Uveitis In Juvenile Idiopathic Arthritis Research Articles

Systematic Review on the Effectiveness of Immunosuppressants and Biological Therapies in the Treatment of Autoimmune Posterior Uveitis

To analyze the effectiveness of immunosuppressants and biological therapies in autoimmune posterior uveitis, chronic anterior uveitis associated with juvenile idiopathic arthritis, and macular edema. Systematic review. We conducted a sensitive literature search in Medline (from 1961) and EMBASE (from 1980) until October 2007. Selection criteria were as follows: (1) population: autoimmune posterior uveitis, chronic anterior uveitis in juvenile idiopathic arthritis, and macular edema; (2) intervention: immunosuppressive and biologic therapies; (3) outcomes: visual acuity, Tyndall, vitreous haze, macular edema, pars planitis, and retinal vasculitis. There were no limitations regarding study design. The quality of each study was evaluated using the Jadad's scale and Oxford Levels of Evidence. Two hundred sixty-five articles were selected for detailed review of the 4235 found in the initial search: 128 records were on immunosuppressants, 105 on biological therapies, and 32 on macular edema. Overall, both the immunosuppressive and the biologic therapies appeared effective in the treatment of autoimmune posterior uveitis, except for daclizumab in uveitis related to Behçet's disease, and for etanercept in any uveitis. In the treatment of macular edema, the drugs tested were also effective. Based on the evidence collated, immunosuppressants and biological therapies (except for daclizumab in Behçet and etanercept) may be effective in autoimmune uveitis and macular edema. No superiority may be inferred from this review.

Uveitis Related to Juvenile Idiopathic Arthritis: Familial Cases and Possible Genetic Implication in the Pathogenesis

Purpose: To describe four cases of familial Juvenile Idiopathic Arthritis (JIA) associated uveitis.Design: Retrospective observational case series.Methods: Clinical data from patients who present familial JIA-associated uveitis are described and possible genetic influence in disease etiology is reviewed.Results: Two sisters, 6- and 7-year-old, developed bilateral anterior uveitis related to oligoarticular JIA. Arthritis in both began by the age of 18 months; uveitis developed simultaneously in one of them and less than one year after arthritis in the other one. Both received topical and systemic treatment to control the ocular disease. Glaucoma occurred in both cases and bilateral cataract in one case. In the other family, a 2-year-old girl developed unilateral uveitis in the context of oligoarticular JIA which was diagnosed by 1-year-old. The disease became soon bilateral and she received topical and systemic immunosuppressive treatment. Her mother suffered from bilateral anterior uveitis associated to oligoarticular inflammatory disease during her infancy, later diagnosed as JIA-associated uveitis.Conclusions: Familial cases of JIA uveitis, although not very common, support the possible role of genetic influence in the pathogenesis of the disease, with horizontal and vertical inheritance being possible. The evolution of ocular disease is similar to the non-familial cases, except for an earlier age of onset.

Male Gender and Poor Visual Outcome in Uveitis Associated With Juvenile Idiopathic Arthritis

To analyze visual outcome in uveitis associated with juvenile idiopathic arthritis (JIA) according to age of onset of uveitis, gender, and initial manifestation of JIA. Retrospective nonrandomized interventional case series. Visual outcome of 117 affected eyes (65 patients) with JIA-associated uveitis was noted at onset of uveitis and after 1, 3, and 5 years. Visual outcome was analyzed according to gender, age of onset of JIA-associated uveitis (<7 years and >7 years), and initial manifestation of JIA (as uveitis or as arthritis). Linear and logistic regression with generalized estimating equation (GEE) was performed. Median age of onset of uveitis was 4.2 years (range 1.5-16). Female-to-male ratio was 3:1. In 15 children (23%) uveitis was diagnosed before arthritis. Visual acuity of boys was significantly worse at 1 and 3 years of follow-up (both P <or= .03) but not at 5 years of follow-up (P = .45). Until 3 years after the diagnosis of uveitis, children with atypical initial manifestation of JIA (uveitis before arthritis) had significantly worse visual acuity compared with children in whom uveitis debuted after arthritis (all P <or= .05). No difference in vision between younger-onset (<7 years) and older-onset (>7 years) groups was noted. Blindness was independently associated with male gender (odds ratio [OR] = 6.61; 95% CI: 1.02-42.98; P = .048). Male gender was an independent risk factor for poor visual prognosis in JIA-associated uveitis. Children in whom uveitis is being diagnosed before arthritis have significantly worse vision until 3 years after uveitis onset.

