Agarwal R, Parente E, Müller SM
… +9 more, Kappos EA, Dittmar T, Kunz M, Dodiuk-Gad RP, Asayag N, Gudjonsson JE, Mühleisen B, Contassot E, Navarini AA
Exp Dermatol
· 2025 Dec · PMID 41466489
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Darier disease (DD) is a rare genetic disorder caused by mutations in the ATP2A2 gene, resulting in calcium dysregulation and impaired keratinocyte adhesion. Due to the paucity of suitable models, understanding the molec...Darier disease (DD) is a rare genetic disorder caused by mutations in the ATP2A2 gene, resulting in calcium dysregulation and impaired keratinocyte adhesion. Due to the paucity of suitable models, understanding the molecular mechanisms of DD has been challenging. In this study, we developed a human epidermal organoid model derived from DD patient keratinocytes to investigate the molecular and phenotypic features of the disease. The model recapitulates key aspects of DD pathology, including acantholysis, desmosomal dysfunction and barrier disruption, with mislocalisation of desmosomal proteins. Furthermore, the transcriptomic landscape of DD organoids reflected broad perturbations in epidermal structure. Enrichment of pathways associated with epidermal development, cell adhesion, cell migration and keratinocyte differentiation underscored the multifaceted disruption of epithelial integrity and homeostasis that defines DD pathology. Our work demonstrates that epidermal organoids derived from patients with Darier disease are a valuable model for studying DD. They provide a platform to study complex genetic epidermal disorders and personalised drug screening.
Usovich M, Meisenheimer J, Rizvi M
… +7 more, Rypka KJ, Liu L, Warshaw EM, Gravely A, Lynch J, Westanmo AD, Goldfarb N
Exp Dermatol
· 2025 Dec · PMID 41416736
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Previous studies have demonstrated a higher prevalence of keratinocyte carcinomas (KC) on sun-exposed areas, particularly for squamous cell carcinoma (SCC) compared to basal cell carcinoma (BCC). Few studies in the Unite...Previous studies have demonstrated a higher prevalence of keratinocyte carcinomas (KC) on sun-exposed areas, particularly for squamous cell carcinoma (SCC) compared to basal cell carcinoma (BCC). Few studies in the United States (US) have compared the prevalence of BCC to SCC by anatomical location. The aim of this study was to determine the KC prevalence in a Midwestern US population standardised by relative tumour density (RTD) per anatomical area, which has not been previously reported in the US. Data was collected from Veterans Affairs' patients with biopsy-proven KCs from October 1999 to September 2020. KCs were divided into BCCs and SCCs. RTD was calculated by standardising frequency of occurrence in a location by body surface area. The proportion of BCCs to SCCs for each location was also analysed. A total of 31 663 KCs (17 776 BCCs and 13 887 SCCs) were identified in 10 933 patients, with the majority on the head and neck. BCCs were more likely overall on the trunk and upper arms than SCCs. SCCs were more common on the hands, forearms, genitals/perineum/perianal area, and ears. Both BCC and SCC occurred more frequently over sun-exposed areas when controlling for body surface area of the location. Higher proportions of BCCs were found on sun-protected areas when compared to SCCs. The relative preponderance of SCCs on the genitals/perineum/perianal area may be due to human papillomavirus.
Abnormal activation of keloid fibroblasts (KFs) within a hypoxic microenvironment is a hallmark of keloid pathogenesis. However, the precise molecular mechanisms by which hypoxia drives fibroblast dysfunction remain insu...Abnormal activation of keloid fibroblasts (KFs) within a hypoxic microenvironment is a hallmark of keloid pathogenesis. However, the precise molecular mechanisms by which hypoxia drives fibroblast dysfunction remain insufficiently understood. This study aimed to investigate the role of Stanniocalcin 2 (STC2), a hypoxia-responsive glycoprotein, in modulating keloid fibroblast behaviour under hypoxic conditions and to elucidate its upstream and downstream regulatory networks. We found the expression of STC2 was significantly upregulated in keloid tissues and primary KFs, with expression levels positively correlating with clinical severity, as assessed by the Vancouver Scar Scale. Mechanistically, hypoxia induced STC2 expression via hypoxia-inducible factor-1α. Functional assays revealed that STC2 silencing under hypoxia markedly reduced KF proliferation, migration and extracellular matrix remodelling, as evidenced by downregulation of fibrosis-associated markers including collagen I, α-SMA, MMP2 and MMP9. These inhibitory effects were accompanied by attenuation of ERK and AKT signalling pathway activation. Thus, targeting STC2 disrupts pro-fibrotic signalling and may represent a promising therapeutic strategy for the clinical management of keloid scars by modulating the aberrant hypoxic microenvironment.
