Clinical, Cosmetic and Investigational Dermatology最新文献

Background: Acne vulgaris is common and often accompanied by depression, but their linking mechanisms remain unclear. Metabolomic profiling helps identify biomarkers and perturbed pathways, so this study explores metabolic associations/pathways in acne comorbid with depression via untargeted metabolomics.

Methods: Seventy-four acne patients were grouped by Patient Health Questionnaire-9 (PHQ-9) scores (≥10: depressive, n=21; <10: non-depressive, n=53). Their plasma was pretreated with cold methanol/acetonitrile, analyzed via Agilent 1290 Ultra-High Performance Liquid Chromatography (UHPLC)-AB Triple TOF 6600 Liquid Chromatography-Mass Spectrometry (LC-MS). Data were processed by XCMS; metabolites annotated via Human Metabolome Database (HMDB)/METLIN. Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used.

Results: We identified differential metabolites using Fold Change (FC) analysis combined with statistical significance testing, defining those with FC > 1.5 (upregulated) or FC < 0.67 (downregulated) and p < 0.05 as significant. Volcano plots and hierarchical clustering heatmaps clearly visualize these metabolites, showing distinct clustering patterns that distinguish the two groups. OPLS-DA modeling further revealed 24 key differential metabolites (VIP > 1 and p < 0.05), including 16 in positive ion mode (eg, hypoxanthine, taurine, L-tryptophan) and 8 in negative ion mode (eg, L-ascorbic acid, palmitic acid). Notably, Clustering patterns aligned with these metabolites (eg, upregulated hypoxanthine, downregulated L-ascorbic acid), confirming reliable differences. KEGG annotated 41 core pathways, with protein digestion and absorption (lowest p-value, annotated with 7 key amino acids) as a top-ranked pathway. Five amino acid metabolism-related pathways were upregulated, indicating enhanced amino acid turnover in acne patients with depression; all metabolites in the protein digestion and absorption pathway were also upregulated in this group.

Conclusion: Hypoxanthine, taurine and branched-chain amino acids may be biomarkers for acne-depression comorbidity. Protein digestion/absorption could be a new prognostic marker/therapeutic target, with metabolic-neuroendocrine imbalance underlying the comorbidity.

Background: Previous studies have indicated an association between alopecia and sleep characteristics, but the causality is not clear. This study aimed to investigate the potential causal relationship between four sleep traits (morningness, sleep duration, insomnia, daytime napping) and four subtypes of alopecia (alopecia areata, androgenic alopecia, scarring, and other non-scarring alopecia).

Methods: A bidirectional mendelian randomization (MR) analysis based on genome-wide association studies (GWAS) data was employed to examine the causal relationship between alopecia and sleep characteristics. Sample sizes ranged from 209 to 452,633 participants for different traits. Various analytical approaches, including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger and Weighted Mode were employed. Instrumental variables were selected based on conventional significance thresholds (P < 5 × 10^-8 for sleep traits) and structured criteria for alopecia. A Bonferroni correction was applied to account for multiple testing. Sensitivity analyses, including Cochran's Q, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods, were subsequently conducted to affirm the robustness of the findings.

Results: IVW method suggested causal associations between genetically predicted insomnia and a higher risk of alopecia areata (OR (95% CI) = 3.88 (1.5-10.04), P = 0.01), genetically predicted alopecia areata and morningness (OR (95% CI) = 1.0102 (1.0005-1.0201), P = 0.04), as well as genetically predicted non-scarring alopecia and reduced sleep duration (OR (95% CI) = 0.9881 (0.9767-0.9997), P = 0.04). However, these associations did not survive multiple testing correction. Cochran's Q test revealed heterogeneity in the analysis between scarring alopecia and daytime nap (Q = 39.29, P = 0.01), indicating potential variability in the genetic effects across different SNPs. Based on MR-PRESSO and leave-one-out analyses, outliers were removed, revealing no evidence of horizontal pleiotropy in this study.

Conclusion: This MR study suggests potential bidirectional causal associations between alopecia and sleep characteristics. However, the findings should be interpreted cautiously due to multiple testing considerations. Future work should investigate mechanisms and generalize findings across populations.

Purpose: Actinic keratosis is a highly prevalent precancerous skin condition and a major risk factor for cutaneous squamous cell carcinoma with a significant risk of malignant transformation. Despite its clinical importance, the causal role of immune factors, especially regulatory T (Treg) cells, in actinic keratosis pathogenesis remains unclear. A two-sample Mendelian Randomization (MR) approach was employed to investigate the potential causal link between distinct characteristics of Treg cells and the likelihood of developing actinic keratosis.

Patients and methods: The analysis utilized publicly available genetic data on 167 Treg cell traits and actinic keratosis risk. The Inverse Variance Weighted (IVW) method was the primary analytical approach, supported by MR-Egger, weighted median, and weighted mode analyses. Sensitivity of the findings was assessed through Cochran's Q test, MR-Egger analysis, the MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out tests.

