Importance:Alopecia areata (AA) is an autoimmune hair loss disorder that affects more than 7 million people in the US. Before US Food and Drug Administration-approved trials of Janus kinase inhibitors, numerous treatments had been explored, with variable efficacy and quality of evidence. The absence of standardized treatment guidelines may lead to poor treatment outcomes and payer coverage. Objective:To establish a consensus on treatment for adults with severe AA in the US. Evidence Review:Systematic literature reviews for all known therapies used for treating AA were performed in PubMed from inception to December 2024. Inclusion criteria required studies to be randomized clinical trials or have an observational design, evaluate adult (≥18 years old) participants with moderate to severe AA (defined by Severity of Alopecia Tool scores >20%), and be published in English. Studies were excluded if they included patients with non-AA hair loss or if they exclusively evaluated pediatric participants or those with mild AA (Severity of Alopecia Tool scores ≤20%). Three rounds of anonymous, iterative online surveys were administered from May through November 2025. Consensus was predefined at an agreement threshold of 70% or greater. A definition of AA severity was proposed for determining patient eligibility. Experts with recent AA-related research and extensive clinical experience treating adults with severe disease indicated their agreement or disagreement with the use of 29 treatments for adults with severe AA. Treatments that reached consensus for inclusion were further explored with respect to therapeutic positioning, treatment regimens, and long-term management. Findings:Thirty-one US-based AA experts completed 3 rounds of iterative surveys. Consensus was achieved on treatment of adults with severe alopecia areata, as defined by the Alopecia Areata Scale. Oral Janus kinase inhibitors represented the primary, long-term therapy for all patients, with dupilumab as an alternative option for patients with comorbid atopy. Supplemental treatments included oral and topical minoxidil; intralesional, oral, and high-potency topical corticosteroids; and topical Janus kinase inhibitors and prostaglandins, with body site-specific indications. Patient support resources should be offered alongside medical treatment. Conclusion and Relevance:This study defines expert-established consensus on treatment of adults with severe AA in the US. Additional high-quality investigations are needed to establish the efficacy of existing therapies in subpopulations and enable head-to-head comparisons of new and existing interventions. These recommendations are not indicated for children, pregnant patients, patients with mild to moderate disease, or those with underlying comorbidities; additional research is needed to inform treatment guidelines for these specific patient populations.
Importance:Pleomorphic dermal sarcomas (PDSs) are classified as sarcomas; however, they share features with cutaneous carcinomas, such as presentation on sun-exposed areas and high tumor mutational burden (TMB). Data regarding management of PDS are limited, and it is unclear whether sarcoma or cutaneous cancer treatment paradigms should apply. At present, there are no published data comparing the mutational genetics of PDSs to other cutaneous tumors and to other soft-tissue sarcomas (STSs). Objective:To compare TMB, UV signature, and single-nucleotide and pathway-level mutational profiles of PDS to cutaneous squamous cell carcinoma (CSCC) and STS. Design, Setting, and Participants:This single-center retrospective cohort study was performed at the Dana-Farber Cancer Institute and Brigham and Women's Hospital from January 1, 2015, to October 20, 2025. Patients diagnosed with PDS, metastatic CSCC, and STS were identified by electronic medical records and included if a 447-tumor gene sequencing assay was performed on tumor tissue. Main Outcomes and Measures:The primary end point was to compare the single-nucleotide variant profiles of PDS, metastatic CSCC, and STS using unsupervised machine learning analysis. The secondary end points were to compare mean TMB, pathway-level mutations, and UV signature status. Results:A total of 9 PDSs, 15 metastatic CSCCs, and 25 STSs were included. At the pathway level, TP53, cell cycle, NOTCH, and receptor tyrosine kinase-Ras pathways were highly mutated in PDS and CSCC, whereas STS lacked major pathway mutations. The mean TMB was 44.6 (95% CI, 37.5-51.8) for PDS, 54.1 (95% CI, 40.4-67.8) for CSCC, and 4.2 (95% CI, 3.2-5.2) for STS. Statistically significant differences in mean TMB were observed between CSCC and STS and between PDS and STS but not between CSCC and PDS. All PDSs and CSCCs displayed UV signature mutations, while none of other STSs did. Principal component analysis of mutational variants and TMB on sequencing assay showed completely overlapping PDS and CSCC clusters and separate, narrow STS clustering. Conclusions and Relevance:In this cohort study, PCA analysis of single-nucleotide variants and comparison of TMB, UV signature, and pathway-level alterations between groups suggested similar genetic profiling between metastatic CSCC and PDS, which were distinct from STS.
