Yu Zhang, Xu Han, Jiayan Ren, Man Zhu, Dake Chu, Yanmin Zhang, Qi Su, Zixi Zhang
{"title":"Identification of RCC2 as a Risk Gene Associated With Basal Cell Carcinoma and Experimental Validation","authors":"Yu Zhang, Xu Han, Jiayan Ren, Man Zhu, Dake Chu, Yanmin Zhang, Qi Su, Zixi Zhang","doi":"10.1111/exd.70082","DOIUrl":"https://doi.org/10.1111/exd.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Basal cell carcinoma (BCC) is a common type of skin cancer that is increasing in prevalence worldwide. Previous genome-wide association studies (GWAS) have identified certain genetic loci associated with BCC. However, many potential disease-causing genes of BCC remain to be discovered. While the sonic hedgehog (SHH) signalling pathway and mutations in PTCH1/2 and SMO are well-established drivers of BCC pathogenesis, novel genetic factors may complement existing therapeutic targets such as vismodegib and sonidegib. The Mendelian Randomization (MR) study used multiple omics datasets including expression quantitative trait loci (eQTL), methylation quantitative trait loci (mQTL), and protein quantitative trait loci (pQTL) to identify genetic factors associated with an increased risk of developing BCC. Transcriptome analysis of the GEO database then verified the specific expression of key genes. In addition, in vitro experiments were used to silence the key gene to observe the effect of this gene on the proliferation ability of A431 cells. Combined with the multi-omics MR Analysis results, six CpG sites were identified with the RCC2 gene associated with BCC risk. Additionally, single-cell transcriptome analysis confirmed the specific expression of RCC2 in the BCC cohort. In the in vitro validation experiment, siRCC2-1/2 was transfected into the A431 cells, significantly decreasing the expression of RCC2 in the cells. Moreover, the proliferation of A431 cells was significantly inhibited after RCC2 was knocked down. We identified a risk gene RCC2 associated with BCC by MR-based bioinformatics analysis and demonstrated that inhibition of RCC2 inhibited the proliferation of A431 in vitro. These findings provide new strategies for targeted therapy of BCC.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689611","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":"Semaphorin 7a Regulates the Expression of IL-4 and IL-33 in a Cell Model of Atopic Dermatitis and Is Associated With Disease Severity","authors":"Mindy Ming-Huey Guo, Kuang-Den Chen, Ho-Chang Kuo","doi":"10.1111/exd.70087","DOIUrl":"https://doi.org/10.1111/exd.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuroimmune interaction is crucial to inducing pruritic sensations in atopic dermatitis (<span>AD</span>). In this study, we examine the neuroimmune pathways involved in children with <span>AD</span>. HumanMethylation450 BeadChip and GeneChip Human Transcriptome Array 2.0 from 24 children with <span>ad</span> and 24 healthy controls were cross-referenced with gene expression data from GSE116486. <i>SEMA7A</i>, which encodes for semaphorin 7a and is associated with neuron development and immune response and was identified on pathway analysis as a crucial gene in children with <span>ad</span>. In addition, we found that <i>SEMA7A</i> cytosine-phosphate-guanine sites (CpG sites) cg13557411 and cg17917837 were hypomethylated, and mRNA expression of <i>SEMA7A</i> was higher in children with <span>ad</span>. Vectors containing <i>SEMA7A</i> were then transfected into Jurkat T cells, which increased the protein excretion of interleukin 4 (IL-4) and the mRNA expression of interleukin 1 receptor-like 1 (IL1RL1, receptor for the cytokine IL-33). Furthermore, stimulation of HaCaT keratinocytes with SEMA7A protein resulted in increased mRNA expression of the genes interleukin 33 (<i>IL33</i>) and <i>IL1RL1</i>, but suppressed mRNA expression of the tight junction protein ZO-1(<i>TJP1</i>). In conclusion, in this study, we found that <i>SEMA7A</i> is overexpressed in patients with AD and is a central gene on pathway analysis. Results of our study suggest that overexpression of <i>SEMA7A</i> is associated with increased expression of <i>IL4, IL33</i> and its receptor <i>IL1RL1</i>, which are associated with pruritic sensation in AD. <i>SEMA7A</i> also appears to suppress the expression of <i>TJP1</i> in keratinocytes, thereby possibly increasing the permeability of the skin barrier. <i>SEMA7A</i> may be an alternative therapeutic target in <span>AD</span>, especially for neuroimmune-related pruritis.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689610","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}
