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International Journal of Molecular... Mar 2019Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the... (Review)
Review
Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.
Topics: Animals; Chronic Disease; Diagnosis, Differential; Disease Susceptibility; Humans; Psoriasis; Skin; Symptom Assessment
PubMed: 30909615
DOI: 10.3390/ijms20061475 -
Journal of the American Academy of... Jan 2023Effective, well-tolerated oral psoriasis treatments are needed. (Randomized Controlled Trial)
Randomized Controlled Trial
Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial.
BACKGROUND
Effective, well-tolerated oral psoriasis treatments are needed.
OBJECTIVE
To compare the efficacy and safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, versus placebo and apremilast in adults with moderate to severe plaque psoriasis.
METHODS
Participants were randomized 2:1:1 to deucravacitinib 6 mg every day (n = 332), placebo (n = 166), or apremilast 30 mg twice a day (n = 168) in the 52-week, double-blinded, phase 3 POETYK PSO-1 trial (NCT03624127). Coprimary end points included response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) with deucravacitinib versus placebo at week 16.
RESULTS
At week 16, response rates were significantly higher with deucravacitinib versus placebo or apremilast for PASI 75 (194 [58.4%] vs 21 [12.7%] vs 59 [35.1%]; P < .0001) and sPGA 0/1 (178 [53.6%] vs 12 [7.2%] vs 54 [32.1%]; P < .0001). Efficacy improved beyond week 16 and was maintained through week 52. Adverse event rates with deucravacitinib were similar to those with placebo and apremilast.
LIMITATIONS
One-year duration, limited racial diversity.
CONCLUSION
Deucravacitinib was superior to placebo and apremilast across multiple efficacy end points and was well tolerated in moderate to severe plaque psoriasis.
Topics: Adult; Humans; Anti-Inflammatory Agents, Non-Steroidal; Severity of Illness Index; Double-Blind Method; Psoriasis; Treatment Outcome
PubMed: 35820547
DOI: 10.1016/j.jaad.2022.07.002 -
International Journal of Dermatology Oct 2018The links between psoriasis and stress are complex. This article proposes a review of the literature on the relationship between stress and psoriasis. In 31-88% of... (Review)
Review
The links between psoriasis and stress are complex. This article proposes a review of the literature on the relationship between stress and psoriasis. In 31-88% of cases, patients report stress as being a trigger for their psoriasis. There was also a reported higher incidence of psoriasis in subjects who had a stressful event the previous year, suggesting that stress may have a role in triggering the disease in predisposed individuals. Stress is also a consequence of psoriasis outbreaks. Understanding the role of stress makes it appropriate to target stress when proposing treatment to patients with psoriasis. Several controlled studies have demonstrated that relaxation, hypnosis, biofeedback, and behavioral and cognitive stress management therapies have been effective in people with psoriasis.
Topics: Humans; Psoriasis; Risk Factors; Severity of Illness Index; Social Stigma; Stress, Psychological; Symptom Flare Up
PubMed: 29729012
DOI: 10.1111/ijd.14032 -
International Journal of Molecular... Sep 2019Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells... (Review)
Review
Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting tumor necrosis factor-α, interleukin (IL)-23, and IL-17 have been developed and approved for the treatment of psoriasis. These biologics have dramatically changed the treatment and management of psoriasis. In contrast, various triggering factors can elicit the disease in genetically predisposed individuals. Recent studies suggest that the exacerbation of psoriasis can lead to systemic inflammation and cardiovascular comorbidity. In addition, psoriasis may be associated with other auto-inflammatory and auto-immune diseases. In this review, we summarize the risk factors, which can be divided into two groups (namely, extrinsic and intrinsic risk factors), responsible for the onset and exacerbation of psoriasis in order to facilitate its prevention.
Topics: Age of Onset; Animals; Comorbidity; Disease Progression; Humans; Psoriasis; Risk Assessment; Risk Factors
PubMed: 31491865
DOI: 10.3390/ijms20184347 -
International Journal of Molecular... May 2021Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The... (Review)
Review
Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.
Topics: Animals; Clinical Trials as Topic; Humans; Models, Biological; Nanomedicine; Nanotechnology; Psoriasis
PubMed: 34067151
DOI: 10.3390/ijms22094983 -
Annals of the Rheumatic Diseases Mar 2005Psoriasis is a common chronic, recurrent, immune mediated disease of the skin and joints. It can have a significant negative impact on the physical, emotional, and,... (Review)
Review
Psoriasis is a common chronic, recurrent, immune mediated disease of the skin and joints. It can have a significant negative impact on the physical, emotional, and, psychosocial wellbeing of affected patients. Psoriasis is found worldwide but the prevalence varies among different ethnic groups. It has a strong genetic component but environmental factors such as infections can play an important role in the presentation of disease. There are several clinical cutaneous manifestations of psoriasis but most commonly the disease presents as chronic, symmetrical, erythematous, scaling papules and plaques. The epidemiology, clinical features, and impact on quality of life of psoriasis are reviewed.
