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Use of Cytokine Mix-, Imiquimod-, and Serum-Induced Monoculture and Lipopolysaccharide- and Interferon Gamma-Treated Co-Culture to Establish In Vitro Psoriasis-like Inflammation Models.
Bocheńska, K, Moskot, M, Gabig-Cimińska, M
Cells. 2021;(11)
Abstract
Psoriasis (Ps), commonly perceived as a skin and joint disorder, has a complex basis and results from disturbances in the sophisticated network between skin and the immune system. This makes it difficult to properly depict the complete pathomechanism on an in vitro scale. Deciphering the complicated or even subtle modulation of intra- and intercellular factors, assisted by the implementation of in vitro human skin models, may provide the opportunity to dissect the disease background step by step. In addition to reconstructed artificial skin substitutes, which mimic the native physiological context, in vitro models are conducive to the broad "3 Rs" philosophy (reduce, refine, and replace) and represent important tools for basic and applied skin research. To meet the need for a more comprehensive in vitro Ps model, a set of various experimental conditions was applied in this study. The selection of in vitro treatment that mimicked the Ps phenotype was illustrated by analyses of discriminating biomarker genes involved in the pathogenesis of the disease, i.e., keratinocyte differentiation markers, antimicrobial peptides, chemokines, and proliferation markers. This resulted in a reproducible protocol for the use of the primary skin keratinocyte (pKC) monoculture treated with a cytokine cocktail (5MIX, i.e., interleukin (IL) 1 alpha (IL-1α), IL-17A, IL-22, oncostatin M (OSM), and tumour necrosis factor alpha (TNF-α)) at a calcium (Ca2+) concentration (i.e., 2 mM) in an applied medium, which best mirrored the in vitro Ps-like inflammatory model. In addition, based on waste skin material, the method has the potential for extensive experimentation, both in detailed molecular studies and preclinical tests.
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Therapeutic Implications of Diet in Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory Diseases.
Jiang, Y, Jarr, K, Layton, C, Gardner, CD, Ashouri, JF, Abreu, MT, Sinha, SR
Nutrients. 2021;(3)
Abstract
Despite being a focal issue to patients, the effect of diet on adult inflammatory bowel disease (IBD) remains underexplored with limited guidance. While promising clinical trials are currently underway, there is a need for further evidence-based recommendations. As such, we summarize the current evidence on various diets used in the treatment of IBD and also explore the potential applications of dietary data from related immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and psoriasis, to provide additional information to inform IBD providers. To date, there have been multiple diets investigated as adjunctive therapy in IBD, but many associated studies are small, non-randomized, and not controlled. Mediterranean, vegetarian/vegan, and reduced-calorie/fasting diets have been studied and have shown some positive results in other IMIDs, which may suggest potential applicability to those with IBD, but larger, well-designed clinical trials are needed for further guidance. Gluten-free and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)diets do not appear to have an impact on IBD disease activity, but low FODMAP may potentially be helpful for those with concurrent functional gastrointestinal symptoms. Specific carbohydrate diets have been mainly assessed in children but show some potential in small adult studies.
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Cardiovascular Risk in Patients With Psoriasis: JACC Review Topic of the Week.
Garshick, MS, Ward, NL, Krueger, JG, Berger, JS
Journal of the American College of Cardiology. 2021;(13):1670-1680
Abstract
Psoriasis is a chronic inflammatory skin disease that affects 2% to 3% of the U.S. population. The immune response in psoriasis includes enhanced activation of T cells and myeloid cells, platelet activation, and up-regulation of interferons, tumor necrosis factor-α, and interleukins (ILs) IL-23, IL-17, and IL-6, which are linked to vascular inflammation and atherosclerosis development. Patients with psoriasis are up to 50% more likely to develop cardiovascular disease (CV) disease, and this CV risk increases with skin severity. Major society guidelines now advocate incorporating a psoriasis diagnosis into CV risk prediction and prevention strategies. Although registry data suggest treatment targeting psoriasis skin disease reduces vascular inflammation and coronary plaque burden, and may reduce CV risk, randomized placebo-controlled trials are inconclusive to date. Further studies are required to define traditional CV risk factor goals, the optimal role of lipid-lowering and antiplatelet therapy, and targeted psoriasis therapies on CV risk.
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Indoor salt water baths followed by artificial ultraviolet B light for chronic plaque psoriasis.
