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Skin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for treatment by identifying microbial and molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy adult subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome, with ADL skin having the greatest divergence. Staphylococcus species, especially S. aureus, were significantly increased in AD patients. Metabolomic profiles were also different between the groups. Dipeptide derivatives are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis of the microbiome and metabolomics data revealed higher co-occurrence of metabolites and bacteria in healthy ADNL compared to ADL. S. aureus co-occurred with dipeptide derivatives in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria, for example, Paracoccus sp., Pseudomonas sp., Prevotella bivia, Lactobacillus iners, Anaerococcus sp., Micrococcus sp., Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, and Roseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.IMPORTANCEThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles in an adult population with mild to moderate atopic dermatitis. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.

Cannabinol (CBN) is a secondary metabolite of cannabis whose beneficial activity on inflammatory diseases of human skin has attracted increasing attention. Here, we sought to investigate the possible modulation by CBN of the major elements of the endocannabinoid system (ECS), in both normal and lipopolysaccharide‐inflamed human keratinocytes (HaCaT cells). CBN was found to increase the expression of cannabinoid receptor 1 (CB1) at gene level and that of vanilloid receptor 1 (TRPV1) at protein level, as well as their functional activity. In addition, CBN modulated the metabolism of anandamide (AEA) and 2‐arachidonoylglicerol (2‐AG), by increasing the activities of N‐acyl phosphatidylethanolamines‐specific phospholipase D (NAPE‐PLD) and fatty acid amide hydrolase (FAAH)—the biosynthetic and degradative enzyme of AEA—and that of monoacylglycerol lipase (MAGL), the hydrolytic enzyme of 2‐AG. CBN also affected keratinocyte inflammation by reducing the release of pro‐inflammatory interleukin (IL)‐8, IL‐12, and IL‐31 and increasing the release of anti‐inflammatory IL‐10. Of note, the release of IL‐31 was mediated by TRPV1. Finally, the mitogen‐activated protein kinases (MAPK) signaling pathway was investigated in inflamed keratinocytes, demonstrating a specific modulation of glycogen synthase kinase 3β (GSK3β) upon treatment with CBN, in the presence or not of distinct ECS‐directed drugs. Overall, these results demonstrate that CBN modulates distinct ECS elements and exerts anti‐inflammatory effects—remarkably via TRPV1—in human keratinocytes, thus holding potential for both therapeutic and cosmetic purposes. [ABSTRACT FROM AUTHOR]

Topical treatment offers a viable alternative for melanoma patients incompatible with surgical interventions. Herein, the study develops a skin‐penetrating peptide (SPP)‐based peptide drone (PD) for the transdermal delivery of antitumor proteins. To achieve cost‐effective therapeutics, Concanavalin A (ConA), which can be prepared through an extraction method, is loaded onto PDs. Compared with free proteins, ConA‐PD complexes (CPCs) demonstrate significantly greater skin permeation. Moreover, the CPCs exhibit potent anticancer activity both in vitro and in vivo, which substantially surpass the efficacy of the Aldara (imiquimod) cream. The CPC‐treated mouse skin remains clear, whereas Aldara cream induces side effects, including psoriasis‐like skin inflammation. The antimetastatic activity of the PD is identified as another advantage of CPC. The use of ConA as an anticancer agent has been significantly limited due to its high hepatotoxicity; however, the transdermal delivery strategy minimizes its hepatic absorption and, in turn, results in negligible hepatotoxicity. These results demonstrate the potential of the CPC as a novel therapeutic agent or an adjunct to other modalities for melanoma treatment, overcoming the limitations of existing materials while exhibiting superior efficacy. [ABSTRACT FROM AUTHOR]

The plasma membrane protein caveolin-1 (CAV-1) regulates signaling by inhibiting a wide range of kinases and other enzymes. Our previous study demonstrated that the downregulation of CAV-1 in psoriatic epidermal cells contributes to inflammation by enhancing JAK/STAT signaling, cell proliferation, and chemokine production. Administration of the CAV-1 scaffolding domain (CSD) peptide suppressed imiquimod (IMQ)-induced psoriasis-like dermatitis. To identify an optimal therapeutic peptide derived from CAV-1, we have compared the efficacy of CSD and subregions of CSD that have been modified to make them water soluble. We refer to these modified peptides as sCSD, sA, sB, and sC. In IMQ-induced psoriasis-like dermatitis, while all four peptides showed major beneficial effects, sB caused the most significant improvements of skin phenotype and number of infiltrating cells, comparable or superior to the effects of sCSD. Phosphorylation of STAT3 was also inhibited by sB. Furthermore, sB suppressed angiogenesis both in vivo in the dermis of IMQ-induced psoriasis mice and in vitro by blocking the ability of conditioned media derived from CAV-1-silenced keratinocytes to inhibit tube formation by HUVEC. In conclusion, sB had similar or greater beneficial effects than sCSD not only by cytokine suppression but by angiogenesis inhibition adding to its ability to target psoriatic inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Canine atopic dermatitis (AD) closely mimics human AD and is recognized as a beneficial animal model. House dust mites (HDM) are a common allergen for both species. The effects of chronic exposure to HDM on the skin have not been studied in this animal model, and it is not known how changes in gene expression correlate to the severity of dermatitis. Methods: We used an established canine model of AD and took biopsies before HDM exposure (D0) and five times during repeated allergen challenges (on Days 1, 2, 8, 15, and 29, hereafter referred to as D1, D2, D8, D15, and D29). The severity of dermatitis was scored on the same days. Results: Trichohyalin (TCHH) gene expression decreased the most (15-fold decrease on D29 vs. D0) and negatively correlated with the severity of dermatitis. Gap-junction protein gene expression increased over 3-fold on D1, D8, and D29 and positively correlated with the severity of dermatitis. Compared to D0, IL-31 gene expression significantly increased on D8 (p = 0.0098), D15 (p = 0.0068), and D29 (p = 0.0187), but the correlation with the severity of dermatitis did not reach significance. Discussion: This is the first report on trichohyalin, a protein belonging to the S100 family, and gap-junction protein gene expression in the context of the clinical severity of AD. We propose that these proteins should be further investigated to better understand their role in this complex disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) are a common and growing type of cancer treatment, but they can cause side effects. This study aims to understand these side effects in patients with kidney cancer and bladder cancer. We compared the types and severity of side effects between these two groups to determine if there are differences. We also compared them to other tumor types to see if there is a unique pattern. The findings will help doctors better predict and manage side effects. This will hopefully lead to improving patient care for those receiving ICI treatment. Background: Immune checkpoint inhibitors (ICIs) have become common lines of therapy for genitourinary cancers (GUcs). Given their widespread use, understanding the risk factors, comparative profiles, and timing of immune-related adverse events (irAEs) is essential. Methods: We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 1 February 2011 and 7 April 2022 at a comprehensive cancer center and its outreach clinics. Dichotomous outcomes were modeled using multivariable logistic regression. Survival outcomes were compared using multivariable Cox regression. Results: Among 3101 patients, 196 had renal cell carcinoma (RCC) and 170 had urothelial tumors. RCC patients were more likely to experience irAEs (OR 1.78; 95% CI 1.32–2.39), whereas urothelial carcinoma patients were not (OR 1.22; 95% CI 0.88–1.67). RCC patients were more prone to dermatitis, thyroiditis, acute kidney injury, and myocarditis, compared to other tumors, while urothelial carcinoma patients were not. The impact of irAEs on survival was not significantly different for GUcs compared to other tumors. Conclusions: RCC primaries have a significantly different irAE profile than most tumors, as opposed to urothelial primaries. Further, RCC was more likely to experience any irAEs. Heterogeneity of survival benefits by irAEs was not seen. [ABSTRACT FROM AUTHOR]

