Dermatology Commons^™

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Faculty, Staff and Student Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …

Longitudinal Follow-Up Of Netherton’S Syndrome, K. Petit, Christina E. Borchers, Julian Trevino

Dermatology Faculty Publications

Netherton’s Syndrome (NS) is a rare, autosomal recessivegenodermatosis caused by mutations in SPINK5 which encodes LETKI, aserine protease inhibitor.2,4 Consequently, unopposed kallikrein activityresults in an impaired skin barrier and desquamation.2 A triad of atopy,ichthyosis linearis circumflexa, and trichorrhexis invaginata (“bamboohair”) is characteristic of this disease.1 Associated findings includehypereosinophilia and elevated IgE. Histologically, a nonspecificpsoriasiform hyperplasia and dermal lymphocytic infiltrate may beobserved.1,6 Clinically, NS is frequently misdiagnosed as atopic dermatitis(AD) and proves difficult to treat.2 Dupilumab, an IL-4/IL-13 inhibitor withFDA approval for the treatment of atopic dermatitis and prurigo nodularis,may be a promising therapy for patients with NS.3 We present alongitudinal …

Pretibial Myxedema: An Unusual Presentation, Dāsha Giger, Christina E. Borchers, Samia Borchers

Dermatology Faculty Publications

Pretibial myxedema presents with indurated nodules or plaques that can be erythematous or vary in color from purple-brown to yellow. It is noted that a peau d’orange appearanceis a characteristic finding. These lesions are typically located on the anterolateral aspect of the lower legs. Non-pitting edema of the shins that evolves into elephantiasis is anotherpotential presentation seen in pretibial myxedema. It is often associated with hyperthyroidism, particularly Graves disease and is more commonly seen in women than men.Typically, it presents during the third or fourth decade of life. Differential diagnoses include but are not limited to stasis dermatitis, hypertrophic lichen …

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.

Exaggerated Cutaneous Responses In Patients With Hematologic Malignancy, Trang Nguyen, Christina E. Borchers, Julian Trevino

Dermatology Faculty Publications

Eosinophilic dermatosis of hematologic malignancy (EDHM) is a cutaneous manifestation rarely seen in Chronic lymphocytic leukemia (CLL) and chronic myelomonocytic leukemia (CMML). EDHM, first described in 19651, is identified by treatment-resistant pruritic papules, eosinophil-rich dermal lymphohistiocytic infiltrate, exclusion of other causes of tissue eosinophilia, and preexisting diagnosis of hematologic malignancy2. Similarly, arthropod hypersensitivity reactions, or insect bite hypersensitivity, also cause significant discomfort and morbidity in individuals with hematologic malignancies. Proposed treatments exist, but assessing exaggerated skin reactions as prognostic markers requires further study. We outline two clinical cases illustrating the potential spectrum of EDHM encounters.

Garetosmab In Fibrodysplasia Ossificans Progressiva: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Maja Di Rocco, Eduardo Forleo-Neto, Robert J Pignolo, Richard Keen, Philippe Orcel, Thomas Funck-Brentano, Christian Roux, Sami Kolta, Annalisa Madeo, Judith S Bubbear, Jacek Tabarkiewicz, Małgorzata Szczepanek, Javier Bachiller-Corral, Angela M Cheung, Kathryn M Dahir, Esmée Botman, Pieter G Raijmakers, Mona Al Mukaddam, Lianne Tile, Cynthia Portal-Celhay, Neena Sarkar, Peijie Hou, Bret J Musser, Anita Boyapati, Kusha Mohammadi, Scott J Mellis, Andrew J Rankin, Aris N Economides, Dinko Gonzalez Trotter, Gary A Herman, Sarah J O'Meara, Richard Delgizzi, David M Weinreich, George D Yancopoulos, E Marelise W Eekhoff, Frederick S Kaplan

Faculty, Staff and Student Publications

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths …

Distinct Camp Signaling Microdomains Differentially Regulate Melanosomal Ph And Pigmentation, Maftuna Yusupova, Dalee Zhou, Jaewon You, Jeydi Gonzalez-Guzman, Megha B. Ghanta, Hong Pu, Zalfa Abdel-Malek, Qiuying Chen, Steven S. Gross, John August D'Orazio, Shosuke Ito, Kazumasa Wakamatsu, Melissa L. Harris, Jonathan H. Zippin

