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BackgroundTo identify new targets for protein-based treatments in psoriasis and evaluate the possible negative impacts of these druggable proteins.MethodsWe carried out an extensive analysis of the entire set of proteins in the blood (proteome-wide) to determine if there are causal links between certain blood proteins and the likelihood of developing psoriasis. The proteins were selected from the UK Biobank Pharma Proteomics Project (UKBPPP) database, which includes genetic data for 2,940 different blood proteins. We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome-wide association study (GWAS) of psoriasis.ResultsOur research discovered a strong genetic link between plasma APOF, ATP6V1G2, IFNLR1, CRELD1, PRSS8, and TNF proteins and a higher chance of having psoriasis. These proteins share genetic variations associated with psoriasis (PPH3+PPH4>0.8). The ROC curves derived from these protein quantity trait loci (pQTLs) demonstrate that they can distinguish between individuals with psoriasis and those without. The druggable gene analysis showed that simvastatin is related to TNF based on the Drug SIGnatures DataBase webtool.ConclusionOur study has explored the causal relationships between six blood proteins and psoriasis, offering a detailed insight into potential therapeutic targets. Among them, simvastatin might have an effect on psoriasis via TNF.Weiterlesen

ObjectiveSecondary failure to biologic disease-modifying antirheumatic drugs (bDMARDs) is challenging and contributes to the complexity of managing psoriatic arthritis (PsA). We aimed to define the frequency and incidence of this phenomenon in PsA and identify the risk factors for its occurrence.MethodsWe retrieved data on patients with PsA from our single-center, specialized-care, prospective observational cohort who initiated and remained on bDMARDs for ≥ 1 year after clinic enrollment between 2000 and 2023. We defined response to therapy at the 1-year visit (baseline) as achievement of ≥ 40% reduction in the swollen joint count (SJC) and either ≥ 50% reduction in Psoriasis Area and Severity Index (PASI) or PASI ≤ 2. We defined secondary failure as the inability to maintain response criteria or as the clinician's judgment of loss of effectiveness. To examine factors associated with secondary failure, we fitted Cox regression models.ResultsOf 482 patients included in the study, 264 (54.8%) were responders at 1 year. Of these, 94 (35.6%) developed secondary failure at a median of 1.6 (IQR 0.7-3.8) years from response. In the multivariable model, higher SJC (hazard ratio [HR] 1.39, 95% CI 1.05-1.84) and PASI (HR 1.14, 95% CI 1.01-1.29) at baseline were associated with secondary failure. Tumor necrosis factor inhibitors (TNFi) vs other bDMARD use (HR 0.39, 95% CI 0.18-0.88), initiation as first-line bDMARD (HR 0.48, 95% CI 0.25-0.91), and treatment initiation during more recent calendar years (HR 0.34, 95% CI 0.12-0.98) were associated with less secondary failure.ConclusionSecondary failure to bDMARD is common in PsA and may be influenced by both disease- and therapy-related factors.Weiterlesen

Objectives: To estimate the prevalence of psoriatic arthritis (PsA) and associated fac-tors in patients with moderate-to-severe psoriasis. Methods: Retrospective, single-center study of a cohort of psoriasis patients in stand-ard follow-up in a dermatology department from July 2008 to January 2024. Patients ≥18 years with moderate-to-severe psoriasis were included and classified into 3 groups according to the treatment received: group 1, biologics or small molecules with or without conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs); group 2, only csDMARDS; and group 3, non-pharmacological treatments. Demographic and clinical variables were collected. The prevalence of PsA was estimated with its 95% confidence interval (CI). The cumulative incidence of PsA was analyzed across groups, and logistic regression models were built. Results: The study population comprised 308 patients (67.2%, 22.7%, 10% in groups 1, 2, and 3, respectively). Dif-ferences between the groups were observed in severity of psoriasis, weight, smoking status, and dyslipidemia (p< 0.05). The prevalence of PsA was 11.7% (95% CI, 8.1-15.3), with most patients in group 1. This group had a high-er risk of PsA following diagnosis of psoriasis or initiation of treatment. Belonging to groups 2 and 3 had a smaller effect than belonging to group 1 in the development of PsA; nail involvement and obstructive sleep apnea (OSA) were associated with development of PsA (p< 0.05). Conclusions: The prevalence estimate was lower than previous estimates, probably owing to the increased use of biologics. Not requiring biologics for disease control had less effect on development of PsA. Nail involvement and OSA were associated with PsA.Weiterlesen

Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases associated with obesity, cardiometabolic disease, and mortality. The glucagon-like peptide-1 (GLP1) pathway has emerged as a key factor in the development of obesity and cardiometabolic disease. GLP1 receptor agonists demonstrably improve insulin resistance, dyslipidemia, obesity, and mortality, with emerging evidence suggesting potential benefit for psoriasis. To evaluate whether GLP1 biology influences psoriatic disease risk, we conducted a Mendelian randomization study. A 22-variant cis-eQTL genetic instrument for GLP1R expression in whole blood from the eQTLGen consortium was generated as a proxy for GLP1R pathway activity (n=31,684). Genetic proxies of GLP1R expression were associated with a lower risk of psoriasis (OR=0.723, 95% CI 0.678-0.771, p=1.08×10 −22 ) and PsA (OR=0.483, 95% CI 0.402-0.580, p=5.33×10 −15 ) in European-ancestry GWAS meta-analyses. Effects persisted after adjustment for genetic proxies of central adiposity, HbA1c, LDL cholesterol, and triglycerides, consistent with potential pathway effects on psoriatic disease, independent of metabolic effects. To determine the specificity of the observed effect, we conducted analyses of seven additional immune-mediated diseases (IMIDs). No protective effects were observed for other IMIDs, including acne and atopic dermatitis. In contrast, risk-increasing effects were observed for Crohn’s disease (OR=1.242, 95% CI 1.107-1.395, p=2.35×10 −4 ) and rheumatoid arthritis (OR=1.502, 95% CI 1.350-1.672, p=1.36×10 −13 ). These findings provide genetic evidence of disease-specific, potentially direct immunomodulatory effects of GLP1R signaling on psoriasis and PsA risk, and support further mechanistic and therapeutic evaluation in randomized trials.Weiterlesen

Enthesitis represents a hallmark feature and central pathological process in psoriatic arthritis and has been proposed as a potential early indicator in patients with psoriasis prior to the onset of clinically apparent psoriatic arthritis. Given the risks associated with delayed diagnosis, there is growing interest in identifying at-risk patients early to enable timely interventions and personalized treatment approaches. In clinical practice, dermatologists are often the first to encounter these patients, highlighting the need for effective screening strategies in their setting. In recent years, efforts have been made to develop validated screening tools for the early detection of musculoskeletal symptoms in patients with psoriasis. Additionally, there has been a greater focus on improving assessments through imaging techniques such as ultrasound and magnetic resonance imaging. However, a universally accepted referral pathway has yet to be established, potentially creating gaps in care during the transition from psoriasis to psoriatic arthritis. This review synthesizes current evidence on the role of enthesitis in psoriatic disease, focusing on its underlying mechanisms, diagnostic approaches, and therapeutic strategies. Importantly, we propose a practical screening and referral pathway designed to support dermatologists in early recognition of at-risk patients, with the goal of facilitating timely rheumatology referral and multidisciplinary management. By emphasizing the complementary roles of questionnaires, clinical assessment, and targeted imaging, our approach aims to bridge existing gaps in care and optimize patient outcomes.Weiterlesen

ObjectivesTo perform the cross-cultural adaptation of the Psoriasis Epidemiology Screening Tool (PEST) questionnaire into Spanish (PEST-S) and conduct a preliminary exploratory assessment of its discriminative ability to identify psoriatic arthritis (PsA) among patients with psoriasis (Ps), osteoarthritis (OA), or both.MethodsThe PEST questionnaire was translated and culturally adapted into Spanish following international guidelines. A cross-sectional study was conducted including adult patients with PsA, Ps, OA, and Ps+OA. The PEST-S was administered to all participants. PsA diagnosis was confirmed using CASPAR criteria. Diagnostic performance was evaluated using sensitivity, specificity, likelihood ratios, area under the ROC curve (AUC), and Cohen's kappa coefficient. Comparisons of individual PEST-S items were performed across diagnostic groups.ResultsA total of 124 patients were included: 32 with PsA, 31 with Ps, 33 with Ps+OA, and 28 with OA. The questionnaire required less than one min to complete. PEST-S scores ≥3 yielded a sensitivity of 100%, specificity of 94.2%, LR+ of 17.2, and LR- of 0. The AUC was 0.97 (95% CI: 0.95-0.99). Agreement between PEST-S and CASPAR classification was 93.2% (κ = 0.838). A statistically significant difference was found in the responses to all five PEST-S items between patients with PsA and those in the other diagnostic groups (p< 0.05).ConclusionThe Spanish version of the PEST questionnaire (PEST-S) demonstrated excellent diagnostic performance in distinguishing PsA from Ps and OA in a Spanish-speaking population. These findings support its clinical utility and justify further validation in a screening context among patients with psoriasis without prior rheumatologic evaluation.Weiterlesen

