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Yakovlev AA, Gaidar EV, Sorokina LS, Nikitina TN, Kalashnikova OV, Kostik MM. Uveitis associated with juvenile idiopathic arthritis and chronic idiopathic uveitis in children: A retrospective cohort study. World J Clin Pediatr 2025; 14:100336. [DOI: 10.5409/wjcp.v14.i2.100336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 01/26/2025] [Accepted: 02/17/2025] [Indexed: 03/18/2025] Open
Abstract
BACKGROUND Chronic idiopathic uveitis (CIU) and juvenile idiopathic arthritis-associated uveitis (U-JIA) are both vision-threatening conditions that share similar autoimmune mechanisms, but treatment approaches differ significantly. In managing U-JIA, various treatment options are employed, including biological and non-biological disease-modifying anti-rheumatic drugs. These drugs are effective in clinical trials. Given the lack of established diagnostic and treatment guidelines as well as the limited number of therapeutic options available, patients with CIU frequently do not receive optimal and timely immunosuppression. This study highlighted the necessity for additional research to develop novel diagnostic techniques, targeted therapies, and enhanced treatment outcomes for young individuals with CIU.
AIM To compare the characteristics and outcomes of U-JIA and CIU.
METHODS A retrospective cohort study analyzed data from 110 pediatric patients (under 18 years old) with U-JIA and 40 pediatric patients with CIU. Data was collected between 2012 and 2023. The study focused on demographic, clinical, treatment, and outcome variables.
RESULTS The median onset age of arthritis was 6.4 years (2.7 years; 9.3 years). In 28.2% of cases uveitis preceded the onset of arthritis. In 17.3% of cases it occurred simultaneously. In 53.6% of cases it followed arthritis. Both groups had similar onset ages, antinuclear antibodies/human leukocyte antigen positivity rates, and ESR levels, with a slight predominance of females (60.9% vs 42.5%, P = 0.062), and higher C-reactive protein levels in the U-JIA group. Anterior uveitis was more prevalent in patients with U-JIA (P = 0.023), although the frequency of symptomatic, unilateral, and complicated forms did not differ significantly. The use of methotrexate (83.8% vs 96.4%) and biologics (64.7% vs 82.1%) was comparable, as was the rate of remission on methotrexate treatment (70.9% vs 56.5%) and biological therapy (77.8% vs 95%), but a immunosuppressive treatment delay in CIU observed. Patients with CIU were less likely to receive methotrexate [hazard ratio (HR) = 0.48, P = 0.005] or biological treatment (HR = 0.42, P = 0.004), but they were more likely to achieve remission with methotrexate (HR = 3.70, P = 0.001).
CONCLUSION Treatment of uveitis is often limited to topical measures, which can delay systemic therapy and affect the outcome. Methotrexate and biological agents effectively manage eye inflammation. It is essential to develop standardized protocols for the diagnosis and management of uveitis, and collaboration between rheumatologists and ophthalmologists is needed to achieve optimal outcomes in the treatment of CIU.
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Affiliation(s)
| | | | - Lyubov Sergeevna Sorokina
- Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Russia
| | - Tatiana Nikolaevna Nikitina
- Department of Ophthalmology, Saint-Petersburg State Pediatric Medical University, Saint Petersburg 194100, Russia
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Acharya NR, Ramanan AV, Coyne AB, Dudum KL, Rubio EM, Woods SM, Guly CM, Moraitis E, Petrushkin HJD, Armon K, Puvanachandra N, Choi JT, Hawley DP, Arnold BF. Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial. Lancet 2025; 405:303-313. [PMID: 39863370 DOI: 10.1016/s0140-6736(24)02468-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 10/19/2024] [Accepted: 11/04/2024] [Indexed: 01/27/2025]
Abstract
BACKGROUND Adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. Data are scarce on the effects of discontinuing adalimumab after control of the disease had been reached. We aimed to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis. METHODS We conducted a multicentre, double-masked, randomised, placebo-controlled trial at 20 ophthalmology and rheumatology clinics across the USA, the UK, and Australia. Patients aged at least 2 years who had controlled arthritis and uveitis for at least 1 year on adalimumab were randomly assigned in a 1:1 ratio using a web-based system to receive adalimumab or placebo, administered subcutaneously every 2 weeks until the 48-week visit or treatment failure. The primary outcome was the time to treatment failure, defined by recurrence of uveitis or arthritis; all participants were included in the primary and safety analysis. Unmasking occurred at treatment failure, and patients were offered open-label adalimumab through 48 weeks of follow-up. This trial was registered with ClinicalTrials.gov (NCT03816397). FINDINGS 87 patients were enrolled from March 3, 2020, to Feb 14, 2024, whereafter the prespecified interim stopping criteria were met and enrolment was stopped. One patient in each group dropped out but data were included in analyses. Six (14%) of 43 patients in the adalimumab group and 30 (68%) of 44 patients in the placebo group had treatment failure (hazard ratio 8·7, 95% CI 3·6-21·2; p<0·0001). The median time to treatment failure in the placebo group was 119 days (IQR 84-243). The median time to re-establishing sustained control of inflammation in the placebo group after restarting adalimumab was 105 days (63-196). 226 non-serious adverse events occurred in the adalimumab group (7·5 events per person-year, 95% CI 6·5-8·5), and 115 non-serious adverse events occurred in the placebo group (6·8 events per person-year, 5·6-8·1). Four serious adverse events were reported, all in the adalimumab group. INTERPRETATION Discontinuing adalimumab led to higher rates of recurrence of uveitis, arthritis, or both in patients with previously controlled juvenile idiopathic arthritis-associated uveitis. However, all patients who had treatment failure successfully regained control of inflammation by the end of the 48-week study period after restarting adalimumab. FUNDING US National Institutes of Health (National Eye Institute).
