Neuropeptide Y (NPY) is a pleiotropic peptide produced in the central nervous system and peripheral organs. Despite conjectures that NPY may have a role in skin physiology and pathology, the effects of NPY in this organ remain poorly understood. In this study, we discovered that chronic overexpression of the stress hormone neuropeptide Y (NPY) results in genome-scale molecular changes and histopathologies within the skin that are consistent with a progressive fibroproliferative disease process. At 22 weeks of age, Npy overexpressing (NPYtet/tet) mice upregulate gene signatures that overlap with diseases and hallmarks associated with fibrosis, psoriasis, asthma, inflammatory response, IFNg response and TLR4 signaling. At 35 weeks, NPYtet/tet skin exhibits a gene expression signature consistent with inflammatory resolution but also upregulation of genes, like Egr1, Fos, FosB and Wdfy1 with known roles in inflammatory skin diseases and fibrosis. At this timepoint, we also observe skin changes that include progressive hair graying secondary to depletion of melanocyte stem cells within hair follicles, epidermal hyperplasia, dermal fibrosis, panniculitis, and an increase in CD206+ M2 macrophages. Together, these results provide long-awaited evidence of NPY’s involvement in skin pathology, providing a background for defining the precise role of NPY in cutaneous homeostasis and disease.

Favour Akinjiyan¹, Anmol Jarang^1,2, Maysoon Harunani^1,2, Leonid Shmuylovich^1,2

¹ Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

² Department of Biomedical Engineering, Washington University in Saint Louis, St. Louis, Missouri

The appearance of acne in darkly pigmented skin (DPS) is often more subtle than lightly-pigmented skin (LPS) and can visually overlap with noninflammatory pigmented lesions. This contributes to systemic acne underestimation and undertreatment in DPS. Short-wave infrared multispectral imaging (SWIR-MSI) may overcome these challenges because it operates in the 1000-1700 nm spectral range which has low melanin sensitivity and high sensitivity to water and lipid (hallmarks of inflammatory acne). Recently we developed a SWIR-MSI system that highlights intradermal fluid with high contrast in DPS. In the current study, we hypothesized that our SWIR-MSI system would 1) provide higher contrast imaging of acne than visible photography, and 2) differentiate acne from pigmented lesions. We enrolled 9 subjects with objectively and subjectively-determined DPS (Individual Typology Angle (ITA) -19° to -37°, Monk G-I, Fitzpatrick VI). Six had inflammatory facial acne, and three had noninflammatory dermatosis papulosa nigra (DPN). SWIR-MSI demonstrated distinguishable differences between acne and DPN and provided clear visualization of acne lesions with a ten-fold enhancement in contrast (relative to visible photography) between acne lesions and unaffected background skin (WeberContrast_Visible=0.04±0.04, WeberContrast_SWIR-MSI=0.49±0.219, p<0.0001). SWIR-MSI shows promise for transforming practice by enhancing diagnostic accuracy and severity assessment of inflammatory skin disorders in diverse populations.

Dany Alkurdi, AB¹, Omar Alani, ScB¹, Ezdean Alkurdi, BS², Dev Patel BS¹, Shiven Sharma JD¹, Zachary Schwager, MD^2
1Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
²UMass Chan Medical School, Worcester, Massachusetts, USA.
³Department of Dermatology, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA.

Clinical trial accessibility is vital for advancing treatments for rare autoimmune skin disorders, which face recruitment challenges due to low prevalence and specialized care needs. The COVID-19 pandemic disrupted healthcare infrastructure, potentially impacting trial availability.

A trend analysis was conducted to evaluate geographic access to clinical trials for autoimmune skin disorders in the U.S. before and after the pandemic using ClinicalTrials.gov data. Population demographics from Census.gov were merged with trial data, and distances between population centers and trial sites were calculated using the Haversine formula. Linear regression and the Mann-Kendall test were used to assess changes in accessibility and temporal trends.

Out of 22,125 clinical trials identified, 14,198 were initiated before 2020 and 7,774 after. On average, 2,809 ZIP codes hosted at least one trial. While linear regression showed a slight, non-significant decrease in average distance to trials (slope = -14.510, p = 0.176), the Mann-Kendall test indicated a significant decline in accessibility (ADF = -3.515, p < 0.05). Post-2020 analysis revealed a significant reduction in accessibility (t-test = 5.648, p < 0.05), suggesting COVID-19 led to a loss in accessibility that has not yet recovered.

The findings highlight a global trend of improving trial accessibility over time; however, the COVID-19 pandemic significantly disrupted local trial availability, resulting in a decline in accessibility that has not yet rebounded. Addressing this gap is critical to ensuring equitable access to clinical trials for patients with autoimmune skin disorders.

Kaitlin Williams, Beita Badiei, James Reilly, Nina Rossa Haddad, Luis Garza

Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, MD

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease marked by painful swelling, abscesses, sinus tracts, and scarring. Although its prevalence is rising, the precise mechanism of its pathogenesis remains unclear. While a minority of HS cases are familial, often involving mutations in the Nicastrin (NCSTN) subunit of the Gamma Secretase complex, most patients lack known genetic variants. Surprisingly, by histology, we discovered low NCSTN protein expression in the dermal fibroblasts of all subjects in a cohort of non-familial HS patients (p<.0001, n=11), despite normal NCSTN levels in other cell types. Cultured fibroblasts from these patients maintained reduced NCSTN expression. RNAseq analysis revealed more profound effects of NCSTN loss in fibroblasts than keratinocytes. In particular, siNCSTN fibroblasts produced more CXCL8 RNA and protein after TNFα stimulation compared to controls (p<.0001), in part due to higher Ser529 phosphorylation of p65 NFKB. Two small molecule IKKB inhibitors normalized high CXCL8 levels in siNCSTN fibroblasts (n=8, p<.0001). Histology of HS lesions showed high P-NFKB (Ser529) and CXCL8 overlap in dermal fibroblasts (n=10, p=.0167). These findings suggest that gamma secretase dysfunction in dermal fibroblasts underlies both familial and non-familial HS and suggests new potential therapeutic targets for the disease.

Laura Bou Delgado,¹ Veda Nagubandi,² Hilena Gebru,² Frances Barg,² Junko Takeshita²

Universidad Central del Caribe School of Medicine, Bayamon, PR¹
University of Pennsylvania, Philadelphia, PA²

Research to understand the causes of racial disparities in atopic dermatitis (AD) outcomes requires diverse study populations and measures of the lived environment. We aimed to understand the perceptions of research participation among Black adults with AD to guide recruitment and retention efforts for a future study of the environmental drivers of disparities in AD severity. We performed semi-structured interviews of nine Black adults with AD. The interview guide included questions about a study that involves wearing an air quality monitor, collecting dust samples, and sharing their GPS location. Interview transcripts were coded by two researchers using an integrated approach. Median (interquartile range) age of the participants was 32 (26, 40) years; 77.8% were female. The main motivators for participating in research were the new knowledge to be gained and the ability to help others. Many participants also expressed a desire to receive personalized recommendations based on their data. The main barrier to research participation was excessive time commitment. Some participants reported discomfort with wearing an air quality monitor that might attract unwanted attention and sharing their GPS location due to privacy concerns. Despite the barriers identified, many participants remained willing to participate in research due to other motivating factors.

