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Prurigo nodularis is an understudied, chronic inflammatory skin disease that disproportionately affects African-Americans and presents with intensely pruritic nodules of unknown etiology. To better characterize immune dysregulation in prurigo nodularis, peripheral blood mononuclear cells and skin biopsies were obtained from majority African American patients with prurigo nodularis and healthy subjects matched by age, race, and sex. Flow cytometric analysis of functional T-cell response comparing prurigo nodularis to healthy subjects identified increased γδT-cells (CD3(+)CD4(−)CD8(−)γδTCR(+)) with Vδ2(+) γδT-enrichment. Activated T-cells demonstrated uniquely increased IL-22 cytokine expression in prurigo nodularis patients when compared to healthy controls. CD4+ and CD8+ T-cells were identified as the source of increased circulating IL-22. Consistent with these findings, RNA-sequencing of lesional prurigo nodularis skin compared to non-lesional prurigo nodularis skin and biopsy site matched control skin demonstrated robust up-regulation of Th22-related genes and signaling networks implicated in impaired epidermal differentiation. Th22-related cytokine upregulation remained significant with stratifications by race and biopsy site. Importantly, the expression of the IL-22 receptors IL22RA1/A2 was significantly elevated in lesional prurigo nodularis skin. These results indicate both systemic and cutaneous immune responses in prurigo nodularis patients are skewed towards a Th22/IL-22 profile. Prurigo nodularis may benefit from immunomodulatory therapies directed at Th22-mediated inflammation.

Mammalian injury responses are characterized by fibrosis and scarring rather than functional regeneration. Limited regenerative capacity in mammals could reflect a loss of pro-regeneration programs or active suppression by genes functioning akin to tumor suppressors. To uncover programs governing regeneration in mammals, we performed comprehensive transcript screening in human subjects after laser rejuvenation treatment. We searched for overlapping transcripts also associated with Wound Induced Hair Neogenesis (WIHN), a rare example of regeneration in mice. We found the anti-viral endoribonuclease RNase L to be a powerful suppressor of regeneration. Rnasel-/- mice exhibit remarkable regenerative capacity and accelerated wound healing following injury, through the production of IL-36α. Consistent with the known role of RNase L to stimulate caspase-1 signaling, we find that pharmacologic inhibition of caspases promotes regeneration in a novel IL-36-dependent manner. We also find a gene set of inner root sheath keratins, such as KRT71, that is associated with poor wound healing in mouse and man, and decreases with caspase inhibition. Finally, these responses are not limited to skin, but occur following intestinal injury as well, suggesting that suppression of regeneration is a general characteristic of epithelial wound healing. In all, this work suggests that RNaseL functions as a regeneration repressor gene in a functional tradeoff that prioritizes host antiviral abilities and is a target to enhance healing in multiple epithelial organs, perhaps even during viral infection.

The dermal elastic fibre network is the primary effector of skin elasticity, enabling it to extend and recoil many times over the lifetime of the individual. Fibrillin-rich microfibrils (FRMs) constitute integral components of the elastic fibre network, with their distribution showing differential deposition in the papillary dermis across individuals of diverse skin ethnicity. Despite these differential findings in histological presentation, it is not known if skin ethnicity influences FRM ultrastructure. FRMs are evolutionarily highly conserved from jellyfish to man and, regardless of tissue type or species, isolated FRMs have a characteristic 'beads-on-a-string' ultrastructural appearance, with an average inter-bead distance (or periodicity) of 56 nm. Here, skin biopsies were obtained from the photoprotected buttock of healthy volunteers (18-27 years; African: n = 5; European: n = 5), and FRMs were isolated from the superficial papillary dermis and deeper reticular dermis and imaged by atomic force microscopy. In the reticular dermis, there was no significant difference in FRM ultrastructure between European and African participants. In contrast, in the more superficial papillary dermis, inter-bead periodicity was significantly larger for FRMs extracted from European participants than from African participants by 2.20 nm (p < .001). We next assessed whether these differences in FRM ultrastructure were present during early postnatal development by characterizing FRMs from full-thickness neonatal foreskin. Analysis of FRM periodicity identified no significant difference between neonatal cohorts (p = .865). These data suggest that at birth, FRMs are developmentally invariant. However, in adults of diverse skin ethnicity, there is a deviation in ultrastructure for the papillary dermal FRMs that may be acquired during the passage of time from child to adulthood. Understanding the mechanism by which this difference in papillary dermal FRMs arises warrants further study.

