A crossroads between dietary habits, alcohol consumption, and smoking in the clinical course of psoriasis: a narrative review.

Psoriasis is a chronic autoimmune disease that affects 1-3% of the population. The pathomechanism of psoriasis development is complex, but genetic (non-modifiable) factors play a key role. However, the importance of environmental factors and lifestyle choices, such as the diet, alcohol consumption, and smoking, is increasing. The objective of this review was to analyse the influence of dietary habits, alcohol consumption, and smoking on the clinical course of psoriasis. Stress, a poor diet, alcohol abuse, and smoking can trigger psoriasis or cause its exacerbation. Therefore, in addition to the correct selection of therapy, it is extremely important to educate patients about the impact of these factors on the onset and progression of psoriasis. This literature review confirms that a holistic and multidisciplinary approach is required for patients with psoriasis, further emphasizing Hippocrates' thesis, "Let food be thy medicine, and medicine be thy food".

Influence of adalimumab on interleukin 12/23 signalling pathways in human keratinocytes treated with lipopolysaccharide A.

Introduction: The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment. Aim: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells. Material and methods: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 µg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 µg/ml and incubated for 2, 8, and 24 h. We used mRNA and miRNA microarray, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay techniques. Results: STAT1, STAT3, STAT5, IL-6, IL-6R, SOCS3, and JAK3 genes differentiated HaCaT cultures with the drug from controls regardless of the time the cells were exposed to the drug. The addition of adalimumab to a culture previously exposed to LPS resulted in silencing of SOCS3 and IL-6 expression compared to the control, while for the other transcripts they were found to be overexpressed compared to the control culture. The assessment indicated the strongest connections between JAK3 and hsa-miR-373-5p (target score 96); SOCS3, STAT5, and hsa-miR-1827 (target score 96). Conclusions: Our study indicates that adalimumab has the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways.

Impact of Alcohol Consumption, Smoking, and Diet on the Severity of Plaque Psoriasis: A Comprehensive Assessment using Clinical Scales and Quality of Life Measures.

BACKGROUND This study aimed to evaluate the effects of alcohol intake, assessed using the Alcohol Use Disorder Identification Test (AUDIT) questionnaire, on the severity of plaque psoriasis using the Body Surface Area (BSA) and Psoriasis Area and Severity Index (PASI) scales, and quality of life using the Dermatology Life Quality Index (DLQI) questionnaire. MATERIAL AND METHODS The diagnosis of psoriasis was made based on the clinical picture. We enrolled 24 patients with psoriasis vulgaris, and the AUDIT test conducted at the time of follow-up indicated a possible risky/harmful pattern of alcohol consumption or alcohol dependence syndrome among the patients (>8 points). The comparison group consisted of 20 psoriatic patients and AUDIT <8 points. The BSA and PASI scales were used to determine the severity of psoriasis, and the DLQI questionnaire assessed patients' quality of life and how they felt during the week preceding the survey. RESULTS As the amount and frequency of alcohol consumed increased, the exacerbation of lesions measured according to the PASI and BSA scales was significantly higher (P<0.05), and the quality of life decreased (P<0.05). We noted that inadequate and excessive dietary intake of total protein, total fat, and assimilable carbohydrates were associated with statistically significantly higher values of BSA and PASI scores and, thus, more severe psoriatic lesions (P<0.05). CONCLUSIONS An unbalanced diet, alcohol abuse, and smoking negatively affect the course of psoriasis vulgaris, hence the importance of patient education.

Evaluation of expression pattern of selected genes associated with IL12/23 signaling paths in psoriatic patients during cyclosporine A therapy.

Molecular analysis is key to a better understanding of drug resistance during therapy. The aim of this study was to evaluate changes in the expression of tumor necrosis factor α (TNF-α), interleukin (IL)-IL12A, IL12B, IL23A, interferon gamma (IFN-γ) in psoriatic patients during 84 days of treatment and TNF-α on the protein level. The study group consisted of 32 psoriatic patients during cyclosporine A therapy. The molecular analysis was made by using real-time reverse transcription polymerase chain assay (RTqPCR) and MALDI ToF mass spectroscopy three times: after 0, 42, 84 days of treatment. Statistically significant differences (p < .05) in transcriptional activity were observed for genes: TNF-α (0 vs. 42nd days p = .006; 0 vs. 84th days p = .005), IL23A (0 vs. 42nd days p = .041), IFN-γ (0 vs. 42th days p = .040; 0 vs. 84th days p = .041), IL17 (0 vs. 42nd p = .000003 0 vs. 84th p = .001650), IL12A (0 vs. 42nd p = .0047 vs. 84th p = .0063). The expression of TNF-α was downregulated during therapy, IL23A was upregulated during CsA treatment, while the expression of IFN-γ and IL17 were higher after 42 days and lower after 84 days compared to 0 days of CsA treatment. It seems that TNF-α, IL12A, IL23A, IFN-γ, and IL17 can be useful complementary molecular markers to assess the efficacy of psoriasis treatment.

The impact of diabetes and metabolic syndromes to the effectiveness of cyclosporine a pharmacotherapy in psoriatic patients.

