Dataset Information

Clinical and Genetic Risk Factors Associated with Psoriatic Arthritis among Patients with Psoriasis.

ABSTRACT:

Introduction

Psoriatic arthritis (PsA) is a chronic, inflammatory arthritis that affects an estimated 30% of patients with psoriasis. PsA is underdiagnosed in primary care and dermatology clinics due to a variety of reasons, including failure of healthcare providers to ask about symptoms, overlap of symptoms and signs with other rheumatologic conditions, and lack of a specific diagnostic test. A delay in PsA diagnosis and treatment, even as short as 6 months, can lead to decreased quality of life, increased joint damage, and worse long-term physical function. In this study, we sought to identify the clinical and genetic factors that help discriminate patients with PsA from those with cutaneous psoriasis only.

Methods

We analyzed a cohort of 974 psoriasis patients at an academic medical center, of whom 175 had confirmed PsA, and performed univariate, multivariate, and predictive modeling to determine factors associated with PsA.

Results

The univariate analysis revealed significant positive associations of PsA with age, nail involvement, scalp involvement, skin fold involvement, elbow/knee involvement, psoriasis severity, plaque subtype, erythrodermic subtype, hypertension, type 2 diabetes, and coronary artery disease, and a significant negative association of PsA with the human leukocyte antigen (HLA)-C*06:02 allele. In the multivariate analysis, nail involvement, type 2 diabetes, and pustular psoriasis remained significantly associated with PsA, while HLA-C*06:02 positivity remained protective. There was a trend towards an association of PsA with older age, younger age of psoriasis onset, and skin fold involvement, while there was protective trend for smoking. A predictive model including both clinical and genetic factors showed reasonable discriminative ability between psoriasis and PsA, with an area under the curve of 0.87 for a receiver operating characteristic curve.

Conclusion

This study identified a number of clinical and genetic features that could help stratify patients who are at higher risk for having PsA and for whom rheumatology referral may be beneficial.

SUBMITTER: Yan D

PROVIDER: S-EPMC6261122 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesPsoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models.MethodsGenome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation.ResultsWe identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10-9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10-45 ) and Wnt signaling (adjusted P = 9.5 × 10-58 ). The heritability of PsA in this cohort was found to be moderate (h2 SNP = 0.63), which was similar to the heritability of PsC (h2 SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data.ConclusionKey biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

Project description:BACKGROUND:The early detection of psoriatic arthritis (PSA) poses a challenge to rheumatologists, even when their diagnosis is aided by sonography. In order to facilitate early detection of PSA among patients with psoriasis (PSO), we retrospectively analyzed of the relationships between serological markers and comorbidities in 629 psoriatic patients, 102 of which had PSA, while the other 527 had PSO. RESULTS:Serological markers were found not to be useful in distinguishing between PSA and PSO (p >?0.05 for all comparisons). The prevalence rate of PSA among PSO patients was around 19.4%. Two components of metabolic syndrome-hyperlipidemia (2.94%) and gout (4.9%)-were significantly more prevalent in PSA patients than in PSO patients (p <?0.05). The odds ratio for PSA is 15.94 in patients with hyperlipidemia with a 95% confidence interval (CI) of 1.64-154.80; meanwhile, the odds ratio for PSA is 3.83 in patients with gout with a 95% CI of 1.19-12.31. Allergic rhinitis (5.88%) was more prevalent in PSA patients than in PSO patients (p <?0.01). The odds ratio was 8.17 in patients with allergic rhinitis with a 95% CI of 2.26-29.50. Plasma hs-miR-210-3p distinguishes PSA from PSO, and its levels can also be distinguished from PSA after treated with anti-TNF? biologics agents (both p <?0.05). CONCLUSIONS:No clinical available serology markers, but hyperlipidemia, gout, axial spondylopathy (inflammatory back pain), or allergic rhinitis, could differentiate between psoriatic arthritis from psoriasis. Plasma hs-miR-210-3p and comorbidities may differentiate psoriatic arthritis from psoriasis. Key Points • Clinical manifestations and comorbidities are different between psoriatic arthritis and psoriasis only patients. • Traditional serology markers are similar between psoriatic arthritis and psoriasis-only patients. • Plasma hs-miR-210-3p distinguishes PSA from PSO, and its levels can also be distinguished from PSA after treated with anti-TNF? biologics agents in our study.