Dermatology Commons^™

Immunosequencing Applications In Cutaneous T-Cell Lymphoma, Jenna Mandel, Laura Gleason, Daniel Joffe, Safiyyah Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and …

Skin Barrier Function: The Interplay Of Physical, Chemical, And Immunologic Properties, Paola Baker, Christina Huang, Rakan Radi, Samara B Moll, Emmanuela Jules, Jack L Arbiser

Student Papers, Posters & Projects

An intact barrier function of the skin is important in maintaining skin health. The regulation of the skin barrier depends on a multitude of molecular and immunological signaling pathways. By examining the regulation of a healthy skin barrier, including maintenance of the acid mantle and appropriate levels of ceramides, dermatologists can better formulate solutions to address issues that are related to a disrupted skin barrier. Conversely, by understanding specific skin barrier disruptions that are associated with specific conditions, such as atopic dermatitis or psoriasis, the development of new compounds could target signaling pathways to provide more effective relief for patients. …

Maximizing Wound Coverage In Full-Thickness Skin Defects: A Randomized-Controlled Trial Of Autologous Skin Cell Suspension And Widely Meshed Autograft Versus Standard Autografting, Sharon Henry, Steven Mapula, Mark Grevious, Kevin N. Foster, Herbert Phelan, Jeffrey Shupp, Rodney Chan, David Harrington, Neil Mashruwala, David A. Brown, Haaris Mir, George Singer, Alfredo Cordova, Lisa Rae, Theresa Chin, Lourdes Castanon, Derek Bell, William Hughes, Joseph A. Molnar

Department of Surgery Faculty Papers

BACKGROUND: Traumatic insults, infection, and surgical procedures can leave skin defects that are not amenable to primary closure. Split-thickness skin grafting (STSG) is frequently used to achieve closure of these wounds. Although effective, STSG can be associated with donor site morbidity, compounding the burden of illness in patients undergoing soft tissue reconstruction procedures. With an expansion ratio of 1:80, autologous skin cell suspension (ASCS) has been demonstrated to significantly decrease donor skin requirements compared with traditional STSG in burn injuries. We hypothesized that the clinical performance of ASCS would be similar for soft tissue reconstruction of nonburn wounds.

METHODS: A …

Potential Chemical Risks From Tattoos And Their Relevance To Military Health Policy In The United States, James D. Blando, Blas A. Guigni

Community & Environmental Health Faculty Publications

We summarize and consolidate disparate sources of information about the practice of tattooing and its potential implications for military population health and policy. Each branch of the United States military has policies about tattoos for service members, but these have varied over time and do not cover health protection. The number of veterans receiving disability payments and the cost of those payments has been rising over time; the broad category of skin conditions accounts for 11% of disability claims. Any additional factor, such as tattoos that may increase the occurrence of adverse skin reactions, can substantially impact veteran benefit expenses …

Reduced Spag17 Expression In Systemic Sclerosis Triggers Myofibroblast Transition And Drives Fibrosis, Paulene Sapao, Elisha D O Roberson, Bo Shi, Shervin Assassi, Brian Skaug, Fred Lee, Alexandra Naba, Bethany E Perez White, Carlos Córdova-Fletes, Pei-Suen Tsou, Amr H Sawalha, Johann E Gudjonsson, Feiyang Ma, Priyanka Verma, Dibyendu Bhattacharyya, Mary Carns, Jerome F Strauss, Delphine Sicard, Daniel J Tschumperlin, Melissa I Champer, Paul J Campagnola, Maria E Teves, John Varga

Journal Articles

Systemic sclerosis (SSc) is a clinically heterogeneous fibrotic disease with no effective treatment. Myofibroblasts are responsible for unresolving synchronous skin and internal organ fibrosis in SSc, but the drivers of sustained myofibroblast activation remain poorly understood. Using unbiased transcriptome analysis of skin biopsies, we identified the downregulation of SPAG17 in multiple independent cohorts of patients with SSc, and by orthogonal approaches, we observed a significant negative correlation between SPAG17 and fibrotic gene expression. Fibroblasts and endothelial cells explanted from SSc skin biopsies showed reduced chromatin accessibility at the SPAG17 locus. Remarkably, mice lacking Spag17 showed spontaneous skin fibrosis with increased …

Skin Cancer Biopsy And Detection Rates With Total Body Skin Examination: A Cross-Sectional Retrospective Analysis., Alexander Sherban, Shayan Waseh, Audra Hugo, Michael Bui, Constantine Daskalakis, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

