Pub Date : 2026-01-28DOI: 10.1001/jamadermatol.2025.5700
Kirstine Duffau, Louise Baandrup, Kirsten Frederiksen, Tatiana Hansen, Allan Jensen, Nina L Mårtensson, Merete Hædersdal, Susanne K Kjær
<p><strong>Importance: </strong>Cutaneous squamous cell carcinoma (cSCC), cSCC in situ (CIS), and keratoacanthoma (KA) pose growing public health challenges, due to their associated morbidity, health care burden and costs. However, many countries lack systematic registration of these extremely frequent keratinocyte neoplasms.</p><p><strong>Objective: </strong>To estimate incidence rates and trends of first-time, histologically confirmed cSCC, CIS, and KA in Denmark (2005-2023) by sex, age, and anatomical site.</p><p><strong>Design, setting, and participants: </strong>A nationwide, population-based study using data from the Danish Pathology Registry and Cancer Registry was conducted, including individuals 20 years or older receiving a first-time diagnosis of cSCC, CIS, or KA from January 1, 2005 to December 31, 2023. Data analyses were conducted from January to July 2025.</p><p><strong>Main outcomes and measures: </strong>Age-standardized incidence rates (ASIRs) as well as age-specific incidence rates per 100 000 person-years with corresponding estimated annual percentage changes (EAPCs) and 95% CIs were calculated.</p><p><strong>Results: </strong>A total of 109 787 histologically confirmed cases were identified in 95 352 unique individuals (55 891 male individuals [50.9%], 53 896 female individuals [49.1%]) 20 years or older in Denmark, receiving a first-time diagnosis of cSCC (n = 54 563), CIS (n = 31 712), or KA (n = 23 512). From 2005 to 2023, cSCC ASIRs increased (EAPC for male individuals, 2.6%; EAPC for female individuals, 3.1%), reaching 131.6 and 77.7 per 100 000 person-years in male individuals and female individuals, respectively. CIS increased markedly (EAPC, for male individuals, 6.4%; EAPC for female individuals, 5.8%), and KA declined. Stratified analyses showed distinct sex-specific anatomic patterns. Predilection sites for cSCC and CIS were the face, scalp, and neck, with particular predominance among male individuals. Female individuals exhibited higher ASIRs on the lower limbs compared with male individuals (male vs female individuals: cSCC, 7.63 vs 12.32 per 100 000; CIS, 6.21 vs 12.63 per 100 000; KA, 3.47 vs 7.20 per 100 000, respectively). KA primarily affected the extremities. Female individuals aged 40 to 59 years showed higher incidence rates than male individuals across all keratinocyte neoplasms (male vs female individuals: cSCC, 131.6 vs. 77.7 per 100 000; CIS, 89.4 vs. 78.6 per 100 000; KA 28.6 vs. 27.6 per 100 000, respectively). Trends among individuals younger than 50 years with cSCC and KA were stable.</p><p><strong>Conclusions and relevance: </strong>In this nationwide cohort study presenting the most comprehensive dataset of incident cSCC, CIS, and KA, with 109 787 histologically confirmed patient cases, covering nearly 2 decades and spanning across all Danish health care sectors, incidence of cSCC and CIS continued to rise, consequently affecting more people, and sex differences diminished. Stabilizing trends i
{"title":"Incidence Trends of Cutaneous Squamous Cell Carcinoma, Carcinoma In Situ, and Keratoacanthoma By Sex, Age, and Anatomical Site.","authors":"Kirstine Duffau, Louise Baandrup, Kirsten Frederiksen, Tatiana Hansen, Allan Jensen, Nina L Mårtensson, Merete Hædersdal, Susanne K Kjær","doi":"10.1001/jamadermatol.2025.5700","DOIUrl":"10.1001/jamadermatol.2025.5700","url":null,"abstract":"<p><strong>Importance: </strong>Cutaneous squamous cell carcinoma (cSCC), cSCC in situ (CIS), and keratoacanthoma (KA) pose growing public health challenges, due to their associated morbidity, health care burden and costs. However, many countries lack systematic registration of these extremely frequent keratinocyte neoplasms.</p><p><strong>Objective: </strong>To estimate incidence rates and trends of first-time, histologically confirmed cSCC, CIS, and KA in Denmark (2005-2023) by sex, age, and anatomical site.</p><p><strong>Design, setting, and participants: </strong>A nationwide, population-based study using data from the Danish Pathology Registry and Cancer Registry was conducted, including individuals 20 years or older receiving a first-time diagnosis of cSCC, CIS, or KA from January 1, 2005 to December 31, 2023. Data analyses were conducted from January to July 2025.