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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.

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Background:
Psoriasis is an immune-mediated chronic skin disease. Despite the low proportion of B cells in human blood, they play an important role in regulating the pathogenesis of psoriasis. Therefore, we investigated the role and clinical significance of B cells in psoriasis by conducting experiments.

Materials and Methods:
Thirty psoriasis patients and 30 healthy volunteers were selected as human subjects for skin biopsy collection and histological analysis, and EDTA anticoagulated blood was collected for flow cytometry and ELISA. The means of two independent samples were compared using an independent samples t-test, and p < 0.05 was considered to be statistically significant.

Results:
Stained pathological sections from psoriasis patients revealed infiltration of a large number of cells in skin lesions. Flow cytometry and ELISA analysis revealed the following comparisons between psoriasis patients and healthy volunteers: significant upregulation of lymphocytes (p < 0.05); no significant difference in CD19+ B cells; significant difference in Bregs, CD19+ CD24+ CD38+ cells (p < 0.05); significant difference in memory B cells, CD19+ CD27+ CD38− cells (p < 0.01); significant difference in naive B cells, CD19+ CD27− CD38+ cells (p < 0.05); BAFF, IgD, and IL-4 serum levels were much higher in PsO patients than those in healthy volunteers (p < 0.05). However, no remarkable difference in IL-10 level (p > 0.05) was found.

Conclusions:
The levels of B cell populations as well as immune molecules including BAFF, IgD, and IL-4 are significantly associated with psoriasis. These findings may lead to further investigations into the role of B cells and their subsets in the pathogenesis of psoriasis.

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Envudeucitinib demonstrated robust skin clearance, achieving high thresholds of clinical response at Week 16 that continued to deepen through Week 24 in both trials. Psoriasis Area and Severity Index (PASI) 90 responses, which emerged as early as Week 4, were achieved by 59.9% and 53.1% of envudeucitinib patients at Week 16 (and by 4.8% and 4.3% of placebo patients), increasing to 68.0% and 62.1% at Week 24. PASI 100 responses followed a similar trajectory, with 29.4% and 27.7% of envudeucitinib patients achieving complete skin clearance at Week 16 (as compared to 0.9% and 0.9% of placebo patients), rising to 41.0% and 39.5% at Week 24.

Envudeucitinib also demonstrated improvements in scalp psoriasis, a high-impact, difficult-to-treat area marked by profound effects on quality of life. At Week 24, approximately three out of four envudeucitinib patients1 achieved clear or almost clear scalp psoriasis, measured by the Scalp Specific Physician’s Global Assessment (ss‑PGA 0/1), with over 30% responding as early as Week 4.

Broad and meaningful clinical benefits emerged early. Notably, quality-of-life and itch improvements appeared before PASI 90 skin clearance responses and continued to deepen through Week 24 across both trials.

• By Week 12, approximately 50% of envudeucitinib patients2 achieved Dermatology Life Quality Index (DLQI) 0/1, demonstrating minimal to no impact of disease on quality of life.
  
• By Week 16, envudeucitinib patients achieved an average improvement of more than 4 points from baseline on the 0–10 Worst Pruritus Numeric Rating Scale (NRS), with clinically meaningful itch relief as early as Week 2—one of the most burdensome symptoms of psoriasis.
  

“What stands out with envudeucitinib in these trials is how quickly patients begin to feel relief from symptoms, and how deeply those improvements continue to build,” said leading dermatologist and psoriasis expert Dr. Andrew Blauvelt. “For people living with the daily burden of plaque psoriasis, this degree of skin clearance and symptom improvement from an oral investigational drug is impressive, especially when high‑impact sites are involved.”

Treatment with envudeucitinib was generally well tolerated through Week 24 in both trials, with a safety profile consistent with the Phase 2 program, including its long-term extension study. No clinically significant laboratory abnormalities or cases of tuberculosis reactivation were observed. Treatment-emergent adverse events were mostly mild, transient, self-limited, or responding to standard therapy, with the most common being headache, nasopharyngitis, upper respiratory tract infection, and acne. No new safety signals were observed.

