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International Journal of Molecular... Nov 2021Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines... (Review)
Review
Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, T1, T2, and T17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis', the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis', an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.
Topics: Animals; Cytokines; Humans; Immunotherapy; Psoriasis; Quality of Life
PubMed: 34884596
DOI: 10.3390/ijms222312793 -
Cellular & Molecular Immunology Feb 2021Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations. Plaque psoriasis, which is the most common manifestation of... (Review)
Review
Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations. Plaque psoriasis, which is the most common manifestation of psoriasis, is located on one end of the spectrum, dominated by adaptive immune responses, whereas the rarer pustular psoriasis lies on the opposite end, dominated by innate and autoinflammatory immune responses. In recent years, genetic studies have identified six genetic variants that predispose to pustular psoriasis, and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis pathogenesis. In this review, we discuss the presentation and clinical subtypes of pustular psoriasis, contribution of genetic predisposing variants, critical role of the IL-36 family of cytokines in disease pathophysiology, and treatment perspectives for pustular psoriasis. We further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.
Topics: Animals; Autoimmunity; Humans; Inflammation; Psoriasis; Suppuration
PubMed: 32814870
DOI: 10.1038/s41423-020-0519-3 -
International Journal of Molecular... Aug 2022A convincing deal of evidence supports the fact that severe psoriasis is associated with cardiovascular diseases. However, the precise underlying mechanisms linking... (Review)
Review
A convincing deal of evidence supports the fact that severe psoriasis is associated with cardiovascular diseases. However, the precise underlying mechanisms linking psoriasis and cardiovascular diseases are not well defined. Psoriasis shares common pathophysiologic mechanisms with atherosclerosis and cardiovascular (CV) risk factors. In particular, polymorphism in the IL-23R and IL-23 genes, as well as other genes involved in lipid and fatty-acid metabolism, renin-angiotensin system and endothelial function, have been described in patients with psoriasis and with cardiovascular risk factors. Moreover, systemic inflammation in patients with psoriasis, including elevated serum proinflammatory cytokines (e.g., TNF-α, IL-17, and IL-23) may contribute to an increased risk of atherosclerosis, hypertension, alteration of serum lipid composition, and insulin resistance. The nonlinear and intricate interplay among various factors, impacting the molecular pathways in different cell types, probably contributes to the development of psoriasis and cardiovascular disease (CVD). Future research should, therefore, aim to fully unravel shared and differential molecular pathways underpinning the association between psoriasis and CVD.
Topics: Atherosclerosis; Cardiovascular Diseases; Humans; Interleukin-23; Lipids; Psoriasis; Risk Factors
PubMed: 36012327
DOI: 10.3390/ijms23169063 -
Clinical Medicine (London, England) May 2021Psoriasis is a clinically heterogeneous lifelong skin disease that presents in multiple forms such as plaque, flexural, guttate, pustular or erythrodermic. An estimated...
Psoriasis is a clinically heterogeneous lifelong skin disease that presents in multiple forms such as plaque, flexural, guttate, pustular or erythrodermic. An estimated 60 million people have psoriasis worldwide, with 1.52% of the general population affected in the UK. An immune-mediated inflammatory disease, psoriasis has a major genetic component. Its association with psoriatic arthritis and increased rates of cardiometabolic, hepatic and psychological comorbidity requires a holistic and multidisciplinary care approach. Psoriasis treatments include topical agents (vitamin D analogues and corticosteroids), phototherapy (narrowband ultraviolet B radiation (NB-UVB) and psoralen and ultraviolet A radiation (PUVA)), standard systemic (methotrexate, ciclosporin and acitretin), biologic (tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors) or small molecule inhibitor (dimethyl fumarate and apremilast) therapies. Advances in the understanding of its pathophysiology have led to development of highly effective and targeted treatments.