</p><p><strong>Main outcomes and measures: </strong>Age-standardized incidence rates (ASIRs) as well as age-specific incidence rates per 100 000 person-years with corresponding estimated annual percentage changes (EAPCs) and 95% CIs were calculated.</p><p><strong>Results: </strong>A total of 109 787 histologically confirmed cases were identified in 95 352 unique individuals (55 891 male individuals [50.9%], 53 896 female individuals [49.1%]) 20 years or older in Denmark, receiving a first-time diagnosis of cSCC (n = 54 563), CIS (n = 31 712), or KA (n = 23 512). From 2005 to 2023, cSCC ASIRs increased (EAPC for male individuals, 2.6%; EAPC for female individuals, 3.1%), reaching 131.6 and 77.7 per 100 000 person-years in male individuals and female individuals, respectively. CIS increased markedly (EAPC, for male individuals, 6.4%; EAPC for female individuals, 5.8%), and KA declined. Stratified analyses showed distinct sex-specific anatomic patterns. Predilection sites for cSCC and CIS were the face, scalp, and neck, with particular predominance among male individuals. Female individuals exhibited higher ASIRs on the lower limbs compared with male individuals (male vs female individuals: cSCC, 7.63 vs 12.32 per 100 000; CIS, 6.21 vs 12.63 per 100 000; KA, 3.47 vs 7.20 per 100 000, respectively). KA primarily affected the extremities. Female individuals aged 40 to 59 years showed higher incidence rates than male individuals across all keratinocyte neoplasms (male vs female individuals: cSCC, 131.6 vs. 77.7 per 100 000; CIS, 89.4 vs. 78.6 per 100 000; KA 28.6 vs. 27.6 per 100 000, respectively). Trends among individuals younger than 50 years with cSCC and KA were stable.</p><p><strong>Conclusions and relevance: </strong>In this nationwide cohort study presenting the most comprehensive dataset of incident cSCC, CIS, and KA, with 109 787 histologically confirmed patient cases, covering nearly 2 decades and spanning across all Danish health care sectors, incidence of cSCC and CIS continued to rise, consequently affecting more people, and sex differences diminished. Stabilizing trends i","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/PMC12853292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063424","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 : 2026-01-21DOI: 10.1001/jamadermatol.2025.5545
Varshini Babu, Daniel B Shin, Lynn Onstad, Joseph A Pidala, George Chen, Catherine J Lee, Carrie L Kitko, Paul A Carpenter, Corey Cutler, Najla El Jurdi, Alison W Loren, Joel M Gelfand, Stephanie J Lee, Emily Baumrin
<p><strong>Importance: </strong>Clinician-reported and patient-reported outcomes are critical measures of therapeutic efficacy in cutaneous chronic graft-vs-host disease (cGVHD) but are not always correlated. Discordance in treatment response between clinicians and patients hinders interpretation of outcomes in clinical trials and complicates therapeutic decision-making in clinical practice.</p><p><strong>Objective: </strong>To identify factors associated with discordance in clinician-reported and patient-reported treatment response assessments and to evaluate the association of clinician-reported and patient-reported responses with survival.</p><p><strong>Design, setting, and participants: </strong>This multicenter longitudinal cohort study included adults 18 years and older with cutaneous cGVHD at study enrollment, assembled from 2 observational studies and 1 randomized clinical trial. Data were collected from August 2007 to March 2024, and data were analyzed from July 2024 to May 2025.</p><p><strong>Main outcomes and measures: </strong>A global 8-point cutaneous cGVHD treatment response assessment (with 1 indicating resolved and 8 indicating very much worse) was reported by clinicians and patients 3 to 6 months after study enrollment. Clinician-reported and patient-reported treatment responses were categorized into improved, stable, and worse from the 8-point scale, and discordance was defined as a difference in response between clinicians and patients. Positive clinician discordance indicates the clinician reported a better response than the patient, and negative clinician discordance indicates the clinician reported a worse response than the patient. The association of clinician-reported and patient-reported responses with survival was measured by nonrelapse mortality.