cohort Study.

BACKGROUND: Homeostasis in the differentiation programme of sebaceous stem cells has been identified as a key step in comedogenesis and should be a target for acne-prone skin care. OBJECTIVE: To report on a multicentre, year-long/real-life use study of a patented natural product containing S. marianum fruit extract proven to modulate molecular actors in the initial steps of comedogenesis. METHODS: An open-label multicentric international study, with a 12 month follow-up, included 54 teenage and young adult subjects with mild to moderate facial acne. The study was aimed at reproducing a real-life use context. RESULTS: Total lesion count mean was 88.3 at inclusion. There was a sustained, highly significant decrease over the months of clinical lesion counts (45.6% improvement after 6 months and 59.6% at 12 months) and on other efficacy markers, associated with a significant decrease in global microcomedone quantity on cyanoacrylate superficial skin surface biopsies. Importantly, the study protocol allowed the dermatologist to prescribe, if needed as in real life, any of the acne drugs registered in the acne guidelines. The exposure to these acne drugs during the whole year was calculated as a percentage of S. marianum fruit extract/352 days of use and happened to be very limited at less than 4%, which indicates a marginal contribution to the sustained clinical improvement. (Oral and local acne treatments: Lymecycline 1.46%; Doxycycline 0.24%; Adapalene 0.16% or gel association with Benzoyl peroxide 1.17%; Clindamycin 0.04%; Benzoyl peroxide 1.5%; Erythromycin 0.75%). The tolerance with daily S. marianum fruit extract long-term use was good. LIMITATIONS: The association with routine prescription acne drugs when needed, even if limited, does not allow a full evaluation of the intrinsic quantitative efficacy of S. marianum fruit extract in lesion reduction. CONCLUSION: This open, real-life, year-long multicentre study confirms a previous 48-week proof of concept study and qualifies the use of S. marianum fruit extract as a "field-dermo cosmetic" contributing to homeostasis of acne-prone skin in association with acne drugs.

Lipid Droplet Proteins in Acne Skin: A Sound Target for the Maintenance of Low Comedogenic Sebum and Acne-Prone Skin Health.

In adipocytes and sebocytes, lipid droplet proteins control the storage of lipids in organized droplets and their release on demand. The contribution of lipid droplet proteins to the pathogenesis of acne is plausible because they control the levels of comedogenic free fatty acids. The expression of two lipid droplet proteins, CIDEA and PLIN2, was analyzed in the skin of patients with acne by immunohistochemistry and western blotting. The design of clinical protocols allowed correlating the expression of CIDEA and PLIN2 with both comedogenesis and the release of free fatty acids. Both proteins were detected by immunohistochemistry in the sebaceous glands of patients with acne, with a disturbed expression pattern of PLIN2 compared with that in the controls. Higher levels of PLIN2 and CIDEA, as detected by western blotting in the infundibulum, significantly correlated with lower ongoing comedogenesis over 48 weeks of Silybum marianum fruit extract application. Accordingly, free fatty acid release from sebum triglycerides was significantly decreased, as shown with two distinct methods. The data are consistent with the expected role of PLIN2 and CIDEA in the prevention of comedogenic free fatty acid release. Modulation of PLIN2 and CIDEA expression appears as a sound target for the maintenance of low comedogenic sebum and acne-prone skin health.

IL-17+ Mast Cell/T Helper Cell Axis in the Early Stages of Acne.

Acne is a multifactorial disease driven by physiological changes occurring during puberty in the pilosebaceous unit (PSU) that leads to sebum overproduction and a dysbiosis involving notably Cutibacterium acnes. These changes in the PSU microenvironment lead to a shift from a homeostatic to an inflammatory state. Indeed, immunohistochemical analyses have revealed that inflammation and lymphocyte infiltration can be detected even in the infraclinical acneic stages, highlighting the importance of the early stages of the disease. In this study, we utilized a robust multi-pronged approach that included flow cytometry, confocal microscopy, and bioinformatics to comprehensively characterize the evolution of the infiltrating and resident immune cell populations in acneic lesions, beginning in the early stages of their development. Using a discovery cohort of 15 patients, we demonstrated that the composition of immune cell infiltrate is highly dynamic in nature, with the relative abundance of different cell types changing significantly as a function of clinical lesion stage. Within the stages examined, we identified a large population of CD69+ CD4+ T cells, several populations of activated antigen presenting cells, and activated mast cells producing IL-17. IL-17+ mast cells were preferentially located in CD4+ T cell rich areas and we showed that activated CD4+ T cells license mast cells to produce IL-17. Our study reveals that mast cells are the main IL-17 producers in the early stage of acne, underlying the importance of targeting the IL-17+ mast cell/T helper cell axis in therapeutic approaches.

