JAMA dermatology最新文献

{"title":"Incidence of and Risk Factors for Cutaneous Malignant Neoplasms After Blood or Marrow Transplant.","authors":"Kristy K Broman, Qingrui Meng, Anna Holmqvist, Nora Balas, Joshua Richman, Wendy Landier, Lindsey Hageman, Elizabeth Ross, Alysia Bosworth, Hok Sreng Te, Britany Hollenquest, F Lennie Wong, Ravi Bhatia, Stephen J Forman, Saro H Armenian, Daniel J Weisdorf, Smita Bhatia","doi":"10.1001/jamadermatol.2024.5129","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5129","url":null,"abstract":"<p><strong>Importance: </strong>Cutaneous malignant neoplasms are the most common subsequent neoplasm after blood or marrow transplant (BMT), but a full assessment among survivors is lacking.</p><p><strong>Objective: </strong>To identify risk factors for subsequent cutaneous malignant neoplasms using the BMT Survivor Study (BMTSS).</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study included patients who underwent transplant from 1974 to 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and survived 2 years or longer, as well as a comparison cohort of siblings. Both groups completed the BMTSS survey. Data analysis took place from October 2022 to October 2024.</p><p><strong>Exposures: </strong>Demographics, pre-BMT and BMT-related therapeutic exposures, chronic graft-vs-host disease (cGVHD), and posttransplant immunosuppression.</p><p><strong>Main outcomes and measures: </strong>Incident cutaneous malignant neoplasms (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) after BMT. Exposures were evaluated for association with subsequent neoplasms using proportional subdistribution hazards models (reported as subdistribution hazard ratio [SHR] and 95% CI).</p><p><strong>Results: </strong>Among the 3880 BMT survivors (median [range] age at BMT, 44.0 [0-78.0] years; 2165 [55.8%] male; 190 [4.9%] Black, 468 [12.1%] Hispanic, 2897 [74.7%] non-Hispanic White, and 325 [8.4%] of other race [including Asian and Pacific Islander] and multiracial) who were followed up for a median (range) of 9.5 (2.0-46.0) years, 605 developed 778 distinct cutaneous neoplasms (BCC, 321; SCC, 231; melanoma, 78; and unknown type, 148). The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% (BCC, 18.0%; SCC, 9.8%; and melanoma, 3.7%). Seventy-year cumulative probabilities of BCC, SCC, and melanoma were considerably higher in BMT survivors than siblings (18.1% vs 8.2%, 14.7% vs 4.2%, and 4.2% vs 2.4%, respectively). Among BMT survivors, risk factors for subsequent cutaneous malignant neoplasms included age of 50 years and older at BMT (BCC: SHR, 1.76; 95% CI, 1.36-2.29; SCC: SHR, 3.37; 95% CI, 2.41-4.72), male sex (BCC: SHR, 1.39; 95% CI, 1.10-1.75; SCC: SHR, 1.85; 95% CI, 1.39-2.45), pre-BMT monoclonal antibody exposure (BCC: SHR, 1.71; 95% CI, 1.27-2.31), allogeneic BMT with cGVHD (BCC: SHR, 1.48; 95% CI, 1.06-2.08; SCC: SHR, 2.61; 95% CI, 1.68-4.04 [reference: autologous BMT]), post-BMT immunosuppression (BCC: SHR, 1.63; 95% CI, 1.24-2.14; SCC: SHR, 1.48; 95% CI, 1.09-2.02; melanoma: SHR, 1.90; 95% CI, 1.16-3.12), and transplant at City of Hope (BCC: SHR, 3.55; 95% CI, 2.58-4.89; SCC: SHR, 3.57; 95% CI, 2.34-5.47 [reference: University of Minnesota]) or University of Alabama at Birmingham (BCC: SHR, 2.35; 95% CI, 1.35-4.23; SCC: SHR, 2.63; 95% CI, 1.36-5.08 [reference: University of Minnesota]). Race and ethnicity other than non-Hispanic White were protective ","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846724","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}

{"title":"Self-Guided vs Clinician-Guided Online Cognitive Behavioral Therapy for Atopic Dermatitis: A Randomized Clinical Trial.","authors":"Dorian Kern, Brjánn Ljótsson, Louise Lönndahl, Erik Hedman-Lagerlöf, Olof Molander, Björn Liliequist, Maria Bradley, Nils Lindefors, Martin Kraepelien","doi":"10.1001/jamadermatol.2024.5044","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5044","url":null,"abstract":"<p><strong>Importance: </strong>Clinician-guided online self-help based on cognitive behavioral therapy (CBT) has been shown to be effective at decreasing symptom severity for people with atopic dermatitis (AD). A brief online self-guided CBT intervention could be more cost-effective and allow for easy implementation and broader outreach compared with more comprehensive clinician-guided interventions.</p><p><strong>Objective: </strong>To investigate whether a brief online self-guided CBT intervention is noninferior to a comprehensive online clinician-guided CBT treatment.