Dermatology Commons^™

From Clinical Phenotype To Genotypic Modelling: Incidence And Prevalence Of Recessive Dystrophic Epidermolysis Bullosa (Rdeb), Shaundra Eichstadt, Jean Y. Tang, Daniel C. Solis, M. Peter Marinkovich, Nedra Whitehead, Fang Fang, Stephen W. Erickson, Mary E. Ritchey, Max Colao, Kaye Spratt, Amir Shaygan, Mark Ahn, Kavita Y. Sarin

Engineering and Technology Management Faculty Publications and Presentations

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited genetic disorder characterized by recurrent and chronic open wounds with significant morbidity, impaired quality of life, and early mortality. RDEB patients demonstrate reduction or structural alteration type VII collagen (C7) owing to mutations in the gene COL7A1, the main component of anchoring fibrils (AF) necessary to maintain epidermal-dermal cohesion. While over 700 alterations in COL7A1 have been reported to cause dystrophic epidermolysis bullosa (DEB), which may be inherited in an autosomal dominant (DDEB) or autosomal recessive pattern (RDEB), the incidence and prevalence of RDEB is not well defined. To date, the …

Immune-Mediated Colitis From Dual Checkpoint Inhibitors., Nishanth Thalambedu, Yasir Khan, Qian Zhang, Shristi Khanal, Ammar Ashfaq

Abington Jefferson Health Papers

Melanoma is a deadly disease with immunotherapy treatment options that emerged in the last few years and have changed the disease outcome. However, it is associated with immune-related toxic effects despite improving survival. We present the case of a 53-year-old woman who had two weeks of diarrhea after she was treated with dual immunotherapy agents for her advanced melanoma. The final workup revealed pancolitis, possibly due to immunotherapy adverse effects. Initial conservative treatment, unfortunately, did not lead to a clinical improvement until a steroid was introduced. We are reporting this case to alert our fellow physicians about the immune-mediated toxicities …

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.

Relating The Gut Metagenome And Metatranscriptome To Immunotherapy Responses In Melanoma Patients., Brandilyn A. Peters, Melissa Wilson, Una Moran, Anna Pavlick, Allison Izsak, Todd Wechter, Jeffrey S. Weber, Iman Osman, Jiyoung Ahn

Department of Medical Oncology Faculty Papers

BACKGROUND: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.

METHODS: In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.

RESULTS: Higher …

Ecthyma Gangrenosum In An Immunocompromised Patient Without Detectable Bacteremia, Jonathan Miles, Alex Mari, Matthew Crabtree, Vinod Nambudiri, Jilian Sansbury

Dermatology

Ecthyma gangrenosum (EG) is typically pathognomonic of Pseudomonas aeruginosa bacteremia among immunocompromised patients, particularly with underlying malignancy. Recently, other pathogens and clinical histories have been implicated, challenging the classic picture of patients with EG. The cutaneous findings in patients follow a pattern of lesion progression from indurated pustules and hemorrhagic vesicles evolving to necrotic ulcers with central black eschar and surrounding erythema. While lesions typically occur on the perineum or lower extremities, their presence has also been described elsewhere. Herein, we describe a case of an immunocompromised man with chronic lymphocytic leukemia and multiple myeloma actively undergoing chemotherapy presenting with …

Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl

Department of Cancer Biology Faculty Papers

The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X …

Quantifying Skin Photodamage With Spatial Frequency Domain Imaging: Statistical Results, Jeffrey B. Travers, Chien Poon, Trevor J. Bihl, Benjamin Rinehart, Christina E. Borchers, Daniel J. Rohrbach, Samia Borchers, Julian J. Trevino, Max Rubin, Heidi Donnelly, Karl Kellawan, Lydia Carpenter, Shalini Bahl, Craig A. Rohan, Elizabeth Muennich, Scott Guenthner, Holly Hahn, Ali Rkein, Marc Darst, Nico Mousdicas, Elizabeth E. Cates, Ulas Sunar

Dermatology Faculty Publications

We investigated the change in optical properties and vascular parameters to characterize skin tissue from mild photodamage to actinic keratosis (AK) with comparison to a published photodamage scale. Multi-wavelength spatial frequency domain imaging (SFDI) measurements were performed on the dorsal forearms of 55 adult subjects with various amounts of photodamage. Dermatologists rated the levels of photodamage based upon the photographs in blinded fashion to allow comparison with SFDI data. For characterization of statistical data, we used artificial neural networks. Our results indicate that optical and vascular parameters can be used to quantify photodamage and can discriminate between the stages as …

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 …

Guidance Of Sentinel Lymph Node Biopsy Decisions In Patients With T1-T2 Melanoma Using Gene Expression Profiling., John T. Vetto, Eddy C. Hsueh, Brian R. Gastman, Larry D. Dillon, Federico A. Monzon, Robert W. Cook, Jennifer Keller, Xin Huang, Andrew Fleming, Preston Hewgley, Pedram Gerami, Sancy Leachman, Jeffrey D. Wayne, Adam C. Berger, Martin D. Fleming

Department of Surgery Faculty Papers

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity?

PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively.

RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors.

CONCLUSION: The 31-gene expression profile test identifies patients …

Sunscreen Efficacy By Chemical Composition And Its Effect On Aquatic Life, Taylor Yates

Student Writing

Sunscreen provides protection against skin cancer by reducing UV exposure to the skin. Active ingredients come in two basic forms, chemical and mineral; ongoing research indicates that some active ingredients in sunscreen are harmful to marine life. This study is an analysis of chemical and mineral SPF 30 sunscreens to determine which provides the highest efficacy for skin protection while also providing the lowest toxicity to aquatic organisms. Sunscreen efficacy was tested by exposing photoreactive chemical paper applied with chemical and mineral sunscreens to the sun. Results of the photo effect paper trial showed a wide variation in the efficacy …

Pediatric Erythromelalgia Treated With Epidural Ropivacaine Infusion, Caroline E. Lee, Kelly Paulk, Kristen Garvie, Elizabeth Grieshaber, Jeffrey Carter, Brian Ball

School of Medicine Faculty Publications

No abstract provided.

Lichen Planus Pemphigoides In A Patient After Combination Ipilimumab And Nivolumab Therapy, Steven Oberlender Md, Phd, Marc T. Mitton Do

Department of Medicine

No abstract provided.

Sapho Syndrome, Diana A. Rivers Do, Megan A. Jones Do, Joshua M. Levin Md

Department of Medicine

No abstract provided.

Multiple Cellular Neurothekeomas, Megan A. Jones Do, Nektarios I. Lountzis Md, Joshua M. Levin Md

Department of Medicine

No abstract provided.

Reactive Angioendotheliomatosis, Naeha Gupta Do, Richard Mccalin Md, Nektarios I. Lountzis Md

Department of Medicine

No abstract provided.

Sterile Neutrophilic Folliculitis With Vasculopathy In A Young Male Patient With Infective Endocarditis, Carl Barrick Do, Naeha Gupta Do, Richard Mccalin Md, Stephen M. Purcell Do

Department of Medicine

No abstract provided.

Shiitake Mushroom-Induced Flagellate Dermatitis, Claire O. Dorfman Do, Nektarios I. Lountzis Md

Department of Medicine

No abstract provided.

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.

Efficacy Of Combination Of Immunotherapies In A Murine In A Murine Squamous Cell Carcinoma Model, E. Correia, C. Portocarrero, U. Rodeck

Phase 1

Introduction: Head and neck squamous cell carcinomas (HNSCCs) are a type of neoplasm found in the epithelium of the oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx. Recent evidence has demonstrated that 70-90% of HNSCC are associated with Human Papillomavirus (HPV), particularly strain 16 producing oncogenic proteins E6/E7. Currently, HNSCCs are treated with surgery, chemotherapy, and radiation, however immunotherapy with immune checkpoint (PD-1) blocking agents promises to improve outcomes in HNSCC.

Objective: This study examined the therapeutic effects of dual and triple combination immunotherapies in a mouse model of HPV-associated HNSCC.

Methods: Treatment modalities included a tumor vaccine (attenuated Listeria monocytogenes …

High Density Of Tumor-Associated Macrophage Staining Correlates With Poor Clinicopathologic Markers In Head And Neck Squamous Cell Carcinoma: A Meta-Analysis, Alexander Knops, Ba, Ayan Kumar, Bs, Brian Swendseid, Md, Ubaldo E. Martinez-Outshoorn, Md, Larry Harshyne, Phd, Nancy Philp, Phd, Ulrich Rodeck, Md, Phd, Christopher Snyder, Adam Luginbuhl, Md, David Cognetti, Md, Jennifer Johnson, Md, Joseph Curry, Md

Phase 1

Background: Head and neck squamous cell carcinoma (HNSCC) develops within a complex cellular microenvironment that promotes tumor growth, but also represents many potential therapeutic targets. Macrophage presence within that environment has been implicated in the growth, aggression, and persistence of HNSCC. Current literature reports variable degrees of association between tumor-associated macrophage (TAMs) density and clinicopathologic markers of disease.Inconsistent findings may result from grouping of TAM subtypes, which include both M1 (pro-inflammatory) and M2 (immunosuppressive). Our aim is to define the prognostic significance of the phenotypes of tumor-associated macrophages in HNSCC.

Methods: We conducted a meta-analysis of the existing publications investigating …

Total Body Skin Exam And Number Needed To Screen, Audra Hugo, Michael Bui, Alexander Sherban, Shayan Waseh, Elizabeth Jones, Md

Phase 1

Introduction/Background: Skin cancer screening could impact mortality and morbidity in US adults; however, the effectiveness of widespread screening remains unclear. Further research is necessary to determine what age groups, with what risk factors, might benefit from routine total body skin exams (TBSE) in the US.

Objective: This study sought to determine, on average, the number of patients, per decade, needed to screen via TBSE to identify one person with skin cancer.

Methods: A retrospective review of Jefferson Dermatology outpatient data in Epic was conducted. All patient charts from 1/1/2017 - 1/1/2018 were reviewed if they received a TBSE. The type …

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.