Disparities of Cutaneous Malignancies in the US Military.

Occupational sun exposure is a well-known risk factor for the development of melanoma and nonmelanoma skin cancer (NMSC), especially among US military personnel who may have inadequate access to sun protection, are located in geographic regions with increased sun exposure, and work with potential carcinogens. Herein, we describe a case of a military service member who developed skin cancer at an early age potentially due to occupational sun exposure. We also provide a review of the literature to examine the risk factors and incidence of melanoma and NMSC in US military personnel and veterans, as well as provide recommendations for skin cancer prevention, screening, and intervention in the military population.

Transcriptomic Profiling of Plaque Psoriasis and Cutaneous T-Cell Subsets during Treatment with Secukinumab.

The IL-17A inhibitor secukinumab is efficacious for the treatment of psoriasis. To better understand its mechanism of action, we investigated its impact on psoriatic lesions from 15 patients with moderate-to-severe plaque psoriasis undergoing secukinumab treatment. We characterized the longitudinal transcriptomic changes of whole lesional skin tissue as well as cutaneous CD4+ and CD8+ T effector cells and CD4+ T regulatory cells across 12 weeks of treatment. Secukinumab was clinically effective and reduced disease-associated overexpression of IL17A , IL17F, IL23A, IL23R, and IFNG in whole tissue as soon as 2 weeks after initiation of treatment. IL17A overexpression in T-cell subsets, primarily CD8+ T cells, was also reduced. Although secukinumab treatment resolved 89‒97% of psoriasis-associated expression differences in bulk tissue and T-cell subsets by week 12 of treatment, we observed expression differences involved in IFN signaling and metallothionein synthesis that remained unresolved at this time point as well as potential treatment-associated expression differences involved in IL-15 signaling. These changes were accompanied by shifts in broader immune cell composition on the basis of deconvolution of RNA-sequencing data. In conclusion, our study reveals several phenotypic and cellular changes within the lesion that underlie clinical improvement from secukinumab.

Useful cytological confirmation of HPV 13 in lesional mucosa enhances diagnosis of focal epithelial hyperplasia.

An 11-year-old female presented with multiple oral lesions for several months. Histopathological findings suggested focal epithelial hyperplasia (FEH), also known as Heck disease. FEH is strongly associated with Human papillomavirus (HPV), especially genotypes 13 and 32. An oral swab of a mucosal lesion was subsequently obtained for cytology, immunohistochemistry and in situ hybridization. In addition, in situ hybridization and immunohistochemistry were also performed retrospectively on the biopsy specimen for correlation. The cytology specimen showed squamous cells with enlarged, slightly atypical nuclei and rare perinuclear halos. The histology findings included papillomatosis with acanthosis, mild nuclear atypia and focal perinuclear halos. The immunohistochemistry for the consensus HPV L1 capsid protein was found in both the cytology and biopsy specimens indicating that the lesion was HPV-related. High viral copy numbers of HPV 13 were detected by in situ hybridization in both the cytology and histology specimens. Although histologic features of FEH have been well characterized in the literature, to our knowledge, this is the first case to describe in FEH with adjunct immunohistochemistry and in situ hybridization results. Furthermore, these findings assisted in our diagnosis since the patient's clinical presentation was a diagnostic challenge with smooth dome-shaped papules instead of the typically described flat-topped verrucous lesions seen in FEH. In summary, our case reveals that there is a high concordance between the HPV 13 detection in the cytology and histology of FEH, and that performing cytology in addition to histology can be used to optimize diagnostic evaluation towards appropriate patient care.

Identification of a novel variant of FOXP3 resulting in severe immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome highlights potential pitfalls of molecular testing.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare genetic disorder that typically presents in the first year of life with severe diarrhea, autoimmune endocrine disorder, and inflammatory dermatitis, most commonly an eczematous dermatitis. IPEX syndrome is caused by variants in the FOXP3 gene leading to dysregulation of T-regulatory (Treg) cells and an aberrant immune response. Here, we present a case of severe IPEX syndrome diagnosed following whole genome sequencing (WGS) in a 2-week-old boy with bloody mucoid diarrhea, failure to thrive, and a diffuse eczematous dermatitis. As multiple variants of interest were identified with WGS, this case highlights the importance of relating the clinical symptoms to the genetic results.

Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer.

BACKGROUND: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. OBJECTIVE: Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. METHODS: We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin. RESULTS: We identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. CONCLUSION: Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.

Ocular Co-Morbidities of Atopic Dermatitis. Part II: Ocular Disease Secondary to Treatments.