Evelyn Schneider, Katja Butter, Benjamin Schnautz, Stephanie Musiol, Johanna Grosch, Sonja Schindela, Manuel Garcia-Käufer, Richard Gminski, Stefan Haak, Martin Ohlmeyer, Carsten B. Schmidt-Weber, Stefanie Eyerich, Julia Esser-von Bieren, Francesca Alessandrini
{"title":"Effects of Emissions From Oriented Strand Board on the Development of Atopic Dermatitis Using Two Different Experimental Mouse Models","authors":"Evelyn Schneider, Katja Butter, Benjamin Schnautz, Stephanie Musiol, Johanna Grosch, Sonja Schindela, Manuel Garcia-Käufer, Richard Gminski, Stefan Haak, Martin Ohlmeyer, Carsten B. Schmidt-Weber, Stefanie Eyerich, Julia Esser-von Bieren, Francesca Alessandrini","doi":"10.1111/exd.70086","DOIUrl":"10.1111/exd.70086","url":null,"abstract":"<p>Atopic dermatitis (AD) is an allergic skin disease widespread in children, which later in life can predispose them to asthma. Oriented strand board (OSB), increasingly used in the construction industry, emits volatile organic compounds in the indoor air, some of which may exacerbate <span>AD</span> development in humans. The aim of this study was to evaluate the effects of OSB emissions on the development of AD and lung inflammation. Two different murine <span>AD</span> models, induced by calcipotriol or oxazolone, were exposed to higher- or lower-emitting OSB throughout the experiments. Physiological, biochemical, and immunological parameters of skin disease development, as well as lung inflammatory parameters, were evaluated. Exposure to higher-emitting OSB, characterised especially by high 3-carene emissions, exacerbated some parameters of <span>AD</span>, such as skin barrier function and thickness, with accumulation of eosinophils and 15-lipoxygenase (15-LOX)-driven mediators in both models, whereas IL-4 or 5-LOX-positive cells were increased in only the calcipotriol or oxazolone model, respectively. In the lungs of calcipotriol-treated mice, higher-emitting OSB increased lung eosinophil recruitment. Exposure to lower-emitting OSB had no or even beneficial effects on the skin or lungs of murine <span>AD</span> models. 3-carene in OSB emissions, alone or in combination with other substances, may promote the development of <span>AD</span> and prime the lungs towards an allergic phenotype. Identification and quantification of potentially harmful emitting sources in indoor air may be important for <span>AD</span> prevention or control.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669585","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}
Magdalena Żychowska, Zofia Bakuła, Przemysław Decewicz, Anita Hryncewicz-Gwóźdź, Mariusz Dyląg, Alina Jankowska-Konsur, Jan Gawor, Robert Gromadka, Anna Żaczek, Tomasz Jagielski
{"title":"The Skin Mycobiome of Patients With Atopic Dermatitis and Healthy Volunteers: A Case–Control Study","authors":"Magdalena Żychowska, Zofia Bakuła, Przemysław Decewicz, Anita Hryncewicz-Gwóźdź, Mariusz Dyląg, Alina Jankowska-Konsur, Jan Gawor, Robert Gromadka, Anna Żaczek, Tomasz Jagielski","doi":"10.1111/exd.70085","DOIUrl":"10.1111/exd.70085","url":null,"abstract":"<p>Atopic dermatitis (AD) is a common inflammatory skin disease, for which dysbiosis of the skin mycobiome is considered a triggering factor. The aim of this study was to explore the skin mycobiome of AD patients and healthy volunteers (HV). The study included 50 AD patients and as many HV. Culture-based species identification involved a battery of conventional phenotypic tests and PCR sequencing of the internal transcribed spacer (ITS) 1 and 2 regions within the rDNA cluster. Culture-independent, metataxonomic sequencing was performed with ITS1 as the target region. The overall culture-positive rate was higher in AD patients than in HV (74% vs 28%). Among the former, <i>Rhodotorula</i> spp. dominated, followed by <i>Candida</i> spp., <i>Malassezia</i> spp. and <i>Naganishia albida</i>. The congruence between PCR sequencing and phenotyping was 68.6%. Upon metataxonomy of AD samples, 33 (66%) demonstrated close clustering with HV samples (‘control-like’ AD), while 17 (34%) displayed a remarkably different mycobiome composition (‘AD-specific’), with <i>Cladosporium</i>, <i>Malassezia</i>, <i>Candida</i>, <i>Diplodia</i>, <i>Saccharomyces</i>, <i>Penicillium</i> and <i>Aspergillus</i> genera showing increased abundance. Patients with ‘AD-specific’ mycobiomes were more commonly exposed to air-conditioning compared to ‘control-like’ AD patients (<i>p</i> = 0.030). A subset of patients with AD has a different cutaneous mycobiome make-up dominated by environmental moulds, and <i>Malassezia</i> and <i>Candida</i> yeasts. Anthropogenic factors may affect the cutaneous mycobiome composition in AD and should be taken into account in microbiome studies.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669640","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}