Markey Cancer Center Faculty Publications

cAMP signaling is a well-established regulator of melanin synthesis. Two distinct cAMP signaling pathways—the transmembrane adenylyl cyclase pathway, activated primarily by the MC1R, and the soluble adenylyl cyclase (sAC) pathway—affect melanin synthesis. The sAC pathway affects melanin synthesis by regulating melanosomal pH, and the MC1R pathway affects melanin synthesis by regulating gene expression and post-translational modifications. However, whether MC1R genotype affects melanosomal pH is poorly understood. We now report that loss of function MC1R does not affect melanosomal pH. Thus, sAC signaling appears to be the only cAMP signaling pathway that regulates melanosomal pH. We also addressed whether MC1R genotype …

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 …

Gut Microbiome In Patients With Early-Stage And Late-Stage Melanoma, Russell G Witt, Samuel H Cass, Tiffaney Tran, Ashish Damania, Emelie E Nelson, Elizabeth Sirmans, Elizabeth M Burton, Manoj Chelvanambi, Sarah Johnson, Hussein A Tawbi, Jeffrey E Gershenwald, Michael A Davies, Christine Spencer, Aditya Mishra, Matthew C Wong, Nadim J Ajami, Christine B Peterson, Carrie R Daniel, Jennifer A Wargo, Jennifer L Mcquade, Kelly C Nelson

Faculty, Staff and Student Publications

IMPORTANCE: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.

OBJECTIVE: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.

DESIGN, SETTING, AND PARTICIPANTS: This single-site case-control study took place at …

Cutaneous Dermal Metastasis Of Inflammatory Breast Carcinoma Mimicking Granuloma Annulare, Vikram Shaw, Jay Patel, Hanna Siatecka, Omid Jalali

Faculty, Staff and Students Publications

Breast cancer can present as a wide range of cutaneous lesions at the time of diagnosis or months to years after a known diagnosis of breast cancer. Cutaneous sequela of breast cancer, including metastasis, have a diverse range of clinical appearances. Here, we describe the case of a 59-year-old female with stage IV metastatic inflammatory breast carcinoma presenting with a chronic worsening rash on her anterior chest wall. Biopsy results demonstrated metastatic carcinoma cells within the dermal lymphatics, consistent with primary breast cancer. To our knowledge, based on a thorough review of the literature, no previous case reports detailing cutaneous …

The Importance Of A Broad Differential Diagnosis: Hepatitis C Virus Associated Cryoglobulinemic Vasculitis, Shadi Jafari-Esfahani, Christine E. Loftis, Juan Naranjo, Emilia Dulgheru

Research Symposium

Introduction: Mixed cryoglobulinemia syndrome (MCS) is a systemic inflammatory syndrome affecting small-medium sized vessels due to the presence of type II or III cryoglobulins in the serum. MSC can manifest as systemic vasculitis with symptoms varying from weakness, arthralgia, palpable purpura, peripheral neuropathy, and renal involvement. The most common cause of MCS includes lymphoproliferative disorders, autoimmune diseases and viral infections, with hepatitis C virus (HCV) being the most common etiology.

Case Presentation: A 60-year-old lady was referred to our office for evaluation of rheumatoid arthritis. She reported history of bilateral thumb pain, bilateral knee pain associated with episodes of swelling, …

Patchy Alopecia In A Young Adult With A Generalized Rash, Oscar Rodrigo Zamudio Herrera, Nevin Varghese

Research Symposium

Background: Syphilis is a sexually transmitted infection that has been increasing in the United States. The prevalence of syphilis rose by 6.8% during 2019-to 2020. Secondary syphilis typically presents with a generalized maculopapular rash on palms and soles, however, can also have subtle dermatological findings such as alopecia. Syphilitic alopecia is an atypical manifestation of secondary syphilis, seen in 2.9 to 7% of the cases.

Case presentation: An 18-year-old Hispanic male presented to the clinic after noticing patchy loss of hair on the scalp for 2 weeks and one week of generalized non pruritic rash. His past medical history was …

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 …

Atopic Dermatitis And The Risk Of Myocardial Infarction And All-Cause Mortality: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Minah Cho, Kyung Do Han, Sang Hyun Cho, Ji Hyun Lee

Faculty, Staff and Student Publications

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various comorbidities. However, inconsistent results on the risk of myocardial infarction (MI) and mortality have been reported in patients with AD. This study was aimed to evaluate the risk of MI and all-cause mortality in patients with AD.

METHODS: This nationwide population-based retrospective cohort study enrolled 56,205 adults ≥ 20 years of age with AD and 3,825,609 controls without AD from the Korean National Health Service (NHIS) database from 2009 to 2016.