Results: The IVW analysis revealed a significant association between resting Treg cell activity and actinic keratosis (OR: 0.9997, p = 0.0420). Additional significant associations included CD39+ resting Treg percentage of CD4 Tregs (OR: 0.9998, p = 0.0123), CD28- double negative (DN) Treg percentage (OR: 0.9995, p = 0.0359), and CD28+ CD45RA- CD8dim Tregs (OR: 1.0002, p = 0.0312). No significant associations were found in supplementary analyses, but sensitivity tests confirmed the reliability of the results.

Conclusion: This study suggests a potential causal relationship between certain Treg cell traits and the risk of actinic keratosis, indicating that further research is needed to clarify the underlying mechanisms of this association.

Leishmaniasis is a complex disease caused by Leishmania parasites and transmitted through the bite of infected sandflies, that is classified into cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). The increase in international travel has resulted in cases of leishmaniasis emerging in nonendemic regions, often creating challenges in diagnosis. We report a case of presumptive MCL and VL in a 20-year-old female who complained of multiple skin rashes on the face and body, accompanied by erosions on the lips and eyes. A physical examination showed erosions on the eyes, lips, vulva, and "volcanic" noduloulcerative skin lesions covered with adherent crusts on the face, neck, upper and lower extremities. A biopsy of the skin lesion revealed structures resembling Leishman-Donovan bodies, then the diagnosis of MCL was established. The patient was given 200 mg/day of itraconazole. On the 12th day of itraconazole treatment, the patient experienced shortness of breath and was hospitalized in the Internal Medicine Department. The laboratory examination showed anemia, thrombocytosis, elevated C-reactive protein, and elevated erythrocyte sedimentation rate levels. Computed tomography of the thorax revealed ground-glass opacity, suggestive of lung inflammation. Bone marrow aspiration showed features of hemophagocytic lymphohistiocytosis, and abdominal ultrasound revealed hepatomegaly. The patient was subsequently diagnosed with VL and was treated with amphotericin B. Unfortunately, the patient died due to respiratory failure. Diagnosing leishmaniasis in nonendemic countries is challenging due to the lack of diagnostic tools to identify the protozoa. Dermatologists must recognize clinical signs, be familiar with supportive examinations, and proficiently treat suspected leishmaniasis.

Introduction: The number of anti-cellulite therapies has been increasing steadily, as cellulite is an undesirable cosmetic defect affecting approximately 90% women worldwide. Despite this plethora of treatments, an objective method to enable their efficacy assessment is yet to be established.

Purpose: The aim of the study was to assess the usefulness of high frequency ultrasonography for evaluating the effectiveness of anti-cellulite therapy.

Patients and methods: Eighty-four women aged 21-66 years with cellulite were randomised to one of 3 groups to receive one of three anti-cellulite treatments - ALIDYA™ mesotherapy treatment [Group 1, G1], cellulite-reducing body wrap treatment [Group 2, G2] or Endermologie^® [Group 3, G3]. All measurements and ultrasound assessments were carried out at baseline and on day 14-18 following treatment completion at the same body location and using identical ultrasound scanner settings.

Results: A significant reduction in subcutaneous tissue thickness, skin echogenicity and surface area of fat protrusions at the dermal-subcutaneous junction was demonstrated. There was a significant reduction of dermal thickness G2 and G3, but not in G1. Reduction in thigh circumference and BMI was also statistically significant in each group. Correlations were demonstrated between cellulite severity and the surface area of fat protrusions at the dermal subcutaneous junction and subcutaneous tissue thickness. The participants in G3 reported highest satisfaction with treatment outcomes.

Conclusion: The present study demonstrated that high frequency ultrasound enables efficacy assessment of anti-cellulite treatments and, as a reliable, available and easy to use assessment method, it has a potential to become a common aspect of daily clinical practice. Further research is warranted to develop a uniform assessment protocol and standards.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with skin barrier disruptions and heightened T helper (Th) 2-mediated inflammation. Dupilumab, a monoclonal antibody targeting interleukin-4 and -13 pathways, has shown efficacy in treating AD and other type 2 inflammatory diseases. However, its safety and effectiveness in special populations (SP) like kidney transplant recipients, cancer patients, and individuals with neurological conditions remain unclear.

Materials and methods: This retrospective case series includes 12 representative cases of SP treated with dupilumab, featuring cases of a kidney transplant recipient, a metastatic melanoma patient, a non-functioning pituitary adenoma patient, and an individual with multiple sclerosis (MS). Clinical data were collected, and outcomes were assessed using various indices.

Results: Dupilumab provided significant AD symptom improvement across all cases, with no adverse effects or recurrence of underlying conditions.

Conclusion: Dupilumab shows promise for managing AD in SP, but careful monitoring and further research are necessary to address safety concerns and optimize treatment strategies. Larger studies with longer follow-ups are needed to fully evaluate its safety and efficacy in SP and those with comorbidities. These findings support the need for personalized treatments and ongoing research to enhance outcomes in patients with complex medical histories.

Purpose: The purpose of this study is to investigate the role of Prox1 in the progression of cutaneous melanoma (CMM) and its relationship with lymphatic metastasis.

