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Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in patients with neurofibromatosis type 1. They can result from premalignant neurofibromas, including neurofibromas with atypia and atypical neurofibromatous neoplasms of uncertain biologic potential. Some phenotypic characteristics have been described as associated with their development. The aim of this study was to outline our use of whole-body positron emission tomography with 18 F-fluorodeoxyglucose/magnetic resonance imaging in adults with neurofibromatosis type 1, especially in the screening of asymptomatic individuals with a higher risk of developing an MPNST, and to study its impact on neurofibroma classification (malignant vs premalignant) and MPNST staging over time. Individuals with neurofibromatosis type 1 who underwent a positron emission tomography with 18 F-fluorodeoxyglucose/magnetic resonance imaging between 2017 and 2021 were included, analyzing separately the screened population. Maximum standard uptake value and diffusion-weighted imaging were assessed. Biopsy/surgery confirmed the diagnosis. In all, 345 positron emission tomography with 18 F-fluorodeoxyglucose/magnetic resonance imaging were performed in 241 patients, including 149 asymptomatic (62%) but at-risk patients. Eight MPNSTs in 8 screened individuals (5%), 6 neurofibromas with atypia in 4 individuals (3%), and 29 atypical neurofibromatous neoplasms of uncertain biologic potential in 23 individuals (15%) were diagnosed. Over time, the proportion of grade 3 MPNST and the malignant/premalignant ratio in screened individuals significantly decreased (P = .03 and P < .001, respectively). This study emphasizes the diagnostic and screening performances of whole-body positron emission tomography with 18 F-fluorodeoxyglucose/magnetic resonance imaging in adults with neurofibromatosis type 1., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with vitiligo incur direct and indirect costs associated with their condition; however, data regarding the economic burden of vitiligo are scarce and outdated. In this retrospective cohort analysis of the Merative MarketScan Commercial Database, healthcare costs and healthcare resource utilization (HCRU) were evaluated among United States patients with vitiligo. Patients with vitiligo were matched (1:2) with individuals without vitiligo (controls) between January 2007 and December 2021. Outcomes included all-cause and vitiligo-related costs (2021 dollars) and all-cause HCRU, including mental health-related HCRU, during a 1-year postindex period. Subgroup analyses were completed for patients on vitiligo treatments with systemic effects (such as phototherapy and oral steroids) or a new mental health diagnosis. The analysis was focused solely on direct costs. Baseline demographics were well-balanced between matched vitiligo (49,512) and control (99,024) cohorts. Patients with vitiligo incurred significantly higher all-cause ($15,551 vs $7735) and vitiligo-related ($3490 vs $54) costs than controls (P < .0001). All-cause and mental health-related HCRU were also significantly higher among patients with vitiligo (P < .0001). Differences in all-cause and vitiligo-related healthcare costs remained significantly higher in patients on treatments with systemic effects/mental health diagnoses than in controls (P < .0001). Taken together, healthcare costs and HCRU were significantly higher among patients with vitiligo than among controls., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Cutaneous neurofibromas (cNF) contribute to the impairment of QOL in individuals with neurofibromatosis 1. The cNF-Skindex, validated in a French population, specifically assesses the cNF-related QOL. In this study, we first defined severity strata using an anchoring approach on the basis of patient's burden. In total, 209 patients answered the anchor question and the cNF-Skindex. We tested the agreement among the three strata, generated by all potential couples of cut-off values of the cNF-Skindex and the three strata defined in the anchor question. The cut-off values 12 and 49 provided the highest Kappa value (κ = 0.685, 95% confidence interval = 0.604-0.765). Second, we validated the score and the strata in a United States population using the answers provided by 220 French and 148 United States adults. In the multivariable linear regression analysis, the country of origin was not a factor associated with the score (P = 0.297). The number of cNF along the different severity strata was similar between the French and the United States populations. In conclusion, stratification constitutes a powerful tool to better interpret the cNF-Skindex in daily practice and in clinical trials. This study validates its use in two populations that together constitute a large cohort of patients willing to participate in clinical research., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Vitiligo has been reported to be associated with a variety of diseases, but it has not been systematically reviewed. Therefore, we aimed to identify prevalent diseases in patients with vitiligo and quantify their associations compared with those in healthy controls. A comprehensive search of MEDLINE and EMBASE from the inception to June 2022 was conducted. Observational studies on prevalent diseases in patients with vitiligo compared with those in healthy controls were included, whereas studies limited to pediatrics or providing only laboratory results were excluded. A total of 78 studies were eligible for analyses. Patients with vitiligo showed higher risks of having comorbid autoimmune and connective tissue diseases, including alopecia areata (OR = 2.63, 95% confidence interval [CI] = 2.50‒2.78), discoid lupus erythematosus (OR = 2.54, 95% CI = 1.74‒3.72), Sjogren's syndrome (OR = 2.50, 95% CI = 1.98‒3.16), myasthenia gravis (OR = 2.30, 95% CI = 1.74‒3.02), systemic lupus erythematosus (OR = 1.96, 95% CI = 1.52‒2.52), and rheumatoid arthritis (OR = 1.82, 95% CI = 1.55‒2.15). Thyroid diseases, diabetes mellitus, metabolic syndrome, sensorineural hypoacusis, and ophthalmic abnormalities were also more prevalent in patients with vitiligo. In conclusion, vitiligo is associated with various systemic diseases. Physicians should evaluate and manage potential comorbid conditions in patients with vitiligo., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Topical calcineurin inhibitors are used off label in the treatment of vitiligo, and there is a lack of placebo-controlled, blinded studies to support their use., Objective: This study aimed to compare the efficacy of tacrolimus 0.1% ointment with that of the vehicle for repigmentation in adult patients with facial vitiligo., Design: This study was a 24-week multicenter randomized parallel double-blind study with a 24-week post-treatment follow-up extension., Population: Participants included were adult patients with recent facial vitiligo target lesions (<2 years) without changes in pigmentation or size over the previous 3 months., Intervention: Patients received either tacrolimus 0.1% ointment or vehicle twice daily., Main Outcomes and Measures: The primary outcome was a therapeutic success, defined as a change ≥75% in the repigmentation of the target lesion between baseline and week 24, measured by ImageJ software. Secondary outcome measures were a variation of the physicians' global assessment scores and patients' satisfaction scores, safety data, and the rate of relapse at week 48., Results: A total of 42 patients were included. Therapeutic success was achieved in 65% of tacrolimus-treated patients versus 0% of vehicle-treated patients at week 24 (P < 0.0001). Only 40% of relapse was observed at 48 weeks., Conclusions and Relevance: Twice-daily tacrolimus 0.1% ointment showed superior efficacy to that of the vehicle through the 24 weeks of intervention and 24 weeks of follow-up in adult patients with facial vitiligo., Trial Registration: This study was registered at ClinicalTrials.gov (identifier: NCT02466997)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

