Dermatology Commons^™

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 …

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 …

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.

Congenital Muscular Dystrophy-Associated Inflammatory Chemokines Provide Axes For Effective Recruitment Of Therapeutic Adult Stem Cell Into Muscles, Vitali Alexeev, Jacquelyn Olavarria, Paolo Bonaldo, Luciano Merlini, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders characterized by muscle weakness. The two most prevalent forms of CMD, collagen VI-related myopathies (COL6RM) and laminin α2 deficient CMD type 1A (MDC1A), are both caused by deficiency or dysfunction of extracellular matrix proteins. Previously, we showed that an intramuscular transplantation of human adipose-derived stem cells (ADSC) into the muscle of the Col6a1-/- mice results in efficient stem cell engraftment, migration, long-term survival, and continuous production of the collagen VI protein, suggesting the feasibility of the systemic cellular therapy for COL6RM. In order for this …

Aberrant Recruitment Of Leukocytes Defines Poor Wound Healing In Patients With Recessive Dystrophic Epidermolysis Bullosa., Taylor Phillips, Leonie Huitema, Rodrigo Cepeda, Diego De Los Cobos, Regina Isabella Matus Perez, Mauricio Salas Garza, Franziska Ringpfeil, Bahar Dasgeb, Jouni Uitto, Julio Cesar Salas-Alanis, Vitali Alexeev, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Poorly healing wounds are one of the major complications in patients suffering from recessive dystrophic epidermolysis bullosa (RDEB). At present, there are no effective means to analyze changes in cellular and molecular networks occurring during RDEB wound progression to predict wound outcome and design betted wound management approaches.

OBJECTIVES: To better define mechanisms influencing RDEB wound progression by evaluating changes in molecular and cellular networks.

METHODS: We developed a non-invasive approach for sampling and analysis of wound-associated constituents using wound-covering bandages. Cellular and molecular components from seventy-six samples collected from early, established and chronic RDEB wounds were evaluated by …

Consensus Reclassification Of Inherited Epidermolysis Bullosa And Other Disorders With Skin Fragility., C Has, J W Bauer, C Bodemer, M C Bolling, L Bruckner-Tuderman, A Diem, J-D Fine, A Heagerty, A Hovnanian, M P Marinkovich, A E Martinez, J A Mcgrath, C Moss, D F Murrell, F Palisson, A Schwieger-Briel, E Sprecher, K Tamai, J Uitto, D T Woodley, G Zambruno, J E Mellerio

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Several new genes and clinical subtypes have been identified since the publication in 2014 of the report of the last International Consensus Meeting on Epidermolysis Bullosa (EB).

OBJECTIVES: We sought to reclassify disorders with skin fragility, with a focus on EB, based on new clinical and molecular data.

METHODS: This was a consensus expert review.

RESULTS: In this latest consensus report, we introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Other disorders with skin fragility, where blisters are a minor part of the clinical picture or are not seen because skin …

Ier5, A Dna Damage Response Gene, Is Required For Notch-Mediated Induction Of Squamous Cell Differentiation, Li Pan, Madeleine E Lemieux, Tom Thomas, Julia M Rogers, Colin H Lipper, Winston Lee, Carl Johnson, Lynette M Sholl, Andrew P. South, Jarrod A Marto, Guillaume O Adelmant, Stephen C Blacklow, Jon C Aster

Department of Dermatology and Cutaneous Biology Faculty Papers

Notch signaling regulates squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is tumor suppressive. Here, we show that conditional activation of Notch in squamous cells activates a context-specific gene expression program through lineage-specific regulatory elements. Among direct Notch target genes are multiple DNA damage response genes, including IER5, which we show is required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes. IER5 is epistatic to PPP2R2A, a gene that encodes the PP2A B55α subunit, which we show interacts with IER5 in cells and in purified systems. Thus, Notch and DNA-damage …

Cells From Discarded Dressings Differentiate Chronic From Acute Wounds In Patients With Epidermolysis Bullosa, Ignacia Fuentes, Christina Guttmann-Gruber, Birgit Tockner, Anja Diem, Alfred Klausegger, Glenda Cofré-Araneda, Olga Figuera, Yessia Hidalgo, Pilar Morandé, Francis Palisson, Boris Rebolledo-Jaramillo, María Joao Yubero, Raymond J Cho, Heather I Rishel, M Peter Marinkovich, Joyce M C Teng, Timothy G. Webster, Marco Prisco, Luis H. Eraso, Josefina Piñon Hofbauer, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings. We show, that the method is able to differentiate chronic from acute wounds, identifying significant increases in …

Splicing Of The Cake Can Affect The Severity Of Epidermolysis Bullosa, D Murrell, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Dermatology Journals And The Impact Factor, Lawrence Charles Parish, W Clark Lambert

Department of Dermatology and Cutaneous Biology Faculty Papers

The noted informatics authority, Eugene Garfield (1925-2017), while working at the Johns Hopkins Medical Library, decided to assist medical librarians in selecting the publications to which they should subscribe. Not only at issue was the expense of subscribing and binding the periodicals, but there was also the physical space for shelving them. This was the birth of the Science Citation Index (SCI), the Impact Factor (IF), and the Institute for Scientific Information (ISI)in Philidelphia.

The role of the SCI has expanded over the years. Libraries may still continue to select journals on the basis of their IF, with many institutions …

Wax Models In Dermatology: Updated Through 2019, Lawrence Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

Wax models have occupied an unique position in the teaching of dermatology. While watercolor depictions of skin lesions and later photographic illustrations have been used, the wax model offers an unique presentation of the morphology, often not captured by other methods .

The Membrane Protein Ankh Is Crucial For Bone Mechanical Performance By Mediating Cellular Export Of Citrate And Atp, Flóra Szeri, Stefan Lundkvist, Sylvia Donnelly, Udo F H Engelke, Kyu Rhee, Charlene J Williams, John P Sundberg, Ron A Wevers, Ryan Tomlinson, Robert S Jansen, Koen Van De Wetering

Department of Dermatology and Cutaneous Biology Faculty Papers

The membrane protein ANKH was known to prevent pathological mineralization of joints and was thought to export pyrophosphate (PPi) from cells. This did not explain, however, the presence of ANKH in tissues, such as brain, blood vessels and muscle. We now report that in cultured cells ANKH exports ATP, rather than PPi, and, unexpectedly, also citrate as a prominent metabolite. The extracellular ATP is rapidly converted into PPi, explaining the role of ANKH in preventing ankylosis. Mice lacking functional Ank (Ankank/ank mice) had plasma citrate concentrations that were 65% lower than those detected in wild type control animals. Consequently, citrate …