Skin and Connective Tissue Diseases Commons^™

Tilsotolimod Exploits The Tlr9 Pathway To Promote Antigen Presentation And Type 1 Ifn Signaling In Solid Tumors: A Multicenter International Phase I/Ii Trial (Illuminate-101), Hani Babiker, Erkut Borazanci, Vivek Subbiah, Sanjiv Agarwala, Alain Algazi, Jacob Schachter, Michael Lotem, Corinne Maurice-Dror, Daniel Hendler, Shah Rahimian, Hans Minderman, Cara Haymaker, Daruka Mahadevan, Chantale Bernatchez, Ravi Murthy, Rolf Hultsch, Nadia Kaplan, Gregory Woodhead, Charles Hennemeyer, Srinivas Chunduru, Peter M Anderson, Adi Diab, Igor Puzanov

Faculty, Staff and Student Publications

PURPOSE: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors.

PATIENTS AND METHODS: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the …

Association Of Apremilast With Vascular Inflammation And Cardiometabolic Function In Patients With Psoriasis: The Vip-A Phase 4, Open-Label, Nonrandomized Clinical Trial, Joel M Gelfand, Daniel B Shin, April W Armstrong, Stephen K Tyring, Andrew Blauvelt, Scott Gottlieb, Benjamin N Lockshin, Robert E Kalb, Robert Fitzsimmons, Justin Rodante, Philip Parel, Grigory A Manyak, Laurel Mendelsohn, Megan H Noe, Maryte Papadopoulos, Maha N Syed, Thomas J Werner, Joy Wan, Martin P Playford, Abass Alavi, Nehal N Mehta

Faculty, Staff and Student Publications

IMPORTANCE: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss.

OBJECTIVE: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition.

DESIGN, SETTING, AND PARTICIPANTS: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites …

Assessment Of Disease Severity And Quality Of Life In Patients With Atopic Dermatitis From South Korea, Sang Wook Son, Ji Hyun Lee, Jiyoung Ahn, Sung Eun Chang, Eung Ho Choi, Tae Young Han, Yong Hyun Jang, Hye One Kim, Moon-Bum Kim, You Chan Kim, Hyun Chang Ko, Joo Yeon Ko, Sang Eun Lee, Yang Won Lee, Bark-Lynn Lew, Chan Ho Na, Chang Ook Park, Chun Wook Park, Kui Young Park, Kun Park, Young Lip Park, Joo Young Roh, Young-Joon Seo, Min Kyung Shin, Sujin Lee, Sang Hyun Cho

Faculty, Staff and Student Publications

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited.

OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea.

METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. …

Allergic Sensitization Pattern In The Korean Dermatologic Patients, Yujin Han, Yu Ri Woo, Hei Sung Kim, Jeong Deuk Lee, Sookhee Choi, Jeesuk Yu, Sang Hyun Cho

Faculty, Staff and Student Publications

BACKGROUND: Avoiding causative allergens is important for controlling the clinical course of allergic diseases. Allergen sensitization is influenced by many factors including the environment and lifestyle. The socioeconomic development, climate, and lifestyle changes have increased the prevalence of allergic diseases worldwide. However, there is little information about changes in the trend of the common allergens over time.

OBJECTIVE: This study was aimed at identifying the trends of the common allergens in Korea over a 10-year period based on the results of the multiple allergosorbent test chemiluminescent assay (MAST-CLA).

METHODS: We retrospectively reviewed the medical records of 5,760 patients aged ≥18 …

Tumor-Intrinsic Sirpa Promotes Sensitivity To Checkpoint Inhibition Immunotherapy In Melanoma, Zhicheng Zhou, Mei-Ju May Chen, Yikai Luo, Kamalika Mojumdar, Xin Peng, Hu Chen, Shweta V Kumar, Rehan Akbani, Yiling Lu, Han Liang