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Affiliation(s)
- Nisha R Acharya
- Francis I Proctor Foundation, University of California San Francisco, San Francisco, CA, USA; Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Institute for Global Health Sciences, University of California San Francisco, San Francisco, CA, USA.
| | - Athimalaipet V Ramanan
- Department of Paediatric Rheumatology, Bristol, UK; Translational Health Sciences, University of Bristol, Bristol, UK
| | - Alison B Coyne
- Francis I Proctor Foundation, University of California San Francisco, San Francisco, CA, USA
| | - Kathryn L Dudum
- Francis I Proctor Foundation, University of California San Francisco, San Francisco, CA, USA
| | - Elia M Rubio
- Francis I Proctor Foundation, University of California San Francisco, San Francisco, CA, USA
| | - Sydney M Woods
- Francis I Proctor Foundation, University of California San Francisco, San Francisco, CA, USA
| | - Catherine M Guly
- Bristol Royal Hospital for Children, Bristol, UK; Bristol Eye Hospital, Bristol, UK; University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Elena Moraitis
- Rheumatology Department, Great Ormond Street Hospital NHS Foundation Trust, London, UK
| | - Harry J D Petrushkin
- Rheumatology Department, Great Ormond Street Hospital NHS Foundation Trust, London, UK
| | - Kate Armon
- Paediatric Rheumatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; School of Medicine, University of Cambridge, Cambridge, UK
| | - Narman Puvanachandra
- Jenny Lind Children's Hospital within Norfolk and Norwich University Hospital NHS Trust, Norwich, UK
| | - Jessy T Choi
- Sheffield Children's Hospital, Sheffield, UK; Sheffield Teaching Hospitals, Sheffield, UK; University of Sheffield, Sheffield, UK
| | | | - Benjamin F Arnold
- Francis I Proctor Foundation, University of California San Francisco, San Francisco, CA, USA; Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; Institute for Global Health Sciences, University of California San Francisco, San Francisco, CA, USA
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Chen WD, Wu CH, Wu PY, Lin CP, Ou LS, Hwang DK, Sheu SJ, Chiang WY, Chang YC, Lin CJ, Chan WC, Fang YF, Chien-Chieh Huang J, Kao TE, Chiu FY, Hsia NY, Hwang YS. Taiwan ocular inflammation society consensus recommendations for the management of juvenile idiopathic arthritis-associated uveitis. J Formos Med Assoc 2024; 123:1218-1227. [PMID: 38423923 DOI: 10.1016/j.jfma.2024.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 11/06/2023] [Accepted: 02/20/2024] [Indexed: 03/02/2024] Open
Abstract
We presented the development of a consensus guideline for managing juvenile idiopathic arthritis-associated uveitis (JIAU) in Taiwan, considering regional differences in manifestation and epidemiology. The Taiwan Ocular Inflammation Society (TOIS) committee formulated this guideline using a modified Delphi approach with two panel meetings. Recommendations were based on a comprehensive evidence-based literature review and expert clinical experiences, and were graded according to the Oxford Centre for Evidence-Based Medicine's "Levels of Evidence" guideline (March 2009). The TOIS consensus guideline consists of 10 recommendations in four categories: screening and diagnosis, treatment, complications, and monitoring, covering a total of 27 items. These recommendations received over 75% agreement from the panelists. Early diagnosis and a coordinated referral system between ophthalmologists and pediatric rheumatologists are crucial to prevent irreversible visual impairment in children with JIAU. However, achieving a balance between disease activity and medication use remains a key challenge in JIAU management, necessitating further clinical studies.
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Affiliation(s)
- Wei-Dar Chen
- Department of Ophthalmology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Hsiu Wu
- Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Po-Yi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chang-Ping Lin
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Liang-Shiou Ou
- School of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - De-Kuang Hwang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shwu-Jiuan Sheu
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Yu Chiang
- School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yo-Chen Chang
- School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Ophthalmology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Ju Lin
- Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Optometry, Asia University, Taichung, Taiwan
| | - Wei-Chun Chan
- Department of Ophthalmology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Yueh-Fu Fang
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | | | - Tzu-En Kao
- Cheng-Ching Eye Center, Kaohsiung, Taiwan
| | - Fang-Yi Chiu
- Department of Ophthalmology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Ning-Yi Hsia
- Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Yih-Shiou Hwang
- School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; Department of Ophthalmology, Xiamen Chang Gung Memorial Hospital, Xiamen, China; Department of Ophthalmology, Jen-Ai Hospital Dali Branch, Taichung, Taiwan.
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Maccora I, Guly C, de Libero C, Caputo R, Ramanan AV, Simonini G. Childhood Chronic Idiopathic Uveitis in a Multicentre International Cohort. Ocul Immunol Inflamm 2024; 32:310-319. [PMID: 36802984 DOI: 10.1080/09273948.2023.2169715] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 01/11/2023] [Accepted: 01/12/2023] [Indexed: 02/23/2023]
Abstract
IMPORTANCE Idiopathic uveitis makes up around 50% of non-infectious uveitis but the clinical characteristics in children are poorly understood. OBJECTIVE To report the demographic, clinical characteristics, and outcomes of children with idiopathic non-infectious uveitis (iNIU) in a multicentric retrospective study. RESULTS There were 126 (61 female) children with iNIU. The median age at diagnosis was 9.3 years (3-16 years) . Uveitis was bilateral in 106 patients and anterior in 68.At onset,impaired visual acuity and blindness in the worse eye were reported, in 24.4% and 15.1% patients but at 3 years of follow-up, there was a significant improvement in visual acuity (mean 0.11 SD ±0.50 vs 0.42 SD ± 0.59 p < .001). CONCLUSIONS AND RELEVANCE There is a high rate of visual impairment at presentation in children with idiopathic uveitis. The majority of patients have a significant improvement in vision, but 1 in 6 had impaired vision or blindness in their worse eye at 3 years.
