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This review provides a comprehensive overview of macrophage heterogeneity, polarisation dynamics, metabolic reprogramming and multicellular interactions of macrophages in psoriasis.

We discuss how single-cell technologies have revealed diverse macrophage subsets and explore the metabolic profile of macrophages in psoriasis. Furthermore, we examine the central role of macrophages in intercellular networks with keratinocytes, T helper 17 (Th17) cells, neutrophils, fibroblasts and sensory neurons.

Additionally, we summarise the novel signal way of macrophages and tissue injury by macrophages. Finally, we summarise emerging therapeutic strategies—including metabolic modulators, signalling pathway inhibitors, advanced delivery systems and cell-based therapies.

By integrating recent insights from single-cell omics, spatial transcriptomics and metabolic studies, this review underscores the potential of macrophage-focused interventions for psoriasis treatment.

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Objective:
This study aims to investigate lifestyle-related factors in patients with psoriatic arthritis (PsA) and their association with disease activity measurements.

Methods:
This multicenter cohort included 938 patients newly diagnosed with PsA, between 2013 and 2023. A composite lifestyle risk score (range 0 to 5) was calculated using five lifestyle-related factors assessed at baseline (BMI outside normal range, abdominal obesity, current smoking, no alcohol consumption, physical inactivity). Higher scores indicate the presence of more lifestyle-related risk factors. One year disease activity outcomes included PsA Disease Activity Score (PASDAS), disease activity in PsA (DAPSA), PASDAS and DAPSA low disease activity (LDA) and remission, and minimal disease activity (MDA).

Results:
The rate of obesity was 33%, abdominal obesity was 51%, current smoking was 19%, and alcohol consumption was 72% with 3% of patients physically inactive. Using multivariable analyses, a higher lifestyle risk score was associated with higher PASDAS (β 0.15; 95%CI 0.08, 0.23), and lower odds for achieving PASDAS-LDA (OR 0.59; 95%CI 0.45, 0.77), and MDA (OR 0.72; 95%CI 0.57, 0.90) at one year follow-up. Similar associations were observed for DAPSA (βadj 1.18; 95%CI 0.65, 1.71) and DAPSA-LDA (OR 0.74; 95%CI 0.59, 0.92). Analysis of individual factors showed that general obesity, abdominal obesity and smoking, were significantly associated with higher PASDAS and DAPSA, and lower odds for achieving PASDAS-LDA and MDA.

Conclusion:
Lifestyle-related risk factors were prevalent in patients with PsA. The associations between lifestyle-related factors and PsA disease activity, mainly obesity and smoking, provide foundation to address lifestyle in PsA care.

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Psoriasis is a chronic inflammatory skin disease influenced by environmental factors, including air pollution. However, large-scale evidence from Asian populations, where particulate matter (PM) exposure is relatively high, remains limited.

This study aimed to evaluate the association between long-term PM exposure and psoriasis incidence, and short-term exposure with exacerbation risk. We conducted a cohort study using the Korean National Health Insurance Service database, involving 8 396 764 individuals.

Long-term exposure was assessed based on annual average concentrations of fine PM (PM2.5) and coarse PM (PM10), while short-term exposure was measured using daily PM levels matched with control days. Long-term exposure to PM2.5 and PM10 was associated with a 19% and 27% higher risk of incident psoriasis (adjusted HR 1.19 and 1.27; 95% CI 1.16–1.22 and 1.25–1.30). Short-term exposure was linked to an increased risk of psoriasis exacerbation (adjusted OR 1.03 for PM2.5, 95% CI 1.00–1.06; adjusted OR 1.01 for PM10, 95% CI 1.00–1.03).

Stronger associations were observed in younger individuals, urban residents, those with lower socioeconomic status, ever-smokers, and patients with comorbid allergic diseases.

These findings suggest that both long-term and short-term PM exposure contribute to psoriasis onset and exacerbation, underscoring air pollution as an important modifiable risk factor in psoriasis development and control.