</p><p><strong>Design, setting, and participants: </strong>This single-blind randomized clinical noninferiority trial was conducted at Karolinska Institutet, Stockholm, Sweden. Adult individuals with AD were enrolled from November 2022 to April 2023. The last postintervention data were collected in December 2023.</p><p><strong>Interventions: </strong>Participants randomized to the self-guided group had access to a self-guided online CBT intervention for 12 weeks without clinician support. Participants randomized to the clinician-guided group received online CBT for 12 weeks.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was change in score from baseline to postintervention to 12-week follow-up on the self-reported Patient-Oriented Eczema Measure (POEM). The predefined noninferiority margin was 3 points on POEM.</p><p><strong>Results: </strong>Of 168 randomized participants, 142 (84.5%) were female, and the mean (SD) age was 39 (10.5) years. A total of 86 participants were randomized to the self-guided group and 82 were randomized to the clinician-guided group. A total of 151 (90.0%) completed the main outcome postintervention assessment. Postintervention, the clinician-guided group had improved 4.20 points (95% CI, 1.94-6.05) on POEM and the self-guided group improved 4.60 points (95% CI, 2.57-6.64), corresponding to an estimated mean difference in change of 0.36 points (1-sided 97.5% CI, -∞ to 1.75), which was below the noninferiority margin of 3 points. No serious adverse events were reported. In the clinician-guided group, clinicians spent a mean (SD) of 36.0 (33.3) minutes (95% CI, 29.2-41.7) on treatment guidance and 14.0 (6.0) minutes (95% CI, 12.9-15.6) on assessments compared to 15.8 (6.4) minutes on assessments in the self-guided group.</p><p><strong>Conclusions and relevance: </strong>In this randomized clinical noninferiority trial, a brief self-guided CBT intervention was noninferior to clinician-guided CBT. Given the limited clinical resources required to deliver self-guided CBT, this treatment might be a promising means to disseminate evidence-based psychological treatment for patients with AD.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05517850.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846761","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}

{"title":"Necrotic Plaque in a Patient With Malignant Hematologic Disease.","authors":"Marika Matsuya, Motoshi Kinouchi, Yuzufumi Sekiguchi","doi":"10.1001/jamadermatol.2024.4868","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.4868","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846752","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}

{"title":"Interobserver and Intraobserver Agreement on the Treatment of Infantile Hemangiomas.","authors":"María Colmenero-Sendra, Javier Del Boz-González, Mercè Grau-Pérez, Ricardo Ruiz-Villaverde, Miguel Ángel Descalzo-Gallego, Ignacio García-Doval, Eulalia Baselga Torres","doi":"10.1001/jamadermatol.2024.5125","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5125","url":null,"abstract":"<p><strong>Importance: </strong>Although clinical practice guidelines exist for the treatment of infantile hemangiomas (IHs), recommendations are heterogeneous, and wide practice variations in IH management have been reported.</p><p><strong>Objective: </strong>To analyze the degree of agreement in treatment choices for IH among pediatric dermatologists in North America and Europe and assess whether there are differences across IH risk categories.</p><p><strong>Design, setting, and participants: </strong>This cross-sectional interrater and intrarater agreement study was conducted through a survey based on the Spanish Academy of Dermatology and Venereology IH prospective cohort. The survey used 50 vignettes of IH cases that were randomly selected from the cohort. It was administered twice in 2023, 1 month apart, to allow for interrater and intrarater agreement assessments. Data were analyzed in January 2024. The study involved pediatric dermatologists from North America (via the Pediatric Dermatology Research Alliance) and Europe (via the European Society of Pediatric Dermatologists).</p><p><strong>Exposures: </strong>Participants were asked to choose 1 of 3 treatment options (propranolol, topical timolol, or observation) for each vignette.</p><p><strong>Main outcome and measure: </strong>The primary outcome was the interrater agreement in treatment choices for IH cases, measured using κ statistics (Gwet AC1 coefficient).