Research Letter

In Vitro And In Vivo Correlation Of Skin And Cellular Responses To Nucleic Acid Delivery, M. Bosnjak, K. Znidar, A. Sales Conniff, T. Jesenko, B. Markelc, Nina Semenova, J. Tur, K. Kohena, S. Kranjc Brezar, L. Heller, M. Cemazar

Bioelectrics Publications

Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immunogenicity of …

A Review Of Fixed Drug Eruption With A Special Focus On Generalized Bullous Fixed Drug Eruption., Hannah J. Anderson, Jason B. Lee, Md

Department of Dermatology and Cutaneous Biology Faculty Papers

Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is ingested. With each recurrence, the eruption can involve additional sites. Lesions can have overlying vesicles and/or bullae, and when they cover a significant percentage of body surface area, the eruption is referred to as generalized bullous fixed drug eruption (GBFDE). Due to the widespread skin denudation that can be seen in this condition, GBFDE may be confused clinically with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). While treatments described for GBFDE include supportive …

In Vitro And In Vivio Evaluation Of A Moisture Treatment Cream Containing Three Critical Elements Of Natural Skin Moisturization, David H. Mcdaniel, Jeffrey S. Dover, Mitchell Wortzman, Diane B. Nelson

Biological Sciences Faculty Publications

Objectives

To evaluate skin barrier and hydration effects of a new rebalancing moisture treatment (TRMT) and to assess efficacy and tolerability in subjects with photodamaged skin.

Methods

In an epidermal skin model, tissues (n = 5/group) were topically treated with 25 µL of TRMT, 25 µL of a market‐leading moisturizer (MLM), or untreated for 60 minutes. Hydration was measured at 0, 15, and 30 minutes. Tissues were harvested for gene expression analysis of markers associated with skin barrier and hydration: Claudin (CLD), Aquaporin (AQP), Hyaluronic Acid Syntheses (HAS), and Hyaluronidase (HYAL). A clinical study evaluated twice‐daily application of TRMT, assessing …

The Influence Of Tumor Regression, Solar Elastosis, And Patient Age On Pathologists' Interpretation Of Melanocytic Skin Lesions., Linda Titus, Raymond L Barnhill, Jason P Lott, Michael W Piepkorn, David E Elder, Paul D Frederick, Heidi D Nelson, Patricia A Carney, Stevan R Knezevich, Martin A Weinstock, Joann G Elmore

Articles, Abstracts, and Reports

It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists' interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist's characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists' clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward …

Increased Expression Of Napdh Oxidase 4 In Systemic Sclerosis Dermal Fibroblasts: Regulation By Transforming Growth Factor Β., Sonsoles Piera-Velazquez, Alma Makul, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1).

METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc …

In Vivo Bioluminescence Imaging To Evaluate Systemic And Topical Antibiotics Against Community-Acquired Methicillin-Resistant Staphylococcus Aureus-Infected Skin Wounds In Mice, Yi Guo, Romela Irene Ramos, John S. Cho, Niles P. Donegan, Ambrose L. Cheung, Lloyd S. Miller

Dartmouth Scholarship

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to devel

Effect Of Oxidative Stress On Protein Tyrosine Phosphatase 1b In Scleroderma Dermal Fibroblasts., Pei-Suen Tsou, Nadine N. Talia, Adam J. Pinney, Ann Kendzicky, Sonsoles Piera-Velazquez, Sergio A. Jimenez, James R. Seibold, Kristine Phillips, Alisa E Koch

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Platelet-derived growth factor (PDGF) and its receptor, PDGFR, promote fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such cells in scleroderma skin lesions produce excessive reactive oxygen species (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken to determine whether the thiol-sensitive PTP1B is affected by ROS in SSc dermal fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type I collagen. This study also sought to investigate the effect of a thiol antioxidant, N-acetylcysteine (NAC), in SSc.

METHODS: Fibroblasts were isolated from the skin …

A Prospective Observational Study Of Mycophenolate Mofetil Treatment In Progressive Diffuse Cutaneous Systemic Sclerosis Of Recent Onset., Fabian A. Mendoza, Md, Sarah J. Nagle, Jason B. Lee, Md, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset.

METHODS: Twenty-five previously untreated consecutive patients with recent-onset (< 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients.

RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR …

Elevated Expression Of Type Vii Collagen In The Skin Of Patients With Systemic Sclerosis. Regulation By Transforming Growth Factor-Beta., Lidia Rudnicka, John Varga, Angela M. Christiano, Renato V. Iozzo, Sergio A. Jimenez, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate the expression of the type VII collagen gene. In this study, we assessed the expression of type VII collagen and TGF-beta in the skin of patients …