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Affiliation(s)
- Ilaria Maccora
- Rheumatology Unit, Meyer Children's Hospital IRCCS, Florence, Italy
- NeuroFARBA department, University of Florence, Florence, Italy
| | | | - Cinzia de Libero
- Pediatric Ophthalmology Unit, Meyer Children University Hospital, Florence, Italy
| | - Roberto Caputo
- Pediatric Ophthalmology Unit, Meyer Children University Hospital, Florence, Italy
| | - Athimalaipet V Ramanan
- Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol, UK
- Translational Health Sciences, University of Bristol, Bristol, UK
| | - Gabriele Simonini
- Rheumatology Unit, Meyer Children's Hospital IRCCS, Florence, Italy
- NeuroFARBA department, University of Florence, Florence, Italy
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van Meerwijk C, Kuiper J, van Straalen J, Ayuso VK, Wennink R, Haasnoot AM, Kouwenberg C, de Boer J. Uveitis Associated with Juvenile Idiopathic Arthritis. Ocul Immunol Inflamm 2023; 31:1906-1914. [PMID: 37966463 DOI: 10.1080/09273948.2023.2278060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 10/27/2023] [Indexed: 11/16/2023]
Abstract
Juvenile idiopathic arthritis (JIA) is the most common cause of uveitis in children. While symptoms are usually mild, persistent eye inflammation could lead to severe complications and impaired vision. It is essential that JIA patients at risk are diagnosed with uveitis early, receive adequate treatment, and avoid developing complications, such as cataract, glaucoma, and amblyopia. The purpose of this mini-review is to summarize the screening strategies and clinical management for JIA-associated uveitis (JIA-U) as well as the current state of molecular markers linked to this condition. Because glaucoma is one of the most common causes of visual loss in JIA-U, special focus will be put on this serious complication. We conclude by describing the current evidence regarding the long-standing question of whether chronic anterior uveitis without arthritis may be the same disease entity as JIA-U.
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Affiliation(s)
- Charlotte van Meerwijk
- Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Jonas Kuiper
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Joeri van Straalen
- Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Viera Kalinina Ayuso
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Roos Wennink
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Anne-Mieke Haasnoot
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Carlijn Kouwenberg
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Joke de Boer
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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Huard J, Mihailescu SD, Muraine M, Raymond S, Grall Lerosey M, Gueudry J. Effectiveness and Safety of Weekly Adalimumab for Non-Infectious Chronic Anterior Uveitis in Children. Ocul Immunol Inflamm 2023; 31:2039-2049. [PMID: 37972236 DOI: 10.1080/09273948.2023.2279682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 10/31/2023] [Indexed: 11/19/2023]
Abstract
PURPOSE Non-infectious chronic anterior uveitis (CAU) remains a therapeutic challenge. The purpose of this study was to analyze the effectiveness and safety of weekly dosing of adalimumab in children with non-infectious refractory CAU. Methods: Demographic and clinical data of children followed by non-infectious CAU treated with adalimumab were retrospectively reviewed. RESULTS Of the 42 children with CAU, 27/42 (64.3%) were treated with adalimumab. Escalation to weekly dosing of adalimumab was necessary for 11/27 children (40.7%). After 3 and 6 months, 7/11 children (63.6%) met the composite endpoint of inflammation control improvement. Children requiring weekly adalimumab had initially more severe uveitis: anterior chamber cells (p = 0.02), aqueous flare (p = 0.02), and presence of macular edema (p = 0.007). No children had serious systemic side effects. CONCLUSION Weekly adalimumab in children with refractory CAU appears to be an effective and safe treatment for inflammation control and corticosteroid sparing, and an alternative before biologic switching. Controlled studies are needed.
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Affiliation(s)
- Justine Huard
- Department of Ophthalmology, CHU ROUEN, Rouen, France
| | - Sorina-Dana Mihailescu
- Innovation, Clinical Research and Educational Unit (CIRCE), Eure-Seine Hospital, Evreux, France
| | - Marc Muraine
- Department of Ophthalmology, CHU ROUEN, Rouen, France
| | | | | | - Julie Gueudry
- Department of Ophthalmology, CHU ROUEN, Rouen, France
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Kouwenberg CV, Spierings J, de Groot EL, de Boer JH, Kalinina Ayuso V. Involvement of the systemic microcirculation in pediatric uveitis. Pediatr Rheumatol Online J 2023; 21:109. [PMID: 37784087 PMCID: PMC10544362 DOI: 10.1186/s12969-023-00896-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 09/14/2023] [Indexed: 10/04/2023] Open
Abstract
BACKGROUND Pediatric uveitis is a severe inflammatory ocular condition that can lead to sight-threatening complications and can negatively impact quality of life. The retinal microcirculation is often affected in intermediate uveitis and panuveitis. Here, we examined the extraocular (i.e., systemic) microcirculation in pediatric uveitis cases and healthy controls using nailfold capillaroscopy (NFC). METHODS We performed NFC in 119 children with noninfectious uveitis and 25 healthy pediatric controls, and assessed the following parameters: capillary density (number of capillaries/mm), dilated capillaries (apex > 20 µm), avascular area, the presence of microhemorrhages, and capillary morphology. Differences in NFC parameters between cases and controls were calculated using regression analysis after adjusting for age and sex. RESULTS The mean (± SD) age of the patient group was 13.7 (± 3) years, with 56% females; 46%, 18%, and 36% of cases presented as anterior uveitis, intermediate uveitis, and panuveitis, respectively, with an overall mean disease duration of 4.7 (± 4.0) years. Compared to the control group, the pediatric uveitis cases had a significantly higher number of dilated capillaries/mm and a higher prevalence of ramified capillaries. Moreover, compared to the control group the intermediate uveitis cases had a significantly higher number of dilated capillaries, whereas the anterior uveitis cases had a lower capillary density and a higher prevalence of ramified capillaries. CONCLUSIONS Children with uveitis without systemic disease can present with changes in systemic microcirculation. These changes vary amongst the subtypes of uveitis.