Bonnie C. Carney, PhD^1,2, Eriks E. Ziedins, BS¹, Cameron D. O’rio, BS¹, Lauren T. Moffatt, PhD^1,2, Jeffrey W. Shupp, MD^1,2,3,4

1. Firefighters Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC
2. Departments of Surgery and Biochemistry and Molecular & Cellular Biology, Georgetown University
   Medical Center, Washington, DC
3. The Burn Center, Department of Surgery, MedStar Washington Hospital Center,
   Washington, DC
4. Department of Plastic Surgery, Surgery and Biochemistry and Molecular & Cellular Biology, Georgetown University
   Medical Center, Washington, DC

Post-burn dyschromia in hypertrophic scars(HTSs) poses significant psychosocial challenges for patients, exacerbated by limited treatments due to a lack of mechanistic understanding about the development of dyschromia. To address this challenge, we used a transgenic mouse strain(Cg-Tg(KRT14-Kitl*)4XTG2Bjl/J; KRT14 mice)(n=40) with epidermal melanocytes in a scald burn model alongside wild type(WT) mice (n=10) without epidermal pigmentation. Full thickness burns were induced and were allowed to heal for 70 days. Melanin levels were assessed non-invasively and scar tissue samples underwent histomorphometric analysis to measure epidermal and dermal thickness. RNA was isolated for qRT-PCR of key genes including collagen-1(Col-1), galectin-1(LGALS1), and transforming growth factor beta(TGFb1), as well as melanogenesis related genes: tyrosinase(TYR) and tyrosinase related proteins-1 and -2(TYRP1, TYRP2). KRT14 mice developed hyper- and de-pigmented scars with increased contracture and reduced pliability compared to WT. These scars were more severe than WT. KRT14 mice had increased melanin index in areas of hyperpigmentation compared to normal skin(p<0.05). KRT14 mice had thicker epidermis and dermis, lacking dermal appendages, and elevated gene expression of COL-1, LGALS1, TGFb1, TYR, TYRP1, and TYRP2 compared to WT(p<0.05). This model offers mechanistic insights into dyschromic scar development, supporting ongoing experiments such as lineage tracing of melanocytes

Aaron S. Farberg,¹ Ross C. Radusky,² Angela Y. Moore,^3,4 George Han,⁵ Jessica Vasquez,⁶ Olivia Choi,^6* Theodore Alkousakis,⁶ Katelyn Rowland,⁶ Daphne Chan,⁶ Jenny Jeyarajah,⁷ Joseph F. Merola,⁸ Alice B. Gottlieb,⁹ Seemal R. Desai^8,10

¹Bare Dermatology, Aubrey, TX, United States; ²Dermatology Treatment & Research Ctr, Dallas, TX, United States; ³Baylor Univ Medical Ctr, Dallas, TX, United States; ⁴Arlington Research Ctr, Arlington, TX, United States; ⁵Northwell Health Physician Partners, NY, NY, United States; ⁶JSA, Horsham, PA, United States; ⁷Janssen R&D, Spring House, PA, United States; ⁸Univ of Texas Southwestern Medical Ctr, Dallas & Plano, TX, United States; ⁹Icahn School of Medicine at Mt Sinai, NY, NY, United States; ¹⁰Innovative Dermatology, Plano, TX, United States

*Presenting Author

VISIBLE- a phase 3b study of GUS in SOC pts with moderate-to-severe plaque psoriasis (PsO; Cohort [Coh]A) and scalp PsO (CohB). High-sensitivity C-reactive protein (hsCRP) is a non-specific inflammation marker used in PsA, but not in PsO. Considering high comorbidity burden in VISIBLE pts, we examined if BL hsCRP impacts clinical outcomes in this population.

Pts were randomized 3:1 to GUS 100mg or placebo through Week(W)16. CohA results were previously presented. Here, CohB GUS-treated pts were stratified by low (<3mg/L) vs high (≥3mg/L) hsCRP at BL. Scalp (PsO Scalp Severity Index [PSSI], scalp-specific Investigator’s Global Assessment [ss-IGA]) and skin (PsO Area and Severity Index [PASI], IGA) measures were assessed through W16.

BL mean hsCRP levels (low [n=39]/high [n=36] groups): 1.2/9.4. BL characteristics were generally balanced, excepting higher mean BMI and higher PsA incidence (high hsCRP). W16 response rates (%) in pts with low/high hsCRP: PSSI90 74.4/55.6; ss-IGA0/1 74.4/61.1; mean change from BL: PSSI -87.9/-87.2; PASI90 53.8/50.0; IGA0/1 69.2/77.8.

Majority of GUS-treated pts achieved skin/scalp clearance notwithstanding BL hsCRP; ~50% of CohB: BL hsCRP ≥3mg/L. Pts with low BL hsCRP trended towards numerically higher W16 scalp clearance. Results suggest BL hsCRP reflects overall systemic inflammatory burden in PsO pts like PsA.

Omobola Onikoyi DO, MSc1, Alexia Collins BS1, Falguni Asrani MD2, Sarah Yagerman MD2, Sharon A. Glick MD1

1. SUNY Downstate Medical Center
2. NYU Langone

Background: Skin cancer, although less common in individuals with skin of color, still presents a significant health concern due to its association with increased morbidity therefore, it is crucial to implement patient education and early detection initiatives to improve outcomes.

Purpose: To analyze preoperative tumor size in individuals with skin cancer in an underserved healthcare community setting, highlighting the need for early detection and intervention in these populations.

Results:   75 patients who underwent Mohs Surgery from our dermatology clinic between September 2021 and November 2022 were analyzed. The cohort comprised 38.6 % Caucasian, 50.6 % Hispanic and 4 % Black patients. The average preoperative tumor size was 1.66 cm for Caucasians, 1.34 cm for Hispanics and 2.46 cm for Blacks.

Conclusions: To conclude, the larger preoperative tumor size observed in the Black population suggests that their cancers may be detected at later stages emphasizing the need for enhanced screening and early detection efforts in this group. Additionally, despite having the smallest average preoperative tumor size, the Hispanic population accounted for the majority of the patients treated, highlighting the importance of inclusive skin cancer screening initiatives and patient education to improve early detection and outcomes across all ethnic groups.

Valeria Cota¹*, Courtney Wille², Harsha Jain¹ Nicole K. Brogden^1,3.

 ¹University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, Iowa City, IA. ²University of Iowa, Institute for Clinical and Translational Science, Iowa City, IA. ³University of Iowa Carver College of Medicine, Department of Dermatology, Iowa City, IA.

Microneedles (MN) form epidermal micropores, improving drug permeability of semisolid formulations. We assessed metronidazole (MTZ) permeability through MN-treated skin from gel vs cream in a crossover pharmacokinetics study.  Subjects were randomly assigned to gel or cream and completed two study arms with 7 days washout between: MN + MTZ (arm 1), vs no MN + MTZ (arm 2). Transepidermal water loss (TEWL) and impedance were measured pre- and post-MN. Blood samples were collected up to 120 hrs (MTZ was removed at 96 hrs). Six subjects (33.5±12 yrs) have completed the study: n=3 each in cream and gel groups. Significant changes in TEWL and impedance confirmed micropore formation. Pharmacokinetic profiles for the gel showed a steep peak early, while a gradual increase over time was observed for the cream. There was no difference in AUC for gel and cream: 194.58±93.24 ng*h/mL and 182.43 ± 53.85 ng*h/mL, respectively. Tmax was lower for gel (12.01± 0.6 hrs) vs cream (80.7± 15.0 hrs), p < 0.001.  Mean Cmax for gel (3.62±2.17 ng/mL) and cream (2.53±1.24 ng/mL) did not differ (p>0.05). Plasma MTZ concentrations were measurable at 120 hrs. This preliminary pharmacokinetic assessment of MTZ plasma levels show initial formulation dependent differences in drug permeation. 

