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A study published in the Journal of the European Academy of Dermatology & Venereology examines the effectiveness of sun safety campaigns in France over the past 30 years. The study found that despite the distribution of messages about sun safety, the number of melanomas and carcinomas in France has increased fivefold. The study surveyed 1000 members of the French population and found that while most respondents were aware of the skin problems caused by too much sun exposure, many still associated a tan with good health and attractiveness. The study suggests that prevention messages should be tailored to specific audiences and emphasizes the importance of dermatologists in educating patients about sun protection. [Extracted from the article]

Introduction: Only a small amount of published data regarding truncal acne is available, and no proper tool to assess its severity exists. Aim: The aim of the study was to provide dermatologists with an easy‐to‐use tool to assess truncal acne (TRASS, truncal acne severity scale) using a global approach. Methods: A scoring tool that assesses the severity of acne (based on GEA and ECLA scales) on the trunk using a global approach was built, including three sub‐scores: family history, clinical signs and quality of life (QoL). In order to test TRASS, the experts used photographs of 47 patients attending their clinics with truncal acne. The regression optimized (ROP) model was applied to assess the diagnosis performance of TRASS and to identify items contributing to the classification of the patients. Internal testing was made to demonstrate the robustness of the model. Correlation analyses between the different items were performed to evaluate the interaction between the different items and their impact on the severity grading of truncal acne. Results: Patients with the most severe acne were identified by TRASS. The error level was 6.6% after internal validation and 10.4% when using the median value or the centile 75th (6.6% and 10.4%). Correlation was significant between systemic treatment and scars (P = 0.0025) and nodules (P = 0.01988) and between location and QoL (P = 0.0095). Conclusion: Truncal acne severity scale is the first global, patient‐centred approach to evaluate truncal acne by scoring the importance of each factor independently from its clinical severity. TRASS may allow the practitioner to choose and validate the most suitable therapy together with the patient in order to treat his or her truncal acne successfully and to limit treatment failure. [ABSTRACT FROM AUTHOR]

Most of these individuals developed Sweet syndrome in association with chronic inflammatory bowel disease.2-6 Our observation is the first to document the efficacy of this treatment in Marshall's syndrome, both for the inflammatory lesions and the elastolysis. The patients in this manuscript have given written informed consent to publication of his case details. [Extracted from the article]

Truncal acne is frequently overlooked in dermatological practice, even though it may result in scars and impact on self‐esteem and body image. Therefore, it is important to identify the disease early in order to initiate treatment in time and, thus, to prevent it from worsening and resulting in physical and psychological sequelae. The aim of this review is to provide an overview of what is currently known about truncal acne, its prevalence, aetiology and physiopathology, how its severity is currently evaluated, how to differentiate it from other skin afflictions and current treatment options. A review of literature considering the issue of truncal acne published up to 2019 and available from PubMed was conducted, and in total, 76 articles were selected from PubMed. Currently, only little information about truncal acne is available. Considered as having the same pathophysiology as facial acne, the clinical picture and treatment response seem to differ. Specific acne severity grading systems and quality of life questionnaires as well as a specific treatment algorithm are still lacking. Filling this gap should allow clinicians to assess truncal acne in the best possible way, choosing suitable treatment options, helping patients to improve treatment adherence and quality of life and finally allowing a better management of truncal acne. In conclusion, more knowledge is required to treat more efficiently truncal acne. [ABSTRACT FROM AUTHOR]

Acne may significantly impact quality of life, self‐esteem and self‐worth. The aim of this paper was to provide an overview of the knowledge and perception of acne and its risk factors in adolescents and young adults. The most critical issues reported for an optimal management of this specific population were identified. A PubMed literature review of results from patient‐oriented surveys published between 2007 and 2018 was conducted. Two different types of survey were used: those using either validated questionnaires or specifically developed questionnaires. No consistency or directly comparable data with regards to age, onset, duration, severity and treatment of acne and by whom and where data were collected were observed. Acne affected female patients psychologically more than male patients. The majority referred to their treating physician in order to obtain information, and all surveys pointed out that specific treatment programs would allow to increase awareness about acne. Beliefs, traditions and economic factors continue to impact the perception of and treatment choices for acne in almost all countries and cultures, maintaining the improvement of awareness about acne a major global health challenge. In conclusion, identifying, considering and managing the patient's concerns about acne may improve the young patient's well‐being and thus decrease additional healthcare expenses for emerging psychological comorbidities. This can be achieved by creating substantial and structured awareness through local and global information campaigns via the treating physicians, Internet, social networks and education. [ABSTRACT FROM AUTHOR]