Faculty, Staff and Student Publications

Checkpoint inhibition immunotherapy has revolutionized cancer treatment, but many patients show resistance. Here we perform integrative transcriptomic and proteomic analyses on emerging immuno-oncology targets across multiple clinical cohorts of melanoma under anti-PD-1 treatment, on both bulk and single-cell levels. We reveal a surprising role of tumor-intrinsic SIRPA in enhancing antitumor immunity, in contrast to its well-established role as a major inhibitory immune modulator in macrophages. The loss of SIRPA expression is a marker of melanoma dedifferentiation, a key phenotype linked to immunotherapy efficacy. Inhibition of SIRPA in melanoma cells abrogates tumor killing by activated CD8+ T cells in a co-culture …

A Patient Perspective On Information Provision During The Care Path Of Lentigo Maligna, Louis P. Ter Meer, Marleen De Mul, Jan Hazelzet, Clemens Van Eijk

Patient Experience Journal

Patients sometimes experience complex diagnostic and treatment procedures. During these processes, they need to rely on the information provided by the care providers. In particular, if they would like to play an active role in the shared decision-making process, it is important that this information is accessible, complete and understandable. A patient with Lentigo Maligna on the nose has been followed during the process of diagnosis, shared decision-making and treatment. Using the autoethnographical methodology, it was evaluated which sources of information available to the patient contributed to a better understanding, a more active role in the treatment process and a …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Isotretinoin, Vitamin A Supplements, And Unintended Pregnancies In Post Roe V Wade America, Praneet S Paidisetty, Leonard K Wang, Dina H Zamil, Shangyi Fu, Zeena Y Nawas

Faculty, Staff and Students Publications

Isotretinoin is a potent vitamin A derivative that is used to treat acne. However, despite its utility in dermatologic care, it is also highly teratogenic and can cause severe life-threatening fetal abnormalities in the first trimester of pregnancy. As a result, existing regulations are stringent in order to prevent accidental pregnancies in women taking isotretinoin. In the unlikely case of an unintended pregnancy, while taking isotretinoin, a woman could terminate her pregnancy with an abortion. However, with the recent overturning of Roe v. Wade, we explore the consequences of this landmark United States Supreme Court ruling with special attention …

Pleomorphic Dermal Sarcoma: A Clinical And Histopathologic Emulator Of Atypical Fibroxanthoma, But Different Biologic Behavior, Michael Carletti, Daniel A. Nguyen, Peter Malouf, Zachary Ingersoll, Gregory A. Hosler, Stephen E. Weis

HCA Healthcare Journal of Medicine

Pleomorphic dermal sarcoma (PDS) can clinically and histopathologically mimic atypical fibroxanthoma (AFX). However, it has a more aggressive clinical course with a higher recurrence rate and metastatic potential. This case presentation aims to report a rapidly-growing, exophytic, 4 cm tumor following a non-diagnostic shave biopsy 2 months prior and to highlight distinctive features between PDS and AFX needed to make the correct diagnosis. Like AFX, PDS occurs on the sun-damaged skin of the elderly, usually on the head and neck. Also, like AFX, PDS histopathologically consists of sheets or fascicles of epithelioid and/or spindle-shaped cells, often with multinucleation, pleomorphism, and …

Innovative Therapeutic Approach To Chemical Burns Produced By Vesicants; An Experimental Study, Cristina Anca Secara, Otilia Liudmila Cinteza, Diana Popescu, Claudia Valentina Popa, Camelia Andreea Hirjeu, Oana Cristina Voinea, Luiza Georgia Serbanescu, Andreea Marilena Pauna, Mihail Tudosie

Journal of Mind and Medical Sciences

Vesicants are compounds that cause severe toxic effects on various tissues. Such chemical action causes tissue necrosis, with clinical expression of skin lesions with a burning character and characteristic blisters. Clinical toxic effects of cutaneous vesicles are correlated with the absorbed dose and exposure time. The goals of the study are to evaluate in vitro the skin toxicity produced by the vesicant chemical compound 2-chloroethyl-ethyl sulfide (CEES), to develop a complex antidote formula, and to optimize the therapeutic efficacy by inclusion in controlled release systems. The experimental protocol aims at the in vitro evaluation of the cytotoxicity of the vesicant …

