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

Abstract

IntroductionPsoriatic 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.MethodsWe 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.ResultsThe 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.ConclusionThis 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.Electronic supplementary materialThe online version of this article (10.1007/s13555-018-0266-x) contains supplementary material, which is available to authorized users.

Evaluation of a Genetic Risk Score for Diagnosis of Psoriatic Arthritis

“…21 Furthermore, a weighted model that only included HLA risk alleles was found to be the best discriminator of all the models tested, which also supports literature asserting the driving force of certain HLA risk alleles in the development of PsA. [20][21][22] Future efforts are aimed in 3 directions. First, recently published data demonstrates the advantages of using large cohorts and a high number of genetic markers (ie, 200 risk alleles) to identify subtle genetic differences that better distinguish PsA from PsO.…”

“…HLA genes are unique in that they code for cell surface antigen proteins responsible for major functions of the immune system. The role of HLA genes in PsA risk is well-documented, 20,21,22 suggesting that an HLA-only PsA GRS could capture a significant proportion of the genetic contribution to developing this disease.…”

Association of Nail Psoriasis With Disease Activity Measures and Impact in Psoriatic Arthritis: Data From the Corrona Psoriatic Arthritis/Spondyloarthritis Registry

“…The prevalence of nail involvement in our study population is lower than that observed in previous real-world studies of patients with varied prior biologic experience, which have reported rates of nail involvement ranging from 50% to 87% among patients with PsA. (33)(34)(35)(36)(37)(38)(39) Notably, approximately 31% of patients in our study population had received biologic therapy and 29% had received conventional synthetic disease-modifying antirheumatic drugs prior to enrollment, which may have ameliorated nail disease in those patients before their participation in the study. (5,26) Additionally, the majority of previous studies specifically enrolled patients with PsA and psoriasis, whereas the presence of psoriasis was not a criterion for enrollment in our study.…”

MHC*IMP – Imputation of Alleles for Genes in the Major Histocompatibility Complex

“…The SNP data used in the construction of the reference panel for this study was drawn from two sources, both reported in previous studies: "UCSF" (Yan et al, 2018) and "University of Dundee" (Nititham et al, 2018).…”