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.

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.

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.

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.

[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.

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.

[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.

[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.

[Iatrogenic skin lesions: a prospective study in premature infants born at less than 33 weeks of amenorrhea at Besançon university hospital]. / Lésions cutanées iatrogènes : étude prospective chez les prématurés de moins de 33 semaines de l'hôpital universitaire de Besançon.

BACKGROUND: Advances in neonatology have markedly improved prognosis for premature babies in recent years. However, they have also entailed the need for recourse to considerable intensive care involving potentially iatrogenic diagnostic and therapeutic acts. Among the resulting iatrogenic events, cutaneous lesions are the most frequent but have been the subject of very few studies. Our own study thus aimed to assess the rate of iatrogenic cutaneous events in premature infants born at less than 33 weeks of amenorrhea and hospitalised at Besançon university hospital and to identify the factors associated with the occurrence of these events. PATIENTS AND METHODS: This was a prospective study carried out in the department of paediatric intensive care and neonatology at Besançon university hospital between May 2011 and April 2012. All babies born before 33 weeks of amenorrhea hospitalised over this period were included. An iatrogenic event was defined as "an adverse event related to a medical procedure". Iatrogenic cutaneous events were reported to the dermatologist by medical and paramedical staff. RESULTS: One hundred and thirthteen newborn babies were included during the study period. Twenty-six iatrogenic cutaneous events were recorded in 19 infants, representing 16.8% of the population involved: nine were associated with ventilation techniques, six with the use of intravenous catheters, five with electrodes, two involved pressure sores, two were linked to the birth, one to disinfectants and one to dressings. The main risk factor was low birth weight (P=0.016). High prematurity and the duration of ventilation increased the risk, although not significantly. The death rate was higher in children with iatrogenic events but the difference was not significant. The duration of hospitalisation was unaffected by the presence or absence of an iatrogenic event. CONCLUSION: The frequency of iatrogenic cutaneous events is high in hospital departments in charge of very premature infants. Awareness by the medical and paramedical staff of the frequency of such iatrogenic events should improve the quality of care.

Microclimate next to the skin: influence on percutaneous absorption of caffeine (ex-vivo study).

BACKGROUND/PURPOSE: Contact between skin surface and external environment induces a microclimate at the skin surface. That microclimate affects skin interaction with xenobiotics substances. We have developed a new device to explore the influence of environmental parameters, on percutaneous absorption. The aim of this study was to study the influence of external humidity and temperature on percutaneous absorption of caffeine. METHODS: Six exposure conditions were tested: four by combining two temperatures (27°C and 42°C) with two relative humidities (28% and 70%), performed by our device and two others by using Franz diffusion cell (unoccluded conditions, with skin surface in contact with ambient laboratory environment (27°C/33%) and in occluded conditions with skin surface covering by impermeable membrane). RESULTS: Kinetic curve profile of percutaneous absorption of caffeine revealed different shapes characteristics depending on environmental exposure conditions. These profiles were related to evaporative process, of deposited preparation on skin surface combined with water uptake resulting from water flux through skin. CONCLUSION: Our results highlight a preponderant role of microclimate above the skin on percutaneous absorption of caffeine. The device used in this study will be a useful tool to investigate ex vivo, the influence of microclimate on percutaneous absorption.

Protease-modulating polyacrylate-based hydrogel stimulates wound bed preparation in venous leg ulcers--a randomized controlled trial.