High bacterial colonization and lipase activity in microcomedones.

BACKGROUND: Although acne vulgaris has a multifactorial aetiology, comedogenesis and bacteria colonization of the pilosebaceous unit are known to play a major role in the onset of inflammatory acne lesions. However, many aspects remain poorly understood such as where and when is the early stage of the Propionibacterium acnes colonization in follicular unit? Our research aimed at providing a precise analysis of microcomedone's structure to better understand the interplay between Propionibacterium acnes and follicular units, and therefore, the role of its interplay in the formation of acne lesions. METHODS: Microcomedones were sampled using cyanoacrylate skin surface stripping (CSSS). Their morphology was investigated with multiphoton imaging and their ultrastructure with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Bacterial lipase activity in the microcomedones was quantified using a dedicated enzymatic test as well as a Fourier Transform Infra-Red (FTIR) analysis. The porphyrin produced by bacteria was analysed with HPTLC and fluorescence spectroscopy. RESULTS: The imaging analysis showed that microcomedones' structure resembles a pouch, whose interior is mostly composed of lipids with clusters of bacteria and whose outer shell is made up of corneocyte layers. The extensive bacteria colonization is clearly visible using TEM. Even after sampling, clear lipase activity was still seen in the microcomedone. A high correlation, r = .85, was observed between porphyrin content measured with HPTLC and with fluorescence spectroscopy. These observations show that microcomedones, which are generally barely visible clinically, already contain a bacterial colonization.

Tolerability and Efficacy of a Medical Device Repairing Emollient Cream in Children and Adults with Mild to Moderate Atopic Dermatitis.

INTRODUCTION: Regular emollient application is recommended for managing atopic dermatitis (AD). Although many emollients are available, only AD-tested medical device repairing emollient creams (MDRECs) can be recommended for treating and preventing AD skin lesions. Here, we evaluated the tolerability and benefit of a new MDREC in an open-label study in infants, young children, and adults with mild to moderate AD. METHODS: Subjects (or their parents or guardians) were instructed to apply the MDREC to AD lesions or areas of dry skin twice daily for 3 weeks. Investigators assessed tolerability and AD severity at days 1, 8, and 22. Subjects assessed AD severity weekly, recorded any adverse events, and reported their satisfaction with the MDREC at day 22. RESULTS: Sixty-one subjects (19 infants, 22 children, and 20 adults) were included and 59 completed the study. At inclusion, 49% of the infants and young children and 15% of the adults were experiencing flares of AD. At day 22, the local tolerability of the MDREC was judged by the investigators as excellent in all the children and in 18 of the 20 adult subjects (90%). All adverse events were mild and transient. Investigator- and subject-assessed AD severity progressively decreased at each assessment for each age subgroup. CONCLUSION: This study shows that the MDREC was well tolerated when applied to AD skin lesions in infants, young children, and adults and suggests this product can be used daily to control the signs and symptoms of AD. FUNDING: Laboratoires Dermatologiques Ducray, Pierre Fabre Dermo-Cosmétique.

Correction to: Efficacy and Tolerability of a Medical Device Repairing Emollient Cream Associated with a Topical Corticosteroid in Adults with Atopic Dermatitis: An Open-label, Intra-individual Randomized Controlled Study.

The original article can be found online.

Tolerability and efficacy of a medical device repairing emollient cream in adults with chronic hand dermatitis.

