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Understanding the drivers of BASDAI and back pain scores in psoriatic arthritis.

Objectives
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is widely used to assess axial disease activity in psoriatic arthritis (PsA). However, 5 of its 6 questions reflect general disease activity rather than axial-specific symptoms. We aimed to evaluate the performance of BASDAI and its back pain subscore in assessing axial disease in PsA.Methods
Patients with BASDAI scores were identified from a longitudinal PsA cohort initiated in 1978. Axial disease was defined radiographically. Trends in BASDAI and back pain scores were compared between patients with and without axial involvement. Associations of total BASDAI and back pain subscore with axial disease were assessed using univariable and multivariable linear mixed models in the entire cohort and stratified subgroups.Results
Of 1059 patients, 449 (42.4%) had axial and 610 (57.6%) had peripheral disease only. The mean age was 44.4 years (SD 12.8), and 55.9% were male. No difference in the BASDAI and back pain trends was observed between the axial and peripheral disease groups. Axial involvement was not associated with total BASDAI scores (β = -0.14, 95% CI -0.05 to 0.33). However, it was associated with a small, yet significant increase in back pain subscore (0.30, 0.06-0.55). Both BASDAI and back pain scores were associated with active peripheral joints, enthesitis, dactylitis, age, Psoriasis Area and Severity Index, and inversely with male sex. These associations were consistent across axial and peripheral disease subgroups.Conclusions
BASDAI and its back pain subscore are influenced by peripheral musculoskeletal and skin disease activity in PsA, limiting their utility for assessing axial activity.Weiterlesen
  • 27 Aufrufe
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Infections during childhood as predisposing factors to develop Psoriasis Vulgaris into early adulthood.

Psoriasis is a chronic inflammatory skin disease associated with an increased risk of developing cardiovascular disease. Various environmental factors contribute to disease development in genetically susceptible individuals. Although infections have been associated with disease initiation and recurrence, the consequences of early exposure to infections, many years before disease manifestation, is unexplored. To investigate the effect of exposure to infections during formative years on the incidence of psoriasis through to early adulthood. ABIS is a large birth cohort in which parents of participating children have answered comprehensive questionnaires on exposure to infections and medication at different age intervals of the children. Information regarding psoriasis was obtained from the Swedish National Patient Register, while data on medication was obtained from the National Prescribed Drug Register. Statistical analyses were performed with custom-written R scripts. Logistic regression analysis on one-year follow-up data revealed that influenza was associated with an increased risk of developing psoriasis later in life (OR 2.47, CI 1.32-4.39; P= 0.006). In line with this, at the third-year evaluation, we found that participants who had tonsillitis at least once during the first three years of life had almost three times greater risk of developing psoriasis into early adulthood compared to controls (OR 2.90, CI 1.46-5.56; P= 0.003). In contrast, at the eight-year evaluation, we found that psoriasis was less frequent in children who had experienced gastroenteritis episodes between ages six and eight, compared to controls (OR 0.42, CI 0.20-0.92; P =0.0028). We demonstrate for the first time the effect of exposure to infections during the first years of life, and their role in the subsequent development of psoriasis extending into early adulthood. Our study indicates that early exposure to infections may influence the development of the adaptive immune system during formative years. This modulation is evidenced by the higher incidence of psoriasis observed in early adulthood, several years after the initial exposure.Weiterlesen
  • 24 Aufrufe
Redaktion

[Medical health apps for psoriasis and psoriatic arthritis].

Chronic inflammatory diseases such as psoriasis (PsO) and psoriatic arthritis (PsA) are associated with a high disease burden and significant healthcare needs. Given limited specialist resources, the use of medical health apps is increasingly coming into focus as a means of supporting patients in self-management and closing gaps in care. This review highlights digital health applications available in Germany for PsO and PsA. Their functions, objectives, and potential benefits in the context of care are analysed. Six relevant apps were identified based on a systematic literature review and a structured search of the popular app stores. None of the applications are currently approved as digital health applications (German: DiGA). The apps differ in terms of their target groups, range of functions, and scientific evidence. While some primarily deal with dermatological aspects (e.g., Sorea, Psoriasis Monitor), others focus more on rheumatological issues (e.g., Mida Rheuma App, Rheuma-Auszeit). The range is supplemented by educational apps (e.g., PSO Kiosk) and therapy-accompanying apps (e.g., MyTherapy). Such digital apps can promote understanding of the disease, contribute to improving therapy adherence and have a positive effect on mental well-being, especially in patients with PsO and PsA, who often experience stress and mental comorbidities. Even though no app has yet achieved DiGA status, individual applications can be a useful addition to care.Weiterlesen
  • 25 Aufrufe
Redaktion

Medication utilization patterns among patients with rheumatoid arthritis and coexisting autoimmune conditions.

