Pub Date : 2026-02-04DOI: 10.1001/jamadermatol.2025.5771
Andrew F Olshan
{"title":"Risk Factors for Acral Melanoma Among US Veterans.","authors":"Andrew F Olshan","doi":"10.1001/jamadermatol.2025.5771","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5771","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119046","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}
Pub Date : 2026-02-04DOI: 10.1001/jamadermatol.2025.5723
Cara Heppell, Ping-Chen Hou, Aimée Longmore, Lidia Shafik, Fatima Ali, Kavita S Subramaniam, Michael Antoniou, Chao-Kai Hsu, Jemima E Mellerio, John A McGrath, Su M Lwin
Importance: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder with wide clinical heterogeneity, ranging from localized skin fragility to life-limiting systemic complications. Understanding genotype-phenotype correlations in COL7A1, the causative gene, is critical for clinical prognostication, genetic counseling, and the rational design of emerging molecular therapies.
Objective: To determine the frequency of genotypic and phenotypic subtypes, and to assess whether variant type or location can predict phenotypic severity and extracutaneous complications in patients with RDEB carrying homozygous variants.
Evidence review: This was a systematic review of all RDEB genotypes and phenotypes reported to the International Dystrophic Epidermolysis Bullosa Patient Registry (DEB Registry) and eligible studies published in English from May 1993 to September 2025. PubMed, Cochrane Library, and Web of Science were searched and eligible studies were reviewed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020) guidelines. Included studies reported bi-allelic COL7A1 variants and clinical phenotypes. Data from the DEB Registry were cross-checked to supplement the published cases. Descriptive statistics were used for data analyses, and Fisher exact and χ2 methods were used to test additional genotype-phenotype correlations in patients with RDEB carrying homozygous variants.
Findings: A total of 1802 patients with RDEB comprising 1002 pathogenic variants within COL7A1 were identified from 217 articles. Among the 706 patients with homozygous variants (mean [SD; range] age, 12.2 [13.0; 0-72] years), 533 (75.5%) had severe RDEB, most frequently associated with frameshift and nonsense variants (388 [72.8%] premature termination codons [PTCs]). In contrast, intermediate and milder subtypes were associated with missense or non-PTC variants. Variant location also influenced phenotype: homozygous variants affecting the noncollagenous 1 domain were associated with severe RDEB in 74 of 83 unique variants (89.2%). Extracutaneous involvement clustered in homozygous PTC carriers and was observed almost exclusively in severe RDEB, with occasional cases in the intermediate subtype and rare instances in the inversa, localized, and self-improving subtypes. Recurrent and population-specific variants suggested founder effects. Splice site and missense variants showed phenotypic variability, with augmented intelligence-based predictions correlating with severity.
Conclusions and relevance: In this systematic review, the type and site of pathogenic variants in COL7A1 correlated with the severity of RDEB phenotype across different nationalities, races, and ethnicities. These findings may provide improved patient prognosis, genetic counseling, and personalized therapeutics.
重要性：隐性营养不良大疱性表皮松解症（RDEB）是一种罕见的单基因起泡疾病，具有广泛的临床异质性，从局部皮肤脆弱到限制生命的全身并发症。了解致病基因COL7A1的基因型-表型相关性对临床预后、遗传咨询和新兴分子治疗的合理设计至关重要。目的：确定基因型和表型亚型的频率，并评估变异类型或位置是否可以预测携带纯合变异的RDEB患者的表型严重程度和皮外并发症。证据回顾：这是一项对国际大疱性营养不良表皮松解症患者登记处（DEB Registry）报告的所有RDEB基因型和表型以及1993年5月至2025年9月以英文发表的符合条件的研究的系统回顾。检索PubMed、Cochrane图书馆和Web of Science，并按照PRISMA（2020年系统评价和荟萃分析首选报告项目）指南对符合条件的研究进行审查。纳入的研究报告了双等位基因COL7A1变异和临床表型。对DEB登记处的数据进行交叉核对，以补充已发表的病例。采用描述性统计进行数据分析，并采用Fisher精确和χ2方法检验携带纯合变异的RDEB患者的其他基因型-表型相关性。结果：从217篇文章中共鉴定出1802例RDEB患者，其中包括COL7A1内的1002种致病变异。706例纯合变异体患者（平均年龄12.2[13.0；0-72]岁）中，533例（75.5%）有严重RDEB，最常与移码和无义变异体相关（388例[72.8%]个过早终止密码子[ptc]）。相反，中度和轻度亚型与错义或非ptc变异相关。变异位置也影响表型：影响非胶原1结构域的纯合变异在83个独特变异中有74个（89.2%）与严重的RDEB相关。皮肤外受累集中在纯合子PTC携带者中，几乎只在严重的RDEB中观察到，偶尔有中间亚型的病例，而在相反、局部和自我改善亚型中则罕见。复发性和群体特异性变异提示奠基者效应。剪接位点和错义变异表现出表型变异性，并增强了与严重程度相关的基于智力的预测。结论和相关性：在本系统综述中，COL7A1致病变异的类型和位点与不同国籍、种族和民族的RDEB表型严重程度相关。这些发现可以改善患者预后，提供遗传咨询和个性化治疗。
