Clin Cosmet Investig Dermatol. 2026 Oct 29;19:642546. doi: 10.2147/CCID.S642546. eCollection 2026.

ABSTRACT

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and compromised epidermal barrier function. Although tight junction disruption is a key pathological hallmark, the upstream transcriptional mechanisms driving the downregulation of core barrier proteins such as claudin-1 (CLDN1) remain insufficiently characterized.

METHODS: We implemented an integrative multi-omics framework combining weighted gene co-expression network analysis (WGCNA), single-cell RNA sequencing (scRNA-seq), and machine-learning algorithms to prioritize core diagnostic features in psoriasis. Upstream transcription factors regulating CLDN1 were computationally predicted using the JASPAR, hTFtarget, and KnockTF databases. The regulatory effect of E74-like ETS transcription factor 3 (ELF3) on the CLDN1 promoter was evaluated using dual-luciferase reporter assays, and the inflammatory response of the axis was examined in TNF-α-stimulated HaCaT keratinocytes via quantitative real-time PCR.

RESULTS: Machine-learning prioritization identified CLDN1 as a robust diagnostic feature that is significantly downregulated in psoriatic lesions. Multi-database integration converged on ELF3 as a candidate negative regulator of CLDN1. Dual-luciferase reporter assays demonstrated that ELF3 overexpression significantly suppressed wild-type CLDN1 promoter activity, whereas mutation of the predicted binding site abolished this repression. In TNF-α-stimulated HaCaT cells, ELF3 was markedly upregulated with a concurrent downregulation of CLDN1.

DISCUSSION : These findings suggest that ELF3 functions as a candidate transcriptional repressor of CLDN1 promoter activity and provide preliminary in vitro and computational insights into the transcriptional alterations associated with epidermal barrier disruption in psoriasis, highlighting potential avenues for restoring structural barrier integrity.

PMID:42974488 | PMC:PMC13726643 | DOI:10.2147/CCID.S642546

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Clin Cosmet Investig Dermatol. 2026 Oct 29;19:620524. doi: 10.2147/CCID.S620524. eCollection 2026.

ABSTRACT

BACKGROUND: Psoriasis and acute myocardial infarction (AMI) are both closely associated with immune-inflammatory dysregulation; however, the shared molecular features of psoriasis-AMI comorbidity remain incompletely characterized. To address this gap, this study aimed to identify novel shared inflammation-related candidate genes between psoriasis and AMI and to characterize their cellular expression patterns using public transcriptomic and single-cell RNA sequencing data. The main finding was the identification of shared inflammation-related candidate genes and their cell-type-specific expression patterns in psoriasis-AMI comorbidity.

METHODS: Transcriptomic datasets related to psoriasis and AMI were obtained from the Gene Expression Omnibus (GEO) database. GSE30999 and GSE66360 were used as discovery cohorts. Differentially expressed genes (DEGs) were identified using limma with adjusted P value < 0.05 and |log2FC| ≥ 1.0. Shared DEGs between the two diseases were extracted. GO and KEGG enrichment analyses were performed, and a PPI network was constructed using STRING and Cytoscape. Consensus hub genes were selected using six cytoHubba algorithms. Candidate gene expression differences were evaluated in the external validation datasets GSE201827 and GSE59867, and ROC curve analysis assessed their discriminatory performance. Finally, scRNA-seq datasets GSE220116 and GSE269269 were analyzed to characterize the cell-type distribution of the final candidate genes.

