Challenges in utilizing ALK expression to distinguish primary cutaneous from systemic anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a CD30+ peripheral T-cell lymphoma with a clinical spectrum including cutaneous and systemic presentations. While primary cutaneous ALCL (pcALCL) has a favorable prognosis, systemic ALCL (sALCL) has poorer survival outcomes. Expression of anaplastic lymphoma kinase (ALK) by malignant cells has been suggested to distinguish sALCL from pcALCL. However, there have been documented cases of ALK-positive ALCL confined to the skin. The present study reviewed characteristics of published cutaneous ALK-positive ALCL cases to distinguish between these two entities. In 23 identified adults with ALK-positive pcALCL, 26% developed systemic involvement and 74% had skin-limited disease. In 14 pediatric patients, 36% had both cutaneous and systemic involvement and 64% had cutaneous disease only. This analysis revealed that pcALCL and sALCL could not reliably be distinguished by ALK expression or nuclear vs. cytoplasmic localization. Localized treatment with frequent monitoring may be sufficient in ALK-positive pcALCL until there is evidence of progression. Physicians should be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK positivity and disease with skin recurrence.

Patterns and determinants of pediatric dermatologic care in the United States: An evaluation of the National Ambulatory Medical Care Survey from 2009 to 2015.

BACKGROUND: Dermatologists and other providers play essential roles in managing the dermatologic care of pediatric patients. This study aims to identify patterns and elucidate factors associated with receiving dermatologic care in the United States. METHODS: The National Ambulatory Medical Care Survey (NAMCS) was used to identify pediatric patients with dermatologic diagnoses from 2009 to 2015. Clinical and demographic information were evaluated, and visit diagnoses were stratified based on provider type (dermatologists vs. non-dermatologists). Multivariate logistic regression analysis was used to identify key predictors of outpatient dermatology care for pediatric patients. National estimates of diagnoses were procured using weights provided within the NAMCS database to project disease incidence. RESULTS: A total of 85,217,557 pediatric patients (survey-weighted) were observed during the study period. Of the sampled patients, 29.3% were evaluated by dermatologists, while 70.7% were seen by non-dermatology providers. Atopic dermatitis was the most common diagnosis encountered by dermatologists in ages 0-3 years, while unspecified contact dermatitis was the most common diagnosis reported by non-dermatologists in all age groups. On multivariable logistic regression, ≥1 year of age, Caucasian race, private insurance versus Medicaid, residence in a metropolitan area, referral from another provider, and longer appointment wait time were associated with an increased likelihood of being evaluated by a dermatologist compared to a non-dermatologist. CONCLUSIONS: Non-dermatologists are responsible for the majority of pediatric dermatologic care. For pediatric patients, health disparities by race, insurance status, and rurality present significant challenges to being evaluated by a dermatologist.

A Case of severe mosquito bite allergy complicated by fatal hemophagocytic lymphohistiocytosis.

Severe mosquito bite allergy (SMBA) is characterized by necrotic skin lesions and systemic symptoms. Chronic active Epstein-Barr virus (EBV) infection, when superimposed with SMBA, is a key driver for catastrophic clinical consequences, such as uncontrolled lymphoproliferation. This interplay is of clinical significance due to its association with hemophagocytic lymphohistiocytosis (HLH) and/or EBV-driven malignancies. Here, we report a case of SMBA that developed in a 14-year-old Hispanic boy that led to fatal secondary HLH.

Review of traction alopecia in the pediatric patient: Diagnosis, prevention, and management.

Hairstyles and practices that frequently apply tension to the hair follicle can result in traction alopecia (TA). Many of the hairstyles and hair practices associated with a higher risk of TA begin at a young age, making early intervention and education advantageous in the pediatric population. Recognizing TA at its reversible stage in the pediatric population is critical as early interventions, and counseling will prevent permanent scarring alopecia. While TA can affect any pediatric patient, this review highlights the reported literature on specific populations with a higher reported prevalence of TA.

Management of classic ulcerative pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis with unclear etiology and is associated with notable morbidity. Due to the rarity of PG, there are limited large, multicentered, randomized trials to guide management. We aim to highlight best practices in PG management through survey responses from expert medical dermatologists.

A cross-sectional study of the distribution of psoriasis subtypes in different ethno-racial groups.

Skin of colored patients with psoriasis are more likely to remain undiagnosed and experience a greater impact on quality of life than their white counterparts. A better understanding of the ethno-racial differences in the presentation of psoriasis can help address these disparities. To compare the prevalence of psoriatic subtypes (plaque, guttate, pustular, erythrodermic, palmoplantar, and inverse) and lesion locations in Caucasian, Asian, and Hispanic/Latino patients, we analyzed cross-sectional, patient-reported, physician-reviewed survey data from 882 adult and 16 pediatric psoriasis patients seen at the University of California, San Francisco Department of Dermatology between 2006 and 2016. Multivariate logistic regression was used to compare the prevalence of psoriasis subtypes and lesional distributions amongst the ethno-racial groups. Asians and Hispanics/Latinos had higher odds of having pustular psoriasis compared to Caucasians (OR=4.36 [95%CI: 1.24-17.62], P=0.026; and OR=5.94 [95%CI: 1.03-31.03], P=0.036, respectively). Asians also had a higher frequency of erythrodermic psoriasis (OR=5.56 [95%CI: 1.41-27.17], P=0.018), but a lower frequency of inverse psoriasis compared to Caucasians (OR=0.26 [95%CI: 0.06-0.80], P=0.036). These differences may relate to genetic or environmental factors or access to care. Clinician awareness of ethno-racial differences in psoriasis subtype and lesion location can facilitate earlier diagnosis and therapeutic intervention.

Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization.

BACKGROUND: Psoriasis impacts 1-3% of the world's population and is characterized by hyper-proliferation of keratinocytes and increased inflammation. At the molecular level, psoriasis is commonly driven by a Th17 response, which serves as a major therapeutic target. Microbiome perturbations have been associated with several immune-mediated diseases such as atopic dermatitis, asthma, and multiple sclerosis. Although a few studies have investigated the association between the skin microbiome and psoriasis, conflicting results have been reported plausibly due to the lack of standardized sampling and profiling protocols, or to inherent microbial variability across human subjects and underpowered studies. To better understand the link between the cutaneous microbiota and psoriasis, we conducted an analysis of skin bacterial communities of 28 psoriasis patients and 26 healthy subjects, sampled at six body sites using a standardized protocol and higher sequencing depth compared to previous studies. Mouse studies were employed to examine dermal microbial-immune interactions of bacterial species identified from our study. RESULTS: Skin microbiome profiling based on sequencing the 16S rRNA V1-V3 variable region revealed significant differences between the psoriasis-associated and healthy skin microbiota. Comparing the overall community structures, psoriasis-associated microbiota displayed higher diversity and more heterogeneity compared to healthy skin bacterial communities. Specific microbial signatures were associated with psoriatic lesional, psoriatic non-lesional, and healthy skin. Specifically, relative enrichment of Staphylococcus aureus was strongly associated with both lesional and non-lesional psoriatic skin. In contrast, Staphylococcus epidermidis and Propionibacterium acnes were underrepresented in psoriatic lesions compared to healthy skin, especially on the arm, gluteal fold, and trunk. Employing a mouse model to further study the impact of cutaneous Staphylcoccus species on the skin T cell differentiation, we found that newborn mice colonized with Staphylococcus aureus demonstrated strong Th17 polarization, whereas mice colonized with Staphylococcus epidermidis or un-colonized controls showed no such response. CONCLUSION: Our results suggest that microbial communities on psoriatic skin is substantially different from those on healthy skin. The psoriatic skin microbiome has increased diversity and reduced stability compared to the healthy skin microbiome. The loss of community stability and decrease in immunoregulatory bacteria such as Staphylococcus epidermidis and Propionibacterium acnes may lead to higher colonization with pathogens such as Staphylococcus aureus, which could exacerbate cutaneous inflammation along the Th17 axis.

RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways.

It has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis. However, little is known about the molecular differences between scalp, palmoplantar, and conventional plaque psoriasis. To investigate the molecular heterogeneity of these psoriasis subtypes, we performed RNA-seq and flow cytometry on skin samples from individuals with scalp, palmoplantar, and conventional plaque psoriasis, along with samples from healthy control patients. We performed differential expression analysis and network analysis using weighted gene coexpression network analysis (WGCNA). Our analysis revealed a core set of 763 differentially expressed genes common to all sub-types of psoriasis. In contrast, we identified 605, 632, and 262 genes uniquely differentially expressed in conventional, scalp, and palmoplantar psoriasis, respectively. WGCNA and pathway analysis revealed biological processes for the core genes as well as subtype-specific genes. Flow cytometry analysis revealed a shared increase in the percentage of CD4+ T regulatory cells in all psoriasis subtypes relative to controls, whereas distinct psoriasis subtypes displayed differences in IL-17A, IFN-gamma, and IL-22 production. This work reveals the molecular heterogeneity of plaque psoriasis and identifies subtype-specific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque 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.

Review of the mechanism of action of coal tar in psoriasis.

PURPOSE: Crude coal tar and its derivatives have been used in modern medicine for the treatment of psoriasis since at least 1925 as part of the Goeckerman regimen. To this day, coal tar remains a safe and highly effective option for the treatment of psoriasis vulgaris. However, the mechanism by which coal tar has its therapeutic effect is unknown. This review summarizes current knowledge of the mechanism by which coal tar has its therapeutic effect in the treatment of psoriasis vulgaris. MATERIAL AND METHODS: A Pubmed search was conducted on March 13, 2017 for relevant English language journal articles on the subject and were relevant journal articles were included in this review. RESULTS: Crude coal tar consists of thousands of ingredients, many of which are unidentified. Of these ingredients, the most research has gone into analyzing polycyclic aryl hydrocarbons. These hydrocarbons are thought to be the most likely component of crude coal tar that leads to its effects in psoriasis. Of the aryl hydrocarbons, carbazole has been the most well studied in psoriasis and is hypothesized as being responsible for the treatment efficacy of crude coal tar. CONCLUSIONS: Polycyclic aryl hydrocarbons, and specifically carbazole, are thought to be the mechanism by which crude coal tar has its effect in psoriasis. However, further research is warranted to fully characterize the mechanism of action of crude coal tar, with the potential to create new therapies for 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.