Kim Yao Ong, Yee Kiat Heng, Xiahong Zhao, Hazel H. Oon
{"title":"Genital Psoriasis in Asians: Impact on Quality of Life and Sexual Health","authors":"Kim Yao Ong, Yee Kiat Heng, Xiahong Zhao, Hazel H. Oon","doi":"10.1111/exd.70072","DOIUrl":"10.1111/exd.70072","url":null,"abstract":"<div>\u0000 \u0000 <p>Genital involvement and sexual dysfunction are common amongst patients with psoriasis. However, the effects of genital psoriasis on quality of life (QOL) and sexual health of psoriasis patients are not well understood. We performed an observational study on adult Asian psoriasis patients attending psoriasis subspecialty clinics in a tertiary dermatology centre in Singapore over 1 year. Participants underwent clinical examination of the whole-body surface, with particular attention to the genitalia and questionnaires to evaluate QOL and psychosexual health were administered. A total of 62 patients participated. Most participants were male (82.3%) with a mean age of 41.7 years (SD 12.5). The mean Psoriasis Area and Severity Index (PASI) score was 7.0 (SD 4.3) with a mean Dermatology Life Quality Index (DLQI) score of 9.8 (SD 6.7), indicating moderately impaired QOL. Higher PASI scores were associated with increasing QOL impairment on DLQI (<i>p</i> = 0.021). The commonest site involved was the suprapubic region (61.3%). Males in whom genital psoriasis prevented sexual intercourse or diminished their libido reported more sexual dysfunction. Females reported a greater severity impact of genital psoriasis in terms of symptoms and embarrassment (<i>p</i> = 0.038) yet were less likely to be on treatment (37.5% vs. 45.0%). Perceived efficacy of treatment was low, and younger patients fared poorly on the Patient Health Questionnaire-9 depression questionnaire (<i>p</i> = 0.047). Clinicians should proactively evaluate for and treat genital psoriasis, as patients may be reluctant to discuss their genital rashes if not prompted, leading to under-recognition and undertreatment.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669586","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":"The Impacts of Seasonal Factors on Psoriasis","authors":"Jundan Yang, Guohao Li, Lixin Yue, Erle Dang, Pei Qiao","doi":"10.1111/exd.70078","DOIUrl":"https://doi.org/10.1111/exd.70078","url":null,"abstract":"<p>Psoriasis is a chronic inflammatory skin condition driven by immune system dysfunction, genetic predisposition and environmental factors. Patients with psoriasis experience a well-known clinical phenomenon of ‘winter severity and summer relief’, in which seasonal environmental factors play critical roles in the onset and progression of psoriasis. These factors include temperature, humidity, infection, light exposure and psychological stress. Seasonal changes in temperature and humidity can compromise skin barrier function and exacerbate inflammatory responses, thereby worsening psoriasis symptoms. Notably, during the winter, decreased light exposure leads to reduced vitamin D (VD) levels, reaching their lowest levels from late winter to early spring. This decline in VD levels is associated with increased disease activity, greater disease severity and more frequent flare-ups in patients with psoriasis. During the winter, influenza and <i>Streptococcus pneumoniae</i> infections are more prevalent, which can further exacerbate psoriasis symptoms. Moreover, the environmental conditions in winter can trigger or intensify feelings of depression, which may adversely affect psoriasis through the brain–skin axis. In this comprehensive review, we thoroughly examined the influence of seasonal environmental factors on the incidence, recurrence and severity of psoriasis. By clarifying these complex relationships, we aimed to support the future development of more personalised and effective treatment and management strategies for patients with psoriasis.