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Background:
Generalized pustular psoriasis (GPP) is a rare, life-threatening disease attributed to aberrant interleukin-36 (IL-36) activity, often due to variants in the IL-36 receptor antagonist gene. Imsidolimab is a novel, humanized, affinity-matured immunoglobulin G4 monoclonal antibody that binds the IL-36 receptor and antagonizes IL-36 signaling.

Methods:
Two phase 3 trials were conducted at 26 clinical sites within 11 countries investigating imsidolimab treatment for GPP. GEMINI-1 was a double-blind, placebo-controlled trial that randomly assigned 45 patients (18–80 years of age) with a GPP flare to receive either a single intravenous dose of 300 mg of imsidolimab, 750 mg of imsidolimab, or placebo. The primary endpoint was GPP Physician Global Assessment (GPPPGA) scores of clear (0) or almost clear (1) at week 4 (range: 0 [clear] to 4 [severe]; minimally clinically important difference, 1.4). GEMINI-2 was a follow-on relapse prevention trial with a primary objective of evaluating the safety of imsidolimab up to 104 weeks. Patients who improved with treatment in GEMINI-1 were randomly assigned to receive either 200 mg of subcutaneous imsidolimab or placebo monthly, whereas partial responders received open-label 200 mg of subcutaneous imsidolimab monthly.

Results:
In GEMINI-1, 53% of patients in the groups that received either 300 mg (n=8/15) or 750 mg (n=8/15) of imsidolimab had GPPPGA scores of 0 or 1 at week 4, compared to 13% in the placebo group (n=2/15) (P=0.023 for both the 300 mg vs. placebo comparison and 750 mg vs. placebo comparison). In GEMINI-2, no serious adverse events led to imsidolimab discontinuation.

Conclusions:
Compared with placebo, a significantly higher proportion of patients with GPP randomly assigned to receive a single intravenous dose of imsidolimab were clear or almost clear of the disease after 4 weeks based on the GPPPGA. There were no serious adverse events that led to treatment discontinuation with imsidolimab up to 104 weeks of treatment.

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Background:
Psoriasis is an immune-mediated inflammatory disease driven by dysregulated crosstalk between immune cells and skin-resident cell populations, particularly keratinocytes and fibroblasts. However, transcriptomic findings across studies remain heterogeneous and incompletely integrated.

Objectives:
To integrate transcriptomic evidence across independent studies to define reproducible immune-gene expression patterns in plaque psoriasis and identify hypothesis-generating pathways beyond canonical immune programmes.

Methods:
We performed a systematic review and meta-analysis of transcriptomic datasets comparing lesional psoriatic skin with non-lesional skin and healthy controls. All analyses were restricted a priori to a curated set of immune-related genes. Forty-four independent studies comprising 975 samples were harmonized; differential expression within each study was combined using random-effects models. Functional enrichment (Reactome/KEGG/GO) and a systematic comparison with curated resources were conducted.

Results:
The meta-analysis identified 1780 immune-related genes consistently dysregulated in lesional psoriasis. Enrichment confirmed established immune programmes (e.g. IL-23/Th17 signalling, cytokine-mediated responses and type I interferon pathways). When cross-referenced with curated disease–gene resources, 1119 genes overlapped with previously reported psoriasis-associated genes, whereas 661 genes were not systematically highlighted. Exploratory enrichment among the less-characterized genes suggested additional processes involving glucose metabolism (gluconeogenesis), FoxO signalling and mitophagy, each supported by small gene sets and borderline adjusted p-values, and therefore interpreted as hypothesis-generating rather than definitive.

Conclusions:
By integrating 44 datasets under an explicit immune-gene framework, this study refines consensus immune signatures in psoriasis and prioritizes metabolic and mitochondrial processes as testable hypotheses for future functional work. These findings contextualize expected immune activation and point to potential interfaces between immunity, cellular energetics and mitochondrial quality control in lesional skin.

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Background:
The efficacy and safety of brodalumab in Japanese patients with palmoplantar pustulosis (PPP) were demonstrated during the 16-week double-blind phase of a randomized controlled trial. However, long-term data are unavailable.

