Claudia

BackgroundPsoriasis is an immune-mediated skin disease where Th17 cell differentiation and IL-17 secretion play critical roles. This study investigates key exosomal ncRNAs regulating the Th17/IL-17 axis in psoriasis and their mechanisms.MethodsWe integrated bulk RNA sequencing datasets from the GEO database to construct and evaluate exosome-related patterns. Subsequently, exosome-related ncRNAs in psoriasis lesions were identified primarily through weighted gene co-expression network analysis and five machine learning algorithms. Additionally, large-scale integrated single-cell RNA sequencing data and genome-wide association study (GWAS) data were included to investigate the mechanisms of key ncRNA, primarily through immune infiltration analysis, gene set enrichment analysis (GSEA), co-expression analysis, and Mendelian randomization. Finally, the mechanisms of key ncRNA were confirmed primarily through cell co-culture and lentiviral transfection, assessed by immunofluorescence, qRT-PCR, and Western blot.ResultsWe identified 10 exosome-related ncRNAs, including PRKCQ-AS1, and constructed five machine learning models with excellent diagnostic performance, emphasizing PRKCQ-AS1's significance. Mendelian randomization demonstrated a causal relationship between PRKCQ-AS1 and psoriasis. Immune infiltration analysis and GSEA indicated that PRKCQ-AS1 influences the infiltration pattern of CD4+T cells, promotes Th17 differentiation, and is related to STAT3. The expression distribution in single-cell RNA sequencing data suggested that exosomal PRKCQ-AS1 may originate from keratinocytes, and co-expression analysis supported its role in STAT3 activation within lymphocytes. Co-culture experiments confirmed that keratinocytes in psoriasis models, as well as keratinocytes overexpressing PRKCQ-AS1, can upregulate PRKCQ-AS1 levels in CD4+T cells via exosomes, promoting Th17 cell differentiation and IL-17 secretion. Consistent results and STAT3 signaling pathway activation were detected in CD4+T cells overexpressing PRKCQ-AS1.ConclusionPRKCQ-AS1 is an exosomal lncRNA from keratinocytes in psoriasis, promoting Th17 differentiation and IL-17 secretion through STAT3 activation. This finding deepens the understanding of psoriasis pathogenesis and provides a basis for targeted therapies.Weiterlesen

BackgroundPsoriasis is a chronic disease with a prevalence of 3% in the general population. The high prevalence of psoriasis has prompted the study of its comorbidities in recent decades. However, no studies have ever analyzed comorbidity patterns including all chronic diseases in psoriatic patients.ObjectivesTo identify comorbidity patterns in psoriatic patients using network analysis and describe them from a clinical point of view.MethodsWe conducted an observational and retrospective study with individuals of the EpiChron Cohort (Aragón, Spain) diagnosed with psoriasis from January 1st, 2010 through December 31st, 2019. The population was stratified by sex and age intervals (0-11, 12-17, 18-44, 45-64 > 65). We built a network for each stratum (ie, 5 for each sex), calculating the tetrachoric correlations of each pair of diseases. We used a cut-off threshold for statistical significance of p-value < 0.01. We applied the Louvain community detection algorithm to identify clusters of diseases.ResultsThe prevalence of psoriasis in Aragón was found to be 2.84%. We identified a total of 31,178 psoriatic patients (54% men, 61% from metropolitan areas). The most common comorbidities were respiratory diseases, cardiometabolic conditions (such as hypertension and dyslipidemia), and mental health disorders (including anxiety and mood disorders). A total of 21 comorbidity patterns were identified, varying by sex and age group.ConclusionsThis is the first study ever conducted with a comprehensive analysis of the disease patterns of psoriatic patients. Our results are a comprehensive map of possible psoriasis-related comorbidities. Further studies should confirm these associations and their pathophysiological relationship with psoriasis, which could help to detect and prevent comorbidities and modifiable risk factors.Weiterlesen

