Objective To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA). Methods Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong. Results Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss. Conclusion This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.

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2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis

To present our preliminary experience with JAK inhibitors in treating patients affected by juvenile idiopathic arthritis (JIA) and associated uveitis. Case series. Four consecutive patients with long-term history of juvenile idiopathic arthritis and severe associated uveitis were included in the study. Indication for treatment with JAK inhibitors was uncontrolled arthritis and/or uveitis despite different treatments with conventional and biologic disease modifying antirheumatic drugs (DMARDs). While on treatment with JAK inhibitors, namely, baricitinib (three cases) and tofacitinib (one case), all our patients showed improvement of uveitis defined as a reduction of intraocular inflammation according to Standardized Uveitis Nomenclature criteria. However, we observed a different response to treatment between the uveitis and the articular disease, as the latter did not respond as favorably as the former. Overall, the treatment was well tolerated by all patients and no ocular discomfort, ocular side effects, or allergic reactions were registered. JAK inhibitors may provide a new valuable treatment option in the therapeutic armamentarium for patients affected with JIA-associated uveitis, particularly in those refractory cases that are not adequately responding to conventional or biologic DMARDs.Key Points• A subset of patients with JIA uveitis either remain unresponsive or experience loss of efficacy• JAK inhibitors may provide a new valuable treatment option in JIA patients with uveitis• The safety profile was good with no occurrence of systemic side effects.

JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common inflammatory joint condition of childhood and represents seven JIA subtypes characterised by distinct clinical and laboratory variables. Genetic and environmental factors are known to influence JIA, although many unanswered questions remain. Measurement of health outcomes in JIA is imperative for both clinical practice and research. Patient-reported outcomes present particular challenges in paediatric rheumatology in view of the importance of collecting reports from both the child/young person and the parent. Another challenge is the need for continuity of outcome measurement across the paediatric-adult interface during the process of transition in terms of both measurement tools and the mechanisms in the system to facilitate tracking of the young person into adult care. Finally, the need for adults with JIA to be seen as a distinct group in adult rheumatology practice is important for both service provision and outcome research.

Update on the epidemiology, risk factors and disease outcomes of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis-associated uveitis.

Background In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians’ experience. Consequently, treatment practices differ widely, within and between nations. Objectives To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. Methods Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). Results In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. Conclusions The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe.

https://ard.bmj.com/content/annrheumdis/77/8/1107.full.pdf

Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative

Objective: Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA, using a genome-wide association study in 522 children with JIA. Methods: Two cohorts of JIA patients with ophthalmologic follow-up data were genotyped. Data were then imputed using a genome-wide imputation reference panel, and an HLA-specific reference panel was used for imputing amino acids and HLA types in the major histocompatibility complex (MHC). After imputation, genome-wide and MHC-specific analyses were performed, and a reverse immunology approach was utilized to model antigen presentation at 13 common HLA–DRβ1 alleles. Results: Presence of the amino acid serine at position 11 (serine 11) in HLA–DRβ1 was associated with an increased risk of uveitis in JIA patients (odds ratio [OR] 2.60, P = 5.43 × 10−10) and was specific to girls (Pfemales = 7.61 × 10−10 versus Pmales = 0.18). Serine 11 resides in the YST motif in the peptide-binding groove of HLA–DRβ1; all 3 amino acids in this motif are in perfect linkage disequilibrium and show identical association with disease. Quantitative prediction of binding affinity revealed that HLA–DRβ1 alleles with the YST motif could be distinguished on the basis of discernable peptide-binding preferences. Conclusion: These findings highlight a genetically distinct, sexually dimorphic feature of JIA with uveitis as compared to JIA without uveitis. The association could be indicative of the potential involvement of antigen presentation by HLA–DRβ1 in the development of uveitis in JIA. The results of this study may advance our progress toward improved treatments for, and possible prevention of, the sight-threatening complications of uveitis in children with JIA.

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Identification of an Amino Acid Motif in HLA-DRβ1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: To establish the impact of uveitis on the Quality of Life (QOL) in adult patients with juvenile idiopathic arthritis (JIA).

METHODS: Adult patients with a history of JIA, with (n=31) or without (n=51) chronic anterior uveitis, were included. Their scores on three validated QOL questionnaires (National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and EuroQol-5D (EQ-5D)) were analyzed to find factors that could influence QOL.

RESULTS: The median overall composite score (OCS) of the NEI VFQ-25 was significantly worse in the uveitis group compared to the non-uveitis group (respectively, 83.4, range 15.2-94.7 and 94.9, range 46.3-100; P < 0.001). Nearly all subscale scores were lower in patients with uveitis than in patients without uveitis (all P < 0.001). After adjusting for duration of arthritis, JIA subtype, arthritis onset before or after 1990, and use of systemic immunomodulatory medication, the QOL was still worse in patients with uveitis (NEI VFQ-25 OCS: Regression coefficient= -11.7, P = 0.002). No significant differences were found between the groups for the SF-36 and the EQ-5D. In the total JIA group, use of systemic medication appeared to negatively influence some general QOL scores.

CONCLUSION: Having a history of uveitis has a substantial negative effect on the vision-related QOL in JIA in adulthood, despite good visual acuity. General QOL scores did not differ between uveitis and non-uveitis patients, but use of systemic immunomodulatory treatment, independent of uveitis, did negatively influence general QOL scores in adult JIA patients. This article is protected by copyright. All rights reserved.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/acr.23224

Anne Mieke J.W. Haasnoot

Papers

Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative

Identification of an Amino Acid Motif in HLA-DRβ1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis.

Impact of Uveitis on Quality of Life in Adult Patients With Juvenile Idiopathic Arthritis.