Topics: Acitretin; Humans; Immunosuppressive Agents; Methotrexate; Phototherapy; Psoriasis
PubMed: 34001566
DOI: 10.7861/clinmed.2021-0257 -
Advances in Therapy May 2020Psoriasis is a systemic inflammatory disorder that involves complex pathogenic interactions between the innate and adaptive immune systems. Individuals with psoriasis... (Review)
Review
Psoriasis is a systemic inflammatory disorder that involves complex pathogenic interactions between the innate and adaptive immune systems. Individuals with psoriasis have an increased risk of developing other chronic health diseases such cardiovascular disorders. The high incidence of cardiovascular events in the population with psoriasis could be explained by several mechanisms. The high prevalence of traditional cardiovascular risk factors and metabolic abnormalities contributes to the high cardiovascular burden in patients with psoriasis. Likewise, the presence of systemic inflammation in combination with metabolic abnormalities may act in a synergistic manner to increase cardiovascular risk in these patients. This review focused on epidemiologic and clinical evidence linking psoriasis to cardiovascular risk factors and cardiovascular disease. We described the possible pathophysiological mechanisms that justify this association and analyzed the best way to stratify the cardiovascular risk in patients with psoriasis. We also described the usefulness of the therapies frequently used in cardiovascular prevention and analyzed the impact of the specific psoriasis medication on cardiovascular risk factors or major atherosclerotic events. Knowledge of the application of different cardiovascular prevention strategies could mean an advantage in performing the difficult task of estimating cardiovascular risk and treating cardiovascular risk factors in this particular group of patients.
Topics: Atherosclerosis; Cardiovascular Diseases; Endothelium, Vascular; Humans; Inflammation; Psoriasis; Risk Factors
PubMed: 32314303
DOI: 10.1007/s12325-020-01346-6 -
Paediatric Drugs Oct 2015Psoriasis 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... (Review)
Review
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.
Topics: Adolescent; Child; Comorbidity; Disease Management; Humans; Prospective Studies; Psoriasis
PubMed: 26072040
DOI: 10.1007/s40272-015-0137-1 -
Annals of Agricultural and... Sep 2020Psoriasis isa quite common, chronic and immune-mediated skin disorder. The prevalence of psoriasis differs in various countries, but it is said to affect 2% of the... (Review)
Review
INTRODUCTION AND OBJECTIVE
Psoriasis isa quite common, chronic and immune-mediated skin disorder. The prevalence of psoriasis differs in various countries, but it is said to affect 2% of the world's population in general. Psoriasis has many different clinical features but all lesions have the same characteristic: erythema, thickening and scale, although other clinical features are also connected, such as psoriatic arthritis, obesity and metabolic syndrome. All of these may lead to conditions impairing the quality of life. This review is an attempt to summarize recent data regarding environmental factors, together with epigenetic markers and processes playing an important role in psoriasis.
STATE OF KNOWLEDGE
Many different environmental factors play a role in genetically predisposed patients. This is causes epigenetic alternations which may be a linking part in the whole process. Many studies have indicated a connection between psoriasis and various genes and antigens. The presence of HLA-Cw6 is common as well a strong link between its presence and the onset of psoriasis being observed. The main alternations are DNA methylation, histone's modifications and the role of microRNA. Excessive reaction is usually not present without a triggering factor. Environmental factors are mostly rated, such as drugs, life style and habits (smoking, alcohol), diet, physical trauma (skin injury provoking Koebner phenomenon), stress, microorganism and infections.
CONCLUSIONS
The correlation between pathogenesis of psoriasis and environmental risk factors, together with epigenetic alternations still require more investigation. Education about diet habits, nutrition, weight loss and healthy lifestyle seems to be important during the treatment of psoriasis.