</p><p><strong>Results: </strong>The global interobserver agreement among 90 pediatric dermatologists was fair (AC1, 0.38; 95% CI, 0.29-0.46). In North America (45 pediatricians), agreement was moderate (AC1, 0.41; 95% CI, 0.33-0.49), while in Europe (45 pediatricians) it was fair (AC1, 0.37; 95% CI, 0.28-0.46). The degree of agreement varied depending on the risk category of IH, with excellent agreement in high-risk IH and only moderate agreement in intermediate-risk and low-risk IHs. Propranolol was predominantly chosen for high-risk IH, while observation was most frequent for low-risk IH (55.9%). The second survey had 61 respondents, with no significant intrarater differences.</p><p><strong>Conclusions and relevance: </strong>The results of this survey study suggest that there is an important variability in the treatment of intermediate-risk and low-risk IH. The study findings support the need for more evidence regarding the role of topical timolol in IH treatment, which may help harmonize treatment approaches and improve consistency in IH management globally.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846729","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}

{"title":"Improving Diversity in a Novel Psoriasis Study: VISIBLE as a Framework for Clinical Trial Quality Improvement.","authors":"Andrew Alexis, Amy McMichael, Neelam Vashi, Tina Bhutani, Adrian O Rodriguez, Jensen Yeung, Olivia Choi, Daphne Chan, Theodore Alkousakis, Denise N Bronner, Laura Park-Wyllie, Long-Long Gao, Pearl Grimes, Mona Shahriari, Geeta Yadav, Chesahna Kindred, Susan C Taylor, Seemal R Desai","doi":"10.1001/jamadermatol.2024.5103","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5103","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Diverse racial and ethnic representation in clinical trials has been limited, not representative of the US population, and the subject of pending US Food and Drug Administration guidance. Psoriasis presentation and disease burden can vary by skin pigmentation, race and ethnicity, and socioeconomic differences. Overall, there are limited primary data on clinical response, genetics, and quality of life in populations with psoriasis and skin of color (SoC). The Varying Skin Tones in Body and Scalp Psoriasis: Guselkumab Efficacy and Safety trial (VISIBLE) is underway and uses strategies aimed at addressing this persistent gap.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To assess the innovative strategies used in the VISIBLE trial to recruit and retain diverse participants in a randomized clinical trial of psoriasis in participants with SoC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;This was an ad hoc quality improvement assessment of participant recruitment and retention approaches used by the VISIBLE trial. VISIBLE enrolled and randomized 211 participants (mean [SD] age, 43 [13] years; 75 females [36%] and 136 males [64%]) with SoC and moderate to severe plaque psoriasis from August 2022 to March 2023 to evaluate guselkumab treatment. The self-identified race and ethnicity of the participants was: 1 American Indian/Alaska Native (0.5%), 63 Asian (29.9%), 24 Black (11.4%), 94 Hispanic/Latino (44.5%), 13 Middle Eastern (6.2%), 1 Pacific Islander/Native Hawaiian (0.5%), 12 multiracial (5.7%), and 3 of other race and/or ethnicity (1.4%). Using a combination of objective (colorimetry to determine Fitzpatrick skin type) and self-reported (race and ethnicity consistent with SoC) parameters, VISIBLE sought to broaden inclusion of participants from various backgrounds.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Observed improvements were that participant enrollment occurred approximately 7 times faster than anticipated (vs historical recruitment data for psoriasis studies); 211 participants (100%) self-identified themselves as a race or ethnicity other than White; and more than 50% had skin tone in the darker half of the Fitzpatrick skin type spectrum (type IV-VI). Innovations implemented by VISIBLE were (1) assessment of the natural history of postinflammatory pigment alteration and improvements over time using combined objective colorimetry and clinician- and patient-reported outcomes; (2) evaluation of genetic and comorbidity biomarkers relevant to participants with SoC; (3) a diverse demographic-driven approach to site selection (emphasizing investigator and staff diversity and experience with populations with SoC); (4) provision of cultural competency training to enhance participant enrollment and retention; (5) collection of patient-reported outcomes data in participants' primary language; and (6) periodic, blinded central review and feedback on investigator efficacy scoring to promote consistency and accuracy in evaluating ","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807129","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}

