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Late-onset adverse events (AEs) of anti-programmed cell death 1 (anti-PD1) antibodies have not been systematically described.The purpose was to evaluate late-onset AEs in melanoma patients treated with anti-PD1 administered for at least 2 years in a real-life setting.Patients were screened from MelBase, a French multicentric biobank dedicated to the prospective follow up of unresectable stage III or IV melanoma. The study included 119 patients who received anti-PD1 during at least 2 years from January 2013 to November 2019. Median follow up was 41.7 months (range, 25.2-57.5 months). Fifty-three patients received nivolumab and 66 patients received pembrolizumab.AEs occurred in 99 patients (83%) with a median time of 13.3 months (range, 0-53.9 months), including severe AEs (grade 3 or 4) in 30 patients (30%). Late-onset AEs, mostly grades 1 or 2, occurred in 51 (43%) patients and led to 5 (4%) hospitalizations, of which 4 were severe. Factors associated with late-onset AEs in multivariate analysis were early-onset AEs (within the first 2 years of treatment) and treatment duration (P = .02 and P = .03, respectively).Our data demonstrate the possibility of late-onset AEs occurring after 2 years of anti-PD1 therapy. Late-onset AEs appear frequently and were mostly mild or moderate. Early-onset AEs and prolonged anti-PD1 treatment may increase the risk of late-onset AEs.

Background Acne is a chronic disease with a varying presentation that requires long-term management. Despite this, the clinical guidelines for acne offer limited guidance to facilitate personalized or longitudinal management of patients. Objectives To generate recommendations to support comprehensive, personalized, long-term patient management that address all presentations of acne and its current and potential future burden. Methods The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists who used a modified Delphi approach to reach consensus on statements related to longitudinal acne management. The consensus was defined as ≥75% voting "agree" or "strongly agree." All voting was electronic and blinded. Results Key management domains, consisting of distinct considerations, points to discuss with patients, and "pivot points" were identified and incorporated into the Personalised Acne Care Pathway. Long-term treatment goals and expectations and risk of (or fears about) sequelae are highlighted as particularly important to discuss frequently with patients. Limitations Recommendations are based on expert opinion, which could potentially differ from patients' perspectives. Regional variations in health care systems may not have been captured. Conclusions The Personalised Acne Care Pathway provides practical recommendations to facilitate the longitudinal management of acne, which can be used by health care professionals to optimize and personalize care throughout the patient journey.

Acne is a multifactorial inflammatory dermatose that affects all age categories from teenagers to adults, resulting in important psychological impacts. Multiple hypotheses currently attempt to decrypt the physiopathology of this disease, and four main actors were identified as highly implicated in it: hyperkeratinization of the pilosebaceous follicle, hyperseborrheae, host factors (innate immunity) and skin microbiota. In this letter, we present results illustrating the impact of skin microbiota on inflammatory skin response, and how far the proper balance between each bacterial community, especially C. acnes and S. epidermidis, is crucial to maintain an appropriate inflammatory response on the skin. The data presented in this study demonstrate that within the skin microbiota, an imbalance between Cutibacterium acnes and Staphylococcus epidermidis, is able to induce the activation of inflammation-related markers such as IL-1ra, IL-6, IL-8, G-CSF and the molecules C5/C5a, soluble CD14 MIP-3beta, Serpin E1, VCAM-1 and beta-defensin-2. Moreover, S. epidermidis appears to have a more important role than C. acnes on the induction of inflammation-related markers, particularly on IL-6. This work is the basis of future in vitro studies to further understand acne physiopathology, inspiring the development of future innovative therapies based on skin microbiota modulation.

Background: Targeted therapy is used to treat patients with a BRAF-mutated metastatic melanoma and is continued until disease progression or severe toxicity. No robust data on the management of patients achieving a complete remission (CR) are available. Main Objective: To determine the relapse rate in the first year after targeted therapy discontinuation in patients in CR. Secondary Objectives: To determine the relapse rates throughout the follow-up and to identify prognostic factors for relapse at 1 year. Methods: A retrospective, monocentric observational study was conducted in patients with advanced melanoma included in the RIC-Mel database who discontinued targeted therapy after achieving a CR confirmed by CT scan and PET/CT scan. Results: Twenty-nine patients were included. Seventeen (58.6%) patients were treated with BRAF inhibitor (BRAFi) alone and 12 (41.4%) with a BRAFi combined with a MEK inhibitor (BRAFi + MEKi). The median treatment duration was 9.7 months. The relapse rates after discontinuation were 69% at 12 months (BRAFi: 70.6%; BRAFi + MEKi: 66.7%) and 76% at 36 months (BRAFi: 76.5%; BRAFi + MEKi: 75%). A non-significant trend towards a higher risk of relapse was found in women (p = 0.1; RR 3.36; 95% CI 0.77–17.07), in patients with an LDH level greater than the upper limits of normal (p = 0.58; RR 2.43; 95% CI 0.10–56.71), and when more than two metastatic sites were involved (p = 0.19; RR 4.6; 95% CI 0.46–46.51). After relapse, targeted therapy was resumed in 17 patients (7 with BRAFi; 10 with BRAFi + MEKi) with a response rate of 53%. Conclusions: This real-life study provided long-term data in patients who discontinued targeted therapy after CR. Most patients experienced a relapse in the first year after targeted therapy discontinuation, of whom 50% were in the first 3 months. After targeted therapy resumption, 53% of relapsing patients achieved an objective response. Patients should be followed during the first year after treatment discontinuation. In addition, patients with less than 3 metastatic sites, a baseline LDH level with normal ranges, men, and patients responding rapidly to treatment would be more likely to maintain a CR after treatment discontinuation.

Introduction Sonidegib is approved to treat locally advanced basal cell carcinoma (laBCC) in the USA, EU, Switzerland, and Australia and metastatic basal cell carcinoma (mBCC) in Switzerland and Australia in patients not amenable to surgery or radiotherapy. Vismodegib is approved to treat patients with mBCC, recurrent laBCC, or those not candidates for surgery or radiation. There is no head-to-head trial comparing Hedgehog inhibitors. We describe time to onset and severity of adverse events (AEs) in two studies reporting cumulative AE incidence every treatment cycle: the sonidegib phase 2 BOLT study and the expanded-access, open-label vismodegib study. Methods This analysis included patients with histologically confirmed laBCC or mBCC from BOLT who received sonidegib 200 mg once daily (QD) and patients from the vismodegib study who received vismodegib 150 mg QD. Cumulative occurrence of AEs and median time to AE onset were calculated on 30-day cycles for sonidegib and 28-day cycles for vismodegib. AEs were graded for severity using the Common Terminology Criteria for Adverse Events. Only common (at least 15% incidence) AEs were analyzed in this study. Results Over 18 treatment cycles, the most common all-grade AEs for sonidegib and vismodegib were muscle spasm (54.4% vs 70.6%; P = 0.0236), alopecia (49.4% vs 58.0%; no significant difference [NS]), and dysgeusia (43.0% vs 70.6%; P = 0.0003); incidences of diarrhea, nausea, fatigue, and weight decrease were 31.6% vs 25.2% (NS), 39.2% vs 19.3% (P = 0.0032), 32.9% vs 19.3% (P = 0.0429), and 30.4% vs 16.0% (P = 0.0217), respectively. Sonidegib-treated patients had more delayed median time to onset for all AEs than vismodegib-treated patients, except fatigue and weight decrease (NS). Most AEs reported were grade ≤ 2. Conclusion This post hoc analysis suggests lower overall incidence and slower onset of certain AEs in patients treated with sonidegib compared with vismodegib. In the absence of head-to-head comparisons, the relevance of these findings needs further studies to provide conclusive evidence.