{"title":"Genotype-Phenotype Correlations in Recessive Dystrophic Epidermolysis Bullosa: A Systematic Review.","authors":"Cara Heppell, Ping-Chen Hou, Aimée Longmore, Lidia Shafik, Fatima Ali, Kavita S Subramaniam, Michael Antoniou, Chao-Kai Hsu, Jemima E Mellerio, John A McGrath, Su M Lwin","doi":"10.1001/jamadermatol.2025.5723","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5723","url":null,"abstract":"<p><strong>Importance: </strong>Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder with wide clinical heterogeneity, ranging from localized skin fragility to life-limiting systemic complications. Understanding genotype-phenotype correlations in COL7A1, the causative gene, is critical for clinical prognostication, genetic counseling, and the rational design of emerging molecular therapies.</p><p><strong>Objective: </strong>To determine the frequency of genotypic and phenotypic subtypes, and to assess whether variant type or location can predict phenotypic severity and extracutaneous complications in patients with RDEB carrying homozygous variants.</p><p><strong>Evidence review: </strong>This was a systematic review of all RDEB genotypes and phenotypes reported to the International Dystrophic Epidermolysis Bullosa Patient Registry (DEB Registry) and eligible studies published in English from May 1993 to September 2025. PubMed, Cochrane Library, and Web of Science were searched and eligible studies were reviewed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020) guidelines. Included studies reported bi-allelic COL7A1 variants and clinical phenotypes. Data from the DEB Registry were cross-checked to supplement the published cases. Descriptive statistics were used for data analyses, and Fisher exact and χ2 methods were used to test additional genotype-phenotype correlations in patients with RDEB carrying homozygous variants.</p><p><strong>Findings: </strong>A total of 1802 patients with RDEB comprising 1002 pathogenic variants within COL7A1 were identified from 217 articles. Among the 706 patients with homozygous variants (mean [SD; range] age, 12.2 [13.0; 0-72] years), 533 (75.5%) had severe RDEB, most frequently associated with frameshift and nonsense variants (388 [72.8%] premature termination codons [PTCs]). In contrast, intermediate and milder subtypes were associated with missense or non-PTC variants. Variant location also influenced phenotype: homozygous variants affecting the noncollagenous 1 domain were associated with severe RDEB in 74 of 83 unique variants (89.2%). Extracutaneous involvement clustered in homozygous PTC carriers and was observed almost exclusively in severe RDEB, with occasional cases in the intermediate subtype and rare instances in the inversa, localized, and self-improving subtypes. Recurrent and population-specific variants suggested founder effects. Splice site and missense variants showed phenotypic variability, with augmented intelligence-based predictions correlating with severity.</p><p><strong>Conclusions and relevance: </strong>In this systematic review, the type and site of pathogenic variants in COL7A1 correlated with the severity of RDEB phenotype across different nationalities, races, and ethnicities. These findings may provide improved patient prognosis, genetic counseling, and personalized therapeutics.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118946","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}
Pub Date : 2026-02-04DOI: 10.1001/jamadermatol.2025.5827
Jonathan C Hwang, Linden B Huhmann, Kelly Cho, Sergey D Goryachev, Nicholas Starink, Martin A Weinstock, Maryam M Asgari, Christy Zheng, Charles Lu, Theodore C Feldman, Nhan V Do, John M Gaziano, Yevgeniy R Semenov, Marc S Hurlbert, Nathanael R Fillmore, Rebecca I Hartman
