Psoriasis Area Severity Index Score Research Articles

Whole blood global DNA methylation [5-methylcytosine (5-mC)] levels in psoriatic patients before and after methotrexate treatment

BackgroundPsoriasis is a chronic inflammatory skin disease characterised by hyperproliferation of keratinocytes and abnormal immune response. It manifests in genetically predisposed individuals exposed to environmental triggers like infections, drugs, stress, and trauma. Epigenetic mechanisms are a critical component of the complex etiopathogenesis of psoriasis, as they modulate gene expression and increase disease risk. There are many conflicting reports regarding DNA methylation in patients with psoriasis. This could well reflect the choice of tissue and technique used. Data on whole blood DNA methylation in psoriasis is sparse. ObjectiveThe present study aims to measure the levels of DNA methylation [5-methylcytosine (5-mC)] in psoriatic patients from whole blood pre and post-treatment with methotrexate and its correlation with disease severity. MethodsWe recruited thirty cases of psoriasis vulgaris and 30 healthy controls. Thirty psoriatic patients were on methotrexate treatment and followed up for three months. 5-methylcytosine was measured using a global DNA methylation ELISA kit. ResultsThe 5-methylcytosine levels from whole blood DNA were 8.13±1.89 % in cases and 5.37±2.33 % in controls, which was statistically significant (p = 0.0001). Post-treatment with methotrexate, there was a significant reduction (p = 0.0001) in the 5-methylcytosine levels in cases (4.54±1.74 %). Pre and post-treatment 5-methylcytosine levels were not significantly associated with the Psoriasis Area Severity Index (PASI) score. ConclusionPatients with psoriasis have whole-blood DNA global hypermethylation. Treatment with methotrexate leads to a significant reduction in DNA hypermethylation.

Elevated Serum Levels of Osteopontin in Patients with Psoriasis: Is It Associated with Ocular Comorbidities?

Introduction: Psoriasis is a chronic inflammatory disease affecting 2%-3% of the global population via immune-mediated mechanisms. Osteopontin plays a crucial role in T-helper 1 and T-helper 17-mediated illnesses, including psoriasis. Ocular complications in psoriasis have been reported and their assessment is of importance. Osteopontin is normally expressed constitutively in ocular structures and is linked to ocular homeostasis. Objective: This study aimed to clarify the role of osteopontin (OPN) in psoriasis (PS) and its correlation with disease severity and ocular manifestations. Methods: A case-control study involving 40 psoriatic patients and an equal number of age and sex-matched healthy subjects was conducted. We used the psoriasis area severity index (PASI) to assess disease severity and performed a comprehensive ophthalmological examination. Additionally, we measured serum osteopontin levels using Enzyme-Linked Immunosorbent Assay (ELISA) in both groups. Results: A significant elevation in serum OPN levels in psoriatic patients compared to controls was found (P=0.00). Furthermore, there was a highly significant positive correlation between serum OPN levels and patient age, disease duration, and PASI scores. Notably, a higher prevalence of ocular complications, including blepharitis, corneal affection, conjunctivitis, keratoconjunctivitis sicca, and cataract, in psoriatic patients compared to controls was observed. Importantly, significant associations between serum OPN levels and the presence of cataracts and intraocular pressure (IOP) were identified. Additionally, significant correlations between serum OPN levels and measures of visual acuity and ocular surface health were found. Conclusions: Osteopontin is considered a marker of psoriasis severity and is associated with ocular comorbidities in psoriasis.

Evaluation of nasal mucociliary clearance in patients with psoriasis.

