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Digitale Gesundheits-Apps können Menschen mit Psoriasis oder Psoriasis-Arthritis beim Umgang mit ihrer Erkrankung unterstützen[1]. Es gibt Apps, die Hautsymptome dokumentieren, wie Sorea oder Psoriasis Monitor, sowie Apps für Gelenkbeschwerden, zum Beispiel Mida Rheuma App oder Rheuma-Auszeit[1]. Lern-Apps wie PSO Kiosk und Therapie-Begleiter wie MyTherapy runden das Angebot ab[1][5]. Die Apps helfen, die Krankheit besser zu verstehen, am Ball zu bleiben und sich mental wohler zu fühlen. Keine App ist bisher als DiGA zugelassen, aber sie können im Alltag trotzdem nützlich sein[1]. Originaltitel: [Medical health apps for psoriasis and psoriatic arthritis]. Link zur Quelle

IntroductionPsoriasis (PsO) in the genital and scalp areas is associated with increased patient burden and impact on quality of life. Effective treatments for PsO in these high-impact areas are essential, though patients are frequently excluded from both biologic clinical trials and treatment because of their often low overall affected body surface area (BSA) despite the disproportionate impact of PsO on their quality of life. Recent guidance also considers these patients as candidates for advanced therapies. Here, we compare the efficacy and safety of risankizumab, an interleukin-23 inhibitor approved for the treatment of moderate-to-severe plaque psoriasis, versus placebo in the treatment of PsO in the genital or scalp region.MethodsUnlIMMited (NCT05969223) is an ongoing phase 4, multicenter, randomized, double-blind, placebo-controlled study for adult patients with moderate-to-severe genital or scalp PsO in patients with < 10% BSA or ≥ 10% BSA involvement. Two parallel studies were conducted with study-G assessing genital PsO and study-S assessing scalp PsO. Patients were randomized 1:1 within each study to receive either 150 mg risankizumab or placebo at weeks 0 and 4. The primary endpoints for the studies were the achievement of static Physician's Global Assessment - Genital (sPGA-G) 0/1 for study-G and scalp Investigator Global Assessment (IGA) 0/1 for study-S, both assessed at week 16. Secondary endpoints are also reported at week 16 in each study assessing skin clearance, symptom resolution, and impact on quality of life. Safety was reported through the first 16 weeks.ResultsAt week 16, in both studies, a significantly higher proportion of patients receiving risankizumab achieved the primary endpoints compared with placebo. In study-G, 69.1% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved sPGA-G 0/1 (P < 0.0001). In study-S, 60.8% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved scalp IGA 0/1 (P < 0.0001). No new safety signals were identified.ConclusionThese results demonstrate that risankizumab is effective in the treatment of genital and scalp psoriasis at week 16, with no new safety signals identified.Trial registration numberClinicalTrials.gov identifier NCT05969223.Weiterlesen

IntroductionMental health status potentially influences treatment responses. The effect of probable anxiety and/or depressive disorder (pADD) on tofacitinib efficacy, patient-reported outcomes (PROs), and safety in psoriatic arthritis (PsA) was assessed.MethodsThis was a post hoc analysis of two phase 3 trials in patients with PsA receiving tofacitinib, adalimumab, or placebo, and an open-label extension study. Outcomes were stratified by presence/absence of baseline pADD (Short Form-36 Health Survey [SF-36] Mental Component Summary score ≤ 38/ > 38). American College of Rheumatology ≥ 20%, ≥ 50%, and ≥ 70% (ACR20/50/70) responses, remission and/or low disease activity based on Psoriatic Arthritis Disease Activity Score and Disease Activity Index for Psoriatic Arthritis score, minimal disease activity, and PROs (pain/Health Assessment Questionnaire-Disability Index/fatigue) were assessed through month 36. Safety was assessed through month 12.ResultsOverall, 323/706 (45.8%) patients had baseline pADD; of these, a higher proportion were female versus male (61.9% vs. 38.1%). Numerically higher proportions achieved efficacy/PRO responses with tofacitinib versus placebo, regardless of baseline pADD (month 3). Responses with tofacitinib were generally similar in patients with versus without baseline pADD (e.g., month 3 ACR20 responses: 54.0% vs. 58.5%); some differences were observed at later time points (e.g., month 9 minimal disease activity: 25.0% vs. 43.8%; p < 0.05). Baseline pADD did not appear to affect the incidence of treatment-emergent adverse events.ConclusionsBaseline pADD was frequent in patients with PsA initiating tofacitinib and was higher in female patients. Tofacitinib-treated patients had generally similar efficacy/safety outcomes, regardless of baseline pADD. Some differences in efficacy outcomes were noted in the longer term (9-12 months). Limitations of this study include small numbers in some analyses and use of SF-36 as pADD proxy.Trial registrationClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.Weiterlesen

