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Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children 治疗成人和儿童特应性皮炎的 0.15% 罗氟司特乳膏
IF 10.9 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-18 DOI: 10.1001/jamadermatol.2024.3121
Eric L. Simpson, Lawrence F. Eichenfield, Javier Alonso-Llamazares, Zoe D. Draelos, Laura K. Ferris, Seth B. Forman, Melinda Gooderham, Mercedes E. Gonzalez, Adelaide A. Hebert, Leon H. Kircik, Mark Lomaga, Angela Moore, Kim A. Papp, Vimal H. Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C. Higham, David H. Chu, David R. Berk
ImportanceSafe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.ObjectiveTo evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.Design, Setting, and ParticipantsTwo phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]).InterventionPatients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks.Main Outcomes and MeasuresThe primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated.ResultsAmong 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site.Conclusions and RelevanceIn 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability.Trial RegistrationClinicalTrials.gov Identifiers: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT04773587?id=NCT04773587&amp;amp;rank=1">NCT04773587</jats:ext-link>, <jats:ext-li
重要性可供特应性皮炎(AD)患者长期使用的安全、有效且耐受性良好的局部治疗方案有限,且依从性较低。目的评估每日一次 0.15%罗氟司特乳膏与载体乳膏在特应性皮炎患者中的疗效和安全性。两项三期随机、双盲、载药对照试验(评价罗氟司特乳膏治疗特应性皮炎的干预试验 1 和 2 [INTEGUMENT-1 和 INTEGUMENT-2])纳入了来自美国、加拿大和波兰研究机构的患者。主要结果和测量指标主要疗效终点是第4周时特应性皮炎研究者全球评估验证成功,即得分为0或1分,且与基线相比至少改善了2个等级。次要终点包括湿疹面积和严重程度指数以及最严重瘙痒数字评分表。结果1337名患者(654名患者接受了INTEGUMENT-1治疗,683名患者接受了INTEGUMENT-2治疗)中,平均(标清)年龄为27.7(19.2)岁,761名参与者(56.9%)为女性。涉及的平均体表面积为 13.6%(标清 = 11.6%;范围为 3.0% 至 88.0%)。达到主要终点的罗氟司特患者明显多于药物治疗患者(INTEGUMENT-1:分别为 32.0% vs 15.2%;P &p;amp;lt; .001;INTEGUMENT-2:分别为 28.9% vs 12.0%;P &p;amp;lt; .001)。第4周时,在湿疹面积和严重程度指数至少减少75%方面,罗氟司特也有显著的统计学差异(INTEGUMENT-1:43.2% vs 22.0%;P&p;amp;amp;lt; .001;INTEGUMENT-2:42.0% vs 19.7%;P&p;amp;amp;lt; .001)。罗氟司特的耐受性良好,治疗中出现的不良反应较少。在每个时间点,研究人员注意到885名接受罗氟司特治疗的患者(≥95%)的用药部位没有刺激症状,885名接受罗氟司特治疗的患者(90%)的用药部位没有感觉或感觉轻微。结论和相关性在2项纳入成人和儿童的3期试验中,根据多个疗效终点,每日一次的0.15%罗氟司特乳膏相对于载体乳膏可改善AD,同时具有良好的安全性和耐受性:NCT04773587, NCT04773600
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引用次数: 0
Estimating Costs in Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa. 估算Beremagene Geperpavec治疗营养不良性表皮松解症的成本。
IF 11.5 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-18 DOI: 10.1001/jamadermatol.2024.2999
Michelle K Y Chen, Artiene Tatian, Deshan Frank Sebaratnam
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引用次数: 0
Consensus on a Patient-Centered Definition of Atopic Dermatitis Flare 以患者为中心的特应性皮炎复发定义共识
IF 10.9 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-11 DOI: 10.1001/jamadermatol.2024.3054
Aaron M. Drucker, Isabelle J. C. Thibau, Bryan Mantell, Katie N. Dainty, Matthew Wyke, Wendy Smith Begolka
ImportanceFlare is a term commonly used in atopic dermatitis (AD) care settings and clinical research, but little consensus exists on what it means. Meanwhile, flare management is an important unmet research and treatment need. Understanding how various therapies might comparatively improve AD flares as a measure of treatment effectiveness may facilitate shared decision-making and enable assessment of effectiveness within and outside clinical settings.ObjectiveTo identify patient-reported attributes associated with an AD flare to develop a patient-centered, consensus-based working definition.Design, Setting, and ParticipantsThis consensus survey study used a modified eDelphi method involving consensus-building focus groups and