Yuyue Zuo, Yueqi Zhang, Zilu Qu, Bei Wang, Yan Zhao, Lei Dai, Liuqing Chen, Li Xu
Excessive proliferation of keratinocytes is a crucial pathological risk feature of psoriasis. Focal adhesion kinase (FAK) is a non-receptor protein that primarily regulates cell proliferation and migration. However, the expression and regulatory mechanism of FAK in psoriasis remains unclear. This study aimed to investigate the regulation of FAK in psoriasis and examined the potential impact of FAK inhibitor on psoriasis. A small molecular selective FAK inhibitor, defactinib, was used to evaluate the effect of FAK on psoriasis in in vitro and in vivo functional assays. In our experiments, imiquimod (IMQ)-induced psoriasis mice and human keratinocytes cells were used to study the potential roles and mechanisms of FAK in psoriasis. FAK phosphorylation has been weakly detected in normal intact skin and is markedly elevated upon IMQ treatment. By reducing FAK phosphorylation (p-FAK), defactinib treatment could attenuate psoriasiform inflammation and epidermal hyperplasia in IMQ-treated mice compared with IMQ-induced mice treated with the vehicle. In in vitro studies, resiquimod (R848) increased (p-FAK) and promoted cell proliferation in human keratinocytes cells, while defactinib reversed this effect. Mechanistically, defactinib can alleviate the proliferation via JNK/YB1 pathway in vitro and in vivo. Defactinib significantly attenuates psoriasiform inflammation and epidermal hyperproliferation through the inhibition of the FAK-mediated axis. The downregulation of phosphorylated FAK then suppressed the activation of JNK/YB1 protein signaling pathway in psoriasis. Our work highlights targeting FAK as a potentially effective strategy for the treatment of psoriasis.
{"title":"Defactinib inhibits FAK phosphorylation and regulates psoriasis via attenuating hyperproliferation of keratinocytes.","authors":"Yuyue Zuo, Yueqi Zhang, Zilu Qu, Bei Wang, Yan Zhao, Lei Dai, Liuqing Chen, Li Xu","doi":"10.1111/1346-8138.17366","DOIUrl":"https://doi.org/10.1111/1346-8138.17366","url":null,"abstract":"<p><p>Excessive proliferation of keratinocytes is a crucial pathological risk feature of psoriasis. Focal adhesion kinase (FAK) is a non-receptor protein that primarily regulates cell proliferation and migration. However, the expression and regulatory mechanism of FAK in psoriasis remains unclear. This study aimed to investigate the regulation of FAK in psoriasis and examined the potential impact of FAK inhibitor on psoriasis. A small molecular selective FAK inhibitor, defactinib, was used to evaluate the effect of FAK on psoriasis in in vitro and in vivo functional assays. In our experiments, imiquimod (IMQ)-induced psoriasis mice and human keratinocytes cells were used to study the potential roles and mechanisms of FAK in psoriasis. FAK phosphorylation has been weakly detected in normal intact skin and is markedly elevated upon IMQ treatment. By reducing FAK phosphorylation (p-FAK), defactinib treatment could attenuate psoriasiform inflammation and epidermal hyperplasia in IMQ-treated mice compared with IMQ-induced mice treated with the vehicle. In in vitro studies, resiquimod (R848) increased (p-FAK) and promoted cell proliferation in human keratinocytes cells, while defactinib reversed this effect. Mechanistically, defactinib can alleviate the proliferation via JNK/YB1 pathway in vitro and in vivo. Defactinib significantly attenuates psoriasiform inflammation and epidermal hyperproliferation through the inhibition of the FAK-mediated axis. The downregulation of phosphorylated FAK then suppressed the activation of JNK/YB1 protein signaling pathway in psoriasis. Our work highlights targeting FAK as a potentially effective strategy for the treatment of psoriasis.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amenamevir is an oral once-daily antiherpesvirus drug that can be administered without dose adjustment in patients with impaired renal function. There are currently no clinical data on immunocompromised patients with herpes zoster treated with amenamevir. Therefore, an exploratory study of the efficacy and safety of amenamevir against herpes zoster in patients with immunosuppression was conducted. Inclusion criteria included patients with acute herpes zoster receiving immunosuppressive drugs or those with malignant tumors or autoimmune diseases. Twenty-four patients were included and received amenamevir (400 mg once daily after meals) for up to 14 days. The primary end point of overall improvement in skin symptoms 7 days after treatment initiation (day 7) was 58.3% for "markedly improved" and 20.8% for "improved." The combined improvement rate was 79.2% (95% confidence interval, 57.8-92.9), and 20.8% of patients experienced "worsened" symptoms. The secondary end points of overall improvement in skin symptoms on day 14 and day 28 were 95.7% and 100%, respectively. The skin symptoms progressed during treatment, peaking on day 7, and then began to heal. By Kaplan-Meier estimation, the median periods to complete crusting and healing were both day 14. There were five adverse events with a possible causal relationship to amenamevir (bacterial skin infection, anemia, hyponatremia, headache, and abnormal liver function) in one of the 24 patients. Although the bacterial skin infection was severe, all events in this patient were reported to be either recovered or recovering. These findings indicate that amenamevir can be effective and safe in immunocompromised patients with herpes zoster. However, as worsening can happen around day 7, it is necessary to carefully monitor such patients and switch to other therapies such as intravenous acyclovir if necessary. Clinical trial identifier: Japan Registry of Clinical Trials jRCTs031190208.