</p><p><strong>Results: </strong>Of 489 adults with cutaneous cGVHD, 192 (39.3%) were female, 297 (60.7%) were male, and the median (IQR) age was 55 (43-62) years. A total of 321 adults (65.6%) had concordant responses and 168 (34.4%) had discordant responses between clinician-reported and patient-reported treatment responses. Patients with sclerotic cGVHD had greater odds of discordance compared with those without sclerosis, with clinicians reporting both better and worse treatment response than patients (positive clinician discordance: adjusted odds ratio, 3.14; 95% CI, 1.41-6.95; P = .005; negative clinician discordance: adjusted odds ratio, 2.33; 95% CI, 1.19-4.56; P = .01). Worsening compared with improved overall cutaneous cGVHD was associated with nonrelapse mortality when reported by clinicians (adjusted hazard ratio, 2.28; 95% CI, 1.46-3.54; P < .001) and patients (adjusted hazard ratio, 1.86; 95% CI, 1.12-3.08; P = .02), while only patient-reported worsening was significantly associated with nonrelapse mortality in patients with sclerotic disease (adjusted hazard ratio, 2.00; 95% CI, 1.02-3.90; P = .04).</p><p><strong>Conclusions and relevance: </strong>In this cohort
{"title":"Discordance in Treatment Response Assessment Between Clinicians and Patients With Skin Chronic Graft-vs-Host Disease.","authors":"Varshini Babu, Daniel B Shin, Lynn Onstad, Joseph A Pidala, George Chen, Catherine J Lee, Carrie L Kitko, Paul A Carpenter, Corey Cutler, Najla El Jurdi, Alison W Loren, Joel M Gelfand, Stephanie J Lee, Emily Baumrin","doi":"10.1001/jamadermatol.2025.5545","DOIUrl":"10.1001/jamadermatol.2025.5545","url":null,"abstract":"<p><strong>Importance: </strong>Clinician-reported and patient-reported outcomes are critical measures of therapeutic efficacy in cutaneous chronic graft-vs-host disease (cGVHD) but are not always correlated. Discordance in treatment response between clinicians and patients hinders interpretation of outcomes in clinical trials and complicates therapeutic decision-making in clinical practice.</p><p><strong>Objective: </strong>To identify factors associated with discordance in clinician-reported and patient-reported treatment response assessments and to evaluate the association of clinician-reported and patient-reported responses with survival.</p><p><strong>Design, setting, and participants: </strong>This multicenter longitudinal cohort study included adults 18 years and older with cutaneous cGVHD at study enrollment, assembled from 2 observational studies and 1 randomized clinical trial. Data were collected from August 2007 to March 2024, and data were analyzed from July 2024 to May 2025.</p><p><strong>Main outcomes and measures: </strong>A global 8-point cutaneous cGVHD treatment response assessment (with 1 indicating resolved and 8 indicating very much worse) was reported by clinicians and patients 3 to 6 months after study enrollment. Clinician-reported and patient-reported treatment responses were categorized into improved, stable, and worse from the 8-point scale, and discordance was defined as a difference in response between clinicians and patients. Positive clinician discordance indicates the clinician reported a better response than the patient, and negative clinician discordance indicates the clinician reported a worse response than the patient. The association of clinician-reported and patient-reported responses with survival was measured by nonrelapse mortality.</p><p><strong>Results: </strong>Of 489 adults with cutaneous cGVHD, 192 (39.3%) were female, 297 (60.7%) were male, and the median (IQR) age was 55 (43-62) years. A total of 321 adults (65.6%) had concordant responses and 168 (34.4%) had discordant responses between clinician-reported and patient-reported treatment responses. Patients with sclerotic cGVHD had greater odds of discordance compared with those without sclerosis, with clinicians reporting both better and worse treatment response than patients (positive clinician discordance: adjusted odds ratio, 3.14; 95% CI, 1.41-6.95; P = .005; negative clinician discordance: adjusted odds ratio, 2.33; 95% CI, 1.19-4.56; P = .01). Worsening compared with improved overall cutaneous cGVHD was associated with nonrelapse mortality when reported by clinicians (adjusted hazard ratio, 2.28; 95% CI, 1.46-3.54; P < .001) and patients (adjusted hazard ratio, 1.86; 95% CI, 1.12-3.08; P = .02), while only patient-reported worsening was significantly associated with nonrelapse mortality in patients with sclerotic disease (adjusted hazard ratio, 2.00; 95% CI, 1.02-3.90; P = .04).</p><p><strong>Conclusions and relevance: </strong>In this cohort","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010569","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 : 2026-01-21DOI: 10.1001/jamadermatol.2025.5443