Peinemann, F, Harari, M, Peternel, S, Chan, T, Chan, D, Labeit, AM, Gambichler, T
The Cochrane database of systematic reviews. 2020;(5):CD011941
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Abstract
BACKGROUND Chronic plaque psoriasis is an immune-mediated, chronic, inflammatory skin disease, which can impair quality of life and social interaction. Disease severity can be classified by the psoriasis area and severity index (PASI) score ranging from 0 to 72 points. Indoor artificial salt bath with or without artificial ultraviolet B (UVB) light is used to treat psoriasis, simulating sea bathing and sunlight exposure; however, the evidence base needs clear evaluation. OBJECTIVES To assess the effects of indoor (artificial) salt water baths followed by exposure to artificial UVB for treating chronic plaque psoriasis in adults. SEARCH METHODS We searched the following databases up to June 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registers, and checked the reference lists of included studies, recent reviews, and relevant papers for further references to relevant trials. SELECTION CRITERIA Randomised controlled trials (RCTs) of salt bath indoors followed by exposure to artificial UVB in adults who have been diagnosed with chronic plaque type psoriasis. We included studies reporting between-participant data and within-participant data. We evaluated two different comparisons: 1) salt bath + UVB versus other treatment without UVB; eligible comparators were exposure to psoralen bath, psoralen bath + artificial ultraviolet A UVA) light, topical treatment, systemic treatment, or placebo, and 2) salt bath + UVB versus other treatment + UVB or UVB only; eligible comparators were exposure to bath containing other compositions or concentrations + UVB or UVB only. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. The primary efficacy outcome was PASI-75, to detect people with a 75% or more reduction in PASI score from baseline. The primary adverse outcome was treatment-related adverse events requiring withdrawal. For the dichotomous variables PASI-75 and treatment-related adverse events requiring withdrawal, we estimated the proportion of events among the assessed participants. The secondary outcomes were health-related quality of life using the Dermatology Life Quality Index, (DLQI) pruritus severity measured using a visual analogue scale, time to relapse, and secondary malignancies. MAIN RESULTS We included eight RCTs: six reported between-participant data (2035 participants; 1908 analysed), and two reported within-participant data (70 participants, 68 analysed; 140 limbs; 136 analysed). One study reported data for the comparison salt bath with UVB versus other treatment without UVB; and eight studies reported data for salt bath with UVB versus other treatment with UVB or UVB only. Of these eight studies, only five reported any of our pre-specified outcomes and assessed the comparison of salt bath with UVB versus UVB only. The one included trial that assessed salt bath plus UVB versus other treatment without UVB (psoralen bath + UVA) did not report any of our primary outcomes. The mean age of the participants ranged from 41 to 50 years of age in 75% of the studies. None of the included studies reported on the predefined secondary outcomes of this review. We judged seven of the eight studies as at high risk of bias in at least one domain, most commonly performance bias. Total trial duration ranged between at least two months and up to 13 months. In five studies, the median participant PASI score at baseline ranged from 15 to 18 and was balanced between treatment arms. Three studies did not report PASI score. Most studies were conducted in Germany; all were set in Europe. Half of the studies were multi-centred (set in spa centres or outpatient clinics); half were set in a single centre in either an unspecified settings, a psoriasis daycare centre, or a spa centre. Commercial spa or salt companies sponsored three of eight studies, health insurance companies funded another, the association of dermatologists funded another, and three did not report on funding. When comparing salt bath plus UVB versus UVB only, two between-participant studies found that salt bath plus UVB may improve psoriasis when measured using PASI 75 (achieving a 75% or more reduction in PASI score from baseline) (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.24 to 2.35; 278 participants; low-certainty evidence). Assessment was conducted at the end of treatment, which was equivalent to six to eight weeks after start of treatment. The two trials which contributed data for the primary efficacy outcome were conducted by the same group, and did not blind outcome assessors. The German Spas Association funded one of the trials and the funding source was not stated for the other trial. Two other between-participant studies found salt bath plus UVB may make little to no difference to outcome treatment-related adverse events requiring withdrawal compared with UVB only (RR 0.96, 95% CI 0.35 to 2.64; 404 participants; low-certainty evidence). One of the studies reported adverse events, but did not specify the type of events; the other study reported skin irritation. One within-participant study found similar results, with one participant reporting severe itch immediately after Dead Sea salt soak in the salt bath and UVB group and two instances of inadequate response to phototherapy and conversion to psoralen bath + UVA reported in the UVB only group (low-certainty evidence). AUTHORS' CONCLUSIONS Salt bath with artificial ultraviolet B (UVB) light may improve psoriasis in people with chronic plaque psoriasis compared with UVB light treatment alone, and there may be no difference in the occurrence of treatment-related adverse events requiring withdrawal. Both results are based on data from a limited number of studies, which provided low-certainty evidence, so we cannot draw any clear conclusions. The reporting of our pre-specified outcomes was either non-existent or limited, with a maximum of two studies reporting a given outcome. The same group conducted the two trials which contributed data for the primary efficacy outcome, and the German Spas Association funded one of these trials. We recommend further RCTs that assess PASI-75, with detailed reporting of the outcome and time point, as well as treatment-related adverse events. Risk of bias was an issue; future studies should ensure blinding of outcome assessors and full reporting.