Abstract: Background: Since 2011, the management of advanced melanoma has radically changed with the availability of new therapies (immunotherapy and BRAF‐targeted therapy) and with BRAF testing. Objectives: Following the introduction of these new therapies, the objectives of this AMEL study were to describe treatment patterns and evaluate overall survival (OS) among unresectable stage III/IV melanoma patients, in a real‐life setting in France. Methods: The AMEL study is a multicentre retrospective record review study. Thirty‐three physicians working in 33 unique treatment centres participated in the study. Two hundred and sixty‐four patients diagnosed between 1 January 2012 and 31 October 2012 with unresectable stage III/IV melanoma were included in the study. Results: 94.7% of the patients received a first‐line antitumour drug treatment, 62.5% a second‐line treatment while 26.9% received a third‐line treatment with no significant differences between patients with a BRAF mutation (50.4%) and BRAF wild type (47.0%). First‐line treatment differs according to the BRAF status: 74.8% of patients with a BRAF mutation received a BRAF inhibitor while 79.3% of the BRAF wild‐type patients were treated with conventional chemotherapy. In second line and over, the treatment patterns were more heterogeneous, depending on the BRAF mutation, the treatment received previously, the speed of progression of the disease and the availability of immunotherapy at the time the treatment was initiated. Conclusion: Regardless of the BRAF mutation status, the median OS of patients was 16 months (95% CI = 14–18). Compared to a similar study conducted in 2007 (MELODY), a gain of 4 months is observed. The gain seems to be higher for patients with a BRAF mutation (18 months) than for those without a BRAF mutation (14 months). The OS of patients who sequentially received both a BRAF inhibitor and ipilimumab (28 months) highlights the benefit of this treatment sequence. [ABSTRACT FROM AUTHOR]

The JEADV has recently published the article 'Incidence, prevalence and risk of acne in adolescent and adult patients with atopic dermatitis - a matched cohort study' by Thyssen I et al i .1 In this article, the authors assessed the prevalence of I acne vulgaris i (acne)in patients with atopic dermatitis and treated with Janus kinase 1 (JAK1) inhibitors through an epidemiological study that was initiated upon results from several clinical trials in moderate-to-severe AD testing JAK 1 and JAK 2 inhibitors reporting cases of acne in patients having been treated with JAK inhibitors. 5 Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. [Extracted from the article]

Abstract: The antifungal voriconazole was given its marketing authorization in 2002. Several kinds of adverse effects have been reported, including acute and chronic cutaneous adverse effects, mainly due to a phototoxicity mechanism. More recently, some authors have reported that voriconazole was involved in the occurrence of multiple and often-aggressive cutaneous squamous cell carcinomas if the treatment was maintained for a long time. According to safety data in studies assessing voriconazole effectiveness, 8% of outpatients may experience phototoxic events. An overview of the different types of phototoxicity and of the concerned population was given by the 61 published case reports of photo-induced voriconazole-related skin adverse events (including 18 cases of squamous cell carcinomas). The most likely mechanisms may be phototoxicity directly related to either voriconazole or to its N-oxide main metabolite, and an interaction with retinoid metabolism; moreover, immunodeficiency may enhance the risk of skin cancer. Several issues remain to be investigated, and studies are needed concerning the phototoxicity and photocarcinogenesis of voriconazole and the prognosis of chronic non-malignant skin lesions. Voriconazole prescription must be associated with strict photoprotection; in case of a phototoxic adverse event, another azole may be recommended. [Copyright &y& Elsevier]

The article presents case studies of an 80-year-old man and a 76-year-old man who were presented with cutaneous squamous cell carcinomas and underwent surgery and adjuvant radiotherapy. Topics discussed include effectiveness of 2 Anti-Programmed Death-1 therapies in the patient with head and neck squamous cell carcinomas and magnetic resonance imaging of patients.