Maria C Schneeweiss, Richard Wyss, Priyanka Anand, Yinzhu Jin, Arash Mostaghimi, John Barbieri, Joseph F Merola, Jonathan I Silverberg, David M Rosmarin, Robert J Glynn, Sebastian Schneeweiss
{"title":"Risk of Acne in Patients With Atopic Dermatitis Starting a JAK Inhibitor vs Th2 Cytokine Inhibitor.","authors":"Maria C Schneeweiss, Richard Wyss, Priyanka Anand, Yinzhu Jin, Arash Mostaghimi, John Barbieri, Joseph F Merola, Jonathan I Silverberg, David M Rosmarin, Robert J Glynn, Sebastian Schneeweiss","doi":"10.1001/jamadermatol.2025.5443","DOIUrl":"10.1001/jamadermatol.2025.5443","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010574","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 : 2026-01-21DOI: 10.1001/jamadermatol.2025.5597
Courtney A Smith, Oumaima Kaabi, Amita K Manatunga, Timothy L Lash, Michael J Silverberg, Darios Getahun, Suma Vupputuri, Courtney E McCracken, Suephy C Chen, Vin Tangpricha, Michael Goodman, Howa Yeung
<p><strong>Importance: </strong>Acne commonly affects transgender individuals prescribed gender-affirming hormone therapy, yet population-level incidence data remain limited.</p><p><strong>Objective: </strong>To compare the incidence of acne and moderate to severe acne in transgender individuals, including those initiating gender-affirming hormone therapy, with matched cisgender individuals.</p><p><strong>Design, setting, and participants: </strong>A retrospective matched cohort study of electronic health record data was carried out across 4 Kaiser Permanente health plan regions. Index dates were the earliest documentation of transgender status, ranging from January 2006 to February 2022, with up to 5 years of follow-up. Participants included individuals without baseline acne, transmasculine individuals, and transfeminine individuals matched with cisgender male and female individuals. Analyses were conducted from November 2024 to November 2025.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was incident acne (first acne-coded visit after the index date). The secondary outcome was moderate to severe acne (incident acne followed by prescription fill for isotretinoin or 30 or more days of oral antibiotics). Exploratory analyses compared acne care utilization by transgender status.</p><p><strong>Results: </strong>Overall, 280 997 individuals without baseline acne, including 11 234 transmasculine and 9486 transfeminine individuals, were matched to 132 462 cisgender men and 127 815 cisgender women on age, self-reported race and ethnicity (25 340 Asian [9.0%]; 23 234 non-Hispanic Black [8.3%]; 56 876 Hispanic [20.2%]; 153 666 non-Hispanic White [54.7%]; 6989 other [2.5%]), enrollment year, and region. Of these, 12 156 transgender individuals initiated gender-affirming hormone therapy after the index date. The mean (SD) age at index date was 27.7 (10.0) years for transmasculine individuals and 33.2 (13.5) years for transfeminine individuals. Cumulative incidence of acne at 5 years was 15.8% in transmasculine individuals, 3.8% in matched cisgender male individuals, and 10.5% in matched cisgender female individuals and was 6.0% in transfeminine individuals, 2.9% in matched cisgender men, and 8.4% in matched cisgender women. Acne risk in transmasculine individuals was highest in the first year after testosterone initiation (vs matched cisgender male individuals: hazard ratio (HR), 8.29; 95% CI, 7.11-9.68; vs matched cisgender female individuals: HR, 2.63; 95% CI, 2.33-2.97) and remained higher in subsequent years than among cisgender men (HR, 5.29; 95% CI, 4.45-6.28) and cisgender women (HR, 1.69; 95% CI, 1.46-1.96). Acne risk was higher in transfeminine individuals after starting estradiol than cisgender men (HR, 1.56; 95% CI, 1.31-1.84) and lower than cisgender women (HR, 0.53; 95% CI, 0.46-0.62). Moderate to severe acne incidence followed similar patterns.</p><p><strong>Conclusions and relevance: </strong>This study revealed disti