Skin vascular endothelial cells (VECs) play a crucial role in regulating vascular function, orchestrating local immune responses, and contributing to the progression of immune-mediated inflammatory skin disorders. Despit...Skin vascular endothelial cells (VECs) play a crucial role in regulating vascular function, orchestrating local immune responses, and contributing to the progression of immune-mediated inflammatory skin disorders. Despite their importance, the shared and distinct features of VECs across various inflammatory skin conditions remain poorly understood. We analysed single-cell data from 94 skin samples, encompassing healthy individuals and patients with psoriasis, atopic dermatitis, and lupus erythematosus and established a comprehensive VEC atlas spanning multiple inflammatory skin diseases. Our results highlight both common and disease-specific features of VECs, particularly in immune cell activation, angiogenesis, metabolic processes, and intercellular communication. Notably, post-capillary VECs (cluster P) emerged as the most activated subpopulation, exhibiting significant enrichment in pro-inflammatory signalling pathways. Interestingly, cluster P showed distinct pseudotemporal relationships with different VEC clusters across different inflammatory conditions, suggesting disease-specific transcriptional state transitions. Besides, VECs employ both disease-specific ligand-receptor networks to recruit immune cells and remodel stromal niches, alongside conserved mechanisms preserving vascular-immune crosstalk across pathologies. Our study provides a detailed characterisation of VEC pathology in various forms of skin inflammation and offers novel insights into the role of vascular biology in the pathogenesis of skin diseases.
Williams SF, Andrew P, Brown K
… +5 more, Chittock J, Pinnock A, Poyner A, Cork MJ, Danby SG
Exp Dermatol
· 2025 Dec · PMID 41408887
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Advancing age is associated with an increasing prevalence of dry skin conditions such as xerosis, asteatotic eczema and atopic dermatitis (AD). Although broad changes in stratum corneum (SC) lipids and AD history have be...Advancing age is associated with an increasing prevalence of dry skin conditions such as xerosis, asteatotic eczema and atopic dermatitis (AD). Although broad changes in stratum corneum (SC) lipids and AD history have been implicated, age-related alterations in the SC lipidome within at-risk populations remain unclear. We characterised SC structure and lipidomic profiles in 58 adults with dry, eczema-prone skin across a wide age range. Assessments included visual dryness, biophysical properties (TEWL, capacitance, skin-surface-pH), irritant sensitivity, ATR-FTIR spectroscopy and lipidomic analysis through quantification of extracted SC lipids via mass spectrometry. Age correlated significantly with increased dryness (r = 0.46, p ≤ 0.0001) and reduced hydration (r = -0.42, p ≤ 0.0001). Spectroscopy revealed declines in total lipids (p < 0.0026), water (p < 0.0009), lipid esters (p < 0.0001) and carboxylates (p < 0.0004) with age. Among 1385 quantified lipid species, triacylglycerol (TAG) was most abundant; TAG 46:1;0 associated with dryness (r = -0.42, p ≤ 0.0001). Ceramides CER[AH] (p < 0.0001), CER[AP] (p < 0.0001), CER[AdS] (p = 0.042), CER[NP] (p = 0.031) and CER[NdS] (p < 0.0001) all significantly increased with age relative to protein. Notably, CER[NdS] species shifted towards shorter (16ºC) acyl chains (+2.23%, p = 0.01) and away from longer (24ºC) chains (-3.9%, p < 0.0001). The CER[NdS]/CER[NH] ratio correlated with age (r = 0.59, p < 0.0001), dryness (r = 0.36, p = 0.0006), and barrier integrity (r = 0.59, p < 0.0001) (all p ≤ 0.0006). Within an at-risk population, SC lipid levels change as the skin ages. These changes, especially an increase in short acyl chain NdS ceramides, were associated with the decline in skin barrier function and may help explain the increased prevalence of xerosis and the (re)emergence of eczema in later life.
