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Iu Tong Mak*, Jay H. Kramer*, Joanna J. Chmielinska*, William B. Weglicki

Department of Biochemistry and Molecular Medicine, The George Washington University, School of Medicine and Health Sciences, Ross Hall, Rm 228, 2300 Eye Street, NW. Washington DC 20037; USA

Erlotinib, an EGFR-TKI, has been used as an effective anti-tumorigenesis agent against several cancers including lung, colon, head and neck. However, it has been reported to cause significant and severe cutaneous side effects. Our previous studies implicated substance P, a neuropeptide, as a significant mediator of skin toxicity. Our present study was designed to determine if the topical application of aprepitant, a specific substance P receptor blocker, would be protective against these skin side effects. Erlotinib in the diet was administered to the rats for 12 weeks. Facial rash and hair loss began to occur after 6 weeks and were most severe at 12 weeks when animals were sacrificed. Topical treatment of aprepitant to the facial area 3 times a week showed dose-dependent and progressive inhibition up to 70% of the induced dermatitis/hair loss. These results were comparable to the effects produced by oral doses in our prior study. At sacrifice, we also found significant elevations of neutrophil superoxide, that were inhibited by topical aprepitant, along with elevated plasma 8-isoprostane levels, that were also suppressed. Facial skin samples revealed increased leukocyte (CD11b positive) infiltration in the erlotinib-treated rats, which were substantially reduced by the topical aprepitant. In conclusion, the indicators of reactive oxidative species (ROS) suggest that neurogenic inflammation played a critical role in causing EGFR-TKI-induced toxicity; it also confirmed that the systemic inhibition of ROS production due to blockade of substance P action was significantly protective against the dermatitis/hair loss pathology.

Roy S. Rogers¹, Suha Zawawi¹, Thais Pincelli²*, Markéta Janovská², Alison Bruce¹

¹Department of Dermatology– Mayo Clinic Florida –Jacksonville, FL, USA

²Department of Oral Medicine, Institute of Dental Medicine, First Faculty of Medicine and General University Hospital, Charles University - Prague, Czech Republic

Roy S. Rogers, III, MD¹; Suha Zawawi MBBS^1*; Thais Pincelli MD¹; Markéta Janovská MDDr.²; Alison Bruce MD¹

¹Department of Dermatology – Mayo Clinic Florida – Jacksonville, FL, USA

²Department of Oral Medicine, Institute of Dental Medicine, First Faculty of Medicine and General University Hospital, Charles University - Prague, Czech Republic.

Jacobus van der Velden^*, Ming Tjiong

Amsterdam UMC, location University of Amsterdam, Gynecologic Oncology, Meibergdreef 9, Amsterdam, the Netherlands

Guidelines recommend adjuvant treatment when positive lymph nodes are found after surgical treatment for squamous cell cancer of the vulva except for cases with a single occult intranodal metastasis. Recent studies questioned these recommendations and showed benefit of adjuvant radiotherapy for all patients with positive nodes irrespective of number of nodes. However, these studies did not take into account important nodal characteristics, such as clinical node status, extranodal spread or size of the metastasis. When these variables are taken into account, adjuvant radiotherapy does not seem to result in a better survival for patients with a single occult intranodal metastasis. Whether the addition of chemotherapy to the radiotherapy for patients with more than one positive node or extracapsular spread results in a better survival remains uncertain. Only a few studies have been published on this subject and come to the conclusion that adding chemotherapy results in a better survival. The conclusion is that adjuvant radiotherapy improves survival of patients with positive groin nodes, with the exception of patients with a single intranodal metastasis. The beneficial effect of chemo radiotherapy for subgroups of patients with positive nodes seems likely, although more data are needed before a definite conclusion can be made.

Rachel E. Kieser^1,2,5#, Shaheerah Khan^1,2,5#, Nada Bejar^1,2,5#, Daniel L. Kiss^1,2,3,4,5*

¹Center for RNA Therapeutics,

²Department of Cardiovascular Sciences,

³Weill Cornell Medical College, New York, NY, USA

⁴Houston Methodist Cancer Center, Houston, TX, USA

⁵Houston Methodist Academic Institute, Houston Methodist Research Institute, 6670 Bertner Ave, R10‑113, Houston 77030, TX, USA

^#These authors have contributed equally

Despite being under development for decades, RNA therapeutics have only recently emerged as viable drug platforms. The COVID-19 mRNA vaccines have demonstrated the promise and power of the platform technology. In response, novel RNA drugs are entering clinical trials at an accelerating rate. As the skin is the largest and most accessible organ, it has always been a preferred target for drug discovery. This holds true for RNA therapies as well, and multiple candidate RNA-based drugs are currently in development for an array of skin conditions. In this mini review, we catalog the RNA therapies currently in clinical trials for different dermatological diseases. We summarize the main types of RNA-related drugs and use examples of drugs currently in development to illustrate their key mechanism of action.