Topics: Environment; Epigenesis, Genetic; Humans; Psoriasis; Risk Factors
PubMed: 32955211
DOI: 10.26444/aaem/112107 -
Dermatologic Therapy Dec 2022Although topical drugs are the mainstay of treatment for patients with mild-to-moderate psoriasis, the developments observed in this field in the last two decades have... (Review)
Review
Although topical drugs are the mainstay of treatment for patients with mild-to-moderate psoriasis, the developments observed in this field in the last two decades have been limited. The most commonly used drugs are still vitamin D analogues and corticosteroids, both with several limitations. The aryl hydrocarbon receptor (AhR) plays a role in the pathogenesis of psoriasis, and tapinarof, a novel, first-in-class, small molecule topical therapeutic AhR-modulating agent has been recently approved by the FDA for the topical treatment of plaque psoriasis in adults. Two large, 12-week, phase III trials, PSOARING 1 and 2, showed that 35.4%-40.2% of patients in the tapinarof 1% cream arm achieved the primary endpoint (Physician's Global Assessment [PGA] score of 0 or 1 and a decrease of ≥2-5 points at week 12) compared with 6.0%-6.3% for vehicle arm, respectively. The most common adverse effects were folliculitis, contact dermatitis, headache and pruritus. In the open label, 40-week, extension trial, PSOARING 3, the efficacy and safety results were similar, with 40.9% of patients achieving a PGA = 0 at least one time during the trial and 58.2% of patients with PGA≥2 achieved PGA = 0/1 at least once during the trial, without tachyphylaxis. There were no new safety signals, with most frequent adverse events being folliculitis, contact dermatitis, and upper respiratory tract infection. Tapinarof 1% cream has shown to be effective and to have a favorable safety profile in the treatment of psoriatic patients, representing an alternative to the current therapeutic options, increasing our armamentarium in the topical treatment of psoriasis.
Topics: Adult; Humans; Dermatitis, Contact; Double-Blind Method; Folliculitis; Psoriasis; Severity of Illness Index; Treatment Outcome
PubMed: 36226669
DOI: 10.1111/dth.15931 -
International Journal of Molecular... Oct 2021The skin barrier is broadly composed of two elements-a physical barrier mostly localised in the epidermis, and an immune barrier localised in both the dermis and... (Review)
Review
The skin barrier is broadly composed of two elements-a physical barrier mostly localised in the epidermis, and an immune barrier localised in both the dermis and epidermis. These two systems interact cooperatively to maintain skin homeostasis and overall human health. However, if dysregulated, several skin diseases may arise. Psoriasis is one of the most prevalent skin diseases associated with disrupted barrier function. It is characterised by the formation of psoriatic lesions, the aberrant differentiation and proliferation of keratinocytes, and excessive inflammation. In this review, we summarize recent discoveries in disease pathogenesis, including the contribution of keratinocytes, immune cells, genetic and environmental factors, and how they advance current and future treatments.
Topics: Cell Membrane Permeability; Humans; Psoriasis; Skin; Skin Physiological Phenomena
PubMed: 34639182
DOI: 10.3390/ijms221910841 -
Frontiers in Immunology 2021Although more and more evidence has supported psoriasis is prone to atherosclerosis, the common mechanism of its occurrence is still not fully elucidated. The purpose of...
BACKGROUND
Although more and more evidence has supported psoriasis is prone to atherosclerosis, the common mechanism of its occurrence is still not fully elucidated. The purpose of this study is to further explore the molecular mechanism of the occurrence of this complication.
METHODS
The gene expression profiles of psoriasis (GSE30999) and atherosclerosis (GSE28829) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of psoriasis and atherosclerosis, three kinds of analyses were performed, namely functional annotation, protein-protein interaction (PPI) network and module construction, and hub gene identification and co-expression analysis.
RESULTS
A total of 94 common DEGs (24 downregulated genes and 70 upregulated genes) was selected for subsequent analyses. Functional analysis emphasizes the important role of chemokines and cytokines in these two diseases. In addition, lipopolysaccharide-mediated signaling pathway is closely related to both. Finally, 16 important hub genes were identified using cytoHubba, including LYN, CSF2RB, IL1RN, RAC2, CCL5, IRF8, C1QB, MMP9, PLEK, PTPRC, FYB, BCL2A1, LCP2, CD53, NCF2 and TLR2.
CONCLUSIONS
Our study reveals the common pathogenesis of psoriasis and atherosclerosis. These common pathways and hub genes may provide new ideas for further mechanism research.
Topics: Atherosclerosis; Databases, Genetic; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Humans; Oligonucleotide Array Sequence Analysis; Protein Interaction Maps; Psoriasis; Signal Transduction; Transcriptome
PubMed: 34122426
DOI: 10.3389/fimmu.2021.667690