BackgroundPsoriasis is a chronic inflammatory skin disorder with unclear etiology. The roles of skin microbiome and metabolic dysregulation in psoriasis pathogenesis are not yet fully understood.MethodsWe conducted an integrated microbiome and untargeted metabolomic analyses on skin samples from 29 patients with psoriasis and 31 healthy controls. The skin microbiota was characterized using 16 S rRNA gene sequencing, and untargeted metabolomic profiling was performed using LC-MS/MS. Multivariate statistical analyses were used to identify differential microbes and metabolites, followed by correlation analyses to explore microbe-metabolite interactions.ResultsPsoriatic lesions exhibited significantly higher skin microbial alpha diversity compared to healthy controls. Principal component analysis revealed distinct microbial community structures between the two groups. At the genus level, Corynebacterium and Staphylococcus were significantly enriched in psoriatic lesions, while Cutibacterium was notably reduced. Metabolomic analysis identified 63 differential metabolites, with 39 upregulated and 24 downregulated in psoriatic lesions. These metabolites were primarily involved in lipid metabolism (particularly phospholipids and sphingolipids), amino acid metabolism, and inflammatory mediator pathways. Correlation analysis revealed significant associations between microbial alterations and metabolic dysregulation. Cutibacterium abundance was negatively correlated with inflammatory lipids and positively correlated with antioxidant metabolites, whereas Staphylococcus and Corynebacterium exhibited the opposite pattern. Notably, the abundance of Propionibacteriaceae strongly correlated with glutathione levels (r = 0.821, P < 0.001), indicating a potential role of microbiome-mediated oxidative stress in psoriasis.ConclusionsThis study highlights significant alterations in both the skin microbiome and metabolome in patients with psoriasis, revealing complex microbe-metabolite interaction networks. The findings suggest that microbial dysbiosis, particularly the decreased abundance of Cutibacterium and the increased abundance of Staphylococcus/Corynebacterium, may contribute to psoriasis pathogenesis by modulating lipid metabolism, inflammatory pathways, and oxidative stress responses.Weiterlesen

ObjectivesBiologic therapies for skin psoriasis (PsO) have been linked to a lower risk of developing psoriatic arthritis (PsA), but their efficacy across different mechanisms of action remains to be fully explored. This study aimed to compare PsA risk in PsO patients prescribed interleukin-23 inhibitors (IL23i) vs interleukin-17 inhibitors (IL17i).MethodsThis retrospective cohort study utilized the TriNetX database to categorize adult PsO patients into two cohorts: those newly prescribed IL23i (without IL17i exposure) and those newly prescribed IL17i (without IL23i exposure). Patients with a history of PsA or previous use of anti-tumor necrosis factor-α or anti-interleukin-12/23 agents were excluded. A total of 5,490 patients, matched 1:1 by propensity scores, were analyzed for PsA risk using hazard ratios (HR) from Cox regression.ResultsThe 5-year cumulative incidence of PsA was significantly lower in IL23i users compared with IL17i users (11.68% vs 19.94%; p <0.001). IL23i treatment was associated with a reduced PsA risk (HR 0.475, 95% CI 0.382-0.590). This reduced risk persisted across various subgroups defined by age, sex, race, PsO subtypes, obesity, and elevated inflammatory markers. Similar results were observed in individual drug comparisons, with lower risks for guselkumab vs secukinumab (0.480, 0.358-0.645) and ixekizumab (0.698, 0.509-0.956), risankizumab vs secukinumab (0.433, 0.306-0.612) and ixekizumab (0.504, 0.347-0.732), and tildrakizumab vs secukinumab (0.339, 0.131-0.875). The comparison of tildrakizumab vs ixekizumab (0.451, 0.171-1.191) also suggested a lower risk but was not statistically significant.ConclusionsPsO patients treated with IL23i had a lower subsequent PsA risk compared with those treated with IL17i.Weiterlesen