<p><strong>Importance: </strong>Acral melanoma (AM), localized to the palms, soles, and nail units, is a unique melanoma subtype less associated with UV radiation. Few studies have evaluated AM risk factors in a population of US veterans.</p><p><strong>Objective: </strong>To identify AM risk factors in US veterans.</p><p><strong>Design, setting, and participants: </strong>Nested case-control study (2000-2024) in the Veterans Affairs (VA) health care system. Individuals with AM were identified using the VA Cancer Registry and a validated natural language processing pipeline applied to pathology reports. Each AM case was matched to 4 nonacral cutaneous melanoma (CM) controls and 4 controls with no melanoma diagnoses at any time by diagnosis year and outpatient visit frequency. Controls with acral, mucosal, or ocular melanoma diagnoses at any time were excluded. Participants were veterans with histologically confirmed AM, nonacral CM controls, and controls with no melanoma diagnoses at any time.</p><p><strong>Exposure: </strong>Age, sex, race and ethnicity, rurality, region, military branch, comorbidities (National Cancer Institute Comorbidity Index), smoking status, unhealthy alcohol use as measured by the Alcohol Use Disorders Identification Test-Consumption, body mass index, Agent Orange exposure (AOE), prior photosensitizing medications, nevi, keratinocyte carcinoma (KC), actinic keratosis (AK), and number of dermatology visits in the 2 years before diagnosis.</p><p><strong>Main outcomes and measures: </strong>Adjusted odds ratios (AORs) comparing AM with controls using conditional logistic regression. Secondary outcomes included analyses limited to Vietnam Era veterans and AM localized to palmoplantar and subungual sites.</p><p><strong>Results: </strong>In total, 1292 individuals with AM (median age, 70.13 [IQR, 61.87-78.66] years; 1215 [94.0%] male) were matched to 5168 controls without melanoma (median age, 73.97 [IQR, 65.53-82.08] years; 5044 [97.6%] male), and 1286 individuals with AM (median age, 70.13 [IQR, 61.97-78.67] years; 1210 [94.1%] male) were matched to 5144 CM controls (median age, 74.58 [IQR, 66.86-82.05] years; 5068 [98.5%] male); 6 individuals with AM were excluded from AM vs CM analyses due to lack of matches. AOE was significantly associated with higher odds of AM vs CM (AOR, 1.31; 95% CI, 1.06-1.62) and vs controls without melanoma (AOR, 1.27; 95% CI, 1.04-1.56). Current smoking was associated with lower odds of AM (vs CM: AOR, 0.65; 95% CI, 0.52-0.81; vs controls without melanoma: AOR, 0.50; 95% CI, 0.40-0.62). Prior KC and AK were associated with higher odds vs controls without melanoma but lower odds vs CM. Prior nevus was associated with higher odds of AM vs controls without melanoma.</p><p><strong>Conclusions and relevance: </strong>Results of this study suggest that several factors were associated with AM in veterans and a need for continued investigation of AM as a distinct entity from CM and may inform future evalua
{"title":"Identification of Risk Factors for Acral Melanoma in US Veterans.","authors":"Jonathan C Hwang, Linden B Huhmann, Kelly Cho, Sergey D Goryachev, Nicholas Starink, Martin A Weinstock, Maryam M Asgari, Christy Zheng, Charles Lu, Theodore C Feldman, Nhan V Do, John M Gaziano, Yevgeniy R Semenov, Marc S Hurlbert, Nathanael R Fillmore, Rebecca I Hartman","doi":"10.1001/jamadermatol.2025.5827","DOIUrl":"10.1001/jamadermatol.2025.5827","url":null,"abstract":"<p><strong>Importance: </strong>Acral melanoma (AM), localized to the palms, soles, and nail units, is a unique melanoma subtype less associated with UV radiation. Few studies have evaluated AM risk factors in a population of US veterans.</p><p><strong>Objective: </strong>To identify AM risk factors in US veterans.</p><p><strong>Design, setting, and participants: </strong>Nested case-control study (2000-2024) in the Veterans Affairs (VA) health care system. Individuals with AM were identified using the VA Cancer Registry and a validated natural language processing pipeline applied to pathology reports. Each AM case was matched to 4 nonacral cutaneous melanoma (CM) controls and 4 controls with no melanoma diagnoses at any time by diagnosis year and outpatient visit frequency. Controls with acral, mucosal, or ocular melanoma diagnoses at any time were excluded. Participants were veterans with histologically confirmed AM, nonacral CM controls, and controls with no melanoma diagnoses at any time.</p><p><strong>Exposure: </strong>Age, sex, race and ethnicity, rurality, region, military branch, comorbidities (National Cancer Institute Comorbidity Index), smoking status, unhealthy alcohol use as measured by the Alcohol Use Disorders Identification Test-Consumption, body mass index, Agent Orange exposure (AOE), prior photosensitizing medications, nevi, keratinocyte carcinoma (KC), actinic keratosis (AK), and number of dermatology visits in the 2 years before diagnosis.