Rheumatoid arthritis (RA) is the most common inflammatory joint disease worldwide. T-cell inhibitors, tumor necrosis factor inhibitors, interleukin inhibitors (ILIs), Janus kinase inhibitors, and B-cell depletion therapy are indicated as second-line therapy and are prescribed for other inflammatory autoimmune conditions (ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn disease, ulcerative colitis) co-occurring in an estimated 7% to 20% of patients with RA but are routinely excluded from RA studies. There is a lack of real-world evidence documenting treatment patterns in the large segment of patients with RA with inflammatory autoimmune comorbidities. To describe RA medication utilization patterns among biologic-naive patients, with and without similarly treated comorbidities. This retrospective cohort study uses administrative health claims from a large national health insurer between 2016 and 2022. Persistence, medication possession ratio (MPR), and utilization patterns were measured for patients with and without similarly treated comorbidities. Differences in means were calculated using a t-test, and Cox proportional hazards regression modeling was used to estimate persistence and hazard ratio (HR). A total of 22,946 patients with RA persisted on the index therapy for an average of 368.2 days (SD, 436). MPR varied across drug classes, with ILIs having the highest MPR at 0.95 (SD, 0.10) and B-cell depletion class having the lowest at 0.82 (SD, 0.19). Patients with RA with psoriatic arthritis were more likely to end the episode with therapy gap restart (HR, 1.1; CI, 1.02-1.22), yet patients with RA with psoriasis were less likely to experience a therapy gap restart (HR, 0.91; CI, 0.83-0.99). Among patients with RA initiated on ILIs, those with psoriasis are more likely to stop or switch compared with those without psoriasis (HR, 1.19; CI, 1.02-1.39). Among patients with RA initiated on Janus kinase inhibitors, those with psoriatic arthritis were more likely to stop or switch therapy compared with patients with RA without psoriatic arthritis (HR, 1.27; CI, 1.02-1.59). RA medication utilization varied significantly and may be influenced by comorbidities differently across RA drug classes. More research is needed to understand why therapies like tumor necrosis factor inhibitors persist longer in patients with RA with ulcerative colitis yet are discontinued earlier in patients with psoriatic arthritis.Weiterlesen
  • 21 Aufrufe
Redaktion

Regulatory T Cells: Subtle and Promising Achilles' Heel of Psoriasis - Atherosclerosis Comorbidity.

Psoriasis is a chronic inflammatory skin disorder affecting 2-3% of the global population. It is increasingly recognized for its systemic comorbidities, especially cardiovascular diseases (CVDs). Notably, severe psoriasis independently increases cardiovascular disease (CVD) risk. This elevation occurs beyond conventional risk factors, such as hypertension and diabetes. It suggests that shared inflammatory pathways underlie the association between severe psoriasis and atherosclerotic conditions, like coronary artery disease (CAD). Atherosclerosis, characterized by lipid-laden plaque formation in arterial walls, remains a leading contributor to CVD-related morbidity and mortality. Emerging evidence underscores the interplay of inflammatory cell heterogeneity and immune dysregulation in its pathogenesis, mirroring mechanisms observed in psoriasis. The overlapping systemic inflammation and immune dysfunction in both diseases suggest potential therapeutic synergies. CD4+ regulatory T cells (Tregs), pivotal immunosuppressive modulators, have shown promise in mitigating autoimmune responses, yet their therapeutic exploitation in psoriasis-atherosclerosis comorbidity remains underexplored. This review summarizes current insights into Tregs' roles in psoriasis and atherosclerosis, emphasizing their dual regulatory functions; in psoriasis, Treg dysfunction exacerbates interleukin-17 (IL-17)/23-driven keratinocyte hyperproliferation, while in atherosclerosis, impaired Treg activity permits pro-inflammatory cytokine cascades and foam cell formation. We, herein, highlight emerging approaches to enhance Treg stability and function, such as nanotechnology-based targeting antibodies and traditional Chinese medicine (TCM). By delineating Treg-centric mechanisms across both diseases, this review proposes a paradigm shift toward immunomodulatory therapies addressing psoriasis-atherosclerosis crosstalk, offering novel strategies to alleviate systemic inflammation and cardiovascular burden in psoriatic patients. Further research into Treg heterogeneity and microenvironmental cues may unlock precision therapies for this comorbid axis.Weiterlesen
  • 24 Aufrufe
Redaktion

The causal relationship between uveitis and psoriatic arthritis: A bidirectional Mendelian randomisation study.

