Sex-specific differences in oxidative stress markers and collagen expression in perioral skin wrinkling.

Wrinkling is the hallmark of skin ageing. We previously reported that perioral wrinkling is more severe in females; however, the molecular basis is unknown. This study assessed sex differences in the molecular expression of key ageing regulators in perioral skin. Twelve subjects (n = 6 male/female) were enrolled in this cross-sectional study and biopsies were taken from the perioral and periocular regions. RNA expression of collagen I, collagen III, cysteine-rich angiogenic inducer 61 (CYR61) and insulin-like growth factor 1 (IGF-1) was assessed by qPCR. There was no difference between females' and males' Griffith's grades (6 and 5.67, respectively, p = 0.092) or periocular wrinkling grades (3.2 and 2.6, p = 0.421), but females had more severe perioral wrinkling grades than males (6.2 and 2.8, p = 0.020). Females not only expressed significantly more CYR61 (p = 0.018) in the perioral region than malesm but also expressed more collagen III (p = 0.016). There was no difference in collagen I (p = 0.115) or IGF-1 (p = 0.124) expression in the perioral region between sexes. In the periocular region, there were no significant differences between sexes in the expression of all four markers. The significant molecular differences in the perioral region between the sexes may contribute to the greater perioral skin wrinkling seen clinically in females.

Skin type specific photobiological response to visible light is mediated by constitutional melanin.

BACKGROUND: Visible light (VL) induces varying photobiological responses between skin types, likely influenced by inherent melanization. Individual typology angle (ITA) objectively measures skin types. We hypothesize that epidermal melanin content and distribution determine VL response. OBJECTIVES: This study describes clinical and histologic responses to VL and examines the potential role of melanin in the underlying mechanistic pathways. METHODS: We grouped enrolled participants by ITA (Light = 5, Intermediate = 4, Dark = 7) per colorimetry (CR-400, Konica Minolta). Photoprotected sites were exposed daily to 480 J/cm2 of VL (Fiber-Lite High Intensity Illuminator, Series 180, Dolan Jenner Industries Inc.) for 4 days (total = 1920 J/cm2 ), as tolerated. Treated and control sites were biopsied 96 h after first exposure. We used hematoxylin and eosin and Fontana-Mason to assess histological changes and melanin deposition, respectively. p53 and Ki67 immunohistochemical stains were done to assess DNA damage and proliferation. Matrix metalloproteinase (MMP)-1 expression was detected by immunohistochemical staining and immunofluorescence microscopy. RESULTS: Darker skin did not tolerate the full VL regimen with blistering occurring in most subjects at doses of 220-880 J/cm2 . Intermediate and Dark skin showed tanning. Light skin developed erythema. p53 counts were highest in Intermediate, followed by Light skin, although this was not statistically significant. VL treatment led to MMP-1 expression and nuclear localization in keratinocytes in Dark and Intermediate but not in Light skin, however differences between groups were not statistically significant. CONCLUSIONS: Skin types demonstrate unique biological responses to VL. The role of melanin in photoprotection is well-defined. However, given the pro-apoptotic function of nuclear MMPs, we suggest a potential mechanism by which melanin may mediate VL-induced phototoxicity.

Clinical and molecular change induced by repeated low-dose visible light exposure in both light-skinned and dark-skinned individuals.

