Cardiometabolic Comorbidities in Patients With Psoriasis: Focusing on Risk, Biological Therapy, and Pathogenesis.
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ABSTRACT:
SUBMITTER: Cai J
PROVIDER: S-EPMC8600112 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is solid epidemiologic evidence linking psoriasis and psoriatic arthritis (PsA) to cardiovascular risk factors and an increased risk of developing cardiovascular disease. Chronic inflammation, with shared pathways and cytokines common to metabolic syndrome, atherosclerosis and psoriasis, might provide the basis for the cardiovascular and metabolic comorbidities of psoriasis and PsA. The purpose of this manuscript is to review recent evidence about the epidemiology and underlying mechanisms of cardiovascular risk factors and cardiovascular disease in patients with psoriasis and/or PsA; the use of analytical determinations, physiologic measures and imaging techniques as surrogate biomarkers of atherosclerosis, endothelial dysfunction and cardiovascular disease in these patients; and the epidemiological and clinical data, including results of clinical trials, supporting a cardioprotective role of anti-inflammatory and disease-modifying treatment in psoriasis and PsA.
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Project description:Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2-3% of the world's population. The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. The modulation of the local neuroendocrine system with the downregulation of pro-inflammatory and the upregulation of anti-inflammatory messengers represent a promising adjuvant treatment in psoriasis therapies. Vitamin D receptors and vitamin D-mediated signaling pathways function in the skin and are essential in maintaining the skin homeostasis. The active forms of vitamin D act as powerful immunomodulators of clinical response in psoriatic patients and represent the effective and safe adjuvant treatments for psoriasis, even when high doses of vitamin D are administered. The phototherapy of psoriasis, especially UVB-based, changes the serum level of 25(OH)D, but the correlation of 25(OH)D changes and psoriasis improvement need more clinical trials, since contradictory data have been published. Vitamin D derivatives can improve the efficacy of psoriasis phototherapy without inducing adverse side effects. The anti-psoriatic treatment could include non-calcemic CYP11A1-derived vitamin D hydroxyderivatives that would act on the VDR or as inverse agonists on RORs or activate alternative nuclear receptors including AhR and LXRs. In conclusion, vitamin D signaling can play an important role in the natural history of psoriasis. Selective targeting of proper nuclear receptors could represent potential treatment options in psoriasis.
| S-EPMC9369120 | biostudies-literature
Project description:A retrospective study of 200 psoriasis patients and 100 healthy donors in a Spanish cohort was carried out to study the comorbidities associated with psoriasis and their association with the response to phototherapy. The results showed a higher incidence of psychiatric disease, liver disease, kidney disease, hypertension, heart disease, vascular disease, diabetes, gastrointestinal disease, autoimmune and infectious diseases, dyslipidemia, and psoriatic arthritis in patients with psoriasis than in the control group. The incidence of comorbidities was higher in psoriasis patients over 40 years old than in the control individuals of the same age, which could be indicative of premature aging. Phototherapy was seen to be an effective treatment in cases of moderate-severe psoriasis, total whitening being achieved in more than 30% of patients, with women showing a better response than men. Narrow-band ultraviolet B was found to be the most effective type of phototherapy, although achievement of PASI100 was lower in patients with liver disease, hypertension, heart disease, vascular disease, or diabetes. Strikingly, liver disease and anemia comorbidities favored therapeutic failure. Finally, zebrafish and human 3D organotypic models of psoriasis point to the therapeutic benefit of inhibiting the glucose transporter GLUT1 and the major regulator of blood glucose dipeptidyl peptidase 4. Our study reveals that specific comorbidities of psoriasis patients are associated to failure of phototherapy and, therefore, need to be considered when planning treatment for these patients.
| S-EPMC9455671 | biostudies-literature
Project description:Psoriasis (PsO) is a chronic immune-mediated inflammatory skin disorder associated with numerous co-morbidities. This descriptive review focuses on the cardiometabolic co-morbidities of PsO with reference to the epidemiology and pathogenetic mechanisms linking PsO and cardiometabolic disease (CMD). Registry-based studies have shown PsO to be associated with an increased risk of cardiovascular morbidity and mortality. Factors linking PsO and CMD include: chronic inflammation, obesity, classic cardiovascular risk factors, and the effects of systemic therapy used to treat PsO. Chronic inflammation is associated with PsO itself, and with obesity. Adipose tissue is responsible for the secretion of various adipokines, which together with pro-inflammatory cytokines arising from the psoriatic plaque, contribute to the pro-inflammatory and pro-atherogenic environment. Systemic therapy aimed at decreasing inflammation has been shown to improve CMD in PsO. Screening for and treating CMD and initiating lifestyle modifications will remain the most important interventions until further data emerge regarding the effect of systemic therapy on CMD progression.