Psoriasis is an autoimmune pathology characterized by chronic inflammation with known multiorgan involvement. In the literature, there are few studies investigating the effects of psoriasis on upper respiratory tract mucosa. Our aim in our study was to investigate the possible effect of psoriasis disease severity and duration on nasal mucosa. A study group was formed from patients with psoriasis and disease duration, Psoriasis Area Severity Index (PASI) and Nasal Obstruction Symptom Evaluation (NOSE) scores of these patients were recorded. Demographic data were noted in all participants with the participation of control group patients, saccharin test was performed to evaluate the nasal mucosa and nasal mucociliary clearance (NMC) times were measured. Psoriasis patients with pathology that may cause nasal obstruction were excluded from the study. A total of 59 people (30 patients and 29 controls) aged 20-65 years were included in the study. There was no difference in age and gender distribution between the two groups. No statistically significant difference in the NMC time between two groups. In the patients group, a correlation was observed between the NMC time to the NOSE test, but no correlation was observed between the NMC time to the duration of the disease and the PASI score. In our study, no difference was observed in NMC time between the two groups and according to the duration or severity of the disease. In addition, NOSE score of patients was also relatively low. No significant impact of psoriasis on nasal functions was found.

Clinical features and effects of cyclosporine in the treatment of psoriasis: a systemic review and meta-analysis.

To systematically evaluate clinical features and effects of cyclosporine in the treatment of psoriasis. Databases including Web of Science, PubMed, The Cochrane Library, Embase, CNKI, Wan Fang, and VIP were electronically searched for studies on the use of cyclosporine in the treatment of psoriasis, from inception to March 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. A meta-analysis was then performed. A total of 12 randomised controlled trial (RCT) studies were included. Compared with the control group, there were statistically significant differences in the effective rate, recurrence rate, erythema regression time, pustular resolution time, fever resolution time, and Psoriasis Area Severity Index (PASI) score of cyclosporine in the treatment of psoriasis. Moreover, the sub-group analysis showed that the effective rate of patients aged less than 40 years was significantly higher than that of the control group and the recurrence rate was significantly lower than that of the control group. The effective rate of psoriasis patients without nail lesions was significantly higher than that of control group. The effective rate of cyclosporin was significantly higher than that of dexamethasone acetate. There was no significant change in pooled sensitivity and specificity after each study was excluded one by one, indicating the stability of the meta-analysis. Cyclosporine had a high effective rate and low recurrence rate in the treatment of psoriasis, but it still had similar rate of adverse reactions compared to other drugs. This study systematically evaluated the effect of cyclosporine in the treatment of psoriasis and provided reference for clinical practice.

Ginseng fruit rare saponins (GFRS) improved inflammatory response: In vitro and in vivo assessment

Inflammation is the body's protective immune response to tissue damage. Ginseng has a long history of medicinal use, and its active ingredient ginsenosides have anti-inflammatory effects. Ginseng fruit rare saponins (GFRS) is a transformation product of ginseng saponins and rich in a variety of rare saponins. We used HPLC-DAD method to study GFRS rare saponins with ginsenoside F4, R-Rg3, SRg3, Rk1, Rg6, Rg5, Rk3 and Rh4. However, there is no study on the use of GFRS to reduce skin inflammation. This study enriched the action pathway of GFRS through network pharmacology and revealed the anti-inflammatory effect of GFRS for the first time. In vitro experiments showed that GFRS could significantly reduce the release of NO in lipopolysaccharide (LPS) -induced RAW264.7 cells and HaCaT cells, and reduce the secretion and expression of inflammation-related factors Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α) and Interleukin-17 A (IL-17 A), thereby reducing cell inflammatory damage. In the imiquimod (IMQ) -induced mouse inflammatory model, the therapeutic effect of GFRS on the pathogenesis of psoriasis-like dermatitis was studied. In vivo experiments showed that the skin erythema, scales, thickness and inflammatory infiltration of GFRS-treated mice were reduced, and the psoriasis area severity index score was significantly lower than that of IMQ group. GFRS restored IMQ-induced spleen size and reduced the secretion and expression of TNF-α, IL-6, Interferon-γ (IFN-γ) and IL-17 A in serum. In summary, our results demonstrate that GFRS alleviates IMQ-induced dermatitis symptoms, effectively reduces the secretion of inflammatory factors, and inhibits IL-17 A expression.