Background The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes. Objective To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance. Methods The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting "agree" or "strongly agree." All voting was electronic and blinded. Results The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae. Limitations The recommendations are based on expert opinion and made in the absence of high-quality evidence. Conclusions The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management.

Skin conditions such as acne, atopic dermatitis, skin toxicity from oncology treatment, and scars are among the most common health conditions and negatively impact quality of life (QoL). Yet the physician perception of this impact often varies greatly from the patient perception. This is important because patient illness perception is closely linked with seeking help and treatment adherence behaviors. The objective of this review is to better understand the impact of these four highly prevalent skin conditions on QoL including their health-related economic factors to improve treatment outcomes. The literature search included literature published on QoL with acne, atopic dermatitis, scars (from any cause) and skin toxicities on PubMed between 2015 and 2020. We found that patients with skin conditions have a much higher frequency of altered QoL and psychological distress than those without. Also, skin conditions negatively impact self-image and can cause feelings of isolation, loneliness, lower self-esteem, and lower body satisfaction. Additionally, physical discomfort adds to the psychological distress. These physical and psychological impacts are an enormous financial burden on patients, their families and society. We found evidence that holistic treatment including treating the skin condition itself, providing wider peer and psychological support as well as shared decision-making, therapeutic patient education and dermatologist involvement improves outcomes. Holistic history-taking, checklists, or the use of more formal QoL scoring tools can be incorporated into routine consultations to better assess patient well-being and provide clinicians with important information for adapting treatment to individual patient requirements. In conclusion, this review highlights the overall impact of skin conditions (including psychological and QoL impacts) and the importance of providing holistic care to optimize treatment outcomes. A comprehensive QoL screening tool would be useful to help provide patient-centered treatment.

Merkel cell carcinoma (MCC) is an aggressive tumour that rapidly evolves to metastasis, however, paradoxically, complete spontaneous regression (CSR) of MCC has been reported. CSR may be linked to the presence of Merkel cell polyomavirus (MCPyV) combined with immune response tumour-infiltrating lymphocytes (TILs). To elucidate the mechanism of CSR by studying the profile of TIL infiltration and the role of MCPyV. We describe a clinical case of CSR with MCC and provide the results of a literature review based on PubMeb and Embase databases, from January 1st 1986 to April 1st 2010, using the terms: "Merkel cell carcinoma" and "complete spontaneous regression". We found 38 clinical cases of CSR of primary MCC at different stages. The rate of MCPyV positivity was 75%, as found generally in MCC. The peritumoural infiltration was mostly composed by CD3+ T cells, whereas the intratumoural infiltration revealed CD8+ T cells, defined as TILs. To further investigate TILs in CSR of MCC, immunohistochemical staining was performed and compared to three non-regressive MCCs. CD8, IFNɣ and LAG3 expression was higher in biopsy samples with tumour regression, mainly inside the tumour nest. TILs were significantly more abundant in regressive MCC than in non-regressive MCC, in which both IFNɣ and LAG3 levels were low. This review and our clinical case confirms the central role of TILs in regressive MCC associated with IFNɣ and LAG3 secretion, thus underlining the interest in checkpoint inhibitors and adoptive T cell therapy in the treatment of MCC.

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by eczematous and pruritic skin lesions. In recent decades, the prevalence of AD has increased worldwide, most notably in developing countries. The enormous progress in our understanding of the complex composition and functions of the epidermal barrier allows for a deeper appreciation of the active role that the skin barrier plays in the initiation and maintenance of skin inflammation. The epidermis forms a physical, chemical, immunological, neuro-sensory, and microbial barrier between the internal and external environment. Not only lesional, but also non-lesional areas of AD skin display many morphological, biochemical and functional differences compared with healthy skin. Supporting this notion, genetic defects affecting structural proteins of the skin barrier, including filaggrin, contribute to an increased risk of AD. There is evidence to suggest that natural environmental allergens and man-made pollutants are associated with an increased likelihood of developing AD. A compromised epidermal barrier predisposes the skin to increased permeability of these compounds. Numerous topical and systemic therapies for AD are currently available or in development; while anti-inflammatory therapy is central to the treatment of AD, some existing and novel therapies also appear to exert beneficial effects on skin barrier function. Further research on the skin barrier, particularly addressing epidermal differentiation and inflammation, lipid metabolism, and the role of bacterial communities for skin barrier function, will likely expand our understanding of the complex etiology of AD and lead to identification of novel targets and the development of new therapies.

Increasing evidence on the impact of the different wavelengths of sunlight on the skin demonstrates the need for tailored recommendations of sunscreen according to skin phototype and dermatoses, which is now possible due to advances in the filters and formulations of sunscreens. A selective literature search was performed by an international expert panel, focusing on the type of sunscreen to recommend for photoaging, skin cancers, photodermatoses, pigmentary disorders and skin inflammatory disorders. Protection against ultraviolet (UV)B is especially important for light skin as there is a high risk of sunburn, DNA damage and skin cancers. Darker skin may be naturally better protected against UVB but is more prone to hyperpigmentation induced by visible light (VL) and UVA. Protection against UVA, VL and infrared A can be helpful for all skin phototypes as they penetrate deeply and cause photoaging. Long‐wave UVA1 plays a critical role in pigmentation, photoaging, skin cancer, DNA damage and photodermatoses. Adapting the formulation and texture of the sunscreen to the type of skin and dermatoses is also essential. Practical recommendations on the type of sunscreen to prescribe are provided to support the clinician in daily practice.

Background Immune checkpoint inhibitors have improved the management of metastatic melanoma, however, we have witnessed an emergence of adverse cardiac events such as myocarditis. Objectives We first aimed to assess the prevalence of adverse cardiac events in patients treated with anti-PD-1 for metastatic melanoma. Our second objective was to determine the role of troponin monitoring in the diagnosis of these events. Materials & methods We retrospectively analysed the prevalence of patients treated with anti-PD-1 in a real-life setting based on a cohort of 183 patients. We then performed a prospective cohort, in which clinical and biological profiles of patients were collected, along with monthly monitoring of troponin levels. Results The prevalence of adverse cardiac events in the retrospective cohort was 2.2%, with three cases of myocarditis and one of myocardial infarction. In the prospective cohort, 14/52 patients had an abnormal baseline troponin T level. All patients had a history of cardiac or vascular complaints. Six patients showed an increase in troponin T level during follow-up, in two patients associated with clinical symptoms. Conclusion Adverse cardiac events with immunotherapy are both frequent and life-threatening. Troponin T may be of interest to detect early adverse cardiac events before any clinical sign, however, the data supporting this remain to be confirmed.