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What do Cochrane systematic reviews say about interventions for treating psoriasis?
Pacheco, RL, Hosni, ND, Latorraca, COC, Martimbianco, ALC, Pachito, DV, Yarak, S, Riera, R
Sao Paulo medical journal = Revista paulista de medicina. 2018;(4):354-360
Abstract
CONTEXT AND OBJECTIVE Psoriasis is a common chronic inflammatory skin disease characterized by abnormal and increased growth of the cells that produce keratin and abnormal functioning of the immune system. We aimed to summarize the evidence available regarding interventions for patients with psoriasis. DESIGN AND SETTING Review of systematic reviews, developed in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. METHODS A systematic search was conducted to identify Cochrane systematic reviews that fulfilled the eligibility criteria. Two authors screened titles and abstracts that had been retrieved through the search strategy. The results from all the Cochrane systematic reviews that were included were summarized and presented in a narrative synthesis. RESULTS We included six Cochrane systematic reviews assessing interventions for treating psoriasis. The findings from high-quality evidence were that (a) etanercept reduced the psoriasis severity index, compared with placebo and (b) steroids plus vitamin D, compared with vitamin D alone, improved the skin clearance rate, as assessed by investigators, but was associated with a higher proportion of participants who dropped out due to adverse events. For all other comparisons, the quality of the evidence ranged from moderate to very low. CONCLUSION This review included six Cochrane systematic reviews that provided evidence ranging in quality from unknown to high, regarding management of psoriasis. Further randomized controlled trials are imperative to reduce the uncertainties relating to several treatments that are already used in clinical practice.
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Ethnopharmacological survey of medicinal plants used by patients with psoriasis in the West Bank of Palestine.
Shawahna, R, Jaradat, NA
BMC complementary and alternative medicine. 2017;(1):4
Abstract
BACKGROUND Psoriasis is a frequent skin inflammatory disorder that inflicts millions of patients around the globe. To meet their healthcare needs, patients with psoriasis often seek treatment outside the allopathic paradigm. Use of medicinal plants has emerged as one of the most common and preferred modalities of complementary and alternative medicine (CAM). The aim of this study was to investigate the use of medicinal plants by patients with psoriasis in the West Bank of Palestine. METHODS The current study was a questionnaire based cross-sectional descriptive study on the use of medicinal plants by psoriasis patients in the West Bank of Palestine. A sample of 149 patients with psoriasis who were visiting outpatient clinics responded to the questionnaire in face to face interviews. RESULTS Medicinal plants were used by 81 (54.4%) patients with psoriasis. Patients used 33 medicinal plants belonging to 26 families. Plants belonging to Lamiaceae and Leguminosae were the most commonly used by the study patients. Aloe vera, Trigonella arabica, Catharanthus roseus and Anthemis cotula were the most frequently used medicinal plants to treat psoriasis. Leaves and fruits were the most commonly used parts by the study patients. Paste was the most commonly used form of preparation. The use of medicinal plants was significantly associated with age and monthly household income of the patients. Enhancement of immunity, improving conventional therapy and reduction of side effects were the most commonly self-reported reasons for using medicinal plants. CONCLUSIONS Patients with psoriasis in Palestine seem to use medicinal plants as a CAM modality to manage their psoriasis. Many medicinal plants were commonly used by patients with psoriasis. More randomized clinical trials are needed to demonstrate safety and efficacy for the majority of these medicinal plants reported to be used by patients with psoriasis in Palestine.
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The impact of topical Saint John's Wort (Hypericum perforatum) treatment on tissue tumor necrosis factor-alpha levels in plaque-type psoriasis: A pilot study.
