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Objective: The aim of the present study was to investigate whether psoriasis disease constitutes a risk factor for OLP, by assessing the prevalance of psoriasis in a test group with OLP and the control group without. Method and materials: A cohort of consecutive patients diagnosed clinically and histologically with OLP between 2014 and 2022 was analyzed. The results were contrasted with those obtained in control series matched for age and sex. The correlations between OLP and sex, age, tobacco, alcohol consumption, and psoriasis were assessed using Pearson chi-square test. Multivariate regression analysis was performed to evaluate the association between psoriasis and OLP. For the assessment of the quality of the statistical models, the Akaike information criterion was used. Results: The study involved 1,016 patients; 738 women (72.6%) and 278 men (27.4%). The average age was 59.38 ± 12.55 years. Of 508 patients with OLP, 16 (3.15%) had comorbid psoriasis, and this was 5 (0.98%) in the control group. Age, sex, smoking, and alcohol habits were not predictive variables in the relationship between psoriasis and OLP in these patients. There were statistically significant differences in relation to the number of locations, with greater extension in patients with OLP and psoriasis (P = .002). According to the multivariate analysis, the odds ratio of OLP for psoriasis was 3.13 (95% CI 1.20-9.68). Conclusions: This is the first study showing the potential association between psoriasis and OLP, and the results should be considered to improve knowledge of comorbidity of OLP. Based on the results, it is recommended that clinicians collect data regarding history of psoriasis in patients with OLP, and consider possible multiple intraoral locations. [ABSTRACT FROM AUTHOR]

Psoriasis, a chronic inflammatory skin disease, is associated with systemic complications that extend beyond cutaneous lesions, including cardiovascular risks and sexual dysfunction. Erectile dysfunction (ED) is notably more prevalent in male psoriasis patients, likely driven by both systemic inflammation and psychological stress. Adalimumab (ADA), a tumor necrosis factor-alpha (TNF-α) inhibitor, has been shown to effectively reduce psoriasis severity, but its effects on sexual and reproductive health remain underexplored. This study investigates the impact of ADA on erectile function, sperm parameters, and hormonal profiles in male psoriasis patients. This six-month prospective observational study included 33 biologic-naïve male patients aged 18–50 years with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] > 10). Patients received ADA according to standard clinical protocols. Erectile function was assessed using the International Index of Erectile Function (IIEF-5). Sperm parameters, including ejaculate volume, sperm concentration, total sperm count, motility, vitality, and morphology, were analyzed following World Health Organization (WHO) 2010 criteria. Hormonal profiles (testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and prolactin) were measured via standardized assays. Statistical analyses were performed using paired t-tests or Wilcoxon signed-rank tests, with p-values < 0.05 considered significant. ADA significantly improved erectile function, as the mean IIEF-5 score increased from 21.3 ± 2.2 to 22.2 ± 1.9 (p = 0.03). The percentage of patients with ED decreased from 51.5% at baseline to 36.4% post-treatment (p < 0.001). Progressive sperm motility and vitality showed statistically significant improvement post-treatment (p = 0.02 and p = 0.04, respectively), while other sperm parameters remained unchanged. Total testosterone levels significantly increased from 3.4 ± 0.4 ng/ml to 3.5 ± 0.4 ng/ml (p = 0.02), while LH, FSH, estradiol, and prolactin levels showed no significant changes. The anti-inflammatory properties of adalimumab, through the inhibition of TNF-α, not only reduce psoriasis severity but also appear to exert positive effects on male sexual and reproductive health. Our study demonstrated significant improvements in erectile function, sperm motility, vitality, and testosterone levels in male psoriasis patients after adalimumab therapy. These findings suggest that beyond its role in controlling psoriatic skin lesions, adalimumab may help mitigate the systemic inflammatory burden that contributes to sexual dysfunction and impaired spermatogenesis. Future long-term studies are essential to further explore the sustained impact of TNF-α inhibition on male fertility and reproductive outcomes. [ABSTRACT FROM AUTHOR]

Psoriasis, an autoimmune inflammatory disease characterized by hyperproliferation of keratinocytes, affects 0.2–4.8% of the global population. The disease manifests primarily as plaque psoriasis, causing chronic physical and psychological burdens. Although numerous treatments exist, there is ongoing exploration for novel therapies due to concerns about the toxicity, efficacy, and costs of current options. An A3 adenosine receptor (A3AR) agonist called Piclidenoson has been shown to reduce inflammation and could be used to treat moderate to severe psoriasis. This meta-analysis evaluates the safety and efficacy of Piclidenoson in psoriasis treatment. This meta-analysis was conducted accordance with the PRISMA guidelines and has been registered on PROSPERO (CRD42024566459). A comprehensive search on Cochrane CENTRAL, PubMed/MEDLINE, and Google Scholar was conducted up to July 2024. Included studies were randomized controlled trials (RCTs) involving Piclidenoson. Efficacy outcomes included PASI 75 and PGA 0 or 1, while safety outcomes included adverse events. Pooled outcomes were presented as odds ratio (OR) with 95% confidence intervals (CI). Statistical analysis employed the Mantel-Haenszel random-effects model, and heterogeneity was assessed using the I2 and X2index. Three RCTs with 574 patients (313 Piclidenoson, 261 placebo) met the inclusion criteria. The pooled analysis showed no significant difference in achieving PASI 75 between Piclidenoson and placebo (OR: 1.62, 95% CI 0.70–3.75, P = 0.26, I2 = 12%). However, Piclidenoson significantly improved PGA scores (OR: 2.74, 95% CI 1.22–6.16, P = 0.01, I²=0%). Safety assessment revealed no significant differences in adverse events, including nervous system, gastrointestinal, musculoskeletal, renal, and infections, compared to placebo. Piclidenoson demonstrates a significant improvement in PGA scores and a favorable safety profile, suggesting it could be a valuable addition to plaque-like psoriasis treatment. Further research with larger, longer-term RCTs is needed to confirm its efficacy and optimize clinical use. [ABSTRACT FROM AUTHOR]

Psoriasis is chronic autoimmune inflammatory skin disorder affecting millions of people worldwide (2–3% of world population). Treatment of psoriasis ranges from use of topicals to biologicals. Although topical treatments are preferred for mild to moderate cases of psoriasis, the thickened, inflamed skin, and the absence of moisturizing properties make conventional topical treatment challenging, hindering the effective management of the condition. The hydrogel-based systems are reported to be excellent vehicles and carriers for overcoming the barriers in topical delivery of drugs by hydrating the thick plaques and providing controlled release of medicament into the tough scaly skin. Recently, many nanocarrier loaded hydrogels-based system has gained popularity for effective delivery of drugs across psoriatic skin. The present review focuses on psoriasis, the deviation from normal skin in psoriatic condition which renders the effective delivery of drugs through topical route a greater challenge and how hydrogels-based system can effectively help alleviate psoriasis through effective drug delivery across the hyperkeratinized skin. In summary, hydrogels have emerged as effective carriers in psoriasis treatment as they provide a soothing effect, better patient acceptance, good penetration, controlled, sustained, and even smart drug release thus providing relief along with treatment. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, psoriasis is a prevalent chronic inflammatory cutaneous disease featured with the development of red plaque with silvery scales, which considerably affects cutaneous health and quality of life of those afflicted. Objective: This research aimed to examine the association between the body roundness index (BRI) and psoriasis, using data sourced from the National Health and Nutrition Examination Survey (NHANES). Methods: Our study used a cross-sectional design, including 8,479 adults, of whom 234 were diagnosed with psoriasis. Multivariable logistic regression was used to analyze the relationship between BRI and psoriasis, with stepwise adjustments for covariables. Results: Results from multivariable logistic regression analyses indicated a significant positive relationship between BRI and the risk of developing psoriasis; specifically, after comprehensive adjustment for covariables, per 1 unit increase in BRI was linked to an 11% rise in psoriasis risk (OR = 1.11, 95% CI = 1.05–1.17). Furthermore, psoriasis patients exhibited higher average BRI compared to non-psoriasis patients and a greater prevalence of comorbidities such as hypertension and smoking. Conclusion: These findings suggest that higher BRI is positively correlated with the risk of psoriasis in the adult population in the US. BRI could potentially act as a practical anthropometric index for more accurately predicting the risk of developing psoriasis. [ABSTRACT FROM AUTHOR]

