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BackgroundPsoriasis is associated with a significant comorbidity burden, especially cardiovascular and metabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RA), such as semaglutide, used to treat obesity and diabetes, could potentially reduce comorbidity in patients with psoriasis.ObjectiveTo investigate all-cause mortality, cardiovascular, inflammatory, psychiatric outcomes, and adverse events in psoriasis patients treated with GLP-1RA.MethodsThis retrospective population-based cohort study utilized real-world data from the US TriNetX database. Patients with psoriasis who were treated for diabetes or obesity with GLP-1RA during the full follow-up period of 2 years were compared with those treated with other systemic anti-diabetic or obesity drugs. After 1:1 propensity-score matching for relevant risk factors, 3,048 participants were included in each cohort. The primary outcomes included the risk of cardiometabolic, psychiatric, and autoimmune sequelae of psoriasis, as well as all-cause mortality and potential adverse drug events. The analysis was repeated using cohorts without psoriasis and results were further validated through two sensitivity analyses involving (i) later follow-up periods, or (ii) exclusion of patients with pustular psoriasis.ResultsIn the matched cohorts of 3,048 patients with psoriasis treated with GLP-1RA (60.37% females, mean age 56.94 years, standard deviation [SD] 12.02 years) versus other antidiabetic and obesity drugs (61.91% females, mean age 56.42 years, SD 14.16 years), GLP-1RA treatment was associated with significantly decreased all-cause mortality (hazard ratio [HR] 0.219, 95% confidence interval [CI] 0.123-0.391, p<0.0001) and reduced risk for major adverse cardiac events (MACE, HR 0.561, 95% CI 0.442-0.714, p<0.0001). Additionally, lower risks for alcohol (HR 0.346, CI 0.174-0.685, p=0.009) and substance abuse (HR 0.510, CI 0.350-0.743, p=0.002) were observed. Typical adverse drug events were not more frequent in the GLP-1RA cohort. The risk reductions were more pronounced in the cohorts with psoriasis compared to persons with obesity or diabetes without psoriasis. Findings were consistent across all sensitivity analyses.ConclusionsGLP-1RA treatment was safe and associated with reduced risks of cardiovascular and psychiatric comorbidities, as well as lower mortality in patients with psoriasis, with risk reductions markedly higher than in cohorts without psoriasis. Physicians should consider this drug class for patients with psoriasis and comorbid obesity or diabetes.Weiterlesen

ObjectiveSecondary failure to biologic DMARDs (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 PsA patients from our single-centre, 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 one-year visit (baseline) as achievement of ≥40% reduction in the swollen joint count (SJC) and either ≥50% reduction in 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 one 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 (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. 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 bDMARDs is common in PsA and may be influenced by both disease- and therapy-related factors.Weiterlesen

BackgroundPsoriatic disease (PsD) is a chronic, multisystem, inflammatory disorder encompassing psoriasis, psoriatic arthritis (PsA), and their associated comorbidities.ObjectiveThe aim of this subanalysis of the global "Psoriasis and Beyond" study was to evaluate patients' experiences of living with PsD in the USA.MethodsThe study included a cross-sectional, quantitative, 25-min online survey of adults with self-reported, healthcare professional-diagnosed, moderate-to-severe psoriasis, with or without PsA. USA-based patients were recruited through online panels by the Institut de Publique Sondage D'Opinion Secteur and The National Psoriasis Foundation.ResultsThis analysis included 793 US patients with psoriasis; 43% also had PsA. Overall, 75% of patients knew that their disease was systemic, and 65% had heard the term "psoriatic disease." Of patients without diagnosed PsA, 50% screened positive for PsA using the Psoriasis Epidemiology Screening Tool. Psoriasis negatively affected emotional well-being and quality of life (QoL) in the majority of patients (87% and 91%, respectively). Overall, 29% of patients reported that they could not work or study in the week prior to the survey; of these, 98% responded that psoriasis had a very or extremely large impact on their QoL. Mean diagnostic delays of 3.7 and 3.3 years for psoriasis and PsA, respectively, were reported.ConclusionsThis analysis of USA-based patients with PsD highlights the profound impact of PsD on emotional well-being and QoL and suggests potential underdiagnosis of PsA. There is a need to ensure early PsD diagnosis and to provide holistic treatment, including mental health support.Weiterlesen

