Experimental Dermatology最新文献

{"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}

{"title":"Glycosylation in Dermatology: Unveiling the Sugar Coating of Skin Disease","authors":"Linxia Shen,&nbsp;Jui-Ming Lin,&nbsp;Jinran Lin,&nbsp;Wenyu Wu","doi":"10.1111/exd.70098","DOIUrl":"https://doi.org/10.1111/exd.70098","url":null,"abstract":"<p>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.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809787","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":"Clinical Responses and Transcriptomic Analysis of Spesolimab in a Girl With Severe Dermatitis, Multiple Allergies and Metabolic Wasting Syndrome","authors":"Jinxiang Yang,&nbsp;Guofang Li,&nbsp;Yidong Tan,&nbsp;Bing Wang,&nbsp;Mingjun Lyu,&nbsp;Yijun Yang,&nbsp;Zhen Zhang,&nbsp;Yan Gu,&nbsp;ZhiRong Yao,&nbsp;Jianying Liang","doi":"10.1111/exd.70097","DOIUrl":"https://doi.org/10.1111/exd.70097","url":null,"abstract":"<div>\u0000 \u0000 <p>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 (<i>DSG1</i>) or desmoplakin (<i>DSP</i>) 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.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809376","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":"Off-Label Use of Topical Ruxolitinib in Dermatology: A Systematic Literature Review and Current Perspectives","authors":"Marco Spadafora,&nbsp;Serena Morsia,&nbsp;Vito Giuseppe Di Lernia,&nbsp;Shaniko Kaleci,&nbsp;Giovanni Pellacani,&nbsp;Caterina Longo","doi":"10.1111/exd.70095","DOIUrl":"https://doi.org/10.1111/exd.70095","url":null,"abstract":"<p>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.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786891","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":"Early Neutrophil Activation in Psoriatic Skin at Relapse Following Dead Sea Climatotherapy","authors":"Thomas Emmanuel,&nbsp;Hakim Ben Abdallah,&nbsp;Elena Baez,&nbsp;Ida Maja Rather,&nbsp;Torben Steiniche,&nbsp;Anne Bregnhøj,&nbsp;Lars Iversen,&nbsp;Claus Johansen","doi":"10.1111/exd.70094","DOIUrl":"https://doi.org/10.1111/exd.70094","url":null,"abstract":"<p>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 <i>OSM</i>, <i>CXCL8</i>, <i>TREM1</i>, <i>CXCL1</i>, <i>CSF3R</i>, <i>BCL2A1</i> and <i>CXCL2</i>, 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.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770369","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":"How Strong Is the Link Between Merkel Cell Carcinoma and the Occurrence of Other Skin Cancer Types? A Meta-Analysis","authors":"Trairong Chokwassanasakulkit,&nbsp;Nigel A. J. McMillan","doi":"10.1111/exd.70092","DOIUrl":"https://doi.org/10.1111/exd.70092","url":null,"abstract":"<p>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, <i>p</i> = 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.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698922","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":"Correction to “The Dynamics of Circulating Tumour DNA (ctDNA) During Treatment Reflects Tumour Response in Advanced Melanoma Patients”","authors":"","doi":"10.1111/exd.70091","DOIUrl":"https://doi.org/10.1111/exd.70091","url":null,"abstract":"<p>L. Di Nardo, L. Del Regno, A. Di Stefani, et al., “The dynamics of circulating tumour DNA (ctDNA) during treatment reflects tumour response in advanced melanoma patients,” Experimental Dermatology 32 (2023):1785–1793.</p><p>In the article, the author, Yelinay Alpay, was added as co-author to aknowledge her involvement in the project .