There is excitement in the air for patients with vitiligo. For the first time in decades, we have early case studies showing that targeted therapies can repigment vitiliginous skin, and well-powered clinical trials are underway. However, at the time of this writing, there is no Food and Drug Administration-approved drug for vitiligo. In a randomized clinical trial by Khemis et al. report negative results on a randomized clinical trial testing the combination of apremilast, a phosphodiesterase 4 inhibitor, and narrowband-ultraviolet B versus placebo and narrowband-ultraviolet B in patients with nonsegmental vitiligo. The results of this trial are a reminder that clinical management of vitiligo is challenging at best, even when combining anti-inflammatory and/or immunomodulating agents with repigmenting agents. However, these negative trials are critical in improving our understanding of this complex and disfiguring disease., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Vitiligo is a chronic autoimmune depigmenting skin disorder that results from a loss of melanocytes. Multiple combinatorial factors have been involved in disease development, with a prominent role of the immune system, in particular T cells. After repigmentation, vitiligo frequently recurs in the same area, suggesting that vitiligo could involve the presence of resident memory T cells (T RM ). We sought to perform a thorough characterization of the phenotype and function of skin memory T cells in vitiligo. We show that stable and active vitiligo perilesional skin is enriched with a population of CD8 T RM expressing both CD69 and CD103 compared with psoriasis and control unaffected skin. CD8 T RM expressing CD103 are mainly localized in the epidermis. Expression of CXCR3 is observed on most CD8 T RM in vitiligo, including the population of melanocyte-specific CD8 T cells. CD8 T RM displayed increased production of IFN-γ and tumor necrosis factor-α with moderate cytotoxic activity. Our study highlights the presence of functional CD8 T RM in both stable and active vitiligo, reinforcing the concept of vitiligo as an immune memory skin disease. The CD8 T RM that remain in stable disease could play a role during disease flares, emphasizing the interest in targeting this cell subset in vitiligo., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Vitiligo is the most common depigmentation disorder, affecting around 1% of population worldwide. There is no cure, and no firm clinical recommendations can be made for the treatment of vitiligo. A European guideline suggests early treatment of small lesions of recent onset and childhood vitiligo with combination of phototherapy and topical agents. Suitable facilities and equipment, such as hand-held portable phototherapy devices, are needed, if this new guideline is to be implemented. Hand-held units are suitable for small lesions, making phototherapy available for patients with limited and/or early vitiligo. Recently, a pilot randomized controlled multicenter trial study was conducted to develop an educational package for patients describing how to use phototherapy at home, adjust the dose, and manage short-term side effects. The pilot trial showed that vitiligo patients are very keen to participate in trials of home phototherapy. The study has successfully demonstrated willingness of participants to be randomized and very good treatment adherence and repigmentation rates, providing evidence of feasibility for a definitive trial. The mean post-trial outputs of hand-held phototherapy devices were lower than the pretrial values. Close collaboration with a local medical physics department is essential. Hand-held phototherapy devices might overcome the need to treat vitiligo in hospital-based phototherapy cabinets and allow early treatment at home that may enhance the likelihood of successful repigmentation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The clinical assessment of vitiligo involves an estimation of the affected body surface area. The most commonly used method is the "palm of hand 1% rule" as integrated in the Vitiligo Area Scoring Index. However, this method can be challenging and time consuming. In this study, we introduce a global Vitiligo Extent Score (VES). In the first part of the study, this measurement instrument was developed and subsequently optimized during a pilot scoring session. In a subsequent stage, the inter- and intrarater reliability of the instrument were tested. Live scoring showed an excellent interrater reliability for the VES (intraclass correlation VES: 0.924 vs. Vitiligo Area Scoring Index: 0.846). Subsequent scoring on pictures was comparable with the live evaluation and demonstrated an excellent intrarater reliability. A high intraclass correlation for the VES (intraclass correlation VES: 0.923 vs. Vitiligo Area Scoring Index: 0.757) was also found in an additional subgroup of patients with extensive vitiligo. Moreover, user-friendliness and timing were scored very favorably. In conclusion, this measurement instrument allows us to monitor accurately and easily the affected body surface area in a standardized way. Moreover, our results provide evidence that the VES can be proposed as a promising tool to measure the vitiligo extent in clinical trials and in daily practice., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Although likely benefits of aromatherapy are well documented, little is known about essential oils consumption and exposure to molecules present in the oils. The aim of our study was to determine usage patterns of 12 types of essential oils among a quite large panel, sorted per sex and quintile of age from birth to 70. A survey was conducted in September 2014 among 1507 French individuals, selected to build a representative panel of the general population. The key point of our study, apart from the fact that it has never been done among general population, was the focus on dermal exposure. Information about types of essential oils used, skin areas exposed, frequencies and quantities were collected. Our work revealed that some sub-populations could be significantly exposed to molecules of toxicological concern, especially in terms of skin sensitization. This work is the first step to assess human exposure to these molecules, and will help safety authorities and risk managers to protect the population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Mechanistic hypotheses suggest that vitamin D may contribute to the prevention of breast cancer. However, epidemiologic evidence is inconsistent, suggesting a potential effect modification by individual factors., Objective: Our objective was to perform exploratory analyses on the prospective associations between the plasma 25-hydroxyvitamin D [25(OH)D] concentration, polymorphisms of genes encoding for the vitamin D receptor (VDR) and vitamin D-binding protein (also known as gc-globulin or group-specific component, GC), and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake., Methods: A nested case-control study was set up in the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort (1994-2007), involving 233 women with breast cancer and 466 matched controls (mean ± SD age: 49 ± 6 y). The plasma total 25(OH)D concentration and gene polymorphisms were assessed on samples obtained at baseline. Conditional logistic regression models were computed., Results: A higher plasma 25(OH)D concentration was associated with a decreased risk of breast cancer for women with a BMI < the median of 22.4 [OR quartile (Q)4 compared with Q1: 0.46; 95% CI: 0.23, 0.89; P-trend = 0.01, P-interaction = 0.002], whereas it was associated with an increased risk for women with a BMI ≥ the median (OR Q4 compared with Q1: 2.45; 95% CI: 1.13, 5.28; P-trend = 0.02, P-interaction = 0.002). A plasma 25(OH)D concentration ≥ 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes ≥ the median of 7.1 g/d (OR ≥10 compared with <10 ng/mL: 0.50; 95% CI: 0.26, 0.95; P = 0.03, P-interaction = 0.03). The genetic analyses were consistent with the results observed with plasma 25(OH)D., Conclusion: In this prospective study, BMI and alcohol intake modified the association between vitamin D [plasma 25(OH)D and vitamin D-related gene polymorphisms] and breast cancer risk. These effect modifications suggest explanations for discrepancies in results of previous studies. This trial was registered at clinicaltrials.gov as NCT00272428., (© 2016 American Society for Nutrition.)