Psoriasis and hypertension (HTN) are known to be closely related. However, at present, no study has systematically examined the epidemiology of this disease pattern on a global scale. We examined six databases from their inception until November 1, 2023 and used the Agency for Healthcare Research and Quality and the Newcastle-Ottawa Scale to assess the quality of observational studies. Data analysis was conducted in R. Meta-regression, sensitivity, and subgroup analyses were used to evaluate interstudy heterogeneity. Egger's test and funnel plots were used to evaluate publication bias. We reviewed 200 studies involving 15,010,888 patients. The overall prevalence of HTN among the patients with psoriasis was 32.22%. Overall, South America had the highest prevalence of hypertension among adult patients with psoriasis (52.36%), the three countries with the highest prevalence were Serbia, Singapore and Brazil. The prevalence of mild and severe psoriasis comorbid with HTN was 31.71% [95% CI: 24.40-40.05%] and 33.19% [95% CI: 27.17-39.81%], respectively. The prevalence of HTN in psoriasis vulgaris was 29.71% [95% CI: 25.10-35.15%], while that in psoriatic arthritis was 34.54% [95% CI: 31.27-38.14%]. Patients with psoriatic arthritis are more predisposed to requiring hypertension risk screening than patients with psoriasis vulgaris. More population-based prospective observational studies are required to elucidate the mechanisms underlying the coexistence of hypertension in patients with psoriasis.Weiterlesen

Psoriasis is an incurable and recurrent skin disease, and the need to develop new strategies for the treatment of psoriasis persists. Smilax glabra Roxb. (SGR) is listed as a key traditional Chinese medicine for the treatment of psoriasis through medicinal bath therapy in "Guideline for the diagnosis and treatment of psoriasis in China"; the active ingredients responsible for its anti-psoriatic effects and their mechanisms of action still require in-depth research. In this study, we first found that the topical application of SGR extract showed an anti-psoriasis effect in mice by using IMQ-induced primary and recurrent psoriasis mouse model. Network pharmacology, molecular docking, supercoiled DNA relaxation assay, luciferase reporter gene assay, and animal pharmacodynamics revealed that astilbin, quercetin, and resveratrol were key anti-psoriatic compounds in SGR extract for treating psoriasis by inhibiting TOP2A and activating AhR. These findings suggested that the synergistic effect of TOP2A inhibition and AhR activation was the key mechanism of SGR for the treatment of psoriasis. The combination of AhR activation and TOP2A inhibition synergistically alleviated psoriasis-like lesions and ameliorated the relapse of psoriasis-like lesions in mice. AhR activation and TOP2A inhibition synergistically regulated the cytokine-cytokine receptor interaction pathway and keratinization progress to prevent the relapse of psoriasis. This study investigates the "multi-component, multi-target" mechanism of SGR in treating psoriasis from the perspective of the interaction between targets, providing a new strategy for psoriasis topical treatment: the combination of TOP2A inhibitors and AhR activators.Weiterlesen

BackgroundThe nature of the relationship between psoriasis and alcohol consumption has been the topic of discussion for many years. Some studies have found that a higher intake of alcohol may be associated with a more severe manifestation of the disease. At the same time, patients with psoriasis often demonstrate elevated levels of alcohol consumption. It has not yet been fully established whether alcohol abuse serves as a trigger for psoriasis or if patients with psoriasis are simultaneously more prone to alcohol abuse.ObjectiveThe objective of this study was to employ Google Trends as a tool for crowdsourcing data on a national level to explore the relationship between psoriasis and the consumption of alcohol in Sweden.MethodsThis study examines crowdsourced web search data related to psoriasis and other skin disease-related search terms (such as utslag [rash]) as well as search interest in different types of alcohol. The analysis covers a 5-year period from 2018 to 2023 in Sweden, focusing on search behavior and correlations across this period.ResultsThe search behavior regarding psoriasis and alcohol-related search terms showed seasonal variations throughout the year. The relative search volume for psoriasis peaked in February, while alcohol-related searches, particularly Systembolaget and vodka, peaked in December and June. Our statistical analysis revealed relationships between the search interest regarding psoriasis and terms related to alcohol consumption, with disparities between different types of alcohol. The term "psoriasis" was negatively correlated with "Systembolaget" (r=-0.210), "vitt vin" (r=-0.224), and "vodka" (r=-0.220) (all P<.001), while the term "utslag" showed positive correlations with these same alcohol-related terms (r=0.278-0.347; P<.001).ConclusionsCrowdsourced data can offer valuable insights into population-level behavior. The observed negative correlations between psoriasis and alcohol-related searches suggest complex interactions, possibly reflecting reduced disease awareness or care during periods of higher alcohol consumption. The direction and strength of the correlations with psoriasis were not consistent across the different types of alcohol investigated in this study, which poses the question whether the relationship might be influenced by the type of beverage consumed. Further research is warranted to explore underlying mechanisms and validate these findings in clinical populations.Weiterlesen

