Nail involvement in psoriasis was reported in 10%-55% of psoriasis patients. Nail psoriasis treatment can be more challenging than treating skin lesions for lack of adequate absorption of topical agents plus the slower n...Nail involvement in psoriasis was reported in 10%-55% of psoriasis patients. Nail psoriasis treatment can be more challenging than treating skin lesions for lack of adequate absorption of topical agents plus the slower nail turnover. To study the demographic and clinical characteristics of psoriasis patients with nail involvement compared to psoriasis patients without nail involvement. Retrospective analysis of all patients attending the psoriasis unit between 2015 and 2020 was performed. Patients with and without nail involvement were compared accordingly. A total of 2888 patients were included in the analysis, 2363 of which had no nail involvement and 525 had clinical involvement of nails (18%). Nail involvement was significantly higher among male patients, smokers, patients with longer disease duration, patients with evidence of psoriatic arthritis and those on metformin. Patients with nail involvement did not show a significant association with diabetes or the manual nature of occupations. The retrospective nature of the study carries the risk of poor registration and has little control over the potential confounders. The involvement of nails in psoriasis was associated with severe disease and was a risk factor for other comorbidities including psoriatic arthritis.
Severe skin injuries and genetic disorders such as epidermolysis bullosa present significant clinical challenges due to limitations in current epidermal replacement therapies. While promising, cultured epithelial autogra...Severe skin injuries and genetic disorders such as epidermolysis bullosa present significant clinical challenges due to limitations in current epidermal replacement therapies. While promising, cultured epithelial autografts (CEAs) suffer from prolonged culture times, cellular senescence, and low-quality clinical outcomes, limiting their widespread application. Recent advancements in iPSC-derived keratinocytes (iKeratinocytes) and in vivo chimerism offer transformative potential for scalable and personalised skin regeneration. Advances in understanding transcriptional networks, mRNA delivery, CRISPR-based genome editing, and automated biomanufacturing processes can enable improved and efficient protocols for generating iKeratinocytes. Despite these advances, there are still challenges for scaling iKeratinocytes, including optimising xeno-free culture systems and developing reproducible methods for generating multilayered skin with appendages. Interspecies chimerism utilising lineage-specific ablation systems and targeted in utero delivery of organ progenitor cells can enable human epidermal tissue development within animal hosts, offering an alternative novel platform for scaling epidermal cell and skin generation. This method, however, requires further refinements for complete ablation and detachment of target cells in the animal hosts and improved human cell integration in chimeric models. Together, iKeratinocytes and in vivo chimerism hold great promise for advancing autologous epidermal cell therapies and enabling broader clinical adoption and improved outcomes for patients with severe skin injuries and genetic disorders.
Foreign body reaction (FBR) is an inflammatory and fibrotic reaction to degradation-resistant foreign materials characterised by the temporal cascade of cellular and molecular dynamics, which remains not fully elucidated...Foreign body reaction (FBR) is an inflammatory and fibrotic reaction to degradation-resistant foreign materials characterised by the temporal cascade of cellular and molecular dynamics, which remains not fully elucidated. The aim of our study was to elucidate the temporal gene expression profiles of FBR. An FBR model was generated by implanting polycaprolactone into the abdominal subcutaneous layer of C57BL/6 mice. RNA sequencing was performed using established FBR tissues at various time points after implantation (FBR group; 2, 4, 8 and 12 weeks, n = 4 for each time points), and normal dorsal skin of mice as the control group (n = 3). We identified distinct gene expression profiles between the control group and the FBR group. Extracellular matrix (ECM), immune, and epigenetics-related genes were significantly enriched in the FBR group compared to normal skin. Within the FBR groups, expression profiles did not show definitive segregation across time points. We observed the highest expression of ECM-related genes (Adamts4, Col9a3, Col6a2, and Furin) and pathways in the 2-week samples, followed by a gradual down-regulation thereafter. In conclusion, our study elucidated distinct expression profiles of FBR in comparison to normal skin, as well as the temporal expression dynamics of FBR.
