Dermatology Commons^™

Expert Opinions And Clinical Experiences With Chlormethine Gel As Maintenance Treatment For Patients With Mycosis Fungoides, Larisa Geskin, Christiane Querfeld, Emmilia Hodak, Neda Nikbakht, Evangelia Papadavid, Marco Ardigò, Ulrike Wehkamp, Martine Bagot

Department of Dermatology and Cutaneous Biology Faculty Papers

Maintenance treatment can be recommended for patients with mycosis fungoides (MF) whose disease responds to primary treatment. While positive outcomes have been observed in small studies with maintenance therapy, there is a lack of practical guidelines and agreement on when and how maintenance therapy for MF should be approached. In this article, we discuss expert opinions and clinical experiences on the topic of maintenance therapy for patients with MF, with a focus on chlormethine gel. Ideally, patients should have a durable response before initiating maintenance therapy. The definition of and required duration of durable response are topics that are open …

Inherited Human Itk Deficiency Impairs Ifn-Γ Immunity And Underlies Tuberculosis, Masato Ogishi, Rui Yang, Rémy Rodriguez, Dominic P Golec, Emmanuel Martin, Quentin Philippot, Jonathan Bohlen, Simon J Pelham, Andrés Augusto Arias, Taushif Khan, Manar Ata, Fatima Al Ali, Flore Rozenberg, Xiao-Fei Kong, Maya Chrabieh, Candice Laine, Wei-Te Lei, Ji Eun Han, Yoann Seeleuthner, Zenia Kaul, Emmanuelle Jouanguy, Vivien Béziat, Leila Youssefian, Hassan Vahidnezhad, V Koneti Rao, Bénédicte Neven, Claire Fieschi, Davood Mansouri, Mohammad Shahrooei, Sevgi Pekcan, Gulsum Alkan, Melike Emiroğlu, Hüseyin Tokgöz, Jouni Uitto, Fabian Hauck, Jacinta Bustamante, Laurent Abel, Sevgi Keles, Nima Parvaneh, Nico Marr, Pamela L Schwartzberg, Sylvain Latour, Jean-Laurent Casanova, Stéphanie Boisson-Dupuis

Department of Dermatology and Cutaneous Biology Faculty Papers

Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in …

Aptamer Proteomics Of Serum Exosomes From Patients With Primary Raynaud's And Patients With Raynaud's At Risk Of Evolving Into Systemic Sclerosis, Sonsoles Piera-Velazquez, Simon T. Dillon, Xuesong Gu, Towia A. Libermann, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: A major unmet need for Systemic Sclerosis (SSc) clinical management is the lack of biomarkers for the early diagnosis of patients with Raynaud's Phenomenon at high risk of evolving into SSc.

OBJECTIVE: To identify proteins contained within serum exosomes employing an aptamer proteomic analysis that may serve to reveal patients with Raynaud's Phenomenon at risk of developing SSc.

METHODS: Exosomes were isolated from serum samples from patients with Primary Raynaud's Phenomenon and from patients with Raynaud's Phenomenon harbouring serum antinuclear antibodies (ANA) who may be at high risk of evolving into SSc. The expression of 1,305 proteins was quantified …

Improvement Of Necrobiosis Lipoidica With Topical Ruxolitinib Cream After Prior Nonresponse To Compounded Topical Tofacitinib Cream, Shannon Nugent, Alexandra J Coromilas, Joseph C English, Misha Rosenbach

Student Papers, Posters & Projects

No abstract provided.