International audience; Background: Targeted therapies such as BRAF and MEK inhibitors and immunotherapies have been made available to treat melanoma.Objectives: To provide an overview of the management of the French Stage III melanoma population after complete lymph node resection prior to new adjuvant therapies.Materials and methods: A subgroup data analysis.Results: Data from 1,835 patients were analysed (15.58% Stage IIIA, 39.24% Stage IIIB, 43.92% Stage IIIC and 1.25% Stage IIID). Superficial spreading melanoma was the most frequent (70.98% in Stage IIIA for whom mutation analysis was performed; BRAF mutation was identified in up to 62% Stage IIIA patients). Sentinel lymph node biopsy was performed in 88.46% of Stage IIIA patients, 42.36% of Stage IIIB, 53.97% of Stage IIIC and 34.78% of Stage IIID. Up to 80% of Stage IIIA patients had no adjuvant treatment follow-up. Ulceration (p = 0.004; RR: 2.98; 95% CI: 1.4-6.3) and age at diagnosis (p = 0.0002; RR: 1.04; 95% CI: 1.02-1.06) were significant predictive factors for survival. Adjuvant interferon-α was administered in up to 13.04% of Stage IIID patients.Conclusion: Only a small number of Stage III melanoma patients were treated with interferon-α in adjuvant settings. New adjuvant therapies are currently having an effect on clinical practice in France, increasing survival and decreasing cost.

International audience; BACKGROUND:Acne severity and its response to treatment may be influenced by internal and external factors: the exposome.OBJECTIVES:The aim of this international real-life survey was to assess the most involved exposome factors in acne.METHODS:11000 individuals, aged between 15 and 39 years, with clinically confirmed acne or without acne, defined by age, gender and prevalence, were invited to participate in an internet survey of 63 questions in order to assess the frequency of identified acne exposome factors.RESULTS:Data from 6679 questionnaires were used for statistical analysis purposes: 2826 from the acne group and 3853 from the control group. Nibbling, consumption of dairy products, sweets, alcohol, or whey proteins, as well as exposure to pollution, stress, certain mechanical factors and humid or hot weather or sun exposure, were significantly (all P≤0.05) more frequently reported for the acne group than for the control group. This was not the case for tobacco consumption. Data regarding the impact of cannabis consumption were insufficient for drawing any conclusions.CONCLUSIONS:Data from this international, anonymized internet questionnaire conducted with more than almost 6700 participants add new arguments to assumptions made that certain exposome factors have an impact on acne. Nutrition, pollution, stress and harsh skin care, as well as climate and sun exposure may be considered the most frequent factors related to acne.

Summary Background During isotretinoin treatment, special attention is required to detect any symptom or change in the mental health of patients. The monitoring is complex for adolescents because of confounding factors such as mood changes associated with adolescence and puberty and the higher psychosocial impairment due to the acne itself. Aim To determine the utility of the Adolescent Depression Rating Scale (ADRS) for monitoring symptoms in adolescents before and during isotretinoin treatment in dermatology real-life practice. Methods This was a national, multicentre prospective study that enrolled a random sample of dermatologists treating adolescents. An algorithm including ADRS score and its changes between consecutive visits was used. At each visit, dermatologists rated their satisfaction with ADRS and its ease of use, while patients rated the acceptability of the ADRS. Results In total, 70 dermatologists used the algorithm for 1227 visits of 283 adolescents receiving isotretinoin. Of these 70 dermatologists, 80.8% were satisfied/very satisfied with the ADRS, 82.7% considered the use of the ADRS in clinical practice to be easy/very easy and 75% considered that the ADRS enabled them to discuss more easily the risk of depression with their patients. For the patients, acceptability of the ADRS was considered good by 93.8%. Conclusions The implementation of the ADRS could be valuable in dermatology practice, optimizing the monitoring of patients and the good use of isotretinoin.

We read with great interest the recent paper by Nenoff et al. regarding the antimicrobial activity of nadifloxacin against Cutibacterium acnes strains isolated from patients with acne1 . However, we would like to add a few points relevant to the subject. Whether C. acnes remains the most prevalent microorganism involved in acne, phylotype determination and potential correlation with some resistant lineages would have been of interest, especially with phylotype IA1 and clonal complex CC32 . We agree that a significant number of resistance with erythromycin and clindamycin are found clinically.

General practitioners (GPs) are playing a key role in skin cancer screening. Non-melanoma skin cancer is frequent and difficult to diagnose. We aimed to assess whether GPs are facing difficulties in diagnosing non-pigmented skin tumours (NPSTs) and whether they would be interested in artificial intelligence (AI) software that could help them with this task. A questionnaire addressing the difficulties in diagnosing NPST and the potential interest in AI as a tool to help diagnose these tumours was emailed to GPs working in two French regions. In total, 147 respondents (98%) had faced difficulties diagnosing NPSTs; 86% agreed that an AI diagnostic tool could be useful in a GP’s office and 83% agreed that it could change their practice. Nevertheless, 68% would not be willing to pay for this kind of software. GPs are facing difficulties in diagnosing NPSTs and would be interested in an AI tool that could help them achieve this. As referral to dermatology practices can be trying, AI diagnostic aids should be developed to help GPs in their gatekeeping task, however at limited cost to the GP.

Background and Objectives: Trifarotene is a topical retinoid selective for retinoic acid receptor gamma that was recently approved for treatment of acne vulgaris. We performed a gene expression analysis to identify the molecular and cellular impact of trifarotene treatment on acne papules.Methods: In this open-label prospective study, subjects with moderate inflammatory acne of the back were treated with trifarotene 0.005% or vehicle cream on dedicated areas for 27 days, and 4 biopsies were collected from each subject (1 from skin without a visible acne lesion and three at the site of an acne papule: one baseline, one after vehicle treatment, and one after trifarotene treatment). Large scale gene expression profiling of the biopsies was performed using Affymetrix technology, treatment-specific gene expression profiles were generated using statistical modeling, and pathway analysis was performed. Using single-cell RNAseq data, in silico deconvolution of transcriptomics data was performed to identify cellular signatures.Results: We discovered a unique set of 67 genes modulated by trifarotene that are primarily involved in cellular migration, inflammation, and extracellular matrix reorganization. Changes in cellular expression were similar in both trifarotene-treated and spontaneously-resolving lesions. However, only trifarotene treatment impacted SPP1+ macrophages, a subset of highly proliferative macrophages recently identified in fibrotic tissue.Conclusions: These results show that trifarotene has a novel action in acne treatment by affecting epidermal and immune components of acne pathogenesis.

