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Diagnosis and Management of Non-Infectious Uveitis in Pediatric Patients

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Abstract

Uveitis in children accounts for 5–10% of all cases. The causes vary considerably. Classically, uveitis is distinguished according to its infectious or inflammatory origin and whether it is part of a systemic disease or represents an isolated ocular disease. It is important to highlight the specificity of certain etiologies among children such as juvenile idiopathic arthritis. The development of visual function can potentially be hindered by amblyopia (children aged < 7 years), in addition to the usual complications (synechiae, macular edema) seen in adult patients. Moreover, the presentation of uveitis in children is often “silent” with few warning signs and few functional complaints from young children, which frequently leads to a substantial diagnostic delay. The diagnostic approach is guided by the presentation of the uveitis, which can be characterized by its location, and corresponds to the initial and main site of intraocular inflammation; its presentation, whether acute or chronic, granulomatous or not; and the response to treatment. Pediatricians have an important role to play and must be aware of the various presentations and etiologies of uveitis in children. Juvenile idiopathic arthritis is the most common etiology of pediatric non-infectious uveitis, but other causes must be recognized. Promptly initiated treatment before complications arise requires early diagnosis, recognition, and treatment. Any dependence on prolonged local corticosteroid therapy justifies discussing the introduction of a corticosteroid-sparing treatment considering the risk to develop corticoid-induced glaucoma and cataracts. Systemic corticosteroid therapy can be required for urgent control of inflammation in the case of severe uveitis. Long-lasting immunosuppressive treatment and biotherapies are most often prescribed at the same time to reinforce treatment efficacy and to prevent relapse and corticosteroid dependency. We review the different causes of uveitis, excluding infection, and the diagnostic and therapeutic management aimed at limiting the risk of irreversible sequelae.

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References

  1. LaMattina KC, Koreishi AF. What is new in paediatric uveitis? Curr Opin Ophthalmol. 2018;29:412.

    Article  PubMed  Google Scholar 

  2. Holland GN, Stiehm ER. Special considerations in the evaluation and management of uveitis in children. Am J Ophthalmol. 2003;135:867–78.

    Article  PubMed  Google Scholar 

  3. Rahman N, Petrushkin H, Solebo AL. Paediatric autoimmune and autoinflammatory conditions associated with uveitis. Ther Adv Ophthalmol. 2020;12:2515841420966451.

    PubMed  PubMed Central  Google Scholar 

  4. Edelsten C, Reddy MA, Stanford MR, Graham EM. Visual loss associated with pediatric uveitis in English primary and referral centers. Am J Ophthalmol. 2003;135:676–80.

    Article  PubMed  Google Scholar 

  5. Engelhard SB, Bajwa A, Reddy AK. Causes of uveitis in children without juvenile idiopathic arthritis. Clin Ophthalmol Auckl NZ. 2015;9:1121–8.

    Article  Google Scholar 

  6. Päivönsalo-Hietanen T, Tuominen J, Saari KM. Uveitis in children: population-based study in Finland. Acta Ophthalmol Scand. 2000;78:84–8.

    Article  PubMed  Google Scholar 

  7. de Boer J, Wulffraat N, Rothova A. Visual loss in uveitis of childhood. Br J Ophthalmol. 2003;87:879–84.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data: results of the first international workshop. Am J Ophthalmol. 2005;140:509–16.

    Article  PubMed  Google Scholar 

  9. Deschenes J, Murray PI, Rao NA, Nussenblatt RB, International Uveitis Study Group. International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm. 2008;16:1–2.

    Article  PubMed  Google Scholar 

  10. Harman LE, Margo CE, Roetzheim RG. Uveitis: the collaborative diagnostic evaluation. Am Fam Physician. 2014;90:711–6.

    PubMed  Google Scholar 

  11. Tugal-Tutkun I. Pediatric uveitis. J Ophthalmic Vis Res. 2011;6:259–69.

    PubMed  PubMed Central  Google Scholar 

  12. Smith JA, Mackensen F, Sen HN, Leigh JF, Watkins AS, Pyatetsky D, et al. Epidemiology and course of disease in childhood uveitis. Ophthalmology. 2009;116(1544–51):1551.e1.