Psoriasis is a chronic inflammatory skin disease. The excessive activation of proinflammatory cytokines interleukin-17 (IL-17), IL-23 and T helper cell 17(Th17) is the main pathogenic factor. In addition, the dysfunction...Psoriasis is a chronic inflammatory skin disease. The excessive activation of proinflammatory cytokines interleukin-17 (IL-17), IL-23 and T helper cell 17(Th17) is the main pathogenic factor. In addition, the dysfunction of suppressor cells such as regulatory T cells (Tregs) and the imbalance of the Th17/Treg ratio also play important roles in the pathogenesis of psoriasis. By testing the immune function of peripheral Tregs in psoriasis, psoriasis treated with anti-IL-17 biologics, and healthy controls, we found that the number and function of psoriatic peripheral Tregs were abnormal, and Tregs differentiated from 'inhibitory' to 'inflammatory' cells in the inflammatory environment, which may be the cause of Tregs dysfunction in psoriasis. We also found through the assay for targeting accessible chromatin with high-throughput sequencing (ATAC-seq) analysis that the chromatin accessibility of psoriatic peripheral Tregs was significantly higher than that of healthy controls and decreased after treatment, which may be related to INO80, a gene that controls changes in chromatin tightness or relaxation status. In addition, the differentially expressed genes (DEGs) of three groups, such as NCAM2, CDH18, ZEB1 and CCDC22, were mainly concentrated in the signalling pathways related to effector T(Teff) cell aggregation and Tregs dysfunction. This study provides an important basis for the study of peripheral Tregs dysfunction in psoriasis.
WNT5a expression is associated with a MAPK inhibitor resistant phenotype in melanoma driving cell polarity and invasion. No small molecules specifically targeting WNT5a are available. Promising results of targeting non-c...WNT5a expression is associated with a MAPK inhibitor resistant phenotype in melanoma driving cell polarity and invasion. No small molecules specifically targeting WNT5a are available. Promising results of targeting non-canonical WNT5a-dependent WNT signalling with a pan-PKC inhibitor in uveal melanoma prompted us to investigate the relevance of PKC inhibition in cutaneous melanoma. We revealed PKC signalling and WNT5a expression to be associated in a positive feedback loop, suggesting pan-PKC inhibitor as a potent inhibitor of WNT5a in cutaneous melanoma. Combinatorial PKC and MAPK pathway inhibition significantly reduced proliferation and invasion by induction of apoptosis in targeted therapy-resistant melanoma in vitro. In in vivo xenograft studies, we found less proliferation and apoptosis induction in the PKC inhibitor single and combination treatment group with MAPK pathway inhibitors than in the standard of care treatment group. Thus, targeting the non-canonical WNT signalling pathway via combinatorial PKC and MAPK pathway inhibition is beneficial for therapy-resistant cutaneous melanoma combating tumour heterogeneity in vivo. With our study, we are providing an alternate treatment strategy we think is worth investigating as future clinical interventions in cutaneous melanoma.
This study aimed to assess the therapeutic effects and underlying mechanisms of topical fluoxetine application in an atopic dermatitis (AD)-like mouse model. An AD-like mouse model was established using 2,4-dinitrochloro...This study aimed to assess the therapeutic effects and underlying mechanisms of topical fluoxetine application in an atopic dermatitis (AD)-like mouse model. An AD-like mouse model was established using 2,4-dinitrochlorobenzene (DNCB) and treated with topical applications of fluoxetine on skin lesions. The therapeutic efficacy was evaluated by measuring the number of scratches, skin thickness, trans-epidermal water loss (TEWL), and skin moisture levels. Histopathological changes were examined through haematoxylin and eosin staining and toluidine blue staining to assess the local inflammatory state. Quantitative PCR (qPCR) was used to measure the expression of Th2-related cytokines (IL-5, IL-13, and IL-31) in skin lesions. Serum levels of IgE and thymus- and activation-regulated chemokine (TARC) were measured by enzyme-linked immunosorbent assay (ELISA). Topical fluoxetine significantly alleviated lesion symptoms in AD-like mice, reducing skin thickness and the number of scratching incidents. The treatment enhanced skin barrier recovery and reduced the infiltration of inflammatory cells, especially mast cells. Levels of Th2-related cytokines (IL-5, IL-13, and IL-31), indicative of local immune status, were also decreased. Serum concentrations of IgE and TARC showed a downward trend, with a more pronounced decrease in TARC levels. Our findings support the therapeutic role of topical fluoxetine in an AD-like mouse model through the repair of the skin barrier and inhibition of the Th2 inflammatory response in skin lesions, while also alleviating pruritus. These results suggest that fluoxetine may be a potential therapeutic candidate for AD.
