Severity Of Psoriatic Disease Research Articles

Effects of the early period of the COVID-19 pandemic on psoriatic disease severity and treatment

Effects of the early period of the COVID-19 pandemic on psoriatic disease severity and treatment

IL17A Blockade with Ixekizumab Suppresses MuvB Signaling in Clinical Psoriasis

Unbiased informatics approaches have the potential to generate insights into uncharacterized signaling pathways in human disease. In this study, we generated longitudinal transcriptomic profiles of plaque psoriasis lesions from patients enrolled in a clinical trial of the anti-IL17A antibody ixekizumab (IXE). This dataset was then computed against a curated matrix of over 700 million data points derived from published psoriasis and signaling node perturbation transcriptomic and chromatin immunoprecipitation-sequencing datasets. We observed substantive enrichment within both psoriasis-induced and IXE-repressed gene sets of transcriptional targets of members of the MuvB complex, a master regulator of the mitotic cell cycle. These gene sets were similarly enriched for pathways involved in the regulation of the G2/M transition of the cell cycle. Moreover, transcriptional targets for MuvB nodes were strongly enriched within IXE-repressed genes whose expression levels correlated strongly with the extent and severity of the psoriatic disease. In models of human keratinocyte proliferation, genes encoding MuvB nodes were transcriptionally repressed by IXE, and depletion of MuvB nodes reduced cell proliferation. Finally, we made the expression and regulatory networks that supported this study available as a freely accessible, cloud-based hypothesis generation platform. Our study positions inhibition of MuvB signaling as an important determinant of the therapeutic impact of IXE in psoriasis.

Promoting Diversity, Equity, and Inclusion for Psoriatic Diseases.

There is increasing evidence of racial and ethnic disparities in the evaluation and treatment of people with psoriasis (PsO) and psoriatic arthritis, and inadequate racial/ethnic diversity in psoriatic disease (PsD) research. At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2021 annual meeting, a program focusing on diversity, equity, and inclusion (DEI) was presented to highlight known health and healthcare disparities in PsD. There is limited understanding of the prevalence and severity of PsD and how it affects quality of life among racial/ethnic minorities with PsD. Educational gaps and lack of diversity in our dermatology workforce may be contributing to challenges in appropriately diagnosing and treating PsO in darker skin types. Racial/ethnic minorities are also inadequately represented in clinical research, including trial recruitment and participation, for PsD. A panel of patient research partners, researchers, and clinicians ended the session with a broad discussion on how GRAPPA can better ensure racial/ethnic DEI in their educational, research, and clinical missions.

Exploring cannabis use and perspectives among psoriatic disease patients

To assess the correlation between cannabis use and psoriatic disease severity, health-related quality of life, pain, psychosocial outcomes, and cytokine levels in psoriasis (PsC) and psoriatic arthritis (PsA) patients. PsC and PsA patients enrolled in the International Psoriasis and Arthritis Research Team (IPART) program were surveyed on cannabis use and were asked to provide a serum and urine sample. Demographic and clinical variables were compared between users and non-users using Student's t-test or Mann-Whitney U test for continuous variables, and chi-square or Fisher's exact test for categorical variables. Of 151 respondents, 30% reported current cannabis use within the last year. Compared to non-users, cannabis users were younger and had a shorter PsA duration and poorer mental health as measured by the SF-36. Other measures of health-related quality of life and pain were comparable between the groups. Respondents' primary perceived benefits of cannabis use were aid in sleep and arthritis pain relief, but there was no difference in pain between users and non-users. No THC was detected in the urine of non-users while users had a mean level of 19.6ng/ml. Serum IL-23 levels were statistically significantly higher in non-users than in users. A third of the patients used cannabis within the past year, and 54.3% of users reported the use of cannabis for arthritis pain relief. However, there was no difference in pain scores. Comprehensive education for providers on the current body of evidence and further studies on cannabis use and outcomes in psoriatic disease are needed. Key Points • A third of patients with psoriatic arthritis have used cannabis in the past year. • Most used it for better sleep and control of pain. • There was no difference in pain scores between users and non-users. • IL-23 levels were significantly higher in non-users.

Endothelial glycocalyx and microvascular perfusion are associated with carotid intima-media thickness and impaired myocardial deformation in psoriatic disease.