</p><p><strong>Main outcomes and measures: </strong>Adjusted odds ratios (AORs) comparing AM with controls using conditional logistic regression. Secondary outcomes included analyses limited to Vietnam Era veterans and AM localized to palmoplantar and subungual sites.</p><p><strong>Results: </strong>In total, 1292 individuals with AM (median age, 70.13 [IQR, 61.87-78.66] years; 1215 [94.0%] male) were matched to 5168 controls without melanoma (median age, 73.97 [IQR, 65.53-82.08] years; 5044 [97.6%] male), and 1286 individuals with AM (median age, 70.13 [IQR, 61.97-78.67] years; 1210 [94.1%] male) were matched to 5144 CM controls (median age, 74.58 [IQR, 66.86-82.05] years; 5068 [98.5%] male); 6 individuals with AM were excluded from AM vs CM analyses due to lack of matches. AOE was significantly associated with higher odds of AM vs CM (AOR, 1.31; 95% CI, 1.06-1.62) and vs controls without melanoma (AOR, 1.27; 95% CI, 1.04-1.56). Current smoking was associated with lower odds of AM (vs CM: AOR, 0.65; 95% CI, 0.52-0.81; vs controls without melanoma: AOR, 0.50; 95% CI, 0.40-0.62). Prior KC and AK were associated with higher odds vs controls without melanoma but lower odds vs CM. Prior nevus was associated with higher odds of AM vs controls without melanoma.</p><p><strong>Conclusions and relevance: </strong>Results of this study suggest that several factors were associated with AM in veterans and a need for continued investigation of AM as a distinct entity from CM and may inform future evalua","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119142","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}
Pub Date : 2026-01-28DOI: 10.1001/jamadermatol.2025.6203
{"title":"Errors in Byline and Figures 3 and 4.","authors":"","doi":"10.1001/jamadermatol.2025.6203","DOIUrl":"10.1001/jamadermatol.2025.6203","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063428","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}
Pub Date : 2026-01-28DOI: 10.1001/jamadermatol.2025.5644
Nawar Tarafdar, Meghna Varambally, Nima Karimi, Edgar Akuffo-Addo, John R Ingram, Vincent Piguet
<p><strong>Importance: </strong>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with high psychosocial burden. Despite growing use of patient-reported outcome measures (PROMs) in HS trials, variance in quality and validation of existing instruments remains to be studied.</p><p><strong>Objective: </strong>To systematically review HS-specific PROMs using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) framework, evaluating development quality and psychometric evidence, and to perform a meta-analysis of key properties to summarize the evidence base and provide recommendations for clinical and research use.</p><p><strong>Data sources: </strong>MEDLINE, Embase, and PubMed were searched from inception to October 23, 2025, for English-language studies.</p><p><strong>Study selection: </strong>Articles describing the development or validation of HS-specific PROMs that evaluated at least 1 psychometric property were included. Generic instruments (eg, Dermatology Life Quality Index, pain numeric rating scale) were excluded. Screening was conducted by 2 independent reviewers.</p><p><strong>Data extraction and synthesis: </strong>Two reviewers independently extracted data, appraised risk of bias with the COSMIN checklist, and graded quality of evidence using COSMIN-modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Random-effects meta-analysis pooled Cronbach α and correlation coefficients; heterogeneity was quantified using I2.</p><p><strong>Main outcomes and measures: </strong>COSMIN-guided appraisal and graded quality of evidence of PROM measurement properties, including content validity, structural validity, internal consistency, reliability, responsiveness, and measurement error.