Hidradenitis suppurativa (HS), also known as acne inversa, is an incapacitating skin disorder of unknown etiology manifested as abscess-like nodules and boils resulting in fistulas and tissue scarring as it progresses. Given that neutrophils are the predominant leukocyte infiltrate in HS lesions, the role of neutrophil extracellular traps (NETs) in the induction of local and systemic immune dysregulation in this disease was examined. Immunofluorescence microscopy was performed in HS lesions and detected the prominent presence of NETs. NET complexes correlated with disease severity, as measured by Hurley staging. Neutrophils from the peripheral blood of patients with HS peripheral also displayed enhanced spontaneous NET formation when compared to healthy control neutrophils. Sera from patients recognized antigens present in NETs and harbored increased antibodies reactive to citrullinated peptides. B cell dysregulation, as evidenced by elevated plasma cells and IgG, was observed in the circulation and skin from patients with HS. Peptidylarginine deiminases (PADs) 1 to 4, enzymes involved in citrullination, were differentially expressed in HS skin, when compared to controls, in association with enhanced tissue citrullination. NETs in HS skin coexisted with plasmacytoid dendritic cells, in association with a type I interferon (IFN) gene signature. Enhanced NET formation and immune responses to neutrophil and NET-related antigens may promote immune dysregulation and contribute to inflammation. This, along with evidence of up-regulation of the type I IFN pathway in HS skin, suggests that the innate immune system may play important pathogenic roles in this disease.

The changing trends in global diversity emphasize the need for skin type-specific expertize. This chapter explores structural variations in skin of color, from clinically apparent to microscopic differences, and examines how these contribute to the unique photobiological response exemplified in ethnic skin. Herein, we discuss the acute and chronic effects of the solar spectrum on skin of color, from ultraviolet and visible light to infrared radiation. In light of these structural and functional differences, we also review special considerations in the classification and management of photoaging in this population.

Background: Although prurigo nodularis (PN) has a significant burden of disease, little is known about its epidemiology and disease burden within the United States. We describe the characteristics of hospitalized patients diagnosed with PN and assess the factors associated with hospitalization. Methods: We performed a cross-sectional study of the 2016 National Inpatient Sample, a representative sample of 20% of hospital discharges nationally. Results: Patients diagnosed with PN accounted for 3.7 inpatient visits per 100,000 discharges nationally in 2016. Patients with PN were more likely to be black (odds ratio (OR) 4.43, 95% CI (3.33&ndash, 6.08), p &lt, 0.001) or Asian (OR 3.44, 95% CI (1.39&ndash, 5.08), p = 0.003) compared with white patients. Patients diagnosed with PN had both a longer length of hospital stay (mean &plusmn, SD, 6.51 &plusmn, 0.37 days vs. 4.62 &plusmn, 0.02 days, p &lt, 0.001) and higher cost of care ($14,772 &plusmn, $964 vs. $11,728 &plusmn, $106, p &lt, 0.001) compared with patients without PN. Patients with PN were significantly more likely to be admitted for HIV complications (OR 78.2, 95% CI (46.4&ndash, 131.8), p &lt, 0.001). PN contributes to increased inpatient cost of care and length of hospitalization. Conclusions: There are racial disparities associated with hospital admission of patients diagnosed with PN.

Background Because of reduced mortality, patients with HIV are living longer and presenting with chronic diseases. Little is known about racial differences in dermatologic conditions associated with HIV infection. Objective This study examines associated dermatologic conditions in a large population of patients with HIV at a tertiary care center with a diverse patient population. Methods Cross-sectional study of patients with HIV seen between July 14, 2013, and July 14, 2018, in a tertiary health care system. The burden of HIV-related dermatologic conditions was collected by using medical records. Patients with HIV were compared with control individuals of the same race, and significance was assessed using the chi-square test. A Bonferroni correction was performed to control for multiple hypothesis testing. Results The study population (N = 4679) was 64.7% male and 69% African American, with 88.7% of patients receiving antiretroviral therapy. African American patients with HIV had a greater risk of oral hairy leukoplakia (odds ratio [OR], 64.49), herpes zoster (OR, 9.27), prurigo nodularis (OR, 8.80), and squamous cell carcinoma (OR, 5.72). Limitations Our data describe patients seen by 1 health care system. Conclusions African American patients with HIV may be at increased risk for pruritic disorders compared with race-matched control individuals and white patients with HIV.

