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Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a new tickborne bandavirus identified in China in 2009 (1), and subsequently in South Korea in 2013 (2), [...]

Dysfunction of vascular endothelial cells (ECs) facilitates imbalanced immune responses and tissue hyperinflammation. However, the heterogeneous functions of skin ECs and their underlying mechanism in dermatoses remain to be determined. Here, focusing on the pathogenic role of skin ECs in psoriasis, we characterized the molecular and functional heterogeneity of skin ECs from healthy individuals and psoriasis patients at the single-cell level. We found that endothelial glycocalyx destruction, a major feature of EC dysfunction in psoriasis, was a driving force during the process of T cell extravasation. Interestingly, we identified a skin EC subset, [IGFBP7.sup.hi] ECs, in psoriasis. This subset actively responded to psoriatic-related cytokine signaling, secreted IGFBP7, damaged the endothelial glycocalyx, exposed the adhesion molecules underneath, and prepared the endothelium for immune-cell adhesion and transmigration, thus aggravating skin inflammation. More importantly, we provided evidence in a psoriasis-like mouse model that anti-IGFBP7 treatment showed promising therapeutic effects for restoring the endothelial glycocalyx and alleviating skin inflammation. Taken together, our results depict the distinct functions of EC clusters in healthy and psoriatic skin, identify [IGFBP7.sup.hi] ECs as an active subset modulating vascular function and cutaneous inflammation, and indicate that targeting IGFBP7 is a potential therapeutic strategy in psoriasis., Introduction Blood vessels are vital life-supporting channels penetrating almost every organ and tissue in the human body. Vascular endothelial cells (ECs), the inner lining of blood vessels, not only form [...]

Background Skin barrier dysfunction may both initiate and aggravate skin inflammation. However, the mechanisms involved in the inflammation process remain largely unknown. Objectives We sought to determine how skin barrier dysfunction enhances skin inflammation and molecular mechanisms. Methods Skin barrier defect mice were established by tape stripping or topical use of acetone on wildtype mice, or filaggrin deficiency. RNA-Seq was employed to analyse the differentially expressed genes in mice with skin barrier defects. Primary human keratinocytes were transfected with formylpeptide receptor (FPR)1 or protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) small interfering RNA to examine the effects of these gene targets. The expressions of inflammasome NOD-like receptor (NLR)C4, epidermal barrier genes and inflammatory mediators were evaluated. Results Mechanical (tape stripping), chemical (acetone) or genetic (filaggrin deficiency) barrier disruption in mice amplified the expression of proinflammatory genes, with transcriptomic profiling revealing overexpression of formylpeptide receptor (Fpr1) in the epidermis. Treatment with the FPR1 agonist fMLP in keratinocytes upregulated the expression of the NLRC4 inflammasome and increased interleukin-1β secretion through modulation of ER stress via the PERK-eIF2α-C/EBP homologous protein pathway. The activation of the FPR1-NLRC4 axis was also observed in skin specimens from old healthy individuals with skin barrier defect or elderly mice. Conversely, topical administration with a FPR1 antagonist, or Nlrc4 silencing, led to the normalization of barrier dysfunction and alleviation of inflammatory skin responses in vivo. Conclusions In summary, our findings show that the FPR1-NLRC4 inflammasome axis is activated upon skin barrier disruption and may explain exaggerated inflammatory responses that are observed in disease states characterized by epidermal dysfunction. Pharmacological inhibition of FPR1 or NLRC4 represents a potential therapeutic target. [ABSTRACT FROM AUTHOR]

This article discusses the development and validation of a prognostic model for predicting flares in generalized pustular psoriasis (GPP). GPP is a rare auto-inflammatory skin disease characterized by recurrent flares of neutrophil-filled sterile pustules. These flares can have a significant impact on the daily activities and overall well-being of patients and can lead to life-threatening complications if left untreated. The study aimed to identify risk factors for GPP flare and construct a predictive model based on clinical characteristics to forecast the occurrence of flares. The model incorporates four features: history of psoriasis vulgaris, risky alcohol use, temperature at fever, and albumin levels. The model achieved promising results in internal and external validation processes and may provide critical insights into GPP flare patterns and help prevent such episodes. [Extracted from the article]

