Molecular mechanisms and drug therapy of metabolism disorders in psoriasis.

Psoriasis is a prevalent skin disease affecting approximately 1%-3% of the population and imposes significant medical, social and economic burdens. Psoriasis involves multiple organs and is often complicated with obesity, diabetes, dyslipidemia, and hypertension. Because of the benefits of lipid-lowering agents and antidiabetic medications for psoriasis, metabolic abnormalities possibly play a pathogenic role in psoriasis.This review focuses on the impacts of a variety of metabolic disorders on psoriasis and the underlying mechanisms.In psoriasis, enhanced glycolysis, glutamine metabolism and altered fatty acid composition in the psoriatic lesion and plasma result in the excessive proliferation of keratinocytes and secretion of inflammatory cytokines. Altered metabolism is associated with the activation of MTORC signaling pathway and transcription factors such as HIF and S6K1. Therefore, MTORC1 can be a target for the treatment of psoriasis. Additionally, there are diabetes drugs and lipid-lowering drugs including TZDs, GLP-1 RAs, Metformin, statins and fibrates, which improve both metabolic levels and psoriasis symptoms.

Relationship of psoriatic arthritis with nail and scalp involvement in Turkish psoriasis patients: Multicentered cross-sectional study.

Psoriasis is a common multisystem inflammatory disease, and arthritis is an essential component of the disorder, requiring early diagnosis and prompt treatment for successful management. In this study, we aimed to investigate the relationship between nail and scalp involvement and other covariates with psoriatic arthritis (PsA). This cross-sectional study, conducted from June 2021 through December 2021, included 763 patients from 11 different centers in Turkey. The severity of involvement was evaluated using psoriasis area severity index (PASI), nail psoriasis severity index (NAPSI), and psoriasis scalp severity index (PSSI) scores. Predictors for PsA were evaluated using univariate and multivariate logistic regression models. PsA (n = 155, 21.5%) was significantly more common in patients having a family history of psoriasis (43.2% vs 30.9%, P = .004), nail involvement (68.4% vs 52.3%, P < .001), and coexistence of nail and scalp involvement (53.7% vs 39.6%, P = .002). Furthermore, patients with PsA had considerably higher PASI (7 vs 5.6, P = .006), NAPSI (5 vs 2, P < .001), and PSSI scores (7 vs 4, P = .002) and longer disease duration (months) (126 vs 108, P = .009). In multivariate analysis, female gender [OR: 3.01, 95% CI (1.861-4.880), P < .001], nail involvement [OR: 2.06, 95% CI (1.293-3.302), P = .002)], and body mass index (BMI) [OR: 1.06, 95% CI (1.017-1.100), P = .005] were identified as independent predictors for PsA. Female gender, nail involvement, and high BMI are significant predictors for PsA and warrant detailed rheumatological assessment. Notably, being female is the strongest predictor of increased risk of PsA in our survey. Scalp involvement appears not to be associated with PsA. Also, the presence of PsA seems related to a more severe skin involvement phenotype.

The relationship between psoriasis and vitiligo: From a comprehensive study.