In 2017, a National Rosacea Society Expert Committee developed and published an updated classification of rosacea to reflect current insights into rosacea pathogenesis, pathophysiology, and management. These developments suggest that a multivariate disease process underlies the various clinical manifestations of the disorder. The new system is consequently based on phenotypes that link to this process, providing clear parameters for research and diagnosis as well as encouraging clinicians to assess and treat the disorder as it may occur in each individual. Meanwhile, a range of therapies has become available for rosacea, and their roles have been increasingly defined in clinical practice as the disorder has become more widely recognized. This update is intended to provide a comprehensive summary of management options, including expert evaluations, to serve as a guide for tailoring treatment and care on an individual basis to achieve optimal patient outcomes.

Given the widespread use of systemic antibiotics for treatment of moderate to severe acne, it is important to understand the associations of such antibiotic use with changes not only in Cutibacterium acnes (formerly Propionibacterium acnes) but also in the complete bacterial community of the skin.To examine the composition, diversity, and resilience of skin microbiota associated with systemic antibiotic perturbation in individuals with acne.This longitudinal cohort study conducted at an academic referral center in Maryland from February 11 to September 23, 2014, included 4 female participants who had received a recent diagnosis of acne vulgaris, showed comedonal and inflammatory acne on the face, were at least 18 years old, and had no recent use of systemic or topical treatments for acne, including antibiotics and retinoids. Data analysis was performed between July 5, 2017, and November 7, 2018.Participants were prescribed oral minocycline, 100 mg, twice daily for 4 weeks. Skin areas on the forehead, cheek, and chin were sampled for 16S ribosomal RNA gene sequencing at baseline, 4 weeks after starting minocycline treatment, and then 1 week and 8 weeks after discontinuation of treatment.Skin microbiota examined with respect to relative abundance of bacterial taxa, α diversity (represents within-sample microbial diversity), and β diversity (represents between-sample microbial diversity). Acne status evaluated with photography and lesion count.Of the 4 patients included in this study, 2 were 25 years old, 1 was 29 years old, and 1 was 35 years old; 2 were white women, 1 was an African American woman, and 1 was an Asian woman. Across all 4 patients, antibiotic treatment was associated with a 1.4-fold reduction in the level of C acnes (difference, -10.3%; 95% CI, -19.9% to -0.7%; P = .04) with recovery following cessation of treatment. Distinct patterns of change were identified in multiple bacterial genera, including a transient 5.6-fold increase in the relative abundance of Pseudomonas species (difference, 2.2%; 95% CI, 0.9%-3.4%; P .001) immediately following antibiotic treatment, as well as a persistent 1.7-fold increase in the relative abundance of Streptococcus species (difference, 5.4%; 95% CI, 0.3%-10.6%; P = .04) and a 4.7-fold decrease in the relative abundance of Lactobacillus species (difference, -0.8%; 95% CI, -1.4% to -0.2%; P = .02) 8 weeks following antibiotic treatment withdrawal. In general, antibiotic administration was associated with an initial decrease from baseline of bacterial diversity followed by recovery. Principal coordinates analysis results showed moderate clustering of samples by patient (analysis of similarity, R = 0.424; P = .001) and significant clustering of samples by time in one participant (analysis of similarity, R = 0.733; P = .001).In this study, systemic antibiotic treatment of acne was associated with changes in the composition and diversity of skin microbiota, with variable rates of recovery across individual patients and parallel changes in specific bacterial populations. Understanding the association between systemic antibiotic use and skin microbiota may help clinicians decrease the likelihood of skin comorbidities related to microbial dysbiosis.

