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Trace Elements Homeostatic Imbalance in Psoriasis: a Meta-Analysis.
Chen, W, Zhou, X, Zhu, W
Biological trace element research. 2019;(2):313-322
Abstract
Studies point out that trace elements take vital roles in immunological and inflammatory reactions, such as psoriasis, while the conclusions are controversial. The purpose of this study was to analyze the existing literatures and explore the relationship between the risk of psoriasis and four trace elements zinc (Zn), copper (Cu), iron (Fe), and selenium (Se). We identified 42 studies through the databases PubMed, Embase, Cochrane Library, Google Scholar, and Web of knowledge. After the meta-analysis, the serum zinc, iron, and selenium levels showed no remarkable difference between psoriasis and controls. The people with psoriasis showed a higher level of zinc in lesion tissue (standard mean difference (SMD) = 14.43; 95% confidence interval (CI), 7.89-20.97; P < 0.0001), and a higher level of serum copper than controls (SMD = 18.23; 95% CI, 5.06-31.40; P = 0.007). Our findings indicated that the trace element of copper and zinc levels are in a homeostatic imbalance in psoriasis patients when compared with controls, which raise the question whether this imbalance can be taken as the therapy target for psoriasis.
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Fumaric acid ester-induced T-cell lymphopenia in the real-life treatment of psoriasis.
Dickel, H, Bruckner, T, Höxtermann, S, Dickel, B, Trinder, E, Altmeyer, P
Journal of the European Academy of Dermatology and Venereology : JEADV. 2019;(5):893-905
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Abstract
BACKGROUND Fumaric acid esters (FAEs) are used to treat psoriasis and are known to cause lymphopenia in roughly 60% of the patients. Much remains to be elucidated about the biological effects of FAEs on lymphocytes. OBJECTIVE To evaluate the influence of long-term FAE (Fumaderm® ) treatment on peripheral blood CD4+ and CD8+ T cells, CD19+ B cells and CD56+ natural killer (NK) cells in psoriasis. METHODS In this single-centre retrospective observational subcohort study, we obtained leucocyte and lymphocyte subset counts before initiating FAE therapy in 371 psoriasis patients (mean age, 47.8 years; 63.3% males) and monitored them during treatment (mean treatment duration, 2.9 years). Multiparametric flow cytometry was used for immunophenotyping. RESULTS FAEs significantly reduced the numbers of CD4+ T, CD8+ T, CD19+ B and CD56+ NK cells. Among lymphocyte subsets, the mean percentage reduction from baseline was always highest for CD8+ T cells, with a peak of 55.7% after 2 years of therapy. The risk of T-cell lymphopenia increased significantly with the age of the psoriasis patients at the time that FAE therapy was initiated. It was significantly decreased for the combination therapy with methotrexate and folic acid (vitamin B9) supplementation. Supporting evidence was found suggesting that T-cell lymphopenia enhances the effectiveness of FAE therapy. CONCLUSIONS Monitoring distinct T-cell subsets rather than just absolute lymphocyte counts may provide more meaningful insights into both the FAE treatment safety and efficacy. We therefore suggest optimizing pharmacovigilance by additionally monitoring CD4+ and CD8+ T-cell counts at regular intervals, especially in patients of middle to older age. Thus, further prospective studies are needed to establish evidence-based recommendations to guide dermatologists in the management of psoriasis patients who are taking FAEs and who develop low absolute T-cell counts.
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Discovery of increased epidermal DNAH10 expression after regeneration of dermis in a randomized with-in person trial - reflections on psoriatic inflammation.
Lagus, H, Klaas, M, Juteau, S, Elomaa, O, Kere, J, Vuola, J, Jaks, V, Kankuri, E
Scientific reports. 2019;(1):19136
Abstract
Because molecular memories of past inflammatory events can persist in epidermal cells, we evaluated the long-term epidermal protein expression landscapes after dermal regeneration and in psoriatic inflammation. We first characterized the effects of two dermal regeneration strategies on transplants of indicator split-thickness skin grafts (STSGs) in ten adult patients with deep burns covering more than 20% of their body surface area. After fascial excision, three adjacent areas within the wound were randomized to receive a permanent dermal matrix, a temporary granulation-tissue-inducing dressing or no dermal component as control. Control areas were covered with STSG immediately, and treated areas after two-weeks of dermis formation. Epidermis-dermis-targeted proteomics of one-year-follow-up samples were performed for protein expression profiling. Epidermal expression of axonemal dynein heavy chain 10 (DNAH10) was increased 20-fold in samples having had regenerating dermis vs control. Given the dermal inflammatory component found in our dermal regeneration samples as well as in early psoriatic lesions, we hypothesized that DNAH10 protein expression also would be affected in psoriatic skin samples. We discovered increased DNAH10 expression in inflammatory lesions when compared to unaffected skin. Our results associate DNAH10 expression with cell proliferation and inflammation as well as with the epidermal memory resulting from the previous regenerative signals of dermis. This study (ISRCTN14499986) was funded by the Finnish Ministry of Defense and by government subsidies for medical research.