BackgroundPsoriasis is a chronic immune-mediated skin disease that significantly impacts patients' quality of life due to its physical, psychological, and systemic burden. Phosphodiesterase-4 (PDE-4) plays a pivotal role in the inflammatory cascade of the disease through the modulation of intracellular cyclic adenosine monophosphate (cAMP) levels. This systematic review evaluates current evidence on the clinical efficacy and safety of novel PDE-4 inhibitors in the treatment of psoriasis.MethodsA systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science databases through January 18th, 2025, to identify clinical studies evaluating PDE-4 inhibitors in patients with psoriasis. Methodological quality and risk of bias were assessed using the National Institutes of Health (NIH) quality assessment tool and the Murad et al.quality assessment tool.ResultsOut of 1,942 related studies, twelve studies with 642 patients met our inclusion criteria. Among oral PDE-4 inhibitors, oral roflumilast demonstrated consistent improvements in the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI), as well as patient-reported outcomes, in cases with moderate to severe plaque psoriasis. Gastrointestinal symptoms were the most common adverse events. Similarly, orismilast and ME3183 also demonstrated significant PASI reductions and favorable tolerability, while topical agents like crisaborole and PF-07038124 showed a rapid localized response in patients suffering from mild to moderate psoriasis, with minimal adverse effects in sensitive areas, including the face and intertriginous regions.ConclusionPDE-4 inhibitors, both oral and topical, demonstrate promising efficacy and acceptable safety profiles in the treatment of psoriasis. To confirm their long-term benefits and improve clinical use, larger-scale studies with longer follow-up and a wider range of patients are required.Weiterlesen

BackgroundPsoriasis is an immune-mediated chronic inflammatory condition characterized by significant neutrophil infiltration in the skin. Given that the spleen is the largest peripheral immune organ in the body, it is important to investigate whether it has any impact on skin inflammation in psoriasis.MethodsTo investigate this mechanism, a psoriatic mouse model was established by IMQ application. Flow cytometry and immunohistochemistry analyses were performed to determine the percentage of various immune cells in the spleen. The role of neutrophils was specifically assessed using the anti-Gr-1 antibody. Splenic granulopoiesis was evaluated using EdU labeling. To understand the spleen's role in skin inflammation, splenectomy was performed on the experimental mice. IL-6 levels were measured by ELISA, and P-STAT3 in neutrophils was detected via immunofluorescence. Further examination of IL-6's effects on neutrophil formation involved treating mice with IL-6 antibody. The severity of psoriasis was evaluated through histological staining and PASI scoring.ResultsOur study revealed that the spleens of psoriatic mice were enlarged compared to those of vehicle mice. Among immune cell populations, neutrophils showed the most significant changes, with marked increases in both spleen and skin of psoriatic mice and patients, contributing to disease progression. Post-splenectomy, neutrophil infiltration in the skin was reduced by approximately 60% in psoriatic mice. This indicates that the neutrophils in the skin were primarily derived from the spleen. Additionally, the spleen showed a notable capacity for granulopoiesis with elevated neutrophils. Moreover, we found elevated IL-6 levels in the skin, blood, and spleen in the model, which was decreased after splenectomy. Treatment with an IL-6 antibody reduced neutrophil formation in both the spleen and skin, which alleviated skin inflammation in psoriatic mice. Additionally, P-STAT3 signaling was decreased following IL-6 antibody treatment. The neutrophil infiltration in spleen and skin was decreased after injection with the inhibitor of P-STAT3, which also alleviated the inflammation of psoriatic model. Thus, IL-6 served as the dominant regulator of spleen granulopoiesis, a process potentially mediated by P-STAT3 signaling.ConclusionsThe spleen plays a crucial role in the immune microenvironment of psoriasis as a major site of granulopoiesis, influencing neutrophil infiltration in the skin of psoriatic mice. Additionally, IL-6 is a key regulator of neutrophil formation in the spleen of psoriatic mice, likely through P-STAT3-dependent mechanisms.Weiterlesen