IntroductionPsoriasis is a chronic disease and prevalent among 2-3% of the global population. Several therapeutic options alongside recent biologics have allowed the decrease and control of psoriasis lesions reaching a Psoriasis Area Severity Index (PASI) clearance of PASI75 or PASI90. Despite clinical improvements in lesions and provided PASI scores by clinicians as treatment success, patients have expressed varied satisfaction and perceptions. We present a case series that provides real-world evidence of combitherapy with calcipotriol and betamethasone dipropionate (Cal/BD) foam and biologics/systemics for the treatment of persistent psoriatic lesions.MethodsA retrospective, single-center study involving 10 patients was conducted from July to December 2023. Data were retrieved before initiation of the combitherapy and at the 6-month follow-up at the Centre Hospitalier Universitaire de Rennes Pontchaillou in France. Patients included were adults (≥ 18 years old), diagnosed with moderate to severe psoriasis by a dermatologist, and treated with Cal/BD foam as well as either biologics and/or systemics medication. Psoriasis severity and the dynamics of the treatments were described using mean (m)PASI, body surface area (BSA) %, sleep disturbance, patient satisfaction, dermatology life quality index (DLQI) scores and itch observation.ResultsPatients were mostly male (n = 7), had a mean age of 53.3 years and psoriasis history of 13.0 years (missing data = 2). All patients were treated by biologics/systemics with Cal/BD combitherapy, and improved mPASI after six months (p < 0.001). Most patients had a reduced BSA (60.0%) (p = 0.024) and lowered itch (70.0%). Sleep disturbance reported by four patients was improved. Most patients reported an improved DLQI (mean score from 11.8 to 0.1). Patient satisfaction was positive.ConclusionsOur insight into treatment combinations of Cal/BD foam may present an opportunity to improve standard care and patient satisfaction for hard-to-treat and persistent psoriasis lesions.Weiterlesen

Psoriasis is a persistent immune-mediated inflammatory dermatosis. The treatment of psoriasis now features natural medicine as an effective new alternative because of its notable effectiveness and few side effects. Nervonic acid (NA), a long-chain fatty acid mostly sourced from the seed oils of some wild plants, exhibits significant antidepressant and anti-inflammatory properties. Nonetheless, the pathogenic effects and mechanism of NA in the pathogenesis of psoriasis are unreported. This work demonstrated that NA markedly mitigated IMQ-triggered psoriasis-like skin inflammation and reduced the mRNA expression levels of chemokines (Cxcl1 and Ccl20) and inflammatory factors (S100a8, S100a9, IL-17, and IL-6) both in vitro and in vivo. Mechanistically, NA blocked the IL-17/IMQ-induced NF-κB and p38MAPK signaling pathways in keratinocytes or tissue lesions, downregulated Ccl20 production, and therefore disrupted positive inflammatory feedback by diminishing Th17 or γδT17 cell infiltration. Furthermore, 16s rRNA sequencing demonstrated that NA therapy significantly elevated the relative abundance of Bacteroidota, but the outcome for Mucispirillum was contrary within the gut microbiota. These bacteria are linked to the onset of psoriasis and inflammation, perhaps contributing to the alleviation of IMQ-induced lesions in mice. In conclusion, NA may alleviate dermatitis in psoriatic mice by inhibiting Th17/γδT17 cell invasion and modulating the gut microbiota. Consequently, NA stands as a highly promising choice for psoriasis treatment.Weiterlesen