Objectives:
To assess the efficacy and safety of brodalumab 210 mg administered subcutaneously (SC) repeatedly until Week 68 in PPP patients with moderate or severe pustules/vesicles in an open-label extension study.

Methods:
In a multicentre, Phase 3, randomized, double-blind, placebo-controlled trial, Japanese adults having a diagnosis of PPP for ≥24 weeks, PPP Area Severity Index (PPPASI) of ≥12, PPPASI subscore of pustules/vesicles of ≥2 and inadequate response to therapy were included. Patients completing the double-blind phase with brodalumab 210 mg or placebo  SC once every 2 weeks (Q2W) for 16 weeks were invited to enter the open-label extension to receive brodalumab for the subsequent 52 weeks.

Results:
By Week 68, 35 patients in the brodalumab group and 43 patients in the placebo-to-brodalumab group completed the study, with discontinuations (28 and 20 patients, respectively) primarily due to patient withdrawal. At Week 68, the mean ± SD improvement of the PPPASI total score from baseline was 23.83 ± 12.28 and 22.37 ± 13.09 in the brodalumab and placebo-to-brodalumab groups, respectively. Continued improvement or trend for improvement was seen in the secondary endpoints such as PPPASI 50/75/90 responses and Dermatology Life Quality Index. The incidence of adverse events was 849.3/100 person-years. Otitis externa had the highest incidence (44.0/100 person-years; Grade 1 or 2 only). Infection-related events were frequent but controllable.

Conclusions:
Brodalumab SC 210 mg Q2W administered for 68 weeks showed a long-term benefit to both dermatological and quality of life indices in these patients. It is expected to be used in appropriate patients, considering both safety risks and efficacy benefits.

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A major strength of the study lies in its thoughtful design, which addresses two key sources of bias that have affected previous analyses: protopathic bias and confounding-by-indication. By excluding PsA cases diagnosed within 1 year of biologic initiation, the authors reduce the likelihood that early, subclinical joint symptoms prompted the switch to biologics. Similarly, by restricting the baseline population to patients who had all received phototherapy—used here as a proxy for moderate-to-severe psoriasis—the study ensures a more comparable starting point between cohorts. This is a notable improvement over earlier claim-based studies that compared biologic users with patients treated only with topicals or mild systemic agents, inadvertently mixing populations with very different baseline risks.

The results are compelling: The fully adjusted hazard ratio for PsA development among biologic users was 0.66, indicating a 34% relative risk reduction. This effect persisted across multiple sensitivity analyses, including age-, sex- and ethnicity-matched cohorts. Although observational data cannot establish causality, the consistency of the findings strengthens the argument that biologics may modify the natural history of psoriatic disease.

Biologically, this hypothesis is plausible. Psoriasis and PsA share overlapping immunopathogenic pathways, particularly involving TNF-α, IL-17 and IL-23. Subclinical entheseal inflammation is well-documented in psoriasis patients, even in the absence of joint symptoms. Early suppression of these inflammatory pathways may theoretically prevent progression to clinical PsA. Indeed, imaging studies have shown that biologics can reduce enthesitis and synovitis detectable by ultrasound or MRI, even in patients without established PsA.

However, several limitations warrant consideration. First, the use of phototherapy as a surrogate for disease severity, while pragmatic, is imperfect; treatment selection is influenced by patient preference, access and physician practice patterns. Second, claims databases lack granular clinical data such as PASI scores, body surface area, nail involvement or family history—factors known to influence PsA risk. Third, although PsA diagnoses were restricted to rheumatologists, misclassification remains possible. Finally, the study does not differentiate between biologic classes; whether IL-23 inhibitors, IL-17 inhibitors, or TNF inhibitors differ in their preventive potential remains debatable.

Despite these limitations, the study adds weight to a growing body of evidence suggesting that early systemic intervention may alter the trajectory of psoriatic disease. If confirmed in prospective studies, this could have meaningful implications for clinical practice. Dermatologists may increasingly consider early biologic therapy not only to control skin inflammation but also to reduce the long-term burden of PsA, a condition associated with irreversible joint damage, disability and reduced quality of life.

