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 T_H0, T_H1 and T_H17). 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.

An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.

Objective: To assess whether the presence of nonspecific musculoskeletal symptoms, their degree, and change over time predict the development of psoriatic arthritis (PsA) in a prospective cohort of psoriasis patients without arthritis at baseline.Methods: This prospective cohort study involved patients with psoriasis who were assessed at baseline to exclude the presence of clinical PsA. The study participants were reassessed annually to determine if they had developed PsA. The presence of musculoskeletal symptoms and the patients’ assessments of pain, fatigue, stiffness, physical function, and psychological distress were recorded at each visit. Cox proportional hazards models were used to assess what symptoms predicted the development of PsA.Results: A total of 57 of 410 psoriasis patients developed PsA. At baseline, the presence of arthralgia in women (hazard ratio [HR] 2.59, P = 0.02), heel pain (HR 4.18, P = 0.02), high fatigue score (HR 2.36, P = 0.007), and high stiffness score (HR 2.03, P = 0.045) predicted subsequent development of PsA. In addition, an increase from baseline in fatigue score (HR 1.27, P = 0.001), pain score (HR 1.34, P < 0.001), and stiffness score (HR 1.21, P = 0.03), and a worsening in physical function score (HR 0.96, P = 0.04) predicted the development of PsA.Conclusion: A preclinical phase exists in patients with PsA prior to the diagnosis of the disease. This phase is characterized by nonspecific musculoskeletal symptoms, including joint pain, fatigue, and stiffness.