Psoriatic disease is associated with vascular and myocardial dysfunction. We aimed to evaluate endothelial glycocalyx barrier properties and microvascular perfusion in psoriatic patients, as well as their correlation with carotid intima-media thickness (cIMT) and markers of left ventricular (LV) myocardial deformation. We examined 297 psoriatic patients and 150 controls, adjusted for age, sex, and atherosclerotic risk factors. The severity of psoriatic disease was estimated using the psoriasis area and severity index (PASI). Perfused boundary region (PBR), a marker of glycocalyx barrier function, was measured non-invasively in sublingual microvessels with a diameter 5-25 μm using Sidestream Dark Field camera (Microscan, GlycoCheck). Increased PBR indicates reduced glycocalyx thickness. Indexes of microvascular perfusion, including red blood cells filling (RBCF) and functional microvascular density, were also calculated. We measured cIMT, coronary flow reserve (CFR) and markers of myocardial deformation by speckle-tracking imaging, namely global longitudinal strain (GLS) and percentage changes between peak twisting and untwisting at mitral valve opening (%dpTw-UtwMVO). Compared to controls, psoriatic patients had higher PBR5-25μm (2.13 ± 0.29μm versus 1.78 ± 0.25μm, p < 0.001) and lower RBCF and functional microvascular density (p < 0.001). Increased PASI was associated with elevated PBR and more impaired cIMT and GLS (p < 0.05). There was an inverse association of PBR with RBCF and functional microvascular density (p < 0.001). In psoriatic population, increased PBR was related to increased cIMT, reduced CFR, impaired GLS and decreased %dpTw-UtwMVO (p < 0.001). Glycocalyx thickness is reduced in psoriatic patients, which in turn impairs microvascular perfusion, and is associated with carotid IMT and impaired coronary and myocardial function.Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT02144857.

Deletion of S100a8 and S100a9 Enhances Skin Hyperplasia and Promotes the Th17 Response in Imiquimod-Induced Psoriasis.

High concentrations of the damage-associated molecular patterns S100A8 and S100A9 are found in skin and serum from patients suffering from psoriasis, an IL-17-related disease. Notably, although the expression of these proteins correlates with psoriatic disease severity, the exact function of S100A8 and S100A9 in psoriasis pathogenesis remains unclear. In this study, we investigated the role of S100A8 and S100A9 in psoriasis-associated skin hyperplasia and immune responses using S100a8-/- and S100a9-/- mice in an imiquimod-induced model of psoriasis. We found that S100a8-/- and S100a9-/- psoriatic mice exhibit worsened clinical symptoms relative to wild-type mice and increased expression of S100A9 and S100A8 proteins in keratinocytes, respectively. In addition, the loss of S100A8 enhances proliferation of keratinocytes and disrupts keratinocyte differentiation. We further detected elevated production of IL-17A and -F from CD4+ T cells in the absence of S100A8 and S100A9, as well as increased infiltration of neutrophils in the skin. In addition, treatment with anti-IL-17A and -F was found to reduce psoriasis symptoms and skin hyperplasia in S100a8-/- and S100a9-/- mice. These data suggest that S100A8 and S100A9 regulate psoriasis by inhibiting production of IL-17A and -F, thereby, to our knowledge, providing new insights into their biological functions.

Coprevalence of Hidradenitis Suppurativa and Psoriasis: Detailed Demographic, Disease Severity and Comorbidity Pattern

