The impact of positive antinuclear antibody on narrowband ultraviolet B phototherapy in patients with vitiligo: A retrospective chart review.

BACKGROUND/PURPOSE: Screening antinuclear antibody (ANA) is not recommended prior to initiating narrowband ultraviolet B (NBUVB) phototherapy in vitiligo patients, unless concern for photosensitivity exists. Guidelines on prescribing NBUVB phototherapy in vitiligo patients with positive ANA are unavailable, prompting this study to uncover trends. METHODS: This retrospective chart review investigated patients 12 years of age or older with a diagnosis of vitiligo between January 2015 and September 2017, positive serum ANA, and NBUVB phototherapy. Demographic information, vitiligo type, ANA titer/pattern, starting dose, peak dose without phototoxicity, phototherapy frequency, total number of phototoxic events and treatments, coexisting photosensitizing disorders, and concomitant photosensitizing medications were collected. RESULTS: Seven (two males, five females) of 1485 charts met inclusion criteria. One Caucasian, two African-Americans, one Asian, and three Hispanic/Latinos patients were represented. Six of seven patients had generalized vitiligo and one had focal vitiligo. ANA titer/patterns and phototherapy frequencies were evaluated. Peak doses of NBUVB without phototoxic event were available in six of seven patients: 274, 290, 532, 618, 700, and 734 mJ/cm2 . Total number of phototoxic events varied: 1 (n = 1), 2 (n = 1), 4 (n = 1), 6 (n = 2), or 8 (n = 1). Total NBUVB treatments ranged between 6 and 132. Coexisting photosensitizing disorders were not identified. One patient had phototoxic events in association with photosensitizing medications. CONCLUSION: With regard to phototoxicity, meaningful trends were not identified that may guide prescription of phototherapy in vitiligo patients with positive ANA, suggesting ANA may not be exclusionary criteria when prescribing NBUVB.

The potential role of antioxidants in mitigating skin hyperpigmentation resulting from ultraviolet and visible light-induced oxidative stress.

Oxidative stress is an integral element that influences a variety of biochemical reactions throughout the body and is known to play a notable role in melanogenesis. Exogenous triggers of oxidative stress, such as ultraviolet radiation (UVR) and visible light (VL), lead to pigment formation through somewhat different pathways, but both share a common endpoint-the potential to generate cosmetically undesirable hyperpigmentation. Though organic and inorganic sunscreens are available to protect against the UVR portion of the electromagnetic spectrum, coverage is lacking to protect against the VL spectrum. In this manuscript, we review the phases of tanning, pathways of melanogenesis triggered by UVR and VL, and the associated impact of oxidative stress. We also discuss the known intrinsic mechanisms and paracrine regulation of melanocytes that influence their response to UVR. Understanding these mechanisms and their role in UVR-induced hyperpigmentation should potentially lead to identification of useful targets that can be coupled with antioxidant therapy to alleviate this effect.

Spectral characteristics of visible light-induced pigmentation and visible light protection factor.

Solar radiation is a major contributor to the development of skin cancer. Recent studies have shown that visible light (VL), a major portion of solar spectrum, induces biologic effects on the skin. Ultraviolet filters in currently available broad-spectrum sunscreens do not offer protection against VL. This study was designed to identify the spectral characteristics of the skin responses induced by VL, which can be utilized for time efficient in vivo VL testing. Thirty-one subjects were irradiated with a light source emitting visible light with less than 0.5% long wavelength UVA1 (VL + UVA1, 370-700 nm), and 41 subjects were irradiated with pure visible light (pure VL, 400-700 nm). Assessments including clinical photography, investigator's global assessment of pigmentation and erythema, and diffuse reflectance spectroscopy (DRS) performed immediately and seven days after irradiation. Clinical and spectroscopic data showed that VL + UVA1 spectral output induced significantly darker and persistent skin responses as compared to those induced by pure VL. Spectroscopic signatures of skin responses induced by both radiation sources were identified. The signatures were found to be specific to the radiation source and time of collection. A method to evaluate VL protection factor, using quantitative information from the spectral signatures obtained, was proposed.