Background and objectivesAtopic dermatitis (AD) and psoriasis (Pso) are frequently associated with psychological distress. This study evaluated the prevalence and correlates of shame-related disorders (SRD), namely body dysmorphic disorder (BDD) and social anxiety disorder (SAD), in patients with AD and Pso.Patients and methodsA monocentric, cross-sectional study was conducted in adult patients from 07/2023 to 03/2024. A trained clinical psychologist assessed subjects for BDD and SAD. Additionally, subjects completed the DLQI. Objective severity of their disease was physician-rated using the EASI or PASI.ResultsOne hundred and fifty-one patients were included, n = 55 (36.4%) with AD and n = 96 (63.6%) with Pso. Among all study participants, the point and lifetime prevalence of SRD was 17.2% and 31.8%, respectively. Point and lifetime prevalence for BDD was 10.6% and 26.5%, and for SAD 12.6% and 17.2%. There were no differences in the point or lifetime prevalence of BDD or SAD between patients with AD or Pso. SRD were associated with younger age and female sex. DLQI was significantly reduced in those suffering from SRD.ConclusionsOur results indicate that SRD are prevalent in AD and Pso and should therefore be further investigated for their use in routine clinical practice.Weiterlesen

No abstract supplied.Weiterlesen

IL-17A spielt eine zentrale Rolle bei der Entzündung an den Sehnenansätzen (Enthesitis) bei Psoriasis-Arthritis. Eine Studie hat gezeigt: Bekamen Betroffene 24 Wochen lang ein Medikament, das IL-17A blockiert, so besserten sich bei 9 von 10 die Symptome deutlich. Es gab weniger „böse“ Entzündungszellen im Gewebe. Gleichzeitig vermehrten sich Zellen, die Entzündungen dämpfen. Auch Hinweise auf schädlichen Knochenumbau, wie er oft bei Psoriasis-Arthritis vorkommt, gingen zurück. Das zeigt: IL-17A-Hemmer können direkt an den betroffenen Stellen für mehr Ruhe sorgen und das Fortschreiten der Erkrankung bremsen[1][2][4]. Originaltitel: Entheseal tissue signature in response to IL-17A inhibition in psoriatic arthritis: results from the EBIO entheseal biopsy study. Link zur Quelle

Im Medizinstudium gibt es jetzt ein neues Seminar, das sich mit Stigmatisierung und psychosozialen Belastungen von Menschen mit sichtbaren Hauterkrankungen wie Psoriasis beschäftigt[1][2][4]. Hier unterrichten Ärztinnen, Psychologinnen und Expertinnen gemeinsam, damit die Studierenden von verschiedenen Blickwinkeln lernen[1][2]. Im Seminar reden sie nicht nur über Juckreiz und Hautprobleme, sondern auch darüber, wie es sich anfühlt, wenn andere negativ reagieren oder Vorurteile haben[1][2]. Die Studierenden üben, wie man Betroffenen besser hilft und sie beraten kann[2]. Fast alle Teilnehmer finden den Unterricht sinnvoll, weil er praktische Tipps liefert und einen offenen Umgang mit schwierigen Themen ermöglicht[2]. Es zeigt auch: Gute Behandlung braucht Wissen über Körper und Psyche. Das Seminar hilft dabei, das besser zu verstehen, und macht das Medizinstudium ein Stück menschlicher[1][2]. Originaltitel: Implementierung eines Team-Teaching-Seminars in der Regellehre des Medizinstudiums zur Stigmatisierung und zu psychosozialen Belastungen von Menschen mit sichtbaren Hauterkrankungen | Publisso Link zur Quelle

Viele Menschen mit rheumatoider Arthritis oder Psoriasis-Arthritis, die seit mindestens sechs Monaten eine stabile Remission oder nur eine geringe Krankheitsaktivität haben, fragen sich, ob sie ihre Medikamente (konventionelle synthetische DMARDs) reduzieren oder sogar ganz absetzen können. Experten empfehlen, eine vorsichtige und schrittweise Reduktion auszuprobieren[1][2]. Ein einfaches, abruptes Absetzen wird nicht empfohlen, da es das Risiko eines Krankheitsschubs erhöhen kann[1]. Es gibt bisher wenig sichere Daten, welche Strategie die beste ist und wie lange der Effekt anhält. Neue internationale Leitlinien raten dazu, gemeinsam mit dem Arzt eine individuelle Entscheidung zu treffen und die Erkrankung weiter engmaschig zu kontrollieren[1]. In etwa 10 bis 20 Prozent der Betroffenen gelingt es, nach und nach ganz auf DMARDs zu verzichten, ohne dass die Krankheit zurückkommt[3]. Doch jeder Körper reagiert anders, daher ist Teamarbeit mit dem Arzt wichtig, damit Beschwerden früh erkannt und behandelt werden können. Originaltitel: Dose reduction and discontinuation of conventional synthetic disease‐modifying anti‐rheumatic drugs (DMARDs) for people with rheumatoid arthritis or psoriatic arthritis in remission or low disease activity Link zur Quelle

