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1.
J Vis Exp ; (205)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38497631

ABSTRACT

Psoriasis plaque severity metrics, such as induration (thickness), erythema (redness), and desquamation (scaliness), are associated with the subsequent development of psoriatic arthritis (PsA) among cutaneous-only psoriasis patients (patients with skin or nail psoriasis but no psoriatic arthritis). These metrics can be used for PsA screening. However, a key challenge in PsA screening is to optimize accessibility and minimize costs for patients, while also reducing the burden on healthcare systems. Therefore, an ideal screening tool consists of questions that patients can answer without a physician's assistance. Although reference images can be used to help a patient self-assess erythema and desquamation severity, a patient would need a tactile induration reference card to self-assess induration severity. This protocol describes how to create an induration reference card, the Psoriasis Thickness Reference Card, as well as how to use it to assess lesion induration severity. Administration of reference images for erythema and desquamation and a Psoriasis Thickness Reference Card for induration to 27 psoriasis patients showed that patients were moderately successful at self-assessing the severity of these three metrics. These findings support the feasibility of a future PsA screening test that patients can complete without the need for physician assistance.


Subject(s)
Arthritis, Psoriatic , Nail Diseases , Psoriasis , Humans , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/pathology , Psoriasis/diagnosis , Skin/pathology , Nail Diseases/pathology , Erythema
2.
Arthritis Care Res (Hoboken) ; 76(3): 421-425, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37691268

ABSTRACT

OBJECTIVE: We aimed to create a question bank about clinical factors for predicting the diagnoses of psoriatic arthritis in patients with psoriasis of various ancestries and skin tones, which can be completed entirely by patients. METHODS: Utah Psoriasis Initiative participants without a psoriatic arthritis diagnosis at enrollment were observed for diagnosis during the study period. We inferred ancestry from exome sequencing data and performed Cox proportional hazards regression to identify clinical predictors of psoriatic arthritis in different ancestry groups. Based on results and literature review, we developed a question bank for assessing psoriatic arthritis risk among patients with psoriasis in various ancestries. RESULTS: Patient-reported untreated psoriasis induration and history of fingernail psoriasis were associated with psoriatic arthritis in participants of European and non-European ancestry. We developed the Psoriatic Arthritis Prediction and Identification Question Bank for Diverse Ancestries (PAPRIKA) version 1.0, which included questions regarding psoriasis characteristics, arthritis symptoms, comorbidities, family history, and demographics. PAPRIKA is accessible at http://bjfenglab.org/. CONCLUSION: The clinical features (untreated psoriasis induration and history of fingernail psoriasis) that can predict psoriatic arthritis in European individuals also work for non-European individuals. PAPRIKA can be used to gather psoriatic arthritis predictive data from patients with psoriasis without provider assistance and is relevant for patients across ancestries.


Subject(s)
Arthritis, Psoriatic , Capsicum , Psoriasis , Humans , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/epidemiology , Arthritis, Psoriatic/drug therapy , Psoriasis/diagnosis , Psoriasis/epidemiology , Psoriasis/drug therapy , Comorbidity
3.
Am J Ind Med ; 65(11): 857-866, 2022 11.
Article in English | MEDLINE | ID: mdl-35301725

ABSTRACT

BACKGROUND: The transportation and utilities industries include establishments engaged in the movement of passengers and freight, or the provision of public power, water, and other services. Along with the warehousing industry, they make up the US National Occupational Research Agenda's Transportation, Warehousing and Utilities (TWU) industry sector. In 2018 the sector composed 5% of the US workforce, with approximately 8 million workers. TWU workers experienced 19% of all fatalities among U.S. workers in 2018 and 7% of total occupational injuries and illnesses. METHODS: Around-the-clock operations, heavy workloads, long and irregular shifts, complicated schedules, and time pressures characterize work across the US TWU sector. However, there are considerable differences in worker priorities and concerns between TWU industries. Major areas of concern within the sector include disparities in work schedules; required training for employee fatigue awareness and prevention; physical and mental job demands; and safety culture. RESULTS: Strategies for fatigue mitigation are critical to reduce the prevalence of injuries, safety-critical events, and crashes in TWU workers. Further research on the incidence and characterization of fatigue among TWU workers will guide the development of effective mitigation strategies. The influence of work scheduling on missed sleep opportunities and disrupted circadian rhythms should be determined. Evaluation of fatigue mitigation strategies can lead to the adoption of the most effective ones for each TWU industry. CONCLUSION: Implementation of effective strategies is critical for the health, safety, wellbeing, and productivity of workers in the TWU sector.


