Sex and Age Influence the Associated Risk of Depression in Patients with Psoriasis: A Retrospective Population Study Based on Diagnosis and Drug-Use.

BACKGROUND: The reported prevalence of depression among individuals with psoriasis varies substantially, and the effect of gender on depression distribution has revealed conflicting results. In addition, using medication to identify cases is uncommon. OBJECTIVE: To study the prevalence of pharmacologically treated depression among individuals with and without psoriasis in a Swedish population using ICD-10 codes and data from the Swedish Prescribed Drug Register. METHODS: A retrospective case-control population-based study was performed including all living individuals (age ≥18 years) in Region Jönköping, southern Sweden (n = 273,536). ICD-10 codes for the diagnosis of psoriasis (L40.*) and depression (F32.* and F33.*), and data on pharmacological treatment from the Swedish Prescribed Drug Register, were extracted from electronic medical records between April 9, 2008 and January 1, 2016. The extraction date was January 1, 2016. RESULTS: The risk of pharmacologically treated depression was increased in individuals with psoriasis (age- and sex-adjusted OR 1.55; CI 1.43-1.68); 21.1% of women with psoriasis received pharmacological treatment for depression during the study period compared to 14.2% in the control population. Prevalence figures for depression were significantly higher in women with psoriasis compared to men. The risk of suffering from depression was highest among male and female patients with psoriasis under the age of 31 years. CONCLUSIONS: Depression is common among patients with psoriasis. The results of the current study underline the need for dermatologists to adopt a holistic approach, looking beyond the skin, when handling patients with psoriasis in every-day clinical practice.

A Cost-utility Analysis of Calcipotriol/Betamethasone Dipropionate Aerosol Foam versus Ointment for the Topical Treatment of Psoriasis Vulgaris in Sweden.

Psoriasis is a chronic inflammatory disorder that imposes a substantial economic burden. We conducted a cost-utility analysis from a Swedish healthcare payers perspective using a decision-tree model with a 12-week time horizon. Patients with psoriasis vulgaris could have two 4-week cycles of topical treatment with calcipotriol 50 µg/g and betamethasone 0.5 mg/g as dipropionate (Cal/BD) foam or Cal/BD ointment before progressing to phototherapy/methotrexate. In the base-case analysis, Cal/BD foam dominated over Cal/BD ointment. The increased efficacy of Cal/BD foam resulted in fewer consultations and a decreased risk of progressing to phototherapy/methotrexate. Although Cal/BD foam costs more than Cal/BD ointment, this was offset by lower costs for phototherapy/methotrexate or consultation visits. Sensitivity analyses revealed that the base-case net monetary benefit was robust to plausible variations in key parameters. In conclusion, Cal/BD foam was predicted to be more cost-effective than Cal/BD ointment in the treatment of psoriasis vulgaris.

Prevalence of Psoriasis and Psoriatic Arthritis and Patient Perceptions of Severity in Sweden, Norway and Denmark: Results from the Nordic Patient Survey of Psoriasis and Psoriatic Arthritis.

Optimal clinical management of psoriasis and psoriatic arthritis (PsA) Optimal clinical management of psoriasis and psoriatic arthritis (PsA) requires understanding of the impact on patients. The NORdic PAtient survey of Psoriasis and PsA (NORPAPP) aimed to obtain current data on disease prevalence and patient perceptions in Sweden, Denmark and Norway. Among 22,050 individuals questioned, the reported prevalence of psoriasis and/or PsA was 9.7% (5.7% physician-diagnosed plus 4.0% self-diagnosed only); prevalence was similar in Sweden (9.4%) and Denmark (9.2%) but significantly higher in Norway (11.9%). Of those reporting a physician's diagnosis, 74.6% reported psoriasis alone, 10.3% PsA alone and 15.1% both. Patients with PsA perceived their disease to be more severe than those with psoriasis; patients with PsA and psoriasis reported greater disease severity than those with each condition alone. Patient's perceptions of psoriasis severity correlated weakly (Spearman's rho 0.42) with clinical severity; both patient perceptions and clinical measures are important in the assessment and management of psoriasis.

Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B.

Changes in the skin microbiome have been shown to promote cutaneous inflammation. The skin microbiome of patients with chronic plaque type psoriasis was analysed before and after treatment with narrowband ultraviolet B (UVB). Swab samples of the microbiome were taken from lesional and non-lesional skin of 26 patients. Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the Illumina MiSeq platform. Lesional skin microbiome diversity correlated with psoriasis severity (measured with the Psoriasis Area and Severity Index; PASI). There was a significantly lower abundance of the phylum Firmicutes and the genus Staphylococcus in lesional skin compared with non-lesional skin before UVB treatment. Responders (> 75% target Psoriasis Severity Index (PSI) improvement) had significantly lower abundance of the phyla Firmicutes in lesional and non-lesional skin and lower abundance of the genera Staphylococcus, Finegoldia, Anaerococcus, Peptoniphilus, Gardnerella, Prevotella and Clostridium in lesional skin after UVB treatment. Pseudomonas significantly decreased in lesional and non-lesional skin of treatment responders. These results suggest that skin microbiome alterations after UVB treatment could be related to treatment and treatment response.

Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in psoriasis skin.

Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV-B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.

Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis.

CD93 is involved in angiogenesis and inflammation, both of which are key processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral blood mononuclear cells and skin of patients with psoriasis and controls. Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms rs2749812 and rs2749817 were assessed in patients with psoriasis compared with controls and the effect of narrowband ultraviolet B (NB-UVB) treatment on CD93 gene expression was evaluated in the skin of patients with psoriasis. CD93 gene expression was significantly increased in lesional and non-lesional skin from patients with psoriasis compared with controls. Immunohistochemistry revealed CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment of patients with psoriasis did not alter skin CD93 gene expression. Increased protein expression of CD93 psoriatic skin and association with the rs2749817 polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.