Menschen mit **Psoriasis** haben ein etwas höheres Risiko, an bestimmten **Krebsarten** zu erkranken[1][4][3]. Gerade **Hautkrebs** kommt bei ihnen häufiger vor, aber auch das Risiko für **Lymphome** ist leicht erhöht[1][4]. Besonders betroffen sind Menschen mit schwerer Psoriasis oder solche, die bestimmte Therapien wie Lichtbehandlung mit PUVA bekommen[1]. Gleichzeitig haben viele Betroffene weitere bekannte Risikofaktoren wie Rauchen oder Übergewicht, die das Krebsrisiko ebenfalls steigern können[3]. Die Forschung zeigt: Nicht jede Studie findet das gleiche Ergebnis – manche zeigen ein klares Mehr an Krebs, andere bleiben unentschlossen[4]. Trotzdem sind sich viele Expertinnen und Experten einig, dass regelmäßige **Krebsvorsorge** bei Psoriasis sinnvoll ist[3]. Originaltitel: Psoriasis and the risk of 26 cancers: pooled population-based cohort studies from Denmark, England, Israel, and Taiwan Link zur Quelle

An neues Seminar für Medizinstudenten an der Uni Hamburg zeigt, wie wichtig das Thema **Stigmatisierung bei sichtbaren Hautkrankheiten wie Psoriasis** ist. Dermatologen, Psychologen und Experten haben sich zusammengetan und unterrichten gemeinsam. Die Studierenden lernen durch Vorträge, Übungen und Diskussionen, was Betroffene erleben und wie sie besser helfen können. Nach dem Seminar fühlen sich die meisten sicherer darin, Patientinnen und Patienten bei psychosozialen Problemen durch Ausgrenzung zu unterstützen. Fast alle finden das Seminar und die Teamarbeit richtig gut und hilfreich[1]. Originaltitel: Implementation of a team-teaching seminar on the stigmatization and psychosocial burdens of people with visible skin diseases in the standard curriculum of medical studies. Link zur Quelle

Viele Menschen mit **Psoriasis** oder **atopischer Dermatitis** kämpfen nicht nur mit ihrer Haut, sondern auch mit seelischem Stress. In einer aktuellen Studie zeigte sich: Jeder dritte Betroffene leidet im Laufe seines Lebens an **Scham-bedingten Störungen** wie **Körperbildstörung** oder **sozialer Angststörung**. Frauen und jüngere Menschen sind besonders oft betroffen. Die Krankheit erschwert ihnen den Alltag und senkt die Lebensqualität. Es gab keinen Unterschied zwischen den Erkrankungen. Ärztinnen und Ärzte sollten Scham-Gefühle ernst nehmen und in der Behandlung beachten[1][4]. Originaltitel: Shame-related disorders in patients with atopic dermatitis and psoriasis - An exploratory, cross-sectional interview study on the prevalence and correlates of body dysmorphic disorder and social anxiety disorder. Link zur Quelle

Forscher aus Deutschland haben mit künstlicher Intelligenz berechnet, wie gut die Behandlung mit Secukinumab bei Menschen mit Psoriasis-Arthritis oder axialer Spondyloarthritis wirkt. Sie haben Daten von fast 2000 Patientinnen und Patienten ausgewertet. Die wichtigsten Faktoren dafür, ob du nach vier Monaten wenig Krankheitsaktivität oder eine bessere Lebensqualität hast, hängen unter anderem davon ab, wie sehr du und dein Arzt deine Krankheit am Anfang einschätzen, wie viele Gelenke wehtun, dein Alter, dein Gewicht und ob du schon vorher mit Biologika behandelt wurdest. Die Methode könnte Ärzten helfen, den Behandlungserfolg besser vorherzusagen und Therapien individueller anzupassen. Originaltitel: Predicting treatment outcomes in patients with psoriatic arthritis or axial spondyloarthritis: An artificial intelligence-driven approach. Link zur Quelle