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Affiliation(s)
- Carlyn V Kouwenberg
- Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
| | - Julia Spierings
- Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Evianne L de Groot
- Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands
| | - Joke H de Boer
- Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands
| | - Viera Kalinina Ayuso
- Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands
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Chen K, Zeng H, Togizbayev G, Martini A, Zeng H. New classification criteria for juvenile idiopathic arthritis. Int J Rheum Dis 2023; 26:1889-1892. [PMID: 37807617 DOI: 10.1111/1756-185x.14813] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 10/10/2023]
Affiliation(s)
- Kexin Chen
- Department of Pediatric Allergy, Immunology and Rheumatology, Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Haisheng Zeng
- Department of Rheumatology and Immunology, Dongguan Children's Hospital, Dongguan, Guangdong Province, China
| | | | - Alberto Martini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Child and Maternal Health, University of Genoa, Genoa, Italy
| | - Huasong Zeng
- Department of Pediatric Allergy, Immunology and Rheumatology, Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
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Zhou A, Babiker F, Philip AM, Anesi SD, Foster CS. Response to "Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany". Arthritis Res Ther 2023; 25:41. [PMID: 36918966 PMCID: PMC10012478 DOI: 10.1186/s13075-023-03021-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 02/27/2023] [Indexed: 03/16/2023] Open
Abstract
We have read the article entitled "Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany" by Heiligenhaus et al. While we appreciate the work conducted by the authors, we have several comments we would like to address. First, the follow-up interval of 2 years is too short to conclude that the clinical course between two chronic pathologies is not significantly different. Second, remission status was determined by uveitis inactivity during the 2-year follow-up visit without any mention of flare frequency or length of remission, which is not a reliable measure of uveitis control. Third, ANA-positive idiopathic anterior uveitis is not a classification with a distinct clinical phenotype, and additional reports of serologic investigations would have been helpful.
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Affiliation(s)
- Avery Zhou
- The Ocular Immunology and Uveitis Foundation, Waltham, MA, USA
- Massachusetts Eye Research and Surgery Institution, 1440 Main St. Ste. 201, Waltham, MA, 02451, USA
| | - Fatima Babiker
- The Ocular Immunology and Uveitis Foundation, Waltham, MA, USA
- Massachusetts Eye Research and Surgery Institution, 1440 Main St. Ste. 201, Waltham, MA, 02451, USA
| | - Andrew M Philip
- The Ocular Immunology and Uveitis Foundation, Waltham, MA, USA
- Massachusetts Eye Research and Surgery Institution, 1440 Main St. Ste. 201, Waltham, MA, 02451, USA
| | - Stephen D Anesi
- The Ocular Immunology and Uveitis Foundation, Waltham, MA, USA
- Massachusetts Eye Research and Surgery Institution, 1440 Main St. Ste. 201, Waltham, MA, 02451, USA
| | - C Stephen Foster
- The Ocular Immunology and Uveitis Foundation, Waltham, MA, USA.
- Massachusetts Eye Research and Surgery Institution, 1440 Main St. Ste. 201, Waltham, MA, 02451, USA.
- Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
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Renton WD, Jung J, Palestine AG. Tumor necrosis factor (TNF) inhibitors for juvenile idiopathic arthritis-associated uveitis. Cochrane Database Syst Rev 2022; 10:CD013818. [PMID: 36239193 PMCID: PMC9562090 DOI: 10.1002/14651858.cd013818.pub2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by intraocular inflammation. Current treatment for JIA-associated uveitis (JIA-U) is largely based on physician experience, observational evidence and consensus guidelines, resulting in considerable variations in practice. OBJECTIVES: To evaluate the effectiveness and safety of tumor necrosis factor (TNF) inhibitors used for treatment of JIA-U. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We last searched the electronic databases on 3 February 2022. SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing TNF inhibitors with placebo in participants with a diagnosis of JIA and uveitis who were aged 2 to 18 years old. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodology and graded the certainty of the body of evidence for seven outcomes using the GRADE classification. MAIN RESULTS We included three RCTs with 134 participants. One study conducted in the USA randomized participants to etanercept or placebo (N = 12). Two studies, one conducted in the UK (N = 90) and one in France (N = 32), randomized participants to adalimumab or placebo. All studies were at low risk of bias. Initial pooled estimates suggested that TNF-inhibitors may result in little to no difference on treatment success defined as 0 to trace cells on Standardization of Uveitis Nomenclature (SUN)-grading; or two-step decrease in activity based on SUN grading (estimated risk ratio (RR) 0.66; 95% confidence interval (CI) 0.21 to 2.10; 2 studies; 43 participants; low-certainty evidence) or treatment failure defined as a two-step increase in activity based on SUN grading (RR 0.31; 95% CI 0.01 to 7.15; 1 study; 31 participants; low-certainty evidence). Further analysis using the individual trial definitions of treatment response and failure suggested a positive treatment effect of TNF inhibitors; a RR of treatment success of 2.60 (95% CI 1.30 to 5.20; 3 studies; 124 participants; low-certainty evidence), and RR of treatment failure of 0.23 (95% CI 0.11 to 0.50; 3 studies; 133 participants). Almost all the evidence was on adalimumab and the evidence on etanercept was very limited. For secondary outcomes, one study suggests that adalimumab may have little to no effect on risk of recurrence after induction of remission at three months (RR 2.50, 95% CI 0.31 to 20.45; 90 participants; very low-certainty evidence) and visual acuity, but the evidence is very uncertain; mean difference in longitudinal logMAR score change over six months was -0.01 (95% CI -0.06 to 0.03) and -0.02 (95% CI -0.07 to 0.03) using the best and worst logMAR measurement, respectively (low-certainty evidence). Low-certainty evidence from one study suggested that adalimumab treatment results in reduction of topical steroid doses at six months (hazard ratio 3.58; 95% CI 1.24 to 10.32; 74 participants who took one or more topical steroid per day at baseline). Adverse events, including injection site reactions and infections, were more common in the TNF inhibitor group. Serious adverse events were uncommon. AUTHORS' CONCLUSIONS Adalimumab appears to increase the likelihood of treatment success and decrease the likelihood of treatment failure when compared with placebo. The evidence was less conclusive about a positive treatment effect with etanercept. Adverse events from JIA-U trials are in keeping with the known side effect profile of TNF inhibitors. Standard validated JIA-U outcome measures are required to homogenize assessment and to allow for comparison and analysis of multiple datasets.