Background Several traditional observational studies have reported an association between uveitis and psoriatic arthritis (PsA). However, the causal relationship between them remains unclear. Objective To investigate whether genetically predicted uveitis is related to the risk of PsA, and vice versa. Methods A two-sample bidirectional Mendelian randomisation (MR) design was employed, conducting a meta-analysis on data sourced from three distinct origins, followed by sensitivity analyses to ensure the robustness of the findings. Results MR analysis revealed a positive causal effect of uveitis on PsA. Meta-analysis results from three data sources revealed an odds ratio (OR) of 1.63, with a 95% confidence interval (CI) ranging from 1.22 to 2.19, and a statistically significant P-value of 0.001. Inverse MR results indicated a positive causal relationship between PsA and uveitis. Meta-analysis results: OR = 1.55, 95%CI = 1.07-2.24, P-value = 0.02. Limitations This study exclusively included individuals of European ancestry, thereby potentially limiting its generalisability to other populations, such as those of Asian or African descent. Secondly, Uveitis is a collective term for various intraocular inflammations, including anterior uveitis, intermediate uveitis, posterior uveitis, and pan uveitis. Conclusions The outcomes of our study indicate a significant association between uveitis and an elevated risk of PsA. Conversely, PsA is associated with an increased risk of uveitis. These findings add to the understanding of the complex relationship between uveitis and PsA, suggesting the possibility of mutual influence.Weiterlesen
  • 20 Aufrufe
Redaktion

Coexistence of Psoriasis and Pemphigus: A Case Report of Pemphigus Vulgaris With a Review of the Literature.

Numerous case reports have documented the coexistence of psoriasis and pemphigus. We present the case of a man with a history of psoriasis who subsequently developed pemphigus. We review relevant case reports published over the past decade. Available evidence suggests that pemphigus may develop in patients with a history of psoriasis.Weiterlesen
  • 17 Aufrufe
Redaktion

Targeting the epigenetic regulator bromodomain-containing protein 4 by BRD4 siRNA lipoplexes and PFI-1 in psoriasis.

Psoriasis is a chronic skin disease characterized by keratinocyte hyperproliferation, epidermal hyperplasia, and immune cell infiltration involving both innate and adaptive immune systems. Bromodomain-containing protein 4 (BRD4), part of the Bromodomain and Extra-Terminal (BET) family, is implicated in various inflammatory and hyperproliferative disorders, though its role in psoriasis is unclear. This study investigates BRD4's role in psoriasis pathogenesis using BRD4-specific small interfering RNA (siRNA) lipoplexes (BRD4-siRNA-LP) and the small molecule inhibitor PFI-1. BRD4's effect was analyzed in human macrophages through gene-specific knockout and overexpression. Transfection of pcDNA5-Flag-BRD4-WT in macrophages activated core inflammatory regulators, while BRD4 disruption via BRD4-siRNA and BRD4 p5188 pSUPER-shRNA inhibited inflammation-related gene transcription. Topical application of BRD4-siRNA-LP and PFI-1 on Imiquimod (IMQ)-treated mice significantly reduced psoriatic plaques and epidermal hyperplasia. BRD4 inhibition notably downregulated pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, TGF-β, and TNF-α. Both in vitro and in vivo findings showed that BRD4 suppression significantly decreased the expression of signaling proteins including p65 NF-κB, MAPKs, and STAT3. Furthermore, BRD4 was found to interact with p65 NF-κB and STAT3, and its inhibition disrupted these protein-protein interactions. Inhibiting BRD4 with BRD4-siRNA-LP and PFI-1 effectively alleviates experimental psoriasis symptoms, making it a promising target for therapeutic intervention in psoriasis.Weiterlesen
  • 22 Aufrufe
Redaktion

Efficacy and Safety of Risankizumab in Genital or Scalp Psoriasis in the UnlIMMited Phase 4 Randomized Clinical Trial at Week 16.