Inflammatory dermatologic diseases have long been viewed as a "skin limited" disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms. Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states. The limited current literature shows potential for links between inflammatory skin diseases and hypercoagulable states. Biomarkers such as F1 + 2, D-dimer, eosinophilic cationic protein, and PAI-1 are currently being studied to outline the mechanisms connecting inflammatory skin disease to the coagulation system. Further study and larger amounts of data are needed to draw definitive conclusions, especially when interpreting biomarkers alone such as PAI-1. The mechanisms, rates of systemic inflammation, and clinical outcomes of traditionally "skin limited" inflammatory diseases remain chronically understudied in dermatology. Many organ systems have well established connections between inflammatory disease and hypercoagulable states, but there are significant gaps in the literature regarding skin diseases. There is a significant need for comprehensive investigation of molecular mechanisms behind inflammatory dermatologic disease and hypercoagulability, how hypercoagulability effects clinical outcomes, and proper intervention to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR-T) cell therapy is a new treatment for cancers, but reports on curing immune-related skin diseases are limited. We report a case of successful CAR-T-cell therapy in a patient with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) who was incidentally cured of chronic generalized plaque psoriasis. The patient, a 65-year-old male who had a known history of psoriasis for 45 years, did not receive immunotherapy for psoriasis during this period. Imaging, molecular biology and immunology diagnostics confirmed DLBCL. After several weeks of standard-dose R-CHOP chemotherapy, the patient achieved partial remission, but according to CT, the patient relapsed, and there was no significant improvement in her psoriasis symptoms. Subsequently, the patient was enrolled in the CD19 CAR-T-cell therapy group. Four weeks after CAR-T-cell infusion, the patient's abdominal pain disappeared, and there was a significant improvement in overall skin lesions. One year later, follow-up results indicated complete remission of R/R DLBCL (confirmed by PET-CT), with only minimal residual psoriatic skin lesions limited to the patient's neck. The results of using CAR-T-cell therapy to achieve an incidental cure for psoriasis highlight the potential for exploring cell-based therapies for complex autoinflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis, a persistent skin condition caused by the disorder of the immune system, impacts approximately 1.25 million individuals globally. Nevertheless, the presence of adverse effects in conventional clinical drugs necessitates further exploration of novel medications or combination therapies to mitigate these reactions and enhance their effectiveness. Methods: Hence, our intention here in this paper is to utilize the lipid nanoparticle delivery system for overcoming the volatility and hydrophobic properties of α-pinene, a naturally occurring compound renowned for its anti-inflammatory and antiviral effects, and further explore its potential pharmacological applications both in vitro and in vivo. Results: The production of α-pinene lipid nanoparticles (APLNs) was achieved through the utilization of high pressure homogenization methods. APLNs was successfully fabricated with enhanced stability and water solubility. Meanwhile, the application of APLNs could drastically reduce the expression of lipopolysaccharide (LPS)-induced inflammation-related factors in THP-1 cells. Administration of APLNs to a mouse model of auricular swelling could effectively reduce redness and swelling in the auricles of mice as well. Furthermore, APLNs were also found to alleviate skin damage in mice with Imiquimod (IMQ)-induced psoriasis model, as well as decrease the levels of psoriasis-related protein nuclear factor kappa-B (NF-κB) and interleukin-17 (IL-17), interleukin-23 (IL-23), and other inflammation-related cytokines. More importantly, utilization of APLNs successfully mitigated the systemic inflammatory reactions in mice, resulting in the reduction of spleen-to-body ratio (wt%) and of inflammatory cytokines' expression in the serum. Discussion: Overall, our results suggest that with the help of lipid nanoparticle encapsulation, APLNs possess a better pharmacological effect in anti-inflammation and could potentially serve as an anti-psoriasis drug. [ABSTRACT FROM AUTHOR]

Background: The physiological relevance of cell-to-cell communication mediated by small extracellular vesicle-encapsulated microRNAs (sEV-miRNAs) remains debated because of the limiting representativity of specific miRNAs within the extracellular pool. We hypothesize that sEV-miRNA non-canonical function consisting of the stimulation of Toll-like receptor 7 (TLR7) may rely on a global shift of the sEV cargo rather than on the induction of one or few specific miRNAs. Psoriasis represents an ideal model to test such hypothesis as it is driven by overt activation of TLR7-expressing plasmacytoid dendritic cells (pDCs) following keratinocyte damage. Methods: To mimic the onset of psoriasis, keratinocytes were treated with a cocktail of psoriatic cytokines or UV-irradiated. SmallRNA sequencing was performed on sEVs released by healthy and UV-treated keratinocytes. sEV-miRNAs were analyzed for nucleotide composition as well as for the presence of putative TLR7-binding triplets. Primary human pDCs where stimulated with sEVs +/- inhibitors of TLR7 (Enpatoran), of sEV release (GW4869 + manumycin) and of TLR7-mediated pDC activation (anti-BDCA-2 antibody). Secretion of type I IFNs and activation of CD8+T cells were used as readouts. qPCR on psoriatic and healthy skin biopsies was conducted to identify induced miRNAs. Results: sEV-miRNAs released by damaged keratinocytes revealed a significantly higher content of TLR7-activating sequences than healthy cells. As expected, differential expression analysis confirmed the presence of miRNAs upregulated in psoriatic skin, including miR203a. More importantly, 76.5% of induced miRNAs possessed TLR7-binding features and among these we could detect several previously demonstrated TLR7 ligands. In accordance with this in silico analysis, sEVs from damaged keratinocytes recapitulated key events of psoriatic pathogenesis by triggering pDCs to release type I interferon and activate cytotoxic CD8+T cells in a TLR7- and sEV-dependent manner. Discussion: Our results demonstrate that miR203a is just one paradigmatic TLR7-activating miRNA among the hundreds released by UV-irradiated keratinocytes, which altogether trigger pDC activation in psoriatic conditions. This represents the first evidence that cell damage shifts the miRNA content of sEVs towards a TLR7-activating cargo capable to propagate inflammation and immunity, offering strong support to the physiological role of systemic miRNA-based cell-to-cell communication. [ABSTRACT FROM AUTHOR]