This case report describes a patient with digital wrinkling following glomus tumor surgical excision.
This genetic association study provides new data on a prior case report of persistent neonatal pemphigus, reclassifying it as genetic rather than autoimmune in origin.
This cross-sectional study identifies trends in the density of dermatologists and total physicians per 100 000 people in rural and urban counties.
Importance:Neurofibromatosis type 1 (NF1) is a multisystem, tumor predisposition syndrome in which vascular manifestations, including cutaneous lesions, remain poorly characterized. Cherry angiomas (CAs) have been sporadically reported in NF1, but their prevalence and biological basis are unknown. Objective:To assess the association between NF1 and CAs and define the histopathologic, cellular, and genetic mechanisms underlying NF1-associated CAs. Design, Setting, and Participants:This prospective, comparative, cross-sectional epidemiological study was conducted from October 2020 to March 2021 at a French national referral center for neurofibromatoses within the dermatology department at Henri-Mondor University Hospital, Créteil, France. It was followed by integrated histopathologic, genomic, and cell-specific molecular analyses. The epidemiological analysis included individuals 15 years or older with confirmed NF1 and controls without NF1. Pathophysiological analyses were conducted on CAs from individuals with NF1 and healthy volunteers following written consent. Data were analyzed in 2022. Main Outcomes and Measures:Outcomes included the prevalence of CAs; age-adjusted and sex-adjusted odds ratios; histopathologic features; detection of somatic NF1 second-hit variants; identification of co-occurring oncogenic variants; localization of NF1 loss within vascular cell populations; and evidence of rat sarcoma-mitogen-activated protein kinase pathway activation. Results:Of 259 participants (125 female individuals [48.3%]), 102 (39.4%) individuals had NF1 (median [range] age, 34 [18-70] years) and 157 (60.6%) were controls (median [range] age, 40 [15-91] years). CAs were more frequent in individuals with NF1 than controls (48% vs 18%; odds ratio, 4.26; 95% CI, 2.44-7.56) and occurred at a younger age. This association persisted after adjustment for age and sex and in propensity score-matched analyses. Somatic NF1 loss-of-function second hits were identified in 26 of 39 of NF1-associated CAs (67%) and none from controls, indicating biallelic NF1 inactivation. Comprehensive genomic profiling revealed frequent co-occurring activating variants, most commonly in GNAQ. Cell-specific sequencing showed that NF1 second hits arose predominantly in endothelial cells and telocytes, with higher variant allele frequencies in endothelial cells. Immunofluorescence demonstrated increased phosphoextracellular signal-regulated kinase signaling in these vascular cell populations. Conclusions and Relevance:The results of this cross-sectional study suggest that CAs represent a frequent and previously unrecognized vascular manifestation of NF1, which is supported by epidemiological enrichment and mechanistic evidence of biallelic NF1 inactivation in vascular cells. These findings potentially expand the spectrum of NF1-associated neoplasms and establish CAs as a model for NF1-related vasculopathy.
This case report describes a patient with a history of myasthenia gravis and thyoma who developed upper extremity myalgias and arthralgias after tapering prednisone.