Vitiligo has a major impact on health-related quality of life. Although a few vitiligo-specific quality of life instruments exist, there is no specific vitiligo burden tool. We developed and validated a specific vitiligo burden tool according to skin phototype. In total, 301 patients completed 35 items of the Vitiligo Impact Patient scale, of whom 235 were of skin phototype I to III and 66 of phototype IV to VI. The dimensionality of the items was evaluated using factor analyses, with results suggesting three factors in fair- and dark-skinned patients ("Psychological effects on daily life," "Relationships and Sexuality," and "Economic Constraints, Care & Management of Disease"). Unidimensionality was confirmed by higher order factor analysis. Cronbach's α were high-and intradimensional coherences all demonstrated good reliability (α > 0.8). The final instrument consists of 29 items (19 items common to all patients, 3 specific to fair skin, and 7 to dark skin). The test-retest reliability demonstrated very good reproducibility. The intraclass correlation of each dimension was greater than 0.90 for each population. External validity was confirmed by the correlation coefficients and Bland and Altman plots of the Vitiligo Impact Patient scale-Fair Skin and Vitiligo Impact Patient scale-Dark Skin versus the Short-Form-12, PVC Metra, Body Image States Scale, and Daily Life Quality Index assessment tools., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Experimental evidence has suggested that vitamin D may be protective against tobacco-related cancers through the inhibition of the formation of tumors induced by tobacco carcinogens. To our knowledge, only one previous epidemiologic study investigated the association between vitamin D status and tobacco-related cancer risk, and no study has focused on vitamin D-related gene polymorphisms., Objective: Our objective was to prospectively study the association between plasma 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers., Design: A total of 209 tobacco-related cancers were diagnosed within the SU.VI.MAX (Supplémentation en vitamines et minéraux antioxydants) cohort (1994-2007) and were matched with 418 controls as part of a nested case-control study. Tobacco-related cancers (i.e., cancers for which tobacco is one of the risk factors) included several sites in the respiratory, digestive, reproductive, and urinary systems. Total plasma 25(OH)D was assessed with the use of an electrochemoluminescent assay. Polymorphisms were determined with the use of a TaqMan assay. Conditional logistic regression models were computed., Results: A 25(OH)D concentration ≥30 ng/mL was associated with reduced risk of tobacco-related cancers (OR for ≥30 compared with <30 ng/mL: 0.59; 95% CI 0.35, 0.99; P = 0.046). This association was observed in former and current smokers (OR for ≥30 compared with <30 ng/mL: 0.43; 95% CI: 0.23, 0.84; P = 0.01) but not in never smokers (P = 0.8). The vitamin D receptor (VDR) FokI AA genotype and retinoid X receptor (RXR) rs7861779 TT genotype were associated with increased risk of tobacco-related cancers [OR for homozygous mutant type (MT) compared with wild type (WT): 1.87; 95% CI: 1.08, 3.23; P-trend = 0.02; OR for heterozygous type (HT) plus MT compared with WT: 1.60; 95% CI: 1.07, 2.38; P = 0.02]., Conclusions: In this prospective study, high vitamin D status [25(OH)D concentration ≥30 ng/mL] was associated with decreased risk of tobacco-related cancers, especially in smokers. These results, which are supported by mechanistic plausibility, suggest that vitamin D may contribute to the prevention of tobacco-induced cancers in smokers and deserve additional investigation. The SU.VI.MAX trial was registered at clinicaltrials.gov as NCT00272428., (© 2015 American Society for Nutrition.)