Future research should focus on prospective cohorts with standardized clinical assessments, imaging biomarkers and stratification by biologic class. Randomized controlled trials designed specifically to evaluate PsA prevention—although challenging—would provide the highest level of evidence. Until then, the findings by Miao et al. represent an important step towards understanding how timely intervention may reshape the natural history of psoriatic disease.

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Systemic therapies are required to control disease severity of patients with psoriasis vulgaris (PsO) and psoriatic arthritis (PsA) experiencing refractory skin lesions that persisted despite systemic therapies.

Various oral medications and biologics are currently available in Japan. The aim of this study was to evaluate the treatment outcomes of refractory regions of PsO and PsA treated with systemic therapy. A total of 77 patients who received oral medications and biologics between 1 January 2010 and 31 March 2019 at the Jichi Medical University Hospital were enrolled.

The PsO group included 39 men and 11 women, whereas the PsA group included 20 men and 7 women. Oral medications included etretinate (7 PsO patients and 3 PsA patients), cyclosporine (39 PsO patients and 20 PsA patients), apremilast (7 PsO patients), and methotrexate (5 PsA patients), including 4 patients treated with etretinate and cyclosporine combination (3 PsO patients and 1 PsA patient). The biologics included infliximab (5 PsO patients and 8 PsA patients), adalimumab (11 PsO patients and 11 PsA patients), ustekinumab (21 PsO patients and 6 PsA patients), guselkumab (5 PsO patients), secukinumab (2 PsO patients and 1 PsA patient), ixekizumab (5 PsO patients and 1 PsA patient), and brodalumab (1 PsO patient).

The most common biologic-resistant regions were the lower extremities, followed by the upper extremities and back in patients with PsO, and the scalp, followed by the lower extremities and abdomen in patients with PsA. Despite the introduction of biologics, no significant differences were observed in the efficacy on the face, neck, palm, and buttocks in patients with PsO and the face, sole, and buttocks in patients with PsA compared to oral medications.

These findings will provide useful information regarding biologic-resistant psoriatic regions in the Japanese patients.

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Background:
Limited evidence exists concerning the relationship between cardiovascular–kidney–metabolic (CKM) health and the incidence and prognosis of psoriasis.

Objectives:
This study aimed to evaluate the associations between CKM status, genetic risk and the risk of developing psoriasis, as well as to examine the impact of CKM syndrome on life expectancy in patients with psoriasis.

Method:
This prospective cohort study included 392,454 participants free of psoriasis from the UK Biobank. CKM syndrome was defined by the presence of metabolic risk factors, chronic kidney disease and cardiovascular disease, categorized into five stages (0–4). The genetic risk of psoriasis was assessed using a polygenic risk score. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the incident risk of psoriasis.

Results:
Compared to participants in stage 0, the multivariable-adjusted HRs (95% CIs) for developing psoriasis in individuals with CKM stages 1, 2, 3 and 4 were 1.21 (1.06–1.38), 1.38 (1.24–1.55), 1.64 (1.42–1.91) and 1.72 (1.47–2.01), respectively. Joint association analyses revealed that participants with CKM stage 4 and high genetic risk had the highest risk of psoriasis compared to those at stage 0 with low genetic risk (HR = 2.82, 95% CI: 2.28–3.49). Notably, there was a significant positive additive interaction between advanced CKM stages and high genetic risk in the development of psoriasis (RERI = 0.82, 95% CI: 0.35–1.32). Additionally, within the psoriasis population, advanced CKM stage (stage 4) was associated with a greater reduction in life expectancy (2.03 years, 95% CI: 0.25–3.81 years).

Conclusions:
Poor CKM health was significantly associated with a higher risk of psoriasis in midlife and older adults, particularly among those with high genetic risk and was further linked to decreased life expectancy among patients with psoriasis.

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Proliferation-associated protein 2G4 (PA2G4) has been identified as a key driver of keratinocyte overgrowth and survival in psoriasis, highlighting a promising new target for treatment.