Developing A Virtual Global Dermatology Curriculum: Qualitative Analysis Based On A Pilot Study In Ethiopia, Rishab Revankar, Aditya Sood, Heli Patel, Kassahun Bilcha, Annisa Befekadu, Howa Yeung, Benjamin Stoff

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Desmoglein-2 Is Important For Islet Function And Β-Cell Survival, Kay K. Myo Min, Darling Rojas-Canales, Daniella Penko, Mark Denichilo, Michaelia P. Cockshell, Charlie B. Ffrench, Emma J. Thompson, Olof Asplund, Christopher J. Drogemuller, Rashmi B. Prasad, Leif Groop, Shane T Grey, Helen E. Thomas, Thomas Loudovaris, Thomas W. Kay, My G. Mahoney, Claire F. Jessup, P. Toby Coates, Claudine S. Bonder

Department of Dermatology and Cutaneous Biology Faculty Papers

Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2). Genetically-modified mice lacking Dsg2 were examined for islet cell mass, insulin production, responses to glucose, susceptibility to a streptozotocin-induced mouse model of hyperglycaemia, and ability to cure diabetes …

Pleomorphic Dermal Sarcoma Of The Scalp: Review Of Management And Distinguishing Features From Atypical Fibroxanthoma, Alexa J Cohen, Sahithi Talasila, Bojan Lazarevic, Laura Gleason, Viral Patel, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Collagen Vii Maintains Proteostasis In Dermal Fibroblasts By Scaffolding Tango1 Cargo, Qingqing Cao, Grace Tartaglia, Michael Alexander, Pyung Hung Park, Shiv Poojan, Mehdi Farshchian, Ignacia Fuentes, Mei Chen, John . A. Mcgrath, Francis Palisson, Julio Salas-Alanis, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Lack of type VII collagen (C7) disrupts cellular proteostasis yet the mechanism remains undescribed. By studying the relationship between C7 and the extracellular matrix (ECM)-associated proteins thrombospondin-1 (TSP1), type XII collagen (C12) and tissue transglutaminase (TGM2) in primary human dermal fibroblasts from multiple donors with or without the genetic disease recessive dystrophic epidermolysis bullosa (RDEB) (n=31), we demonstrate that secretion of each of these proteins is increased in the presence of C7. In dermal fibroblasts isolated from patients with RDEB, where C7 is absent or defective, association with the COPII outer coat protein SEC31 and ultimately secretion of each of …

Pruritic Annular Erythematous Eruption After Receiving The Covid-19 Vaccine, Devon E. Cross, James Garritano, Amanda E. Zubek, Alicia J. Little

COVID-19 Papers, Posters, and Presentations

No abstract provided.

The 2-Methoxymethyl Modification Of P -Phenylenediamine Reduces The Sensitization Risk For Hairdressers To Hair Dyes-An Occupational Hand Exposure-Based Risk Assessment, Emanuele Marco Gargano, Brunhilde Blömeke, Anthony Gaspari, Carsten Goebel

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Allergic contact dermatitis involving the hands is a common occupational skin disease for hairdressers and the potent sensitizers p -phenylenediamine (PPD) and toluene-2,5-diamine (PTD) are associated with the development of occupational allergic contact dermatitis.

Objective: The aim of the study was to analyze whether the use of the moderate sensitizer 2-methoxymethyl-PPD (ME-PPD) in professional hair dyes is a suitable tool to reduce the occupational contact allergy risk for hairdressers.

Methods: Hand exposure of hairdressers (N = 11) to ME-PPD was analyzed under routine hair coloring conditions in commercial salons. By accounting for wet work and uneven hand exposure, the …

Elevated Serum Levels Of Interleukin-15 In Pemphigus Vulgaris Patients: A Potential Therapeutic Target, Maedeh Kheirodin, Zohreh Tehranchinia, Yasaman Ketabi, Soheil Tavakolpour, Sahar Dadkhahfar, Masoomeh Faghankani, Hassan Vahidnezhad, Nikoo Mozafari

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction: Pemphigus vulgaris (PV) is a rare autoimmune disease that causes painful blistering. Interleukin-15 (IL-15) as a member of the immunoregulatory cytokines family is associated with the development of the chronic inflammatory or autoimmune disease. There is not much information available in the literature on the exact role IL-15 plays in PV. Objectives: The goal of this study was to evaluate the serum levels of IL-15 in patients with PV and assess the association of IL-15 with anti-desmoglein antibodies and the severity of the disease. Methods: Fifty-three individuals affected with active PV and 38 age- and gender-matched healthy controls were …

