Clinical, Cosmetic and Investigational Dermatology最新文献

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex etiology involving genetic and immune factors. Emerging evidence suggests that epigenetic age acceleration, measured by DNA methylation clocks, may contribute to immune dysregulation and aging-related processes. However, the causal link between epigenetic age acceleration and AD remains unclear.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between epigenetic age acceleration and AD. Summary statistics were obtained from the FinnGen consortium (394,476 AD cases and 421,381 controls) and a large genome-wide association study meta-analysis of epigenetic age acceleration in 34,710 European participants. Genetic instruments were constructed for four widely used epigenetic clocks: HannumAge, HorvathAge, PhenoAge, and GrimAge. Causal estimates were primarily derived from inverse variance weighted analysis, complemented by MR-Egger regression, weighted median, and weighted mode approaches. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out tests.

Results: Genetically predicted AD was positively associated with HannumAge acceleration (IVW, p = 0.046, 95% CI: 0.003-0.276), with no evidence of heterogeneity or pleiotropy. No significant associations were observed between AD and HorvathAge, PhenoAge, or GrimAge. Reverse MR analysis did not reveal a causal effect of epigenetic age acceleration on AD. Sensitivity analyses confirmed the robustness of the findings.

Conclusion: This study provides genetic evidence that AD is causally related to acceleration of HannumAge, suggesting a potential role of immune system aging in AD pathogenesis. These findings highlight epigenetic aging as a novel perspective in dermatology and support further research into the mechanisms linking AD, inflammaging, and biological aging. Future studies in diverse populations and mechanistic experiments are warranted to validate and expand upon these results.

Purpose: Large and balanced datasets are required to train artificial intelligence (AI) algorithms but are often difficult to acquire using clinical dermatologic photographs. We aimed to develop a new diffusion-based generative AI algorithm that generates patient photographs with modifiable details, thereby creating large and balanced datasets for neural network training. The newly developed model was tested using lateral canthal lines, a common patient's reason for seeking treatment.

Patients and methods: Five hundred and sixty-six photographs of the lateral oblique face of graded by certified dermatologists according to the severity of lateral canthal lines. We developed a zero-shot and few-shot image generation model that adds structured compositional labels as control variables to the diffusion model. This allows us to create synthetic images from original photos while adjusting the severity of lateral canthal lines with only a few examples. The generated images were used to train a convolutional neural network (CNN) with ResNet-34 backbone for classifying the grade of lateral canthal lines.

Results: We successfully generated 10,500 patient images similar to the original photographs with different grades of lateral canthal lines. The accuracy (82% vs 91%) and the area under the receiver operating characteristic curve (0.935 vs 0.981) of the classification CNN remarkably improved after training with the new dataset containing generated images.

Conclusion: The compositional zero-shot and few-shot generation model is able to generate images similar to original clinical photographs, and the features of the images can be modified to match the needs of the specific task, allowing researchers to create a larger and more balanced dataset to improve neural network training outcomes. This is especially important in dermatology, where large-scale clinical photographs are difficult to acquire for machine learning. The results of this study are limited by low patient diversity and a lack of external validation.

Background: Non-melanoma skin cancer (NMSC) poses a significant health burden to the elderly globally. This study seeks to comprehensively assess the burden of NMSC among elderly adults in various regions and countries worldwide, covering the time frame from 1990 to 2021.

Methods: Using data from the Global Burden of Disease (GBD) 2021 study, we analyzed global trends in NMSC incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Joinpoint regression was used to evaluate temporal trends, and an Age-Period-Cohort (APC) model was applied to assess underlying influences. Future projections were made using the Bayesian Age-Period-Cohort (BAPC) model.

Results: Data indicates that among all assessment metrics, both the number of cases and age-standardized rates are higher in males than in females, suggesting a more pronounced increase in the disease burden of NMSC among men. Concurrently, the disease burden is significantly higher in the elderly population compared to younger age groups. Across the 21 GBD regions worldwide, the disease burden is heaviest in high-income North America, particularly evident in age-standardized incidence rates (ASIR): from 395.30 (336.70-456.10)/100,000 (95% UI) in 1990, it rose to 1251.80 (1158.40-1341.20)/100,000 (95% UI) in 2015. Additionally, the disease burden and mortality rates in Australasia and Western Europe were generally higher than in other regions. East Asia exhibited a high annual estimated percentage change (EAPC) in age-standardized incidence of 7.1 (6.2-7.9) (95% CI), indicating that NMSC in this region is undergoing a rapid rise, thereby increasing the urgency for prevention and control.