Circulating cell-free DNA (cfDNA) is a large molecule that plays a central role in the pathogenesis of SLE. It is the target antigen of autoantibodies and the main component of immune complexes. Due to the large differen...Circulating cell-free DNA (cfDNA) is a large molecule that plays a central role in the pathogenesis of SLE. It is the target antigen of autoantibodies and the main component of immune complexes. Due to the large differences in the content of cfDNA detected in different studies, cfDNA cannot be used as a strong diagnostic basis for SLE at present. As an active component of cfDNA, the correlation between double-stranded DNA (dsDNA) and SLE has not been fully studied. The detection of dsDNA may provide a more accurate diagnosis and treatment basis for SLE, and the in-depth study of SLE patients is helpful to further understand the pathogenesis of SLE. Blood samples were collected from 173 SLE patients and 2970 healthy controls. The concentration of serum dsDNA was determined by fluorescence quantitative method. Propensity score matching (PSM) method was used to match 444 healthy controls and 148 SLE patients according to age and gender. Serum dsDNA levels were compared between SLE patients and matched healthy controls. At the same time, blood exosomes were extracted to explore the correlation between serum dsDNA and exosome dsDNA. As demonstrated herein, serum dsDNA levels in SLE patients were shown to be considerably higher than in healthy controls. Meanwhile, In SLE patients, serum dsDNA level was correlated with season and other clinical indicators, but not with temperature and ultraviolet. Additionally, a statistically significant connection between serum and exosome dsDNA was discovered. We also found that the gene encoding the dsDNA receptor was upregulated. The presented data suggest that detection of dsDNA is promising as a rapid and simple tool for assessing disease progression in SLE, which can help physicians and patients in disease management. The mechanism of elevated dsDNA in SLE patients requires more research.
Hidradenitis suppurativa is a solely human disease for which-unlike for other inflammatory dermatoses-applied animal models are not available. In order to study skin cell immunology under conditions which approximate the...Hidradenitis suppurativa is a solely human disease for which-unlike for other inflammatory dermatoses-applied animal models are not available. In order to study skin cell immunology under conditions which approximate the in vivo functions, maintenance of structural tissue integrity in experimental models is essential. Consequently, several ex vivo human models using lesional, perilesional hidradenitis suppurativa and control healthy skin, have been described, which claim to represent fast and relatively simple methods to investigate the pathophysiology of hidradenitis suppurativa and to preclinically detect the effectiveness of candidate therapeutic agents. At least some of these models seem to approximate the in vivo situation by maintaining patients' skin architecture for several days and expressing biomarkers also detected in hidradenitis suppurativa skin in vivo. Validation still remains to be performed for the majority of the models by evaluating the ex vivo efficacy of drugs, which are introduced in clinical studies and/or have been approved for HS treatment.
The 13th Conference of the European Hidradenitis Suppurativa Foundation (EHSF) e.V. took place on 7-9 February 2024 in Lyon, France. With 188 high-level scientific contributions and 695 participants from 51 countries, th...The 13th Conference of the European Hidradenitis Suppurativa Foundation (EHSF) e.V. took place on 7-9 February 2024 in Lyon, France. With 188 high-level scientific contributions and 695 participants from 51 countries, this 13th EHSF e.V. Conference added a large amount of new knowledge to this rapid developing dermatological field. This issue of Experimental Dermatology includes the extended abstracts of all contributions. The 14th EHSF Conference will take place on 12-14 February 2025, as a physical presence event in Vilnius, Lithuania.
This article reflects on the position of HS in dermatology in the past decades, discusses important highlights and status in the field of HS awareness, treatment and research. HS has evolved from a disease with neglible...This article reflects on the position of HS in dermatology in the past decades, discusses important highlights and status in the field of HS awareness, treatment and research. HS has evolved from a disease with neglible treatment options, rarely seen in dermatology four to five decades ago, to the current situation where dermatologists are in the lead with treatment options giving significant relief to patients. HS surgery, treatment with adalimumab, the anti-IL17s and fostering by the EHSF e.V. has greatly contributed to this positive development. To reach the next level in precision medical treatment, paving the way to disease modification, dissection of the disease 'to the DNA' is necessary. The focus should be on gene discovery, immunology, disease stratification, phenotypes and endotypes based on multi-omics, with special attention for early disease alterations in the hair follicle.
