Literature mapping: association of microscopic skin microflora and biomarkers with macroscopic skin health.

Associations between skin microbes or biomarkers and pathological conditions have been reported in the literature. However, there is a lack of clarity on the interaction between the coexistence of common skin microbes with skin physiology and subsequent development of clinical symptoms, and the role of biomarkers in mediating these changes before the development of skin disease. In this review, we aim to identify areas in which extensive research for the studied factors has already been conducted, and which research areas are under-represented. The SciFinder database was searched for articles containing key words including specific skin microbes, biomarkers, skin physiology and diseases from the beginning of the SciFinder data record to 26 April 2016, and we included an additional relevant recent publication from our group. Among the 8000 + articles selected, the frequency of keyword pairs between two roles [microscopic markers (microflora or biomarkers) and reactions (skin physiology or clinical symptoms, or skin disease)] was investigated. Associated research between the individual factors such as skin microflora or biomarkers (chosen based on our earlier publication) and specific biophysical parameters, symptoms or skin disease was identified. The present research heatmap emphasizes the significance of a structured review of research on concerned factor associations to identify early/subclinical clues that can be used to prevent progression to overt skin disease with the help of precise skin care or early intervention, as indicated by skin microflora, biomarkers and an interactive skin biophysics profile. The findings provide a novel approach to explore such associations and may guide future research directed towards predicting disease from early/subclinical symptoms.

Male versus female skin: What dermatologists and cosmeticians should know.

INTRODUCTION: The skin is important for the perception of health and beauty. Knowledge of the physiological, chemical, and biophysical differences between the skin of male and female patients helps dermatologists develop a proper approach not only for the management of skin diseases but also to properly take care of cosmetic issues. The influence of genetic and environmental factors on skin characteristics is also critical to consider. METHODS: A literature search of PubMed and Google was conducted to compare the biophysical and biomechanical properties of the skin of male and female patients using the keywords "skin", "hydration", "water loss", "sebum", "circulation", "color", "thickness", "elasticity", "pH", "friction", "wrinkle", "sex", "male", and "female". RESULTS: A total of 1070 titles were found. After removing duplications and non-English papers, the number was reduced to 632. Of the 632 titles, 57 were deemed suitable for inclusion in this review. The studies show that the skin parameters of hydration, transepidermal water loss, sebum, microcirculation, pigmentation, and thickness are generally higher in men but skin pH is higher in women. CONCLUSIONS: These parameters can be considered as age markers in some cases and are susceptible to change according to environment and life style. Biometrological studies of the skin provide useful information in the selection of active principles and other ingredients of formulations to develop a specific approach for cosmetic treatments.

Bateman purpura (dermatoporosis): a localized scurvy treated by topical vitamin C - double-blind randomized placebo-controlled clinical trial.

BACKGROUND: Bateman purpura is characterized by diffuse senile skin atrophy, senile purpura and spontaneous stellar pseudocicatrices. Cutaneous changes in the course of ageing have been related to lower levels of ascorbic acid into the dermis of elderly people. OBJECTIVE: In this study, we postulate that senile purpura could be linked to dermal vitamin C deficiency and could be corrected by topical administration of this vitamin. METHODS: A 12-weeks, hemi-member (forearm or leg), randomized double-blind comparative study was conducted in 18 patients with Bateman purpura aged over than 60 years. At each visit, clinical assessment and biometrological measurements were performed. Clinical examination and scoring by experts showed a significant improvement on the vitamin C-treated side compared with the control, with reduction of haemorrhage areas, increase of dermal thickness. RESULTS: Twice-daily application of 5% topical vitamin C led to a clinically apparent improvement of the skin symptoms and allows beneficial effects on skin elasticity and thickness. Bateman purpura, a classical sign of photoaging whose origin has not clearly been recognized could be improved by vitamin C applied on to the skin. CONCLUSION: These results confirm the hypothesis of the underlying role of vitamin C deficiency in the determinism of Bateman purpura.

Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species.

This corrects the article DOI: 10.1038/onc.2017.175.

[Giardia duodenalis and its involvement in skin diseases]. / Giardia duodenalis et son implication dans diverses dermatoses.