Florentia Dimitriou¹, Ashish Damania², Priyadharsini Nagarajan³, Sabitha Prabhakaran⁴, Neus Bota⁴, Mark Knafl⁴, Randy Chu⁴, Pranoti V Sahasrabhojane², Yasmine Hoballah², Devarati Mitra⁵, Roi Weiser¹, Shirley Y Su⁶, Ehab Hanna⁶, Bita Esmaeli⁷, Travis Sims⁸, Curtis A Pettaway⁹, Rodabe Amaria¹⁰, Isabella C Glitza¹⁰, Jillian S Losh², Nadim J Ajami², Scott E Woodman⁴, Jennifer A Wargo¹, Andrew Futreal⁴, Jennifer L McQuade⁵

1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2. Platform for Innovative Microbiome & Translational Research (PRIME-TR), Moon Shots™ Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4. Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
5. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
6. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
7. Orbital Oncology & Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
8. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
9. Division of Surgery, Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
10. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

MM is a rare melanoma subtype with distinct biology and low response rates to ICIs. Patients (pts) with MM presenting to MD Anderson are being prospectively enrolled for longitudinal collection for molecular, microbiome, and lifestyle factor profiling. 82 pts with sequenced fecal specimens and mucosal surfaced swabs have been enrolled. Initial analysis of gut and mucosal surface swabs’ microbiome by MM primary site displayed wide range of intrasample heterogeneity and microbial signatures that correlate with the MM primary site. DSP analysis from available biopsy specimens showed a variable immune infiltration with co-localization of the T-cell, lymphoid- and myeloid-cell markers. Subgroup analysis from 78 pts treated with ICIs displayed compositional differences in fecal specimens collected at baseline/early (week 0 – 6, N = 43) vs midpoint/late (from week 7, N = 35). Results from an initial analysis indicate compositional differences in the presence and proportion of bacterial taxa in responders (R), compared to non-responders (NR). This is an ongoing prospective study that is expected to drive insights into the tumor/microenvironment/host interactions and factors regulating immunogenicity to predict response and resistance to ICIs in a rare and understudied melanoma subtype.

Laura Kord Ferris,¹ Jerry Bagel,² Yu-Huei Huang,³ Andrew Pink,⁴ Stephen K. Tyring,⁵ Georgios Kokolakis,⁶ Amy M. DeLozier,⁷ Shu Li,⁸ Yaung-Kaung Shen,⁸ Kristen Foster,^9* Takayuki Ota,⁷ Robert Bissonnette¹⁰

¹University of Pittsburgh, Pittsburgh, PA, USA; ²Psoriasis Treatment Center of Central NJ, East Windsor, NJ, USA; ³Department of Dermatology at Chang Gung Memorial Hospital and the School of Medicine at Chang Gung University, Taoyuan City, Taiwan; ⁴NHS Foundation Trust Great Maze Pond, London, England; ⁵Center for Clinical Studies, Webster, TX, USA; ⁶Psoriasis Research and Treatment Center, Department of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; ⁷Johnson and Johnson Innovative Medicine, San Diego, CA, USA; ⁸Johnson and Johnson Innovative Medicine, Spring House, PA, USA; ⁹Janssen Scientific Affairs, LLC, Horsham, PA, USA; ¹⁰Innovaderm Research, Montreal, Quebec, Canada

JNJ-77242113 showed superior efficacy versus placebo in moderate-to-severe psoriasis in FRONTIER-1. FRONTIER-2 was a long-term extension, phase 2b study. FRONTIER-1 randomized patients 1:1:1:1:1:1 to JNJ-77242113 25mg daily(QD), 25mg twice daily(BID), 50mg QD, 100mg QD, 100mg BID, or placebo (PBO) through Week(W) 16. In FRONTIER-2, patients completing FRONTIER-1 (W16) continued assigned dose through W52; those randomized to placebo crossed over to 100mg QD (PBO→100mg). Primary endpoint: proportion of patients achieving PASI75 at W52. Response rates were estimated using non-responder imputation and FRONTIER-1 baseline data. At W52, proportions of patients achieving PASI75: 25mg QD 48.8%, 25mg BID 58.5%, 50mg QD 69.8%, 100mg QD 65.1%, 100mg BID 76.2%, and PBO→100mg 65.7%; corresponding rates for PASI90/PASI100: 27.9%/14.0%, 36.6%/17.1%, 41.9%/20.9%, 51.2%/25.6%, 64.3%/40.5%, 57.1%/34.3%, respectively. Proportions of patients achieving IGA 0/1 and IGA 0: 25mg QD 37.2%/14.0%, 25mg BID 46.3%/19.5%, 50mg QD 60.5%/23.3%, 100mg QD 60.5%/30.2%, 100mg BID 73.8%/42.9%, PBO→100mg 65.7%/31.4%. Across treatment groups, 58.6% of patients experienced AEs, with no evidence of dose-dependent increase in AEs, including gastrointestinal disorders. Serious AEs were considered unrelated to study treatment. In psoriasis patients receiving JNJ-77242113, rates of near-complete/complete skin clearance from FRONTIER-1 were maintained through W52; 100mg BID yielded the highest response rates. No safety signals were identified.

Mackenzie O. Gipple^1*, Ramneek K Dhami^2*, Emile Latour³, Jesse J. Keller³

¹Oregon Health & Science University School of Medicine, Portland, OR, USA. ²University of Nevada, Reno School of Medicine, Reno, NV, USA. ³Department of Dermatology, Oregon Health & Science University, Portland, OR, USA.

Morgellons disease (MD) is poorly understood with limited data regarding its impact on quality of life (QoL) compared to other dermatoses, leading to higher healthcare utilization as individuals seek help from multiple specialists for issues like pruritus, sleep, and social engagement. MD disproportionately affects patients with lower socioeconomic status, psychiatric comorbidities, amphetamine/opioid use, and iron deficiency. We aim to measure MD’s QoL burden and compare it to well-funded dermatologic conditions including PN, AD, and psoriasis.

A qualitative cross-sectional survey comprising Dermatology Life Quality Index, Pittsburgh Sleep Quality Index, and 5D Pruritus Scale was distributed to fifty patients with untreated MD presenting at Oregon Health & Science University dermatology clinic from July 2022 to July 2023. The mean DLQI, PSQI, and 5D pruritus scales were 20.0 ± 8.64, 11.3 ± 4.59, and 16.1 ± 5.58, respectively. MD had significantly higher DLQI scores than PN, AD, and psoriasis, and significantly higher PSQI scores than AD and psoriasis.

Notably, MD imposes greater disease burden on QoL compared to PN, AD, and psoriasis. Understanding MD’s QoL impact compared to other dermatological diseases has significant clinical implications, guiding healthcare professionals in providing targeted support for MD patients.

Tammy Gonzalez, Sujad Younis, Laura Padula, Natasha Strbo, Hadar Lev-Tov, Barry Resnik, Irena Pastar

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by malodorous drainage, pain, and scarring. Although specific microbial dysbiosis characterizes HS tunnels or sinus tracts, the pathogenic role of specific individual microorganisms remains unclear. This study provides the first functional analysis of Actinotignum schaalii, a Gram-positive, facultative anaerobic bacillus associated with urinary tract infections and cutaneous abscesses. Despite limited knowledge about this microorganism, genomic sequencing reveals that A. schaalii from HS tunnel bears genes for adhesion, host cell internalization, antimicrobial resistance, and resistance to reactive oxygen species. We isolated A. schaalii from severe HS patients using traditional culture methods. Whole genome sequencing identified key pathogenic markers and antimicrobial resistance in A. schaalii isolated from severe HS. Ex-vivo human skin infection with A. schaalii increased IL-6 and IL-1b expression, while mouse models showed acute abscess formation following intradermal infection with the A. schaalii. These findings underscore the virulence of HS-isolated A. schaalii strains, paralleling HS inflammation. Our results suggest that A. schaalii plays a significant role in HS pathogenesis, potentially guiding the optimization of treatment strategies. This workflow has been optimized for additional anaerobes present in HS tunnels to establish the role bacterial-driven mechanisms in HS progression and inflammation.

