Journal of Dermatology最新文献

{"title":"The interleukin-1α stimulated expression of the wrinkle-inducing elastase neprilysin in adult human dermal fibroblasts is mediated via the intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1","authors":"Mariko Takada,&nbsp;Uma Chandula Pinnawala,&nbsp;Shinichi Hirano,&nbsp;Genji Imokawa","doi":"10.1111/1346-8138.17520","DOIUrl":"10.1111/1346-8138.17520","url":null,"abstract":"<p>Neprilysin is a skin wrinkle-inducing membrane bound elastase that is expressed abundantly in UV-exposed and in aged dermal fibroblasts. The overexpression of neprilysin is closely associated with enhanced epithelial-mesenchymal cytokine interactions mainly via interleukin (IL)-1α, which has the distinct potential to stimulate the expression of neprilysin by human dermal fibroblasts (HDFs). The over-expression of neprilysin also accelerates the formation of wrinkles, accompanied by disruptions of the three-dimensional architecture of dermal elastic fibers that are responsible for the loss of skin elasticity. Because the signaling pathway(s) that lead to the IL-1α-stimulated expression of neprilysin in HDFs remain unclear, we characterized the signaling pathway involved, including their related transcription factors, in IL-1α-treated HDFs. Since qRT-PCR analysis revealed that the mRNA expression level of neprilysin is stimulated to a stronger extent in adult HDFs (aHDFs) by IL-1α than in neonatal HDFs, we used aHDFs for the signaling analysis. Western blotting analysis of the phosphorylation of signaling factors revealed that IL-1α significantly stimulated the phosphorylation of ERK1/2, RSK, JNK, p38, MSK1, NFkB, c-Jun, ATF-2, CREB, and STAT3. Analysis using various signaling inhibitors demonstrated that inhibiting ERK and JNK but not p38, MSK1, NFkB, or STAT3 significantly abrogated the IL-1α stimulated expression of neprilysin at the mRNA, protein, and enzyme activity levels. Furthermore, silencing c-Fos significantly down-regulated the IL-1α-increased expression of neprilysin at the protein and enzyme activity levels. These findings strongly suggest that the IL-1α-stimulated expression of neprilysin in aHDFs is mediated via the intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1.</p>","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 1","pages":"24-34"},"PeriodicalIF":2.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1346-8138.17520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559922","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":"A case of bullous pemphigoid after nemolizumab administration","authors":"Yuriko Ishikawa,&nbsp;Ken Washio","doi":"10.1111/1346-8138.17528","DOIUrl":"10.1111/1346-8138.17528","url":null,"abstract":"","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 3","pages":"e258-e259"},"PeriodicalIF":2.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524042","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":"Hematologic diseases in patients with cutaneous sarcoidosis","authors":"Ryuto Mukaiyama,&nbsp;Toshiyuki Yamamoto","doi":"10.1111/1346-8138.17525","DOIUrl":"10.1111/1346-8138.17525","url":null,"abstract":"","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 3","pages":"e251-e252"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524043","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":"A case of rapidly progressive hair loss due to azathioprine, and the prevalence of NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single-center retrospective observational study","authors":"Sho Katayama,&nbsp;Kentaro Izumi,&nbsp;Inkin Ujiie,&nbsp;Hideyuki Ujiie","doi":"10.1111/1346-8138.17515","DOIUrl":"10.1111/1346-8138.17515","url":null,"abstract":"<p>Autoimmune blistering diseases (AIBDs), classified into pemphigus and pemphigoid, consist of relatively rare skin disorders caused by autoantibodies that target desmosomal and hemidesmosomal proteins, respectively. Although systemic corticosteroids are used as a first-line treatment for AIBDs, azathioprine is frequently co-administered as a steroid-sparing agent. Azathioprine is metabolized into thioguanine nucleotides (TGNs) which are its major active metabolites. The enzyme nudix hydrolase 15 (NUDT15) plays a key role in regulating TGNs. Serious side effects of azathioprine, including leukopenia and alopecia, are known to be particularly problematic in individuals with <i>NUDT15</i> variants. The single-nucleotide polymorphism c.415C &gt;T (p.Arg139Cys) is one of the most frequent <i>NUDT15</i> variants associated with severe thiopurine toxicity. Recently, we treated a case of pemphigus vulgaris in a patient with <i>NUDT15</i> variants in which the patient developed rapidly progressive diffuse hair loss and myelosuppression while receiving azathioprine. Previous reports on <i>NUDT15</i> polymorphisms mainly focused on patients with inflammatory bowel disease or hematological malignancies, and the prevalence of <i>NUDT15</i> polymorphisms remains unknown in AIBDs. This highlights the urgent need for research on <i>NUDT15</i> polymorphisms in AIBDs to achieve a better understanding of the genetic factors influencing adverse reactions to azathioprine. To clarify the prevalence of <i>NUDT15</i> variants in Japanese patients with AIBDs, we retrospectively reviewed the medical records of 78 patients with AIBDs (26 with bullous pemphigoid, 26 with pemphigus vulgaris, 17 with pemphigus foliaceus, and nine with other AIBDs) who had come to Hokkaido University Hospital between 2018 and 2023. The frequencies of <i>NUDT15</i> variants of Arg/Arg, Arg/Cys, and Cys/Cys in these patients were approximately 72%, 23%, and 5%, respectively. Our findings indicate a prevalence of <i>NUDT15</i> variants in AIBD patients that is similar to the prevalences of previous studies on patients with other diseases. These results emphasize the importance of screening for <i>NUDT15</i> variants prior to initiating azathioprine treatment in Japanese patients with AIBDs.