Treatments used for managing atopic dermatitis (AD) may have adverse ocular effects that permanently affect vision. The objective of this review is to raise awareness among dermatologists regarding the potential ocular adverse effects of various AD therapies, including corticosteroids, calcineurin inhibitors, an interleukin-4 receptor α (IL-4Rα) antagonist, and phototherapy. Pertinent potential short- and long-term risks of these therapies include elevations in intraocular pressure from use of topical corticosteroids and conjunctivitis from use of dupilumab. Since some of these adverse effects may not exhibit symptomatology until permanent vision impairment occurs, it is important for dermatologists to understand these risks and proactively ensure their patients are receiving appropriate measures to prevent them.

Ocular Co-Morbidities of Atopic Dermatitis. Part I: Associated Ocular Diseases.

Ocular diseases associated with atopic dermatitis (AD) may be sight-threatening. A general understanding of the pathophysiology, diagnosis, and treatment of atopic eye disease may assist dermatologists in knowing when to refer to ophthalmology and in co-managing these diseases with ophthalmologists. Ocular diseases associated with AD include eyelid dermatitis, keratoconjunctivitis, keratoconus, cataract, and retinal detachment. AD patients are also at higher risk for bacterial and viral ocular infections. The objective of this article is to provide a current review of ocular diseases that commonly affect AD patients. The pathogenesis, clinical manifestations, diagnosis, and treatment of ocular co-morbidities of AD will be discussed.

Clinical Features of Neutrophilic Dermatosis Variants Resembling Necrotizing Fasciitis.

Importance: Pyoderma gangrenosum and necrotizing Sweet syndrome are diagnostically challenging variants of neutrophilic dermatosis that can clinically mimic the cutaneous and systemic features of necrotizing fasciitis. Improved characterization of these rare variants is needed, as improper diagnosis may lead to inappropriate or delayed treatment and the potential for morbidity. Objective: To determine the characteristics of necrotizing neutrophilic dermatosis to improve diagnostic accuracy and distinguish from infection. Design, Setting, and Participants: A case series of patients with necrotizing neutrophilic dermatosis treated at 3 academic hospitals (University of California San Francisco, Oregon Health and Science University, and University of Minnesota) from January 1, 2015, to December 31, 2017, was performed along with a literature review of related articles published between January 1, 1980, and December 31, 2017. Data were obtained from medical records as well as Medline and Embase databases. All patients had signs resembling necrotizing infection and had a final diagnosis of pyoderma gangrenosum with systemic features or necrotizing Sweet syndrome. Patients were excluded if a diagnosis other than neutrophilic dermatosis was made, if key clinical information was missing, and if reported in a non-English language. Main Outcomes and Measures: Description of key characteristics of necrotizing neutrophilic dermatosis. Results: Overall, 54 patients with necrotizing neutrophilic dermatosis were included, of which 40 had pyoderma gangrenosum with systemic features and 14 had necrotizing Sweet syndrome. Of the 54 patients, 29 (54%) were male and 25 (46%) were female, with a mean (SD) age of 51 (19) years. Skin lesions commonly occurred on the lower (19 [35%]) and upper (13 [24%]) extremities and developed after a surgical procedure (22 [41%]) or skin trauma (10 [19%]). Shock was reported in 14 patients (26%), and leukemoid reaction was seen in 15 patients (28%). Of the patients with necrotizing neutrophilic dermatosis, 51 (94%) were initially misdiagnosed as necrotizing fasciitis and subsequently received inappropriate treatment. Debridement was performed in 42 patients (78%), with a mean (SD) of 2 (2 [range, 1-12]) debridements per patient. Four amputations (7%) were performed. Forty-nine patients (91%) received antibiotics when necrotizing neutrophilic dermatosis was misdiagnosed as an infection, and 50 patients (93%) received systemic corticosteroids; all patients responded to immunosuppressants. Conclusions and Relevance: A complex spectrum of clinical findings of pyoderma gangrenosum and Sweet syndrome with prominent systemic inflammation exists that defines a new subset of neutrophilic dermatoses, termed necrotizing neutrophilic dermatoses; recognizing the difference between this variant and severe infection may prevent unnecessary surgical procedures and prolonged disease morbidity associated with a misdiagnosis and may expedite appropriate medical management.

A Simulation-Based Workshop to Improve Dermatologists' Communication Skills: A Pilot for Continuing Medical Education.