Advance Trends In Targeting Homology-Directed Repair For Accurate Gene Editing: An Inclusive Review Of Small Molecules And Modified Crispr-Cas9 Systems, Forough Shams, Hadi Bayat, Omid Mohammadian, Somayeh Mahboudi, Hassan Vahidnezhad, Mohsen Soosanabadi, Azam Rahimpour

Jefferson Institute of Molecular Medicine Papers and Presentations

Introduction: Clustered regularly interspaced short palindromic repeat and its associated protein (CRISPR-Cas)-based technologies generate targeted modifications in host genome by inducing site-specific double-strand breaks (DSBs) that can serve as a substrate for homology-directed repair (HDR) in both in vitro and in vivo models. HDR pathway could enhance incorporation of exogenous DNA templates into the CRISPR-Cas9-mediated DSB site. Owing to low rate of HDR pathway, the efficiency of accurate genome editing is diminished. Enhancing the efficiency of HDR can provide fast, easy, and accurate technologies based on CRISPR-Cas9 technologies. Methods: The current study presents an overview of attempts conducted on the …

A Case Series Of Primary Cutaneous B-Cell Lymphomas With Atypical Presentations: Diagnostic And Therapeutic Challenges, Emily Correia, Jisun Cha, Shalini Krishnasamy, Megan O'Donnell, Wenyin Shi, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

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

Secondary Syphilis Mimicking Marginal Zone B-Cell Lymphoma, E. Correia, Laura Gleason, Shalini Krishnasamy, Alexa Cohen, Safiyyah Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Reactive Oxygen Species Reprogram Macrophages To Suppress Antitumor Immune Response Through The Exosomal Mir-155-5p/Pd-L1 Pathway, Xiang Li, Shaomin Wang, Wei Mu, Jennifer Barry, Anna Han, Richard L Carpenter, Bing-Hua Jiang, Stephen C Peiper, M G Mahoney, A E Aplin, Hong Ren, Jun He

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Cancer cells have an imbalance in oxidation-reduction (redox) homeostasis. Understanding the precise mechanisms and the impact of the altered redox microenvironment on the immunologic reaction to tumors is limited.

Methods: We isolated exosomes from ovarian cancer cells through ultracentrifuge and characterized by Western-blots and Nanoparticle Tracking Analysis. 2D, 3D-coculture tumor model, and 3D live cell imaging were used to study the interactions between tumor cells, macrophages and CD3 T cells in vitro. The role of exosomal miR-155-5p in tumor growth was evaluated in xenograft nude mice models and immune-competent mice models. Flow cytometry and flow sorting were used to …

Evaluating A Targeted Cancer Therapy Approach Mediated By Rna, Katharina Woess, Yuchen Sun, Hanae Morio, Anna Stierschneider, Anna Kaufmann, Stefan Hainzl, Lisa Trattner, Thomas Kocher, Birgit Tockner, Victoria Leb-Reichl, Markus Steiner, Gabriele Brachtl, Andrew P. South, Johann W Bauer, Julia Reichelt, Tomomi Furihata, Verena Wally, Ulrich Koller, Josefina Piñón Hofbauer, Christina Guttmann-Gruber

Department of Dermatology and Cutaneous Biology Faculty Papers

Conventional anti-cancer therapies based on chemo- and/or radiotherapy represent highly effective means to kill cancer cells but lack tumor specificity and, therefore, result in a wide range of iatrogenic effects. A promising approach to overcome this obstacle is spliceosome-mediated RNA trans-splicing (SMaRT), which can be leveraged to target tumor cells while leaving normal cells unharmed. Notably, a previously established RNA trans-splicing molecule (RTM44) showed efficacy and specificity in exchanging the coding sequence of a cancer target gene (Ct-SLCO1B3) with the suicide gene HSV1-thymidine kinase in a colorectal cancer model, thereby rendering tumor cells sensitive to the prodrug ganciclovir (GCV). In …

Reactive Granulomatous Dermatitis Associated With Ovarian Cancer And A Review Of Its Role As A Harbinger For Malignancy, Alexander Sherban, Jisun Cha, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

