British Journal of Dermatology最新文献

Background: A common complication of wounds is the excessive production of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. Currently, no treatments with good evidence for preventing excessive scar tissue formation are available. We explored the use of microneedle patches containing small interfering RNA (siRNA) to inhibit SPARC mRNA in reducing the volume of postoperative scars.

Objectives: To compare differences in postoperative scar volume with the daily application of siRNA-embedded dissolving microneedle patches vs. silicone sheets.

Methods: This was an 8-week, single-blinded intraindividually controlled randomized trial at a tertiary dermatological centre. Patients with 2-week-old postoperative wounds were included. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at days 0, 30 and 60. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000558729).

Results: At day 30, scars treated with microneedle patches had a lower geometric mean volume of 0.79 mm3 vs. scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.7%. At day 60, scars treated with microneedle patches had a statistically significant lower volume (8.88 mm3) compared with the side treated with silicone sheets (12.77 mm3; P = 0.005), with a difference in mean percentage reduction of 9.7%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume vs. baseline on the side treated with microneedle patches (mean 83.8%) compared with the side treated with silicone sheets (mean 74.1%).

Conclusions: There was a significantly greater reduction in the volume of postoperative scars on the side of the scar treated with microneedle patches compared with the side treated with silicone sheets. This demonstrates the use of transdermal gene-silencing technology in scar inhibition and that siRNA microneedle patches can be effective and safe in reducing scar tissue formation.

Background: Vitiligo is an autoimmune skin disorder characterized by depigmented patches of skin, which can have significant psychological impacts.

Objectives: To estimate the lifetime incidence of vitiligo, overall, by ethnicity and across other sociodemographic subgroups, and to investigate the impacts of vitiligo on mental health, work and healthcare utilization.

Methods: Incident cases of vitiligo were identified in the Optimum Patient Care Database of primary care records in the UK between 1 January 2004 and 31 December 2020. The lifetime incidence of vitiligo was estimated at age 80 years using modified time-to-event models with age as the timescale, overall and stratified by ethnicity, sex and deprivation. Depression, anxiety, sleep disturbance, healthcare utilization and work-related outcomes were assessed in the 2 years after vitiligo diagnosis and compared with matched controls without vitiligo. The study protocol for this retrospective observational study was registered with ClinicalTrials.gov (NCT06097494).

Results: In total, 9460 adults and children were newly diagnosed with vitiligo during the study period. The overall cumulative lifetime incidence was 0.92% at 80 years of age [95% confidence interval (CI) 0.90-0.94]. Cumulative incidence was similar in female (0.94%, 95% CI 0.92-0.97) and male patients (0.89%, 95% CI 0.86-0.92). There were substantial differences in lifetime incidence across ethnic groups, listed by Office for National Statistics criteria [Asian 3.58% (95% CI 3.38-3.78); Black 2.18% (95% CI 1.85-2.50); Mixed/multiple 2.03% (95% CI 1.58-2.47); Other 1.05% (95% CI 0.94-1.17); and White 0.73% (95% CI 0.71-0.76)]. Compared with matched controls, people with vitiligo had an increased risk of depression [adjusted odds ratio (aOR) 1.08, 95% CI 1.01-1.15]; anxiety (aOR 1.19, 95% CI 1.09-1.30); depression or anxiety (aOR 1.10, 95% CI 1.03-1.17); and sleep disturbance [adjusted hazard ratio (aHR) 1.15, 95% CI 1.02-1.31]. People with vitiligo also had a greater number of primary care encounters (adjusted incidence rate ratio 1.29, 95% CI 1.26-1.32) and a greater risk of time off work (aHR 1.15, 95% CI 1.06-1.24). There was little evidence of disparities in vitiligo-related impacts across ethnic subgroups.

Conclusions: Clinicians should be aware of the markedly increased incidence of vitiligo in people belonging to Asian, Black, Mixed/multiple and Other groups. The negative impact of vitiligo on mental health, work and healthcare utilization highlights the importance of monitoring people with vitiligo to identify those who need additional support.

Background: Previous studies have reported the mutational landscape in extramammary Paget disease (EMPD); however, the prognostic implications of genetic alterations remain unexplored. While CDKN2A loss is known to be associated with tumour progression or poor prognosis in some types of cancer, its significance in EMPD has not been investigated.

Objectives: To examine the association between common genetic alterations and prognosis in EMPD.

Methods: A retrospective cohort study was carried out to analyse the data of patients with EMPD registered up to January 2024 in the Center for Cancer Genomics and Advanced Therapeutics database, a nationwide database that records clinical data and comprehensive genomic profiling (CGP) test results in Japan.