Real-world data on the long-term effectiveness of dupilumab in moderate-to-severe atopic dermatitis (AD) remains limited, particularly concerning regional disparities in improvement and the outcomes of extended dosing in...Real-world data on the long-term effectiveness of dupilumab in moderate-to-severe atopic dermatitis (AD) remains limited, particularly concerning regional disparities in improvement and the outcomes of extended dosing interval regimens. To evaluate the anatomical region-specific responses to dupilumab and the long-term effectiveness under extended dosing-interval regimens. This retrospective cohort study included moderate-to severe AD patients treated with dupilumab. Eczema Area and Severity Index (EASI)-75/90, Numerical Rating Scale (NRS) ≤ 1, and regional EASI reductions were assessed at 6/12/18 months. Patients reaching EASI-75 switched to extended dosing (every 3/4 weeks), with long-term effectiveness and influencing factors evaluated. 108 patients were included. Percentage reductions in EASI scores from baseline at 4, 6 and 12 months were as follows: head/neck: 58.52%, 82.36% and 89.36%; trunk: 77.95%, 85.82% and 94.68%; upper limbs: 77.11%, 86.49% and 95.45%; and lower limbs: 66.34%, 84.03% and 90.34%, respectively. EASI-75/90 and NRS ≤ 1 responses increased over 18 months, reaching 100%/96.97% and 96.97% respectively. No significant differences in effectiveness were observed between the every-three-weeks and every-four-weeks dosing groups. Dupilumab demonstrates sustained, region-specific effectiveness in moderate-to-severe AD, with delayed but progressive improvement in head and neck region(s). Patients achieving EASI-75 with stable disease can safely transition to every-three-weeks or every-four-weeks dosing regimens.
Tranexamic acid (TXA), a well-known anti-fibrinolytic agent, has been proven effective in the treatment of hyperpigmentation, particularly melasma. Oestrogen is known as an important cause of melasma and has been reporte...Tranexamic acid (TXA), a well-known anti-fibrinolytic agent, has been proven effective in the treatment of hyperpigmentation, particularly melasma. Oestrogen is known as an important cause of melasma and has been reported to induce pigmentation through the oestrogen receptor or the G protein-coupled oestrogen receptor. Although various mechanisms by which TXA improves skin pigmentation have been reported, its effect on oestrogen (17β-estradiol, E2)-induced pigmentation has not yet been elucidated. In this study, we investigated the effect of TXA on melanogenesis induced by 17β-estradiol. Cell viability was assessed in primary human epidermal melanocytes treated with 17β-estradiol or TXA. The effect of TXA on pigmentation was evaluated by western blot analysis, measuring the protein levels of phosphorylated CREB (p-CREB), MITF, and tyrosinase following treatment with 17β-estradiol. First, 17β-estradiol increases melanin production through the induction of the protein expressions of melanogenesis-associated molecules, including p-CREB, MITF, and tyrosinase. Our findings demonstrate that TXA inhibits 17β-estradiol-induced melanogenesis by downregulating the cAMP-PKA pathway. Given that TXA also reduces α-MSH-induced pigmentation via decreased phospho-PKA levels, our results suggest that TXA likely inhibits E2-induced melanogenesis by modulating the cAMP-PKA-CREB-MITF axis, contributing to its depigmenting effect.