</p>","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 2","pages":"363-366"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515610","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":"Pemphigus relapse: Mechanisms, risk factors, and agents associated with disease recurrence","authors":"Gaurav N. Pathak,&nbsp;Priya Agarwal,&nbsp;Sydney M. Wolfe,&nbsp;Kush H. Patel,&nbsp;Jimmy Dhillon,&nbsp;Babar K. Rao","doi":"10.1111/1346-8138.17505","DOIUrl":"10.1111/1346-8138.17505","url":null,"abstract":"<p>Pemphigus represents a spectrum of potentially life-threatening autoimmune-mediated skin blistering conditions caused by antibody production against desmoglein 1 and 3 (anti-DSG 1 and 3) in keratinocytes. Greater than 50% of pemphigus patients experience relapse, which complicates long-term medical management, including risks associated with re-treatment and complications such as infection and dehydration. This review aims to elucidate mechanisms, risk factors, and medications associated with pemphigus relapse. Mechanisms of relapse include the persistence of auto-reactive B-cell populations post-treatment and CD20- B-cell populations that reactivate after B-cell depletion therapy. Risk factors for relapse include high body surface area (BSA) of pemphigus involvement, high body mass index, high severity according to the Pemphigus Disease Area Index (PDAI) at onset, treatment delay, and high anti-DSG1 and DSG3 titers post-treatment. Targeted B-cell localization is associated with better clinical outcomes, including less frequent relapses. Rituximab is currently the gold standard of treatment for moderate–severe pemphigus and has relapse rates of 11%–44% in selected studies, with a mean time to relapse of 5.8 months to 36 months following treatment. Relapse rates across lymphoma dosing (375 mg/m²) versus rheumatoid arthritis dosing (1 g dosing weekly) was inconsistent; however, more frequent dosing, earlier treatment, and higher cumulative dosing were associated with lower relapse rates. Alternative agents that have clinical efficacy include corticosteroid monotherapy, mycophenolate mofetil, azathioprine, and intravenous immunoglobulin. Future studies should include head-to-head comparators over long follow-up periods to identify the best treatment agents associated with the least relapse risk.</p>","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"51 12","pages":"1533-1546"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515616","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":"Immune checkpoint inhibitor-associated bullous pemphigoid: A retrospective and real-world study based on the United States Food and Drug Administration adverse event reporting system","authors":"Haowen Tan,&nbsp;Xiubi Chen,&nbsp;Ying Chen,&nbsp;Xuan Ou,&nbsp;Tao Yang,&nbsp;Xida Yan","doi":"10.1111/1346-8138.17517","DOIUrl":"10.1111/1346-8138.17517","url":null,"abstract":"<p>This study aimed to describe bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICIs) reported in the United States Food and Drug Administration adverse event reporting system (FAERS). We obtained reports of ICI-associated BP from the first quarter of 2011 to the first quarter of 2024 in the FAERS database. The reporting odds ratio (ROR) method of the disproportionality analysis was performed to assess the potential risk for ICI-associated BP. We also described the clinical characteristics of ICI-associated BP and evaluated the time to onset (TTO) of BP developed after treatment with ICIs. Eight hundred and six cases of ICI-associated BP were gathered, in which 56.58% of the patients were aged 65 years or older. The majority of patients were male, accounting for 68.49% of all cases. The prevalent potential cancer type was skin cancer (31.64%). The results of the disproportionality analysis showed that males (ROR = 2.10 [1.78–2.49]), patients aged 65 or older (ROR = 2.13 [1.79–2.55]), and patients with skin cancer (ROR = 2.08 [1.80–2.43]) were more likely to develop ICI-associated BP. In comparison to cytotoxic T-lymphocyte-associated antigen 4 inhibitor and programmed cell death ligand 1 inhibitor, programmed cell death 1 inhibitor-associated BP has a higher risk of development (ROR = 24.45 [22.52–26.56]). ICI-associated BP had a median TTO of 204 days (interquartile range 57–426 days). ICI-associated BP is a rare but important immune-related adverse event. Our study provided helpful information to help medical professionals further understand ICI-associated BP.