British Journal of Dermatology最新文献

{"title":"The causal association between polyunsaturated fatty acids and acne: A two-sample Mendelian randomization study.","authors":"Bo Ri Kim, Gahyun Kim, Seon-Pil Jin, Chong Won Choi, Jinho Kim, Hyunsun Park","doi":"10.1093/bjd/ljaf052","DOIUrl":"https://doi.org/10.1093/bjd/ljaf052","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have demonstrated a close association between polyunsaturated fatty acids (PUFAs) and acne. However, the findings of clinical trials have been inconsistent, leaving the causal relationship between PUFAs and acne unclear.</p><p><strong>Objectives: </strong>To investigate the causal association between genetically proxied PUFAs and acne risk.</p><p><strong>Methods: </strong>Mendelian randomization (MR) was performed using single-nucleotide polymorphisms associated with PUFAs as instrumental variables. The causal associations between PUFAs and acne were estimated among 115,006 UK biobank participants and 363,927 participants of Finnish descent.</p><p><strong>Results: </strong>Genetically predicted docosahexaenoic acid (DHA) levels (Beta= -0.303; 95% CI: -0.480 to -0.126; p = 7.74E-04) and its percentage to total fatty acids (Beta= -0.402; 95% CI: -0.651 to -0.258; p = 5.91E-06) showed a significant causal association with a decreased risk of acne. Conversely, genetically predicted percentages of linoleic acid (LA) in total fatty acids (Beta=0.768; 95% CI: 0.411-0.126; p = 2.87E-04) and omega-6: omega-3 (Beta=0.373; 95% CI: 0.142-0.604; p = 4.48E-03) were robustly associated with an increased risk of acne. These effects were attenuated after excluding a genetic variant of rs174528 located upstream of fatty acid desaturase 1 (FADS1), highlighting the biological link between FADS1 and delta-5 desaturase activity. Multivariable MR analysis indicated that PUFAs were causally associated with acne, independent of body mass index.</p><p><strong>Conclusions: </strong>Our study indicates that high DHA levels and their ratios to total fatty acids have causal protective effects against acne, while high LA levels and omega-6: omega-3 ratio are associated with increased acne risk. This association was largely attributable to the influence of genetic variants related to FADS1.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global study of 17,009 women reveal significant skin condition changes associated with irregular menstrual cycles.","authors":"Christos C Zouboulis, Claire Deloche, Charbel Skayem, Stéphanie Leclerc-Mercier, Philippe Martel, Beatriz Sant'Anna, Charles Taieb, Thierry Passeron","doi":"10.1093/bjd/ljae484","DOIUrl":"https://doi.org/10.1093/bjd/ljae484","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focusing on antigen-specific T cells.","authors":"Takashi Inozume, Satoshi Fukushima","doi":"10.1093/bjd/ljaf050","DOIUrl":"https://doi.org/10.1093/bjd/ljaf050","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Diagnosis: A Skin of Color Patient's Journey with Acral Lentiginous Melanoma.","authors":"Sharon Lopez, Sach Thakker, Kira Minkis","doi":"10.1093/bjd/ljaf047","DOIUrl":"https://doi.org/10.1093/bjd/ljaf047","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal dominant SLURP1 variants cause palmoplantar keratoderma and progressive symmetric erythrokeratoderma.","authors":"Xingyuan Jiang, Ryland D Mortlock, Ivan B Lomakin, Jing Zhou, Ronghua Hu, María Laura Cossio, Christopher G Bunick, Keith A Choate","doi":"10.1093/bjd/ljaf049","DOIUrl":"10.1093/bjd/ljaf049","url":null,"abstract":"<p><strong>Background: </strong>Epidermal differentiation disorders (EDDs, a.k.a. ichthyosis and palmoplantar keratoderma) are severe heritable skin conditions characterized by localized or generalized skin scaling and erythema.</p><p><strong>Objectives: </strong>To identify novel genetic variants causing palmoplantar keratoderma (PPK) and progressive symmetric erythrokeratoderma (PSEK) phenotypes.</p><p><strong>Methods: </strong>We performed whole exome sequencing in a large EDD cohort including PPK and PSEK phenotypes to identify novel genetic variants. We investigated the variant consequence using in silico predictions, assays in patient keratinocytes, high-resolution spatial transcriptomics, and quantitative cytokine profiling.</p><p><strong>Results: </strong>We identified three unrelated kindreds with autosomal dominant transmission of heterozygous SLURP1 variants affecting the same amino acid within the signal peptide (c.65C>A, p.A22D, and c.65C>T, p.A22V). One (p.A22V) had isolated PPK, and two others (p.A22D) had PSEK and PPK. In silico modeling suggested that both variants alter pro-SLURP1 cleavage, appending two amino acids to the secreted protein, which we subsequently confirmed with mass spectrometry. In patient keratinocytes we found increased differentiation-induced SLURP1 expression and secretion compared to healthy control cells. Spatial transcriptomics revealed increased NF-κB signaling and innate immune activity which may contribute to epidermal hyperproliferation in dominant SLURP1-PPK/PSEK.</p><p><strong>Conclusions: </strong>Our results expand the phenotypic spectrum of EDD due to SLURP1 pathogenic variants. While autosomal recessive Mal de Meleda is due to biallelic loss-of-function SLURP1 variants, our finding of autosomal dominant SLURP1 pathogenic variants in kindreds with PPK and PSEK suggests a novel mechanism of action. We found that heterozygous p.A22V and p.A22D SLURP1 variants append two amino acids to secreted SLURP1, increase differentiation-induced SLURP1 expression and secretion, and upregulate NF-κB signaling in PSEK cases.