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645689","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":"Altered Sensory and Stress Responses in Atopic Dermatitis: Effects of Acute Stress on Lesional and Non-Lesional Skin","authors":"Macarena Tejos-Bravo, Dixon Cid, Fernanda Espinoza, Felipe Rojas-Thomas, Gustavo Torres, María-Laura Cossio, Arturo Borzutzky, Margarita Calvo","doi":"10.1111/exd.70083","DOIUrl":"https://doi.org/10.1111/exd.70083","url":null,"abstract":"<div>\u0000 \u0000 <p>Itch and pain are both mediated by small sensory fibres. Atopic dermatitis (AD) patients usually report stress-induced flares, but the impact of stress on sensory fibres in lesional and non-lesional skin remains inconclusive. This observational study assessed the effect of acute stress on sensory profiles in subjects with AD (<i>n</i> = 18) and healthy controls (HC, <i>n</i> = 21). Participants completed clinical and psychological questionnaires, and quantitative sensory testing was performed on lesional and non-lesional skin in AD and healthy skin in HC. Assessments were done before and after the Montreal Imaging Stress Task, an acute stress protocol. Stress responses were evaluated by anxiety ratings, heart rate (HR) and salivary cortisol (CORT). Cortisol binding globulin (CBG) was quantified as an indirect measure for circulating CORT. AD participants reported higher anxiety, depression and stress perception than HC. HR was similar between groups, but AD participants showed a blunted CORT response post-stress and lower CBG levels, suggesting altered stress regulation. Acute stress reduced cold sensitivity in HC and non-lesional AD skin but had no effect on lesions. These findings indicate that the effects of stress on small fibres depend on the condition of the skin and emphasise the sensory alterations experienced by AD patients.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632904","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":"Comparative Analysis of the Skin Microbiota of Rosacea, Steroid-Induced Rosacea and Perioral Dermatitis","authors":"Akiko Mochizuki, Toshifumi Osaka, Yasuko Fukuya, Naoko Yanagisawa, Naoko Ishiguro","doi":"10.1111/exd.70084","DOIUrl":"https://doi.org/10.1111/exd.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Rosacea, steroid-induced rosacea, also known as corticosteroid-induced rosacea-like dermatitis, and perioral dermatitis cause erythema, red papules, and pustules on the face. Tetracycline therapy is often effective for these skin diseases, suggesting that skin bacteria may be involved in these pathogeneses. To explore the etiologic significance of skin bacteria, we examined the microbiota of rosacea, steroid-induced rosacea, and perioral dermatitis, as well as healthy participants (<i>n</i> = 50), using swab specimens that were obtained by rubbing the skin surface and vellus hair specimens that were collected from the perioral lesions. Skin microbiota was determined with short-amplicon sequence analysis for 16S rRNA gene (V1–V2 regions). Comparative analysis of the microbiota showed that the bacterial composition in perioral dermatitis cases was clearly different from that of rosacea cases and healthy participants but similar to that of some cases of steroid-induced rosacea. The uncultured <i>Neisseriales</i> bacterium was prevalent in the skin microbiota of some cases of steroid-induced rosacea and perioral dermatitis cases. After antibiotic therapy to steroid-induced rosacea and perioral dermatitis cases, the uncultured <i>Neisseriales</i> bacterium disappeared with improvement of the skin rash. These results indicate that the skin bacteria involving unculturable bacterium in the skin microbiota had a significant impact on steroid-induced rosacea and perioral dermatitis pathogeneses, and that microbiota-targeted treatment may be effective for steroid-induced rosacea and perioral dermatitis.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632903","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":"Altered Arginine Metabolism Affects Proliferation and Radiosensitivity of Keloids","authors":"Wei Li, Xiaoqian Li, Yange Zhang, Baochen Zhu, Xuewen Xu, Haitao Xiao, Shuyu Zhang","doi":"10.1111/exd.70077","DOIUrl":"https://doi.org/10.1111/exd.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Keloid is characterised by the reprogramming of cellular metabolism, wherein keloid cells adapt their metabolic pathways to meet the demands for energy and biosynthetic precursors. Investigating the intricate relationship between cellular metabolism and the biological behaviour of keloid holds the potential to yield novel therapeutic strategies for keloid. To elucidate the molecular alterations and potential underlying regulatory mechanisms in keloids, we created comprehensive metabolic profiling at the pathway level by analysing metabolomic, transcriptomic and single-cell RNA-sequencing data from keloids and adjacent skin. Viability assay and clonogenic assay were performed to validate the function of the metabolic pathway(s) in primary keloid fibroblast cells. Integrated analysis revealed an upregulation