Tubulointerstitial nephritis and uveitis in Northern Ireland

Objectives This paper looks at patients with a diagnosis of tubulointerstitial nephritis and uveitis (TINU) presenting to the Northern Ireland regional adult and paediatric uveitis service in the Belfast Health and Social Care Trust. The demographic distribution, treatment required and the visual and renal outcomes of these patients are documented. Methods Data were collected retrospectively on 24 patients with TINU using the Northern Ireland Electronic Care Record, central pathology records alongside the adult and paediatric uveitis databases from 2011 to 2021. Patients were categorised into two groups using the Mandeville classification system. Standard Uveitis Nomenclature (SUN) was used to classify the uveitis. Results The population prevalence is at least 12.6 cases per million based on a population of 1.9 million. Nineteen of 24 cases were definite TINU and five of 24 probable. Seventeen out of 24 had biopsy-positive TIN, all of which met all of the Mandeville clinical diagnostic features required for a definite diagnosis. All but one presented with acute bilateral anterior uveitis. The paediatric cases ranged from age 12 to 18 at age of onset with a mean age of 14. Of the 18 adult onset cases, the age ranged from 20 to 76 years. The mean age of onset for the adult cases was 53 years. Of these patients 71% were female; 42% required second-line immunosuppression for ocular disease. Visual acuity was maintained. Follow-up time ranged from 3 months to 16 years. No patient developed long-term renal impairment. Conclusions TINU is a cause of uveitis in both the paediatric and adult populations. In Northern Ireland average age with TINU was older than much of the published literature. Long-term immunosuppression for uveitis may be required as ongoing ocular, rather than renal inflammation seemed to require treatment.

Paediatric cataract in the uveitis setting

Background/aims: Cataract formation is common in uveitis and is visually more threatening in the paediatric cohort due to the risk of amblyopia. In addition, paediatric uveitis can often be difficult to manage. We report our experience with IOL placement in cataract surgery in the setting of paediatric uveitis. Methods: This non-comparative, retrospective interventional case series examined our cases of paediatric cataract occurring in patients with uveitis from 2003 to 2016. Parameters examined included visual acuity (VA), underlying diagnosis, immunosuppression status, intra-operative complications and requirement for further surgery. Results: In total, 10 eyes of seven patients were identified. The mean age at diagnosis of uveitis was 7.7 years (range 5.2–14 years) with onset of cataract at a mean of 29.3 months later (range 0–66 months). Three cases were bilateral and four cases were unilateral. Final visual outcomes were excellent with 80% showing improvement in VA achieving greater than 6/9.5 ( p < 0.05). These patients had significant co-morbidities with concurrent glaucoma, band keratopathy and cystoid macular oedema. Uveitis was quiet for a minimum of 6 months in all cases prior to surgery with augmentation of immunosuppression pre-operatively as well as intra-operative local or intra-venous steroids. Tight post-operative care was necessary as 80% developed further flare-up of uveitis requiring increased immunosuppression and surgical interventions to manage their uveitis. Conclusion: Paediatric uveitis patients who develop cataract can have good visual outcomes with IOL insertion at the time of surgery when there is aggressive control of uveitis in the pre, peri and post-operative period.

P19 Mycophenolate mofetil in paediatric uveitis: an early experience

Background Juvenile idiopathic arthritis (JIA) is the commonest cause of uveitis in children. Uveitis is a significant cause of visual impairment in children with potential complications such as band keratopathy, cataract, posterior synechiae, glaucoma, cystoid macular oedema and a retinal problems. Following the initial treatment with topical and systemic corticosteroids, a wide variety of immunosuppressant agents have been used in the treatment of non-infective uveitis including methotrexate (MTX) and biologic therapy, most of which are administered parenterally. Mycophenolate Mofetil (MMF) is an oral immunosuppressant that inhibits the proliferation of T and B lymphocytes, which has been tried in children with uveitis with mixed results. We started using MMF in children seen in our paediatric uveitis clinic initially as a third line agent when the inflammation is not well controlled despite therapeutic doses of MTX and Adalimumab, as the NHS England Clinical Commissioning Policy does not recommend the use of Infliximab in uveitis not associated with JIA. Buoyed by some favourable result, we have since then used MMF as second line and even first line agent in children with uveitis. Methods Retrospective analysis of the clinical profile of children with uveitis on MMF at a tertiary paediatric rheumatology centre with focus on response to treatment. Results Of the 8 patients who received MMF, six (75%) were girls. Half of them (4/8) had idiopathic uveitis and the rest, associated with JIA. 2/8 patients had MMF as third line agent on top of MTX and Adalimumab, while five of them had it as second line agent on top of Adalimumab due to either MTX intolerance or needle phobia. One patient was started on MMF as first line agent following topical steroids. 6 (75%) of the patients responded/stayed in remission following the addition of/switch to MMF. Conclusion MMF has shown initial promise in the treatment of uveitis in children with uveitis in this small cohort, in line with some existing evidence. It was initially used in patients who were not keen on injections/intolerant to MTX or had failed all existing options. This is a small cohort of patients and we would welcome more research in this area. Conflicts of Interest The authors declare no conflicts of interest.

