A Case of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm Treated With a Bcl-2 Inhibitor.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive primary cutaneous lymphoma characterized by transformed plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA) also known as CD123. In addition to several therapies currently undergoing clinical trials, Tagraxofusp-erzs (Stemline Therapeutics, Inc., NY) is a single FDA-approved option available for treatment of adults and children over 2 years of age suffering from BPDCN. It was designed to target CD123 overexpression in BPDCN as a CD123-directed cytotoxin consisting of a recombinant human interleukin-3 fused to a truncated diphtheria toxin. We discuss a case of a male patient in his late 70s’ who presented with an asymptomatic rash involving the back and the right knee that initially developed as pink patches, progressed into plaques, and subsequently rapidly evolved into a tumor involving the right knee that was confirmed as BPDCN on skin biopsy and was accompanied by bone marrow involvement. Upon initiation of first line tagraxofusp-erzs therapy, the patient did not achieve improvement. However, off-label use of venetoclax (AbbVie Inc, IL and Genentech-USA, CA), a Bcl2 inhibitor currently in a Phase I clinical trial, resulted in a satisfactory clinical outcome, nearly complete resolution of a right knee tumor lesion, and deferment of bone marrow transplant. We believe that our case exemplifies the complexity of BPDCN, briefly reviews current treatment and management options that are only in their infancy and raises awareness towards success with alternative off-label therapies such as venetoclax when treating BPDCN. J Drugs Dermatol. 20(5):550-551. doi:10.36849/JDD.5373.

The 100 most influential skin cancer publications: a citation analysis.

BACKGROUND: As skin cancer is the most common cancer in the U.S., many publications focus on cutaneous malignancies. The objective was to identify and analyze the 100 most-cited articles pertaining to skin cancers to provide clarity on past, and insight for future research. METHODS: Using a two-stage search of Thomson Reuters Web of Science database, the 100 most-cited skin cancer articles between 1945 and 2018 were identified and analyzed. RESULTS: The articles were cited an average total of 558.49 times (range: 259 to 3429). There were relatively few significant publications until 1988. Linear correlation revealed that journal impact factor was not correlated with average number of citations per year per article (R2=0.06). Molecular pathogenesis and UV exposure were the most common topics. The topics that received the highest average citations per year per article were prevention (50.44 citations per year), diagnosis (47.32 citations per year), and management (41.37 citations per year). Basic science articles accounted for the most publications, followed by narrative literature reviews. CONCLUSIONS: These results may indicate that future publications with similar characteristics are more likely to be cited and thus, more influential.

Examining the Safety and Efficacy of Low-Level Laser Therapy for Male and Female Pattern Hair Loss: A Review of the Literature.

PURPOSE: Pattern hair loss is the most common type of alopecia. Standard of care involves long-term use of topical medications with limited effectiveness. Low-level laser therapy (LLLT) has become a popular alternative treatment. Here, we examine published clinical trials to establish whether the breadth of evidence supports LLLT for pattern hair loss. METHODS: A literature search was conducted within the PubMed, Embase, Scopus, and Cochrane Trials databases to identify original articles evaluating hair regrowth following LLLT. Articles were selected based on use of 600-1,100 nm wavelengths, treatment time ≥16 weeks, and objective evaluation for hair regrowth. RESULTS: Ten randomized controlled trials were included, of which 8 compared LLLT to sham device and 1 to no treatment. The study populations varied, with 3 studies evaluating only women. All sham-device controlled studies demonstrated statistically significant increase in hair diameter or density (p < 0.01) following LLLT. DISCUSSION: Based on our review of the literature, LLLT appears to be effective for treating pattern hair loss in both men and women. These laser devices have good safety profiles, with only minor adverse effects reported. However, physicians should be cautious when drawing conclusions as some studies included have a relationship with industry.

Advances in Stem Cell-Based Therapy for Hair Loss.

OBJECTIVE: Hair loss is a quite common condition observed in both men and women. Pattern hair loss also known as androgenetic alopecia is the most common form of hair loss that is thought to affect up to 80% of Caucasian men and up to 40% of Caucasian women by age of 70, and it can have quite devastating consequences on one's well-being, including lower self-esteem, depression and lower quality of life. To date there have only been 2 FDA approved medications, minoxidil and finasteride, but their effects are often unsatisfactory and temporary, in addition to having various adverse effects. Stem cell-based therapies have recently received lots of attention as potential novel treatments that focus on reactivating hair follicle stem cells and in this way enhance hair follicle growth, regeneration and development. Stem cell-based therapy approaches include stem cell transplant, stem cell-derived conditioned medium and stem cell-derived exosomes. MATERIALS AND METHODS: A combination of following key words was utilized for a PubMed search: cell-based therapy, hair loss, alopecia, hair regrowth; abstracts were screened and included based on the content relevant to hair loss and stem-cell based therapy. RESULTS: Preclinical research utilizing these approaches has blossomed in the past decade along with a more limited number of clinical studies, overall demonstrating very promising findings. CONCLUSION: However, stem cell-based therapies for hair loss are still at their infancy and more robust clinical studies are needed to better evaluate their mechanisms of action, efficacy, safety, benefits and limitations. In this review, we provide the resources to the latest preclinical studies and a more detailed description of the latest clinical studies concerning stem cell-based therapies in hair loss.