“Envudeucitinib delivered the level of skin clearance, symptom relief, and safety in Phase 3 that the TYK2 mechanism has long promised but that has not been fully realized—until now—with sustained, maximal 24-hour inhibition of the IL-23 / IL-17 pathways,” said Dr. Jörn Drappa, Chief Medical Officer of Alumis. “The depth of clinical response, together with the favorable safety profile observed, underscores a differentiated clinical profile among marketed and investigational oral options and supports envudeucitinib’s potential to play a leading role in the treatment of patients with moderate‑to‑severe plaque psoriasis.”

Alumis is continuing to evaluate the long-term efficacy and safety of envudeucitinib in the ONWARD3 long-term extension trial and plans to submit a New Drug Application to the U.S. Food and Drug Administration in the second half of this year.

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Psoriasis is a chronic inflammatory skin disease in which the IL-23/Th17/IL-17 axis plays a central pathogenic role while also contributing to antifungal defence. IL-17-targeting biologics such as secukinumab and ixekizumab are increasingly used in its management.

This study aimed to characterize changes in the diversity and composition of oral fungal and bacterial communities in psoriasis patients before and after treatment with IL-17 inhibitors. Oral swabs were collected from psoriasis patients at baseline and after 3 months of IL-17 inhibitor therapy, as well as from healthy controls. Direct microscopy and fungal culture were performed. Microbial DNA was extracted and subjected to amplicon sequencing of the fungal ITS1 region and the bacterial 16S rRNA V3-V4 region using the Illumina HiSeq platform.

A total of 36 patients and 38 healthy controls were enrolled in this study. Fungal microbiome analysis revealed significantly increased alpha diversity after treatment compared with baseline (p < 0.05), accompanied by markedly elevated beta diversity (p < 0.001). The dominant fungal genera were Blumeria, Pichia and Aspergillus. The relative abundance of Candida was significantly higher in psoriasis patients at baseline than in controls (16.00% vs. 6.43%, p < 0.05) and decreased significantly after therapy (6.12%, p < 0.05). In the bacterial microbiome, beta diversity decreased significantly following treatment (p < 0.001), whereas alpha diversity increased (p < 0.05). The predominant bacterial genera were Streptococcus, Neisseria and Rothia. After treatment, the relative abundance of Haemophilus was significantly lower than at baseline (9.18% vs. 10.14%, p < 0.05). Streptococcus showed a higher trend in patients versus controls (29.74% vs. 16.48%) and declined post-treatment (23.71%).

In conclusion, IL-17 inhibitor therapy in psoriasis alters the oral fungal and bacterial microbiota, with notable shifts in Candida, Haemophilus and Streptococcus. These findings provide new insights into the oral microbial changes associated with biologic therapy and may inform clinical monitoring of mucocutaneous microbial imbalance during treatment.

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Introduction:
Psoriasis is a recurrent immune-mediated systemic disease. Adiponectin (APN), a key regulator of metabolism, is also known for its anti-inflammatory properties in several inflammatory disorders. The study aims to investigate the anti-inflammatory properties of APN on human immortalized keratinocyte cells (HaCaT) and to evaluate its therapeutic potential in an imiquimod (IMQ)-induced psoriasis mouse model.

Methods:
HaCaT cells were treated with 5, 10, or 20 μg/ml APN, and cell viability was assessed. A psoriasis-like cellular model was created by exposing HaCaT cells to TNF-α (50 ng/ml) for a duration of 24 h. Apoptosis was analyzed using flow cytometry, and the secretion of inflammatory cytokines was measured through enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA expression levels of AdipoR1, AdipoR2, and T-cadherin(T-cad). Aurora kinase A (AURKA) and Forkhead transcription factor 1 (FOXM1) were analyzed using Western blotting (WB) and RT-qPCR. The anti-psoriatic effect of APN was also evaluated in IMQ-induced psoriatic dermatitis. Additionally, ELISA and WB were used to assess cytokines and key signaling proteins in mouse skin tissues.

Results:
APN significantly inhibited the proliferation of HaCaT cells and enhanced their apoptosis. Additionally, it decreased the production of interleukin (IL)-1β, IL-8, and IL-6. APN upregulated AdipoR1 and AdipoR2 mRNA levels while downregulating the mRNA and protein levels of T-cad. Mechanistically, APN mitigated the inflammatory response in keratinocytes by suppressing the TNF-α-induced upregulation of AURKA and FOXM1. This mechanism was substantiated in vivo, where APN treatment alleviated IMQ-induced psoriatic dermatitis in mice, concurrently reducing levels of IL-1β, CXCL2 and IL-6, and modulating the expression of AdipoR1, AdipoR2, AURKA, and FOXM1 in mouse skin.