Amanda Costa; Fernando Costa^*

Department of Dental Clinics, Oral Pathology and Oral Surgery, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

Stephanie V Shimon^1,2, BS; Loren E Hernandez, BS²; Keyvan Nouri, MD, MBA²

¹Nova Southeastern University, Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL.

²Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL.

Yasmine Oprea¹, Patricia Cerri-Droz², Urmi Khanna¹

¹ Albert Einstein College of Medicine/Montefiore Medical Center

² Renaissance School of Medicine at Stony Brook University

The first human infection with monkeypox virus was reported in 1970, and infections have subsequently been recorded in endemic areas such as Central and West Africa or linked to international travel to these regions. However, the emergence of the 2022 monkeypox outbreak has involved multiple non-endemic countries and continents without links to travel to endemic areas. The first cases in the current outbreak were reported in May of 2022. The primary mode of transmission is atypical and is thought to occur through direct contact with infected skin lesions. The rapid increase in case numbers prompted the World Health Organization to declare this disease outbreak as a public health emergency of international concern. Robust efforts are being made by global public health authorities to develop effective antiviral treatment options and vaccination strategies to reduce the spread of this disease. The objective of this manuscript is to provide a comprehensive review of the 2022 mpox outbreak with respect to its unique epidemiology, clinical features, complications, and management options.

Ishita Aggarwal BA; Carolina Puyana MD, MSPH^*; Neha Chandan MD, MPH; Roger Haber, MD

University of Illinois at Chicago, Department of Dermatology, 1801 W. Taylor St., Chicago, IL 60612-7307

Introduction: Androgenetic alopecia (AGA) is the most common type of hair loss worldwide and is estimated to affect about 80 million people in the United States. Recent trends suggest that incidence and severity of the disease are increasing across all genders and races. Randomized controlled trials (RCTs) involving diverse patient populations are necessary to individualize treatment.

Objective: Evaluate enrollment and subgroup analysis of people falling in racial/ethnic minority groups in phase II and III RCTs for AGA published in the United States within the past 10 years.

Methods: We examined completed published phase II and III randomized, double-blind, placebo-controlled trials investigating AGA. Race/ethnicity data was extracted for each RCT using US Census Bureau guidelines.

Results: 20 total RCTs with a total of 1855 participants were included in the analysis. 8 (40%) of RCTs included race/ethnicity data. Among these, 3 (15%) studies included only race and 5 (25%) included both. The majority of study patients were white (n= 862/1063, 81.1%) followed by African American (n=127/1063, 11.9%) and Asian (n=33/1063, 3.1%). Six (0.56%) patients identified as American Indian/Alaska Natives, 5 (0.47%) as Hawaiian/Pacific Islander, and 16 (1.5%) as another race or race was unknown. Ethnicity was reported in 5 (25%) of trials, totaling 317 participants; 60 (18.9%) patients identified as Hispanic.

Conclusions: Non-Caucasian patients remain underrepresented in RCTs despite AGA being a highly prevalent condition, reducing the generalizability of trial outcomes to the general population. Future RCTs should update definitions of race/ethnicity and include more diversity among AGA patients.

Alison Tran, M.D., M.A., Ed.M.^1* and Lio Yu, M.D., DABR²

¹Menter Dermatology Research Institute, Baylor University Medical Center; Heights Dermatology, Dallas, TX

²Director of Radiation Oncology, Laserderm Dermatology, Smithtown, NY

Simon J. Madorsky, MD^*, Orr A. Meltzer, BS, Alexander Miller, MD

Skin Cancer and Reconstructive Surgery Center (SCARS Center) at 180 Newport Center Drive, Suite 158, Newport Beach, CA 92660

Superficial radiotherapy (SRT) treatment for non-melanoma skin cancer has been reported to yield variable cure rates. When patients are highly selected, adequate margins of treatment are chosen, and hypofractionation is avoided, cure rates of SRT can approach that of Mohs surgery.

The objective of this study is to evaluate long term results of our center’s SRT selection criteria and define proper decision-making parameters of optimal candidates for treatment, and to review the literature. A retrospective chart analysis was done of all SRT cases from 2012-2018. Location, size, type and depth of the treated tumors were defined. Treatment energy, fractionation, and radiation field size were documented. Recurrences and complications were analyzed. Of 131 treated lesions treated, head and neck lesions (105, 80%) were the most common location, primarily on the lower nose (60, 46%). Of 122 lesions analyzed for recurrence, 2 (1.6%) recurred, with a mean follow-up time of 5 years. Acute ulcerations in 29 (28%) head and neck lesions, 5 (63%) trunk lesions, and 9 (50%) leg lesions occurred. Delayed ulcerations occurred in 5 (28%) leg lesions. In conclusion, when patients are highly selected, long-term SRT cure rates up to 98% can be achieved.