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Affiliation(s)
- William D Renton
- Rheumatology Unit, Department of General Medicine, The Royal Children's Hospital, Melbourne, Australia
| | - Jennifer Jung
- Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Alan G Palestine
- Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado, USA
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11
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McDonald J, Cassedy A, Altaye M, Andringa J, Cooper AM, Drews-Botsch C, Engelhard G, Hennard T, Holland GN, Jenkins K, Lambert SR, Lipscomb J, McCracken C, McCurdy DK, Mwase N, Prahalad S, Shantha J, Stahl E, Miraldi Utz V, Walker AA, Yeh S, Angeles-Han ST. Comprehensive Assessment of Quality of Life, Functioning, and Mental Health in Children With Juvenile Idiopathic Arthritis and Noninfectious Uveitis. Arthritis Care Res (Hoboken) 2022; 74:1311-1320. [PMID: 33421338 PMCID: PMC8267048 DOI: 10.1002/acr.24551] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 12/15/2020] [Accepted: 01/05/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Pediatric uveitis can lead to sight-threatening complications and can impact quality of life (QoL) and functioning. We aimed to examine health-related QoL, mental health, physical disability, vision-related functioning (VRF), and vision-related QoL in children with juvenile idiopathic arthritis (JIA), JIA-associated uveitis (JIA-U), and other noninfectious uveitis. We hypothesized that there will be differences based on the presence of eye disease. METHODS A multicenter cross-sectional study was conducted at four sites. Patients with JIA, JIA-U, or noninfectious uveitis were enrolled. Patients and parents completed the Pediatric Quality of Life Inventory (PedsQL; health-related QoL), the Revised Childhood Anxiety and Depression Scale (RCADS; anxiety/depression), the Childhood Health Assessment Questionnaire (C-HAQ; physical disability), and the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) (VRF/vision-related QoL). Clinical characteristics and patient-reported outcome measures were compared by diagnosis. RESULTS Of 549 patients, 332 had JIA, 124 had JIA-U, and 93 had other uveitis diagnoses. Children with JIA-U had worse EYE-Q scores compared to those with JIA only. In children with uveitis, those with anterior uveitis (JIA-U and uveitis only) had less ocular complications, better EYE-Q scores, and worse C-HAQ and PedsQL physical summary scores compared to those with nonanterior disease. In children with anterior uveitis, those with JIA-U had worse PedsQL physical summary and C-HAQ scores than anterior uveitis only. Further, EYE-Q scores were worse in children with bilateral uveitis and more visual impairment. There were no differences in RCADS scores among groups. CONCLUSION We provide a comprehensive outcome assessment of children with JIA, JIA-U, and other uveitis diagnoses. Differences in QoL and function were noted based on underlying disease. Our results support the addition of a vision-specific measure to better understand the impact of uveitis.
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Affiliation(s)
- Joseph McDonald
- Division of Rheumatology, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
| | - Amy Cassedy
- Division of Biostatistics and Epidemiology and Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH
| | - Mekibib Altaye
- Division of Biostatistics and Epidemiology and Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH
| | - Jennifer Andringa
- Division of Biostatistics and Epidemiology and Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH
| | - Ashley M. Cooper
- Division of Rheumatology, Children’s Mercy Hospital, Kansas City, MO and Department of Pediatrics, University of Missouri-Kansas City
| | - Carolyn Drews-Botsch
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
| | - George Engelhard
- Division of Educational Psychology, The University of Georgia, Athens, GA
| | - Theresa Hennard
- Division of Rheumatology, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
| | - Gary N. Holland
- UCLA Stein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | | | | | - Jessi Lipscomb
- Division of Biostatistics and Epidemiology and Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH
| | - Courtney McCracken
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
| | - Deborah K. McCurdy
- Department of Pediatrics and David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Najima Mwase
- Division of Rheumatology, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
| | - Sampath Prahalad
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
- Childrens Healthcare of Atlanta
| | - Jessica Shantha
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA
| | - Erin Stahl
- Section of Pediatric Ophthalmology, Children’s Mercy Hospital, Kansas City, MO and Department of Ophthalmology, University of Missouri-Kansas City
| | - Virginia Miraldi Utz
- Division of Ophthalmology, Cincinnati Children’s Hospital Medical Center and Department of Ophthalmology, University of Cincinnati, Cincinnati, OH
| | | | - Steven Yeh
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA
| | - Sheila T. Angeles-Han
- Division of Rheumatology, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
- Section of Pediatric Ophthalmology, Children’s Mercy Hospital, Kansas City, MO and Department of Ophthalmology, University of Missouri-Kansas City
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12
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Foeldvari I, Maccora I, Petrushkin H, Rahman N, Anton J, de Boer J, Calzada-Hernández J, Carreras E, Diaz J, Edelsten C, Angeles-Han ST, Heiligenhaus A, Miserocchi E, Nielsen S, Saurenmann RK, Stuebiger N, Baquet-Walscheid K, Furst D, Simonini G. New and Updated Recommendations for the Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis and Idiopathic Chronic Anterior Uveitis. Arthritis Care Res (Hoboken) 2022; 75:975-982. [PMID: 35638697 DOI: 10.1002/acr.24963] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 04/26/2022] [Accepted: 05/24/2022] [Indexed: 01/11/2023]
Abstract
OBJECTIVE The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to update the current guidelines, and the objective here was to produce this document to guide clinicians managing children with juvenile idiopathic arthritis-associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU). METHODS The group analyzed the literature published between December 2014 and June 2020 after a systematic literature review conducted by 2 clinicians. Pediatric rheumatologists were paired with ophthalmologists to review the eligible 37 publications. The search criteria were selected to reflect those used for the 2018 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, in order to provide an update, rather than a replacement for that publication. The summary of the current evidence for each SHARE recommendation was presented to the expert committee. These recommendations were then discussed and revised during a video consensus meeting on January 22, 2021, with 14 voting participants, using a nominal group technique to reach consensus. RESULTS JIAU treatment was extended to include CAU. Fourteen recommendations regarding treatment of JIAU und CAU with >90% agreement were accepted. CONCLUSION An update to the previous 2018 SHARE recommendations for the treatment of children with JIAU with the addition of CAU was created using an evidence-based consensus process. This guideline should help support clinicians to care for children and young people with CAU.
