Dermatology Commons^™

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 …

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 …

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 .

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 …

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.

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.

Molluscum Contagiosum Infection With Features Of Primary Cutaneous Anaplastic Large Cell Lymphoma., Doaa Shalabi, John Ringe, Jason B. Lee, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

CD30+ T cell pseudolymphomas (CD30+ PSL) are a group of benign inflammatory cutaneous disorders that can develop in settings of viral infections or drug reactions. Owing to their histological similarities to malignant lymphomas, these benign infiltrates are occasionally misdiagnosed as malignant, causing significant concerns for patients and physicians. Herein, we report a patient with CD30+ PSL associated with molluscum contagiosum whose initial biopsy revealed atypical large CD30-expressing cells, leading to a misdiagnosis of primary cutaneous anaplastic large cell lymphoma and referral to our cutaneous lymphoma clinic. We report this case to demonstrate that reactive CD30+ infiltrate associated with molluscum contagiosum …

Hypotrichosis With Juvenile Macular Dystrophy: Combination Of Whole-Genome Sequencing And Genome-Wide Homozygosity Mapping Identifies A Large Deletion In Cdh3 Initially Undetected By Whole-Exome Sequencing-A Lesson From Next-Generation Sequencing., Amir Hossein Saeidian, Hassan Vahidnezhad, Leila Youssefian, Soheila Sotudeh, Meisam Sargazi, Sirous Zeinali, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Hypotrichosis with juvenile macular dystrophy (HJMD) is an autosomal recessive disorder characterized by abnormal growth of scalp hair and juvenile macular degeneration leading to blindness. We have explored the genetic basis of HJMD in a large consanguineous family with 12 affected patients, 1-76 years of age, with characteristic phenotypes.

METHODS: We first applied genome-wide homozygosity mapping to 10 affected individuals for linkage analysis to identify the genomic region of the defective gene. All affected individuals shared a 7.2 Mb region of homozygosity on chromosome 16q21-22.3, which harbored 298 genes, including CDH3, previously associated with HJMD. However, whole-exome sequencing (WES) …

Why Medical (And Dermatologic) Practice Has Become So Convoluted: The Complexity/Convolutional/Obfuscatory Kleptocracies., W. Clark Lambert, Jennifer L. Parish, Lawrence Charles Parish, Shreya Patel, Loka Thangamathesvaran, Amer Ali Almosshen

Department of Dermatology and Cutaneous Biology Faculty Papers

Consider dermatology (or medical) practice from the aspect of those who manage, and seek to glean a profit from, medical management corporations, including but not limited to third party payers. Although much of the complexity burden thrust upon doctors’ offices is borne by the offices and doctors, there is also much that is borne by the companies, and the entire process appears to make no sense whatsoever. How can the business professionals who run these outfits make such blunders? Let us approach this question by examining another industry: fast food franchising.

Eosinophilic Dermatosis Of Hematologic Malignancy Responding To Dupilumab In A Patient With Chronic Lymphocytic Leukemia., Annie Jin, Bobak T. Pousti, Kevin T. Savage, Nicholas K. Mollanazar, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

Leukemia cutis (LC) and eosinophilic dermatosis of hematologic malignancy (EDHM) are rare cutaneous manifestations of hematologic malignancies. Various therapeutic options have been reported, with largely underwhelming responses. We present a patient with chronic lymphocytic leukemia (CLL) with concomitant LC and EDHM who was treated with dupilumab.