    PubMed  Google Scholar 

  13. Majumder PD, Biswas J. Pediatric uveitis: an update. Oman J Ophthalmol. 2013;6:140–50.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chebil A, Chaabani L, Kort F, Ben Youssef N, Turki F, El Matri L. Epidemiologic study of pediatric uveitis: a series of 49 cases. J Fr Ophtalmol. 2012;35:30–4.

    Article  CAS  PubMed  Google Scholar 

  15. Nissen M, Guex-Crosier Y. Prise en charge des uvéites non infectieuses liées à une maladie systémique: guide pour les praticiens. Rev Médicale Suisse. 2020;16:2059–73.

    Article  Google Scholar 

  16. Maleki A, Anesi SD, Look-Why S, Manhapra A, Foster CS. Pediatric uveitis: a comprehensive review. Surv Ophthalmol. 2022;67:510–29.

    Article  PubMed  Google Scholar 

  17. Shivpuri A, Turtsevich I, Solebo AL, Compeyrot-Lacassagne S. Pediatric uveitis: role of the pediatrician. Front Pediatr. 2022;10:874711.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Maleki A, Patel PD, Foster CS. Juvenile idiopathic arthritis and its associated uveitis. Expert Rev Clin Immunol. 2023;2023:1–13.

    Google Scholar 

  19. Malagon C, Van Kerckhove C, Giannini EH, Taylor J, Lovell DJ, Levinson JE, et al. The iridocyclitis of early onset pauciarticular juvenile rheumatoid arthritis: outcome in immunogenetically characterized patients. J Rheumatol. 1992;19:160–3.

    CAS  PubMed  Google Scholar 

  20. De Silvestri A, Capittini C, Poddighe D, Marseglia GL, Mascaretti L, Bevilacqua E, et al. HLA-DRB1 alleles and juvenile idiopathic arthritis: diagnostic clues emerging from a meta-analysis. Autoimmun Rev. 2017;16:1230–6.

    Article  PubMed  Google Scholar 

  21. Ashton JJ, Latham K, Beattie RM, Ennis S. Review article: the genetics of the human leucocyte antigen region in inflammatory bowel disease. Aliment Pharmacol Ther. 2019;50:885–900.

    Article  CAS  PubMed  Google Scholar 

  22. Kone-Paut I, Barete S, Bodaghi B, Deiva K, Desbois A-C, Galeotti C, et al. French recommendations for the management of Behçet’s disease. Orphanet J Rare Dis. 2021;16:352.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Turk MA, Hayworth JL, Nevskaya T, Pope JE. Ocular manifestations of Behçet’s disease in children and adults: a systematic review and meta-analysis. Clin Exp Rheumatol. 2021;39(Suppl. 132):94–101.

    Article  PubMed  Google Scholar 

  24. Sungur GK, Hazirolan D, Yalvac I, Ozer PA, Yuksel D, Vural ET, et al. Clinical and demographic evaluation of Behçet disease among different paediatric age groups. Br J Ophthalmol. 2009;93:83–7.

    Article  CAS  PubMed  Google Scholar 

  25. de Menthon M, Lavalley MP, Maldini C, Guillevin L, Mahr A. HLA-B51/B5 and the risk of Behçet’s disease: a systematic review and meta-analysis of case-control genetic association studies. Arthritis Rheum. 2009;61:1287–96.

    Article  PubMed  Google Scholar 

  26. Rathinam SR, Vijayalakshmi P, Namperumalsamy P, Nozik RA, Cunningham ET. Vogt-Koyanagi-Harada syndrome in children. Ocul Immunol Inflamm. 1998;6:155–61.

    Article  CAS  PubMed  Google Scholar 

  27. Shindo Y, Inoko H, Yamamoto T, Ohno S. HLA-DRB1 typing of Vogt-Koyanagi-Harada’s disease by PCR-RFLP and the strong association with DRB1*0405 and DRB1*0410. Br J Ophthalmol. 1994;78:223–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang XY, Wang XM, Hu TS. Profiling human leukocyte antigens in Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol. 1992;113:567–72.

    Article  CAS  PubMed  Google Scholar 

  29. Patil YB, Garg R, Rajguru JP, Sirsalmath M, Bevinakatti VA, Kumar M, et al. Vogt-Koyanagi-Harada (VKH) syndrome: a new perspective for healthcare professionals. J Fam Med Prim Care. 2020;9:31–5.

