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.
Psoriasis is a prevalent chronic inflammatory disease. The inflammatory response is driven by T cells and mediated by multiple cytokines such as tumor necrosis factor and the interleukins IL-17 and ...IL-23. Moderate-to-severe psoriasis is treated systemically, using either biologics or conventional treatments with small-molecule drugs. The newer biologics are very effective and well tolerated, but not all patients respond to treatment with biologics, so there is a need for new treatment options for psoriasis. Janus kinase (JAK) inhibitors are a new drug class that may be of use in this respect. These inhibitors are already on the market for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. They block the intracellular signal pathway mediated by JAK and signal transducer and activator of transcription (STAT) proteins, thereby inhibiting gene transcription of proinflammatory cytokines. JAK inhibitors are currently being tested as potential treatments for psoriasis. They have shown clinical efficacy as measured by the Psoriasis Area and Severity Index 75 response in both phase 2 and 3 trials, and appear to be well tolerated overall. This review provides an overview of the mechanisms underlying the actions of JAK inhibitors in psoriasis, together with the results of clinical trials testing their efficacies when used to treat the disease.
Human skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central ...role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combine advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantify 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and previously undescribed proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research ( https://skin.science/ ).
Psoriasis is linked with increased risk of cardiovascular disease (CVD) that is underestimated by traditional risk stratification. We conducted a large-scale plasma proteomic analysis by use of a ...proximity extension assay in 85 patients with a history of moderate-to-severe psoriasis with or without established atherosclerotic CVD. Differentially expressed proteins associated with CVD were correlated with subclinical atherosclerotic markers including vascular inflammation determined by
F-fluorodeoxyglucose positron emission tomography/computed tomography, carotid intima-media thickness (CIMT), carotid artery plaques, and coronary artery calcium score (CCS) in the patients without CVD and statin treatment. We also examined the association between the neutrophil-to-lymphocyte ratio (NLR) and subclinical atherosclerosis. In unadjusted analyses, growth differentiation factor-15 (GDF-15) levels and NLR were increased, while tumor necrosis factor (TNF)-related activation-inducing ligand (TRANCE) and TNF-related apoptosis-induced ligand (TRAIL) levels were decreased in patients with established CVD compared to those without CVD. Among patients with psoriasis without CVD and statin treatment, GDF-15 levels were negatively associated with vascular inflammation in the ascending aorta and entire aorta, and positively associated with CIMT and CCS. NLR was positively associated with vascular inflammation in the carotid arteries. Our data suggest that circulating GDF-15 levels and NLR might serve as biomarkers of subclinical atherosclerosis in patients with psoriasis.
Abstract Background Psoriasis is a chronic inflammatory skin disease often seen in patients with a genetic susceptibility. MicroRNAs (miRNA) are endogenous, short RNA molecules that can bind to parts ...of mRNA target genes, thus inhibiting their translation and causing accelerated turnover or transcript degradation. MicroRNAs are important in the pathogenesis of human diseases such as immunological disorders, as they regulate a broad range of biological processes. Objective We investigated miRNA–mRNA interactions in involved (PP) and non-involved (PN) psoriatic skin compared with healthy skin (NN). Methods Biopsies were obtained from PP, PN and NN, the miRNA and mRNA expression was analyzed by microarray techniques and a subset of miRNAs and mRNAs were validated by q-RT-PCR. Novel target interactions in psoriasis were found using PubMed, miRBase and RNAhybrid. In addition, TIMP3 protein expression was studied in PP, PN and NN. Finally, the miR-221/2– TIMP3 target interaction was studied in primary human keratinocytes by endogenous overexpression of the miRNAs. Results We identified 42 upregulated miRNAs and 5 downregulated miRNAs in PP compared with NN, and only few deregulated miRNAs in PN compared with NN. Based on the miRNA and mRNA profiles miR-21, -205, -221 and -222 were found to have the following potential mRNA targets in psoriatic skin: PDCD4 , TPM1 , P57 , C-KIT , RTN4 , SHIP2 , TIMP3 , RECK and NFIB . The identified target mRNAs were likely to be involved in cellular growth, proliferation, apoptosis and degradation of the extracellular matrix. Finally we found that TIMP3 is downregulated in psoriatic skin. In vitro overexpression of miR-221 and miR-222 lead to degradation of TIMP3 resulting in decreased TIMP3 protein level. Conclusion Our data indicate several novel important associations for miRNAs in psoriasis and in particular the miR-221/2– TIMP3 target interaction could among others play a role in the psoriasis pathogenesis.
