Shedding new light on actinic keratoses and squamous cell carcinoma in situ.

ABSTRACT: Cutaneous squamous cell carcinoma can arise from various premalignant lesions such as actinic keratosis, Bowen disease, and premalignant genital squamous cell lesions. Identification and treatment can prevent malignant transformation and death. This article describes the causes, epidemiology, and characteristics of suspicious premalignant squamous cell lesions so that clinicians can identify these lesions and refer patients for specialist treatment as appropriate.

Extracellular vesicles: a comprehensive review of their roles as biomarkers and potential therapeutics in psoriasis and psoriatic arthritis.

Psoriasis is a chronic immune-mediated condition that affects the skin and joints, with current treatments still unable to offer a cure and long-term use of treatments posing health risks. Understanding the pathogenesis of the disease has helped identify new targets that have allowed for the expansion of the therapeutic arsenal. Extracellular vesicles (EVs) have recently emerged as pathophysiological mediators of psoriasis, and there have been increasing reports of EVs as potential biomarkers and therapeutics. Given their innate role as natural vehicles for cell-to-cell communication, EVs have vast potential in their ability to determine disease status based on EV-specific cargo as well as act as therapeutics because of their anti-inflammatory properties and potential for enhancement. In this review we summarize the role of EVs in the pathogenesis of psoriasis and discuss EVs as both diagnostic and therapeutic agents.

Therapeutic Use of Trace Elements in Dermatology.

Trace elements (microminerals) play a role in many physiological functions, including hormone production and cellular growth. However, their importance in diagnosing and treating dermatologic disease has not been well examined. In this review, we discuss the functions, sources, and recommended requirements of each micromineral. In addition, we analyze the systemic and dermatological manifestations associated with micromineral imbalances. The pathogenesis of genodermatoses, such as Wilson disease, Menkes disease, acrodermatitis enteropathica, and allergic dermatitis, are also discussed. Included are studies examining the potential therapeutic role of zinc, selenium, and copper in inflammatory diseases, skin cancer, and photoaging.

A review of Merkel cell carcinoma.

ABSTRACT: Merkel cell carcinoma (MCC) is a rare and aggressive type of metastatic, nonmelanoma skin cancer derived from Merkel cells in the epidermis. MCC can be induced by sun exposure or via Merkel cell polyomavirus (MCV) gene expression. MCV is found in most patients with MCC and is associated with a lower recurrence rate of MCC. MCC has a wide range of clinical presentations that make diagnosis challenging. Histologic examination is performed using unique markers to differentiate it from other diagnoses. This article reviews the pathogenesis, clinical presentation, histopathology, differential diagnosis, and treatment of MCC.

Nonsurgical treatment options for basal cell carcinoma.

ABSTRACT: Basal cell carcinoma (BCC) is the most common form of nonmelanoma skin cancer. Surgery, including Mohs micrographic surgery, is considered the gold standard for the management of BCC, yet some patients may be unable to undergo surgery. This article describes effective nonsurgical options for treating superficial BCCs as well as some nodular and infiltrative BCCs.

Systematic review of Mohs micrographic surgery in children: Identifying challenges and practical considerations for successful application.

BACKGROUND: Few data exist to guide the application of Mohs micrographic surgery (MMS) in the pediatric population. OBJECTIVE: We sought to summarize the clinical characteristics of children undergoing MMS, identify challenges that limit the use of MMS in this population, and examine how these challenges can be overcome. METHODS: A systematic review of PubMed and EMBASE, from inception of databases to November 2, 2019, identified all cases of pediatric skin lesions treated with MMS. RESULTS: A total of 111 patients were included. The median patient age was 11 years (range 6 weeks to 17 years). The most commonly treated tumor was dermatofibrosarcoma protuberans (n = 62), followed by basal cell carcinoma (n = 30). The most common location was the head and neck (n = 34), followed by the trunk (n = 28) and the extremities (n = 23). The most commonly cited challenges in the application of MMS in children included patient cooperation, concerns for the safety of prolonged general anesthesia, availability of a MMS service in the pediatric setting, and access to a histopathology laboratory experienced in MMS sectioning. LIMITATIONS: Many articles did not report specific patient characteristics. CONCLUSION: Multiple obstacles limit the application of MMS in pediatric patients. This review describes practical methods to circumvent these obstacles to facilitate the appropriate use of MMS in children.