{"title":"An exploratory study of the efficacy and safety of amenamevir for the treatment of herpes zoster in patients receiving immunosuppressive drugs.","authors":"Shinichi Imafuku, Satoshi Takeuchi, Kazunori Urabe, Masataka Arakawa, Ryo Sasaki, Daigo Oka, Takenobu Yamamoto, Fumitake Ono, Shigeho Shirahama, Shinichiro Yasumoto, Hiroaki Fukuda","doi":"10.1111/1346-8138.17364","DOIUrl":"https://doi.org/10.1111/1346-8138.17364","url":null,"abstract":"<p><p>Amenamevir is an oral once-daily antiherpesvirus drug that can be administered without dose adjustment in patients with impaired renal function. There are currently no clinical data on immunocompromised patients with herpes zoster treated with amenamevir. Therefore, an exploratory study of the efficacy and safety of amenamevir against herpes zoster in patients with immunosuppression was conducted. Inclusion criteria included patients with acute herpes zoster receiving immunosuppressive drugs or those with malignant tumors or autoimmune diseases. Twenty-four patients were included and received amenamevir (400 mg once daily after meals) for up to 14 days. The primary end point of overall improvement in skin symptoms 7 days after treatment initiation (day 7) was 58.3% for \"markedly improved\" and 20.8% for \"improved.\" The combined improvement rate was 79.2% (95% confidence interval, 57.8-92.9), and 20.8% of patients experienced \"worsened\" symptoms. The secondary end points of overall improvement in skin symptoms on day 14 and day 28 were 95.7% and 100%, respectively. The skin symptoms progressed during treatment, peaking on day 7, and then began to heal. By Kaplan-Meier estimation, the median periods to complete crusting and healing were both day 14. There were five adverse events with a possible causal relationship to amenamevir (bacterial skin infection, anemia, hyponatremia, headache, and abnormal liver function) in one of the 24 patients. Although the bacterial skin infection was severe, all events in this patient were reported to be either recovered or recovering. These findings indicate that amenamevir can be effective and safe in immunocompromised patients with herpes zoster. However, as worsening can happen around day 7, it is necessary to carefully monitor such patients and switch to other therapies such as intravenous acyclovir if necessary. Clinical trial identifier: Japan Registry of Clinical Trials jRCTs031190208.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ohsang Kwon, Matthew Wallace, Paolo Messina, Agota Szende, Jee Woong Choi, Rachel S Newson, Dong Hyun Koo, Joo Hee Lee
Alopecia areata (AA) is a clinically heterogeneous, immune-mediated, non-scarring hair loss disorder. This real-world chart review sought to characterize treatment patterns and healthcare resource use among patients with severe AA in South Korea. A web-based chart review of 40 dermatologists was conducted in which the medical charts of 151 adult patients diagnosed with severe AA between May 2019 and April 2021 were reviewed. Anonymized data on patient characteristics, treatment patterns, healthcare resource use, and clinical outcomes were extracted from the date of severe disease diagnosis until the date of data collection (September-November 2022). Sixty-six percent of patients were diagnosed with severe disease at initial presentation, while 34% were re-classed to severe during the disease course. Mean estimated patient age at the time of diagnosis of severe AA was 37.1 (range 22-68) years. Fifty-three percent of patients were male. Most patients (93.4%) received pharmacological treatment for their condition; 45.5% received ≥2 lines of treatment with a mean duration of 24 months. First-line treatment discontinuation due to lack of efficacy occurred in 46.0% of cases. Hair regrowth occurred in 71.0% of patients, 59.2% of whom experienced major regrowth (≥60%) during the follow-up period. Median (95% confidence interval) time to regrowth was 13.7 (11.0-20.6) months. Treatment visit rates per person-year ranged from two (phototherapy) to 10 (topical treatment), dermatologist visits occurred at a rate of 12.9 per person-year and 6.0% of patients were hospitalized due to alopecia areata. The majority of hospitalizations were related to treatment and occurred in patients who received pulse systemic corticosteroid therapy. The patient and economic burden of AA in South Korea is high and there remains a critical unmet need among patients with severe AA with respect to the effectiveness of commonly used treatment strategies.