Psoriasis is an autoimmune skin disease associated with increased incidence and severity of chronic kidney disease and hypertension. The mechanisms linking psoriasis skin inflammation with these comorbidities remain unclear. We used flow cytometry, radiotelemetric blood pressure measurements, and histological and ELISA-based assessments of renal damage in mice with experimental psoriasis induced by keratinocyte-specific overexpression of Tie2 (KC-Tie2) and their littermate controls. Compared with littermate controls, KC-Tie2 mice with chronic skin inflammation developed albuminuria, histological evidence of glomerulosclerosis, and elevated blood pressure. KC-Tie2 mice had a selective and marked increase in circulating and renal neutrophils, along with increased neutrophil extracellular trap formation in the kidneys by flow cytometry. KC-Tie2 mice also exhibited increased bone marrow granulopoiesis along with increases in cutaneous and systemic G-CSF (granulocyte colony-stimulating factor), the primary mediator of granulopoiesis. Finally, neutralization of G-CSF decreased renal neutrophils and kidney damage in KC-Tie2 mice. Our findings demonstrate G-CSF-dependent increases in renal neutrophil accumulation and renal damage in a mouse model of psoriasis. Results suggest a novel link between chronic psoriasiform skin inflammation and renal damage via G-CSF-mediated granulopoiesis, providing new insight into interorgan communication in psoriasis and a potential new therapeutic target for the treatment of psoriasis-related renal dysfunction.Weiterlesen

Menschen mit Psoriasis haben oft auch andere Krankheiten wie Herzprobleme oder Übergewicht. Neue Forschung zeigt: Wer zusätzlich mit GLP-1-Rezeptor-Agonisten (zum Beispiel Semaglutid) behandelt wird, hat ein deutlich geringeres Risiko, an Herz-Kreislauf-Erkrankungen oder psychiatrischen Problemen zu erkranken und sogar ein geringeres Sterberisiko. Das Medikament gilt als sicher, besonders für Menschen mit Psoriasis und gleichzeitigem Übergewicht oder Diabetes. Ärztinnen und Ärzte könnten diese Medikamente deswegen bei passender Vorgeschichte in Erwägung ziehen[1][2][5]. Originaltitel: GLP-1RA and reduced mortality, cardiovascular and psychiatric risks in psoriasis: a large-scale cohort study. Link zur Quelle

Eine neue Methode mit Fluoreszenz-Bildgebung (FOI) kann helfen, zu unterscheiden, ob jemand Psoriasis-Arthritis oder eine erosive Handarthrose hat[2]. Bei FOI bekommt man nach einer Farbstoff-Injektion Bilder, die zeigen, wie stark die Gelenke entzündet sind. In der Studie hatten Menschen mit Handarthrose vor allem an den Mittel- und Endgelenken (PIP und DIP) eine stärkere Entzündung als Menschen mit Psoriasis-Arthritis. Umgekehrt kam ein spezielles Muster, der sogenannte „Werner sign“, deutlich häufiger bei Psoriasis-Arthritis vor. Das macht die Diagnose genauer und hilft dabei, die passende Behandlung zu finden[2]. Originaltitel: Differential diagnosis between psoriatic arthritis and hand osteoarthritis using indocyanine green-based fluorescence optical imaging. Link zur Quelle