a survey conducted from January 10 through October 24, 2023. Focus groups were conducted virtually, and the online survey was advertised to National Eczema Association members. US adults aged 18 years or older with AD were recruited via convenience sampling.ExposureLived experience of AD.Main Outcomes and MeasuresThe main outcome was consensus on which attributes of AD to include in a patient-centric definition of flare. Using a rating scale (range, 1-9), consensus for the modified eDelphi statement rating was defined as at least 70% of participants rating a statement as 7 to 9 (critical to a flare definition) and less than 15% rating it as 1 to 3 (not important).ResultsTwenty-six participants with AD who completed focus group activities (24 aged 18-44 years [92.3%] and 2 aged 45-64 years [7.7%]; 18 women [69.2%]) and 631 participants with AD (mean [SD] age, 45.5 [18.1] years; 533 women [84.5%]) who completed the survey were included in the analysis. Fifteen statements reached consensus from the focus groups, and of those, 12 reached consensus from survey participants. More than half (334 of 631 [52.9%]) of survey participants reported alignment with their health care practitioner on what a flare is, and most (478 of 616 [77.6%]) reported that a patient-centered definition would be useful when communicating with their health care practitioner about their condition.Conclusions and RelevanceIn this study, participants with AD reached consensus on what an AD flare means from the patient perspective. This understanding may improve research and care by addressing this key patient-centered aspect of evaluating treatment effectiveness.
重要性复发是特应性皮炎(AD)护理和临床研究中常用的术语,但对其含义却鲜有共识。同时,复发管理也是一项尚未得到满足的重要研究和治疗需求。了解各种疗法如何相对改善特应性皮炎发作,并将其作为衡量治疗效果的标准,可促进共同决策,并有助于在临床环境内外对疗效进行评估。目标确定患者报告的与特应性皮炎发作相关的属性,以制定以患者为中心、基于共识的工作定义。焦点小组以虚拟方式进行,在线调查则向全国湿疹协会会员进行宣传。主要结果和测量方法主要结果是就以患者为中心的发作定义中应包含哪些AD属性达成共识。使用评分表(范围为 1-9),对修改后的 eDelphi 语句评分达成共识的定义是:至少 70% 的参与者将某一语句评为 7 至 9 分(对病情发作的定义至关重要),少于 15% 的参与者将其评为 1 至 3 分(不重要)。结果完成焦点小组活动的 26 位注意力缺失症参与者(24 位年龄在 18-44 岁之间 [92.3%] ,2 位年龄在 45-64 岁之间 [7.7%];18 位女性 [69.2%])和完成调查的 631 位注意力缺失症参与者(平均 [SD] 年龄为 45.5 [18.1] 岁;533 位女性 [84.5%])被纳入分析。焦点小组就 15 项陈述达成共识,其中 12 项陈述在调查参与者中达成共识。超过半数的调查参与者(631 人中的 334 人 [52.9%])表示与他们的医护人员就什么是发作达成了一致,大多数人(616 人中的 478 人 [77.6%])表示,以患者为中心的定义将有助于他们与医护人员就自己的病情进行沟通。这种理解可以通过解决评估治疗效果的这一以患者为中心的关键问题来改善研究和护理。
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引用次数: 0
Widespread Micropapular Eruption. 广泛的小丘疹糜烂。
IF 11.5 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-11 DOI: 10.1001/jamadermatol.2024.2531
Chun Hei Lee, Christopher Mow, Senhong Lee
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引用次数: 0
Prescription Cost-Saving Platforms in Dermatology. 皮肤科处方成本节约平台。
IF 11.5 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-11 DOI: 10.1001/jamadermatol.2024.3070
Alana L Ferreira, Jules B Lipoff, Stephanie K Fabbro
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引用次数: 0
Cord Blood Serum Levels of IL-31 and CCL17, Cutaneous Markers, and Development of Atopic Dermatitis 脐带血血清中 IL-31 和 CCL17 的水平、皮肤标记物与特应性皮炎的发展
IF 10.9 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-11 DOI: 10.1001/jamadermatol.2024.3178
Angelo Massimiliano D’Erme, Cristian Fidanzi, Matteo Bevilacqua, Thomas Bieber, Cristina Tuoni, Aldo Paolicchi, Maria Franzini, Riccardo Morganti, Francesca Papadia, Agata Janowska, Valentina Dini, Marco Romanelli