Subject(s)
Industry , Occupational Injuries , Fatigue/prevention & control , Humans , Occupational Injuries/epidemiology , Occupational Injuries/prevention & control , Organizations , Transportation
4.
JAMA Dermatol ; 157(11): 1306-1315, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34643650

ABSTRACT

IMPORTANCE: Psoriasis relapse may involve compensatory T-cell activation pathways in the presence of CD28-CD80/CD86 blockade with abatacept. OBJECTIVE: To determine whether costimulatory signaling blockade with abatacept prevents psoriasis relapse after ustekinumab withdrawal. DESIGN, SETTING, AND PARTICIPANTS: Psoriasis Treatment with Abatacept and Ustekinumab: a Study of Efficacy (PAUSE), a parallel-design, double-blind, placebo-controlled randomized clinical trial, was conducted at 10 sites in the US and Canada. Participant enrollment opened on March 19, 2014, and concluded on April 11, 2016. Participants were adults with moderate to severe plaque psoriasis and received ustekinumab in a lead-in phase. Those who responded to ustekinumab at week 12 were randomized 1:1 to either the continued with ustekinumab group (ustekinumab group) or the switched to abatacept group (abatacept group). Treatment was discontinued at week 39, and participants were followed up for psoriasis relapse until week 88. Statistical analyses were performed in the intention-to-treat (ITT) and safety samples from May 3, 2018, to July 6, 2021. INTERVENTIONS: Participants received subcutaneous ustekinumab at weeks 0 and 4 (45 mg per dose for those ≤100 kg; 90 mg per dose for those >100 kg). Participants randomized to the abatacept group at week 12 received subcutaneous abatacept, 125 mg weekly, from weeks 12 to 39 and ustekinumab placebo at weeks 16 and 28. Participants randomized to the ustekinumab group received ustekinumab at weeks 16 and 28 and abatacept placebo weekly from weeks 12 to 39. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of participants with psoriasis relapse (loss of ≥50% of the initial Psoriasis Area and Severity Index improvement) between weeks 12 and 88. Secondary end points included time to psoriasis relapse, proportion of participants with psoriasis relapse between weeks 12 and 40, and adverse events. The psoriasis transcriptome and serum cytokines were evaluated. RESULTS: A total of 108 participants (mean [SD] age, 46.1 [12.1] years; 73 [67.6%] men) were treated with open-label ustekinumab; 91 were randomized to blinded treatment. Similar proportions of participants in the abatacept group and the ustekinumab group relapsed between weeks 12 and 88 (41 of 45 [91.1%] vs 40 of 46 [87.0%]; P = .41). Median time to relapse from the last dose of ustekinumab was similar between groups as well: 36 weeks (95% CI, 36-48 weeks) in the abatacept group vs 32 weeks (95% CI, 28-40 weeks) in the ustekinumab group. Similar numbers and rates of adverse events occurred. Abatacept did not maintain suppression of the pathogenic IL-23-mediated psoriasis molecular signature in lesions after ustekinumab withdrawal, and serum IL-19 levels increased. CONCLUSIONS AND RELEVANCE: This parallel-design, double-blind randomized clinical trial found that abatacept did not prevent psoriasis relapse that occurred after ustekinumab withdrawal because it did not completely block the pathogenic psoriasis molecular pathways that led to relapse. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01999868.


Subject(s)
Psoriasis , Ustekinumab , Abatacept/adverse effects , Adult , Double-Blind Method , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Psoriasis/chemically induced , Psoriasis/drug therapy , Severity of Illness Index , Treatment Outcome , Ustekinumab/therapeutic use
5.
Dermatol Ther (Heidelb) ; 11(4): 1079-1083, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34236691

ABSTRACT

The Psoriasis Area and Severity Index (PASI) is the most widely used clinical measure in clinical trials to assess disease severity of plaque psoriasis. However, the PASI is not a precise measure of severity with less precision when the regional area of involvement is < 10% of the BSA of a specific anatomical region. Degradation of precision results from the area score defaulting to '1' when the area of involvement within an anatomical region falls between 0% and 10% of the BSA for a given anatomical region. We describe a modification to the PASI, termed PASI-high discrimination (PASI-HD), for determination of more accurate psoriasis severity in body regions where < 10% of the body surface area is affected. The methodology for assessing disease severity in these conditions is described.

