Inflammasome Signaling and Impaired Vascular Health in Psoriasis.

Objective- Psoriasis is an inflammatory skin disease which heightens the risk of cardiovascular disease. This study directly investigated vascular endothelial health and systemically altered pathways in psoriasis and matched controls. Approach and Results- Twenty patients (mean age, 40 years; 50% male) with active psoriasis and 10 age-, sex-matched controls were recruited. To investigate systemically alerted pathways, a deep sequencing omics approach was applied, including unbiased blood transcriptomic and targeted proteomic analysis. Vascular endothelial health was assessed by transcriptomic profiling of endothelial cells obtained from the brachial veins of recruited participants. Blood transcriptomic profiling identified inflammasome signaling as the highest differentially expressed canonical pathway ( Z score 1.6; P=1×10-7) including upregulation of CASP5 and interleukin ( IL) -1ß. Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1ß ( Z score 3.7; P=1.02×10-23) as an upstream activator of the observed upregulated proteins. Direct profiling of harvested brachial vein endothelial cells demonstrated inflammatory transcript (eg, IL-1ß, CXCL10, VCAM-1, IL-8, CXCL1, Lymphotoxin beta, ICAM-1, COX-2, and CCL3) upregulation between psoriasis versus controls. A linear relationship was seen between differentially expressed endothelial inflammatory transcripts and psoriasis disease severity. IL-6 levels correlated with inflammatory endothelial cell transcripts and whole blood inflammasome-associated transcripts, including CASP5 and IL-1ß. Conclusions- An unbiased sequencing approach demonstrated the inflammasome as the most differentially altered pathway in psoriasis versus controls. Inflammasome signaling correlated with psoriasis disease severity, circulating IL-6, and proinflammatory endothelial transcripts. These findings help better explain the heightened risk of cardiovascular disease in psoriasis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03228017.

Androgens in women: Androgen-mediated skin disease and patient evaluation.

Androgens are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, and in other tissues, like the skin. Several androgens are found normally in women, including dehydroepiandrosterone, dehydroepiandrosterone-sulfate, testosterone, dihydrotestosterone, and androstenedione. These androgens are essential in the development of several common cutaneous conditions in women, including acne, hirsutism, and female pattern hair loss (FPHL)-androgen-mediated cutaneous disorders (AMCDs). However, the role of androgens in the pathophysiology of these diseases is complicated and incompletely understood. In the first article in this Continuing Medical Education series, we discuss the role of the skin in androgen production and the impact of androgens on the skin in women. Specifically, we review the necessary but insufficient role that androgens play in the development of acne, hirsutism, and FPHL in women. Dermatologists face the challenge of differentiating physiologic from pathologic presentations of AMCDs in women. There are currently no dermatology guidelines outlining the indications for endocrinologic evaluation in women presenting with acne, hirsutism, or FPHL. We review the available evidence regarding when to consider an endocrinologic workup in women presenting with AMCDs, including the appropriate type and timing of testing.

Androgens in women: Hormone-modulating therapies for skin disease.

Androgen-mediated cutaneous disorders (AMCDs) in women, including acne, hirsutism, and female pattern hair loss, can be treated with hormone-modulating therapies. In the second article in this Continuing Medical Education series, we discuss the hormone-modulating therapies available to dermatologists for the treatment of AMCDs, including combined oral contraceptives, spironolactone, finasteride, dutasteride, and flutamide. Available hormone-modulating treatments used for each AMCDs are reviewed, along with mechanisms of androgen modulation, safety profile, contraindications, monitoring parameters, and evidence of efficacy. Medications discussed include those that are approved by the US Food and Drug Administration for certain AMCDs and some that are used off-label. Despite the ubiquity of hormone-modulating therapies used for AMCDs, this review highlights the need for more rigorous studies to evaluate these therapies for acne, hirsutism, and female pattern hair loss.

Factors Related to Migraine Patients' Decisions to Initiate Behavioral Migraine Treatment Following a Headache Specialist's Recommendation: A Prospective Observational Study.

Objective: To evaluate the frequency with which migraine patients initiated behavioral migraine treatment following a headache specialist recommendation and the predictors for initiating behavioral migraine treatment. Methods: We conducted a prospective cohort study of consecutive patients diagnosed with migraine to examine whether the patients initiated behavioral migraine treatment following a provider recommendation. The primary outcome was scheduling the initial visit for behavioral migraine treatment. Patients who initiated behavioral migraine treatment were compared with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. Results: Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment. Fifty-three (76.8%) patients referred for behavioral treatment were reached by phone. The mean duration from time of referral to follow-up was 76 (median 76, SD = 45) days. Thirty (56.6%) patients initiated behavioral migraine treatment. There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control (P > 0.05). Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not. Time constraints were the most common barrier cited for not initiating behavioral migraine treatment. Conclusions: Less than one-third of eligible patients were referred for behavioral treatment, and only about half initiated behavioral migraine treatment. Future research should further assess patients' decisions regarding behavioral treatment initiation and methods for behavioral treatment delivery to overcome barriers to initiating behavioral migraine treatment.

Clinical Characteristics of Synthetic Cannabinoid Use in a Large Urban Psychiatric Emergency Setting.

BACKGROUND: Increasing reports of synthetic cannabinoid (SC)-related adverse events have largely comprised case reports and analyses of calls to poison control centers. Existing studies have also mostly involved white male populations. OBJECTIVES: The purpose of this study is to systematically describe clinical characteristics of SC use in a relatively large, diverse, urban sample presenting to a psychiatric emergency setting. METHODS: SC users (n = 110) were identified by reviewing charts (n = 948) from the psychiatric emergency service of a large, urban public hospital in the United States for November 2014, which was randomly selected from the 12 months of that year. Sociodemographic data were collected from administrative databases and clinical data were collected from the electronic medical record. RESULTS: SC users were mostly non-white (90.0%) males (95.5%), who were likely to be police-involved (34.5%) and homeless (84.5%). SC users also had significant and often pre-existing psychiatric and substance use comorbidity, including acute psychotic symptoms (70.0%), more than one comorbid psychiatric diagnosis (31.8%) and primary psychotic disorder diagnosis (40.0%), past psychiatric visits to the hospital (70.9%), comorbid substance use (62.7%), agitation requiring intervention (22.7%), and the need for extended psychiatric observation (15.5%) and inpatient admission (34.5%). Relatively limited medical complications were identified. Conclusions/Importance: In this sample, SC use affected a sociodemographically disadvantaged and mentally ill population, likely exacerbating existing psychiatric problems. This is one of the only studies to systematically examine the clinical effects of SC use in a significant clinical sample, and the first study in an urban, racial/ethnic minority, and vulnerable sample.