BACKGROUND: Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.
OBJECTIVE: Characterize lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.
METHODS: Skin microdialysis samples from patients with atopic dermatitis (AD, n=6), psoriasis vulgaris (PSO, n=7) or prurigo nodularis (PN, n=6), as well as healthy controls (n=7) were subjected to proteomics and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.
RESULTS: Among the top 20 enriched GO annotations, NAD metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched KEGG pathways in these three groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of MCP-1 compared to nonlesional skin. IL-8 was elevated in lesional vs nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA-seq data revealed identical cellular sources of these cytokines in AD, PSO and PN.
CONCLUSIONS: Based on microdialysate, proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1 and IL-12p40 might be suitable markers for minimally invasive molecular profiling.

UNASSIGNED: This study aimed to measure the associations between different inflammatory factors, namely interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hs-CRP), and atherosclerosis in patients with psoriasis vulgaris.
UNASSIGNED: A cross-sectional study was conducted at two hospitals in Hanoi, Vietnam. A total of 125 patients with psoriasis vulgaris and 50 healthy controls were recruited. Clinical characteristics and atherosclerosis were assessed. IL-17A, TNF-α, and hs-CRP levels were measured.
UNASSIGNED: Psoriasis vulgaris patients with atherosclerosis had higher levels of hs-CRP (median = 1.22; interquartile range-IQR = 0.34-12.11) and IL-17A (median = 1.30; IQR = 0.43-4.28), but a lower level of TNF-α (median = 0.54; IQR = 0.13-3.41) compared to those without atherosclerosis (p < 0.05). Only LogIL-17A was positively related to atherosclerosis in psoriasis patients (Odds Ratio-OR = 2.16, 95% CI = 1.06-4.38, p < 0.05). After excluding systemically treated patients, LogIL-17A and Log TNF-α were associated with the likelihood of atherosclerosis (p < 0.05).
UNASSIGNED: This study suggests a link between elevated levels of IL-17A and TNF-α and subclinical atherosclerosis. Further investigation on a larger scale is required to establish the causality of this relationship.

Several studies have indicated a potential causal relationship between plasma standard lipids, such as high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and psoriasis. However, few studies have offered causal evidence of lipid species beyond these standard lipids. We conducted an analysis using a genome-wide association study (GWAS) dataset comprising 179 lipid species, including 13 types across four major categories, to identify instrumental variables (IVs) associated with plasma lipids. We utilized two GWAS datasets from the IEU and Finngen for psoriasis vulgaris as the outcome. A two-sample Mendelian randomization (MR) analysis was used to explore the causal relationship between 179 lipid species and psoriasis vulgaris in two datasets. Lipid species showing causal association in both psoriasis datasets were compared for overlap. Our study identified potential causal relationships between six lipid species and psoriasis vulgaris: phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylcholine (18:1_20:4), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1). In summary, elevated plasma levels of phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1) may increase the risk of psoriasis vulgaris. Conversely, plasma phosphatidylcholine (18:1_20:4) may play a protective role against psoriasis vulgaris.

Psoriasis (PsO) is a prevalent chronic inflammatory skin disease. It is a complex condition that is affected by environmental and hereditary variables. Numerous pathogens, including viruses, bacteria, and even fungi, have been linked to PsO. One of the mechanisms that clears infections is autophagy. The mechanism by which a cell feeds itself is called autophagy by reusing cytoplasmic components in the lysosome. The autophagy-related (ATG) proteins are essential components of the system that control the strictly regulated process of autophagy. Among these 41 proteins, ATG5 is one that is required in order for autophagic vesicles to develop. This research aimed to compare ATG5 levels in serum among those suffering from psoriasis vulgaris and healthy controls. This cross-sectional research was carried out on 45 individuals with vulgaris psoriasis and 45 healthy, sex and age-matched control subjects. All participants underwent a clinical examination, a laboratory investigation, and a history taking, including lipid profiles and serum ATG5. The mean age of the control and PsO were 40.6 ± 9.6, and 43.7 ± 9.3 years respectively. The mean total PASI score was 13.9 ± 8.9, with a median of 11.7 (8.8). According to the PASI score, about 38% (n = 17) had mild disease (PASI < 10), and about 62% (n = 28) had moderate/severe disease (PASI ≥ 10). There was a significantly higher median (IQR) (25th-75th) ATG5 level in PsO 206 (97) (145-242) ng/ml than in the control 147 (98) (111-209) ng/ml (p = 0.002). An insignificant higher median level (IQR) was observed in PsO with mild disease 207(95) compared with those with moderate/severe disease 183(98.5) (p = 0.057). Dissimilarly, the median (IQR) ATG5 level was significantly lower in PsO individuals with metabolic syndrome 170(72) compared with those without 207(104) (p = 0.044). Four predictors were identified following sex and age adjustments, in the final linear regression model: PASI score, triglyceride, High-Density Lipoprotein, and presence of metabolic syndrome. There can be a connection between autophagy as measured by ATG5 and psoriasis vulgaris. ATG5 was elevated in the serum of individuals with psoriasis vulgaris. However, it decreased in patients with metabolic syndrome. No relation was found between serum ATG5 and PASI score. Psoriasis vulgaris patients may benefit from using an autophagy enhancer as a potential treatment target.