Since nail psoriasis restricts the patient's daily activities, therapeutic intervention based on reliable and reproducible evaluation is critical. The Nail Psoriasis Severity Index (NAPSI) is a validated scoring tool, but its usefulness is limited by interobserver variability. This study aimed to develop a reliable and accurate NAPSI scoring tool using deep learning. The tool "NAPSI calculator" includes two parts: nail detection from images and NAPSI scoring. NAPSI was annotated by nine nail experts who are board-certified dermatologists with sufficient experience in a specialized clinic for nail diseases. In the final test set, the "NAPSI calculator" correctly located 137/138 nails and scored NAPSI with higher accuracy than the compared six non-board-certified residents: 83.9% vs 65.7%; P = 0.008 and four board-certified non-nail expert dermatologists: 83.9% vs 73.0%; P = 0.005. The "NAPSI calculator" can be readily used in a clinical situation, contributing to raising the medical practice level for nail psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Emerging evidence suggests that psoriasis and periodontitis are linked via systemic inflammation. However, the role of angiogenesis as an additional connecting mechanism between these diseases remains unclear. Methods: This case control study explored the effect of psoriasis on the gingival crevicular fluid (GCF) levels of vascular endothelial growth factor A (VEGF-A) in patients with different stages of periodontitis. Thirty-one patients with psoriasis (P) and thirty healthy controls (C) underwent physical and intraoral evaluations, with diagnoses confirmed by dermatologists and periodontists. GCF VEGF-A was measured using a multiplex-bead immunoassay. Statistical analyses included Fisher exact tests, Student's T-tests, linear regression models, and mediation analyses. Results: Psoriasis patients had significantly lower GCF VEGF-A levels compared to controls (p =0.008). Psoriasis was negatively associated with GCF VEGF-A (p =0.006), while severe periodontitis was positively associated with GCF VEGF-A levels, regardless of tobacco use (p =0.027). Further analyses revealed that severe periodontitis significantly increased GCF VEGF-A levels only in the C group (p =0.038), but not in psoriasis patients (p >0.610). Mediation analyses confirmed a significant direct and total effect of psoriasis on GCF VEGF-A (p >0.002), with no significant indirect effect through periodontitis (p =0.699). Discussion: Psoriasis and severe periodontitis are associated with GCF levels of VEGF-A in opposite and independent ways. In subjects with psoriasis, the impact of the dermatosis is direct with no mediation from periodontitis. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common autoimmune and chronic inflammatory dermatological disease that is mainly associated with aberrant immune response and oxidative stress (OS). OS, a crucial pathogenic factor in psoriasis, contributes to psoriasis-like inflammation mediated by the IL-23/IL-17 inflammatory axis. Sleep disturbances (SDs), highly prevalent in patients with psoriasis, exacerbate the condition by disrupting circadian rhythms and reducing melatonin levels, thus promoting OS and inflammation. Xiaoyin-Anshen formula (XYAS), a traditional Chinese medicine (TCM) formula, is composed of the Liangxue-Jiedu (LXJD) and Qingxin-Anshen (QXAS) TCM compounds and has been demonstrated to be effective in treating psoriasis complicated by SDs. However, its exact pharmacological mechanism remains uncertain. Thus, this study used animal experiments to verify whether XYAS can exert therapeutic effects on the disease by regulating melatonin (MLT) levels, protecting against OS, and inhibiting psoriasis-like skin inflammation. Methods: A mouse model for psoriasis combined with SDs was established by smearing 62.5 mg of 5% imiquimod (IMQ) cream for seven consecutive days, along with a daily injection of p-chlorophenyl alanine (PCPA) solution at a dosage of 300 mg/kg at days 6–7. The IMQ cream was continued to be used for maintaining the model at days 8–14. Mice were randomly divided into groups: control, model, MLT, XYAS, LXJD, QXAS. Each group was treated according to its designation at days 8–14, receiving either an oral gavage of XYAS/LXJD/QXAS solution at a dosage of 2 mL/100 g per day, or a daily injection of MLT solution at a concentration of 0.25 mg/mL, with a dosage of 5 mg/kg. Immunohistological analysis, pentobarbital-induced sleep test, Western blotting, and enzyme-linked immunosorbent assay (ELISA) were performed to assess and compare pathological features, sleep conditions, localization and/or levels of manganese-dependent superoxide dismutase (mnSOD), mitochondrial cytochrome c (Cyt-C), MLT, retinoid-related orphan nuclear receptor-α (RORα), and pro-inflammatory cytokines interleukin (IL)-6, IL-17A, and tumor necrosis factor-alpha (TNF-α) among groups. Results: MLT, XYAS, LXJD, and QXAS exhibited varying therapeutic effects on RORα regulation, OS inhibition, mitochondrial protection, and anti-inflammation. Compared to the model, the lesion severity/thickness and serum IL-6, IL-17A, and TNF-α levels were gradually reduced in the MLT, QXAS, LXJD, and XYAS. However, no statistical difference in TNF-α levels was identified between the MLT and the model groups. Additionally, skin MLT levels gradually increased in the MLT, QXAS, and XYAS groups, while RORα levels gradually increased in the MLT, QXAS, LXJD, and XYAS groups. All treatments increased mnSOD levels and reduced Cyt-C levels in skin lesions, with XYAS showing the most significant changes. Conclusion: XYAS may treat psoriasis complicated by SDs through two main mechanisms: (1) Improving melatonin-RORα axis in the skin can lead to an increase in mnSOD and a reduction in Cyt-C levels, which provide protection against oxidative stress, mitochondrial damage, and psoriatic inflammation. (2) Reducing IL-6, IL-17A, and TNF-α production to suppress IL-23/Th17 pro-inflammatory signaling axis and epidermal hyperplasia in psoriasis. [ABSTRACT FROM AUTHOR]

Purpose: Biological treatment has been a game changer in the management of moderate‐to‐severe psoriasis. In Denmark, biological treatment for psoriasis is registered in two data sources. We aimed to describe the utilization of biologics for psoriasis in Denmark using data from both data sources separately. Methods: We used data from two different nationwide Danish data sources: The healthcare registries and the clinical quality database, Dermbio. Utilization patterns were described by three different parameters: (1) distribution of drugs used in the first treatment episodes, (2) treatment cascade on a population level, and (3) drug survival using Kaplan Meier (KM) analysis and the proportion of patients covered (PPC) method. Results: From January 1, 2011, to December 31, 2018, we found 1878 users of biologics in the healthcare registries and 2264 in Dermbio. Adalimumab, ustekinumab, and secukinumab were the most common first‐choice treatments throughout the study period. According to the healthcare registries, it was most common to have more than one treatment episode with the same drug. In Dermbio, most were registered to have only one observable treatment episode overall in the study period. Ustekinumab showed the longest drug survival in both databases. Drug survival was longer for all biologics in Dermbio than in the healthcare registries. Conclusion: Adalimumab, ustekinumab, and secukinumab were the most common first‐choice treatments in Denmark. Overall, ustekinumab showed the longest drug survival. We observed important differences in treatment cascades and drug survival between Dermbio and the healthcare registries, which should be considered when using these data sources to perform drug utilization studies on biologics. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background and Objective: Erosions 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 Methods: A 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. Results: Patients 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. Conclusions: This 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. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background and Objectives: Up to 30% of psoriasis (PsO) is clinically associated with psoriatic arthritis (PsA). A large proportion of new onset of PsA is diagnosed at a later stage, despite the necessity of early effective treatment to prevent structural damage. This study aimed to identify the routine screening practices used for PsA in patients with PsO. Patients and Methods: This non‐interventional, prospective, epidemiological, cross‐sectional study conducted in Germany focuses on screening activity and treatment selection of dermatological practices in suspected PsA. Descriptive statistics and patient characteristics were analyzed for different center types. Results: One hundred ninety‐five patients from 34 office‐based physicians, five non‐university hospitals, and nine university hospitals were included. Questionnaires or imaging techniques were not routinely used (< 45%). Especially, ultrasounds (≤ 5%) and MRIs (< 6.3%) were rarely performed. Between 30% and 75% of suspected PsA could be confirmed. Referral to rheumatologists and/or appropriate therapy initiation were the most frequent consequences. Conclusions: Results of this study reflect the status of PsA screening activity by dermatologists. Imaging techniques, particularly ultrasound or MRIs to detect early forms of PsA, were inadequately used, which may have contributed to continued underdiagnoses. Collaboration between dermatologists and rheumatologists should be reviewed with a view to improving effective PsA screening. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with treated solid tumors (TST) are a highly heterogeneous and difficult-to-treat population due to the risk of disease progression/recurrence or infection. Methods: We conducted an observational, retrospective, single-center study at the Dermatology Clinic of Turin with a focus on the special population of cancer patients with psoriasis treated with biologics. Results: As of July 2023, 52 psoriatic patients with a prior/concomitant history of malignancy had taken biologic drugs. The median age was 67 years, and the median age of cancer onset was 55 years. The most common tumors were gastrointestinal cancer and melanoma. After the tumor diagnosis, 61% received an anti-IL17 drug; 37 patients continued the initiated biologic therapy, while 12 switched drugs due to secondary inefficacy. The estimated biologic DS was 55.6% at 50 months. Evidence suggests that IL-17 is a key pathogenic factor involved in tumorigenesis, resulting in a lower risk of malignancies in subjects managed with IL-17 inhibitors. Similarly, IL-23 plays a role in suppressing innate immunity and promoting tumor and metastases development. This is a consistent real-life case series that support the use of biologic drugs in patients with TST. Conclusions: IL-23 and IL-17 inhibitors, being immunomodulators rather than immunosuppressants, may be a safe option for patients in an active oncological setting and for immune-correlated adverse events. [ABSTRACT FROM AUTHOR]