Menschen mit generalisierter pustulöser Psoriasis (GPP) bekommen nach der Diagnose meist **kortisonhaltige Cremes** verschrieben, danach oft auch **Kortison-Tabletten**[3]. Bei Patienten mit GPP und normaler Psoriasis gab es häufiger **Biologika** als bei denen mit nur GPP[3]. Das liegt daran, dass es damals keine zugelassenen speziellen Therapien für GPP gab[3]. Problematisch ist, dass ein **Absetzen von Kortison** oft zu einem neuen Krankheitsschub führt[3]. Die Behandlung wurde oft gewechselt, weil viele Medikamente nicht langfristig helfen und immer noch ein großer **Bedarf an besseren Therapien** besteht[1]. Originaltitel: Real-world treatment patterns in patients with generalized pustular psoriasis (GPP). Link zur Quelle

Bei der GRAPPA-Tagung 2024 haben Dermatologen und Rheumatologen lebhaft darüber gestritten, wer bei Muskelschmerzen und Gelenkbeschwerden bei Menschen mit Schuppenflechte das Sagen haben soll. Rheumatologen wie Dr. Proft meinen, sie sollten die Behandlung steuern, weil sie Entzündungen mit speziellen Untersuchungen erkennen können. Dermatologen wie Dr. Savage sehen sich aber oft als die ersten Ansprechpartner und wissen, wie wichtig es ist, Frühzeichen zu erkennen und früh zu behandeln. Beide Seiten sind sich einig: Am besten arbeiten beide Fachrichtungen zusammen, damit Haut und Gelenke optimal behandelt werden[2][4]. Originaltitel: Managing Musculoskeletal Symptoms in Patients With Psoriasis: Who Should Be in the Driver's Seat? Link zur Quelle

Mit Fluoreszenz-Optischer Bildgebung (FOI) kann man verschiedene rheumatische Erkrankungen an den Händen schnell und genau voneinander unterscheiden. Forschende haben typische Muster gefunden, zum Beispiel für entzündete Gelenke, Haut oder Nägel. Ein Atlas dieser FOI-Merkmale hilft, Krankheiten wie Rheumatoide Arthritis, Psoriasis-Arthritis, Kollagenosen oder Arthrose zu erkennen. Besonders Arthrose lässt sich sehr sicher von den anderen Krankheiten abgrenzen, bei Autoimmun-Erkrankungen gibt es verschiedene Merkmale. FOI kann so die Diagnose beschleunigen und als Ergänzung zu anderen Bildgebungsverfahren genutzt werden[1][2][3]. Originaltitel: To optimise the diagnostic process of rheumatic diseases affecting the hands using fluorescence optical imaging (FOI). Link zur Quelle

Bei Menschen mit schwerer, pustulöser Psoriasis steigt während eines Schubs der Spiegel des Botenstoffs **microRNA-223** an[3]. Die Behandlung mit dem Medikament **Spesolimab** kann diesen Anstieg gezielt steuern[1]. Das hilft, die Entzündungen im Körper besser zu kontrollieren. Spesolimab ist extra für solche Schübe entwickelt und kann das Risiko für neue Schübe um 84 Prozent senken[2]. Damit gibt es für Betroffene eine wichtige neue Behandlungsmöglichkeit. Originaltitel: MicroRNA-223 expression during flares in patients with generalized pustular psoriasis is regulated by spesolimab treatment. Link zur Quelle

Hidradenitis suppurativa (HS) ist eine chronische Hautkrankheit, die oft mit entzündeten Knoten und Abszessen an Stellen wie Achseln oder Leisten beginnt[1][5]. Der genaue Grund für die Entstehung ist noch nicht vollständig bekannt, aber Forscher vermuten, dass eine gestörte Immunabwehr, die Zusammensetzung der Hautbakterien und die Gene eine Rolle spielen[5][3]. Faktoren wie Übergewicht, Rauchen und Diabetes können das Risiko erhöhen[1][5]. HS kann den Alltag stark belasten und führt oft zu psychischen Problemen[1]. Die Behandlung ist kompliziert, da viele Methoden kombiniert werden müssen, zum Beispiel Medikamente, Operationen und Änderungen des Lebensstils[1][5]. Neue Medikamente geben Hoffnung auf besseres Ansprechen in Zukunft[5]. Originaltitel: Hidradenitis suppurativa: complexity in pathogenesis and management - Authors' reply. Link zur Quelle