Importance:Basal cell carcinoma (BCC) is the most common type of skin cancer worldwide. Particularly on the face, its locally destructive growth leads to functional and aesthetic impairment. Early diagnosis enables less invasive treatment. Line-field confocal optical coherence tomography (LC-OCT) is an effective noninvasive imaging method for the diagnosis of BCC. Objectives:To investigate whether LC-OCT paired with artificial intelligence (AI)-assisted image recognition can identify subclinical BCCs through systematic screening of inconspicuous facial skin in patients at high risk of developing BCC. Design, Setting, and Participants:This prospective cross-sectional feasibility study was conducted from April 2025 to October 2025 at the Department of Dermatology, Uniklinikum Erlangen, in Erlangen, Germany. Consecutive patients receiving inpatient care who had at least 2 established BCC risk factors were enrolled in the study. Exposure:After the exclusion of lesions macroscopically suggestive of BCC, inconspicuous facial skin was systematically examined using AI-assisted LC-OCT. Main Outcome and Measure:The prespecified main outcome was positive predictive value (PPV) of AI-assisted LC-OCT for histologically confirmed subclinical BCC. Results:Among 150 patients (mean [SD] age, 72.9 [10.3] years; 57 [38.0%] female; 93 [62.0%] male), 17 subclinical BCCs were identified in 14 patients (9.3%). Of 18 lesions diagnosed as BCC with AI-assisted LC-OCT, 15 were histologically confirmed, corresponding to a PPV of 83.3% (95% CI, 58.1%-96.4%). One lesion had a false-positive result (actinic keratosis); 2 patients declined biopsy. In a sensitivity analysis including the 2 nonbiopsied lesions that were confirmed with expert analysis, PPV was 94.4% (95% CI, 72.7%-99.9%). The distribution of BCC subtypes included 13 cases of superficial BCCs (76.5%), followed by 3 cases of nodular BCCs (17.6%), and 1 case of infiltrative BCC (5.9%). Subtype classification was accurate in 13 of 15 histologically confirmed cases (86.7% [95% CI, 59.5%-98.3%]). Conclusions and Relevance:In this cross-sectional feasibility study, the findings suggest that systematic screening with AI-assisted LC-OCT may be a feasible approach for BCC detection at a preclinical stage in populations at high risk for BCC. Further prospective studies are needed to assess the sensitivity and cost-effectiveness of this method, and whether early detection translates to tangible clinical benefit before implementation in routine care can be recommended.
This economic evaluation examines the diagnostic threshold, step therapy, and prescriber requirements from commercial health plans for covering 7 US Food and Drug Administration–approved atopic dermatitis medications.
This Viewpoint describes growing concerns about antifungal resistance in the treatment of patients with seborrheic dermatitis.
Background:Alopecia areata (AA) is an autoimmune disease that can affect the quality of life of affected individuals. Publicly available online conversations and search behavior provide valuable insights into public awareness, understanding, and information related to AA. An infodemiology approach, therefore, offers an opportunity to characterize these perspectives across Gulf countries. This study evaluated the understanding and awareness of AA in Bahrain, Kuwait, Oman, Qatar, and the United Arab Emirates based on AA-related mentions and internet searches. Objective:Despite its prevalence, AA is often misunderstood, particularly in the Middle East. By examining the data from social media platforms, online forums, and internet searches, this study provided insight into the regional AA perceptions and awareness in these 5 Gulf countries. Methods:Online discussions in English and Arabic mentioning AA and related terms were analyzed from the 5 countries between January 2022 and April 2023. Results:The analysis of more than 8500 mentions of AA over 16 months revealed significant online engagement, especially from the United Arab Emirates. Educational content dominated the discussions, with a notable increase following the Oscars incident in April 2022. Gulf news platforms and X (formerly Twitter) were the primary discussion platforms, with health care professionals mainly using English and patients using both English and Arabic. Common topics included potential contributors to AA, emotional distress, and the AA patient journey. Conclusions:The study identified gaps in awareness and understanding of AA among patients, health care professionals, and medical facilities in the Gulf region through online discussions and search patterns. These insights can facilitate the development of targeted educational initiatives, support strategies, improve awareness, reduce stigma, and enhance support networks for those affected by AA.