Oral Polypodium Leucotomos Extract and Its Impact on Visible Light-Induced Pigmentation in Human Subjects

BACKGROUND: Visible light (VL) has multiple effects on the skin that currently available sunscreens do not protect against. Polypodium leucotomos extract (PLE) has properties that may offer protection against VL. OBJECTIVES: To determine the effectiveness of PLE in preventing VL-induced effects. METHODS: Twenty-two subjects with Fitzpatrick skin phototype IV-VI were enrolled. On day 0, subjects were irradiated with VL. Clinical Investigator's Global Assessment (IGA) scoring and spectroscopic evaluations were performed immediately, 24 hours, and 7 days after irradiation. Subjects then received a 28-day supply of PLE (480 mg daily). Irradiation and evaluation were repeated. Three 4-mm punch biopsies were obtained for immunohistochemistry analysis: one from normal unirradiated skin and the other two twenty-four hours after irradiation, pre- and post-PLE, from sites irradiated with highest dose of VL. RESULTS: All subjects had immediate pigment darkening, persistent pigment darkening, and delayed tanning both pre- and post-PLE. For the highest VL dose (480 J/cm²) spectroscopic assessments demonstrated a statistically significant decrease in persistent pigment darkening and delayed tanning post-PLE. In addition, there was a significant decrease in cyclooxygenase-2, and a trend towards decreases in the markers for cellular damage post-PLE. While there was a trend towards lower IGA scores post-PLE, statistical significance was not reached possibly due to lack of sensitivity of the visual IGA scoring system in detecting small changes. CONCLUSIONS: Spectroscopic data and immunohistochemistry indicate an effect of PLE on visible light induced effects. As such, PLE may be used as an adjuvant to traditional means of photoprotection to protect against the effects of VL. Clinical trial registration number: NCT02904798. J Drugs Dermatol. 2019;18(12):1198-1203.

Update on the Management of Vitiligo

Vitiligo is an acquired, autoimmune disease characterized by depigmented macules and patches on the skin, which occur secondary to melanocyte destruction. Available therapeutic options are broadly divided into medical, surgical and phototherapy, though treatment of vitiligo can be challenging. Early diagnosis and management can maximize treatment efficacy. The purpose of this discussion is to review updates in the management of vitiligo, including existing and emerging therapies.

Dihydroxyacetone: A Review.

The sunless tanning industry has experienced rapid growth due to public education on the dangers of ultraviolet radiation on skin and improvements in products. Dihydroxyacetone (DHA) is a 3-carbon sugar allowed by the Food and Drug Administration (FDA) as a color additive in sunless tanning products. Bronzers, a product removed with soap and water, may also contain DHA. We aim to review the literature on DHA. DHA is intended for external application, not including the mucous membranes or in or around the eye area. DHA has been used in spray-tan booths and by airbrushing it onto consumers, although these are unapproved uses, as contact with the color additive is not restricted to the external part of the body. Consequently, the FDA recommends customers shield their eyes, lips, and mucous membranes, as well as refrain from ingestion or inhalation of DHA. Unlike sunscreens, products that protect against ultraviolet radiation and are regulated by the FDA as non-prescription drugs, sunless tanning products are regulated as cosmetics and cannot provide any protection from exposure to ultraviolet radiation. There are reports of non-cosmetic uses of DHA that are not FDA approved. With the wide-spread use of DHA, additional studies on its safety are warranted.

J Drugs Dermatol. 2018;17(4):387-391.

Hidradenitis suppurativa in children: The Henry Ford experience.

BACKGROUND: Although recent hidradenitis suppurativa studies have shown that early-onset disease is associated with a positive family history and more widespread disease, research in pediatric hidradenitis suppurativa is limited. METHODS: Thirty-three children diagnosed with hidradenitis suppurativa during an 18-month period were included in this institutional review board-approved, retrospective chart review. Information on demographic characteristic, family history, and timing of onset (prepubescent vs postpubescent) was extracted. The Fisher exact test, Cochran-Armitage exact trend test, and chi-square test were used to examine the association between prepubescent or postpubescent onset of hidradenitis suppurativa and sex, disease severity, and family history. RESULTS: A significantly higher percentage of patients with postpubescent onset were female (85.7%) than male (14.3%), whereas those with prepubescent onset were more likely to be male (58.3%) than female (41.7%; P = .02). Associations between disease onset and positive family history of hidradenitis suppurativa (P = .47) or higher Hurley stage of disease (P = .15) were not statistically significant. CONCLUSION: Boys are more likely to have prepubescent onset of hidradenitis suppurativa and girls to have postpubescent onset. This shift in sex distribution is unexplained, but we hypothesize that, whereas the role of ovarian hormones in the pathogenesis of HS may underlie much of adult-onset disease, it is less important in prepubescent disease.