Bimekizumab hilft vielen Menschen mit *Psoriasis*, nicht nur die Haut, sondern auch die Nägel komplett von Schuppenflechte zu befreien. Die Auswertung von mehreren Studien zeigt, dass mit Bimekizumab deutlich mehr Patientinnen und Patienten eine vollständige Heilung von Haut und Nägeln erreichen als mit den Vergleichsmedikamenten Adalimumab, Ustekinumab oder Secukinumab. Je nach Studie schafften bis zu 63% mit Bimekizumab den Maximalwert, während die anderen Mittel oft unter 40% lagen. Das Ergebnis blieb sogar langfristig stabil, egal ob Betroffene dauerhaft Bimekizumab bekamen oder erst später darauf umstiegen[1][3][4]. Originaltitel: Bimekizumab Complete Clearance of Both Skin and Nail Psoriasis: Comparative Efficacy in Phase III/IIIb Studies. Link zur Quelle

Upadacitinib ist ein Mittel gegen Rheuma, Psoriasis-Arthritis und ähnliche Krankheiten. Forschende haben die Sicherheit bei über 8.600 Patientinnen und Patienten über fast 30.000 Behandlungsjahre untersucht. Häufige Nebenwirkungen sind Erkältungen, COVID-19, Gürtelrose, Harnwegsinfekte und Akne[2]. Schwerwiegende Nebenwirkungen wie Infektionen, Herzprobleme oder Blutgerinnsel kommen selten vor und sind meist stabil geblieben. Im Vergleich zu anderen Medikamenten treten einige Nebenwirkungen wie Gürtelrose und Hautkrebs etwas öfter auf[2]. Insgesamt bestätigen die Studien, dass Upadacitinib auch über längere Zeit genutzt werden kann[2]. Originaltitel: Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease. Link zur Quelle

Secukinumab hilft Kindern und Jugendlichen mit mittelschwerer bis schwerer Plaque-Psoriasis langfristig gut. Fast 80 Prozent der Teilnehmenden hielten vier Jahre durch und erzielten dauerhaft deutliche Verbesserungen der Haut. Bei beiden Dosierungen blieb die Haut meist zu mindestens 75 Prozent klar, oft sogar noch besser. Die Lebensqualität stieg und auch die Sicherheit war über vier Jahre hinweg unauffällig. Schwerwiegende Nebenwirkungen traten selten und ähnlich häufig auf, unabhängig von der Dosis. Wachstum und Entwicklung wurden durch die Behandlung nicht beeinflusst[1]. Originaltitel: Long-Term Efficacy and Safety of Secukinumab in Children and Adolescents with Moderate-to-Severe Chronic Plaque Psoriasis: Four-Year Results of a Randomized, Phase III, Open-Label Trial. Link zur Quelle

Bei Psoriasis läuft der Fettstoffwechsel in der Haut oft aus dem Ruder: Ein Enzym namens FADS2 spielt dabei eine Schlüsselrolle. Bei Betroffenen ist FADS2 in der Haut weniger aktiv, das fördert Entzündungen durch mehr NF-κB-Signale und lockt Entzündungszellen an[2]. Das Problem: FADS2 macht aus bestimmten Fetten entzündungshemmende Stoffe wie DHA. Fehlendes FADS2 heißt weniger DHA, also mehr Entzündung. Ein Schalter für FADS2 ist PPARα. Wird PPARα aktiviert, wird FADS2 hochgefahren und die Entzündung gebremst. Neue Therapien könnten sich diesen Mechanismus zunutze machen[2][5]. Originaltitel: Reprogramming of Fatty Acid Metabolism via PPARα-Orchestrated FADS2 in Keratinocytes Modulates Skin Inflammation in Psoriasis. Link zur Quelle