Hymenoptera venom anaphylaxis is the most frequent cause of anaphylaxis and responsible for about 20% of all fatal anaphylaxis cases in adults. We report two cases of fatal hymenoptera venom anaphylaxis with undiagnosed underlying mastocytosis and review the risk factors for severe or fatal hymenoptera venom anaphylaxis, as well as the specificities of its association with mastocytosis. As hymenoptera venom allergic patients with underlying clonal mast cell disorder generally lack typical skin lesions of mastocytosis, its diagnosis can easily be missed, underscoring the importance and need for diagnostic strategies in order to correctly identify these patients. Predominant cardiovascular symptoms in the absence of urticaria or angioedema following an insect sting are suggestive of underlying clonal mast cell disorder, and should be distinguished from panic attack or vasovagal syncope. Similarly, an unexplained syncope or an "idiopathic" anaphylaxis might reveal mastocytosis or hereditary alpha-tryptasemia. Acute and basal serum tryptase measurements should always be integrated in the diagnostic work-up of an insect sting reaction or unexplained syncope or shock of any origin., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: Smoothened (SMO) inhibitors, blocking the sonic hedgehog pathway, have been approved for advanced basal cell carcinoma (aBCC). Safety analyses reveal a high rate of adverse events (AEs) and, most of the time, vismodegib is most commonly stopped when the best overall response is reached. The long-term evolution of aBCC after vismodegib discontinuation is poorly described. The aim of this study is to evaluate the efficacy and safety of the SMO inhibitors (SMOis) available (vismodegib and sonidegib) following rechallenge after complete response (CR) following an initial treatment by vismodegib., Materials and Methods: This real-life, retrospective, multicenter and descriptive study is based on an extraction from the CARADERM accredited database, including 40 French regional hospitals, of patients requiring BCC systemic treatment., Results: Of 303 patients treated with vismodegib, 110 achieved an initial CR. The vast majority of these patients (98.2%) stopped vismodegib, notably due to poorly tolerated AEs. The CARADERM database provided a median follow-up of 21 months (13.5-36.0 months) after CR. Of the 110 patients, 48.1% relapsed after a median relapse-free survival of 24 months (13.0-38.0 months). Among them, 35 patients were retreated by an SMOi and the overall response rate was 65.7% (34.3% of CR and 31.4% of partial response). The median duration of retreatment was 6.0 months (4.0-9.5 months)., Conclusion: Our real-life study, carried out on patients with complex clinical pictures, shows that after treatment discontinuation, 48.1% of patients achieved CR relapse within an average of 24 months (13.0-38.0 months). It emphasized that even though rechallenge can be considered as a therapeutic option, efficacy seems to decrease, suggesting the development of resistance mechanisms., Competing Interests: Disclosure EMN: Consulting or advisory role: Novartis, Pierre Fabre, Bristol-Myers Squibb, MSD. EM: Consulting or advisory role: MSD, Pierre Fabre, Novartis, Sanofi; research funding: MSD (Inst); travel, accommodations, expenses: MSD Oncology, Pierre Fabre, Novartis. NM: Consulting or advisory role or research funding: Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Merck, Sanofi, Sun Pharmaceutical Industries. MB-B: Research funding: Roche; consulting or advisory role: Sun Pharmaceutical Industries. NB-S: Consulting or advisory role: Sanofi, Sun Pharmaceutical Industries. LM: Consulting or advisory role: Sanofi, Sun Pharmaceutical Industries, MSD Oncology, Bristol-Myers Squibb, Novartis. The remaining authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors (ICI) completely upset the therapeutic algorithm of several type of solid cancer conferring in some patients a long clinical benefit with an acceptable toxicity. ICI rechallenge is an attractive option