Systemic and skin-limited delayed-type drug hypersensitivity reactions associate with distinct resident and recruited T cell subsets.

Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype, and function of pathogenic T cells across the spectrum of severity require investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRMs) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling, and single-cell RNA-sequencing (scRNA-Seq) plus cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) plus T cell receptor sequencing (TCR-Seq) supported clonal expansion and recruitment of cytotoxic CD8+ T cells from circulation into skin along with expanded and nonexpanded cytotoxic CD8+ skin TRM in SJS/TEN. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic CD8+ T cells from circulation, implicating TRMs as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRMs were sufficient to mediate MDE. Concomitantly, SJS/TEN displayed a reduced Treg signature compared with MDE. DRESS demonstrated recruitment of cytotoxic CD8+ T cells into skin as in SJS/TEN, yet a pro-Treg signature as in MDE. These findings have important implications for fundamental skin immunology and clinical care.

Why different types of patients seek cosmetic treatments.

The extent to which demographics drive patients to pursue minimally invasive cosmetic procedures is not well-understood. The aim of this project was to better understand how patient demographics impact motivations for cosmetic procedures, irrespective of the procedure desired. Patient-level information from the Cosmetic Motivation Database was evaluated using linear regression analyses to determine whether geographic region, age, gender, race, and education independently influence patients to pursue any cosmetic treatment or consultation. Patients in the Midwest reported fewer motivations related to cosmetic appearance, mental/emotional health, physical health, social life, and school/work success than those in the South. Patients younger than 45 years reported more mental/emotional health and cost/convenience motives compared to older patients. Men noted fewer motives related to cosmetic appearance, mental/emotional health, and cost/convenience but more related to school/work success. Non-White patients reported more cost/convenience motives. Participants with up to a high school diploma cited more mental/emotional health, physical health, social life, and school/work success motivations than those with post-bachelor's education. College graduates cited more school/work success motives than those with graduate-level education. In summary, patient's gender, education, age, location, and race affect why they seek cosmetic treatments. Future research may study younger and less educated patients to improve their access to treatment.

Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma.

PURPOSE: Cemiplimab is approved for treating locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). Solid organ transplant recipients have been excluded from immunotherapy trials, given concern for allograft rejection despite their increased risk of skin cancers. Chronic immunosuppression is necessary to prevent organ rejection but may attenuate antitumor response with PD-1 inhibitors. METHODS: We report a phase I study of cemiplimab for kidney transplant recipients (KTRs) with advanced CSCC. After cross-taper to a mammalian target of rapamycin (mTOR) inhibitor and pulsed dose corticosteroids (prednisone 40 mg once daily, the day before and on days 1-3 of each cycle, followed by 20 mg once daily on days 4-6, then 10 mg once daily until the day before each subsequent cycle), patients received cemiplimab 350 mg intravenously once every 3 weeks for up to 2 years and were assessed for response every 8 weeks. The primary end point was the rate of kidney rejection, with key secondary end points including rate and duration of response, and survival. RESULTS: Twelve patients were treated. No kidney rejection or loss was observed. A response to cemiplimab was observed in five of 11 evaluable patients (46%; 90% CI, 22 to 73), including two with durable responses beyond a year. Median follow-up was 6.8 months (range, 0.7-29.8). Treatment-related grade 3 or greater adverse events occurred in five patients (42%), including diarrhea, infection, and metabolic disturbances. One patient died of angioedema and anaphylaxis attributed to mTOR inhibitor cross-taper. CONCLUSION: mTOR inhibitor and corticosteroids represent a favorable immunosuppressive regimen for KTRs with advanced CSCC receiving immunotherapy. This combination resulted in durable antitumor responses with no kidney rejection events (funded by Regeneron Pharmaceuticals [ClinicalTrials.gov identifier: NCT04339062]).

Industry Payments Comparison Between Female and Male Mohs Surgeons From 2015 to 2021.

BACKGROUND: There are limited data on female Mohs surgeon industry relationships. OBJECTIVE: To evaluate industry payment activity between female and male Mohs surgeons. MATERIALS AND METHODS: A retrospective review of the U.S. Centers for Medicare and Medicaid Services open payments data was performed between 2015 and 2021 for Mohs surgeons in the United States. Gender, academic affiliation, practice region, annual total payment, cumulative payment, and industry payment type was collected. RESULTS: Male Mohs surgeons received higher mean total payments than female Mohs surgeons ( p = .04), which persisted when data were stratified based on industry payment type and practice region. Both genders had similar median total payments ( p = .4). Females in academic practice received higher mean total payments than those in private practice. Females experienced a significant lower mean total payment compared with males in the South ( p = .03). CONCLUSION: High total payments received by male Mohs surgeons skewed the data, which is supported by a significant mean total payment difference despite a similar median total payment distribution. Female Mohs surgeons receiving the top payments may address this mean payment difference. Females seem to have higher payments if they practice in the Northeast and are in academics. Further studies are needed to evaluate this payment gap.