An updated review of the sebaceous gland and its role in health and diseases Part 1: Embryology, evolution, structure, and function of sebaceous glands.

Sebaceous glands are sebum-secreting components of pilosebaceous units. The embryological development of the sebaceous gland follows that of the hair follicle and epidermal tissue, beginning between weeks 13 and 16 of fetal development. New sebaceous glands do not normally develop following birth, but their size increases with age. Sebocytes express a multitude of hormone receptors and are heavily regulated to secrete sebum by androgens. There is a large increase of sebum excretion at birth and again at puberty, until approximately age 17. In adulthood, sebum production remains stable and declines to zero in postmenopausal women and in men aged 60-70. Besides the production and release of sebum, sebaceous glands function to lubricate the skin and hair, provide thermoregulation, and exhibit antimicrobial activity. Research has shown sebaceous glands to possess the cellular capability to transcribe genes necessary for androgen metabolism. Dysfunction of the sebaceous gland can be seen primarily in steatocystoma simplex and multiplex, sebaceous gland hyperplasia, sebaceoma, sebaceous adenoma, sebaceous carcinoma, nevus sebaceus, and folliculosebaceous cystic hamartoma. Sebaceous glands are secondarily involved in acne vulgaris, seborrheic dermatitis, and androgenic alopecia.

An updated review of the sebaceous gland and its role in health and diseases Part 2: Pathophysiological clinical disorders of sebaceous glands.

Sebaceous glands are sebum-secreting components of pilosebaceous units. In the second of this two-part series, we review the pathologies in which sebaceous glands are primarily and secondarily implicated. They are primarily involved in steatocystoma simplex and multiplex, sebaceous gland hyperplasia, sebaceoma, sebaceous adenoma, sebaceous carcinoma, nevus sebaceus, and folliculosebaceous cystic hamartoma. Sebaceous glands are secondarily involved in acne vulgaris, seborrheic dermatitis, and androgenic alopecia. Steatocystoma multiplex is a benign congenital anomaly presenting as yellow cysts primarily on the upper body. Sebaceous gland hyperplasia is characterized by yellow, telangiectatic papules with a central dell, and it can be treated with topical retinoids or surgical excision. Sebaceoma clinically presents on the head and neck region as a skin-colored nodule and can be distinguished by immunohistochemistry. Stains used in the diagnosis of sebaceous adenoma and carcinoma include epithelial membrane antigen and adipophilin immunoperoxidase. Surgical excision is the preferred treatment for sebaceoma, sebaceous adenoma, and sebaceous carcinoma. Excision is not always indicated for nevus sebaceus. Folliculosebaceous cystic hamartoma is a relatively rare condition exhibiting both epithelial and mesenchymal components. Patients with acne vulgaris commonly present with papules of closed and open comedones displaying hypercornification. Seborrheic dermatitis presents as sharply demarcated yellow or red patches or plaques; antifungal agents, corticosteroids, and combination antifungal/anti-inflammatory therapies are common treatment modalities. As a result of hair follicle miniaturization, females with androgenic alopecia present with diffuse hair thinning, while men tend to present with balding and hairline recession.

Beyond Mohs surgery and excisions: A focused review of treatment options for subtypes of basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. It originates from undifferentiated cells in the basal cell layer of the epidermis or from the outer root sheath of the hair follicle. The most important factor in development of BCC is ultraviolet radiation. Surgery is considered the gold standard of treatment for BCC. However, nonsurgical options are available for individuals who are unsuitable for surgery. The purpose of this review is to summarize the efficacy and indications of alternative, nonsurgical treatments that can be used in the management of BCC. An extensive literature review was performed for the nonsurgical options for the treatment of BCC. Resources searched included PubMed and Google Scholars, limited to the years 1995 to 2020. Key words searched included BCC, destructive methods, photodynamic therapy (PDT), radiotherapy, topical medication, laser, hedgehog pathway inhibitors (HPIs). The most relevant results such as systematic reviews, randomized controlled trials, or comparative studies were selected to provide a summary for the most common nonsurgical methods used for treating BCC. Effective nonsurgical treatments for BCC include destructive methods (eg, curettage alone, cryosurgery, or electrodessication), PDT, topical medications, radiotherapy, laser, and HPIs. Nonsurgical therapeutic alternatives are safe and effective for the treatment of BCC. Factors such as tumor location, size, and histopathological subtype should be taken into consideration when selecting optimal treatment. In addition to clinical factors, cosmetic results and patient preference should be considered.