ImportanceAtopic dermatitis (AD) is the most prevalent chronic skin condition characterized by inflammation and itching. Currently, there is no reliable method for identifying which newborns might have an increased risk of developing AD.ObjectiveTo evaluate the predictive value of serological biomarkers, such as CCL17/thymus- and activation-regulated chemokine, CCL18, CCL22, CCL27, IL-31, and thymus stromal lymphopoietin, with transepidermal water loss (TEWL) and hydration rate and the development of AD in infants.Design, Setting, and ParticipantsThis observational prospective study included 40 consecutive full-term newborns from a single university hospital in Pisa, Italy. The cutaneous markers of infants were assessed at 1, 6, and 12 months of age, while the biomarkers from the 10-mL sample of cord blood taken at birth were measured after delivery. Data were collected from March to December 2018 and analyzed from January to April 2019.Main Outcomes and MeasuresLevel of serological biomarkers associated with TEWL and hydration rate, as well as the emergence of AD during the first 12 months of life.ResultsAll 40 included infants (27 male [68%]) completed the study. At 6 months, 16 infants presented symptoms and signs of AD (AD group) and 24 did not (non-AD group). Infants with AD signs had statistically significant anterior cubital fossa TEWL values at 1, 6, and 12 months of age compared to those without AD signs. No statistically significant correlations were observed between the TEWL measured at the anterior part of knee and hydration rate at the anterior cubital fossa at first month in the 2 groups. With regard to the blood biomarkers, at birth those in the AD group vs the non-AD group had statistically significant higher levels of CCL17/thymus- and activation-regulated chemokine (median [IQR], 716 [509-951] pg/mL vs 419 [24-566] pg/mL; P = .003) and IL-31 (median [IQR], 212 [114-409] pg/mL vs 97 [52-277] pg/mL; P = .04); in contrast, no statistically significant serum level differences were registered for thymus stromal lymphopoietin (median [IQR], 105 [66-295] pg/mL vs 88 [43-187] pg/mL), CCL18 (median [IQR], 1236 [1115-1605] pg/mL vs 1255 [1188-1677] pg/mL), CCL22 (median [IQR], 1032 [936-1454] pg/mL vs 1096 [932-1536] pg/mL), and CCL27 (median [IQR], 172 [122-251] pg/mL vs 120 [90-265] pg/mL).Conclusions and RelevanceIn this observational study, the analysis of TEWL at the anterior cubital fossa area occurred prior to and correlated with the clinical signs of AD. Quantification of cytokines indicated that assessing cord blood serum levels of CCL17 and IL-31 could offer new perspectives in identifying newborns who might be susceptible to AD. Larger studies are needed to validate these findings.
重要性特应性皮炎(AD)是以炎症和瘙痒为特征的最常见慢性皮肤病。目的 评估血清学生物标志物(如 CCL17/胸腺和活化调节趋化因子、CCL18、CCL22、CCL27、IL-31 和胸腺基质淋巴细胞生成素)与经表皮失水率 (TEWL) 和水合率以及婴儿 AD 发病的预测价值。这项前瞻性观察研究包括来自意大利比萨一家大学医院的 40 名连续足月新生儿。在婴儿1、6和12个月大时对其皮肤标记物进行评估,同时在分娩后测量出生时采集的10毫升脐带血样本中的生物标记物。数据收集时间为 2018 年 3 月至 12 月,分析时间为 2019 年 1 月至 4 月。主要结果和测量与 TEWL 和水合率相关的血清学生物标志物水平,以及出生后前 12 个月出现 AD 的情况。结果所有 40 名纳入研究的婴儿(27 名男性 [68%])均完成了研究。6 个月大时,16 名婴儿出现注意力缺失症的症状和体征(注意力缺失症组),24 名婴儿没有(非注意力缺失症组)。与无 AD 征兆的婴儿相比,有 AD 征兆的婴儿在 1、6 和 12 个月大时肘窝前 TEWL 值具有统计学意义。在两组中,膝关节前部测量的 TEWL 与 1 个月大时肘窝前部的水合率之间没有统计学意义上的相关性。在血液生物标志物方面,出生时,AD 组与非 AD 组相比,CCL17/胸腺和活化调节趋化因子(中位数 [IQR], 716 [509-951] pg/mL vs 419 [24-566] pg/mL;P = .003)和 IL-31 (中位数 [IQR], 212 [114-409] pg/mL vs 97 [52-277] pg/mL;P = .04);相反,胸腺基质淋巴细胞生成素(中位数 [IQR], 105 [66-295] pg/mL vs 88 [43-187] pg/mL)、CCL18(中位数 [IQR]、1236 [1115-1605] pg/mL vs 1255 [1188-1677] pg/mL)、CCL22(中位数[IQR],1032 [936-1454] pg/mL vs 1096 [932-1536] pg/mL)和 CCL27(中位数[IQR],172 [122-251] pg/mL vs 120 [90-265] pg/mL)。结论和相关性在这项观察性研究中,对肘窝前区 TEWL 的分析发生在 AD 临床症状出现之前,并与之相关。细胞因子的定量分析表明,评估脐带血血清中 CCL17 和 IL-31 的水平可为识别可能易患 AD 的新生儿提供新的视角。还需要更大规模的研究来验证这些发现。