Importance:Alopecia areata (AA) is a chronic, systemic immune-mediated disease characterized by nonscarring hair loss. Many patients do not experience improvements with available treatment options and only ritlecitinib is approved for adolescent patients; therefore, there remains a clear unmet need for additional and improved systemic therapies. Objective:To evaluate the efficacy and safety of upadacitinib-an oral selective Janus kinase inhibitor-in adult and adolescent patients with severe AA. Design, Setting, and Participants:This global clinical program included 2 parallel phase 3 replicate randomized clinical trials (UP-AA1 and UP-AA2) conducted from October 2023 to July 2025, to evaluate upadacitinib in adolescent and adult patients (age 12 to <64 years old) with severe AA, defined as a Severity of Alopecia Tool (SALT) score of 50 or greater. Both trials included a 24-week placebo-controlled, double-blinded treatment period (period A) and a 28-week blinded extension treatment period (period B). Data were analyzed from July 2025 to October 2025. Interventions:Eligible patients were randomized 2:2:1 to once daily 15- or 30-mg upadacitinib or matching placebo. Main Outcomes and Measures:Achievement of (multiplicity controlled) SALT score of 20 or less at week 24. Multiplicity-controlled secondary efficacy end points included achievement of improvements in clinician-reported outcomes for eyebrows and eyelashes; achievement of SALT scores of 20 or less at weeks 4, 8, and 12; achievement of SALT score of 10 or less; SALT score 0 at week 24; patients' global impression of change of AA score of much better or moderately better at weeks 4 and 24; and other AA-specific health-related quality of life measures at week 24. Results:A total of 1399 patients were randomized (mean [range] age, 36 [12-64] years; 826 female [59.0%]), 676 patients from the UP-AA1 and 723 patients from the UP-AA2, to either 15-mg upadacitinib (270 and 289 patients, respectively), 30-mg upadacitinib (271 and 289), or placebo (135 and 145). Their mean (SD) SALT score was 83.9 (18.9) at baseline. The proportion of patients who achieved SALT score of 20 or less at week 24 was significantly higher for the 15-mg upadacitinib (122 [45.2%] and 129 [44.6%]) and the 30-mg upadacitinib (149 [55.0%] and 157 [54.3%]) groups, respectively, than for the placebo (2 [1.5%] and 5 [3.4%]) group. The safety profile of both doses was similar in adults and adolescents and consistent with approved indications; no new safety findings were identified. Treatment-emergent adverse events reported by more than 5% of patients in any treatment group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis. Across both studies, treatment-emergent serious adverse events occurred in 9 (1.6%), 13 (2.3%), and 1 (0.4%) of patients receiving 15-mg upadacitinib , 30-mg upadacitinib, or placebo, respectively. Conclusions and Relevance:In these 2 parallel phase 3 replicate randomized clinical trials, upadacitinib demonstrated a positive benefit-risk profile in adults and adolescents with severe AA. Upadacitinib may be a potentially effective treatment option for this patient population. Trial Registration:ClinicalTrials.gov Identifier: NCT06012240.
This case report describes a man in his 50s who presented with a 2-day history of abrupt-onset, painful lesions on the trunk and all 4 extremities, accompanied by fever.
Importance Alopecia areata (AA) is a chronic, systemic immune-mediated disease characterized by nonscarring hair loss. Many patients do not experience improvements with available treatment options and only ritlecitinib is approved for adolescent patients; therefore, there remains a clear unmet need for additional and improved systemic therapies. Objective To evaluate the efficacy and safety of upadacitinib—an oral selective Janus kinase inhibitor—in adult and adolescent patients with severe AA. Design, Setting, and Participants This global clinical program included 2 parallel phase 3 replicate randomized clinical trials (UP-AA1 and UP-AA2) conducted from October 2023 to July 2025, to evaluate upadacitinib in adolescent and adult patients (age 12 to <64 years old) with severe AA, defined as a Severity of Alopecia Tool (SALT) score of 50 or greater. Both trials included a 24-week placebo-controlled, double-blinded treatment period (period A) and a 28-week blinded extension treatment period (period B). Data were analyzed from July 2025 to October 2025. Interventions Eligible patients were randomized 2:2:1 to once daily 15- or 30-mg upadacitinib or matching placebo. Main Outcomes and Measures Achievement of (multiplicity controlled) SALT score of 20 or less at week 24. Multiplicity-controlled secondary efficacy end points included achievement of improvements in clinician-reported outcomes for eyebrows and