Dihuangzicao Granules Regulate the AGE/RAGE/NF-κB Signaling Pathway to Inhibit Inflammation in Psoriatic Mice via Network Pharmacology and Experimental Validation.

Psoriasis is an immune-mediated skin disease that occurs worldwide and is characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological damage to psoriasis patients. The active ingredients in Dihuang Zicao granules (DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients of DHZCG and their potential mechanisms for treating psoriasis. The effective components of DHZCG were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed. Important molecular biological processes and signaling pathways were screened via GO and KEGG analyses. Molecular docking of the active ingredients and key targets was performed via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group (M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining was performed to determine the pathological changes in the skin of each group of mice, and the Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒ PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was used to measure IL-1β and TNF-a expression in skin tissues. Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding IL-6, TNF-a, AKT1, IL-1β, TP53, NFKB1, BCL2, and MAPK3, were identified. Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL- 23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE signaling pathway. DHZCG reduces inflammation and alleviates psoriasis by downregulating the AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis for the development of drugs for psoriasis and for offering personalized treatment strategies for the clinical management of psoriasis.

Systematic analysis of serum peptidase inhibitor 3 in psoriasis diagnosis and treatment.

Psoriasis is a chronic inflammatory skin disease. To date, there are no serum biomarkers for psoriasis that have been validated to diagnose or treat psoriasis. Peptidase inhibitor 3 (PI3) levels in serum were measured using chemiluminescence immunoassay (CLIA) in two independent cohorts including healthy controls (HC) and patients diagnosed with chronic urticaria (CU), chronic eczema (CE), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis vulgaris (PV). Receiver operating characteristic (ROC) curve analysis determined the diagnostic performance of PI3 in patients with psoriasis. The correlation between PI3 levels and the Psoriasis Area Severity Index (PASI) score was analyzed using the Spearman correlation method. Additionally, the study evaluated PI3 expression and treatment response of PV patients 12weeks before and after topical treatment with calcipotriol betamethasone and calcipotriol ointment (T#1) or topical therapy plus PSORI-CM01 granules (T#2). In cohort #1, PI3 levels effectively discriminate PV patients from HC and CU patients, with AUCs of 0.909 and 0.840, respectively. In cohort #2, AUCs for detecting PV patients among HC, CU, CE, SLE, and RA patients were 0.940, 0.926, 0.802, 0.989, and 0.951, respectively. For PsA patients, AUCs were 0.989, 0.986, 0.910, 1.000, and 0.984 compared to HC, CU, CE, SLE, and RA patients, respectively. In both cohorts, PI3 levels correlated significantly with PASI scores in PV patients (cohort #1, r = 0.433; cohort #2, r = 0.634) and PsA patients (cohort #2, r = 0.718). Moreover, univariate logistic regression analyses revealed that PV patients with higher PI3 expression had a significantly higher risk of treatment resistance, with an odds ratio of 3.45 [95% confidence interval (CI) 1.54, 7.74, p = 0.003]. Finally, PI3 levels decreased nearly 35-fold more in the responder than in the non-responder group before and after treatment. Serological PI3 is a reliable biomarker for PV diagnosis and may have the potential to predict and monitor the progression of PV before and after treatment. Key Points • This study validated PI3's diagnostic performance in two independent psoriasis cohorts using CLIA. • PI3 expression is significantly correlated with the psoriasis severity and with patients who benefited from the treatments. • Serological PI3 is a reliable biomarker for psoriasis diagnosis and may have the potential to monitor the psoriasis progression with and without treatments.

Serum Interleukin (IL)-6, Lipid Profile, and Association With Disease Severity in Patients With Psoriasis: A Cross-Sectional Study.