斑秃(AA)是一种临床异质性、免疫介导的非瘢痕性脱发疾病。这项真实病历回顾旨在描述韩国严重脱发患者的治疗模式和医疗资源使用情况。我们对 40 名皮肤科医生进行了网络病历审查,审查了 2019 年 5 月至 2021 年 4 月期间被诊断为重度 AA 的 151 名成年患者的病历。从严重疾病诊断之日起至数据收集之日(2022 年 9 月至 11 月),提取了有关患者特征、治疗模式、医疗资源使用和临床结果的匿名数据。66%的患者在初次发病时被诊断为重症,34%的患者在病程中被重新分类为重症。据估计,重症 AA 患者确诊时的平均年龄为 37.1 岁(22-68 岁不等)。53%的患者为男性。大多数患者(93.4%)接受了药物治疗;45.5%的患者接受了≥2个疗程的治疗,平均疗程为24个月。46.0%的患者因疗效不佳而中断一线治疗。71.0%的患者毛发再生,其中59.2%的患者在随访期间毛发再生率大幅提高(≥60%)。头发再生时间的中位数(95% 置信区间)为 13.7(11.0-20.6)个月。每人每年的治疗就诊率从2次(光疗)到10次(局部治疗)不等,皮肤科医生的就诊率为每人每年12.9次,6.0%的患者因斑秃而住院。大多数住院治疗都与治疗有关,而且都发生在接受脉冲全身皮质类固醇治疗的患者身上。在韩国,AA 给患者和经济造成的负担很重,而对于常用治疗策略的有效性,严重 AA 患者的需求仍未得到满足。
{"title":"Treatment patterns and healthcare resource utilization among patients with alopecia areata: A real-world chart review in South Korea.","authors":"Ohsang Kwon, Matthew Wallace, Paolo Messina, Agota Szende, Jee Woong Choi, Rachel S Newson, Dong Hyun Koo, Joo Hee Lee","doi":"10.1111/1346-8138.17380","DOIUrl":"https://doi.org/10.1111/1346-8138.17380","url":null,"abstract":"<p><p>Alopecia areata (AA) is a clinically heterogeneous, immune-mediated, non-scarring hair loss disorder. This real-world chart review sought to characterize treatment patterns and healthcare resource use among patients with severe AA in South Korea. A web-based chart review of 40 dermatologists was conducted in which the medical charts of 151 adult patients diagnosed with severe AA between May 2019 and April 2021 were reviewed. Anonymized data on patient characteristics, treatment patterns, healthcare resource use, and clinical outcomes were extracted from the date of severe disease diagnosis until the date of data collection (September-November 2022). Sixty-six percent of patients were diagnosed with severe disease at initial presentation, while 34% were re-classed to severe during the disease course. Mean estimated patient age at the time of diagnosis of severe AA was 37.1 (range 22-68) years. Fifty-three percent of patients were male. Most patients (93.4%) received pharmacological treatment for their condition; 45.5% received ≥2 lines of treatment with a mean duration of 24 months. First-line treatment discontinuation due to lack of efficacy occurred in 46.0% of cases. Hair regrowth occurred in 71.0% of patients, 59.2% of whom experienced major regrowth (≥60%) during the follow-up period. Median (95% confidence interval) time to regrowth was 13.7 (11.0-20.6) months. Treatment visit rates per person-year ranged from two (phototherapy) to 10 (topical treatment), dermatologist visits occurred at a rate of 12.9 per person-year and 6.0% of patients were hospitalized due to alopecia areata. The majority of hospitalizations were related to treatment and occurred in patients who received pulse systemic corticosteroid therapy. The patient and economic burden of AA in South Korea is high and there remains a critical unmet need among patients with severe AA with respect to the effectiveness of commonly used treatment strategies.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dystrophic epidermolysis bullosa (DEB) is a rare, but severe, subtype of epidermolysis bullosa. It is characterized mainly by blisters and miliary rashes of the skin, while oral mucosa-dominated cases are extremely rare. Here, we report the characteristics of oral mucosa lesions in a Chinese familial case of DEB with a novel compound heterozygous COL7A1 mutation. We further analyzed the genetic and molecular features of the proband and the two related mutation carriers. Our study further elucidates the genetic and phenotypic heterogeneity of DEB.