Psoriasis, a chronic inflammatory skin condition affecting approximately 2–3% of the global population, is characterised by excessive keratinocyte proliferation and impaired differentiation. While current therapies have improved disease management, a subset of patients experience inadequate response or loss of efficacy over time, underscoring the need for novel therapeutic strategies.

Study Highlights PA2G4 Role in Psoriasis Progression:
In this study, researchers investigated the role of PA2G4, a transcription factor previously studied primarily in cancer biology, where it is known to promote cell growth and inhibit apoptosis. Using a combination of bulk, single-cell, and spatial RNA sequencing alongside immunohistochemistry, the researchers found that PA2G4 expression was significantly elevated in psoriatic skin compared with non-lesional controls. Notably, its expression was largely confined to basal keratinocytes, the primary proliferating cells in the epidermis.

Importantly, PA2G4 levels were positively correlated with disease severity, epidermal thickening (acanthosis), neutrophil infiltration, and the expression of genes associated with psoriasis pathology. These findings suggest a central role for PA2G4 in driving disease activity.

Functional experiments provided further insight. Using CRISPR/Cas9-mediated knockout of PA2G4 in primary human keratinocytes, researchers observed a shift from proliferation towards differentiation. This was accompanied by reduced expression of proliferation- and inflammation-related genes, including MKI67, IL20, VEGFA, and HIF1A, alongside increased expression of differentiation markers.

In laboratory models, loss of PA2G4 reduced keratinocyte proliferation, limited inflammation-induced epidermal thickening, and increased cell death. Similarly, pharmacological inhibition using the small molecule WS6 replicated these effects, suppressing pathways linked to cell growth and survival.

Clinical Potential of PA2G4 Targeting in Psoriasis:
Together, these findings position PA2G4 as a critical regulator of epidermal homeostasis in psoriasis. Targeting this protein could offer a novel therapeutic approach aimed at restoring the balance between keratinocyte proliferation and differentiation.

Further research is needed to validate these findings in clinical settings, but the study provides a strong foundation for the development of PA2G4-targeted therapies in psoriasis.

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Background:
Erythrodermic psoriasis (EP) is a rare but severe condition. Because of its low prevalence, there are no standardized treatment recommendations for EP. Specific EP guidelines are outdated, prioritizing conventional disease-modifying antirheumatic drugs (cDMARDs) and tumor necrosis factor-alpha (TNF-α) inhibitors.

Methods:
We conducted a multicenter retrospective chart analysis in five academic centers in Bavaria, Germany (Augsburg, Erlangen, LMU Munich, TU Munich, Regensburg). Patients diagnosed with EP between 2019 and 2024 who received systemic treatment were included in the study.

Results:
A total of 29 patients were included. cDMARDs were initiated in 8 patients (27.6%). Biologics were used in 21 patients (72.4%). Psoriasis Area and Severity Index (PASI) decreased from 31.9 to 10.8 across all therapies (p < 0.001). PASI 75 was achieved with methotrexate, cyclosporine, fumarates, infliximab, ustekinumab, ixekizumab, secukinumab, risankizumab, and guselkumab. PASI 100 was achieved with infliximab, ustekinumab, and risankizumab. Adverse events occurred most frequently in the cDMARDs group.

Conclusion:
There is a wide variety of treatment approaches. Standardized guidelines are needed. Biologic therapies, especially interleukin (IL)17 and IL23-inhibitors, showed favorable outcomes in this cohort and warrant prospective evaluation.

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Background:
Biologic therapies have revolutionized psoriasis management, yet inter-individual response varies significantly and reliable predictors of complete skin clearance remain unclear.

Objectives:
This study aimed to identify prognostic predictors of biologic efficacy in patients with psoriasis through a systematic review and meta-analysis.

Methods:
We systematically searched four databases (from their inception to January 28, 2026). Studies were screened and data extracted per predefined criteria; quality was assessed using the Newcastle-Ottawa Scale (NOS), and analyses were performed in Stata 15.0.

