Uveitis In Juvenile Idiopathic Arthritis Research Articles

Frequency and Identification of Risk Factors of Uveitis in Juvenile Idiopathic Arthritis: A Long-term Follow-up Study in a Cohort of Italian Children.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood. The JIA-associated uveitis represents the most common extra-articular manifestation. The main aim of this study was to evaluate frequency and risk factors of uveitis in a pediatric population affected by JIA. One hundred eight Italian children with JIA were followed during a follow-up period of 13 years. Association between uveitis, antinuclear antibodies (ANAs), and subtype of arthritis has been estimated, and Kaplan-Meier curves were generated to assess the probability of ocular complications during the follow-up period. Twenty-one patients developed uveitis, after 96.5 ± 50.4 months from the enrollment. According to JIA subtypes, the oligoarthritis subtype was characterized by the highest prevalence (39%) of uveitis. The greatest risk of uveitis has been detected in oligoarthritis patients associated to ANA positivity (risk ratio, 8.6; 95% confidence interval, 2.27-32.9; χ = 20.4), whereas the worst evolution was revealed in patients with oligoarthritis and high levels of ANAs, with a progression time of 36 months (log-rank χ = 16.39; p < 0.0001; risk ratio, 18; 95% confidence interval, 7.3-44.2). Patients with early-onset ANA-positive oligoarticular JIA have the highest risk of developing uveitis. A routine ophthalmological follow-up is required at regular intervals, even though the joint disease is clinically quiescent.

Juvenile idiopathic arthritis-associated uveitis: a retrospective analysis from a centre of South Italy

PurposeTo investigate the clinical and laboratory characteristics of the children affected by juvenile idiopathic arthritis (JIA) who developed uveitis.MethodsIn this retrospective study, we have examined data of 109 patients aged from 3 to 16 years, affected by JIA and followed at Paediatrics Rheumatology Clinic and Ophthalmology Clinic of University Hospital of Messina in the period from 2007 to 2017. The main outcome measures were clinical and laboratory findings related to JIA and ocular involvement. The prevalence of ocular signs and symptoms was determined and correlated with age.ResultsTwenty-one (19.3%) subjects developed uveitis. Two different peaks of age with ocular involvement were registered. The first occurred between 4 and 6 years and the second between 10 and 12 years. All subjects in the first group resulted to be female, presented oligoarticular arthritis and chronic anterior uveitis. In the second group, the 84% of patients were male with different types of JIA and acute anterior uveitis. The prevalence of ocular complications was higher in the first group.ConclusionsTwo peaks of age emerged and were characterized by different clinical outcomes of arthritis and ocular involvement. The first occurred between 4 and 6 years and interested females affected by oligoarticular JIA who develop chronic anterior uveitis. The second appeared at 10–12 years and interested older males affected by different types of JIA with acute anterior uveitis. Early diagnosis and cooperation between paediatric rheumatologist and ophthalmologist are of great importance in the proper management of JIA children with uveitis.

Visual Function And Quality Of Life In A Cohort Of Swedish Children With Juvenile Idiopathic Arthritis.

PurposeTo evaluate quality of life (QoL) in children with juvenile idiopathic arthritis (JIA).MethodsForty children with a mean age of 7.9 years were included. The children underwent an ophthalmological examination and completed questionnaires on physical function (CHAQ) and vision-related (VR) QoL (EYE-Q).ResultsNo differences regarding visual acuity (VA), refraction, intraocular pressure or physical or VRQoL were found between those with JIA without (n=33) and those with JIA-associated uveitis (n=7). When comparing physical function measured by CHAQ disability index and JIA subtype, a difference was found; children with polyarthritis scored the worst (p=0.0098). Children with subnormal VA scored worse on EYE-Q compared with those with normal VA (p=0.013). We found correlations between duration of JIA and CHAQ disability index (r=−0.42, p=0.0007) and CHAQ well-being (r=−0.34, p=0.022).ConclusionThis study indicates the importance of measuring not only physical function but also VRQoL in children with JIA and JIA-associated uveitis.

Areas of agreement in the management of childhood non-infectious chronic anterior uveitis in the UK

Background/aimsThere is a paucity of high-level evidence to support the management of childhood uveitis, particularly for those children without juvenile idiopathic arthritis uveitis (JIA). We undertook a modified Delphi consensus...