Sepideh Hamzehlou¹, Donald Glass^{1, 2}

1. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
2. McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Fibrosis, characterized by excessive collagen deposition in response to injury, is a leading cause of mortality in developed countries, contributing to up to 45% of deaths. It affects various organs, with keloid formation serving as a representative model of fibrosis in the skin. To identify key transcription factors involved in enhanced collagen production, we performed bulk RNA sequencing comparing keloid and normal tissue samples. Our analysis highlighted RUNX2 as a prominent transcription factor upregulated in keloid tissue. Subsequent validation using qPCR and western blotting confirmed elevated levels of RUNX2 and phosphorylated RUNX2 in keloid fibroblasts compared to normal dermal fibroblasts.

To delve deeper into the role of RUNX2 in keloid pathogenesis, we employed siRNA-mediated knockdown of RUNX2 in keloid fibroblasts followed by transcriptome sequencing. Our findings revealed significant downregulation of collagen genes COL11A1, COL5A3, COL15A1, and COL6A6, which was corroborated by qPCR and western blot analyses. Furthermore, using a Runx2-knockout mouse model, we observed significantly reduced dermal thickness and collagen content, as assessed by hydroxyproline assay, Masson’s Trichrome, and picrosirius staining techniques.

These results underscore the critical involvement of RUNX2 in regulating collagen production in keloid formation, suggesting its potential as a therapeutic target for managing fibrotic disorders.

Maysoon Harunani^1,2, Patricia K. Mansfield¹ Leonid Shmuylovich^1,2

¹ Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri
² Department of Biomedical Engineering, Washington University in Saint Louis, St. Louis, Missouri

Skin color assessment can inform disease diagnosis and management in clinical practice, and in research can ensure diversity in clinical studies. Skin color assessment through colorimetry offers a more objective approach than subjective tools like Fitzpatrick, Taylor, or recently proposed Monk color scales. In particular, the Individual Typology Angle (ITA), derived from CIELAB color space, has been used to objectively measure pigmentation for decades. However, existing colorimeters are costly and they are too bulky for measuring small or curved anatomic sites. To provide a less costly and more accessible solution, we sought to repurpose the dermatoscope as a colorimeter. We enrolled 23 subjects with dark to very light pigmentation (ITA -52° to 65°) and determined ITA at the same anatomic location using both a Konica Minolta CM700d spectrophotometer (ITA_{gold_standard}) as well as dermoscopic photographs taken with a miniature (9.5x5.6mm) 30-color calibration target in the field of view, where ITA was determined both before (ITA_{photo_uncalibrated}) and after (ITA_{photo_calibrated}) software-based color target calibration. ITA_{gold_standard} demonstrated stronger correlation to and lower mean error (ME) with ITA_{photo_calibrated} (r²=0.96, ME=18°±9.8) than ITA_{photo_uncalibrated} (r²=0.77, ME=29°±24). Color-calibrated dermoscopic photography can help overcome limitations of existing colorimeters and bring objective assessment of pigmentation within reach of every dermatologist.

Courtney M. Johnson M.D., Ph.D.¹, Soroosh Solhjoo, Ph.D. ², Weishan Li, B.S.³, Iman Ali B.S.¹, Kalvin Nash B.S.¹, Ron Sweren M.D.¹Stephanie Hicks, Ph.D. ³ and Winston Timp Ph.D. ⁴

¹Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, ²Department of Medicine, F. Edward Hébert School of Medicine, Bethesda, MD, USA,

³Department of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA ,⁴Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

25% of early-stage mycosis fungoides (eMF) patients will develop late-stage (lMF) disease, which is associated with higher mortality and poorer prognosis. Black and Hispanic patients present with a higher incidence of lMF, younger age at diagnosis, and lower survival than matched White patients. The tumor microenvironment (TME) of eMF is associated with cancer-associated fibroblasts (CAF) that support tumor growth and are associated with worse prognosis. CAF subtypes have not been classified in lesional MF tissue. Single-cell RNA sequencing was applied to skin tissue from unaffected, eMF, and lMF subjects. Canonical gene markers were used to identify the cell types within the skin. Analysis of the isolated fibroblast population revealed eight distinct clusters, including five CAF subtypes: inflammatory (PDGFRA/IL-6), myofibroblast (ACTA2/TAGLN), antigen-presenting (CD74/INF-y), MF-specific CAF (FAP), and MF-specific CAF (CXCL12). There was a significantly higher expression of myofibroblast markers in eMF than in lMF (p<0.05), but no difference in the other CAF subtypes. There was a significantly higher expression of MF-specific FAP in Black patients (p<0.05) and a higher expression of MF-specific CXCL12 in White patients (p<0.05). These findings may explain the differences in clinical outcomes as CXCL12 is associated with better outcomes and FAP is associated with an immunosuppressive TME.

Samson Kosemani¹ and Gustavo P. Amarante-Mendes^1,2

¹Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, Brazil
²Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (INCT), São Paulo, Brazil.

Email: samsonkosemani@icb.usp.br

Ultraviolet radiation (UVR) is a major environmental mutagen. In skin, UVR can initiate cancer through the induction of mutagenic DNA damage and promote its progression. The Ras-Association Domain Family (RASSF) is composed of Ras effector proteins that shares a common RA domain (Ralgds/AF6) and is categorized into C-terminal (RASSF1-6) and N-terminal (RASSF7-10) groups based on RA domain location. At least one of its members, RASSF9, has been identified as a gene whose expression is induced upon continuous exposure to UV radiation in mouse skin. RASSF9 is mostly expressed in the stratified epithelium, where it plays an important role in maintaining epidermal homeostasis. In addition, RASSF9 was shown to act as a tumor suppressor in some cancers by interfering with cellular proliferation. Here, we investigated whether the expression of RASSF9 or other members of the family is modulated by UVR in murine melanoma cell lines. Indeed, RASSF7, RASSF8, RASSF9 and RASSF10 were upregulated in response to UVR in vitro. We are currently working to investigate the response of RASSF members to other genotoxic stressors and the signaling modules that control this response.

Keywords: Ras Association Domain Family Members, RASSF9; Melanoma; Ultraviolet radiation

Financial support: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Yingzi Liu¹, Katie Hinchee-Rodriguez¹, Allison Billi², Natasha Mesinkovska¹, Bogi Andersen¹, Johann Gudjonsson², Maksim Plikus¹

¹University of California, Irvine
²University of Michigan

Skin diseases disproportionately affect different ethnic groups, and often manifest at specific body locations. These differences likely stem from ancestral influences on normal skin cell homeostasis. Differences in skin tone, epidermal thickness, hair density, and texture in different ancestries correlate with disease susceptibility. However, the related epithelial, mesenchymal, pigment, and immune cell features remain largely unknown. Our research indicates that single-cell sequencing analyses are far less comprehensive for African American, Hispanic, Middle Eastern, and Asian populations compared to those for Caucasian ancestry. To elucidate the ancestral differences in skin biology and pathology, we collected skin tissues from individuals of these four ancestral groups from various body sites, including the scalp, forearm, and lower back, and processed them for single-cell RNA-sequencing. Our findings provide a detailed deconvolution of cellular compositions at different body locations across various ancestries. Our research will enhance the understanding of baseline differences in the skin across different ancestries and shed light on the factors driving disproportionate disease prevalence in these populations.

