Dermatology Commons^™

Immunosequencing Applications In Cutaneous T-Cell Lymphoma, Jenna Mandel, Laura Gleason, Daniel Joffe, Safiyyah Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and …

Utility Of T-Cell Immunosequencing In Distinguishing Mycosis Fungoides Progression From Treatment Related Cutaneous Adverse Events, Safiyyah Bhatti, Daniel Joffe, Lauren Banner, Sahithi Talasila, Jenna Mandel, Jason Lee, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a …

Xtx101, A Tumor-Activated, Fc-Enhanced Anti-Ctla-4 Monoclonal Antibody, Demonstrates Tumor-Growth Inhibition And Tumor-Selective Pharmacodynamics In Mouse Models Of Cancer, Kurt A. Jenkins, Miso Park, Magali Pederzoli-Ribeil, Ugur Eskiocak, Parker Johnson, Wilson Guzman, Megan Mclaughlin, Deborah Moore-Lai, Caitlin O'Toole, Zhen Liu, Benjamin Nicholson, Veronica Flesch, Huawei Qiu, Tim Clackson, Ronan C. O'Hagan, Ulrich Rodeck, Margaret Karow, Jennifer O'Neil, John C. Williams

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb.

METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region …

A Desmosomal Cadherin Controls Multipotent Hair Follicle Stem Cell Quiescence And Orchestrates Regeneration Through Adhesion Signaling, William V. J. Hariton, Katja Schulze, Siavash Rahimi, Taravat Shojaeian, Laurence Feldmeyer, Roman Schwob, Andrew M. Overmiller, Beyza S. Sayar, Luca Borradori, Mỹ G. Mahoney, Arnaud Galichet, Eliane J. Müller

Department of Dermatology and Cutaneous Biology Faculty Papers

Stem cells (SCs) are critical to maintain tissue homeostasis. However, it is currently not known whether signaling through cell junctions protects quiescent epithelial SC reservoirs from depletion during disease-inflicted damage. Using the autoimmune model disease pemphigus vulgaris (PV), this study reveals an unprecedented role for a desmosomal cadherin in governing SC quiescence and regeneration through adhesion signaling in the multipotent mouse hair follicle compartment known as the bulge. Autoantibody-mediated, mechanical uncoupling of desmoglein (Dsg) 3 transadhesion activates quiescent bulge SC which lose their multipotency and stemness, become actively cycling, and finally delaminate from their epithelial niche. This then initiates a …

Advances In Melanoma: Epidemiology, Diagnosis, And Prognosis, Shayan Waseh, Jason B. Lee

Department of Dermatology and Cutaneous Biology Faculty Papers

Unraveling the multidimensional complexities of melanoma has required concerted efforts by dedicated community of researchers and clinicians battling against this deadly form of skin cancer. Remarkable advances have been made in the realm of epidemiology, classification, diagnosis, and therapy of melanoma. The treatment of advanced melanomas has entered the golden era as targeted personalized therapies have emerged that have significantly altered the mortality rate. A paradigm shift in the approach to melanoma classification, diagnosis, prognosis, and staging is underway, fueled by discoveries of genetic alterations in melanocytic neoplasms. A morphologic clinicopathologic classification of melanoma is expected to be replaced by …

The Overlap Of Skin And Blood T-Cell Clones In Early-Stage Mycosis Fungoides, Daniel Joffe, Safiyyah Bhatti, Lauren Banner, Romsin Zaya, Laura Gleason, Anjali Mishra, Ilan Kirsch, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Distinguishing Dystrophic Calcification From Calciphylaxis, Elizabeth Jones, Alexander Valiga, Miriam Solowey

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

Calcinosis cutis, a disorder in which calcium salts deposit in skin and subcutis, is categorized into five subtypes: dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification, and calciphylaxis.

Dystrophic calcification, the most common subtype, typically results from local tissue damage1,2 and is proposed to be caused by the release of phosphate binding proteins by necrotic cells in response to tissue damage, inflammation, or hypoxia.2 The condition often presents with nontender nodules of the skin or subcutis and normal serum calcium.

Calciphylaxis is believed to be caused by impaired inhibition of calcification in the microvasculature.3 …

An Unusual Presentation Of Pigmented Purpuric Lichenoid Dermatitis, Christine De Antonis, Jordan T. Hyde, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

Pigmented purpuric lichenoid dermatitis (PPLD) is a rare subtype of pigmented purpuric dermatosis, which classically presents with a mixture of lichenoid papules and patches on the bilateral lower extremities. Herein, we describe an unusual case of a 47-year-old man with PPLD who presented with 1-3mm discrete papules without the presence of larger patches. The diagnosis of PPLD should be considered for patients presenting with bilateral symmetric discrete papules on the legs.