Glycosylation is a common and complex post-translational modification (PTM) of proteins, involving the attachment of glycans under the regulation of various enzymes such as glycosyltransferases. Glycosylation facilitates...Glycosylation is a common and complex post-translational modification (PTM) of proteins, involving the attachment of glycans under the regulation of various enzymes such as glycosyltransferases. Glycosylation facilitates the correct folding of peptide chains, modifies protein conformation and activity, enhances protein stability and influences inter-protein interactions. N-glycosylation and O-glycosylation are two prevalent forms, encompassing a wide range of modifications, including sialylation, fucosylation and galactosylation. In skin tumours, abnormal glycosylation promotes tumour cell proliferation, migration, invasion and metastasis, enhances anti-tumour immunity, and potentially affects immune checkpoint therapy. In inflammatory and autoimmune skin diseases, abnormal glycosylation in T and B lymphocyte subpopulations regulates antigen recognition, signal transduction, inflammatory factor secretion and immunoglobulin function, disrupting immune system homeostasis and impacting biologic therapy efficacy. Glycosylation correlates with the severity and activity of skin diseases, serving as a potential biomarker for diagnosis, condition assessment and prognosis determination. This review provides an overview of the role of protein glycosylation in melanoma, basal cell carcinoma, squamous cell carcinoma, psoriasis, systemic lupus erythematosus, dermatomyositis and skin aging. It analyses the biosynthetic process of glycosylation, elucidates functional changes in glycoproteins and their metabolism, and offers a theoretical basis for developing new targeted therapies.
Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM) is a rare inherited disorder caused by biallelic loss-of-function mutations in the desmoglein-1 (DSG1) or desmoplakin (DSP) genes. Previous stud...Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM) is a rare inherited disorder caused by biallelic loss-of-function mutations in the desmoglein-1 (DSG1) or desmoplakin (DSP) genes. Previous studies have demonstrated that acitretin and systemic biologics targeting IL-17, IL-12/IL-23, and IL-4 are effective in treating SAM syndrome. We report the case of an 8-year-old girl diagnosed with SAM syndrome who suffered from recurrent rash episodes due to infections and achieved remission with a combination therapy of Spesolimab and acitretin. Comprehensive diagnostic workup, including serum inflammatory factor assays, flow cytometry, skin immunohistochemical staining, and skin RNA sequencing (RNA-seq), revealed elevated IL-36G levels in SAM syndrome, which may be associated with the pathogenesis of generalised pustular psoriasis (GPP) through shared IL-36-mediated mechanisms. This case highlights the therapeutic potential of targeting the IL-36 pathway in SAM syndrome and supports the use of skin RNA-seq for personalised selection of anti-inflammatory biologics in rare dermatological disorders. This report marks the first clinical application of Spesolimab in SAM syndrome, offering a novel therapeutic approach.
Spadafora M, Morsia S, Di Lernia VG
… +3 more, Kaleci S, Pellacani G, Longo C
Exp Dermatol
· 2025 Apr · PMID 40192197
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JAK inhibitors are used to treat various inflammatory skin diseases. However, systemic formulations are associated with an increased risk of major adverse events. Ruxolitinib 1.5% cream is a selective topical JAK1 and JA...JAK inhibitors are used to treat various inflammatory skin diseases. However, systemic formulations are associated with an increased risk of major adverse events. Ruxolitinib 1.5% cream is a selective topical JAK1 and JAK2 inhibitor, which has recently been approved by EMA and MHRA for treating non-segmental vitiligo, while being FDA-approved for both vitiligo and atopic dermatitis. Recent literature has reported the off-label use of topical Ruxolitinib for several skin conditions, but data are mostly limited to single case reports and series and few prospective studies, with mixed results. We conducted a systematic review of the literature to investigate the potential efficacy of topical Ruxolitinib in various skin diseases in an off-label setting. The following keywords were used for searching the MEDLINE (Pubmed) and Scopus databases from inception to September 2024: "ruxolitinib cream and dermatology" and "topical ruxolitinib and dermatology". Reviews, articles not focusing on the main topic, books and book chapters, and articles with no English text were excluded. A total of 170 studies were screened, of which 112 fell within exclusion criteria and 58 were assessed for eligibility. Of these, 28 studies, published between 2012 and 2024, were selected. Ruxolitinib cream resulted in being used off-label mostly for treating lichenoid and granulomatous dermatoses, as well as alopecia areata. While for the former skin conditions, topical ruxolitinib proved to be effective and safe, results on efficacy in alopecia areata were controversial. Topical ruxolitinib might be a promising therapeutic option for lichenoid and granulomatous dermatoses. Noteworthily, despite the exciting results from the oral formulation, no consistent data were described for topical ruxolitinib in alopecia areata. Our review reported encouraging results for many inflammatory skin conditions that should be investigated in further studies.
