Faculty Bibliography

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.

Secondary Raynaud's phenomenon (RP) is often the sentinel clinical finding in systemic sclerosis and may precede systemic disease by several years. Altered nitric oxide metabolism plays a critical role in both fibrosis and severe secondary RP phenotypes in these patients. Increased flux through inducible nitric oxide synthase (iNOS) drives cutaneous fibrosis. Failure of flux through endothelial nitric oxide synthase (eNOS) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by eNOS is in part due to increased levels of asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased ADMA levels may be counteracted increasing serum L-arginine, which is often an effective treatment strategy in these patients. As such, L-arginine based therapies should be considered in managing secondary RP, particularly given their favorable safety and tolerability profile. While there is no established dosing regimen, studies of oral L-arginine in secondary RP suggest that divided dosing may begin at 1-2g/day and may be titrated up to 10g/day. Conversely, primary RP is not associated with increased ADMA production which likely accounts for the failure of L-arginine trials to show benefit in primary RP.

Treatment of malignancy with anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors can cause mucocutaneous side effects resulting from T cell activation. Due to their recent development, the full side effect profile remains to be fully elucidated, however dermatologic adverse events are most common. The main oral toxicities of these immune checkpoint inhibitors include: xerostomia, dysgeusia, and lichenoid reactions. Oral mucositis occurs more rarely in the setting of PD-1 inhibition, and few other reports of a Grade 3 or higher, severe, stomatitis have been reported in the literature. We present a case of a 78-year-old woman with Grade 3 ulcerative oral mucositis that occurred 13 months after initiation of PD-1 inhibitor, pembrolizumab, for the treatment for lung adenocarcinoma. She was successfully treated with prednisone, and pembrolizumab was temporarily held by her oncologist. Physicians should be aware of the possibility of severe mucositis in the setting of PD-1 inhibitors, as well as the management. J Drugs Dermatol. 2018;17(7):807-809.

BACKGROUND:Multiple placebo controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP). OBJECTIVES/OBJECTIVE:The objective of this meta-analysis was to assess the effects of local topical nitrates in primary and secondary RP with respect to a combined endpoint integrating parameters of digital blood flow and clinical severity. METHODS:A systematic review was performed using MEDLINE, Embase and the Cochrane library. Only trials comparing locally applied topical nitrates to placebo comparators were included. Studies were appraised for bias by two independent reviewers. RESULTS:Seven placebo controlled trials including 346 patients were used in meta-analysis. Four trials used nitroglycerin ointments, two used MQX-503 and one used compounded nitrite. Meta-analysis results support a moderate to large treatment effect in Raynaud's phenomenon, standardized mean difference (SMD)=0.70, (0.35 to 1.05, p<0.0001). Subgroup analyses showed a large treatment effect in secondary RP, SMD=0.95 (0.25 to 1.65, p=0.008) and moderate effect in primary RP, SMD=0.45 (0.05 to 0.85, p=0.03). LIMITATIONS/CONCLUSIONS:Limitations include the inclusion of multiple topical nitrate preparations and integration of different outcomes assessments. CONCLUSION/CONCLUSIONS:Local topical nitrates have significant efficacy in the treatment of both primary and secondary Raynaud's phenomenon.

Platelet-rich plasma and microneedling have been investigated recently as potential therapeutic options for the treatment of hair disorders. Evidence from laboratory studies indicates that these treatments enhance growth factor production that in turn facilitates hair follicle development and cycling. Several small studies and case reports have presented encouraging findings regarding the use of these treatments for alopecia areata. Future investigations will be needed to validate these therapeutic techniques for patients with alopecia areata and further refine which subtypes of the disease these methods are best indicated for.