Reactive granulomatous dermatitis (RGD) is a rare dermatosis with a variety of cutaneous manifestations unified by a dermal granulomatous infiltrate on histology. Rheumatoid arthritis and autoimmune disease are classic associations, but an increasing number of cases have been attributed to covert malignancy. Only 41 cases of paraneoplastic RGD have been documented to our knowledge and we present an additional case that manifested eight months prior to the diagnosis of ovarian cancer and clinically mimicked morphea. Histopathologic examination identifying palisaded CD68+ cells and collagen degeneration are helpful in diagnosing this entity which may mimic a host of other cutaneous processes, including …

Oxidative Stress Induced By Reactive Oxygen Species (Ros) And Nadph Oxidase 4 (Nox4) In The Pathogenesis Of The Fibrotic Process In Systemic Sclerosis: A Promising Therapeutic Target, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise …

Dark Side Of Cancer Therapy: Cancer Treatment-Induced Cardiopulmonary Inflammation, Fibrosis, And Immune Modulation, Boopathi Ettickan, Chellappagounder Thangavel

Department of Dermatology and Cutaneous Biology Faculty Papers

Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers include surgical intervention and the application of chemotherapy with ionizing radiation. Despite these advances, cancer therapy-related cardiopulmonary dysfunction (CTRCPD) is one of the most undesirable side effects of cancer therapy and leads to limitations to cancer treatment. Chemoradiation therapy or immunotherapy promote acute and chronic cardiopulmonary damage by inducing reactive oxygen species, DNA damage, inflammation, fibrosis, deregulation of cellular immunity, cardiopulmonary failure, and non-malignant related deaths among cancer-free patients who received cancer therapy. CTRCPD is a complex …

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 …

Neutrophil-Rich, Noncollagenous 16a Domain-Negative Bullous Pemphigoid Associated With Psoriasis, Morgan E Sussman, Shoshana K Grossman, Sylvia Hsu, Jason B. Lee, Kiran Motaparthi

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Development Of The Biohybrid Assay: Combining Primary Human Vascular Smooth Muscle Cells And Blood To Measure Vascular Calcification Propensity, Armand M G Jaminon, Asim C Akbulut, Niko Rapp, Rafael Kramann, Erik A L Biessen, Lieve Temmerman, Barend Mees, Vincent Brandenburg, Robert Dzhanaev, Willi Jahnen-Dechent, Juergen Floege, Jouni Uitto, Chris P Reutelingsperger, Leon J Schurgers

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Vascular calcification is an active process that increases cardiovascular disease (CVD) risk. There is still no consensus on an appropriate biomarker for vascular calcification. We reasoned that the biomarker for vascular calcification is the collection of all blood components that can be sensed and integrated into a calcification response by human vascular smooth muscle cells (hVSMCs).

METHODS: We developed a new cell-based high-content assay, the BioHybrid assay, to measure in vitro calcification. The BioHybrid assay was compared with the o-Cresolphthalein assay and the T50 assay. Serum and plasma were derived from different cohort studies including chronic kidney disease (CKD) …

Severe Acute Generalized Exanthematous Pustulosis With Toxic Epidermal Necrolysis-Like Desquamation: A Case Series Of 8 Patients, Simo Huang, Amara Ahmed, Sylvia Hsu, Jason B. Lee, Kiran Motaparthi

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Mutagenic Analysis Of The Putative Abcc6 Substrate-Binding Cavity Using A New Homology Model, Flóra Szeri, Valentina Corradi, Fatemeh Niaziorimi, Sylvia Donnelly, Gwenaëlle Conseil, Susan P C Cole, D Peter Tieleman, Koen Van De Wetering

Department of Dermatology and Cutaneous Biology Faculty Papers

Inactivating mutations in ABCC6 underlie the rare hereditary mineralization disorder pseudoxanthoma elasticum. ABCC6 is an ATP-binding cassette (ABC) integral membrane protein that mediates the release of ATP from hepatocytes into the bloodstream. The released ATP is extracellularly converted into pyrophosphate, a key mineralization inhibitor. Although ABCC6 is firmly linked to cellular ATP release, the molecular details of ABCC6-mediated ATP release remain elusive. Most of the currently available data support the hypothesis that ABCC6 is an ATP-dependent ATP efflux pump, an un-precedented function for an ABC transporter. This hypothesis implies the presence of an ATP-binding site in the substrate-binding cavity of …