Background Acne affects more than 80% of adolescents and young adults, who most often develop acne scars. Supporting data on the effect of acne scars on patient’s health-related quality of life (HRQOL) are limited. Objective The aim was to determine how the severity of acne scars impacts the HRQOL of afflicted individuals. Methods In this population-based cross-sectional study, 723 adults with facial acne scars but without active acne lesions self-completed the Self-assessment of Clinical Acne-Related Scars (SCARS) questionnaire formulated to investigate degree of acne scarring. The Facial Acne Scar Quality of Life (FASQoL), Dermatology Life Quality Index (DLQI), and Dysmorphic Concern Questionnaire (DCQ) were completed to assess the attitude of these patients toward their scars and the impact of scarring on their HRQOL. Results The mean (standard error) DLQI score for facial acne scars was 6.26 (0.22). Acne scars were considered a ‘very large’ or ‘extremely large’ concern by 19.3% of participants with mild scars as compared to 20.1% and 34.0% of participants with moderate and severe/very severe scars, respectively (P = 0.003). Higher FASQoL scores were associated with increased severity of scarring (P = 0.001). In total, 16.9% of participants had clinical features of dysmorphia (i.e., DCQ > 13). DCQ scores were significantly higher among participants with more severe scarring (mean DCQ score of 8.04 [0.28], 8.40 [0.18], and 10.13 [0.08] among participants with mild, moderate, and severe/very severe acne scars, respectively; P = 0.001). Most commonly reported signs of emotional distress were self-consciousness (68.0%) and worry about scars not going away (74.8%). Conclusions This study highlights the significant psychosocial impact of atrophic acne scars in the form of embarrassment and self-consciousness. Individuals with mild scars also expressed significant impact on quality of life that increased with aggravation of scar severity. Patient-reported outcomes provide an insight into the physical, functional, and psychological impact of acne scarring from the patient’s perspective. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00628-1.

Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%, partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS &lt, 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients.

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.

We developed an artificial intelligence algorithm (AIA) for smartphones to determine the severity of facial acne using the GEA scale and to identify different types of acne lesion (comedonal, inflammatory) and postinflammatory hyperpigmentation (PIHP) or residual hyperpigmentation. Overall, 5972 images (face, right and left profiles) obtained with smartphones (IOS and/or Android) from 1072 acne patients were collected. Three trained dermatologists assessed the acne severity for each patient. One acne severity grade per patient (grade given by the majority of the three dermatologists from the two sets of three images) was used to train the algorithm. Acne lesion identification was performed from a subgroup of 348 images using a tagging tool; tagged images served to train the algorithm. The algorithm evolved and was adjusted for sensibility, specificity and correlation using new images. The correlation between the GEA grade and the quantification and qualification of acne lesions both by the AIA and the experts for each image were evaluated for all AIA versions. At final version 6, the GEA grading provided by AIA reached 68% and was similar to that provided by the dermatologists. Between version 4 and version 6, AIA improved precision results multiplied by 1.5 for inflammatory lesions, 2.5 for non‐inflammatory lesions and by 2 for PIHP; recall was improved by 2.6, 1.6 and 2.7. The weighted average of precision and recall or F1 score was 84% for inflammatory lesions, 61% for non‐inflammatory lesions and 72% for PIHP.

Background We conducted a retrospective analysis to evaluate the impact of concomitant acid-reducing agents (ARAs) and vemurafenib dose on the efficacy of vemurafenib in patients with BRAFV600 mutation–positive unresectable or metastatic melanoma treated with vemurafenib or cobimetinib plus vemurafenib. Methods Data were pooled for patients treated with vemurafenib or cobimetinib plus vemurafenib in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. The primary end-points were progression-free survival and overall survival across patient subgroups defined by vemurafenib dose (full vs reduced) and concomitant ARA use (yes vs no). Objective response rate (ORR) was also analysed. Steady-state vemurafenib concentrations were evaluated according to vemurafenib dosing and concomitant ARA use across treatment cohorts in a subset of patients from BRIM-7 and coBRIM with available concentration data. Results Efficacy analyses included 920 patients: 641 in the vemurafenib cohort and 279 in the cobimetinib plus vemurafenib cohort. Overall, no significant differences in survival outcomes were observed across subgroups according to vemurafenib dose and ARA use, with or without adjustment for known prognostic covariates, in both treatment cohorts. ORR was also similar across subgroups in both treatment cohorts. Steady-state vemurafenib concentrations were analysed in 389 patients (193 in the vemurafenib cohort and 196 in the cobimetinib plus vemurafenib cohort) and were generally similar across vemurafenib dose subgroups, regardless of ARA use in both treatment cohorts. Conclusions Results of this retrospective pooled analysis suggest that ARAs can be used concomitantly with vemurafenib, alone or in combination with cobimetinib, without compromising the efficacy of vemurafenib.

Scarring is a frequent consequence of acne. Our objective was to evaluate the effect of up to 48 weeks’ treatment with adapalene 0.3%/benzoyl peroxide 2.5% (A0.3/BPO2.5) gel on atrophic scars in moderate or severe acne vulgaris. In Part 1 of this two-part study, A0.3/BPO2.5 gel or vehicle was applied on each half-face for 24 weeks in a randomized, investigator-blinded, split-face design. Part 2 was a 24-week, open-label extension phase during which A0.3/BPO2.5 gel was applied on both sides of the face. Assessments included investigator atrophic acne scar count, Scar Global Assessment (SGA), acne lesion count, local tolerability, and safety. Of the 45 subjects entering Part 2, 41 completed the 48-week study. At baseline (Part 1), most subjects had moderate acne (93.3%) with mild scars (62.2%). The scar count decrease from baseline was 21.7% at week 24 and 26.9% at week 48 on the half-face treated for 48 weeks with A0.3/BPO2.5. For the half-face treated with vehicle followed by 24 weeks’ A0.3/BPO2.5, scar count increased by 16.7% at week 24 (under vehicle) and decreased by 22.7% between weeks 24 and 48. The half-face that received 48 weeks’ A0.3/BPO2.5 had a lower final atrophic scar count (mean 8.4 vs. 9.9 for the half-face with 24 weeks’ vehicle then 24 weeks’ A0.3/BPO2.5) and a higher percentage of SGA clear/almost clear. High reductions in acne lesions between baseline and week 48 were observed for both sides of the face. Long-term treatment with A0.3/BPO2.5 was safe and well-tolerated. Reductions in atrophic acne scars and acne lesions observed after 24 weeks of treatment with A0.3/BPO2.5 gel were maintained with treatment up to 48 weeks. The additional improvement in atrophic scar count with 48 weeks’ A0.3/BPO2.5 treatment, compared to delayed application at 24 weeks, highlights the importance of early initiation of effective acne treatment to prevent and reduce the formation of acne scars. ClinicalTrials.gov identifier NCT02735421.