RESULTS: The risk of MI (adjusted hazard ratio [aHR], 1.111, 95% confidence interval [CI], 1.050-1.176) was …

Maximizing Wound Coverage In Full-Thickness Skin Defects: A Randomized-Controlled Trial Of Autologous Skin Cell Suspension And Widely Meshed Autograft Versus Standard Autografting, Sharon Henry, Steven Mapula, Mark Grevious, Kevin N. Foster, Herbert Phelan, Jeffrey Shupp, Rodney Chan, David Harrington, Neil Mashruwala, David A. Brown, Haaris Mir, George Singer, Alfredo Cordova, Lisa Rae, Theresa Chin, Lourdes Castanon, Derek Bell, William Hughes, Joseph A. Molnar

Department of Surgery Faculty Papers

BACKGROUND: Traumatic insults, infection, and surgical procedures can leave skin defects that are not amenable to primary closure. Split-thickness skin grafting (STSG) is frequently used to achieve closure of these wounds. Although effective, STSG can be associated with donor site morbidity, compounding the burden of illness in patients undergoing soft tissue reconstruction procedures. With an expansion ratio of 1:80, autologous skin cell suspension (ASCS) has been demonstrated to significantly decrease donor skin requirements compared with traditional STSG in burn injuries. We hypothesized that the clinical performance of ASCS would be similar for soft tissue reconstruction of nonburn wounds.

METHODS: A …

Atmospheric Pressure Plasma Treatment Of Skin: Penetration Into Hair Follicles, Kseniia Konina, Theresa A. Freeman, Mark J. Kushner

Department of Orthopaedic Surgery Faculty Papers

Sterilization of skin prior to surgery is challenged by the reservoir of bacteria that resides in hair follicles. Atmospheric pressure plasma jets (APPJs) have been proposed as a method to treat and deactivate these bacteria as atmospheric plasmas are able to penetrate into structures and crevices with dimensions similar to those found in hair follicles. In this paper, we discuss results from a computational investigation of an APPJ sustained in helium flowing into ambient air, and incident onto a layered dielectric similar to human skin in which there are idealized hair follicles. We found that, depending on the location of …

Mavs Is A Double-Edged Sword, Christina Huang, Jack L. Arbiser

Student Papers, Posters & Projects

No abstract provided.

The Safety And Efficacy Of Spironolactone Versus Oral Antibiotics For Moderate-Severe Acne In Post-Adolescent Females, Bhav Patel

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

• Acne is a common skin condition when the pores are clogged by particles like dead skin or oil, affecting approximately 50 million individuals in the U.S.¹
• Over a third of females experience moderate-severe forms that persist into adulthood and that number seems to be on the rise³
• Persistent moderate-severe acne often requires systemic medications and oral antibiotics are the most frequently prescribed therapy²
• Dermatologists prescribe more antibiotics per provider than any other specialty, and often for longer durations than recommended²
• The inappropriate use of oral antibiotics is contributing to bacterial resistance and disruption of the …

The Impact Of Intralesional 5-Fluorouracil In The Treatment Of Keloid Scars, Madeline Derham

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

- The American Academy of Dermatology (AAD) defines a keloid scar as a type of raised scar extending past the initial area of injury¹

- Approximately 10% of the general population affected - significant risk factors include +family history, darker skin tones, mechanism of injury (burn, surgical)³

- Symptom presentation: pain, pruritus, burning, increased sensitivity³

- Varying existing treatment methods with high resistance and recurrence rates leading to no agreed upon standard approach⁵

• Most widely adopted method currently : intralesional (ILS) steroid ^injection5

Leser-Trélat Sign As A Marker For Underlying Pancreatic Cancer, Kalpit Modi, Richard Chen, Layla Abubshait

Einstein Health Papers

Case Presentation: Early diagnosis and rapid treatment of cancer is essential for good clinical outcomes for patients. In this case, an 85-year-old man presented with failure to thrive and was noted to have rapid-onset, multiple seborrheic keratoses (Leser-Trélat sign) on his chest and back. He was ultimately diagnosed with pancreatic cancer using computed tomography.

Discussion: Leser-Trélat sign is a rare cutaneous marker for underlying malignancy. Identification of this sign can help guide diagnostic imaging and lab work to identify an occult internal malignancy, resulting in more rapid diagnosis, earlier treatment, and potentially better clinical outcomes.