Among the occupational skin diseases, bird mite dermatitis (gamasoidosis) is an infrequent and under-reported condition. A report is presented of a group of workers employed in a habitat restoration centre who developed episodes of pruritus and skin rashes associated with bird mites. The mite bites resolved approximately two weeks after each episode, without specific medical intervention and despite ongoing work activities. A workplace health-risk assessment and microscopic analysis of 'swabs' of the work environment aided the identification of bird mite as the causative agent. The source of the bird mites was infested red-winged starlings nesting in the roof of the workplace facility. Incidents of gamasoidosis as described are considered occupational dermatoses since they were acquired in the workplace and the diagnosis was based on clinical--parasitological analysis. When diagnosing gamasoidosis, the clinical history and physical examination provide useful clues, but the clinical features of skin lesions of arthropod or other insect bites are very similar. Microscopic detection of the mite is confirmatory. [ABSTRACT FROM AUTHOR]

Occupational dermatoses impose a significant socioeconomic burden. Allergic contact dermatitis related to occupation is prevalent among healthcare workers, cleaning service personnel, individuals in the beauty industry and industrial workers. Among risk factors, the exposure to preservatives is frequent, since they are extensively added in products for occupational use. The goal of this study is to investigate the contact allergy patterns in order to understand the linkage among hypersensitivity to preservatives, occupational profiles, patients' clinical and demographic characteristics. Patch test results were collected from monosensitized patients to Formaldehyde 2%, KATHON 0.02%, thimerosal 0.1%, and MDBGN 0.5%; information was also collected for an extended MOAHLFA (Male-Occupational-Atopic-Hand-Leg-Face-Age) index. To assess the relationship between allergen group and occupational-related ACD, the chi-square test for independence was utilized. To uncover underlying relationships in the data, multiple correspondence analysis (MCA) and categorical principal components analysis (CATPCA), which are machine learning approaches, were applied. Significant relationships were found between allergen group and: occupation class, atopy, hand, leg, facial, trunk, neck, head dermatitis, clinical characteristics, ICDRG 48 h and ICDRG 72 h clinical evaluation. MCA and CATPCA findings revealed a link among allergen group, occupation class, patients' demographic and clinical characteristics, the MOAHLFA index, and the ICDRG scores. Significant relationships were identified between the allergen group and various manifestations of dermatitis. The utilization of machine learning techniques facilitated the discernment of meaningful patterns in the data. [ABSTRACT FROM AUTHOR]

This study investigates the mechanism through which paeoniflorin inhibits TSLP expression to regulate dendritic cell activation in corticosteroid-dependent dermatitis treatment. Utilizing databases like TCMSP, we identified paeoniflorin's components, targets, and constructed networks. Molecular docking and gene enrichment analysis helped pinpoint key targets and pathways affected by paeoniflorin. In vitro and in vivo models were used to study CD80, CD86, cytokines, T-cell activation, skin lesions, histopathological changes, TSLP, CD80, and CD86 expression. Our study revealed paeoniflorin's active constituent targeting IL-6 in corticosteroid-dependent dermatitis. In vitro experiments demonstrated reduced TSLP expression, CD80, CD86, and cytokine secretion post-paeoniflorin treatment. In vivo, paeoniflorin significantly decreased skin lesion severity, cytokine levels, TSLP, CD80, and CD86 expression. The study highlights paeoniflorin's efficacy in inhibiting TSLP expression and suppressing dendritic cell activation in corticosteroid-dependent dermatitis, suggesting its potential as a therapeutic intervention. Additionally, it offers insights into the complex molecular mechanisms underlying paeoniflorin's anti-inflammatory properties in treating corticosteroid-dependent dermatitis. [ABSTRACT FROM AUTHOR]

Background: Fragrance substances are a frequent cause of contact allergy worldwide. Fragrance exposure varies by sex, age and possibly country, influenced by cosmetic availability, environmental conditions and cultural practices. Objectives: To systematically review and gather prevalence of sensitization to fragrance mix I (FM I) and fragrance mix II (FM II) in consecutively patch tested European dermatitis patients. Method: A total of 4134 publications on patch test results of European dermatitis patients, published from 1981 to 2022, were systematically reviewed according to a previously registered and published PROSPERO protocol. Results: Eighty‐four eligible original articles were analysed. Overall prevalence of sensitization to fragrance mix I (FM I) was 6.81% (95% CI: 6.37–7.28), and FM II was 3.64% (95% CI: 3.3–4.01). Sensitization to FM I was most prevalent in Central and Eastern Europe and to FM II in Western Europe. No clear time trends were observed. Among paediatric dermatitis patients, sensitization prevalence for FM I and FM II was 4.09% (95% CI: 3.37–4.96) and 2.17% (95% CI: 1.53–3.07). Conclusion: The frequency of positive patch test results for both FMI and FMII remains high. Sensitization is also prevalent among children. Enhanced regulation and labelling of cosmetic products play a vital role in averting exposure and sensitization to fragrance allergens. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a common chronic inflammatory disease with an unclear aetiology. Keratinocytes in psoriasis are susceptible to exogenous triggers that induce inflammatory cell death. Objectives To investigate whether gasdermin E (GSDME)-mediated pyroptosis in keratinocytes contributes to the pathogenesis of psoriasis. Methods Skin samples from patients with psoriasis and from healthy controls were collected to evaluate the expression of GSDME, cleaved caspase-3 and inflammatory factors. We then analysed the data series GSE41662 to further compare the expression of GSDME between lesional and nonlesional skin samples in those with psoriasis. In vivo, a caspase-3 inhibitor and GSDME-deficient mice (Gsdme–/–) were used to block caspase-3/GSDME activation in an imiquimod-induced psoriasis model. Skin inflammation, disease severity and pyroptosis-related proteins were analysed. In vitro , tumour necrosis factor (TNF)-α-induced caspase-3/GSDME-mediated pyroptosis in the HACAT cell line was explored. Results Our analysis of the GSE41662 data series found that GSDME was upregulated in psoriasis lesions vs. normal skin. High levels of inflammatory cytokines such as interleukin (IL)-1β, IL-6 and TNF-α were also found in psoriasis lesions. In mice in the Gsdme –/– and caspase-3 inhibitor groups, the severity of skin inflammation was attenuated and GSDME and cleaved caspase-3 levels decreased after imiquimod treatment. Similarly, IL-1β, IL-6 and TNF-α expression was decreased in the Gsdme –/– and caspase-3 inhibitor groups. In vitro , TNF-α induced HACAT cell pyroptosis through caspase-3/GSDME pathway activation, which was suppressed by blocking caspase-3 or silencing Gsdme. Conclusions Our study provides a novel explanation of TNF-α/caspase-3/GSDME-mediated keratinocyte pyroptosis in the initiation and -acceleration of skin inflammation and the progression of psoriasis. [ABSTRACT FROM AUTHOR]