Dawson M, Pye D, Mahon R
… +6 more, Taylor G, Shahmalak A, Farjo B, Farjo N, Harries M, Purba TS
Exp Dermatol
· 2025 Dec · PMID 41387231
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Alopecia areata (AA) is an inflammatory hair loss disorder caused by an immune-mediated attack of the hair follicle (HF) bulb. Active disease is characterised by a peribulbar proinflammatory infiltrate, HF immune privile...Alopecia areata (AA) is an inflammatory hair loss disorder caused by an immune-mediated attack of the hair follicle (HF) bulb. Active disease is characterised by a peribulbar proinflammatory infiltrate, HF immune privilege collapse and premature catagen induction, yet the underlying drivers of AA remain poorly understood. With comparable autoimmune inflammatory conditions displaying metabolic alterations, we hypothesised that AA is marked by similar pathobiological changes. To investigate this, we utilised an exploratory metabolomics-based discovery liquid chromatography mass spectrometry (LC-MS) approach. This yielded 32 putatively annotated metabolites significantly altered between lesional and nonlesional AA scalp. Notably, 13-HODE, a linoleic acid metabolite linked to vascular function, was decreased, whilst uric acid (UA), a purine degradation metabolite linked to vascular dysfunction, was increased in the lesional scalp. Moreover, serum LC-MS revealed elevated UA in AA compared to controls, which is linked to systemic endothelial dysfunction. CD31+/ICAM-1+ immunofluorescence co-expression analysis revealed elevated vascular inflammation and endothelial cell activation in the AA scalp. We also experimentally provoked the same response in ex vivo human HF culture via UA or fructose (which increases UA) supplementation. Interestingly, the fructose-generating polyol pathway enzymes, AKR1B1 and SORD, are expressed in the HF, with significantly increased AKR1B1 immunoreactivity in lesional AA HFs, suggesting that fructose can be locally generated by the HF and may contribute to elevated UA levels in AA. Together, these metabolic changes point towards UA-linked microvascular dysfunction in AA, inviting exploration of whether strategies to improve endothelial function and regulate UA are effective in managing AA.
Sensitive skin is characterised by unpleasant skin sensations in response to normally non-provocative stimuli. While its pathophysiology remains incompletely understood, environmental factors and impaired barrier functio...Sensitive skin is characterised by unpleasant skin sensations in response to normally non-provocative stimuli. While its pathophysiology remains incompletely understood, environmental factors and impaired barrier function are key contributors. Because many of these environmental factors also promote extrinsic skin aging, a link between sensitive skin and skin aging phenotypes has been proposed. To examine this hypothesis, we analysed data from 810 participants of the Chinese Taizhou Longitudinal Study (2012-2014). Sensitive skin was classified into subtypes based on questionnaire responses, and skin aging phenotypes were assessed using a subset of items from the SCINEXA (Score of Intrinsic and Extrinsic Skin Aging). Associations between sensitive skin subtypes and specific skin aging phenotypes were examined using multivariate regression models. Environmentally triggered sensitive skin was associated with the presence of pigment spots on the cheeks in participants aged ≥ 50 years, particularly among women. Intrinsically triggered sensitive skin was associated with perioral wrinkles, again most prominently in older women. This is the first large-scale study demonstrating objective associations between sensitive skin subtypes and specific skin aging phenotypes. The findings identify subpopulations potentially more vulnerable to environmental stressors, underscoring the need for targeted prevention strategies.
Atopic dermatitis (AD) is a chronic inflammatory skin disease with high heritability, yet its genetic basis, especially in non-European populations, is not fully elucidated. To identify genetic variants associated with A...Atopic dermatitis (AD) is a chronic inflammatory skin disease with high heritability, yet its genetic basis, especially in non-European populations, is not fully elucidated. To identify genetic variants associated with AD and to evaluate polygenic risk scores (PRS) for predicting AD risk, severity, and serum IgE levels in a Taiwanese Han population. We conducted a genome-wide association study (GWAS) using data from the China Medical University Hospital Biobank (1031 AD cases, 2106 controls). Two PRS models were developed: PRS_AD (AD risk) and PRS_IgE (IgE levels). The cohort was split into discovery and replication sets (8:2 ratio). Logistic regression, adjusted for age, sex, and population stratification, was used. The GWAS identified a novel AD-associated locus: rs905307 in RANBP2 (OR = 0.66, p = 2.75 × 10). PRS_IgE was significantly associated with increased AD risk (OR = 2.230, 95% CI = 1.815-2.741, p < 0.001) and correlated with serum IgE levels (r = 0.168, p < 0.001). Patients requiring systemic treatment for severe AD had significantly higher PRS_IgE scores (p = 0.017). This study identified a novel genetic locus associated with AD and highlights a shared genetic basis between IgE levels and AD. PRS_IgE demonstrates potential for predicting AD risk and severity, suggesting opportunities for early intervention and personalized management in the Taiwanese Han population. Further research is needed to confirm these findings and explore clinical applications.