萎缩性表皮松解症(DEB)是表皮松解症的一种罕见但严重的亚型。它主要表现为皮肤水疱和皮疹,而以口腔黏膜为主的病例则极为罕见。在此,我们报告了一例中国家族性 DEB 病例的口腔黏膜病变特征,该病例存在新型 COL7A1 复合杂合子突变。我们进一步分析了该病例和两个相关突变携带者的遗传和分子特征。我们的研究进一步阐明了 DEB 的遗传和表型异质性。
{"title":"Dystrophic epidermolysis bullosa characterized by mucosal lesions in a Chinese familial case with a novel compound heterozygous mutation of COL7A1.","authors":"Qingying Lan, Hong Hua, Peiru Zhou","doi":"10.1111/1346-8138.17397","DOIUrl":"https://doi.org/10.1111/1346-8138.17397","url":null,"abstract":"<p><p>Dystrophic epidermolysis bullosa (DEB) is a rare, but severe, subtype of epidermolysis bullosa. It is characterized mainly by blisters and miliary rashes of the skin, while oral mucosa-dominated cases are extremely rare. Here, we report the characteristics of oral mucosa lesions in a Chinese familial case of DEB with a novel compound heterozygous COL7A1 mutation. We further analyzed the genetic and molecular features of the proband and the two related mutation carriers. Our study further elucidates the genetic and phenotypic heterogeneity of DEB.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder primarily affecting the intertriginous and anogenital regions. Guidelines recommend various treatments for HS, including biologic agents like adalimumab for moderate to severe cases. Adalimumab is a type of human monoclonal IgG1 antibody designed to target tumor necrosis factor α. Recent studies have shown the effectiveness of adalimumab, either alone or combined with surgery, in managing HS. We retrospectively analyzed the medical chart of HS patients in a southern Taiwan medical center from 2019 to 2022 and investigated clinical features and treatment response. The institutional review board at Chang Gung Medical Foundation granted approval for the study. We primarily focused on moderate to severely affected patients. One hundred and two clinically diagnosed HS patients participated, with a male-to-female ratio of 2:1 and an average age of 31.8 at diagnosis. Among them, 41.2% were in Hurley stage III and 32.4% in stage II. Nineteen patients received excision with pre-surgical adalimumab; their average age at diagnosis was 31.1, with a gender ratio of 5.3:1. Surgery was most common on the buttocks (68%), axillae (21%), and groin (10%). Excision patients were primarily in advanced stages (Hurley III 94.7%, II 5.3%) with high body mass index. Adalimumab and surgery combined yielded a 68.4% improvement rate, while 15.8% remained stable and 15.8% did not respond as expected. In addition, smoking and obesity were prevalent among patients. Adalimumab showed promising results in moderate to severe HS, with significant improvement observed in our cases. The combination of adalimumab and surgery appeared effective in advanced HS patients with larger involved areas and more tunnels. No severe adverse events were reported. However, our study was limited by its retrospective nature and the lack of a control group. Despite these limitations, our study revealed the benefits of integrating adalimumab with suitable surgical procedures in managing patients experiencing moderate to severe HS in real-world scenarios.
