Clinical, Cosmetic and Investigational Dermatology最新文献

Purpose: Psoriasis is frequently associated with dyslipidemia, yet the role of specific unsaturated fatty acid (UFA) metabolic pathways in disease pathogenesis and treatment response remains poorly understood. This study aimed to characterize the landscape of UFA metabolic reprogramming in psoriasis and evaluate its clinical relevance for predicting response to biologic therapy.

Patients and methods: We performed an integrated multi-omics analysis incorporating transcriptomic data from human psoriatic lesions, single-cell RNA sequencing, and lipidomic profiling. Gene set variation analysis (GSVA) was used to evaluate UFA pathway activity. Logistic regression and LASSO were employed for biomarker selection and predictive modeling.

Results: We identified eight significantly dysregulated UFA metabolic pathways in psoriatic lesions, six of which were associated with key pathogenic processes in psoriasis. All pathways were reversibly modulated by biologic agents targeting TNF-α, IL-12/23, and IL-17A. We derived a three-gene biomarker signature (PLA2G4D, PLA2G4A, and FADS2) that robustly predicts response to IL-12/23 inhibition prior to treatment initiation (AUC = 0.902). Single-cell RNA sequencing revealed keratinocytes as the primary cellular contributors to UFA metabolism and identified an expanded PLA2G4D-high keratinocyte subpopulation in psoriatic skin, which was associated with the accumulation of Lysophosphatidylcholine (LysoPC) and Lysophosphatidylethanolamine (LysoPE).

Conclusion: Our findings elucidate the pathway-level metabolic basis of psoriasis inflammation and provide a clinically applicable tool for predicting response to biologic therapy. The results highlight the importance of UFA metabolic reprogramming in psoriatic pathogenesis and offer new avenues for treatment personalization.

Background: Emerging evidence suggests that protein palmitoylation plays a critical role in regulating cellular signaling, yet its involvement in skin aging remains largely unexplored. Additionally, the epigenetic regulation of palmitoylation-related genes in age-related dermal changes has not been systematically studied. This research aimed to investigate the causal relationship between palmitoylation genes, DNA methylation, and facial skin aging using Mendelian randomization (MR) methods.

Methods: We performed an integrated genetic analysis using two-sample MR and summary-data-based MR (SMR) to identify palmitoylation-related genes with a potential causal role in facial skin aging. For significant genes, we further conducted a two-step MR mediation analysis to investigate whether DNA methylation influences facial aging by altering these palmitoylation genes, complemented by sensitivity tests to evaluate the robustness of findings. Analyses utilized large-scale datasets, including facial aging genome-wide association study (GWAS) summary statistics (n = 423,992), gene expression data from eQTLGen, and methylation profiles from GoDMC.

Results: The initial two-sample MR identified a significant positive association between ZDHHC17 expression and facial aging risk (p = 0.0112). SMR analysis confirmed the link between ZDHHC17 transcription and facial aging traits. Further mediation analysis revealed that DNA methylation at cg23935522 positively regulates ZDHHC17 expression (p = 0.00188), indirectly increasing facial aging susceptibility (p = 0.0227). The mediation effect accounted for 25.29% of the total association between the methylation site and facial aging risk. Sensitivity analyses demonstrated no evidence of horizontal pleiotropy, and the MR-PRESSO global test showed no significant outliers for ZDHHC17. Heterogeneity tests showed consistent effect estimates across genetic instruments, supporting the robustness of the results.

Conclusion: Collectively, this study offers new insights into the molecular mechanisms of skin aging and highlights ZDHHC17 methylation as a potential biomarker or therapeutic target in age-related dermatological intervention.

The skin microbiome plays a vital role in maintaining skin homeostasis by regulating immune responses, preserving barrier integrity, and inhibiting pathogen colonization. This review systematically explores the mechanisms underlying its dysregulation in conditions such as acne, atopic dermatitis, psoriasis, and impaired wound healing, with a focus on key factors including microbial over colonization, diminished diversity, and host immune dysregulation. The influence of microbial metabolites, such as short-chain fatty acids and porphyrins, is also examined. We further evaluate emerging microbial-targeted therapeutic strategies, including live biotherapeutic products, skin microbiota transplantation, epigenetic and metabolic interventions, and precision antimicrobial polymers. These approaches aim to restore microbial balance rather than achieve broad-spectrum sterilization, representing a significant shift in the treatment paradigm for cutaneous diseases. In contrast to previous reviews, this article places special emphasis on the mechanisms of multi-organ interactions within the gut-skin axis and discusses the potential of integrating multi-omics technologies and artificial intelligence to advance the clinical translation of personalized microbial therapies, thereby providing a forward-looking perspective on the field.