Conclusion:
Our findings suggest that APN inhibits keratinocyte hyperproliferation and suppresses inflammation in TNF-α-induced keratinocytes. Moreover, APN treatment attenuates IMQ-induced psoriatic dermatitis in mice, supporting its potential as a therapeutic approach for psoriasis.

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Objective:
The psoriatic immune microenvironment (PIME) is central to psoriasis pathogenesis, yet its mechanistic drivers are incompletely defined. This study aimed to delineate immune cell infiltration patterns and identify pivotal disease-related immune genes through a systematic analysis of the PIME.

Methods:
We evaluated the infiltration levels of 28 immune cell subtypes in 11 psoriasis-related microarray datasets using single-sample gene set enrichment analysis (ssGSEA). Subsequent differential expression, consensus clustering, and weighted gene co-expression network analysis (WGCNA) were employed to identify key genes. These findings were validated using human psoriatic tissue samples and an imiquimod-induced murine psoriasis model to construct a predictive model termed IMscore.

Results:
Our analysis identified five pivotal immune-related differentially expressed genes (ImDEGs): CXCL8, CXCL9, CCL18, RGS1, and SAMSN1. A novel predictive model, IMscore, was constructed based on these ImDEGs to assess psoriasis risk. Furthermore, immune infiltration profiling and gene set enrichment analysis demonstrated that these ImDEGs are functionally associated with psoriasis-related inflammatory pathways, validating the diagnostic utility of the IMscore framework.

Conclusion:
These results provide new insights into the immunological mechanisms underlying psoriasis and establish a multi-gene signature with potential for improving early diagnosis and therapeutic development.

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Objective:
To examine the association between radiographic structural damage and physical function (PF) in psoriatic arthritis (PsA).

Methods:
Data were analyzed from a large longitudinal PsA cohort. PF was measured using the Health Assessment Questionnaire (HAQ, 0-3) and Short Form-36 PF subscale (SF-36, 0-100); radiographic joint damage using modified Steinbrocker score (mSS, 0-168). Associations between PF and mSS were analyzed using linear mixed models. We also evaluated the impact of presence of any damaged joint (grade 2-4), joint damage by individual grades, and number of damaged joints (grade 2-4) per patient on PF.

Results:
Of 1177 patients (mean age 44.61 ± 12.76 years; 55.8% males), baseline mSS was 2 (IQR 0-8.5), HAQ 0.62 (0.12-1.12), and SF-36 PF 60 (35-85). Higher mSS was significantly associated with worse SF-36 PF (β= -0.10; 95%СI -0.15, -0.05) and HAQ (0.003; 0.002, 0.004) after controlling for swollen joint count, sex, and disease duration. The number of damaged joints was associated with worse SF-36 PF (-0.23; -0.38, -0.08) and HAQ (0.005; 0.002, 0.009). The presence of a damaged joint (grade 2-4) alone didn't impact PF. However, the presence of a joint with grade-4 destruction was associated with substantially worse SF-36 PF (-3.04; -5.93, -0.15) and HAQ (0.09; 0.03, 0.15). Increasing counts of grade-4 joints demonstrated a strong dose response with SF-36 PF (-0.54; -0.81, -0.26) and HAQ (0.01; 0.01, 0.02).

Conclusion:
Radiographic structural damage, particularly severe joint destruction, is independently associated with impaired PF in PsA, highlighting the importance of early detection and prevention of damage.

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Purpose:
Psoriasis is a common, chronic epidermal hyperplastic and inflammatory skin disease. Studies have shown that the reduction of skin-derived glucocorticoids (GC) may be one of the pathogenic factors of psoriasis. However, the clinical significance of the glucocorticoid receptor (GR) in patients with psoriasis remains unclear. This study aims to investigate the immunohistochemical expression of GR in psoriatic lesional tissues and its quantitative correlation with psoriasis severity, as well as to clarify the direction of this association (positive or negative).