</p><p><strong>Results: </strong>Of 504 records screened, 26 studies (14 developmental, 12 validation) met the criteria (total number of patients across 26 studies was 5811; age ranged from median 33.9 [range, 25-41] to mean [SD] 46.9 [14.1] years), identifying 15 unique HS-specific PROMs (10 health-related quality of life, 4 symptom, 1 treatment benefit). Fourteen achieved sufficient content validity and 8 met the highest standards for rigorous instrument development. Meta-analysis demonstrated strong internal consistency and construct validity for the 17-item Hidradenitis Suppurativa Quality of Life (HiSQOL-17) PROM (pooled Cronbach α = 0.94; I2 = 81.3%; pooled Pearson r = 0.84; I2 = 74%; pooled Spearman r = 0.88, I2 = 29%). Of 7 evaluated PROMs, 2 displayed sufficient internal consistency. The remainder were indeterminate due to absent or low-quality evidence for unidimensionality. Test-retest reliability was sufficient in 9 PROMs, and responsiveness was rated sufficient in 5. No studies evaluated measurement error. Seven PROMs met COSMIN criteria for recommendation.</p><p><strong>Conclusions and relevance: </strong>In this study, 7 PROMs demonstrated sufficiency of both content
{"title":"Hidradenitis Suppurativa Patient-Reported Outcome Measures: A Systematic Review and Meta-Analysis.","authors":"Nawar Tarafdar, Meghna Varambally, Nima Karimi, Edgar Akuffo-Addo, John R Ingram, Vincent Piguet","doi":"10.1001/jamadermatol.2025.5644","DOIUrl":"10.1001/jamadermatol.2025.5644","url":null,"abstract":"<p><strong>Importance: </strong>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with high psychosocial burden. Despite growing use of patient-reported outcome measures (PROMs) in HS trials, variance in quality and validation of existing instruments remains to be studied.</p><p><strong>Objective: </strong>To systematically review HS-specific PROMs using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) framework, evaluating development quality and psychometric evidence, and to perform a meta-analysis of key properties to summarize the evidence base and provide recommendations for clinical and research use.</p><p><strong>Data sources: </strong>MEDLINE, Embase, and PubMed were searched from inception to October 23, 2025, for English-language studies.</p><p><strong>Study selection: </strong>Articles describing the development or validation of HS-specific PROMs that evaluated at least 1 psychometric property were included. Generic instruments (eg, Dermatology Life Quality Index, pain numeric rating scale) were excluded. Screening was conducted by 2 independent reviewers.</p><p><strong>Data extraction and synthesis: </strong>Two reviewers independently extracted data, appraised risk of bias with the COSMIN checklist, and graded quality of evidence using COSMIN-modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Random-effects meta-analysis pooled Cronbach α and correlation coefficients; heterogeneity was quantified using I2.</p><p><strong>Main outcomes and measures: </strong>COSMIN-guided appraisal and graded quality of evidence of PROM measurement properties, including content validity, structural validity, internal consistency, reliability, responsiveness, and measurement error.</p><p><strong>Results: </strong>Of 504 records screened, 26 studies (14 developmental, 12 validation) met the criteria (total number of patients across 26 studies was 5811; age ranged from median 33.9 [range, 25-41] to mean [SD] 46.9 [14.1] years), identifying 15 unique HS-specific PROMs (10 health-related quality of life, 4 symptom, 1 treatment benefit). Fourteen achieved sufficient content validity and 8 met the highest standards for rigorous instrument development. Meta-analysis demonstrated strong internal consistency and construct validity for the 17-item Hidradenitis Suppurativa Quality of Life (HiSQOL-17) PROM (pooled Cronbach α = 0.94; I2 = 81.3%; pooled Pearson r = 0.84; I2 = 74%; pooled Spearman r = 0.88, I2 = 29%). Of 7 evaluated PROMs, 2 displayed sufficient internal consistency. The remainder were indeterminate due to absent or low-quality evidence for unidimensionality. Test-retest reliability was sufficient in 9 PROMs, and responsiveness was rated sufficient in 5. No studies evaluated measurement error. Seven PROMs met COSMIN criteria for recommendation.</p><p><strong>Conclusions and relevance: </strong>In this study, 7 PROMs demonstrated sufficiency of both content ","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063361","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}