A Case Report of a Rapidly Growing Giant Pilomatrixoma on the Posterior Shoulder in a 12-Year-Old Male Patient.

INTRODUCTION: Giant pilomatrixomas are quite rare and can be clinically challenging to diagnose. CASE PRESENTATION: Here, we report a case of a rapidly growing mass on the shoulder of a 12-year-old previously healthy boy. The lesion on his right shoulder appeared as a painless, pink-blue-colored solitary mass that started 6 months ago and rapidly enlarged to 4.5 × 6 cm in size. Previous biopsy results were inconclusive, showing only hypercellular spindle cell proliferation in a collagenous stroma. There was concern for malignancy versus mixed lymphatic venous malformation or benign soft tissue tumor. An excisional biopsy was done and demonstrated features of a pilomatrixoma. Complete surgical removal with clear margins was curative. CONCLUSION: Diagnosis and management of rapidly enlarging skin lesions in children can be difficult for clinicians and dermatopathologists. Excisional biopsy can be both diagnostic and therapeutic. A timely exclusion of malignancy is of utmost importance.

The Potential Impact of Social Genomics on Wound Healing.

Significance: Human skin wounds carry an immense epidemiologic and financial burden, and their impact will continue to grow with an aging population and rising incidence of comorbid conditions known to affect wound healing. To comprehensively address this growing clinical issue, physicians should also be aware of how conditions of the human social environment may affect wound healing. Here we provide a review of the emerging field of social genomics and its potential impact on the wound healing. Recent Advances: Multiple studies using human and animal models have correlated social influences and their contributing effects to acute and chronic stress with delays in wound healing. Furthermore, observations between nongenetic factors such as nutrition, socioeconomic, and educational status have also shown to have a direct or indirect impact on clinical outcomes of wound healing. Critical Issues: Nutrition, financial burden, socioeconomic and education status, and acute and chronic stress are variables that have either direct (epigenetic) or indirect impact on wound healing and patients' quality of life. Wound care is costly and remains a challenge placing economic burden on patients. Furthermore, poor clinical outcomes and complications including loss of mobility and disability may lead to job loss, further contributing to socioeconomic related stress. Thus, the economic burden and inadequate wound healing are intertwined, making each other worse. Future Directions: Although some evidence regarding the specific changes in genetic pathways imparted by conditions of the social environment exists, further studies are warranted to identify potential mechanisms, interventions, and prevention approaches.

Carpal tunnel syndrome and associated nail changes: Review and examples from the author's practice.

Carpal tunnel syndrome (CTS) is commonly seen by general practitioners and often presents with neurologic symptoms of nocturnal pain and paresthesia along the median nerve distribution. Approximately 20% of patients also present with cutaneous findings (ulcerations, blistering, sclerodactyly, nail dystrophy) characterizing a severe form called necrotic CTS. Necrotic CTS can also be associated with bone changes (acro-osteolysis). In the author's practice, combined nail and skin findings are not an uncommon presentation of CTS, although this form remains overlooked and underreported in the dermatological textbooks and studies. This manuscript aims to review the literature on CTS cases, with a specific focus on using associated nail findings as diagnostic clues. The literature review along with a few additional recent cases from the author's practice demonstrate that CTS is frequently accompanied by a variety of nail changes including koilonychia, longitudinal fissuring, Beau's lines, onychomadesis, melanonychia, nail thickening, hyperkeratosis, and ischemic ulcerations with paronychia. Furthermore, when these changes are limited to the second and third fingernails, they should prompt the diagnosis of CTS. Once suspected, diagnostic evaluation is not difficult and surgical management can resolve cutaneous findings and prevent irreversible changes such as acro-osteolysis.

A Case Report of a Patient with Turner Syndrome, Multiple Comorbidities, and Pustular Psoriasis: Correlation or Coincidence?

Turner syndrome (TS) is one of the most common chromosomal abnormalities. Patients with TS are at an increased risk for the development of metabolic syndrome, hypertension (HTN), diabetes mellitus type II (DM2), hyperlipidemia (HLD), obesity, and cardiovascular disease. The association between psoriasis and the aforementioned conditions including metabolic syndrome, HTN, HLD, obesity, and cardiovascular disease has also been established. Although the mechanism for heightened risk in TS patients is yet to be elucidated, patients suffering from TS and cardiometabolic diseases are likely to be at an even higher risk for developing psoriasis than patients suffering from TS alone. We present a case of a 53-year-old Hispanic woman with a mosaic TS and multiple comorbidities who presented with pustular psoriasis. For this patient, management can be challenging considering her numerous medical comorbidities and the presence of both TS and psoriasis.

The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond.