Ethnopharmacological relevancePsoriasis is a chronic immune-mediated skin disease characterized by the infiltration of multiple inflammatory cells and abnormal differentiation of keratinocytes in the skin. The treatment of psoriasis is primarily based on immunosuppressive drugs; however, their long-term use can lead to various adverse effects. Euphorbia humifusa Willd. (EuH) is used in traditional Chinese medicine for its anti-inflammatory properties and effects on skin diseases such as psoriasis.Aim of the studyThis study aimed to evaluate the anti-psoriasis effects of EuH extract, and explore its underlying mechanisms.Methods and materialsThe main components of EuH extract were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technology. Then, we administered EuH extract to imiquimod-induced psoriasis mice for 6 consecutive days, and evaluated the effects according to the psoriasis area and severity index (PASI), spleen index, histological analysis, immunohistochemical and immunofluorescence staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and flow cytometry analysis. The potential mechanism was revealed using RNA sequencing (RNA-seq) and validated by target prediction, ELISA, qRT-PCR and western blot (WB) analysis.ResultsThe UPLC-QTOF-MS/MS analysis showed that phenolics were the essential components in the water extracts of EuH, including flavonoids, phenolic acids, and gallotannins. Treatment with EuH alleviated psoriatic symptoms including skin condition, high PASI scores (erythema, scaling, and thickness), and spleen index values in imiquimod-induced mice. EuH treatment also inhibited keratinocyte hyperproliferation, reduced epidermal thickness, reduced inflammatory cell infiltration into skin lesions, decreased the mRNA levels of inflammatory factors, and restored T and Treg cellular balance in the spleen. RNA-seq, ELISA, qRT-PCR and WB analyses indicated that EuH extract reduced the inflammatory response and keratinocyte hyperproliferation by inhibiting the IL-17 signaling pathway.ConclusionsOur findings suggest that EuH extract suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting the IL-17 signaling pathway, supporting EuH as a potential treatment for psoriasis.Weiterlesen

Background and objectiveErosions of the skin and mucous membranes with epidermal dysmaturation are a known side effect of cytostatic chemotherapy regimens and can also be observed during low-dose methotrexate (MTX) therapy. The study aimed to delineate the clinical and histopathological alterations.Patients and methodsA database search of the archive for dermatopathology was conducted, identifying 22 patients who developed epidermal dysmaturation on low-dose MTX. Clinical and laboratory changes, along with an array of histologic parameters were analyzed and statistically evaluated using SPSS.ResultsPatients were predominantly female with a mean age of 69.1 years. The main indications were psoriasis vulgaris and rheumatoid arthritis. Clinically, patients mostly presented erosive plaques at the injection site, on mucosal surfaces, and disseminated lesions. Most patients showed normal laboratory values. Histopathologically, key findings included enlarged keratinocytes with pale cytoplasm and enlarged nuclei with prominent nucleoli, along with the degeneration of the basal layer. Consistent observations in the dermal compartment included infiltration of neutrophilic granulocytes, lymphocytes, and histiocytes.ConclusionsThis study proposes clinicopathological criteria for the diagnosis of MTX-associated skin toxicity, aiming to increase awareness among clinicians and pathologists for early diagnosis. Early recognition can prevent potentially life-threatening progression.Weiterlesen

ObjectiveTo construct a predictive model for Psoriatic Arthritis (PsA) based on clinical and ultrasonic characteristics in patients with plaque psoriasis (PsP).Patients and methodsDemographic, clinical, and ultrasound data were collected from patients with PsP and PsA between May 2019 and December 2022.ResultsA total of 212 patients with PsP and 123 with PsA in the training cohort, whereas the validation cohort comprised 91 patients with PsP and 49 with PsA. The multivariate logistic regression identified nail psoriasis (odds ratio [OR] 1.88, 95% CI: 1.07-3.29), synovitis (OR 18.23, 95% CI: 4.04-82.33), enthesitis (OR 3.71, 95% CI: 1.05-13.14), and bone erosion (OR 11.39, 95% CI: 3.05-42.63) as effective predictors for PsA. The area under the curve was 0.750 (95% CI, 0.691-0.806) and 0.804 (95% CI, 0.723-0.886) for the training and validation cohorts, respectively. The Hosmer-Lemeshow goodness-of-fit test showed good consistency for both the training cohort (p = 0.970) and the validation cohort (p = 0.967). Calibration curves also indicated good calibration for both cohorts. The DCA revealed that the predictive model had good clinical utility.ConclusionsWe have developed a quantitative, intuitive, and convenient predictive model based on nail psoriasis, synovitis, enthesitis, and bone erosion to assess the risk of PsA in patients with plaque psoriasis.Weiterlesen