Background and Objectives: Hidradenitis suppurativa (HS) and plaque psoriasis (Pso) are supposed to have a coprevalence. However, data showing a more detailed description of patients with both diseases are rare. In this study, we characterized patients with both skin diseases in terms of onset, disease course, severity, concomitant diseases and therapeutical management. Patients and Methods: Data from 28 patients with a confirmed codiagnosis of HS and Pso from 2 university hospitals presented between 2015 and 2019 were evaluated retrospectively. For further characterization, patients were divided into different cohorts depending on whether HS or Pso was diagnosed as the first disease. Results: The average age of patients with a coprevalence of both diseases was 44.4 years with a female/male ratio of 1:1.15. Fifteen patients were diagnosed first with HS at an average age of 22.8 years, 13 patients first showed symptoms of Pso at a mean age of 21.7 years. The average time to the onset of the corresponding second disease was 14.3 years. Patients with HS as first disease showed a significantly severer form of HS compared to patients with a first diagnosis of Pso (mean highest International Hidradenitis Suppurativa Severity Score System: 23.5 vs. 8.2; p = 0.02). Severity of psoriatic disease in patients with HS at first diagnosis was numerically lower but not significant compared to the cohort with Pso at first diagnosis (mean highest Psoriasis Area and Severity Index: 7.8 vs. 13.2; p = 0.299). The most frequent comorbidity in all patients was obesity (64.3%; mean body mass index: 32.2) followed by psychiatric complaints (25%) and psoriatic arthritis (21.4%). Adalimumab was the most commonly used drug that had a positive effect on both diseases, HS and Pso. Conclusions: In patients with a coprevalence of HS and Pso, the disease which occurs first appears to take a severer course, with an increased risk of development of obesity and psychiatric comorbidity in both cohorts.

Adherence to the Mediterranean diet model and psoriatic disease (skin, joint and metabolic expression of psoriasis)

Psoriasis is a chronic disease, characterized by systemic inflammation with skin, joint and metabolic involvement. The most common tools to evaluate the severity of each disease is respectively the Psoriasis Area Severity Index (PASI) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). The association between psoriasis and obesity and the role of visceral fat in producing an inflammatory state have been demonstrated. The Mediterranean Diet (MD) has been recommended as a model of healthy diet on the basis of scientific evidence and considered as an adjuvant therapy for all patients affected by chronic inflammatory diseases. Our study evaluated the association between adherence to MD (assessed with the Predimed questionnaire) and psoriatic disease severity. 80 patients (40 with psoriasis and 40 with psoriatic arthritis) were evaluated for disease severity (PASI, DAPSA) and were assessed for Metabolic Syndrome according to the International Diabetes Federation (IDF) definition. To evaluate adherence to the MD, each patient was administered the Predimed questionnaire which includes 14 questions. Our study shows a correlation between low adherence to MD and a high expression of psoriasis, considering cutaneous, joint symptoms and the metabolic profile.

Left Atrial Mechanical Functions, Atrial Electromechanical Delay and P Wave Dispersion in Patients with Mild to Moderate Psoriasis

bACkgrOunD: Many systemic diseases, including cardiovascular disturbances, have been described in patients with psoriasis. In previous studies, left ventricular (LV) subclinical myocardial dysfunction has been reported in psoriatic patients. ObjECTivE: To evaluate the effect of psoriasis on left atrial (LA) functions, which is an important determinant in left ventricular filling, atrial electromechanical coupling and P wave dispersion, in patients with mild to moderate psoriasis. METHODS: Thirty patients with psoriasis (mean [± SD] age 39±13 years) and 30 controls (mean age 34±8 years) were enrolled. Psoriatic disease severity was evaluated by the Psoriasis Area and Severity Index. LA volumes were measured using the biplane area-length method, and LA mechanical function parameters were calculated using echocardiography. Atrial electromechanical delays were measured by tissue Doppler imaging. P wave dispersion was calculated using 12-lead electrocardiograms. rESuLTS: There were no significant differences between the groups for LA mechanical function indices. No difference was detected between the groups with regard to interatrial electromechanical delay (PA lat –PA tricus ) and intra-atrial electromechanical delay (PA sep –PA tricus ) (14.4±5.7 ms versus 12.5±4.2 ms; P>0.05 and 6.3±3.5 ms versus 5.1±3.4 ms; P>0.05, respectively). There were no differences between groups with regard to P wave dispersion. COnCLuSiOnS: The present study showed that LA mechanical functions were not impaired in patients with mild to moderate psoriasis. Interatrial electromechanical delays were not changed in the psoriasis group. In addition to this, P wave dispersion was not different between two groups.

SAT0293 High Prevalence of Metabolic Syndrome in Psoriatic Arthritis Patients is Associated With Severity of Underlying Psoriatic Disease

BackgroundWhile Psoriatic Arthritis (PsA) is characterized by inflammation of both skin and joints there has been an increased recognition that PsA is associated with modest increase in the risk of...