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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 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 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... 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 -
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 -
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 -
The Journal of Investigative Dermatology Mar 2022The use of preclinical animal models of psoriasis has significantly increased over the last three decades, with each model having unique strengths and limitations. Some... (Review)
Review
The use of preclinical animal models of psoriasis has significantly increased over the last three decades, with each model having unique strengths and limitations. Some models translate better to human disease, and many have provided unique insight into psoriasis disease pathogenesis. In this comprehensive review, we present a comparative description and discussion of genetic mouse models, xenograft approaches, and elicited methods using cytokine injections into and topical imiquimod onto mice. We provide an inclusive list of genetically modified animals that have had imiquimod applied to or cytokines injected into their skin and describe the outcomes of these manipulations. This review will provide a valuable resource for those interested in working with psoriasis animal models.
Topics: Animals; Cytokines; Disease Models, Animal; Humans; Imiquimod; Mice; Psoriasis; Skin
PubMed: 34953514
DOI: 10.1016/j.jid.2021.06.019 -
The Yale Journal of Biology and Medicine Mar 2020Psoriasis is a frequent inflammatory skin disease. Fundamental research on the pathogenesis of psoriasis has substantially increased our understanding of skin... (Review)
Review
Psoriasis is a frequent inflammatory skin disease. Fundamental research on the pathogenesis of psoriasis has substantially increased our understanding of skin immunology, which has helped to introduce innovative and highly effective therapies. Psoriasis is a largely T lymphocyte-mediated disease in which activation of innate immune cells and pathogenic T cells result in skin inflammation and hyperproliferation of keratinocytes. B cells have thus far largely been neglected regarding their role for the pathogenesis of psoriasis. However, recent data shed light on their role in inflammatory skin diseases. Interestingly, interleukin (IL)-10-producing regulatory B cells have been assumed to ameliorate psoriasis. In this review, we will discuss the development of disease, pathogenicity, and current developments in therapeutic options. We describe different roles of T cells, B cells, and cytokines for the immunopathology and disease course of psoriasis.
Topics: Biological Products; Humans; Immunity, Innate; Immunosuppressive Agents; Psoriasis; Skin
PubMed: 32226340
DOI: No ID Found -
International Journal of Molecular... Oct 2020Psoriasis is an immune cell-mediated inflammatory skin disease. The interleukin (IL)23/IL17 axis plays an important role in the development of psoriasis. The... (Review)
Review
Psoriasis is an immune cell-mediated inflammatory skin disease. The interleukin (IL)23/IL17 axis plays an important role in the development of psoriasis. The effectiveness of biologic treatments such as tumor necrosis factor (TNF)α inhibitors (infliximab, adalimumab, certolizumab pegol), IL23 inhibitors (ustekinumab, guselkumab, tildrakizumab, risankizumab), and IL17 inhibitors (secukinumab, ixekizumab, brodalumab) have verified these findings. Immune-related cells such as dendritic cells (DCs) and macrophages, in addition to Toll-like receptors and cytokines such as interferon (IFN)α, TNFα, IFNɤ, IL12, IL22, IL23, and IL17, are related to the pathogenesis of psoriasis. Here, we first review new insights regarding the pathogenesis of psoriasis, as it relates to DCs, Langerhans cells, macrophages, the signal transducer and activator of transcription 3 pathway, and aryl hydrocarbon receptor in cutaneous vascular endothelial cells. Based on these findings, we summarize currently available oral treatments and biologics. Furthermore, we describe a new treatment option including Janus kinase inhibitor, tyrosine kinase 2 inhibitor, modulator of sphingosine 1-phosphate receptor 1, and Rho-associated kinase 2 inhibitor.
Topics: Animals; Biomarkers; Dendritic Cells; Disease Management; Disease Susceptibility; Humans; Molecular Targeted Therapy; Psoriasis; Signal Transduction
PubMed: 33050592
DOI: 10.3390/ijms21207488