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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.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/cmRepeated 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.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.

IMPORTANCE: Topical formulations of tretinoin precursors (retinol and its ester derivatives) are widely available over the counter and may offer similar clinical benefits to those of tretinoin for treatment of photoaging. However, which of the many purported molecular effects of retinoids most strongly drives clinical improvements in tretinoin-treated skin remains unclear. OBJECTIVES: To evaluate the clinical efficacy of topical tretinoin precursors (TTP) vs tretinoin (RA) in treating moderate to severe facial photodamage and to identify potential biomarkers that correlate with clinical efficacy. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, single-center, parallel-arm study of 24 patients with moderate to severe facial photodamage was conducted at an academic referral center from November 2010 to December 2011, with data analysis performed from January 2012 to December 2021. INTERVENTIONS: Daily topical application of 0.02% RA or 1.1% TTP formulation containing retinol, retinyl acetate, and retinyl palmitate for 24 weeks. MAIN OUTCOMES AND MEASURES: Photoaging and tolerability were assessed by dermatologist evaluations and patient-reported outcomes. Target gene expression was assessed by real-time quantitative polymerase chain reaction of biopsied tissue from treated areas. RESULTS: A total of 20 White women were ultimately analyzed (9 randomized to TTP, 11 randomized to RA). At week 24, there was no significant difference in Griffiths photoaging scores among patients receiving TTP vs RA (median, 4 vs 5) (TTP − RA difference: −1; 95% CI, −2 to 1; P = .27). Treatment with TTP was associated with erythema 6 times less frequently than RA (11% vs 64%) (TTP − RA difference: −0.53; 95% CI, −0.88 to −0.17; P = .01). Target gene analysis showed significant CRABP2 messenger RNA (mRNA) induction (confirming retinoic acid receptor signaling) but no significant changes in procollagen I or MMP1/3/9 mRNA in TTP-treated samples. Instead, MMP2 mRNA, which encodes a type IV collagenase, was significantly reduced in TTP-treated samples (week 24 − baseline mRNA difference: −5; 96% CI, −33 to 1.6; P = .02), and changes in MMP2 were strongly correlated with changes in fine wrinkles (r = 0.54; 95% CI, 0.12 to 0.80; P = .01). Interestingly, patients with severe baseline wrinkles exhibited greater improvements (r = −0.74; 95% CI, −0.89 to −0.43; P

Background Photoaging is premature skin aging resulting from oxidative stress generated by exposure to solar radiation. A key clinical feature is solar lentigines, areas of hyperpigmentation on sun-exposed skin. Skin pigmentation is determined by cross-talk between keratinocytes and melanocytes, which is exquisitely sensitive to oxidative stress. Toll-like receptor (TLR) signaling and NF-E2-related factor 2 (NRF2) signaling, an endogenous antioxidant system, serve as a bridge between the oxidative stress response and immune regulation. Moreover, TLR-mediated induction of IL-6 production has been shown to prevent ultraviolet (UV)-induced hyperpigmentation. Methods Shave biopsies of solar lentigines were obtained from 14 individuals. An additional 7 subjects applied broccoli sprout extract (BSE) containing sulforaphane daily or vehicle on photodamaged skin. Immunofluorescence staining was used to determine total and phosphorylated NRF2 in the lentiginous skin. Dermoscopy and Fontana & Masson staining were used to assess the effect of topical BSE on UV-induced pigmentation. Similar topical treatments were performed in a mouse model of UVB-induced hyperpigmentation utilizing WT, Nrf2-/-, or K14-Cre-ERT2IL-6Rαfl/fl C57BL/6 mice. Results NRF2 expression is altered in solar lentigines, and UV-induced skin pigmentation in humans could be ameliorated with topical BSE. Corresponding mouse models replicated the authors' clinical findings and identified a potential mechanistic link to IL-6Rα signaling in keratinocytes. Conclusion The authors' findings suggest that dysregulation of NRF2 signaling is involved in the pathogenesis of UV-induced skin pigmentation and pharmacological activation of NRF2 may represent a potential therapeutic target in photoaging.