RESULTS: A total of 57 shared DEGs were identified in the psoriasis and AMI discovery cohorts, including 51 commonly upregulated and 6 commonly downregulated genes. Enrichment analysis showed that these genes were mainly involved in processes related to cellular response to lipopolysaccharide, chemotaxis, cytokine activity and chemokine activity, and were significantly enriched in the IL-17, NF-κB, TNF and chemokine signaling pathways, as well as lipid and atherosclerosis-related pathways. PPI network and cytoHubba analyses identified 9 consensus hub genes. External validation and ROC analyses showed that S100A9, S100A12 and CXCL1 were significantly upregulated in both psoriasis and AMI validation datasets and showed moderate discriminatory performance between groups. Single-cell analysis showed that S100A9 and S100A12 exhibited prominent myeloid inflammation-related expression profiles in psoriatic lesions and AMI peripheral immune cells, whereas CXCL1 expression was relatively restricted, suggesting that it may primarily reflect chemokine-mediated inflammatory cell recruitment.

CONCLUSION: This study identified S100A9, S100A12 and CXCL1 as candidate genes potentially associated with shared inflammatory features of psoriasis-AMI comorbidity. These findings suggest that myeloid cell activation and chemokine-mediated recruitment of inflammatory cells may contribute to the molecular link between the two diseases; however, further clinical and experimental validation is required.

PMID:42974441 | PMC:PMC13726512 | DOI:10.2147/CCID.S620524

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J Nutr Metab. 2026 Nov 1;2026:7365660. doi: 10.1155/jnme/7365660. eCollection 2026.

ABSTRACT

Psoriasis is a chronic inflammatory skin disorder characterized by dysregulated immune responses and excessive keratinocyte proliferation, with substantial effects on patients' quality of life. Evidence suggests that the gut microbiota and the gut-skin-immune axis may contribute to systemic inflammation and immune dysregulation associated with psoriasis. This narrative review examines the potential immunomodulatory role of probiotics in psoriasis, with particular emphasis on strain-specific biological effects and the mechanisms linking intestinal microbial modulation to psoriasis-related inflammation. Probiotics may influence intestinal microbial composition, epithelial barrier integrity, microbial metabolite production, and immune signaling. Clinical studies have reported potential improvements in psoriasis severity, inflammatory biomarkers, or quality of life following probiotic supplementation; however, the available evidence remains limited and heterogeneous, with substantial variation in probiotic strains, formulations, doses, treatment durations, concomitant therapies, and clinical outcomes. Unlike previous systematic reviews and meta-analyses that primarily summarize clinical outcomes, this review integrates clinical findings with strain-specific mechanistic and experimental evidence to provide a biologically contextualized interpretation of the potential role of probiotics in psoriasis.

PMID:42973828 | PMC:PMC13725134 | DOI:10.1155/jnme/7365660

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Biomark Med. 2026 Nov 3:1-16. doi: 10.1080/17520363.2026.2756984. Online ahead of print.

ABSTRACT

AIM: This systematic review and meta-analysis aimed to quantitatively evaluate calcitonin gene-related peptide (CGRP) concentrations across autoimmune diseases (psoriasis, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis) and assess its clinical utility as a neuro-immune biofluid biomarker.

MATERIALS AND METHODS: PRISMA-compliant meta-analyses using random-effects models calculated standardized mean differences (SMDs, Hedges' g) from major databases, evaluating circulating biofluids (serum/plasma; 10 studies, 16 cohorts) both overall across all selected autoimmune diseases and stratified by individual disease entities, separately from localized compartments.

RESULTS: Primary synthesis of circulating biofluids (533 cases, 363 controls) showed significant systemic CGRP elevation in autoimmune conditions (SMD = 0.63, 95% CI: 0.46-0.80, p < 0.0001; I² = 14.4%). Subgroup analyses confirmed elevated circulating CGRP in rheumatoid arthritis (SMD = 0.72), psoriasis (SMD = 0.73), and IBD (SMD = 0.57). Multiple sclerosis showed elevated serum CGRP during progressive phases (SMD = 1.06) versus unchanged CSF levels (SMD = 0.04). Trim-and-fill analysis confirmed estimate stability (adjusted SMD = 0.58).