Pediatric teledermatology: A review of the literature.

Skin complaints are common among pediatric patients, yet as of 2020, fewer than 400 board-certified pediatric dermatologists currently practice in the United States. Pediatric teledermatology may address barriers to dermatologic care in children, assisting with distant geographic locations and long wait times. A review of the literature was conducted to synthesize important features of teledermatology for pediatric dermatologists. We summarize types of telemedicine platforms, common dermatologic conditions seen by pediatric teledermatologists, diagnostic accuracy and concordance, and guidelines from the American Academy of Dermatology and the American Telemedicine Association regarding teledermatology. This report highlights the utility of pediatric telemedicine in both the outpatient and inpatient dermatology setting to increase access to high-quality dermatologic care.

Vitamins A, B, C, and D: A Short Review for the Dermatologist.

BACKGROUND: Vitamins and their derivatives are used extensively in the field of dermatology to treat a range of conditions, both benign and malignant. Additionally, over the past decade, vitamin supplements have been heavily advertised for improving overall health. Due to the widespread use of vitamins and their derivatives for dermatologic conditions, a comprehensive review of the evidence is needed. OBJECTIVE: Here we review several of the well-established uses of vitamins A, B, C, and D in the management of dermatologic conditions ranging from acne vulgaris to malignant melanoma. Additionally, we examine the dermatologic consequences of both deficiency and excess of vitamins A, B, C, and D. Finally, we delve into newer applications for these vitamins and evaluate the evidence behind them. CONCLUSION: Vitamins, in both topical and oral forms, play a key role in treating many dermatologic conditions. Some of the newer applications of vitamins, such as the use of vitamin B3 for non-melanoma skin cancer prevention, vitamin B6 for prevention of chemotherapy-induced alopecia, and vitamin C as an adjuvant treatment for malignant melanoma, appear promising. Further data is needed to validate these findings. Additionally, many people use vitamin B7 for hair, skin, and nail health. There is evidence that supports vitamin B7 supplementation in patients with uncombable hair syndrome, brittle nail syndrome, and seborrheic dermatitis. Some studies Some studies have also demonstrated a benefit in healthy individuals, although other studies have shown a neutral effect. Further randomized controlled trials are needed. Likewise, the use of vitamin D for the treatment of atopic dermatitis has conflicting results and requires further investigation. New research continues to emerge regarding vitamin supplementation, and it is an important topic for dermatologists.

The effect of the "stay-at-home" policy on requests for dermatology outpatient clinic visits after the COVID-19 outbreak.

The Coronavirus Disease 2019 (COVID-19) emerged late in Turkey but it showed a rapid progression later. We aimed to investigate the changes in the number of patients who requested a dermatology outpatient clinic visit due to the increased social and medical burden caused by COVID-19 in Turkey during the first days of the pandemic. We also examined the most common dermatologic diseases diagnosed during the COVID-19 outbreak. A statistically significant negative correlation was found between the number of COVID-19 patients in the country and the number of patients requesting a dermatology outpatient clinic visit in the secondary and tertiary care hospitals during self-quarantine. In the first 10 days after the COVID-19 outbreak, acne (28.2%), urticaria (12.8%), scabies (12.8%), irritant contact dermatitis (10.3%), and xerosis cutis (10.2%) were the most common diseases seen in the dermatology clinic at the secondary care hospital, while acne (23.3%), warts (5.4%), seborrheic dermatitis (4.5%), urticaria (3.8%), and psoriasis (3.32%) were the most common diseases seen in the dermatology clinic at the tertiary care hospital. This is our first study on the frequency and nature of outpatient dermatology visits during this novel coronavirus pandemic. Understanding the trends and impacts of dermatologic diseases on patients and health systems during this pandemic will allow for better preparation of dermatologists in the future.

Collision tumors: A review of their types, pathogenesis, and diagnostic challenges.

