Dermatology Commons^™

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 …

Characteristics Of Nontuberculous Mycobacterial Infections At A Midwestern Tertiary Hospital: A Retrospective Study Of 365 Patients., Claire E Hannah, Bradley A Ford, Jina Chung, Dilek Ince, Karolyn A Wanat

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease.

Methods: We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, …

Dermatologists In The Wild West, 1870-1900: The Early Pioneers From The Mississippi River To The Pacific Coast., Leonard J Hoenig, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

During the Wild West era of American history (approximately 1870-1900), at least 53 dermatologists settled between the Mississippi River and the Pacific Coast. In 1870, two dermatologists began their practice in the city of St Louis, Missouri (William Augustus Hardaway and Solomon Claiborne Martin, Sr) and one dermatologist started his practice in San Francisco, California (George J. Bucknall). By 1900, 50 more dermatologists had settled in 19 cities located in the American West (Tables 1,2). There, they established practices, initiated academic programs, and pioneered dermatology as a medical specialty in the western United States. This contribution provides brief biographic profiles …

Molecular Genetics Of Keratinization Disorders - What's New About Ichthyosis, Jouni Uitto, Leila Youssefian, Amir Hossein Saeidian, Hassan Vahidnezhad

Department of Dermatology and Cutaneous Biology Faculty Papers

The heritable forms of keratinization disorders, including various forms of ichthyosis and keratodermas, comprise a phenotypically heterogeneous group of diseases which can be divided into syndromic and non-syndromic forms. In the non-syndromic forms, the clinical manifestations are limited to the cutaneous structures while the syndromic ones are associated with a spectrum of extracutaneous manifestations. The inheritance in different families can be autosomal dominant, autosomal recessive or either X-linked dominant or recessive. Currently at least 67 distinct genes have been associated with different forms of ichthyosis. These genes can be grouped on the basis of their physiological involvement, including genes encoding …

Public Social Media Consultations For Dermatologic Conditions: An Online Survey, Elizabeth Schoenberg, Doaa Shalabi, Jordan Wang, Nazanin Saedi, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

The use of social media in medicine has been increasingly studied in recent years, especially concerning its role in patient outreach, education, diagnosis, and management. Dermatology is a unique field in that patients can post photographs of their skin ailments when seeking online medical advice and information. This study examines the role of public social media consultations for dermatologic conditions. A large portion of patients utilize social media for dermatologic consultations and many do not seek care from a dermatologist afterward. Future studies should trend this phenomenon, especially as the use of social media continues to expand.

Disestablishmentarianism: Or Why Political Correctness Is Racist, Anti-Gay, Anti-Transgender, Misogynist, Anti-Science, And Anti-You., W Clark Lambert, Shreya Patel, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

Disestablishmentarianism is known to most of us as one of the longest words in the English language (before some over-eager college students, even a few doctors, invented some mostly quite silly longer ones). A few may also know it as a rather dull, perhaps equally silly facet of British history. This is a shame, because this rather bizarre movement that began in eighteenth century England, has much to teach us about modern times.

Tailored For Real-World: A Whole Slide Image Classification System Validated On Uncurated Multi-Site Data Emulating The Prospective Pathology Workload., Julianna D. Ianni, Rajath E. Soans, Sivaramakrishnan Sankarapandian, Ramachandra Vikas Chamarthi, Devi Ayyagari, Thomas G. Olsen, Michael J. Bonham, Coleman C. Stavish, Kiran Motaparthi, Clay J. Cockerell, Theresa A. Feeser, Jason B. Lee

Department of Dermatology and Cutaneous Biology Faculty Papers

Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system's use of deep-learning-based confidence scoring as a criterion to consider the result as …

Covid-19, Serendipity, And Strange Interlude: Gloria In Absurdicum With An Apology To Ovid, Lawrence Charles Parish, W Clark Lambert

Department of Dermatology and Cutaneous Biology Faculty Papers

The absurd edicts initially issued by several governors, including those of Michigan and New York, prohibiting physicians from ordering hydroxychloroquine for patients suspected of or diagnosed with COV-19 are reprehensible. Their reasoning is beyond the pale.

Hydroxychloroquine was first approved by the FDA in 1955 and has a remarkable safety record in its use as a preventative for malaria and in the treatment of several immunologic and/or light induced diseases. Its use came about serendipitously, and its mechanism of action is unclear, but the fact remains that it seems to work.

Mirna- And Cytokine-Associated Extracellular Vesicles Mediate Squamous Cell Carcinomas, Joseph P. Flemming, Brianna L. Hill, Mohammed W. Haque, Jessica Raad, Claudine S. Bonder, Larry A. Harshyne, Ulrich Rodeck, Adam J. Luginbuhl, James K. Wall, Iii, Kenneth Y. Tsai, Peter J Wermuth, Andrew M. Overmiller, Mỹ G. Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.