Background: The role of folate in skin carcinogenesis is unclear, with experimental data suggesting potentially protective but also deleterious effects., Objective: Our main objective was to investigate the prospective association between dietary folate intake and risks of skin cancer (overall), nonmelanoma skin cancer (NMSC), and basal cell carcinoma (BCC). As an exploratory analysis, we also investigated the prospective association between erythrocyte folate concentration and skin cancer risk., Design: In this study, we included 5880 participants in the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort (follow-up: 1994-2007) who completed at least six 24-h dietary records during the first 2 y of the study. Associations between sex-specific tertiles of dietary and erythrocyte folate and skin cancer risk were assessed by using multivariate Cox proportional hazards models., Results: After a median follow-up of 12.6 y, 144 incident skin cancers were diagnosed. Dietary folate intake was associated with increased risk of overall skin cancer [HR for tertile 3 compared with tertile 1 (HR(T3vs.T1)): 1.79; 95% CI: 1.07, 2.99; P-trend = 0.03], NMSC (HR(T3vs.T1): 1.85; 95% CI: 1.06, 3.23; P-trend = 0.03), and BCC (HR(T3vs.T1): 1.78; 0.98, 3.24; P-trend = 0.05). This association was observed in women (corresponding P-trend = 0.007, 0.009, and 0.009, respectively) but not in men (P-trend = 0.8, 0.8, and 0.9, respectively). P-interaction values between tertiles of dietary folate intake and sex were 0.04, 0.02, and 0.02 for overall skin cancer, NMSC, and BCC, respectively. Erythrocyte folate concentration was directly associated with increased risk of overall skin cancer (HR(T3vs.T1): 2.54; 95% CI: 0.95, 6.81; P-trend = 0.03), NMSC (HR(T3vs.T1): 3.49; 95% CI: 1.11, 11.0; P-trend = 0.01), and BCC (HR(T3vs.T1): 7.44; 95% CI: 1.57, 35.3; P-trend = 0.004) (men and women combined)., Conclusions: This prospective study suggests an association between dietary folate intake and erythrocyte folate concentration and increased risk of overall skin cancer, NMSC, and BCC. Although several mechanistic hypotheses and 2 previous large prospective studies on BCC are in line with these results, epidemiologic literature is limited, and future research is needed to better elucidate the potential role of folate in the cause of skin cancers., (© 2015 American Society for Nutrition.)

