Experimental Dermatology最新文献

{"title":"Lichen Planus Pemphigoides as an Adverse Reaction to Medication Use: A Retrospective Analysis of Commonly Implicated Medication Triggers Using the FDA Adverse Events Reporting Database","authors":"Gaurav N. Pathak, Priya Agarwal, Babar K. Rao","doi":"10.1111/exd.70103","DOIUrl":"https://doi.org/10.1111/exd.70103","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Kinase C Inhibition Overcomes Targeted Therapy Resistance in Cutaneous Melanoma","authors":"Corinne I. Stoffel,&nbsp;Ossia Eichhoff,&nbsp;Phil F. Cheng,&nbsp;Luzia Seiler,&nbsp;Flavia Tellenbach,&nbsp;Andreas Dzung,&nbsp;Francesca Chiovaro,&nbsp;Reinhard Dummer,&nbsp;Mitchell P. Levesque","doi":"10.1111/exd.70093","DOIUrl":"https://doi.org/10.1111/exd.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Correlation Between Double-Stranded DNA and Systemic Lupus Erythematosus","authors":"Qin Qin,&nbsp;Yirui Wang,&nbsp;Sihao Yan,&nbsp;Guangbo Qu,&nbsp;Yuanyuan Li,&nbsp;Chang Zhang,&nbsp;Yuanming Bai,&nbsp;Daiyue Wang,&nbsp;Sihan Luo,&nbsp;Bao Li,&nbsp;Yang Han,&nbsp;Weiwei Chen,&nbsp;Qi Zhen,&nbsp;Liangdan Sun","doi":"10.1111/exd.70102","DOIUrl":"https://doi.org/10.1111/exd.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical Application of Fluoxetine Improves DNCB-Induced Atopic Dermatitis in Mice","authors":"Xue Jiang,&nbsp;Xiaobin Wu,&nbsp;Fujin Yang,&nbsp;Yanxi Li","doi":"10.1111/exd.70096","DOIUrl":"https://doi.org/10.1111/exd.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Genotype–Phenotype Correlations of Desmoplakin Splice Site Variants","authors":"Maria C. Bolling,&nbsp;Mathilde C. S. C. Vermeer","doi":"10.1111/exd.70099","DOIUrl":"https://doi.org/10.1111/exd.70099","url":null,"abstract":"&lt;p&gt;Evidence provided by Pascolini et al. [&lt;span&gt;1&lt;/span&gt;], supports our previous observation that splice site variant &lt;i&gt;DSP&lt;/i&gt;:c.273 + 5G &gt; A is disease-modifying by reducing the total dose of desmoplakin and aggravating the phenotype in combination with a nonsense variant on the other allele [&lt;span&gt;2&lt;/span&gt;]. Pathogenic &lt;i&gt;DSP&lt;/i&gt; variants have previously been associated with phenotypes like palmoplantar keratoderma, woolly hair or epidermolysis bullosa and/or dilated, non-compaction or arrhythmogenic cardiomyopathy. This is a good example of human pathology providing new pointers of modulatory elements of splicing, which up until today remains mostly an enigma.&lt;/p&gt;&lt;p&gt;The unique case of &lt;i&gt;DSP&lt;/i&gt;:c.273 + 5G &gt; A teaches us new lessons. Firstly, functional minigene assays fall short in establishing human desmoplakin pathology. With this assay, only aberrantly spliced products, with either partial or full retention of intron 2, were observed. While in contrast, none of these aberrantly spliced RNA products were detected in cells from two affected patients. In patient cells, only native splicing was detected, although western blot revealed a reduced protein dose from this allele. Generally, minigene assays are artificial, simplified versions of a gene, and due to the enormous size of the &lt;i&gt;DSP&lt;/i&gt; gene (332 kDa protein), only a small portion of this gene could be inserted into the plasmid vector. Other non-included segments of &lt;i&gt;DSP&lt;/i&gt; could possess regulatory elements that influence the outcome of splicing. The splicing of most introns seems to involve a choice between multiple possible splice sites, both real and pseudo sites [&lt;span&gt;3&lt;/span&gt;]. This variant seems to affect this choice by decreasing the recognition of the real site. Hence, the native splice site is weakened, and other pseudo sites are strengthened. As a result, the fine balance of isoforms produced by alternative and normally spliced exons is disturbed.&lt;/p&gt;&lt;p&gt;The majority of reported &lt;i&gt;DSP&lt;/i&gt; variants lack functional data to support their pathogenicity [&lt;span&gt;4&lt;/span&gt;]. In the ClinVar database, over 65 variants in donor and acceptor splice sites spanning the 24 exons of the &lt;i&gt;DSP&lt;/i&gt; gene have been reported. Besides the &lt;i&gt;DSP&lt;/i&gt;:c.273 + 5G &gt; A variant modifying exon/intron 2 splicing, only a few of these were functionally investigated (Table 1). Variant c.423 − 1G &gt; T was shown to cause exon 4 skipping with a subsequent premature termination codon (PTC) by means of RNA sequencing of patient-derived cells. However, no protein data were available to further support this. Variant c.939 + 1G &gt; A caused retention of intron 7 and introduction of a PTC, which induced nonsense mediated mRNA decay (NMD) and no protein expression. Lastly, variant c.2876_2877 + 3del abrogating the donor splice site of exon 20 caused read through of intron 20 and a PTC, and while