being a palliative chemotherapy the only alternative treatment in most of cases. Despite this strategy recently entered into the clinical practice, no widely recognized recommendation is currently available to select the good candidates. Anti-Cytotoxic T Lymphocyte Antigen 4 (Anti-CTLA4) rechallenge and a sequential administration of anti-CTLA4 and anti-Programmed cell Death protein 1 (anti-PD1) or Anti-Programmed Death Ligand 1 (anti-PDL1) agents have been explored in melanoma patients in several clinical trials while the anti-PD1/anti-PDL1 rechallenge has been little investigated. Here we performed a literature revision about efficacy and tolerability of ICI rechallenge across solid tumors also focusing on inclusion criteria used into clinical trials., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Since 2011, significant progress was observed in metastatic melanoma (MM), with the commercialisation of seven immunotherapies or targeted therapies, which showed significant improvement in survival. In France, in 2004, the cost of MM was estimated at €1634 per patient; this cost has not been re-estimated since. This study provided an update on survival and cost in real-life clinical practice., Methods: Clinical and economic data (treatments, hospitalisations, radiotherapy sessions, visits, imaging and biological exams) were extracted from the prospective MelBase cohort, collecting individual data in 955 patients in 26 hospitals, from diagnosis of metastatic disease until death. Survival was estimated by the Kaplan-Meier method. Costs were calculated from the health insurance perspective using French tariffs. For live patients, survival and costs were extrapolated using a multistate model, describing the 5-year course of the disease according to patient prognostic factors and number of treatment lines., Results: Since the availability of new drugs, the mean survival time of MM patients has increased to 23.6 months ( 95% confidence interval [CI] :21.2;26.6), with 58% of patients receiving a second line of treatment. Mean management costs increased to €269,682 ( 95% CI:244,196;304,916) per patient. Drugs accounted for 80% of the total cost., Conclusion: This study is the first that evaluated the impact of immunotherapies and targeted therapies both on survival and cost in real-life conditions. Alongside the introduction of breakthrough therapies in the first and subsequent lines, MM has been associated with a significant increase in survival but also in costs, raising the question of financial sustainability., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: There are few population-based studies assessing the prevalence of skin diseases., Objectives: To estimate the prevalence of five chronic skin inflammatory diseases, i.e. atopic dermatitis (AD), psoriasis, alopecia areata (AA), vitiligo and hidradenitis suppurativa (HS) in France, using validated self-diagnostic questionnaires., Methods: Population-based study using a representative sample of the French general population aged more than 15 years and sampling with replacement design. All participants were asked (ii) to fill in a specific questionnaire including socio-demographic characteristics, (ii) to declare if they have been diagnosed with one or more skin problem or skin diseases during their life, and (iii) to fill in five validated self-reported questionnaires for AD, psoriasis, AA, vitiligo and HS., Results: A total of 20.012 adult participants responded to the questionnaire of whom 9760 were men (48.8%) and 10.252 (51.2%) were women. We identified a prevalence of 4.65% for AD (931 individuals), 4.42% for psoriasis (885 individuals), 1.04% for AA (210 individuals), 0.46% for vitiligo (93 individuals) and 0.15% for HS (29 individuals), respectively., Limitations: Questionnaire-based study and possible disease misclassifications., Conclusion: This is the largest population-based study aiming to estimate the prevalence of five chronic skin inflammatory diseases., (© 2018 European Academy of Dermatology and Venereology.)

