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BackgroundPsoriasis is a chronic inflammatory disease associated with multiple comorbidities, including metabolic syndrome and cardiovascular disease. Although specific dietary interventions, such as intermittent fasting and caloric restriction, have been shown to ameliorate inflammation and promote weight loss, the effect of these interventions independent of weight loss remains unclear. Time-restricted eating (TRE), a type of intermittent fasting, limits the daily eating window to a fixed number of hours. Recent studies suggest TRE may improve immune function in individuals with metabolic syndrome and cardiovascular risk factors. A crucial advantage of TRE over other investigated dietary restriction strategies is its reported high adherence rate, making it a more feasible intervention for long-term use. Therefore, exploring the effects of TRE on metabolic and immunological parameters in psoriasis is warranted.ObjectiveThis study was designed to evaluate the effects of short-term, isocaloric TRE, independent of weight loss, on immune cell function and serum metabolite profiles of volunteers with mild-to-moderate psoriasis compared to healthy individuals.MethodsThis case-control, prospective study was performed on 10 healthy male participants and 10 age-, BMI-, and sex-matched individuals with mild-to-moderate psoriasis. All individuals with psoriasis had stable disease and were being treated with topical therapies without any exposure to immunomodulatory biologics. This study was conducted at the National Institutes of Health Clinical Center. Immune profiles, glucose handling, energy expenditure, and participants' weights were assessed at baseline and after 3 days of TRE following a daily 6-hour eating window and 18-hour fast.ResultsThe trial commenced in June 2021 and was completed in February 2023. A total of 20 participants were enrolled-10 with mild-to-moderate psoriasis and 10 age-, BMI-, and sex-matched healthy individuals. As of the time of manuscript submission, data processing is ongoing. Multiomic datasets, including gene expression, surface and intracellular protein levels, and metabolite profiles, are being generated from peripheral blood mononuclear cells, CD4+-enriched T-cells, and serum samples. The integrated bioinformatics analyses will be reported once the data analysis is completed.ConclusionsThis clinical protocol was designed to characterize the effects of short term (3-day) TRE on psoriasis, independent of weight loss, by comparing immune cell regulatory responses between healthy individuals and those with psoriasis. More specifically, we aim to map the molecular pathways activated by TRE and assess how they affect immune cell composition, activation, and metabolism. Additionally, components of the metabolic response to isocaloric TRE are being explored. Insights into how dietary interventions impact metabolism and the immune system will enhance our understanding of the pathogenesis of psoriasis and may reveal new therapeutic avenues for managing this inflammatory condition.Trial registrationClinicalTrials.gov NCT04728165; https://clinicaltrials.gov/study/NCT04728165.Weiterlesen

BackgroundPsoriasis is a persistent inflammatory skin condition. Several studies have revealed that obesity significantly contributes to both the initiation and advancement of psoriasis. The metabolic score for visceral fat (METS-VF) represents an innovative measure designed to forecast visceral obesity, integrating factors such as insulin resistance metabolic score, waist-to-hip ratio (WHR), age, and gender. The present study aimed to investigate the association between METS-VF and psoriasis prevalence, using information gathered from the National Health and Nutrition Examination Survey (NHANES).MethodsThis study utilized the data from a nationally representative cohort of 8023 adults from NHANES from 2003-2006 to 2009-2014, of which 234 declared a psoriasis history. Multivariate logistic regression analysis and restricted cubic spline (RCS) analyses were used to investigate the association between METS-VF and psoriasis, followed by subgroup analysis to identify populations that may exhibit higher sensitivity.ResultsAfter adjusting for confounding variables, the results of the multivariate logistic regression analysis showed a significant positive association between METS-VF and the risk of psoriasis. One-unit increasement in METS-VF corresponded to a 47% rise in psoriasis risk (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.96). Finally, the results were uniform across all subgroups (P for interaction > 0.05). The results from the RCS analysis indicated a notable linear association.ConclusionThis research indicated that elevated levels of METS-VF are linked to a higher occurrence of psoriasis, suggesting the potential of METS-VF as a predictive anthropometric index for assessing the risk of developing psoriasis.Weiterlesen