Topics: Health Status Indicators; Humans; Psoriasis; Quality of Life
PubMed: 15708928
DOI: 10.1136/ard.2004.033217 -
Dermatology (Basel, Switzerland) 2016Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis consisting of a genetic component, immune dysfunction, and environmental factors. It... (Review)
Review
Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis consisting of a genetic component, immune dysfunction, and environmental factors. It is associated with numerous comorbidities including psoriatic arthritis, cardiovascular disease, metabolic syndrome, and obesity. Evidence suggests that obesity is a risk factor for incident psoriasis, aggravates existing psoriasis, and that weight reduction may improve the severity of psoriasis in overweight individuals. Excess body weight may interfere with the medical treatment used in psoriasis and adds to the cardiovascular risk profile in these patients, which underscores the importance of effective weight control regimens. In this review we examine the current literature with regard to the association between obesity and psoriasis.
Topics: Comorbidity; Humans; Obesity; Psoriasis; Risk Factors; Weight Loss
PubMed: 28226326
DOI: 10.1159/000455840 -
The British Journal of Dermatology Apr 2020Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques.... (Review)
Review
BACKGROUND
Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques. Psoriasis pathogenesis is driven by proinflammatory cytokines and psoriasis is associated with increased risk for comorbidities, including, but not limited to, psoriatic arthritis, cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease compared with the general population.
OBJECTIVES
To explore the pathophysiological relationship between psoriasis and its common comorbidities and discuss the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis.
METHODS
This narrative review summarizes the published evidence related to the ability of biological therapies to ameliorate the consequences of systemic inflammation in patients with psoriasis.
RESULTS
Current evidence suggests that preventing damage associated with inflammation, and preventing development of future inflammatory damage and comorbidities, may be a potentially achievable treatment goal for many patients with moderate-to-severe plaque psoriasis when biological therapies are utilized early in the disease. Encouraging data from recent studies suggest that the loftier goal of reversing existing inflammatory damage and improving signs and symptoms of inflammatory comorbidities could also possibly be attainable.
CONCLUSIONS
Results from ongoing prospective studies regarding the effects of biologics on markers of systemic inflammation in patients with psoriasis will strengthen the clinical evidence base that can be used to inform treatment decisions for patients with moderate-to-severe psoriasis. What's already known about this topic? Psoriasis is a systemic inflammatory disease and treatments are needed to optimize patient outcomes. What does this study add? This review discusses new psoriasis treatment paradigms that may potentially reduce effects of systemic inflammation. Evidence demonstrating that biological treatment may prevent or reverse inflammatory damage associated with psoriasis comorbidities is reviewed.
Topics: Arthritis, Psoriatic; Cardiovascular Diseases; Humans; Obesity; Prospective Studies; Psoriasis
PubMed: 31225638
DOI: 10.1111/bjd.18245 -
Annual Review of Immunology 2014The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT).... (Review)
Review
The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases.
Topics: Animals; Comorbidity; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Mice; Psoriasis; Skin; Skin Physiological Phenomena
PubMed: 24655295
DOI: 10.1146/annurev-immunol-032713-120225 -
Actas Dermo-sifiliograficas May 2022Nail involvement in psoriasis is common. It is seen in up to 80% of patients with psoriatic lesions and may be the only manifestation in 6% of cases. Nail psoriasis is... (Review)
Review
Nail involvement in psoriasis is common. It is seen in up to 80% of patients with psoriatic lesions and may be the only manifestation in 6% of cases. Nail psoriasis is correlated with more severe disease, characterized by earlier onset and a higher risk of psoriatic arthritis. Accordingly, it can also result in significant functional impairment and reduced quality of life. Psoriasis involving the nail matrix causes pitting, leukonychia, red lunula and nail dystrophy, while nail bed involvement causes splinter hemorrhages, onycholysis, oil spots (salmon patches), and subungual hyperkeratosis. Common evaluation tools are the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI, and the f-PGA (Physician's Global Assessment of Fingernail Psoriasis). Treatment options include topical therapy, intralesional injections, and systemic and biologic agents. Treatment should therefore be assessed on an individualized basis according to the number of nails involved, the part of the nail or nails affected, and the presence of concomitant nail and/or joint involvement.
Topics: Arthritis, Psoriatic; Humans; Nail Diseases; Nails; Psoriasis; Quality of Life; Severity of Illness Index
PubMed: 35697407
DOI: 10.1016/j.ad.2022.01.006