Roberto Maglie¹, Simone Baldi², Giulia Nannini², Elena Niccolai², Emiliano Antiga¹, Amedeo Amedei²

¹Department of Health Sciences, Section of Dermatology, University of Florence, Florence, Italy.
²Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy.

The role of gut microbiota and its metabolites, including short chain fatty acids (SCFA), in bullous pemphigoid (BP) remains elusive. SCFA protect against autoimmunity, promoting intestinal barrier integrity and regulatory T-cells activation. They counterbalance the pro-inflammatory effects of medium (MCFA) and long chain fatty acids (LCFA), whose serum concentration increases with gut dysbiosis.

We sought to profile the expression of circulating 7 SCFA,4  MCFA and 3 LCFA in patients with BP.

These metabolites were measured in sera of 36 BP patients and 36 sex-and age-matched controls by gas chromatography and mass spectrometry, and then correlated with disease activity and serum levels of zonulin, a biomarker of gut permeability.

We found that the profile of SCFA, MCFA and LCFA, determined by principal component analysis, differed significantly between patients and controls: while SCFA decreased in BP patients, MCFA and LCFA increased. No significant correlations with disease activity emerged. Serum zonulin was up-regulated in BP sera and correlated negatively with SCFA, including acetic and propionic acids.

In sum, we showed a profound imbalance of circulating free fatty acids toward a pro-inflammatory profile in BP patients. Specific dietary interventions, e.g. SCFA supplementation, may restore intestinal barrier function and reduce systemic inflammation in BP.

Aryan Naik^a,b, Tomas Rodriguez^b, Sarah K. Whitley^b,c,d

The University of Vermont Larner College of Medicine^a, Burlington, VT
Department of Dermatology^b, Autoimmune Therapeutics Institute^c, NeuroNexus Institute^d, University of Massachusetts Chan Medical School, Worcester, MA

Hidradenitis suppurativa (HS) is characterized inflammatory nodules, abscesses and draining sinuses. Pain due to HS is debilitating and remains a major contributor to the disease burden. While HS is attributed to type 17 inflammation, the role of nociception in inflammation remains unclear. Transient receptor potential vanilloid type 1 (TRPV1+) nociceptors are known to release the neuropeptides CGRP, VIP, and substance P in response to stress. This may contribute to local inflammation by promoting immune cell recruitment, and cytokine release. Here, we identify neuropeptide receptor expression within immune cell populations in HS.

We used publicly available scRNA-seq data from 8 HS skin samples from NCBI’s Gene Expression Omnibus (GEO) database (GSE220116). We used Seurat (v4.3.0.1) in R (v4.3.1) to perform differential gene expression (DGE) analysis of CGRP receptors (RAMP1, RAMP2, RAMP3, CALCRL) and VIPR2.

RAMP1 and CALCRL was expressed in Langerhans cells and dendritic cells. A smaller portion of natural killer and B cells also expressed RAMP1. Mast cells expressed RAMP2, RAMP3, and CALCRL. DGE revealed significant downregulation of RAMP2, RAMP1, VIPR2 and CALCRL in HS cells (p < .001) Our findings expand on the complex interplay between pain, and the characteristic cyclical inflammation of HS, and identifies possible future therapeutic targets.

Allen S.W. Oak¹, Shanelle Jackson¹, Yuri Veklich², Gordon Ruthel³, Elaine Kim¹, Leonel D. Joannas^4,5, Arben Nace¹, Ruifeng Yang¹, Ying Zheng¹, John T. Seykora¹, Rebecca G. Wells^6,7 and George Cotsarelis¹

¹Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁷Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Corresponding Author: George Cotsarelis, M.D., Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, BRB 1053, 421 Curie Boulevard, Philadelphia, PA 19104, cotsarel@pennmedicine.upenn.edu

Central centrifugal cicatricial alopecia (CCCA) and traction alopecia (TA) are painful scarring alopecias that predominantly affect Black women. Traction-inducing hairstyles, including weaves and braids, cause TA and are thought to contribute to CCCA. In CCCA, increased hair fragility is thought to play a role since some patients carry a heterozygous mutation in PADI3—encoding an enzyme that provides structural integrity to hairs.

To interrogate the role of traction in scarring hair loss, we developed a novel protocol that exerts traction on murine hair and engineered Padi3 KO mice using CRISPR/Cas9. Since hair follicles subjected to traction displayed signs of mechanical strain on histology, we hypothesized that traction induces fibrosis by engaging mechanotransduction—a potent profibrotic pathway triggered by mechanical stress. To test this, skin samples from mice that underwent chronic traction (duration=28 days, one complete hair cycle) were analyzed with second harmonic generation microscopy and qPCR to reveal elevated levels of mechanotransduction and matrix remodeling. Scanning electron microscopy of hair and whiskers from Padi3 heterozygotes demonstrated deep fissures with exposed cortical fibers. Overall, our findings suggest that traction-inducing hairstyles trigger mechanotransduction to drive scarring in CCCA/TA with Padi3 mutation lowering the hair’s damage threshold to promote hair breakage and scarring.

Heuijoon Park^1,2, Sonali Lad¹, Kelsey Boland¹, Kelly Johnson¹, Nyssa Readio¹, Guangchun Jin², Samuel Asfaha², Kelly S. Patterson², Ashok Singh¹, Xiangdong Yang², Douglas Londono³, Anupama Singh¹, Carol Trempus⁴, Stephanie M. Holtorf¹, Jennifer Boyle¹, Derek Gordon³, Timothy C. Wang² and Rebecca J. Morris¹ 

The Hormel Institute, University of Minnesota, Austin, MN¹; Columbia University, New York, NY², Rutgers University, Piscataway, NJ³; National Institute of Environmental Health Sciences, Research Triangle Park, NC⁴. 

Non-melanoma skin cancers (NMSCs) are a serious and growing public health problem despite a plethora of sunscreens and repeated calls for sun avoidance. In some patients, NMSCs can become intractable and ultimately deadly, leading us to wonder whether some of the cancer cells might originate in the bone marrow, an incubator for numerous stem and progenitor cells. The purpose of our study was to explore the role of bone marrow derived cells (BMDCs) in cutaneous malignancy. 

 We used allogeneic bone marrow transplantation (BMT) along with a multistage cutaneous carcinogenesis model to look for the recruitment of BMDCs into skin tumors that were initiated with the carcinogen, dimethylbenz[a]anthracene (DMBA), and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). Naïve female mice receiving BMTs from DMBA-treated donors developed benign and malignant cutaneous lesions after TPA promotion alone. The donor BMDCs clustered in the recipient lesional epithelium, expressed cytokeratins, proliferated, and stratified.  

 We wanted to investigate further what bone marrow cells might be responsible for initiating and promoting skin tumors. We hypothesized that there might be a progenitor population of epithelial cells in the bone marrow responsible. Using flow cytometry, immunofluorescence microscopy, and mining of single cell RNA sequencing datasets, we identified a potential population of bone marrow stem cells with classic epithelial markers such as EpCAM (epithelial cell adhesion molecule), keratins, and E-cadherin. We conclude that a subset of squamous lesions long thought to be solely local in origin have a distinct systemic component. These findings may suggest new targets for diagnosis and surveillance of NMSCs.