Prurigo nodularis (PN) is an intensely pruritic, chronic inflammatory skin disease that disproportionately affects black patients. However, the pathogenesis of PN is poorly understood. We performed single-cell transcriptomic profiling, ligand receptor analysis and cell trajectory analysis of 28,695 lesional and non-lesional PN skin cells to uncover disease-identifying cell compositions and genetic characteristics. We uncovered a dysregulated role for fibroblasts (FBs) and myofibroblasts as a key pathogenic element in PN, which were significantly increased in PN lesional skin. We defined seven unique subclusters of FBs in PN skin and observed a shift of PN lesional FBs towards a cancer-associated fibroblast (CAF)-like phenotype, with WNT5A+ CAFs increased in the skin of PN patients and similarly so in squamous cell carcinoma (SCC). A multi-center PN cohort study subsequently revealed an increased risk of SCC as well as additional CAF-associated malignancies in PN patients, including breast and colorectal cancers. Systemic fibroproliferative diseases were also upregulated in PN patients, including renal sclerosis and idiopathic pulmonary fibrosis. Ligand receptor analyses demonstrated increased FB1-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV, suggesting a fibroblast-neuronal axis in PN. Type I IFN responses in immune cells and increased angiogenesis/permeability in endothelial cells were also observed. As compared to atopic dermatitis (AD) and psoriasis (PSO) patients, increased mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype between atopic dermatitis and psoriasis. These findings identify a pathogenic role for CAFs in PN, including a novel targetable WNT5A+ fibroblast subpopulation and CAF-associated malignancies in PN patients.

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.This study describes clinical and histologic responses to VL and examines the potential role of melanin in the underlying mechanistic pathways.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/cmDarker skin did not tolerate the full VL regimen with blistering occurring in most subjects at doses of 220-880 J/cmSkin 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.

Acne vulgaris is a common inflammatory disease. Among patients with darker skin phototypes (Fitzpatrick III–VI), the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation and post-inflammatory erythema in all skin tones, although post-inflammatory hyperpigmentation is more common in darker skin and post-inflammatory erythema in lighter skin. These pigmentary alterations can be long lasting and are often more distressing to patients than the active acne lesions. This article discusses what is known about acne-related pigmentation, much of which is extrapolated from general study of nonspecific pigment deposition. Because dyspigmentation poses both a significant clinical concern to patients and a therapeutic challenge to clinicians, we formed a working group consisting of pigmentary experts with the aim of increasing awareness and education of acne-related pigmentary sequelae.

BACKGROUND: Dry, itchy skin can lower quality of life (QoL) and aggravate skin diseases. Moisturizing skin care products can have beneficial effects on dry skin. However, the role of a daily skin care routine is understudied. OBJECTIVE: To understand how daily skin care with a mild cleanser and moisturizer impacts skin health and patients’ QoL, in dry skin population. METHODS: A randomized, investigator-blinded study of 52 participants with moderate to severe dry skin. The treatment group (n=39) used mild cleanser and moisturizer twice daily for two weeks whereas the control group (n=13) used mild cleanser without moisturizer. Total Clinical Score (TCS; erythema, scale and fissures), Visual Dryness Score (VDS) and subjective itch-related quality of life (ItchyQoL) were collected. RESULTS: The treatment group showed significantly more improvement in TCS and VDS compared to the control group after two weeks. Among the three components of the ItchyQoL (symptoms, functioning, and emotions), symptom showed significantly greater improvement in the treatment compared to the control group. Over 80% of participants in the treatment group agreed that the regimen led to decrease in dryness/pruritus and improved skin texture. CONCLUSIONS: A consistent skin care regimen should be an integral component of management of dry skin.