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Affiliation(s)
| | - Ilaria Maccora
- Meyer Children's Hospital, University of Florence, Florence, Italy
| | - Harry Petrushkin
- Moorfields Eye Hospital and Great Ormond Street Hospital, NHS Foundation Trust, London, UK
| | - Najiha Rahman
- Moorfields Eye Hospital, NHS Foundation Trust, London, UK
| | - Jordi Anton
- Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
| | - Joke de Boer
- University Medical Center Utrecht, Utrecht, The Netherlands
| | | | | | - Jesus Diaz
- Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
| | - Clive Edelsten
- Great Ormond Street Hospital, NHS Foundation Trust, London, UK
| | - Sheila T Angeles-Han
- Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio
| | - Arnd Heiligenhaus
- St. Franziskus Hospital, Muenster, and University of Duisburg-Essen, Essen, Germany
| | | | | | | | - Nicole Stuebiger
- Universitätsklinikum Hamburg-Eppendorf, Augenklinik, Hamburg, Germany
| | | | - Daniel Furst
- University of California, Los Angeles, University of Washington, Seattle, and University of Florence, Florence, Italy
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13
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Kouwenberg CV, Wennink RA, Shahabi M, Bozkir I, Ayuso VKK, de Boer JH. Clinical course and outcome in pediatric idiopathic chronic anterior uveitis. Am J Ophthalmol 2022; 241:198-205. [PMID: 35513031 DOI: 10.1016/j.ajo.2022.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 02/25/2022] [Accepted: 04/20/2022] [Indexed: 11/01/2022]
Abstract
PURPOSE To examine the clinical course and outcome in children with idiopathic chronic anterior uveitis (iCAU) and compare the results with age-matched children with juvenile idiopathic arthritis-associated uveitis (JIA-U). DESIGN Retrospective cohort study. METHODS Data regarding ocular complications, visual acuity, and systemic treatment were retrospectively collected for two patient groups that were matched regarding age and year of uveitis diagnosis. Outcome was evaluated using survival analysis. RESULTS The iCAU and JIA-U groups included 48 patients with 83 affected eyes and 48 patients with 73 affected eyes, respectively. Multivariate analyses showed that iCAU was associated with a higher prevalence of posterior synechiae (adjusted hazard rate [aHR]: 3.63; P < 0.001) and cataract surgery (aHR: 2.90; P = 0.006). Baseline visual acuity was worse in the iCAU group compared to the JIA-U group (20/25 vs. 20/20, respectively; P < 0.001), but improved in the iCAU group after 5 years (20/20 vs. 20/20, respectively; P = 0.052). At the 5-year follow-up, the younger children with iCAU (≤8 years of age at diagnosis) had a higher prevalence of posterior synechiae (aHR: 2.56; P = 0.007), secondary glaucoma (aHR: 16.0; P = 0.020), and cataract surgery (aHR: 4.79; P = 0.004) compared to older children with iCAU (≥9 years at diagnosis). CONCLUSIONS Vision-threatening ocular complications are more common in children with iCAU compared to children with JIA-U, particularly in cases in which the onset of uveitis occurred at ≤8 years of age. However, the long-term vision of these children can be improved with adequate treatment.
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14
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Heiligenhaus A, Deuter C. Uveitis in Juvenile Idiopathic Arthritis - Case Reports on Guideline-based Diagnostic Work-up and Treatment. Klin Monbl Augenheilkd 2022; 239:676-685. [PMID: 35320873 DOI: 10.1055/a-1686-5158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVES Case report based presentation of the current German interdisciplinary guideline on the diagnosis and management of juvenile idiopathic arthritis-associated (JIA) uveitis. MATERIAL AND METHODS Guideline of the German Society of Ophthalmology, the Society of Paediatric and Adolescent Rheumatology, the German Society of Rheumatology, the Professional Association of German Ophthalmologists, with the participation of patient representatives. Recent primary publications were critically graduated for evidence and recommendations; the methodology included consensus building through Delphi rounds and external peer review. The outcomes are presented with typical case studies. OUTCOMES Once JIA is first diagnosed, periodic ophthalmological check-ups should promptly be instituted ensuring that uveitis is diagnosed before irreversible sequelae become manifest. High-quality patient care can be provided depending on the severity of each uveitis case. At present, anti-inflammatory treatment relies on corticosteroids, conventional synthetic (cs), biological (b) and other disease-modifying anti-rheumatic drugs (DMARDs). CONCLUSIONS Timely diagnosis and state-of-the-art guideline-based management can significantly improve the long-term outcome of JIA-associated uveitis.
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Affiliation(s)
| | - Christoph Deuter
- Department für Augenheilkunde, Universitätsklinikum Tübingen, Deutschland
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15
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Abstract
ZusammenfassungIm Gebiet der Kinderrheumatologie gab es in den letzten Jahrzehnten immense
Fortschritte, die sowohl die Diagnostik, als auch die Therapie nachhaltig
verbessert haben. Obwohl erst seit 2003 in Deutschland offiziell als
Zusatzbezeichnung anerkannt, stehen heutzutage über 200 Kinder- und
Jugendrheumatologen (d. h. 1,4 Kinderrheumatologen pro 100 000
Kinder) für die Erkennung und Behandlung von rheumatischen Erkrankungen
bei Kindern und Jugendlichen bundesweit zur Verfügung. Neue Erkenntnisse
in der Pathogenese rheumatischer Erkrankungen und die sich stetig
weiterentwickelnde genetische Diagnostik haben das rheumatische
Krankheitsspektrum und die Behandlungsmöglichkeiten dramatisch erweitert
Internationale Forschungsnetzwerke und eine spezielle Gesetzgebung für
die Entwicklung von pädiatrischen Medikamenten führten zur
Zulassung von zahlreichen neuen Rheumamedikamenten, deren Sicherheit im
klinischen Alltag seit der Jahrtausendwende systematisch in Deutschland
untersucht wird. Maßnahmen zur Sicherung der Versorgungsqualität
wurden implementiert, Standardinstrumente zur Bewertung der
Krankheitsaktivität und Krankheitslast aus Patientensicht
eingeführt sowie Initiativen zur Verbesserung der Versorgung Betroffener
(z. B. die ProKind-Initiative) auf den Weg gebracht. Diese
Veränderungen haben die Prognose und Lebensperspektive rheumakranker
Kinder und Jugendlicher verbessert, wenngleich noch weiterer Optimierungsbedarf
besteht.
