Psoriasis and comorbid diseases: Epidemiology.

Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being recognized as a systemic inflammatory disorder. Psoriatic arthritis is a well-known comorbidity of psoriasis. A rapidly expanding body of literature in various populations and settings supports additional associations between psoriasis and cardiometabolic diseases, gastrointestinal diseases, kidney disease, malignancy, infection, and mood disorders. The pathogenesis of comorbid disease in patients with psoriasis remains unknown; however, shared inflammatory pathways, cellular mediators, genetic susceptibility, and common risk factors are hypothesized to be contributing elements. As additional psoriasis comorbidities continue to emerge, education of health care providers is essential to ensuring comprehensive medical care for patients with psoriasis

Psoriasis and comorbid diseases: Implications for management.

: As summarized in the first article in this continuing medical education series, the currently available epidemiologic data suggest that psoriasis may be a risk factor for cardiometabolic disease. Emerging data also suggest associations between psoriasis and other comorbidities beyond psoriatic arthritis, including chronic kidney disease, inflammatory bowel disease, hepatic disease, certain malignancies, infections, and mood disorders. Recognizing the comorbid disease burden of psoriasis is essential for ensuring comprehensive care of patients with psoriasis. The clinical implications of the comorbid diseases that are associated with psoriasis and recommendations for clinical management are reviewed in this article.<br/

Prevalence and treatment patterns of psoriatic arthritis in the UK.

OBJECTIVES: The objectives of this study were to determine the prevalence of PsA in The Health Improvement Network (THIN), a large population-based medical records database in the UK, to examine factors associated with prevalent PsA among patients with psoriasis and to describe the use of DMARDs in patients with PsA. METHODS: Two cohorts were derived from THIN to examine the prevalence of PsA in a cross-sectional study among all patients aged 18-90 years and among a subcohort of 4900 psoriasis patients aged 45-65 years. Prescription codes were used to describe therapies after the diagnosis of PsA. Associations for prevalent PsA among psoriasis patients were assessed using logistic regression analysis. RESULTS: Among 4.8 million patients in THIN between the ages of 18 and 90 years, 9045 patients had at least one medical code for PsA, giving an overall prevalence of 0.19% (95% CI 0.19%, 0.19%). Of those patients, 45.9% with PsA have been prescribed DMARDs. Among the 4064 confirmed psoriasis patients, the prevalence of PsA was 8.6% (95% CI 7.7%, 9.5%). PsA was more prevalent among patients with severe psoriasis [odds ratio (OR) 3.34; 95% CI 2.40, 4.65], obesity (OR 1.77; 95% CI 1.30, 2.41) and duration of psoriasis for ≥10 years (OR 7.42; 95% CI 3.86, 14.25) in the fully adjusted model. CONCLUSION: The prevalence of PsA in THIN is consistent with previous population-based estimates. Limitations include a definition of PsA based on a diagnostic code rather than Classification Criteria for Psoriatic Arthritis (CASPAR) criteria. Given the large population of PsA patients, THIN is an important resource for the study of PsA

Tofacitinib in Patients With Psoriatic Arthritis and Metabolic Syndrome: A Post hoc Analysis of Phase 3 Studies

Objective: Metabolic syndrome (MetS) is a cluster of concurrent risk factors for cardiovascular disease and type 2 diabetes. This post hoc analysis explored key efficacy and safety endpoints in patients with psoriatic arthritis (PsA) and MetS treated with tofacitinib. Methods: Tofacitinib 5 and 10 mg twice daily and placebo data were pooled from two Phase 3 studies (OPAL Broaden [12 months; ClinicalTrials.gov identifier NCT01877668]; OPAL Beyond [6 months; ClinicalTrials.gov identifier NCT01882439]); patients received one background conventional synthetic disease‐modifying antirheumatic drug. Patients were stratified by baseline presence/absence of MetS. Efficacy and safety were reported to month 3 (tofacitinib and placebo) and 6 (tofacitinib only). Efficacy outcomes included: American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire‐Disability Index (HAQ‐DI) response, Psoriasis Area Severity Index (PASI)75 response, and enthesitis/dactylitis resolution rates; and changes from baseline (Δ) in C‐reactive protein, HAQ‐DI, Patient’s/Physician’s Global Assessment of Arthritis, and patient‐reported outcomes. Safety outcomes included treatment‐emergent all‐causality adverse events (AEs), Δ in lipid/hepatic values, and liver parameter increases. Results: Of 710 patients, 41.4% (n = 294) had baseline MetS. All efficacy outcomes improved with both tofacitinib doses versus placebo, to month 3; tofacitinib efficacy was consistent to month 6, regardless of MetS status. MetS did not appear to affect the incidence of AEs or Δ in lipid/hepatic values with tofacitinib up to month 3 or 6. Arterial thromboembolism and myocardial infarction (adjudicated major adverse cardiovascular events) were each reported once in tofacitinib‐treated patients with MetS. Conclusion: Regardless of baseline MetS status, tofacitinib showed greater efficacy versus placebo in patients with active PsA. The tofacitinib safety profile appeared similar in patients with versus without MetS