Vitiligo, an acquired pigmentary disorder of unknown origin, is the most frequent cause of depigmentation worldwide, with an estimated prevalence of 1%. The disorder can be psychologically devastating and stigmatising, especially in dark skinned individuals. Vitiligo is clinically characterised by the development of white macules due to the loss of functioning melanocytes in the skin or hair, or both. Two forms of the disease are well recognised: segmental and non-segmental vitiligo (the commonest form). To distinguish between these two forms is of prime importance because therapeutic options and prognosis are quite different. The importance of early treatment and understanding of the profound psychosocial effect of vitiligo will be emphasised throughout this Seminar., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.

The risk of relapse after successful repigmentation in vitiligo is estimated to 40% within the first year. It has been shown in atopic dermatitis that continuous low-level use of topical corticosteroids and calcineurin inhibitors in previously affected skin can prevent new flares. We hypothesized that a twice-weekly application of 0.1% tacrolimus ointment might be effective for maintaining repigmentation in therapeutically repigmented lesions of vitiligo patients. After randomization, sixteen patients with 31 patches were assigned to the placebo group and 19 patients with 41 patches were assigned to the tacrolimus group. In the intention-to-treat analysis, 48.4% of lesions showed depigmentation in the placebo group, whereas 26.8% did in the tacrolimus group (P=0.059). The intention-to-treat results did not remain significant after adjustment for within-patient clustering, odds ratio (OR) 2.55; 95% confidence interval (CI; 0.65-9.97); P=0.1765. The per-protocol analysis (n=56) showed that 40% of lesions had some depigmentation in the placebo group, whereas only 9.7% did in the tacrolimus group (P=0.0075). The per-protocol results remained significant after adjustment for within-patient clustering: OR 6.22; 95% CI (1.48-26.12); P=0.0299. Our study shows that twice-weekly application of 0.1% tacrolimus ointment is effective in preventing the depigmentation of vitiligo patches that have been previously successfully repigmented.

Very few studies have investigated the determinants of serum vitamin D levels using a set of variables that include simultaneously sun exposure, phototype, dietary intake, sociodemographics, anthropometric, lifestyle data, and genetic polymorphisms. Our objective was to investigate the associations between all these parameters and vitamin D status in a large sample of French adults. This cross-sectional survey was based on 1,828 middle-aged Caucasian adults from the SU.VI.MAX (SUpplémentation en VItamines et Minéraux AntioXydants) study. Plasma 25-hydroxyvitamin D (25OHD) concentration was lower among women (P<0.0001), older subjects (P=0.04), obese/underweight (P<0.0001), those living at higher latitudes (P<0.0001), those whose blood draw occurred in early spring (P<0.0001), less physically active (P<0.0001), with low sun exposure (P<0.0001), and with no-to-low alcohol intake (P=0.0001). Mutant GC rs4588 and rs7041 single nucleotide polymorphisms were associated with lower and higher 25OHD concentrations, respectively (P<0.0001). Dietary intake was not a major determinant of vitamin D status (P=0.7). This study provides an overall picture of determinants of vitamin D status. Several modifiable factors were identified, such as daily-life moderate sun exposure, physical activity, and normal-weight maintenance, which should be targeted by public health policies in order to improve vitamin D status in the general population, while avoiding active/intensive sun exposure, in line with recommendations for skin cancer prevention.