Ixekizumab is a monoclonal antibody used in the treatment of moderate-to-severe psoriasis and psoriatic arthritis by targeting interleukin-17 A (IL-17 A). It has demonstrated efficacy in controlling inflammation in autoimmune diseases, though adverse reactions can arise. This case study reports a case of 25-year-old female with psoriatic arthritis undergoing treatment with ixekizumab, who developed acute enlargement and inflammation of a pre-existing sebaceous cyst located posterior to the left auricle, occurring two days after the administration of a routine ixekizumab dose. The present study investigates the potential association between the inflammatory process observed within the cyst and the immunomodulatory mechanisms of ixekizumab. Literature review revealed no prior reports directly linking ixekizumab with sebaceous cyst inflammation. However, related adverse effects, including paradoxical inflammation, infectious complications, and immune dysregulation have been described in patients treated with IL-17 A inhibitors. These include IBD exacerbation, eczematous eruptions, paradoxical psoriasis, and rare systemic complications, suggesting broader immunological effects of IL-17 blockade.Weiterlesen

Psoriasis is a chronic inflammatory skin disease driven by immune dysregulation and often exacerbated by metabolic comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for type 2 diabetes mellitus (T2DM) and weight management, have emerged as a promising treatment due to their anti-inflammatory and immunomodulatory properties. This review evaluates the clinical efficacy, mechanisms of action, and limitations of GLP-1RAs, such as liraglutide, exenatide, and semaglutide, in the management of psoriasis. A comprehensive literature review was conducted, including evidence from case reports, randomized controlled trials, prospective cohorts, and experimental studies, to assess the role of GLP-1RAs in psoriasis treatment. Evidence suggests that GLP-1RAs mitigate psoriasis severity through systemic effects, including weight loss and improved glycemic control, and local immunomodulation, such as the regulation of invariant natural killer T (iNKT) cells and AMPK activation in psoriatic plaques. These benefits are particularly notable in patients with coexisting metabolic conditions. However, the existing evidence is limited by small cohort sizes, heterogeneous patient populations, and confounding effects of concurrent therapies, limiting its generalizability. GLP-1RAs offer a novel integrative approach to managing psoriasis by targeting both inflammatory and metabolic pathways. Larger, long-term randomized controlled trials are needed to validate their efficacy, optimize dosing, and determine their role as standalone or adjunctive therapies, particularly in patients without metabolic comorbidities.Weiterlesen

BackgroundThere are only limited histomorphological data on the response of psoriatic skin lesions to topical dithranol. In vivo reflectance confocal microscopy (RCM) in psoriatic skin is highly correlated with histopathological findings and allows non-invasive monitoring of treatment effects on a cellular level.Patients and methodsProspective, single-center pilot study at a university-based clinic of dermatology between January 1st and August 30th, 2016. Psoriatic lesions of 20 patients receiving dithranol treatment were assessed by RCM at baseline, day 4 and 8 of treatment.ResultsRCM measurements of psoriatic lesions receiving dithranol treatment revealed epidermal histomorphological changes with a strong median reduction of baseline hyperkeratosis by 45.0% (p < 0.001), acanthosis by 38.2% (p < 0.001), and epidermal thickness by 66.5% (p < 0.001) from baseline until day 8. Moreover, semiquantitative measurements of parakeratosis also showed a significant reduction until day 8 (p < 0.001). Correspondingly, RCM revealed dermal histomorphological changes with a decrease in diameter of dermal papillae by 32.1% (p < 0.001), decrease in diameter of papillary vessels by 16.9% (p = 0.002) and a strong semiquantitative reduction of the inflammatory infiltrate (p < 0.001).ConclusionsResults from our pilot study indicate that topical dithranol treatment of psoriatic lesions may induce a rapid and marked reduction of pathologic epidermal and dermal RCM features.Weiterlesen

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BackgroundThe pathogenesis of nummular eczema (NE) remains unclear, and no targeted therapy has been approved. Apremilast is a small molecule inhibitor targeting phosphodiesterase-4.Patients and methodsA phase IIb randomized, double-blind, placebo-controlled study evaluating the effects of apremilast or placebo in patients with NE. Patients received apremilast (30 mg BID) or placebo until week 16 followed by an open label phase in which all patients were treated with apremilast until week 32. The primary endpoint was the number of patients achieving an improvement in Physician's Global Assessment (PGA) by two or more points or an absolute PGA of 0 or 1 at week 16. Secondary endpoints included changes in skin physiology, life quality, or dermato-pathology.Results33 patients were enrolled, of whom 31 were randomized to apremilast (n = 15) or placebo (n = 16). 1/15 (6.7%) patients in the apremilast group and 4/16 (25.0%) in the placebo group reached the primary endpoint (p = 0.369). There was no difference between placebo and apremilast with regard to all secondary endpoints at week 16 and week 32. The safety profile was in accordance with the known safety profile of apremilast.ConclusionPhosphodiesterase-4 inhibition by apremilast showed no beneficial effects for the treatment of NE.Weiterlesen

