Faculty Bibliography

Vitiligo, an acquired depigmentation disorder, results from autoimmune targeting of melanocytes. Vitiligo can be triggered following exposure to phenols such as monobenzone (MBEH) and 4-tertiary butyl phenol (4-TBP). Melanocytes from individuals with idiopathic vitiligo (trigger is not known) are more sensitive to MBEH and 4-TBP. We hypothesized that stress response pathways activated following exposure to vitiligo triggers may be dysregulated in individuals who develop the disorder. We delineated the response of melanocytes from normally pigmented individuals (NMs) to challenge with MBEH and 4-TBP and identified two key survival pathways activated following exposure: the NRF2-regulated antioxidant response and the unfolded protein stress response (UPR). NRF2 knockdown sensitized NMs to MBEH (p < 0.0001), while NRF2 activation by knockdown of its repressor KEAP significantly decreased sensitivity (p < 0.0001). Similarly, inhibition of the PERK-eIF2alpha arm of the UPR with the chemical inhibitor GSK2606414 increased sensitivity to MBEH (cleaved PARP observed at 250 muM MBEH with GSK2606414 and 400 muM without). Activation of NRF2-regulated antioxidant responses and PERK-mediated phosphorylation of eIF2alpha following MBEH exposure was impaired in melanocytes from individuals who developed vitiligo. We have thus identified two stress response pathways that may be dysfunctional in vitiligo and contribute to the onset of depigmentation

Tinea incognito (TI) describes a common dermatophytosis with often atypical clinical features attributed to inappropriate use of topical immunomodulatory agents, usually corticosteroids. Given the high prevalence of TI and limited literature detailing this condition, we conducted a retrospective review of cases of pediatric dermatophytosis presenting to the Faculty Group Practice of the Ronald O. Perelman Department of Dermatology, New York University School of Medicine (New York, New York), between 2005 and 2016. Among microbiologically confirmed dermatophytosis cases, we found that even with prior treatment, TI often presented with classic features of tinea such as annularity and scale. The majority of cases were treated with oral antifungals, though some were treated with topical antifungals alone. This case series underscores the need to maintain a high clinical suspicion for TI.

PURPOSE/OBJECTIVE:Washing and over-the-counter cleansers are common interventions in acne vulgaris (AV), but the clinical evidence for their benefit is poorly understood. This systematic review presents clinical studies of washing and cleanser efficacy in acne vulgaris to guide treatment recommendations of dermatologists. MATERIALS AND METHODS/METHODS:We surveyed English-language articles indexed in MEDLINE (1951-March 2017) and EMBASE (1974-March 2017). Articles were required to be prospective studies of a single over-the-counter cleanser or washing intervention in AV with an objective AV outcome measurement published in a peer-reviewed journal. RESULTS AND CONCLUSIONS/CONCLUSIONS:Fourteen prospective studies representing 671 participants were included in this review. Modalities investigated included face washing frequency, true soap/syndet cleansing bars, antiseptic cleansers, alpha and beta-hydroxy (i.e. salicylic) acid cleansers, and several proprietary formulations. Given the low number of well-performed clinical studies of cleansers and washing, it is difficult to formulate reliable recommendations. We hope that our findings highlight the necessity of further investigation in this area.

Keratosis pilaris is a common skin disorder comprising less common variants and rare subtypes, including keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Data, and critical analysis of existing data, are lacking, so the etiologies, pathogeneses, disease associations, and treatments of these clinical entities are poorly understood. The present article aims to fill this knowledge gap by reviewing literature in the PubMed, EMBASE, and CINAHL databases and providing a comprehensive, analytical summary of the clinical characteristics and pathophysiology of keratosis pilaris and its subtypes through the lens of disease associations, genetics, and pharmacologic etiologies. Histopathologic, genomic, and epidemiologic evidence points to keratosis pilaris as a primary disorder of the pilosebaceous unit as a result of inherited mutations or acquired disruptions in various biomolecular pathways. Recent data highlight aberrant Ras signaling as an important contributor to the pathophysiology of keratosis pilaris and its subtypes. We also evaluate data on treatments for keratosis pilaris and its subtypes, including topical, systemic, and energy-based therapies. The effectiveness of various types of lasers in treating keratosis pilaris and its subtypes deserves wider recognition.

BACKGROUND:Little is known about how dermatologists prescribe hormonal antiandrogen acne treatment (HAAT). OBJECTIVE:The aim of this study was to investigate dermatologists' HAAT-prescribing habits and HAAT's impact on systemic antibiotic use in women with acne. METHODS:We performed a retrospective study at an academic medical center of female patients receiving HAAT (combined oral contraceptive [COC], spironolactone) for acne from January 2005 to October 2015. Data from a control group of female acne patients who never received HAAT were also collected. RESULTS:A total of 672 female patients received HAAT. Out of all systemic medications for acne, antibiotics were used as first-line treatment in 39% of patients, COCs in 12%, and spironolactone in 21%. Mean antibiotic durations in patients who initiated HAAT for the first time at the study site (250.4 days) were significantly longer than in patients who received HAAT prior to presentation and continued HAAT at the study site (192.0 days) (p = 0.021). A statistically significant inverse association was found between HAAT use and mean antibiotic duration (p = 0.016). CONCLUSIONS:HAAT is not typically used as a first-line systemic therapy in women with acne. HAAT usage is associated with shorter cumulative antibiotic durations and early HAAT initiation can decrease systemic antibiotic use in acne treatment.