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.We sought to analyze skin color patterns in African Americans and compare them with those of Caucasians.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.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.Our study was limited by the sample size and focal geographic source.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.

Introduction Atrophic scarring occurs throughout the course of inflammatory acne and across the spectrum of severity. This study evaluates perceptions of the general population toward individuals with clear skin and acne scars. Methods An online survey administered in the USA, UK, Japan, Germany, France and Brazil to respondents 18 years and over presented three facial pictures of clear skin or digitally superimposed acne scars (but no active acne lesions) in a random fashion. At least one clear and one scar picture were presented to each participant. Results Among the 4618 responders, 33% themselves had facial acne scars. The skin was the first thing noticed about the face by 41% when viewing pictures with scars vs 8% viewing clear skin (p

Background Periocular dark circles (PDCs) are a common cosmetic complaint. Grading systems based on objective measures have been used but no standard system is in place. Objective To determine factors associated with subjective and objective PDC severity. Methods Enrolled patients (n=100) completed a questionnaire comprised of demographic variables, medical history, and self-perception of PDC. Those perceiving PDC graded dissatisfaction on a 10-point scale. Clinical severity (grades 0~4) and subtype (constitutional, post-inflammatory, vascular, shadow effects, or others) were determined. A Konica Minolta CR-400 chromameter was used to obtain colorimetry measurements (L*a*b* values). The objective average difference in darkness (ΔL*) between the periocular region and the cheek was determined. Comparisons were made using Spearman correlation coefficients (r). Results Patient dissatisfaction correlated with both clinical severity (r=0.46, p

Background Pruritus has been associated with cancer. However, limited data are available on the types of underlying malignancies associated with pruritus. Objective We sought to characterize the association between pruritus and different cancer types, as well as variations by racial group. Methods Cross-sectional study of patients ≥18 years of age seen at the Johns Hopkins Health System during 2013-2017. Patients with pruritus were compared with patients without pruritus. Analyses were stratified by race. Results Patients with pruritus were more likely to have concomitant malignancy than those without pruritus (odds ratio 5.76, 95% confidence interval 5.53-6.00). Most strongly associated were cancers of the liver, gallbladder and biliary tract, hematopoietic system, and skin. Compared with white patients, black patients more frequently had soft tissue, dermatologic, and hematologic malignancies and less frequently had liver, respiratory, gastrointestinal, and gynecologic malignancies. Limitations The cross-sectional design precludes analysis of the temporal association between pruritus and malignancy. The study is limited to a single tertiary care center. Conclusion Pruritus is most strongly associated with cancers of the liver, skin, and hematopoietic system. Black patients with pruritus have a higher likelihood of skin, soft tissue, and hematologic malignancies than white patients, while whites have higher likelihoods of liver, respiratory, gastrointestinal, and gynecologic malignancies.

SummaryBackground Striae gravidarum (SG), or ‘stretch marks’ of pregnancy, begin as erythematous streaks, and mature over months to years to become permanent scar-like bands that may be hypopigmented, atrophic and lax. Objectives To investigate early molecular alterations that may promote laxity of mature SG, we investigated the dermal elastic fibre network, which provides human skin with elastic properties. Methods We obtained skin samples of newly developed, erythematous abdominal SG in healthy pregnant women. The elastic fibre network was examined by Verhoeff elastic staining and immunofluorescence staining of skin sections. Gene expression was measured by real-time polymerase chain reaction. Results The normal elastic fibre network appeared markedly disrupted in SG, compared with perilesional abdominal skin or control (normal-appearing hip skin). This disruption was accompanied by the emergence of short, disorganized, thin, thread-like ‘fibrils’, which were observed prominently in the mid-to-deep dermis. These fibrils were rich in tropoelastin (the main component of normal elastic fibres), and persisted into the postpartum period without forming normal-appearing elastic fibres. The emergence of these fibrils was accompanied by increased gene expression of tropoelastin and fibrillin-1, but not other elastic fibre components, including fibrillin-2 and fibulin-1, -2 or -5. Conclusions In early SG, the elastic fibre network appears markedly disrupted, and newly synthesized tropoelastin-rich fibrils emerge, likely as a result of uncoordinated synthesis of elastic fibre components. Because they are thin and disorganized, tropoelastin-rich fibrils likely do not function as normal elastic fibres do. These observations provide the foundations for elucidating pathogenic mechanisms by which laxity may develop in SG.