Topical retinoids are the cornerstone of current acne management due to their actions on multiple facets of acne pathophysiology. Retinoids are a family of compounds that structurally and functionally resemble vitamin A, an essential nutrient with a key role in cellular growth and differentiation. In the skin, retinoids exert their effects by binding retinoic acid receptors (RARs) in the cell nucleus with subsequent regulation of gene transcription. There are three subtypes of RARs, and the topical retinoids currently approved for acne have differing receptor binding profiles which may translate to clinical differences, since the specific RAR subtypes activated dictate the biological response of target cells. The activity of a retinoid depends on cellular transport, receptor-binding pattern and affinity, and the genes activated. This review discusses physiologic pathways in skin that are affected by topical retinoids during acne therapy, with a focus on new data from trifarotene, a retinoid which is highly selective for the RAR-gamma; receptor. Recently, bioinformatic data comparing gene expression in acne lesions treated with trifarotene versus spontaneously resolving acne lesions showed that trifarotene significantly modulates 67 genes that do not appear in the spontaneously resolving lesion. These genes are involved in cellular migration, activation of adaptive immunity, inflammation, and matrix reorganization. Expression of these trifarotene-regulated genes after treatment and in an active lesion occurred in opposite directions, providing clues to the molecular and genetic response to trifarotene in resolving acne. J Drugs Dermatol. 2022;21(7):734-740. doi:10.36849/JDD.6890.

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 µm(2)) compared to controls (347.879 ± 539.624 µm(2), 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.

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.

Laser resurfacing treatments for photoaged skin have improved dramatically over the past decades, but few studies have examined the molecular mechanisms underlying differences in clinical response. Seventeen white female participants with moderate-to-severe photoaging received nonablative fractional laser treatment on the face and forearm once monthly for 6 months. Biopsies for microarray analysis were performed at baseline and 7 days after facial treatment and at baseline and 1, 7, 14, and 29 days after forearm treatment in each participant, resulting in 119 total samples. Participants were stratified into fast (n = 11) and slow (n = 6) responders on the basis of the presence of clinical improvement after the first treatment. Microarray analysis revealed the upregulation of genes associated with matrix metalloproteinases, collagen and extracellular components, TGF-β signaling, double-stranded RNA signaling, and retinoic acid synthesis after treatment that did not differ significantly between fast and slow responders. Cluster and enrichment analyses suggested significantly greater activation of lipid metabolism and keratinocyte differentiation in fast responders, who showed greater upregulation of acyltransferases, fatty acid elongases, fatty acid 2-hydroxylase, fatty acid desaturases, and specific keratins that may contribute to epidermal barrier function. These results create, to our knowledge, a previously unreported atlas of molecular changes that correlate with improvements in photoaging after laser therapy.

Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in QOL. Although there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concentrations in patients with PN (n = 20) along with matched healthy controls and utilized an unsupervised machine learning algorithm to identify disease endotypes. We found two distinct clusters of patients with PN with noninflammatory (cluster 1) and inflammatory (cluster 2) plasma profiles. Cluster 2 had more African Americans (82%, n = 9 vs. 33%, n = 3; P = 0.028), higher Worst Itch Numeric Rating Scale scores (9.5 ± 0.9 vs. 8.3 ± 1.2; P = 0.036), and lower QOL as reflected by higher Dermatology Life Quality Index scores (21.9 ± 6.4 vs. 13.0 ± 4.1; P = 0.015). In addition, cluster 1 had a higher rate of myelopathy (67%, n = 6 vs. 18%, n = 2; P = 0.028). Compared with cluster 1, cluster 2 had higher levels of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α. With population-level analysis, African American patients with PN had higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils and lower transferrin than Caucasian patients with PN. These findings indicate discrete clusters of patients with PN with plasma biomarker profiles corresponding to distinct demographic and clinical characteristics, potentially allowing for precision medicine approaches to treat PN.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]

Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti–human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.