Lineage-Coupled Clonal Capture Identifies Clonal Evolution Mechanisms And Vulnerabilities Of Brafv600e Inhibition Resistance In Melanoma, Ze-Yan Zhang, Yingwen Ding, Ravesanker Ezhilarasan, Tenzin Lhakhang, Qianghu Wang, Jie Yang, Aram S Modrek, Hua Zhang, Aristotelis Tsirigos, Andrew Futreal, Giulio F Draetta, Roel G W Verhaak, Erik P Sulman

Faculty, Staff and Student Publications

Targeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed "CAPTURE", a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRAF

Clinical And Pathological Characteristics And Outcomes Among Patients With Subcutaneous Panniculitis-Like T-Cell Lymphoma And Related Adipotropic Lymphoproliferative Disorders, Joan Guitart, Aaron R Mangold, Maria Estela Martinez-Escala, Christina J Walker, Nneka I Comfere, Mellissa Pulitzer, Kerri E Rieger, Carlos A Torres-Cabala, Laura B Pincus, Erica S Kumar, Erica Bo Kyung Wang, Katherine E Park, Maria L Espinosa, Madeleine Duvic, Youn H Kim, Steven Horwitz

Faculty, Staff and Student Publications

IMPORTANCE: There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date.

OBJECTIVE: To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort …

Effect Of Roflumilast Cream Vs Vehicle Cream On Chronic Plaque Psoriasis: The Dermis-1 And Dermis-2 Randomized Clinical Trials, Mark G Lebwohl, Leon H Kircik, Angela Y Moore, Linda Stein Gold, Zoe D Draelos, Melinda J Gooderham, Kim A Papp, Jerry Bagel, Neal Bhatia, James Q Del Rosso, Laura K Ferris, Lawrence J Green, Adelaide A Hebert, Terry Jones, Steven E Kempers, David M Pariser, Paul S Yamauchi, Matthew Zirwas, Lorne Albrecht, Alim R Devani, Mark Lomaga, Amy Feng, Scott Snyder, Patrick Burnett, Robert C Higham, David R Berk

Faculty, Staff and Student Publications

IMPORTANCE: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis.

OBJECTIVE: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis.

DESIGN, SETTING, AND PARTICIPANTS: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between …

Social Media Impact Of Articles Published By Dermatology Residents During Medical School: Cross-Sectional Study, Austin Huang, Harrison Zhu, Kelvin Zhou, R Parker Kirby, Nina Dasari, Gianmarco A Calderara, Kathryn Cordova, Ryan Sorensen, Anshul Bhatnagar, Soo Jung Kim

Faculty, Staff and Students Publications

BACKGROUND: The Altmetric score (AS) is a novel measure of publication impact that is calculated by the number of mentions across various social media websites. This method may have advantages over traditional bibliometrics in the context of research by medical students.

OBJECTIVE: This study aimed to determine whether dermatology matriculants who graduated from higher-ranked medical schools published more articles with greater impact (ie, a higher AS) than those from lower-ranked institutions.

METHODS: A PubMed search for articles published by dermatology residents who started medical school in 2020 was conducted. Demographic information and Altmetric data were collected, and medical schools were …

Coexistence Of Cutaneous Squamous Cell Carcinoma And Basal Cell Carcinoma In A Renal Transplant Recipient: A Case Report., Diana Voloshyna, Tanveer Ahamad Shaik, Sunita Shrestha, Ajmat Ansari, Faraz Saleem, Muhammad Abu Zar Ghaffari

Faculty and Staff Scholarship

In solid organ transplant patients, non-melanoma skin cancer remains a leading cause of mortality. The most common skin malignancies in solid organ transplant patients are squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In organ transplant patients, SCC is 100 times more prevalent, and BCC is 10 times more prevalent than in the general population. Many risk factors for developing such malignancies are equivalent to those in the general population. However, in the transplant population, such cancers occur at an earlier age, act more aggressively, and often appear at multiple locations. Thus, assiduousness on the patient's part and healthcare …