Beth Pecha PhD^1,2, Meghan Koch PhD²

¹Medical Scientist Training Program, University of Washington; Seattle, WA, USA
²Division of Basic Sciences, Fred Hutchinson Cancer Center; Seattle, WA, USA

The association between breastfeeding and the development of atopic dermatitis is not well understood though substantial data have shown alterations in the gut microbiota of atopic dermatitis patients. We previously found mice that do not receive breast milk antibodies exhibit dysregulated microbiota-derived T follicular helper (Tfh) cell and germinal center (GC) B cell responses in the gut-associated lymphoid tissues at the time of weaning. To explore the long-term consequences of this response on intestinal immunity and whether this can be linked to atopic dermatitis, we performed 16s rRNA sequencing of intestinal microbes to look at alterations in intestinal composition, RT-PCR of the bacterial 16s rRNA gene to look at abundance of wall-associated microbes, infection studies with Salmonella typhimurium and Citrobacter rodentium to assess functional capacity of the gut microbiota, microbiota flow cytometry to look at antibody binding to own intestinal microbes, and fecal IgA ELISAs to look at intestinal antibody levels. We found no differences in mice that received or were devoid of maternal antibodies across all of the tested parameters. In summary, our data suggest that breast milk antibodies do not alter intestinal microbiota composition and abundance and that breast milk antibodies alone are unlikely to cause the gut dysbiosis seen in individuals with atopic dermatitis.

Rolando Perez-Lorenzo¹, Danial Khayatan¹, Limin Li¹, Angela M. Christiano^1,2.

Departments of ¹Dermatology, and ²Genetics and Development. Columbia University, New York

Acral lentiginous melanoma (ALM) has a disproportionately higher burden in people of Hispanic, African and Asian descent. ALM responds poorly to current therapeutics, underscoring the need for novel strategies to improve OS. The activity of the protein kinase CK2 is upregulated in several cancers, including melanoma, contributing to malignant phenotypes and resistance to therapy. We investigated the potential of CK2 inhibition to overcome resistance to targeted therapy in ALM preclinical models. in vitro treatment of acral melanoma cells, with the CK2inh CX4945 and GO289 reduced cell viability and downregulated PI3K and MAPK/ERK signaling. CK2inh had an antiproliferative synergistic effect with targeted therapies, e.g., MEKinh and BRAFinh. In colony formation assays, CX4945 significantly reduced the emergence of trametinib-resistant colonies in ALM-derived cell lines. To demonstrate translational relevance, we treated mice bearing NF1-null melanoma xenografts with CX4945 and observed a significant reduction in tumor growth that resulted in stable disease. Using the B16 melanoma model, CK2inh enhanced the therapeutic response to anti-CTLA4 immunotherapy and modified the immune TME. Together, our findings suggest that CK2inh promotes tumor control by directly suppressing tumor cells and modifying the TME, and that the combination with MEKinh, and other TKIs, may improve the therapeutic outcome in ALM.

Britney T. Nguyen, BS^1,2, Hira Rizwi, MBBS^1,2, Anand Ganesan, MD, PhD¹, Jessica Shiu, MD, PhD¹ 

¹University of California Irvine, Department of Dermatology 
²These authors contributed equally to this work   

Background: Vitiligo, an autoimmune disorder characterized by CD8+ destruction of melanocytes, significantly impacts quality of life. Recent studies indicate vitiligo carries a greater burden on skin of color patients but whether disease manifestations are similar across different ethnic backgrounds is unclear.  

Methods: Using an IRB-approved protocol, we conducted a retrospective chart review of vitiligo patients based on ICD-10 codes. A RedCap survey collected demographic data on 591 patients, including age, ethnicity, sex, Fitzpatrick skin type (FST), types of treatment, body surface area (BSA), and Vitiligo Area Scoring Index (VASI) scores. Patients without clear vitiligo subtypes or dermatology visits were excluded, yielding 319 patients.  

Results: Of 319 patients, 20% identified as Hispanic and 79.9% as non-Hispanic. Vitiligo subtype in the Hispanic demographic were generalized (42.2%), localized (23.4%) and acrofacial (25%). Non-Hispanics had similar presentation, with generalized (42%), localized (33.3%) and acrofacial (15.2%). Analysis showed significant variation in the vitiligo distribution among ethnicities (p=0.023 < 0.05). Specifically, inflammatory vitiligo was prevalent in Caucasians (p=0.003) and localized vitiligo in Asians (p=0.0026). No statistical significance was found between FST and vitiligo classification. Baseline VASI scores were similar in different ethnic groups.  

Limitations: This single institution limits general applicability. Studies addressing treatment disparities are underway. 

Archana Samynathan, MD,^1,2, Lauren Ching, BS, ⁴, Caroline Brooks BS,⁴, Ria Sandeep BS,⁴, Laura Belovs, BS,¹, Sorana Raiciulescu MS,¹ , Jeffrey Shupp, MD,^1,3,4, Helena B. Pasieka MD, MS, ^1,2,3,4

1. Uniformed Services University, Bethesda, MD
2. MedStar Washington Hospital Center/ Georgetown University, Department of Dermatology, Washington, DC
3.  The Burn Center, MedStar Washington Hospital Center, Washington D.C.
4. Georgetown University School of Medicine, Washington, D.C.

Timely diagnosis and treatment are critical for favorable outcomes in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN). We conducted a retrospective analysis to examine the impact of race, employment status, insurance, and Social Vulnerability Index (SVI) on SJS/TEN patients' in-hospital mortality and access to care. Studying 129 patients (70 Female; Age 48.9 ± 19.0 years; Self-reported race, 27 White, 72 Black, 33 Other; Insurance, 24 Medicaid, 57 Medicare, 29 Private, 6 Uninsured; 41 Employed, 25 Unemployed, 20 Retired; SVI, 40 Low, 28 Low-Medium, 30 Medium-High, 31 High) at our institution, we found significantly higher in-hospital mortality among Black patients compared to non-Black patients (OR 3.5, p=0.01, univariable analysis). Black race remained predictive of mortality (p=0.004) in multivariable analysis controlling for SVI, despite its strong and significant correlation with higher SVI (χ 2(3, N = 129) = 30.62, p<0.001). Time to access dermatology consult did not significantly differ by race, insurance type, or employment status. Likely reflecting institutional efforts toward equitable care through community awareness, streamlined patient intake, and efficient deployment of multidisciplinary care. The ongoing study is investigating poorer outcomes among Black patients with SJS/TEN, focusing on comorbidities contributing to mortality and exploring potential differences in their treatment and care.

Sungrim Seirin-Lee^1,2, Yuhki Yanase³, Shunsuke Takahagi⁴, Michihiro Hide⁴

KUIAS¹ and Graduate School of Medicine², Kyoto University, Kyoto, 606-8315, JAPAN.
Department of Pharmacotherapy³ and Department of Dermatology⁴, Hiroshima University, Hiroshima, 734-8551, JAPAN

Chronic spontaneous urticaria (CSU) is a persistent skin disease that causes red itchy skin eruptions, called wheals, that are of various shapes. These wheals repeatedly appear and disappear daily for up to weeks or even decades, severely impacting the quality of life of those affected. Although urticaria symptoms are induced by skin mast cell degranulation and mediator release, the mechanism of CSU remains elusive, largely due to the lack of animal models and specific biomarkers. To address this, we developed an interdisciplinary research framework combining mathematical modeling, in vitro experiments, and clinical data analysis that links the shape of wheals in patients to their molecular-level pathological states.