ObjectiveTo investigate the association between peripheral disease activity and pre-eclampsia, gestational hypertension, preterm birth and fetal growth in women with psoriatic arthritis (PsA).MethodsData from a Norwegian nationwide register (RevNatus) were linked with data from the Medical Birth Registry of Norway (MBRN). Cases were singleton births in women with PsA with available disease activity assessment (n=109) included in RevNatus 2010 to 2019. Singleton births registered in MBRN during the same decade served as population controls (n=575 798). Disease activity was assessed by Disease Activity Score based on 28 joints using C reactive protein (DAS28-CRP) in 2nd and 3rd trimester. Active PsA was defined as DAS28-CRP≥2.6 (n=34) and inactive PsA as DAS28-CRP<2.6 (n=75).ResultsPre-eclampsia was most frequent in women with active PsA (3/34, 8.8%), with a risk difference of 6.1% (95% CI 0.3 to 20.3, p=0.036) compared with population controls (2.6%). Gestational hypertension occurred in 2/34 (5.9%) of women with active PsA, with a risk difference of 4.2% (95% CI 0.0 to 17.4, p=0.065) compared with population controls (1.7%). Pre-eclampsia and gestational hypertension occurred in similar proportions in women with inactive PsA (1.3%, p=0.59 and 2.7%, p=0.24, respectively) and population controls. The occurrence of preterm birth and abnormal fetal growth was comparable in cases and population controls.ConclusionHypertensive disorders of pregnancy occurred more often in women with active, but not inactive PsA. We found no increased risk for preterm birth or abnormal fetal growth in women with PsA.Weiterlesen

Online health information (OHI) in dermatology often exceeds the recommended sixth-grade reading level, hindering patient comprehension. This study aimed to assess the utility of three artificial intelligence large language models (LLMs) - ChatGPT-3.5, ChatGPT-4, and Google Gemini - in enhancing the readability of OHI on generalized pustular psoriasis (GPP) while preserving the reliability and quality of the source material. Texts from the top 20 search results for GPP were reworded by LLMs to a sixth-grade level and evaluated using the enhanced DISCERN instrument and readability indices. Pairwise comparisons of means for each reading scale and DISCERN scores with Tukey's test were also performed. All LLMs significantly reduced readability (p<0.01) but scored lower on the DISCERN instrument compared to the original text (p<0.01). While LLMs improved readability, they did not preserve the original content's reliability and quality. These findings suggest hesitancy in using LLMs for dermatological patient education.Weiterlesen

IntroductionCardiovascular disease is a leading co-morbidity in psoriasis patients. The cutaneous benefits of biologic therapies for severe plaque psoriasis are well-established, but the impact of biologics on major adverse cardiovascular events (MACE) in psoriatic patients requires further elucidation. This study aimed to investigate the impact of biologic therapies on the risk of MACE in patients with chronic plaque psoriasis.MethodsWe conducted a systematic review and meta-analysis on 10 May 2022, using Medline, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR) and EMBASE databases for relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) methodology was applied, and all studies were critically appraised. All studies selected for inclusion were randomised control trials (RCTs) that contained data on MACE and compared licensed biologic therapies with placebo or other biologics in adults with moderate-severe plaque psoriasis.ResultsThe search of the databases revealed 36 papers (reporting on 43 RCTs) which met the inclusion criteria. No statistically significant difference in the risk for MACE between biologic therapies and placebo was found [Peto odds ratio (POR) 1.26, 95% confidence interval (CI) 0.53-3.01, P = 0.59]. A comparison of specific types of biologics also revealed no significant effect in adult patients with moderate-to-severe plaque psoriasis: tumour necrosis factor (TNF)-alpha inhibitors (adalimumab, infliximab, etanercept) (POR 1.13, 95% CI 0.29-4.32 P = 0.86), interleukin (IL)-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab) (POR 0.60, 95% CI 0.16-2.25, P = 0.45); IL 12/23 inhibitors (usetekinumab) (POR 3.80, 95% CI 0.37-39.44, P = 0.26) and IL-23 (guselkumab, risankizumab, tildrakizumab) (POR 1.75, 95% CI 0.25-12.43 P = 0.58).ConclusionsAnti-psoriatic biologics were not associated with an increased risk of MACE in psoriasis patients. Given that most included RCTs were of relatively short duration, longer-term studies and post-marketing surveillance are needed to clarify the cardiovascular safety profile of biologic therapies. Further large-scale studies with extended follow-up are warranted.Study registrationThis study was prospectively registered on PROSPERO (identification number CRD42022325792).Weiterlesen