Exploring comorbidity and pharmacological treatment patterns in psoriasis - a retrospective population-based cross-sectional study.

Background: Individuals with psoriasis face an increased risk of suffering from various comorbid conditions. However, there haven´t been any studies conducted in Sweden to examine the frequency of comorbidities and the corresponding treatment for these conditions among psoriasis patients. Methods: The Cosmic electronic medical record represents a comprehensive repository of medical information including all residents of Region Jönköping. To conduct a population-based retrospective cross-sectional study, all individuals diagnosed with psoriasis between April 9, 2008 and July 1, 2016, were identified via the electronic medical records using ICD-10 codes. Data on comorbidity and dispensation of prescribed drugs against these comorbid conditions were analyzed. Results: During the study period, 1.7% of the population (4,587 individuals) were diagnosed with psoriasis, with 74.3% of cases classified as mild to moderate psoriasis and 25.7% as severe. The remaining 268,949 individuals did not receive a psoriasis diagnosis. The study showed that psoriasis patients had higher odds of experiencing the majority of the comorbid conditions examined. Arthritis other than psoriasis arthritis was found to be the most prevalent comorbid diagnosis among psoriasis patients (adjusted OR 7.2, CI 95% 6.4-8.2, p < 0.001), followed by obesity (OR 2.4, CI 95% 1.9-3.1, p < 0,001). There was no significant difference in drug prescription for comorbid diseases between patients with psoriasis and patients without psoriasis except for arthritis and smoking cessation treatment. Conclusions: Individuals with psoriasis are more susceptible to experiencing multiple comorbid conditions compared to the general population, particularly those with severe psoriasis. There is no evidence of undertreatment of comorbidity except for arthritis among psoriasis patients.

Narrowband-UVB treatment reduces levels of mediators of the Th17 pathway and chemotaxis in psoriatic skin without any concurring effect on mediator levels in serum

Background: Narrowband-UVB (NB-UVB) is a common and effective psoriasis treatment. It exerts its effect locally and is therefore a better model for exploring dynamics of serum biomarkers reflecting psoriasis skin disease activity compared to other treatments with systemic uptake. Objectives: To perform an exploratory study to assess potential roles of multiple disease mediators as biomarkers for psoriasis disease activity, and increase understanding of NB-UVB treatment effects in psoriatic skin. Materials & Methods: Patients with plaque psoriasis were sampled (lesional, non-lesional skin, serum) before and after full NB-UVB treatment. Samples were assessed for 78 different mediators using Luminex assays. Correlation networks were analysed to explore interactions between lesional skin mediators before and after NB-UVB treatment. Results: None of the studied serum mediators were significantly affected by NB-UVB treatment after correction for multiple testing. Thirty mediators revealed a significant difference in lesional skin compared to non-lesional skin before treatment including interleukin 23 (IL-23) and C-C motif chemokine ligand 20 (CCL20), but also novel mediators such as angiopoietin-like 4 (ANGPTL4) and pentraxin 3 (PTX3). The levels of 25 mediators in skin decreased significantly, and network analysis revealed markedly reduced cluster formations and correlations after NB-UVB. Conclusion: NB-UVB treatment reduced the concentration of mediators of the Th17 inflammatory pathway and chemotaxis in psoriatic lesional skin, but also affected less studied and novel mediators. Although the treatment affected the levels of a majority of mediators in skin, no corresponding effect was observed in serum, thus challenging the possibility of a serum biomarker reflecting skin disease activity.

Psoriasis is Associated with a High Comedication Burden: A Population Based Register Study.

INTRODUCTION: A large body of evidence supports the association between psoriasis and concomitant diseases. However, the study of comedication for these diseases in patients with psoriasis is limited. The current study aimed to investigate the prescription and drug dispensation for comorbidity associated with psoriasis. METHODS: We conducted a retrospective case-control study from 9 April 2008 until 1 January 2016 using an electronic medical records database covering the entire population of the County of Jönköping and the Swedish Prescribed Drug Register. ICD-10 and Anatomical Therapeutic Chemical codes were used to identify patients with psoriasis and dispensed pharmaceutical prescriptions. Individuals without psoriasis were selected as controls. Patients receiving systemic treatment for psoriasis were considered as having moderate-severe psoriasis. Odds ratios for being dispensed pharmaceutical prescriptions and differences in mean number of dispensed prescriptions were explored. RESULTS: A total of 4587 patients with psoriasis were identified in the medical records, and 268,949 individuals served as controls. Patients with psoriasis had a significantly higher number of different drug dispensations compared to controls. Only 1.3% of all patients with psoriasis were without any prescription (excluding medication for psoriasis) during the study period while the number in the general population was 9.3%. Sex- and age-adjusted odds ratios for dispensation of drug groups related to comorbid disease were significantly higher among patients with psoriasis including drug groups such as anxiolytics and sedatives as well as drugs targeting COPD, migraine and erectile dysfunction. The most frequently dispensed comedications were oral antibiotics and analgesics including an increased risk for dispensation of opioids. Sex predisposed dispensation frequency for a variety of drug groups. Drugs targeting obesity, osteoporosis, psychiatric disease and anti-mycotics/-fungals were more frequent among women. CONCLUSION: Patients with psoriasis have significantly increased numbers of different dispensed prescriptions than those without psoriasis. This underlines previous findings on increased comorbidity and health care costs for patients with psoriasis.

Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin.

WNT/ß-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohn's disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.

Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum.

S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity. Trial Registration: DRKS 00014817.