| S-EPMC6107739 | biostudies-other
Project description:Diffuse large B-cell lymphoma (DLBCL) has striking clinical and molecular variability. Although a more precise identification of the multiple determinants of this variability is still under investigation, there is a consensus that high-clinical-risk DLBCL cases require a risk-adapted therapy, since intensification of chemotherapy with autologous stem-cell transplantation (ASCT) has been shown to improve the prognosis for high-risk patients in randomised clinical trials. In spite of this, the protocols used for these patients have a high morbidity, associated with ASCT and the use of multiple drugs. This makes it important to identify patients that may take benefit from risk-adapted therapies, through the recognition of biological markers that provide information about both the tumoral cells and the microenvironment. Unfortunately, many of the studies so far performed have relied on heterogeneous series of patients, staged or treated with different protocols. For instance, some of the variability in DLBCL arises from the fact that this diagnosis is applied to de novo and secondary tumours, nodal and extranodal, irrespective of clinical stage, patient age and associated infections. Additionally, DLBCL includes some specific variants, such as mediastinal DLBCL and T/HRBCL, with specific prognostic parameters. This could prevent the identification of potential predictive biomarkers, because the results of many studies show that the search for predictive biomarkers should be promoted in the context of samples of clinically homogeneous patients enrolled in clinical trials. A further source of variability is the dependence of some predictive markers on specific therapeutic approaches, as is the case for the Bcl6 expression in DLBCL, since Bcl-6+ cases have been shown not to benefit from the addition of R to CHOP. Here we have analysed a series of high-clinical-risk DLBCLs by a two-stage approach, first identifying functional signatures by expression analysis, then analysing surrogate biomarkers using tissue microarrays (TMAs). This eclectic approach could reveal new aspects of the relationship between the neoplastic cells and the microenvironment, leading to the identification of previously unknown prognostic markers. At the same time, the use of functional signatures to analyse expression-profiling data avoids the poor reproducibility of the data obtained from gene-by-gene analysis, and benefits from the existence of a growing body of data concerning the major pathways deregulated in DLBCL. To avoid the bias of semiquantitative scoring, in this study we have quantified the markers included in the multivariate analysis. Keywords: new biological variables, risk-adapted therapies
2008-03-01 | GSE9429 | GEO
Project description:Psoriasis is a chronic, immune-mediated and inflammatory skin disease. Although various biological drugs are available for psoriasis treatment, some patients have poor responses or do not respond to treatment. The aim of the present study was to highlight the molecular mechanism of responsiveness to current biological drugs for psoriasis treatment. To this end, we reviewed previously published articles that reported genes associated with treatment response to biological drugs in psoriasis, and gene ontology analysis was subsequently performed using the Cytoscape platform. Herein, we revealed a statistically significant association between NF-kappaB signaling (p value = 3.37 × 10-9), regulation of granulocyte macrophage colony-stimulating factor production (p value = 6.20 × 10-6), glial cell proliferation (p value = 2.41 × 10-5) and treatment response in psoriatic patients. To the best of our knowledge, we are the first to directly associate glial cells with treatment response. Taken together, our study revealed gene ontology (GO) terms, some of which were previously shown to be implicated in the molecular pathway of psoriasis, as novel GO terms involved in responsiveness in psoriatic disease patients.
| S-EPMC10459906 | biostudies-literature
Project description:BackgroundThe close relationship between psoriasis and concomitant diseases is widely accepted. However, a comprehensive analysis of organ-based comorbidities in psoriasis is still lacking.ObjectiveThe authors aimed to present the risk of organ-based comorbidities in psoriasis by comparing the general population.MethodsThe authors retrieved a search of Pubmed, EMBASE, and Cochrane databases for studies reporting organ-based comorbidities in psoriasis versus the general population. Observational studies that met the following criteria were assessed: 1) Psoriasis diagnosis; 2) Cardiovascular or kidney or liver or respiratory or cerebrovascular outcomes; 3) Comparison group of individuals without psoriasis. Pooled Relative Risks (pRRs) and 95% Confidence Intervals (CIs) were calculated by using the random-effect model.ResultsFifteen observational studies with 216,348 psoriatic patients and 9,896,962 individuals from the general population were included. Psoriasis showed a greater risk of organ-based comorbidities. Compared to the general population, pRR for all organ-based comorbidities was 1.20 (95% CI 1.11‒1.31) in psoriasis, and pRR was lower in mild 0.61 (95% CI 0.46‒0.81) than in moderate/severe patients. pRR was 1.20 (95% CI 1.11‒1.30) for cardiovascular, 1.56 (95% CI 1.20‒2.04), and 1.75 (95% CI 1.33‒2.29) for cerebrovascular and liver diseases, respectively. pRR for coexisting renal and cardiovascular events was 1.09 (95% CI 1.01‒1.18). pRR for coexisting renal and cerebrovascular events was 1.28 (95% CI 0.99‒1.66). pRR for coexisting renal and liver diseases was 1.46 (95% CI 1.10‒1.94). pRR for coexisting cardiovascular and liver diseases was 1.41 (95% CI 1.11‒1.80).Study limitationsThere is heterogeneity.ConclusionPsoriasis has a higher risk of single and multiple organ-based comorbidities than the general population. The present study will further improve attention to psoriasis as a systemic inflammatory disease.