RNA/protein studies were lacking, immunohistochemistry on the biallelic patient-derived biopsy showed that ","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"13th European Hidradenitis Suppurativa (EHSF) e.V. Conference—Imaging Future Transitions","authors":"Christos C. Zouboulis,&nbsp;Philippe Guillem,&nbsp;Axel P. Villani","doi":"10.1111/exd.70032","DOIUrl":"https://doi.org/10.1111/exd.70032","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 S1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"13th EHSF Conference 2024 Extended Abstracts","authors":"","doi":"10.1111/exd.70036","DOIUrl":"https://doi.org/10.1111/exd.70036","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 S1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Getting Into the DNA of Hidradenitis Suppurativa","authors":"Errol P. Prens","doi":"10.1111/exd.70088","DOIUrl":"https://doi.org/10.1111/exd.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 S1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidradenitis Suppurativa Preclinical Studies: Models and Results","authors":"Christos C. Zouboulis","doi":"10.1111/exd.70089","DOIUrl":"https://doi.org/10.1111/exd.70089","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 S1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidences of Herpes Zoster and Acne by Age in Japanese Patients With Atopic Dermatitis During Treatment With Baricitinib or Upadacitinib: A Single-Centre Retrospective Study","authors":"Ayu Watanabe,&nbsp;Masahiro Kamata,&nbsp;Yoshiki Okada,&nbsp;Yayoi Tomura,&nbsp;Yayoi Tada","doi":"10.1111/exd.70100","DOIUrl":"https://doi.org/10.1111/exd.70100","url":null,"abstract":"&lt;p&gt;Oral Janus kinase (JAK) inhibitors showed efficacy and effectiveness for moderate-to-severe atopic dermatitis (AD) in clinical trials and real-world data [&lt;span&gt;1, 2&lt;/span&gt;]. However, increased risks of herpes zoster (HZ) and acne are major concerns during treatment. Previous evidence revealed that elderly patients with rheumatoid arthritis were at a higher risk of developing HZ [&lt;span&gt;3&lt;/span&gt;] and that younger AD patients were at a higher risk of developing acne [&lt;span&gt;4&lt;/span&gt;], but their incidences by age in AD patients were unknown. We retrospectively investigated their incidences by age in Japanese AD patients.&lt;/p&gt;&lt;p&gt;All AD patients treated with baricitinib or upadacitinib in our department between January 2021 and May 2024 were included. The incidences of HZ and acne (per 100 patient years [PY]) were calculated. To ensure balanced representation across age groups, patients were categorised into age ranges: 12–14, 15–24, 25–34, 35–44 and 45 years and older. We counted acne as an adverse event when patients newly developed acne or when patients having acne at initiation of the drug showed exacerbation during the treatment with baricitinib or upadacitinib.&lt;/p&gt;&lt;p&gt;Data from 84 patients, of whom 42 were treated with baricitinib (female, 15; male, 27) and 42 with upadacitinib (10; 32), were analysed. The mean ages and standard deviations of patients treated with baricitinib or upadacitinib and of all patients were 33.8 ± 11.4, 28.9 ± 13.0 and 31.3 ± 12.4 years, respectively. Before receiving baricitinib, 9 patients were treated with dupilumab, 3 with cyclosporine and 1 with upadacitinib. Before receiving upadacitinib, 6 patients were treated with dupilumab and 13 with baricitinib. The total observation periods of patients treated with baricitinib and upadacitinib were 39.0 PY and 49.4 PY. With one exception, no patients had a history of HZ at the initiation of baricitinib or upadacitinib.&lt;/p&gt;&lt;p&gt;The incidences of HZ were 5.1, 8.1 and 6.8/100 PY in patients treated with baricitinib and upadacitinib, and total patients (Figure 1A). The odds ratio of upadacitinib against baricitinib was 2.1. HZ was not observed in patients aged 15–44 years receiving baricitinib or in those aged 12–24 years receiving upadacitinib. Patients over 45 years showed the highest incidences of HZ in each treatment group (29.1, 27.3 and 28.1/100 PY). The mean duration of baricitinib treatment at developing HZ was 4.5 ± 2.5 months, that of upadacitinib was 15.5 ± 11.4 and that of either drug was 11.8 ± 10.8. No evident tendency by age was observed. One in two patients who developed HZ during baricitinib treatment had received cyclosporine before initiating baricitinib, and the other had never received systemic therapy. Two in four patients who developed HZ during upadacitinib treatment had received dupilumab, and the others had received baricitinib before initiating upadacitinib.&lt;/p&gt;&lt;p&gt;The incidences of acne were 15.4, 44.6 and 31.7/100 PY (Figure 1B). The odds ratio of upad","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}