Nucleotide excision repair (NER) is an important DNA repair pathway involved in the removal of a wide array of DNA lesions. The absence or dysfunction of NER results in the following distinct disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS), cerebro-oculo-facio-skeletal (COFS) syndrome, UV-sensitive syndrome (UVSS), trichothiodystrophy (TTD), or combined syndromes including XP/CS, XP/TTD, CS/TTD, and COFS/TTD. In addition to their well-characterized role in the NER signaling pathway, NER factors also seem to be important in biological processes that are not directly associated with DNA damage responses, including mitochondrial function and redox homeostasis. The potential causative role of these factors in the large clinical spectrum seen in NER diseases is discussed in this review.

Background: Intake of long-chain n-3 polyunsaturated fatty acid (PUFAs) supplementation has been reported to be associated with reduced UVB-erythemal sensitivity, but their relationship to photoaging has not been studied to date., Objective: To investigate associations between daily n-3 PUFA intake and the severity of skin photoaging., Methods: A cross-sectional study was conducted on 2919 subjects aged 45-60 years from the SU.VI.MAX cohort. At baseline, trained investigators graded the severity of facial skin photoaging using a validated 6-grade scale during a clinical examination. Intake of α-linolenic (ALA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic acids (DHA) were evaluated by dietary source using ten 24-h dietary record questionnaires during the first 2.5 years of the follow-up period., Results: After adjustment for possible confounders, severe photoaging was found to be inversely associated with higher intake of ALA in men and with higher intake of EPA in women. When considering the different food sources of ALA for men, an inverse association appeared between severe photoaging and ALA from vegetable oils, as well as with ALA from fruit and vegetables, whereas no association was observed for ALA from dairy products. In women, ALA from vegetable oils also tended to be inversely linked to photoaging., Conclusions: These findings suggest a possible benefit effect of n-3 PUFAs on skin aging. Nonetheless, further epidemiological studies are necessary to confirm our results and to gain additional insights into underlying mechanisms., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

A genome-wide association study (GWAS) was conducted on 502 French middle-aged Caucasian women to identify genetic factors that may affect skin aging severity. A high-throughput Illumina Human Omni1-Quad beadchip was used. After single-nucleotide polymorphism (SNP) quality controls, 795,063 SNPs remained for analysis purposes. Possible stratification was first examined using the Eigenstrat method, and then the relationships between genotypes and four skin aging indicators (global photoaging, lentigines, wrinkles, and sagging) were investigated separately by linear regressions adjusted on age, smoking habits, lifetime sun exposure, hormonal status, and the two main Eigen vectors. One signal passed the Bonferroni threshold (P=1.53 × 10(-8)) and was significantly associated with global photoaging. It was also correlated with the wrinkling score and the sagging score. According to HapMap, this SNP, rs322458, was in linkage disequilibrium (LD) with intronic SNPs of the STXBP5L gene, which is expressed in the skin. In addition, it was also in LD with another SNP that increases the expression of the FBXO40 gene in the skin. These two genes, which were not previously described in the context of aging, may constitute good candidates for the investigation of molecular mechanisms of skin photoaging.

Background: Tyrosinase (TYR) is a key pigmentation gene that is highly polymorphic and responsible for the most common form of autosomal recessive albinism, OCA1., Objective: To assess the role of frequent and rare TYR variants in predisposition to skin cancer (SK) in the French population., Methods: We genotyped a frequent TYR variant (p.R402Q) in 1273 patients {1047 cutaneous melanoma (CM) and 226 basal cell carcinoma (BCC)} and 925 controls, and the full coding region of TYR was sequenced in 287 patients suspected of genetic predisposition to SK (familial and/or multiple SK and/or onset before 40 years) and 187 controls., Results: The homozygous p.R402Q variant was significantly associated with SK risk (P value=0.008; OR=1.57), and was mostly associated with multiple CM risk (P value=0.021; OR=2.50) and familial CM risk (P value=0.022; OR=2.16). In addition, 19 rare TYR variants, mainly albinism mutations, were identified in 15 patients and 8 controls. Among these, 3 clearly deleterious mutations (1 non-sense and 2 affecting mRNA splicing) were identified in 3 patients, one of which was homozygous., Conclusion: Our data confirmed the association of TYR p.R402Q with SK risk in the French population, and support that rare deleterious TYR variants may also play a role in multi-factorial genetic predisposition to SK. These results should be confirmed by replications studies., (Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Generalized vitiligo is a common autoimmune disease in which acquired patchy depigmentation of skin, hair, and mucous membranes results from loss of melanocytes from involved areas. Previous genetic analyses have focused on vitiligo susceptibility, and have identified a number of genes involved in disease risk. Age of onset of generalized vitiligo also involves a substantial genetic component, but has not previously been studied systematically. In this study, we report a genome-wide association study of vitiligo age of onset in 1,339 generalized vitiligo patients, with replication in an independent cohort of 677 cases. We identified a quantitative trait locus for vitiligo age of onset in the major histocompatibility complex (MHC) class II region, located near c6orf10-BTNL2 (rs7758128; P=8.14 × 10(-11)), a region that is also associated with generalized vitiligo susceptibility. In contrast, there was no association of vitiligo age of onset with any other MHC or non-MHC loci that are associated with vitiligo susceptibility. These findings highlight the differing roles played by genes involved in vitiligo susceptibility versus vitiligo age of onset, and illustrate that genome-wide analyses can be used to identify genes involved in quantitative aspects of disease natural history, as well as disease susceptibility per se.

