Redaktion

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

No abstract supplied.Weiterlesen

ObjectivesPsoriatic arthritis (PsA) increases cardiovascular disease risk. Emerging evidence suggests biologic Disease-Modifying Antirheumatic Drugs (DMARDs) may offer protective effects, though their advantage over conventional therapy remains under investigation.MethodsA retrospective cohort study was conducted using the Chang Gung Memorial Research Database in Taiwan. Patients with PsA were identified from 2001 to 2022. The study included 2,383 patients who had used at least one disease-modifying antirheumatic drugs (DMARDs), divided into two groups: 1,190 on bDMARDs and 1,193 on conventional DMARDs (cDMARDs). The primary outcome was defined as a major adverse cardiovascular event (MACE), including stroke, myocardial infarction, cardiovascular mortality or coronary revascularization. Potential confounding was mitigated using inverse probability of treatment weighting.ResultsThe average follow-up period was 5.1 years for the bDMARD group and 5.0 years for the cDMARD group. The incidence of MACE was 0.34 and 0.55 events per 100 person-years in the bDMARDs and cDMARDs groups, respectively. All-cause mortality occurred at rates of 0.73 and 1.86 per 100 person-years in the bDMARDs and cDMARDs groups, respectively. The results showed that the bDMARDs group had lower risks of MACE (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.43-0.96), all-cause mortality (HR: 0.44; 95% CI: 0.35-0.57) and cardiovascular mortality (HR: 0.54; 95% CI: 0.32-0.92), but a higher incidence of infection-related admission (subdistribution HR: 1.45; 95% CI: 1.18-1.78).ConclusionsbDMARDs may reduce cardiovascular events and mortality in PsA, but infection risks warrant close monitoring. Further research is needed to refine treatment strategies.Weiterlesen

IntroductionTargeted biologic therapies have transformed outcomes for individuals with psoriasis, a common immune-mediated inflammatory skin disease. The widespread use of these highly effective treatments has led to a growing number of individuals with clear or nearly clear skin remaining on continuous, long-term treatment. Personalised strategies to minimise drug exposure may sustain long-term disease control while reducing treatment burden, associated risks and healthcare costs. This study aims to evaluate the feasibility of a definitive pragmatic effectiveness trial of two personalised dose minimisation strategies compared with continuous treatment (standard care) in adults with well-controlled psoriasis receiving the exemplar biologic risankizumab.Methods and analysisThis is a multicentre, assessor-blind, parallel group, open-label randomised controlled feasibility trial in the UK, evaluating two personalised biologic dose minimisation strategies for psoriasis. 90 adults with both physician-assessed and patient-assessed clear or nearly clear skin on risankizumab monotherapy for ≥12 months will be randomised in a 1:1:1 ratio to (1) patient-led 'as-needed' treatment, where risankizumab is administered at the first sign of self-assessed psoriasis recurrence, (2) therapeutic drug monitoring-guided treatment, with personalised dosing intervals determined using a pharmacokinetic model or (3) continuous treatment as per standard care, for 12 months. Participants will be invited to submit self-reported outcomes and self-taken photographs every 3 months using a bespoke remote monitoring system (mySkin app) and will attend an in-person assessment at 12 months. They may also request additional patient-initiated follow-up appointments during the trial if needed. The primary outcome is the practicality and acceptability of the two personalised biologic dose minimisation strategies, assessed as a composite measure including recruitment and retention rates, adherence to the assigned strategies and acceptability to both patients and clinicians. The feasibility of collecting healthcare cost and resource utilisation data will also be evaluated to inform a future cost-effectiveness analysis. A nested qualitative study, involving semistructured interviews with patients and clinicians, will explore perspectives on the personalised biologic dose minimisation strategies. These findings will inform the design of a future definitive trial.Ethics and disseminationThis study received ethical approval from the Seasonal Research Ethics Committee (reference 24/LO/0089). Results will be disseminated through scientific conferences, peer-reviewed publications and patient/public engagement events. Lay summaries and infographics will be codeveloped with patient partners to ensure the findings are accessible for the wider public.Trial registration numberISRCTN17922845.Weiterlesen

ObjectivesThis is a protocol for a Cochrane Review (intervention). The objectives are as follows: To investigate the benefits and harms of dose reduction and discontinuation of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in adults with rheumatoid arthritis or psoriatic arthritis, who have been in sustained remission or low disease activity. This is a common review protocol, outlining the approach for two separate Cochrane reviews for people with rheumatoid arthritis or psoriatic arthritis. Dose reduction or discontinuation of csDMARDs in adults with rheumatoid arthritis, who have been in sustained remission or low disease activity Dose reduction or discontinuation of csDMARDs in adults with psoriatic arthritis, who have been in sustained remission or low disease activity.Weiterlesen