This study estimated the lipid profile and inflammatory biomarker (interleukin-6, IL-6) levels in patients with psoriasis and explored the association between lipid profiles and inflammatory biomarkers (IL-6) in assessing the severity of the disease. This cross-sectional study was conducted in the Department of Biochemistry, in association with the Department of Dermatology, at the Veer Surendra Sai Institute of Medical Sciences and Research, Burla, from November 2022 to June 2023. A fully automated analyzer (Cobas C311, Roche Diagnostics, Mannheim, Germany) was used to estimate the lipid profile, while the enzyme-linked immunosorbent assay (Erba, Transasia Bio-medicals Ltd., Mumbai, India) was used to estimate the inflammatory marker (IL-6). Data were analyzed using Statistical Package for the Social Sciences version 21.0 (IBM Corp., Armonk, NY). An unpaired t-test was conducted to examine the relationship between two variables. A p value of <0.05 was considered significant. The correlation among IL-6, lipid profile, and psoriasis area severity index (PASI) score was analyzed using Pearson's correlation coefficient. Quantitative data were expressed as means and standard deviations. Of the 102 study participants, 68 had psoriasis alone, and 34 had psoriasis with arthritis (psoriatic arthritis, PsA). Higher mean serum concentrations of IL-6, total cholesterol (TC), low-density lipoprotein, and triglycerides were found in patients with PsAcompared to those with psoriasis alone. In patients with PsA, TCand IL-6showed a strong positive correlation with the PASIscore. In contrast, high-density lipoprotein showed a negative correlation with PASI (r = -0.036, p < 0.05). In conclusion, our study revealed lipid profile abnormalities and increased IL-6activity in PsA patients. By measuring inflammatory markers (IL-6) and lipid profiles early in the disease process, we can employ preventive strategies to better manage and improve survival and quality of life in patients with psoriasis.

Dysbiosis of pro-inflammatory and anti-inflammatory salivary cytokines during psoriasis providing a therapeutic window and a valuable diagnostic aid in future.

The objective of this article is to evaluate the salivary levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 in patients with active psoriasis and compare them with those in healthy control subjects. This study included 60 subjects who were clinically diagnosed cases with active psoriasis (categorized further into 33 mild to moderate and 27 severe cases based on the Psoriasis Area Severity Index score) and 60 age- and gender-matched healthy control subjects. Levels of TNF-α, IFN-γ, IL-2, and IL-10 in the unstimulated saliva of subjects were determined via enzyme-linked immunosorbent assay (BT Lab). The salivary levels of TNF-α, IFN-γ, and IL-2 were significantly higher, whereas IL-10 concentration was significantly reduced in psoriatic patients in comparison to controls, and the difference increased with the progressing severity of the disease. Assessment of cytokine profiles in psoriasis patients is significant for diagnostic validation and monitoring the disease severity. Saliva offers an alternate, noninvasive, and readily available biological sample for evaluating cytokine levels. Extensive research in this field has been recommended for better scientifically proven conclusions.

Psoriasis treatment and biologic switching: The association with clinical characteristics and laboratory biomarkers over a 13-year retrospective study.

The advent of biologics has greatly improved patient outcomes, yet some patients are compelled to switch therapies. Predicting these therapeutic failures is important; however, the factors associated with switching biologics have not been fully explored. This study examined patterns and determinants of biologics switching in psoriasis treatment retrospectively over 13 years. We focused on the association between clinical characteristics, basal laboratory data, and frequency of biologics switching. The findings revealed that elevated Psoriasis Area Severity Index scores and the presence of arthritis were observed in patients who experienced two or more treatment switches compared with those without treatment switches. Moreover, neutrophil to lymphocyte ratio was associated with higher biologics switching rates, indicating that systemic inflammation significantly impacts treatment adherence. A treatment approach, taking into account both the clinical presentation and inflammatory biomarkers, may be important for optimizing patient management in psoriasis.

Rapid Efficacy of riSankizumab in pretibial psoriasis invOLVEment: RESOLVE.