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Drugs for psoriasis.
The Medical letter on drugs and therapeutics. 2019;(1574):89-96
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Photodynamic Therapy of Psoriasis Using Photosensitizers of Vegetable Origin.
Bruschi, ML, da Silva, JB, Rosseto, HC
Current pharmaceutical design. 2019;(20):2279-2291
Abstract
Psoriasis is an immune-mediated, chronic and recurrent inflammatory skin disease, prevalent worldwide, and represents an important burden in life quality of patients. The most common clinical variant is termed as psoriasis vulgaris or plaque psoriasis, which with an individualized and carefully monitored therapy can decrease the patients' morbidity and improving their life quality. The aim is to achieve disease control, minimize the adverse drug effects, and tailor the treatment to individual patient factors. Photodynamic therapy (PDT) is based on local or systemic administration of a non-toxic photosensitizer followed by irradiation with a particular wavelength to generate reactive oxygen species (ROS), mainly highly cytotoxic singlet oxygen (1O2). The generation of these species results in the attack to substrates involved in biological cycles causing necrosis and apoptosis of affected tissues. Photosensitizers are found in natural products and also obtained by partial syntheses from abundant natural starting compounds. They can be isolated at low cost and in large amounts from plants or algae. Therefore, this manuscript reviews the use of molecules from vegetal sources as photosensitizer agents for the PDT of psoriasis. Psoriasis pathogenesis, management and treatment were reviewed. PDT principles, fundamentals and utilization for the treatment of psoriasis were also discussed. Photosensitizers for PDT of psoriasis are also reviewed focusing on those from vegetal sources. Despite the PDT is utilized for the treatment of psoriasis, very little amount of photosensitizers from plant sources are utilized, such as chlorophyll derivatives and hypericin; however, other natural photosensitizers such as curcumin, could also be investigated. They could constitute a very important, safe and cheap alternative for the successful photodynamic treatment of psoriasis.
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Is probiotic use beneficial for skin lesions in patients with inflammatory bowel disease?
Satta, R, Pes, GM, Rocchi, C, Pes, MC, Dore, MP
The Journal of dermatological treatment. 2019;(6):612-616
Abstract
Background: Inflammatory bowel diseases (IBDs) are associated with extraintestinal manifestations including skin lesions. The intestinal microflora plays a key role in the development and course of IBD. Aim: To examine the efficacy of probiotics and the occurrence of skin lesions in patients with IBD. Methods: The occurrence of cutaneous lesions in IBD patients from Northern Sardinia was analyzed according to demographic, anthropometrics, clinical features, treatments, and probiotic use expressed as the ratio of disease duration under probiotic treatment and the total disease duration. Results: In 170 IBD patients (59.4% women; UC: 61.2%) at least one skin lesion was present (8.2%) at diagnosis and in 30.6% developed during the follow-up. Psoriasis, erythema nodosum, and pyoderma gangrenosum were the most frequent. An inverse trend was observed between probiotics use and skin lesions occurrence after adjusting for confounders, including conventional treatment for IBD. The risk of developing at least one skin lesion was 1.40 for probiotic use between 5-19% of disease duration and 0.3 for probiotic use > 50%. Body mass index, Crohn phenotype, marriage, and potency of IBD-treatment were significant predictors for developing skin lesions. Conclusion: These findings suggest that probiotics may be an additional tool in the treatment of IBD.
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The journey for US psoriasis patients prescribed a topical: a retrospective database evaluation of patient progression to oral and/or biologic treatment.