We found that geometric measurements of wheals can be classified into five categories and verified that the wheal data from 105 CSU patients could be categorized into these five types by six individual dermatologists with 87.6% agreement. We then analyzed how these types are related to pathological networks. Additionally, we successfully developed a mathematical tool that estimates patients' pathological states from individual images of patients' wheals, facilitating accurate diagnosis and consequently better clinical management. This approach may also be more widely applied to other skin diseases.

Morinola Shobajo, MD,¹  Safiyya Abdulkadir, MD,² Christina N. Kraus,  MD,³  Jessica Shiu, MD, PhD⁴

^a College of Medicine, University of Illinois at Chicago, Chicago, Illinois
^b Department of Dermatology, University of California Irvine, Irvine, California
* Corresponding author. E-mail address: shoba006@umn.edu

Anogenital conditions are an underserved area in dermatology.¹ Many neoplastic and inflammatory dermatoses affect genital skin, but studies have shown that even in high-risk skin cancer clinics, genitalia is often excluded from skin examinations.¹ This is particularly relevant for skin of color (SOC) patients, where melanoma (and squamous cell carcinoma in organ transplant patients) more frequently involves the anogenital region.^2,3 Genital melanomas are associated with more aggressive disease courses and racial disparities exist in melanoma diagnosis and outcome.⁴

Medical textbooks with representative clinical images are some of the main resources residents and students use to obtain information on the diagnosis and treatment of anogenital conditions. Studies have shown that SOC is underrepresented in educational resources, which contributes to racial disparities in the diagnosis and management of SOC patients.⁵ We sought to evaluate anogenital images and representation of SOC in commonly used dermatology, gynecology, and urology residency textbooks. We evaluated anogenital SOC images in 9 educational textbooks (Table 1) commonly utilized by dermatology, gynecology, and urology residents, as well as in a genital dermatology atlas. Our analysis revealed a total of 1,973 anogenital images, classified as FST I–IV or V–VI. Overall, anogenital images in SOC were underrepresented in educational textbooks, with 17% of anogenital images depicting SOC, 22% in dermatology texts, and 12% in gynecology and urology texts. Sexually transmitted infections (STIs) were overrepresented in SOC overall. 

Anogenital images in SOC patients are lacking in key educational resources utilized by dermatology, gynecology, and urology (Table 2). STIs were overrepresented in SOC images, including a genital dermatology atlas. Increased efforts to expand SOC images in medical textbooks should also focus on the inclusion of SOC anogenital images, with a particular emphasis on non-infectious genital conditions including inflammatory dermatoses as well as pigmented lesions.

Keywords: skin of color, anogenital, pigmented lesions, sexually transmitted infections

Faith Simmonds¹, Julian Zulueta¹, Rolando Perez-Lorenzo²

1. Vagelos College of Physicians and Surgeons, Columbia University, NY, NY, US
2. Department of Dermatology, Columbia University, NY, NY, US

Acral lentiginous melanoma (ALM) is a cutaneous melanoma (CM) that develops in glabrous skin. It has a higher prevalence in individuals of color, suggesting a distinct etiology compared to superficially spreading CM. To determine the epidemiologic characteristics of ALM across racial/ethnic groups in the United States, we retrieved clinicopathologic data for ALM cases (2010-2021) using the Surveillance, Epidemiology, and End Results (SEER) registry. Data for age, sex, race/ethnicity, Breslow thickness, ulceration, lymph node status, and mitotic rate were analyzed. Age-adjusted incidence rates were also calculated. The 2485 ALM patients included in our study were 66% (n=1642) non-Hispanic White (NHW), 19% (n=472) Hispanic, 7.73% (n=192) non-Hispanic Asian/Pacific Islander (NHAPI), and 7.20% (n=179) non-Hispanic Black (NHB). Hispanic populations had the highest incidence rate across all racial/ethnic groups (3.1 per 1,000,000). We observed a larger proportion of NHB, NHAPI, and Hispanic patients with increased tumor severity as measured by Breslow thickness, ulceration, and mitotic rate. More patients of color (22%) had a cause of death attributed to ALM compared to NHW (13.34%). Our results indicate that NHB, NHAPI, and Hispanic patients have a worse prognosis for ALM, underscoring the urgent need to further investigate the biological mechanisms underlying these differences across racial/ethnic populations.

Han-Chi Tseng M.D.

Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Taiwan

Nonsegmental vitiligo is an autoinflammatory disease because loss of melanocytes. Commensal skin dysbiosis is associated with various inflammatory diseases, including atopic dermatitis and psoriasis. Previous studies showed Proteobacteria and Streptococcus were enriched in vitiligous skin, but dynamic changes of skin microbiome after treatment remains obscured. We sequenced full-length 16S rRNA genes (V1-V9 regions) to analyze skin swabs in 6 healthy control and 21 vitiligo patients (15 with topical steroid alone and 6 with additional narrow band UVB). At baseline, Bifidobacterium pseudocatenulatum and Mediterraneibacter faeci were more abundant in healthy control than in vitiligo patients. Although overall a and b diversity did not alter in significantly after treatment, there were increased abundances of Porphyromonas, Bacteroides salyersiae, and Enterobacter kobei in vitiligo. While Paracoccus sp. were enriched, the pyruvate fermentation pathway to isobutanol was impaired in combined treatment group as compared to those in the steroid treatment alone group.  Although large-scale composition of bacteria did not shift significantly after treatment, there was dysbiosis and dysmetabolism during repigmentation of vitiligo after phototherapy and topical steroid.

Aayushi Uberoi^1*, Sofia Murga², Preeti Bhanap², Clementina Mesaros², Thomas Sutter³, Elizabeth Grice^2*

¹Washington University School of Medicine at St. Louis
²University of Pennsylvania
³University of Memphis                             

The skin epidermis is the body's main defense against dehydration and harmful substances. We used germ-free mice to show that the microbiota is essential for proper differentiation and repair of the epidermal barrier. This effect is mediated by the aryl hydrocarbon receptor (AHR), a regulator of epidermal differentiation. We hypothesized that the skin microbiota activates AHR to promote barrier repair. Tryptophan metabolites, which are potent AHR ligands, are enriched in the skin's outermost layer (stratum corneum) and can be produced by microbial metabolism. We constructed metabolic enzyme profiles and mined them against healthy human skin metagenomes. These analyses revealed motif enrichment for enzymes that metabolize tryptophan to indole and its derivatives. To identify microbially regulated tryptophan metabolites in vivo, we established a gnotobiotic model with 50 skin commensals from healthy humans and performed targeted mass spectrometry on murine skin. We found three novel indole-related metabolites that are regulated by microbes and tested therapeutic efficacy in a murine model of atopic dermatitis. We provide a novel ecological framework that demonstrates that microbiota regulates skin barrier formation and repair via tryptophan metabolism. This knowledge can guide the development of precise microbe-based therapies for various skin disorders characterized by impaired epidermal barrier function.

Lourdes Valdez¹; University of Nevada Reno School of Medicine, Adriana Richmond²; University of California, San Diego School of Medicine, Letitia Bradford MD³; Nth Dimensions Chesahna Kindred, MD⁴, MBA, FAAD; Kindred Hair & Skin Center

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with a predilection for African American and female patients. HS consists of recurrent abscesses and sinus tracts in intertriginous areas. While there are currently many treatments available, treatment of severe cases remains difficult, leading to patient frustration and lack of follow-up. This study aims to explore the rationale of HS patient-initiated loss to follow-up.