Emmanuel T, Ben Abdallah H, Baez E
… +5 more, Rather IM, Steiniche T, Bregnhøj A, Iversen L, Johansen C
Exp Dermatol
· 2025 Apr · PMID 40181552
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Psoriasis, a chronic inflammatory skin disorder characterised by erythematous and scaly plaques, can be both physically and emotionally distressing for patients. Dead Sea climatotherapy (DSC), a treatment modality combin...Psoriasis, a chronic inflammatory skin disorder characterised by erythematous and scaly plaques, can be both physically and emotionally distressing for patients. Dead Sea climatotherapy (DSC), a treatment modality combining sun exposure, mineral-rich water and mud therapy during 4 weeks at Ein Gedi, Israel, is used for a small group of patients with psoriasis. This study aimed to investigate the cellular composition of psoriatic skin lesions at relapse after complete clearance from DSC. Skin biopsies from baseline, end of treatment and relapse were collected from eight patients with plaque psoriasis who achieved complete clearance from Dead Sea climatotherapy treatment. These biopsies were subjected to immunohistochemistry, RNA sequencing and quantitative polymerase chain reaction analysis (qPCR). Our findings demonstrate that DSC effectively reduces inflammatory markers to levels comparable to baseline non-lesional skin in the short term. The differential expression analysis identified several upregulated differentially expressed genes, including OSM, CXCL8, TREM1, CXCL1, CSF3R, BCL2A1 and CXCL2, in relapsed psoriasis skin compared with baseline lesional skin. These findings were confirmed by qPCR analysis. Pathway enrichment analysis indicated a marked upregulation of neutrophil-associated pathways in relapse skin compared with baseline lesional skin. Immunohistochemical staining for neutrophil markers, such as CD11b, CD15, CD66b, CD207, MPO and NE, showed a non-significant trend towards enhanced neutrophil infiltration and activation at relapse. In conclusion, while DSC provides short-term effectiveness in managing psoriasis, the initial relapse phase is associated with neutrophil activation and migration. Thus, targeting neutrophils early in the psoriasis disease course may disturb the evolution of psoriasis, potentially preventing disease chronicity.
Exp Dermatol
· 2025 Mar · PMID 40134331
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This meta-analysis presents findings from nine studies involving 4626 cases of primary Merkel cell carcinoma (MCC), aimed at evaluating the relationship between primary MCC and the incidence of a second skin cancer. The...This meta-analysis presents findings from nine studies involving 4626 cases of primary Merkel cell carcinoma (MCC), aimed at evaluating the relationship between primary MCC and the incidence of a second skin cancer. The analysis reveals a significant association, with a calculated risk ratio of 2.97 (95% CI, 1.70-5.19, p = 0.0001), indicating that individuals diagnosed with primary MCC are nearly three times more likely to develop the second skin cancer compared to patients with other second cancers. Among the second skin cancers analysed, basal cell carcinoma (BCC) showed the highest risk (0.69, 95% CI 0.35-1.37), followed by squamous cell carcinoma (SCC) (0.45, 95% CI 0.23-0.90) and melanoma (0.31, 95% CI 0.19-0.50). While geographic analysis showed that patients in Northern Europe have a non-significant 1.7-fold increased likelihood of developing the second skin cancer relative to those in North America (USA), where the likelihood of developing the second skin cancer is significantly lower at 0.7 times. The results underscore the importance of implementing enhanced surveillance and preventive strategies for individuals at increased risk. By identifying these associations, we may improve the early detection of the second skin cancer in patients with MCC.