6.
J Rheumatol ; 48(10): 1559-1565, 2021 10.
Article in English | MEDLINE | ID: mdl-33858978

ABSTRACT

OBJECTIVE: Delays in the diagnosis and treatment of psoriatic arthritis (PsA) are common. These delays contribute to impairments in quality of life and joint damage. This study aims to calculate the incidence rate of PsA over time and identify clinical features that may be used for PsA prediction in patients with psoriasis (PsO). METHODS: The study population for PsA incidence analysis included 1128 participants enrolled in the Utah Psoriasis Initiative between 2002 and 2014. Clinical evaluation and medical record review were performed to identify new cases of PsA after enrollment. To identify PsO features associated with PsA, the population was restricted to 627 participants who did not have PsA before PsO phenotyping and had been followed up for subsequent PsA diagnosis. We conducted Cox proportional hazard regressions to estimate the HR of PsA associated with PsO characteristics and other health-related features. RESULTS: PsA incidence rate increased for > 60 years following PsO onset (trend P < 0.0001). There was a significant association between PsA and induration severity in untreated lesions (P < 0.001, HR 1.46), history of fingernail involvement (P < 0.001, HR 2.38), pustular PsO (P < 0.001, HR 3.32), fingernail involvement at enrollment (P < 0.001, HR 2.04), and Koebner phenomenon (P < 0.001, HR 1.90). Multivariate analysis yielded a model that included a history of fingernail involvement (P < 0.001, HR 2.16) and untreated induration (P < 0.001, HR 1.41). CONCLUSION: Risk of PsA increases steadily for > 60 years following PsO onset. Patient-reported history of PsO characteristics has greater predictive power than physician-measured features at enrollment visits. The characteristics identified in this study provide guidance for screening for PsA risk in patients with PsO.


Subject(s)
Arthritis, Psoriatic , Psoriasis , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/epidemiology , Early Diagnosis , Humans , Incidence , Quality of Life
7.
Dermatol Ther (Heidelb) ; 11(2): 385-400, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33512665

ABSTRACT

Psoriasis is an immune-mediated inflammatory skin disease associated with numerous inflammatory comorbidities, including increased cardiovascular risk. The interleukin (IL)-23/IL-17 axis plays a central role in the immunopathogenesis of psoriasis and related comorbidities by acting to stimulate keratinocyte hyperproliferation and feed-forwarding circuits of perpetual T cell-mediated inflammation. IL-17 plays an important role in the downstream portion of the psoriatic inflammatory cascade. This review discusses the distinct mechanisms of action of IL-17 and IL-23 in the immunopathogenesis of psoriasis and related comorbidities plus the significant therapeutic benefits of selectively inhibiting these cytokines in patients with moderate to severe plaque psoriasis.

8.
J Drugs Dermatol ; 18(10): 1059-1060, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31603636

ABSTRACT

To the Editor: Patients with psoriasis are at increased risk of developing non melanoma skin cancer (NMSC), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).1,2 The risk is especially elevated among those who previously received systemic treatment or phototherapy.2 Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors.3


Subject(s)
Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Dermatologic Agents/adverse effects , Psoriasis/drug therapy , Skin Neoplasms/epidemiology , Biological Products/adverse effects , Carcinoma, Basal Cell/chemically induced , Carcinoma, Squamous Cell/chemically induced , Humans , Longitudinal Studies , Methotrexate/adverse effects , Registries/statistics & numerical data , Risk Assessment , Risk Factors , Skin Neoplasms/chemically induced
9.
Accid Anal Prev ; 126: 37-42, 2019 May.
Article in English | MEDLINE | ID: mdl-29530304

ABSTRACT

This article summarizes the recommendations on data and methodology issues for studying commercial motor vehicle driver fatigue of a National Academies of Sciences, Engineering, and Medicine study. A framework is provided that identifies the various factors affecting driver fatigue and relating driver fatigue to crash risk and long-term driver health. The relevant factors include characteristics of the driver, vehicle, carrier and environment. Limitations of existing data are considered and potential sources of additional data described. Statistical methods that can be used to improve understanding of the relevant relationships from observational data are also described. The recommendations for enhanced data collection and the use of modern statistical methods for causal inference have the potential to enhance our understanding of the relationship of fatigue to highway safety and to long-term driver health.