Despite extraordinary improvements in the management of psoriasis in recent times, some areas of the body, such as the pretibial area, still show an unsatisfactory response and a more significant impact on patient quality of life. This multicentre study focuses on psoriasis affecting sensitive areas (particularly the pretibial area), its impact on quality of life and the therapeutic response to risankizumab. This multicentre prospective observational study recruited patients with moderate-to-severe psoriasis with pretibial area involvement. All patients underwent treatment with risankizumab (150 mg every 3 weeks), and efficacy was assessed after 24 weeks. The study included 128 patients with a mean age of 51 years, suffering from moderate-to-severe psoriasis with involvement of the pretibial area with median total Psoriasis Area Severity Index score of 17.05 and Dermatology Life Quality Index of 16.27. The group was further divided into two sub-groups: the 'mother patch' group, in whom the very first psoriatic plaque appeared in the pretibial region (45 patients), and the 'non-mother patch' group, in whom the psoriatic lesion in the pretibial region was present but not as the first manifestation (83 patients). In order to better assess the involvement of psoriasis in the pretibial area, the pretibial plaque lesion severity index was also calculated at baseline in all patients: extent 2.75, erythema 2.64, infiltration 2.45 and desquamation 2.38. All participants in this study showed a good therapeutic response, with a reduction in all scores. The pretibial area is becoming an object of therapeutic interest due to some resistance to clearance and the consequent impairment of patient quality of life. This study showed that risankizumab can give favourable therapeutic results not only in patients with moderate-to-severe psoriasis with involvement of the difficult-to-treat areas but particularly in patients with recalcitrant plaques in the pretibial area.

Expert consensus on systemic therapy for plaque psoriasis with limited skin involvement in JAPAN: Results from a DELPHI study.

Our objective was to establish consensus on (1) which patients with plaque psoriasis and limited skin involvement (body surface area [BSA] <10%) are suitable for systemic treatment, and (2) a definition of 'topical therapy failure'. A steering committee refined 13 statements drawn from literature related to the study objectives. An independent panel of 45 clinical experts from Japan indicated their agreement to each statement using a 10-point Likert scale (Round 1; strong consensus, ≥70% of responses = 7-10 and median value ≥8). The steering committee reviewed Round 1 results and refined the statements for Round 2, as necessary. In Round 2, the panel indicated their agreement to each statement using a 3-point scale (strong consensus, ≥70% of responses and median value of 3) and were shown Round 1 responses before voting. Forty-five clinicians participated in Round 1 and 41 of those (91%) participated in Round 2. Consensus was achieved on the criteria of eligibility for systemic treatment among patients with limited skin involvement as disease involvement at special or difficult to treat areas, psoriasis-induced psychological distress, uncontrolled symptoms (e.g., scaling, bleeding, pruritus, insomnia) affecting their social life, psoriatic arthritis, or failure of topical therapy. Consensus on criteria for topical failure were persistent symptoms (e.g., itchiness, pain) and plaques, poor patient satisfaction with treatment, a need to increase medication quantity or application time after treatment with two topicals for 4 weeks; or if the Psoriasis Area Severity Index score of >3 or Physician Global Assessment Score of ≥2 after 8 weeks treatment. Our Delphi panel proposes criteria to help physicians identify patients with psoriasis and limited skin involvement who would benefit from systemic therapy and suggests a definition for topical therapy 'failure' which could indicate a move to systemic treatment is warranted.

Predicting psoriasis severity using machine learning: A systematic review.

In dermatology, the applications of machine learning (ML), an artificial intelligence (AI) subset that enables machines to learn from experience, have progressed past the diagnosis and classification of skin lesions. A lack of systematic reviews exists to explore the role of ML in predicting the severity of psoriasis. This systematic review aims to identify and summarize the existing literature on predicting psoriasis severity using ML algorithms and identify gaps in current clinical applications of these tools. OVID Embase, OVID MEDLINE, ACM Digital Library, Scopus, and IEEE Xplore were searched from inception to August, 2024. A total of 30 articles met our inclusion criteria and were included in this review. One article used serum biomarkers, while the remaining 29 used image-based models. The most common severity assessment score employed by these ML models was the Psoriasis Area Severity Index score, followed by Body Surface Area, with fifteen and five articles, respectively. The small size and heterogeneity of the existing literature are the primary limitations of this review. Progress in assessing skin lesion severity through ML in dermatology has advanced, but prospective clinical applications remain limited. ML and AI promise to improve psoriasis management, especially in non-image-based applications requiring further exploration. Large-scale prospective trials using diverse image datasets are necessary to evaluate and predict the clinical value of these predictive AI models.