Evaluating Predictors of Patient Satisfaction With Facial Appearance After Mohs Micrographic Surgery Using the FACE-Q.

BACKGROUND: Although patient satisfaction with reconstructive outcomes after facial skin cancer resection is an important consideration in Mohs surgery, there is limited information evaluating this concern using validated patient-reported outcome tools. OBJECTIVE: To characterize predictors that may be associated with increased postoperative patient satisfaction with facial appearance after Mohs surgery using the FACE-Q/Skin Cancer survey, a patient-reported outcome tool that has been validated in various studies. METHODS: A total of 202 patients who underwent Mohs surgery for facial skin cancer at the Brigham and Women's Faulkner Hospital between April 2017 and November 2021 were included after completing the postoperative Satisfaction with Facial Appearance scale (FACE-Q scale). RESULTS: Male patients were significantly more likely to have higher satisfaction scores compared with female patients (aOR 2.4, 95% CI 1.1-5.1). Increased preoperative facial satisfaction scores was directly correlated with increased postoperative facial satisfaction scores ( p < .01). Patients with tumors on the lower face/neck (aOR 3.88; 95% CI 1.4-10.7) had significantly greater satisfaction scores compared with those with tumors on their nose/nasolabial folds. CONCLUSION: Potential interventions and counseling methods can be tailored toward specific patient populations with lower satisfaction scores to increase their overall satisfaction with reconstructive outcomes.

Validation of the 2022 National Comprehensive Cancer Network Risk Stratification for Cutaneous Squamous Cell Carcinoma.

Importance: The 2022 National Comprehensive Cancer Network (NCCN) reclassified cutaneous squamous cell carcinoma (CSCC) into low-, high-, and very high-risk groups to better risk stratify tumors. Mohs micrographic surgery (Mohs) or peripheral and deep en face margin assessment (PDEMA) became preferred surgical modalities for high- and very high-risk tumors. This new risk stratification and the recommendation for Mohs or PDEMA in high- and very high-risk groups have not been validated. Objective: To compare outcomes in very high-, high-, and low-risk NCCN groups of CSCCs and in CSCCs treated with Mohs or PDEMA compared with wide local excision (WLE). Design, Setting, and Participants: This retrospective cohort study of CSCCs was performed in 2 tertiary care academic medical centers. Patients 18 years or older and diagnosed between January 1, 1996, and December 31, 2019, at Brigham and Women's Hospital and Cleveland Clinic Foundation were included. Data were analyzed from October 20, 2021, to March 29, 2023. Exposures: NCCN risk group, Mohs or PDEMA, and WLE. Main Outcomes and Measures: Local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). Results: A total of 10 196 tumors from 8727 patients were stratified by NCCN guidelines into low-, high-, and very high-risk groups (6003 [59.0%] men; mean [SD] age, 72.4 [11.8] years). Compared with the low-risk group, the high- and very high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio [SHR], 1.99 [95% CI, 1.21-3.27; P = .007]; very high-risk SHR, 12.66 [95% CI, 7.86-20.39; P < .001]), NM (high-risk SHR, 4.26 [95% CI, 1.28-14.23; P = .02]; very high-risk SHR, 62.98 [95% CI, 19.24-206.17; P < .001]), DM (high-risk SHR, 2.2 × 107 [95% CI, 4.7 × 103-1.1 × 1011; P < .001]; very high-risk SHR, 6.3 × 108 [95% CI, 1.4 × 105-2.9 × 1012; P < .001]), and DSD (high-risk SHR, 4.02 [95% CI, 1.18-13.71; P = .03]; very high-risk SHR, 93.87 [95% CI, 29.19-301.85; P < .001]). Adjusted 5-year cumulative incidence was significantly higher in very high- vs high- and low-risk groups for LR (9.4% [95% CI, 9.2%-14.0%] vs 1.5% [95% CI, 1.4%-2.1%] and 0.8% [95% CI, 0.5%-1.2%], respectively), NM (7.3% [95% CI, 6.8%-10.9%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.03%-0.3%], respectively), DM (3.9% [95% CI, 2.6%-5.6%] vs 0.1% [95% CI, 0.04%-0.2%] and 0.01% [95% CI, not applicable], respectively), and DSD (10.5% [95% CI, 10.3%-15.4%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.04%-0.3%], respectively). Compared with CSCCs treated with WLE, those treated with Mohs or PDEMA had lower risk of LR (SHR, 0.65 [95% CI, 0.46-0.90]; P = .009), DM (SHR, 0.38 [95% CI, 0.18-0.83]; P = .02), and DSD (SHR, 0.55 [95% CI, 0.36-0.84]; P = .006). Conclusions and Relevance: The findings of this cohort study suggest that the NCCN high- and very high-risk groups identify CSCCs at greatest risk for developing poor outcomes. Further, Mohs or PDEMA resulted in lower LR, DM, and DSD compared with WLE.