Introduction
Psoriasis (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.Methods
UnlIMMited (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.Results
At 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.Conclusion
These 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 number
ClinicalTrials.gov identifier NCT05969223.Weiterlesen
  • 52 Aufrufe
Redaktion

Pre-eclampsia is more common in women with active psoriatic arthritis in pregnancy: a population-based study.

Objective
To investigate the association between peripheral disease activity and pre-eclampsia, gestational hypertension, preterm birth and fetal growth in women with psoriatic arthritis (PsA).Methods
Data 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).Results
Pre-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.Conclusion
Hypertensive 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
  • 34 Aufrufe
Redaktion

Utility and Limitations of Large Language Models to Simplify Online Content on Generalized Pustular Psoriasis.

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
  • 21 Aufrufe
Redaktion

Response to Tofacitinib in Patients with Psoriatic Arthritis and Probable Anxiety/Depressive Disorder: A Post Hoc Analysis of Phase 3 Trials.

Introduction
Mental 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.Methods
This 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.Results
Overall, 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.Conclusions
Baseline 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 registration
ClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.Weiterlesen
  • 37 Aufrufe
Redaktion

Psoriasis-like inflammation induces structural and functional changes in mitochondria.

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
  • 26 Aufrufe
Redaktion

Biologic Therapies and Major Cardiovascular Events in Psoriasis: Updated Systematic Review and Meta-analysis.

Introduction
Cardiovascular 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.Methods
We 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.Results
The 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).Conclusions
Anti-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 registration
This study was prospectively registered on PROSPERO (identification number CRD42022325792).Weiterlesen
  • 21 Aufrufe
Redaktion

Dermatologic and Metabolic Benefits of Semaglutide in Psoriasis with Obesity: A Six-Month Prospective Cohort Study.

Background
Psoriasis 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.Objective
To 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.Methods
In 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.Results
After 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.Conclusions
In 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
  • 39 Aufrufe
Redaktion

Expert Opinion Report on the Challenges in the Management of Psoriatic Arthritis in United Arab Emirates: A Focus on Interleukin-17 Inhibitors.

Purpose
To 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.Methods
Nine 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.Results
There 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.Conclusion
The 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
  • 30 Aufrufe
Redaktion

Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis.

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
  • 30 Aufrufe
Redaktion

The concept of severity in psoriatic arthritis: a scoping review of the literature.

Objective
The 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.Methods
A 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.Results
Of 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.Conclusion
The 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
  • 31 Aufrufe
Redaktion

Changes in weight associated with tumor necrosis factor inhibition in psoriatic arthritis: results from a retrospective cohort study.

Objectives
Several 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.Methods
We 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.Results
Of 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.Conclusions
TNFi 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
  • 31 Aufrufe
Redaktion

Characteristics of peripheral blood lymphocyte subsets in elderly patients with psoriasis.

Objective
To 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.Methods
This 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.Results
The 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.Conclusions
Elderly 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
  • 17 Aufrufe
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Circulating metabolites associated with psoriasis in the UK Biobank and the HUNT Study: A cross-sectional study of 270,848 participants

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
  • 27 Aufrufe
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Clinical Considerations for the Use of Biologic Agents in Psoriasis Patients With a History of Lymphoma.

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
  • 26 Aufrufe
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Extrapolating Guselkumab Efficacy to Juvenile Psoriatic Arthritis from Adult Psoriatic Arthritis and Adult and Pediatric Psoriasis Data.

Background
Psoriatic 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.Aims
The 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.Methods
One-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.Results
Serum 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.Conclusion
Comparable 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 registration
The clinical trials included in this analysis are registered at www.Clinicaltrials
gov with the identifiers: NCT02207231 (VOYAGE 1), NCT02207244 (VOYAGE 2), NCT03162796 (DISCOVER-1), NCT03158285 (DISCOVER-2), and NCT03451851 (PROTOSTAR).Weiterlesen
  • 26 Aufrufe
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The Role of Pharmacy Benefit Managers in Access to Biologics for Dermatologic Conditions.

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
  • 33 Aufrufe
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The co-impact of diabetes and psoriasis on mortality risk for all causes and specific causes.

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
  • 28 Aufrufe
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