Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis.

PURPOSE: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment. EXPERIMENTAL DESIGN: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021. RESULTS: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions. CONCLUSIONS: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.

Image Quality Assessment Using Convolutional Neural Network in Clinical Skin Images.

The image quality received for clinical evaluation is often suboptimal. The goal is to develop an image quality analysis tool to assess patient- and primary care physician-derived images using deep learning model. Dataset included patient- and primary care physician-derived images from August 21, 2018 to June 30, 2022 with 4 unique quality labels. VGG16 model was fine tuned with input data, and optimal threshold was determined by Youden's index. Ordinal labels were transformed to binary labels using a majority vote because model distinguishes between 2 categories (good vs bad). At a threshold of 0.587, area under the curve for the test set was 0.885 (95% confidence interval = 0.838-0.933); sensitivity, specificity, positive predictive value, and negative predictive value were 0.829, 0.784, 0.906, and 0.645, respectively. Independent validation of 300 additional images (from patients and primary care physicians) demonstrated area under the curve of 0.864 (95% confidence interval = 0.818-0.909) and area under the curve of 0.902 (95% confidence interval = 0.85-0.95), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 300 images were 0.827, 0.800, 0.959, and 0.450, respectively. We demonstrate a practical approach improving the image quality for clinical workflow. Although users may have to capture additional images, this is offset by the improved workload and efficiency for clinical teams.

ItchyQoL reveals differences in itch symptom experience in routine dermatologic care.

Itch is a common symptom of dermatologic diseases associated with significant impairment of health-related quality of life (QoL). This study reveals disparities in itch symptom experience and itch impact on QoL. A retrospective study of patient-reported outcome measure (PRO) data (ItchyQoL, Itch NRS, Pain Interference, Anxiety) for 387 outpatient dermatology visits to characterize the impact of itch on patients' QoL and itch symptom experience based on skin color in patients with dermatologic disease. Most patients were Caucasian females (67%) with mean age of 48 years. Correlative analyses showed mild itch associated with emotional impacts on QoL (p < 0.01), while severe itch associated with functional and emotional impacts on QoL (p < 0.01). African American (AA) patients reported more "severe-range" answers for 15 (68%) ItchyQoL items and had higher ItchyQoL mean scores (p = 0.001). ItchyQoL demonstrated an emotional impact on QoL by mild itch, but a functional and emotional impact on QoL by severe itch. Further, AAs suffered from greater itch-related impairment in QoL than Caucasian patients, especially due to scarring and sleeplessness.

Barriers and Facilitators Affecting Long-Term Antibiotic Prescriptions for Acne Treatment.

Importance: Dermatologists prescribe more oral antibiotics per clinician than clinicians in any other specialty. Despite clinical guidelines that recommend limitation of long-term oral antibiotic treatments for acne to less than 3 months, there is little evidence to guide the design and implementation of an antibiotic stewardship program in clinical practice. Objective: To identify salient barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Design, Setting, and Participants: This qualitative study assessed data collected from stakeholders (including dermatologists, infectious disease physicians, dermatology resident physicians, and nonphysician clinicians) via an online survey and semistructured video interviews between March and August 2021. Data analyses were performed from August 12, 2021, to January 20, 2024. Main Outcomes and Measures: Online survey and qualitative video interviews developed with the Theoretical Domains Framework. Thematic analyses were used to identify salient themes on barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Results: Among 30 participants (14 [47%] males and 16 [53%] females) who completed the study requirements and were included in the analysis, knowledge of antibiotic guideline recommendations was high and antibiotic stewardship was believed to be a professional responsibility. Five salient themes were to be affecting long-term antibiotic prescriptions: perceived lack of evidence to justify change in dermatologic practice, difficulty navigating patient demands and satisfaction, discomfort with discussing contraception, iPLEDGE-related barriers, and the absence of an effective system to measure progress on antibiotic stewardship. Conclusions and Relevance: The findings of this qualitative study indicate that multiple salient factors affect long-term antibiotic prescribing practices for acne treatment. These factors should be considered in the design and implementation of any future outpatient antibiotic stewardship program for clinical dermatology.

Barriers and Facilitators to Teledermatology and Tele-Eye Care in Department of Veterans Affairs Provider Settings: Qualitative Content Analysis.