</p><p>The correct list of authors and affiliations should read:</p><p><b>Lucia Di Nardo</b>^<b>1</b> <b>| Laura Del Regno</b>^<b>2</b> <b>| Alessandro Di Stefani</b>^<b>2</b> <b>| Maria Mannino</b>^<b>2</b> <b>| Barbara Fossati</b>^<b>2</b> <b>| Silvia Catapano</b>^<b>2</b> <b>| Laura Quattrini</b>^<b>2</b> <b>|Yelinay Alpay</b>^<b>13</b> <b>|Cristina Pellegrini</b>^<b>3</b> <b>| Alessio Cortellini</b>^<b>4,5</b> <b>| Alessandro Parisi</b>^<b>6,7</b> <b>| Ettore Capoluongo</b>^{<b>8,9,10</b>} <b>| Chiara Autilio</b>^<b>11</b> <b>| Maria Concetta Fargnoli</b>^<b>3,12</b> <b>| Ketty Peris</b>^<b>1,2</b></p><p>¹Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy</p><p>²UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A, Gemelli –IRCCS, Rome, Italy.</p><p>³Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy</p><p>⁴Medical Oncology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.</p><p>⁵Department of Surgery &amp; Cancer, Imperial College London, London, UK</p><p>⁶Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy</p><p>⁷Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy</p><p>⁸Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Naples, Italy</p><p>⁹CEINGE, Advanced Biotechnology, Naples, Italy</p><p>¹⁰Department of Clinical Pathology and Genomics, Ospedale Cannizzaro, Catania, Italy</p><p>¹¹Department of Biochemistry and Molecular Biology and Research Institute Hospital, Complutense University, Madrid, Spain</p><p>¹²Dermatology Unit, San Salvatore Hospital, L'Aquila, Italy</p><p>¹³Salisbury NHS Foundation Trust, Salisbury, UK</p><p>The online version of the article has been corrected.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707486","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":"Hyperuricemia Exacerbates Psoriatic Inflammation by Inducing M1 Macrophage Activation and Th1 Cell Differentiation","authors":"Shu-Yi Wei,&nbsp;Shuang He,&nbsp;Xiao-Yan Wu,&nbsp;Yan Zhang,&nbsp;Ying-Ping Xu,&nbsp;Bin Yang,&nbsp;Yu-Zhe Sun","doi":"10.1111/exd.70090","DOIUrl":"https://doi.org/10.1111/exd.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>A higher prevalence of hyperuricemia is observed in psoriasis, yet the precise involvement of hyperuricemia in psoriasis remains unclear. Therefore, we investigated the relationship between hyperuricemia and psoriasis, as well as the potential mechanisms through which hyperuricemia may promote psoriatic inflammation. Firstly, a literature review on psoriasis and serum uric acid (SUA) levels and a retrospective analysis on PASI scores and SUA of 147 psoriasis patients at the Dermatology Hospital of Southern Medical University were performed. Then mouse models of hyperuricemia and psoriasis were established to assess the impact of hyperuricemia on psoriasis. Finally, assays examined monosodium urate (MSU) on macrophage M1 polarisation, Th1 differentiation and expressions of NLRP3 and ASC. The literature review indicated inconsistent SUA-psoriasis links; however, our clinical data indicated a positive correlation between PASI scores and SUA. Mouse model results indicated that hyperuricemia exacerbated psoriatic lesions and upregulated the transcription of inflammatory cytokines (IL-17A, IL-17F, IL-23A, IL-8, TNF-α and IL-1β) in skin lesions, effects which were reversed with allopurinol treatment. GO-BP, KEGG and GSEA enrichment analyses of RNA-seq data from mice skin lesions and spleens revealed increased enrichment of Toll-like receptor pathways, TNF-α signalling pathways and innate immune cell migration pathways. CIBERSORTx analysis showed increased M1 cell infiltration in skin lesions and Th1 differentiation in splenic lymphocytes under hyperuricemic conditions. In vitro, MSU enhanced IMQ or LPS-induced macrophage M1 polarisation and Th1 differentiation when co-cultured with M1 cells, which depends on TLR4 expression. In conclusion, hyperuricemia may exacerbate psoriasis by promoting macrophage M1 polarisation, increasing Th1 differentiation and psoriatic inflammation.</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":"143689609","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}