{"title":"Adopting adalimumab combined surgery in the management of moderate to severe hidradenitis suppurativa: Experience from a single medical center in southern Taiwan.","authors":"Po-Ta Lai, Han-Chi Tseng","doi":"10.1111/1346-8138.17375","DOIUrl":"https://doi.org/10.1111/1346-8138.17375","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS) is a chronic inflammatory disorder primarily affecting the intertriginous and anogenital regions. Guidelines recommend various treatments for HS, including biologic agents like adalimumab for moderate to severe cases. Adalimumab is a type of human monoclonal IgG1 antibody designed to target tumor necrosis factor α. Recent studies have shown the effectiveness of adalimumab, either alone or combined with surgery, in managing HS. We retrospectively analyzed the medical chart of HS patients in a southern Taiwan medical center from 2019 to 2022 and investigated clinical features and treatment response. The institutional review board at Chang Gung Medical Foundation granted approval for the study. We primarily focused on moderate to severely affected patients. One hundred and two clinically diagnosed HS patients participated, with a male-to-female ratio of 2:1 and an average age of 31.8 at diagnosis. Among them, 41.2% were in Hurley stage III and 32.4% in stage II. Nineteen patients received excision with pre-surgical adalimumab; their average age at diagnosis was 31.1, with a gender ratio of 5.3:1. Surgery was most common on the buttocks (68%), axillae (21%), and groin (10%). Excision patients were primarily in advanced stages (Hurley III 94.7%, II 5.3%) with high body mass index. Adalimumab and surgery combined yielded a 68.4% improvement rate, while 15.8% remained stable and 15.8% did not respond as expected. In addition, smoking and obesity were prevalent among patients. Adalimumab showed promising results in moderate to severe HS, with significant improvement observed in our cases. The combination of adalimumab and surgery appeared effective in advanced HS patients with larger involved areas and more tunnels. No severe adverse events were reported. However, our study was limited by its retrospective nature and the lack of a control group. Despite these limitations, our study revealed the benefits of integrating adalimumab with suitable surgical procedures in managing patients experiencing moderate to severe HS in real-world scenarios.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A case of acquired idiopathic generalized anhidrosis with limited CD8<sup>+</sup> T cell infiltration following pembrolizumab treatment.","authors":"Kazuo Kurihara, Reiko Kageyama, Akihito Hata, Takatoshi Shimauchi, Tetsuya Honda","doi":"10.1111/1346-8138.17361","DOIUrl":"https://doi.org/10.1111/1346-8138.17361","url":null,"abstract":"","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Darier's disease (DD) is a rare autosomal dominant genetic disorder caused by a mutation in ATP2A2, which encodes calcium (Ca2+) ATPase pumps in the endoplasmic reticulum. In this report, we present the first documented case in Japan successfully treated with apremilast. An 18-year-old female presented with red or brown hyperkeratotic papules and plaques on her head, neck, and chest. Histopathological examination revealed a hyperkeratotic, acanthotic epidermis, along with suprabasal acantholysis characterized by corps ronds and grains. Exome sequencing of DNA from peripheral blood mononuclear cells identified a missense mutation in ATP2A2. Based on the above results, we diagnosed her with DD despite the absence of a family history. Given the effectiveness of apremilast, a phosphodiesterase 4 inhibitor, in treating Hailey-Hailey disease (HHD), a genetically related disorder involving ATPases in epidermal calcium channels, we opted for apremilast therapy. Eight weeks post-initiation, significant improvement was observed in the patient's skin lesions on the head, neck, and chest. In this paper, we discuss the successful treatment of DD and HHD cases with apremilast, providing insights into its therapeutic potential, and offer a comprehensive review.
