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The PERK branch of the unfolded protein response and Nrf2-regulated antioxidants maintain melanocyte survival: Implications for vitiligo initiation [Meeting Abstract]

Arowojolu, OA; Orlow, SJ; Manga, P
ISI:000380028800655
ISSN: 1523-1747
CID: 2216132

Microbes and atopic dermatitis: The Yin and Yang of barrier and immune dysfunction [Review]

Cohen, BE; Orlow, SJ
Atopic dermatitis (AD) is a chronic, inflammatory skin condition caused by a complex interaction of genetic and environment factors. Inherited defects within the stratum corneum are increasingly recognised as a key causative factor in the development of AD. Patients with AD also demonstrate a high rate of colonisation by microbes, notably Staphylococcus aureus. Controversy exists regarding the use of antimicrobial agents in the management of AD. We briefly review the role of stratum corneum dysfunction in AD, the influence of cutaneous colonisation and infections, and provide an update on the utility of anti-staphylococcal treatment in AD.
ISI:000373865900003
ISSN: 1814-7453
CID: 2098082

Comparison of Childhood Vitiligo Presenting with or without Associated Halo Nevi

Cohen, Brandon E; Mu, Euphemia W; Orlow, Seth J
BACKGROUND: Previous studies have characterized differences in vitiligo associated with halo nevi, but the features of vitiligo presenting with halo nevus in children have yet to be fully described. AIMS: We sought to provide an epidemiologic and clinical comparison of cases of childhood vitiligo presenting with or without associated halo nevi. MATERIALS AND METHODS: This was a retrospective chart review of children diagnosed with vitiligo in an academic pediatric dermatology practice from January 1990 to November 2014. The characteristics of children with vitiligo with or without associated halo nevi were compared. RESULTS: Halo nevi were identified in 55 (26%) of 208 children with vitiligo. Patients with halo nevi were significantly more likely to be male and develop vitiligo at a later age. Children with vitiligo associated with halo nevi were more likely to present with generalized vitiligo, defined according to the presence of bilateral macules. DISCUSSION: There was no significant association between groups in the percentage of body surface area with vitiligo or family history of vitiligo or autoimmune diseases. Patients with halo nevi were no more likely to develop new areas of vitiligo during the follow-up period, but there was a nonsignificant trend toward a higher rate of repigmentation in vitiligo associated with halo nevus. CONCLUSION: Halo nevi are a common finding in children with vitiligo. The presence of a halo nevus in a child with vitiligo is associated with generalized vitiligo. The presence of a halo nevus does not significantly alter the risk of disease progression and rate of treatment.
PMID: 26573093
ISSN: 1525-1470
CID: 2040302

Segmental stiff skin syndrome (SSS): A distinct clinical entity

Myers, Kathryn L; Mir, Adnan; Schaffer, Julie V; Meehan, Shane A; Orlow, Seth J; Brinster, Nooshin K
BACKGROUND: Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles. OBJECTIVE: We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases. METHODS: This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search. RESULTS: Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups. LIMITATIONS: This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases. CONCLUSIONS: We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features.
PMID: 26944597
ISSN: 1097-6787
CID: 2009542

The use of oral antibiotics before isotretinoin therapy in patients with acne

Nagler, Arielle R; Milam, Emily C; Orlow, Seth J
BACKGROUND: Systemic antibiotics are used widely to treat moderate to severe acne, but increasing antibiotic resistance makes appropriate use a priority. OBJECTIVE: We sought to determine the duration of systemic antibiotic use in patients with inflammatory/nodulocystic acne who eventually required isotretinoin. METHODS: We performed a retrospective, single-site chart review of patients with acne diagnostic codes evaluated January 1, 2005 to December 31, 2014, at a dermatology practice in an academic medical center. Included patients were prescribed isotretinoin during the study period and received 30 days or more of antibiotics. RESULTS: The average duration of antibiotic use was 331.3 days. In all, 21 patients (15.3%) were prescribed antibiotics for 3 months or less, 88 patients (64.2%) for 6 months or more, and 46 patients (33.6%) for 1 year or longer. Patients treated only at the study site had a mean duration of antibiotic treatment of 283.1 days whereas patients who also received antibiotics from another institution had a mean duration of 380.2 days. This difference approached statistical significance (P = .054). LIMITATIONS: This study was limited to a single center. CONCLUSION: Expert guidelines recommend responsible use of antibiotics in acne in light of emerging resistance. We found that patients who eventually received isotretinoin had extended exposure to antibiotics, exceeding recommendations. Early recognition of antibiotic failure and the need for isotretinoin can curtail antibiotic use.
PMID: 26525749
ISSN: 1097-6787
CID: 1825782

Alternative Systemic Treatments for Vitiligo: A Review

Cohen, Brandon E; Elbuluk, Nada; Mu, Euphemia W; Orlow, Seth J
Vitiligo is a common, acquired disorder of skin pigmentation that can significantly impact quality of life. It often represents a therapeutic challenge, which has resulted in interest in alternative treatments such as herbal and vitamin supplements. In this review, we provide an overview of the most commonly studied complementary agents, describe proposed mechanisms of action, identify potential adverse effects, and discuss the primary evidence supporting their use. Our discussion focuses on L-phenylalanine, Polypodium leucotomos, khellin, Ginkgo biloba, and vitamins and minerals, including vitamins B12, C, and E, folic acid, and zinc used as monotherapy or in combination with other treatments for the management of vitiligo.
PMID: 26329814
ISSN: 1175-0561
CID: 1761762