CONCLUSION: Circulating CGRP is elevated across specific autoimmune pathologies, functioning as a dynamic indicator of active neuro-immune inflammation rather than a static universal marker. Clinical implementation requires prospective, longitudinal studies and standardized, isoform-specific quantification assays.

PROSPERO REGISTRATION NUMBER: CRD420261458044.

PMID:42973234 | DOI:10.1080/17520363.2026.2756984

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Ann Med. 2026 Dec;58(1):2749195. doi: 10.1080/07853890.2026.2749195. Epub 2026 Nov 2.

ABSTRACT

BACKGROUND: Hyperkeratotic palmoplantar lesions (HPPLs), primarily encompassing palmoplantar psoriasis (PPP) and hyperkeratotic palmoplantar eczema (HPKE), present a significant diagnostic challenge due to overlapping clinical morphological features. This study evaluates the diagnostic accuracy of dermoscopy as a non-invasive bridge between clinical evaluation and standard histopathology.

METHODS: An observational cross-sectional study was conducted on 44 adult patients presenting with clinically diagnosed HPPLs at a tertiary care center over an 18-month period. Patients underwent thorough clinical examination, dermoscopic evaluation (using a DermLite DL200 Hybrid), and a standard 4.0 mm punch biopsy for histopathological confirmation. Inter-method agreement and diagnostic concordance among the three modalities were analyzed using Cohen's kappa statistic.

RESULTS: The study cohort (mean age 40.32 years) was histopathologically confirmed to have psoriasis in 31 cases (70.45%) and eczema in 11 cases (25%). Dermoscopically, regularly distributed red dots and globules strongly indicated psoriasis (45.16% vs. 0% in eczema), whereas irregular vascular patterns predominated in eczema (54.55%). Concordance between dermoscopic and histopathological diagnoses was remarkably high, showing good agreement (81.81% concordance, κ = 0.652, p < 0.0001). Conversely, clinical-histopathological agreement was poor (56.82%, κ = 0.041), and clinical-dermoscopic agreement was fair (65.90%, κ = 0.350).

CONCLUSIONS: The findings of dermoscopy align closely with histopathology. Dermoscopy serves as an effective adjunctive tool to minimize reliance on invasive skin biopsies, rather than completely replacing them.

PMID:42973050 | DOI:10.1080/07853890.2026.2749195

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J Dermatol Sci. 2026 Oct 14:S0923-1811(26)00174-X. doi: 10.1016/j.jdermsci.2026.10.002. Online ahead of print.

NO ABSTRACT

PMID:42971898 | DOI:10.1016/j.jdermsci.2026.10.002

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J Am Acad Dermatol. 2026 Nov 2:S0190-9622(26)03840-5. doi: 10.1016/j.jaad.2026.10.085. Online ahead of print.

ABSTRACT

BACKGROUND: The NPF/IPC statement exempts routine tuberculosis (TB) testing for IL-17/IL-23 inhibitors in low-burden settings, but elimination may be unsafe in high-burden regions.

OBJECTIVE: To develop and evaluate a clinical score estimating the probability of a high pretreatment interferon-γ release assay (IGRA) response in psoriasis patients before biologic therapy in China.

METHODS: Adult patients with psoriasis scheduled to initiate biologic therapy who underwent pretreatment screening were retrospectively included from four Chinese hospitals. Logistic regression was used to develop and evaluate the score.

RESULTS: The psoriasis TB risk score (PTRS) comprised six items: age>43.0 years (1), BMI>24.8 kg/m² (2), married status (1), smoking (2), alcohol consumption (3), and acitretin use (-2). The AUC was 0.799 (95% CI, 0.758-0.840) in the development cohort, 0.697 (0.625-0.768) in validation cohort 1, and 0.621 (0.462-0.780) in the exploratory Shenzhen cohort. Positivity rates in the development, validation, and external validation cohorts were 2.4%/8.8%/33.2%, 3.7%/11.8%/20.8%, and 2.9%/8.8%/13.7% for the low-, intermediate-, and high-risk groups, respectively.