Background: Psoriasis (PSO) involves about 1–3% of the population, and around 75% of women develop PSO before the age of 40. Official guidelines on the treatment of woman with anti-IL17 and anti-IL23 during this potential childbearing time are not currently available. Objective: To investigate the effectiveness and safety of biologic treatments in women of childbearing age. Methods: At the Dermatology Clinic of the University of Turin, Italy, 172 women aged 20–55 years underwent IL-17 and IL-23 inhibitor therapy for moderate-severe PSO and were followed up to 52 weeks in a real-life, retrospective, single-center study. Results: Overall, 40% of patients achieved PASI 100 at week 16, and 72% at week 52. A similar trend was observed for PASI 90 and PASI < 3 with almost 80% and 90% of patients achieving the target at 52 weeks. As for PASI 100, a statistically significant difference (p = 0.004) was found at 16 weeks, with 23.84% of patients achieving PASI 100, with IL-17 and 15.70% with the IL-23 inhibitor. No statistically significant differences were found at 28 and 52 weeks. No statistically significant differences in PASIs at any time points were recorded across the different biologic agents. Forty-six patients discontinued treatment. The most reported side effects were headache, nausea, asthenia, injection site pain, and rhinitis. Conclusions: This study showed that biologic drugs are effective and safe in women of childbearing age, with negligible side effects. [ABSTRACT FROM AUTHOR]

Background/Objectives: Children and adolescents with psoriasis can have severe and long-lasting disease requiring early and effective therapy. The range of associated comorbidities is comparable to adult patients with additional problems deriving from their growth and maturation. Therefore, tailored information and interdisciplinary teamwork is necessary to effectively manage pediatric psoriasis. Methods: We reflected on our experience with therapy management of children and adolescents with psoriasis coming to our university outpatient clinic and summarized the challenges and special features of these patients together with approved medications and recommendations for treatment. We present our algorithm for managing these patients in an interdisciplinary setting. Results: Children can develop psoriasis very early in their life, and they show specific patterns of skin involvement depending on age. Scores such as the cDLQI and the PASI help to quantify the clinical severity and burden of the disease, and the upgraded criteria should reflect that children's needs are different from adults'. The choice of medication is limited to a few, but increasing approvals for children and the close exchange of information and preparations with pediatricians and other specialties before initiating systemic therapies are crucial for children to support compliance. We emphasize the focus on vaccinations and the treatment of chronic infections, e.g., the management of TBI, which is different from adults. Conclusions: With the increased options for the systemic treatment of children with psoriasis, clear and adapted information for the child, guardian and pediatrician is essential to assure a well-managed environment and to prevent the unnecessary termination of effective therapy. [ABSTRACT FROM AUTHOR]

Psoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body's immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients' quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a prevalent, long-lasting inflammatory skin condition characterised by various clinical manifestations and arising from the interaction of genetic, environmental, and immunological factors. It has been found to be associated with several medical conditions, such as hypertension, diabetes, Cardiovascular (CV) diseases, and metabolic syndrome. Aim: To compare the Electrocardiographic P Wave Dispersion (PWD) in individuals with and without psoriasis and to correlate PWD with the Psoriasis Area Severity Index (PASI) score. Materials and Methods: This was a hospital-based crosssectional study comparing the electrocardiographic PWD in 30 patients with psoriasis to that of 30 age- and gender-matched subjects without psoriasis who attended Government Medical College, Trivandrum, Kerala, India, during a period of one year (February 2021 to January 2022). A structured questionnaire was used to record history and examination findings. A 12-lead Electrocardiogram (ECG) was performed on study participants from both groups in a supine position following 15 minutes of rest. Categorical and quantitative variables were expressed as frequency (percentage) and mean±SD, respectively. The Karl Pearson test was used to find correlations. A p-value of ≤0.05 was considered statistically significant. Results: Ten (33.3%) patients belonged to the age group of 41-50 years. The duration of the disease ranged from six months to 21 years. Seventeen (56.7%) patients had a PASI score between 10-20, and 5 (16.7%) patients had a PASI score of less than 10. The maximum value of the P wave and PWD was higher in the case group and was statistically significant (p≤0.001 and p≤0.001, respectively). A statistically significant correlation was found between the severity of psoriasis and PWD (r=0.564, p≤0.001) and between the duration of psoriasis and PWD (r=0.372, p=0.04) in this study. Conclusion: PWD was found to be higher in psoriasis patients, with a significant correlation between PWD and both the severity and duration of the disease. Therefore, ECG should be considered as a screening test for Atrial Fibrillation (AF) in all psoriasis patients. [ABSTRACT FROM AUTHOR]

Objective: This study was performed to explore the clinical significance of the expression of human beta-defensin 2 (HBD-2) and chemokine ligand 1/2 (CXCL-1/2) in psoriasis vulgaris. Methods: This study retrospectively included the study group (n = 160) and control group (n = 100) for analysis. The levels of inflammatory indicators, blood biochemical indicators, and immune indicators using ELISA. The psoriasis area and severity index (PASI) was used to evaluate disease severity. Levels of HBD-2, CXCL-1, CXCL-2 and CCL20 were determined by RT-PCR. The correlations of HBD-2, CXCL-1 and CXCL-2 levels with CCL20 and PASI scores were analyzed. The diagnostic value of HBD-2, CXCL-1 and CXCL-2 in psoriasis vulgaris was analyzed by ROC curve. Results: HBD-2, CXCL-1 and CXCL-2 were highly expressed in the lesions of psoriasis vulgaris patients, and were positively correlated with CCL20 and PASI score. HBD-2, CXCL-1 and CXCL-2 alone or in combination had high diagnostic value for psoriasis vulgaris and severe psoriasis, and the combined diagnostic value of the three was higher than that of a single indicator. Conclusion: HBD-2, CXCL-1, and CXCL-2 levels are closely related to the severity of psoriasis vulgaris and can effectively diagnose the occurrence and progression of psoriasis vulgaris. [ABSTRACT FROM AUTHOR]