Mitochondrial structural and functional changes accompany psoriasis, yet the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts remains unexplored. In this study, we investigated the effect of psoriasis-like inflammation (PLI) induced by a cytokine cocktail (interleukin (IL)-17A, IL-22 and tumour necrosis factor (TNF)-α) on mitochondrial network morphology and function in cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both cell types, PLI triggered the expression of psoriasis-related Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-α, IFN-β, IFN-γ), and chemokines (C-C motif chemokine 5 (CCL5) and IL-8), accompanied by increased mitochondrial membrane potential, reactive oxygen species (ROS) production, respiration suppression, network fragmentation, swelling and cristae disassembly. Stimulated emission depletion (STED) nanoscopy revealed the disappearance of mitochondrial cristae in response to PLI, with the process starting more quickly and being more pronounced in keratinocytes than in fibroblasts. These findings highlight cell-specific mitochondrial responses to psoriatic inflammation, guiding future investigations towards new pharmacological targets for managing psoriasis.Weiterlesen

BackgroundPsoriasis is a chronic inflammatory skin disease often associated with obesity and metabolic dysfunction, which may worsen disease severity. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, have shown metabolic and anti-inflammatory effects, but their impact on psoriasis in non-diabetic patients with obesity remains unclear.ObjectiveTo evaluate the effects of a six-month semaglutide treatment on psoriasis severity and clinical, metabolic, inflammatory, and psychosocial parameters in patients with psoriasis and obesity.MethodsIn this prospective cohort study, 43 patients received weekly semaglutide along with lifestyle counseling. Psoriasis severity (PASI), quality of life (DLQI), depressive symptoms (BDI), nutritional ultrasound, and biochemical markers were assessed baseline and after six months. Correlations between PASI improvement (ΔPASI) and baseline variables and their changes were analyzed, adjusting for age and weight loss.ResultsAfter six months, participants showed significant reductions in PASI (-48%), BMI, preperitoneal and superficial fat, along with improvements in DLQI, BDI, and metabolic markers. Baseline disease severity, depressive symptoms, insulin resistance, and preperitoneal fat were negatively associated with PASI improvement. These associations remained significant after adjustment (e.g., HOMA-IR, r = -0.82; preperitoneal fat, r = -0.66). ΔPASI was most strongly correlated with reductions in superficial fat (r = 0.89), DLQI (r = 0.55), and BDI (r = 0.51). Changes in BMI and glycemic markers were not significantly associated after adjustment.ConclusionsIn patients with psoriasis and obesity, semaglutide improves both skin disease and systemic health. The clinical benefit appears associated with specific fat loss and psychosocial improvement, beyond overall weight reduction.Weiterlesen

PurposeTo seek recommendations from a panel of experts in psoriatic arthritis (PsA) on the current management challenges, local practices, and role of interleukin (IL)-17 inhibitors in the United Arab Emirates (UAE) using evidence from phase III trials as background.MethodsNine rheumatologists who treat PsA in the UAE completed a structured survey and attended a meeting to discuss topics/issues identified in the survey. A literature search was performed to identify phase III randomized trials of IL-17 inhibitors available in the UAE for PsA.ResultsThere was general agreement among the panel on the most common PsA domains presenting in patients (most commonly psoriasis [75-95% of patients], peripheral arthritis [50-90%], and enthesitis [40-90%]). In general, IL-17 inhibitors were among the preferred treatment options for managing PsA, particularly for patients with axial-, enthesitis-, or psoriasis-related symptoms. Current unmet needs and challenges included a lack of disease awareness among the general population and other healthcare professionals; the lack of a single medication to cover all domains/comorbidities; and lack of universal insurance coverage. The panel had experienced success with the IL-17 inhibitors ixekizumab and secukinumab, with many citing no preference for either agent. The literature search identified publications relating to 10 key phase III clinical trials of IL-17 inhibitors.ConclusionThe panel advocates for the use of the domain-based Group for Research and Assessment of Psoriasis and Psoriatic Arthritis treatment recommendations and generally considers IL-17 inhibitors (ixekizumab or secukinumab) as the preferred treatment options for managing PsA.Weiterlesen

Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (TH17) cells, with several clinical subtypes. While self-reactive immune responses have been observed, the role of autoantigens in Pso remains unclear. Using immunopeptidomics, we identified serpin family B member 3 (SERPINB3) and SERPINB4 as candidate autoantigens in Pso skin. In a mouse model, the SERPINB3 ortholog Serpinb3b enhanced inflammation, promoted tissue-resident memory T cells, and skewed immunity toward a TH2 phenotype. In humans, SERPINB3 reactivity was specifically associated with "eczematized psoriasis" (EczPso), a subtype marked by TH2/TH17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined TH2/TH17 stimulation. Lesional T cells from EczPso-but not from eczema or classical plaque Pso-proliferated in response to SERPINB3 and induced EczPso-like features in a skin model. Our findings identify SERPINB3 as an autoantigen driving a distinct Pso subtype, supporting more precise diagnosis and therapy.Weiterlesen

ObjectiveThe concept of severity in psoriatic arthritis (PsA) remains inconsistently defined, often conflated with disease activity. This scoping review aimed to explore how severity has been defined in the PsA literature and to identify criteria used to characterize severe disease.MethodsA scoping review was conducted in April 2025 following PRISMA-ScR guidelines. PubMed was searched for English-language articles from the last 25 years, alongside abstracts from major rheumatology conferences. Eligible studies had to explicitly define or discuss PsA severity. Articles focusing solely on activity, isolated disease manifestations, or other conditions were excluded. Data were extracted on the type of article, definitions of severity, and criteria used.ResultsOf 4,014 records screened, 32 studies met inclusion criteria. Definitions of severity varied widely and were categorized into imaging (e.g., erosions), clinical (e.g., dactylitis, joint counts), and functional (e.g., HAQ-DI scores) criteria. The most commonly used indicators were structural damage, polyarticular involvement, dactylitis, arthritis mutilans, and validated composite indices such as CPDAI. Only a few studies incorporated functional impairment or patient-reported outcomes. While some guidelines, including GRAPPA and ACR/NPF, proposed multidomain frameworks, a standardized definition remains lacking.ConclusionThe concept of PsA severity has evolved beyond mere disease activity to encompass long-term outcomes, radiographic damage and overall disease burden. However, considerable heterogeneity persists across studies, reflecting the complexity of PsA. A standardized, multidimensional definition of severity, distinct from disease activity, would enhance patient stratification, guide treatment decisions, and support clinical research.Weiterlesen

ObjectivesSeveral studies have reported weight gain with tumor necrosis factor inhibitors (TNFi) in psoriatic disease. However, such analyses have not accounted for the natural propensity for weight gain over time. We aimed to investigate whether therapy with TNFi in psoriatic arthritis (PsA) patients is associated with a change in the rate of weight gain post-treatment initiation.MethodsWe included patients with at least two weight measurements prior to, and after commencing TNFi and used change point analysis to assess the differences in the rate of weight gain based on the mean slope before and after TNFi initiation, adjusting for clinically relevant variables.ResultsOf 234 patients eligible for inclusion, 62.8% were males. At the first clinic visit, the mean (standard deviation) age was 41.8 (12.2) years, while the mean disease duration was 5.1 (6.8) years. The mean weight immediately prior to TNFi use was 83.8 (17.2) kg, while that at the last available visit on TNFi was 86.4 (18.6) kg (p = 0.39), over an average period of 7.9 (5.8) years. The mean values of the pre- and post-TNFi slopes were 0.52 (95% confidence interval [CI] 0.18-0.87) and 0.28 (95% CI - 0.05-0.61), respectively (p = 0.09); thus, there was a trend towards lower rate of weight gain followed the initiation of TNFi therapy.ConclusionsTNFi treatment is not associated with an increase in weight above the expected gain in PsA. Prior trajectory of weight gain with age must be considered while studying the impact of treatment on weight.Key points• TNFi are commonly used in the management of psoriatic disease and may influence body weight. • TNFi treatment is not associated with a significant increase in body weight when accounting for the trend of weight gain with time. • The trends in weight change may differ between etanercept and monoclonal antibody TNFi agents.Weiterlesen