{"title":"Risk of Death Due to Melanoma and Other Causes in Patients With Thin Cutaneous Melanomas.","authors":"Serigne N Lo, Gabrielle J Williams, Anne E Cust, David W Ollila, Alexander H R Varey, Sydney Ch'ng, Richard A Scolyer, John F Thompson","doi":"10.1001/jamadermatol.2024.4900","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.4900","url":null,"abstract":"<p><strong>Importance: </strong>Most patients who present with primary cutaneous melanomas have thin tumors (≤1.0 mm in Breslow thickness, ie, pT1a and pT1b). Although their prognosis is generally considered to be excellent, there is limited precise information on the association of risk of death with specific Breslow measurements in thin lesions.</p><p><strong>Objective: </strong>To assess the relative effect of a 0.8-mm Breslow thickness threshold with respect to the incidence of both melanoma-related and nonmelanoma-related death.</p><p><strong>Design, setting, and participants: </strong>Registry data for all Australians diagnosed with thin invasive primary melanomas between 1982 and 2014 were analyzed. Data were extracted from all 8 Australian state and territory population-based cancer registries. Dates and causes of death were obtained from the Australian National Death Index. Adults diagnosed with a first invasive primary melanoma of 1.0 mm or smaller in thickness were included.</p><p><strong>Exposure: </strong>First invasive primary melanoma between 1982 and 2014.</p><p><strong>Main outcomes and measures: </strong>The primary outcomes were melanoma-related deaths and nonmelanoma-related deaths. Competing-risk regression analyses and cause-specific analyses were performed to investigate the relationships between Breslow thickness subcategory (<0.8 mm versus ≥0.8 mm by 0.1-mm increments) and the primary outcomes.</p><p><strong>Results: </strong>Overall, a cohort of 144 447 participants was included. The median (range) age was 56 (18-101) years and 78 014 (54.0%) were men. Median (IQR) follow-up was 15.0 (9.5-23.3) years. Crude incidence rates of melanoma-related death 20 years after diagnosis were 6.3% (95% CI, 6.1%-6.5%) for the whole cohort, 6.0% (95% CI, 5.7%-6.2%) for tumors smaller than 0.8 mm, and 12.0% (95% CI, 11.4%-12.6%) for tumors 0.8 to 1.0 mm. The corresponding 20-year melanoma-specific survival rates were 91.9% (95% CI, 91.6%-92.1%), 94.2% (95% CI, 94.0%-94.4%), and 87.8% (95% CI, 87.3%-88.3%), respectively. On multivariable analysis, tumor thickness of 0.8 to 1.0 mm was significantly associated with both a greater absolute risk of melanoma-related death (subdistribution hazard ratio, 2.92; 95% CI, 2.74-3.12) and a greater rate of melanoma-related death (hazard ratio, 2.98; 95% CI, 2.79-3.18) than thinner tumors (<0.8 mm). Risk of death from nonmelanoma-related causes was not associated with Breslow thickness.</p><p><strong>Conclusions and relevance: </strong>In this study, the risk of melanoma-related death increased significantly for patients with primary tumors of 0.8 to 1.0 mm in thickness. The risk of death from nonmelanoma-ralated causes was similar across Breslow thicknesses of 0.1 to 1.0 mm. This analysis suggests that a 0.8-mm threshold for guiding the care of patients with thin primary melanomas.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807241","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}

{"title":"Melanoma Tumor Mutational Burden and Indoor Tanning Exposure.","authors":"Grace B Hanrahan, Anita Giobbie-Hurder, Blair Allais, Jayne Vogelzang, Christopher Fay, Hillary C Tsibris","doi":"10.1001/jamadermatol.2024.4819","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.4819","url":null,"abstract":"<p><strong>Importance: </strong>UV-induced mutagenesis leads to a higher tumor mutational burden (TMB) in cutaneous melanoma relative to other cancer types. TMB is an important prognostic marker in advanced melanoma; higher TMB is associated with greater clinical response to immune checkpoint inhibition and improved survival.</p><p><strong>Objective: </strong>To evaluate the association between cutaneous melanoma TMB and indoor tanning exposure, as well as other demographic, dermatologic, and tumor characteristics.