Gender Differences in Clinical Practice and Medicare Reimbursement Among Mohs Surgeons.

OBJECTIVE: To evaluate Medicare reimbursement and clinical activity between male and female dermatologic surgeons. MATERIALS AND METHODS: A retrospective review of the Medicare Provider Utilization and Payment data from 2018 was performed for all dermatologists performing MMS. Provider gender, place of service, number of services, and average payment per service was recorded for all relevant procedure codes. RESULTS: Women represented 31.5% of the 2,581 surgeons who performed MMS in 2018. Women were paid significantly less than men (mean difference, -$73,033). On average, women performed 123 fewer cases than their male counterparts. When surgeons were stratified by productivity, remuneration was the same. CONCLUSION: Remuneration from CMS was disparate between male and female dermatologic surgeons, which may be attributed to submission of fewer charges by women. Further efforts are necessary to better evaluate and address causes for this discrepancy, because greater parity of opportunity and pay would greatly benefit this subspecialty of dermatology.

Comparative effectiveness of ice packs versus topical lidocaine-prilocaine mixture for pain control in laser hair removal of the axilla: A rater-blinded randomized controlled trial.

BACKGROUND: Laser hair removal is associated with moderate acute pain. OBJECTIVE: To compare effectiveness of ice pack to topical lidocaine-prilocaine for pain reduction during axillary laser hair removal. METHODS: Participants were randomly assigned to receive topical anesthetic to one axilla and ice packs to the other before each of 3, monthly 810 nm diode laser sessions. The primary endpoint was participant-reported pain on the visual analog scale (VAS) immediately following and 5 minutes after laser session. Posttreatment erythema, overall edema, and perifollicular edema were assessed by 2 blinded photoraters. Skin temperatures, patient preferences, and adverse events were recorded. RESULTS: Eighty-eight of 90 (98%) planned laser treatments were delivered and randomized. Participants reported higher VAS scores immediately after laser treatment with lidocaine-prilocaine compared to ice (P = .03). Five minutes after, participants reported higher VAS scores with ice (P = .03). After 53 of the 88 treatments (60.2%), participants reported preferring ice (P = .055). No serious adverse events were reported. LIMITATIONS: All participants were Caucasian or Asian with Fitzpatrick skin type I to III and coarse dark axillary hair, which may limit generalizability. CONCLUSIONS: While pain control with ice and topical anesthesia is associated with time after treatment, the 2 modalities do not differ in terms of degree of pain reduction associated with axillary laser hair removal.

A systematic review of patient-reported outcome measures for advanced skin cancer patients.