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Affiliation(s)
- Johannes-Peter Haas
- German Center for Rheumatology in Children and
Adolescents/Deutsches Zentrum für Kinder- und
Jugendrheumatologie Garmisch-Partenkirchen, Garmisch-Partenkirchen,
Deutschland
- Center for treatment of pain in young people/Zentrum
für Schmerztherapie junger Menschen, Deutschland
| | - Kirsten Minden
- Klinik für Pädiatrie mit Schwerpunkt Pulmonologie,
Immunologie und Intensivmedizin Charitè Centrum17,
Charité-Universitätsmedizin Berlin, Berlin,
Deutschland
- Deutsches Rheumaforschungszentrum, Leibniz-Gemeinschaft, Berlin,
Deutschland
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16
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Haas JP, Weimann V, Feist E. [Polyarticular juvenile idiopathic arthritis and rheumatoid arthritis : Common features and differences]. Z Rheumatol 2021; 81:4-13. [PMID: 34713333 DOI: 10.1007/s00393-021-01114-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2021] [Indexed: 10/20/2022]
Abstract
The spectrum of polyarthritic diseases in childhood as well as in adulthood is wide. In the differential diagnostics different age-related diseases must be taken into consideration. Although, a clear similarity is obvious in all age groups for the classical diseases of polyarticular juvenile idiopathic arthritis and rheumatoid arthritis with respect to the pathogenesis, clinical manifestation and treatment options, this review points to specific differences. The prognosis of polyarthritis in children mainly depends on the joint manifestation, whereas extra-articular comorbidities play a predominant role in the older adult population.
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Affiliation(s)
- Johannes-Peter Haas
- Deutsches Zentrum für Kinder- und Jugendrheumatologie, Zentrum für Schmerztherapie junger Menschen, Kinderklinik Garmisch-Partenkirchen gGmbH, Gehfeldstr. 24, 82467, Garmisch-Partenkirchen, Deutschland.
| | - Vincent Weimann
- Rheumatologie, Helios Fachklinik Vogelsang-Gommern, Vogelsang-Gommern, Deutschland
| | - Eugen Feist
- Rheumatologie, Helios Fachklinik Vogelsang-Gommern, Vogelsang-Gommern, Deutschland
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17
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Carlsson E, Beresford MW, Ramanan AV, Dick AD, Hedrich CM. Juvenile Idiopathic Arthritis Associated Uveitis. CHILDREN-BASEL 2021; 8:children8080646. [PMID: 34438537 PMCID: PMC8393258 DOI: 10.3390/children8080646] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/20/2021] [Accepted: 07/23/2021] [Indexed: 01/31/2023]
Abstract
Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. The development of associated uveitis represents a significant risk for serious complications, including permanent loss of vision. Initiation of early treatment is important for controlling JIA-uveitis, but the disease can appear asymptomatically, making frequent screening procedures necessary for patients at risk. As our understanding of pathogenic drivers is currently incomplete, it is difficult to assess which JIA patients are at risk of developing uveitis. Identification of specific risk factors for JIA-associated uveitis is an important field of research, and in this review, we highlight the genomic, transcriptomic, and proteomic factors identified as potential uveitis risk factors in JIA, and discuss therapeutic strategies.
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Affiliation(s)
- Emil Carlsson
- Department of Women’s and Children’s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L14 5AB, UK;
- Correspondence: (E.C.); (C.M.H.); Tel.: +44-151-228-4811 (ext. 2690) (E.C.); +44-151-252-5849 (C.M.H.)
| | - Michael W. Beresford
- Department of Women’s and Children’s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L14 5AB, UK;
- Department of Rheumatology, Alder Hey Children’s NHS Foundation Trust Hospital, Liverpool L14 5AB, UK
- National Institute for Health Research Alder Hey Clinical Research Facility, Alder Hey Children’s NHS Foundation Trust Hospital, Liverpool L14 5AB, UK
| | - Athimalaipet V. Ramanan
- Bristol Royal Hospital for Children & Translational Health Sciences, University of Bristol, Bristol BS2 8DZ, UK;
| | - Andrew D. Dick
- Translational Health Sciences, University of Bristol, Bristol BS2 8DZ, UK;
- UCL Institute of Ophthalmology, London EC1V 9EL, UK
- NIHR Biomedical Research Centre, Moorfields Eye Hospital, London EC1V 2PD, UK
| | - Christian M. Hedrich
- Department of Women’s and Children’s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L14 5AB, UK;
- Department of Rheumatology, Alder Hey Children’s NHS Foundation Trust Hospital, Liverpool L14 5AB, UK
- National Institute for Health Research Alder Hey Clinical Research Facility, Alder Hey Children’s NHS Foundation Trust Hospital, Liverpool L14 5AB, UK
- Correspondence: (E.C.); (C.M.H.); Tel.: +44-151-228-4811 (ext. 2690) (E.C.); +44-151-252-5849 (C.M.H.)