Introduction: Biologic treatments have made complete skin clearance in moderate to severe plaque psoriasis a real possibility. Although clinical trials demonstrated the superiority of bimekizumab over secukinumab, adalimumab, and ustekinumab, direct comparisons with other biologics are not available. This systematic literature review (SLR) and network meta-analysis (NMA) aimed to evaluate the 1-year efficacy and safety of bimekizumab versus other biologic systemic therapies for moderate to severe plaque psoriasis. Methods: We conducted an SLR to retrieve published randomised controlled trials (RCTs) in patients with moderate to severe plaque psoriasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and PsycINFO on 13 January 2022. Two NMA types were used to analyse the long-term achievement of 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100): (1) NMA of cumulative clinical benefits, based on the area under the curve, from week 0 to 52; (2) multinomial NMA at weeks 44‒60. Binomial NMA was used to evaluate long-term serious adverse events (SAEs). Results: The SLR identified 38 RCTs, of which 19 were included in the NMA. Bimekizumab 320 mg administered every 4 weeks to week 16 then every 8 weeks (Q4W/Q8W) showed a greater cumulative average number of days of PASI 100 response compared with all other biologics. These differences were statistically significant versus all biologics, except risankizumab 150 mg. The multinomial NMA demonstrated that interleukin (IL)-17 and IL-23 inhibitors were the most efficacious treatments. No significant differences were found in long-term occurrence of SAEs. Conclusion: Bimekizumab 320 mg Q4W/Q8W was superior to most other treatments in maintaining complete skin clearance during the first year of treatment. It demonstrated a greater cumulative average number of days with completely clear skin while displaying a comparable safety profile compared with all other biologics. [ABSTRACT FROM AUTHOR]

Introduction: Poor persistence to biologics can result in suboptimal health outcomes and increased economic burden for chronic conditions, including psoriasis (PsO). In Japan, studies evaluating factors responsible for biologic treatment persistence in patients with PsO are limited. We assessed biologic treatment persistence (median treatment duration and overall treatment survival) and associated factors in patients with PsO in a real-world setting. Methods: This retrospective analysis of insurance claims records from the Japan Medical Data Center (JMDC) database included patients with PsO [International Classification of Diseases (ICD) code: L40.x] ≥ 18 years of age who had received biologic treatment. Treatment persistence was analyzed using data from 2016 to 2020 by biologic class and by individual biologics (infliximab, adalimumab, ustekinumab, guselkumab, secukinumab, ixekizumab, and brodalumab) in bio-naïve (who initiate first biologic at index) and bio-experienced patients. Kaplan–Meier survival (treatment persistence), and multivariate Cox proportional hazard regression (predictive factors) analyses were used. Results: Overall, 1528 patients with PsO were included (mean age 47.4 years). Infliximab had the longest median treatment duration (33.6 months), while brodalumab had the shortest (9.7 months) among biologics evaluated. Of the biologics evaluated, 1-year treatment survival was highest with guselkumab (83%), and lowest with brodalumab (45%). Bio-experienced patients showed slightly longer median treatment duration than bio-naïve patients (22.8 versus 18.1 months). Factors predictive of treatment persistence were sex [male; hazard ratio (HR) 0.84, p = 0.016] and specific PsO diagnostic codes, such as L40.0 (PsO vulgaris; HR 0.69; p = 0.006), L40.1 (generalized pustular PsO; HR 0.75; p = 0.034), and L40.9 (PsO unspecified; HR 0.72; p = 0.001). Meanwhile, age and Charlson Comorbidity Index score were significantly associated with adalimumab and infliximab treatment persistence, respectively. Conclusion: Among biologics evaluated, infliximab had the longest median treatment duration, and guselkumab had the highest 1-year treatment survival. Sex and specific PsO diagnostic codes influenced overall treatment persistence. These findings could inform long-term treatment plans for PsO in real-world clinical settings. [ABSTRACT FROM AUTHOR]

Introduction: Guselkumab, a human monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has shown efficacy in psoriasis and psoriatic arthritis. However, long-term real-world data on its effectiveness in patients with inadequate response to ustekinumab are limited. This study investigates guselkumab's long-term effectiveness and safety in patients with psoriasis with partial response to ustekinumab. Methods: We performed a retrospective multicentric study analyzing data of patients with psoriasis from seven Italian hospitals between January 2021 and May 2024. The study included 169 patients who switched from ustekinumab to guselkumab. Primary endpoints were Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100, and absolute PASI ≤ 2. Site-specific Physician Global Assessment (PGA) scores were also collected for difficult-to-treat areas. Results: The study included 169 patients. After 3 years of treatment, PASI 75, PASI 90 and PASI 100 were achieved by 88.4%, 55.8%, and 32.6% of patients, respectively. Site-specific PGA showed significant improvements, especially in the scalp and genital areas. After 3 years of treatment, no significant impact of higher body mass index (BMI) or cardiometabolic comorbidities on guselkumab effectiveness was detected. No severe adverse events were reported during the study period. Conclusions: In our study, guselkumab provided significant long-term effectiveness and safety in patients partially responsive to ustekinumab, improving both PASI score and site-specific PGA and confirming its potential use for patients with psoriasis switching from ustekinumab. [ABSTRACT FROM AUTHOR]

Vitiligo is a chronic depigmenting disorder that significantly impacts the quality of life of patients. Though there have been significant advancements in targeted therapies in skin diseases such as psoriasis or eczema, the progress in the treatment of vitiligo has been slow, with minimal studies assessing the effect of biologics, though there has been recent evidence of the effectiveness of JAK inhibition. This paper reviews the published case reports and studies for the use of systemic targeted therapies including biologics and JAK inhibitors in vitiligo. [ABSTRACT FROM AUTHOR]