Bacteria, Fungi, and Scalp Psoriasis: Understanding the Role of the Microbiome in Disease Severity.

Background: Psoriasis is a chronic skin condition affected by genetic and environmental factors. Changes in the skin microbiome may affect the immune system and skin barrier functions, thereby contributing to the development and progression of psoriasis. The scalp, which is a common site for psoriasis, is often resistant to therapy. Although several studies have investigated the scalp microbiome, analyses focusing on both bacteria and fungi remain scarce. Methods: We examined the scalp microbiomes of 11 patients with psoriasis complicated with scalp lesions and categorized them according to their Psoriasis Area Severity Index (PASI) scores. The bacterial and fungal data were analyzed using QIIME2 pipeline version 2021.04 and the UNITE database version 8.3, respectively. Results: The Shannon indices for mild (2 patients), moderate (4 patients), and severe (5 patients) groups were 0.97, 1.38, and 1.88, respectively. A significant correlation was observed between increased mycobiome diversity and disease severity (p = 4.07 × 10-5, Spearman's correlation: 0.9269). Compared with the mild and moderate groups, the severe group exhibited a higher abundance of Malassezia globosa. Pseudomonas and Staphylococcus were, respectively, more prevalent in the moderate and severe groups than in the mild group. Conclusions: This study highlights the potential role of increased fungal diversity and specific microbial compositions in the severity of scalp psoriasis, suggesting a possible avenue for targeted therapeutic interventions.

Helicobacter pylori infection in psoriatic patients and its relation to psoriasis severity: Cross Sectional Study.

Psoriasis is a prevalent inflammatory skin condition that can be recognized by silvery-white scales on plaques and erythematous papules, despite the fact that psoriasis appears to have multiple causes. Helicobacter pylori (H. pylori) has been investigated recently as a potential infectious etiological component. The objective of the study was to evaluate the prevalence of H. pylori infection in psoriatic patients compared to that of healthy controls and determine whether the degree of psoriasis and H. pylori infection were related. The dermatology, venerology, and andrology department at South Valley University Outpatient Clinic carried out this cross-sectional study. Psoriatic patients of both sexes and ages were included. In addition to the control group, H. Pylori antigen was measured from psoriatic and control groups by using H. pylori stool antigen-enzyme linked immunosorbent assay (HpSA-ELISA), a test for H. pylori stool antigen. More than 20ng/mL of antigen proved positive, or less than 15ng/mL proved negative. There was a significant difference between psoriatic patients and control regarding H. pylori infection (p=0.046): (30.66%) positive in controls, (45.33%) positive in psoriatic patients. Both groups were matched for age (p=0.908), that is, the mean age of psoriatic patients was 37.44±15.79 years, and the control group was 37.15±15.15 years. Twenty-five psoriatic patients in each group: mild, moderate, and severe psoriasis according to the Psoriasis Area Severity Index (PASI) score. No significant correlation between H. pylori infection and PASI, age, or duration of illness in psoriatic patients. Patients with psoriasis had greater rates of H. pylori infection but didn't affect the severity of psoriasis.

Etanercept versus Methotrexate in the Treatment of Psoriasis and Associated Metabolic Syndrome: 12 Months Open-Label Comparative Study.