Subject(s)
Automobile Driving/statistics & numerical data , Fatigue/complications , Occupational Diseases/complications , Accidents, Traffic/prevention & control , Data Collection/methods , Humans , Risk Assessment , Risk Factors
10.
Psoriasis (Auckl) ; 8: 65-74, 2018.
Article in English | MEDLINE | ID: mdl-30324088

ABSTRACT

BACKGROUND: The product of Physician Global Assessment and Body Surface Area (PGA × BSA) is a new outcome measure for psoriasis severity and response to therapy. The objective of this study was to evaluate PGA × BSA as an alternative to Psoriasis Area and Severity Index (PASI) for psoriasis assessments. METHODS: The relationship between PASI and PGA × BSA was assessed in a post hoc analysis of pooled data from the PRISTINE (NCT00663052) and PRESTA (NCT00245960) trials in patients with moderate-to-severe psoriasis who received etanercept 50 mg/week. Data were analyzed using Spearman and intra-class correlation coefficients, effect sizes, scatterplots, Bland-Altman plots, and Kappa statistics. RESULTS: Spearman correlations at baseline, week 12, and week 24 were strong for PGA × BSA versus PASI (r=0.78, 0.87, and 0.90, respectively; all P<0.0001) as were intra-class correlations (0.76 [95% confidence interval 0.73-0.80], 0.80 [0.76-0.83], and 0.85 [0.82-0.87], respectively). The effect size was -1.53 for PASI and -0.94 for PGA × BSA (baseline to week 24). Scatterplots and Bland-Altman plots detected a trend across the range of measurement. Kappa statistics (at 12 and 24 weeks) between PASI50/75/90 and 50/75/90% improvement in PGA × BSA showed good agreement (0.58-0.69 at week 12 and 0.63-0.67, respectively; all P<0.0001). At baseline, the Spearman correlation coefficients were 0.96, 0.51, 0.19, and 0.17 for PGA × BSA versus BSA, PGA, Patient Global Assessment, and Dermatology Life Quality Index, respectively (all P<0.001). CONCLUSION: PGA × BSA has advantages over PASI for measuring moderate-to-severe psoriasis; it is intuitive, sensitive, and easy to use.

11.
Nat Commun ; 9(1): 4178, 2018 10 09.
Article in English | MEDLINE | ID: mdl-30301895

ABSTRACT

Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in ~30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with >7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve >90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment.


Subject(s)
Arthritis, Psoriatic/genetics , Gene Expression Profiling , Risk Assessment , Biomarkers/metabolism , Cohort Studies , Enhancer Elements, Genetic/genetics , Genetic Loci , Humans , Meta-Analysis as Topic
12.
Aerosp Med Hum Perform ; 89(6): 536-546, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29789087

ABSTRACT

INTRODUCTION: Future deep space missions will expose astronauts to more intense stressors than previously encountered. Isolation will be greater and more prolonged, living and work areas more confined, and communications and resupply channels to Earth longer and less reliable. Astronauts will need to function more autonomously, with less guidance and support from Earth. Thus, it is important to select and train astronauts who can adapt and function effectively under extreme and variable conditions. In order to identify factors linked to individual adaptability, we conducted a systematic review of the literature on cognitive and behavioral adaptation to isolated, confined, and extreme (ICE) environments. METHODS: We searched PubMed, Embase, Web of Science, and PsychINFO databases for studies addressing individual adaptability to ICE environments. Studies were rated for quality and fidelity to long-duration space missions and key results extracted. RESULTS: There were 73 studies that met all inclusion criteria. Adaptability attributes for ICE environments include intelligence, emotional stability, self-control, openness, achievement facets of conscientiousness, optimism, mastery, introversion, hardiness, task-oriented coping, past experience, low need for social support, and adequate sleep. DISCUSSION: This review identifies individual factors linked to adaptability under ICE conditions. Further studies are needed to verify causal directions and determine the relative importance of these factors.Bartone PT, Krueger GP, Bartone JV. Individual differences in adaptability to isolated, confined, and extreme environments. Aerosp Med Hum Perform. 2018; 89(6):536-546.