Methods and results: By analyzing the data from the Cancer Genome Atlas (TCGA), we found that the expression of Prox1 and LYVE1 was significantly upregulated in the metastatic melanoma group. Additionally, elevated levels of Prox1 were associated with shorter survival times. Correlation analysis demonstrated a significant relationship between Prox1 and markers associated with lymphangiogenesis, including LYVE1, FLT4, FOXC2, and ANGPT2. A clinical study involving 32 cases of CMM was conducted to analyze Prox1 expression and its relationship with lymphangiogenesis and clinicopathological characteristics. Research revealed that Prox1 was expressed significantly higher in patients with lymph node (LN) metastasis and in those classified as stage 3C-4. Additionally, the density of lymphatic vessels(LVD) in the LN metastasis group and the stage 3C-4 group was markedly higher than in the group without lymph node metastasis and in the stage 0-3B group. Furthermore, Breslow thickness was found to correlate with both Prox1 expression and LVD. Prox1-positive expression was associated with increased LVD. Further investigation was conducted on the role of Prox1 in the CMM cell line A375 and its derived exosomes. Exosomes were collected from CMM^nc and CMM^shProx1 to verify the changes in Prox1 expression, respectively. It was observed that the proliferation, migration, and tube formation abilities of human lymphatic endothelial cells(HLECs) diminished with the downregulation of Prox1. Additionally, VEGFR3 activation was reduced in HLECs following the reduction of Prox1.

Conclusion: Prox1 played an important role in promoting cell proliferation, migration, and lymphangiogenesis, which is related to tumor metastasis and poor prognosis. These results indicated the potential importance of Prox1 as a biomarker, which is expected to lead to the development of a new insight for anti-tumor therapy.

Objective: Acute Generalized Exanthematous Pustulosis (AGEP) is a rare but potentially life-threatening cutaneous adverse drug reaction. Due to its poor clinical outcomes and unclear pathogenesis, this study aimed to systematically evaluate the drug-related risk factors for AGEP using data from the FDA Adverse Event Reporting System (FAERS).

Methods: This real-world, retrospective pharmacovigilance study analyzed all AGEP-related reports submitted to the FAERS database between Q1 2004 and Q4 2024. Disproportionality analysis was performed using reporting odds ratios (RORs), with Bonferroni-adjusted p-values to identify high-risk drugs. Drugs identified by univariate analysis were further evaluated through LASSO regression and multivariable logistic regression to determine risk factors associated with AGEP.

Results: A total of 6,880 AGEP cases were identified, with a predominance of female patients (54.5%) and a median age of 59 years. Disproportionality analysis revealed 148 drugs with a significant signal for AGEP, mainly including antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and antivirals. LASSO and multivariate logistic regression identified 17 drugs as risk factors for AGEP, including ceftriaxone (OR = 49.87), pantoprazole (OR = 31.39), and hydroxychloroquine (OR = 28.38). The model showed moderate predictive accuracy with an AUC of 0.69.

Conclusion: This study identified multiple drug classes significantly associated with AGEP using FAERS-based adverse event data. The findings highlight a higher susceptibility in middle-aged and younger populations and underscore the importance of enhanced monitoring for high-risk medications. Given the inherent limitations of spontaneous reporting systems, further prospective studies are needed to confirm these associations and explore underlying mechanisms.

Patients with erythrodermic psoriasis (EP) complicated by end-stage renal disease (ESRD) requiring hemodialysis are extremely rare in clinical practice, and treatment options for this specific population remain highly limited. Herein we report a case of an EP patient with ESRD, in whom treatment with an interleukin-17 (IL-17) inhibitor secukinumab not only rapidly alleviated erythrodermic symptoms but also resulted in a certain degree of improvement in renal function. At the 7-month follow-up, the patient maintained skin lesion clearance with no deterioration in renal function-a finding that has not been consistently documented in previous literature. This case suggests that for patients with psoriasis complicated by kidney disease IL-17 inhibitors may serve as a potentially favorable therapeutic option.

Cutaneous fibrosis - including hypertrophic scars and keloids - arises when immune, epithelial, and stromal signals fail to re-equilibrate after injury. Langerin⁺ dendritic cells (DCs) - epidermal Langerhans cells and dermal cDC1 - sit at the center of this process. These DC subsets generate latent transforming growth factor-β1 (TGF-β1) that keratinocyte integrins αvβ6/αvβ8 locally activate, creating an epidermal "cytokine gate" that restrains immunity in homeostasis yet seeds fibrosis when overdriven. Downstream, active TGF-β1 cooperates with mechanosensitive YAP/TAZ to drive fibroblast activation and matrix stiffening, while immune skewing (Th2/Th17/Treg and M2 macrophages) sustains a pro-fibrotic milieu. We synthesize how epithelial integrins, DC programs, and fibroblast mechanotransduction converge on TGF-β1; compare normal wound resolution with hypertrophic scar and keloid; highlight insights from single-cell and spatial omics; and outline therapeutic strategies targeting the αv integrin-TGF-β1 axis, YAP/TAZ, and immune cues. Framing cutaneous fibrosis through a DC-centric lens clarifies testable hypotheses and points toward mechanism-guided, combinatorial therapies.