We identified 72 patients at a single center with dermatologist-diagnosed HS seen within the last 12 months (06/30/2021-06/30/2022). Of those 72 patients, 35 were determined to be severe, and of those 35 patients, 11 were lost to follow-up. These individuals were polled to explore the discontinuation of treatment. Of the 11 patients, 4 did not respond. Of the remaining 7 patients, 3 (27. 27%) reported discontinued care due to scheduling conflicts, 1 (9.09%) had improvement of symptoms, 1 (9.09%) lost medical coverage, 1 (9.09%) cost, and 1 (9.09%) discontinued care due to competing comorbidity.

Tools of population health can help physicians effectively address barriers to care. It’s possible that if these barriers are addressed earlier severe complications, a decrease in patient quality of life, and an increased use of high-cost resources can be avoided.

Megan Hoang BA¹, Samer Wahood BA¹, Carmen Hollifield BS², Uzoamaka Okoro MD, MSc³, Michelle Bongiorno MD³

¹The Warren Alpert Medical School of Brown University, Providence, RI; ²Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, Las Vegas, NV; ³Walter Reed National Military Medical Center, Bethesda, MD.

Linear morphea, a subtype of localized scleroderma, is an inflammatory skin disorder primarily affecting children—potentially causing bone/joint deformities. Cases involving the jaw and tongue are rare. We aim to demonstrate that linear morphea can affect the jaw and tongue.

An 11-year-old Hispanic male with Fitzpatrick skin type IV presented with a two-year history of two 7-8 mm hyperpigmented atrophic papules on the right chin and a 4 cm atrophic, linear, hyperpigmented plaque extending from the right lower cutaneous lip to the upper neck. Physical examination revealed decreased fullness of the right lower face, jaw deviation to the right, and right tongue atrophy. The unusual locations posed a diagnostic challenge.

A punch biopsy indicated early morphea with periadnexal chronic inflammation, hyalinized collagen bundles, and sparse subcutaneous adipose. Anti-Scl-70 antibody and ANA tests were negative.

Clinicopathologic correlation supported a diagnosis of linear morphea with concern for Parry-Romberg syndrome, characterized by hemifacial atrophy. The patient was treated with oral prednisone, methotrexate, and tocilizumab.

This case illustrates linear morphea’s rare effect on the jaw and tongue in skin of color and its association with Parry-Romberg syndrome. It highlights the need for prompt diagnosis and treatment to prevent further impacts on quality of life.

Samer Wahood BA¹, Fadwa Ahmed MD¹, Shelbie Serad MPH^2,3, Sara Yumeen MD⁴, Megan M. Tran BS¹, Lauryn Orsillo BS⁵, Alyssa Iurillo BA⁶, Tatiana Abrantes MD¹, Dillon Imbriano BS⁷, Claire Baptiste MPH⁸, Allison B. Robbins MD⁹, Matthew Clark MD¹⁰, Jill Conway PA-C¹¹, Samuel Christensen PA-C¹¹, Robert A. Swerlick MD¹², Oliver J. Wisco DO^1,11

¹ Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, RI
² Oregon Health & Science University, Portland, OR
³ Portland State University School of Public Health, Portland, OR
⁴ Department of Dermatology, University of Miami Leonard Miller School of Medicine, Miami, FL
⁵ Western University of Health Sciences, Lebanon, OR
⁶ Indiana University School of Medicine, Indianapolis, IN
⁷ University of New England College of Osteopathic Medicine, Biddeford, ME
⁸ The Robert Larner College of Medicine at the University of Vermont, Burlington, VT
⁹ Dermatology Associates, Portland, ME
¹⁰ Dermatologic Surgery of the Carolinas, Charlotte, NC
¹¹ Dermatology Health Specialists, Bend, OR
¹² Department of Dermatology, Emory University School of Medicine, Atlanta, GA

Skin biopsies are crucial for diagnosing and managing skin cancer, but overutilization can result in unnecessary healthcare costs and patient harm. Traditional metrics like the Number Needed to Biopsy (NNB) have limitations. This study introduces three novel performance measures: Biopsy Accuracy (BA), Diagnostic Accuracy (DA), and Utilization Appropriateness Ratio (UAR), aimed at providing a more comprehensive evaluation of clinician performance in skin cancer diagnosis.

A retrospective analysis of 1,265 skin biopsies performed by four clinicians (two Mohs micrographic surgery fellowship-trained dermatologists and two general dermatology physician associates) in a private dermatology practice between March 2019 and November 2021 was conducted. Data on rule-out diagnosis, lesion size, location, provider type, and histopathological diagnosis were extracted. Overall, BA was 39.5%, DA was 84.4%, and UAR was 0.82. BA and UAR were lower for melanoma rule-out biopsies (BA 8.4%, UAR 0.18) compared to non-melanoma skin cancer (BA 53.6%, UAR 1.24). DA remained consistent across various rule-out diagnoses and lesion characteristics.

The proposed BA, DA, and UAR metrics offer a more nuanced understanding of biopsy utilization and accuracy in skin cancer care, improving upon the NNB metric. This framework could serve as a standardized performance measure and warrants further prospective studies.

Yue Xing¹, Ilana Reznikov¹, Ikjot Sidhu^1,2, Jill Wisnewski³, Aleksandr Prystupa^1,2, Piotr Konieczny¹, Stephen T. Yeung⁴, Kody Mansfield⁵, Madeline Kim⁶, Meredith Manson⁶, Qingrong Huang⁷, Ata S. Moshiri⁸, Amanda W. Lund^1,8,9, Kamal M. Khanna^4,9, Emma, Guttman-Yassky⁶, Niroshana Anandasabapathy¹⁰, and Shruti Naik^{1, 7, 9, 11}

1. Department of Pathology, NYU Langone Health, New York, NY, USA
2. Applied Bioinformatics Laboratories, NYU Langone Health, New York, NY, USA
3. Department of Biology, MIT, Cambridge, MA, USA
4. Department of Microbiology, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
5. Department of Cell Biology, NYU Langone Health, New York, NY, USA
6. Department of Dermatology and Department of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
7. Center for Discovery & Innovation, Hackensack Meridian Health
8. Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
9. Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
10. Department of Dermatology, Microbiology and Immunology, Meyer Cancer Center, Englander Institute of Precision Medicine, Weill Cornell Medicine, New York, NY, USA
11. Department of Medicine, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA

Atopic and allergic diseases predominantly manifest in early life, a period of profound growth and maturation. Yet, there is a dearth of information on factors governing early life sensitivity to allergens and the impact of developmental parameters on these immunological processes. Here we demonstrate that common allergens, including house dust mite (HDM), elicited potent type 17 responses in neonatal but not adult mice. HDM-induced acute inflammation was abolished in RORgt-, gd T cell-, or epithelial IL-17RC- deficient animals and surprisingly did not require nociceptors or lymph node engagement. Instead, neonatal CD301b+ type 2 conventional dendritic cells (cDC2s) abundantly engulfed allergen and activate gd T 17s in the skin. Despite up taking equivalent antigen, adult cDC2s do not promiscuously activate in the skin. This discrepancy was not attributable to cell-intrinsic differences arising from the distinct developmental origins, or changes in the skin parenchyma of neonatal and adult cDC2s. Instead, lower systemic glucocorticoid levels resulting from an immature hypothalamic-pituitary-adrenal (HPA) axis in early life permitted neonatal cDC2 hyperactivation, and was reversible by cortisol administration. These findings present a new paradigm of heightened innate immune activity in early life that is restrained in adult animals by glucocorticoids and bring to fore the influence of organismal developmental factors in shaping early life immunity.