Denise Ann Tsang^1*, Chee Leong Cheng², Laura Hui¹

¹Singapore General Hospital, Department of Dermatology

²Singapore General Hospital, Department of Pathology

Stan J. Monstrey

Ghent University Hospital, Ghent, Belgium

Samantha D. Verling^*, Noreen Mohsin^#, Loren E Hernandez, Teresa Ju, Keyvan Nouri

Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA

Daniela Frasca^1,2*, Natasa Strbo^1,2

¹Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL USA

²Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL USA

Obesity represents a serious health problem as it is rapidly increasing worldwide. Obesity is associated with reduced health span and life span, decreased responses to infections and vaccination and increased frequency of inflammatory conditions. In this review, we summarize published data showing that obesity increases the risk of different types of infections, with a special focus on skin infections. Obesity also induces skin changes and conditions (inflammation-based and hypertrophic) which are often associated with fungi or bacteria overgrowth. The association of obesity with the skin microbiome has been established in both mice and humans. Balance of commensal microbes controls skin homeostasis and the host immune response, while changes in normal physiologic skin microbiome composition and pathologic bacteria contribute to skin diseases. We also summarize the major steps in wound healing and how obesity affects each of them. The role that immune cells have in this process is also described. Although the studies summarized in this review clearly demonstrate the deleterious effects of obesity on wound healing, additional studies are needed to better characterize the cellular and molecular mechanisms involved and identify specific targets of intervention.

David Solano¹, Kush R. Patel^1#, Adelaida B. Perez^1#, Lindsey Seldin^1-4*

¹Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA

²Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA

³Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

⁴Atlanta Veterans Affairs Medical Center, Decatur, GA, USA

^#Authors contributed equally

Alison M Mackay

Division of Musculoskeletal and Dermatological sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

Photodynamic therapy (aPDT) has become an important component in the treatment of human infection. This report highlights the scientific literature and clinical guidelines on aPDT in the context of dermatology and considers the treatment of skin infection in all settings now, and in the future. Antibiotic resistance, infection control strategies and technologies able to eradicate microbes without building up new resistance are considered, and their mechanisms of action are described. Published work and National Institute for Clinical Excellence (NICE) Technology appraisals (TA) and research recommendations within Clinical Guidelines were used to identify future applications for PDT. Nanotheranostics can include PDT and were found to be highly relevant, and so treatment combinations and their novel applications will be subject to TA and Randomised Clinical Trials (RCTs). The resistance of some microbes to antibiotics can be reversed through use of supplementary drugs, and so they are likely to remain a mainstay of treatment for skin infection.

Laura Andrews, BS^1*; Chelsea Shope, BA¹; Alan Snyder, MD MSCR², Manuel Valdebran MD³

¹College of Medicine, Medical University of South Carolina

²Department of Dermatology & Dermatologic Surgery, Medical University of South Carolina

³Department of Dermatology & Dermatologic Surgery, Division of Pediatric Dermatology Medical University of South Carolina

Deborah H Yates^1,2,3*, Susan E Miles^4,5

¹Department of Respiratory Medicine, St Vincent’s Public Hospital

²St Vincents Clinical School, UNSW

³Holdsworth House Medical Practice, Sydney, NSW

⁴Department of General Medicine at Calvary Mater Newcastle

⁵University of Newcastle, Newcastle, NSW, Australia 2308

Dermatological manifestations of connective tissue diseases (CTDs) are common and frequently precede other symptoms. Thus, dermatologists may be the first clinicians to diagnose these disorders. Silica exposure is an acknowledged cause of several CTDs, but this is under-appreciated by clinicians, who may also be unaware of the wide range of jobs in which silica exposure can occur. The CTDs associated with silica exposure include systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis and overlap syndromes. Silica-related systemic sclerosis (Si-SSc) is associated with a specific antibody profile and more severe disease. Silicosis has re-emerged worldwide recently due to several new workplace exposures, including a new type of silicosis (artificial stone (AS) silicosis), which is associated with a particularly high rate of auto-antibody formation. Dangerous work practices are still occurring. This article summarises recent literature on the topic of the resurgence of silicosis and silica-induced CTDs and reminds dermatologists of the importance of taking a thorough occupational history in all patients. Early intervention in CTDs and reduction in dust exposure can reduce risk and improve prognosis. Treatment options are rapidly improving.