Results:
Thirty studies (n = 13,902) were included. Negative predictors of clearance included older age (odds ratio [OR] 0.99, 95% CI 0.98–0.99, p < 0.001), higher body mass index (OR 0.94, 95% CI 0.92–0.97, p < 0.001), comorbidities (OR 0.75, 95% CI 0.63–0.9, p = 0.002), and involvement of special areas (OR 0.71, 95% CI 0.56–0.89, p = 0.003). Conversely, a positive family history (OR 1.42, 95% CI 1.18–1.71, p < 0.001) emerged as a significant predictor associated with better outcomes. No significant associations were observed for other analysed variables.

Conclusions:
Older age, higher comorbidity burden, obesity, and special-site involvement are associated with poorer biologic response in psoriasis, whereas family history is associated with better outcomes. These readily available baseline factors facilitate phenotype-based risk stratification and may guide treatment selection in clinical practice.

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Background:
Paradoxical psoriasis (PP) is a known adverse event of anti-tumor necrosis factor (anti-TNF) agents in hidradenitis suppurativa (HS), yet evidence regarding its management remains limited. The objective was to assess the effectiveness of interleukin-17 inhibitors (IL-17i) in treating anti-TNF-induced PP in patients with HS.

Methods:
This multicenter retrospective study included 40 adults with HS who developed PP during anti-TNF therapy and were subsequently treated with IL-17i. Outcomes for PP were measured using the Physician's Global Assessment (PGA); HS severity was evaluated using the International Hidradenitis Suppurativa Severity Score System (IHS4) and Hurley scores. Paired comparisons were performed using the Wilcoxon signed-rank or McNemar's test, as appropriate. Multivariate analysis was performed using LASSO-regularized logistic regression. Missing data were managed by multiple imputation.

Results:
Of the patients, 27.5% achieved a clinically meaningful PP response, while 45% experienced worsening. Female sex, older age at HS onset, and prior exposure to secukinumab were associated with nonresponse. Conversely, HS severity improved significantly in 70% of patients (p < 0.001).

Conclusions:
IL-17i showed limited effectiveness for anti-TNF-induced PP in HS, though improvement in hidradenitis was observed.

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Psoriasis, an immune-mediated skin disorder, affects over 125 million people worldwide. Its primary manifestations include abnormal keratinocyte proliferation, epidermal inflammatory cell infiltration, and excessive neovascularization, and no fundamental intervention is currently available.

Although siRNA therapy based on the RNA interference mechanism has opened a new avenue for the definitive treatment of psoriasis, its clinical application is limited by rapid degradation and low transfection efficiency, compounded by the skin's dense structure that hinders noninvasive transdermal delivery. To address these issues, we developed a transdermal siRNA delivery system using polyethylenimine (PEI) and Tween 80-modified transfersomes (TCPL) as carriers for NF-κB p65 siRNA (TCPL@siNF-κB).

By embedding Tween 80 and PEI into the TCPL, the system achieves excellent proton buffering capacity, enabling multilayer encapsulation of siNF-κB at both the core and surface levels, effectively preventing its degradation in serum and enzymatic environments. This strategy resolves the molecular weight-dependent conflict between the transfection efficiency and toxicity of PEI, achieving a balanced performance. Moreover, TCPL exhibits ultradeformability, and this study demonstrates the advantages of Tween 80 in promoting transdermal gene transfection.

TCPL@siNF-κB demonstrated efficient lysosomal escape and intracellular delivery via clathrin-mediated endocytosis and macropinocytosis, achieving high transfection efficiency. In vitro inflammatory models and a psoriasis-like mouse model confirmed that TCPL@siNF-κB enables efficient gene delivery through simple topical application, effectively silences NF-κB signaling, modulates the immune microenvironment, inhibits aberrant angiogenesis, and significantly alleviates psoriatic symptoms, while exhibiting excellent biocompatibility.

Therefore, this study offers a promising non-invasive gene therapy strategy for psoriasis and other potential inflammatory skin disorders.