Acne vulgaris is a common inflammatory disease. Among patients with darker skin phototypes (Fitzpatrick III-VI), the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation and post-inflammatory erythema in all skin tones, although post-inflammatory hyperpigmentation is more common in darker skin and post-inflammatory erythema in lighter skin. These pigmentary alterations can be long lasting and are often more distressing to patients than the active acne lesions. This article discusses what is known about acne-related pigmentation, much of which is extrapolated from general study of nonspecific pigment deposition. Because dyspigmentation poses both a significant clinical concern to patients and a therapeutic challenge to clinicians, we formed a working group consisting of pigmentary experts with the aim of increasing awareness and education of acne-related pigmentary sequelae.

Background Associations between acne and gastrointestinal comorbidities suggest that microbial dysbiosis and intestinal permeability may promote inflammatory acne, a condition often managed with oral antibiotics. Objective We performed a case-control study to investigate the skin and gut microbiota in 8 acne patients before and after receiving oral minocycline compared to controls matched by age ±5 years, sex, and race. Methods DNA was extracted from stool samples and facial skin swabs. Sequencing of the V3V4 region of the bacterial 16S rRNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software. Results Acne patients included 7 female and 1 male, ages 20~32. Shannon diversity was not significantly different between the skin (p=0.153) or gut (p

BACKGROUND: The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea. OBJECTIVE: We performed a case–control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race. METHODS: Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software. RESULTS: Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%). CONCLUSIONS: The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity., During wound induced hair follicle neogenesis (WIHN), stem cells regenerate hair follicles but how this arises is unclear. Here, the authors show that self-noncoding dsRNA activates the antiviral receptor TLR3 to induce intrinsic retinoic acid, which stimulates WIHN in mice, and in isolated human keratinocyte cells.

Acne vulgaris is among the most common dermatologic diagnoses observed, including skin color (SOC) populations. This project sought to help clarify the existing published data and provide consensus statements on acne presentation, prevention, treatment, and maintenance in SOC populations to help improve patient outcomes.Six SOC dermatologists convened for a virtual meeting and used a modified Delphi process to address: 1) Are there racial/ethnic differences in the clinical presentation and sequela of acne? 2) Are there racial/ethnic differences in the therapeutic endpoint of acne treatment and patient expectations? 3) Is there a need for specialized approaches to therapeutic options and skincare in acne patients with SOC? The results of a literature review and the outcome of discussions, coupled with the panel's expert opinion and experience, are intended for health care providers caring for acne patients and clinician-researchers.Racial/ethnic differences in the clinical presentation, sequelae, and desired treatment outcomes for acne have been reported. Notwithstanding limitations in the number, size, and methodologies of studies to date, the available data suggest that strategies that improve outcomes in acne patients with SOC include: Early initiation and maintenance of treatment regimens and careful consideration of tolerability of active ingredients, vehicles, and dosing. Using pH-balanced, non-irritating cleansers and non-comedogenic ceramides containing moisturizers help minimize irritation or dryness.There a need for specialized approaches to therapeutic options and skincare in acne patients with SOC. OTC skincare products are recommended before and during prescription therapy and as part of a maintenance regimen. J Drugs Dermatol. 2021;20(7):716-725. doi:10.36849/JDD.6169 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Topical retinoids are well-established as the first-line and foundational treatment for acne. Topical retinoids used in the treatment of acne include all-trans retinoic acid (tretinoin), adapalene, tazarotene, and the emerging fourth-generation topical retinoid trifarotene. Retinoids encompass the family of natural and synthetic vitamin A derivatives which exert their effects through binding to retinoid receptors within the cellular nucleus leading to a multitude of downstream effects including keratinocyte differentiation and proliferation, cytokine signaling, and embryonic development. In the treatment of acne, retinoids aid in decreasing follicular keratinization and keratinocyte cohesiveness, thus reducing follicular occlusion and comedone formation. More importantly, numerous studies have demonstrated the efficacy of topical retinoids in treating post-acne sequelae such as atrophic scarring and post-inflammatory hyperpigmentation.