{"title":"Acne Incidence and Severity in Transgender Individuals.","authors":"Courtney A Smith, Oumaima Kaabi, Amita K Manatunga, Timothy L Lash, Michael J Silverberg, Darios Getahun, Suma Vupputuri, Courtney E McCracken, Suephy C Chen, Vin Tangpricha, Michael Goodman, Howa Yeung","doi":"10.1001/jamadermatol.2025.5597","DOIUrl":"10.1001/jamadermatol.2025.5597","url":null,"abstract":"<p><strong>Importance: </strong>Acne commonly affects transgender individuals prescribed gender-affirming hormone therapy, yet population-level incidence data remain limited.</p><p><strong>Objective: </strong>To compare the incidence of acne and moderate to severe acne in transgender individuals, including those initiating gender-affirming hormone therapy, with matched cisgender individuals.</p><p><strong>Design, setting, and participants: </strong>A retrospective matched cohort study of electronic health record data was carried out across 4 Kaiser Permanente health plan regions. Index dates were the earliest documentation of transgender status, ranging from January 2006 to February 2022, with up to 5 years of follow-up. Participants included individuals without baseline acne, transmasculine individuals, and transfeminine individuals matched with cisgender male and female individuals. Analyses were conducted from November 2024 to November 2025.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was incident acne (first acne-coded visit after the index date). The secondary outcome was moderate to severe acne (incident acne followed by prescription fill for isotretinoin or 30 or more days of oral antibiotics). Exploratory analyses compared acne care utilization by transgender status.</p><p><strong>Results: </strong>Overall, 280 997 individuals without baseline acne, including 11 234 transmasculine and 9486 transfeminine individuals, were matched to 132 462 cisgender men and 127 815 cisgender women on age, self-reported race and ethnicity (25 340 Asian [9.0%]; 23 234 non-Hispanic Black [8.3%]; 56 876 Hispanic [20.2%]; 153 666 non-Hispanic White [54.7%]; 6989 other [2.5%]), enrollment year, and region. Of these, 12 156 transgender individuals initiated gender-affirming hormone therapy after the index date. The mean (SD) age at index date was 27.7 (10.0) years for transmasculine individuals and 33.2 (13.5) years for transfeminine individuals. Cumulative incidence of acne at 5 years was 15.8% in transmasculine individuals, 3.8% in matched cisgender male individuals, and 10.5% in matched cisgender female individuals and was 6.0% in transfeminine individuals, 2.9% in matched cisgender men, and 8.4% in matched cisgender women. Acne risk in transmasculine individuals was highest in the first year after testosterone initiation (vs matched cisgender male individuals: hazard ratio (HR), 8.29; 95% CI, 7.11-9.68; vs matched cisgender female individuals: HR, 2.63; 95% CI, 2.33-2.97) and remained higher in subsequent years than among cisgender men (HR, 5.29; 95% CI, 4.45-6.28) and cisgender women (HR, 1.69; 95% CI, 1.46-1.96). Acne risk was higher in transfeminine individuals after starting estradiol than cisgender men (HR, 1.56; 95% CI, 1.31-1.84) and lower than cisgender women (HR, 0.53; 95% CI, 0.46-0.62). Moderate to severe acne incidence followed similar patterns.</p><p><strong>Conclusions and relevance: </strong>This study revealed disti","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010580","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 : 2026-01-14DOI: 10.1001/jamadermatol.2025.5496
Ivo Abraham, Adewole S Adamson, Kanade Shinkai
{"title":"Biologics Prescribing in Dermatology by Advanced Practice Clinicians-Trends in the Practice of Advanced Practice Clinicians in Dermatology.","authors":"Ivo Abraham, Adewole S Adamson, Kanade Shinkai","doi":"10.1001/jamadermatol.2025.5496","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5496","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966143","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 : 2026-01-14DOI: 10.1001/jamadermatol.2025.5414
Xingyuan Jiang, Mark Y Jeng, Zhou Yang, Nelson Ugwu, Yuan Cheng, Caroline Echeandia-Francis, Ryland D Mortlock, Mitra V Mani, Natasha Rekhtman, Anna J Podolanczuk, Elizabeth Fiorino, Andrew Plodkowski, Ramrada Lekwuttikarn, Joyce Teng, Michael F Walsh, Helena A Yu, Zhimiao Lin, Keith A Choate
Importance: Acanthosis nigricans (AN) is commonly associated with impaired glucose tolerance, but early, severe presentation in individuals with normoglycemia may identify individuals at risk for systemic disease. While gain of function epidermal growth factor receptor (EGFR) pathogenic variants are associated with pulmonary cancers, their role in syndromic skin disease has not been clearly defined. This study identified activating EGFR variants that were associated with a syndrome characterized by generalized acquired keratoderma accentuated at flexural sites, woolly hair, palmoplantar keratoderma, and pulmonary disease with lung nodules, and the results suggest EGFR inhibitor therapeutic efficacy.