A collision tumor is a neoplastic lesion comprised of two or more distinct cell populations that maintain distinct borders. Collision tumors, which are rare but well documented, can be composed of two benign tumors, a benign and malignant tumor, and two malignant tumors. Although case reports and reviews on specific types of collision tumors exist, a cohesive source discussing these tumors is lacking. We critically reviewed the literature by analyzing case reports and retrospective studies in order to evaluate the following regarding collision tumors: definitions, types, pathogenesis, diagnosis, and management. Reports of these tumors are infrequent but not insignificant, and accurate classification and diagnosis will lead to better patient outcomes.

Rickets in association with skin diseases and conditions: A review with emphasis on screening and prevention.

BACKGROUND: Rickets is a common disease worldwide. In the developed world, its prevalence dramatically decreased but still diagnosed in at-risk populations. The skin plays a critical role in vitamin D synthesis. Therefore, several skin diseases, especially keratinization disorders, could lead to impaired vitamin D metabolism and vitamin D deficient rickets. OBJECTIVE: The article aimed to summarize the current knowledge of skin diseases and conditions associated with rickets. METHODS: To examine the association between rickets and skin diseases, we performed a systematic review of the literature using PubMed database. The search included studies published from the database inception to August 2019. RESULTS: A total number of 75 articles were included. Identified conditions associated with rickets were ichthyosis being a more common skin diseases, alopecia, epidermal and melanocytic nevi, xeroderma pigmentosum, mastocytosis, psoriasis, and atopic dermatitis. Three types of rickets were identified: vitamin D-dependent rickets, hypocalcemic vitamin D-dependent rickets type 2, and hypophosphatemic rickets. Cutaneous skeletal hypophosphatemia syndrome is a newly described and under-recognized condition. It is defined by the association of epidermal or melanocytic nevi, hypophosphatemic rickets, and elevated levels of fibroblast growth factor 23. Rickets in patients with ichthyosis was mainly due to impaired ability of ichthyotic skin to synthesize vitamin D, poor UV penetration of the skin caused by keratinocyte proliferation, and dark phototype. The latter may be considered a risk factor for rickets in patients with ichthyosis. CONCLUSION: Despite its rarity, these associations should be properly recognized by dermatologists. Early diagnosis of rickets is important to prevent growth retardation and skeletal deformities.

The Therapeutic Use of Antioxidants for Melasma.

Melasma is a chronic dermatologic condition with an incompletely understood pathogenesis and well-demonstrated impact on patient quality of life. Melasma is a common cause for seeking dermatologic care, and with no universally efficacious therapy or cure, com-bination treatment is the best approach for many cases. Numerous studies have demonstrated the role of oxidative stress in patients with melasma, prompting investigation into several antioxidants for melasma therapy. In this review, we discuss the well-defined role of oxidative stress in melasma and the therapeutic efficacy of various antioxidants for patients suffering from melasma. We focus our discussion on studies investigating the role of vitamin C, azelaic acid, cysteamine, glutathione, carotenoids, and numerous other antioxidants in disorders of hyperpigmentation. There is promising evidence for the use of these antioxidants, as topical, oral, and intra-venous preparations, both in isolation and in conjunction with other melasma therapies. J Drugs Dermatol. 2020;19(8):788-792. doi:10.36849/JDD.2020.5079.

Multiple Primary Melanomas Occurring Around the Same Time: A Review of Terminology and Implications.

Multiple primary melanomas (MPMs) have been reported to occur in 2-10% of melanoma patients. This study conducted a review of the literature to elucidate the definitions of terminology used to describe MPMs that were diagnosed in close temporal proximity as well as explore common risk factors. Terminology found in the literature included “concurrent”, “simultaneous” and “synchronous” with varying definitions that ranged from 0-6 months between diagnoses of the first and subsequent melanomas. Eight cases are described in chronological order, and the incidence of MPMs diagnosed around the same time were reported as 22-39%. Nevus spilus was identified as a potential risk factor for MPMs. This study highlights that MPMs are not uncommon, and clinicians should remain aware that MPMs can be diagnosed at or around the same time, warranting thorough skin exams. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.4953.

Current and emerging treatment options for metastatic melanoma: a focused review.