Vitiligo is an autoimmune disease with a localized or generalized depigmentation in the skin, and characterized by psychological stress induced by unattractive appearance. Psychological stress induces alterations in immune cell populations through hormones and cytokines, however, the pathogenesis of psychological stress on vitiligo remains unclear. This review discussed the effects of psychological stress-derived hormones and cytokines including macrophage migration inhibitory factor, progesterone, glucocorticoids, estrogens, and norepinephrine on immunocytes including regulatory T cells, natural killer cells, dendritic cells, B cells, monocytes, and neutrophils. In addition, the review also explored the relationship between melanocytes and immune cells, as well as the conditions of several major animal models simulating the peripheral blood in human vitiligo. This review intended to provide better insights into the complex pathogenesis of vitiligo related to psychological stress, and developing new targets for the prevention and treatments of vitiligo.

Background: Pyoderma gangrenosum (PG) is a rare disease causing painful skin ulcers, typically starting with tender pustules that quickly develop into painful ulcers. Traditional treatments like glucocorticoids and immunosuppressants often have adverse effects and limited efficacy, making them unsuitable for all patients. Recent evidence shows that biological agents are more effective and safer, leading to increased acceptance. However, selecting the most suitable biological agent from the many available options remains a significant challenge for both physicians and patients.

Objective: To systematically review the treatment outcomes of two biologics: TNF (tumour necrosis factors)-α inhibitors and IL (interleukin) inhibitors in pyoderma gangrenosum.

Methods: A search of Pubmed was conducted on September 7, 2024. A total of 107 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

Results: A total of 139 patients were included. Ninety-two were treated with TNF-α inhibitors and 47 with IL inhibitors. The number of included cases and the efficacy are Infliximab (n=52, 88.4%), Adalimumab (n=23, 91.3%), Etanercept (n=13, 84.6%), Certolizumab (n=3, 66.6%), Golimumab (n=1, 100.0%), Anakinra (n=11, 100.0%), Canakinumab (n=7, 100.0%), Secukinumab (n=5, 40.0%), Brodalumab (n=3, 100.0%), Ixekizumab (n=1, 100.0%), Ustekinumab (n=12, 100.0%), Spesolimab (n=3, 100.0%), Guselkumab (n=2, 100.0%), Tildrakizumab (n=2, 100.0%), Risankizuma (n=1, 100.0%). Among them, 46.0% (n=64) achieved complete remission, including 47 (33.8%) who used TNF-α inhibitors and 17 (12.2%) with IL inhibitors. And the total effective rate of IL- inhibitors (93.6%) was higher than that of TNF-α inhibitors (88.0%), but had no statistical significance (p>0.05). However, it takes less time for IL inhibitors to reach partial remission or complete remission. Additionally, in infliximab group, the number of adverse events that occurred was large and varied.

Conclusion: Difference in effective rate shows no statistical significance between two kinds of agents. However, IL inhibitors demonstrate an advantage with shorter treatment cycles. Additionally, Infliximab has a wider range of side effects and should be used with caution.PROSPERO number: CRD42024608039.

Background: Cutaneous malignant melanoma (CMM) represents a substantial health burden for the elderly; however, data regarding its impact and epidemiology within this demographic remain scarce. This study aims to evaluate the global, regional, and national trends of CMM among individuals aged 60 and elderly from 1990 to 2021.

Methods: We retrieved data on the age-standardized incidence, prevalence, and mortality rates, and disability-adjusted life years (DALYs) of CMM among individuals aged 60 and above across 204 countries and territories from 1990 to 2021, sourced from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study 2021. We calculated the estimated annual percentage changes in age-standardized incidence and DALY rates of CMM, categorized by age, sex, and socio-demographic index (SDI), to quantify temporal trends. Additionally, we employed Spearman correlation analysis to examine the relationship between age-standardized rates and SDI.

Results: This study analyzed global trends in CMM from 1990 to 2021 using the GBD database. The findings indicate a significant increase in the incidence (EAPC=0.65, 95% CI: 0.33-0.96) and prevalence (EAPC=1.02, 95% CI: 0.64-1.41) of CMM, while a significant decreasing trend was observed for mortality (EAPC=-0.43, 95% CI: -0.57- -0.30) and DALYs (EAPC=-0.67, 95% CI: -0.82- -0.53). In 2021, high-income North America exhibited the highest prevalence of CMM but the lowest growth rate. In contrast, the Middle East and North Africa experienced the fastest growth rate, while Latin America also demonstrated a significant increase in prevalence. The growth rates of incidence and prevalence were notably higher among male patients compared to females, reflecting gender-specific behavioral differences. Furthermore, an analysis of the relationship between the burden of disease and the SDI for CMM across various regions from 1990 to 2021 revealed that the burden of disease in Australia significantly exceeded model predictions. The APC analysis indicated that the prevalence of CMM among elder population (≥60 years old) declined with age, but the overall disease burden continues to rise annually, demonstrating higher prevalence rates in later birth cohorts. Similar trends were observed for incidence, DALYs, and mortality.