BACKGROUND: Veterans Affairs health care systems have been early adopters of asynchronous telemedicine to provide access to timely and high-quality specialty care services in primary care settings for veterans living in rural areas. Scant research has examined how to expand primary care team members' engagement in telespecialty care. OBJECTIVE: This qualitative study aimed to explore implementation process barriers and facilitators to using asynchronous telespecialty care (teledermatology and tele-eye care services). METHODS: In total, 30 participants including primary care providers, nurses, telehealth clinical technicians, medical and program support assistants, and administrators from 2 community-based outpatient clinics were interviewed. Semistructured interviews were conducted using an interview guide, digitally recorded, and transcribed. Interview transcripts were analyzed using a qualitative content analysis summative approach. Two coders reviewed transcripts independently. Discrepancies were resolved by consensus discussion. RESULTS: In total, 3 themes were identified from participants' experiences: positive perception of telespecialty care, concerns and challenges of implementation, and suggestions for service refinement. Participants voiced that the telemedicine visits saved commute and waiting times and provided veterans in rural areas more access to timely medical care. The mentioned concerns were technical challenges and equipment failure, staffing shortages to cover both in-person and telehealth visit needs, overbooked schedules leading to delayed referrals, the need for a more standardized operation protocol, and more hands-on training with formative feedback among supporting staff. Participants also faced challenges with appointment cancellations and struggled to find ways to efficiently manage both telehealth and in-person visits to streamline patient flow. Nonetheless, most participants feel motivated and confident in implementing telespecialty care going forward. CONCLUSIONS: This study provided important insights into the positive perceptions and ongoing challenges in telespecialty care implementation. Feedback from primary care teams is needed to improve telespecialty care service delivery for rural veterans.

Factors Affecting Treatment Selection Among Patients With Hidradenitis Suppurativa.

Importance: Despite the US Food and Drug Administration's approval of adalimumab for the treatment of hidradenitis suppurativa (HS), prescription rates remain low, indicating a critical gap between evidence-based guidelines and clinical practice. Understanding the medical decision-making process that these patients use when considering biologic agents and other HS therapies may uncover opportunities for improved patient-physician communication and HS disease control. Objective: To elucidate factors that affect the medical decision-making process for patients with HS, with an emphasis on biologic therapies. Design, Setting, and Participants: Open-ended semistructured interviews were conducted with English-speaking adults with HS (aged ≥18 years) recruited from 2 dermatology clinics that are part of Emory University School of Medicine in Atlanta, Georgia. All participants had an average 7-day pain score of 1 or higher on a 0- to 10-point numeric rating scale. Surveys were conducted between November 2019 and March 2020, and data were analyzed from December 2021 to August 2022. Data collection continued until thematic saturation was reached at 21 interviews. Results: A total of 21 participants (median [IQR] age, 38.5 [27.9-43.4] years; 16 females [76%]) were included in the analysis. Almost all participants (96%) had Hurley stage II or III disease, and 15 (71%) had a history of adalimumab use. Suffering threshold, perceptions of treatment risk, treatment fatigue, disease understanding, and sources of information (included dermatologists, the internet, advertisements, and friends and loved ones) were identified as factors affecting participants' decisions to initiate new treatments for HS. Conclusions and Relevance: Results of this qualitative study suggest that mitigating misconceptions about treatment risk, identifying gaps in disease knowledge, and emphasizing early treatment to prevent scarring and disease progression may empower patients with HS to engage in treatment planning and to try new therapies.

Lived Experience of Acne and Acne Treatment in Transgender Patients.