INTRODUCTION: Communication skills influence the quality of health care and patient experience; both may affect provider reimbursement. There are few opportunities available for practicing physicians to receive direct feedback on communication in patient encounters. The purpose of this simulation-based patient encounter workshop was for dermatologists to practice and obtain feedback on their communication skills. METHODS: In March 2016, dermatologists participated in a workshop with four simulated patient encounters. Cases were developed based on a prior needs assessment. Standardized patient educators evaluated participants' communication using the Master Interview Rating Scale and provided verbal feedback. Physicians rated the usefulness of the simulation and the feedback received through a survey upon workshop completion. RESULTS: Of the 170 physicians who registered, 103 participated in the simulation. The workshop was highly rated in meeting its three learning objectives (score of 4.5-4.6 out of a maximum score of 5). The lowest-rated communication skills were as follows: allowing the patient to share their narrative thread (3.1), summarizing the patient's history from the provider (3.8), and assessing patient understanding (3.8). CONCLUSIONS: Participants reported that this communication workshop effectively satisfied its learning objectives. Opportunities to practice and improve communication skills as part of continuing medical education will benefit the clinical experience of patients and physicians alike, and the workshop may be formatted to serve physicians of other specialties. The lowest-scoring communication areas identified in this study present an opportunity to develop a tailored curriculum for physician-patient communication in the future.

Pediatric primary cutaneous blastomycosis clinically responsive to itraconazole.

Primary cutaneous blastomycosis is a rare infection, especially among children. We present the case of a 16-year-old immunocompetent adolescent boy with primary cutaneous blastomycosis arising after falling into a flowerbed in a region where the fungus Blastomyces dermatitidis is hyperendemic. Following treatment with itraconazole 200 mg 3 times daily for 3 days, followed by 200 mg 2 times daily for 6 months, the lesion healed with only residual dyschromia.

The impact of genital psoriasis on quality of life: a systematic review.

Psoriasis is a chronic immune-mediated inflammatory disease with significant medical and psychological comorbidities. In addition to having increased cardiovascular risk and mortality, psoriasis patients are more likely to be depressed, anxious, and endorse suicidal ideation than the general population. These patients often have low self-esteem and feel stigmatized due to their skin disease, which can prevent them from pursuing relationships, dating, and attending social activities. Up to 63% of adult psoriasis patients experience psoriatic lesions on their genital area during their lifetime, but often do not discuss these issues with their physicians due to embarrassment, stigmatization, or shyness about this sensitive location. However, psoriasis in sensitive areas, such as the genitals, may result in quality of life impairment greater than that of patients with psoriasis elsewhere on their body, particularly in respect to romantic relationships, intimacy, and sexual function. This article evaluates the current literature regarding the impact of genital psoriasis on the quality of life of affected patients.

Profile of tildrakizumab-asmn in the treatment of moderate-to-severe plaque psoriasis: evidence to date.

Plaque psoriasis is an immune-mediated skin disease that affects roughly 3% of adults in the United States. Advances over the past 20 years in understanding the immune-mediated pathophysiology of psoriasis have led to the development of targeted biologic therapies for this condition. Currently, biologic medications approved for the treatment of plaque psoriasis include tumor necrosis factor α inhibitors, interleukin (IL)-17 or IL-17 receptor inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors. Tildrakizumab-asmn is a monoclonal antibody that targets the p19 subunit of IL-23 and is approved for use in adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article reviews the current pharmacologic, efficacy, and safety data on tildrakizumab-asmn.

Recent Developments in Atopic Dermatitis.

Atopic dermatitis (AD) is a bothersome and common skin disease affecting ∼10.7% of children in the United States. This skin condition significantly decreases quality of life in not only patients, but in their families as well. Pediatricians are often the first physicians to diagnose and manage these patients and thus are relied on by families to answer questions about this disease. AD is complex, multifactorial, and has historically had limited therapeutic options, but the landscape of this disease is now rapidly changing. Pathways contributing to the pathogenesis of this disease are continually being discovered, and new therapies for AD are being developed at an unprecedented rate. With this article, we will review the current guidelines regarding the management of AD, outline updates in the current understanding of its pathophysiology, and highlight novel developments available for the treatment of this burdensome disease.

Treatment of Genital Psoriasis: A Systematic Review.