Pioneers In Dermatology And Venereology: An Interview With Prof. Lawrence C. Parish., Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Assessment Of The Risk And Characterization Of Non-Melanoma Skin Cancer In Kindler Syndrome: Study Of A Series Of 91 Patients., Sara Guerrero-Aspizua, Claudio J. Conti, Maria Jose Escamez, Daniele Castiglia, Giovanna Zambruno, Leila Youssefian, Hassan Vahidnezhad, Luis Requena, Peter Itin, Gianluca Tadini, Ivelina Yordanova, Ludovic Martin, Jouni Uitto, Cristina Has, Marcela Del Rio

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of …

Randomized Phase 3 Evaluation Of Trifarotene 50 Μg/G Cream Treatment Of Moderate Facial And Truncal Acne., Jerry Tan, Diane Thiboutot, Georg Popp, Melinda Gooderham, Charles Lynde, James Del Rosso, Jonathan Weiss, Ulrike Blume-Peytavi, Jolanta Weglovska, Sandra Johnson, Lawrence Parish, Dagmara Witkowska, Nestor Sanchez Colon, Alessandra Alió Saenz, Faiz Ahmad, Michael Graeber, Linda Stein Gold

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied.

OBJECTIVES: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne.

METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator's Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from …

Speaking Good (And Safe) Dermatologic English, Lawrence Charles Parish, W. Clark Lambert

Department of Dermatology and Cutaneous Biology Faculty Papers

Periodically, our feathers become ruffled about the use or misuse of English in dermatology. 1, 2 We have railed against the derogatory term for crusted scabies3, suggested a contrived term to lessen the burden connoted by decubitus ulcers4, and discouraged renaming atopic dermatitis to atopiform dermatitis. 5 Imagine what the dermatologic lexicographers, Morris Leider (1908-1987) 6and Morris Rosenbaum, might be saying were they here today. 7

Using an appropriate word or words to describe an anatomic part or a portion of the skin is just good medical practice. We do not believe a lightning bolt will descend as portrayed in …

The Practice Of Dermatology Ain't What It Used To Be: The Preauthorization Catastrophe., Lawrence Charles Parish, Jennifer L. Parish, W. Clark Lambert, Carmela Ciferni

Department of Dermatology and Cutaneous Biology Faculty Papers

Many of us remember when a dermatology practice was cash only, and $5 cash was considered appropriate for a specialist. The general practitioner received $2 for an office visit and $4 for a home call. If you recall those days, “dearie you are much older than I.” 1

Not so long ago, the practitioner was confronted with obtaining a referral from the Health Maintenance Organization (HMO) in order to see the patient. Some plans permitted only four such referrals for specialists, annually, so the patient, who might have had a visit or two for gastritis and a similar number of …

An Atypical Presentation Of A Rare Disease, Elizabeth Schoenberg, Kathleen P. Mcguinn, Deirdre Connolly, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

A 76-year-old white woman presented for evaluation of asymptomatic skin lesions on her right shin, right buttock, and left arm. All lesions initially underwent slow growth and plateaued and then remained stable in size. A complete review of systems revealed normal results. She had 3 well-demarcated erythematous round plaques ranging from 1.5 to 3 cm, all with a central depression, yellow hue, and prominent telangiectasias (Figs 1 and 2). An excisional biopsy was performed. Histologically, there were palisading granulomas within the papillary and reticular dermis, predominantly composed of a histiocytic cell population with multiple large giant cells (S100^-; …

Genetic Susceptibility To Alopecia., Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

The Doctor's Office Is The Best Setting For Most Cutaneous Procedures., Hannah J. Anderson, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

Although most dermatologic procedures are done in an office setting, some providers are performing them instead in ambulatory surgery centers (ASCs). This relocation of care comes with significantly higher expenses for patients and insurers. Compounding the issue of increased costs is the paucity of evidence demonstrating better outcomes associated with the use of ASCs. The most common cutaneous procedures have low complication rates when performed in an office setting and regular use of ASCs for these procedures is not justified.

Koebner Phenomenon: Pemphigus Vulgaris Following Mohs Micrographic Surgery., Georgette Hattier, Sarah Beggs, Joya Sahu, Joshua Trufant, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

Koebnerization of pemphigus vulgaris (PV) is an infrequently reported reaction. We present a 65-year-old man with Koebnerized pemphigus vulgaris after Mohs microscopic surgery for a basal cell carcinoma. We present this case to heighten awareness of the phenomenon in the dermatological community.