Importance: While acne is common in transgender and gender-diverse people and is associated with gender-affirming hormone therapy, little research has examined these factors and their impact in gender minority groups. Objective: To examine the lived experiences of acne and acne treatment in transgender and gender-diverse participants. Design, Setting, and Participants: This mixed-methods analysis was conducted at a multidisciplinary gender center at a public safety-net hospital and endocrinology and dermatology clinics at a tertiary academic center from January 4, 2021, to April 7, 2022, using semistructured interviews and surveys. Participants were transgender or gender-diverse adults who had received gender-affirming hormone therapy. Data analysis was performed from November 11, 2021, to March 31, 2023. Exposure: Current diagnosis of acne. Main Outcomes and Measures: Interviews exploring the experience of acne and acne treatment were audio recorded, transcribed verbatim, coded using minority stress theory and the socioecological model, and analyzed using thematic analysis. Themes were triangulated with survey data on gender, self-reported acne severity, skin-specific quality-of-life impact, and treatment experience. Results: A total of 32 participants were included in the study (mean [range] age, 32 [18-57] years; 17 transgender men, 11 transgender women, and 4 nonbinary participants). Ten participants (31%) self-rated their skin as currently clear or almost clear, 11 (34%) reported mild acne, and 11 (34%) had moderate to severe acne. Participants described experiences of rejection and bullying related to acne and admitted avoiding social interactions in which they anticipated acne-related discrimination, which led to feelings of depression and anxiety. Acne worsened body appearance dissatisfaction. Transgender women reported acne interfering with feminine gender expression. Transgender men often normalized acne development, sometimes viewing acne positively as an early sign of testosterone action. Most participants tried over-the-counter acne treatments and commonly sought acne treatment advice from physicians, peers, online forums, and social media. Barriers to acne treatments included cost, lack of multidisciplinary care, mistrust toward the health care system, and lack of transgender-specific acne care education. Conclusions and Relevance: In this mixed-methods study, transgender and gender-diverse individuals reported experiencing acne-related stigma and facing barriers to acne treatment. Multilevel changes, such as developing strategies to reduce acne stigma, providing transgender-specific acne care education, facilitating multidisciplinary acne care, and expanding transgender-friendly clinical environments, are recommended to reduce the impact of acne in transgender individuals.

Cutaneous and Noncutaneous Adverse Effects in Patients with Advanced Melanoma Receiving Immunotherapy.

Relationships between cutaneous adverse effects (CAEs) and noncutaneous adverse effects (NCAEs) of melanoma immunotherapy may help identify patterns tied to distinct immunologic pathways. The objective of this study was to determine the associations between CAEs and NCAEs among patients with stages III-IV melanoma receiving immunotherapy and who were enrolled in a prospective cohort. Electronic medical record data were abstracted from the first immunotherapy infusion until 1 year later. CAEs were rash or itch. NCAEs were symptoms and/or laboratory abnormalities documented as immunotherapy related. NCAE onset and time to NCAE were compared between participants with and without CAEs using ORs and Wilcoxon rank sum tests. Of 34 participants, 11 (32.4%) developed no adverse effects, 7 (20.1%) developed CAEs only, 3 (8.8%) developed NCAEs only, and 13 (38.2%) developed both CAEs and NCAEs. After adjustment for age, sex, and immunotherapy regimen, CAE was associated with higher odds of NCAE development (OR = 9.72; 95% confidence interval = 1.2-76.8). Median NCAE onset was 63 days in those with CAEs and 168 days in those without CAEs (P = 0.41). Limitations included a small sample size, and larger prospective studies should be performed to confirm findings. CAE was associated with NCAE development. Early identification and treatment of NCAEs may reduce symptom burden and hospitalizations associated with NCAEs.

Implementation evaluation of a teledermatology virtual clinic at an academic medical center.

BACKGROUND: Teledermatology (TD) is an evidence-based practice that may increase access to dermatologic care. We sought to use the Exploration, Preparation, Implementation, and Sustainment (EPIS) and the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) frameworks to evaluate implementation of TD at Duke. METHODS: The EPIS and RE-AIM frameworks were deployed to design and implement a TD program that leveraged the strengths of the Duke University Health System and addressed previously reported barriers to implementation of store-and-forward and synchronous TD models. In the resultant hybrid TD model, trained primary care providers (PCPs) sent e-comm referrals with clinical and dermatoscopic images to dermatology. These e-consults were reviewed asynchronously and patients were scheduled for a synchronous video visit with dermatology within days. Dermatologists managed the patient plan. This hybrid TD model was piloted at four primary care clinics. Pertinent outcomes from a TD-adapted RE-AIM framework were tracked using electronic health record data. Patient satisfaction was assessed using a post-video visit survey (n = 18). Implementation barriers and facilitators were also collected through provider surveys (n = 24 PCPs, n = 10 dermatologists, n = 10 dermatology residents). RESULTS: At four PCP clinics throughout 9/1/2021-4/30/2022, there were 218 TD referrals. Video visits occurred on average 7.5 ± 0.5 days after referral and 18/18 patients completing the post-visit survey were satisfied. Adoption varied between clinics, with one placing 22% of all dermatology referrals as TD and another placing 2%. The primary PCP barriers to TD were time burdens, lack of fit in clinic flow, and discomfort with image taking. Top-endorsed potential facilitating interventions included allowing for rash referrals without dermoscopy and assurance for clinical evaluation within 3 days. CONCLUSIONS: The use of implementation science frameworks allowed for identification of system and contextual strengths which informed the hybrid TD pilot. Barriers and facilitating interventions will provide guidance for expansion and ongoing maintenance of TD.