Early-onset childhood vitiligo is associated with a more extensive and progressive course

Mu, Euphemia W; Cohen, Brandon E; Orlow, Seth J
OBJECTIVES: Vitiligo commonly presents in children, with half of all cases developing before 20 years of age. Although studies have characterized differences between pediatric and adult vitiligo, little is known about vitiligo presenting in early childhood. The purpose of this study was to compare clinical features of early-onset (<3 years old) and later-onset (3-18 years old) childhood vitiligo. METHODS: This retrospective case series examined patients given a diagnosis of vitiligo in a pediatric dermatology practice at an academic medical center from 1990 to 2014. Characteristics of the early- and later-onset groups were compared by chi2 and t test for categorical and continuous variables, respectively. RESULTS: Of the 208 children in the study, 31 had early-onset and 177 had later-onset disease. Early-onset vitiligo was associated with higher percentages of body surface area involvement and increased rates of disease progression during an average 1.9 years of follow-up. There were no significant differences between the 2 groups in repigmentation, vitiligo type, halo nevi, gender ratio, or personal and family history of autoimmune diseases. LIMITATIONS: This was a retrospective, single-institution study. CONCLUSION: Patients given a diagnosis of vitiligo at younger ages tend to have more extensive and progressive disease.
PMID: 26118892
ISSN: 1097-6787
CID: 1649742

Culinary Metaphors in Dermatology: Eating Our Words

Milam, Emily C; Mu, Euphemia W; Orlow, Seth J
PMID: 25714065
ISSN: 2168-6084
CID: 1473842

Dermatologists' Attitudes, Prescription, and Counseling Patterns for Isotretinoin: A Questionnaire-based Study

Nagler, Arielle R; Orlow, Seth J
Isotretinoin, the most effective therapy for severe acne, has engendered controversy. These controversies impact dermatologists' opinions of isotretinoin and prescription behaviors. This study was designed to characterize dermatologists' opinions of controversies surrounding isotretinoin, as well as counseling and prescribing practices. A 25-question survey was emailed to 7,013 dermatologists included in a proprietary database (MBD, Inc.) and anonymous responses were collected. 591 board-certified dermatologists participated. Thirty-seven percent of the responding dermatologists believe that isotretinoin may cause psychiatric disturbances. Dermatologists' opinions on this relationship did not significantly impact prescription practices in patients with history of depression (P=0.056) or in patients being treated with an antidepressant (P=0.118). A larger percentage of dermatologists surveyed believe there is a causal relationship between isotretinoin and psychiatric disturbances than isotretinoin and IBD. Of the surveyed dermatologists, 2.7% believe there is a causal association between isotretinoin and inflammatory bowel disease IBD. In addition, physicians with 20 or fewer years of experience, which included 50% of the responding dermatologists, were significantly less likely to have read the patient brochure (P=0.004), and more likely to prescribe isotretinoin to patients who had not failed systemic antibiotics (P =0.015). This questionnaire also may highlight a practice gap, as more recently trained dermatologists appear less likely to require failure of systemic antibiotics prior to initiating isotretinoin

J Drugs Dermatol 2015;14(2):184-189.
PMID: 25689814
ISSN: 1545-9616
CID: 1466112

Activation of melanocyte antioxidant response pathways following exposure to vitiligo-inducing phenols: Implications for vitiligo pathogenesis [Meeting Abstract]

Arowojolu, O A; Orlow, S J; Manga, P
Vitiligo is a common disorder characterized by progressive melanocyte death. Vitiligo can be induced in an occupational setting by exposure to vitiligo-inducing phenols (VIPs) such as 4 tert-butyl phenol (4TBP) and monobenzyl ether of hydroquinone (MBEH). These VIPs are believed to specifically target melanocytes due to their structural similarity to tyrosine and competition for binding to tyrosinase, the rate-limiting enzyme for melanin synthesis. By exposing normal melanocytes to VIPs and using microarray analysis and bioinformatics approaches for gene expression profiling, we identified key signaling pathways that are involved in the melanocyte response to VIP exposure. In particular, we hypothesized that exposure of primary human melanocytes to VIPs would result in oxidative stress that triggers antioxidant responses in order to protect melanocytes from cell death. Following melanocyte exposure to VIPs, HO-1 was upregulated (4TBP exposure: 5.49-fold; MBEH exposure: 25.98- fold). HO-1 is a direct target of Nrf2, a key regulator of the Nrf2- ARE antioxidant response. Activation of Nrf2 and its targets, HO- 1 and NQO1, was confirmed by conventional Western blot analysis and quantitative RT-PCR. We are now characterizing the mechanisms that regulate Nrf2 activation in response to VIPs. Additional antioxidants including SOD2 (4TBP: 10.5-fold; MBEH: 38.5-fold), peroxiredoxin 6 (4TBP: 2.44-fold; MBEH: 15.18-fold), and Nrf2 binding partners, MafK (4TBP: 2.12-fold; MBEH: 2.50- fold) and MafF (4TBP: 2.32-fold; MBEH: 3.16-fold) were also upregulated with VIP exposure and are being investigated further. Several studies have revealed dysfunctional antioxidant responses in melanocytes from patients with vitiligo, however the underlying mechanisms that reduce their efficacy are yet to be determined. We hypothesize that investigation of VIP-induced pathways may lead to the characterization of these mechanisms and provide opportunities for development of targeted therapeutics for the treatment of vitiligo
EMBASE:71656845
ISSN: 1755-1471
CID: 1362922