Dry skin (xerosis) often involves skin barrier disruption, especially after laser treatment. Moisturisers are crucial for managing dry skin, yet optimal formulations for skin barrier recovery are limited. This study aims...Dry skin (xerosis) often involves skin barrier disruption, especially after laser treatment. Moisturisers are crucial for managing dry skin, yet optimal formulations for skin barrier recovery are limited. This study aims to evaluate the effectiveness of a novel moisturiser containing an AIMP1-derived peptide (AdP) in alleviating xerosis after laser treatment and to investigate its effect on skin barrier disruption in vitro. In our randomised controlled clinical trial, we measured transepidermal water loss (TEWL) and Investigative Global Assessment (IGA) scores in participants using AdP-containing moisturisers (ADMP group) versus other moisturisers (CTRL group). The ADMP group demonstrated significant TEWL reduction and improved IGA scores without complications. In vitro study showed that TNF-α levels increased in laser-irradiated skin compared to non-irradiated skin. TNF-α treatment on HaCaT cells disrupted tight junction function, which was rescued by AdP treatment. Additionally, TNF-α affected tight junction proteins ZO-1 and occludin even at very low doses. TNF-α treatment upregulated the downstream signalling proteins TRAF2 and NF-kB, and this effect was mitigated by AdP treatment. Our findings suggest that AdP-containing moisturisers enhance skin barrier function and effectively manage xerosis after laser treatment. These results highlight AdP's potential as a therapeutic cosmeceutical ingredient for treating irradiated and post-procedural dry skin. Trial Registration: ClinicalTrials.gov identifier: NCT05982509.
Foerster Y, Mayer KE, Biedermann T
… +1 more, Persa OD
Exp Dermatol
· 2025 Dec · PMID 41355329
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Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer, predominantly affecting elderly and immunosuppressed patients. Despite recent therapeutic advances, including the introduction of immune checkpoin...Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer, predominantly affecting elderly and immunosuppressed patients. Despite recent therapeutic advances, including the introduction of immune checkpoint inhibitors, outcomes for patients with metastatic or recurrent disease remain poor, underscoring the need for new therapeutic approaches and reliable biomarkers to identify patients at high risk of progression. In this context, receptor tyrosine kinase-like orphan receptor 1 (ROR1), previously associated with poor prognosis and targeted therapeutically in other malignancies, has not yet been investigated in cSCC. This study aimed to evaluate ROR1 expression in cSCC and investigate its potential role as a biomarker for tumour aggressiveness. ROR1 expression was analysed via immunofluorescence in a tissue microarray of 360 cSCC samples from a biobank cohort at the University Hospital Cologne. Fluorescence intensity was quantified and correlated with clinicopathologic features and patient outcomes. High ROR1 expression was detected in 42.5% of samples, predominantly localised at tumour invasive fronts. Elevated ROR1 levels were significantly associated with poor tumour differentiation (p < 0.001), lymph node metastasis (p = 0.007), and perineural invasion (p = 0.005). Although higher ROR1 expression correlated with worse progression-free and metastasis-free survival, these differences did not reach statistical significance. In conclusion, this study identifies ROR1 as a novel marker of aggressive cSCC, linked to poor differentiation, lymphatic spread and perineural invasion. ROR1 holds potential both as a prognostic biomarker and as a therapeutic target, encouraging future exploration of ROR1-directed therapies in advanced cSCC.