Objectives: To determine the genetic basis of early-onset, syndromic AN and assess response to pathogenesis-directed therapy.
Design, setting, and participants: Patients included 2 individuals with normoglycemia with early-onset periorificial hyperpigmentation and flexural skin thickening that subsequently generalized and 1 individual with an original diagnosis of widespread epidermal nevus. Participants underwent whole-exome sequencing and studies of affected skin and keratinocytes.
Main outcomes and measures: EGFR variant identification and assessment of pathway activation in lesional skin and keratinocytes, pulmonary function testing, lung imaging, and clinical response to EGFR inhibition.
Results: All 3 participants (aged 8, 18, and 17 years; 2 male individuals and 1 female individual) had an EGFR L858R variant, which arose as either de novo in generalized cases or a somatic variant in mosaic disease. Lesional skin and cultured keratinocytes demonstrated increased EGFR pathway activity, which was suppressed by pharmacologic inhibition in vitro. Systemic treatment with EGFR inhibitors was associated with skin disease regression, improvement in pulmonary disease, and resolution or reduction of the number of pulmonary nodules.
Conclusions and relevance: The findings of this case series study define a syndromic disorder with increased risk of pulmonary disease and lung nodules in patients with acquired, generalized AN that is associated with activating EGFR variants. Pulmonary nodules are precursor lesions for lung cancer, and treatment with EGFR inhibitions is associated with near-complete resolution of skin and pulmonary disease. Early recognition of syndromic EGFR AN will permit identification of individuals at risk for systemic disease who are candidates for EGFR-targeted therapy.
{"title":"De Novo Germline L858R EGFR Variants and Generalized Acanthosis Nigricans.","authors":"Xingyuan Jiang, Mark Y Jeng, Zhou Yang, Nelson Ugwu, Yuan Cheng, Caroline Echeandia-Francis, Ryland D Mortlock, Mitra V Mani, Natasha Rekhtman, Anna J Podolanczuk, Elizabeth Fiorino, Andrew Plodkowski, Ramrada Lekwuttikarn, Joyce Teng, Michael F Walsh, Helena A Yu, Zhimiao Lin, Keith A Choate","doi":"10.1001/jamadermatol.2025.5414","DOIUrl":"10.1001/jamadermatol.2025.5414","url":null,"abstract":"<p><strong>Importance: </strong>Acanthosis nigricans (AN) is commonly associated with impaired glucose tolerance, but early, severe presentation in individuals with normoglycemia may identify individuals at risk for systemic disease. While gain of function epidermal growth factor receptor (EGFR) pathogenic variants are associated with pulmonary cancers, their role in syndromic skin disease has not been clearly defined. This study identified activating EGFR variants that were associated with a syndrome characterized by generalized acquired keratoderma accentuated at flexural sites, woolly hair, palmoplantar keratoderma, and pulmonary disease with lung nodules, and the results suggest EGFR inhibitor therapeutic efficacy.</p><p><strong>Objectives: </strong>To determine the genetic basis of early-onset, syndromic AN and assess response to pathogenesis-directed therapy.</p><p><strong>Design, setting, and participants: </strong>Patients included 2 individuals with normoglycemia with early-onset periorificial hyperpigmentation and flexural skin thickening that subsequently generalized and 1 individual with an original diagnosis of widespread epidermal nevus. Participants underwent whole-exome sequencing and studies of affected skin and keratinocytes.</p><p><strong>Main outcomes and measures: </strong>EGFR variant identification and assessment of pathway activation in lesional skin and keratinocytes, pulmonary function testing, lung imaging, and clinical response to EGFR inhibition.