BACKGROUND: Visible light (VL) is known to induce pigmentation in dark-skinned individuals and immediate erythema in light-skinned individuals. However, the effects of accumulated low-dose VL exposure across skin types are not well established. METHODS: Thirty-one healthy subjects with light (Fitzpatrick skin types [FST] I-II, n = 13) and dark (FST V-VI, n = 18) skin types were enrolled. Subjects' buttocks were exposed daily to VL, wavelength 400-700 nm, with a dose of 120 J/cm2 at 50 mW/cm2 , for four consecutive days. Microarray using Affymetrix GeneChip (49,395 genes) was performed followed by qRT-PCR on skin samples. RESULTS: Repeated low-dose VL irradiation induced immediate pigment darkening and delayed tanning in dark-skinned individuals while no discernable pigmentation and erythema were observed in light-skinned individuals. Top ten upregulated genes by repeated VL exposure in microarray included melanogenic genes such as tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), dopachrome tautomerase (DCT), premelanosome protein (PMEL), melan-A (MLANA), and solute carrier family 24, member 5 (SLC24A5) and genes involved in inflammation/matrix remodeling/cell signaling including chemokine (C-C motif) ligand 18 (CCL18), BCL2-related protein A1 (BCL2A1), and cartilage oligomeric matrix protein (COMP). In qRT-PCR CCL18 was upregulated in light skin with a greater extent (mean fold change ± SD; 4.03 ± 3.28, p = .04) than in dark-skinned individuals (1.91 ± 1.32, p = .07) while TYR was not significantly upregulated in both skin types. CONCLUSION: This study highlights the genes upregulated by cumulative VL exposure involved in pigmentation, immune response, oxidation/reduction, and matrix remodeling across skin types providing relevant information on daily solar exposure.

Leveraging Tissue Engineering for Skin Cancer Models.

Bioengineered in vitro three-dimensional (3D) skin model has emerged as a promising tool for recapitulating different types of skin cancer and performing pre-clinical tests. However, a full-thickness 3D model including the epidermis, dermis, and hypodermis layers is scarce despite its significance in human physiology and diverse biological processes. In this book chapter, an attempt has been made to summarize various skin cancer models, including utilized skin layers, materials, cell lines, specific treatments, and fabrication techniques for three types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Subsequently, current limitations and future directions of skin cancer models are discussed. The knowledge of the current status of skin cancer models can provide various potential applications in cancer research and thus a more effective way for cancer treatment.

The association of photo-induced collagen degeneration and the development of telangiectasias in rosacea.

Rosacea is a chronic, often progressive disorder characterized by facial erythema, telangiectasias, papules, pustules, and/or rhinophyma. In this study, we investigated the tissue structure in rosacea compared to controls. We performed a case-control study between five patients with mild-to-moderate erythematotelangiectatic rosacea (ETR) and five matched controls. Facial biopsy samples from rosacea patients and controls were stained with picrosirius red for collagen and CD31 for microvessel identification. Mean collagen content was significantly greater in control samples (19.603% ±8.821%) compared to rosacea samples (16.812% ± 7.787%, p = 0.030). In contrast, mean microvessel density was significantly higher in rosacea patients (4.775 E-5 ± 1.493 E-5 µm-3 ) compared to controls (2.559 E-5 ± 8.732 E-6 µm-3 , p = 0.004). Mean microvessel lumen area was also significantly higher in rosacea patients (491.710 ± 610.188 µm2 ) compared to controls (347.879 ± 539.624 µm2 , p = 0.003). We identified a correlation between decreased collagen content and increased microvessel size and density in rosacea patients that was not observed in controls. These structural changes to the dermal matrix may contribute to the characteristic vessel growth and dilation in rosacea.

Comparison of the skin microbiota in acne and rosacea.

Acne and rosacea, despite their similar clinical presentations, follow distinct clinical courses, suggesting that fundamental differences exist in their pathophysiology. We performed a case-control study profiling the skin microbiota in rosacea and acne patients compared to matched controls. Nineteen rosacea and eight acne patients were matched to controls by age ± 5 years, sex and race. DNA was extracted from facial skin swabs. The V3V4 region of the bacterial 16S rRNA gene was sequenced using Illumina MiSeq and analysed using QIIME/Metastats 2.0 software. The mean relative abundance of Cutibacterium acnes in rosacea with inflammatory papules and pustules (20.454% ±16.943%) was more similar to that of acne (19.055% ±15.469%) than that of rosacea without inflammatory papules and pustules (30.419% ±21.862%). C acnes (P = .048) and Serratia marcescens (P = .038) were significantly enriched in individuals with rosacea compared to acne. Investigating the differences between the skin microbiota in acne and rosacea can provide important clues towards understanding the disease progression in each condition.

Sun Protective Clothing and Sun Avoidance: The Most Critical Components of Photoprotection in Patients With Melanoma.