Subject(s)
Adaptation, Psychological , Astronauts/psychology , Confined Spaces , Extreme Environments , Social Isolation , Space Flight , Humans , Individuality , Stress, Psychological
13.
Hum Mol Genet ; 26(21): 4301-4313, 2017 11 01.
Article in English | MEDLINE | ID: mdl-28973304

ABSTRACT

Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10-8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10-7, OR = 0.707; TYK2: pburden = 6.17 × 10-4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.


Subject(s)
Psoriasis/genetics , Tumor Necrosis Factor Ligand Superfamily Member 15/genetics , Alleles , Case-Control Studies , Cohort Studies , Exome , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genetic Variation/genetics , Genome-Wide Association Study , Genotype , Humans , Interferon-Induced Helicase, IFIH1/genetics , Interferon-Induced Helicase, IFIH1/metabolism , Male , Polymorphism, Single Nucleotide/genetics , Psoriasis/physiopathology , Risk Factors , TYK2 Kinase/genetics , TYK2 Kinase/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 15/metabolism , Exome Sequencing
14.
Nat Commun ; 8: 15382, 2017 05 24.
Article in English | MEDLINE | ID: mdl-28537254

ABSTRACT

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8+ T-cells and CD4+ T-cells including TH0, TH1 and TH17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10-89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.


Subject(s)
Genetic Loci/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Psoriasis/genetics , White People/genetics , Age of Onset , Gene Regulatory Networks/genetics , Gene Regulatory Networks/immunology , Humans , Interferons/immunology , Interferons/metabolism , NF-kappa B/immunology , NF-kappa B/metabolism , Polymorphism, Single Nucleotide , Protein Interaction Maps/genetics , Protein Interaction Maps/immunology , Psoriasis/immunology , Signal Transduction/genetics , Signal Transduction/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
15.
J Am Acad Dermatol ; 76(2): 290-298, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27908543

ABSTRACT

BACKGROUND: An urgent need exists in the United States to establish treatment goals in psoriasis. OBJECTIVE: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. METHODS: The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. RESULTS: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. LIMITATIONS: Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. CONCLUSION: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.


Subject(s)
Psoriasis/therapy , Body Surface Area , Foundations , Humans , Patient Care Planning , Practice Guidelines as Topic , Specialty Boards , United States
16.
J Invest Dermatol ; 136(2): 365-371, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26802234

ABSTRACT

Psoriasis is a chronic inflammatory skin condition resulting from a complex interplay among the immune system, keratinocytes, susceptibility genes, and environmental factors. However, the pathogenesis of psoriasis is not completely elucidated. microRNAs represent a promising class of small, noncoding RNA molecules that function to regulate gene expression. Although microRNA research in psoriasis and dermatology is still relatively new, evidence is rapidly accumulating for the role of microRNAs in the pathogenesis of psoriasis and other chronic inflammatory conditions. In this article, we present a comprehensive review of what is known about microRNAs and their role in the pathogenesis of psoriasis.


Subject(s)
Genetic Predisposition to Disease , MicroRNAs/genetics , Psoriasis/genetics , Psoriasis/physiopathology , Female , Gene Expression Profiling , Gene Expression Regulation , Humans , Male , Sensitivity and Specificity
17.
J Dermatolog Treat ; 27(1): 27-30, 2016.
Article in English | MEDLINE | ID: mdl-26247843

ABSTRACT

No validated instrument exists to measure desire for improvement in psoriasis patients. To address this void, we conducted a single-center longitudinal study of 268 moderate-to-severe psoriasis patients to psychometrically validate the Desired Improvement Tool (DIT). The DIT is a single-item instrument scored 0-5 by the patient. A 0 indicates the patient is satisfied with disease level and does not desire further treatment. A 5 indicates a large amount of improvement is desired. The DIT demonstrated high test-retest reliability (Spearman, r = 0.97). Predictive and construct validity were moderate-to-high: r = 0.70 for BSA, 0.67 for PASI, and 0.56 for PGA and r = 0.67 for Life Quality Assessment (LQA), respectively. A sensitivity analysis revealed the DIT responded to changes in BSA. As a psychometrically valid tool, the DIT may guide clinical management of psoriasis patients by capturing an important clinical construct in an expedient and quantifiable manner.