</p><p><strong>Results: </strong>All 3 participants (aged 8, 18, and 17 years; 2 male individuals and 1 female individual) had an EGFR L858R variant, which arose as either de novo in generalized cases or a somatic variant in mosaic disease. Lesional skin and cultured keratinocytes demonstrated increased EGFR pathway activity, which was suppressed by pharmacologic inhibition in vitro. Systemic treatment with EGFR inhibitors was associated with skin disease regression, improvement in pulmonary disease, and resolution or reduction of the number of pulmonary nodules.</p><p><strong>Conclusions and relevance: </strong>The findings of this case series study define a syndromic disorder with increased risk of pulmonary disease and lung nodules in patients with acquired, generalized AN that is associated with activating EGFR variants. Pulmonary nodules are precursor lesions for lung cancer, and treatment with EGFR inhibitions is associated with near-complete resolution of skin and pulmonary disease. Early recognition of syndromic EGFR AN will permit identification of individuals at risk for systemic disease who are candidates for EGFR-targeted therapy.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966217","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 : 2026-01-14DOI: 10.1001/jamadermatol.2025.5498
Edward L Kong, Arash Mostaghimi
{"title":"Advanced Practice Clinicians and Dermatology Drug Spending.","authors":"Edward L Kong, Arash Mostaghimi","doi":"10.1001/jamadermatol.2025.5498","DOIUrl":"10.1001/jamadermatol.2025.5498","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966125","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}
<p><strong>Importance: </strong>ICP-332 is a tyrosine kinase 2 inhibitor currently under investigation for the treatment of atopic dermatitis (AD).</p><p><strong>Objective: </strong>To evaluate the safety and efficacy of ICP-332 for moderate to severe AD.</p><p><strong>Design, setting, and participants: </strong>This double-blind, placebo-controlled, phase 2 randomized clinical trial was conducted between February 6 and November 7, 2023, across 19 centers in China. Individuals aged 18 to 75 years who had diagnosis of AD for 1 year or longer and a history of contraindication or inadequate response to topical therapies were included.</p><p><strong>Intervention: </strong>Participants were randomized 1:1:1 to receive ICP-332 at 80 mg or 120 mg, or placebo orally once daily for 4 weeks. Study participants and personnel were blinded to group assignment.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was safety. The key efficacy outcome was the percentage change from baseline in Eczema Area and Severity Index (EASI) at week 4. Other outcomes included percentages of patients achieving EASI-75 (a ≥75% improvement in EASI) and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or more points improvement.</p><p><strong>Results: </strong>This study included 75 patients (mean [SD] age, 37.3 [18.0] years in the ICP-332 groups and 44.5 [17.4] years in the placebo group; 21 women [28%] and 54 men [72%]). Among the 74 patients included in the safety set, 17 of 25 (68%) in the placebo group, 19 of 25 (76%) in the 80-mg ICP-332 group, and 18 of 24 (75%) in the 120-mg ICP-332 group experienced treatment-emergent adverse events, with all events being mild or moderate. The most common adverse event was decreased blood fibrinogen (1 of 25 [4%] in the placebo group, 6 of 25 [44%] in the 80-mg ICP-332 group, and 5 of 24 [21%] in the 120-mg ICP-332 group). Percentage reductions in EASI at week 4 were -78.2% (95% CI, -89.8% to -66.6%) in the 80-mg ICP-332 group, -72.5% (95% CI, -84.3% to -60.7%) in the 120-mg ICP-332 group, and -16.7% (95% CI, -28.7% to -4.6%) for those receiving placebo. Mean differences vs placebo for percentage reductions from baseline at week 4 in EASI were -61.6% (95% CI, -78.4% to -44.7%; P < .001) and -55.8% (95% CI, -72.8% to -38.9%; P < .001) for 80-mg ICP-332 and 120-mg ICP-332, respectively. There was a statistically significant higher EASI-75 response rate with both ICP-332 doses (64.0% for each; difference vs placebo, 56.0%; 95% CI, 34.4%-77.6%; P < .001) than with placebo and a greater percentage of Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and improvement of 2 or more points at week 4 in the 80-mg ICP-332 group vs placebo (36.0%; difference vs placebo, 32.0%; 95% CI, 11.7%-52.3%; P = .005).</p><p><strong>Conclusions and relevance: </strong>In this phase 2 randomized clinical trial, ICP-332 demonstrated a favorable safety pro