</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study took place at Dana-Farber Cancer Institute, a tertiary-care cancer treatment center in Boston, Massachusetts, between 2013 and 2022. Patients with a diagnosis of cutaneous melanoma for whom next-generation sequencing data and tanning bed exposure history were available were included.</p><p><strong>Exposures: </strong>Indoor tanning exposure history, tumor characteristics, demographics, and dermatologic history were collected via retrospective medical record review.</p><p><strong>Main outcomes and measures: </strong>The association of tanning bed use with TMB was modeled using inverse probability of treatment weighted, multivariable modeling.</p><p><strong>Results: </strong>Among 617 patients (median [IQR] age at diagnosis, 61 [50-71] years; 337 [62.9%] male), there was no association between indoor tanning exposure and TMB after adjustment for demographic, tumor, and dermatologic characteristics (yes vs no: log2 TMB [SE], 4.07 [0.44] vs 3.97 [0.45]; P = .39). However, there was a statistically significant association between higher TMB and older age at diagnosis, history of nonmelanoma skin cancer, and head and neck tumors relative to other primary sites. Average TMB was statistically significantly lower in patients with a history of abnormal nevi (yes vs no: log2 TMB [SE], 3.89 [0.44] vs 4.15 [0.44]; P = .01).</p><p><strong>Conclusions and relevance: </strong>This cohort study suggests that indoor tanning exposure, while known to increase risk of melanoma, may not be meaningfully associated with melanoma TMB. Additional characteristics were associated with higher TMB and, thus, potentially improved immune checkpoint inhibitor response.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807196","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}

{"title":"Successful Treatment of Mogamulizumab-Associated Rash With Upadacitinib: Evidence From 2 Cases.","authors":"Daniel Martín-Torregrosa, Ignacio Torres-Navarro, Miguel Mansilla-Polo, Fernando Navarro-Blanco, Blanca de Unamuno-Bustos, Vicent Martínez I Cózar, Rafael Botella-Estrada","doi":"10.1001/jamadermatol.2024.4582","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.4582","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807253","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}

{"title":"Safety and Efficacy of Anti-IL-23 Monoclonal Antibody QX004N for Patients With Psoriasis: A Randomized Clinical Trial.","authors":"Xiaojiao Li, Bing Li, Deming Yang, Meng Wang, Qianqian Li, Nan Wang, Min Fang, Jingrui Liu, Hong Zhang, Min Wu, Cuiyun Li, Xiaoxue Zhu, Yanhua Ding, Shanshan Li","doi":"10.1001/jamadermatol.2024.5059","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5059","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Psoriasis is a chronic, immune-mediated skin disease with an unmet need for biologic treatment options.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To assess the safety, pharmacokinetics, and efficacy of QX004N in healthy individuals and patients with moderate to severe plaque psoriasis in China.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;This randomized clinical trial was composed of 2 parts. Part 1 was a first-in-human, single-ascending-dose, phase 1a clinical trial conducted from November 2, 2021, to January 16, 2023. Part 2 was a double-blind, multiple dose-escalation, phase 1b clinical trial conducted from February 15, 2023, to January 5, 2024, at 5 clinical centers in China, involving patients with moderate to severe plaque psoriasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;In part 1, healthy participants in each cohort were assigned in a 4:1 ratio to receive a single subcutaneous injection of QX004N (ranging from 10 mg to 600 mg) or placebo. In part 2, patients in each cohort were assigned in a 4:1 ratio to receive QX004N or placebo at doses of 150 mg, 300 mg, and 600 mg once every 2 weeks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;For part 1, the primary outcome was the safety of a single dose of QX004N in healthy participants, and the secondary outcome was the pharmacokinetic profile. For part 2, the primary efficacy end point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) by week 12; other efficacy end points were considered secondary.