Biologika sind spezielle Medikamente gegen Psoriasis, die gezielt Teile des Immunsystems ausschalten[4][7][8]. Das ist anders als bei älteren Mitteln, die die Abwehr komplett bremsen. Je nach Biologikum werden zum Beispiel die Botenstoffe TNF-alpha, IL-17 oder IL-23 unterdrückt. Diese spielen eine wichtige Rolle bei der Entzündung und den Hautveränderungen[4][8]. Die neuen Wirkstoffe helfen oft schnell und stark, trotzdem bleibt manchmal an einigen Stellen noch etwas von der Krankheit sichtbar – das nennt man „residuales PASI“. Dabei fällt auf, dass bestimmte Biologika an verschiedenen Körperstellen besser wirken als an anderen[1]. Einige reduzieren die Entzündung besonders an der Kopfhaut, andere eher an den Nägeln oder Gelenken. Ärzte können dadurch gezielter behandeln, sodass jeder Patient die beste Therapie für seine Problemzonen bekommt[1][8]. Biologika werden meist als Spritzen alle paar Wochen verabreicht, je nach Wirkstoff[4][7]. Originaltitel: Biologic treatments for psoriasis have different anatomical specificities in residual PASI Link zur Quelle

**Psoriatische Arthritis und Uveitis: Wie hängen sie zusammen?** Psoriatische Arthritis (PsA) ist eine chronische Entzündungskrankheit, die oft mit Uveitis in Verbindung gebracht wird. Uveitis ist eine Entzündung im Auge, die Sehprobleme verursachen kann. Wissenschaftler haben nun herausgefunden, dass PsA das Risiko für Uveitis erhöht. **Die Studie: Was wurde entdeckt?** Eine Studie hat gezeigt, dass Menschen mit PsA fast doppelt so häufig Uveitis entwickeln wie andere. Der genaue Mechanismus wie diese Krankheiten miteinander zusammenhängen, ist noch nicht vollständig geklärt. Die Studie nutzte eine Methode namens Mendelian Randomization, um die kausale Beziehung zu untersuchen. Das Ergebnis: PsA führt zu einem erhöhten Risiko für Uveitis. **Was bedeutet das für Betroffene?** Für Menschen mit PsA ist es wichtig, regelmäßig Augenkontrollen durchführen zu lassen, um mögliche Augenprobleme frühzeitig zu erkennen. Die Forschung zu PsA und Uveitis hilft, die Verbindung zwischen diesen Krankheiten besser zu verstehen. Originaltitel: Integrative Mendelian randomization and transcriptomic analysis reveals the causal association between psoriatic arthritis and uveitis Link zur Quelle

No abstract supplied.Weiterlesen

Psoriasis is a chronic inflammatory skin disease that forms a vicious cycle with psychological stress. Whether and how the hypothalamic-pituitary (HP) axis-mediated neuroendocrine system regulates psoriasis remains obscure. Here, we report elevated levels of the pituitary hormone prolactin (PRL) in both psoriasis patients and imiquimod (IMQ)-induced psoriasis mice. Mechanistically, PRL acts on dermal PRLR-expressing fibroblasts to promote the production of the chemokines CCL2 and CCL7, which then recruit monocytes/macrophages into psoriatic lesional skin, thereby activating local IL-17A-producing T cells. Accordingly, pharmacological targeting of PRL signaling inhibits the recruitment of monocytes/macrophages, decreases the frequency of IL-17A-producing T cells, and alleviates IMQ-induced psoriasis in mice. In summary, our results delineate a mechanism by which the neuroendocrine hormone PRL aggravates psoriasis and highlight a potential therapeutic strategy of inhibiting PRL-PRLR signaling, particularly in psoriasis patients experiencing psychological stress.Weiterlesen