A case note review of uveitis screening of children diagnosed with juvenile idiopathic arthritis

Introduction The prevalence of uveitis in juvenile idiopathic arthritis (JIA) overall is approximately 8–30%, but in young oligoarticular onset group it may be as high as 45–57%. The annual incidence of JIA in the UK is 1:10 000 with a prevalence of 1:1000. The uveitis in JIA is asymptomatic and therefore screening by slit-lamp is essential for diagnosis. Early detection and treatment can prevent the development of complications and can prevent permanent visual impairment. These complications are more frequent and more severe in younger children and are often asymptomatic. British Society for Paediatric and Adolescent Rheumatology and the RCPOphth guideline recommends that, the initial screening examination should occur as soon as possible and no later than 6 weeks from referral. Patients with symptoms or patients suspected of cataracts or synechiae should be seen within a week of referral. Aim To review the referral pattern of children diagnosed with JIA to ophthalmology clinic for uveitis screening and compare it with BSPAR standards Methods A retrospective case note review was performed for 22 patients with JIA attending rheumatology clinic at local district general hospital. Data were collected by reviewing the clinic letters using a proforma for data collection. Results A total of 22 case notes where reviewed. 12 patients were females and 10 males. Diagnoses included six polyarthritis, six oligoarthritis, four enthesitis related arthritis, three psoariatic arthritis, one systemic onset arthritis, two others. Of 22 patients audited 20 patients had uveitis screen, one was never referred and another awaiting to be seen on the date of audit. None of the patients screened had Uveitis. 17 out of 21 patients were referred within 7 days of diagnosis. Number of days from diagnosis to first seen in ophthalmology clinic ranged from 35 to 298 days with a mean of 70.5 days. Out of 20 patients referred to ophthalmology, only two were seen within 6 weeks, thus failing to achieve BSPAR standard. Conclusion Majority of the patients though diagnosed with JIA on the first appointment in rheumatology clinic, experienced delay in being seen in ophthalmology clinic, a few of them had inordinate delay.

The importance of visual function in the quality of life of children with uveitis

Studies of quality of life (QOL) in children with juvenile idiopathic arthritis (JIA) have focused on changes in musculoskeletal function secondary to arthritis. The role of visual functionality as a result of JIA-associated uveitis and its complications has not been examined. We evaluated the individual impact of physical and visual disability on QOL in children with and without uveitis. We administered patient-based questionnaires that measured visual function, physical function, and overall QOL to 27 children with JIA or idiopathic uveitis. Demographic data, assessed joint involvement, and reviewed medical records were recorded. Groups with and without uveitis were compared for differences in arthritis and uveitis disease characteristics with use of the Wilcoxon-Mann-Whitney, chi2, and Fisher exact tests. Associations between physical or visual function, and overall QOL were measured with use of Pearson's correlation coefficient. Of 27 patients, 85.2% had had arthritis and 51.9% had had uveitis. The group without uveitis had increased morning stiffness (p = 0.036). Patients with uveitis reported more eye redness (p = 0.033) and photophobia (p = 0.013) than those without uveitis. We observed moderate associations between overall QOL and visual function in the uveitis group (r = -0.579) and overall QOL and physical function in the nonuveitis group (r = -0.562). This study demonstrates that visual impairment is an important component of QOL in children with uveitis. It suggests that QOL studies should incorporate both visual and physical function measures in their analyses, especially because many children with JIA also suffer from uveitis and visual impairment.

Juvenile Idiopathic Arthritis Associated Uveitis in Adults: A Case Series

Purpose: To report a series of adults with uveitis following juvenile idiopathic arthritis (JIA) and uveitis as children.Methods: The clinical features, treatment, complications, and visual outcome were ascertained for 17 patients at a single centre.Results: Seventeen adults with previously diagnosed JIA and ongoing uveitis (30 eyes) were identified. All required at least topical steroids. The complication rate was high (15 patients, 23 eyes), most frequently cataract (57%), glaucoma (33%), and posterior synechiae (30%). The rate of visual acuity loss to 6/12 threshold (6/12 or worse) for patients with uveitis < 15 years (Group A) was 13.3%, (and 6.7% to 6/60 threshold) and for patients with uveitis >15 years (Group B) was 26.7% (and 20% to 6/60 threshold). Overall, the rate of visual acuity loss to 6/12 threshold was 20% (6 eyes) and to 6/60 threshold, 13.3% (4 eyes).Conclusions: JIA may be associated with ongoing uveitis and complications in adulthood.