An update on the modern management of paediatric uveitis

Uveitis in children and young people (CYP) is often painless, chronic and persistent. It is an often silent blinding condition. Uveitis can be isolated or develop as a manifestation of a systemic disease. Due to the symptomless nature, it can present late with advanced ocular comorbidities such as band keratopathy, hypotony, cataracts. Inadequate control of the eye inflammation can result in permanent and severe ocular complications, structural damage and visual loss. One of the most common systemic associations is juvenile idiopathic arthritis where uveitis has a cumulative incidence of approximately 10%–14% (though wide variation in incidence is reported) after 5 years. Appropriately targeted uveitis screening is recommended to continue for at least 7 years in some subgroups. Paediatric uveitis poses multiple diagnostic and therapeutic challenges. Clinical manifestation and disease course may differ significantly from adult-onset uveitis. However, some CYP are still managed by adult specialists alone, without the opportunity for the prompt use of National Health Service England approved therapy. Optimal management of paediatric uveitis requires a multidisciplinary approach involving coordinated working of different specialities and healthcare professionals. This article highlights the evidence-based practice for the contemporary management of paediatric uveitis to readers in different specialities who may come across this condition. It raises awareness of early systemic treatment aiming to achieve early and complete disease inactivity thereby improving the chances of a long-term positive outcome.

Association of toll-like receptor 10 polymorphisms with paediatric idiopathic uveitis in Han Chinese

AimsWe aimed to determine whether paediatric idiopathic uveitis (PIU) and juvenile idiopathic arthritis associated paediatric uveitis (JIA-PU) have an association with Toll-like receptor 10 (TLR10) gene polymorphisms in Han Chinese.MethodsTen tag single nucleotide polymorphisms (SNPs) of TLR10 were analysed in 992 PIU patients, 127 JIA-PU patients and 1600 controls using the Sequenom MassARRAY system and iPLEX Gold assay. Genotype and allele frequencies were analysed using the χ2 test. A stratified analysis was performed according to the clinical features of PIU.ResultsIncreased frequencies of the rs2101521 A allele, rs10004195 A allele, rs11725309 CC genotype and rs6841698 AA genotype were found in PIU patients compared with controls (corrected p values (Pc)=1.81×10-4, Pc= 1.12×10-2, Pc=2.41×10-2 and Pc=3.29×10-3, respectively). There was no association between these 10 tag SNPs and JIA-PU. In the stratified analysis, the frequency of the rs6841698 A allele was higher in PIU patients with cataract (Pc=1.45×10-6). The frequencies of the rs2101521 A allele and rs6841698 AA genotype were increased in PIU patients with band keratopathy (BK) (Pc=2.32×10-2, Pc=3.30×10-3, respectively).ConclusionTLR10 gene polymorphisms (rs2101521, rs10004195, rs11725309 and rs6841698) confer susceptibility to PIU in Han Chinese. In a stratified analysis, rs2101521 and rs6841698 are associated with PIU with BK, and rs6841698 correlates with PIU with cataract.

Genetic aspects of idiopathic paediatric uveitis and juvenile idiopathic arthritis associated uveitis in Chinese Han

BackgroundIdiopathic paediatric uveitis (IPU) and juvenile idiopathic arthritis associated uveitis (JIA-U) are the two most common entities in paediatric uveitis. This study addressed the possible association of IPU and JIA-U with genes that had been shown earlier to be associated with juvenile idiopathic arthritis.MethodsWe carried out a case-control association study involving 286 IPU, 134 JIA-U patients and 743 healthy individuals. A total of 84 candidate single nucleotide polymorphisms (SNPs) in 60 genes were selected for this study. The MassARRAY platform and iPLEX Gold Genotyping Assay was used to genotype 83 candidate SNPs and the remaining SNP (rs27293) was analysed using the TaqMan SNP Genotyping Assay.ResultsNo evidence was found for an association of the candidate polymorphisms tested with IPU. Six SNPs (PRM1/rs11074967, JAZF1/rs73300638, IRF5/rs2004640, MEFV/rs224217, PSMA3/rs2348071 and PTPN2/rs7234029) showed an association with JIA-U (p<1.0×10−2).ConclusionOur findings showed associations of six SNPs (PRM1/rs11074967, JAZF1/rs73300638, IRF5/rs2004640, MEFV/rs224217, PSMA3/rs2348071 and PTPN2/rs7234029) with JIA-U. No association was detected between the 84 tested SNPs and IPU.