Background: Psoriasis is a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation. Objectives: We aimed to identify circulating metabolites associated with psoriasis, including cutaneous activity, severity, and psoriatic arthritis. Further, we investigated whether the signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs). Methods: We performed a cross-sectional analysis of 270,848 White/European individuals from the UK Biobank (n=253,924) and HUNT (n=16,924). Both cohorts used nuclear magnetic resonance spectroscopy to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications. Results: The metabolomic profile of psoriasis was largely consistent across cohorts. In the model adjusted for age and sex, 116 metabolic measures were associated with psoriasis in both cohorts. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient [95% CI]: 0.09 [0.07-0.11] in UK Biobank and 0.11 [0.06-0.17] in HUNT). Despite more substantial metabolic alterations in cutaneous-active psoriasis, GlycA was also elevated in HUNT participants reporting no active psoriasis rash (coefficient [95% CI]: 0.12 [0.04-0.20] in non-cutaneous-active and 0.11 [0.03-0.19] in cutaneous-active psoriasis). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both cohorts, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (coefficient [95% CI]: 0.41 [0.20-0.62] in UK Biobank and 0.47 [0.28-0.67] in HUNT). All IMIDs showed elevated GlycA and reduced albumin, with milder changes in atopic dermatitis. Psoriasis in the HUNT cohort exhibited a distinct lipoprotein profile compared to other IMIDs. Conclusions: This large-scale, cross-cohort study confirms metabolic alterations in individuals with psoriasis and highlights elevated GlycA levels regardless of cutaneous activity. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis.Weiterlesen

BackgroundPsoriatic arthritis (PsA) and juvenile PsA (jPsA) are chronic inflammatory diseases with similar features that differ by age and sequence of symptom onset. PsA and psoriasis (PsO) share comparable pathology across ages, with interleukin (IL)-23 as a key mediator. Prior to the recent US FDA approval of guselkumab for treatment of pediatric plaque PsO and active jPsA, no approved pediatric treatment selectively targeted IL-23 signaling. Guselkumab (a fully human, dual-acting, IL-23p19 subunit inhibitor) was shown to be safe and effective in adult PsO and PsA, with consistent clinical benefits and safety in pediatric PsO. As jPsA shares features, including clinical characteristics and pathogenesis, with PsO and PsA, findings were extrapolated to jPsA using a similar approach previously applied to support ustekinumab and golimumab use in jPsA, which served as precedents for these analyses with guselkumab.AimsThe aim of this study was to demonstrate the similarity of serum guselkumab concentrations, clinical response, and safety among children and adults with PsO and/or PsA in guselkumab randomized controlled trials.MethodsOne-year data from participants receiving guselkumab at Week (W)0, W4, then every 8 weeks in VOYAGE 1/2 (adult PsO; N = 1221), DISCOVER-1/-2 (adult PsA; N = 375), and PROTOSTAR (pediatric PsO; N = 92; n = 3 with concurrent jPsA) were included. Serum guselkumab concentrations, Investigator Global Assessment of clear/minimal (IGA 0/1) and Psoriasis Area and Severity Index (PASI) 75/90/100 response rates and safety outcomes were summarized.ResultsSerum guselkumab concentrations over 1 year were similar between pediatric (max median: 3.2 µg/mL) and adult PsO (3.7 µg/mL), adult PsO and PsA (4.2 µg/mL), and pediatric PsO and adult PsA. IGA 0/1 response rates at W16 were approximately similar in guselkumab-treated participants with pediatric PsO (66%), adult PsO (84%), and adult PsA (77%). W16 PASI 75/90/100 response rates were comparable across guselkumab-treated participants with pediatric PsO without jPsA (PASI 75: 77%; PASI 90: 56%; PASI 100: 33%), pediatric PsO with jPsA (1 of 2 participants achieved all PASI improvement levels), and adult PsA (77%; 55%; 22%). Guselkumab safety outcomes were similar across ages and diseases.ConclusionComparable pharmacokinetic and clinical findings with guselkumab in children with PsO (3 with concurrent jPsA) and adults with PsO and PsA support the extrapolation of efficacy and safety data from adults to children with jPsA, supporting guselkumab use in jPsA.Clinical trials registrationThe clinical trials included in this analysis are registered at www.Clinicaltrialsgov with the identifiers: NCT02207231 (VOYAGE 1), NCT02207244 (VOYAGE 2), NCT03162796 (DISCOVER-1), NCT03158285 (DISCOVER-2), and NCT03451851 (PROTOSTAR).Weiterlesen