Conclusion: This study reveals that the burden of CMM disease is rapidly increasing among populations residing at lower latitudes. The findings underscore the necessity for dynamic optimization of global prevention and control strategies, considering regional disparities.

Atopic dermatitis (AD) affects 5-20% of the global population, with moderate-to-severe cases frequently requiring systemic therapy. The introduction of Janus kinase inhibitors (JAKi) has transformed therapeutic options, warranting a comprehensive analysis of the evolving research landscape. This bibliometric and visualized review aimed to identify global research hotspots, collaboration networks, and influential contributors in JAKi-related AD research. Publications were retrieved from the Web of Science Core Collection (2014-2024) using the terms "(Janus kinase inhibitors OR JAK) AND (atopic dermatitis)". Of 797 publications identified, 776 met inclusion criteria. Bibliometric mapping and visualization were conducted with VOSviewer, Excel, and Draw.io. The United States produced the most publications (34%), followed by Germany (12.62%), Japan (11.87%), and China (8.5%). The Icahn School of Medicine at Mount Sinai and Oregon Health & Science University led institutional output, while Kyoto University demonstrated the highest citation impact (82.57 citations per publication). Among authors, Emma Guttman-Yassky (25 publications) and Eric Simpson (22 publications) were the most prolific. Journal of Dermatological Treatment and Journal of the European Academy of Dermatology and Venereology were the leading publishing journals, while The Journal of Allergy and Clinical Immunology was the most co-cited. The most frequently cited reference was Oetjen (2017), with 674 citations. Keyword analysis highlighted "atopic dermatitis", "JAK inhibitors", "upadacitinib", and "baricitinib" as central themes, with abrocitinib and biologics emerging as newer hotspots. This study provides an updated overview of global research activity on JAK inhibitors in AD, addressing knowledge gaps, collaboration patterns, and future directions in targeted therapy.

Background: Rosacea involves immune, neurovascular, and microbial factors, but its complex mechanisms are poorly understood, hindering effective treatment development. This study aims to examine research trends and significant contributions in the treatment of rosacea.

Methods: Publications related to rosacea treatment were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using VOSviewer, CiteSpace, and the R package "bibliometrix".

Results: By June 7, 2024, 1389 English-language publications published between 1970 and 2024 were identified for analysis. The leading research countries were the United States (446 articles) and China (149 articles), with the Central South University (95 articles) being the most productive institution. Key journals included Journal of the American Academy of Dermatology (impact factor = 12.8) and the British Journal of Dermatology (impact factor = 11). James Q. Del Rosso was identified as a major contributor (h-index = 20). Keywords cluster analysis revealed five prominent themes: 1) pharmacological treatment and clinical trials, 2) epidemiology and associated risk factors, 3) pathophysiology and pathogenesis, 4) skin barrier function and related dermatoses, and 5) laser and physical therapies. Representative terms of emerging trends include "pathogenesis", "pathophysiology", and "standard classification", suggesting increasing focus on immune dysregulation, neurovascular mechanisms, and microbiome-related pathways. These insights indicate that future rosacea treatment research may shift toward targeted, mechanism-based therapeutic strategies.

Conclusion: This study underscores the dynamic landscape of research in rosacea treatment, synthesizes current areas of emphasis, and forecasts future trends. Future developments in rosacea research may concentrate on integrating precision medicine approaches by linking molecularly defined pathogenic mechanisms with standardized classification systems, thereby facilitating targeted and multidisciplinary treatment strategies.

Background: Granular parakeratosis (GP) is a rare keratinization disorder. Recent studies have suggested a possible association with exogenous irritants such as benzalkonium chloride (BAK); however, the clinical features of related cases have not yet been systematically characterized.

Aim: To analyze the clinical features, histopathological findings, and treatment outcomes of patients with GP induced by BAK exposure, with the aim of enhancing clinical recognition and management of this etiological subtype of GP.

Methods: A single-center retrospective study was conducted on eight patients diagnosed with BAK-associated GP confirmed both clinically and histopathologically, who presented between June 2024 and June 2025. Demographic data, clinical manifestations, histopathological changes, and treatment outcomes were collected and analyzed.

Results: Among the eight patients, six were male, with ages ranging from 4 to 43 years; four were children. Lesions were primarily distributed over the groin, trunk, neck, and upper chest, all presenting as erythematous-brown patches with characteristic parchment-like scaling. Histopathological examination in all cases revealed parakeratosis and retention of basophilic granules within the stratum corneum. Following definitive diagnosis and cessation of BAK exposure, combined with the use of emollients, complete resolution of lesions was achieved within 2 weeks to 1 month.

Conclusion: BAK can induce GP, which presents with certain characteristic features, notably the presence of parchment-like scaling that serves as a valuable clue for differential diagnosis. Early identification and elimination of the causative irritant are key to effective treatment. Pediatric patients may be more susceptible, and the development of GP may be related to individual predisposition and cumulative BAK exposure, warranting further investigation.