Biomarkers of Chronic Uveitis in Juvenile Idiopathic Arthritis: Predictive Value of Antihistone Antibodies and Antinuclear Antibodies

To study the predictive value of antinuclear autoantibody (ANA) tests and antihistone antibodies (AHA) as risk factors for development of chronic asymptomatic uveitis of insidious onset in juvenile idiopathic arthritis (JIA). ANA by indirect immunofluorescence using HEp-2 cells (IF-ANA), ELISA for ANA (E-ANA), and AHA were analyzed in sera of 100 children with recent-onset JIA and in 58 control sera. Clinical features, including age at onset, JIA subgroup, and presence of uveitis, were recorded in this prospective population-based cohort study. E-ANA was positive in 4 of the 100 sera, and was not associated with uveitis. Chronic uveitis developed in 16 children with JIA: in 14 of 68 positive for IF-ANA >/= 80, and in 13 of 44 positive for AHA >/= 8 U/ml. IgM/IgG AHA were found in higher proportions in children with uveitis (mean 12.4 U/ml) than in those with JIA and no uveitis (mean 6.9 U/ml) or in healthy controls (mean 4.3 U/ml). No association was found between E-ANA and uveitis, and most IF-ANA-positive sera were E-ANA-negative. E-ANA is not clinically relevant in this setting and should never be used to determine frequencies of eye examinations to detect new uveitis in JIA. AHA >/= 8 U/ml, IF-ANA titer >/= 320, and young age at onset of arthritis were significant predictors for development of chronic uveitis. The diagnostic value of AHA >/= 8 U/ml as a biomarker of chronic uveitis in JIA is very similar to IF-ANA >/= 80.

TNFα-blocking Agents or Conventional Immunosuppressive Drugs in the Therapy of Children with Uveitis? – An Evidence Based Approach

Treatment of childhood uveitis associated with juvenile idiopathic arthritis (JIA) is a challenge for both, ophthalmologists and pediatricians. In this study, we use the tools of evidence based medicine (EBM) to analyse studies concerning disease-modifying antirheumatic drugs (DMARD)/ immunosuppressive drugs and tumor necrosis factor alpha (TNFalpha) blocking agents. Most experience among DMARD's/ immunosuppressive drugs has been obtained with methotrexate (MTX) in juvenile idiopathic arthritis. However, controlled studies in uveitis are still missing, so that treatment with MTX and all other immunosuppressive drugs (ciclosporine A, azathioprine, mycophenolate mofetil) only reaches an evidence level III (expert opinion, clinical experience or descriptive study). Studies on TNFalpha-blocking agents reach an evidence level II-III, depending on the substance. In future, MTX will have to be examined in comparison to the new biological substance classes (e.g., tumor necrosis factor-alpha-blockers) for the treatment of uveitis in juvenile idiopathic arthritis. Controlled studies which have led to the approval of drugs for JIA are needed for uveitis in order to have the most effective and safe therapy for children with uveitis, who do not respond to conventional therapy with local and systemic steroids.

Retrospective analysis of children with uveitis treated with infliximab

Tumor necrosis factor-alpha (TNF-alpha) antagonists have been successfully used in refractory cases of pediatric uveitis.(1-7) We report our experience with the monoclonal anti-TNF-alpha antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy.

Adalimumab and severe uveitis in juvenile idiopathic arthritis (JIA) therapy

Results When Enbrel plus Methotrexate was started she got into remission. After one year of this therapy, she presented uveitis in both eyes, so oral steroids were started again. She obtained only partial ocular improvement, even when she received Infliximab associated with Methotrexate. Meantime she underwent cataract surgery with visus reduction. After one year, Infliximab was suspended because of an adverse reaction (dyspnea and rash) and Adalimumab (0.7 mg/kg subcutaneous/14 days) associated with Methotrexate was started, with no side effects. Fourteen months later there are no flare for uveitis and/or arthritis. Following SUN criteria [1] we demonstrated ocular clinical improvement, not withstanding the presence of signs of cataract and glaucoma.