ObjectiveTo investigate the distribution characteristics of peripheral blood lymphocyte subsets in elderly psoriasis patients and analyze the interactions between immunosenescence and psoriasis and their impact on immune cell subpopulations.MethodsThis cross-sectional study enrolled 318 psoriasis patients and 167 healthy controls, stratified by age into elderly (≥ 65 years) and non-elderly (18-64 years) groups. Peripheral blood lymphocyte subsets, including CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and NK cells, were analyzed using four-color flow cytometry. Generalized linear models were employed to analyze associations between PASI scores and lymphocyte subsets, and correlation network analysis was constructed to evaluate interaction patterns among immune cell populations.ResultsThe elderly psoriasis group demonstrated significantly reduced CD8+ T cell percentage compared to controls (24.52% vs. 28.62%, P < 0.001), accompanied by an elevated Th/Ts ratio (1.57 vs. 1.27, P < 0.001) and significantly increased NK cell percentage and absolute count. Generalized linear modeling revealed a significant negative interaction effect between psoriasis and age on CD8+ T cell percentage (β = -3.979, P = 0.019), while the Th/Ts ratio exhibited a significant positive interaction effect (β = 0.230, P = 0.010). B cell absolute count showed a positive correlation with PASI score (r = 0.180, P = 0.001), with this correlation being more pronounced in elderly patients (r = 0.308, P = 0.014). Network analysis demonstrated reduced connectivity density among immune cell subpopulations in elderly patients.ConclusionsElderly psoriasis patients exhibit age-related alterations in peripheral blood lymphocyte subset distribution, characterized by decreased CD8+ T cells, elevated Th/Ts ratio, and increased NK cells. B cells may serve as potential biomarkers for assessing disease severity in elderly psoriasis patients.Weiterlesen

Background: Managing psoriasis in patients with a history of lymphoma presents a unique clinical challenge. Psoriasis is associated with significant comorbidities such as cardiovascular disease and inflammatory arthritis, making optimal treatment vital. Systemic treatments like biologic agents may help mitigate these sequelae of systemic inflammation. However, concerns about immunosuppression in the context of lymphoma recurrence and progression complicate therapeutic decisions. Purpose: This review aims to examine the role of IL-12, IL-17, IL-23, and TNF-α in psoriasis and explores the safety of biologic therapies in this population, with a focus on impact on lymphoma recurrence and progression. Research Design: A narrative review of the current medical literature was conducted. Study Sample: The analysis synthesizes evidence from preclinical studies, clinical trials, post-marketing surveillance registries, retrospetive cohort studies, and case reports concerning the use of biologic agents in psoriasis. Data Collection: Relevant literature was identified an analyzed to compare the mechanisms of action, degree of immunosuppression, and available safety data of different biologic agent classes. Results: Based on current evidence, we propose that IL-17 and IL-23 inhibitors as preferred options due to their targeted mechanisms and favorable safety profiles. In contrast, TNF-α inhibitors are less favored due to their comparatively greater immunosuppressive effects and potential association with lymphoma risk. IL-12/23 inhibitors are questionable given their potential impact on tumor immunosurveillance. Conclusion: For psoriasis patients with a history of lymphoma, IL-17 and IL-23 inhibitors represent the most suitable biologic options, while TNF-α inhibitors and IL-12/23 inhibitors should be used with caution. Clinical data overall remains limited, however, as lymphoma patients are routinely excluded from clinical trials. Further research is needed to clarify long-term safety and optimize treatment strategies for this high-risk population.Weiterlesen