BACKGROUND: Ultraviolet radiation is the main modifiable risk factor for melanoma which can be reduced by avoiding excess sun exposure. OBJECTIVE: We sought to explore (1) sun protective practices, (2) effectiveness of these sun protective practices, and (3) vitamin D supplementation in patients with melanoma. METHODS: Using the National Health Interview Survey, the authors conducted a cross-sectional analysis to investigate sun protective behaviors and sunburns among adults with melanoma compared with those without skin cancer. We calculated adjusted odds ratio (aOR), 95% confidence interval (95% CI), and p-values using logistic regression. RESULTS: Patients with melanoma reported increased use of sun avoidance, shade, sunscreen, long sleeves, and hats, but had similar sunburn rates compared with those without skin cancer. Only sun avoidance and long sleeves were associated with decreased odds of sunburn. Patients with melanoma also reported decreased vitamin D supplementation. CONCLUSION: Although it is reassuring that patients with melanoma practice sun protective behaviors, this does not always translate into reduced sunburns. Physicians should emphasize the importance of photoprotection, especially sun avoidance and sun protective clothing, to reduce future melanoma risk.

Concerns, Expectations, and Management Gaps Relating to Acne and Associated Scarring Identified from Survey Data.

INTRODUCTION: Our objective was to identify concerns, burden of disease, education gaps, and expectations of acne/acne scarring respondents and investigate acne/acne scarring related burden. Also, to consider perception of acne/acne scarring and additional education needs through responses from the general population. METHODS: One online survey from 1000 respondents aged 14–26 years old who currently had moderate to severe acne and/or acne scarring (AcnePop) and one from 2000 nationally representative USA respondents aged ≥14 years old [general population (GenPop)]. RESULTS: Among the AcnePop, 26% had never consulted a healthcare professional and 36% never received a prescription for acne/acne scarring. Of those who had seen a medical professional, 72% consulted a dermatologist, 45% a primary care physician, and 23% a therapist/psychiatrist. The vast majority (94%) were dissatisfied with information they received from the healthcare provider. Topics they desired more information on included available treatment options (46%), how different skin types are affected by acne (44%), acne triggers (44%), and their acne severity (43%). Of GenPop (n=781) who had given unsolicited advice to people with acne, the most common suggestions were to see a doctor (47%), change their hygiene habits (39%), or change their diet (37%). CONCLUSION: AcnePop are often dissatisfied with the information they receive from healthcare providers and more comprehensive information should be provided to help them understand their condition and available treatment options. J Drugs Dermatol. 2021;20(6):600-606. doi:10.36849/JDD.5920.

Evidence-based update on rosacea comorbidities and their common physiologic pathways.

Rosacea is a common chronic inflammatory disease affecting the facial skin whose etiology and pathophysiology are the subject of much investigation. Risk factors include genetic and environmental elements that may predispose individuals to localized inflammation and abnormal neurovascular responses to stimuli. Recent studies have introduced an array of systemic rosacea comorbidities, such as inflammatory bowel disease and neurologic conditions, that can be challenging to synthesize. We critically review the current data behind reported rosacea comorbidities and identify and highlight underrecognized physiologic mediators shared among rosacea and associated comorbidities. This information may be helpful in addressing patient questions about potential systemic implications of rosacea and can serve as a candidate platform for future research to understand rosacea and improve treatments.

Chronological Aging in African-American Skin: A Reliable Photonumeric Scale Demonstrates Age and Body Mass Index as Contributing Factors.

BACKGROUND: Increased photoprotection by natural melanin allows for African-Americans to be less impacted by photoaging than Caucasians. However, less is known about chronological aging in this population. OBJECTIVE: To create a photonumeric scale for African-Americans to evaluate chronological skin aging and to explore contributing elements to intrinsic aging. METHODS: Standardized photographs of the upper inner arm were taken from 75 African-American participants. Five participants were chosen as standards to create a 9-point photonumeric scale (0 = none, 8 = most severe). The scale was utilized by three blinded dermatologists to independently rate participants' photographs. RESULTS: The interrater agreements were 0.768 (95% CI: 0.671-0.834) for trial 1 and 0.725 (0.608-0.794) for trial 2. The intrarater agreements were 0.757 (0.596-0.875), 0.850 (0.771-0.903), and 0.790 (0.686-0.855) for the three raters. Averaged chronological aging scores were correlated with participants' survey responses, which revealed age as a significant predictor (r = 0.72, p < 0.001). LIMITATION: Our study was limited by the sample size, although the number of study participants was similar on a investigation in Caucasians. CONCLUSION: This study created the first reliable photonumeric scale for chronologic skin aging in African-Americans and found increased age and greater BMI as contributors to intrinsic skin aging phenotype in this population.