BACKGROUND: Emollients are recommended for managing chronic hand dermatitis (CHD). Medical device repairing emollient creams (MDRECs) are suitable for treating CHD-associated skin lesions, unlike most cosmetic emollient products that can only be used on healthy skin. OBJECTIVES: The aim of this study was to examine the tolerability and benefit of a MDREC, Dexyane MeD® , in adults with CHD. METHODS: In an open-label study, adults aged 18-65 years with mild-to-moderate CHD were instructed to apply the MDREC on both hands twice daily for 3 weeks. Investigators assessed tolerability and CHD severity on days 1, 8, and 22. Subjects assessed CHD severity weekly and completed the Dermatology Life Quality Index on days 1, 8, and 22. Differences from baseline were compared by Wilcoxon matched-pairs signed-rank test or paired t test. Satisfaction with the MDREC was assessed by subjects. RESULTS: Forty subjects were included and completed the study. Tolerability was good to excellent for all subjects. Subjects and investigators reported decreased severity of CHD at days 8 and 22 compared with Day 1 (P < 0.001), and subjects reported decreased pain and pruritus (P < 0.001). Quality of life improved, and most subjects were satisfied with the MDREC's characteristics and application. CONCLUSIONS: The MDREC was well tolerated and may help manage mild-to-moderate CHD.

Efficacy and Tolerability of a Medical Device Repairing Emollient Cream Associated with a Topical Corticosteroid in Adults with Atopic Dermatitis: An Open-label, Intra-individual Randomized Controlled Study.

INTRODUCTION: Medical device repairing emollient creams (MDRECs) are designed to repair and protect the skin barrier. In this study, we examined the added clinical benefit and tolerability of a MDREC when used in association with a moderately potent topical corticosteroid (TCS) for adults with atopic dermatitis (AD). METHODS: This was an intra-individual randomized controlled trial in adults with moderate to severe AD (EudraCT no. 2014-002,194-10). Symmetrical lesions on each arm of the subjects were randomized to treatment for 10 days with twice-daily TCS (desonide) cream alone or with combined TCS + MDREC. Subjects were then included in a following 2-week maintenance phase if the AD on at least one test area had sufficiently improved so that the treatment was no longer needed. During the maintenance phase, treatment with the TCS cream was stopped, but twice-daily application of the MDREC was continued on the same test area previously assigned to receive it. The primary outcome measure was the change in local Scoring Atopic Dermatitis (SCORAD) index between day 1 and 3 based on investigators' assessment. Secondary measures of lesion severity included changes in the local patient-oriented SCORAD index, pruritus intensity according to subjects' assessments, and global assessments by subjects and investigators. RESULTS: The study included 54 subjects. The change in investigator-observed local SCORAD index between day 1 and 3 was - 14.4% with TCS alone and - 24.5% for TCS + MDREC (p = 0.0005). Between baseline and the end of the treatment phase, all secondary measures of lesion severity decreased more with the combined TCS + MDREC treatment than with the TCS cream alone. The MDREC also reduced the relapse of AD lesions during the maintenance phase. Tolerability was very good, and the product was well accepted by subjects. CONCLUSION: These results support using the MDREC in association with TCS during AD flares and as a maintenance therapy after treatment with TCS has stopped. FUNDING: Laboratoires Dermatologiques Ducray, Pierre Fabre.

Visualization of dendritic cells' responses in atopic dermatitis: Preventing effect of emollient.

Atopic dermatitis (AD) is a chronic and multifactorial inflammatory skin disease involving various dendritic cells such as epidermal Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDECs). Most of the clinical studies was performed on isolated cells, and thus, it would be useful to characterize directly on the human epidermal tissue the first cellular events occurred during the AD. The suction blister method was used to obtain whole epidermis samples and interstitial cutaneous fluids. Employing multiphoton microscopy, we analyzed the early dynamic behavior of inflammatory cells using Dermatophagoides pteronyssinus atopy patch test (Derp-APT) and evaluated the effects of emollient pre-application. Derp-APT application provoked rapid and strong infiltration of IDECs, and proliferation and activation of LC in the AD subjects' epidermis. Moreover, emollient pre-application strengthened the defective skin barrier and had positive effects on inflammatory cells' behavior, characterized by the complete inhibition of IDEC influx and the presence of immature LC.