BACKGOUND: Over the last thirty years, the scientific community has become increasingly interested in the intestinal flora, whether commensal or pathogenic, and its impact on other organs. In dermatology, the correlation between intestinal microbial agents and cutaneous lesions is well established. Giardia duodenalis, an intestinal parasite, has been particularly widely studied. The aim of this work is to provide a review of studies demonstrating the involvement of G. duodenalis in various forms of dermatosis. PATIENTS AND METHODS: The data were obtained by an English-language literature search of Medline, PubMed and Google Scholar for the period 1975-2015. Among the thirty case reports since 1976, we selected the twenty most objective and clinically relevant. RESULTS AND DISCUSSION: This review demonstrates that intestinal giardiasis may be an etiological factor, either alone or in combination with other agents, of various dermatoses through inflammatory and allergic mechanisms or intestinal hyperpermeability. The mucocutaneous lesions are varied: urticaria, angioedema, atopic dermatitis, erythema nodosum, Wells syndrome, among others. The role and origin of the infection are often unknown, and it is thus difficult to determine the interval between parasite infestation and the onset of skin lesions. Consequently, a fecal examination to identify G. duodenalis should be considered in chronic urticaria or angioedema, and where atopic dermatitis occurs in adulthood without any specific etiology. Therapeutic test should be done in every suspicion.

Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species.

Activation of Ras signalling occurs in ~30% of human cancers; however, activated Ras alone is not sufficient for tumourigenesis. In a screen for tumour suppressors that cooperate with oncogenic Ras (RasV12) in Drosophila, we identified genes involved in the autophagy pathway. Bioinformatic analysis of human tumours revealed that several core autophagy genes, including GABARAP, correlate with oncogenic KRAS mutations and poor prognosis in human pancreatic cancer, supporting a potential tumour-suppressive effect of the pathway in Ras-driven human cancers. In Drosophila, we demonstrate that blocking autophagy at any step of the pathway enhances RasV12-driven epithelial tissue overgrowth via the accumulation of reactive oxygen species and activation of the Jun kinase stress response pathway. Blocking autophagy in RasV12 clones also results in non-cell-autonomous effects with autophagy, cell proliferation and caspase activation induced in adjacent wild-type cells. Our study has implications for understanding the interplay between perturbations in Ras signalling and autophagy in tumourigenesis, which might inform the development of novel therapeutics targeting Ras-driven cancers.

Exudates absorption and proteases trapping in venous leg ulcers.

OBJECTIVE: In venous leg ulcer (VLU), the impaired healing has been shown to be associated with excessive levels of protease activities such as matrix metalloproteinases (MMPs) and elastases found in exudates. The present study focused on exudates absorption and proteases trapping capacity of a new generation of polyacrylate superabsorbent, Tegaderm superabsorber (TS), compared with a traditional dressing such as Zetuvit. METHOD: We studied the proteases implicated in VLU (MMP-1, MMP-2, MMP-9 and PMN elastase). Absorption was tested using an artificial exudate like fluid, over 30 minutes. The protein trapping ability was obtained using ELISA assays (enzyme-linked immunosorbent assay) to determine the amount retained by the dressings from spiked fluid samples. RESULTS: TS had a higher exudate absorption capacity (72.8±1.7%) compared with the standard dressing (36.5±1.6%), and was also able to trap and retain proteases while the standard dressing released them. The difference was shown to be much larger for MMP-2 and PMN elastase. CONCLUSION: In our knowledge, this is the first comparative in vitro study evaluating absorption capacity as well as protease trapping capacity of a polyacrylate dressing for the four most implicated proteases in VLU. TS could be an appropriate alternative to improve the management of VLU by trapping MMPs and PMN elastse with a particularly high affinity for MMP-2 and PMN elastase.

Reflectance confocal microscopy for the evaluation of sensitive skin.

BACKGROUND: Nowadays, the diagnosis for sensitive skin relies on subjective assessment or on the combination of subjective and objective evaluation. No quantitative evaluation is available. It could be expected that confocal microscopy imaging could be of interest to better define the condition. METHODS: Total 166 healthy female subjects were recruited in this study. Firstly, all subjects completed the sensitive questionnaire. Then, the cutaneous structures were measured by the reflectance confocal microscopy (RCM) on the face and fossa cubitalia. The lactic acid sting test was conducted finally. According to the results of self-perception sensitive skin questionnaire and lactic acid stinging test to evaluate facial skin sensitivity the both positive subjects were regarded as sensitive skin group and both negative group as healthy control group. RESULT: The results of RCM indicating that the proportion of 'disarranged honeycomb pattern' and 'spongiform edema' in the sensitive group and healthy control group were statistically different (P < 0.05), respectively; The following report 'damaged dermal papilla rings' was not a distinctive pattern, with no significant statistical difference (P > 0.05). The epidermal thickness was 38.88 ± 6.81 µm, healthy control group was 40.31 ± 9.37 µm in, respectively, sensitive skin group and healthy control group, there was no significant statistical difference between the two groups (P > 0.05). The honeycomb structure depth of sensitive group was 20.57 ± 4.86 µm. It was for 23.27 ± 6.38 µm, healthy control group the difference being statistically different between the two groups (P < 0.05). CONCLUSION: Based on the RCM results, 'epidermal honeycomb structure' and 'spongiform edema' may be used as new skin signs of RCM evaluation of sensitive skin effectively. Indeed, sensitive skin honeycomb structure depth was thinner compared with healthy control group. Such a specific pattern has good clinical and monitoring value for the further exploration. RCM could provide new data and patterns for the evaluation of sensitive skin.