Although warmth is a key sign of inflammatory skin lesions, an objective assessment and follow‐up of the temperature changes are rarely done in dermatology. The recent availability of accurate, sensitive and cost‐effective thermography devices has made the implementation of thermography in clinical settings feasible. The aim of this scoping review is to summarize the evidence around the value and pitfalls of infrared thermography (IRT) when used in the dermatology clinic. A systematic literature search was done for original articles using IRT in skin disorders. The results concerning the potential of IRT for diagnosis, severity staging and monitoring of skin diseases were collected. The data on the sensitivity and specificity of IRT were extracted. Numerous studies have investigated IRT in various skin diseases, revealing its significant value in wound management, skin infections (e.g. cellulitis), vascular abnormalities and deep skin inflammation (e.g. hidradenitis suppurativa). For other dermatological applications such as the interpretation of intradermal and patch allergy testing, hyper−/anhidrosis, erythromelalgia, cold urticaria and lymph node metastases more complex calculations, provocation tests or active cooling procedures are required. Dermatologists should be aware of a learning curve of IRT and recognize factors contributing to false positive and false negative results. Nonetheless, enough evidence is available to recommend IRT as a supplement to the clinical evaluation for the diagnosis, severity and follow‐up of several skin diseases. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chitinase‐3‐like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti‐CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. Experimental Approach: The effect of CHI3L1 antibody on phthalic anhydride‐induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis‐related cytokines were determined using an enzyme‐linked immunosorbent assay, and RT‐qPCR, STAT3 and CXCL8 signalling were measured by western blotting. Key Results: Anti‐CHI3L1 antibody suppressed phthalic anhydride‐induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride‐induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride‐treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis‐related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL‐4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein‐association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL‐1β, IL‐4, CXCL8, TSLP, and the expression of CHI3L1 and p‐STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p‐STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. Conclusion and Implications: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Aplasiо cutis congenita is a heterogeneous group of disorders characterized by absence of skin layer in a localized or wide spread area at birth. Aplasio cutis congenita is rare anomaly within the newborn population. The incidence is approximately 3 cases in 10000 births. Etiological factors include influence of genetic factors, teratogens, compromised vasculature to the skin, infection, neural tube defects and trauma. Case report: In August 2022 a male infant was born with membranous type of aplasiо cutis congenita in the parietal skin area above the large fontanel, round, diameter 10 cm without associated malformations on the rest of the body. The lesion of the head was treated with medical oil, three times a day. After one month the lesion of the scalp was better; the superficial veins partially were obliterated and during this period only one episode of bleeding was recorded. The bleeding was stopped with local compression. After three months the lesion was completely resolved and only very thin blood vessels were noticed. During this period the baby was in good condition and proper weight gain. After discharge of the hospital, heart and brain ultrasounds were performed and they were normal. Follow up consultations with a dermatologist and a geneticist recommended continuous observation of the skin lesion and the development of the baby in general. Conclusion: The treatment of our case demonstrated that beside the very wide spread lesion on the scalp, we prevented: further destruction of the epiderm, bleeding from the very thin and fragile superficial veins, infection and achieved obliteration of superficial veins. The medical oil that was used in this particular case (lesion with diameter more than 3 cm) comprised of: butyrum bovis, skin lipids, pyrus malus fruit extract, pentylene glycol, stellaroides longibracteata leaf extract, tocopheryl acetate, tocopherol. These components have preventing effect of skin inflammation, healing of damaged skin and preservation of skin integrity. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Skin inflammation with the potential sequel of moist epitheliolysis and edema constitute the most frequent breast radiotherapy (RT) acute side effects. The aim of this study was to compare the predictive value of tissue-derived radiomics features to the total breast volume (TBV) for the moist cells epitheliolysis as a surrogate for skin inflammation, and edema. Radiomics features were extracted from computed tomography (CT) scans of 252 breast cancer patients from two volumes of interest: TBV and glandular tissue (GT). Machine learning classifiers were trained on radiomics and clinical features, which were evaluated for both side effects. The best radiomics model was a least absolute shrinkage and selection operator (LASSO) classifier, using TBV features, predicting moist cells epitheliolysis, achieving an area under the receiver operating characteristic (AUROC) of 0.74. This was comparable to TBV breast volume (AUROC of 0.75). Combined models of radiomics and clinical features did not improve performance. Exclusion of volume-correlated features slightly reduced the predictive performance (AUROC 0.71). We could demonstrate the general propensity of planning CT-based radiomics models to predict breast RT-dependent side effects. Mammary tissue was more predictive than glandular tissue. The radiomics features performance was influenced by their high correlation to TBV volume. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Reports of allergic contact dermatitis (ACD) to phytonadione epoxide (PE) in cosmetics suggest that PE is as powerful a sensitiser as its parent compound phytonadione.To evaluate a case series of ACD to PE in Spain.We reviewed the records of 20 patients with ACD to cosmetics containing PE diagnosed across Spain between January 2019 and June 2023.All 20 patients developed patch test (PT) or repeated open application test (ROAT) reactions to cosmetics containing PE. All involved women with eyelid eczema. PT or ROAT with PE preparations were positive in 17/20 (85%). PE at 1%, 5%, 10% and 20% in pet. was patch‐tested in 8/17, 14/17, 11/17 and 8/17 patients; being positive in 6/8 (75%), 13/14 (92.85%), 11/11 (100%) and 8/8 (100%), respectively.Regulators should, not only ban the specific dangerous cosmetic ingredients, but also consider to ban or keep under close surveillance those closely related products or derivatives that might potentially cause similar harmful effects. PTs with PE are suggested to be performed at a 5% concentration in pet. Higher concentrations (10% pet.) should be tested whenever PTs with 5% pet. PE are negative. [ABSTRACT FROM AUTHOR]