Protection afforded by sunscreens containing inorganic sunscreening agents against blue light sensitivity induced by aminolevulinic acid.

BACKGROUND: Application of aminolevulinic acid (ALA) for photodynamic therapy induces significant sensitivity to visible light. OBJECTIVE: To determine whether sunscreens containing inorganic agents are effective against sensitivity to blue light induced by ALA application. METHODS & MATERIALS: Twenty subjects received application of ALA on the arm. Thirty minutes before blue light exposure, two sun protection factor 50 inorganic-based sunscreens containing iron oxide 3.2% and 0.2% were applied on separate areas where ALA was applied; a third area received no sunscreen. Small areas of skin were exposed to increasing fluences of blue light 3 or 18 hours later, and the minimal phototoxic dose (MPD) was noted. RESULTS: Three hours after ALA application MPD was 29.2 and 22.6 J/cm(2) for skin protected with sunscreen containing iron oxide 3.2% and 0.2%, respectively, and 10.6 J/cm(2) for unprotected skin (p=.003 and .0497 respectively). At 18 hours after ALA application, MPD for sunscreen containing iron oxide 3.2% was 5.78, compared with 0.33 for unprotected skin (p<.001) with a blue light protection factor of 21. CONCLUSION: The sunscreen containing iron oxide 3.2% afforded significant protection against blue light sensitivity induced by ALA application.

Comparative benefit of two thermal spring waters after photodynamic therapy procedure.

INTRODUCTION: Photodynamic therapy (PDT) is commonly used to treat actinic keratoses, superficial cutaneous carcinoma, photodamage, and/or acne. The aim of this study was to compare the usefulness of Avène thermal spring water (ATSW), a low mineral content spring water, to a high mineral content spring water. We evaluated post-PDT clinical symptoms and findings when used as an adjunctive therapy in postprocedure skin care. METHODS: A double-blind monocentric comparative study was conducted on 25 patients suffering from either vulgaris acne or photodamage with or without actinic keratoses. The patients were treated with 5-aminolevulinic acid (5-ALA) activated with an intense pulsed light and/or blue light source. Patients were randomized so that 12 patients treated their faces with ATSW and 13 were treated with a comparative water spray. Clinical signs were evaluated by the investigator at day 0, before and 15 min after the first spraying, at days 2, 4, and 7, and each day from day 0 to day 6 by patients. Clinical signs (erythema, stinging, pruritus, pain, and tightening) were evaluated by the use of a 4-point grading scale. RESULTS: The intragroup analysis showed that pain was significantly reduced by ATSW spraying at days 2, 4, and 7. The evaluation by patients showed that only ATSW alleviates pain from day 3 to day 6. The between-group analysis revealed that pruritus was significantly reduced by ATSW at day 7. Erythema, stinging, and tightening were not significantly reduced by both waters. Patients wished to continue using ATSW in 83% of cases. CONCLUSION: This comparative clinical trial demonstrates that ATSW, a low mineral content spring water, can be useful after ALA-PDT in reducing postprocedure cutaneous inflammation and patient discomfort better than a high mineral content spring water.

Combined 0.1% retinaldehyde/ 6% glycolic acid cream in prophylaxis and treatment of acne scarring.

BACKGROUND: Acne often results in permanent, badly tolerated, difficult to treat scars. OBJECTIVE: To evaluate the efficacy and safety of a 0.1% retinaldehyde/6% glycolic acid (RALGA) cream at preventing and treating acne scarring in patients previously treated for moderate acne. METHODS: A double-blind vehicle-controlled study was conducted in 145 patients randomized to apply RALGAor vehicle cream every evening for 3 months. Global scarring score and patient's assessment of global efficacy, then residual acne lesions, quality of life and tolerance were evaluated at inclusion and each month until study completion. RESULTS: Global scarring score, number of inflammatory lesions and comedones significantly improved in each group from day 28 (p<0.0001). Number of inflammatory lesions were significantly decreased only in the RALGA group. RALGA cream was more efficient than vehicle on scarring after 3 months in compliant patients (p=0.007) due to erythema and hyperpigmentation improvement. CONCLUSION: RALGA cream is efficient at preventing and treating acne scarring in patients with moderate acne.