Psoriasis is one of the most common chronic inflammatory skin diseases and is characterised by the uncontrolled proliferation of keratinocytes and their abnormal differentiation. Sirtuins are a group of enzymes that play an important role in post-translational modifications of proteins, such as deacetylation, poly-ADP-ribosylation, demalonylation and lipoamidation. They are found in various cell types and are involved in ribosomal DNA recombination, gene silencing and DNA repair. This study aimed to examine the plasma levels of sirtuin 3, 4 and 5 in patients with psoriasis and correlate these levels with clinical parameters. The study included 43 patients with plaque-type psoriasis and 28 healthy controls. The plasma concentrations of sirtuin 3 were statistically significantly increased in patients with psoriasis compared to the control subjects. The plasma concentrations of sirtuin 4 and 5 were statistically significantly lower in patients with psoriasis than in the control group. No statistically significant correlations were found between the plasma levels of sirtuin 3 and 4 and the psoriasis activity tools of PASI, DLQI and the BSA index or the selected clinical parameters in patients with psoriasis. Plasma concentrations of sirtuin 5 correlated statistically significantly with the BSA index, haemoglobin and leukocytes. The results of this study suggest the involvement of sirtuin 3, 4 and 5 in the pathogenesis of psoriasis. However, an explanation of the role of sirtuins in psoriasis requires further research.Weiterlesen

It is challenging to distinguish nail psoriasis (NP) from nonspecific nail changes, contributing to heterogeneity in clinical trials. Existing scoring tools for NP are currently used to assess severity after diagnosis is established. The aim of this study is to evaluate the diagnostic performance of two of these severity scoring tools. A cohort study was conducted with psoriasis patients and matched controls. Fingernails were scored using the Nail Psoriasis Severity Index (NAPSI) and the Nijmegen-Nail Psoriasis Activity Index Tool (N-NAIL). To determine their diagnostic properties, cutoff values were established. Receiver operating characteristic (ROC) curves were constructed, and sensitivity and specificity were calculated for various cutoff points. The best cutoff value was chosen based on the Youden Index and clinical reasoning. In total, 104 psoriasis patients were included, of which 68 were clinically diagnosed with NP. For the N-NAIL, a cutoff value of 2 showed the best accuracy in the psoriasis population (sensitivity = 83.8% and specificity = 83.3%) and the general population (sensitivity = 83.8% and specificity = 67.3%). For the NAPSI, a cutoff value of 7 showed the best accuracy in the psoriasis population (sensitivity = 80.9% and specificity = 69.4%), while a cutoff value of 10 was optimal in the general population (sensitivity = 72.1% and specificity = 70.2%). Both N-NAIL and NAPSI provide accurate cutoff values in a psoriasis population. Therefore, these scoring tools may not only be used to assess severity but also in clinical trials for the inclusion of NP patients in a psoriasis population to create homogeneity between studies. We prefer using the N-NAIL, with a cutoff value of 2, because it showed better accuracy compared to the NAPSI.Weiterlesen

Psoriasis is an immune-mediated chronic inflammatory skin disease affecting over 60 million adults and children worldwide and can occur at any age, from childhood to adulthood. If the patient has a diffuse form of psoriasis, affecting more than ten percent of the body surface, or involving sensitive areas such as the face, scalp, nails, and/or palmoplantar region, he or she is a candidate for systemic therapy. Currently, several drugs are approved for the treatment of moderate to severe chronic plaque psoriasis in Europe and US. These are classified into conventional systemics, biologics, and small molecules. These immunomodulatory agents are available in different forms of administration, such as oral, subcutaneous, and intravenous. Novel treatments, including biologics and small molecules, can provide reliable disease control with a good safety profile even in the long term and have greatly improved the quality of life for many patients. Nevertheless, biologics can be expensive, placing a significant burden on national healthcare systems and creating a barrier to access for patients in need of these life-changing therapies. A biosimilar drug is a biologic medical product that is highly similar to an already approved reference biologic drug (also known as the originator). Biosimilars have no clinically meaningful differences in terms of safety, purity, and efficacy compared to the reference product. Biosimilar drugs have been on the market-and therefore in clinical practice-for several years now, helping to overcome these challenges. Biosimilars have the potential to improve access to biologic therapies for psoriasis while reducing healthcare costs. The aim of this narrative review is to describe biosimilars and the potential cost-saving benefits their use can offer. In this review, we will discuss adalimumab, infliximab, etanercept, and ustekinumab, as well as their corresponding biosimilars.Weiterlesen

