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.

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.

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.

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.

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.

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.

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.

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.

Surgical procedures for hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that can have a considerable social and psychosocial impact in patients with skin of color. The lesions are difficult to treat and often present with notable frustration for both patients and physicians. Although current treatment ladders can delay procedures and surgical intervention, some believe that surgery should be introduced earlier in the management of HS. In this article, we review current surgical procedures for the management of HS. It is imperative that dermatologists are informed about the different techniques available for treating this disease to determine the best route to care for their patients.

Recent Developments in the Diagnosis and Management of Photosensitive Disorders.

Photodermatoses occur in males and females of all races and ages. Onset can be variable in timing and influenced by genetic and environmental factors. Photodermatoses are broadly classified as immunologically mediated, chemical- and drug-induced, photoaggravated, and genetic (defective DNA repair or chromosomal instability) diseases. Advances in the field have led to improved recognition and treatment of many photodermatoses. The purpose of this focused review is to provide an update on the diagnosis and management of a variety of photodermatoses, both common and less common, with review of recent updates in the literature pertaining to their diagnosis and management.

Ertapenem - a potent treatment for clinical and quality of life improvement in patients with hidradenitis suppurativa.

BACKGROUND: A paucity of knowledge exists regarding the use of ertapenem in hidradenitis suppurativa. Our retrospective chart review and telephone interview aims to investigate the utility of intravenous ertapenem in severe, refractory hidradenitis suppurativa. METHODS: This retrospective chart review and telephone interview included patients with severe, refractory hidradenitis suppurativa treated with intravenous ertapenem between March 2013 and December 2016. Data were obtained from medical charts. During the telephone interview, patients were asked questions relating to satisfaction, quality of life changes, and disease state changes with ertapenem therapy. RESULTS: A total of 36 patients including 22 females and 14 males with Hurley stage II or III hidradenitis suppurativa were included. Thirty-five patients (97.2%), demonstrated improvements in hidradenitis suppurativa with ertapenem treatment. In total, 28 patients participated in our telephone interview. Twenty patients (71.4%) were very satisfied (n = 12) or satisfied (n = 8). Quality of life improved in 85.7% of patients (n = 24). CONCLUSION: Following ertapenem therapy, patients reported improvements in quality of life. This treatment appears promising as an adjunct to biologics or as a bridge to surgery in the treatment of severe, refractory hidradenitis suppurativa.

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.

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.