LIMITATIONS: Retrospective design without longitudinal TB outcomes; performance declined in the geographically distinct cohort.

CONCLUSIONS: The PTRS stratified the probability of a high pretreatment IGRA response in Chinese cohorts; local validation is required before the score is used to modify testing practice.

PMID:42971476 | DOI:10.1016/j.jaad.2026.10.085

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Int Immunopharmacol. 2026 Nov 2;191(Pt 1):117608. doi: 10.1016/j.intimp.2026.117608. Online ahead of print.

ABSTRACT

BACKGROUND: Generalized pustular psoriasis (GPP) is a severe autoinflammatory dermatosis driven by excessive IL-1/IL-36-neutrophil activation, with high disease burden and limited therapeutic options. The mechanisms underlying dysregulated neutrophil recruitment remain incompletely understood, and the lack of mechanistic models that capture key inflammatory features of GPP has limited mechanistic and therapeutic investigations of GPP. Cathepsin S (CTSS), a cysteine protease involved in IL-36γ activation and neutrophil recruitment, has not been investigated in GPP.

METHODS: CTSS expression in GPP lesions was analyzed using public bulk RNA sequencing, single-cell RNA sequencing, and patient samples. A mouse model capable of mimicking the neutrophilic inflammatory phenotype of GPP was established by combining topical imiquimod (IMQ) treatment with intradermal CTSS injection (IMQ + CTSS). Histological, transcriptomic, flow cytometry, ELISA, and cross-species bioinformatics analysis were performed to assess consistency between patients and mice. In vitro experiments and pharmacological inhibition with LY3000328 were used to investigate the functional role of CTSS.

RESULTS: CTSS was markedly elevated in GPP lesions, predominantly enriched in myeloid cells, and closely associated with neutrophil chemotaxis signatures. The IMQ + CTSS model captured key neutrophil-dominant clinical and histopathological features associated with GPP patients. Mechanistically, CTSS promoted keratinocyte-mediated neutrophil recruitment via NF-κB and p38/MAPK signaling pathways, upregulating IL-8 and ICAM-1 expression. Notably, pharmacological inhibition of CTSS with LY3000328 significantly attenuated neutrophilic inflammation in vivo and in vitro.

CONCLUSION: CTSS functions as a critical amplifier of neutrophilic inflammation in GPP and represents a potential therapeutic target. The IMQ + CTSS mouse model provides a mechanistic platform for investigating neutrophilic inflammation and evaluating potential therapeutic strategies targeting CTSS in GPP.

PMID:42971142 | DOI:10.1016/j.intimp.2026.117608

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Dermatologie (Heidelb). 2026 Nov 2. doi: 10.1007/s00105-026-05804-0. Online ahead of print.

ABSTRACT

A 60-year-old chemistry lab technician underwent a tertiary individual prevention program due to hand eczema that was believed to be work-related and refractory to treatment. While the clinical signs on her hand were inconclusive, discrete psoriasiform skin lesions were observed on the glutes. Molecular classification confirmed the diagnosis. After switching to calcipotriol and acitretin, the condition improved significantly, and the patient regained her ability to work. This case underscores the importance of a full-body examination and molecular diagnostics in unclear cases of occupational dermatology.

PMID:42970104 | DOI:10.1007/s00105-026-05804-0

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Acta Derm Venereol. 2026 Nov 2;106:0624. doi: 10.2340/actadv.v106.adv-2026-0624.

NO ABSTRACT

PMID:42969559 | PMC:PMC13725811 | DOI:10.2340/actadv.v106.adv-2026-0624

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Arch Rheumatol. 2026 Sep 9. doi: 10.5152/ArchRheumatol.2026.25145. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: This study aimed to assess the utility of the neutrophil‑to‑lymphocyte ratio (NLR), C‑reactive protein (CRP), and skin lesion severity for identifying arthritic manifestations in individuals with psoriasis.