Caveolae are flask-shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components that allow compartmentalization and orchestration of various signalling molecules. In this review, we discuss how pleiotropic functions of caveolin-1 (Cav1) and its intricate roles in numerous cellular functions including lipid trafficking, signalling, cell migration and proliferation, as well as cellular senescence, infection and inflammation, are integral for normal development and functioning of skin and its appendages. We then examine how disruption of the homeostatic levels of Cav1 can lead to development of various cutaneous pathophysiologies including skin cancers, cutaneous fibroses, psoriasis, alopecia, age-related changes in skin and aberrant wound healing and propose how levels of Cav1 may have theragnostic value in skin physiology/pathophysiology.

Folliculitis Decalvans and Lichen Planopilaris Phenotypic Spectrum-A Series of 7 New Cases With Focus on Histopathology.

BACKGROUND: Folliculitis decalvans (FD) and lichen planopilaris (LPP) are classified as neutrophilic and lymphocytic cicatricial alopecias according to the North American Hair Research Society. Recently, a clinical phenotype combining concomitant or sequential features for both was described as a FD LPP phenotypic spectrum (FDLPPPS). OBJECTIVES: To review the most common phenotypic presentation of FDLPPPS with a main focus on histopathology. METHODS: We reviewed retrospectively series of 7 patients with a similar phenotypic presentation with special focus on the histologic pattern. All patients presented with concomitant features for FD and LPP and recalcitrant course unresponsive to topical and systemic immunomodulatory/anti-inflammatory agents. RESULTS: The most common clinical phenotype was that of hairless patches on the vertex with lost follicular ostia and perifollicular scale and the following diagnostic findings: (1) polytrichia; (2) positive bacterial culture for Staphylococcus in over 50% of the samples isolated from pustules and hemorrhagic crusts; (3) "mixed" histologic features for primary cicatricial alopecia including multicompound follicular structures of average 2-5 follicles (follicular packs), atrophy of the follicular epithelium, lymphohistiocytic infiltrate with granulomas, and prominent plasma cells, but absence of neutrophilic infiltrate in all cases except scarce neutrophils in one; and (4) clinical improvement with adjuvant systemic antimicrobials. CONCLUSIONS: The FDLPPPS may be underreported and should be considered in all cases of LPP recalcitrant to treatment. Dermatologists and dermatopathologists should recognize this phenotypic spectrum to guide optimal clinical management consisting of immunomodulatory and anti-inflammatory agents along with systemic antimicrobials.

Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling.

Diabetic foot ulcers (DFUs) are a life-threatening disease that often results in lower limb amputations and a shortened life span. Current treatment options are limited and often not efficacious, raising the need for new therapies. To investigate the therapeutic potential of topical statins to restore healing in patients with DFUs, we performed next-generation sequencing on mevastatin-treated primary human keratinocytes. We found that mevastatin activated and modulated the EGF signaling to trigger an antiproliferative and promigratory phenotype, suggesting that statins may shift DFUs from a hyperproliferative phenotype to a promigratory phenotype in order to stimulate healing. Furthermore, mevastatin induced a migratory phenotype in primary human keratinocytes through EGF-mediated activation of Rac1, resulting in actin cytoskeletal reorganization and lamellipodia formation. Interestingly, the EGF receptor is downregulated in tissue biopsies from patients with DFUs. Mevastatin restored EGF signaling in DFUs through disruption of caveolae to promote keratinocyte migration, which was confirmed by caveolin-1 (Cav1) overexpression studies. We conclude that topical statins may have considerable therapeutic potential as a treatment option for patients with DFUs and offer an effective treatment for chronic wounds that can be rapidly translated to clinical use.

Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

The clinical field of wound healing is challenged by numerous hurdles. Not only are wound-healing disorders complex and multifactorial, but the corresponding patient population is diverse, often elderly and burdened by multiple comorbidities such as diabetes and cardiovascular disease. The care of such patients requires a dedicated, multidisciplinary team of physicians, surgeons, nurses and scientists. In spite of the critical clinical need, it has been over 15 years since a treatment received approval for efficacy by the FDA in the United States. Among the reasons contributing to this lack of effective new treatment modalities is poor understanding of mechanisms that inhibit healing in patients. Additionally, preclinical models do not fully reflect the disease complexity of the human condition, which brings us to a paradox: if we are to use a "mechanistic" approach that favours animal models, we can dissect specific mechanisms using advanced genetic, molecular and cellular technologies, with the caveat that it may not be directly applicable to patients. Traditionally, scientific review panels, for either grant funding or manuscript publication purposes, favour such "mechanistic" approaches whereby human tissue analyses, deemed "descriptive" science, are characterized as a "fishing expedition" and are considered "fatally flawed." However, more emerging evidence supports the notion that the use of human samples provides significant new knowledge regarding the molecular and cellular mechanisms that control wound healing and contribute to inhibition of the process in patients. Here, we discuss the advances, benefits and challenges of translational research in wound healing focusing on human subject research.