Many patient-reported outcome measures (PROMs) have been used to study quality of life (QOL) in the skin cancer population. Advanced melanoma and non-melanoma skin cancer (NMSC) may be associated with increased morbidity, mortality, and treatment side effects; however, it is unclear which PROM is valid and appropriate to use in these populations for both clinical and research purposes. We aimed to identify the PROMs that have been used to measure QOL in advanced skin cancer patients and determine which of these PROMs have been validated to assess QOL outcomes in this population. A PubMed and EMBASE search was conducted from its inception to March 2021 according to PRISMA guidelines with a comprehensive list of search terms under three main topics: (1) PROM; (2) advanced skin cancer; and (3) staging and interventions. We included articles utilizing a PROM measuring QOL and having a patient population with advanced skin cancer defined as melanoma stage > T1a or non-melanoma AJCC stage T3 or greater. Advanced skin cancer patients were also defined as those with metastasis or requiring adjuvant therapy (systemic chemotherapy, radiation, and immunotherapy). Studies were excluded according to the following criteria: mix of low-risk and advanced skin cancer patients in the study population without stratification into low-risk and advanced groups, stage T1a melanoma or mix of stages without stratification, low-risk NMSC, no PROM (i.e., study specific questionnaires), non-English publication, review article or protocol paper, conference abstract, or populations including non-skin cancers. A total of 1,998 articles were identified. 82 met our inclusion criteria resulting in 22 PROMs: five generic health-related (QWB-SA, AQoL-8D, EQ-5D, SF-36, and PRISM), six general cancer (EORTC QLQ-C30, EORTC QLQ-C36, LASA, IOC, Rotterdam Symptom Checklist, and FACT-G), nine disease-focused or specialized (EORTC QLQ-H&N35, EORTC QLQ-MEL38, EORTC QLQ-BR23, Facial Disability Index, FACT-H&N, FACT-BRM, FACT-B, FACT-M, and scqolit), and two general dermatology (Skindex-16 and DLQI) PROMs. All PROMs have been generally validated except for EORTC QLQ-MEL38. Only two PROMs have been validated in the advanced melanoma population: FACT-M and EORTC QLQ-C36. No PROMS have been validated in the advanced NMSC population. The PROMs that were validated in the advanced melanoma population do not include QOL issues unique to advanced skin tumors such as odor, bleeding, itching, wound care burden, and public embarrassment. Breast cancer and head and neck cancer instruments were adapted but not validated for use in the advanced skin cancer population due to the lack of an adequate instrument for this population. This study highlights the need for PROM instrument validation or creation specifically geared toward the advanced skin cancer population. Future studies should aim to develop and validate a PROM to assess QOL in this population.

Immune status does not independently influence cutaneous squamous cell carcinoma metastasis and death when stratified by tumor stage: A dual-center retrospective cohort analysis of primary N0 disease.

BACKGROUND: Although immunocompromised patients have a higher risk of developing cutaneous squamous cell carcinomas, it is unknown whether immune status is an independent risk factor for poor outcomes. OBJECTIVE: To compare cutaneous squamous cell carcinoma outcomes in immunocompromised and immunocompetent patients when controlling for T-stage. METHODS: We performed a retrospective cohort study at 2 tertiary care centers, examining 989 primary tumors from 814 immunocompromised patients (solid organ transplant: 259 [31.7%], chronic lymphocytic leukemia: 113 [13.9%]) and 6608 tumors from 4198 immunocompetent patients. Our primary outcome was the composite of disease-specific death or tumor metastasis ("poor outcomes"). RESULTS: Immunocompromised patients had 50% more high T-stage tumors (ie, Brigham and Women's Hospital stage T2b and T3), than immunocompetent patients (3.3% vs 4.9%, respectively; P < .001). Significant predictors of poor outcomes included tumor stage (sub hazards ratio [SHR], 14.8 for high T-stage tumors; 95% confidence interval [CI], 8.0-27.6; P < .001) and male sex (SHR, 2.3; 95% CI, 1.4-3.8; P = .002). Immune status was not a significant predictor (SHR, 1.04; 95% CI, 0.69-1.6; P = .85). LIMITATIONS: This study is retrospective. CONCLUSION: Although immunocompromised patients had 50% more high T-stage tumors than immunocompetent patients, immunocompromised patients had a similar chance of metastasis and disease-specific death when adjusting for T-stage in our cohort of primary tumors.

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Keratinocyte carcinomas (KCs) are the most diagnosed cancers worldwide and are commonly excised via complete margin assessment (CMA) or excision with sectional assessment (SA). National Comprehensive Cancer Network guidelines encourage CMA for KC with high-risk features. OBJECTIVE: To systematically compare recurrence outcomes for CMA vs SA in high-risk KC based on National Comprehensive Cancer Network guidelines criteria. MATERIALS AND METHODS: EMBASE and MEDLINE were searched for articles reporting recurrences of high-risk KC undergoing excision using CMA or SA. High-risk KCs were defined as recurrent, having perineural invasion (PNI), or basal cell carcinomas (BCC) with aggressive histology. Chi-squared tests and risk ratios evaluated differences between CMA and SA groups, and a random-effects meta-analysis was performed. RESULTS: Twenty-eight studies met inclusion criteria. Pooled percentages of locoregional recurrences were significantly lower with CMA vs SA for all KCs (3.9% [95% CI: 2.9-4.9] vs 13.5% [7.7, 19.2, p = .001]), cutaneous squamous cell carcinoma with PNI (9.8% [5.4-14.1] vs 32.0% [25.0-39.0], p < .001), and recurrent BCC (4.4% [2.9-5.9] vs 11.9% [8.0-15.8], p < .001). CONCLUSION: For high-risk KCs, recurrence risk was over 3-times greater with SA compared with CMA. Expanded access to CMA for high-risk KC is likely to reduce recurrence risk and improve clinical outcomes.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.