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 …

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 …

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 …

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.

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 …

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.

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 …

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 …

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 …

Therapeutics Development For Pseudoxanthoma Elasticum And Related Ectopic Mineralization Disorders: Update 2020., Hongbin Luo, Qiaoli Li, Yi Cao, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), the prototype of heritable ectopic mineralization disorders, manifests with deposition of calcium hydroxyapatite crystals in the skin, eyes and arterial blood vessels. This autosomal recessive disorder, due to mutations in ABCC6, is usually diagnosed around the second decade of life. In the spectrum of heritable ectopic mineralization disorders are also generalized arterial calcification of infancy (GACI), with extremely severe arterial calcification diagnosed by prenatal ultrasound or perinatally, and arterial calcification due to CD73 deficiency (ACDC) manifesting with arterial and juxta-articular mineralization in the elderly; the latter disorders are caused by mutations in ENPP1 and NT5E, respectively. The …

Pd1 Inhibitor Induced Inverse Lichenoid Eruption: A Case Series, Mansha Sethi, Vaibhav Garg, Jason Lee, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

The increased use of monoclonal antibodies that target the immune checkpoint T cell receptor programmed death-1 (PD1) to treat numerous solid tumors has led to several reports describing associated cutaneous adverse events. Although lichenoid reactions have been well described, we propose that PD1 inhibitor-induced inverse lichenoid eruption (PILE) is a distinct variant. We describe two patients who presented with nearly identical deeply erythematous, malodorous, eroded anogenital plaques with focal crusting. Diagnosis of PILE was established given the biopsy findings and temporal association with PD1 inhibitor therapy. Treatment with clobetasol ointment was successful without necessitating discontinuation of immunotherapy. The findings were …

Arrhythmogenic Right Ventricular Cardiomyopathy In Patients With Biallelic Jup-Associated Skin Fragility., Hassan Vahidnezhad, Leila Youssefian, Masoomeh Faghankhani, Nikoo Mozafari, Amir Hossein Saeidian, Fatemeh Niaziorimi, Fahimeh Abdollahimajd, Soheila Sotoudeh, Fateme Rajabi, Liaosadat Mirsafaei, Zahra Alizadeh Sani, Lu Liu, Alyson Guy, Sirous Zeinali, Ariana Kariminejad, Reginald T. Ho, John A Mcgrath, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Arrhythmogenic right ventricular cardiomyopathy (ARVC), with skin manifestations, has been associated with mutations in JUP encoding plakoglobin. Genotype-phenotype correlations regarding the penetrance of cardiac involvement, and age of onset have not been well established. We examined a cohort of 362 families with skin fragility to screen for genetic mutations with next-generation sequencing-based methods. In two unrelated families, a previously unreported biallelic mutation, JUP: c.201delC; p.Ser68Alafs*92, was disclosed. The consequences of this mutation were determined by expression profiling both at tissue and ultrastructural levels, and the patients were evaluated by cardiac and cutaneous work-up. Whole-transcriptome sequencing by RNA-Seq revealed JUP as …

Plasma Inorganic Pyrophosphate Deficiency Links Multiparity To Cardiovascular Disease Risk., Almudena Veiga-Lopez, Visalakshi Sethuraman, Nastassia Navasiolava, Barbara Makela, Isoken Olomu, Robert Long, Koen Van De Wetering, Ludovic Martin, Tamas Aranyi, Flóra Szeri

Department of Dermatology and Cutaneous Biology Faculty Papers

Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum …

Bullous Hemorrhagic Sweet Syndrome With Cryptococcoid Neutrophils In Patients Positive For Antineutrophil Cytoplasmic Antibody Without Primary Vasculitis., Alex Sherban, Collin Fuller, Mansha Sethi, Eleni Mcgeehin, Dawn Hirokawa, Courtney Guerrieri, Jason B. Lee, Md, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

A Dog Lover's Dilemma: Airborne Allergic Contact Dermatitis To Tylosin., Aditi Kale, Anthony A Gaspari

Department of Dermatology and Cutaneous Biology Faculty Papers

Airborne allergic contact dermatitis (AACD) can be caused by airborne chemicals settling on exposed body parts. Repeated exposure to an allergen can induce AACD in the areas of exposed skin (typically, the face, hands, and forearms).

Case Report: A 67-year-old White woman presented in October 2019 with a 4-month history of severe pruritic facial and hand dermatitis, which began in June or July 2019.