Effect of Age, Gender, and Sun Exposure on Ethnic Skin Photoaging: Evidence Gathered Using a New Photonumeric Scale.

BACKGROUND: African-Americans are less affected by photoaging than lighter skin individuals. Although scales for photoaging have been developed for Caucasians and Asians, no scale exists for African-Americans. AIM: To develop a photonumeric scale for photoaging and to determine factors that contribute to photoaging in African-Americans. METHODS: Five participants' photographs were selected as standards to create a 9-point photonumeric scale (0 = none, 8 = most severe). Three blinded dermatologists used the scale to grade the remaining participants' photographs. RESULTS: Interrater reliabilities were 0.775 (95% CI: 0.635, 0.880) for trial 1 and 0.832 (0.747, 0.883) for trial 2. Intrarater reliabilities, assessed over a 1 week interval, were 0.863 (0.727, 0.940), 0.928 (0.890, 0.954), and 0.866 (0.739, 0.935) for the three graders, indicating strong agreement. Photoaging scores were then correlated with participants' survey on lifestyle factors, which yielded age as a significant predictor (r = 0.91, p < 0.001). Furthermore, multiple regression model to predict facial photoaging (adjusted R2 = 0.849) selected age (b1 = 0.111, p < 0.001), sun exposure (b2 = 0.206, p = 0.014), and gender (b2 = -0.388, p = 0.063) as the most important variables. CONCLUSIONS: A reliable photonumeric scale for photoaging in African Americans was developed. Age, sun exposure, and male gender were found to be contributory factors to photoaging.

YouTube Videos on Botulinum Toxin A for Wrinkles: A Useful Resource for Patient Education.

BACKGROUND: Patients interested in botulinum toxin type A (BTX-A) for wrinkles search for videos on YouTube, but little is known about the quality and reliability of the content. OBJECTIVE: The authors examined the quality, reliability, content, and target audience of YouTube videos on BTX for wrinkles. MATERIALS AND METHODS: In this cross-sectional study, the term "Botox" was searched on YouTube. Sixty relevant videos in English were independently categorized by 2 reviewers as useful informational, misleading informational, useful patient view, or misleading patient view. Disagreements were settled by a third reviewer. Videos were rated on the Global Quality Scale (GQS) (1 = poor, 5 = excellent). RESULTS: Sixty-three percent of the BTX YouTube videos were useful informational (GQS = 4.4 ± 0.7), 33% as useful patient view (GQS = 3.21 ± 1.2), 2% as misleading informational (GQS = 1), and 2% as misleading patient view (GQS = 2.5). CONCLUSION: The large number of useful videos, high reliability, and the wide range of content covered suggests that those who search for antiwrinkle BTX videos on YouTube are likely to view high-quality content. This suggests that YouTube may be a good source of videos to recommend for patients interested in BTX.

Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (NMSC): A population-based study.

BACKGROUND: Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit ultraviolet exposure. OBJECTIVE: We sought to determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. METHODS: We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI), taking into account the complex survey design. RESULTS: Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% vs 27.0%; aPOR 1.41; 95% CI 1.16-1.71), long sleeves (20.5% vs 7.7%; aPOR 1.55; 95% CI 1.21-1.98), a wide-brimmed hat (26.1% vs 10.5%; aPOR 1.52; 95% CI 1.24-1.87), and sunscreen (53.7% vs 33.1%; aPOR 2.11; 95% CI 1.73-2.59), but did not have significantly lower odds of recent sunburn (29.7% vs 40.7%; aPOR 0.95; 95% CI 0.77-1.17). Among those with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. LIMITATIONS: Self-reported cross-sectional data and unavailable information quantifying regular sun exposure are limitations. CONCLUSION: Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen.