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Press play for impact: enhancing BJD article appeal through video.","authors":"John A McGrath","doi":"10.1093/bjd/ljaf044","DOIUrl":"https://doi.org/10.1093/bjd/ljaf044","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-reported outcome measures are highly needed for patients with skin of colour with atopic dermatitis.","authors":"Laura von Kobyletzki, Åke Svensson","doi":"10.1093/bjd/ljaf043","DOIUrl":"https://doi.org/10.1093/bjd/ljaf043","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the complex pathogenesis of hidradenitis suppurativa.","authors":"John W Frew","doi":"10.1093/bjd/ljae238","DOIUrl":"https://doi.org/10.1093/bjd/ljae238","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS) is a complex inflammatory disease, with rapid advances being made in our understanding of the complex immunological pathogenesis of the condition. New insights into the genomic landscape of HS have identified a number of genes that contribute to the development of HS in a polygenic manner, contributing to inflammatory dysregulation and alterations in epidermal stem cell fate in the follicular unit. These genomic variations can explain unique aspects of the disease such as the development and presence of epithelialized tunnels and abnormalities in wound healing. From genetic and translational studies, it is likely that these genetic alterations predispose to an innate immune dysregulation that can be triggered through sex hormone-responsive transcription factors with hormonal changes such as puberty, pregnancy and the menstrual cycle. The role of sex hormones in HS also has direct effects upon the development and maturation of inflammatory cells such as monocytes, which has the potential to explain differential patient response to treatments such as interleukin-23 antagonism. The role of adipose tissue as an active immunological organ also plays a role in the immune dysregulation seen in the disease. Fibrotic tissue and immunologically active fibroblasts play a significant role in the perpetuation of inflammation and development of adaptive immune dysfunction in the disease. The cutaneous and gut microbiomes play significant roles in the activation of innate immunity, although conflicting data exist as to their central or peripheral role in disease pathogenesis. Overall, our understanding of disease pathogenesis in HS is moving toward a more nuanced, complex paradigm in which patient heterogeneity in presentation and immunological characteristics are moving closer to the identification of therapeutic biomarkers to guide therapeutic modalities in the management of this burdensome condition.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":"192 Supplement_1","pages":"i3-i14"},"PeriodicalIF":11.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging genotypes and phenotypes to implement precision medicine in hidradenitis suppurativa management.","authors":"Lynn Petukhova, Annelise Colvin, Nicole D K Koerts, Barbara Horváth","doi":"10.1093/bjd/ljae399","DOIUrl":"10.1093/bjd/ljae399","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with many unmet needs. It is characterized by significant clinical heterogeneity, which suggests that a diagnosis of HS captures multiple distinct disease entities and that research aimed at identifying medically relevant HS subtypes will improve its management. Precision medicine is an approach to disease management that uses information encoded in a patient's genome, and operationalized in clinical presentations and drug responses, to identify disease subtypes. Prior research aimed at identifying HS subtypes has largely focused on phenotypic classifications derived from clinical features of cutaneous lesions. Limitations of existing HS taxonomies emphasize a need for a more nuanced understanding of disease subtypes. Evidence that has emerged from initial genetic studies of HS suggests the presence of at least three HS subtypes, each of which has different clinical implications in terms of disease risks and drug responses. These preliminary findings are instructive in terms of expanding our definitions of HS phenotypes to not only include characteristics of skin lesions, but also disease comorbidities and molecular and cellular phenotypes. Here we provide a comprehensive review of HS phenotype and genotype knowledge, and propose a strategic framework for implementing precision medicine in HS management. Future research should focus on expanding phenotype assessments to include data on multiple scales. Iterative research designs performed with phenotype and genotype data from large diverse cohorts are needed to rigorously define clinically relevant HS subtypes.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":"192 Supplement_1","pages":"i22-i29"},"PeriodicalIF":11.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An evolutionary tale on clinical trials in hidradenitis suppurativa.","authors":"Christopher J Sayed, Rayad B Shams, Bria Midgette, Amit Garg","doi":"10.1093/bjd/ljae318","DOIUrl":"https://doi.org/10.1093/bjd/ljae318","url":null,"abstract":"<p><p>The therapeutic pipeline for moderate-to-severe hidradenitis suppurativa (HS) is robust. Successes and lessons learned have led to improvements in trial designs aimed at avoiding prior pitfalls, as well as high placebo response in HS, which remains a fundamental threat to drug development. Herein, we review the evolutions in HS trials over the last 20 years with respect to overall design, sample size, diversity in enrolment, inclusion criteria, concomitant medications, rescue therapy, endpoints and statistical design analysis plans. Areas of focus that merit future consideration are also highlighted.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":"192 Supplement_1","pages":"i15-i21"},"PeriodicalIF":11.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}