Neutrophilic Panniculitis Associated With Myelodysplastic Syndrome/Myeloproliferative Neoplasm: A Case Report And Literature Review, Alexa J. Cohen, Laura K. Gleason, Safiyyah A. Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: Neutrophilic panniculitis (NP) is a rare subtype of neutrophilic dermatosis, a group of neutrophil-rich inflammatory skin disorders that can present in association with myeloid neoplasms. NP is defined by the presence of a neutrophilic infiltrate in the fat lobules of the subcutis in the absence of either infection or vasculitis. We herein describe a 65-year-old woman with a recent diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome (MDS/MPN) who abruptly developed painful, pruritic nodules consistent with NP.

CASE PRESENTATION: A 65-year-old woman with MDS/MPN presented for evaluation of painful and pruritic nodules on her upper and lower extremities. A biopsy …

Phenotype And Genotype Heterogeneity Of Pla2g6-Associated Neurodegeneration In A Cohort Of Pediatric And Adult Patients, Ali Zare Dehnavi, Maryam Bemanalizadeh, Seyyed Mohammad Kahani, Mahmoud Reza Ashrafi, Mohammad Rohani, Mehran Beiraghi Toosi, Morteza Heidari, Sareh Hosseinpour, Behnam Amini, Shaghayegh Zokaei, Zahra Rezaei, Hajar Aryan, Man Amanat, Hassan Vahidnezhad, Pouria Mohammadi, Masoud Garshasbi, Ali Reza Tavasoli

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6.

METHODS: An extensive review of the patients' data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In …

Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy: A Case Report, Laura Gleason, Volkan Tekmen, Alexa Cohen, Safiyyah Bhatti, Burcu Beksac, Jisun Cha, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction:

Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management.

We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis.

Case presentation:

We performed a mutational analysis of dermal mast cells after enrichment by laser capture in …

Maintenance Of Chronicity Signatures In Fibroblasts Isolated From Recessive Dystrophic Epidermolysis Bullosa Chronic Wound Dressings Under Culture Conditions, Cristian De Gregorio, Evelyng Catalán, Gabriel Garrido, Pilar Morandé, Jimena Castillo Bennett, Catalina Muñoz, Glenda Cofré, Ya-Lin Huang, Bárbara Cuadra, Paola Murgas, Margarita Calvo, Fernando Altermatt, María Joao Yubero, Francis Palisson, Andrew P. South, Marcelo Ezquer, Ignacia Fuentes

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients.

RESULTS: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, …

Trametinib-Induced Epidermal Thinning Accelerates A Mouse Model Of Junctional Epidermolysis Bullosa, Grace Tartaglia, Pyung Hung Park, Michael H. Alexander, Alexander Nyström, Joel Rosenbloom, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Junctional epidermolysis bullosa (JEB) patients experience skin and epithelial fragility due to a pathological deficiency in genes associated with epidermal adhesion. Disease severity ranges from post-natal lethality to localized skin involvement with persistent blistering followed by granulation tissue formation and atrophic scarring. We evaluated the potential of utilizing Trametinib, an MEK inhibitor previously shown to target fibrosis, with and without the documented EB-anti-fibrotic Losartan for reducing disease severity in a mouse model of JEB; Lamc2jeb mice. We found that Trametinib treatment accelerated disease onset and decreased epidermal thickness, which was in large part ameliorated by Losartan treatment. Interestingly, a range …

Incidence Of Cutaneous Melanoma And Merkel Cell Carcinoma In Patients With Primary Cutaneous B-Cell Lymphomas: A Population Study Of The Seer Registry, Lauren Banner, Daniel Joffe, Emily Lee, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction: The increased incidence of cutaneous melanoma (CM) and Merkel cell carcinoma (MCC) in patients with hematologic malignancies (HM) is well established. While the risk of CM has been assessed in some subtypes of HM including cutaneous T-cell lymphoma, the incidence in patients with primary cutaneous B-cell lymphoma (PCBCL) has not been interrogated.