UNASSIGNED: Psoriasis is a common autoimmune disease in clinical practice, and previous observational studies have suggested that PPARG agonists such as Pioglitazone may be potential therapeutic agents. However, due to interference from various confounding factors, different observational studies have not reached a unified conclusion. We aim to evaluate the potential use of PPARG agonists for treating psoriasis from a new perspective through drug-targeted Mendelian randomization (MR) analysis.
UNASSIGNED: This study includes data on 8,876 individuals for acute myocardial infarction from GWAS, and LDL cholesterol data from 343,621 Europeans. FinnGen contributed psoriasis vulgaris data for 403,972 individuals. The DrugBank10 databases function to identify genes encoding protein products targeted by active constituents of lipid-modifying targets. A two-sample MR analysis and summary-data-based MR (SMR) analysis estimated the associations between expressions of drug target genes and symptoms of psoriasis vulgaris. A multivariable MR study was further conducted to examine if the observed association was direct association.
UNASSIGNED: SMR analysis revealed that enhanced PPARG gene expression in the blood (equivalent to a one standard deviation increase) was a protective factor for psoriasis vulgaris (beta = -0.2017, se = 0.0723, p = 0.0053). Besides, there exists an MR association between LDL mediated by PPARG and psoriasis vulgaris outcomes (beta = -3.9169, se = 0.5676, p = 5.17E-12). These results indicate that PPARG is a therapeutic target for psoriasis, suggesting that psoriasis may be a potential indication for PPARG agonists.
UNASSIGNED: This study confirms that therapeutic activation of PPARG helps suppress the development of psoriasis. Psoriasis may be a new indication for PPARG agonists, such as Pioglitazone. In the future, new anti-psoriatic drugs could be developed targeting PPARG.

Inflammatory back pain is a characteristic of spondyloarthritis. It is not, however, an exclusive symptom of inflammatory rheumatic diseases as it can also be associated with non-inflammatory entities. Infrequently, the etiology can be found in neoplastic conditions such as malignant lymphoma. Even in the presence of comorbidities indicatory of underlying rheumatic disease, like psoriasis vulgaris, the clinician should not be led astray. It is essential to pay attention to contradictory findings, as treatment crucially differs depending on diagnosis. Herein, we report on a psoriasis patient who presented with characteristic inflammatory back pain and deceptive imaging results. While the patient was initially thought to suffer from an inflammatory rheumatic disease with axial involvement, it was the accompanying atypical circumstances, particularly her age, that instantly challenged the diagnosis of axial psoriatic arthritis. She was eventually diagnosed with stage IV follicular lymphoma that manifested with rare and exclusively extranodal lesions and spondyloarthritis-like morphology. This case effectively demonstrates the importance of a thorough diagnostic workup and how certain clinical factors, such as the patient\'s age, should be considered when confronted with inflammatory back pain.

Psoriasis vulgaris, also known as plaque-type psoriasis, is the most common form of psoriasis. It is characterized by erythematous plaques covered with scales. Among the available treatments, the fully human monoclonal antibodies ustekinumab (UST) and guselkumab (GUS) have low immunogenicity. Additionally, GUS has not been found to have a significant risk of inducing the development of clinically relevant neutralizing antibodies. Therefore, we sometimes consider switching to GUS when UST is insufficiently effective. However, switching to another biological agent usually requires an induction phase, potentially incurring additional costs. We herein present the first case of a successful transition from UST 90 mg to an extended dosing interval of GUS without an induction phase. This approach may be a viable and cost-saving option, especially for patients with relatively low disease activity.

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One of the immune-related adverse events from immune checkpoint inhibitors (ICIs) is skin toxicity. Oral corticosteroids are the first-line treatment for severe cutaneous immune-related adverse events. However, corticosteroids may conflict with the efficacy of ICIs. A 55-year-old Japanese man with a history of psoriasis vulgaris was diagnosed with small-cell lung cancer (Stage ⅣA) and administered combined chemoimmunotherapy, including atezolizumab, which resulted in exacerbation of psoriasis. In response, he was treated with biological agents, such as anti-IL-23 and IL-17 antibodies, risankizumab, and secukinumab, respectively, and achieved long-term survival with continued treatment with atezolizumab. This case report suggests that biological agents might be the best course of treatment against autoimmune-related adverse events caused by ICI therapy.

BACKGROUND: Prior research has explored the relationship between inflammatory skin disorders and breast cancer (BC), yet the causality of this association remains uncertain.
METHODS: Utilizing a bidirectional two-sample Mendelian randomization (MR) approach, this study aimed to elucidate the causal dynamics between various inflammatory skin conditions-namely acne, atopic dermatitis, psoriasis vulgaris, urticaria, and rosacea-and BC. Genetic variants implicated in these disorders were sourced from comprehensive genome-wide association studies representative of European ancestry. In the forward MR, BC was posited as the exposure, while the reverse MR treated each inflammatory skin disease as the exposure. A suite of analytical methodologies, including random effects inverse variance weighted (IVW), weighted median (WME), and MR-Egger, were employed to probe the causative links between inflammatory skin diseases and BC. Sensitivity analyses, alongside evaluations for heterogeneity and pleiotropy, were conducted to substantiate the findings.
RESULTS: The MR analysis revealed an increased risk of acne associated with BC (IVW: OR = 1.063, 95% CI = 1.011-1.117, p = 0.016), while noting a decreased risk of atopic dermatitis (AD) in BC patients (IVW: OR = 0.941, 95% CI = 0.886-0.999, p = 0.047). No significant associations were observed between BC and psoriasis vulgaris, urticaria, or rosacea. Conversely, reverse MR analyses detected no effect of BC on the incidence of inflammatory skin diseases. The absence of pleiotropy and the consistency of these outcomes strengthen the study\'s conclusions.
CONCLUSIONS: Findings indicate an elevated incidence of acne and a reduced incidence of AD in individuals with BC within the European population.