Background: The advent of novel biologics has led to an increase in biologic‐switching as patients and clinicians pursue improved clinical outcomes. However, guidance on treatment sequencing in an Australian setting is sparse. This study examines the patterns of care across two tertiary centres in Australia and characterizes the factors contributing to biologic‐switching. Methods: A retrospective study of patients who attended the outpatient Dermatology biologic clinics across two tertiary hospitals was conducted. Data on treatment sequencing and patients' PASI at every visit from April 2006 to December 2020 were collected. Patterns of biologic‐switching were examined. The speed of treatment response for each biologic was determined by the time to achieve PASI‐90 and ‐100 for each treatment course. Results: A total of 440 treatment courses were analysed. Ustekinumab and adalimumab were the most frequently prescribed first‐line biologics. The highest proportion of biologic‐switching was observed among patients on TNF‐α inhibitors (63.8%). After 2015, more patients were prescribed IL‐12/23 and IL‐17 inhibitors in favour of TNF‐α inhibitors. IL‐17 inhibitors demonstrated the most rapid treatment response and low PASI scores relative to other biologics. Patients who did not switch biologics had lower rates of psoriatic arthritis and lower BMI, compared to patients who switched biologics. The median PASI on discontinuation generally exceeded 3.0, while on continuation, it was less than 1.2, reflecting patients' and clinicians' thresholds for biologic‐switching. Conclusions: This study demonstrates an increased uptake of more novel biologics as they become available, due to improved safety profiles and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: In comparison with TNF‐α inhibitors, anti‐IL‐17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation. Methods: In this study, we aimed to evaluate the TB infection status and serial QuantiFERON‐TB‐Gold in tube test (QFT) results of psoriasis patients using IL‐17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real‐world setting from a tuberculosis‐endemic country. Patients who used an anti‐IL‐17 agent for at least 3 months in our follow‐up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records. Results: A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti‐IL‐17 agent was 14,147 patient‐months, 9743 patient‐months for SEC and 4404 patient‐months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti‐IL‐17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow‐up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected. Conclusion: In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti‐IL‐17 treatment duration. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory disease often associated with serious cardiovascular comorbidities. The aim of this study was to investigate the systemic inflammatory burden in psoriasis by examining various inflammatory markers and to assess the relationship between these markers and the severity of the disease. Methods: This retrospective study was conducted on medical records of patients who visited the dermatology outpatient clinic between 1 January 2016 and 31 December 2022. The study included patients with psoriasis vulgaris and healthy volunteers. Demographic data, Psoriasis Area and Severity Index score, C‐reactive protein, monocyte‐high‐density lipoprotein cholesterol ratio, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, systemic immune‐inflammation index, and Systemic Inflammation Response Index were analysed and compared. Results: A total of 278 psoriasis patients and 90 healthy volunteers were analysed. Compared to the control group, psoriasis patients showed significantly higher systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, serum C‐reactive protein levels, neutrophil count, monocyte count, body mass index, and waist circumference (p < 0.001, p = 0.001, p < 0.001, p = 0.014, p < 0.001, p < 0.001, p = 0.046, p < 0.001, and p = 0.011, respectively). Among patients with severe psoriasis (Psoriasis Area and Severity Index >10), systemic immune‐inflammation index, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and serum C‐reactive protein levels were significantly higher compared to patients with mild/moderate psoriasis (Psoriasis Area and Severity Index ≤10). In the ROC curve analysis, the optimal cut‐off (AUC, sensitivity, specificity) values for neutrophil‐to‐lymphocyte ratio, systemic immune‐inflammation index, and platelet‐to‐lymphocyte ratio were found to be 2.11 (0.592, 62%, 57%), 552.9 (0.579, 61%, 58%), and 111.9 (0.578, 64%, 46%), respectively. The inflammatory parameters that showed correlation with Psoriasis Area and Severity Index were systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, monocyte‐to‐lymphocyte ratio, and C‐reactive protein. Conclusion: The findings of this study suggest that systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, and C‐reactive protein values have the potential to serve as simple and cost‐effective markers for assessing the inflammatory burden in individuals with psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a multifactorial, chronic, and inflammatory disease that severely impacts patients' quality of life. The disease is caused by genetic irregularities affected by epigenetic and environmental factors. Some of these factors may include seasonal changes, such as solar radiation, air pollution, and humidity, and changes in circadian rhythm, especially in the temporal and polar zones. Thus, some psoriasis patients report seasonal variability of symptoms. Through a comprehensive review, we aim to delve deeper into the intricate interplay between seasonality, environmental factors, and the genetic and epigenetic landscape of psoriasis. By elucidating these complex relationships, we strive to provide insights that may inform targeted interventions and personalized management strategies for individuals living with psoriasis. [ABSTRACT FROM AUTHOR]

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients' quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine's impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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 12 weeks before and after topical treatment with calcipotriol betamethasone and calcipotriol ointment (T#1) or topical therapy plus PSORI-CM01 granules (T#2). Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease characterized by the hyperproliferation of keratinocytes and an overactive autoimmune response. Photodynamic therapy (PDT) has been established as a promising intervention for alleviating psoriasis. However, the current transdermal delivery of photosensitizers is inefficient and imprecise. In this study, we developed a foamed microemulsion nanodroplets system containing chlorin e6 (Ce6 FM), exhibiting precise epidermal targeting and retention, which targeted the aberrantly proliferating epidermal cells at psoriatic skin lesions and avoided the damage to the normal cutaneous cells. Upon application in a psoriatic mouse model, Ce6 FM efficiently induced keratinocyte apoptosis by generating reactive oxygen species under laser. Furthermore, Ce6 FM-based PDT activated the cyclooxygenase-2-induced immunosuppressive pathway in keratinocytes, resulting in the amelioration of the autoimmune microenvironment in psoriatic skin. Additionally, Ce6 FM-based PDT did not induce skin damage or atrophy associated with non-targeted halometasone treatment. Overall, Ce6 FM-based PDT holds promise as an effective, safe and compliant strategy for psoriasis treatment. [ABSTRACT FROM AUTHOR]

The current work aims to develop a bigel-containing clobetasol propionate-loaded PLGA microparticles and further assess its in vitro, ex vivo, and in vivo behavior for psoriasis management. PLGA microparticles (2%w/w) containing clobetasol propionate were developed by solvent evaporation technique. For the developed particles, size, drug loading, entrapment efficiency, and surface morphology were determined. Further, the particles were suspended into bigel developed from oleogel and hydrogel (40:60) and assessed for stability, in vitro drug release, ex vivo skin permeation, retention, and in vivo study in BALB c mice for antipsoriatic potential. PLGA microparticles developed by solvent evaporation were found to have a mean particle size of 19.45 ± 1.74 μm. Drug loading and entrapment efficiency for clobetasol were found to be 43.5 ± 4.94% and 94.5 ± 3.68%, respectively. For the developed bigel, sustained in vitro drug release was observed till 7 h. Ex vivo skin permeation with the developed formulation was found to be higher than the marketed formulation and drug suspended in bigel. A retention study performed on pig skin suggested the topical skin retention of the drug. Further, the psoriatic model was developed in BALB c mice with IMQ cream, and it was observed that the developed formulation helped considerably reduce the irritation score and PASI scoring in mice as compared to the standard treatment. The same is corroborated with the help of histopathological studies performed by Hematoxylin and Eosin (H&E) staining in the same animals. The study findings suggest that clobetasol microparticle-loaded bigel formulation appeared to be a promising therapy option for psoriasis. [ABSTRACT FROM AUTHOR]

Objective: Inhibitors of the interleukin 13 (IL‐13) pathway, such as dupilumab, are licensed for atopic dermatitis and asthma. Adverse events resembling psoriatic disease after dupilumab initiation have been reported, but evidence is limited to case reports with uncertain causality. We aimed to investigate whether genetically mimicked IL‐13 inhibition (IL‐13i) is associated with risk of psoriatic arthritis (PsA) and psoriasis. Methods: We instrumented IL‐13i using a protein‐coding variant in the IL13 gene, rs20541, that is associated with circulating eosinophil count (biomarker of IL‐13i) at genome‐wide significance in a study of 563,946 individuals. Outcome genetic data were taken from studies of PsA, psoriasis, and related spondyloarthritis traits in up to 10,588 cases and 209,287 controls. Colocalization analysis was performed to examine genetic confounding. We additionally used circulating IgE as a biomarker to test whether associations were replicated, both in the test and in an independent genetic dataset. We also replicated analyses using individual‐level data from the UK Biobank. Results: Genetically proxied IL‐13i was associated with increased risk of PsA (odds ratio [OR] 37.39; 95% confidence interval [95% CI] 11.52–121.34; P = 1.64 × 10−9) and psoriasis (OR 20.08; 95% CI 4.38–92.01; P = 1.12 × 10−4). No consistent associations were found for Crohn disease, ulcerative colitis, ankylosing spondylitis, or iritis. Colocalization showed no strong evidence of genetic confounding for psoriatic disease. Results were replicated using circulating IgE for the exposure, using independent outcome data and using individual‐level data. Conclusion: We provide supportive genetic evidence that IL‐13i is linked to increased risk of PsA and psoriasis. Physicians prescribing IL‐13 inhibitors should be vigilant for these adverse events. [ABSTRACT FROM AUTHOR]