| S-EPMC9453528 | biostudies-literature
Project description:Background and Objectives: Psoriasis is a chronic, long-term, incurable skin inflammatory disease characterized by the excessive proliferation of epidermal keratinocytes, dilation of blood vessels, thickening of the skin, and the formation of visible red patches of variable sizes. The impact on patients differs with the severity of the disease, leading to physiological discomfort and psychological distress, which significantly affect the quality of life. The etiology of psoriasis is not completely clear, but immune cells, including type 1 and type 17 cytokine-producing cells modulated by regulatory T cells (Tregs), play a critical role in driving the disease pathogenesis. With the ability to specifically target inflammatory markers, biologics can efficiently inhibit the spread of inflammation to achieve therapeutic effects. The goal was to explore the changes in body image and quality of life in psoriasis patients undertaking therapies with biologic agents. Materials and Methods: This study employed a quasi-experimental, single-sample, pretest-posttest design. Forty-four psoriasis patients were recruited from the dermatology outpatient clinics at two medical centers in northern Taiwan. A structured questionnaire, including demographic information, the Body Image Scale (BIS), and the Dermatology Life Quality Index (DLQI), was used as a research tool. Questionnaire assessments were conducted both before and three months after the biologic agent intervention. Statistical analyses were performed using SPSS version 22.0. Results: Our results indicated a significant difference in body image between psoriasis patients before and after intervention with biologic agents. In addition, overall quality of life (QoL) also showed significant improvements before and after biologic agent intervention. There was a positive correlation between body image and quality of life in psoriasis patients. Conclusions: The treatment for psoriasis has evolved rapidly in recent years, and biologic agents have proven to be effective therapies to improve the quality of life for psoriasis patients. Our study suggests that health-related education and psychological support can further benefit psoriasis patients to willingly and positively undertake treatment and therefore improve their positive body image and quality of life.
| S-EPMC10819774 | biostudies-literature
Project description:Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic and cardiovascular risk. Although the mechanisms involved in the development of these disorders may vary, OSA patients frequently present an increase in transforming growth factor beta (TGFβ), the activity of which is higher still in patients with hypertension, diabetes or cardiovascular morbidity. Smad4 is a member of the small mother against decapentaplegic homologue (Smad) family of signal transducers and acts as a central mediator of TGFβ signalling pathways. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with an apnoea-hypopnoea index (AHI) ≥30 and 26 healthy volunteers. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in HIF1α, mTOR and circadian genes. Moreover, we associated high concentrations of Smad4 plasma protein with the presence of diabetes, dyslipidaemia and hypertension in these patients. Results suggest that increased levels of SMAD4, mediated by intermittent hypoxaemia and circadian rhythm deregulation, may be associated with cardiometabolic comorbidities in patients with sleep apnoea.
| S-EPMC7464800 | biostudies-literature
Project description:Psoriasis is a common chronic immune-mediated inflammatory skin disorder and begins in childhood in almost one-third of the cases. Although children present with the same clinical subtypes of psoriasis seen in adults, lesions may differ in distribution and morphology, and their clinical symptoms at presentation may vary from those reported by adult patients. Nevertheless, diagnosis of psoriasis is primarily based on clinical features. Pediatric psoriasis can have a profound long-term impact on the psychological health of affected children. Additionally, pediatric psoriasis has been associated with certain comorbidities, such as obesity, hypertension, hyperlipidemia, diabetes mellitus and rheumatoid arthritis, making early diagnosis and management essential. As guidelines are lacking and most (systemic) treatments are not approved for use in children, treatment of pediatric psoriasis remains a challenge. A prospective, multicenter, international registry is needed to evaluate these treatments in a standardized manner and ultimately to develop international guidelines on pediatric psoriasis. This article reviews current concepts in pediatric psoriasis including epidemiology, clinical features, diagnosis, the role of topical and systemic agents and the association with other morbidities in childhood.
| S-EPMC4744260 | biostudies-other