Afamelanotide in the Treatment of Dermatologic Disease

Afamelanotide, an α-melanocyte stimulating hormone analogue, has become an emerging therapeutic option for a variety of skin conditions previously refractory to other treatments. Its efficacy has been demonstrated in several dermatologic conditions, including erythropoietic protoporphyria (EPP), solar urticaria, polymorphic light eruption (PMLE), vitiligo, acne, and Hailey-Hailey disease. Its relatively low risk side effect profile makes it an attractive treatment option and also paves the way for innovative use in other disorders.

Vitiligo Surgery: Shuffling Melanocytes.

Vitiligo is a disorder characterized by the development of depigmented macules and patches secondary to melanocyte destruction. Several treatment options are available, including medical, light-based, and surgical therapies, that are often used in combination to achieve maximal repigmentation. Vitiligo surgery is an effective yet underperformed treatment, mainly because of lack of awareness and availability. The purpose of this article is to review one method of vitiligo surgery, the melanocyte-keratinocyte transplantation procedure, and discuss its utility in treating vitiligo.

Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

Inhibition of the late sodium current slows t-tubule disruption during the progression of hypertensive heart disease in the rat.

The treatment of heart failure (HF) is challenging and morbidity and mortality are high. The goal of this study was to determine if inhibition of the late Na(+) current with ranolazine during early hypertensive heart disease might slow or stop disease progression. Spontaneously hypertensive rats (aged 7 mo) were subjected to echocardiographic study and then fed either control chow (CON) or chow containing 0.5% ranolazine (RAN) for 3 mo. Animals were then restudied, and each heart was removed for measurements of t-tubule organization and Ca(2+) transients using confocal microscopy of the intact heart. RAN halted left ventricular hypertrophy as determined from both echocardiographic and cell dimension (length but not width) measurements. RAN reduced the number of myocytes with t-tubule disruption and the proportion of myocytes with defects in intracellular Ca(2+) cycling. RAN also prevented the slowing of the rate of restitution of Ca(2+) release and the increased vulnerability to rate-induced Ca(2+) alternans. Differences between CON- and RAN-treated animals were not a result of different expression levels of voltage-dependent Ca(2+) channel 1.2, sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, ryanodine receptor type 2, Na(+)/Ca(2+) exchanger-1, or voltage-gated Na(+) channel 1.5. Furthermore, myocytes with defective Ca(2+) transients in CON rats showed improved Ca(2+) cycling immediately upon acute exposure to RAN. Increased late Na(+) current likely plays a role in the progression of cardiac hypertrophy, a key pathological step in the development of HF. Early, chronic inhibition of this current slows both hypertrophy and development of ultrastructural and physiological defects associated with the progression to HF.

Mask-related skin changes among healthcare workers in a community-based hospital.

CONTEXT: During the COVID-19 pandemic, dermatologists within the Beaumont Farmington Hills' Dermatology program noticed an increase in conditions associated with mask wearing, such as "maskne" (acne in a mask distribution, thought to be caused by mask wearing), as well as worsening of previously diagnosed dermatologic conditions. OBJECTIVES: The goal of our study was to explore various factors that impacted mask-related skin changes and how these skin changes affected quality of life. METHODS: A cross-sectional study was performed. The primary 10-item survey instrument administered was the Dermatology Life Quality Index (DLQI). Respondents were asked a series of 10 additional questions concerning the degree to which abnormal mask-related skin conditions affect their skin symptoms, possible embarrassment/self-consciousness, and perceived impact of mask-related skin changes. A series of descriptive statistics, cross-tabulation charts, and graphical examinations of data was utilized to evaluate sample subgroup and outcome distributional patterns. Pearson r bivariate correlation coefficients between possible collinear predictive measures on the primary study outcome were calculated. A series of simple inferential chi-squared (Χ2) tests of independence were also conducted. RESULTS: A total of 370 out of 430 (86.0%) Beaumont Health employees noticed some degree of skin changes since the work-hours face mask requirement was instituted, while 378 out of 430 (87.9%) felt that their skin was better when not wearing a mask. The majority of respondents, 283 (65.8%), reported having at least a little symptomatic skin (i.e., itchy, painful, sore, stinging) during the prior week. Furthermore, 72.3% reported that they were at least a little embarrassed or self-conscious of their skin. Chi-squared analysis of composite DLQI score categories by the number of types of masks utilized (Pearson X2=19.0, df=8, p=0.015), and some degree of symptomatic skin (Pearson X2=156.4, df=4, p<0.001) were found to be statistically significant. CONCLUSIONS: A large number of healthcare workers are affected by mask-related skin changes. Further research should be directed at better understanding how skin changes associated with mask wearing impact one's quality of life and mental health.