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Background/purposeWhile biologics and small-molecule inhibitors are first-line systemic treatments for psoriasis, phototherapy remains an alternative for patients unable to access these treatments because of medical or financial constraints. Narrow-band ultraviolet B (NB-UVB) is effective for localized psoriasis but less so for extensive disease. To address this limitation, bathwater delivery of psoralen plus ultraviolet A (bath-PUVA) was introduced in 2004. This study evaluates the efficacy, safety, and patient characteristics associated with bath-PUVA therapy in a large cohort.MethodsThis retrospective analysis included 229 patients (180 males, 49 females) treated with bath-PUVA from 2004 to September 2021. Baseline characteristics and treatment outcomes were assessed using the psoriasis area and severity index (PASI). Statistical analyses examined relationships between treatment outcomes and factors, including baseline PASI, body mass index (BMI), and smoking status.ResultsThe mean baseline PASI score was 24.9. Bath-PUVA achieved PASI 75 in 80.4% of patients, PASI 90 in 44.1%, and PASI 100 in 2.6%, with efficacy comparable to biologics. Patients achieving PASI 90 had significantly higher baseline PASI scores (p = 0.005), while the number of irradiations required did not differ (p = 0.692). Higher baseline PASI scores correlated with elevated BMI (p = 0.002), but BMI did not influence improvement rates (p = 0.094). Smokers had significantly higher baseline PASI scores (p = 0.004) compared with non-smokers, yet smoking status did not affect improvement rates (p = 0.862).ConclusionBath-PUVA demonstrates efficacy comparable with biologics for psoriasis, regardless of BMI or smoking status. This analysis supports its use as an effective and accessible treatment option for patients with extensive disease.Weiterlesen

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Psoriasis is a common chronic inflammatory skin disease that significantly affects patients'quality of life. There is no cure for psoriasis, and available treatments are not completely effective. We have previously found that hydroxytyrosol (HT) has anti-psoriatic effects in vitro. In the present study, we aimed to investigate the therapeutic effects of HT on psoriasis in vivo and to explore the underlying mechanisms. We explored the effects and molecular mechanisms of HT on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice and an M5-induced in vitro cell model using real-time PCR, western blotting, hematoxylin-eosin staining, immunohistochemistry, and enzyme-linked immunosorbent assay. HT (10 mg/kg/d or 50 mg/kg/d, by gavage) ameliorated IMQ-induced clinical manifestations in mice. Moreover, HT ameliorated the histopathological changes and decreased the spleen index and levels of pro-inflammatory cytokines, such as interleukin (IL)-17 A, IL-23, and IL-22, in mouse serum or skin. Mechanistically, HT application inhibited the activation of ERK and NF-кB signaling in the skin samples. Consistently, in vitro analysis showed that HT significantly inhibited inflammation via ERK and NF-κB signaling in a cellular model of psoriasis. Our results indicate that HT alleviates IMQ-induced psoriasis-like dermatitis by inhibiting the ERK and NF-κB signaling pathways, suggesting that HT has a promising therapeutic application in psoriasis treatment.Weiterlesen

BackgroundGenetic susceptibility to psoriasis involves multiple loci, including TYK2 (Tyrosine Kinase 2), which is associated with various autoimmune diseases. However, its specific role and mechanisms in psoriasis remain unclear. This study aimed to identify psoriasis-associated proteins using Summary-based Mendelian Randomization (SMR) and to explore their regulatory mechanisms.MethodsSMR analysis integrating pQTL data was conducted to identify proteins linked to psoriasis, revealing ICAM1 (Intercellular Adhesion Molecule 1) as a potential pathogenic factor. A key SNP, rs34536443 (P1104A), located in TYK2, was found to regulate ICAM1. To assess its function, THP-1 cells carrying the TYK2-P1104A mutation were generated, and ICAM1 and cytokine expression were analyzed following LPS stimulation. The effect of the TYK2 inhibitor Deucravacitinib was tested in an imiquimod (IMQ)-induced psoriasis mouse model.ResultsSMR identified ICAM1 as a causal protein for psoriasis, regulated by the TYK2 SNP rs34536443. In TYK2-P1104A mutant THP-1 cells, LPS-induced ICAM1 expression was significantly reduced, with ICAM5 unaffected. The mutation also suppressed IL-1β, TNF-α, IL-6, and IL-18 expression, suggesting anti-inflammatory effects. Single-cell RNA-seq revealed enrichment of TYK2, ICAM1, and ICAM5 in dendritic cells and monocytes. In vivo, Deucravacitinib significantly downregulated ICAM1 in the IMQ-induced psoriasis model, with minimal effect on ICAM5.ConclusionThis study identifies ICAM1 as a key mediator in psoriasis via SMR analysis and implicates the TYK2 SNP rs34536443 in its regulation. The TYK2-P1104A variant attenuates ICAM1 and cytokine expression, and Deucravacitinib downregulates ICAM1 in vivo. These findings provide mechanistic insights into the TYK2-ICAM1 axis and support the therapeutic potential of TYK2 inhibitors for psoriasis.Weiterlesen