{"title":"Cord Blood Serum Levels of IL-31 and CCL17, Cutaneous Markers, and Development of Atopic Dermatitis","authors":"Angelo Massimiliano D’Erme, Cristian Fidanzi, Matteo Bevilacqua, Thomas Bieber, Cristina Tuoni, Aldo Paolicchi, Maria Franzini, Riccardo Morganti, Francesca Papadia, Agata Janowska, Valentina Dini, Marco Romanelli","doi":"10.1001/jamadermatol.2024.3178","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.3178","url":null,"abstract":"ImportanceAtopic dermatitis (AD) is the most prevalent chronic skin condition characterized by inflammation and itching. Currently, there is no reliable method for identifying which newborns might have an increased risk of developing AD.ObjectiveTo evaluate the predictive value of serological biomarkers, such as CCL17/thymus- and activation-regulated chemokine, CCL18, CCL22, CCL27, IL-31, and thymus stromal lymphopoietin, with transepidermal water loss (TEWL) and hydration rate and the development of AD in infants.Design, Setting, and ParticipantsThis observational prospective study included 40 consecutive full-term newborns from a single university hospital in Pisa, Italy. The cutaneous markers of infants were assessed at 1, 6, and 12 months of age, while the biomarkers from the 10-mL sample of cord blood taken at birth were measured after delivery. Data were collected from March to December 2018 and analyzed from January to April 2019.Main Outcomes and MeasuresLevel of serological biomarkers associated with TEWL and hydration rate, as well as the emergence of AD during the first 12 months of life.ResultsAll 40 included infants (27 male [68%]) completed the study. At 6 months, 16 infants presented symptoms and signs of AD (AD group) and 24 did not (non-AD group). Infants with AD signs had statistically significant anterior cubital fossa TEWL values at 1, 6, and 12 months of age compared to those without AD signs. No statistically significant correlations were observed between the TEWL measured at the anterior part of knee and hydration rate at the anterior cubital fossa at first month in the 2 groups. With regard to the blood biomarkers, at birth those in the AD group vs the non-AD group had statistically significant higher levels of CCL17/thymus- and activation-regulated chemokine (median [IQR], 716 [509-951] pg/mL vs 419 [24-566] pg/mL; <jats:italic>P</jats:italic> = .003) and IL-31 (median [IQR], 212 [114-409] pg/mL vs 97 [52-277] pg/mL; <jats:italic>P</jats:italic> = .04); in contrast, no statistically significant serum level differences were registered for thymus stromal lymphopoietin (median [IQR], 105 [66-295] pg/mL vs 88 [43-187] pg/mL), CCL18 (median [IQR], 1236 [1115-1605] pg/mL vs 1255 [1188-1677] pg/mL), CCL22 (median [IQR], 1032 [936-1454] pg/mL vs 1096 [932-1536] pg/mL), and CCL27 (median [IQR], 172 [122-251] pg/mL vs 120 [90-265] pg/mL).Conclusions and RelevanceIn this observational study, the analysis of TEWL at the anterior cubital fossa area occurred prior to and correlated with the clinical signs of AD. Quantification of cytokines indicated that assessing cord blood serum levels of CCL17 and IL-31 could offer new perspectives in identifying newborns who might be susceptible to AD. Larger studies are needed to validate these findings.","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142176174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melanoma Incidence and Mortality Trends in Sweden. 瑞典黑色素瘤发病率和死亡率趋势。
IF 11.5 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-08 DOI: 10.1001/jamadermatol.2024.3514
Hildur Helgadottir, Rasmus Mikiver, Karina Schultz, Kari Nielsen, Francesca Portelli, Jan Lapins, Susana Puig, Karolin Isaksson