Sachslehner AP, Lachner J, Mlitz V
… +4 more, Golabi B, Hess C, Sipos W, Eckhart L
Exp Dermatol
· 2025 Dec · PMID 41319262
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The epidermal differentiation complex (EDC) is a cluster of genes implicated in the control of the skin barrier. However, some EDC genes are also expressed at high levels in the human oesophagus. To determine whether the...The epidermal differentiation complex (EDC) is a cluster of genes implicated in the control of the skin barrier. However, some EDC genes are also expressed at high levels in the human oesophagus. To determine whether the expression of EDC genes in the oesophagus is evolutionarily conserved, we performed comparative transcriptomic analyses of the skin and the oesophagus in humans, mice and chickens. Transcriptomes from public databases and newly generated RNA-sequencing data of the chicken oesophagus were compared. We found that the EDC of both mammals and birds contains genes that are predominantly expressed in the skin and others that are predominantly expressed in the oesophagus. Cornulin is strongly enriched in the oesophagus of humans and chickens. Similar to small proline-rich proteins in the human and murine oesophagus, an EDC protein rich in proline is predominantly expressed in the chicken oesophagus. Further oesophagus-enriched EDC genes are specific to phylogenetic lineages. This study indicates that the EDC plays evolutionarily ancient roles not only in the epidermis of the skin but also in the epithelium of the oesophagus. In line with the dual function of the EDC, dysregulation of EDC gene expression is associated with pathological changes in both stratified epithelia.
Discoid lupus erythematosus (DLE) is the most common variant of cutaneous lupus. Histopathology remains the gold standard for diagnosis, but it carries a risk of scarring in a disease already prone to cicatricial outcome...Discoid lupus erythematosus (DLE) is the most common variant of cutaneous lupus. Histopathology remains the gold standard for diagnosis, but it carries a risk of scarring in a disease already prone to cicatricial outcomes. Additionally, diagnostic delays may occur due to variable processing times, particularly in challenging cases. Line-field confocal optical coherence tomography (LC-OCT) is a novel non-invasive imaging technique offering high-resolution, histology-like features. This study evaluates its diagnostic accuracy in DLE by assessing concordance with histopathology. A cross-sectional study enrolled histologically confirmed DLE from three tertiary referral hospitals. Eleven histological criteria were assessed using LC-OCT and subsequently compared to histopathology. Concordance was evaluated using Cohen's Kappa coefficient (K), with McNemar's test applied to detect significant differences (α = 0.05). Twenty-eight patients with DLE participated in the study. LC-OCT demonstrated strong agreement with histopathology in key diagnostic features of DLE. Near-perfect concordance (K = 1, 100% agreement) was observed for interface dermatitis, dermal vessel dilation, epidermal atrophy, and incontinentia pigmenti. Substantial agreement was found for epidermal disarray (K = 0.85), spongiosis (K = 0.70), necrotic keratinocytes (K = 0.70), and infundibular dilation (K = 0.79). Overall, LC-OCT achieved a Cohen's Kappa of 0.74 with 87.66% concordance, and no statistically significant differences were observed between the two methods (McNemar p = 0.627). LC-OCT is a rapid, effective, and non-invasive diagnostic tool for DLE, demonstrating strong concordance with histopathology and potential for early diagnosis and clinical implementation.
Exosomes, the extracellular organelles, have an important and defined role as cellular communication mediators and are explored for their therapeutic application. Few recent studies have also highlighted their involvemen...Exosomes, the extracellular organelles, have an important and defined role as cellular communication mediators and are explored for their therapeutic application. Few recent studies have also highlighted their involvement in vitiligo pathogenesis. However, the effect of keratinocyte-derived exosomes on stressed melanocytes, is still far from clear. Oxidative stress is one of the hallmarks of vitiligo pathogenesis that primarily affects melanocytes leading to the disruption of the epidermal-melanin unit. This study aims to determine whether supplementation with healthy keratinocyte-derived exosomes can reduce melanocyte stress induced by mitochondrial dysfunction or not. Primary human cell culture of keratinocytes and melanocytes were established. Stress was created in melanocytes through overexpressing the miR-2909 using an expression vector. Exosomes isolated from healthy keratinocytes were co-cultured with stressed melanocytes and the relative uptake of exosomes by stressed melanocytes was visualised and its effect on melanogenesis and mitochondrial functions was analysed. Previously in our studies we demonstrated that miR-2909 is involved in vitiligo pathogenesis and leads to the generation of ROS and decreased melanin synthesis inside melanocytes. Hence, in this study miR-2909-treated stressed melanocytes were used as a cellular vitiligo model to study the effect of exosomes. Results revealed that stressed melanocytes had significantly more uptake of exosomes compared to healthy melanocytes. These exosomes were able to increase melanocyte viability, and the expression of genes associated with melanogenesis. They also improved mitochondrial functions linked to melanocyte function restoration. Moreover, the uptake of fibroblast exosomes was less compared to those of keratinocytes. Our results revealed that exosomes from healthy keratinocytes have the potential to not only reduce stress, but also increase melanin functions through the mitochondrial activity of stressed melanocytes. This might open up new dimensions in exploring better therapeutics for vitiligo.