Background The ability of Cutibacterium acnes strains to form biofilms has been correlated with their virulence. Objective This study examined biofilm and skin microbiota in acne patients in order to understand their role in the development of acne lesions. Methods Thin sections of punch biopsy specimens of (i) uninflamed comedones, (ii) inflammatory lesions, and (iii) uninvolved adjacent skin of acne patients were examined. Epiflourescence and confocal laser scanning microscopy were used for biofilm detection, and pyrosequencing with taxonomic classification of 16s rRNA gene amplicons was used for microbiota analysis. Results Of the 39 skin specimens from patients with mild-moderate acne (n = 13) that were studied, nine (23%) contained biofilm. Among these specimens, biofilm was most frequently detected in comedones (55.6%) and less frequently in inflammatory papules (22.2%) and uninvolved skin (22.2%). Comedones demonstrated the highest mean alpha diversity of all the lesion subtypes. The relative abundance of Staphylococcus was significantly higher in comedones (11.400% ± 12.242%) compared to uninvolved skin (0.073% ± 0.185%, P = 0.024). Conclusions The microenvironment of the comedone differs from that of inflammatory lesions and unaffected skin. The increased frequency of biofilm in comedones may account for the lack of host inflammatory response to these lesions.

Mottled skin pigmentation and solar lentigines from chronic photodamage with aging involve complex interactions between keratinocytes and melanocytes. However, the precise signaling mechanisms that could serve as therapeutic targets are unclear. Herein, we report that expression of nuclear factor erythroid 2–related factor 2 (NRF2), which regulates reduction-oxidation reactions, is altered in solar lentigines and photodamaged skin. Moreover, mottled skin pigmentation in humans could be treated with topical application of the NRF2 inducer sulforaphane (SF). Similarly, UV light–induced pigmentation of WT mouse ear skin could be treated or prevented with SF treatment. Conversely, SF treatment was unable to reduce UV-induced ear skin pigmentation in mice deficient in NRF2 or in mice with keratinocyte-specific conditional deletion of IL-6Rα. Taken together, NRF2 and IL-6Rα signaling are involved in the pathogenesis of UV-induced skin pigmentation, and specific enhancement of NRF2 signaling could represent a potential therapeutic target., Pharmacological activation of NRF2-signaling resulted in improved skin hyperpigmentation in human and mouse skin.

Importance The ability to predict the efficacy of systemic psoriasis therapy based on immune profiles in skin biopsies could reduce the use of inappropriate treatment and its associated costs and adverse events. It could considerably decrease drug development trial costs as well. Objective To develop a bioinformatic gene signature score derived from skin mRNA to predict psoriasis treatment outcomes for a variety of therapies. Design, Setting, and Participants In this decision analytical model using 1145 skin samples from different cohorts of 12 retrospective psoriasis studies, samples were analyzed using the CIBERSORT algorithm to define the immune landscape of psoriasis lesions and controls. Random forest classification and principal component analysis algorithms were used to estimate psoriatic microenvironment (PME) signature genes and construct a PME score. Overall, 85 and 421 psoriasis lesions from 1 and 4 independent cohorts were used as discovery and validation studies, respectively. Among them, 157, 71, 89, and 90 psoriasis lesions were treated with etanercept, tofacitinib, adalimumab, and methotrexate, respectively. Main Outcomes and Measures Number of weeks after treatment initiation when responders and nonresponders could be predicted. Results Overall, 22 immune cell subtypes formed infiltration patterns that differentiated psoriasis lesions from healthy skin. In psoriasis lesions, the expression of 33 PME signature genes defined 2 immune phenotypes and in aggregate could be simplified to a numerical PME score. A high PME score, characterized by keratinocyte differentiation, correlated with a better treatment response (Psoriasis Area and Severity Index [PASI] reduction, 75.8%; 95% CI, 69.4% to 82.2%;P = .03), whereas a low PME score exhibited an immune activation signature and was associated with a worse response (PASI reduction, 53.5%; 95% CI, 45.3% to 61.7%;P = .03). The PME score at week 4 after treatment initiation correlated with future responder vs nonresponder to treatment status 8 to 12 weeks earlier than PASI reduction for etanercept, methotrexate plus adalimumab, and tofacitinib. Conclusions and Relevance The PME score is a biometric score that may predict clinical efficacy of systemic psoriasis therapy in advance of clinical responses. As an application of personalized medicine, it may reduce the exposure of patients with psoriasis to ineffective and expensive therapies.