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The phase 1a clinical trial (part 1) enrolled 55 healthy participants (mean [SD] age, 35.9 [6.0] years; 30 [54.5%] female), and the phase 1b clinical trial (part 2) enrolled 30 patients with moderate to severe plaque psoriasis. The mean (SD) age of QX004N-treated participants in part 2 was 41.4 (7.5) years, and 19 of 24 QX004N-treated participants (79.2%) were male. The mean (SD) age of the placebo cohort in part 2 was 35.3 (8.4) years, and 5 of 6 placebo-treated participants (83.3%) were male. QX004N exhibited linear pharmacokinetics and was tolerated well in both healthy participants and patients with psoriasis. Most adverse events were mild to moderate in severity, with no drug-related serious adverse events reported. The proportion of patients receiving QX004N who achieved PASI 75 at week 12 and PASI 90 (90% improvement in PASI) at week 16 in the 150-mg, 300-mg, and 600-mg cohorts was 100%, significantly higher than that in the placebo cohorts (33.3%). The maximum proportion of patients achieving Investigator's Global Assessment score of 0 or 1 was 100% in the 3 QX004N cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;In this randomized clinical trial, QX004N was well tolerated and demonstrated superior efficacy compared to placebo in patients with moderate to severe plaque psoriasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;Chinese Clinical Trial Reg","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807251","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}

{"title":"Clinical and Genetic Findings in Patients With Palmoplantar Keratoderma.","authors":"Stine Bjørn Gram, Klaus Brusgaard, Ulrikke Lei, Mette Sommerlund, Gabrielle Randskov Vinding, Sondre Olai Kjellevold Sleire, Alex Hørby Christensen, Sanne Pedersen Fast, Rasmus Bach, Anette Bygum, Lilian Bomme Ousager","doi":"10.1001/jamadermatol.2024.4824","DOIUrl":"10.1001/jamadermatol.2024.4824","url":null,"abstract":"<p><strong>Importance: </strong>Palmoplantar keratoderma poses diagnostic challenges due to its clinical and genetic heterogeneity, and knowledge on the value of systematic genetic testing on clinically well-described patient cohorts is sparse.</p><p><strong>Objective: </strong>To improve knowledge of the clinical and genetic spectrum of patients with palmoplantar keratoderma.</p><p><strong>Design, setting, and participants: </strong>This cohort study prospectively recruited patients and affected family members with palmoplantar keratoderma between September 1, 2016, and December 31, 2022. Patients were recruited from private practitioners in dermatology and dermatology departments in Denmark. Study participants were patients 18 years or older either newly diagnosed with palmoplantar keratoderma or being followed up for the disease at referral centers.</p><p><strong>Main outcomes and measures: </strong>Phenotypes and clinical subtypes were classified. Genetic testing was performed by whole-exome or genome sequencing using an in silico panel containing genes related to palmoplantar keratoderma, or by Sanger sequencing for specific variants. Descriptive analysis, such as proportions and frequency, were used to describe clinical characteristics, distribution of disease-causing variants, and genotype-phenotype associations.</p><p><strong>Results: </strong>This study included 142 study participants from 76 families (90 [63%] female; median [range] age, 52 [18-92] years). Clinical subtypes included 42 punctate (55%), 26 diffuse (34%), 5 focal (7%), and 3 striate (4%). A genetic diagnosis was found in 63 of 76 families (83%), including 27 disease-causing variants within 13 different genes: AAGAB (n = 39), DSG1 (n = 8), KRT1 (n = 3), DSP (n = 2), KRT9 (n = 2), AQP5 (n = 2), KRT16 (n = 1), SERPINA12 (n = 1), ABCA12 (n = 1), COL7A1 (n = 1), CARD14 (n = 1), DST (n = 1), and LORICRIN (n = 1). All participants with AAGAB variants presented with punctate palmoplantar keratoderma, showing a clear genotype-phenotype correlation. The other subtypes (diffuse, focal, and striate) proved more challenging to clinically subclassify, and disease-causing variants were identified in 12 genes, contributing to more complex genotype-phenotype patterns. Patients with palmoplantar keratoderma due to DSP variants were found, which is important to identify because of an associated risk of cardiomyopathy.</p><p><strong>Conclusion and relevance: </strong>This study provides novel insights into the clinical and genetic spectrum of patients with palmoplantar keratoderma. It demonstrates the value of genetic testing for accurate diagnoses and to distinguish between different subtypes. The established and well-described cohort lays the foundation for future research in palmoplantar keratoderma.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768991","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}