Acne is an inflammatory and multifactorial skin disease. Different external and internal factors, including air pollution, aggressive skincare products, medication, mechanical, hormonal and familial factors and, more recently, lifestyle and stress, have been suggested as having an impact on acne. Moreover, for many years nutrition was believed to cause or worsen acne. Over the last decades, however, it has become a dermatological doctrine that there is no direct association between diet and acne. Even if recent research has allowed to identify certain nutritional elements and behaviour that may impact on acne, including the excessive intake of dairy products and hyperglycaemic food, modern lifestyle nutrition, obesity and eating disorders, knowledge about the role of nutrition in the physiopathology of acne still remains sparse and hypotheses and myths continue to dominate the debate. Thus, further clinical and translational research is necessary to investigate and confirm the association between nutrition and acne., (© 2018 European Academy of Dermatology and Venereology.)

Background: Mucosal melanomas are rare and highly aggressive tumours. Few studies evaluated mucosal melanomas of locations other than the head and neck region, and other than those of the Asian population., Objectives: The objective of this study was to analyse the clinical and histological features, as well as the mutational status of c-kit and b-raf gene of mucosal melanoma in any localization in a French series., Methods: We investigated clinical (sex, age, performance status, survival, treatment of the patients and lack of pigmentation of the tumours) and histopathological features (ulceration, Breslow's index, mitotic rate), as well as the mutational status of c-kit and b-raf of 86 mucosal melanomas diagnosed in 15 years in four French University Hospitals., Results: Most melanomas affected women (72%) and the genital region (46.5%). A fifth of melanomas were amelanotic. 81% of melanomas had a Breslow's index ≥1, whereas all glans melanomas, and most vulvar melanomas had a Breslow index ≤1 mm. Overall survival was 54% at 3 years; 11.6% of the 43 tested mucosal melanomas were c-kit-mutated while the 15 tested genital melanomas were not. The c-kit gene mutation did not influence the overall survival. Age ≥ 50, amelanotic type and performance status ≥1 were not poor prognostic factors in our series., Conclusion: This study confirmed that mucosal melanomas are rare and could be difficult to diagnose being often amelanotic and in hidden sites. Most melanomas were thick at the diagnosis, but glans and vulvar melanomas were thinner probably because of their greater visibility. The frequency of the c-kit mutation varied depending on the initial tumour site. In our series, the prognosis was poor, independently from c-kit mutations and the patient's general health and age. The presence of metastasis at diagnosis was associated with a worse prognosis indicating the importance of an early diagnosis., (© 2017 European Academy of Dermatology and Venereology.)

Summary: Food allergy to pumpkin seed is considered very rare, and only some isolated case reports have so far been published. We report here a case of food anaphylaxis to pumpkin seed in an eight-year-old boy, who tolerated all other edible seeds, peanut and tree nuts, as well as pulp of different kinds of pumpkins and other fruits of the Cucurbitaceae family. From this observation, a review of the botanical, historical, medicinal and allergenic aspects of pumpkin and its seeds is proposed. With the advent of diets rich in omega-3 and omega-6 polyunsaturated fatty acids, edible seeds like pumpkin seed have been incorporated in the modern diet. Their incremental use in the food-processing industry might contribute to an increase in food allergy to pumpkin seed in the future.

Cell migration, growth, and survival is modulated by focal adhesions linking extracellular matrix proteins, cell adhesion molecules, and the cytoskeleton. Zyxin is a focal adhesion phosphoprotein that shares homology with Listeria ActA protein in promoting actin filament assembly; it also has specialized protein-protein interface domains implicating an important role in cell growth and differentiation. We investigated the distribution of zyxin in normal and migrating human keratinocytes in wounds in vitro and in situ using confocal laser microscopy. Zyxin expression in high-density nonmigrating keratinocytes versus low-density migrating keratinocytes was determined by western immunoblotting and time lapse image analysis. In normal epidermis, zyxin exhibited a punctate staining pattern throughout the cytoplasm and was excluded from the intercellular spaces. In wounds, the punctate staining also localized in the edge of the migrating keratinocyte sheets; however, intercellular spaces were absent. Likewise, in vitro keratinocytes showed punctate staining throughout the cytoplasm. Migrating cultured keratinocytes next to wounds, however, had large focal contacts in the cell periphery where actin bundles converged at focal adhesions. Western immunoblots and confocal experiments with protein synthesis inhibition by cycloheximide confirmed that this difference in distribution of zyxin in migrating versus nonmigrating keratinocytes is due to the redistribution and not upregulation of zyxin. The abundance of zyxin and its relative change in distribution from normal to migrating keratinocytes in wounds is consistent with its role in cytoskeletal organization of actin bundles.