Erythrodermic psoriasis is a rare subtype of psoriasis with widespread skin lesions, with some patients experiencing severe systemic symptoms. We aimed to develop and validate an artificial intelligence-driven model for accurate classification of erythrodermic psoriasis severity by integrating clinical and laboratory indicators. A retrospective cohort study was conducted at Peking Union Medical College Hospital (2005-22). Patients were divided into mild and moderate-to-severe groups using k-means clustering. After imputing missing values, we trained seven candidate algorithms-K-Nearest Neighbors, Artificial Neural Network, Random Forest, Extreme Gradient Boosting, Support Vector Machine, Bayesian classifier, and logistic regression-using repeated, stratified ten-fold cross-validation with three repeats (10 × 3 CV); performance was summarized by the mean area under the receiver operating characteristic curve across folds. Feature importance was assessed using SHAP (Shapley Additive exPlanations), a game-theoretic approach that quantifies each features contribution to individual model predictions, ten indicators were incorporated into a diagnostic scoring system. The optimal cut-off for mild/moderate-to-severe cases classification was selected with the Youden index on the cross-validated receiver operating characteristic curve. Of 260 screened records, 242 erythrodermic patients met the study criteria. Histology confirmed psoriasis in 108 cases, while the remaining patients were diagnosed based on clinical presentation and medical history. K-means clustering assigned 94 patients to the moderate-to-severe group and 148 to the mild group. Moderate-to-severe erythrodermic psoriasis was characterized by a higher inflammatory burden (median neutrophil-to-lymphocyte ratio 4.11 vs 2.70, p < 0.001), more frequent fever (88% vs 41%, p < 0.001), greater edema severity (16% vs 1.4%, p < 0.001), lower albumin and higher calcium levels (both p < 0.001), and longer hospitalization (median 26 vs 20 days, p = 0.005). After adjustment for age and sex, moderate-to-severe cases required systemic therapy roughly twice as often as mild cases (odds ratio 2.21, p < 0.05). Of seven machine-learning algorithms, the Artificial Neural Network yielded the highest mean validation area under the curve. The SHAP analysis highlighted the ten most influential predictors adopted from the Artificial Neural Network-edema, edematous erythema (defined as the combination of both redness and swelling of the skin), fever, albumin, neutrophil-to-lymphocyte ratio, serum calcium, white blood cell count, acute-phase reactants (C-reactive protein or erythrocyte sedimentation rate), pruritus, and superficial lymphadenopathy-and these were converted to integer points to form the bedside score. The receiver operating characteristic analysis identified 33.5 points as the optimal threshold for distinguishing between mild and moderate-to-severe cases. The model, named 'EPICS' (Erythrodermic Psoriasis Integrated Classification System), effectively stratified patients, as evidenced by internal validation. This model is currently available online ( https://pumch-dermatology.shinyapps.io/classification/ ). The EPICS model is a robust tool for assessing erythrodermic psoriasis severity, offering precise classification based on easily accessible clinical and laboratory indicators. However, its effectiveness in clinical practice requires further validation through additional research.Weiterlesen

Psoriasis is an immune-mediated dermatosis characterized by systemic inflammation and multifactorial pathogenesis. Among its many triggers, psychological stress has emerged as a pivotal yet underappreciated contributor to disease onset and exacerbation. Although the pathomechanisms by which psychological stress is involved in the pathogenesis of psoriasis are not clear, evidence suggests a regulatory role of psychologic stress in immune functions, including increasing expression levels of proinflammatory cytokines and intracellular adhesion molecule-1 (ICAM-1), and decreasing anti-inflammatory cytokines and the function of glucocorticoid receptors, possibly in part via activation of corticotropin-releasing hormone (CRH)-proopiomelanocortin (POMC)-adrenocorticotropic hormone (ACTH)-corticosteroids axis. In addition, the onset and/or worsening of psoriasis can also be attributed to psychological stress-induced defective epidermal permeability barrier function. Moreover, the bidirectional nature of this relationship often leads to a vicious cycle of flare-ups and psychological distress, further complicating patient management and quality of life. This review aims to synthesize current evidence on the relationship between stress and psoriasis, examining mechanistic pathways through which psychosocial stress contributes to immune dysregulation in psoriatic pathology. It also underscores the significance of psychological interventions in the management of psoriasis.Weiterlesen