BACKGROUND: Both psoriasis and vitiligo are autoimmune skin diseases. Previous observational studies have indicated a relationship between the two conditions, and simultaneous onset of both diseases poses increased health risks to patients. However, limited research has explored the causal relationship between psoriasis and vitiligo. OBJECTIVES: To investigate whether a causal association exists between psoriasis and vitiligo. METHODS: A case of Chinese patients diagnosed with psoriasis and vitiligo has been reported. Transcriptome sequencing was performed on normal, psoriasis, vitiligo, and co-morbid skin tissues of the patients, and single-cell transcriptome sequencing was conducted on the co-morbid skin tissues. A comprehensive Mendelian randomization analysis of Genome-wide association studies (GWAS) was performed on a cohort of 261 018 European individuals with psoriasis from the IEU Open GWAS Project and vitiligo from the National Institutes of Health (NIH) Database of Genotypes and Phenotypes. RESULTS: Case report and transcriptome results showed that skin tissue with vitiligo combined with psoriasis exhibited both vitiligo and psoriasis. Single-cell transcriptome sequencing results showed that in comparison to normal skin and psoriatic skin, the proportions of CD8+ T cells, natural killer cells, naive T cells, T helper cells 17, regulatory T cells, conventional type 1 dendritic cells, Conventional type 2 dendritic cells, and plasmacytoid dendritic cells were all increased in skin tissue with vitiligo combined with psoriasis. Mendelian randomization analysis included 4510 patients with psoriasis and 4680 patients with vitiligo. The results showed no causal relationship between vitiligo and psoriasis in the forward direction (p = 0.192; odds ratio [OR], 1.059; 95% confidence interval [CI], 0.971-1.155) or in the reverse direction (p = 0.459; OR, 0.927; 95% CI, 0.757-1.134). CONCLUSIONS: This study suggests that the association between psoriasis and vitiligo may be closely related to immunity, however, Mendelian randomization studies do not support a causal relationship. These findings hold significant implications for clinicians aiming to enhance their understanding and treatment approaches for psoriasis and vitiligo.

The involvement of keratinocytes in pruritus of chronic inflammatory dermatosis.

Frequent itching and incessant scratching are commonly observed in various chronic inflammatory skin conditions, including atopic dermatitis and psoriasis. The persistent and prolonged nature of pruritus can worsen one's quality of life. Keratinocytes (KCs), the predominant cells of the epidermis, have been confirmed to interact with sensory neurons and immune cells and be involved in chronic skin inflammatory diseases associated with pruritus. Initially, KCs and sensory neurons form a unique synapse-like connection within the epidermis, serving as the structural foundation for their interaction. Additionally, several receptors, including toll-like receptors and protease-activated receptor 2, expressed on KCs, become activated in an inflammatory milieu. On the one hand, activated KCs are sources of pro-inflammatory cytokines and neurotrophic factors, such as adenosine triphosphate, thymic stromal lymphopoietin, and nerve growth factor, which directly or indirectly participate in stimulating sensory neurons, thereby contributing to the itch sensations. On the other hand, KCs also function as primary transducers alongside intraepidermal nerve endings, directly initiating pruritic responses. This review summarizes the current literature and highlights the critical role of KCs in the development and persistence of chronic itch in inflammatory skin disorders.

Synergistic impact of psoriasis and hypertension on all-cause mortality risk: A prospective cohort study.

BACKGROUND: The linkage between psoriasis and hypertension has been established through observational studies. Despite this, a comprehensive assessment of the combined effects of psoriasis and hypertension on all-cause mortality is lacking. The principal aim of the present study is to elucidate the synergistic impact of psoriasis and hypertension on mortality within a representative cohort of adults residing in the United States. METHODS: The analysis was conducted on comprehensive datasets derived from the National Health and Nutrition Examination Study spanning two distinct periods: 2003-2006 and 2009-2014. The determination of psoriasis status relied on self-reported questionnaire data, whereas hypertension was characterized by parameters including systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, self-reported physician diagnosis, or the use of antihypertensive medication. The assessment of the interplay between psoriasis and hypertension employed multivariable logistic regression analyses. Continuous monitoring of participants' vital status was conducted until December 31, 2019. A four-level variable amalgamating information on psoriasis and hypertension was established, and the evaluation of survival probability utilized the Kaplan-Meier curve alongside Cox regression analysis. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed to scrutinize the correlation between psoriasis/hypertension and all-cause mortality. RESULTS: In total, this study included 19,799 participants, among whom 554 had psoriasis and 7,692 had hypertension. The findings from the logistic regression analyses indicated a heightened risk of hypertension among individuals with psoriasis in comparison to those devoid of psoriasis. Throughout a median follow-up spanning 105 months, 1,845 participants experienced all-cause death. In comparison to individuals devoid of both hypertension and psoriasis, those with psoriasis alone exhibited an all-cause mortality HR of 0.73 (95% CI: 0.35-1.53), individuals with hypertension alone showed an HR of 1.78 (95% CI: 1.55-2.04), and those with both psoriasis and hypertension had an HR of 2.33 (95% CI: 1.60-3.40). In the course of a stratified analysis differentiating between the presence and absence of psoriasis, it was noted that hypertension correlated with an elevated risk of all-cause mortality in individuals lacking psoriasis (HR 1.77, 95% CI: 1.54-2.04). Notably, this association was further accentuated among individuals with psoriasis, revealing an increased HR of 3.23 (95% CI: 1.47-7.13). CONCLUSIONS: The outcomes of our investigation demonstrated a noteworthy and positive association between psoriasis, hypertension, and all-cause mortality. These findings indicate that individuals who have both psoriasis and hypertension face an increased likelihood of mortality.