Background and objectivesImproved understanding of the immunopathogenesis of psoriasis has led to the development of effective targeted therapies, but patients who respond to treatment without total skin clearance have residual disease. The aim of this study was to demonstrate the existence of specific residual disease (or residual PASI) anatomical localizations related to different biologic agents.Methods and patientsThis retrospective, observational, multi-center study analyzed clinical data of patients affected by psoriasis who had received biologic treatments for at least 6 months. The data analysis focused on patients with residual PASI.ResultsA total of 228 of 1,000 patients showed residual disease despite achieving PASI 90 at weeks 24-28 of biologic treatment. The anatomical sites most frequently involved in residual disease were the lower limbs (44.3%). We observed differences among the biologic agents in terms of frequency and localization of residual disease. The localization of residual skin lesions to lower limbs was associated with treatment switching/interruption. The drugs with the highest and lowest proportion of patients with residual disease in the lower limbs were, respectively, secukinumab and risankizumab.ConclusionsTreatment with anti-IL-17 and anti-IL-23 drugs is characterized by the persistence of residual skin lesions with differences in terms of frequency and anatomical localizations.Weiterlesen

IntroductionDifficult-to-treat psoriatic arthritis (D2T-PsA) is increasingly recognized as a complex clinical entity characterized by persistent disease burden despite multiple targeted therapies. Its identification is essential to improve patient outcomes and to guide the development of new therapeutic strategies.Areas coveredIn this perspective article, we discuss the evolving concept of D2T-PsA, including its epidemiology, clinical characterization, and underlying pathophysiological mechanisms. We highlight the role of gender differences, psychosocial comorbidities, and central sensitization in shaping disease persistence and patient-reported impact. We also examine the limitations of current disease activity indices (DAPSA, PsAID, PASDAS) in capturing heterogeneity and the need for multidimensional frameworks. A structured literature search was conducted in PubMed/MEDLINE and Scopus databases (January 2020-June 2025), restricted to English-language publications, using combinations of the terms psoriatic arthritis, difficult-to-treat, refractory, and difficult-to-manage. Additional references were identified from conference abstracts and relevant bibliographies.Expert opinionRecognizing D2T-PsA as a distinct, multifactorial entity is critical to advancing personalized medicine. Future directions will involve harmonizing EULAR and GRAPPA frameworks, integrating biomarker discovery, digital tools, and adaptive trial designs, and embedding patient perspectives. This multidimensional approach is expected to transform treatment from empirical cycling toward precision care in psoriatic arthritis.Weiterlesen

BackgroundPsoriasis is associated with increased risk of depression. Although cognitive behavioral therapy (CBT) is an evidence-based treatment, access remains limited.ObjectivesTo evaluate the feasibility, acceptability, and preliminary efficacy of a smartphone-delivered, coach-led CBT program for depression among individuals with psoriasis.MethodsThis single-arm, 8-week pilot study (Mindset trial, NCT06216691) enrolled adults with psoriasis and at least mild depressive symptoms (PHQ-9 ≥5). Participants engaged in a smartphone-based CBT program guided by bachelor's-level lay coaches. Primary outcomes were feasibility as evaluated by module completion and acceptability as evaluated by the Client Satisfaction Questionnaire-8 (CSQ-8]) and User Version of the Mobile Application Rating Scale (uMARS). Secondary outcomes included changes in the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Appearance Anxiety Inventory, Skindex-16, and Psoriasis Symptom Inventory.ResultsOf 30 participants, 63.3% completed ≥4/8 modules and 43.3% completed ≥6/8 modules. Mean CSQ-8 and uMARS scores were 27.2 (SD 4.5) and 4.0 (SD 0.7), respectively, supporting high satisfaction. Statistically and clinically significant improvements were observed in PHQ-9 (mean change -4.4; Cohen's d = 0.92), GAD-7 (-2.8; d = 0.63), and Skindex-16 symptoms (5.0; d = 0.78), emotions (10.0; d = 0.95), and functioning (6.4; Cohen's d = 0.71) subscales as well as the Psoriasis Symptom Inventory (3.1; d = 0.43).ConclusionsThis study supports the feasibility, acceptability, and preliminary efficacy of smartphone-delivered CBT for individuals with psoriasis and depressive symptoms. Given the scalability of this model, future randomized trials are warranted to assess broader effectiveness in dermatology care settings.Weiterlesen