Metabolic diseases concurrent with psoriasis may considerably affect the intensity of its symptoms and therapy efficacy. Cyclosporine A (CsA) is one of the medicines used in conventional therapy of psoriasis. The aim of the study was to determine whether Diabetes 2 and metabolic syndromes influence the efficacy of the CsA therapy in psoriatic patients. The sample group was composed of 32 patients with diagnosed moderate to severe forms of psoriasis vulgaris. The group was divided into subgroups, with regard to concurrently occurring Diabetes 2 and metabolic syndromes. The subgroups were composed of as follows: with diabetes-7 patients, without diabetes-25, with metabolic syndrome-15, without concurrent metabolic syndrome-17, with a metabolic syndrome without diabetes-8 and with both a metabolic syndrome and diabetes-7 patients. The efficacy of therapy was evaluated in each subgroup on the basis of the following scales: PASI, BSA, DLQI on the day of therapy commencing, after 42 and 84 days of the CsA therapy. The statistical analysis was performed with the use of STATISICA 12 (Cracow, Poland; p < .05). The following tests were used: The ANOVA Friedeman test, the posthoc test for ANOVA Friedeman test, the Mann-Whitney U test. We observed clinical improvement measured with PASI BSA scales in each subgroup. The patients themselves also reported improved comfort in their lives, which is confirmed by the lower score in the DLQI scale after 42 and 84 days of the pharmacotherapy. Differences in the values of each scale in a given subgroup turned to be statistically significant. The biggest differences occur after the first 42 days of therapy and they last in the later period of observations. We did not determine any statistically significant differences as a response to treatment in the subgroups subject to comparison. Diabetes and a metabolic syndrome concurrent with psoriasis vulgaris do not affect the efficacy of CsA therapy, which indicates no necessity to modify the standard dosage of the medicine and therapy regime.

Clinical and molecular evaluation of therapy with the use of cyclosporine A in patients with psoriasis vulgaris.

BACKGROUND: Psoriasis course involves increased secretion of pro-inflammatory cytokines, among others, a beta transforming growth factor (TGFßs) and its receptors. Cyclosporine A (CsA), an immunosuppressive medicine with the molecular mechanism of operation connected with the properties of cell cycle suppression, is often used in the treatment of severe forms of psoriasis. The efficacy of therapy is assessed based on the disease clinical progression indexes - Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Dermatology Life Quality Index (DLQI). The aim of the study was the evaluation of the efficacy of the CsA treatment of patients with psoriasis vulgaris, based on the clinical parameters and an assessment of the expression profiles of TGFßs and TGFßRs, depending on the concurrent diabetes and metabolic syndrome. METHODS: The group under study composed of 32 patients (15 with the metabolic syndrome, seven with diabetes) treated with CsA for 84 days. The molecular analysis included extraction of RNA, assessment of TGßF1-3, TGFßRI-III gene expression with the use of the RTqPCR method. The clinical assessment of the effects of this pharmacotherapy involved evaluation of the parameters: PASI, BSA, DLQI before therapy commencement, on the 42nd and 84th days of therapy. RESULTS: A statistically significant change in the transcription activity of TGFß1 in patients with and without diabetes (P = 0.018) and patients with and without metabolic syndrome (P = 0.023) was shown that on the 84th day of therapy. CONCLUSIONS: TGFb1 may be claimed as the supplementary molecular marker to evaluate the efficacy of CsA therapy. It seems that systemic diseases have an effect on the efficacy of the applied pharmacotherapy and the course of psoriasis.

Variances in the mRNA expression profile of TGF-ß1-3 isoforms and its TGF-ßRI-III receptors during cyclosporin a treatment of psoriatic patients.

INTRODUCTION: Psoriasis is a chronic, immunologic, multi-factor inflammatory skin disease, strongly associated with a higher level of a number of cytokines, such as isoforms of transforming growth factor ß (TGF-ß1-3) and its receptors (TGF-ßRI-III). One of the most popular and important drugs used to treat this disease is cyclosporin A (CsA). AIM: The aim of this study was to investigate the expression of genes encoding the transforming growth factor (TGF)-ß isoforms and receptors of the cytokine TGF-ßRs in psoriatic patients during an 84-day long observation of the effects of cyclosporin A therapy. It made an attempt to determine the usefulness of testing mRNA expression of TGF-ß1-3 and its receptors TGF-ßRI-III as the supplementary molecular markers of lost sensitivity to the medicine. MATERIAL AND METHODS: The study group consisted of 32 patients with psoriasis (20 men and 12 women) treated with cyclosporin A. The changes in expression patterns of TGF-ß1-3 and TGF-ßRI-III were performed by real-time quantitative reverse transcription PCR (RTqPCR). RESULTS: The expression of TGF-ß1-3 and TGF-ßRI-III were detected in the whole period of therapy with CsA. Changes in transcriptional activities of TGF-ß1-3 and TGF-ßRI-III during pharmacotherapy were observed. Differences in the expression of these genes were found before and after 42 and 84 days of using CsA. CONCLUSIONS: The changes in expression profiles of TGF-ß1-3 and TGF-ßRI-III during CsA therapy can be a useful molecular marker of lost sensitivity to the medicine.

Successful therapy of cyclosporin A in pityriasis lichenoides et varioliformis acuta preceded by hand, foot and mouth disease.

To our knowledge, there are no previously published cases of enteroviral infection complicated by pityriasis lichenoides et varioliformis acuta (PLEVA). A 30-year-old woman is reported with a severe form of PLEVA, preceded by hand, foot and mouth disease. Immunosuppressive treatment with cyclosporin A resulted in rapid clinical improvement.