Anterior uveitis (AU) in childhood may be the first manifestation of juvenile idiopathic arthritis (JIA). We identified factors that may help to differentiate JIA-associated AU from the more common idiopathic AU (IAU) before the onset of arthritis.
Children with IAU and with JIA-associated AU were analyzed for their demographics, age at onset of uveitis, uveitis course and complications, ocular surgery, antiinflammatory medication, and best corrected visual acuity (BCVA).
AU was associated with JIA in 88 cases, and was idiopathic in another 49. In the JIA group, 60% of patients were female compared to 47% in the IAU group (p = 0.154). Antinuclear antibody (ANA) was significantly more frequent in the JIA group (88% vs 33%; p < 0.001, OR 14.4, 95% CI 5.8-35.6). Insidious uveitis onset occurred more often in JIA than in IAU patients (67% vs 31%; p < 0.001, OR 4.6, 95% CI 2.2-9.8). Persistent uveitis was found in 82% of JIA patients, and in 57% of IAU patients (p = 0.003, OR 3.4, 95% CI 1.5-7.4). Median age of AU onset was 5 years in JIA and 9 years in IAU (p < 0.001). Uveitis complications at first presentation at our institutions were more frequent in JIA than in IAU patients (79% vs 61%; p = 0.027, OR 2.5, 95% CI 1.1-5.3). During followup, 69 surgical procedures (51% of patients, 1.31 per patient) were performed in the JIA group, and 18 in IAU patients (0.57 per patient) (p = 0.008). BCVA was better in the IAU patients at first presentation (p = 0.001).
The IAU and JIA-associated AU in childhood differ in their clinical course. ANA positivity, presence of uveitis complications at first manifestation, insidious onset, duration over 3 months, BCVA of 20/50 or less, and an age of 3 years or younger might help to detect AU associated with JIA. JIA uveitis manifests earlier, has more complications, and more often requires systemic immunosuppression and surgical intervention.
"JIA-related uveitis may develop before, at the same time as, or after the arthritis onset.7 Risk factors for the development of uveitis in children with JIA are early onset of the disease, oligoarticular subtype, ANA-positive titers, female sex, specific human leukocyte antigen markers, and short duration of disease.8,9 It is associated with a high rate of complications,5,10 including posterior synechiae, cataract, glaucoma, and band keratopathy, causing visual impairment in the affected children. Moreover, in many cases, the significant ocular morbidity carried by this disease lasts well into adulthood. "
[Show abstract][Hide abstract] ABSTRACT: Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.
Drug Design, Development and Therapy 03/2014; 8:341-348. DOI:10.2147/DDDT.S54207 · 3.03 Impact Factor
"We tested for allergy associations by mining unstructured clinical notes and coded data. Although the methods applied have been validated in other studies [7,9,18-21], as an internal validation we reproduced previously reported associations of uveitis including age [22-26], oligoarticular-onset disease [3,22-25,27], antinuclear antibody (ANA) status [22-25,27], rheumatoid factor (RF) status [22,23,28], and the presence of psoriasis in the patient or in immediate relatives . This study adds to a growing literature demonstrating the potential of analyzing clinical data warehouses for rapidly evaluating a clinically formed hypotheses using practice-based evidence [11,30]. "
[Show abstract][Hide abstract] ABSTRACT: Juvenile idiopathic arthritis is the most common rheumatic disease in children. Chronic uveitis is a common and serious comorbid condition of juvenile idiopathic arthritis, with insidious presentation and potential to cause blindness. Knowledge of clinical associations will improve risk stratification. Based on clinical observation, we hypothesized that allergic conditions are associated with chronic uveitis in juvenile idiopathic arthritis patients.
This study is a retrospective cohort study using Stanford's clinical data warehouse containing data from Lucile Packard Children's Hospital from 2000--2011 to analyze patient characteristics associated with chronic uveitis in a large juvenile idiopathic arthritis cohort. Clinical notes in patients under 16 years of age were processed via a validated text analytics pipeline. Bivariate-associated variables were used in a multivariate logistic regression adjusted for age, gender, and race. Previously reported associations were evaluated to validate our methods. The main outcome measure was presence of terms indicating allergy or allergy medications use overrepresented in juvenile idiopathic arthritis patients with chronic uveitis. Residual text features were then used in unsupervised hierarchical clustering to compare clinical text similarity between patients with and without uveitis.
Previously reported associations with uveitis in juvenile idiopathic arthritis patients (earlier age at arthritis diagnosis, oligoarticular-onset disease, antinuclear antibody status, history of psoriasis) were reproduced in our study. Use of allergy medications and terms describing allergic conditions were independently associated with chronic uveitis. The association with allergy drugs when adjusted for known associations remained significant (OR 2.54, 95% CI 1.22--5.4).
This study shows the potential of using a validated text analytics pipeline on clinical data warehouses to examine practice-based evidence for evaluating hypotheses formed during patient care. Our study reproduces four known associations with uveitis development in juvenile idiopathic arthritis patients, and reports a new association between allergic conditions and chronic uveitis in juvenile idiopathic arthritis patients.
"ANAs are mainly associated with oligoarticular-onset JIA patients, but are also present in polyarticular and psoriatic subtypes [38,39]. Several reports have documented the association between the presence of ANAs and uveitis in JIA patients . Distinct autoantigens that contribute to ANA positivity have not yet been identified. "
[Show abstract][Hide abstract] ABSTRACT: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients.
A pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs.
Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis.
The NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.
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