Immune-mediated comorbidities in patients with psoriasiform eczema are common. It can be challenging to manage multiple immune-mediated diseases, especially considering that biologic treatments are prone to causing paradoxical effects. The aim of this retrospective observational case series was to describe the course of both psoriasiform eczema and immune-mediated comorbidities in five patients treated with upadacitinib for psoriasiform dermatitis. Five patients, all male, were included. All the patients suffered from psoriasiform eczema. Moreover, two of the patients suffered from alopecia areata, two from vitiligo, one from ulcerative colitis and one from hidradenitis suppurativa. In all cases, the treatment with upadacitinib was rapidly effective on the eczema. The effectiveness on alopecia areata was good in both cases, while the results on vitiligo were only partial. The only case of ulcerative colitis achieved complete remission, while the case of hidradenitis suppurativa experience partial improvement. In conclusion, upadacitinib was effective in treating not only psoriasiform eczema, but also several immune mediated comorbidities. Additional studies are necessary to determine the efficacy of upadacitinib in alopecia areata, vitiligo and hidradenitis suppurativa. [ABSTRACT FROM AUTHOR]

Psoriasis is characterized by keratinocyte (KC) hyperproliferation and inflammatory cell infiltration, but the mechanisms remain unclear. In an imiquimod-induced mouse psoriasiform model, p38 activity is significantly elevated in KCs and p38α specific deletion in KCs ameliorates skin inflammation. p38α signaling promotes KC proliferation and psoriasis-related proinflammatory gene expression during psoriasis development. Mechanistically, p38α enhances KC proliferation and production of inflammatory cytokines and chemokines by activating STAT3. While p38α signaling in KCs does not affect the expression of IL-23 and IL-17, it substantially amplifies the IL-23/IL-17 pathogenic axis in psoriasis. The therapeutic effect of IL-17 neutralization is associated with decreased p38 and STAT3 activities in KCs and targeting the p38α-STAT3 axis in KCs ameliorates the severity of psoriasis. As IL-17 also highly activates p38 and STAT3 in KCs, our findings reveal a sustained signaling circuit important for psoriasis development, highlighting p38α-STAT3 axis as an important target for psoriasis treatment. p38α signaling promotes keratinocyte proliferation and psoriasis-related proinflammatory gene expression in psoriasis by activating STAT3, and further amplifies the IL-23/IL-17 pathogenic axis. [ABSTRACT FROM AUTHOR]

Natural caffeic acid (CA) and its analogues have been studied for their potential applications in the treatment of various inflammatory and infectious skin diseases. However, the molecular mechanism underlying the effects of the CA remains largely unknown. Here, we report that CA and its two analogues, caffeic acid phenethyl ester (CAPE) and caffeic acid methyl caffeate (CAMC), inhibit TRPV3 currents in their concentration- and structure-dependent manners with IC50 values ranging from 102 to 410 μM. At the single-channel level, CA reduces the channel open probability and open frequency without alteration of unitary conductance. CA selectively inhibits TRPV3 relative to other subtypes of thermo-TRPs, such as TRPA1, TRPV1, TRPV4, and TRPM8. Molecular docking combined with site-specific mutagenesis reveals that a residue T636 in the Pore-loop is critical for CA binding to TRPV3. Further in vivo evaluation shows that CA significantly reverses TRPV3-mediated skin inflammation induced by skin sensitizer carvacrol. Altogether, our findings demonstrate that CA exerts its anti-inflammatory effects by selectively inhibiting TRPV3 through binding to the pocket formed by the Pore-loop and the S6. CA may serve as a lead for further modification and identification of specific TRPV3 channel inhibitors. [ABSTRACT FROM AUTHOR]

The transcription factor ΔNp63 plays a pivotal role in maintaining the integrity of stratified epithelial tissues by regulating the expression of distinct target genes involved in lineage specification, cell stemness, cell proliferation and differentiation. Here, we identified the ABC transporter subfamily member ABCC1 as a novel ΔNp63 target gene. We found that in immortalized human keratinocytes and in squamous cell carcinoma (SCC) cells, ∆Np63 induces the expression of ABCC1 by physically occupying a p63-binding site (p63 BS) located in the first intron of the ABCC1 gene locus. In cutaneous SCC and during the activation of the keratinocyte differentiation program, ∆Np63 and ABCC1 levels are positively correlated raising the possibility that ABCC1 might be involved in the regulation of the proliferative/differentiative capabilities of squamous tissue. However, we did not find any gross alteration in the structure and morphology of the epidermis in humanized hABCC1 knock-out mice. Conversely, we found that the genetic ablation of ABCC1 led to a marked reduction in inflammation-mediated proliferation of keratinocytes, suggesting that ABCC1 might be involved in the regulation of keratinocyte proliferation upon inflammatory/proliferative signals. In line with these observations, we found a significant increase in ABCC1 expression in squamous cell carcinomas (SCCs), a tumor type characterized by keratinocyte hyper-proliferation and a pro-inflammatory tumor microenvironment. Collectively, these data uncover ABCC1 as an additional ∆Np63 target gene potentially involved in those skin diseases characterized by dysregulation of proliferation/differentiation balance. [ABSTRACT FROM AUTHOR]