Vitamin D deficiency is associated with higher disease activity and the risk for uveitis in juvenile idiopathic arthritis - data from a German inception cohort

ObjectiveThe objective was to evaluate the 25(OH) vitamin D (25(OH)D) status of patients with juvenile idiopathic arthritis (JIA) and determine whether the 25(OH)D level is associated with disease activity and the course of JIA.MethodsPatients ≤ 16 years of age with recently diagnosed JIA (< 12 months) were enrolled in the inception cohort of patients with newly diagnosed JIA (ICON), an ongoing prospective observational, controlled multicenter study started in 2010. Clinical and laboratory parameters were ascertained quarterly during the first year and half-yearly thereafter.Of the 954 enrolled patients, 360 patients with two blood samples taken during the first 2 years after inclusion and with follow up of 3 years were selected. The serum 25(OH)D levels were determined and compared with those of subjects from the general population after matching for age, sex, migration status and the month of blood-drawing.ResultsNearly half of the patients had a deficient 25(OH)D level (< 20 ng/ml) in the first serum sample and a quarter had a deficient level in both samples. Disease activity and the risk of developing JIA-associated uveitis were inversely correlated with the 25(OH)D level (β = − 0.20, 95% CI − 0.37; 0.03, hazard ratio 0.95, 95% CI 0.91; 0.99, respectively).ConclusionIn this study, 25(OH)D deficiency was common and associated with higher disease activity and risk of developing JIA-associated uveitis. Further studies are needed to substantiate these results and determine whether correcting 25(OH)D deficiency is beneficial in JIA.

Risk Factors and Biomarkers for the Occurrence of Uveitis in Juvenile Idiopathic Arthritis: Data From the Inception Cohort of Newly Diagnosed Patients With Juvenile Idiopathic Arthritis Study.

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.

Differentiated Approach to the Surgical Treatment of Chronic Uveitis in Juvenile Idiopathic Arthritis

The purposeis to analyze the results of complex treatment of chronic uveitis in juvenile idiopathic arthritis.Patients and methods. The study included 26 children (46 eyes) with uveitis associated with JIA aged from 5 to 16 years. All children underwent a comprehensive ophthalmological examination. The patients were divided into 3 groups. The first group included children with anterior uveitis (18 eyes), 3 eyes had iridocyclitis without changing of optical media transparency; precipitates on the endothelium in combination with the rear adhesions and complicated cataract were revealed in 15 eyes. The second group included children with middle and posterior uveitis (12 eyes), where effusion into the vitreous in combination with retinal edema in macular area were shown. The third group included children with panuveitis (16 eyes), where ribbon-like corneal dystrophy in combination with the rear adhesions, complicated cataract, and pericardial effusion of varying severity in the vitreous body traction syndrome, macular edema were revealed. Treatment tactics in each group depended on the characteristics of the pathological process.Results. In the first group, visual acuity in the postoperative period was 0.5–0.8. In the second group, after the conservative drug anti-inflammatory treatment, the pathological process subsided and visual acuity increased up to 0.6–0.8 in 4 eyes. In 3 eyes with a pronounced traction component on the periphery and the presence of vitreomacular traction syndrome, where vitrectomy was performed, visual acuity was 0.3–0.5. After intravitreal “Ozurdex” implantation (5 eyes), diffuse macular edema decreased and visual acuity increased up to 0.7–0.8. In the third group, in cases of intense opacity of the vitreous body due to exudative effusion, a 3-port 25–27G vitrectomy with silicone oil tamponade was performed. Visual acuity after the surgery varied from 0.2 to 0.5.Conclusion. High functional results in children with uveitis associated with JIA were achieved due to modern methods of preoperative diagnosis, advanced surgical techniques, as well as proper management of the patients in the postoperative period.

Comparison of uveitis in the course of juvenile idiopathic arthritis with isolated uveitis in children - own experiences.

ObjectivesUveitis and juvenile idiopathic arthritis (JIA) relatively often coexist. Inflammatory changes in the anterior segment of the eye are the most common extra-articular symptom in children with JIA, and JIA is, in turn, the main systemic cause of anterior uveitis in children. The aim of our study was to compare the course of anterior uveitis accompanying JIA and isolated uveitis.Material and methodsWe analyzed 25 children with JIA and uveitis (group I) and 28 children with isolated uveitis (group II). The study population was retrospectively selected from the patients treated in our center in the years 1998–2016 through a search of the hospital database. All data were presented as descriptive statistics.ResultsIn group I there was a higher percentage of girls than in group II (64% vs. 50%) and uveitis occurred at a significantly younger age (8.7 years vs. 11.6). Patients from group I more often presented with immunological abnormalities (positive antinuclear antibodies or HLA-B27 antigen). The majority of children from group I developed uveitis prior to (44%) or simultaneously with (20%) arthritis. In patients who first presented with uveitis, arthritis appeared on average after 28 months (median 12 months). In children in whom arthritis developed first, uveitis appeared on average after 51 months (median 36 months). In some patients the time interval between the involvement of these two organs was as long as 9–10 years. Four children from group I and three from group II were qualified for biological treatment.ConclusionsThe results of our analysis indicate the need for constant cooperation between the pediatric rheumatologist and the ophthalmologist. Although the risk of uveitis in JIA decreases with the disease duration, in some cases this complication can develop after many years. Children with present antinuclear antibodies, at younger age and of female gender should be subject to particularly close observation.