Atopic Dermatitis and Bullying Among US Adolescents.

This cross-sectional study compares the prevalence and frequency of bullying among US adolescents with and without atopic dermatitis.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

BACKGROUND: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. METHODS: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. RESULTS: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. CONCLUSIONS: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

The Cost Utility of Nonpregnancy Laboratory Monitoring for Persons on Isotretinoin Acne Therapy.

We sought to project the 1-year cost utility of nonpregnancy laboratory monitoring cessation among patients initiating isotretinoin. We conducted a model-based cost utility analysis comparing (i) current practice (CP) and (ii) cessation of nonpregnancy laboratory monitoring. Simulated 20-year-old persons initiating isotretinoin were maintained on therapy for 6 months, unless taken off because of laboratory abnormalities in CP. Model inputs included probabilities of cell-line abnormalities (0.12%/wk), early cessation of isotretinoin therapy after detection of an abnormal laboratory result (2.2%/wk, CP only), quality-adjusted life-years (0.84-0.93), and laboratory monitory costs ($5/wk). We collected adverse events, deaths, and quality-adjusted life-years and costs (2020 USD) from a health care payer perspective. Over 1 year, and for 200,000 people on isotretinoin in the United States, the CP strategy resulted in 184,730 quality-adjusted life-years (0.9236 per person), and nonpregnancy laboratory monitoring resulted in 184,770 quality-adjusted life-years (0.9238 per person). The CP and nonpregnancy laboratory monitoring strategies resulted in 0.08 and 0.09 isotretinoin-related deaths, respectively. Nonpregnancy laboratory monitoring was the dominating strategy, realizing $24 million savings per year. No variation of a single parameter across its plausible range changed our cost utility findings. Cessation of laboratory monitoring could realize savings of $24 million per year for the US health care system and improve patient outcomes, with negligible effects on adverse events.

Implementation Evaluation of a Teledermatology Virtual Clinic at an Academic Medical Center.

Background: Teledermatology (TD) is an evidence-based practice that may increase access to dermatologic care. We sought to evaluate implementation of TD at four Duke primary care practices. Methods: We implemented a hybrid TD program where trained primary care providers (PCPs) sent referrals with clinical and dermatoscopic images to dermatology. Patients were seen by dermatologists over video visit within days, and dermatologists managed the patient plan. We evaluated implementation using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework using electronic health record data. Implementation barriers and facilitators were collected through surveys (n = 24 PCPs, n = 10 dermatologists, n = 10 dermatology residents). Results: At four PCP clinics throughout 9/1/2021-4/30/2022 there were 218 TD referrals. Video visits occurred on average 7.5 days after referral and 18/18 patients completing the post-visit survey were satisfied. Adoption varied between clinics, with one placing 22% of all dermatology referrals as TD and another placing 2%. The primary PCP barriers to TD were time burdens, lack of fit in clinic flow, and discomfort with image taking. Top-endorsed potential facilitating interventions included allowing for rash referrals without dermoscopy and assurance for clinical evaluation within 3 days. Conclusions: Addressing TD process fit into PCP clinic flow and reducing time burdens may increase PCP uptake of TD.

Financial toxicity and skin cancer care in the US: population-based survey from 2011 to 2018.

This cross-sectional study aimed to examine financial toxicity among people with skin cancer using pooled National Health Interview Survey data from adults in 2011-2018. Material, behavioral, and psychological markers of financial toxicity were compared by lifetime skin cancer history (any melanoma, any skin cancer beside melanoma, and no skin cancer) using multivariable logistic regression models. Of 257,652 total participants, 1874 (0.73%) had known melanoma and 7073 (2.75%) had any skin cancer beside melanoma. History of skin cancers was not independently associated with increased markers of financial toxicity after adjustment for sociodemographic and medical co-morbidities.

Patient-Reported Outcome Measures and Their Clinical Applications in Dermatology.