We previously carried out a genome-wide association study of generalized vitiligo (GV) in non-Hispanic whites, identifying 13 confirmed susceptibility loci. In this study, we re-analyzed the genome-wide data set (comprising 1,392 cases and 2,629 controls) to specifically test association of all 33 GV candidate genes that have previously been suggested for GV, followed by meta-analysis incorporating both current and previously published data. We detected association of three of the candidate genes tested: TSLP (rs764916, P=3.0E-04, odds ratio (OR)=1.60; meta-P for rs3806933=3.1E-03), XBP1 (rs6005863, P=3.6E-04, OR=1.17; meta-P for rs2269577=9.5E-09), and FOXP3 (rs11798415, P=5.8E-04, OR=1.19). Association of GV with CTLA4 (rs12992492, P=5.9E-05, OR=1.20; meta-P for rs231775=1.0E-04) seems to be secondary to epidemiological association with other concomitant autoimmune diseases. Within the major histocompatibility complex (MHC), at 6p21.33, association with TAP1-PSMB8 (rs3819721, P=5.2E-06) seems to derive from linkage disequilibrium with major primary signals in the MHC class I and class II regions.

The objective of this study was to assess the association between melanocortin-1 receptor (MC1R) variants and the severity of facial skin photoaging. The study population comprised 530 middle-aged French women. A trained dermatologist graded the severity of facial skin photoaging from photographs using a global scale. Logistic regressions were performed to assess the influence of MC1R polymorphisms on severe photoaging with adjustment for possible confounders (demographic and phenotypic data and sun exposure intensity). Among the fifteen MC1R variants identified, the nine most common were V60L, V92M, R151C, R160W, R163Q, R142H, D294H, D84E, and I155T. One hundred and eighty-five individuals (35%) were WT homozygotes, 261 (49%) had one common variant, 78 (15%) had two common variants, and six (1%) had at least one rare variant. After adjustment for possible confounders, the presence of two common variants was already a risk factor for severe photoaging (AOR (95% confidence interval): 2.33 (1.17-4.63)). This risk reached 5.61 (1.43-21.96) when two major diminished-function variants were present. Surprisingly, the minor variant, V92M, was associated with increased risk of photoaging (2.57 (1.23-5.35)). Our results suggest that genetic variations of MC1R are important determinants for severe photoaging.

Unlabelled: Gambiense human African trypanosomiasis is still assumed to be endemic in many part of West Africa, particularly in Guinea coastal area with mangrove swamp. Diagnosis is usually made during active medical screening or by passive initiative., Objectives: To describe clinical and epidemiological characteristics of Gambiense human African trypanosomiasis in the coastal area of Guinea., Methods: Exhaustive and retrospective analysis of all patients attending the trypanosomiasis center in the coastal area of Guinea between January 2005 and December 2007 with a diagnosis of human African trypanosomiasis., Results: A total of 196 patients were recruited for the study. Out of them, 55 % of the 73 patients diagnosed during active screening were classified stage 1 (haemolymphatic stage) or early stage 2 (meningoencephalitic stage). Contrarily, 115 of the 120 diagnosed by passive procedure were classified late stage 2, which features more specific signs and neurological symptoms, and leads to coma and death. More than 90 % of all cases presented cervical lymph nodes with identification of trypanosome on direct examination of fluid puncture. Less than one third of the patients were reexamined three months later., Discussion: In the coastal area of Guinea with mangrove swamp, direct examination of lymph node fluid puncture seems to be the most contributive test for the diagnosis of human African trypanosomiasis. Hence, associating clinical examination of cervical lymph nodes area and direct examination of fluid puncture may allow an early diagnosis of Gambiense human African trypanosomiasis and favor the implementation of efficient therapeutic strategies., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