Background: Tissue temperature monitoring during cutaneous laser therapy can lead to safer and more effective treatments. In this study, we investigate the use of speckle variance optical coherence tomography (svOCT) to monitor real-time temperature changes in the excised human skin tissue sample during laser irradiation. Methods: To accomplish this, we combined the pulse laser system with a reference-based svOCT system. To calibrate the svOCT, the ex-vivo human skin samples from three individuals with tissues collected from the arm, face, and back were heated with 1-degree increments. Additionally, linear regression was used to extract and evaluate the linear relationship between the temperature and normalized speckle variance value. Experiments were conducted on excised human skin sample to monitor the temperature change during laser therapy with a svOCT system. Thermal modeling of ex-vivo human skin was used to numerically simulate the laser-tissue interaction and estimate the thermal diffusion and peak temperature of the tissue during the laser treatment. Results and Conclusion: These results showed that normalized speckle variance had a linear relationship with the tissue temperature before the onset of tissue coagulation (52°) and we were able to measure the rapid increase of the tissue temperature during laser therapy. The result of the experiment is also in good agreement with the numerical simulation result that estimated the laser-induced peak temperature and thermal relaxation time., Tissue temperature monitoring during cutaneous laser therapy can lead to safer and more effective treatments. In this study, we investigate the use of speckle variance optical coherence tomography (svOCT) to monitor real-time temperature changes in the excised human skin tissue sample during laser irradiation. To accomplish this, we combined the pulse laser system with a reference-based svOCT system. To calibrate the svOCT, the ex-vivo human skin samples from three individuals with tissues collected from the arm, face, and back were heated with 1-degree increments. Additionally, linear regression was used to extract and evaluate the linear relationship between the temperature and normalized speckle variance value. Experiments were conducted on excised human skin sample to monitor the temperature change during laser therapy with a svOCT system. Thermal modeling of ex-vivo human skin was used to numerically simulate the laser-tissue interaction and estimate the thermal diffusion and peak temperature of the tissue during the laser treatment. These results showed that normalized speckle variance had a linear relationship with the tissue temperature before the onset of tissue coagulation ($52^{\circ}$) and we were able to measure the rapid increase of the tissue temperature during laser therapy. The result of the experiment is also in good agreement with the numerical simulation result that estimated the laser-induced peak temperature and thermal relaxation time.

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 2 = 0.849) selected age (b 1 = 0.111, p 2 = 0.206, p = 0.014), and gender (b 2 = −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.

In 2002, the National Rosacea Society assembled an expert committee to develop the first standard classification of rosacea. This original classification was intended to be updated as scientific knowledge and clinical experience increased. Over the last 15 years, significant new insights into rosacea's pathogenesis and pathophysiology have emerged, and the disorder is now widely addressed in clinical practice. Growing knowledge of rosacea's pathophysiology has established that a consistent multivariate disease process underlies the various clinical manifestations of this disorder, and the clinical significance of each of these elements is increasing as more is understood. This review proposes an updated standard classification of rosacea that is based on phenotypes linked to our increased understanding of disease pathophysiology. This updated classification is intended to provide clearer parameters to conduct investigations, guide diagnosis, and improve treatment.