BACKGROUND: Stringent control of proteolytic activity represents a major therapeutic approach for wound-bed preparation. OBJECTIVES: We tested whether a protease-modulating polyacrylate- (PA-) containing hydrogel resulted in a more efficient wound-bed preparation of venous leg ulcers when compared to an amorphous hydrogel without known protease-modulating properties. METHODS: Patients were randomized to the polyacrylate-based hydrogel (n = 34) or to an amorphous hydrogel (n = 41). Wound beds were evaluated by three blinded experts using photographs taken on days 0, 7 and 14. RESULTS: After 14 days of treatment there was an absolute decrease in fibrin and necrotic tissue of 37.6 ± 29.9 percentage points in the PA-based hydrogel group and by 16.8 ± 23.0 percentage points in the amorphous hydrogel group. The absolute increase in the proportion of ulcer area covered by granulation tissue was 36.0 ± 27.4 percentage points in the PA-based hydrogel group and 14.5 ± 22.0 percentage points in the control group. The differences between the groups were significant (decrease in fibrin and necrotic tissue P = 0.004 and increase in granulation tissue P = 0.0005, respectively). CONCLUSION: In particular, long-standing wounds profited from the treatment with the PA-based hydrogel. These data suggest that PA-based hydrogel dressings can stimulate normalization of the wound environment, particularly in hard-to-heal ulcers.

Development of an in vitro fibrin clot model to evaluate fibrinolytic agents for wound care application.

OBJECTIVE: To describe an in vitro fibrin clot model that could reliably assess the fibrinolytic activity of enzymatic debriding agents for wound care application. METHOD: A model of a fibrin clot was reconstructed in vitro by mixture of human fibrinogen and (alpha)-thrombin supplemented with factor XIII. These clots were then treated with enzymatic ointments. Fibrinolytic activity was investigated by measuring D-dimer levels, using an automated immunoturbidimetric Liatest D-dimer assay. RESULTS: Collagenase and papain-urea ointments demonstrated fibrinolytic activity which was macroscopically visible. Their effect was identical on the in vitro reconstructed fibrin clot and ex vivo collected wound fibrin clot; collagenase and papain-urea both induced a complete degradation and dissolution of both fibrin clots after 24 hours of treatment. This was associated with an increase in D-dimer concentration. CONCLUSION: This reconstructed fibrin clot in vitro model has the potential to predict the efficacy of fibrinolytic agents and therefore appears to be a suitable model for in vitro assays. DECLARATION OF INTEREST: This study was supported by a grant from URGO Laboratory.

Can leg ulcer fibroblasts phenotype be influenced by human amniotic membrane extract?

Prevalence of leg ulcer in general population is important and new efficient treatments are now needed, especially for chronic leg ulcers. Human amniotic membrane (HAM) can be used as an alternative treatment for recalcitrant leg ulcers. The aim of this study is to investigate the effects of a HAM extract on normal fibroblasts (NF) and ulcer fibroblasts (UF). NF and UF were obtained from biopsies by explants technique. HAM extract was used at 10 µg of total proteins per ml. Single patient-matched NF and UF were compared, without or with HAM extract. Studied parameters were proliferation rate, retraction of free-floating lattices, alpha smooth muscle actin expression by flow cytometry, and synthesis of elastin, glycosaminoglycans (GAGs), pro-collagen I, MMP-1 and TIMP-1. Our results show that UF had a specific phenotype compared to NF: low proliferation, high expression of alpha-SM actin and high synthesis of MMP-1, TIMP-1 and elastin. HAM extract significantly increased the synthesis of GAGs, pro-collagen I and MMP-1 in NF and decreased retraction of free lattices. HAM extract transiently increased UF proliferation, slowed down lattices retraction and decreased elastin synthesis. In conclusion, HAM extract has little effect on UF for the parameters studied and NF are more responsive than UF. However, clinical beneficial effect of HAM application on leg ulcers was previously observed and might rather be related to an action on keratinocytes and/or a modulation of the highly inflammatory environment of these chronic wounds.

[The challenge for dermatologists of early APECED diagnosis]. / Diagnostic précoce du syndrome APECED : un défi pour le dermatologue.

