Risk Factors and Biomarkers for the Occurrence of Uveitis in Juvenile Idiopathic Arthritis

Abstract

ObjectiveTo analyze the prognostic value of demographic, clinical, and therapeutic factors and laboratory biomarkers and to assess their role in predicting uveitis occurrence in patients with juvenile idiopathic arthritis (JIA).MethodsPatients with JIA were enrolled within the first year after JIA diagnosis. Demographic and clinical parameters were documented. Serum samples were collected at study enrollment, at 3‐month follow‐up visits within the first year, and then every 6 months. A multivariable Cox regression analysis was performed to evaluate the impact of demographic, clinical, laboratory, and therapeutic parameters on uveitis onset.ResultsWe included 954 JIA patients (67.2% female, 54.2% antinuclear antibody [ANA] positive, mean ± SD age at onset 7.1 ± 4.6 years). Uveitis occurred in 133 patients (observation period 44.5 months). Young age at JIA onset and ANA positivity were significantly associated with the onset of uveitis (both P < 0.001). Treatment of arthritis with methotrexate alone (hazard ratio [HR] 0.18 [95% confidence interval (95% CI) 0.12–0.29], P < 0.001) or combined with etanercept (HR 0.10 [95% CI 0.04–0.23], P < 0.001) or adalimumab (HR 0.09 [95% CI 0.01–0.61], P = 0.014) reduced the risk of uveitis onset and the occurrence of uveitis‐related complications. Predictors of uveitis onset included elevated erythrocyte sedimentation rate at baseline (HR 2.36 [95% CI 1.38–4.02], P = 0.002) and continuing moderate or high disease activity during follow‐up as measured by the 10‐joint clinical Juvenile Arthritis Disease Activity Score (HR 4.30 [95% CI 2.51–7.37], P < 0.001). Additionally, S100A12 levels ≥250 ng/ml at baseline were significantly associated with the risk of uveitis (HR 2.10 [95% CI 1.15–3.85], P = 0.016).ConclusionApart from demographic risk factors and treatment modalities, JIA disease activity scores and laboratory biomarkers could be used to better define the group of JIA patients at high risk of uveitis onset.

Predictive factors and biomarkers for the 2-year outcome of uveitis in juvenile idiopathic arthritis: data from the Inception Cohort of Newly diagnosed patients with Juvenile Idiopathic Arthritis (ICON-JIA) study

“…Elevated ESR appeared as a valid baseline prognostic factor for uveitis occurrence in JIA patients [13, 27, 29, 33, 34]. According to our present data, it did not appear as a useful predictor of the further uveitis course, which is probably influenced by anti-inflammatory treatment instituted for JIA.…”

“…Previous data disclosed that S100 serum levels in JIAU patients were higher in patients with active uveitis and suggested that they may reflect eye disease [16]. High S100A12 levels in JIA patients were significantly associated with the risk for uveitis [34]. Our presented data show that S100A12 might not be a useful biomarker for monitoring uveitis activity during the course of JIA, probably influenced by the DMARDs being used to treat the underlying rheumatic disease [35].…”

Identification of Ocular Autoantigens Associated With Juvenile Idiopathic Arthritis-Associated Uveitis

“…There is increasing evidence indicating that B and plasma cells, representing the predominant cellular infiltrate, play a crucial role in the disease (13–16). This hypothesis is supported by the observation that 80% of JIAU patients are positive for serum anti-nuclear antibodies (ANA), which represent an important risk factor for uveitis occurrence in JIA patients (6, 8). However, the pathogenic contribution of ANA or autoantibodies to JIAU is still largely undefined.…”

“…Uveitis in children and adolescents is frequently related to JIA (3–5), and, vice versa, represents a common extra-articular manifestation of disease (5, 6). JIA-associated uveitis (JIAU) occurs in 9 to 12% of children with JIA and is observed particularly frequently in the oligoarthritis subtype (7, 8).…”

Adjunctive vitamin D for the treatment of active juvenile idiopathic arthritis: An open‑label, prospective, randomized controlled trial

“…As a result of chronic inflammation, patients with JIA suffer from joint pain, swelling, restricted range of motion and joint deformity (1). Severe extra-articular abnormalities may also accompany this disease, including uveitis, which occurs more frequently in antinuclear antibody (ANA)-positive patients and can lead to blindness, and macrophage activation syndrome (MAS), a complication of sJIA that can lead to multi-organ insufficiency and even mortality (3,4) Previous studies indicated that vitamin D played an important role in maintaining both the skeletal and immune systems (5,6). Vitamin D regulates the innate and adaptive immune systems by activating the vitamin D receptor, which is distributed widely on immune cells (7,8).…”