eyelashes; achievement of SALT scores of 20 or less at weeks 4, 8, and 12; achievement of SALT score of 10 or less; SALT score 0 at week 24; patients’ global impression of change of AA score of much better or moderately better at weeks 4 and 24; and other AA-specific health-related quality of life measures at week 24. Results A total of 1399 patients were randomized (mean [range] age, 36 [12-64] years; 826 female [59.0%]), 676 patients from the UP-AA1 and 723 patients from the UP-AA2, to either 15-mg upadacitinib (270 and 289 patients, respectively), 30-mg upadacitinib (271 and 289), or placebo (135 and 145). Their mean (SD) SALT score was 83.9 (18.9) at baseline. The proportion of patients who achieved SALT score of 20 or less at week 24 was significantly higher for the 15-mg upadacitinib (122 [45.2%] and 129 [44.6%]) and the 30-mg upadacitinib (149 [55.0%] and 157 [54.3%]) groups, respectively, than for the placebo (2 [1.5%] and 5 [3.4%]) group. The safety profile of both doses was similar in adults and adolescents and consistent with approved indications; no new safety findings were identified. Treatment-emergent adverse events reported by more than 5% of patients in any treatment group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis. Across both studies, treatment-emergent serious adverse events occurred in 9 (1.6%), 13 (2.3%), and 1 (0.4%) of patients receiving 15-mg upadacitinib , 30-mg upadacitinib, or placebo, respectively. Conclusions and Relevance In these 2 parallel phase 3 replicate randomized clinical trials, upadacitinib demonstrated a positive benefit-risk profile in adults and adolescents with severe AA. Upadacitinib may be a potentially effective treatment option for this patient population. Trial Registration ClinicalTrials.gov Identifier: NCT06012240
Importance Blood or marrow transplant (BMT) recipients are at increased risk of developing subsequent cutaneous malignant neoplasms. There is a need to develop risk stratification tools to identify those at highest risk to inform dermatologic surveillance and evaluate risk mitigation strategies. Objective To develop and validate a risk stratification tool for subsequent cutaneous malignant neoplasms among BMT recipients that incorporates readily available patient and treatment information. Design, Setting, and Participants This prognostic study included participants in the multi-institutional, longitudinal BMT Survivor Study (BMTSS), which included individuals who underwent autologous or allogeneic BMT from January 1, 1974, to December 31, 2014, at 1 of 3 participating sites in California, Minnesota, and Alabama and survived 2 or more years after BMT. The present cohort was restricted to individuals who underwent a single transplant and completed at least 1 BMTSS survey. Data were analyzed from December 3, 2024, to June 3, 2026. Exposures Risk stratification models included the following candidate variables: age at BMT, sex, race, ethnicity, prior cutaneous malignant neoplasm, pretransplant exposure to monoclonal antibodies, total body irradiation, chronic graft vs host disease, and posttransplant immunosuppression. Main Outcomes and Measures The main outcomes were incident basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or melanoma after BMT, ascertained based on participant report with medical record validation when available. Models for risk stratification were developed and validated using time-dependent area under the receiver operating characteristic (AUC) curve with repeated random partitioning into training and testing cohorts. Results were averaged to make a final model. Individuals were classified into low or high risk for subsequent cutaneous malignant neoplasm based on clinically meaningful risk stratification score thresholds. Results Of the 3448 included BMTSS participants (1917 [55.6%] male; mean [SD] age at BMT, 41.9 [19.2] years) who were alive without a cutaneous malignant neoplasm event 2 years after BMT, 282 (8.2%) were diagnosed with BCC, 183 (5.3%) with SCC, and 73 (2.1%) with melanoma. At 15 years after BMT, the test model AUCs were 0.81 (95% CI, 0.76-0.85) for BCC, 0.90 (95% CI, 0.86-0.93) for SCC, and 0.83 (95% CI, 0.74-0.90) for melanoma. The 15-year cumulative incidence of BCC, SCC, and melanoma in the low-risk group was 2.4% (95% CI, 1.5%-3.9%), 3.2% (95% CI, 2.4%-4.2%), and 0.8% (95% CI, 0.4%-1.5%), respectively. In the high-risk group, the 15-year cumulative incidence of BCC, SCC, and melanoma was 13.3% (95% CI, 11.6%-15.4%), 13.6% (95% CI, 11.2%-16.5%), and 4.4% (95% CI, 3.2%-6.1%), respectively. Conclusions and Relevance In this prognostic study, risk stratification models demonstrated excellent performance, highlighting potential utility for identifying BMT recipients who are at greatest risk of subsequent cutaneous malignant neoplasms.