Psoriasis is a chronic inflammatory systemic disease accompanied by systemic damage that leads to the development of multiple comorbidities including metabolic syndrome. Conventional systemic therapies for psoriasis are associated with toxicity and have a greater burden on the patients. The study aimed to assess the effectiveness of etanercept (ETN) monotherapy in comparison to methotrexate (MTX) monotherapy. In this prospective interventional comparative open-label study, 117 patients with psoriasis were randomized to 2 groups; one group of 42 patients; 32(67.2%) males and 10(23.8%) females treated with MTX, and the second group of 75 patients; 54(72%) males and 21(28%) females treated with ETN. Full laboratory investigations, body mass index (BMI), measurement of skin disease severity which was performed using Psoriasis Area Severity Index (PASI), and the reduction of 75% of the skin lesions (PASI 75) were calculated for all participants. In the MTX group, there were no significant differences in BMI, or blood pressure after 12 weeks of the study. There is a reduction in the values of FBS, TSC, LDL, TRIG, ESR, CRP, and PASI, but this reduction was statistically not significant. Ten (23.8%) patients achieved PASI 75. In the ETN group, except for BMI, systolic and diastolic blood pressure, all other metabolic syndrome components, inflammatory markers, and PASI were decreased; the reduction was statistically significant. Sixty (80%) patients achieved PASI 75. Etanercept monotherapy is superior to methotrexate monotherapy in the treatment of moderate to severe plaque-type psoriasis as it achieved greater reductions in PASI score and greater achievement of PASI 75 after 12 weeks. Etanercept monotherapy is superior to methotrexate monotherapy in the improvement of all components of the associated metabolic syndrome except for BMI, which was increased in etanercept-treated patients.

Tetrastigma hemsleyanum polysaccharides alleviate imiquimod-induced psoriasis-like skin lesions in mice by modulating the JAK/STAT3 signaling pathway

BackgroundThe pathogenesis of psoriasis involves the interaction between keratinocytes and immune cells, leading to immune imbalance. While most current clinical treatment regimens offer rapid symptom relief, they often come with significant side effects. Tetrastigma hemsleyanum polysaccharides (THP), which are naturally nontoxic, possess remarkable immunomodulatory and anti-inflammatory properties. MethodsIn this study, we utilized an imiquimod (IMQ)-induced psoriasis mouse model and a LPS/IL-6-stimulated HaCaT model. The potential and mechanism of action of THP in psoriasis treatment were assessed through methods including Psoriasis Area Severity Index (PASI) scoring, histopathology, flow cytometry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR). ResultsPercutaneous administration of THP significantly alleviated symptoms and manifestations in IMQ-induced psoriatic mice, including improvements in psoriatic skin appearance (erythema, folds, scales), histopathological changes, decreased PASI scores, and spleen index. Additionally, THP suppressed abnormal proliferation of Th17 cells and excessive proliferation and inflammation of keratinocytes. Furthermore, THP exhibited the ability to regulate the JAK/STAT3 signaling pathway. ConclusionFindings from in vivo and in vitro studies suggest that THP can inhibit abnormal cell proliferation and excessive inflammation in lesional skin, balance Th17 immune cells, and disrupt the interaction between keratinocytes and Th17 cells. This mechanism of action may involve the modulation of the JAK/STAT3 signaling pathway, offering potential implications for psoriasis treatment.

Unlocking milk thistle’s anti-psoriatic potential in mice: Targeting PI3K/AKT/mTOR and KEAP1/NRF2/NF-κB pathways to modulate inflammation and oxidative stress

Silybum marianum, known as milk thistle (MT), is traditionally used to manage liver diseases. This study aimed to investigate the role of MT extract topical application as a potential treatment for imiquimod (IMQ)-induced psoriatic lesions in mice with particular emphasis on phosphoinositol-3 Kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and Kelch-like ECH-associated protein 1 (KEAP1)/ nuclear factor erythroid-2-related factor (NRF2)/ nuclear factor-kappa B (NF-κB) molecular cascades involvement. To address this aim, forty male Swiss albino mice were subdivided into four groups (n = 10 mice/group): control, IMQ model, standard group where mice were treated topically with IMQ, then the anti-psoriatic mometasone cream, and MT extract-treated group where mice were treated topically with IMQ followed by MT extract. In most measured parameters, MT extract, rich in silymarin, exhibited potent anti-psoriatic activity comparable to the standard cortisone treatment. MT extract mitigated dorsal skin erythema, scaling, and epidermal thickening, reflected by lowering the Psoriasis Area Severity Index (PASI) score. Moreover, it alleviated IMQ-induced splenomegaly. Mechanistically, the PI3K/AKT/mTOR pathway was the main functional pathway behind such improvements, where it was significantly inhibited by MT extract application. This led to NRF2 activation via KEAP1 downregulation with subsequent anti-inflammatory effect proven by reducing NF-κB, interleukin (IL)–23, and IL-17A and antioxidant ability proven by boosting the antioxidant glutathione and heme oxygenase-1. Such improvements were confirmed by alleviating the histopathological alteration. Thus, MT extract could be a promising therapeutic agent for psoriasis treatment by inhibiting PI3K/AKT/mTOR cascade, along with NRF2 signaling activation.