Psoriasis is a chronic, complex immune-mediated inflammatory disorder with cutaneous and systemic manifestations in which keratinocytes, dendritic cells and T cells have central roles. UBE2L3 may be a protective biomarker that regulates the pathogenesis of psoriasis. Here, we identify the IL-17A signaling similarity between human psoriatic skin and Ube2l3 conditional knockout mouse skin in the epidermis rather than dermis. IL-17A is regulated by CXCR6+ Vγ2+ γδT cells in mouse while CXCR6+ CD8+ T cells in human. CXCL16 is the only chemokine that binds to and stimulates CXCR6. Ube2l3 reduction in keratinocytes activates IL-1β and then promotes CXCL16 expression through STAT3 signaling. Up-regulated CXCL16 in keratinocytes and cDC2/mDC then attracts Vγ2+ γδT17 or CD8+ T cells to secrete IL-17A and form a positive feedback loop in keratinocytes supporting psoriatic lesions. Thus, UBE2L3 is a keratinocyte-intrinsic suppressor of epidermal IL-17 production in Vγ2+ γδT cells in mouse and CD8+ T cells in human through the CXCL16/CXCR6 signaling pathway in psoriasis.Weiterlesen

Inflammatory monocytes are increasingly recognized as key amplifiers of psoriasis, yet the epigenetic drivers of their pathogenic signature remain unclear. Here, we demonstrate that the histone demethylase KDM6B is markedly upregulated and catalytically active in classical monocytes during the imiquimod (IMQ)-induced psoriasis model. This is associated with reduced levels of the repressive histone mark H3K27me3, an epigenetic modification linked to chromatin compaction and transcriptional silencing, at the Il1b, Tnf, Pgam1, Pgk1, and Aldoa promoters, together with an enhanced inflammatory and glycolytic gene signature. Pharmacological blockade of KDM6B after disease onset using GSK-J4, a cell-permeable prodrug that is intracellularly converted to the active KDM6B inhibitor GSK-J1, restores H3K27me3 at inflammatory and metabolic loci, suppresses Il1b/Tnf transcription, normalizes bioenergetic profiles, and reduces monocyte and neutrophil recruitment to the inflamed skin. Single-cell transcriptomic profiling further reveals that KDM6B inhibition represses cytokine-mediated signaling, glycolysis, and chemotaxis pathways in monocytes, yet enriches antigen presentation modules, consistent with a shift toward a homeostatic, antigen-presenting surveillance program in myeloid cells and a Treg-supportive milieu. Collectively, our data identify KDM6B as an epigenetic-metabolic switch that sustains monocyte-driven inflammation in the IMQ-induced psoriasis model. Importantly, we provide preclinical evidence that targeting KDM6B can reduce maladaptive inflammatory response even in progressed diseases. These findings propose KDM6B inhibitors as a promising adjunct to current biologics for psoriasis and other myeloid-driven autoinflammatory disorders.Weiterlesen

IntroductionPsoriatic arthritis (PsA) presents various imaging abnormalities in joints and diverse nail changes, but the link between nail and joint findings remains unclear. This study aimed to gain a better understanding of the relationships between nail manifestations and abnormal articular architectures by investigating the associations between nail abnormalities and articular findings in PsA-affected interphalangeal joints.MethodsA total of 106 nails adjacent to PsA-affected distal interphalangeal joints were examined in 29 patients who underwent comprehensive systemic evaluation and imaging for the diagnosis and treatment of PsA. Imaging studies, including X-ray, magnetic resonance imaging, and iodine-enhanced dual-energy computed tomography, were conducted to examine the acral joints.ResultsNail manifestations were observed in 81 among 106 fingers or toes (76.4%). Pitting, the most common nail finding (75/106, 70.8%), was observed in isolation on 22/75 nails (29.3%), while other nail manifestations were observed in isolation on ≤ 3/50 nails (6.0%). Among the 81 examined nail lesions, 49 (61.3%) preceded the onset of articular symptoms in the adjacent interphalangeal joints, 9 (11.2%) followed the joint symptoms, and 23 (28.8%) occurred simultaneously. Articular bone findings, such as bone erosion and bone proliferation, were positively associated with subungual hyperkeratosis, leukonychia, crumbling, and/or transverse grooves. In contrast, soft tissue findings, including tenosynovitis, synovitis, and periarthritis, were negatively associated with onycholysis, subungual hyperkeratosis, leukonychia, and/or pitting.ConclusionThe study suggests that nail manifestations may be positively associated with bone abnormalities and negatively associated with soft tissue inflammation in PsA. Nail examinations may help estimate articular conditions. Key points • More than 60% of nail manifestations precede the onset of articular symptoms in the adjacent interphalangeal joints. • Nail manifestations may be positively associated with bone abnormalities and negatively with soft tissue inflammation in PsA. • Nail examination may aid in estimating articular status, prompting appropriate evaluation and early treatment for the affected joints.Weiterlesen

No abstract supplied.Weiterlesen