Importance: Over the past decades, many global regions have experienced a steady increase in the incidence of cutaneous melanoma. However, more recently, a downward trend has been observed in the younger age groups in Australia and the US. Yet, in Europe, none of the countries have reported any significant decline in melanoma incidence for any age group.

Objective: To assess melanoma incidence and mortality trends in Sweden, with a focus on individuals younger than the average age of melanoma onset.

Design, setting, and participants: This cohort study used data on the national population from the Swedish Melanoma Registry and the Swedish Cancer Registry, which cover more than 99% of all primary invasive cutaneous melanomas diagnosed in the country. All patients diagnosed from 1990 to 2022 were included.

Main outcomes and measures: Incidence and mortality rates per 100 000 inhabitants were calculated for each year and shown as average annual rates for every 5-year period from 1990 to 2022. Joinpoint regression models were used to evaluate statistical significance of temporal trends and points of change.

Results: There were 34 800 primary invasive cutaneous melanomas (19 582 [56.3%] in females and 15 218 [43.7%] in males) reported in 33 324 individuals younger than 60 years (median [IQR] age, 48 [36-58] years) from 1990 to 2022. A consistent rise in melanoma incidence was observed among those 50 to 59 years old. The age groups from 20 to 29 years, 30 to 39 years, and 40 to 49 years showed an incidence peak in 2013 to 2015 followed by stable or significantly declining rates until 2022. In patients younger than 20 years, melanoma incidence remained low with no significant trends. There was also a significant decline in melanoma mortality among 30- to 59-year-old individuals, but not in those 60 years and older.