Impaired Wound Healing, Fibrosis, And Cancer: The Paradigm Of Recessive Dystrophic Epidermolysis Bullosa, Grace Tartaglia, Qingqing Cao, Zachary Padron, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a devastating skin blistering disease caused by mutations in the gene encoding type VII collagen (C7), leading to epidermal fragility, trauma-induced blistering, and long term, hard-to-heal wounds. Fibrosis develops rapidly in RDEB skin and contributes to both chronic wounds, which emerge after cycles of repetitive wound and scar formation, and squamous cell carcinoma—the single biggest cause of death in this patient group. The molecular pathways disrupted in a broad spectrum of fibrotic disease are also disrupted in RDEB, and squamous cell carcinomas arising in RDEB are thus far molecularly indistinct from other sub-types of …

Elevated Apobec Mutational Signatures Implicate Chronic Injury In Etiology Of An Aggressive Head-And-Neck Squamous Cell Carcinoma: A Case Report., Jena Patel, Nicoline Y. Den Breems, Madalina Tuluc, Jennifer Johnson, Joseph M. Curry, Andrew P. South, Raymond J. Cho

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Aggressive squamous cell carcinomas (SCCs) present frequently in the context of chronic skin injury occurring in patients with the congenital blistering disease recessive dystrophic epidermolysis bullosa. Recently, these cancers were shown to harbor mutation signatures associated with endogenous deaminases of the active polynucleotide cytosine deaminase family, collectively termed APOBEC, and clock-like COSMIC [Catalogue of Somatic Mutations in Cancer] signatures, which are associated with normal aging and might result from cumulative DNA replication errors. We present a case of a nasal septal SCC arising in the context of recurrent injury, but also modest past tobacco use. Our genetic analysis of …

A Diverse Nation Calls For A Diverse Healthcare Force., Autumn L Saizan, Annyella Douglas, Nada Elbuluk, Susan Taylor

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Skin Manifestations In Covid-19 Patients: Are They Indicators For Disease Severity? A Systematic Review, Parnian Jamshidi, Bahareh Hajikhani, Mehdi Mirsaeidi, Hassan Vahidnezhad, Masoud Dadashi, Mohammad Javad Nasiri

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction: Until now, there are several reports on cutaneous manifestations in COVID-19 patients. However, the link between skin manifestations and the severity of the disease remains debatable. We conducted a systematic review to evaluate the temporal relationship between different types of skin lesions and the severity of COVID-19. Methods: A systematic search was conducted for relevant studies published between January and July 2020 using Pubmed/Medline, Embase, and Web of knowledge. The following keywords were used: "SARS-CoV-2" or "COVID-19" or "new coronavirus" or "Wuhan Coronavirus" or "coronavirus disease 2019" and "skin disease" or "skin manifestation" or "cutaneous manifestation." Results: Out of …

Establishing The Relationship Between Mendelian Nafld And Skin Pathology, Anthony Medvedev, Hassan Vahidnezhad, Phd, Leila Youssefian, Phd, Jouni Uitto, Md, Phd

Phase 1

Introduction:

It is estimated that 25% of the world’s population has some form of Nonalcoholic Fatty Liver Disease (NAFLD), a pathology associated with the development of cirrhosis, varices, and hepatocellular carcinoma. The discovery of a biallelic mutation in ABHD5 established the link between NAFLD and Chanarin-Dorfman syndrome. Consequently, it was hypothesized that additional NAFLD-inducing mutations could be associated with dermatologic manifestations.

Methods:

International NAFLD patients from consanguineous families underwent whole exome sequencing. These results were then filtered by frequency and pathogenicity prediction algorithms (e.g. Mutation Taster, Polyphen, CADD) to yield novel mutations. Concurrently, a literature review via PubMed identified …