Pub Date : 2026-01-28DOI: 10.1001/jamadermatol.2025.5449
Elise Edwards, Ladonya Jackson-Cowan, Nicole Khalil, Qai Ven Yap, Gil Yosipovitch
{"title":"Sleep Disturbance as a Mediator Between Itch and Quality of Life.","authors":"Elise Edwards, Ladonya Jackson-Cowan, Nicole Khalil, Qai Ven Yap, Gil Yosipovitch","doi":"10.1001/jamadermatol.2025.5449","DOIUrl":"10.1001/jamadermatol.2025.5449","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063391","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}
Pub Date : 2026-01-28DOI: 10.1001/jamadermatol.2025.5331
Heba Ahmed, Sarah Elsayed, Ghada El-Kamah, Heba El-Sayed, Khalda Amr, Randa M A M El-Mofty, Mohamed H M El-Komy
{"title":"Novel Sodium-Dependent Multivitamin Transporter Variant Mimicking Acrodermatitis Enteropathica.","authors":"Heba Ahmed, Sarah Elsayed, Ghada El-Kamah, Heba El-Sayed, Khalda Amr, Randa M A M El-Mofty, Mohamed H M El-Komy","doi":"10.1001/jamadermatol.2025.5331","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5331","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063422","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}
Pub Date : 2026-01-28DOI: 10.1001/jamadermatol.2025.5662
Elena C de Rosas, Justin C Wang, Christina K Zigler, Kathryn S Torok
<p><strong>Importance: </strong>Currently, there are no treatments approved by the US Food and Drug Administration for juvenile localized scleroderma (JLS), a rare disease. While methotrexate (MTX) is regularly used as a first-line therapy, emerging data from case series and applications in systemic sclerosis suggest that mycophenolate mofetil (MMF) may be clinically comparable, with potential benefits in tolerability and adherence.</p><p><strong>Objective: </strong>To compare clinical outcomes of patients with JLS treated with MTX and MMF using standardized clinical outcome measures.</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study of patients with clinician-diagnosed JLS who were enrolled in the National Registry of Childhood Onset Scleroderma was conducted at UPMC Children's Hospital of Pittsburgh. Data were from January 2010 to January 2023 and first analyzed in April 2023. All patients were evaluated and followed up by the same physician. Patients were included if they had disease onset before age 18 years and a localized scleroderma diagnosis and enrollment in the National Registry of Childhood Onset Scleroderma before age 21 years. Patients were required to be receiving MTX monotherapy, MMF monotherapy, or combination therapy (CT) of the 2 for their localized scleroderma.</p><p><strong>Exposures: </strong>Patients were treated with MTX, MMF, or CT as prescribed by the examining physician.</p><p><strong>Main outcomes and measures: </strong>This study measured comparative medication treatment response through associations with disease activity, as measured using the Localized Scleroderma Cutaneous Assessment Tool.</p><p><strong>Results: </strong>Of 114 patients, 77 (67.5%) were female, and the median (IQR) age at onset was 8.3 (5.4-11.2) years. The MTX, MMF, and CT groups included 68 (59.6%), 28 (24.6%), and 18 patients (15.8%), respectively. There were no significant differences in baseline demographic characteristics, disease subtype, or disease severity between groups, but patients in the MMF group had longer disease duration. Mixed-effects modeling showed statistically significant decreases in activity across all groups (β = -0.14; 95% CI, -0.62 to 0.33). A Kaplan-Meier analysis showed no significant difference in disease flare rate over the follow-up interval (hazard ratio, 0.85; 95% CI, 0.51-1.33). However, patients treated with MTX compared with those treated with MMF had significantly higher rates of fatigue (47% vs. 11%, P = .001) and nausea (60% vs. 7%; P = .001).</p><p><strong>Conclusions and relevance: </strong>The study results suggest that MMF demonstrated a similar response to treatment as MTX in reducing disease activity in JLS, with comparable flare rates and improved tolerability. These initial findings support MMF as a potential candidate for first-line treatment of JLS. Prospective, randomized, noninferiority trials are warranted to confirm these results and guide future treatment
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