We previously reported that a pathogenic abnormality in the barrier and water-holding functions of the stratum corneum (SC) in the skin of patients with atopic dermatitis (AD) is mainly attributable to significantly decreased levels of total ceramides in the SC. That decrease is mediated by the abnormal expression of a novel ceramide-reducing enzyme, sphingomyelin/glucosylceramide deacylase (SGDase), which is the β-subunit (ASAH1b) of acid ceramidase. In this study, we determined whether mice overexpressing ASAH1b in their epidermis develop AD-like skin symptoms. We generated transgenic (TG) mice overexpressing ASAH1b, regulated by the involucrin promoter, to localize its expression in the upper epidermis. After hair removal using a depilatory cream containing glycolic acid, the TG mice without any visible skin inflammation at 8 weeks of age had increased levels of ASAH1b and decreased levels of SC ceramide, with disrupted barrier functions measured by trans-epidermal water loss compared to the wild-type (WT) mice. Interestingly, enzymatic assays revealed that SGDase activity was not detectable in the skin of the TG mice compared to WT mice. Immunological staining revealed that there was an increased expression level of IL-33 in the epidermis and an accumulation of macrophages in the dermis of TG mice compared to WT mice, which are phenotypic characteristics of AD, that were exacerbated by tape-stripping of the skin. In the skin of the TG mice, the mRNA levels of IL-5, CCL11, IL-22, CXCL10, and IFNγ were significantly upregulated compared to the WT mice, and tape-stripping significantly increased the mRNA levels of IL-4, IL-33, CXCL1, CXCL12, TLR9, and CD163 compared to WT mice. These findings strongly indicate that the skin of the depilatory cream-treated TG mice exists in an atopic dry skin condition that is highly sensitive to various environmental stimuli. The sum of our results suggests that ASAH1b itself, even in the absence of its enzymatic activity, is a major etiologic factor for atopic dry skin symptoms via an unknown mechanism. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Due to its high prevalence, considerable morbidity, and chronicity, there is a need for the accurate in vivo evaluation of treatment efficacy. Line-field confocal optical coherence tomography (LC-OCT) is a new emerging imaging technique able to perform a non-invasive, real-time examination of the epidermis and the upper dermis. LC-OCT may represent a promising tool in the diagnosis and treatment follow-up of chronic eczematous skin diseases with barrier defects. Objectives: We aimed to investigate the role of LC-OCT in the non-invasive monitoring of the treatment effect on five patients with severe atopic dermatitis during dupilumab treatment. Materials and Methods: LC-OCT imaging was performed on five patients (three women and two men) aged between 14 and 85 years old at the baseline and at 2, 4, and 6 weeks of treatment with dupilumab. The LC-OCT scans were performed at two sites, the lesional skin in the antecubital fossa and the extensor part of the arm, considered a control site on each patient for comparison. The captured images were later evaluated. Descriptive statistics and a t-test were used to compare the analyzed parameters over time and between involved atopic skin and clinically healthy skin. Results: The LC-OCT imaging was able to detect the difference in stratum corneum (SC) thickness and quality and epidermal thickness (ET) and the changes before and after treatment with high accuracy. The main findings include a significant reduction in the epidermal and stratum corneum thickness and decreased epidermal spongiosis and inflammation, with better quality of the stratum corneum indicating restoration of its tightness at both lesional and control sites. Conclusions: This study demonstrates that clinical improvement of affected and unaffected atopic skin under dupilumab treatment correlates with the LC-OCT findings. LC-OCT represents a novel, non-invasive tool examining the in vivo skin barrier and inflammation and can help to monitor the treatment efficacy among patients with atopic dermatitis in daily practice. [ABSTRACT FROM AUTHOR]

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed the transcriptomic changes observed in epidermal PPARγ-deficient mice (Pparg-/-epi). A gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis, and cell survival. Single-cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils, and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and/or mouse actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) revealed a strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AKs and SCCs. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity, while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably, these changes were not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes, while Ppard was highly expressed in myofibroblasts, suggesting that PPARδ has a role in myofibroblast differentiation. In conclusion, these data provide strong evidence that PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs. [ABSTRACT FROM AUTHOR]

Eyelid dermatitis (ED) affects a cosmetically significant area and leads to patients' distress. Despite ongoing and recent research efforts, ED remains a multidisciplinary problem that needs further characterization. We aimed to evaluate the atopic eyelid dermatitis (AED) frequency in ED patients and to perform their clinical profiling. PubMed databases were searched from 01.01.1980 till 01.02.2024 to PRISMA guidelines using a search strategy: (eyelid OR periorbital OR periocular) AND (dermatitis or eczema). Studies with patch-tested ED patients were included. Proportional meta-analysis was performed using JBI SUMARI software. We included 65 studies across Europe, North America, Asia and Australia, with a total of 21,793 patch-tested ED patients. AED was reported in 27.5% (95% CI 0.177, 0.384) of patch-tested ED patients. Isolated ED was noted in 51.6% (95% CI 0.408, 0.623) of 8453 ED patients with reported lesion distribution, including 430 patients with isolated AED. Our meta-analysis demonstrated that the AED frequency in patch-tested ED patients exceeded the previous estimate of 10%. Isolated AED was noted in adult patients, attending contact allergy clinics. Future studies are needed to elucidate the global prevalence and natural history of isolated AED in adults. [ABSTRACT FROM AUTHOR]

Introduction: Adult dermatomyositis (DM) and juvenile dermatomyositis (JDM) are rare autoimmune diseases with characteristic skin rashes, weakness, and other systemic features. Upregulated interferon signaling has been consistently described in both adult and juvenile DM which makes janus kinase inhibitors (jakinibs) an attractive therapeutic agent that has a targeted mechanism of action. Areas covered: Herein is a review of the growing literature of jakinib use in adult and juvenile DM, including reports on specific disease features and safety of jakinibs in this population and a comparison between adult and juvenile DM. We performed a literature review using PubMed including all English-language publications before 1 February 2024 and abstracts from key recent rheumatology conferences. Expert opinion: Jakinibs are an exciting and promising treatment in both adult and juvenile DM. Current Phase 2 and 3 randomized placebo-controlled trials of jakinibs in both adult and JDM will provide significant insights into the efficacy of this class of medication as a potentially more mechanistically targeted treatment of both skin and muscle disease. In fact, these results will likely inform the treatment paradigm of dermatomyositis in that it may even be considered as first or second line. The next five years in the therapeutic landscape of both juvenile and adult DM is an exciting time for both patients and medical providers. [ABSTRACT FROM AUTHOR]

Psoriasis is a common chronic inflammatory skin disease that significantly impacts the patients' quality of life. Recent studies highlighted the function of the interleukin (IL)-1 family member IL-38 in skin homeostasis and suggested an anti-inflammatory role for this cytokine in psoriasis. In this study, we generated mice specifically overexpressing the IL-38 protein in epidermal keratinocytes. We confirmed IL-38 overexpression in the skin by Western blotting. We further detected the protein by ELISA in the plasma, as well as in conditioned media of skin explants isolated from IL-38 overexpressing mice, indicating that IL-38 produced in the epidermis is released from keratinocytes and can be found in the circulation. Unexpectedly, epidermal IL-38 overexpression did not impact the global severity of imiquimod (IMQ)-induced skin inflammation, Similarly, keratinocyte activation and differentiation in IMQ-treated skin were not affected by increased IL-38 expression and there was no global effect on local or systemic inflammatory responses. Nevertheless, we observed a selective inhibition of CXCL1 and IL-6 production in response to IMQ in IL-38 overexpressing skin, as well as reduced Ly6g mRNA levels, suggesting decreased neutrophil infiltration. Epidermal IL-38 overexpression also selectively affected the desquamation process during IMQ-induced psoriasis, as illustrated by reduced plaque formation. Taken together, our results validate the generation of a new mouse line allowing for tissue-specific IL-38 overexpression. Interestingly, epidermal IL-38 overexpression selectively affected specific disease-associated readouts during IMQ-induced psoriasis, suggesting a more complex role of IL-38 in the inflamed skin than previously recognized. In particular, our data highlight a potential involvement of IL-38 in the regulation of skin desquamation. [ABSTRACT FROM AUTHOR]

