TRASS: a global approach to assess the severity of truncal acne.

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.

Fatal hymenoptera venom anaphylaxis by undetected clonal mast cell disorder: A better identification of high risk patients is needed.

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.

Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database.

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.

FDG PET biomarkers for prediction of survival in metastatic melanoma prior to anti-PD1 immunotherapy.

Our aim was to analyse whether biomarkers extracted from baseline 18F-FDG PET before anti-PD1 treatment contribute to prognostic survival information for early risk stratification in metastatic melanoma. Fifty-six patients, without prior systemic treatment, BRAF wild type, explored using 18F-FDG PET were included retrospectively. Our primary endpoint was overall survival (OS). Total metabolic tumoral volume (MTV) and forty-one IBSI compliant parameters were extracted from PET. Parameters associated with outcome were evaluated by a cox regression model and when significant helped build a prognostic score. Median follow-up was 22.1 months and 21 patients died. Total MTV and long zone emphasis (LZE) correlated with shorter OS and served to define three risk categories for the prognostic score. For low, intermediate and high risk groups, survival rates were respectively 91.1% (IC 95 80-1), 56.1% (IC 95 37.1-85) and 19% (IC 95 0.06-60.2) and hazard ratios were respectively 0.11 (IC 95 0.025-0.46), P = 0.0028, 1.2 (IC 95 0.48-2.8), P = 0.74 and 5.9 (IC 95 2.5-14), P < 0.0001. To conclude, a prognostic score based on total MTV and LZE separated metastatic melanoma patients in 3 categories with dramatically different outcomes. Innovative therapies should be tested in the group with the lowest prognosis score for future clinical trials.

Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: analysis of the MelBase French cohort data☆.

BACKGROUND: The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy. PATIENTS AND METHODS: This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out. RESULTS: A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI. CONCLUSION: The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution.

Truncal acne, what do we know?

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.

[Stage III melanoma: Sentinel node biopsy, completion lymph node dissection and prospects of adjuvant therapy. A French national survey on current and envisaged practices]. / Mélanome au stade ganglionnaire : analyse du ganglion sentinelle, curage ganglionnaire, perspective des traitements adjuvants. Enquête nationale française sur les pratiques actuelles et envisagées.

BACKGROUND: The recent publication of randomized trials investigating the efficacy of adjuvant therapy and completion lymph node dissection at microscopic stage III melanoma calls for a reappraisal of melanoma management from different angles: indications for sentinel lymph node biopsy, indications for completion lymph node dissection in microscopic-stage disease, and adjuvant therapies. Our objective was to evaluate current practices and to question French onco-dermatologists about any changes they envisaged in their practices in the light of recent publications. METHODS: We conducted a national survey among members of the Cutaneous Oncology Group of the French Society of Dermatology in October 2017. RESULTS: Forty French health centers were included, and 53 individual responses were collected. Sentinel lymph node biopsy for melanoma was performed at 75 % of the centers. Before the summer of 2017 and the publication of MSLT-II (proving the absence of any therapeutic benefits for complete lymph node dissection in microscopic stage III melanoma), when a positive sentinel lymph node was diagnosed, immediate completion lymph node dissection was performed at 90 % of the centers. After the publication of MSLT-II, 45 % of the respondents considered stopping this practice. The risk-benefit ratio prompted prescription of nivolumab and of combined dabrafenib+trametinib as adjuvant therapy by respectively 96 % and 79 % of respondents, while the corresponding rates for interferon and ipilimumab were only 21 % and 15 %. CONCLUSION: Early melanoma management stands on the verge of major changes thanks to the arrival of efficient adjuvant therapies and a decrease in immediate completion lymph node dissections for patients with microscopic stage III is also anticipated.

Acne from the young patient's perspective.

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.

Current opinions in immune checkpoint inhibitors rechallenge in solid cancers.

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.

[Reprint of: New guidelines for stage III melanoma (the French Cutaneous Oncology Group)]. / Republication de : Actualisation des données concernant le mélanome stade III : nouvelles recommandations du groupe français de cancérologie cutanée.

Improved knowledge of sentinel node procedures coupled with the results of adjuvant clinical trials in stage III melanoma have prompted the French Cutaneous Oncology Group to propose new guidelines for the management of stage III melanoma. These guidelines comply with the principles of the evidence-based medicine.

[New guidelines for stage III melanoma (the French Cutaneous Oncology Group)]. / Actualisation des données concernant le mélanome stade III : nouvelles recommandations du groupe français de cancérologie cutanée.

Improved knowledge of sentinel node procedures coupled with the results of adjuvant clinical trials in stage III melanoma have prompted the French Cutaneous Oncology Group to propose new guidelines for the management of stage III melanoma. These guidelines comply with the principles of the evidence-based medicine.

Update of survival and cost of metastatic melanoma with new drugs: Estimations from the MelBase cohort.

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.

Age-Dependent Protective Effect of Selenium against UVA Irradiation in Primary Human Keratinocytes and the Associated DNA Repair Signature.

Few studies have focused on the protective role of selenium (Se) against skin aging and photoaging even though selenoproteins are essential for keratinocyte function and skin development. To the best of our knowledge, the impact of Se supplementation on skin cells from elderly and young donors has not been reported. Therefore, the main objective of our study was to evaluate the effects of Se supplementation on skin keratinocytes at baseline and after exposure to ultraviolet A (UVA) irradiation. Low doses of Se (30 nM) were very potently protective against UVA-induced cytotoxicity in young keratinocytes, whereas the protection efficiency of Se in old keratinocytes required higher concentrations (240 nM). Additionally, the DNA repair ability of the old keratinocytes drastically decreased compared with that of the young keratinocytes at baseline and after the UVA exposure. The Se supplementation significantly enhanced the DNA repair of 8-oxoguanine (8oxoG) only in the keratinocytes isolated from young donors. Therefore, aged keratinocytes have an increased vulnerability to oxidative DNA damage, and the Se needs in the elderly should be considered. Strengthening DNA repair activities with Se supplementation may represent a new strategy to combat aging and skin photoaging.

Acne and nutrition: hypotheses, myths and facts.

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.

Sex- and age-adjusted prevalence estimates of five chronic inflammatory skin diseases in France: results of the « OBJECTIFS PEAU ¼ study.

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.