No abstract supplied.Weiterlesen

No abstract supplied.Weiterlesen

Background and objectivesPatients with cutaneous lymphomas (CL) are at an increased risk of developing secondary malignancies. This study aimed to assess the frequency of association between CL and Kaposi sarcoma (KS) and to identify factors that may promote the co-occurrence of these two diseases.Patients and methodsOn January 25, 2024, we conducted a systematic search of four electronic medical databases to identify all published cases of KS associated with CL. The clinical course and outcomes of these patients were summarized. For critical appraisal, we applied the JBI Checklist for Case Reports. The study was registered in the PROSPERO database (CRD42022313204).ResultsA total of 40 articles reporting on 45 patients were assessed for eligibility. We included 27 cases in the final analysis (26 cutaneous T-cell lymphomas, 1 cutaneous B-cell lymphoma). In 71% of cases, the diagnosis of CL preceded KS. Nearly half (48%) of the patients had erythrodermic mycosis fungoides or Sézary syndrome. KS lesions were predominantly limited to the skin, with complete remission achieved in 53% of cases.ConclusionsThe association between KS and CL is rare, limiting our study due to the small sample size and potential reporting bias. Skin-targeted therapies, a restricted T-cell repertoire, and impaired T-cell responses in erythrodermic CTCL patients may contribute to the development of KS.Weiterlesen

BackgroundPsoriasis skin lesions are generally thought to occur before psoriatic arthritis (PsA) develops. However, PsA may be challenging to diagnose in the absence of psoriasis and might be underdiagnosed when occurring before psoriasis. We tested the hypothesis that PsA may commonly occur before psoriasis, but without psoriasis skin lesions, is diagnosed as another form of arthritis.MethodsA single-center retrospective chart review was performed to identify patients with qualifying diagnoses from January 1, 2023, until December 31, 2023. This study was performed using electronic health records at a large tertiary care medical center. Inclusion criteria were (1) the presence of inflammatory or non-inflammatory arthritic conditions, (2) prior to the diagnosis of psoriasis, atopic dermatitis, or rosacea. Diagnoses were screened using International Classification of Diseases, Tenth Revision (ICD-10) codes.ResultsDuring 2023, we identified 2780 patients with rosacea, 1672 with psoriasis, and 5195 patients with atopic dermatitis, of whom 436 had preceding arthritis (239 with psoriasis [14.3%], 189 with rosacea [6.8%], and 126 with eczema [2.4%, p < 0.0001]).ConclusionsArthritic symptoms are common in psoriatic patients before psoriasis develops, and psoriasis skin lesions do not necessarily precede psoriatic arthritis.Weiterlesen

IntroductionSB17 is a ustekinumab (UST) biosimilar targeting interleukin-12/23 for treating immune-mediated inflammatory diseases (IMIDs). The development of UST biosimilars like SB17 may help address the high cost of innovator biologics, offering affordable alternatives without compromising efficacy or safety.Areas coveredThis review encompasses the totality of evidence supporting SB17's similarity to UST, its regulatory approval, and indication extrapolation. It also discusses SB17's lower immunogenicity relative to UST.Expert opinionThe approval of UST biosimilars represents a significant advancement in managing chronic IMIDs including psoriasis, plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis, providing cost-effective, efficacious alternatives. A randomized double-blind 28-week study involving over 500 patients with moderate-to-severe chronic plaque psoriasis demonstrated SB17's equivalence to UST, with more than 80% of patients achieving over 90% improvement in psoriasis severity indices. Treatment-emergent adverse events were comparable between SB17 and UST. Despite their potential to transform clinical outcomes, economic burdens, and drug utilization patterns, the adoption of UST biosimilars faces challenges, including concerns about equivalence and regulatory inconsistencies. Addressing these issues through education, consistent regulatory frameworks, real-world data, and ongoing monitoring is crucial for their successful integration into clinical practice.Weiterlesen