In this commentary, we discuss the role of pharmacy benefit managers (PBMs) on access to biologics for patients with psoriasis. We highlight structural and system level barriers to biologics access, as well as how PBMs work as intermediaries between insurers, pharmacies, and drug manufactures to influence prescription formularies and generate health savings. We also discuss how controversial PBM practices such as step therapy, prior authorizations, and spread pricing may limit access to biologics and potentially increase cost for patients. Finally, we highlight how dermatologists and national organizations such as the National Psoriasis Foundation can collaborate and advocate for legislative reforms to increase transparency among PBMs.Weiterlesen

Diabetes and psoriasis are known to increase the risk of each other, yet their combined impact on long-term mortality remains unclear. This prospective cohort study examined the associations between the coexistence of diabetes and psoriasis and all-cause and cause-specific mortality in a nationally representative sample of U.S. adults. Data were obtained from 16,852 participants in the National Health and Nutrition Examination Surveys (NHANES). Survival was assessed using the Kaplan-Meier method, and a weighted Cox proportional hazards model was employed. In fully adjusted models (adjusted for age, sex, race, BMI, smoking status, and comorbidities), individuals with both diabetes and psoriasis demonstrated significantly increased risks of all-cause mortality (hazard ratio [HR]: 1.76, 95% confidence interval [CI]: 1.04-3.00) and cancer-specific mortality (HR: 2.90, 95% CI: 1.28-6.54), but not cardiovascular mortality (HR: 0.87, 95% CI: 0.18-4.35). Comorbidity was significantly associated with elevated risks of all-cause and cancer mortality (P < 0.05). These findings suggest a notable association between the coexistence of these two chronic conditions and elevated overall and cancer mortality risks, while no significant effect was found on cardiovascular mortality. Exploratory analyses also indicated a possible dose-response relationship between psoriasis severity and cardiovascular mortality, warranting further investigation.Weiterlesen

Once hailed as a breakthrough in psoriasis research, the imiquimod (IMQ) mouse model is now overused, inconsistently applied, and increasingly disconnected from human disease. Nearly a decade after our initial critique, the field remains reliant on a tool that models acute, innate inflammation rather than chronic, adaptive immunity. In this paper, we revisit the limitations of the IMQ model, highlighting methodological drift, poor transcriptomic overlap with psoriasis, and the illusion of mechanistic discovery. We argue that progress in psoriasis research now depends on moving beyond this model toward more faithful systems that reflect the complexity of human disease.Weiterlesen

Plaque psoriasis is a chronic skin disorder involving dysregulated inflammation. While numerous biologic therapies targeting inflammatory mediators have been approved for moderate-to-severe psoriasis, their safety profiles may include an increased risk of adverse events (AEs), such as infections, cardiovascular diseases, and malignancies. Because patients with psoriasis also have increased incidence of comorbidities, long-term real-world AE monitoring is critical to further evaluate the safety of biologic therapies postapproval. Brodalumab is a recombinant, fully human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. The safety profile of brodalumab has been established in clinical trials and industry-sponsored US pharmacovigilance reports. Herein, we summarize AEs reported in nonsponsored open-label and real-world studies of brodalumab. Across all studies, most common AEs were similar to those listed in the brodalumab package insert. While AEs of special interest were not reported comprehensively, their rates were generally low, with 3 cases of major adverse cardiac events, 2 cases of malignancy, 11 cases of depression, and no completed suicides in the overall safety population (N = 1701). There were 6 cases of serious infection and no serious fungal infections. Studies evaluating AEs of interest for brodalumab showed no causal link to suicide and no increase in risk of cardiac events or serious infection compared with other biologics. Together, these studies support a consistent safety profile of brodalumab in real-world use.Weiterlesen