Background: Evidence describing the types and annual costs of biological treatments for psoriasis in Latin America is scarce. This study aimed to estimate the frequency of use and costs of biologic therapy for psoriasis in Colombia in 2019. Methods: This secondary data analysis uses the International Classification of Diseases terms associated with psoriasis, excluding those related to psoriatic arthritis, based on data from the registry of the Colombian Ministry of Health. We estimated the prevalence of psoriasis per 100,000 inhabitants; then, we retrieved the frequency of use of biologic therapy in patients with psoriasis and estimated the cost per year of each and overall therapies in 2019 in US dollars (USD). Results: There were 100,823 patients with psoriasis in Colombia in 2019, which amounts to a prevalence of 0.2% in the general population. Of those patients, 4.9% received biologic therapy, most frequently males (60%). The most commonly used biological therapies for psoriasis in Colombia in 2019 were ustekinumab (35.2%), with an annual cost per patient of $12,880 USD; adalimumab (26%), with a yearly cost per patient of $7130 USD; and secukinumab (19.8%), with an annual cost per patient of $6825 USD. Conclusion: This is the first study to describe the use and cost of biological therapy for psoriasis in Colombia. It provides valuable cost‐awareness information for the Colombian health system. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is an immune‐mediated inflammatory skin disorder with a multifaceted pathogenesis. Immune dysregulation and immune cell dysfunction are among the mechanisms involved. TEA domain family member 4 (TEAD4) is suggested to play a role in psoriasis development. TEAD4 expression in keratinocytes may have a chemotactic effect and could disturb the function of FOXP3‐positive T lymphocytes. This study aimed to evaluate the expressions of TEAD4 and FOXP3 in lesional, nonlesional psoriatic, and healthy skin and assess the clinical impact of their expression. Methods: This case–control study included 32 cases with psoriasis vulgaris and 32 control groups. Hematoxylin and eosin‐stained slides were examined to evaluate the histopathological findings. Moreover, other sections were immunohistochemically stained with FOXP3 and TEAD4. Results: FOXP3 was expressed in inflammatory cells in 56.5, 37.5, and 12.5% of lesional, nonlesional, and healthy skin, whereas it was entirely negative in the keratinocytes. TEAD4 was expressed in keratinocytes in 93.7 and 46.9% of lesional and nonlesional skin, while negative in healthy skin. Significant differences were observed between their lesional, nonlesional, and healthy skin expressions. Furthermore, FOXP3 expression in lesional skin was significantly associated with early onset (P = 0.016), low PASI score (P = 0.002), mild psoriasis (P = 0.007), and axial affection (P = 0.022), while TEAD4 expression was associated with progressive course (P = 0.032), high PASI score (P = 0.002), severe psoriasis (P = 0.001), severe inflammation (P = 0.001), and progressive course (P = 0.017). Conclusion: TEAD4 expression was higher in lesional than nonlesional skin and absent in healthy skin, suggesting a role in psoriasis development. TEAD4 expression was also associated with severe and progressive psoriasis. This may be mediated by the downregulation of FOXP3 and dysfunction of Treg cells. TEAD4 could serve as a promising therapeutic target in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Generalized pustular psoriasis (GPP) is a rare, potentially life‐threatening skin disease often requiring long‐term therapy. We aimed to evaluate the use of Interleukin (IL)‐17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. Methods: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96‐week follow‐up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). Results: Using the as‐observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91–1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High‐adherence therapy (MPR ≥ 80%) was significantly superior to the low‐adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low‐adherence group. No new safety signals occurred. Conclusion: IL‐17A inhibitors led to effective and sustained improvement in GPP patients, and high‐adherence therapy had long‐term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long‐term clinical management. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) and psoriasis (PsO) are distinct chronic autoimmune conditions with varying impacts on patients' lives. While the co-occurrence of MS and PsO has been reported, the underlying pathogenic link remains unclear. This study aimed to investigate the prevalence of PsO in a MS outpatient clinic population and explore the potential interplay between these conditions. Methods: 316 MS patients who had at least one visit at our MS center in the last year, were selected from our outpatient MS Clinic electronic database and were e-mailed in August 2023 and inquired about a previous diagnosis of PsO. Demographic and MS history data were retrospectively gathered for two groups: MS patients without and with PsO. Information about MS phenotype, Expanded Disability Status Scale (EDSS) score at the diagnosis and at last follow-up, disease modifying therapy (DMT) were collected retrospectively from our MS data set. PsO diagnosis was confirmed by an experienced dermatologist and severity was assessed with the Psoriasis Area and Severity Index (PASI). Results: Among 253 respondents, 5.85% reported a PsO diagnosis that was confirmed after the dermatological evaluation Among patients with psoriasis 66.67% had progressive course of MS (p = 0.032) and the onset of PsO typically occurred after MS diagnosis. 9 out 15 patients had a PASI score of 0 and 6 are currently undergoing treatment with an anti-CD20 therapy. Notably, a subset of our patients were on anti-CD20 therapy and did not experience a worsening of dermatological symptoms. Discussion and conclusion: The prevalence of PsO in our outpatient MS population aligns with previous studies. Treatment approaches should be tailored to individual patient needs, emphasizing collaboration between neurologists and dermatologists. Medications like dimethyl fumarate, effective in both conditions, could be considered. The data from our study also suggest that anti-CD20 therapy may be a viable option for some patients with concurrent MS and mild PsO, without a significant worsening of dermatological symptoms. Further research is needed to elucidate the complex relationship between MS and PsO and to develop more effective therapeutic strategies for patients with both conditions. [ABSTRACT FROM AUTHOR]

Psoriasis, an inflammatory disease, is largely mediated by T-helper 17 cytokines. We have previously identified the immune system-released activating agent (Israa) as a novel gene that connects the nervous and immune systems. This research aims to investigate the role of the Israa gene in psoriasis in vivo using the imiquimod-induced psoriasis model. We established the model in C57BL/6 wildtype mice, which were then treated with 200 pg/mouse, 400 pg/mouse, or 800 pg/mouse of recombinant ISRAA compared to methotrexate. Subsequently, we also induced psoriasis in Israa-knockout mice to confirm the effect of Israa. Results consistently showed improvement in psoriasis in all groups receiving recombinant ISRAA. The 200 pg/mouse dose eliminated the disease, reduced the cutaneous release of IL-17 to one-third and TNF-α to one-sixth, increased IL-10 release to over 500 pg, completely resolved parakeratosis, decreased epidermal thickness to one-half, and reduced the expression of CD4 and neutrophil elastase in the skin (all p < 0.05). Israa-knockout mice exhibited less severe psoriasis in all scoring, biochemical, and histological parameters compared to wild-type mice (p < 0.05). This study highlights Israa as a crucial molecule in psoriasis and confirms its immunomodulatory role in inflammatory diseases. [ABSTRACT FROM AUTHOR]

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18–40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41–54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients’ scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3–6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals. [ABSTRACT FROM AUTHOR]

Metabolic disorders are common in patients with psoriasis and contribute significantly to an increased cardiovascular risk. While biologic therapy is very successful in clearing skin lesions, its impact on metabolic parameters is uncertain. Our aim was to investigate the residual metabolic burden in psoriasis patients successfully treated with biologic therapy. We conducted a cross-sectional study of 80 young patients (54 men, 26 women, aged 30–45 years) successfully treated with either adalimumab, secukinumab or guselkumab and topical therapy or methotrexate, and 20 healthy controls. Anthropometric parameters, lipid levels and metabolic indices (HOMA-IR, TyG index and FIB-4 index) were measured. Patients did not receive any other treatments to exclude confounding effects. After analysis, we found that patients treated with three different biologics had similar metabolic status, only the FIB-4 index was higher in the adalimumab group than in the secukinumab and guselkumab treatment groups. There were no significant differences between the patients treated with biologics and the control group. The comparison with patients treated topically or with methotrexate showed that only triglyceride levels, HOMA-IR, TyG index, and FIB-4 index were elevated in patients treated with adalimumab compared to patients treated with topical therapy. Finally, metabolic status was also similar in patients treated with methotrexate or topical therapy. In conclusion, this study suggests that psoriasis patients successfully treated with biologics have similar metabolic parameters to the control group and patients treated with topical therapy or methotrexate. This indicates that there is no significant residual metabolic burden in young patients successfully treated with biologics. These results are clinically relevant and should be considered in the treatment of psoriasis patients. The study is registered at (identifier: NCT05957120). Date of registration: 24th of July 2023. [ABSTRACT FROM AUTHOR]