Incidence and predictors of Uveitis in juvenile idiopathic arthritis in a Nordic long-term cohort study

BackgroundThe incidence of uveitis associated with juvenile idiopathic arthritis (JIA) varies around the world. Our aim was to investigate the incidence and predictors of uveitis in a Nordic population-based cohort.MethodsConsecutive JIA cases from defined geographical areas in Denmark, Finland, Sweden and Norway with disease onset between January 1997 to June 2000 were followed for median 98 months in this prospective longitudinal cohort study. Potential clinical and immunological predictors of uveitis were identified with logistic regression analysis.ResultsUveitis occurred in 89 (20.5%) of the 435 children with regular ophtalmologic follow-up among the 500 included. Chronic asymptomatic uveitis developed in 80 and acute symptomatic uveitis in 9 children. Uveitis developed at a median interval of 0.8 (range − 4.7 to 9.4) years after onset of arthritis. Predictors of uveitis were age < 7 years at JIA onset (Odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5), presence of antihistone antibodies (AHA) > 15 U/ml (OR 4.8 (1.8 to 13.4)) and antinuclear antibodies (ANA) (OR 2.4 (1.5 to 4.0)). Mean combined IgM/IgG AHA was significantly higher in the uveitis group (19.2 U/ml) than in the non-uveitis group (10.2 U/ml) (p = 0.002). Young age at JIA onset predicted uveitis in girls (p < 0.001), but not in boys (p = 0.390).ConclusionEarly-onset arthritis and presence of AHA in girls, as well as presence of ANA in both genders, were significant predictors of chronic uveitis. The high incidence of uveitis in this long-term Nordic JIA cohort may have severe implications in a lifelong perspective.

Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis

To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment. A retrospective, multicenter, cohort study. Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43). Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

Cytokine profile changes in children with juvenile idiopathic arthritis-associated uveitis

to identify the differences between serum cytokine profiles in juvenile idiopathic arthritis (JIA) with or without uveal tract inflammation. Serum cytokine profiles were studied in two groups of patients: 20 children with JIA and JIA-associated uveitis and 33 children, who had no signs of uveitis under basic therapy for their JIA. All the patients showed drug remission of articular syndrome. Inflammation of the choroid took the form of chronic anterior uveitis. The process was active in 95% of cases. The control group consisted of 35 children without rheumatic disease or other acute condition at the time of examination. Groups were comparable in terms of age and sex. Serum levels of TNF-α, IFN-γ, IL-17, IL-10 were measured by the enzyme multiplied immunoassay technique. A statistically significant increase in TNF-α, IFN-γ, IL-17, and IL-10 levels was found in all patients as compared to the control group. A comparison drawn between serum cytokine levels of JIA patients and those, who also suffered from JIA-associated uveitis, revealed a decrease in IFN-γ and an increase in IL-10 in the latter group. There was also a statistically significant positive correlation between TNF-α and IFN-γ serum levels in patients with JIA-associated uveitis. Development of uveitis in patients with drug remission of JIA occurs on the background of cytokine imbalance in the serum, in particular, increased concentrations of proinflammatory TNF-α and IL-17 cytokines along with reduced IFN-γ and increased IL-10 levels. This may be regarded as risk factors for ocular inflammation and should be taken into account when making treatment decisions.

Evidence for Tocilizumab as a Treatment Option in Refractory Uveitis Associated with Juvenile Idiopathic Arthritis.

To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy. A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit. TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.

Association of TRAF1-C5 with risk of uveitis in juvenile idiopathic arthritis

ObjectivesNumerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. MethodsSNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30. We retrospectively included 104 JIA patients, fulfilling the ILAR classification criteria. Association between SNPs and JIA clinical subtypes, the presence of ANA, risk of uveitis and age at onset was evaluated using a Chi2 test or a Fischer test. ResultsNo associations between different clinical subtypes as well as presence of ANA and the 6 SNPs were found. However, the AA genotype of TRAF1-C5 appeared associated in a subgroup of patients with uveitis in oligoarticular and polyarticular forms [OR 3.77 (95% CI: 1.1067, 12.8527); P=0.066]. Furthermore, AA TRAF1-C5 was significantly more frequent in antinuclear antibodies (ANA) positive patients presenting uveitis, compared to patients without uveitis and without ANA (P<0.05). ConclusionTRAF1-C5 genotype could identify JIA patients with a risk to develop uveitis especially in oligo and polyarticular forms and among ANA-positive children. Given the moderate size of our cohort, this association has to be confirmed in other studies.

Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis

Background/aimsTo evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis.MethodsEight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate...

Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis

Objectives: Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy.Method: A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution.Results: A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26–167) months; LEF was given for a median of 12 (range 4–47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008).Conclusions: Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

Erythrocyte Sedimentation Rate as Baseline Predictor for the Development of Uveitis in Children With Juvenile Idiopathic Arthritis

To analyze inflammatory parameters as possible predictors for the development of uveitis in juvenile idiopathic arthritis (JIA) patients. Further, to analyze the predictive value of demographic and clinical factors at the onset of arthritis. Retrospective cohort study. In 358 children with oligoarthritis and rheumatoid factor-negative polyarthritis, erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, presence of antinuclear antibodies (ANA), presence of human leukocyte antigen (HLA-)B27, age of onset of JIA, and sex were analyzed for their predictive value for the onset of uveitis. One hundred forty-seven patients (41%) were diagnosed with chronic anterior uveitis. Young age of onset, presence of ANA, and elevated ESR appeared to be predictive factors according to univariate analyses (P = .029, P = .007, and P = 5E(-4), respectively). According to multivariate analysis, young age of onset and elevated ESR appeared to be predictive after adjusting for the other relevant factors (P = .004 and P = .001, respectively). A prediction model was developed. Elevated ESR appears to be a predictor for the occurrence of uveitis in patients with JIA. Since ESR is already routinely tested in patients with recently diagnosed arthritis, its use as a biomarker can easily be implemented in daily practice.

Histone antibodies as a biomarker of uveitis in JIA

Uveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA). The nature of JIA-associated uveitis is often insidious and asymptomatic, and baseline predictors can aid early diagnosis of eye disease for prompt and adequate treatment. Antihistone antibodies (AHA) are among subtypes of antinuclear antibodies (ANA) identified in children with JIA. An association between early-onset JIA, oligoarthritis and uveitis is shown in some studies, and we have previously shown that AHA is a significant predictor of chronic uveitis in a Norwegian JIA cohort. New interest for histones has emerged because epigenetic alterations of these DNA-binding molecules may be involved in the pathological processes of autoimmunity.

TNF inhibitors in the treatment of uveitis in the course of juvenile idiopathic arthritis

Uveitis is the most common extraarticular complication of juvenile idiopathic arthritis (JIA). TNF inhibitors are a promising new therapeutic option in the treatment of chronic uveitis in JIA.

Autoantibodies Predictive of Uveitis in Juvenile Idiopathic Arthritis (Aperture): a proof of concept study

Method: Nucleic Acid Programmable Protein Array (NAPPA) enables the production of multiple proteins from DNA templates which are immobilized on a solid phase. These can then be probed for the presence of autoantibodies in patient’s serum. NAPPA slides with 2200 genes were produced. PubMed search identified ∼60 genes associated with uveitis pathology and ∼30 genes associated with arthritis development. The remaining ∼2100 genes were randomly identified from a ∼12 000 human gene collection (http://dnasu.asu.edu) (Fig. 1). The arrays were then probed using plasma from JIA patients with (n = 20) and without uveitis (n = 20) and from healthy age and sex matched controls (n = 20). Results: Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. Differences in the levels of potential autoantibodies were revealed between JIA patients with and without uveitis. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. Conclusion: The NAPPA platform has the potential to identify novel autoantibodies that robustly forecast the development of uveitis in children with Juvenile idiopathic arthritis. This predictive tool could enable the development of a more appropriate, effective and efficient clinical management algorithm.

Pathophysiology of JIA-associated Uveitis

Juvenile idiopathic arthritis (JIA)-associated uveitis is an intriguing manifestation of JIA and an important contributor of long-term damage. Its pathophysiology is still poorly understood. This review summarizes current concepts. JIA is both a multifactorial and polygenetic disease. In the past 2 decades, multiple studies have indicated that the genetic contribution to both JIA and JIA-associated uveitis is modest. From an ophthalmological point of view, much of the pathophysiological data is derived from studies in experimental uveitis animal models. The pathophysiology of the arthritic manifestations of JIA has been studied extensively in humans. These studies have focused on the principal cells of the adaptive immune system, in particular different subsets of regulatory and effector T cells, as well as on antigen presenting cells or dendritic cells. With advancing technology and advancing knowledge of the underlying mechanisms of JIA-associated uveitis, new targets for therapy might evolve in the coming years.