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18
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Wennink RAW, de Boer JH, Hiddingh S, Haasnoot AMJW, Kalinina Ayuso V, de Hoop T, van Setten J, Spierings E, Kuiper JJW. Next-Generation HLA Sequence Analysis Uncovers Shared Risk Alleles Between Clinically Distinct Forms of Childhood Uveitis. Invest Ophthalmol Vis Sci 2021; 62:19. [PMID: 34254975 PMCID: PMC8287043 DOI: 10.1167/iovs.62.9.19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Purpose Classical alleles of the human leukocyte antigen (HLA) complex have been linked to specific entities of pediatric noninfectious uveitis, yet genetic predisposition encoded by the HLA super-locus across the patient population remains understudied. Methods We performed next-generation full-length sequencing of HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1 in 280 cases. Dense genotype data from 499 Dutch controls from Genome of the Netherlands were imputed using an HLA-specific reference panel (n = 5225 samples from European ancestry). Cases and controls were compared using logistic regression models adjusting for sex. Results In total, 179 common and rare alleles were detected. Considering all cases and controls, HLA-DQB1*04:02 and HLA-DRB1*08:01 were identified as the principal HLA association, which was mainly driven by 92 cases with juvenile idiopathic arthritis-associated uveitis (JIA-U). The HLA-DQB1*04:02-HLA-DRB1*08:01 haplotype was also the primary association for the phenotypically similar idiopathic chronic anterior uveitis without arthritis (CAU). Also, HLA-DQB1*05:03 was an independent risk allele for CAU, but not in JIA-U. Analysis of 185 cases with other forms of uveitis revealed HLA-wide associations (P < 2.79 × 10−4) for HLA-DRB1*01:02, HLA-DRB1*04:03, and HLA-DQB1*05:03, which could be primarily attributed to cases with panuveitis. Finally, amino acid substitution modeling revealed that aspartic acid at position 57 that distinguishes the risk allele HLA-DQB1*05:03 (for CAU and panuveitis) from nonrisk alleles, significantly increased the binding capacity of naturally presented ligands to HLA-DQ. Conclusions These results uncovered novel shared HLA associations among clinically distinct phenotypes of pediatric uveitis and highlight genetic predisposition affecting the antigen presentation pathway.
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Affiliation(s)
- Roos A W Wennink
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, The Netherlands.,Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Joke H de Boer
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Sanne Hiddingh
- Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Anne-Mieke J W Haasnoot
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Viera Kalinina Ayuso
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Talitha de Hoop
- Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Jessica van Setten
- Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Eric Spierings
- Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | - Jonas J W Kuiper
- Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, The Netherlands.,Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, The Netherlands
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19
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Gunzinger J, Moore P, Athimalaipet R, Dick A. Adalimumab in the treatment of pediatric patients with chronic noninfectious anterior uveitis. EXPERT REVIEW OF OPHTHALMOLOGY 2021. [DOI: 10.1080/17469899.2021.1935240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
| | - Phoebe Moore
- Department of Uveitis, Bristol Eye Hospital, Bristol, UK
| | - Ramanan Athimalaipet
- Bristol Royal Hospital for Children, Upper Maudlin St, Bristol BS2 8BJ, University Hospitals Bristol NHs Foundation Trust & Translational Health Sciences, University of Bristol, Bristol, UK
| | - Andrew Dick
- Bristol Eye Hospital, Institute of Ophthalmology and the National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital and University College London, London, UK
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Sur LM, Gaga R, Duca E, Sur G, Lupan I, Sur D, Samasca G, Lazea C, Lazar C. Different Chronic Disorders That Fall within the Term Juvenile Idiopathic Arthritis. Life (Basel) 2021; 11:life11050398. [PMID: 33925491 PMCID: PMC8146979 DOI: 10.3390/life11050398] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 04/26/2021] [Indexed: 12/12/2022] Open
Abstract
Juvenile idiopathic arthritis (JIA) represents a significant challenge for pediatricians who intend to diagnose and treat this pathology. The classification criteria for JIA subtypes are rigid and often do not fully satisfy the possibilities of classification in the subtype. The objective of this study was to identify clearer criteria for classifying JIA subtypes. The 2019 expert committee meeting (PRINTO) shows the difficulties of this classification and proposes new research directions for the identification of disease subtypes. Four different chronic disorders are used to define JIA in a concise and easy to follow classification system. However, dates from the literature suggest that at least 10% of cases are still difficult to classify. Possibly in the future, different classifications of JIA based on pathophysiological and genetic criteria would be necessary.
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Affiliation(s)
- Lucia M. Sur
- Department Pediatrics I, University of Medicine and Pharmacology “Iuliu Hațieganu”, 3400 Cluj-Napoca, Romania; (L.M.S.); (C.L.); (C.L.)
- Pediatrics I Department, Emergency Clinical Hospital for Children, 3400 Cluj-Napoca, Romania
| | - Remus Gaga
- Pediatrics II Department, Emergency Clinical Hospital for Children, 3400 Cluj-Napoca, Romania; (R.G.); (E.D.); (G.S.)
| | - Emanuela Duca
- Pediatrics II Department, Emergency Clinical Hospital for Children, 3400 Cluj-Napoca, Romania; (R.G.); (E.D.); (G.S.)
| | - Genel Sur
- Pediatrics II Department, Emergency Clinical Hospital for Children, 3400 Cluj-Napoca, Romania; (R.G.); (E.D.); (G.S.)
| | - Iulia Lupan
- Molecular Biology Department, Babes Bolyai University, 3400 Cluj-Napoca, Romania;
| | - Daniel Sur
- The Oncology Institute “Prof. Dr. Ion Chiricuta”, 3400 Cluj-Napoca, Romania;
| | - Gabriel Samasca
- Department Pediatrics I, University of Medicine and Pharmacology “Iuliu Hațieganu”, 3400 Cluj-Napoca, Romania; (L.M.S.); (C.L.); (C.L.)
- Correspondence: ; Tel.: +40-(264)-532216
| | - Cecilia Lazea
- Department Pediatrics I, University of Medicine and Pharmacology “Iuliu Hațieganu”, 3400 Cluj-Napoca, Romania; (L.M.S.); (C.L.); (C.L.)
| | - Calin Lazar
- Department Pediatrics I, University of Medicine and Pharmacology “Iuliu Hațieganu”, 3400 Cluj-Napoca, Romania; (L.M.S.); (C.L.); (C.L.)
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Biological classification of childhood arthritis: roadmap to a molecular nomenclature. Nat Rev Rheumatol 2021; 17:257-269. [PMID: 33731872 DOI: 10.1038/s41584-021-00590-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2021] [Indexed: 12/21/2022]
Abstract
Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages.
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