BACKGROUND: The shave biopsy using a razor with an open blade is the current standard of care for sampling superficial skin lesions. OBJECTIVE: To enhance safety, the authors developed a novel biopsy device with a closed blade design for removing the epidermal layer of skin and evaluated against the open razor blade for tolerability, scarring, and accuracy in histological diagnosis. MATERIALS AND METHODS: Shave biopsies were performed using the novel device or razor blade on benign epidermal skin lesions in 10 patients on comparable body parts. Digital photography, colorimetry, scar scale evaluations, and questionnaires were used to evaluate the efficacy and tolerability of the devices. RESULTS: For all patients, accurate histological diagnoses were made regardless of device type. No statistically significant differences were detected between the novel device and razor blade in terms of scar scale assessments, colorimetry, and questionnaire responses. Both patients and the participating dermatologist reported satisfaction with the safety and performance of the novel device. No injuries to the provider occurred with either instrument. CONCLUSION: The rotating sphere biopsy device is a potential alternative to the razor blade with comparable tolerability, scarring, and accuracy in histological diagnoses, offering improved safety for patients and health care providers.

Acne has long been understood to have a complex physiological basis involving several main factors: hormonally-stimulated sebum production, abnormal keratinization of the pilosebaceous duct, and an inflammatory immune response to Propionibacterium acnes. Recent studies at the molecular and cellular level have begun clarifying how all of these factors interact, and the role of the innate immune system is better appreciated. Inflammation has been demonstrated in all acne lesions - the preclinical microcomedo, comedones, inflammatory lesions, 'post-inflammatory' erythema or hyperpigmentation, and scarring. Inflammation localized to the pilosebaceous unit can be considered the defining feature of acne and should be addressed via multiple therapeutic pathways. Clinicians tend to think oral antibiotics should be used to 'calm' inflammatory acne, but there is good evidence showing that topical retinoids also have anti-inflammatory properties as a class effect. For best therapeutic outcomes, most patients with acne should be treated first line with a topical retinoid plus an antimicrobial agent, as has been demonstrated in thousands of patients involved in clinical trials and recommended by the Global Alliance to Improve Outcomes in Acne for more than a decade. Moving away from reliance on antibiotic therapy for acne is particularly important in an era of worsening antimicrobial resistance and worldwide calls to reduce antibiotic use. Improved understanding about the role of P. acnes and the innate immune system in acne should help clinicians in designing efficacious treatment strategies.

International audience; Background: One major sequelae of acne is atrophic scarring, yet objective tools to assess scars are lacking. Neither depth nor volume of atrophic scars is readily evaluable clinically and standard 2D photography is significantly affected by lighting and shadows. The aim of our study was to define and evaluate parameters of 3D imaging that can be used to assess severity of atrophic acne scarring.Methods: Single center study of 31 patients with acne scarring. A target area of 3 × 3 cm was defined on the face. The global severity of atrophic acne scarring in the target area was evaluated by 5 dermatologists and scars were counted and categorized by size (scars < 2 mm, 2-4 mm, and > 4 mm in diameter). Three dimensional images of the target area were acquired with the LifeViz Micro® system and analysis was performed using MountainsMaps® software. An algorithm was developed to quantify the scar volume loss: shape removal step, with an order 5 polynomial, and to calculate the Valley void volume 80% (Vvv 80%) defined in the ISO-25178 standard for 3D surface texture.Results: Correlation coefficient of the Vvv parameter to mean global severity at the target area rating was 0.77. The volume of scars evaluated with the Vvv parameter was mainly impacted by scars > 2 mm. The evaluations demonstrated good repeatability (with an intra-class correlation coefficient ICC = 0.98).Conclusions: We demonstrate convergent validation to clinical assessment and repeatability of 3D skin imaging in atrophic acne scarring. Image analysis is straightforward and can be integrated into an automated workflow.