Relationship of psoriatic arthritis with nail and scalp involvement in Turkish psoriasis patients: Multicentered cross-sectional study.

Psoriasis is a common multisystem inflammatory disease, and arthritis is an essential component of the disorder, requiring early diagnosis and prompt treatment for successful management. In this study, we aimed to investigate the relationship between nail and scalp involvement and other covariates with psoriatic arthritis (PsA). This cross-sectional study, conducted from June 2021 through December 2021, included 763 patients from 11 different centers in Turkey. The severity of involvement was evaluated using psoriasis area severity index (PASI), nail psoriasis severity index (NAPSI), and psoriasis scalp severity index (PSSI) scores. Predictors for PsA were evaluated using univariate and multivariate logistic regression models. PsA (n = 155, 21.5%) was significantly more common in patients having a family history of psoriasis (43.2% vs 30.9%, P = .004), nail involvement (68.4% vs 52.3%, P < .001), and coexistence of nail and scalp involvement (53.7% vs 39.6%, P = .002). Furthermore, patients with PsA had considerably higher PASI (7 vs 5.6, P = .006), NAPSI (5 vs 2, P < .001), and PSSI scores (7 vs 4, P = .002) and longer disease duration (months) (126 vs 108, P = .009). In multivariate analysis, female gender [OR: 3.01, 95% CI (1.861-4.880), P < .001], nail involvement [OR: 2.06, 95% CI (1.293-3.302), P = .002)], and body mass index (BMI) [OR: 1.06, 95% CI (1.017-1.100), P = .005] were identified as independent predictors for PsA. Female gender, nail involvement, and high BMI are significant predictors for PsA and warrant detailed rheumatological assessment. Notably, being female is the strongest predictor of increased risk of PsA in our survey. Scalp involvement appears not to be associated with PsA. Also, the presence of PsA seems related to a more severe skin involvement phenotype.

Inflammatory Cytokines and Clinical Outcome Following Biological Therapy in Adult Bio-Naïve Psoriasis Patients.

Inflammatory cytokines may hold the key to the clinical evolution of psoriasis. The aims of this study are to find a correlation between levels of inflammatory cytokines such as TNF-α, IL-23, IL-17A, and IL-17F and disease duration and severity scores in psoriasis; to test if the decrease in any of the aforementioned cytokines is correlated with an amelioration in disease severity scores; and to analyze if any of the four biologic agents used are linked with a greater decrease in overall cytokine levels. We enrolled 23 adult patients under treatment with ixekizumab, secukinumab, guselkumab, or adalimumab and measured psoriasis disease severity scores PASI (Psoriasis Area Severity Index) and DLQI (Dermatology Life Quality Index), as well as the levels of the aforementioned cytokines at the start of therapy and after 3 months of continuous treatment. Inclusion criteria were the presence of psoriasis, age above 18 years and the need to initiate biological therapy (lack of response to standard treatment). Biological therapies resulted in an amelioration of PASI and DLQI scores, as well as levels of TNF-α, IL-23 and IL-17F. Disease duration and PASI and DLQI scores did not correlate with cytokine levels except DLQI and IL-23 score, in a paradoxically inversely proportional manner. IL-23, in particular, could be a useful biomarker for checking treatment response in psoriasis.