Chelsea Shope, BA^1*, Laura Andrews, BS¹, Alan Snyder, MD MSCR², Manuel Valdebran MD³

¹College of Medicine, Medical University of South Carolina

²Department of Dermatology & Dermatologic Surgery, Medical University of South Carolina

³Department of Dermatology & Dermatologic Surgery, Division of Pediatric Dermatology Medical University of South Carolina

Jose Manuel Carrascosa¹, Francisco José Rebollo^2*

¹Hospital Universitario Germans Trias I Pujol, Badalona, Spain

²Pfizer SLU, Madrid, Spain

Katieli da Silva Souza Campanholi^1*, Ranulfo Combuca da Silva Junior ¹, Gustavo Braga ^1,3, Flávia Amanda Pedroso de Morais ^1,2, Rodolfo Bento Balbinot², Wilker Caetano ¹

¹Chemistry Department, State University of Maringa, Maringa, Parana, Brazil.

²Department of basic health sciences, State University of Maringa, Maringa, Parana, Brazil.

³Federal Institute of Education, Science and Technology of Parana, Telemaco Borba, Parana, Brazil.

The therapeutic benefits of copaiba oil-resin have encouraged its use in developing dermatological emulsions. Here, the anti-inflammatory, healing, antimicrobial, analgesic, and permeation-promoting properties of this medicinal oil are shown by reviewing articles from 2005 to 2021. Their properties encourage research to develop an herbal medicinal effective in treating skin diseases and cutaneous leishmaniasis.

Loren E Hernandez, BS^1*; Fabio Stefano Frech, BS¹; Noreen Mohsin, BS¹; Isabella Dreyfuss, BS²; Keyvan Nouri, MD, MBA¹

¹Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA

²Nova Southeastern University, Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, Florida, USA

Nodular melanoma is the second most common subtype of melanoma. Unlike other subtypes, nodular melanoma is characterized by early vertical growth rather than the typical initial radial growth of most melanomas. As a result, nodular melanoma presents clinically in a more aggressive phenotype. Given its more aggressive nature and intrinsic ability to mimic benign lesions, a modified acronym has been developed to allow clinicians to better evaluate, diagnose and treat nodular melanoma in earlier stages. Surgical excision with wide margins is the gold standard of nodular melanoma therapy; however, an emphasis in early detection, diagnosis, staging, and treatment needs to be emphasized among clinicians due to its dismal prognosis in later stages, as compared to other subtypes. A better understanding of the molecular pathophysiology that allows nodular melanoma to act aggressively very early in diagnosis is necessary for the development of therapeutics that may effectively target lesions in more advanced stages.

Toni O. Mortimer, Rachel Morris, Abigail Schekall, Kai Barlow, Kim L. O’Neill* 

Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah 84602

Cancer is one of the leading causes of death worldwide. In the U.S. alone, almost 2 million people will be diagnosed with cancer each year and just over a quarter of those diagnosed will pass away from the disease. Skin cancers are the most common forms of cancer. Early detection of cancer and cancer biomarkers enables clearer understanding of cancer progression in a patient and more effective treatments in response to the disease. Clinically relevant biomarkers are not only tools for early diagnosis of cancer but may also prove useful as immune targets for various immunotherapies, such as monoclonal antibody-based therapy and chimeric antigen receptor (CAR) T-cell therapy. This review provides a brief overview of the rescue pathway enzyme thymidine kinase 1 (TK1) and its history and biology, as well as discusses its role as a biomarker and potential immune target.

Margaret A. Kaszycki^1*, Jonathan Leventhal² 

¹Frank H. Netter MD School of Medicine

²Yale School of Medicine

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, and their use in combination with radiation therapy (RT) has become increasingly utilized to optimize positive outcomes. The cutaneous adverse reactions from RT as well as ICIs are both well documented; however, in combination these cutaneous toxicities can be exacerbated. ICIs and RT may work synergistically to create an enhanced immune response against the tumor cells. This synergistic effect has been reported to occur both locally at the site of RT, as well as systemically via an abscopal effect. Fortunately, this combination of treatment does not increase the incidence of cutaneous reactions, although several cases have reported enhanced skin toxicity at the site of RT. RT is thought to create an ‘immunocompromised skin district’ or localized immune dysregulation in irradiated skin. This review summarizes previously published case reports and discusses the cutaneous adverse reactions from ICI and RT combination therapy. Properly identifying ICI and RT induced skin reactions depends on several factors including patient history, sequence of therapies, timing of reaction, and histological findings. Skin reactions from combination therapy can range in severity and include ICI-induced radiation recall dermatitis, as well as uncommon presentations of Stevens-Johnson syndrome, lichen planus, and bullous pemphigoid which are localized to or enhanced within areas of prior radiation exposure. It is important for oncologists and dermatologists alike to be aware of the spectrum of reactions associated with ICI and RT.