Conclusions and relevance: The findings of this cohort study showed a significant recent downward trend in both melanoma incidence and melanoma mortality in the age group 30 to 49 years in Sweden. The reasons for these declines are unclear but may include UV protection, public health campaigns, changing population demographics, and the introduction of effective melanoma treatment. None of these possibilities were evaluated; further study is needed.

重要性:过去几十年来,全球许多地区的皮肤黑色素瘤发病率持续上升。不过,最近在澳大利亚和美国,年轻群体的发病率呈下降趋势。然而,在欧洲,没有一个国家报告任何年龄组的黑色素瘤发病率有明显下降:评估瑞典的黑色素瘤发病率和死亡率趋势,重点关注低于黑色素瘤平均发病年龄的人群:这项队列研究使用了瑞典黑色素瘤登记处和瑞典癌症登记处的全国人口数据,这两个登记处涵盖了瑞典99%以上的原发性侵袭性皮肤黑色素瘤患者。1990年至2022年期间确诊的所有患者均被纳入其中:计算每年每 10 万居民的发病率和死亡率,并以 1990 年至 2022 年每 5 年的平均年率表示。采用连接点回归模型来评估时间趋势和变化点的统计意义:从 1990 年到 2022 年,在 33 324 名年龄小于 60 岁的人(中位数[IQR]年龄为 48 [36-58] 岁)中,共报告了 34 800 例原发性侵袭性皮肤黑色素瘤(女性为 19 582 [56.3%] 例,男性为 15 218 [43.7%] 例)。在 50 至 59 岁的人群中,黑色素瘤发病率持续上升。20至29岁、30至39岁和40至49岁年龄组的发病率在2013年至2015年达到高峰,随后保持稳定或显著下降,直至2022年。在20岁以下的患者中,黑色素瘤的发病率仍然很低,没有明显的趋势。30至59岁人群的黑色素瘤死亡率也明显下降,但60岁及以上人群的黑色素瘤死亡率没有明显下降:这项队列研究的结果表明,瑞典 30 至 49 岁年龄组的黑色素瘤发病率和黑色素瘤死亡率近期均呈显著下降趋势。下降的原因尚不清楚,但可能包括紫外线防护、公共卫生运动、人口结构变化以及引入有效的黑色素瘤治疗方法。对这些可能性都没有进行评估;需要进一步研究。
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引用次数: 0
Low-Dose Metformin and Profibrotic Signature in Central Centrifugal Cicatricial Alopecia. 低剂量二甲双胍与中枢性角化性脱发的蜕变特征
IF 11.5 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-04 DOI: 10.1001/jamadermatol.2024.3062
Aaron Bao, Aasheen Qadri, Aditi Gadre, Elizabeth Will, Dina Collins, Rexford Ahima, Lindsey A Bordone, Crystal Aguh

Importance: Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia predominantly affecting Black female individuals. Current conventional treatments target inflammation but not the underlying fibrotic processes, often leading to permanent hair loss.

Objective: To investigate the associations of low-dose oral metformin, an antidiabetic medication with antifibrotic properties, with clinical symptoms and scalp gene expression patterns in patients with CCCA.

Design, setting, and participants: This retrospective clinical case series and transcriptomic analysis included patients treated at a single tertiary academic medical center between January 2023 and March 2024. All patients had biopsy-confirmed CCCA refractory to standard treatments. Transcriptomic analysis was performed on patients with previously banked, paired scalp biopsies before and after treatment with adjuvant metformin for at least 6 weeks.

Exposure: Extended-release metformin, 500 mg, once daily was added to participants' baseline CCCA treatment regimens.

Main outcomes and measures: Clinical assessments included pruritus, inflammation, scalp resistance, and hair regrowth. Gene expression profiling via bulk RNA sequencing analysis evaluated differential gene expression and pathway enrichment.