Contribution of OCT to evaluate macular disease in JIA associated uveitis

Abstract Purpose To examine the frequency and characteristics of macular lesions observed in Juvenile Idiopathic Arthritis (JIA) uveitis, using Optical Coherence Tomography (OCT). Methods In this cross‐sectional study, 38 consecutive patients were recruited from a tertiary referral center in uveitis. All eyes with JIA uveitis underwent complete ophthalmic examination including OCT 3. Exclusion criterion was the inability to obtain OCT scans. Flare and visual acuity were also analyzed by using linear regression. Results We analyzed foveal thickness (FT) and central foveal thickness (CFT) using the software mapping, to describe macular lesions in 61 eyes. Maculopathy was observed in 51 eyes (84%), compared to 12% in the literature (P&lt;0.0001) and comprised four types: perifoveolar thickening in 45 eyes (74%), macular edema in 29 eyes (48%), foveal detachment in 11 eyes (18%), and atrophic changes in 6 eyes (10%). Only 4 eyes did not demonstrate any lesion. Conclusion Among children with JIA‐uveitis, macular involvement is frequent, and characterized by perifoveolar thickening and serous retinal detachment. OCT is a non‐invasive instrument. It may easily show this maculopathy, which could impair visual function, and conditioned a therapeutic intensification.

Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis

To evaluate the efficacy of adalimumab in juvenile idiopathic arthritis (JIA)-associated uveitis. Retrospective observational study of 20 patients with JIA and chronic uveitis on adalimumab treatment. The ocular inflammation and improvement was assessed according to the Standardization of Uveitis Nomenclature criteria. At the initiation of adalimumab, the mean age of patients was 13.4 yrs and the mean duration of uveitis 8.7 yrs. Seventeen (85%) patients had polyarticular JIA and 19 (95%) had previously been on anti-TNF treatment. The mean duration of adalimumab therapy was 18.7 months. Of the 20 patients, 7 (35%) showed improved activity, 1 (5%) worsening activity and in 12 (60%) no change was observed in the activity of uveitis. Those with improved activity were younger and had shorter disease duration. The mean number of flares/yr decreased from 1.9 to 1.4 during adalimumab treatment. Serious adverse events or side-effects were not observed. Seven patients discontinued adalimumab during the follow-up: six because of inefficacy and one because of inactive uveitis. Adalimumab is a potential treatment option in JIA-associated uveitis, even in patients non-responsive to previous other anti-TNF therapy.

Resolution of Juvenile Idiopathic Arthritis-Associated Uveitis after Development of Common Variable Immunodeficiency

To describe the occurrence of common variable immunodeficiency (CVID) in a patient with juvenile idiopathic arthritis (JIA) and JIA-associated uveitis. Case report. A 29-year-old woman was followed-up since the age of 10 years because of right eye JIA-associated recurrent anterior uveitis. She was treated with steroids and immunosuppressants with good control of uveitis and arthritis. At the age of 17 years, she did not experience any further relapse of uveitis or arthritis and both diseases were considered to be in remission. Concomitantly, she started to have recurrent infections and later she underwent splenectomy because of autoimmune hemolytic anemia and thrombocytopenia. Liver biopsy disclosed granulomatous hepatitis. She was ultimately diagnosed with CVID at the age of 23 years when her blood tests revealed neutropenia and severe panhypogammaglobulinemia. She has been treated since then with intravenous immunoglobulins with good control of the disease. Since the development of CVID, she has had no relapses of uveitis or arthritis during a follow-up period of 12 years. Common variable immunodeficiency (CVID) is the most common primary immunodeficiency where defective antibody formation is the most common feature with B-cell differentiation failure. Ocular complications have been rarely documented and included bacterial conjunctivitis, retinal vasculitis and multifocal choroiditis. We herein report on the occurrence of JIA-associated uveitis as a comorbid manifestation of CVID. We speculate a role for B cells in the pathogenesis of JIA and JIA-associated uveitis here, as this patient had total remission of both conditions with the onset of CVID.

Maculopathy in uveitis of juvenile idiopathic arthritis: an optical coherence tomography study

Aim:The aim of this study was to examine the frequency and characteristics of macular lesions observed in juvenile idiopathic arthritis (JIA) uveitis, using optical coherence tomography (OCT).Methods:In this cross-sectional study,...

EBM Analyse: Klassische DMARDs (Disease modifying antirheumatic drugs) und Immunsuppressiva bei Arthritis und Uveitis

The best experience in the use of DMARDs/immunosuppressive drugs for treatment of juvenile idiopathic arthritis (JIA) and JIA-associated uveitis has been obtained with MTX. Controlled studies on the treatment of uveitis in JIA, however, are still lacking; this is also true for other DMARDs/immunosuppressive drugs. Thus, the grading of the evidence level for these substances only reaches evidence level III (expert opinion, clinical experience or descriptive studies). For the treatment of uveitis in JIA the utility of MTX in comparison to the new biological substance classes (e. g., tumor necrosis factor-alpha, blockers, interleukin-1 receptor antagonist) will have to be examined. Experience with Mycophenolate mofetil (MMF) in JIA uveitis is limited to single cases. According to data from a retrospective analysis cyclosporin A (CsA) appears to have a limited efficacy in JIA uveitis. The results with azathioprine are not consistent. Controlled studies which led to the approval of drugs for JIA are also mandatory for uveitis to offer the most effective and safe therapy for children.

Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide study in Germany: suggested modification of the current screening guidelines

To analyse the prevalence and complications of uveitis and their predictors in a large cohort of patients with juvenile idiopathic arthritis (JIA). Data of 3271 JIA patients as classified by International League of Associations for Rheumatology (ILAR) criteria included in a national database during 1 yr were analysed. Uveitis prevalence was 12% of all JIA patients. The most frequent were oligoarthritis extended (25%) and persistent (16%). JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs 7.0 yrs) or ANA-positive (86% vs 42%) than the patients without uveitis. Predictors of uveitis included age at onset (P= 0.03) and ANA-positivity (P< 0.01) besides the presence of a certain JIA subgroup (P= 0.04). Uveitis was clinically silent in 75% of the oligoarthritis but in none of the enthesitis-related arthritis patients. The median onset of uveitis was 5.5 months after arthritis manifestation. In 73%, 77% and 90%, uveitis developed within 1, 2 and 4 yrs after arthritis, respectively. Anterior uveitis was the most common anatomic type of uveitis (83%). Uveitis complications at mean follow-up of 5.6 yrs were common (56%), and predictors for complications included presence of complications at first visit (P< 0.001) and uveitis manifestation before arthritis (P= 0.001), but not ANA positivity. The JIA subgroups markedly differ with respect to the prevalence and course of associated uveitis. Ophthalmological screening should be initiated early after arthritis onset and the intervals be related to the JIA subgroup. A modification of the current screening guidelines is suggested.

Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: A long‐term followup study

To assess the prevalence, risk factors, and long-term outcome of uveitis in patients with juvenile idiopathic arthritis (JIA). An inception cohort of all 1,081 patients diagnosed as having JIA at a single tertiary care center was established. A questionnaire and followup telephone calls were used to confirm the diagnosis of uveitis. Ophthalmologists' records of patients with uveitis were collected. Kaplan-Meier and Cox regression analyses were used to assess risk factors for developing uveitis and for complications of uveitis. After a mean followup time of 6.9 years, 142 of 1,081 patients (13.1%) had developed uveitis. Risk factors were young age at diagnosis, female sex, antinuclear antibody positivity, and the subtype of JIA. The relative contribution of these risk factors was different for the different subtypes of JIA. Until the end of the study, uveitis complications had developed in 53 of 142 patients with uveitis (37.3%; 4.9% of the total cohort). Only 16 of 175 involved eyes (9.1%) in 14 of 108 patients (13%; 1.3% of the total cohort) for whom ophthalmology reports were available had best corrected visual acuity less than 20/40 (mean followup time for uveitis of 6.3 years). Abnormal vision was associated with synechiae or cataract. Risk factors for developing uveitis were different among subtypes of JIA. The long-term outcome of JIA-associated uveitis in our cohort was excellent despite the high rate of complications.

Association of HLA-DRB1*13 with susceptibility to uveitis in juvenile idiopathic arthritis in two independent data sets

Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease of childhood. Uveitis is the commonest eye complication of JIA, potentially leading to eye surgery and/or visual loss. JIA is a complex genetic trait with well-established HLA-DRB1 associations. The aim of this study was to investigate the involvement of HLA-DRB1 in JIA-associated uveitis. A set of 130 UK Caucasian simplex families consisting of healthy parent(s) and a child affected with juvenile oligoarticular idiopathic arthritis (of which 31 had developed uveitis) had previously been screened for multiple markers in the major histocompatibility complex region. Associations with uveitis were investigated through haplotype pattern mining (HPM) and the extended transmission disequilibrium test (ETDT). A further set of 228 UK Caucasian patients with long-standing JIA were fully genotyped for HLA-DRB1 using PCR with sequence-specific primers. Associations of HLA-DRB1 alleles in patients with uveitis (n = 50) were examined individually using the chi 2 test. In the first cohort, HPM identified significant associations of HLA-DRB1*13 with uveitis in juvenile oligoarthritis (P = 0.002). The ETDT confirmed overtransmission of this allele in the families (empirical global P = 0.018). In the second cohort, the significant association of uveitis with HLA-DRB1*13 was replicated (P = 0.0002, odds ratio 3.4, 95% confidence interval 1.7-6.5). This study has established the HLA-DRB1*13 association with uveitis in JIA. Further work is necessary in order to explore the prognostic potential of this marker.