Mitigating Visible Light and Long Wavelength UVA1-induced Effects with Topical Antioxidants.

The role of topical antioxidants (AOs) on visible light plus ultraviolet A1 (VL+UVA1)-induced skin changes were evaluated. Twenty subjects with skin phototypes (SPTs) I-VI had placebo and concentrations of an AO blend applied to their back (AO 0.5%, 1.0% and 2.0%). Treated and control sites were irradiated with VL+UVA1. Colorimetric and diffuse reflectance spectroscopy (DRS) assessments were performed immediately, 24 h and 7 days after irradiation. Subjects with SPT I-III had erythema that faded within 24 h, while SPT IV-VI had persistent pigmentation. SPT I-III demonstrated significantly less erythema at the 2% AO site while SPT IV-VI demonstrated significantly less immediate pigmentation at 2% AO site and less pigmentation (approaching significance, P = 0.07) on day 7 compared with control. Immunohistochemistry from biopsies of 2% AO and placebo at 24 h did not demonstrate a significant change in COX-2 or MART-1 for any SPT. There was a decrease in cyclin D1 for SPT IV-VI which was approaching significance (P = 0.06) but not for SPT I-III. The results indicate that topical AO inhibits erythema in SPT I-III and reduces pigmentation in SPT IV-VI caused by VL+UVA1. AO may help prevent worsening of pigmentary disorders and should be incorporated into photoprotection.

An unusual presentation of cutaneous metastatic lobular breast carcinoma.

Breast cancer is the most common malignancy to metastasize to the skin in women. Cutaneous breast carcinoma may arise as cutaneous metastasis or secondary to direct tumor extension to the skin. This report describes an unusual presentation of cutaneous metastatic lobular breast carcinoma that involved diffuse cutaneous lesions and rapid progression from onset of breast mass to development of clinically apparent metastatic skin lesions.

Quantitative measurement of skin surface oiliness and shine using differential polarized images.

Excess amounts of skin surface oil can lead to adverse psychological consequences. Grease-spot photometry-based techniques measure sebum production rate. However, besides being tedious, these measurements are influenced by contact area, applied pressure, and time of application. Image analysis of polarized images has the potential to provide objective, quantitative information of skin oiliness. This study was designed to set up an imaging device for capturing and enhancing the changes in skin surface oiliness and to clinically and quantitatively, (via image analysis), evaluate varying levels of skin surface oiliness. Mineral oil was used to simulate skin surface oil. 40.5 µL of the mineral oil was applied within a two inch square area of interest on facial skin in twelve steps, from 1 to 40.5 µL, at 40% increments. The results indicate a strong correlation between the quantitative skin surface oiliness measurements and the clinical assessments. This sensitive technique has the potential to be utilized in future studies to evaluate product efficacies in reducing skin oiliness.

Trichloroacetic acid model to accurately capture the efficacy of treatments for postinflammatory hyperpigmentation.

Postinflammatory hyperpigmentation (PIH) occurs following cutaneous injury and is common following resolution of acne especially in patients with skin of color. The objective of this study was to further validate a trichloroacetic acid (TCA)-induced PIH model and compare it to acne-induced PIH using topical bakuchiol, a botanical extract that has been shown to have antimicrobial, anti-inflammatory, antioxidant, and antiacne properties. A prospective, non-randomized clinical trial was conducted on subjects with skin phototypes IV-VI with a history of acne-induced PIH. Subjects applied bakuchiol or vehicle cream twice daily to 2 acne-induced and 2 TCA-induced PIH lesions for 28 days with a third lesion serving as a control in each group. Degree of improvement was defined as the change in the Investigator Global Assessment (IGA) score over 28 days of treatment. Twenty subjects (6 males, 14 females) completed the study. For TCA-induced PIH sites, there was a statistically significant (p < 0.05) degree of improvement with bakuchiol treatment (- 0.50 ± 0.18) compared to vehicle (0.05 ± 0.15) and control (- 0.06 ± 0.17). For acne-induced PIH, there was a greater degree of improvement for bakuchiol (- 1.06 ± 0.23) when compared to vehicle (- 0.56 ± 0.16) and control (- 0.69 ± 0.18); however, statistical significance was not reached (p > 0.05). TCA-induced PIH sites were uniform in size and pigment intensity thereby allowing better comparison among sites. This emphasizes the relevance of using this model for PIH which may help reduce the barriers in clinical trials and help improve access to treatments for patients who suffer from PIH. The results suggest that topical bakuchiol may decrease the severity of PIH.

Long-wavelength Ultraviolet A1 and Visible Light Photoprotection: A Multimodality Assessment of Dose and Response.