Ultraviolet A1 (UVA1) radiation generates reactive oxygen species and the oxidative stress is known as a mediator of DNA damage and of apoptosis. We exposed cultured human cutaneous fibroblasts to UVA1 radiation (wavelengths in the 340-450-nm range with emission peak at 365 nm) and, using the alkaline unwinding method, we showed an immediate significant increase of DNA strand breaks in exposed cells. Apoptosis was determined by detecting cytoplasmic nucleosomes (enzyme-linked immunosorbent assay method) at different time points in fibroblasts exposed to different irradiation doses. In our conditions, UVA1 radiation induced an early (8 h) and a delayed (18 h) apoptosis. Delayed apoptosis increased in a UVA dose-dependent manner. Zinc is an important metal for DNA protection and has been shown to have inhibitory effects on apoptosis. The addition of zinc (6.5 mg/L) as zinc chloride to the culture medium significantly decreased immediate DNA strand breaks in human skin fibroblasts. Moreover, zinc chloride significantly decreased UVA1-induced early and delayed apoptosis. Thus, these data show for the first time in normal cutaneous cultured cells that UVA1 radiation induces apoptosis. This apoptosis is biphasic and appears higher 18 h after the stress. Zinc supplementation can prevent both immediate DNA strand breakage and early and delayed apoptosis, suggesting that this metal could be of interest for skin cell protection against UVA1 irradiation.

The levels of antioxidant molecules and lipid peroxidation, under basal conditions, were measured in normal, human cutaneous keratinocytes and fibroblasts. Total glutathione, glutathione peroxidase and superoxide dismutases are significantly higher in normal keratinocytes compared to normal fibroblasts (respectively +248%, +193% and +155%). Under the same conditions, lipid peroxidation is significantly lower in basal keratinocytes compared to fibroblasts. UV-A1 cytotoxicity was investigated in both cutaneous cell types showing that diploid keratinocytes are more resistant to UV-A1 oxidative stress than fibroblasts (by a factor of around 8). We studied the same parameters in two keratinocyte cell lines, NCTC2544 and HaCaT cells, and in MRC5 fibroblasts. Antioxidant content and lipid peroxidation under basal conditions are quite different in these cell lines compared to those of the normal corresponding cells. Furthermore, NCTC2544 keratinocytes are more sensitive to UV-A1 radiation than normal keratinocytes whereas HaCaT keratinocytes are more resistant, and MRC5 fibroblasts are more resistant than normal cutaneous fibroblasts. These findings suggest that (i) cultured epidermal and dermal cells have different sensitivities to UV-A1 radiation that may be linked to different antioxidant capacities and (ii) cell line response to UV-A1 radiation may differ from that of normal cells.

The sensitivity of human dermal fibroblasts to UVA radiation has been linked to a decrease in intracellular glutathione (GSH) levels. GSH (gamma-glutamyl-cysteinyl-glycine) is a radical scavenger and a cofactor for protective enzymes such as selenium-dependent GSH peroxidases. In this study, we examine the possibility of a cooperative interaction between three cysteine delivery systems and selenium in protecting human cultured fibroblast exposed to UVA radiation. Cells were irradiated (9, 15 and 20 J cm-2) following incubation with N-acetyl-cysteine (NAC, 5 mM), N-acetyl-homocysteine-thiolactone (citiolone (CIT), 1 mM) or L-2-oxothiazolidine-4-carboxylate (OTC, 1 mM). The modulation of the intracellular GSH levels by the addition of the different compounds was determined by enzymatic and separative methods. Cells were harvested for survival analysis by measuring the ability of the cell to adhere and proliferate. Treatments with NAC and CIT resulted in a significant rise in GSH levels compared with control cells, with protection against UVA radiation. OTC did not induce any rise in GSH level; nevertheless, the protective effect afforded by OTC is similar to that observed with NAC and CIT. Moreover, selenium (0.1 mg 1-1), as sodium selenite, significantly increased the protective efficiency of NAC and CIT, but not of OTC. Although the precise mechanism is not known, thiol molecules can inhibit the deleterious effects of UVA radiation. These results provide evidence that compounds capable of inducing GSH synthesis can act with selenium to protect cells against UVA damage.