Introduction Scarring is an unfortunate clinical outcome of acne. Current treatment options for atrophic acne scars are dominated by non-pharmacological, invasive procedures which may not be suitable or affordable to all patients. This phase II, single-center, open-label, exploratory study assessed the efficacy, safety and subject-reported outcomes of adapalene 0.3% gel in the treatment of atrophic acne scars. Methods The study included subjects aged 18–50 years with past history of acne and moderate to severe facial atrophic acne scars. Subjects received adapalene 0.3% gel once daily for the first 4 weeks and twice daily for the following 20 weeks. Assessments were performed at baseline, day 10 and weeks 4, 8, 16 and 24, and at post-treatment follow-ups (weeks 36 and 48–72). Results At week 24, investigator and subject assessments reported improvement in skin texture/atrophic scars in 50% and > 80% of subjects, respectively. Subjects were satisfied with the treatment and reported improvements in quality of life. Conclusion Daily use of adapalene 0.3% gel for the treatment of atrophic acne scars showed promising clinical efficacy, a favorable tolerability profile, and improvement in quality of life. Funding Nestlé Skin Health–Galderma R&D. Trial Registration ClinicalTrials.gov Identifier NCT01213199.

Background Striae gravidarum (SG), or stretch marks of pregnancy, begin as erythematous streaks, and mature into hypopigmented atrophic bands. Objectives To investigate molecular alterations that may promote atrophy of SG, we investigated dermal type I collagen fibrils, which provide human skin with support. Methods We obtained skin samples of recently developed, erythematous abdominal SG from pregnant women. To examine the organization of collagen fibrils, second-harmonic generation imaging was performed using multiphoton microscopy. Immunostaining was used to determine protein expression and localization of type I procollagen, the precursor of type I collagen fibrils. Real-time polymerase chain reaction was used to determine gene expression levels. Results In control (hip) and stretched, normal-appearing perilesional abdominal skin, dermal collagen fibrils were organized as tightly packed, interwoven bundles. In SG, collagen bundles appeared markedly separated, especially in the mid-to-deep dermis. In the spaces separating bundles, loosely packed wavy collagen fibrils lacking organization as bundles were present. These disorganized fibrils persisted into the postpartum period and failed to form densely packed bundles. Numerous large fibroblasts displaying type I procollagen expression were in close proximity to the disorganized fibrils, suggesting that the fibrils are newly synthesized. Supporting this possibility, immunostaining and gene expression of type I procollagen were increased throughout the dermis of SG. Conclusions Early SG display marked separation of collagen bundles and emergence of disorganized collagen fibrils that fail to form bundles. These alterations may reflect ineffective repair of collagen bundles disrupted by intense skin stretching. Persistent disruption of the collagenous extracellular matrix likely promotes formation and atrophy of SG. This article is protected by copyright. All rights reserved.

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 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.

Although there have been few formal studies, scarring is a known bothersome companion of acne vulgaris. We performed a prospective study of subjects consulting a dermatologist for active acne to assess the frequency of acne scarring. Investigators performed a short questionnaire on all acne patients seen at their office for one consecutive 5-day work week to assess scar frequency. Additionally, the first four subjects with acne scars identified were enrolled for a second phase (scar cohort) of the study during which the investigator collected further medical history and performed a clinical evaluation and the patient completed a self-administered questionnaire about scar perceptions and impact on quality of life. A total of 1,972 subjects were evaluated by 120 investigators. Among these, 43 percent (n=843) had acne scarring. Subjects with acne scars were significantly more likely to have severe or very severe acne (P less than .01); however, 69% of the subjects with acne scars had mild or moderate acne at the time of the study visit. Risk factors correlated with increased likelihood of scarring were acne severity, time between acne onset and first effective treatment, relapsing acne, and male gender. Treatments that can completely resolve acne scars are not yet available - prevention and early treatment remain a primary strategy against scars. It is vital for clinicians who manage individuals with acne to institute effective therapy as early as possible, since treatment delay is a key modifiable risk factor for scarring.