BackgroundThe pathogenesis of psoriasis is characterized by dysregulated post-translational modifications, with particular emphasis on fucosylation-a glycosylation process mediated by fucosyltransferases (FUTs). Keratin 17 (K17), overexpressed in psoriatic keratinocytes, drives inflammation and proliferation, but its interplay with fucosylation remains unclear. This study aimed to elucidate the role of fucosylation in psoriasis, specifically focusing on the regulation of K17 stability by FUT11.MethodsTo investigate fucosylation dynamics, we employed single-cell RNA sequencing (scRNA-seq) to analyze N-glycan biosynthesis activity in psoriatic versus healthy keratinocytes. Fucosylation levels were assessed in human and murine psoriatic lesions, as well as in cytokine-stimulated keratinocytes, using Aleuria aurantia lectin (AAL). An imiquimod (IMQ)-induced psoriasis-like mouse model and primary keratinocytes treated with psoriasis-associated cytokines (Pso-Mix) (IL-17, TNF-α, IL-1α, OSM and IL-22) were utilized to evaluate the effects of 2-fluorofucose (2-FF) and FUT11 siRNA. We further explored the mechanisms regulating K17 stability through immunoprecipitation, ubiquitination assays, and cycloheximide chase experiments.ResultsOur findings revealed that psoriatic keratinocytes exhibited elevated levels of fucosylation, which correlated with upregulation of FUT11. Administration of 2-FF or silencing FUT11 significantly attenuated IMQ-induced inflammation, as evidenced by reductions in epidermal thickness, immune cell infiltration, and the expression of pro-inflammatory mediators such as IL-17A and CCL20. We demonstrated that FUT11 mediates α-1,3-fucosylation of K17, stabilizing it through K63-linked ubiquitination facilitated. Notably, silencing FUT11 disrupted the interaction between ubiquitination and fucosylation, leading to accelerated K17 degradation and a subsequent decrease in keratinocyte proliferation.ConclusionsOur results indicate that FUT11-driven fucosylation is integral to the stabilization of K17 via K63 ubiquitination, thereby perpetuating psoriatic inflammation. Targeting FUT11 or inhibiting fucosylation with 2-FF presents a novel therapeutic strategy for psoriasis management. This study highlights the critical interplay between glycosylation and ubiquitination in the pathophysiology of psoriasis, positioning FUT11 and K17 as pivotal targets for intervention.Weiterlesen

Epidemiological association between psoriasis and T2DM suggests shared pathophysiology that are to be explored. Microarray expression profiles for psoriasis and T2DM were obtained from the Gene Expression Omnibus (GEO) database. The "limma" package in R software was used to screen the differentially expressed genes (DEG). GO and KEGG enrichment analysis were further conducted to explore the functions of co-DEGs. By intesecting genes of the key disease-related modules from WGCNA with co-DEGs, candidate co-driver genes were identified and their PPI network was constructed. Hub genes with good diagnostic potential were obtained by ROC analysis and their expression was further compared in validation datasets as well as clinical samples. The crucial co-driver genes, identified by a consistently differential expression pattern, were further subjected to a series of analyses, including Gene Set Enrichment Analysis (GSEA), immune cell infiltration analysis, gene-chemistry networks analysis, gene-transcription factors (TF) network analysis, and gene-miRNA regulatory network analysis. In our study, 71 co-DEGs were identifed from psoriasis and T2DM training datasets. KEGG analysis revealed enrichment of pathways including toll-like receptor signaling pathway, cytokine-cytokine receptor interactions, chemokine signaling pathway, NOD-like receptor signaling pathway and cytosolic DNA-sensing pathway. By intersecting the critical WCGNA modules with co-DEGs, 33 candidate co-driver genes were obtained. 11 of them showed interactions with others on PPI network and 7 revealed good diagnostic value with AUC > 0.7 by ROC analysis. 4 genes, namely BEX5, EPHX2, GPRASP1, and RBP4 were finally identified as crucial co-driver genes with a consistent differential expression pattern in both training and validation datasets as well as validation experiments using clinical samples. GSEA analysis revealed that these crucial co-driver genes were involved in cytokine receptor interaction, proteasome, ribosome, apoptosis and so on. Immune cell infiltration and correlation analyses highlighted their roles in the immune microenvironment. Lastly, these genes targeted 76 skin and metabolic diseases and 135 chemicals were predicted to exert an modulatory effect of their expression. 13 TFs and 79 miRNAs were identified to modulate their expression. The integrated bioinformatics analysis conducted in our study identified co-DEGs and enriched immune-inflammatory pathways, providing novel insights into the pathogenesis underlying the comorbidity of psoriasis and T2DM. The crucial co-driver genes warrants further experimental validation and exploration to unveal the common pathophysiology.Weiterlesen

No abstract supplied.Weiterlesen

No abstract supplied.Weiterlesen

No abstract supplied.Weiterlesen