Phosphatidylethanolamine (PE) and phosphatidylserine (PS), along with phosphatidylcholine (PC), are key phospholipids (PL) in cell membranes and lipoproteins, prone to oxidative modifications. Their oxidized forms, OxPE and OxPS, play significant roles in inflammation and immune response. This review explores their structural oxidative changes under non‐enzymatic conditions and their roles in physiological and pathological contexts, influencing inflammation, and immunity. Specific oxidations of PE and PS significantly alter their physicochemical properties, leading to enhanced biological functions, reduced activity, or inactivation. OxPE may show pro‐inflammatory actions, similar to well‐documented OxPC, while the OxPS pro‐inflammatory effects are less noted. However, OxPS and OxPE have also shown an antagonistic effect against lipopolysaccharides (LPS), suggesting a protective role against exacerbated immune responses, similar to OxPC. Further research is needed to deepen our understanding of these less‐studied OxPL classes. The role of OxPE and OxPS in disease pathogenesis remains largely unexplored, with limited studies linking them to Alzheimer's disease, diabetes, rheumatoid arthritis, traumatic brain injury, and skin inflammation. These findings highlight the potential of OxPE and OxPS as biomarkers for disease diagnosis, monitoring, and therapeutic targeting. [ABSTRACT FROM AUTHOR]

Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials. ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS–TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran–Mantel–Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov : ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349). Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS–TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS–TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS–TCI versus placebo plus TCS–TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7–18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6–19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8–22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6–20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS–TCI and placebo plus TCS–TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS–TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS–TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred. Nemolizumab plus TCS–TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved. Galderma. [ABSTRACT FROM AUTHOR]

Objective: This scoping review aimed to map the adverse reactions in the oral mucosa and face caused by the use of natural products. Methodology: This review was performed according to the Joanna Briggs Institute Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, with a protocol registered in the Open Science Framework (DOI 10.17605/OSF.IO/R57D8). The search was carried out systematically using PubMed, Scopus, Web of Science, Embase, LILACS, and LIVIVO databases, as well as gray literature through Google Scholar and OpenGrey. Reports of clinical cases on the adverse effects of natural products on the oral mucosa or perioral region of the face resulted from inappropriate use or self-medication were included. Data from the included studies were described in a narrative form. Results: Seven hundred and six studies were identified, and after removing duplicates and applying the eligibility criteria, 28 studies were included. The year of publication ranged from 1976 to 2022. The studies were conducted in 19 countries. Fifty patients were mentioned in the included studies and 34 were female (68%). The natural products most related to adverse reactions were propolis (n = 17), with manifestations such as perioral eczema, edema, erosions, erythema, allergic contact dermatitis, and garlic (n = 9), with manifestations such as chemical burn, burning sensation, vesicles and blisters, crusts, and ulcerations. Conclusion: Propolis and garlic were the natural products with the most reported adverse effects on the oral mucosa and perioral region. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO), a carbon-based material with oxygen-containing functional groups, can be applied in biomedicine for drug delivery, cancer therapy, and tissue regeneration. We have previously shown that nanoscale-sized graphene oxide (NGO), an oxidized graphene derivative, exhibits effective anti-inflammatory activity in a murine model of sepsis mediated by T helper (Th)1-promoting cytokines such as IFNγ and TNFα. However, whether NGO influences Th2-induced skin inflammation remains unclear. To address this issue, we employed an ovalbumin (OVA) plus aluminum hydroxide (Alum)-induced Th2-mediated skin inflammation model in conjunction with OVA-specific DO11.10 T cell receptor transgenic Balb/c mice. In vivo NGO injection upon OVA/Alum sensitization down-regulated OVA-elicited antigen-specific Th2 cells and GATA3-expressing Th2-type regulatory T cells. Next, we examined the effect of NGO injection on OVA/Alum-induced atopic dermatitis (AD)-like skin inflammation. NGO-injected mice exhibited significantly decreased Th2 disease phenotypes (e.g., a lower clinical score, decreased epidermal thickness and Th2 cell differentiation, and fewer infiltrated mast cells and basophils in skin lesions) compared with vehicle-injected control mice. Overall, our results suggest that NGOs are promising therapeutic materials for treating allergic diseases such as AD. [ABSTRACT FROM AUTHOR]

Subcutaneous granuloma annulare (SGA) is a rare clinicopathologic subtype of granuloma annulare characterized by the presence of subcutaneous nodules. There are no present reviews synthesizing the clinical features and treatment modalities in SGA. We conducted a systematic review following PRISMA guidelines [CRD42022344672] on all peer‐reviewed English‐language studies that reported one or more cases of SGA. A total of 97 studies, comprising 26 case series and 71 case reports with 324 patients, were included for analysis. Most cases were predominantly pediatric, with 78.9% of the cases identified being age 16 or lower and a median age of diagnosis of 6. There was no overall gender predisposition. Although over two‐thirds of patients did not have any comorbidities, diabetes mellitus was the most common comorbidity present in 4% of cases. The most common feature of SGA was nodules, which were present in 99.6% of patients. Pain or tenderness was reported in 15.4%, and erythema of overlying skin in 11.0% of cases. Surgical excision was performed in 96/141 (68.1%) patients. Among the 27/141 (18.0%) patients who were conservatively managed, 87.0% spontaneously improved, including 60.0% who completely self‐resolved. Topical and intralesional steroids were used in 3.40% and 1.85% of patients, respectively, resulting in complete or partial resolution in 54.6% and 100%. Among patients who were followed up, 83/324 (25.6%) patients experienced recurrence after a median duration of 26 weeks. SGA is predominantly a pediatric disease that frequently occurs on the limbs and the head. Juxta‐articular lesions are more commonly observed in adults than in children. Surgical excision is common and effective in most patients. Spontaneous improvement occurs in most untreated cases, and intralesional steroids but not topical steroids may be beneficial for non‐resolving cases and to reduce time to resolution. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Bovine digital dermatitis (BDD) is an important cause of lameness in dairy cows worldwide. However, very little is known about this disease in Australian herds, which are predominantly managed on pasture. The primary objectives of this cross-sectional study were to describe the presence and prevalence of BDD in Australian dairy herds and to characterize the microbiota of healthy skin and M4 lesions of BDD-affected, pasture-managed cows. Cows from 71 dairy herds were examined at milking time to identify the presence of BDD lesions. True prevalence was estimated using Bayesian methods with informative priors for sensitivity and specificity. Biopsy samples (n = 60) were collected from cows with and without BDD lesions in 7 pasture-based herds. The microbiota in the superficial and deep strata of each tissue biopsy were characterized via sequencing of the V3–V4 region of the bacterial ribosomal RNA gene. Lesions were detected in 1,817 (11.5%) of 15,813 cows and in 68 of 71 (95.8%) herds. The median herd-level apparent and true prevalences of BDD were 8.5% and 18.1%, respectively, but prevalences varied considerably between farms. On farms with BDD, M4 lesions accounted for 70% to 100% of all lesions (interquartile range = 95.1%–100%, median = 100%); M2 lesions (i.e., large ulcerative lesions) were observed at low prevalence (<2.2%) in the few herds (7/71, 9.9%) where they were found. There was a significant difference in the composition of the microbiota between healthy skin and M4 lesions but not between superficial and deep tissue layers. Several gut- and effluent-associated bacterial taxa, including Lentimicrobium and Porphyromonas , which have previously been associated with BDD, were abundant in BDD lesions but not in control biopsies. Our study supports the idea that such taxa are involved in, although possibly not essential to, lesion development and persistence in pasture-managed cows in Australia. Our results also suggest that Dichelobacter may contribute to the disease process. We conclude that BDD is likely to occur in most Australian dairy farms, but that further studies are needed to identify its effect on cow welfare and productivity. Further investigation of the etiology of BDD in Australian dairy herds is also necessary to inform prevention and control strategies. [ABSTRACT FROM AUTHOR]