of arginine and proline metabolism in keloids. According to single-cell RNA-seq data, elevated expression of genes related to arginine and proline metabolism, such as <i>P4HA3, P4HA2, P4HA1, PYCR1, OAT</i> and <i>ASS1</i>, was predominately highly expressed in fibroblast-2. Fibroblast-2 displayed more obvious phenotypes of mesenchymal fibroblast. Critical genes from integrated analysis including <i>P4HA3, P4HA2, P4HA1, PYCR1</i> and <i>AZIN2</i>, and metabolites including fumaric acid and 2-oxo-5-amino-pentanoic acid showed prognostic relevance with disease-free survival of keloid. Additionally, an In vitro study showed that arginine deprivation therapy (ADT) inhibited and radiosensitised the proliferation of keloid-derived fibroblasts. In conclusion, our thorough multiomics study deepens our understanding of the link between arginine and proline metabolism and keloid proliferation and radiosensitivity. Elevated activity of arginine and proline metabolism in mesenchymal fibroblasts may be a potential therapeutic pathway for keloid.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632902","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":"New Characteristics of Eccrine Sweat Glands in Acquired Idiopathic Generalised Anhidrosis as Determined via Three-Dimensional Fluorescence Imaging of Cleared Skin Tissue","authors":"Satoshi Yoshida, Ryosuke Kawakami, Yosuke Niko, Yasuhiro Fujisawa, Masamoto Murakami","doi":"10.1111/exd.70038","DOIUrl":"https://doi.org/10.1111/exd.70038","url":null,"abstract":"<p>Acquired idiopathic generalised anhidrosis (AIGA) is an acquired condition characterised by a noticeable decrease in sweating without an obvious cause [<span>1</span>]. The diagnostic guidelines for AIGA in Japan state that examination of a skin biopsy by optical microscopy and electron microscopy may demonstrate lymphocytic infiltration around the sweat glands and swelling of the secretory cells of the sweat glands; however, microscopy does not reveal marked morphological defects of sweat glands [<span>1</span>].</p><p>We treated a 47-year-old man with AIGA who presented with a 6-year history of reduced sweating involving the trunk and limbs. AIGA was diagnosed using the established criteria [<span>1</span>]. Blood tests, computed tomography, sialometry and Schirmer's test were performed. Differential diagnosis excluded neuropathy, exocrine gland dysfunction, and Sjögren's syndrome. A starch–iodine test confirmed anhidrosis affecting more than 95% of the trunk and limbs (Figure S1). Despite undergoing three courses of methylprednisolone pulse therapy during the past year, the patient's anhidrosis exhibited no improvement. We took 2-mm-diameter punch biopsy from an anhidrotic region of the lumbar back skin. Haematoxylin and eosin (H&E) staining revealed a lack of eccrine secretory glands. To investigate a potential decrease in sweat gland number due to atrophic changes, we took a 6-mm-diameter punch biopsy. The results were consistent with the initial examination, showing no eccrine secretory glands (Figure 1A). By contrast, tissue samples from patients without AIGA showed multiple glands within the same 6 mm range. Therefore, these results seem to imply that patients with AIGA may lose eccrine sweat gland structures.</p><p>However, conventional H&E staining provides only two-dimensional images and has limitations in evaluating the total number and density of ducts and eccrine secretory glands because of their complex three-dimensional architecture. Therefore, we used a new three-dimensional fluorescence deep-imaging technique to compare the skin of patients with and without AIGA [<span>2</span>]. Briefly, we used HistoBright (Funakoshi, Tokyo, Japan), which is an improved solvatochromic fluorescent dye based on LipiORDER (Data S1) [<span>3</span>]. Sections of skin tissue were fixed with 4% paraformaldehyde in phosphate-buffered saline and stored frozen. Next, samples were stained with Hoechst and optically cleared using the LUCID method to enhance transparency and fluorescent dye penetration [<span>4</span>]. Finally, three-dimensional fluorescence imaging was performed using two-photon microscopy (TPM; AXE R MP; Nikon, Tokyo, Japan). The Ehime University Graduate School of Medicine Ethics Committee approved the study protocol, and the study was performed in accordance with the Declaration of Helsinki.</p><p>Before evaluating the patient's skin, we imaged a 2-mm punch-biopsy lumbar back skin specimen from a patient without AIGA (Figu","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602674","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}