Purpose: Patients with atopic dermatitis (AD) require both skills and support to effectively manage life with the disease. Here, we developed an agenda-setting tool for consultations with patients ...with AD to establish a collaborative agenda that enhances patient involvement and prioritizes on self-management support.Purpose: Patients with atopic dermatitis (AD) require both skills and support to effectively manage life with the disease. Here, we developed an agenda-setting tool for consultations with patients with AD to establish a collaborative agenda that enhances patient involvement and prioritizes on self-management support.Materials and methods: Using the design thinking process, we included 64 end-users (patients and healthcare professionals (HCPs)) across the different phases of design thinking. We identified seven overall categories that patients find important to discuss during consultations, which informed the development of a tool for co-creating a consultation agenda (conversation cards, CCs).Materials and methods: Using the design thinking process, we included 64 end-users (patients and healthcare professionals (HCPs)) across the different phases of design thinking. We identified seven overall categories that patients find important to discuss during consultations, which informed the development of a tool for co-creating a consultation agenda (conversation cards, CCs).Results: Through iterative user testing of the CCs, patients perceived the cards as both inspiring and an invitation from HCPs to openly discuss their needs during consultations. Healthcare professionals have found the CCs easy to use, despite the disruption to the typical consultation process.Results: Through iterative user testing of the CCs, patients perceived the cards as both inspiring and an invitation from HCPs to openly discuss their needs during consultations. Healthcare professionals have found the CCs easy to use, despite the disruption to the typical consultation process.Conclusion: In summary, the CCs provide a first-of-its-kind agenda-setting tool for patients with AD. They offer a simple and practical method to establishing a shared agenda that focuses on the patients' needs and are applicable within real-world clinical settings.Conclusion: In summary, the CCs provide a first-of-its-kind agenda-setting tool for patients with AD. They offer a simple and practical method to establishing a shared agenda that focuses on the patients' needs and are applicable within real-world clinical settings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The immune mechanisms involved in atopic dermatitis (AD) are complex and little is known about the possible role of the gut microbiota in the aetiopathogenesis of AD. A systematic review of the ...literature was performed according to PRISMA guidelines, and included 44 of 2,199 studies (26 observational and 18 interventional studies). Detection of gut microbiota was performed by either 16s rRNA PCR, or by culture. Observational studies were diverse regarding the age of study participants and the bacterial species investigated. Overall, the results were conflicting with regard to diversity of the gut microbiota, specific bacterial colonization, and subsequent risk of AD. Nearly half of the included interventional studies showed that an altered gut microbial colonization due to use of probiotics had a positive effect on the severity of AD. The remaining studies did not show an effect of probiotics on the severity of AD despite an alteration in the gut microbial composition. The role of the gut microbiome for the onset and severity of pre-existing AD remains controversial.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prurigo nodularis is a pruritic dermatosis with poor treatment options. To describe treatment patterns, comorbidities, pruritus, and quality of life a survey was administered to 92 patients with ...prurigo nodularis. A total of 52 patients completed the survey. The most frequently used treatments were topical corticosteroids, which were prescribed to 49/52 patients, with positive effect in 13/49. A total of 46/52 patients were treated with ultraviolet B, and 9/46 reported a positive effect. A positive effect was reported for topical corticosteroids under occlusion in 21/40, for zinc dressing treatment in 17/37, for steroid injection in 9/14, for methotrexate in 5/16, and for thalidomide in 4/12 of treated patients. Thirty-six patients reported a Pittsburgh Sleep Quality Index >5, indicating poor sleep. Patients with prurigo nodularis are severely bothered by pruritus negatively affecting quality of life. Various treatments are prescribed; most frequently topical corticosteroids and ultraviolet B. Surprisingly, patients reported topical corticosteroids under occlusion, zinc-dressing treatment and steroid injection as the most effective.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Ocular comorbidities are common in atopic dermatitis (AD) as the result of the disease itself or the use of medication. No large-scale epidemiologic data exist on the prevalence of ocular ...comorbidities in adults with AD. Objectives We sought to examine the prevalence and risk of selected ocular comorbidities in adult patients with AD. Methods All Danish individuals ≥18 years of age were linked in nationwide registries. Adjusted hazard ratios (HRs) were estimated by means of Cox regression. Results A total of 5766 and 4272 adults were categorized as having mild and severe AD, respectively. At least 1 prescription of anti-inflammatory ocular agents was claimed in 12.0% and 18.9% of patients with mild and severe AD, respectively. In adjusted analysis, the HR of conjunctivitis was 1.48 (95% confidence interval CI, 1.15-1.90) for mild AD and 1.95 (95% CI, 1.51-2.51) for severe AD. The HR of keratitis was 1.66 (95% CI, 1.15-2.40) for mild AD and 3.17 (95% CI, 2.31-4.35) for severe AD. For adults with severe AD, the HR for keratoconus was 10.01 (95% CI, 5.02-19.96). AD was associated with “cataract only” in individuals <50 years of age. Limitations A limitation of the study is that observational studies cannot establish causality. Conclusions Adults with AD had a significant and disease severity–dependent increased risk of development of conjunctivitis, keratitis, and keratoconus compared with that of the general population.
Autoimmune diseases in adults with atopic dermatitis Andersen, Yuki M.F., MD; Egeberg, Alexander, MD, PhD; Gislason, Gunnar H., MD, PhD ...
Journal of the American Academy of Dermatology,
02/2017, Letnik:
76, Številka:
2
Journal Article
Recenzirano
Background An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. Objective We examined the co-occurrence ...of selected autoimmune diseases in adult patients with AD. Methods Nationwide health registers were used. Adult patients with a hospital diagnosis of AD in Denmark between 1997 and 2012 were included as cases (n = 8112) and matched with controls (n = 40,560). The occurrence of autoimmune diseases was compared in the 2 groups. Logistic regression was used to estimate odds ratios. Results AD was significantly associated with 11 of 22 examined autoimmune diseases. In addition, AD was associated with having multiple autoimmune comorbidities. Patients with a history of smoking had a significantly higher occurrence of autoimmune comorbidities compared to nonsmokers. Limitations This study was limited to adult patients with AD. No information about AD severity or degree of tobacco consumption was available. Results from a hospital population of AD patients cannot be generalized to the general population. Conclusions Our results suggest a susceptibility of autoimmune diseases in adult patients with AD, especially in smokers. While we cannot conclude on causality based on these data, an increased awareness of autoimmune comorbidities in patients with AD may be warranted.
PDF