Case report and brief literature review: possible association of secukinumab with Guillain-Barré syndrome in psoriasis.

The etiology of Guillain-Barré syndrome (GBS) may be autoimmune. About two-thirds of patients typically experience their first symptoms within 5 days to 3 weeks after common infectious diseases, surgery, or vaccination. Infection is a triggering factor for over 50% of patients. In recent years, a growing number of studies have indicated that some immune checkpoint inhibitors and COVID-19 may also contribute to the occurrence of GBS. However, drugs are considered a rare cause of GBS. The patient in our case was a 70-year-old man who developed GBS after initiating secukinumab for psoriasis. Upon diagnosis suggesting a potential association between secukinumab and the development of GBS, as per the Naranjo adverse drug reaction (ADR) probability scale, we decided to discontinue the drug. Following this intervention, along with the administration of immunoglobulin, the patient exhibited a significant improvement in extremity weakness. The association of GBS with secukinumab treatment, as observed in this case, appears to be uncommon. The underlying mechanisms that may link secukinumab to the development of GBS are not yet fully understood and warrant further scientific inquiry and rigorous investigation. However, we hope that this report can raise greater awareness and vigilance among medical professionals to enhance the safety of patients' medication.

Assessing the relationship between psoriasis and thyroid dysfunction through two sample MR analysis.

BACKGROUND: The association between psoriasis and hyperthyroidism/hypothyroidism remains inconclusive, with conflicting findings in prior studies. OBJECTIVES: This study employs Mendelian randomization methods to assess the potential relationship. METHODS: Given the inability to accurately observe the link between psoriasis and thyroid dysfunction, we prioritized utilizing known genetic variants to investigate the potential impacts of the disease.We analyzed data from genome-wide association studies (GWASs), FinnGen, and UK Biobank to extract information on psoriasis, hyperthyroidism, and hypothyroidism. Three MR approaches (MR Egger, weighted median, and inverse variance weighted) were used to scrutinize the causal link. RESULTS: Our analysis revealed no correlation between psoriasis and hyperthyroidism/hypothyroidism. However,  vulgar psoriasis and guttate psoriasis were associated with hypothyroidism/myxedema (IVW odds ratio (OR) = 1.00, 95% confidence interval (CI) = 1.00-1.00, P = 2.53E-03), and Graves' disease (IVW OR = 0.86, 95% CI = 0.72-1.01, P = 4.75E-02).In a subsequent analysis, we observed that hypothyroidism with mucinous edema showed no correlation with Graves' disease in the opposite(P = 9.33E-01). CONCLUSION: This MR analysis suggests no association between psoriasis and thyroid dysfunction, but highlights associations of vulgar/guttate psoriasis with hypothyroidism/myxedema and Graves' disease. In clinical practice, diagnosing guttate psoriasis requires vigilance for associated risks from hypothyroidism and Graves' disease. For patients with both vulgar psoriasis and hypothyroidism, careful monitoring for mucinous edema is crucial, as it may signal a hypothyroid crisis.

CASE OF THE TRANSFORMATION OF PSORIASIS INTO CUTANEOUS T-CELL LYMPHOMA.