Human skin is exposed to visible light (VL; 400-700 nm) and long-wavelength ultraviolet A1 (UVA1) radiation (370-400 nm) after the application of organic broad-spectrum sunscreens. The biologic effects of these wavelengths have been demonstrated; however, a dose-response has not been investigated. Ten subjects with Fitzpatrick skin phototype IV-VI were enrolled. Subjects were irradiated with 2 light sources (80-480 J cm-2 ): one comprising VL with less than 0.5% UVA1 (VL+UVA1) and the other pure VL. Skin responses were evaluated for 2 weeks using clinical and spectroscopic assessments. 4-mm punch biopsies were obtained from nonirradiated skin and sites irradiated with 480 J cm-2 of VL+UVA1 and pure VL 24 h after irradiation. Clinical and spectroscopic assessments demonstrated a robust response at VL+UVA1 sites compared with pure VL. Histology findings demonstrated a statistically significant increase in the marker of inflammation (P < 0.05) and proliferation (P < 0.05) at the irradiated sites compared with nonirradiated control. Threshold doses of VL+UVA1 resulting in biologic responses were calculated. Results indicate that approximately 2 h of sun exposure, which equates to VL+UVA1 dose (~400 J cm-2 ), is capable of inducing inflammation, immediate erythema and delayed tanning. These findings reinforce the need of photoprotection beyond the UV range.

An Update on Drug-Induced Pigmentation.

Drug-induced pigmentation accounts for up to 20% of all cases of acquired pigmentation. A thorough review of medical history and previous and ongoing medications as well as a complete skin examination can guide diagnosis. Implicated agents include alkylating/cytotoxic agents, analgesics, antiarrhythmics, anticoagulants, antiepileptics, antimalarials, antimicrobials, antiretrovirals, metals, prostaglandin analogs, and psychotropic agents, among others. Confirming true drug associations can be challenging, especially in the setting of delayed onset of pigmentation and coexisting polypharmacy.

Patient-reported outcomes in hidradenitis suppurativa.

Hidradenitis suppurativa, also known as acne inversa, is a chronic recurrent inflammatory disease of the skin making management challenging and continuously evolving. A large number of modalities exist aimed at quantifying the efficacy of treatment in studies on hidradenitis suppurativa. Both physician-reported and patient-reported outcomes are used as endpoints in these studies; however, the vast majority of the modalities used to survey these reported outcomes lack validation and congruence between studies. Heterogeneity of outcome measures and lack of standardization from study to study make it difficult to design future hidradenitis suppurativa trials and to compare results. This high variability between studies further contributes to the lack of high-quality evidence available to guide clinical management decisions of this inflammatory skin disease. Therefore this review aims to assess the modalities frequently used to assess patient-reported treatment outcomes in hidradenitis suppurativa. Patient-reported outcomes in hidradenitis suppurativa include outcomes regarding symptoms and disease progression, measures of treatment satisfaction, quality of life surveys, impairment of function, pain, and patient-reported outcomes combined with physician-reported outcomes. Nearly all surveys demonstrate significant heterogeneity, lack standardization, and many are not validated or constructed specifically for the assessment of hidradenitis suppurativa. Yet patient-reported outcomes on symptoms and disease severity, treatment satisfaction, and quality of life are instrumental in evaluating hidradenitis suppurativa treatment efficacy in clinical trials. As such, standardization and validation of patient-reported outcome instruments are essential for comparability among studies and improved quality of evidence.

Impact of Long-Wavelength Ultraviolet A1 and Visible Light on Light-Skinned Individuals.

Solar radiation is known to be a major contributor to the development of skin cancer. Most sunscreen formulations, including those with broad spectrum, offer minimal protection in long-wavelength ultraviolet A1 (UVA1; 370-400 nm) and visible light (VL; 400-700 nm) domain. There is limited information regarding the impact of this broad waveband (VL + UVA1, 370-700 nm) on those with light skin. In this study, ten healthy adult subjects with Fitzpatrick skin phototypes I-III were enrolled. On day 0, subjects' lower back was exposed to a VL + UVA1 dose of 480 J cm-2 . A statistically significant increase in erythema immediately after irradiation compared with subjects' baseline nonirradiated skin was observed. Clinically perceptible erythema with VL + UVA1 is a novel finding since the erythemogenic spectrum of sunlight has primarily been attributed to ultraviolet B and short-wavelength ultraviolet A (320-340 nm). The results emphasize the need for protection against this part of the solar spectra and warrant further investigation.