Methods: Here we evaluated the standardized incidence ratio (SIR) of CM and MCC in 5,179 PCBCL patients compared to approximately 1.5 billion individuals in the general population using the Surveillance, Epidemiology and End Results (SEER) database. Among patients with PCBCL, we identified subgroups that were at increased …

Alopecia In Patients With Collagen Vi-Related Myopathies: A Novel/Unrecognized Scalp Phenotype, Michela Starace, Francesca Pampaloni, Francesca Bruni, Federico Quadrelli, Stephano Cedirian, Carlotta Baraldi, Cosimo Misciali, Alberto Di Martino, Patrizia Sabatelli, Luciano Merlini, Bianca Maria Piraccini

Department of Dermatology and Cutaneous Biology Faculty Papers

Collagen VI-related myopathies are characterized by severe muscle involvement and skin involvement (keratosis pilaris and impaired healing with the development of abnormal scars, especially keloids). Scalp involvement and hair loss have not been reported among cutaneous changes associated with collagen VI mutations. The aim of this study is to describe the clinical, trichoscopic, and histological findings of the scalp changes in patients affected by COL VI mutations and to estimate their prevalence. Patients with Ullrich congenital muscular dystrophy were enrolled and underwent clinical and trichoscopic examinations and a scalp biopsy for histopathology. Five patients were enrolled, and all complained of …

Whole Transcriptome-Based Skin Virome Profiling In Typical Epidermodysplasia Verruciformis Reveals Α-, Β-, And Γ-Hpv Infections, Amir Hossein Saeidian, Leila Youssefian, Mahtab Naji, Hamidreza Mahmoudi, Samantha M Barnada, Charles Huang, Karim Naghipoor, Amir Hozhabrpour, Jason S Park, Flavia Manzo Margiotta, Fatemeh Vahidnezhad, Zahra Saffarian, Kambiz Kamyab-Hesari, Mohammad Tolouei, Niloofar Faraji, Seyyede Zeinab Azimi, Ghazal Namdari, Parvin Mansouri, Jean-Laurent Casanova, Vivien Béziat, Emmanuelle Jouanguy, Jouni Uitto, Hassan Vahidnezhad

Department of Dermatology and Cutaneous Biology Faculty Papers

HPVs are DNA viruses include approximately 450 types that are classified into 5 genera (α-, β-, γ-, μ-, and ν-HPV). The γ- and β-HPVs are present in low copy numbers in healthy individuals; however, in patients with an inborn error of immunity, certain species of β-HPVs can cause epidermodysplasia verruciformis (EV), manifesting as recalcitrant cutaneous warts and skin cancer. EV presents as either typical or atypical. Manifestations of typical EV are limited to the skin and are caused by abnormal keratinocyte-intrinsic immunity to β-HPVs due to pathogenic sequence variants in TMC6, TMC8, or CIB1. We applied a transcriptome-based computational pipeline, …

A Rare Presentation Of Secondary Multiple Miliary Osteoma Cutis, Ana Duarte-Summers, Anna Bistline, Viral Patel, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Demographic Data Associated With Digital Inequity Reported In Patient-To-Provider Teledermatology Studies In The United States From 2011 To 2021: Scoping Review, John Miller, Patrick Ioffreda, Shannon Nugent, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Patient-to-provider teledermatology relies on a patient’s access to technology to ensure a successful visit. However, access to broadband internet and technology varies across populations in the United States—leading to the digital divide. While teledermatology has been recognized as a model to improve access, little is known about how often demographic data associated with digital inequity are captured in studies. Objective: Given the expansion of teledermatology over the past decade, we sought to determine how often demographic data associated with digital inequity are reported in patient-to-provider teledermatology studies. Methods: A scoping literature review search was conducted using the search term …

Multiple Fibrofolliculomas Within A Fibrous Cephalic Plaque In A Patient With Tuberous Sclerosis, Justin Raman, Annie Jin, Jennifer J. Parker, Conor M. Vickers, Daniela M. Proca, Sylvia Hsu, Jason B. Lee

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Atezolizumab-Induced Psoriasiform Drug Eruption Successfully Treated With Ixekizumab: A Case Report And Literature Review, Laura Gleason, E Hunter, Alexa J. Cohen, Jayson Suriano, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Immune-related cutaneous adverse events (ircAE) are commonly seen with immune checkpoint inhibitors such as atezolizumab. Atezolizumab-induced psoriasis has been previously reported as an ircAE, especially in patients with pre-existing psoriasis. The severity of the reaction influences treatment of the cutaneous eruption. Biologics should be considered as a treatment option for severe refractory psoriasiform eruptions even in patients with complex medical conditions like chronic infections and malignancy. This is the first reported case of successful treatment of atezolizumab-induced psoriasiform eruption with ixekizumab, a neutralizing IL17A monoclonal antibody, to the best of our knowledge. Herein, we present a 63-year-old man with a …

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 …