Psoriasis is a long-known skin pathology, the incidence of which is constantly rising, though it is not possible to clearly establish the trend due to the differences in the research design. In recent years, the number of cases among children and adolescents has increased. Psoriasis becomes more aggressive, severe forms are more common. It can be combined with other diseases but is rarely complicated. Isolated cases of the transformation of psoriatic plaques into skin cancer have already been described in the literature. Probable causes were the long-term use of photosensitizers and phototherapy, naphthalene, and tar. However, in general, the risk of the malignant recurrence in patients with psoriasis does not increase significantly. We present a clinical observation of the transformation of psoriasis into cutaneous T-cell lymphoma in a patient with more than 37 years of psoriasis experience, where on the background of typical psoriatic rashes, fungal growths of doughy consistency appeared, which were initially misinterpreted as a warty form of psoriasis. Based on the data of additional methods of examination and the results of histological examination, the diagnosis was clarified. Specific treatment was prescribed, which proved its effectiveness. The probable causes of degeneration, in our opinion, are prolonged irritating external therapy and excessive insolation.

Generalized Pustular Psoriasis and Systemic Organ Dysfunctions.

This review explores the intricate relationship between generalized pustular psoriasis (GPP) and various systemic diseases, shedding light on the broader impacts of this severe skin condition beyond its primary dermatological manifestations. GPP is identified as not only a profound contributor to skin pathology but also a significant risk factor for systemic diseases affecting cardiovascular, hepatic, renal, pulmonary, and skeletal systems, as well as associated with an increased incidence of anemia, depression, anxiety, and arthritis. The research highlights the complex interplay of cytokines, particularly IL-17 and IL-36, which are central to the pathophysiology of GPP and implicated in the exacerbation of systemic conditions. Key findings indicate a higher incidence of cardiovascular events in GPP patients compared to those with other severe forms of psoriasis, notably with a stronger correlation between myocardial infarction history and GPP development. Liver disturbances, frequently reversible upon psoriasis remission, suggest a cytokine-mediated link to hepatic health. Renal dysfunction appears elevated in GPP sufferers, with IL-17 and IL-36 potentially driving renal fibrosis. Similarly, interstitial lung disease and osteoporosis in GPP patients underscore the systemic reach of inflammatory processes initiated in the skin. The associations with anemia, depression, anxiety, and arthritis further complicate the clinical management of GPP, requiring a multidisciplinary approach. The study concludes that managing GPP effectively requires a holistic approach that addresses both the cutaneous and systemic dimensions of the disease, advocating for continued research into the mechanisms that connect GPP with broader health implications to refine therapeutic strategies.

Association between psoriasis and asthma: a systematic review and bidirectional meta-analysis.

BACKGROUND: The risk of asthma in patients with psoriasis has been identified in previous studies, but the bidirectional association between the two has not been fully explored. METHODS: We thoroughly searched PubMed, Embase, and the Cochrane Library to find relevant observational studies published from the inception of these databases to October 2023. All the risk and bias assessments were analyzed by STATA 16.0. Where the heterogeneity was less than 50%, the fixed effect model was utilized. While where the level of heterogeneity was more than 50%, the random effect model was applied. Moreover, to identify publication bias, a visual funnel chart, and Egger's test were applied. RESULTS: A total of 12,396,911 participants from 16 studies, published between 2011 and 2023 were included in this meta-analysis. We found that psoriasis patients had a higher risk of developing asthma (OR = 1.48, 95%CI 1.28-1.68). Meanwhile, asthma patients also had a higher overall risk of developing psoriasis (OR = 1.33, 95%CI 1.23-1.44). In the subgroup analysis, we found that the type of study, age, and severity of the psoriasis were significant factors in the survey of asthma risk in psoriasis patients. CONCLUSIONS: In the present systematic review and meta-analysis, we found a bidirectional association between psoriasis and asthma with significantly increased risk. As a result, clinicians should make patients aware of the connection between the two, particularly adolescents or patients with moderate to severe psoriasis who need to be informed about the rising likelihood of developing asthma. TRIAL REGISTRATION: Registration number CRD42023390111 .

The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis.