Background:Outdoor workers receive significantly more UV radiation exposure than indoor workers, increasing their skin cancer risk. Hispanic individuals comprise a large proportion of the outdoor workforce in the United States, but have limited access to culturally tailored prevention resources. Objective:This exploratory study assessed the perceptions of a culturally tailored narrative video to promote skin cancer prevention among Spanish-speaking Hispanic outdoor workers. Methods:A qualitative study was conducted using two focus groups with Hispanic outdoor workers. Prior to viewing the video, participants completed surveys assessing sociodemographic factors, sun exposure, and protective behaviors. Focus group discussions explored video comprehension, cultural relevance, emotional engagement, and dissemination strategies. Quantitative data were summarized descriptively, and qualitative data were analyzed using rapid qualitative analysis. Results:Among 19 participants, the mean age was 46.5 (SD 15.5) years, and 94.7% (18/19) identified as male. While 47.4% (9/19) reported 6-9 hours of outdoor work per day, more than half (10/19, 52.6%) reported not engaging in sun protection. Participants described the video as culturally resonant, realistic, and engaging. Identification with characters and family-centered themes increased perceived relevance and message credibility. Many participants reported increased awareness of skin cancer risk and greater confidence in adopting sun-protective behaviors. Dissemination recommendations included workplaces, social media, schools, daycares, clinics, and other community settings. Conclusions:Our video shows promise in improving skin cancer awareness and prevention, reflecting strong acceptability among participants. Future randomized controlled studies are needed to assess its effectiveness in enhancing long-term sun-protective behaviors.
Importance:Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by sterile ulcerative skin lesions. Multiple comorbidities and clinical features have been associated with PG, but no standardized guidelines exist for classifying PG phenotypes. Objective:To develop an expert-established classification framework for PG phenotypes to inform treatment guidelines and future research endeavors. Evidence Review:In this modified Delphi consensus study that included 23 board-certified dermatologists and Medical Dermatology Society members with expertise in PG, panelists completed 5 rounds of anonymous, iterative online surveys that were administered from December 2023 through July 2025. Before the beginning of the consensus exercise, a literature review was performed by nonvoting researchers to summarize existing data on PG clinical associations and comorbidities. A PubMed search from inception to September 2023 identified observational studies, narrative reviews, systematic reviews, and meta-analyses describing PG clinical associations and comorbidities that were published in English. Experts indicated their agreement with proposed PG phenotypes and disease modifiers with a consensus threshold of 70% or greater. Anonymous comments and aggregated results were presented in each subsequent round. In the final round, a framework of PG phenotypes and disease modifiers was proposed for agreement. Findings:Twenty-three board-certified dermatologists and Medical Dermatology Society members with expertise in PG completed 5 rounds of iterative surveys. Consensus was reached on the final set of PG phenotypes and disease modifiers, with 83% of experts in agreement. PG phenotypes were overall classified into 2 major groups: PG with autoinflammatory syndromes and nonsyndromic PG. Nonsyndromic PG included 4 phenotypes: inflammatory bowel disease-associated PG, PG in association with hematologic cancers and blood dyscrasias, drug-induced PG, and other (including idiopathic) PG. Disease modifiers of PG phenotype presentations included involvement of special sites (head/neck, genitals, or peristomal skin) and extracutaneous manifestations. Conclusions and Relevance:This expert-established, descriptive framework provides a standardized classification system for distinct PG phenotypes and its modifiers. This nomenclature may inform upcoming clinical guidelines and allow for consistency in reporting epidemiological research and outcomes among patients with PG.