MATERIALS AND METHODS: A total of 102 patients with psoriasis vulgaris (PsV), 74 with psoriatic arthritis (PsA), and 60 healthy controls were enrolled. Demographic and laboratory data were systematically examined. Skin lesion severity, measured by the Psoriasis Area and Severity Index (PASI), was compared between PsV and PsA groups. Correlation analysis, receiver operating characteristic (ROC) curves, and multivariate regression were performed to evaluate the associative strength of various indicators with PsA and their role in risk stratification.

RESULTS: No significant intergroup differences were found in age, sex, BMI, smoking/alcohol history, or family history of psoriasis (all P > .05). The PsA group exhibited higher WBC, NEU, CRP, and NLR than the PsV and control groups (all P < .001). Platelet‑to‑lymphocyte ratio (PLR) was higher in PsA than in PsV (P = .017), whereas PLT did not differ across groups (P = .296). Joint symptom frequency (arthralgia, synovial thickening, etc) and PASI score were higher in PsA than in PsV (all P < .05). Correlation analysis showed positive associations of NLR and CRP with arthritic symptoms and PASI (all P < .05). ROC analysis revealed that NLR (area under the curve [AUC] = .739), CRP (AUC = .787), and PASI (AUC = .783) had moderate individual discriminative value; the combination NLR+CRP+PASI yielded the highest performance (AUC = .891, sensitivity 82.43%, specificity 83.33%). Multivariate regression indicated that NLR and CRP were independently associated with PsA (both P < .001).

CONCLUSION: NLR, CRP, and PASI are closely linked to arthritic symptoms in psoriasis patients. As independent correlates of PsA, NLR and CRP, along with skin lesion severity, may offer a clinical reference for early arthritis detection and risk assessment.

PMID:42969409 | DOI:10.5152/ArchRheumatol.2026.25145

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eGastroenterology. 2026 Oct 30;4(4):e100708. doi: 10.1136/egastro-2026-100708. eCollection 2026.

ABSTRACT

Interleukin (IL)-23 inhibition is now an established therapeutic strategy in inflammatory bowel disease (IBD), supported by the efficacy of selective IL-23p19 monoclonal antibodies in both Crohn's disease (CD) and ulcerative colitis (UC). Advances in peptide engineering have also enabled direct oral targeting of the IL-23 receptor (IL-23R), introducing an alternative approach to inhibition of the same inflammatory pathway. This narrative review examines the biological rationale for targeting the IL-23-IL-23R axis and the clinical evidence establishing selective IL-23p19 inhibition in IBD. Particular attention is given to the clinical development of icotrokinra, an oral macrocyclic peptide IL-23R antagonist. Phase 3 studies in psoriasis have established the efficacy of oral IL-23R antagonism, while the phase 2b ANTHEM-UC study has provided clinical evidence of efficacy in IBD, with improvements in clinical and endoscopic outcomes accompanied by translational evidence of pathway suppression. Ongoing phase 3 programmes in UC and CD will determine whether oral IL-23R antagonism can achieve durable clinical and endoscopic efficacy and establish its place alongside existing IL-23p19 monoclonal antibodies. If successful, this approach could represent a broader shift towards highly selective oral targeting of extracellular inflammatory pathways that have traditionally required biological therapy.

PMID:42968944 | PMC:PMC13723900 | DOI:10.1136/egastro-2026-100708

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J Biomed Mater Res A. 2026 Nov;114(11):e70182. doi: 10.1002/jbm.a.70182.