BACKGROUND Severe nodular acne is characterized by inflammatory nodules and scarring. Their natural evolution and duration are insufficiently investigated. AIM To investigate the evolution and duration of untreated acne nodules. METHODOLOGY Four-week, single-centre, non-interventional, prospective study in subjects with severe nodular acne on the back. Nodule evolution and duration was assessed using standardized photographs taken twice weekly. RESULTS Data from 23 subjects were evaluable. Mean age was 25.1 ± 4.9 years, 87% were males, and mean acne duration was 9.7 ± 6.7 years. At baseline, the overall total nodule count was 132 (mean number: 5.7 ± 3.0 nodules/subject). Among others, the following two main pathways were observed: nodules evolving directly into atrophic scars (31.8%) and nodules evolving towards papules into atrophic scars (37.9%). After 4 weeks, 77.3% of baseline nodules had evolved into atrophic scars. After baseline visit, a total of 247 new nodules (3.1 ± 2.2 nodules/week/subject) with a mean duration of 4.9 ± 2.6 days were observed. The mean duration of new nodules was significantly longer in subjects (n = 16) with ≥6 new nodules compared to subjects (n = 7) with

Purpose: Previous investigations identified transcriptional signatures associated with innate resistance to anti–programmed cell death protein 1 therapy in melanoma. This analysis aimed to increase understanding of the role of baseline genetic features in the variability of response to BRAF and MEK inhibitor therapy for BRAFV600-mutated metastatic melanoma. Patients and Methods: This exploratory analysis compared genomic features, using whole-exome and RNA sequencing, of baseline tumors from patients who had complete response versus rapid progression (disease progression at first postbaseline assessment) on treatment with cobimetinib combined with vemurafenib or vemurafenib alone. Associations of gene expression with progression-free survival or overall survival were assessed by Cox proportional hazards modeling. Results: Whole-exome sequencing showed that MITF and TP53 alterations were more frequent in tumors from patients with rapid progression, while NF1 alterations were more frequent in tumors from patients with complete response. However, the low frequency of alterations in any one gene precluded their characterization as drivers of response/resistance. Analysis of RNA profiles showed that expression of immune response–related genes was enriched in tumors from patients with complete response, while expression of keratinization-related genes was enriched in tumors from patients who experienced rapid progression. Conclusions: These findings suggest that enriched immune infiltration might be a shared feature favoring response to both targeted and immune therapies, while features of innate resistance to targeted and immune therapies were distinct.

Background Acne is a common skin disease that mostly affects teenagers, with a negative impact on quality of life. Recently, adult acne and acne relapses have increased in frequency, for yet unknown reasons. Objective This non‐interventional, real‐life study sought to investigate the rate of acne relapses and their impact on quality of life and productivity (loss/absenteeism) among teenagers and adults. Methods An online self‐administered questionnaire was proposed to ≥15‐year‐olds suffering from acne who spontaneously consulted their dermatologist. To ensure homogeneous assessment of acne severity, the global acne severity scale was applied. Quality of life was assessed via Cardiff Acne Disability Index (CADI), SF12‐physical score and SF12‐mental score questionnaires. Productivity loss or absenteeism in middle/high school was estimated based on the number of days off work or school over the last 30 days. Results Overall, 1048 questionnaires were considered assessable, with 448 (43%) mild acne, 434 (41%) moderate acne and 166 (16%) severe acne. Overall, 755 (72%) participants were in middle/high school, 267 (25%) employed and 26 (3%) with no professional activity. Considering the population by age groups, 68% (n = 716) were ≤20‐year‐olds and 32% (n = 332) >20‐year‐olds, with a mean age of 20.26 (SD: 7.43) years. Acne relapses were reported by 44% of respondents. Analyses revealed that poorer quality of life scores was observed in acne relapsers vs. non‐relapsers, with a significant difference for CADI scores (P < 0.01) in >20‐year‐olds. Acne‐related absenteeism was recorded in 5.7% of cases. On multivariate analyses, after adjusting for other variables, acne relapse was proven a significant determinant of absenteeism/productivity loss. Conclusion This real‐life study first demonstrated acne relapse rates of 44%, which appeared to be generation‐dependent, affecting 39.9% of ≤20‐year‐olds vs. 53.3% of >20‐year‐olds. Acne relapses were significantly associated with impaired quality of life and productivity loss/absenteeism.

Background: Cutibacterium acnes has been identified as one of the main triggers of acne. However, increasing knowledge of the human skin microbiome raises questions about the role of other skin commensals, such as Staphylococcus epidermidis, in the physiopathology of this skin disease. Summary: This review provides an overview of current knowledge of the potential role of S. epidermidis in the physiopathology of acne. Recent research indicates that acne might be the result of an unbalanced equilibrium between C. acnes and S. epidermidis,according to dedicated interactions. Current treatments act on C. acnesonly. Other treatment options may be considered, such as probiotics derived from S. epidermidis to restore the naturally balanced microbiota or through targeting the regulation of the host’s AMP mediators. Key Messages: Research seems to confirm the beneficial role of S. epidermidis in acne by limiting C. acnes over-colonisation and inflammation.

Background Truncal acne is common and burdensome for patients; however, there is paucity of evidence and guidance for the management of truncal acne. Currently, clinical practice guidelines provide very little guidance on the assessment or management of truncal acne. Objectives To identify unmet needs in truncal acne and make recommendations to address clinical and management gaps using an international consensus. Methods The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists, who used a modified Delphi approach to reach a consensus on statements related to clinically relevant aspects of truncal acne evaluation and management. A consensus was defined as ≥75% of the panelists voting "agree" or "strongly agree." The voting was electronic and blinded. Results The panel identified gaps and made recommendations related to truncal acne identification, assessment, and grading; the evaluation of the impact on patients; and treatment goals and factors to be considered for its management. Limitations The recommendations are based on expert opinion, in the absence of high-quality evidence. Conclusions We highlighted addressing not just facial acne but also truncal acne during patient consultations. The recommendations made herein may help facilitate the care of patients who present with truncal acne, with or without facial acne.

Adoptive cell transfer (ACT) of tumor-specific T lymphocytes represents a relevant therapeutic strategy to treat metastatic melanoma patients. Ideal T-cells should combine tumor specificity and reactivity with survival in vivo, while avoiding autoimmune side effects. Here we report results from a Phase I/II clinical trial (NCT02424916, performed between 2015 and 2018) in which 6 metastatic HLA-A2 melanoma patients received autologous antigen-specific T-cells produced from PBMC, after peptide stimulation in vitro, followed by sorting with HLA-peptide multimers and amplification. Each patient received a combination of Melan-A and MELOE-1 polyclonal specific T-cells, whose specificity and anti-tumor reactivity were checked prior to injection, with subcutaneous IL-2. Transferred T-cells were also characterized in terms of functional avidity, diversity and phenotype and their blood persistence was evaluated. An increase in specific T-cells was detected in the blood of all patients at day 1 and progressively disappeared from day 7 onwards. No serious adverse events occurred after this ACT. Clinically, five patients progressed and one patient experienced a partial response following therapy. Melan-A and MELOE-1 specific T-cells infused to this patient were diverse, of high avidity, with a high proportion of T lymphocytes co-expressing PD-1 and TIGIT but few other exhaustion markers. In conclusion, we demonstrated the feasibility and safety of ACT with multimer-sorted Melan-A and MELOE-1 specific T cells to metastatic melanoma patients. The clinical efficacy of such therapeutic strategy could be further enhanced by the selection of highly reactive T-cells, based on PD-1 and TIGIT co-expression, and a combination with ICI, such as anti-PD-1. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02961-0.