{"title":"Safety and Efficacy of ICP-332 for Moderate to Severe Atopic Dermatitis: A Phase 2 Randomized Clinical Trial.","authors":"Jinhua Xu, Litao Zhang, Yunsheng Liang, Chao Ji, Ai'e Xu, Zhiming Li, Linfeng Li, Tiechi Lei, Chunlei Zhang, Rixin Chen, Xiaohua Tao, Ruzhi Zhang, Hong Fang, Jie Zheng, Wenlin Yang, Guoqiang Zhang, Xinsuo Duan, Yangfeng Ding, Wenhao Yin, Wei Zhou, Danbing Fan, Yue Du","doi":"10.1001/jamadermatol.2025.5295","DOIUrl":"10.1001/jamadermatol.2025.5295","url":null,"abstract":"<p><strong>Importance: </strong>ICP-332 is a tyrosine kinase 2 inhibitor currently under investigation for the treatment of atopic dermatitis (AD).</p><p><strong>Objective: </strong>To evaluate the safety and efficacy of ICP-332 for moderate to severe AD.</p><p><strong>Design, setting, and participants: </strong>This double-blind, placebo-controlled, phase 2 randomized clinical trial was conducted between February 6 and November 7, 2023, across 19 centers in China. Individuals aged 18 to 75 years who had diagnosis of AD for 1 year or longer and a history of contraindication or inadequate response to topical therapies were included.</p><p><strong>Intervention: </strong>Participants were randomized 1:1:1 to receive ICP-332 at 80 mg or 120 mg, or placebo orally once daily for 4 weeks. Study participants and personnel were blinded to group assignment.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was safety. The key efficacy outcome was the percentage change from baseline in Eczema Area and Severity Index (EASI) at week 4. Other outcomes included percentages of patients achieving EASI-75 (a ≥75% improvement in EASI) and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or more points improvement.</p><p><strong>Results: </strong>This study included 75 patients (mean [SD] age, 37.3 [18.0] years in the ICP-332 groups and 44.5 [17.4] years in the placebo group; 21 women [28%] and 54 men [72%]). Among the 74 patients included in the safety set, 17 of 25 (68%) in the placebo group, 19 of 25 (76%) in the 80-mg ICP-332 group, and 18 of 24 (75%) in the 120-mg ICP-332 group experienced treatment-emergent adverse events, with all events being mild or moderate. The most common adverse event was decreased blood fibrinogen (1 of 25 [4%] in the placebo group, 6 of 25 [44%] in the 80-mg ICP-332 group, and 5 of 24 [21%] in the 120-mg ICP-332 group). Percentage reductions in EASI at week 4 were -78.2% (95% CI, -89.8% to -66.6%) in the 80-mg ICP-332 group, -72.5% (95% CI, -84.3% to -60.7%) in the 120-mg ICP-332 group, and -16.7% (95% CI, -28.7% to -4.6%) for those receiving placebo. Mean differences vs placebo for percentage reductions from baseline at week 4 in EASI were -61.6% (95% CI, -78.4% to -44.7%; P < .001) and -55.8% (95% CI, -72.8% to -38.9%; P < .001) for 80-mg ICP-332 and 120-mg ICP-332, respectively. There was a statistically significant higher EASI-75 response rate with both ICP-332 doses (64.0% for each; difference vs placebo, 56.0%; 95% CI, 34.4%-77.6%; P < .001) than with placebo and a greater percentage of Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and improvement of 2 or more points at week 4 in the 80-mg ICP-332 group vs placebo (36.0%; difference vs placebo, 32.0%; 95% CI, 11.7%-52.3%; P = .005).</p><p><strong>Conclusions and relevance: </strong>In this phase 2 randomized clinical trial, ICP-332 demonstrated a favorable safety pro","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966220","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}
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