Background Acne is a chronic dermatological disease predominantly afflicting young adults and is often associated with the development of scars. Acne scarring is usually avoidable when acne is managed early and effectively. However, acne patients often fail to seek early treatment. New and innovative tools to raise awareness are needed. Objective This study presents the development and assessment of a tool aiming to assess the risk of atrophic acne scars. Methods A systematic literature review of clinical risk factors for acne scars, a Delphi-like survey of dermatological experts in acne and secondary data analysis, were conducted to produce an evidence-based risk assessment tool. The tool was assessed both with a sample of young adults with and without scars and was assessed via a database cross-validation. Results A self-administered tool for risk assessment of developing atrophic acne scars in young adults was developed. It is a readily comprehensible and practical tool for population education and for use in medical practices. It comprises of four risk factors: worst ever severity of acne, duration of acne, family history of atrophic acne scars and lesion manipulation behaviours. It provides a dichotomous outcome: lower vs. higher risk of developing scars, thereby categorizing nearly two-thirds of the population correctly, with sensitivity of 82% and specificity of 43%. Conclusion The present tool was developed as a response to current challenges in acne scar prevention. A potential benefit is to encourage those at risk to self-identify and to seek active intervention of their acne. In clinical practice, we expect this tool may help clinicians identify patients at risk of atrophic acne scarring and underscore their requirement for rapid and effective acne treatment.

Summary Photoaging is frequently encountered in a dermatologic practice. This systematic literature review aims to explore the etiology of photoaging and address the evidence behind its current management. A comprehensive search of MEDLINE, EMBASE, UpToDate, and the Cochrane Library was conducted. Articles were limited to those relating to photoaging. There are two major approaches in the current management of photoaging. This includes strategies to prevent against ultraviolet damage (e.g. sunscreen) and medications that attempt to reverse existing skin damage (topical retinoids and 5-fluorouracil). There has been a large growth in the variety of treatment options in recent years. While it is important for such growth to continue, prevention via sensible photoprotection methods still remains the best current management option.

This article discusses photoaging or premature skin aging from chronic ultraviolet exposure. This is an important cosmetic concern for many dermatologic patients. Clinical signs include rhytids, lentigines, mottled hyperpigmentation, loss of translucency, and decreased elasticity. These changes are more severe in individuals with fair skin and are further influenced by individual ethnicity and genetics. Photoaging may be prevented and treated with a variety of modalities, including topical retinoids, cosmeceuticals, chemical peels, injectable neuromodulators, soft tissue fillers, and light sources.

Summary Background Antitumour necrosis factor (anti-TNF)-α therapy has made a significant impact on the treatment of psoriasis. Despite these agents being designed to neutralize TNF-α activity, their mechanism of action in the resolution of psoriasis remains unclear. Objectives To understand better the mechanism of action of etanercept by examining very early changes in the lesional skin of patients with psoriasis responding to etanercept. Methods Twenty patients with chronic plaque psoriasis were enrolled and received etanercept 50 mg twice weekly. Skin biopsies were obtained before treatment and on days 1, 3, 7 and 14 post-treatment. Skin mRNA expression was analysed by quantitative reverse-transcription polymerase chain reaction and microarray; cytokine and phosphoprotein levels were assessed using multiplexed bead arrays. Results In etanercept responders, we observed no significant changes in interleukin (IL)-17A, IL-22 or interferon-γ mRNA or protein in the first week of treatment; however, there was a 2·5-fold downregulation of IL-17 receptor C (IL-17RC) mRNA (P

Nonmelanoma skin cancers (NMSCs) are the most common malignancies in the United States in immunocompetent patients. Among the solid-organ transplant recipients, NMSCs represent a significant disease burden, and they tend to be multiple and more aggressive. While the precise mechanisms responsible for the higher risk of developing cutaneous squamous cell carcinomas (SCCs) have not been completely elucidated, ultraviolet (UV) light has been established to be critical in initiation and promotion of tumor development. More recently, significant emphasis has been placed on the role of the mammalian target of rapamycin (mTOR) pathway in SCC pathogenesis. Furthermore, some studies have demonstrated the ability of mTOR inhibitors to decrease the incidence of new SCCs in the immunosuppressed transplanted patient population. In this review, we will highlight and examine the most recent available data on the role of UV radiation and its interaction with mTOR pathway signaling in SCC pathogenesis.