Methods:
Skin tissue and corresponding patient information were collected from 15 patients with chronic eczema (CE), 15 patients with lichen planus (LP), 26 patients with psoriasis, and 15 healthy adults. The skin tissue was embedded in paraffin and sectioned, followed by immunohistochemical staining using a GR antibody. The clinicopathological data were then correlated with the staining results. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator’s Global Assessment (IGA), and Dermatology Life Quality Index (DLQI) scoring systems.

Results:
We compared GR levels in skin tissues among healthy adults and patients with psoriasis, CE, and LP. Compared with normal skin tissues, GR levels were reduced in lesional skin of both CE and LP, with an even more pronounced decrease observed in psoriasis tissues (p < 0.01). Among the three psoriasis subtypes (ordinary psoriasis [psoriasis], pustular psoriasis [PP], and psoriatic arthritis [PA]), GR expression was the highest in the lesional skin of PA patients, exceeding that found in psoriasis patients, while expression was lower in PP lesions (p < 0.01). Strong positive correlation was found between PASI and BSA (r = 0.8). In comorbidity analysis, psoriasis with obesity (PO) showed increased GR levels (p < 0.01), whereas psoriasis associated with hyperuricemia (PH) did not, confirming GR as a reliable diagnostic marker for psoriasis despite comorbidities.

Conclusion:
GR level shows promise as an immunohistochemical biomarker for identifying psoriasis and assessing its severity. While comorbidities like obesity may affect its utility as a diagnostic marker, in the case of hyperuricemia, GR levels remain a reliable indicator.

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Background:
Psoriasis is a chronic relapsing systemic inflammatory disease with a high prevalence of psychiatric comorbidities, especially depression. However, the precise role of inflammation in the relationship between psoriasis and depression remains unclear.

Method:
We explored the association among psoriasis, systemic inflammatory biomarkers, and depression in a large, ethnically diverse sample from the 2009–2014 National Health and Nutrition Examination Survey (NHANES) data. Psoriasis was estimated by the questionnaire. Depression was evaluated using the 9-item Patient Health Questionnaire (PHQ-9). Systemic inflammation response index (SIRI) and neutrophil-to-lymphocyte ratio (NLR) were determined using the examination data. Meanwhile, multivariable logistic and linear regression analyses explored the relationship between psoriasis, systemic inflammatory markers, and depression. On the basis of restricted cubic spline (RCS) regression, we further explored the potential linear relationship between systemic inflammatory biomarkers and depression. Finally, a mediation model was established to explain the intermediary role of systemic inflammatory biomarkers in this relationship.

Result:
Among the 12,734 participants in this study, 1172 participants had a depression score ≥ 10. After full adjustment, psoriasis was positively associated with depression and systemic inflammatory markers (for depression, OR [95% CI]: 2.000 [1.500, 2.668]; for LnSIRI, β [95% CI]: 0.091 [0.033, 0.150]; for LnNLR, β [95% CI]: 0.053 [0.006, 0.099]). Meanwhile, systemic inflammatory marker levels were linearly associated with depression (LnSIRI: Pnon-linear = 0.696; LnNLR: Pnon-linear = 0.921). Further mediation analysis indicated that SIRI and NLR mediated a marginal portion of the potential effects of psoriasis on depression, with proportions of 1.64% and 2.00%, respectively.

Conclusion:
Psoriasis is a risk factor for depression. Blood-based systemic inflammatory biomarkers are an easily accessible and cost-effective tool for identifying psoriasis and partially mediating the association between psoriasis and depression. It may provide important insights into guiding anti-inflammatory treatment strategies to prevent depression.

• have an infection that does not go away or that keeps coming back;
  
• have tuberculosis (TB) or have been in close contact with someone with TB;
  
• have recently received or are scheduled to receive an immunisation (vaccine). Avoid receiving live vaccines during treatment;
  
• have kidney problems;
  
• are pregnant or plan to become pregnant;
  
• are breastfeeding or plan to breastfeed;
  

• Prescription medicines
  
• Over-the-counter medicines
  
• Vitamins
  
• Herbal supplements
  

• Fever, sweat, or chills
  
• Muscle aches, weight loss or a cough
  
• Warm, red, or painful skin or sores on your body different from your psoriasis
  
• Diarrhoea or stomach pain
  
• Shortness of breath
  
• Blood in your mucus or phlegm 
  
• burning when you urinate or urinating more often than normal