Wide local excision constitutes the standard of care for Merkel cell carcinoma, but the optimal margin width remains controversial.To assess whether narrow margins (0.5-1 cm) were associated with outcome.Patients were recruited from a retrospective French multicentric cohort and included if they had had excision of primary tumor with minimum lateral margins of 0.5 cm. Factors associated with mortality and recurrence were assessed by multivariate regression.Among the 214 patients included, 58 (27.1%) had undergone excision with narrow margins (0.5-1 cm) versus 156 (72.9%) with wide margins (1 cm). During a median follow-up of 50.7 months, cancer-specific survival did not differ between groups (5-year specific survival rate 76.8% [95% confidence interval 61.7%-91.9%] and 76.2% [95% confidence interval 68.8%-83.6%], respectively). Overall survival, any recurrence-free survival, and local recurrence-free survival did not significantly differ between groups. Cancer-specific mortality was associated with age, male sex, American Joint Committee on Cancer stage III, and presence of positive margins.Retrospective design, heterogenous baseline characteristics between groups.Excision with narrow margins was not associated with outcome in this cohort, in which most patients had clear margins and postoperative radiation therapy. Residual tumor, mostly found on deep surgical margins, was independently associated with prognosis.

The ability of early (first weeks of treatment) ctDNA kinetics to identify primary resistance to anti-PD1 immunotherapies was evaluated with a validation cohort of 49 patients treated with anti‑PD1 for metastatic BRAF or NRAS-mutated melanoma, alone and pooled with the 53 patients from a previously described derivation cohort. BRAF or NRAS mutations were quantified on plasma DNA by digital PCR at baseline and after two or four weeks of treatment. ctDNA kinetics were interpreted according to pre-established biological response criteria. A biological progression (bP, i.e., a significant increase in ctDNA levels) at week two or week four was associated with a lack of benefit from anti-PD1 (4-month PFS = 0%, 1‑year OS = 13%, n = 12/102). Patients without initial bP had significantly better PFS and OS (4-month PFS = 78%, 1‑year OS = 73%, n = 26/102), as did patients whose ctDNA kinetics were not evaluable, due to low/undetectable baseline ctDNA (4-month PFS = 80%, 1‑year OS = 81%, n = 64/102). ctDNA detection at first-line anti-PD1 initiation was an independent prognostic factor for OS and PFS in multivariate analysis. Overall, early ctDNA quantitative monitoring may allow the detection of primary resistances of metastatic melanoma to anti-PD1 immunotherapies.

Background Acne confers an increased risk of physical, psychiatric, and psychosocial sequelae, potentially affecting multiple dimensions of health-related quality of life (HRQoL). Morbidity associated with truncal acne is poorly understood. Objective To determine how severity and location of acne lesions impact the HRQoL of those who suffer from it. Methods A total of 694 subjects with combined facial and truncal acne (F+T) and 615 with facial acne only (F) participated in an online, international survey. Participants self-graded the severity of their acne at different anatomical locations and completed the dermatology life quality index (DLQI). Results The F+T participants were twice as likely to report "very large" to "extremely large" impact on HRQoL (ie, DLQI > 10 and children's DLQI [CDLQI] > 12) as compared with the F participants (DLQI: odds ratio [OR] 1.61 [95% confidence interval {CI} 1.02-2.54]; CDLQI: OR 1.86 [95% CI 1.10-3.14]). The impact of acne on HRQoL increased with increasing acne severity on the face (DLQI and CDLQI P values = .001 and .017, respectively), chest (P = .003; P = .008), and back (P = .001; P = .028). Limitations Temporal evaluation of acne impact was not estimated. Conclusions Facial and truncal acne was associated with a greater impact on HRQoL than facial acne alone. Increasing severity of truncal acne increases the adverse impact on HRQoL irrespective of the severity of facial acne.

Treatment of lentigo maligna (LM) is challenging because of the potential functional and esthetic surgical sequelae. Imiquimod has been proposed as a treatment for LM. Reflectance confocal microscopy (RCM) is a noninvasive method for the diagnosis of LM and margin assessment.To compare the overall LM score (LMS) assessed by RCM before and 1 month after the start of imiquimod treatment compared to placebo and to define the immunohistochemical (IHC) profile of responders to imiquimod.A controlled randomized study was conducted. Forty patients underwent RCM examination with calculation of the LMS at baseline and after 1 month of treatment. An IHC analysis of excised tissues was performed.The 1-month LMS was significantly lower in patients treated with imiquimod compared to those treated with placebo (P .001). The criteria in the imiquimod-treated patients that demonstrated significant decrease were nonedged papillae; large, round pagetoid cells; atypical cells at the dermoepidermal junction; and follicular location of atypical cells. IHC analysis showed a higher level of interferon gamma in the resected specimens of patients responding to imiquimod (P = .04).Sample size was small.Assessing the LMS by RCM was useful to monitor LM response to imiquimod accurately.

Sézary syndrome (SS) and mycosis fungoides (MF), 2 types of cutaneous T-cell lymphoma, cause significant morbidity and adversely affect patients' quality of life (QoL). The present study assessed the QoL measurement changes in patients receiving mogamulizumab versus vorinostat.A multicenter phase III trial was conducted of patients with stage IB-IV MF/SS with ≥ 1 failed systemic therapy. The QoL measures included Skindex-29 and the Functional Assessment of Cancer Therapy-General. The symptoms, function, and QoL subdomains were longitudinally modeled using mixed models with prespecified covariates. Meaningful change thresholds (MCTs) were defined using distribution-based methods. The categorical changes by group over time and the time to clinically meaningful worsening were analyzed.Of the 372 randomized patients, mogamulizumab demonstrated improvement in Skindex-29 symptoms (cycles 3, 5, and 7; P .05) and functional (cycles 3 and 5; P .05) scales. A significantly greater proportion of mogamulizumab-treated patients improved by MCTs or more from baseline in the Skindex-29 symptoms domain (cycles 3, 5, 7, and 11) and functioning domain (cycle 5). Significant differences in the Functional Assessment of Cancer Therapy-General physical well-being (cycles 1, 3, and 5; P .05) were observed in favor of mogamulizumab and a greater proportion of patients had declined by MCTs or more at cycles 1, 3, 5, and 7 with vorinostat treatment. The median time to symptom worsening using Skindex-29 was 27.4 months for mogamulizumab versus 6.6 months for vorinostat. In the patients with SS, the time to worsening favored mogamulizumab (P .005) for all Skindex-29 domains. The time to worsening was similar for the 2 MF treatment arms.The symptoms, function, and overall QoL of patients with MF/SS favored mogamulizumab over vorinostat across all time points. Patients with the greatest symptom burden and functional impairment derived the most QoL benefit from mogamulizumab.