[New paradigms and metaphors in cutaneous melanoma treatment]. / Nouveaux paradigmes et métaphores du traitement du mélanome cutané.

In recent years, new drugs have been designed for treating advanced cutaneous malignant melanoma, in particular the metastases. They afford modest benefits despite the fact they are commonly heralded as breakthroughs in the lay press and by some medical opinion leaders. Unfortunately, the use of inflated descriptors of the drug efficacy leads to misunderstandings among the clinicians in charge of patients. Currently, vemurafenib, ipilimumab, pembrolizumab and nivolumab have demonstrated their relative activity in the control of advanced malignant melanoma. The results expected from surrogate markers of efficacy are magnified and idealized regarding the expectations from many patients. The recent therapeutic advance improves the median overall survival for a few months. Some combined treatments could possibly boost the current beneficial effects.

Au cours des récentes années, de nouveaux médicaments ont été offerts pour le traitement du mélanome cutané avancé et, en particulier, de ses métastases. Ils apportent des bénéfices qualifiés de modestes par certains malgré leur présentation en tant qu'innovations par divers médias et par quelques médecins et biologistes élevés au rang de leaders d'opinion. Malheureusement, l'emploi de descripteurs inflationnistes de l'efficacité des médicaments entraîne certaines incompréhensions parmi les cliniciens en charge de ces patients. A ce jour, le vémurafénib, l'ipilimumab, le pembrolizumab et le nivolumab ont démontré leurs activités relatives dans le contrôle du mélanome avancé. Le bénéfice escompté par certains marqueurs de substitution de l'efficacité est magnifié et idéalisé par rapport aux attentes de beaucoup de patients. Les avancées thérapeutiques récentes procurent un accroissement de quelques mois à la survie médiane. Des traitements combinés pourraient améliorer le bénéfice dès à présent atteint.

Scribble acts as an oncogene in Eµ-myc-driven lymphoma.

Scribble complex proteins maintain apicobasal polarity, regulate cell fate determination and function as tumour suppressors in epithelial tissue. Despite evidence that the function of Scribble is maintained in the lymphocyte lineage, we still understand little about its role as a tumour suppressor in haematological malignancies. Using the Eµ-myc model of Burkitt's lymphoma we investigated the role of Scribble in lymphomagenesis. We found that contrary to its well-documented tumour suppressor role in epithelial tissue, loss of Scribble expression delayed the expansion of peripheral B cells and delayed the onset of Eµ-myc-driven lymphoma. This was despite upregulated ERK phosphorylation levels in Scribble-deficient tumours, which are associated with loss of Scribble expression and the development of more aggressive Burkitt's lymphoma. Interestingly, the developmental stage of lymphoma was unaffected by Scribble expression challenging any role for Scribble in fate determination in the haematopoetic lineage. These data provide evidence for oncogenic properties of Scribble in Myc-driven B-cell lymphomagenesis, reinforcing recent findings that overexpression of a mutant form of Scribble can act as an oncogene in epithelial cells. Our results support the growing appreciation that the tumour regulatory functions of Scribble, and other polarity protein family members, are context dependent.

Long-term assessment of effectiveness and quality of life of OnabotulinumtoxinA injections in provoked vestibulodynia.

BACKGROUND: Provoked vestibulodynia is a relatively common condition that affects sexual activity. Multidisciplinary care is indicated and OnabotulinumtoxinA injections are safe and effective treatment in this indication. AIMS: To assess the long-term efficacy of OnabotulinumtoxinA in provoked vestibulodynia. MATERIALS AND METHODS: Twenty-one patients treated with OnabotulinumtoxinA injections (50U in each bulbospongiosus muscle) 24 months prior to the study were included. Data on pain [assessed using a visual analogue scale (VAS)], quality of life [measured by the Dermatology Life Quality Index (DLQI)] and quality of sex life [assessed using the Female Sexual Function Index (FSFI)] were collected before treatment, and 3 and 24 months after injection. RESULTS: Nineteen patients participated in the study and 37% had no pain after 24 months. Significant improvements were noted in the VAS, DLQI and FSFI scores between baseline and 24 months post treatment (P < 0.0001). After 24 months, 18 patients (95%) were able to have sexual intercourse. This study was open and non-controlled. DISCUSSION AND CONCLUSION: 100U OnabotulinumtoxinA injections constitute an effective treatment in provoked vestibulodynia with results maintained after 2 years. They significantly improve pain, and have a positive impact on patient quality of life and sex life. Beneficial effects continue in the long-term, allowing patients to resume sexual activity.