BackgroundPsoriasis is a chronic inflammatory skin disease, and the risk of developing cancer has been postulated due to the presence of several plausible underlying mechanisms. Understanding the association between psoriasis and cancer is imperative to the provision of optimal psoriasis care.ObjectivesTo examine the risk of developing cancer in individuals with psoriasis.MethodsPopulation-based cohort studies were conducted in Denmark, England, Israel, and Taiwan through the use of linked electronic health records. Individuals aged at least 18 years of age with a diagnosis of psoriasis in the country-specific study period were matched to up to 6 comparators with no record of psoriasis prior to index date. Country-specific hazard ratios for the risk of cancer development overall and for 26 site-specific cancers between individuals with and without psoriasis were calculated through Cox regression. Country-specific estimates were pooled using random effects modelling.ResultsWe included 702,022 individuals with psoriasis and 4,185,342 matched comparators. In models implicitly controlled for age, sex and calendar time by matching, there was a small association between psoriasis and cancer overall (pooled HR [pHR]:1.08;95%CI, 1.04-1.13; I2= 92.4%). Adjustment for potential confounding factors resulted in a slight attenuation of risk (pHR:1.05; 95%CI, 1.01-1.09; I2=81.2%). When restricted to those with moderate-to-severe psoriasis, the risk of cancer overall was slightly higher (pHR:1.16;95%CI, 1.04-1.28; I2=92.8%) and confounder adjusted models (pHR: 1.09;95%CI, 1.03-1.15; I2=60.6%). Associations with psoriasis were present for oral cavity (pHR: 1.29; 95%CI, 1.12-1.47; I2=55.4%), pharynx (pHR:1.30;95%CI, 1.07-1.58; I2=58.4%), oesophagus (pHR:1.17;95%CI, 1.03-1.33; I2=56.6%), liver (pHR:1.53;95%CI, 1.33-1.77; I2=75.1%), pancreas (pHR:1.09;95%CI, 1.02-1.17; I2=0.0%), kidney (pHR:1.19;95%CI, 1.11-1.27; I2=0.0%), bladder (pHR: 1.13; 95%CI, 1.06-1.20; I2=28.7%), and keratinocyte cancers (pHR:1.37;95%CI, 1.16-1.63; I2=97.5%), Hodgkin lymphoma (pHR:1.56;95%CI, 1.16-2.11; I2=69.7%), non-Hodgkin lymphoma (pHR:1.16;95%CI, 1.07-1.26; I2=35.5%) and leukaemia (pHR:1.18; 95%CI, 1.08-1.29; I2=41.9%). Site-specific associations generally persisted, with slight risk exacerbations and additional associations for lung and ovarian cancers, when limited to people with moderate-to-severe psoriasis.ConclusionPsoriasis was associated with an increased risk of developing 14 of 26 investigated site-specific cancers, including cancers with poor prognosis, such as liver, lung, and oesophageal cancer. Our findings can be used to reinforce cancer prevention strategies in psoriasis care.Weiterlesen

No abstract supplied.Weiterlesen

Dysregulated copper homeostasis is implicated in inflammatory skin diseases such as psoriasis and atopic dermatitis (AD), but the role of cuproptosis remains poorly defined. This study aimed to elucidate the role and mechanism of cuproptosis in inflammatory skin diseases. Transcriptome analysis of patient lesions revealed significant alterations in cuproptosis-related genes correlating with disease-specific pathological features. These cuproptosis-related gene expression signatures demonstrated strong clinical relevance to therapeutic efficacy in both psoriasis and AD cohorts. Functional validation using disease models showed that pharmacologically inhibiting cuproptosis with the copper chelator tetrathiomolybdate (TTM), or genetically knocking down the copper importer SLC31A1, effectively alleviated chronic skin inflammation and hallmark pathological changes induced by imiquimod (IMQ) or calcipotriol (MC903). Mechanistically, we uncovered that SLC31A1-mediated cuproptosis promotes intracellular α-ketoglutarate (α-KG) accumulation, driving activation of the lysine demethylase KDM5B. Activated KDM5B specifically demethylates H3K4me3 marks at the promoter of the ferroptosis regulator ferritin heavy chain 1 (FTH1), suppressing its transcription and consequently sensitizing keratinocytes to ferroptotic cell death, thereby amplifying inflammatory tissue damage. Our findings establish a fundamental pathogenic SLC31A1/KDM5B/FTH1 molecular axis linking dysregulated copper metabolism and cuproptosis to ferroptosis execution in psoriasis and AD, providing significant mechanistic insights and pinpointing promising therapeutic targets for these refractory skin disorders.Weiterlesen