Subject(s)
Psoriasis/psychology , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , Psoriasis/drug therapy , Psychometrics , Reproducibility of Results , Severity of Illness Index
18.
Arthritis Care Res (Hoboken) ; 68(2): 267-74, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25779603

ABSTRACT

OBJECTIVE: To evaluate long-term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in the GO-REVEAL trial. METHODS: The GO-REVEAL trial was a phase III, randomized, double-blind trial with placebo-control through week 24 followed by an open-label extension of golimumab 50/100 mg treatment up to 5 years. In these post-hoc analyses, MDA was defined by the presence of ≥5 of 7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity score ≤20 [range 0-100], Health Assessment Questionnaire disability index [HAQ DI] ≤0.5, and ≤1 tender enthesis point). RESULTS: Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at week 14 (23.5% versus 1.0%; P < 0.0001), week 24 (28.1% versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was achieved at least once by ∼50% of golimumab-treated patients overall. Irrespective of treatment randomization, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ DI) and overall disease activity (patient global assessment of disease activity) at week 256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1-unit higher baseline HAQ DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio 0.514 [95% confidence interval 0.321-0.824]; P = 0.006) and ≥4 (odds ratio 0.480 [95% confidence interval 0.290-0.795]; P = 0.004) consecutive visits. CONCLUSION: Among golimumab-treated PsA patients, better long-term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/drug therapy , Disease Progression , Humans , Radiography , Retrospective Studies , Treatment Outcome
19.
Am J Hum Genet ; 97(6): 816-36, 2015 Dec 03.
Article in English | MEDLINE | ID: mdl-26626624

ABSTRACT

Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.


Subject(s)
Arthritis, Psoriatic/genetics , Genetic Loci , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Psoriasis/genetics , Adolescent , Adult , Arthritis, Psoriatic/pathology , Bayes Theorem , Case-Control Studies , Cornified Envelope Proline-Rich Proteins/genetics , DNA-Binding Proteins/genetics , Female , Genome-Wide Association Study , HLA-C Antigens/genetics , Humans , Intracellular Signaling Peptides and Proteins/genetics , Linkage Disequilibrium , Male , Nuclear Proteins/genetics , Psoriasis/pathology , Receptors, Interleukin/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 9/genetics , Tumor Necrosis Factor alpha-Induced Protein 3
20.
J Drugs Dermatol ; 14(8): 805-12, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26267724

ABSTRACT

Psoriasis is a systemic inflammatory disease. Effective management requires treatment with agents targeting inflammation in skin, joints, and other tissues. Biologics for psoriasis are directed at more specific targets, have a better safety profile, are better tolerated, and are more effective than conventional systemic agents. Despite these advances, many patients with psoriasis remain undertreated, and overall patient satisfaction remains low. The dichotomy between ideal therapeutic outcomes and suboptimal outcomes (which are currently commonplace) is likely largely due to misperceptions about psoriasis and biologic treatments. This article discusses these misperceptions, including the notions that psoriasis is a benign disorder, and that conventional systemic therapies are safer than biologics and adequate for most patients with moderate-to-severe disease. We present practical and evidence-based discussions to refute these misconceptions and provide useful resources for providers and patients that support access to advanced therapies. We believe that biologics represent optimal treatment for most patients with moderate-to-severe psoriasis, and until more effective approaches are generated, these efficacious and target-specific approaches should become the standard of care.


Subject(s)
Attitude of Health Personnel , Biological Products/therapeutic use , Dermatologic Agents/therapeutic use , Practice Patterns, Physicians' , Psoriasis/drug therapy , Acitretin/therapeutic use , Adalimumab/economics , Adalimumab/therapeutic use , Biological Products/adverse effects , Biological Products/economics , Cyclosporine/therapeutic use , Dermatologic Agents/economics , Etanercept/economics , Etanercept/therapeutic use , Humans , Infliximab/economics , Infliximab/therapeutic use , Methotrexate/therapeutic use , Perception
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