[Congenital hemangiomas: Report on ten patients]. / Hémangiomes congénitaux : à propos de dix cas.

INTRODUCTION: Congenital hemangiomas (CHs) are rare congenital vascular tumors seldom mentioned in the literature. MATERIALS AND METHODS: We carried out a retrospective study of all the cases of CH diagnosed and treated at Besançon Hospital from 2008 to 2014. The clinical, radiological, and histological data of each case were collected. All the children were seen again in 2014. RESULTS: Ten CHs (seven rapidly involuting CHs, RICH and three non-involuting CH, NICH), predominantly full-term eutrophic male infants, were enrolled. RICHs were located on the head (n=2), trunk (n=2), and lower limbs (n=3), and NICHs were found on the hands. Diagnosis was clinical for all ten infants. All CHs resembled "tumor" congenital lesions: single, oval-shaped, nonpulsatile, and well delimited, and their size did not increase after birth. Two RICHs were warm, one had phlebolites, and two had draining veins at the first visit. The mean age of the RICH involution onset was 1.7 months and the mean time to complete involution was 10.4 months. One CH was classified as a PICH (partially involuting CH) due to partial regression, two RICHs were still in the involution process at the age of 10 and 15 months, and one regressed very quickly within 7 days. No complications were observed in the NICH. Two RICHs presented benign complications (ulcerations and bleeding). Two RICHs regressed entirely, and five regressed with sequelae: lipoatrophy (n=3), cutaneous excess (n=2), dysplastic veins (n=3), a pigmented area (n=1), and an anemic halo (n=2). DISCUSSION: The small number of patients in our cohort, in spite of the length of the study, confirms the rarity of CH. The sex-ratio in favor of male infants and the location of NICH on the hands have not been reported. The most discriminating element remained the follow-up over 1 year. The initial clinical aspect of the NICH and the progression of one RICH into a NICH suggested possible overlapping forms between RICH and NICH. Some CHs, including one PICH, presented clinical and radiological criteria similar to those of vascular malformations (warm lesion, dysplastic veins, and echo-Doppler results in favor of vascular malformation). RICH regressed with sequelae in most cases. CONCLUSION: This study reveals a polymorphous clinical presentation of CH and provides a thorough description of their progression. It underlines the existence of overlapping phenomena between RICH and NICH, and between CH and vascular malformations, thus suggesting a possible link between proliferation and malformation phenomena at the origin of these lesions.

[Vulvar oedema revealing systemic mastocytosis]. / Œdème vulvaire révélant une mastocytose systémique.

BACKGROUND: Systemic mastocytosis is characterised by abnormal proliferation of mast cells in various organs. We report an original case of systemic mastocytosis revealed by vulvar oedema. PATIENTS AND METHODS: A 24-year-old patient was examined in the dermatology department for vulvar oedema appearing during sexual intercourse. She presented vasomotor dysfunction of the lower limbs, urticaria on the trunk on exertion, diarrhoea and bone pains. Laboratory tests showed serum tryptase of 29.7µg and plasma histamine at twice the normal value. Myelogram results showed infiltration by dysmorphic mast cells. Screening for c-kit D816V mutation was positive. Duodenal biopsies revealed mast-cell clusters with aggregation involving over 15 mast cells. CD2 staining was inconclusive and CD25 staining could not be done. Trabecular osteopenia was found, and we thus made a diagnosis of indolent systemic mastocytosis (ISM variant Ia) as per the WHO 2008 criteria. Symptomatic treatment was initiated (antiH1, H2, antileukotrienes) and clinical and laboratory follow-up was instituted. DISCUSSION: The cutaneous signs leading to diagnosis in this patient of systemic mastocytosis involving several organs were seemingly minimal signs associated with mastocyte degranulation. This is the third recorded case of mastocytosis revealed by vulvar oedema and the first case revealing systemic involvement. The two previously reported cases of vulvar oedema revealed cutaneous mastocytosis alone. Mastocytosis, whether systemic or cutaneous, must be included among the differential diagnoses considered in the presence of vulvar oedema.