Psoriasis is a significant global health challenge due to limited treatment efficacy. Paris saponin VII (PSVII) shows anti-inflammatory and anti-proliferative potential but its role in psoriasis is unclear. In this study, PSVII was identified from a library of natural compounds as a therapeutic candidate for psoriasis. In a murine model, PSVII reduced skin lesion severity, epidermal thickness, and inflammatory factor expression, preliminaryly indicating its anti-inflammatory properties. In vitro, PSVII inhibited HaCaT cell hyperproliferation, regulated the cell cycle, induced apoptosis, and modulated reactive oxygen species (ROS). Bioinformatics analyses suggested that signal transducer and activator of transcription 3 (STAT3), cysteine aspartate specific protease 1 (Caspase-1), and the process of pyroptosis are likely targets and mechanisms of PSVII action. PSVII could reduce cell mortality in psoriatic cells and lowered expression levels of NLR Family Pyrin Domain Containing 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD), Interleukins (IL)-18, and IL-1β, underscoring its potential role in modulating pyroptosis within these cells. Mechanistically, PSVII may suppress the STAT3/nuclear factor kappa B (NFκB) signaling pathway. Consequently, PSVII plays a significant role in psoriasis management. PSVII could modulate pyroptotic cell death in psoriatic cells by targeting the STAT3/NFκB signaling cascade, leading to anti-inflammatory and anti-proliferative effects, and thereby ameliorating psoriasis symptoms.Weiterlesen

BackgroundPsoriasis and psoriatic arthritis are chronic autoimmune inflammatory conditions frequently associated with a range of comorbidities, including oncological diseases. Managing these conditions in patients with a history of cancer requires careful consideration of treatment efficacy and safety. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, has shown promise in the treatment of psoriasis and psoriatic arthritis. However, data on its use in oncological patients remain limited.MethodsThis retrospective observational study evaluated the efficacy and safety of Apremilast in 79 patients with a history of cancer who were treated for psoriasis and/or psoriatic arthritis over a period of approximately five years. Clinical outcomes were assessed using the Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Visual Analog Scale for pain (PAIN VAS) to monitor disease severity, quality of life, and articular involvement, respectively. Regular oncological assessments were conducted concurrently with Apremilast therapy to ensure patient safety and identify potential interactions.ResultsOver the five-year treatment period, significant improvements were observed in PASI, DLQI, and PAIN VAS scores, indicating effective management of both dermatological and articular symptoms. Patients reported enhanced quality of life and reduced pain levels, reflecting the therapeutic benefits of Apremilast. Oncological evaluations revealed no significant adverse interactions between Apremilast and the patients' cancer history or treatments, underscoring the drug's safety profile in this population.ConclusionThis study highlights the efficacy and safety of Apremilast as a treatment option for psoriasis and psoriatic arthritis in oncological patients. The findings support its role in improving disease outcomes and quality of life, emphasizing the importance of personalized treatment strategies in managing complex cases involving a history of cancer. Further research is warranted to validate these results in larger patient cohorts.Weiterlesen

The Psoriasis Area and Severity Index (PASI) is widely used to evaluate psoriatic disease activity in clinical settings; however, its limitations hinder its practicality in routine use. The Simple-Measure for Assessing Psoriasis Severity (S-MAPA) has emerged as a promising tool addressing these limitations, providing a more feasible approach for assessing disease severity. This study aimed to evaluate the S-MAPA as a sensitive and practical alternative to existing instruments for measuring psoriasis severity. Patients with psoriasis were assessed using body surface area (BSA), the Physician's Global Assessment (PGA), S-MAPA, PASI, and Dermatology Life Quality Index (DLQI). Plasma high-sensitivity C-reactive protein (hs-CRP) levels were also measured. Spearman's correlation analysis compared the relationships between these assessment tools and hs-CRP levels. In total, 100 assessments were conducted between January and July 2019. The S-MAPA score and PASI showed a strong positive correlation with disease severity (r=0.9315, p<0.01). Both the S-MAPA score and PASI exhibited comparable correlations with hs-CRP levels (r=0.5299 vs. 0.5316) and the DLQI (r=0.2533 vs. 0.2641). The S-MAPA score demonstrated stronger correlations with the PASI, DLQI, and hs-CRP level than with BSA or the PGA score. The area under the receiver operating characteristic curve for the S-MAPA was 0.9787, with an optimal cut-off value of 138 for predicting severe psoriasis (sensitivity, 92.59%; specificity, 95.89%). Based on our findings, the S-MAPA is a reliable and practical alternative for assessing the severity of psoriasis in clinical practice, offering advantages over conventional measures.Weiterlesen