Interfollicular epidermal melanocytes are continually subjected to environmental challenges and activate protective stress responses for survival. Dysregulation of these responses may increase susceptibility to autoimmune-mediated destruction resulting in progressive skin depigmentation typical of vitiligo. We have shown that challenging melanocytes from normally pigmented individuals (NMs) with chemicals known to trigger vitiligo, such as monobenzone, results in activation of the unfolded protein response (UPR). In this study, we investigated the impact of the PERK-eIF2alpha (activated PERK phosphorylates eIF2alpha) and IRE1alpha-XBP1 (activated IRE1alpha promotes splicing and expression of XBP1) axes of the UPR on melanocyte viability and sensitivity to monobenzone. NMs exhibited high basal PERK-eIF2alpha signaling compared to keratinocytes and dermal fibroblasts, and PERK knockdown substantially reduced melanocyte viability (p < 0.01), even in the absence of challenge. PERK inhibition increased sensitivity to monobenzone, while inhibition of IRE1alpha kinase activity, did not affect melanocyte toxicity. NMs that survive PERK knockdown were used to establish long-term cultures (shPERKLT), which exhibited a paradoxical increase in phospho-eIF2alpha with reduced sensitivity to monobenzone. Sustained eIF2alpha phosphorylation was reduced with downregulation of PKR and GCN2, alternative eIF2alpha kinases, suggesting a role for these kinases in melanocyte adaptation. Melanocytes from individuals with idiopathic vitiligo (VMs) exhibited increased sensitivity to monobenzone compared to NMs. VMs markedly activated the IRE1alpha/XBP1 pathway, reflected by an increase in XBP1 splicing. VMs also did not phosphorylate eIF2alpha in response to monobenzone treatment. Dysfunction of this protective response in VMs, in combination with increased IRE1alpha/XBP1 activity which promotes expression of chemokines, such as interleukin 6, that recruit immune cells to the skin, may contribute to the onset of autoimmunity in vitiligo. The UPR may thus represent a novel therapeutic target for vitiligo

The mechanisms that initiate vitiligo are poorly understood. Vitiligo triggers, such as monobenzone (MB) exposure, induce stress. Understanding the survival responses that combat this stress is key to determining why melanocytes become immune targets. MB induces oxidative and endoplasmic reticulum (ER) stress, which activates the unfolded protein response (UPR). PERK, a UPR initiator, phosphorylates eIF2alpha and master antioxidant regulator, NRF2. Here, we investigated the impact of PERK-eIF2alpha/-NRF2 activation on sensitivity to MB. Basal phospho-eIF2alpha and NRF2 levels are higher in melanocytes compared to fibroblasts or keratinocytes. PERK downregulation significantly reduced melanocyte viability (implicated in several autoimmune disorders) may link exposure to vitiligoinducing triggers with onset of autoimmunity

BACKGROUND: To some degree, acne vulgaris affects nearly every individual worldwide. Oral antibiotic therapy is routinely prescribed for the treatment of moderate to severe inflammatory acne; however, long-term use of oral antibiotics for acne may have unintended consequences. OBJECTIVE: The aim of this study was to provide a systematic evaluation of the scientific evidence on the efficacy and appropriate use of oral antibiotics in the treatment of acne. METHODS: A systematic search of MEDLINE was conducted to identify randomized controlled clinical trials, systematic reviews, and meta-analyses evaluating the efficacy of oral antibiotics for acne. Overall, 41 articles that examined oral antibiotics compared with placebo, another oral therapy, topical therapy, alternate dose, or duration were included in this study. RESULTS: Tetracyclines, macrolides, and trimethoprim/sulfamethoxazole are effective and safe in the treatment of moderate to severe inflammatory acne. Superior efficacy of one type or class of antibiotic could not be determined, therefore the choice of antibiotic is generally based on the side-effect profile. Although different dosing regimens have been studied, there is a lack of standardized comparator trials to determine optimal dosing and duration of each oral antibiotic used in acne. The combination of oral antibiotics with a topical therapy is superior to oral antibiotics alone. CONCLUSION: This article provides a systematic evaluation of the scientific evidence of the efficacy of oral antibiotics for acne. Due to heterogeneity in the design of the trials, there is insufficient evidence to support one type, dose, or duration of oral antibiotic over another in terms of efficacy; however, due to increasing resistance to antibiotics, dermatologists should heed consensus guidelines for their appropriate use.