The use of medications which target the JAK-STAT signaling pathway, also known as janus kinase (JAK) inhibitors, has rapidly increased in recent years. Patient perceptions, opinions, and concerns regarding the use of JAK inhibitors are largely uninvestigated. Our objective is to better understand patient concerns, reported side effects, and sentiments regarding the use of JAK inhibitors for dermatologic disease. The authors performed a cross-sectional analysis of the most frequented subreddits for dermatologic disease in which JAK inhibitors have obtained FDA approval (r/atopic dermatitis, r/psoriasis, r/alopecia areata, r/vitiligo, and r/eczeJAKS). The sentiment, central theme, and engagement level of each post was evaluated using previously utilized methods. Nine hundred twenty-three posts were analyzed, with the majority focusing on efficacy (433, 47%) and medication-related side effects (150, 16%). Other themes of interest to patients were Payment/Insurance (84, 9%), Study Results/News (69, 7%), Administration/Dosage (33, 4%), and Medication Interactions (31, 3%). The most frequently reported side effects were acne/folliculitis (24, 22%), nausea/gastrointestinal disturbance (11,10%), and fatigue/muscle aches (10, 9%). At the same time, the medication interactions garnering the most concern were sunscreens/facial moisturizers (5, 16%), topical calcineurin inhibitors (4, 13%), and Marijuana/THC (3, 9.%). This analysis highlights that patients are most concerned about the efficacy and side effects of JAK inhibitors in addition to issues regarding access to JAK inhibitors. Providers can use the insights gained from this study to address hesitancy better and guide comprehensive, patient-centered discussions with patients regarding JAK inhibitor use. [ABSTRACT FROM AUTHOR]

Background: For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice. Objective: We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics. Methods: This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥ 50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI < 10 and ≥ 50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice–Williams–Peterson Gap time model) was used to predict relapse and generate a predictive model. Results: This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability. Conclusions: These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases. [ABSTRACT FROM AUTHOR]

Objective. To determine the annual incidence of psoriatic arthritis (PsA) in a United Kingdom primary care population with preexisting psoriasis (PsO) followed prospectively over 2 years after excluding baseline prevalence of existing disease. Methods. Total Burden of Psoriasis (TUDOR; ISRCTN registry: ISRCTN38877516) was a multicenter, prospective, 2-arm parallel-group cluster randomized controlled trial of the early identification of PsA by annual rheumatological assessment (termed "Enhanced Surveillance") vs standard care in people with PsO identified in primary care. Incidence of PsA is reported at 12 months and 24 months using patients from the Enhanced Surveillance arm, which allows for the exclusion of patients with prevalent PsA at baseline. Results. Fourteen of 511 participants attending a 12-month screen developed PsA over that interval, giving an incidence of 2.74/100 patient-years (PYs; 95% CI 1.32-4.16). Another 7/444 participants attending the 24-month visit developed PsA, giving an incidence of 1.58/100 PYs (95% CI 0.42-2.74). The combined incidence over 2 years was 2.20/100 PYs (95% CI 1.27-3.13). Conclusion. The estimated annual incidence of PsA over a 2-year period was 2.20/100 PYs, which is in keeping with studies including clinical assessment rather than relying on health records alone. Extended follow-up of the TUDOR cohort with accrual of larger numbers of incident cases will allow risk factors for PsA to be explored in more depth. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic, inflammatory articular disease regarded as a specific subtype of psoriasis. Long‐term assessment for PsA using ultrasonography has not yet been investigated. The present study was conducted to delineate the changes in articular lesions after the initiation of biologics using ultrasonography, and to provide the evidence of the utility of ultrasonography in long‐term follow‐up of PsA patients. We retrospectively recruited 17 Japanese PsA patients treated with biologics who met the classification criteria for psoriatic arthritis. Ultrasonographic images were recorded using a high‐frequency linear 18 MHz probe through Doppler‐ and B‐modes. Before the treatment with biologics, all examined patients (100%) had enthesitis and extensor tendinitis, while only six patients (35.3%) had loss of the fibrillar pattern of the tendon (LFP). There were significant changes over time in the numerical rating scale score for pain, and in the degree of ultrasonographic findings, including enthesitis, extensor tendinitis, and LFP. Also, there were significant changes over time between these ultrasonographic findings. The study identified the improvement course for a specific PsA lesion after the initiation of biologics. The improvement courses in enthesitis, extensor tendinitis, and LFP were found to differ from each other. These results may contribute to deeper understanding of the pathogenesis of PsA. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is an inflammatory skin condition where immune cells play a significant role. The importance of the cross-talk between keratinocytes and immune cells in the pathogenesis of psoriasis has recently been reaffirmed. Recent studies have found that several S1PR functional antagonists, other than S1PR2, are effective in improving psoriasis. This study aims to investigate the role of S1PR2 in psoriasis, that has not been investigated before. Methods: Spatial transcriptomics, RT-qPCR, and flow cytometry were used to map the immune cell landscape and its association with metabolic pathways in an imiquimod (IMQ)-induced psoriasis-like inflammation in S1pr2fl/fl K14-Cre mice that could not sense sphingosine-1-phosphate (S1P) in the epidermis through the S1PR2 receptor. Results: Our analysis suggests that S1PR2 in keratinocytes plays a major role in psoriasis-like inflammation compared to other S1PRs. It acts as a downregulator, inhibiting the recruitment of Th17 cells into the skin. In IMQ-induced psoriasis skin, both S1pr2-/- and S1pr2fl/fl K14-Cre mice showed higher expressions of proinflammatory cytokines such as TNF-a, IL-17A, and IL-1b together with higher expressions of MyD88/NF-kB pathway compared to the wild-type mice. Remarkably, in IMQ-treated mice, the deletion of S1pr2 in keratinocytes only resulted in a larger population of Th17 cells in skin-draining lymph nodes. Other S1PR modulators did not improve the worsening of psoriasis-like inflammation caused by S1PR2 deficiency in keratinocytes. Conclusion: This study reaches two main conclusions: signals from keratinocytes play a central role in creating an immune environment that promotes the development of psoriasis, and stimulating S1PR2, instead of suppressing it, represents a potential therapeutic approach for psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a skin disease that is inflammatory and persistent, causing a high rate of recurrence, poor quality of life, and significant socioeconomic burden. Its main pathological manifestations are abnormal activation and infiltration of T cells and excessive proliferation of keratinocytes (KCs). The great majority of patients with psoriasis will relapse after remission. It usually lasts a lifetime and necessitates long‐term treatment strategies. During periods of activity and remission, one of the main cell types in psoriasis is memory T cells, which include tissue‐resident memory T (TRM) cells, central memory T (TCM) cells, and effector memory T (TEM) cells. They work by releasing inflammatory factors, cytotoxic particles, or altering cell subpopulations, leading to increased inflammation or recurrence. This review summarizes the role of memory T cells in the pathology and treatment of psoriasis, with a view to potential novel therapies and therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza, which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis. Methods: An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway. Results: The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines. Conclusions: Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization. [ABSTRACT FROM AUTHOR]