Conclusion: From 1990 to 2021, the global burden of NMSC has increased significantly. Elderly populations in various countries with high Standardized Disease Index values are facing a substantial disease burden.

Background: Head and neck dermatitis (HND) is a recalcitrant subtype of atopic dermatitis (AD). Despite conventional therapies, including topical corticosteroids, calcineurin inhibitors, and biologics such as dupilumab, many patients remain refractory to treatment. Janus kinase (JAK) inhibitors, such as abrocitinib, offer a novel therapeutic approach targeting multiple inflammatory pathways implicated in HND.

Purpose: To evaluate the efficacy of abrocitinib in refractory HND and compare its effectiveness with other JAK inhibitors (upadacitinib, baricitinib).

Patients and methods: We retrospectively analyzed three patients with HND treated with abrocitinib (100-200 mg/day). Treatment response was assessed using Eczema Area and Severity Index (EASI) scores and the Investigator's Global Assessment (IGA) of the head and neck. A PubMed literature review was conducted to compare abrocitinib with other JAK inhibitors in HND.

Results: All three abrocitinib-treated patients achieved rapid skin lesion relief within 1-2 weeks and near-complete lesion clearance by Week 8. These results are consistent with clinical trial data highlighting the strong early efficacy of JAK inhibitors for head and neck lesions. While abrocitinib and upadacitinib demonstrated robust clinical responses, baricitinib showed comparatively weaker efficacy in the head and neck.

Conclusion: JAK inhibitors, particularly abrocitinib and upadacitinib, may be considered as first-line therapies for refractory HND. They offer both rapid symptom relief and sustained efficacy.

Background: Upper eyelid rejuvenation with monopolar radiofrequency (MRF) is a minimally invasive option for patients with eyelid laxity. However, outcomes vary widely, and conventional evaluation methods rely on subjective photographic assessment and physician judgment, which are prone to observer bias and limited reproducibility. This lack of standardized, objective outcome measures complicates treatment planning and patient counseling.

Objective: To develop and validate a deep learning-based automated scoring system for predicting and assessing clinical outcomes following eyelid MRF treatment.

Methods: A retrospective, multicenter study of 50 patients (47 women, 3 men) treated with eyelid MRF was conducted. Pre- and post-treatment images were used to train a hybrid model combining a convolutional neural network (CNN) and U-Net architecture. The U-Net performed periorbital segmentation, while the CNN generated quantitative improvement scores. Ground truth ratings were provided by five board-certified dermatologists. Model performance was evaluated using root mean square error (RMSE) and mean absolute percentage error (MAPE).

Results: The CNN-U-Net model achieved a RMSE of 0.4 and a MAPE of 0.08, with predicted scores closely aligning with dermatologist evaluations. No significant differences in predictive accuracy were observed across patient age or sex subgroups.

Conclusion: This proof-of-concept study demonstrates the feasibility of an automated deep learning-based scoring system for eyelid MRF outcomes. By providing objective, consistent, and reproducible evaluations, the system has the potential to enhance patient counseling, guide individualized treatment planning, and enable standardized research comparisons across clinics. Larger and more diverse datasets with longer follow-up are needed for further validation.

Lichen amyloidosis (LA), a form of primary localized cutaneous amyloidosis, is often refractory to conventional therapies. We report two LA patients who showed inadequate response to 100mg abrocitinib daily but achieved significant improvement with dupilumab. A 29-year-old woman and a 31-year-old man with chronic, pruritic LA lesions experienced rapid itch relief with abrocitinib but minimal skin improvement after 4-6 months, along with adverse effects, such as diarrhea, acneiform eruptions, and herpes simplex reactivation. After switching to dupilumab, both patients maintained pruritus control and exhibited marked lesion regression, with no side effects. While abrocitinib effectively alleviated itch, dupilumab demonstrated superior lesion resolution, possibly due to its dual inhibition of IL-4 and IL-13 signaling, which may more comprehensively address the underlying inflammation in LA. This is the first report of dupilumab's efficacy after low dose abrocitinib failure in LA, suggesting its potential as a therapeutic option for refractory cases. Further studies are needed to confirm these findings.

Background: Drug-induced skin pigmentary changes are an underrecognized yet clinically significant type of adverse event (AE). Despite growing awareness, labeling for many implicated drugs remains incomplete.

Objective: To conduct a comprehensive pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database (2010-2024) to identify drugs associated with skin hyperpigmentation, hypopigmentation, or both, and to explore their clinical implications and repurposing potential.