Melanoma is responsible for nearly 9,000 deaths each year in the United States. Until the early 2000s, chemotherapeutic agents were the mainstay of treatment for metastatic disease. Currently approved treatments include therapies that block signal transduction pathways (BRAF inhibition), increase anti-tumor immune responses (CTLA-4 blockade), or stimulate tumor-infiltrating T cells (IL2). In recent years, various new strategies have emerged. Radiation therapy has been widely underutilized, but it can prime tumor cells that are distant from the field of radiation, a phenomenon termed the abscopal effect. Other therapies such as pembrolizumab disrupt the tumor cells' typical mechanisms of T-cell avoidance. Various other treatments involving imiquimod, adoptive T-cell therapy, and vaccines are currently being studied and can play a role in metastatic melanoma treatment in the future. Herein, we review the past treatment modalities, currently approved treatments, and potentially effective options for the future. We also provide strengths of recommendation and level of evidence for each treatment.

Use of Eye Shields for Mohs Micrographic Surgery of the Eyelids and Periorbital Area.

BACKGROUND: Internal eye shields are designed for use in periorbital procedures, but their use in Mohs micrographic surgery (MMS) of the eyelids has rarely been reported in the literature. OBJECTIVE: The authors aim to discuss different types of internal eye shields as well as their indication, proper use, and potential complications. MATERIALS AND METHODS: The authors performed a literature search on PubMed with the keywords "internal eye shield," "corneal shield," "scleral shield," and "periorbital Mohs micrographic surgery" with no restriction on publication time frame due to the scarcity of relevant literature. RESULTS: Experts seem to agree that use of eye shield for MMS of the eyelids is a reasonable measure to undertake to prevent operative injuries. Although either plastic or stainless steel eye shield can be used, plastic eye shields are often preferred and recommended in procedures where electrosurgical devices need to be used. CONCLUSION: Although the authors recommend the use of internal eye shields for MMS of the eyelids for preventing operative injuries, this recommendation (Grade C) is based on very limited evidence (Level 5). More research and higher-powered studies are needed for conclusive evidence and to establish clear guidelines for providers.

Ashy dermatosis: a review.

Ashy dermatosis is characterized by asymptomatic, symmetrically-distributed, gray-colored macules located on the trunk, neck, face, and upper extremities. The condition occurs most commonly in patients with Fitzpatrick phototype III-V skin. The etiology is unknown, but drug ingestion, infection, and genetic factors have been suggested to elicit ashy dermatosis. No gold standard treatments have been established yet. The most successful treatment to date has been clofazimine, although topical tacrolimus, oral dapsone, narrowband ultraviolet light B phototherapy, and isotretinoin have shown treatment success. Ashy dermatosis is primarily a cosmetic concern, but can be a very distressing condition, especially for dark skinned individuals. Therefore, an increase in clinician awareness and more studies are needed to further understand the etiology and treatment options for this disease. This review serves as a single source for clinicians to stay up-to-date regarding the history, clinical presentation, histology, pathogenesis, differential diagnosis, and management options for ashy dermatosis. It also suggests an alternative name that more appropriately encompasses the clinical and histopathologic features, while acknowledging our lack of understanding of its etiology: macular hyperpigmentation of indeterminate etiology.

Extramammary Paget disease.

In 1874, Sir James Paget first described Paget disease of the nipple, also known as mammary Paget disease. In 1889, extramammary Paget disease (EMPD) of the scrotum and penis was identified. Although mammary and extramammary Paget disease are both characterized by epidermal Paget cells and share a similar clinical presentation, their uniqueness lies in anatomical location and histogenesis. EMPD presents as an erythematous plaque on apocrine gland bearing areas (i.e. vulva, perineum, perianal region, scrotum, and penis) in older men and women. It can be a focal, multifocal, or an ectopic process. Immunohistochemical staining allows for differentiation between primary and secondary EMPD in addition to the many other disease entities that clinically resemble this malignancy. When diagnosing a patient with EMPD, a full history and physical should be performed given the possibility of an underlying malignancy. Surgical excision currently is first line therapy and the prognosis is often favorable. Recent advances within the field have examined the expression of chemokine receptors within tumors, which may be applicable in determining prognosis. This review addresses the history, epidemiology, pathogenesis, clinical presentation, histopathology, differential diagnosis, diagnosis, management, and new observations with respect to extramammary Paget disease.