Generalized pustular psoriasis (GPP) is a rare and potentially life‐threatening skin disease and the clinical heterogeneity of which is largely unknown. Retrospective cohort analysis was conducted on hospitalized GPP patients between January 2010 and November 2022. A total of 416 patients with GPP and psoriasis vulgaris (PV) respectively were included, matched 1:1 by sex and age. The heterogeneity of GPP was stratified by PV history and age. Compared with PV, GPP was significantly associated with prolonged hospitalization (11.7 vs. 10.3 day, p < 0.001), elevated neutrophil lymphocyte ratio (NLR) (5.93 vs. 2.44, p < 0.001) and anemia (13.9% vs. 1.2%, p < 0.001). Moreover, GPP alone (without PV history) was a relatively severer subtype with higher temperature (37.6°C vs. 38.0°C, p = 0.002) and skin infections (5.2% vs. 11.4%, p = 0.019) than GPP with PV. For patients across different age, compared with juvenile patients, clinical features support a severer phenotype in middle‐aged, including higher incidence of anaemia (7.5% vs. 16.0%, p = 0.023) and NLR score (3.83 vs. 6.88, p < 0.001). Interleukin‐6 (r = 0.59), high density lipoprotein cholesterol (r = −0.56), albumin (r = −0.53) and C‐reactive protein‐to‐albumin ratio (r = 0.49) were the most relevant markers of severity in GPP alone, GPP with PV, juvenile and middle‐aged GPP, respectively. This retrospective cohort suggests that GPP is highly heterogeneous and GPP alone and middle‐aged GPP exhibit severe disease phenotypes. More attention on the heterogeneity of this severe disease is warranted to meet the unmet needs and promote the individualized management of GPP. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, refractory inflammatory skin disease, with a high prevalence of psychiatric comorbidities, including depression, anxiety, and even suicidality, which may in turn initiate or exacerbate skin inflammation. However, the causal relationships between these comorbidities remain unclear. To investigate the cause–effect relationships between psoriasis and mental disorders including depression, anxiety, and suicidality, we conducted a bidirectional two‐sample Mendelian randomization (MR) study utilizing summary statistics from the most comprehensive genome‐wide association studies of psoriasis (n = 306 123), broad depression (n = 500 199), major depressive disorder (n = 173 005), anxiety (n = 17 310), and suicide attempts (n = 50 264). Using the random‐effects inverse‐variance weighted method as primary method, the forward MR analyses indicated that psoriasis was significantly associated with higher odds of broad depression (odds ratio [OR] 1.030, 95% confidence interval [CI] 1.010–1.051, P = 0.003) and suggestively associated with an increased risk of major depressive disorder (OR 1.054, 95% CI 1.002–1.109, P = 0.040), but not with the risk of anxiety (P = 0.160) or suicide attempts (P = 0.648). In reverse MR analyses, significant causal impact of broad depression (OR 1.363, 95% CI 1.103–1.684, P = 0.004) and major depressive disorder (OR 1.890, 95% CI 1.285–2.781, P = 0.001), but not anxiety (P = 0.787) and suicide attempts (P = 0.961) on psoriasis risk was observed. In addition, the results of primary analysis are consistent across sensitivity analyses, albeit the MR–Egger regression model produced wide CIs and negative results in several analyses. In conclusion, this MR study indicates a bidirectional causal relationship between psoriasis and depression that was previously unrecognized, which highlights the significance of screening for depression in psoriasis patients and initiating appropriate interventions. Further studies are required to elucidate the pathophysiology of the bidirectional causal relationship between these two conditions. [ABSTRACT FROM AUTHOR]