Auricular chondritis of unknown cause was suspected in a 10‐year‐old male Bolognese dog with a five‐month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals. [ABSTRACT FROM AUTHOR]

A 9‐month‐old mixed‐breed dog developed generalised pustular dermatitis, accompanied by lethargy and hyperthermia, 7 days after oral fluralaner administration. Dermatopathological and microbiological evaluations were consistent with a pustular acantholytic dermatitis. A 4‐month course of immunosuppressive therapy resulted in complete remission of lesions, which did not recur after therapy was withdrawn. [ABSTRACT FROM AUTHOR]

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder with aberrant skin scaling and increased transepidermal water loss (TEWL). Current treatments for ARCI are limited and suboptimal. We present the case of a 27-year-old man with ARCI resulting from a homozygous missense variant in TGM1. RNA-sequencing of lesional skin revealed aberrant Janus kinase–signal transducer and activator of transcription signalling, providing a rationale for innovative treatment with a Janus kinase inhibitor. We prescribed oral tofacitinib (11 mg daily) for 26 weeks. Rapid improvements in erythema and fissuring occurred within the first month. Sustained reductions in 5-D itch scale and Dermatology Life Quality Index scores were also observed. TEWL decreased for the first 10 weeks but increased thereafter. Tofacitinib downregulated inflammatory genes and pathways, while enhancing skin barrier markers. Moreover, transglutaminase 1 distribution was normalized although enzymatic activity remained deficient. This study suggests that oral tofacitinib may be a useful therapy to consider for patients with ARCI. [ABSTRACT FROM AUTHOR]

Glucocorticoids are often used and highly effective anti-inflammatory medications, but prolonged topical application may alter the epidermis' normal structure and function, potentially resulting in a number of adverse effects. Topical glucocorticoid-induced skin inflammation is a dangerous condition that develops after topical glucocorticoid use. The patients become dependent on the medication and, even after the medication is stopped, the dermatitis symptoms recur, severely impairing their quality of life. Thus, the need to aggressively confront Topical glucocorticoid-induced skin inflammation is critical. Prior research has demonstrated that topical administration of licorice's flavonoid component liquiritin stimulates epidermal proliferation, which in turn enhances the creation of collagen and the healing of wounds. Therefore, the purpose of this work was to determine if topical use of liquiritin carbomer gel can treat glucocorticoid-induced changes in mice skin epidermal function, and the mechanisms involved. The findings demonstrated that, in the mice model of topical glucocorticoid-induced skin inflammation, liquiritin carbomer gel aided in the restoration of skin barrier function. These outcomes may have been caused by enhanced expression of the proteins Aquaporin 3, Keratin 10, and Claudin-1, as well as the restoration of epidermal hyaluronan content. In the meantime, liquiritin carbomer gel dramatically decreased the expression of TNF-α, IL-1β, IL-6, IFN-γ, and IgE in mice, according to ELISA tests. Furthermore, topical treatment of liquiritin carbomer gel boosted the expression of superoxide dismutase, catalase, and decreased malondialdehyde expression, potentially counteracting the detrimental effects of glucocorticoids on the epidermis. In summary, these findings imply that topical liquiritin carbomer gel can treat glucocorticoid-induced skin damage through various mechanisms of action. [ABSTRACT FROM AUTHOR]

Traditionally, skin involvement in chronic myelomonocytic leukemia (CMML) has been considered to be either specific (leukemia cutis) or non‐specific, with granulomatous dermatitis included in the latter group. More recently, the true nature of the myeloid cells present in the cutaneous infiltrates of this theoretically reactive dermatitis is being clarified with the use of new molecular techniques such as next‐generation sequencing. The same mutations in bone marrow (BM) myeloid neoplastic cells and in the cells of cutaneous infiltrates have been found. We present the case of a 77‐year‐old man who presented with spread and treatment‐resistant skin granulomatous lesions previous to the diagnosis of CMML. The same clonal mutations in SRSF2, IDH1, and RUNX1 were found in both skin and BM with resolution of the lesions after the initiation of azacytidine. In conclusion, we report an exceptional case in which specific granulomatous cutaneous lesions have preceded and allowed the earlier diagnosis of an underlying CMML and a review of all previous similar cases in the literature, including molecular alterations. [ABSTRACT FROM AUTHOR]

Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions. [ABSTRACT FROM AUTHOR]

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti‐inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro‐inflammatory cytokines IL‐1β to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17β‐Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Shiitake mushroom‐induced flagellate dermatitis is a rare but important condition to consider in patients presenting with pruritic skin lesions following mushroom ingestion, especially in regions where such cases are uncommon. Early recognition and appropriate management with oral and topical steroids are crucial for effective symptom resolution and preventing complications. Clinicians should be aware of the characteristic rash and the temporal relationship between mushroom consumption and rash onset. Educating patients about the risks associated with consuming raw or undercooked shiitake mushrooms is essential to prevent recurrence. [ABSTRACT FROM AUTHOR]