BACKGROUND: Polyglandular auto-immune syndrome type 1 (PAS-1) or auto-immune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder linked to auto-immune regulator (AIRE) gene mutations. Herein, we report the case of a 3-year-old boy with APECED emphasizing the wide phenotypic variability and the extent of skin lesions. PATIENTS AND METHODS: A 3-year-old boy with a history of auto-immune hepatitis was referred for a generalized pruriginous urticaria-like eruption present for one month. He was born to non-consanguineous parents. Cutaneous examination revealed twenty-nail dystrophy, which had been present since the age of 2 years. Both direct microscopy and culture of nail samples were negative for Candida albicans. Esophagogastroduodenoscopy revealed esophageal candidiasis. A diagnosis of APECED was suspected and subsequently confirmed by molecular analysis of the AIRE gene, which showed two mutations. No other auto-immune endocrinopathies were found. DISCUSSION: Our case report illustrates the phenotypic variability of APECED with the absence of typical manifestations such as Addison's disease and hypoparathyroidism. APECED should thus be systematically suspected in young children presenting with cutaneous lesions associated with mucocutaneous candidiasis or auto-immune disease, even in the absence of known endocrinopathies. CONCLUSION: Dermatologists should be aware of this association since early diagnosis of APECED is critical in preventing life-threatening endocrinological crises.

Assessment of the efficacy of a new formulation for plantar wart mummification: new experimental design and human papillomavirus identification.

Cutaneous warts are caused by infection of the epidermis with human papillomavirus (HPV). Cryotherapy using liquid nitrogen is one of the most common local treatments. In this study, we used a novel ex vivo approach to compare the efficacy of a new product with conventional liquid-nitrogen cryotherapy by studying epidermal histology and assessing the presence of HPV types 1 and 2 DNA in plantar warts. The studied formulation, which acts by tissues mummification, is a combination of nitric acid, organic acids and metallic salts. We found that, similar to liquid nitrogen, the studied product induced alterations in the wart structure. In addition, unlike liquid nitrogen, this product also reduced the amount of HPV DNA. The results suggest that there is a poor correlation between the histological response and the antiviral efficacy of standard wart treatment.

Algorithm for dermocosmetic use in the management of cutaneous side-effects associated with targeted therapy in oncology.

Currently, numerous patients who receive targeted chemotherapy for cancer suffer from disabling skin reactions due to cutaneous toxicity, which is a significant problem for an increasing number of patients and their treating physicians. In addition, using inappropriate personal hygiene products often worsens these otherwise manageable side-effects. Cosmetic products for personal hygiene and lesion camouflage are part of a patients' well-being and an increasing number of physicians feel that they do not have adequate information to provide effective advice on concomitant cosmetic therapy. Although ample information is available in the literature on pharmaceutical treatment for cutaneous side-effects of chemotherapy, little is available for the concomitant use of dermatological skin-care products with medical treatments. The objective of this consensus study is to provide an algorithm for the appropriate use of dermatological cosmetics in the management of cutaneous toxicities associated with targeted chemotherapy such as epidermal growth factor receptor inhibitors and other monoclonal antibodies. These guidelines were developed by a French and German expert group of dermatologists and an oncologist for oncologists and primary care physicians who manage oncology patients. The information in this report is based on published data and the expert group's opinion. Due to the current lack of clinical evidence, only a review of published recommendations including suggestions for concomitant cosmetic use was conducted.

[Bilateral spontaneous carotid-cavernous fistula revealing Ehler-Danlos disease]. / Fistules carotido-caverneuses spontanées bilatérales révélant une maladie d'Ehlers-Danlos de type IV.

PATIENTS AND METHODS: A 34-year-old woman with an extensive surgical history developed two spontaneous carotido-cavernous fistula bilaterally. Skin examination revealed an acrogeric form of vascular Ehlers-Danlos syndrome and this diagnosis was confirmed by genetic analysis. DISCUSSION: Vascular Ehlers-Danlos syndrome is a rare autosomal dominant genetic disease that may be suspected on the grounds of clinical symptoms. Severe complications can occur in early life and are associated with a high mortality rate. The prognosis of vascular Ehlers-Danlos syndrome has been radically changed by the use of beta-blockers. CONCLUSION: The originality of our observation lies in the long time to onset of the initial complications in the absence of any problems during the numerous operations undergone by the patient, as well as the two childbirths.