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Objectives:
Obesity is highly prevalent in psoriatic arthritis (PsA) and associates with worse disease outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly being used for weight loss and diabetes, but their impact on PsA outcomes remains unclear. We aimed to characterize patients with PsA initiating GLP-1RAs and assess longitudinal changes in weight, PsA activity and cardiometabolic parameters.

Methods:
We conducted a retrospective analysis of patients with PsA who initiated GLP-1RAs. PsA disease activity data and cardiometabolic parameters from clinical visits within 1 year before and after GLP-1RA initiation along with demographics and comorbidities were collected.

Results:
48 patients with a median BMI 34.9 were included. Significant weight loss was observed post-treatment (-6.43 kg (95% CI -9.5, -2.0), p< 0.0001), with 60% losing ≥5 % of their baseline bodyweight. CRP levels (-1.1 mg/L, p=0.002), pain scores (-1.0, p=0.01), and triglyceride levels (-0.35 mmol/L, p=0.02) decreased significantly. Each 1% reduction in body weight was associated with significant improvements in DAPSA [β=-0.49 (95% CI: -0.94, -0.03)], tender joint count [β=-0.18 (95% CI: -0.32, -0.05)], EQ-5D [β=0.0016 (95% CI: 0.008, 0.023)], LDL [β=-0.05 (95% CI: -0.10, -0.003)], and systolic blood pressure [β=-0.67 (95% CI: -1.18, -0.15)].

Conclusion:
In this real-world study, GLP-1RA therapy in PsA was associated with clinically meaningful weight loss and improvements in systemic inflammation, pain, and cardiometabolic markers. Improvements in psoriatic outcomes were proportional to the degree of weight loss. These findings warrant further investigation in prospective controlled studies to evaluate the role of GLP-1RAs in PsA management and comorbidities.

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Skin pain is a common but poorly understood symptom of psoriasis, affecting only a subset of patients.

Using imiquimod and interleukin-17A-induced psoriasiform mouse models that exhibited pain-like behaviors, we found that nerve growth factor (NGF) levels were elevated in lesional skin, activating TrkA signaling in dorsal root ganglion neurons and promoting Schwann-cell hypertrophy.

Normally, Schwann cells (SCs) limit NGF signaling in cutaneous peripheral nerves through the p75NTR receptor. However, inflammation driven by interleukin-17A increased non-muscle myosin II activity and elevated NGF levels, leading to the internalization and degradation of p75NTR. The resulting depletion of p75NTR caused local NGF accumulation, excessive TrkA activation, and heightened pain sensitivity.

These findings reveal that psoriatic inflammation converts SCs from protective buffers into drivers of pain, offering a mechanistic explanation for why only some patients experience cutaneous pain in psoriasis. 

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Background:
Palmoplantar psoriasis exhibits greater treatment resistance compared to other psoriatic plaques and presents clinical and histopathological overlap with palmoplantar eczema. This study aimed to investigate treatment resistance mechanisms in palmoplantar psoriasis and assess the contribution of IL-17, IL-23, and IL-36α to the differential diagnosis of palmoplantar psoriasis and eczema. Immunohistochemical levels of these cytokines were measured in paired acral and non-acral psoriatic samples.

Methods:
We retrospectively included 73 patients: 25 with only palmoplantar psoriasis, 25 with palmoplantar eczema, and 23 with both conditions and concurrent plaque psoriasis. Clinical and histopathological diagnoses were confirmed. Immunohistochemical analyses were conducted using preparations stained for IL-17, IL-23, and IL-36α.

Results:
In psoriasis cases, immunohistochemical examination of biopsies from both body and palmoplantar regions showed lower IL-17 and IL-36α expression in acral regions compared to non-acral regions. In palmoplantar eczema patients, IL-17 and IL-23 expression was higher than in palmoplantar psoriasis patients; however, IL-36α expression was similar in both conditions.

Conclusions:
The diminished expression of IL-17 and IL-36α in palmoplantar psoriasis compared to other body sites may contribute to variable responses to targeted treatments. These findings suggest the potential for developing distinct biological treatments for these regions.