Hartmann D, Stärr L, Maurer M
… +6 more, Stohldreier Y, Buttgereit L, Swarlik A, Sattler EC, French LE, Deußing M
Exp Dermatol
· 2025 Nov · PMID 41250583
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Inflammatory skin diseases are common and often difficult to differentiate. Ex vivo confocal laser scanning microscopy (EVCM) offers a rapid and promising approach. This study aimed to assess the diagnostic utility of EV...Inflammatory skin diseases are common and often difficult to differentiate. Ex vivo confocal laser scanning microscopy (EVCM) offers a rapid and promising approach. This study aimed to assess the diagnostic utility of EVCM in differentiating inflammatory dermatoses, particularly eczema, psoriasis and lichen planus, by comparing its performance with gold standard histopathology. Tissue samples of 110 patients presenting with inflammatory skin conditions were subjected to both EVCM and conventional histopathology. EVCM images were analysed by three blinded observers, with varying knowledge in histopathology and EVCM, utilising pattern analysis based on Ackermann's classification and single-cell analysis focusing on neutrophil (neutrophils) and eosinophil (eosinophils) granulocytes. Sensitivity and specificity were calculated using contingency tables. We used Cohen's Kappa coefficient and Firth's logistic regression models to evaluate the correlations between disease-associated histopathological features observed via EVCM and histopathology, as well as their impact on accurate histopathological diagnoses. Our findings demonstrate that EVCM provides rapid and insightful visualisation of characteristic features associated with inflammatory dermatological diseases. Diagnostic accuracy varied based on observer experience. The specialist proficient in both EVCM and histopathology achieved the highest accuracy rates for correctly diagnosing lichen planus (97.27%), psoriasis (95.45%) and eczema (92.73%). In conclusion EVCM emerges as a promising adjunct to histopathology, offering a swift and meaningful visualisation of inflammatory disease features. The integration of EVCM could significantly contribute to expediting diagnostic workflows and facilitating prompt, targeted therapeutic interventions. Further research and validation are warranted to establish EVCM's role in routine clinical practice.
Vitiligo is a multifactorial chronic depigmentary disorder characterised by the loss of functional melanocytes. Its pathogenesis involves complex interactions among genetic predisposition, environmental factors, and auto...Vitiligo is a multifactorial chronic depigmentary disorder characterised by the loss of functional melanocytes. Its pathogenesis involves complex interactions among genetic predisposition, environmental factors, and autoimmune dysregulation. In recent years, extensive research has highlighted the critical role of epigenetic regulation in vitiligo development, including aberrant DNA methylation, dysregulated histone modifications, and non-coding RNA (ncRNA) expression disturbances. These abnormal epigenetic modifications contribute to disease progression by disrupting melanogenesis, promoting oxidative stress-induced melanocyte apoptosis, and driving autoimmune responses. From a translational perspective, specific epigenetic alterations show potential as diagnostic biomarkers, disease severity indicators, and therapeutic response monitors. Furthermore, epigenetic drugs, CRISPR/dCas9-based epigenetic editing, and targeted epigenetic reprogramming of tissue-resident memory T cells demonstrate promising clinical applications. This review systematically summarises the molecular mechanisms underlying epigenetic dysregulation in vitiligo pathogenesis and explores its translational implications, providing a theoretical foundation for advancing disease understanding and developing novel therapeutic strategies.