International audience; Treatment of patients with melanoma has considerably improved over the past decade and more recently with adjuvant therapies for patients with American Joint Committee on Cancer (AJCC) stage III (loco-regional metastases) or IV (distant metastases) totally resected melanoma, in order to prevent recurrence. In the adjuvant setting, two options are available to patients with BRAFV600-mutant AJCC stage III totally resected melanoma: anti-PD-1 blockers (nivolumab or pembrolizumab) or BRAF plus MEK inhibitors (dabrafenib plus trametinib). In the absence of comparative studies, it is difficult to determine which of these options is best. Our aim was to review published studies focusing on the management of patients with BRAFV600-mutant melanoma in the adjuvant setting. We also reviewed the main clinical trials of BRAF plus MEK inhibitors and immunotherapy in advanced (i.e. unresectable metastatic) BRAF-mutant melanoma in an attempt to identify results potentially affecting the management of patients on adjuvants. More adverse events are observed with targeted therapy, but all resolve rapidly upon drug discontinuation, whereas with immune checkpoint blockers some adverse events may persist. New therapeutic strategies are emerging, notably neoadjuvant therapies for stage III patients and adjuvant therapies for stage II patients; the place of the adjuvant strategy amidst all these options will soon be re-evaluated. The choice of adjuvant treatment could influence the choice of subsequent treatments in neo-adjuvant or metastatic settings. This review will lead clinicians to a better understanding of the different adjuvant treatments available for patients with totally resected AJCC stage III and IV BRAFV600-mutant melanoma before considering subsequent treatment strategies.

Acne is one of the most common skin inflammatory diseases, representing the top three most prevalent skin conditions in the general population worldwide (Johnson and Roberts, Vital Health Stat 11 (212):i–v, 1–72, 1978; Wolkenstein et al., Arch Dermatol 139(12):1614–9, 2003; Rea et al., Br J Prev Soc Med 30(2):107–14, 1976; Bhate and Williams, Br J Dermatol 168(3):474–85, 2013). The complex physiopathology of this dermatosis involves several key players: sebaceous gland, activation of innate immunity and microbiome with a commensal bacteria Cutibacterium acnes. In this book chapter, we propose to give an overview of the most current findings about acne physiopathology and future medical challenges ahead. This chapter will focus on the commensal bacterium Cutibacterium acnes, as it has a pivotal role in acne physiopathology, its interaction with the different microorganisms constituting skin microbiota and the innate immune system. Based on the scientific literature, this book chapter will also review the innovative therapeutic options that will be developed in the future years.

International audience; Background Acne is a long-lasting disease in adolescents and adults impacting the patient's daily life. Currently, there is no specific questionnaire that assesses its impact in adult patients. Aim To build a self-administered questionnaire assessing the impact of acne on the daily life in adult patients. Method A multidisciplinary working group was created, including 3 experts in healthcare questionnaires and dermatologists specialized in acne. A questionnaire using a standardized methodology for designing self-administered patient questionnaires according to conceptual, development and validation phases was developed. A cultural and linguistic validation into US English was conducted, based on the original French version. Results A 14-item questionnaire demonstrating consistency, reproducibility and high reliability was build. The questionnaire significantly correlated with the SF-12 mental and SF-12 physical scores and CADI, indicating good external validity. Conclusion The present acne burden questionnaire AI-ADL allows the practioner to assess quickly and easily the burden of acne in patients during his daily clinical practice. Moreover, its short format allows patients to express easily and quickly their feelings and to initiate a conversation between the practioner and his patient. Thus, AI-ADL may help to better understand the multidimensional nature of acne, as well as the individual impact on the acne patient's daily life and moreover, it may play a key role in the decision-making process of treatment initiation and involvement of the patient in the management of his acne.

Resume Introduction Le mycosis fongoide (MF) est le lymphome cutane le plus frequent et se manifeste classiquement par des lesions maculeuses ou des plaques erythemato-squameuses. Sa presentation clinique ou histologique peut etre variee. Nous rapportons le cas d’une forme tres rare, le MF bulleux. Observation Un homme de 73 ans presentait depuis 4 mois des plaques erythemato-squameuses infiltrees prurigineuses sur le tronc et egalement des lesions bulleuses depuis 2 mois, qui apparaissaient au niveau du tronc et des membres inferieurs, sur les plaques de MF, mais egalement sur peau apparemment saine. L’examen histologique confirmait le diagnostic de mycosis fongoide bulleux. La recherche de rearrangement de genes du recepteur T montrait un profil monoclonal dans la peau. Une pemphigoide bulleuse etait ecartee par l’immunofluorescence directe et indirecte negatives ainsi que l’Elisa BP 180 et 230. Le patient etait successivement traite par interferon, bexarotene, methotrexate puis vorinostat qui permettait d’obtenir une remission partielle. Discussion Les cas de MF bulleux sont tres rares. Dans la litterature, la presentation clinique en est variee, avec des bulles tendues ou flasques, apparaissant sur peau paraissant saine ou sur des plaques erythemateuses. Les bulles apparaissent le plus souvent apres les plaques. Le niveau de decollement peut etre sous-epidermique ou plus rarement intra-epidermique. La physiopathologie est mal expliquee. Son traitement est mal codifie, mais suit le traitement habituel du MF dans sa forme classique. Conclusion Le MF bulleux est une entite tres rare, qui peut mimer une maladie bulleuse auto-immune, qui est donc un diagnostic a eliminer.

Background: Acne vulgaris is a common skin disorder, but studies on the epidemiologic features of prepubertal acne are limited. Objectives: The aim of this study was to determine the prevalence and severity of prepubertal acne and to identify factors influencing acne severity and poor response to treatment. Methods: A retrospective study was conducted on 683 patients with acne from our database who visited the dermatology department of Nantes University hospital between October 2014 and May 2018. Patients of prepubertal acne (7-12 years) were included in this study. Results: Of the 683 patients with acne, 24 (3.5%) had prepubertal acne. Prepubertal acne was more common in female patients (75%). Acne severity assessment showed that severe acne (Groupe Expert Acné global acne severity scale 4) was the most common form (33%), and mild and moderate forms (Global Evaluation Acne Group, global acne severity scales 2 and 3) accounted for 25% each. There was a high predominance of phylotype IA1 of Cutibacterium acnes (belonging to CC18 subgroup). The analysis of patients’ lifestyle and acne features identified three factors associated with an increased risk of poor response or resistance to acne treatment. Initially severe acne grading (grade 4) was the most strongly associated parameter (p < .028), followed by regular milk consumption and taking other medications in addition to acne treatment (p < .049 for each). Conclusion: This study reported on prepubertal acne features and identified three factors associated with a high risk of treatment failure or relapse. Adequate and prompt treatment is needed in this subgroup of patients to minimize disease burden and prevent subsequent disease worsening.