ABSTRACT

Enzyme therapeutics are often limited by poor stability, rapid clearance, and systemic effects that reduce therapeutic efficacy and necessitate high dosing. Enzyme-biomaterial conjugation can address these limitations and improve outcomes by localizing therapeutics at the tissue site of intended action. In particular, indoleamine 2,3-dioxygenase (IDO), a potent immunomodulatory enzyme, has demonstrated therapeutic effectiveness when retained locally at sites of inflammation through fusion to a carbohydrate-binding protein. Here, we report a complementary biomaterial-mediated delivery strategy to prolong retention time and investigate efficacy in an imiquimod-induced model of psoriasis. IDO maintained enzyme activity after bioconjugation to polyethylene glycol maleimide (PEG-MAL) microgels. Localized delivery of IDO-conjugated microgels reduced psoriatic scores compared to soluble IDO or unconjugated microgels. Additionally, fibrotic capsule thickness decreased 30% in the IDO-conjugated microgel group compared to the unconjugated microgel. These findings demonstrate the efficacy of localized IDO delivery via covalent attachment to granular hydrogels, which may serve as a platform for other immunomodulatory enzymes.

PMID:42968485 | DOI:10.1002/jbm.a.70182

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J Dermatol. 2026 Nov 1. doi: 10.1111/1346-8138.70560. Online ahead of print.

ABSTRACT

Vunakizumab is a humanized anti-IL-17A monoclonal antibody approved in China for moderate-to-severe plaque psoriasis. Real-world data on its effectiveness and predictors of response remain scarce. This prospective, single-center, observational study enrolled 34 adults receiving vunakizumab (240 mg subcutaneously at weeks 0, 2, and 4, then every 4 weeks). PASI, PGA, BSA, and DLQI were assessed at baseline and weeks 2, 4, 8, and 12. Univariate logistic regression with Benjamini-Hochberg correction screened baseline predictors of week-4 PASI 90 and week-12 PASI 100. A separate stratification analysis compared week-12 PASI 100 rates between BMI groups using the Chinese-specific threshold of 24 kg/m² (Fisher exact test). All 34 patients completed the 12-week follow-up (79.4% male; median age 37.5 years; median baseline PASI 10.0). At week 12, PASI 75, PASI 90, and PASI 100 rates were 100%, 91.2%, and 64.7%, respectively, and PGA 0/1 was 100%. Median DLQI decreased from 6.0 at baseline to 0 at week 12 (p < 0.001). Adverse events occurred in 17.6% of patients, all Grade 1. In exploratory analysis, higher BMI was associated with lower week-4 PASI 90 rates (q = 0.032), though the association with week-12 PASI 100 rates did not survive Benjamini-Hochberg correction (q = 0.450). On BMI stratification, normal-weight patients had higher week-12 PASI 100 rates than overweight or obese patients (92.9% vs. 45.0%, p = 0.009). Vunakizumab achieved high PASI 90 and PASI 100 response rates at week 12, with adverse events limited to Grade 1. In this small exploratory cohort, higher BMI was associated with a lower probability of PASI 100 at week 12. Whether this association is reproducible and, if so, whether it should inform patient selection requires prospective evaluation in larger cohorts.

PMID:42968219 | DOI:10.1111/1346-8138.70560

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Eur J Pharm Biopharm. 2026 Nov 1:115284. doi: 10.1016/j.ejpb.2026.115284. Online ahead of print.

ABSTRACT

Overcoming the thickened stratum corneum is critical for effective topical psoriasis therapy. To address this, we engineered chemically cross-linked sodium alginate/poly(vinyl alcohol) hydrogels enriched with Aloe vera. These incorporate thermosensitive carriers co-loaded with salicylic acid and fluocinolone acetonide, enabling sustained drug release and enhanced penetration. Crucially, evaluation in a 3D in vitro psoriasis model confirmed the biocompatibility of the formulations and their potent anti-inflammatory activity, significantly downregulating IL-6, DEFB4, elafin, S100A7, and S100A12. Using this advanced 3D model provides critical insights into the formulation's mechanism of action, highlighting its potential for targeted, safe psoriasis management.

PMID:42967517 | DOI:10.1016/j.ejpb.2026.115284

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