Mansouri, P, Mirafzal, S, Najafizadeh, P, Safaei-Naraghi, Z, Salehi-Surmaghi, MH, Hashemian, F
Journal of postgraduate medicine. 2017;(4):215-220
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Abstract
CONTEXT Psoriasis is an inflammatory disorder, formed by inappropriate interaction of T lymphocytes with keratinocytes, and consequent eruption of immune responses. High concentrations of tumor necrosis factor-alpha (TNFα) are found in the skin lesions and plasma of patients with psoriasis. Hypericum perforatum, a phytomedicine that has both anti-inflammatory and antiproliferative properties, has been recently reported to be clinically helpful for improvement of psoriatic lesions. AIMS The aim of the present study was to investigate the effects of topical H. perforatum on TNFα levels in psoriatic lesions for possible identification of the mechanism by which Hypericum reduces inflammation and modulates the disease in patients with plaque-type psoriasis. SETTINGS AND DESIGN A double-blind, placebo-controlled, pilot study with intraindividual comparison was conducted on twenty patients with mild to moderate plaque-type psoriasis. SUBJECTS AND METHODS TNFα levels in tissue samples were measured with immunohistochemistry method. Moreover, Psoriasis Area Severity Index (PASI) scores and histological and clinical changes were investigated after topical application of Hypericum extract. STATISTICAL ANALYSIS USED The Wilcoxon signed-rank test was used to evaluate the possible differences between the drug and placebo group. RESULTS TNFα concentrations in dermis (p= 0.025), endothelial cells (p=0.033), and dendrite cells (p=0.014) were significantly reduced in lesions treated with drug and the reduction observed in epidermis was superior to placebo (p=0.046). Results of PASI scores showed that erythema, scaling, and thickness were significantly lower where the ointment had been applied compared to application of placebo (p=0.014, p=0.004, p=0.003, respectively). Moreover, significant improvement in clinical and histological features of treated lesions in comparison with untreated lesions was observed (P < 0.05). CONCLUSIONS H. perforatum ointment can help decrease PASI scores and TNFα levels in psoriatic tissue. Its efficacy is probably related to its effect on lowering cytokines including TNFα.
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Environmental Risk Factors in Psoriasis: The Point of View of the Nutritionist.
Barrea, L, Nappi, F, Di Somma, C, Savanelli, MC, Falco, A, Balato, A, Balato, N, Savastano, S
International journal of environmental research and public health. 2016;(5)
Abstract
Psoriasis is a common, chronic, immune-mediated skin disease with systemic pro-inflammatory activation, where both environmental and genetic factors contribute to its pathogenesis. Among the risk factors for psoriasis, evidence is accumulating that nutrition plays a major role, per se, in psoriasis pathogenesis. In particular, body weight, nutrition, and diet may exacerbate the clinical manifestations, or even trigger the disease. Understanding the epidemiological relationship between obesity and psoriasis is also important for delineating the risk profile for the obesity-related comorbidities commonly found among psoriatic patients. Moreover, obesity can affect both drug's pharmacokinetics and pharmacodynamics. Additionally, the overall beneficial effects on the obesity-associated comorbidities, clinical recommendations to reduce weight and to adopt a healthy lifestyle could improve the psoriasis severity, particularly in those patients with moderate to severe disease, thus exerting additional therapeutic effects in the conventional treatment in obese patients with psoriasis. Education regarding modifiable environmental factors is essential in the treatment of this disease and represents one of the primary interventions that can affect the prognosis of patients with psoriasis. The goal is to make psoriatic patients and health care providers aware of beneficial dietary interventions. The aim of this review is to assess the relevance of the environmental factors as modifiable risk factors in psoriasis pathogenesis, with particular regard to the involvement of obesity and nutrition in the management of psoriasis, providing also specific nutrition recommendations.
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Profile of patients receiving medical care at a reference, support, and treatment center for psoriasis patients at a university hospital.
Cordeiro, TG, Andrade, BP, Palitot, EB, Piuvezam, MR, Mascarenhas, SR
Anais brasileiros de dermatologia. 2016;(5):691-693
Abstract
Psoriasis is a chronic, inflammatory, immune-mediated disease affecting 1-3% of the population worldwide. This work seeks to draw a profile of patients with psoriasis, analyzing socioeconomic, anthropometric, and clinical aspects. For this, medical records from 81 individuals who received medical care in a university hospital in 2014 were consulted. It was observed that the patients were mostly dark-skinned black adult men, with a low education level and a low income, who were sedentary, former smokers, obese, with an increase in waist circumference, and who did not consume alcohol. Psoriasis vulgaris predominated, beginning mainly on the scalp, hands, and feet. In addition, many presented some type of associated comorbidity and had relatives with psoriasis.
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Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population.
Yin, X, Wineinger, NE, Wang, K, Yue, W, Norgren, N, Wang, L, Yao, W, Jiang, X, Wu, B, Cui, Y, et al
Journal of psychiatry & neuroscience : JPN. 2016;(6):413-421
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BACKGROUND Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. METHODS We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. RESULTS We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10-8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10-16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. LIMITATIONS Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. CONCLUSION We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.