Genital psoriasis affects approximately 63% of psoriasis patients at least once in their lifetime. More than any other area on the body, genital lesions significantly impair patients' psychologic well-being and quality of life. We aimed to systematically review the published evidence on the safety, efficacy, and tolerability of treatments of genital psoriasis and synthesize the available clinical data. A total of 1 randomized controlled trial, 11 open-label studies, and 26 case reports were included in our analysis, representing a total of 458 patients, of which 332 were adults and 126 were children. Topical corticosteroids were commonly used first-line for genital psoriasis and were well tolerated. Nonsteroidal agents, such as topical calcineurin inhibitors or vitamin D analogs, were also efficacious, but were often irritating. One systemic agent, ixekizumab, demonstrated efficacy in reducing genital psoriasis symptoms in a large, randomized, placebo-controlled trial. Various systemic and topical medications may improve genital psoriasis lesions, but there is a lack of high-quality evidence to guide clinical decision-making. Specific reporting of efficacy for genital psoriasis in larger controlled studies of psoriasis treatments are necessary to improve the available evidence regarding the optimal treatment regimen for genital psoriasis.

Building a Citizen Pscientist: Advancing Patient-Centered Psoriasis Research by Empowering Patients as Contributors and Analysts.

INTRODUCTION: To design and implement a novel cloud-based digital platform that allows psoriatic patients and researchers to engage in the research process. METHODS: Citizen Pscientist (CP) was created by the National Psoriasis Foundation (NPF) to support and educate the global psoriatic disease community, where patients and researchers have the ability to analyze data. Psoriatic patients were invited to enroll in CP and contribute health data to a cloud database by responding to a 59-question online survey. They were then invited to perform their own analyses of the data using built-in visualization tools allowing for the creation of "discovery charts." These charts were posted on the CP website allowing for further discussion. RESULTS: As of May 2017, 3534 patients have enrolled in CP and have collectively contributed over 200,000 data points on their health status. Patients posted 70 discovery charts, generating 209 discussion comments. CONCLUSION: With the growing influence of the internet and technology in society, medical research can be enhanced by crowdsourcing and online patient portals. Patient discovery charts focused on the topics of psoriatic disease demographics, clinical features, environmental triggers, and quality of life. Patients noted that the CP platform adds to their well-being and allows them to express what research questions matter most to them in a direct and quantifiable way. The implementation of CP is a successful and novel method of allowing patients to engage in research. Thus, CP is an important tool to promote patient-centered psoriatic disease research.

Guselkumab for the treatment of moderate-to-severe plaque psoriasis.

INTRODUCTION: Guselkumab is a human monoclonal antibody targeting the p19 subunit of IL-23 that has been approved for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This medication blocks the IL-23/IL-17 axis, which has been implicated in playing a key role in the pathogenesis of psoriasis. Areas covered: This review outlines the pharmacologic properties, safety, and efficacy of guselkumab for the treatment of plaque psoriasis. Expert commentary: Guselkumab is the first IL-23 specific inhibitor to be approved for the treatment of plaque psoriasis. Phase II and III clinical trial results have demonstrated excellent safety and efficacy of guselkumab. IL-23 inhibitors may offer potential benefits over existing therapies for moderate-to-severe plaque psoriasis in terms of safety, frequency of administration, and efficacy. Long-term safety data will be critical in evaluating the role of guselkumab in the treatment of psoriasis.

Diagnosis and management of peristomal pyoderma gangrenosum: A systematic review.

BACKGROUND: Peristomal pyoderma gangrenosum (PPG) is an uncommon subtype of pyoderma gangrenosum. PPG is a challenging condition to diagnose and treat; no evidence-based guidelines exist. OBJECTIVE: We sought to identify important clinical features of PPG and effective treatments available for its management. METHODS: A systematic literature review of PPG was performed using PubMed, Medline, and Embase databases. RESULTS: We describe 335 patients with PPG from 79 studies. Clinical features include a painful, rapidly progressing ulcer with undermined, violaceous borders with a history of ostomy leakage and local skin irritation or trauma. Systemic steroids are first-line therapy; infliximab and adalimumab provide concomitant control of active inflammatory bowel disease. Combination local and systemic therapy was commonly used. Wound dressings, vehicle selection, and appropriate ostomy devices to minimize leakage, irritation, and pressure-induced ischemia can improve healing. Distinct from classic ulcerative pyoderma gangrenosum, surgical approaches, such as stoma closure and resection of active inflammatory bowel disease, have an effective role in PPG management. LIMITATIONS: PPG is a rare disease lacking randomized trials or diagnostic guidelines. Treatment duration and follow-up time among studies are variable. CONCLUSIONS: Key clinical characteristics of PPG are highlighted. Several treatments, including a more prominent role for surgical intervention, may be effective for PPG treatment.