International audience; Background: Anti-PD1 immunotherapy has shown a sustainable clinical activity in patients with metastatic melanoma. However, strong predictive factors of the long-term response or risk of relapse remain to be identified.Objectives: To determine whether FDG-PET imaging could be superior to CT scan in distinguishing residual tumours versus the absence of tumour in patients with a partial response (PR) or stable disease (SD) and whether a complete metabolic response (CMR) was associated with better outcomes.Methods: Retrospective study conducted in all patients with metastatic melanoma treated with anti-PD1 immunotherapy between October 2014 and October 2017 considered to be in complete remission. The primary outcome was the occurrence of a relapse during the follow-up. CT scan and FDG-PET scan had to be performed within a maximum of 2 months of treatment discontinuation. For CT imaging, the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 were used and included progressive disease (PD), SD, PR and complete response (CR). For FDG-PET imaging, the metabolic responses were classified as progressive metabolic disease, stable metabolic disease, residual FDG avidity (RFA) and CMR.Results: Twenty-six patients were in complete remission after collegial decision. Two patients had a SD on CT scan and a CMR on FDG-PET scan, and none of them relapsed. Ten patients had a PR on CT scan and a CMR on FDG-PET scan, and none of them relapsed. The mean treatment duration to achieve a complete remission was 7 months (3-23). A univariate analysis showed that a RFA assessed on the FDG-PET scan was significantly associated with a relapse (P = 0.00231).Conclusions: Most patients with a PR on the CT scan and a CMR on the FDG-PET scan should be considered with a CR. Our study showed that FDG-PET imaging could play a crucial role in predicting the long-term outcome and help to decide whether treatment should be discontinued.

Our understanding of the role of Cutibacterium acnes in the pathophysiology of acne has recently undergone a paradigm shift: rather than C. acnes hyperproliferation, it is the loss of balance between the different C. acnes phylotypes, together with a dysbiosis of the skin microbiome, which results in acne development. The loss of diversity of C. acnes phylotypes acts as a trigger for innate immune system activation, leading to cutaneous inflammation. A predominance of C. acnes phylotype IA1 has been observed, with a more virulent profile in acne than in normal skin. Other bacteria, mainly Staphylococcus epidermis, are also implicated in acne. S. epidermidis and C. acnes interact and are critical for the regulation of skin homeostasis. Recent studies also showed that the gut microbiome is involved in acne, through interactions with the skin microbiome. As commonly used topical and systemic antibiotics induce cutaneous dysbiosis, our new understanding of acne pathophysiology has prompted a change in direction for acne treatment. In the future, the development of individualized acne therapies will allow targeting of the pathogenic strains, leaving the commensal strains intact. Such alternative treatments, involving modifications of the microbiome, will form the next generation of ‘ecobiological’ anti-inflammatory treatments.

Background We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) on ppOS. Methods Recursive partitioning analysis (RPA) was performed to model relationships between prespecified covariates and ppOS in patients with BRAFV600-mutated metastatic melanoma who had experienced progressive disease (PD) following treatment with cobimetinib plus vemurafenib, vemurafenib monotherapy, or dacarbazine in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. Prognostic subgroups identified by RPA were then applied to pooled treatment cohorts. The primary endpoint was ppOS, defined as time from first PD to death from any cause. Results RPA identified baseline lactate dehydrogenase (LDH), baseline disease stage, Eastern Cooperative Oncology Group performance status at PD, and ppRx as significant prognostic factors for ppOS. Median ppOS was longest in patients with normal baseline LDH, stage M1c disease at baseline, and ppRx with immunotherapy or targeted therapy (12.2 months; 95% CI 10.3–16.1) and shortest in those with elevated baseline LDH > 2 × upper limit of normal (2.3 months; 95% CI 1.8–2.7). Original treatment assignment did not impact ppOS. Across treatment cohorts, patients treated with immunotherapy or targeted therapy after PD had better ppOS than those given other treatments. Conclusion A combination of factors at baseline (LDH, disease stage) and PD (performance status, ppRx) impact ppOS outcomes. ppRx with immunotherapy or targeted therapy is an independent prognostic factor for improved overall survival following progression regardless of original treatment. Trial registration The trials included in this analysis are registered with ClinicalTrials.gov: NCT00949702 (BRIM-2), NCT01006980 (BRIM-3), NCT01271803 (BRIM-7), and NCT01689519 (coBRIM).

International audience; In BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure. This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included. Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%. Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy.

Circulating tumour DNA (ctDNA) can be used to identify gene alterations. The purpose of this study was to determine whether the detection of ctDNA, based on the identification of BRAF and NRAS mutations before systemic treatment initiation, was associated with the prognosis of metastatic melanoma. In total, 68 BRAF or NRAS-mutated stage IV or unresectable stage III metastatic cutaneous melanoma patients were included and tested for the presence of BRAF and NRAS mutations in circulating DNA before treatment initiation, using the Cobas BRAF/NRAS Mutation Test (Roche). The expected mutation was detected in the plasma of 34/68 patients (50% sensitivity). ctDNA detection was associated with AJCC stage, along with the number and nature of metastases. ctDNA was less frequently detected in NRAS-mutated than in BRAF-mutated melanoma (36% and 66%, respectively). At initiation of first-line treatment, ctDNA detection was associated with poor prognosis in Progression Free Survival (PFS) and Overall Survival (OS) in univariate analysis (log-rank: p = 0.002 and p &lt, 0.0001, respectively). In multivariate analysis, ctDNA detection was an independent factor of poor prognosis in OS, after adjustment for AJCC stage, number and nature of metastases and gender (HR = 4.384, 95% CI: (1.308, 14.699), p = 0.017).

The practice of tattoo is developing more and more all over the world. Infections are known. but chronic inflammatory reactions have often resulted in a variety of clinical manifestations. In addition to allergic reactions, non-allergic reactions prevail in black tattoos and manifest themselves as "papulonodular" lesions. The importance of biopsy of papulonodular lesions to confirm the diagnosis should be emphasized. Carbon black nanoparticles agglomerate in the dermis over time to form sarcoid granulomas. Pigment-bound foreign-body granuloma and sarcoidosis are often difficult to distinguish. The black color seems to be the most common. Other aetiologias than pigment are evoked, such as the role of an infectious agent, but to date none has been identified, a particular genetic terrain remains to be defined. Systemic localizations being possible, the extension assessment is important to carry out. It is also important, as a preventive measure, that subjects and their treating physician be informed of the potential risk associated with these drugs indicated for specific serious pathologies.

Background: The etiology and different inflammatory steps associated with the development of an acne nodule remain unsolved. Objectives: This study aimed to investigate the main biological processes involved in acne nodules and compare them to those of papules. Methods: Nodules, papules, and non-involved skin of the back (control) were biopsied to perform proteomic analysis using mass spectrometry, Luminex assay, and elastase staining on skin sections. Results: Many factors involved in the migration and function of immune cells, particularly those impacting leukocytes and neutrophils, were strongly and significantly higher in nodules than in papules and non-involved skin, while several enzymes involved in lipid metabolism were lower. Elastase staining confirmed strong neutrophil infiltration within and around the nodules. Conclusions: Our results highlight the role of neutrophils during nodule formation in severe nodular acne of the back.

PURPOSE To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). PATIENTS AND METHODS Patients, predominantly men, with their CSSCs’ immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort’s objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy–General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1– patients, was assessed for ORR, disease control rate, and safety, but not survival. RESULTS Median age of all patients was 79 years. The primary cohort’s ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1– patients (17%; P = .02). Responders’ W15 total FACT-G score had improved ( P = .025) compared with nonresponders. CONCLUSION First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.