OBJECTIVE: To evaluate the association between psoriasis (PSO), psoriatic arthritis (PsA) and periodontitis (PE), and the Oral Health-Related Quality of Life (OHRQoL) impacts on individuals with psoriatic disease's daily activities compared to the non-psoriatic ones. MATERIALS & METHODS: 296 individuals with psoriatic disease (PSO n = 210, APS n = 86) (cases) and 359 without these diseases (controls) were included. Complete periodontal examinations and collection of variables of interest were performed. The Brazilian version of the Oral Impacts on Daily Performance (OIDP) instrument was applied. RESULTS: The prevalence of PE was higher in PsA (57.0%; OR = 2.67 95%CI 1.65-4.32; p<0.001) than in PSO (34.3%; OR = 1.05 95% CI 0.73-1.51; p<0.001) compared to controls (33.1%). Both PsA and PSO groups showed more sites and teeth with 4-6mm probing depth (PD) and had higher OIDP scores than controls (p<0.001), thus indicating worse self-reported quality of life. PE, PSO+PE and consumption of alcohol/anxiolytics significantly influenced OHRQoL (p<0.05). The influence of periodontal parameters on OHRQoL was observed for the presence of PE; PD >6 mm; clinical attachment level >6 mm; higher plaque index, % sites and teeth with bleeding on probing (p<0.05). CONCLUSION: Negative impacts of PE on the OHRQoL were demonstrated. The ones having PSO and especially PsA and PE presented significantly worse indicators.

Exploring the pathogenesis and immunological profiles of psoriasis complicated with MASLD.

BACKGROUND: Both psoriasis and metabolic dysfunction-associated steatotic liver disease (MASLD) are immune-mediated chronic inflammatory diseases. Psoriasis manifests itself mainly as skin damage, while MASLD mainly involves the liver promoting liver fibrosis, which has a significant impact on patient health and quality of life. Some clinical studies have shown that there are mutually reinforcing mechanisms between these two diseases, but they are not clearly defined, and this paper aims to further explore their common pathogenesis. METHODS: Gene expression profiling datasets (GSE30999, GSE48452) and single cell datasets (GSE151177, GSE186328) for psoriasis and MASLD were downloaded from the Gene Expression Omnibus (GEO) database. Common differential gene sets were obtained by gene differential analysis, and then functional enrichment of differential genes was performed to find associated transcription factors and PPI protein network analysis. Single-cell datasets were validated for gene expression and explored for cellular communication, gene set differential analysis and immune infiltration analysis. RESULTS: We identified seven common differential genes, all of which were upregulated.The IL-17 pathway, tumor necrosis factor (TNF-α) pathway were shown in strong association with both diseases, and five transcription factors regulating the differential genes were predicted. Two key genes (MMP9, CXCL10) and three key transcription factors (TF) (IRF1, STAT1, NFKB1) were obtained by PPI protein network analysis. Single cell dataset verified the expression of key genes, and combined with gene set differential analysis, immune infiltration revealed that CD4+ T cells, NK cells and macrophages were heavily infiltrated in both diseases. IL-17, IL-1 and cGAS-STING pathways were highly expressed in both diseases, and both diseases share a similar immune microenvironment. CONCLUSIONS: Our study reveals the common pathogenesis of psoriasis and MASLD from gene expression to immune cell similarities and differences, identifies key genes and regulatory pathways common to both, and elucidates the similarities in the immune microenvironment of both diseases, providing new ideas for subsequent studies on targeted therapy.

Using Guidelines of Care to Lower Cardiovascular Risk in Patients with Psoriasis.

National guidelines define psoriasis as a risk enhancer for cardiovascular disease and recommend increased monitoring and more intense management of cardiovascular risk factors in these patients, who face an increased burden of cardiovascular disease morbidity and mortality. Screening for modifiable cardiovascular risk factors, including blood pressure, weight, cholesterol, glucose, and smoking, can be efficiently incorporated into routine dermatology clinical practice. Partnerships with primary care providers and preventive cardiologists are essential to improving management of cardiovascular risk in patients with psoriasis.