A genomewide scan for Attention-Deficit/Hyperactivity Disorder in an extended sample: Suggestive linkage on 17p11

Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is a common, highly heritable neurobehavioral disorder of childhood onset, characterized by hyperactivity, impulsivity, and/or inattention. As part of an ongoing study of the genetic etiology of ADHD, we have performed a genomewide linkage scan in 204 nuclear families comprising 853 individuals and 270 affected sibling pairs (ASPs). Previously, we reported genomewide linkage analysis of a “first wave” of these families composed of 126 ASPs. A follow-up investigation of one region on 16p yielded significant linkage in an extended sample. The current study extends the original sample of 126 ASPs to 270 ASPs and provides linkage analyses of the entire sample, using polymorphic microsatellite markers that define an ∼10-cM map across the genome. Maximum LOD score (MLS) analysis identified suggestive linkage for 17p11 (MLS=2.98) and four nominal regions with MLS values >1.0, including 5p13, 6q14, 11q25, and 20q13. These data, taken together with the fine mapping on 16p13, suggest two regions as highly likely to harbor risk genes for ADHD: 16p13 and 17p11. Interestingly, both regions, as well as 5p13, have been highlighted in genomewide scans for autism

Barriers to and Facilitators of a Career as a Physician‐Scientist Among Rheumatologists in the US

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113102/1/acr22569.pd

The Smoking Paradox in the Development of Psoriatic Arthritis among Psoriasis Patients – A Population-Based Study

Objectives: Smoking is strongly associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among psoriasis patients. We sought to clarify the possible methodologic mechanisms behind this paradox. Methods: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among psoriasis patients. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders. Results: Of 6.65 million subjects without PsA at baseline, 225,213 participants had psoriasis and 7,057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (RR, 1.27; 95% CI, 1.19-1.36), but with a decreased risk among psoriasis patients (RR 0.91; 95% CI, 0.85-0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both RRs = ~1.50), it could reverse the biased estimate of effect of smoking among psoriasis patients (RR=0.9). Conclusions: In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among psoriasis patients. Conditioning on a causal intermediate variable (psoriasis) can reverse the association between smoking and PsA, explaining the smoking paradox for the risk of PsA among psoriasis patients

International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials

© 2017 Published by the BMJ Publishing Group Limited. Objective To identify a core set of domains (outcomes) to be measured in psoriatic arthritis (PsA) clinical trials that represent both patients' and physicians' priorities. Methods We conducted (1) a systematic literature review (SLR) of domains assessed in PsA; (2) international focus groups to identify domains important to people with PsA; (3) two international surveys with patients and physicians to prioritise domains; (4) an international face-To-face meeting with patients and physicians using the nominal group technique method to agree on the most important domains; and (5) presentation and votes at the Outcome Measures in Rheumatology (OMERACT) conference in May 2016. All phases were performed in collaboration with patient research partners. Results We identified 39 unique domains through the SLR (24 domains) and international focus groups (34 domains). 50 patients and 75 physicians rated domain importance. During the March 2016 consensus meeting, 12 patients and 12 physicians agreed on 10 candidate domains. Then, 49 patients and 71 physicians rated these domains' importance. Five were important to >70% of both groups: musculoskeletal disease activity, skin disease activity, structural damage, pain and physical function. Fatigue and participation were important to >70% of patients. Patient global and systemic inflammation were important to >70% of physicians. The updated PsA core domain set endorsed by 90% of OMERACT 2016 participants includes musculoskeletal disease activity, skin disease activity, pain, patient global, physical function, health-related quality of life, fatigue and systemic inflammation. Conclusions The updated PsA core domain set incorporates patients' and physicians' priorities and evolving PsA research. Next steps include identifying outcome measures that adequately assess these domains

The Relative Composition of the Inflammatory Infiltrate as an Additional Tool for Synovial Tissue Classification

10.1371/journal.pone.0072494PLoS ONE88-POLN