With more disease- and symptom-specific measures available and research pointing to increased usefulness, patient-reported outcome measures (PROMs) can be routinely used in clinical care. PROMs increase efficiency in healthcare, improve the clinician-patient relationship, and increase patient satisfaction with their care. PROMs can be administered before, during, and after clinic visits using paper-and-pencil, mobile phones, tablets, and computers. Herein, we combine available literature with expert views to discuss overcoming barriers and helping dermatologists incorporate PROMs into routine patient-centered care. We believe dermatology patients will benefit from broader PROM implementation and routine clinical use. However, a few major barriers exist: (1) cost to implement the technology, (2) selecting the right PROMs for each disease, and (3) helping both patients and clinicians understand how PROMs add to and complement their current clinical experience. We provide recommendations to assist dermatologists when considering whether to implement PROMs in their practices.

Pain experiences among those living with hidradenitis suppurativa: a qualitative study.

BACKGROUND: Pain is rated by patients with hidradenitis suppurativa (HS) as the disease's most impactful symptom. HS therapies are often insufficient to control inflammatory disease activity and pain. A better understanding of patient experiences with pain may improve patient-provider relationships and help identify strategies for addressing HS pain. OBJECTIVES: This qualitative study sought to characterize lived pain experiences of those with HS. METHODS: English-speaking patients ≥ 18 years old with a dermatologist-confirmed diagnosis of HS and an average numerical rating scale pain score of ≥ 1 over the preceding week were recruited from a single academic medical centre in Atlanta, Georgia, USA. Semistructured interviews were conducted from November 2019 to March 2020 to explore participants' HS pain experiences and the subsequent impact on their lives. Thematic saturation was reached after interviewing 21 participants. Interviews were audio recorded, transcribed, and analysed using thematic analysis. RESULTS: Among 21 study participants, the median 7-day average pain score was 6 (interquartile range 3-7; scale ranges from 0 to 10, with 10 being most pain). Participants' descriptions of pain were consistent with nociceptive pain, neuropathic pain and itch. Pain impacted multiple life domains, including physical limitations (decreased mobility and impaired sleep), decreased psychological wellbeing (irritability, depression, loss of control, and difficulty communicating pain experiences) and impaired social relationships (social isolation, intimacy problems and difficulty fulfilling social responsibilities). Although participants reported chronic discomfort, acutely painful and unpredictable HS disease flares caused more distress and quality-of-life (QoL) burden. Participants frequently treated their pain without input from the medical team, sometimes with unsafe medication doses or combinations. Factors contributing to self-management of pain included difficulty accessing timely outpatient care during disease flares and fear of stigma from healthcare providers. CONCLUSIONS: When present, HS-related pain may impact not only physical wellbeing but also mental health and relationships. In addition to therapies that target the inflammatory disease burden, treating the symptom of pain may improve patients' QoL and wellbeing. Because patients with HS have difficulty explaining their pain, proactively asking them about pain may identify unmet needs, facilitate better pain control and improve QoL. Further, the influence of HS-related pain on numerous aspects of QoL suggests the need for multidisciplinary, patient-centred approaches to HS pain management.

Survival and tumor characteristics of patients presenting with single primary versus second primary melanoma lesions.

BACKGROUND: Patients with single primary melanomas have an increased risk of developing subsequent melanomas. Secondary tumors diagnosed within and after 3 months are termed "synchronous" and "asynchronous," respectively. OBJECTIVE: To compare tumor distributions and survival characteristics between patients with second primary melanomas and those with single primary melanomas. METHODS: Retrospective cohort study. Data were collected from an institutional database from 14,029 patients with a diagnosis of a primary melanoma seen between 1970 and 2004. RESULTS: The synchronous and asynchronous cohorts demonstrated significantly improved survival probabilities compared with the single primary cohort (P = .04 and .002, respectively). Single primary lesions (2.2 ± 2.3 mm) were significantly thicker than the first-identified synchronous (2.0 ± 1.7 mm) and asynchronous (1.7 ± 1.3 mm) lesions. Synchronous lesions were more likely to be anatomically concordant compared with asynchronous lesions (55.7% vs 38.2%, P < .001). LIMITATIONS: Single-center study design and incomplete records for second primary melanoma Breslow depth and histopathology. CONCLUSION: Patients with second primary melanomas demonstrated a significant survival advantage and thinner lesions compared with those with single primary melanomas. Our reported tumor distributions support the role of full body skin examinations, with attention to the region of initial diagnosis.