Methods: The study analyzed case reports from the FAERS database using the OpenVigil 2.1 platform. Pigmentary AEs were identified based on the MedDRA Preferred Terms "skin hyperpigmentation" and "skin hypopigmentation." To ensure consistency, all drug names were standardized to their generic forms using the DrugBank database before inclusion in the analysis. Disproportionality analysis was performed using the Reporting Odds Ratio (ROR) to detect significant associations between drugs and pigmentary AEs.

Results: A spectrum of agents demonstrated strong associations with pigmentary changes. Minocycline (ROR 115.66) and setmelanotide (ROR 1506.82) showed high RORs for hyperpigmentation, while triamcinolone (ROR 37.20) and ribociclib (ROR 60.20) were strongly linked to hypopigmentation. Several drugs, including dupilumab, tretinoin, and clobetasol, exhibited bidirectional pigmentary modulation. Notably, a substantial proportion of implicated drugs lacked labeling for these effects.

Conclusion: This study identifies notable pigmentary AE signals associated with several commonly prescribed drugs. These findings emphasize the importance of early recognition and dermatologic monitoring during prolonged therapy. Considering the odds ratio and analysis results, the drugs found to be associated with hyperpigmentation or hypopigmentation warrant further investigation.

Background: Sun sensitivity is a significant factor influencing the risk of sunburn and skin cancer. Given that current assessments mainly depend on self-reported information, exploring objective biochemical indicators may provide complementary insights. The purpose of this research was to determine whether anion gap and albumin-corrected anion gap can function as objective and easily accessible biomarkers for sun sensitivity in US adults.

Methods: We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Survey collected between 2003-2006 and 2009-2018. Weighted logistic regression, restricted cubic splines, and subgroup analyses were conducted to examine the association between AG and ACAG and sun sensitivity.

Results: The analysis was conducted on a total of 17,739 participants. We found a positive correlation between both AG and ACAG with increased sun sensitivity (AG: OR = 1.04, 95% CI = 1.01-1.07, P = 0.012; ACAG: OR = 1.04, 95% CI = 1.01-1.07, P = 0.004). It was observed that participants in the highest quartile (Q4) of AG and ACAG presented with heightened sensitivity to sunlight (AG: OR = 1.23, 95% CI = 1.02-1.50, P = 0.034; ACAG: OR = 1.29, 95% CI = 1.07-1.57, P = 0.01). Subgroup analyses indicated a consistent trend across various subgroups.

Conclusion: Our study demonstrates that heightened levels of AG and ACAG are related to an elevated degree of sun sensitivity.

The autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) is a relatively novel clinical entity characterized by the emergence of autoimmune-like manifestations triggered by exposure to substances with immunostimulatory potential in genetically predisposed individuals. Such substances, called adjuvants, encompass infectious and toxic agents, substances utilized in the cosmetic industry, as well as in aesthetic and regenerative medicine. In this manuscript, we present a case of a 46-year-old female patient with multiple colored tattoos and a medical history of hypothyroidism and vulvar lichen sclerosus, who developed progressive musculoskeletal, neurological and cutaneous manifestations. Our study further emphasizes the critical need for differential diagnosis between ASIA syndrome and other immune-mediated pathologies, while advocating for enhanced clinical vigilance with thorough attention to the subjective examination, comprehensive review of prior medical conditions, and detailed assessment of potential exposure to adjuvants.

Purpose: The modified Ferriman-Gallwey score, currently used to clinically evaluate and quantify excessive hair growth in women with hirsutism, has limitations because of its subjective nature. Therefore, we aim to investigate whether we could quantify terminal hairs on the output of a digital microscope camera to improve the clinical evaluation of hirsutism.

Patients and methods: This feasibility cross-sectional study included 20 healthy men and 15 healthy women. Two independent researchers used a digital microscope camera to obtain photos of the upper lip and chin in all participants. The hair thickness (when ≥ 60 µm), number of terminal hairs and hair color were determined to indicate mean differences between men and women by an independent t-test. Additionally, intraclass correlation coefficients were determined to assess the inter-observer variability.

Results: The mean (standard deviation) number of terminal hairs on the upper lip was 27 (15) in men and 0 (1) in women. On the chin, men had a mean (standard deviation) of 29 (18) terminal hairs, compared to 0 (0) in women. This corresponds to mean differences of 27 hairs (range: 19-34) on the upper lip and 28 hairs (range: 19-39) on the chin between men and women. Minimal inter-observer variability was observed, particularly in visible light analyses (intraclass correlation coefficient: 0.998).

Conclusion: Digital microscopy with visible light may contribute to a more objective method for diagnosing hirsutism by the quantification of terminal hair. Future studies should focus on the applicability of this new method in women with hirsutism.