Faculty Bibliography

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) -1β. Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1β( 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-1β, 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-1β. 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 are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, as well as in other tissues, like the skin. Several androgens are found normally in women, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), testosterone, dihydrotestosterone (DHT), 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 as well as 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, and/or FPHL. We review available evidence regarding when to consider an endocrinologic work-up in women presenting with AMCDs, including the appropriate type and timing of testing.

Androgen-mediated cutaneous disorders (AMCDs) in women including acne, hirsutism, and female pattern hair loss (FPHL) can be treated with hormone-modulating therapies. In the second part of 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 utilized for each AMCDs are reviewed, along with mechanisms of androgen modulation, safety profile, contraindications, monitoring parameters, and evidence of efficacy. Medications discussed include ones that are FDA-approved for certain AMCDs as well as 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 FPHL.