Correction to: Pain, Psychological Comorbidities, Disability, and Impaired Quality of Life in Hidradenitis Suppurativa.

The original version of this article contains an error in the spelling of the title. The title should read: Pain, Psychological Comorbidities, Disability, and Impaired Quality of Life in Hidradenitis Suppurativa.

Pain, Psychological Comorbidities, Disability, and Impaired Quality of Life in Hidradenitis Suppurativa [corrected].

PURPOSE OF REVIEW: Hidradenitis suppurativa (HS) is a chronic, painful dermatologic disease characterized by recurrent inflammatory nodules and abscesses of intertriginous areas such as the axilla and groin. People with HS suffer from greater pain and associated psychological comorbidities, including depression, anxiety, disability, and impairments in quality of life (QoL), compared to those with other dermatologic conditions. Our review focuses on the occurrence of pain and these relationships. RECENT FINDINGS: The existing literature indicates that acute and chronic pain, depression, anxiety, and disability all contribute to poor quality of life in individuals with HS. Despite the central role of pain and distress in the presentation of HS, few studies have empirically evaluated the impact of pain and gaps remain in the existing psychosocial literature. There are no formal guidelines for treating HS-specific pain or psychological comorbidities. The results of this review show a clear and pressing need to develop treatment recommendations and effective interventions for addressing acute and chronic pain, psychological comorbidities, disability, and impaired quality of life among people with HS. This review outlines a multidisciplinary approach to treating and managing pain and psychological comorbidities.

The metabolomics of psoriatic disease.

Metabolomics is an emerging new "omics" field involving the systematic analysis of the metabolites in a biologic system. These metabolites provide a molecular snapshot of cellular activity and are thus important for understanding the functional changes in metabolic pathways that drive disease. Recently, metabolomics has been used to study the local and systemic metabolic changes in psoriasis and its cardiometabolic comorbidities. Such studies have revealed novel insights into disease pathogenesis and suggest new biochemical signatures that may be used as a marker of psoriatic disease. This review will discuss common strategies in metabolomics analysis, current findings in the metabolomics of psoriasis, and emerging trends in psoriatic metabolomics.

National Psoriasis Foundation Priorities for Patient-Centered Research: Proceedings from the 2016 Conference.

The National Psoriasis Foundation (NPF) is developing an agenda for patient-centered research to help patients and their caregivers make more informed health care decisions by engaging psoriasis patients in prioritizing comparative effectiveness research (CER) topics. The NPF has created a novel patient-centered research platform known as Citizen Pscientist (CP), allowing patients with psoriasis and psoriatic arthritis to register and contribute their health data. The CP Governance Council administered an online 23-question CER survey to the CP community and held a structured meeting on December 3, 2016, with patients and researchers to review CER survey results and discuss patient-centered research priorities. Of the 2,945 patients surveyed, 792 patients responded. Three CER topics were deemed to be of high priority for the research agenda: 1) Treat-to-target therapy for psoriasis, 2) Psoriatic arthritis screening questionnaires for early detection and treatment of psoriatic arthritis, and 3) Comparative effectiveness of home-based phototherapy for psoriasis.

Monoclonal antibodies inhibiting IL-12, -23, and -17 for the treatment of psoriasis.

Psoriasis is a chronic, inflammatory, immune-mediated skin condition that affects 3 to 4% of the adult US population, characterized by well-demarcated, erythematous plaques with silver scale. Psoriasis is associated with many comorbidities including cardiometabolic disease and can have a negative impact on quality of life. The current armamentarium of psoriasis treatment includes topical therapies, phototherapy, oral immunosuppressive therapies, and biologic agents. Over the past 2 decades, there has been rapid development of novel biologic therapies for the treatment of moderate-to-severe plaque psoriasis. This article will review the role of IL-12, IL-23, and IL-17 in the pathogenesis of psoriasis and the monoclonal antibodies (ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab) that target these cytokines in the treatment of this disease.

The Role of the Skin and Gut Microbiome in Psoriatic Disease.

PURPOSE: To understand the changes in the microbiome in psoriatic disease, we conducted a systematic review of studies comparing the skin and gut microbiota in psoriatic individuals and healthy controls. FINDINGS: Our review of studies pertaining to the cutaneous microbiome showed a trend towards an increased relative abundance of Streptococcus and a decreased level of Propionibacterium in psoriasis patients compared to controls. In the gut microbiome, the ratio of Firmicutes and Bacteroidetes was perturbed in psoriatic individuals compared to healthy controls. Actinobacteria was also relatively underrepresented in psoriasis patients relative to healthy individuals. SUMMARY: Although the field of the psoriatic microbiome is relatively new, these first studies reveal interesting differences in microbiome composition that may be associated with the development of psoriatic comorbidities and serve as novel therapeutic targets.