</p>","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 2","pages":"309-316"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515615","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":"Extramammary Paget's disease treated with of anti-programmed cell death protein 1 therapy after docetaxel therapy failure","authors":"Midori Narasaki,&nbsp;Junji Kato,&nbsp;Sayuri Sato,&nbsp;Tokimasa Hida,&nbsp;Kohei Horimoto,&nbsp;Yoshiyuki Matsui,&nbsp;Nobuaki Shigyo,&nbsp;Hisashi Uhara","doi":"10.1111/1346-8138.17500","DOIUrl":"10.1111/1346-8138.17500","url":null,"abstract":"<p>Extramammary Paget's disease (EMPD) is a rare skin cancer with no standard treatment for advanced-stage disease. Although docetaxel-based chemotherapy is common, no standard treatment exists. Pembrolizumab is approved for solid tumors with a high tumor mutation burden (TMB) and/or high microsatellite instability, and nivolumab was approved in Japan in February 2024 for unresectable advanced or recurrent epithelial skin malignancies. However, there is a lack of real-world data regarding the efficacy of anti-programmed cell death protein 1 (PD-1) therapy for EMPD. We present the case details of three EMPD patients treated with anti-PD-1 therapy after docetaxel treatment, with TMB values of 17.8, 14.3, and 5.0 mut/Mb, respectively, and we review similar reported cases. Even in the cases with a high TMB, the response to anti-PD-1 therapy was not sufficient. Most cases involve second-line or later treatments, so further research is needed to determine the precise effectiveness of anti-PD-1 therapy as a first-line treatment.</p>","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 2","pages":"359-362"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515613","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":"Clinical characteristics and outcomes of autoimmune blistering diseases in Japan","authors":"Maria Rosa Noliza Encarnacion,&nbsp;Ryota Kawai,&nbsp;Hiroto Kuwabiraki,&nbsp;Nanaka Ban,&nbsp;Hisako Yoshida,&nbsp;Ayumi Shintani,&nbsp;Daisuke Tsuruta,&nbsp;Sho Hiroyasu","doi":"10.1111/1346-8138.17518","DOIUrl":"10.1111/1346-8138.17518","url":null,"abstract":"<p>Autoimmune blistering diseases (AIBDs), including pemphigoid and pemphigus, are intractable dermatological disorders clinically characterized by blistering and erosion affecting mucosal membranes and the skin. Due to their rarity and the limited coverage for less severe cases under Japanese medical subsidies, comprehensive epidemiological analyses encompassing less severe cases have not been conducted in Japan. In this study, we analyzed the epidemiology of AIBDs in Japan, utilizing data from a Japanese nationwide database. We identified 9796 cases of bullous pemphigoid (BP), 62 cases of epidermolysis bullosa acquisita (EBA), 871 cases of pemphigus vulgaris (PV), and 578 cases of pemphigus foliaceous (PF). BP patients exhibited an older age distribution compared to EBA, PV, and PF, with median ages of 81, 72, 65, and 70 years, respectively. Higher rates of comorbidities such as Alzheimer's disease, spondylopathies, and extrapyramidal and movement disorders were observed only in BP cases, while other neurodegenerative disorders such as polyneuropathies, unspecified dementia, and schizophrenia were frequent in both BP and EBA. Dipeptidyl peptidase-4 inhibitors were more commonly prescribed before the onset of BP and EBA compared to PV and PF. Treatment patterns indicated that PV patients were more frequently administered higher doses of oral corticosteroids compared to other AIBDs. Additionally, aggressive therapies, including steroid pulse, intravenous immunoglobulin, and plasmapheresis therapies, were more frequently applied in PV cases. In-hospital mortality rates were higher in BP and EBA at 8.0% and 11.3%, respectively, compared to PV and PF at 2.8% and 5.9%, respectively. Kaplan–Meier analysis indicated that BP and EBA reached a 5-year in-hospital mortality rate of approximately 0.21 and 0.34, while PV and PF rates were approximately 0.07 and 0.11, respectively. The Cox hazard model revealed that higher age is the risk factor for in-hospital mortality in all diseases. Kaplan–Meier analysis indicated a cumulative steroid cessation probability of 0.25 at 3 years for BP, and at 6 and 5 years for PV and PF, respectively. The Cox hazard model revealed that higher age and lower maximum corticosteroid dose contribute to the steroid cessation probability in BP, PV, and PF. This study provides insights into the epidemiology, treatment patterns, comorbidities, and outcomes of AIBDs in Japan.</p>","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 2","pages":"299-308"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515612","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":"Plate-like osteoma cutis along Blaschko line: A case report and published work review of lesion distribution","authors":"Ko Matsuoka,&nbsp;Yoshiyuki Nakamura,&nbsp;Shoichiro Ishizuki,&nbsp;Toshifumi Nomura","doi":"10.1111/1346-8138.17526","DOIUrl":"10.1111/1346-8138.17526","url":null,"abstract":"","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 3","pages":"e253-e254"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515617","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":"Potential sitosterolemia in necrobiotic xanthogranuloma: Comment on “Extensive yellowish masses in bilateral orbit and neck”","authors":"Peng-Yu Chen,&nbsp;Yuan-Yu Hong,&nbsp;HuiTing New,&nbsp;Zhuang-Li Tang,&nbsp;Sui-Qing Cai","doi":"10.1111/1346-8138.17524","DOIUrl":"10.1111/1346-8138.17524","url":null,"abstract":"","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 3","pages":"e260-e261"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515618","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}