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Psoriasis and psoriatic arthritis are chronic autoimmune diseases characterized by dysregulated immune responses, particularly involving Th17 cells. Immune checkpoint molecules such as programmed death-1 (PD-1) and its ligands (PD-L1/PD-L2) are critical for maintaining immune tolerance. Disruptions in these pathways contribute to psoriatic disease pathogenesis. Notably, immune checkpoint inhibitors used in cancer therapy have been linked to the development of psoriasis or its exacerbation. This highlights the complex role of checkpoint pathways in psoriatic diseases. Thus, immune checkpoint agonists could be a therapeutic strategy aimed at restoring immune balance without widespread immunosuppression. Preclinical studies demonstrate that PD-1 agonists can mitigate inflammation by enhancing inhibitory signaling. Additionally, early-phase clinical trials in autoimmune diseases such as rheumatoid arthritis and ulcerative colitis suggest potential benefits of PD-1 modulation in psoriasis. This review explores immune checkpoint agonists in psoriatic disease as a promising alternative to conventional immunosuppressants by selectively suppressing pathogenic T-cell activity.Weiterlesen

ObjectivesThrough this meta-analysis, we aim to provide an overview and statistical synthesis of the prevalence of MetS and its components in psoriatic arthritis (PsA) compared to the general populations, patients with cutaneous psoriasis (PsO), and patients with other inflammatory arthropathies.MethodA search was conducted in Ovid Medline, Web of Science, and Scopus up to February 2024. Original articles investigating the prevalence of MetS in PsA in adults compared to one or more comparison populations were included. Bias risk was assessed by means of a funnel plot. The data was analyzed by means of a random effects model and presented in forest plots.ResultsOf 1526 articles in the original search, 20 relevant were identified. Meta-analyses showed an increased prevalence of MetS in PsA compared to the general population, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) (LogOR 0.93, 0.63, and 1.04, respectively). Meta-analysis showed no difference in the prevalence of MetS in PsA compared to PsO (LogOR 0.15, I2 0.63). Meta-analysis of the prevalence of the different components of MetS in PsA compared to RA showed an increased prevalence of central obesity, hypertriglyceridemia, impaired glucose tolerance, and diabetes mellitus.ConclusionsPsA was associated with an increased risk of MetS compared to the risk in the general population, in RA and in AS, respectively. This emphasizes the importance of screening for and taking necessary measures to prevent MetS in patients with PsA. Key Points • Patients with PsA have an increased risk of MetS compared to the general population as well as patients with RA or AS. • According to this meta-analysis, the risk of MetS is the same in patients with PsA as in patients with PsO.Weiterlesen

Abstract Psoriasis is a chronic skin condition characterized by the rapid growth of skin cells, leading to the formation of thick, scaly patches. Detecting these lesions accurately is crucial for early diagnosis and effective treatment. However, the variability in lesion size, shape, and appearance across different skin types presents significant challenges for automated detection systems. Traditional methods often struggle with these variations, leading to reduced accuracy and efficiency. In recent years, convolutional neural networks (CNNs) have emerged as a powerful tool for medical image analysis, particularly in the detection of skin conditions. This paper introduces a novel approach for psoriasis lesion detection using convolutional neural networks (CNNs). The challenge of accurately identifying lesions across various skin types and lesion sizes is addressed by leveraging a scale-aware strategy. In this method, a CNN first estimates the scale distribution of psoriasis lesions within an image by predicting a scale histogram. This histogram serves as a guide for image scaling operations, ensuring that lesions are brought to a uniform scale for subsequent detection. By applying zoom-in and zoom-out transformations based on the predicted scale histogram, the model reduces computational overhead while maintaining high detection accuracy. The proposed approach demonstrates improved efficiency and accuracy in identifying psoriasis lesions, as compared to traditional multi-scale testing techniques, with reduced computational demands. Extensive qualitative and quantitative evaluations on various skin datasets show that the scale-aware strategy significantly enhances lesion detection performance, making it a promising tool for automated psoriasis diagnosis. Weiterlesen