RALGA (Diacneal) decreases melanin content in a human skin model.

BACKGROUND: Retinaldehyde and glycolic acid RALGA (Diacneal) are both effective in the topical treatment of acne. A decrease in the postinflammatory pigmentation has been observed after application of Diacneal during 3 months. AIM: To verify the effect of this association on pigmentation using an original model of surviving human skin. METHODS: Human skin explants were maintained alive in organ culture for 14 days. Diacneal was applied every day. Pigmentation of skin, depending on the transfer of melanosomes from melanocytes to keratinocytes, was visualized histologically by Fontana-Masson staining. The number of melanocytes was determined after the DOPA reaction. RESULTS: A decrease in melanin content was shown after application of Diacneal. The number of melanocytes was not modified. CONCLUSION: These results suggest that RALGA (Diacneal) may be of interest to prevent the postinflammatory pigmentation of acne.

Ultrasound imaging demonstration of the improvement of non-ablative laser remodeling by concomitant daily topical application of 0.05% retinaldehyde.

BACKGROUND: Retinaldehyde has been proven to be effective in the reduction of facial wrinkles. It has also demonstrated its usefulness when used before and after laser skin resurfacing. OBJECTIVE: A monocentric, comparative, randomized, double-blind study was performed to evaluate the efficacy of retinaldehyde versus excipient in combination with non-ablative laser remodeling treatment. METHODS: A total of 16 female patients (mean age 45 years) were enrolled for neck line and forehead rhytid treatment. They were randomly assigned into two groups. The RAL group (eight patients) was treated with a non-ablative laser (1540 nm Er:glass, 10 J/cm2 per pulse, three pulses, 2 Hz repetition rate, 4 mm spot, +5 degrees C cooling) and daily topical application of 0.05% retinaldehyde immediately after the first laser treatment and up to 3 months after the fifth treatment. The CTRL group (eight patients) was treated under similar conditions, except with a daily application of excipient. The thickness of the skin (forehead and neck) was measured by ultrasound imaging before the first treatment, 1 month after the third treatment, 1 month after the fifth treatment and 3 months after the fifth treatment. RESULTS: An increase of dermal thickness was observed for all patients treated by laser (groups RAL and CTRL) on the forehead and neck. However, the increase was greater for the RAL group (retinaldehyde) when compared with the CTRL group (excipient). Three months after the fifth treatment, the increase in dermal thickness (%) was, respectively, 5.27 versus 1.13 for the forehead and 10.54 versus 3.57 for the neck. The difference between groups was statistically significant in favor of the retinaldehyde group for the forehead (p<0.05) and of limited significance for the neck (p=0.08). CONCLUSION: When considering the reduced number of patients in each group, the statistical analysis demonstrates an evident advantage of using retinaldehyde versus excipient. This study demonstrates that irradiation with a 1540 nm Er:glass laser can be potentiated with concomitant daily topical application of 0.05% retinaldehyde.

The Cardiff Acne Disability Index: cultural and linguistic validation in French.

BACKGROUND: The Cardiff Acne Disability Index (CADI) evaluates the impact of acne on the patient's life. OBJECTIVE: The objective of the present study was to translate the CADI into French and to validate the French version. METHOD: The CADI was translated into French following international methodological recommendations (translation, quality control, back-translation and pilot test). RESULTS: Compatibility difficulties between the cultural background of UK and France were identified and resolved by the translation process, which should guarantee that specific words and phrases reflect the cultures in the respective countries. A pilot test in volunteers demonstrated the clarity and understandability of the questions across social classes and ages. A preliminary test-retest comparison of the final scale showed sufficient reliability, with a correlation coefficient of 0.90 for the total CADI score of the French version. Moreover, the good internal consistency of the scale was demonstrated with a Cronbach alpha of 0.87. CONCLUSION: The CADI, a valuable tool for assessing the impact of acne on a patient's life, can now be used in French.