Wu, JJ, Lu, M, Veverka, KA, Smulders, M, Papademetriou, E, Yu, J, Feldman, SR
The Journal of dermatological treatment. 2019;(5):446-453
Abstract
Background: A specific sequence for psoriasis (PsO) therapy has not been defined. Objectives: This retrospective, observational cohort study characterized pathways of PsO treatment over 3 years for newly diagnosed patients initially treated with a topical medication. Methods: Adult PsO patients from the Explorys database (March 1 2011 to June 30 2015) were grouped according to medication-use patterns: 1) discontinued therapy; 2) topical therapy only; 3) switched/added an oral agent; and 4) switched/added a biologic agent. Results: Of 6875 patients, 907 (13.2%) discontinued treatment; 2544 (37.0%) used topical only, and 3319 (45.7%) and 819 (11.9%) switched/added-on an oral and/or biologic agent, respectively. Patients progressed to biologic treatment faster than to oral agents (median 254 vs. 378 d; p < .0001). Using an oral agent before a biologic significantly delayed biologic initiation compared to progressing to biologic directly from topical (median 456 vs. 90 d; p < .0001). Limitations: Disease severity and the reason for treatment transitions were not assessed. Conclusions: Patients initiating topical PsO treatment progressed to biologics faster than to oral agent using an oral agent prior to a biologic significantly delayed biologic initiation. Maintaining patients on an effective topical treatment may minimize the need for a switch to oral and biologics.
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Pooling analysis regarding the impact of human vitamin D receptor variants on the odds of psoriasis.
Li, J, Sun, L, Sun, J, Yan, M
BMC medical genetics. 2019;(1):161
Abstract
BACKGROUND The study aims at scientifically investigating the genetic effect of four polymorphisms (rs7975232, rs1544410, rs2228570, and rs731236) within the human Vitamin D Receptor (VDR) gene on the odds of psoriasis through an updated meta-analysis. METHODS We searched eight databases and screened the studies for pooling. Finally, a total of eighteen eligible case-control studies were included. BH (Benjamini & Hochberg) adjusted P-values of association (Passociation) and odd ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated under the allele, homozygote, heterozygote, dominant, recessive, and carrier models. RESULTS Compared with the negative controls, no statistically significant difference in the odds of psoriasis was detected for the cases under any genetic models (BH adjusted Passociation > 0.05). We also performed subgroup meta-analyses by the source of controls, ethnicity, country, Hardy-Weinberg equilibrium, and genotyping method. Similar results were observed in most subgroup meta-analyses (BH adjusted Passociation > 0.05). Besides, data of Begg's and Egger's tests excluded the significant publication bias; while the sensitivity analysis data further indicated the statistical reliability of our pooling results. CONCLUSION The currently available data fails to support a robust association between VDR rs7975232, rs1544410, rs2228570 and rs731236 polymorphisms and psoriasis susceptibility, which still required the support of more case-control studies.
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Vasoconstrictor potency of fixed-dose combination calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) cutaneous foam versus other topical corticosteroids used to treat psoriasis vulgaris.
Queille-Roussel, C, Nielsen, J, Lacour, JP
The Journal of dermatological treatment. 2019;(6):529-533
Abstract
Background: It is important to determine the vasoconstrictor potencies of topical corticosteroids used to treat psoriasis to ensure appropriate clinical use. Objective: To compare the vasoconstrictive potencies of fixed-dose combination calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) (Cal/BD) cutaneous foam with other topical corticosteroids. Methods: In this Phase I, single-center, healthy volunteer study, Cal/BD foam, clobetasol propionate 0.05% cream (CP; very potent), BD 0.05% ointment (potent), mometasone furoate 0.1% cream (MF; potent), hydrocortisone-17-butyrate 0.1% ointment (HB; moderately potent), and foam vehicle were applied, then removed after 16 h. Skin blanching was visually assessed 2 h later (scale of 0-4). Results: Thirty-six volunteers were randomized. Skin blanching with Cal/BD foam (median [range], 2.00 [0.75-3.00]) was significantly lower than CP cream (3.00 [1.75-4.00]; p < .001), was not significantly different from BD ointment (1.75 [0.75-3.00]; p = .30) and MF cream (2.00 [1.00-3.75]; p = .22), and was significantly greater than HB ointment (1.25 [0.50-3.00]; p < .001) and vehicle (0 [0-0.50]; p < .001). There were no local tolerability reactions or adverse events. Conclusions: The corticosteroid potency of Cal/BD foam was not significantly different from BD ointment and MF cream, significantly stronger than HB ointment, but weaker than CP cream in healthy volunteers.
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Long-term safety results from a phase 3 open-label study of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis.
Lebwohl, MG, Sugarman, JL, Gold, LS, Pariser, DM, Lin, T, Pillai, R, Martin, G, Harris, S, Israel, R
Journal of the American Academy of Dermatology. 2019;(1):282-285