Results: A total of 167 patients with EMPD were recorded in the database, with CDKN2A loss being the most frequent genetic variant. Survival analysis was conducted on data from 127 patients. Survival from the initiation of chemotherapy was analysed, adjusting for length bias inherent in the database with the Kaplan-Meier estimator, an established method of adjustment. Patients with BRCA2-mutant tumours (n = 18) had a worse prognosis than those with BRCA2 wildtype (WT) tumours [n = 109; hazard ratio (HR) 2.97, 95% confidence interval (CI) 1.46-6.01 (P = 0.003)]. Additionally, patients in the CDKN2A mutant group (n = 72) had a significantly worse prognosis compared with those in the CDKN2A WT group [n = 55; HR 1.81, 95% CI 1.06-3.07 (P = 0.029)]. Most CDKN2A variants were pathogenic, primarily characterized by loss, while most BRCA2 variants were variants of uncertain significance. In the survival analysis of CGP enrolment based on Eastern Cooperative Oncology Group performance status (ECOG-PS), patients with an ECOG-PS of 1 at the time of CGP enrolment had a significantly poorer prognosis compared with those with an ECOG-PS of 0 (P = 0.034; median survival time 531 vs. 259 days).

Conclusions: A somatic CDKN2A variant, mainly exhibiting loss, may be associated with a poor prognosis in EMPD. Patients with EMPD with BRCA2-mutant disease might also have a worse prognosis. In addition, CGP testing before ECOG-PS deteriorates is preferable, considering that the observed median survival of individuals undergoing CGP tests in an ECOG-PS 1 condition was < 9 months.

Background: The pathophysiology of seborrhoeic dermatitis (SebD) is complex and is likely to be related to an interplay of the microbial colonization of the skin and local immunity. There are also genetic components to the illness. At least two forms of SebD exist, infantile (ISebD), which has onset early in life, and SebD with later onset.

Objectives: We aimed to improve our understanding of SebD by evaluating whether maternal history of SebD is associated with increased risk of ISebD or childhood-onset SebD (CSebD, with onset after 5 years of life).

Methods: We performed a prospective cohort study of mother-child pairs using data from a large UK primary care electronic medical records database.

Results: We analysed 1 023 140 children with linked maternal data. The mean (SD) time of follow-up for the children was 10.2 (7.9) years for a total follow-up of more than 10 million person-years. Proportional hazards models [HRs (95% confidence intervals)] were used to examine the association between presence of SebD in mothers and SebD in the child. Maternal history of SebD was associated with development of SebD [1.99 (1.91-2.09)], ISebD [1.86 (1.74-1.99)] and CSebD [2.12 (1.97-2.29)] in their children. However, ISebD in a child was not associated with that child later developing CSebD [0.91 (0.82-1.01)].

Conclusions: Maternal history of SebD is a risk factor for the development of SebD in children. While we cannot fully differentiate SebD risk due to mother's genetics (inheritance) from a newborn's environment, our results lend credence to the possible role of genetics in SebD. A child with ISebD does not appear to be at risk for developing CSebD.

Background: Approximately 2-20% of cutaneous melanomas (CMs) are diagnosed as amelanotic/hypopigmented melanoma (AHM) and represent a challenge for early diagnosis.

Objectives: To investigate loss-of-function mutations in key pigmentation genes in matched germline and AHM, as well as pigmented melanoma (PM), tumour DNA samples.

Methods: Analysis of clinical and histopathological characteristics - together with whole-exome sequencing data of 34 fresh frozen primary CMs, graded according to the amount of pigmentation present - was performed. Together with germline and somatic variant analysis, 30 samples had previously been analysed for copy number aberration (CNA) changes. This study focused on germline and somatic variants in the coding region of 16 genes known to be associated with albinism/hypopigmentation or variation in human pigmentation in all samples. Chromosomal regions encompassing these 16 genes were examined for DNA copy loss or gain.

Results: The finding that red hair-related MC1R and TYR R402Q loss-of-activity gene variant alleles and genotypes are associated with AHM was confirmed. Germline AHM-related gene variants were enriched in 70% (n = 7/10) of patients with AHM vs. 8% (n = 2/24) of those with PM. This surprisingly high frequency of rare germline variants in people with AHM constitutes the 'first hit' and confirms that those with AHM are more likely to be albinism allele carriers than individuals with PM. Next, in CNA analysis of each tumour sample, 50% (n = 4/8) of AHM samples with a pigmentation gene variant had loss of heterozygosity (LOH) in the region containing the corresponding gene and 25% (n = 2/8) had LOH in chromosomal regions of two AHM-related genes.

Conclusions: This study proposes that the likely molecular mechanism for the development of amelanogenesis in AHM is carriage of an albinism/hypopigmentation allele followed by LOH of the corresponding gene in the tumour.