Results: A total of 12 Black female participants were included in the study, and transcriptomic analysis was performed in 4 participants. After at least 6 months of metformin treatment, 9 participants experienced improvement in disease, including scalp pain, inflammation, and/or pruritus, and 6 demonstrated clinical evidence of hair regrowth. The addition of metformin led to reversal of many prominent gene pathways previously identified in CCCA. Transcriptomic analysis revealed upregulation of pathways and genes (keratin-associated proteins [KRTAPs]) involved in keratinization, epidermis development, and the hair cycle (absolute log2-fold change > 4), with concomitant downregulation of fibrosis-related pathways and genes (eg, MMP7, COL6A1) (fold change >1.5; all false discovery rate <.05). Gene set analysis showed reduced expression of helper T cell 17 and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and KRTAPs after metformin treatment.

Conclusions and relevance: In this case series of patients with treatment-refractory CCCA, low-dose oral metformin was associated with symptomatic improvement and dual modulation of gene expression, stimulating hair growth pathways while suppressing fibrosis and inflammation markers. These findings provide a rationale for future clinical trials studying metformin as a targeted therapy for CCCA and other cicatricial alopecias.

重要性:中枢性离心卡他性脱发(CCCA)是一种瘢痕性脱发,主要影响黑人女性。目前的常规治疗方法针对炎症,但不针对潜在的纤维化过程,往往导致永久性脱发:目的:研究低剂量口服二甲双胍(一种具有抗纤维化特性的抗糖尿病药物)与 CCCA 患者临床症状和头皮基因表达模式的关系:这项回顾性临床病例系列和转录组分析包括 2023 年 1 月至 2024 年 3 月期间在一家三级学术医疗中心接受治疗的患者。所有患者均经活检确诊为标准疗法难治性 CCCA。在使用二甲双胍辅助治疗至少6周之前和之后,对患者先前储存的配对头皮活检组织进行转录组分析。主要结果和测量指标:临床评估包括瘙痒、炎症、头皮抵抗力和毛发再生。通过大量 RNA 测序分析进行基因表达谱分析,评估差异基因表达和通路富集情况:结果:共有 12 名黑人女性参加了这项研究,其中 4 人进行了转录组分析。经过至少 6 个月的二甲双胍治疗后,9 名参与者的头皮疼痛、炎症和/或瘙痒等症状有所改善,6 名参与者有头发再生的临床证据。加入二甲双胍后,以前在 CCCA 中发现的许多重要基因通路都发生了逆转。转录组分析显示,参与角质化、表皮发育和毛发周期的通路和基因(角蛋白相关蛋白 [KRTAPs])上调(绝对对数2倍变化>4),同时纤维化相关通路和基因(如 MMP7、COL6A1)下调(对数变化>1.5;所有假发现率均为结论和相关性):在这组难治性 CCCA 患者病例中,小剂量口服二甲双胍与症状改善和基因表达的双重调节有关,在刺激毛发生长途径的同时抑制了纤维化和炎症标记物。这些发现为今后将二甲双胍作为CCCA和其他卡他性脱发的靶向疗法进行临床试验提供了依据。
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引用次数: 0
Characteristics of Hispanic Patients With Dermatomyositis. 西班牙裔皮肌炎患者的特征
IF 11.5 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-01 DOI: 10.1001/jamadermatol.2024.2623
Rachel R Lin, Kimberly N Williams, Peyton V Warp, David Alvarez Cespedes, Scott A Elman, Andrea D Maderal
{"title":"Characteristics of Hispanic Patients With Dermatomyositis.","authors":"Rachel R Lin, Kimberly N Williams, Peyton V Warp, David Alvarez Cespedes, Scott A Elman, Andrea D Maderal","doi":"10.1001/jamadermatol.2024.2623","DOIUrl":"10.1001/jamadermatol.2024.2623","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Primary Cutaneous Cryptococcosis. 原发性皮肤隐球菌病。
IF 11.5 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-01 DOI: 10.1001/jamadermatol.2024.1899
Ying-Hsiang Wang, Jui Lan, Shang-Hung Lin
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引用次数: 0
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JAMA dermatology
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