Disseminated gonococcal infection is the causative agent of approximately 0.6%-1.2% of septic arthritis cases in North America and Europe. Typical presentations of this disorder include tenosynovitis, dermatitis, polyarthralgia, or oligoarticular purulent arthritis affecting the distal joints. Diagnosis is contingent on clinical presentation, with urine nucleic acid amplification testing as the preferred diagnostic modality. Synovial fluid cultures, along with imaging, can confirm diagnosis. The recommended treatment is a third-generation cephalosporin, such as intravenous ceftriaxone for 7-14 days and a dose of oral azithromycin. [ABSTRACT FROM AUTHOR]

Facial skin redness can be an indicator of skin inflammation, however the physiological connection between facial redness and inflammatory status, as well as its role in age‐related skin changes, remains poorly understood. This study aims to investigate the association between the pattern of facial skin redness and biological inflammatory status, as well as age‐related changes occurring in the skin. Four studies were conducted recruiting healthy Northern Asian females. Disordered spatial patterns of facial skin redness signals were assessed using image analysis, i.e., the a* gradient algorithm, which quantifies the disordered shape and pattern of localized redness signals on facial skin. This redness pattern was compared with (1) inflammatory protein markers (IL‐1Ra/ IL‐1α and IL‐8) measured from stripped corneocyte samples, (2) gene expression profiles obtained through transcriptome analysis using skin biopsy samples, and (3) the distribution pattern of blood vessel measured using a photoacoustic microscope. The association between the skin redness pattern and current and future ageing‐related skin changes was examined through a longitudinal study tracking the same subjects for 10 years. A significant correlation was observed between the a* gradient and the levels of inflammatory cytokines (IL‐1Ra/IL‐1α and IL‐8). Transcriptome analysis revealed upregulation of genes related to acute inflammation, chronic inflammation, cellular senescence, and angiogenesis in subjects with higher a* gradients. The high a* gradient group exhibited an extension of blood vessel diameter and increased blood vessel density, while the medium a* gradient group only exhibited blood vessel extension. Lastly, the 10‐year longitudinal study demonstrated that the a* gradient was associated with current and future skin ageing‐related attributes, such as increased skin texture and wrinkle formation. The spatial pattern of localized redness on the skin reflects the biological inflammatory status, and this inflammatory condition helps predict current and future age‐related skin changes. [ABSTRACT FROM AUTHOR]

Acne is a chronic inflammatory skin condition that involves Cutibacterium acnes (C. acnes), which is classified into six main phylotypes (IA1, IA2, IB, IC, II and III). Acne development is associated with loss of C. acnes phylotype diversity, characterised by overgrowth of phylotype IA1 relative to other phylotypes. It was also shown that purified extracellular vesicles (EVs) secreted by C. acnes can induce an acne‐like inflammatory response in skin models. We aimed to determine if the inflammatory profile of EVs secreted by C. acnes phylotype IA1 from an inflammatory acne lesion was different from C. acnes phylotype IA1 from normal skin, thus playing a direct role in the severity of inflammation. EVs were produced in vitro after culture of two clinical strains of C. acnes phylotype IA1, T5 from normal human skin and A47 from an inflammatory acne lesion, and then incubated with either human immortalised keratinocytes, HaCaT cells, or skin explants obtained from abdominoplasty. Subsequently, quantitative PCR (qPCR) was performed for human β‐defensin 2 (hBD2), cathelicidin (LL‐37), interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17α and IL‐36γ, and ELISA for IL‐6, IL‐8 and IL‐17α. We found that EVs produced in vitro by C. acnes derived from inflammatory acne lesions significantly increased the pro‐inflammatory cytokines and anti‐microbial peptides at both transcriptional and protein levels compared with EVs derived from normal human skin. We show for the first time that C. acnes EVs from inflammatory acne play a crucial role in acne‐associated inflammation in vitro and that C. acnes phylotype IA1 collected from inflammatory acne lesion and normal skin produce different EVs and inflammatory profiles in vitro. [ABSTRACT FROM AUTHOR]

Background: There is a dearth of effective treatments to counter retinol‐induced skin irritation. Objective: This study aimed to investigate the efficacy of three potential mitigants: (i) phytosteryl/octyldodecyl lauroyl glutamate (PLG), (ii) a physiologic lipid mixture (PLM) comprised of ceramide three and cholesterol, and (iii) niacinamide, in ameliorating irritation instigated by retinol. Methods: An occlusive human patch test, spanning 5 days, was undertaken on 18 Chinese participants aged between 23 and 40. It was designed as a randomized, double‐blind, and vehicle‐controlled study. Clinician erythema assessment (CEA) and instrumental evaluations were employed pre and post‐test. Subsequently, a 4‐week consumer in‐use test, randomized and double‐blind in nature, was executed to substantiate the soothing effects of PLG. Results: Data from CEA and bioengineering assessments revealed that, in comparison to the vehicle control, both 2% PLG and 5% PLM notably curbed retinol‐induced skin erythema and inflammation. Notably, PLG outperformed PLM. Conversely, 3% niacinamide did not offer relief against retinol‐induced discomfort. The subsequent consumer in‐use test affirmed that treatments with 2% PLG were better tolerated than those with the vehicle alone. Conclusion: To the best of our knowledge, this study represents the first confirmation that physiologic lipids effectively mitigate retinol‐induced irritation. Given their capacity to counter retinol‐induced irritation, physiologic lipids, particularly PLG, are recommended for incorporation in retinol regimens. Additionally, the Visia‐CR a* value can serve as a robust objective measure for interpreting patch test outcomes. [ABSTRACT FROM AUTHOR]

Background: Plaque psoriasis is relatively straightforward to identify. When diagnostic concerns arise in atypical cases, a biopsy is needed. It is widely accepted that the Munro microabscess and the spongiform pustule of Kogoj are diagnostic pathological features. However, the diagnostic dilemma is likely to arise in cases without these specific pathological changes and typical clinical features. This study aimed to investigate clinical and pathological clues in distinguishing atypical plaque psoriasis from its mimics. Methods: We evaluated the clinicopathological features of 20 cases of atypical plaque psoriasis and 40 cases of psoriasis mimics as controls including pityriasis rosea (n = 10), pityriasis lichenoides chronica (n = 8), and subacute dermatitis (n = 22). Results: A retrospective analysis of the clinicopathological characteristics of patients with atypical plaque psoriasis and controls was performed. Pathologically, there were significant differences between the two groups in the types of parakeratosis (P = 0.046), epidermal capture of extravasated erythrocytes (P = 0.011), focal basal liquefied degeneration (P = 0.017), types of inflammatory cells (P = 0.000), and depth of inflammation (P = 0.000). Clinically, we found the presence of scales and crusts was significantly different between the two groups. Conclusion: This study offers insight into the clinicopathological features of atypical plaque psoriasis. These differential diagnostic features, compared with its mimics, are proposed to assist the clinician in the diagnosis and treatment of atypical plaque psoriasis. [ABSTRACT FROM AUTHOR]