Uveitis associated with juvenile idiopathic arthritis

Sen, Ethan S; Dick, Andrew D.; Ramanan, Athimalaipet V

doi:10.1038/nrrheum.2015.20

Cited by 91 publications

(72 citation statements)

References 105 publications

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“…A diagnosis of uveitis is made based on features of inflammation on slit lamp examination. These include cells in the anterior chamber (AC) [35] and AC flare resulting from protein leakage into the AC due to breakdown of the bloodaqueous humour barrier [36]. The SUN criteria provide a grading system for intra-ocular inflammation, which takes into account AC cells, AC flare, vitreous cells, and vitreous haze or debris (Box 2).…”

Section: Diagnosis/screeningmentioning

confidence: 99%

Juvenile idiopathic arthritis-associated uveitis

Sen

Ramanan

2017

Best Practice & Research Clinical Rheumatology

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Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4 + T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.

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Section: Diagnosis/screeningmentioning

confidence: 99%

Juvenile idiopathic arthritis-associated uveitis

Sen

Ramanan

2017

Best Practice & Research Clinical Rheumatology

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“…The prognosis is still poor because of frequent sight-threatening complications. To date, chronic JIA-associated uveitis represents a challenge for pediatric rheumatologists and ophthalmologists because standardization of AU management is still pending, even though an early interdisciplinary approach significantly reduces the risk of severe visual impairment 1 .…”

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confidence: 99%

“…Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children and among its extraarticular manifestations, anterior uveitis (AU) is the most important 1 . The prognosis is still poor because of frequent sight-threatening complications.…”

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confidence: 99%

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

Cecchin

Zannin²,

Ferrari³

et al. 2018

J Rheumatol

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Objective.Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years.Methods.Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics.Results.Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX.Conclusion.At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

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“…об-зор Sen E.S. et al, 2015), показывают, что в целом у 28-67 % детей возникают осложнения [6,84,102], а у 9,2-36 % детей высока вероятность существенно-го ухудшения зрения (< 20/40 оба глаза) [6,14,102] из-за формирования катаракты (20,5 %), глаукомы (18,9 %) и лентовидной кератопатии (15,7 %).…”

Section: таблицаunclassified

Proteomic Profile of Tears for the Diagnosis of Uveitis Associated with Juvenile Idiopathic Arthritis: Setting Targets to Achieve Results

et al. 2017

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The paper presents epidemiologic and pathophysiological aspects of the problem statement for early recognition of Uveitis (Uv) associated with Juvenile Idiopathic Arthritis (JIA) in terms of the proteomic profile of tears as well as the results of an attempt to solve this problem by means of the Tandem Mass-Spectrometry (TMS). The solution of this problem is of the highest relevance due to revolutionary changes in treatment strategies after introducing highly effective biologics. Content analysis of literature reviews reveals the following: 1. the incidence of JIA-Uv in the Northwest Federal District of Russian Federation averages 0.5-0.7 per 100 000 of children with the prevalence being ten-fold higher than incidence, 2. without Methotrexate treatment 4-7 years after the diagnosis of JIA-Uv cataract is revealed in 35-40% of children and in 5% – glaucoma as well, 3. even with Methotrexate in 28-40% of children the complications of JIA-Uv inevitably will be revealed with blurred vision in 10-36% of children, 4. timely diagnosis of JIA-Uv and adequate treatment reduce the risk of complications by 4% per year, 5. current medical care system reveals in one third of children already the complications of JIA-Uv. Revelation in tears of the motif mode for protein interaction network, triggering mobilization/inhibition of cells which moderate Uv would contradict the traditional point of view on existing natural anatomic and physiologic barriers, isolating the intraocular space, but however seems to be possible since JIA is a systemic disease and Uv leads to damage of the blood-retinal barriers. To reveal protein biomarkers of JIA-Uv tears of 31 children aged 2-17 years were studied: 17 – chronic JIA-Uv, 4 – JIA without Uv, 4 – idiopathic Uv, 3 – systemic vasculitis, 3 – healthy children. We used the current clinical guidelines and standards to diagnose the pathology and TMS with hierarchical clustering methodology for protein identification: nano C18 column attached to Shimadzu nano LC coupled in-line to LTQ Orbitrap XL tandem mass spectrometer, data-dependent 4-event scan method, a survey FT-MS parent scan followed by sequential data dependent FT-MS/MS scans on the three most abundant peptide ions. Proteins were identified from the mass spectra results with Proteome Discoverer 1.2 software for protein database search using the International Protein Index (IPI) and Human Protein Database. Quantification was conducted using SIEVE 2.0 after normalization to albumin keeping in mind the validity of proportional change of its concentration after stimulation of lacri-mation. Data from SIEVE were exported to IPA (Ingenuity Pathway Analysis) for filtering. The extracellular proteins selected in Ingenuity were further analyzed for disease relation and networks formation. TMS revealed more than 3000 proteins in tears and 300 of them have been considered to be the first row candidates to be biomarkers of JIA-Uv. The top two proteins, lactoferrin and lipocalin were upregulated over ten-fold in children with Uv. Pathway analysis placed these proteins into the inflammation-related IL-1 and TNF-α related networks which also included proteins involved in the development of endothelial dysfunction, inflammation and retinopathy. In addition, IL-23, which was previously linked to Uveitis, was found to be upregulated. Taken together, our proof-of-principle study presents a novel and yet untested approach for detection of early biomarkers of Uveitis and identified several candidate proteins.

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Uveitis associated with juvenile idiopathic arthritis

Cited by 91 publications

References 105 publications

Juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis-associated uveitis

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

Proteomic Profile of Tears for the Diagnosis of Uveitis Associated with Juvenile Idiopathic Arthritis: Setting Targets to Achieve Results

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