In dieser Studie wird untersucht, wie wirksam, sicher und verträglich **TAK-279** (auch bekannt als Zasocitinib) bei Erwachsenen mit mittelschwerer bis schwerer Plaque-Psoriasis ist. Die Teilnehmenden werden zufällig einer von drei Gruppen zugeordnet: Sie erhalten entweder TAK-279, das bereits zugelassene Medikament Apremilast (Otezla) oder ein Placebo. Ziel ist es, herauszufinden, ob TAK-279 die Hautsymptome (wie Rötung, Schuppung und Verdickung) besser reduziert als die Vergleichsmedikamente und wie gut es insgesamt vertragen wird. Die wichtigsten Messgrößen sind, wie viele Patient:innen nach 16 Wochen eine fast oder ganz erscheinungsfreie Haut erreichen und wie stark sich der Schweregrad der Psoriasis verbessert. **TAK-279** ist ein sogenannter **TYK2-Inhibitor** (Tyrosin-Kinase-2-Hemmer). Das bedeutet, dass die Substanz gezielt einen bestimmten Signalweg im Immunsystem blockiert, der bei der Entstehung von Entzündungen und Autoimmunerkrankungen wie Psoriasis eine Rolle spielt. Im Unterschied zu vielen bisherigen Therapien handelt es sich bei TAK-279 um eine Tablette, die täglich eingenommen wird. In früheren Studien zeigte sich, dass TAK-279 bei vielen Patient:innen zu einer deutlichen Besserung der Haut führte, ohne dass schwere Nebenwirkungen wie bei anderen Immunmodulatoren auftraten. Häufige Nebenwirkungen waren milde Beschwerden wie Durchfall oder Hautausschläge. Originaltitel: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo- and Active Comparator-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-279 in Subjects with Moderate-to-Severe Plaque Psoriasis Erkrankung: mittelschwere bis schwere Plaque-Psoriasis Phase: III Firma: Takeda Development Center Americas Inc. Art der Verabreichung: Tablette https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505841-22-00

In dieser Studie wird untersucht, wie wirksam, sicher und verträglich die Substanz TAK-279 bei Erwachsenen mit mittelschwerer bis schwerer Plaque-Psoriasis ist. Die Teilnehmer erhalten entweder TAK-279, ein Placebo oder Apremilast (ein bereits zugelassenes Medikament) und werden über einen Zeitraum von bis zu 69 Wochen behandelt. Ziel ist es herauszufinden, ob TAK-279 die Hautveränderungen (Plaques) besser reduziert als Placebo oder der aktive Vergleichspartner. TAK-279 ist ein sogenannter TYK2-Inhibitor – das heißt, er blockiert gezielt ein Enzym (Tyrosin-Kinase 2), das eine Rolle bei Entzündungsprozessen im Körper spielt. Durch diese Blockade sollen entzündliche Reaktionen unterdrückt werden, die für die Schuppenflechte typisch sind. Im Unterschied zu vielen anderen Therapien handelt es sich um eine Tablette zur oralen Einnahme – also keine Spritze oder äußerliche Anwendung. Die wichtigsten Ziele der Studie sind: Wie viele Patienten erreichen nach 16 Wochen eine fast oder komplett erscheinungsfreie Haut? Und wie viele schaffen eine Verbesserung um mindestens 75 % im sogenannten PASI-Wert (ein Maß für den Schweregrad der Psoriasis)? Auch weitere Verbesserungen wie PASI-90 und PASI-100 sowie Veränderungen an Nägeln und Kopfhaut werden betrachtet. Originaltitel: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo- and Active Comparator-Controlled Study With a Randomized Withdrawal and Retreatment Period to Evaluate the Efficacy, Safety, and Tolerability of TAK-279 in Subjects With Moderate-to-Severe Plaque Psoriasis Erkrankung: mittelschwere bis schwere Plaque-Psoriasis Phase: III Firma: Takeda Development Center Americas Inc. Art der Verabreichung: Tablette (oral) https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505842-24-00

Bei Menschen mit Psoriasis-Arthritis können bestimmte Botenstoffe, die Th17-Zellen fördern, die Funktion der schützenden Treg-Zellen stören. Das Immunsystem gerät aus dem Gleichgewicht: Die Treg-Zellen werden zwar in ihrer Erbsubstanz aktiviert, machen daraus aber keinen Nutzen und bremsen Entzündungen nicht besser. Wird das Treg-Umfeld künstlich entzündlich gemacht, verlieren die Treg-Zellen durch Veränderungen am FOXP3-Gen weiter an Kraft. Das deutet darauf hin, dass chronische Entzündung die Schutzmechanismen des Körpers schwächen kann[4]. Originaltitel: Influence of a Th17-Inducing Cytokine Milieu on Phenotypical and Functional Properties of Regulatory T Cells in Chronic Inflammatory Arthritis. Link zur Quelle