Objective: In health research, ordinal scales are extensively used. Reproducibility of ratings using these scales is important to assess their quality. This study aimed to compare two methods analyzing reproducibility: weighted Kappa statistic and log-linear models., Study Design and Setting: Contributions of each method to the reproducibility assessment of ratings using ordinal scales were compared using intra- and interobserver data chosen in three different fields: Crow's feet scale in dermatology, dysplasia scale in oncology, updated Sydney scale in gastroenterology., Results: Both methods provided an agreement level. In addition, log-linear models allowed evaluation of the structure of agreement. For the Crow's feet scale, both methods gave equivalent high agreement levels. For the dysplasia scale, log-linear models highlighted scale defects and Kappa statistic showed a moderate agreement. For the updated Sydney scale, log-linear models underlined a null distinguishability between two adjacent categories, whereas Kappa statistic gave a high global agreement level., Conclusion: Methods that can investigate level and structure of agreement between ordinal ratings are valuable tools, since they may highlight heterogeneities within the scales structure and suggest modifications to improve their reproducibility.

Objective: Malaria is increasing worldwide due to the emergence and spread of drug resistant strains. As globalization in business and commerce and appetites for more adventurous travel increase, more people from non-endemic countries are being exposed to malaria. The management of travelers before departure or returning from visiting endemic countries with malaria is a challenge, both for exposed individuals and for physicians, considering the weak knowledge of the disease., Methods: A survey was conducted among French individuals traveling to endemic areas to evaluate their knowledge and perception of malaria. An observational study using guided questionnaires was made on 103 travelers recruited in the Bordeaux University Hospital travel clinic, France., Results: The findings of the survey were consistent with previously reported data concerning the knowledge of signs and symptoms of malaria, as well as with the global level of knowledge on the disease, and with the number of travelers not understanding the mode of infection appropriately. Irrelevant data was reported concerning the typical pattern of the disease, the objectives of malaria management for travelers, and the attention given to the most susceptible groups: children, pregnant women, and immuno-compromised individuals., Conclusion: Our findings show a link between gender and adhesion to prophylactic measures, and an inverse gradient in the subgroup of frequent overseas travelers, between knowledge and risk perception of illness.

This research aimed to test whether supplementation with a combination of antioxidant vitamins and minerals could reduce the risk of skin cancers (SC). It was performed within the framework of the Supplementation in Vitamins and Mineral Antioxidants study, a randomized, double-blinded, placebo-controlled, primary prevention trial testing the efficacy of nutritional doses of antioxidants in reducing incidence of cancer and ischemic heart disease in the general population. French adults (7876 women and 5141 men) were randomized to take an oral daily capsule of antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium, and 20 mg zinc) or a matching placebo. The median time of follow-up was 7.5 y. A total of 157 cases of all types of SC were reported, from which 25 were melanomas. Because the effect of antioxidants on SC incidence varied according to gender, men and women were analyzed separately. In women, the incidence of SC was higher in the antioxidant group [adjusted hazard ratio (adjusted HR) = 1.68; P = 0.03]. Conversely, in men, incidence did not differ between the 2 treatment groups (adjusted HR = 0.69; P = 0.11). Despite the small number of events, the incidence of melanoma was also higher in the antioxidant group for women (adjusted HR = 4.31; P = 0.02). The incidence of nonmelanoma SC did not differ between the antioxidant and placebo groups (adjusted HR = 1.37; P = 0.22 for women and adjusted HR = 0.72; P = 0.19 for men). Our findings suggest that antioxidant supplementation affects the incidence of SC differentially in men and women.

Purpose: The aim of this study was to test the influence of phototype and vitamin D status feature on the bone mineral density (BMD) of the femoral neck in a group of middle-aged women considered at risk of osteoporosis (low levels of vitamin D [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL])., Methods: This two-step study was conducted on 122 French women enrolled in the SUVIMAX (supplémentation en vitamines et minéraux antioxydants: antioxidant vitamin and mineral supplementation) cohort. The impact of various variables on BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun exposure intensity and phototype was investigated using regression models., Results: No statistical link was found between BMD and the variables documenting vitamin D status and parathormone levels, nor phototype. Nevertheless, fair phototypes tended to be associated with lower BMD values. However, BMD decreased with age and increased with BMI and physical activity level., Conclusions: Whatever their phototype, adult women concerned about precarious vitamin D status should undergo a vitamin D supplementation in combination with an adequate calcium intake all year long and a proper sun protection. Moreover, a physical activity maintenance should provide an additional benefit for prevention of osteoporosis.