{"title":"Successful treatment of Darier's disease with apremilast and review of reported cases.","authors":"Yusuke Muto, Kengo Kinjyo, Yoshihide Asano","doi":"10.1111/1346-8138.17392","DOIUrl":"https://doi.org/10.1111/1346-8138.17392","url":null,"abstract":"<p><p>Darier's disease (DD) is a rare autosomal dominant genetic disorder caused by a mutation in ATP2A2, which encodes calcium (Ca<sup>2+</sup>) ATPase pumps in the endoplasmic reticulum. In this report, we present the first documented case in Japan successfully treated with apremilast. An 18-year-old female presented with red or brown hyperkeratotic papules and plaques on her head, neck, and chest. Histopathological examination revealed a hyperkeratotic, acanthotic epidermis, along with suprabasal acantholysis characterized by corps ronds and grains. Exome sequencing of DNA from peripheral blood mononuclear cells identified a missense mutation in ATP2A2. Based on the above results, we diagnosed her with DD despite the absence of a family history. Given the effectiveness of apremilast, a phosphodiesterase 4 inhibitor, in treating Hailey-Hailey disease (HHD), a genetically related disorder involving ATPases in epidermal calcium channels, we opted for apremilast therapy. Eight weeks post-initiation, significant improvement was observed in the patient's skin lesions on the head, neck, and chest. In this paper, we discuss the successful treatment of DD and HHD cases with apremilast, providing insights into its therapeutic potential, and offer a comprehensive review.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingjing Chen, Yijin Luo, Yuanyuan Duan, Liangchun Wang, Hai Long, Yi Liu, Xu Yao, Qianjin Lu
Lupus erythematosus panniculitis (LEP) is a chronic inflammatory skin disease with a significant impact on the overall well-being of patients. The safety and efficacy of oral baricitinib for the treatment of LEP have not been studied. This study aimed to explore the efficacy of oral baricitinib in patients with LEP who are recalcitrant or intolerant to conventional therapies. Patients (aged ≥18 years) with active LEP (with a revised cutaneous lupus erythematosus disease area and severity index [RCLASI]-active score ≥4] were randomly assigned 2:1 to baricitinib (4 mg) or placebo (once daily for 20 weeks). The placebo group was switched to baricitinib (4 mg) at week 13, and the final evaluation was conducted at week 24. The primary endpoint was the proportion of patients with an RCLASI-A score decreased by 20% at week 12. The secondary endpoints included the changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index active-(CLASI-A) score, the Dermatology Life Quality Index (DLQI), the Physician's Global Assessment (PGA) score, and safety. Five patients were enrolled. Three patients received baricitinib (4 mg), and two patients were treated with placebo. Two patients in the baricitinib treatment group showed a significant RCLASI-A decrease at week 12 and week 24. Two patients in the placebo group had no change in RCLASI-A at week 12 and a significant decrease at week 24. No new safety events were observed. Treatment with baricitinib was effective and well tolerated in patients with LEP.
{"title":"A double-blind pilot study of oral baricitinib in adult patients with lupus erythematosus panniculitis.","authors":"Jingjing Chen, Yijin Luo, Yuanyuan Duan, Liangchun Wang, Hai Long, Yi Liu, Xu Yao, Qianjin Lu","doi":"10.1111/1346-8138.17354","DOIUrl":"https://doi.org/10.1111/1346-8138.17354","url":null,"abstract":"<p><p>Lupus erythematosus panniculitis (LEP) is a chronic inflammatory skin disease with a significant impact on the overall well-being of patients. The safety and efficacy of oral baricitinib for the treatment of LEP have not been studied. This study aimed to explore the efficacy of oral baricitinib in patients with LEP who are recalcitrant or intolerant to conventional therapies. Patients (aged ≥18 years) with active LEP (with a revised cutaneous lupus erythematosus disease area and severity index [RCLASI]-active score ≥4] were randomly assigned 2:1 to baricitinib (4 mg) or placebo (once daily for 20 weeks). The placebo group was switched to baricitinib (4 mg) at week 13, and the final evaluation was conducted at week 24. The primary endpoint was the proportion of patients with an RCLASI-A score decreased by 20% at week 12. The secondary endpoints included the changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index active-(CLASI-A) score, the Dermatology Life Quality Index (DLQI), the Physician's Global Assessment (PGA) score, and safety. Five patients were enrolled. Three patients received baricitinib (4 mg), and two patients were treated with placebo. Two patients in the baricitinib treatment group showed a significant RCLASI-A decrease at week 12 and week 24. Two patients in the placebo group had no change in RCLASI-A at week 12 and a significant decrease at week 24. No new safety events were observed. Treatment with baricitinib was effective and well tolerated in patients with LEP.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}