Efficacy And Safety Of Topical Hypericin Photodynamic Therapy For Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The Flash Phase 3 Randomized Clinical Trial, Ellen J Kim, Aaron R Mangold, Jennifer A Desimone, Henry K Wong, Lucia Seminario-Vidal, Joan Guitart, James Appel, Larisa Geskin, Edward Lain, Neil J Korman, Nathalie Zeitouni, Neda Nikbakht, Kenneth Dawes, Oleg Akilov, Joi Carter, Michi Shinohara, Timothy M Kuzel, Warren Piette, Neal Bhatia, Amy Musiek, David Pariser, Youn H Kim, Dirk Elston, Erin Boh, Madeleine Duvic, Auris Huen, Theresa Pacheco, Jeffrey P Zwerner, Seung Tae Lee, Michael Girardi, Christiane Querfeld, Kimberly Bohjanen, Elise Olsen, Gary S Wood, Adam Rumage, Oreola Donini, Andrea Haulenbeek, Christopher J Schaber, Richard Straube, Christopher Pullion, Alain H Rook, Brian Poligone

Faculty, Staff and Student Publications

IMPORTANCE: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).

OBJECTIVES: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.

DESIGN, SETTINGS, AND PARTICIPANTS: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 …

The Effect Of Body Mass Index On Therapeutic Response To Bacterial Vaginosis In Pregnancy, Kevin P Lee, Misha V Koshelev, D3code Team, Omar Pacha

Faculty, Staff and Student Publications

No abstract provided.

A Case Of Perifollicular Macular Amyloidosis, Imran T Baig, Jamael L Thomas, Misha V Koshelev

Faculty, Staff and Student Publications

Macular amyloidosis is a common type of primary localized cutaneous amyloidosis. We present a case report of a 74-year-old patient with no significant past medical history who was evaluated for dark macules and pruritus for over a year. On exam, follicular-based brown macules on the upper and lower back, bilateral shoulders, and bilateral dorsal upper arms were noted. The morphology and distribution of follicular-based macules was unusual, so the differential included follicular lichen planus, follicular eczema, and macular amyloidosis. Punch biopsy showed deposits of eosinophilic fibrillary material along with pigmentary incontinence in the papillary dermis, consistent with macular amyloidosis. Additionally, …

Acyclovir-Resistant Anogenital Herpes Simplex Virus In An Hiv Patient With Pseudoepitheliomatous Hyperplasia Resembling Squamous Cell Carcinoma, Jean Elizze M. Charles, Stephen E. Weis, Gregory A. Hosler

HCA Healthcare Journal of Medicine

Background

Herpes simplex virus (HSV) is a common infection. However, it may present atypically when patients are immunocompromised, such as with slowly expanding, long-lasting ulcerative or hypertrophic lesions. The histopathologic finding of pseudoepitheliomatous hyperplasia (PEH) can occur in a variety of situations where there is chronic inflammation and can be seen in patients with chronic HSV. Atypical presentations of HSV, particularly hypertrophic lesions with histopathologic findings of PEH, can be misinterpreted as squamous cell carcinoma, create difficulty in diagnosis and hinder appropriate treatment.

Case Description

We report a case of a 59-year-old female with a past medical history of human …

Relieving Immune Suppression In The Melanoma Tumor Microenvironment, Gretel Torres Santiesteban

Dartmouth College Ph.D Dissertations

The high immunogenicity of melanoma tumors makes these malignancies an attractive target for immunotherapeutic treatment, as evidenced by the success of ipilimumab and nivolumab. However, most immunotherapeutic approaches have had limited success, partly due to the suppression of innate and adaptive immune responses by tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). TAM redirection may relieve immunosuppression in the TME, directly inhibiting melanoma growth and potentially enhancing the efficacy of additional targeted and immuno-therapies.

We have shown that synthetic oleanane triterpenoid CDDO-Me (or C-Me) enhances immune activation in the melanoma TME by reprogramming TAMs from immunosuppressive to immunostimulatory. CDDO-Me is …