Pigmentation in African American skin decreases with skin aging.

BACKGROUND: Tristimulus colorimetry, which uses the Commission Internationale de l'Eclairage L*a*b* model to quantify color, has previously been used to analyze pigmentation and erythema in human skin; however, colorimetry of African American skin is not well characterized. OBJECTIVE: We sought to analyze skin color patterns in African Americans and compare them with those of Caucasians. METHODS: Colorimetry readings of the sun-protected buttock and sun-exposed back of forearm were taken from 40 Caucasian and 43 African American participants from March 2011 through August 2015. African American participants also completed a lifestyle questionnaire. Correlation coefficients, paired t tests, and multivariable linear regression analyses were used for statistical comparisons. RESULTS: Forearm skin was lighter in African Americans ages 65 years and older versus 18 to 30 years (P = .02) but darker in Caucasians ages 65 years or older versus 18 to 30 years (P = .03). In African Americans ages 18 to 30 years, the buttock was darker than the forearm (P < .001), whereas in Caucasians the buttock was lighter than the forearm (P < .001). A lighter forearm than buttock was correlated with supplement use, smoking (ages 18-30 years), and less recreational sun exposure (ages ≥65 years) in African Americans. LIMITATIONS: Our study was limited by the sample size and focal geographic source. CONCLUSIONS: Pigmentation patterns regarding sun-protected and sun-exposed areas in African Americans may differ from that of Caucasians, suggesting that other factors may contribute to skin pigmentation in African Americans.

Perioral wrinkles are associated with female gender, aging, and smoking: Development of a gender-specific photonumeric scale.

BACKGROUND: Perioral wrinkling is commonly reported among older adults, but its objective evaluation and causes remain poorly understood. OBJECTIVE: We sought to develop a photonumeric scale for perioral wrinkling and to elucidate contributory lifestyle factors. METHODS: In this cross-sectional study, we recruited participants for facial photographs and a survey. A gender-specific photonumeric scale for perioral wrinkling was developed and used by 3 graders to evaluate participant photographs. Scores and survey responses were used to create a multiple regression model to predict perioral wrinkling. RESULTS: In all, 143 participants aged 21 to 91 years were enrolled. Intraclass correlation coefficient values for interrater and intrarater reliability were high (>0.8) across 2 trials and 3 graders. A multiple regression model for prediction of perioral wrinkling severity included age, gender, and years of smoking as variables. LIMITATIONS: The study was limited by sample size and a predominantly Caucasian study population. CONCLUSION: We created a photonumeric scale that accounts for gender differences in perioral wrinkling and highlighted contributory variables to photoaging in this anatomical location.

Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study.

BACKGROUND: Rosacea is a common chronic inflammatory dermatosis of unclear origin. It has been associated with systemic comorbidities, but methodical studies addressing this association are lacking. OBJECTIVE: We evaluated: (1) the association between rosacea and systemic comorbidities; and (2) if the severity of rosacea is impacted by comorbidities. METHODS: This was a case-control study: patients with rosacea were matched (1:1) to rosacea-free control subjects by age, sex, and race. Relative risk estimates were calculated using logistic regression as odds ratios with 95% confidence intervals. RESULTS: Among 130 participants (65 patients/65 control subjects), we observed a significant association between rosacea and allergies (airborne, food), respiratory diseases, gastroesophageal reflux disease, other gastrointestinal diseases, hypertension, metabolic and urogenital diseases, and female hormone imbalance. Compared with mild rosacea, moderate to severe rosacea was significantly associated with hyperlipidemia, hypertension, metabolic diseases, cardiovascular diseases, and gastroesophageal reflux disease. LIMITATIONS: This was a case-control study with moderate sample size. Associated medical conditions were self-reported and could not always be confirmed by medication use and medical records. CONCLUSIONS: Rosacea is associated with numerous systemic comorbid diseases in a skin severity-dependent manner. Physicians should be aware of these associations to provide comprehensive care to patients with rosacea, especially to those with more severe disease.