    Article  Google Scholar 

  30. Hou S, Li N, Liao X, Kijlstra A, Yang P. Uveitis genetics. Exp Eye Res. 2020;190:107853.

    Article  CAS  PubMed  Google Scholar 

  31. Tabbara KF, Chavis PS, Freeman WR. Vogt-Koyanagi-Harada syndrome in children compared to adults. Acta Ophthalmol Scand. 1998;76:723–6.

    Article  CAS  PubMed  Google Scholar 

  32. Al-Kharashi AS, Aldibhi H, Al-Fraykh H, Kangave D, Abu El-Asrar AM. Prognostic factors in Vogt-Koyanagi-Harada disease. Int Ophthalmol. 2007;27:201–10.

    Article  PubMed  Google Scholar 

  33. Dollfus H, Häfner R, Hofmann HM, Russo RAG, Denda L, Gonzales LD, et al. Chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease syndrome: ocular manifestations in a recently recognized chronic inflammatory disease of childhood. Arch Ophthalmol. 2000;118:1386–92.

    Article  CAS  PubMed  Google Scholar 

  34. Nathan N, Sileo C, Calender A, Pacheco Y, Rosental P-A, Cavalin C, et al. Paediatric sarcoidosis. Paediatr Respir Rev. 2019;29:53–9.

    PubMed  Google Scholar 

  35. Sergi CM. Pediatric sarcoidosis with diagnostic and therapeutical insights. Curr Opin Pulm Med. 2021;27:472–7.

    Article  CAS  PubMed  Google Scholar 

  36. Sève P, Jamilloux Y, Tilikete C, Gerfaud-Valentin M, Kodjikian L, El Jammal T. Ocular sarcoidosis. Semin Respir Crit Care Med. 2020;41:673–88.

    Article  PubMed  Google Scholar 

  37. Ma SP, Rogers SL, Hall AJ, Hodgson L, Brennan J, Stawell RJ, et al. Sarcoidosis-related uveitis: clinical presentation, disease course, and rates of systemic disease progression after uveitis diagnosis. Am J Ophthalmol. 2019;198:30–6.

    Article  PubMed  Google Scholar 

  38. Coulon C, Kodjikian L, Rochepeau C, Perard L, Jardel S, Burillon C, et al. Ethnicity and association with ocular, systemic manifestations and prognosis in 194 patients with sarcoid uveitis. Graefes Arch Clin Exp Ophthalmol. 2019;257:2495–503.

    Article  CAS  PubMed  Google Scholar 

  39. Groen-Hakan F, Eurelings L, Rothova A, van Laar J. Lymphopaenia as a predictor of sarcoidosis in patients with a first episode of uveitis. Br J Ophthalmol. 2019;103:1296–300.

    Article  PubMed  Google Scholar 

  40. Jones NP, Tsierkezou L, Patton N. Lymphopenia as a predictor of sarcoidosis in patients with uveitis. Br J Ophthalmol. 2016;100:1393–6.

    Article  CAS  PubMed  Google Scholar 

  41. Rochepeau C, Jamilloux Y, Kerever S, Febvay C, Perard L, Broussolle C, et al. Long-term visual and systemic prognoses of 83 cases of biopsy-proven sarcoid uveitis. Br J Ophthalmol. 2017;101:856–61.

    Article  PubMed  Google Scholar 

  42. Niederer RL, Al-Janabi A, Lightman SL, Tomkins-Netzer O. Serum angiotensin-converting enzyme has a high negative predictive value in the investigation for systemic sarcoidosis. Am J Ophthalmol. 2018;194:82–7.

    Article  CAS  PubMed  Google Scholar 

  43. Grumet P, Kodjikian L, de Parisot A, Errera M-H, Sedira N, Heron E, et al. Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (uveitis: clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis). Autoimmun Rev. 2018;17:331–43.

    Article  PubMed  Google Scholar 

  44. Gedalia A, Khan TA, Shetty AK, Dimitriades VR, Espinoza LR. Childhood sarcoidosis: Louisiana experience. Clin Rheumatol. 2016;35:1879–84.

    Article  PubMed  Google Scholar 

  45. Hoffmann AL, Milman N, Byg KE. Childhood sarcoidosis in Denmark 1979–1994: incidence, clinical features and laboratory results at presentation in 48 children. Acta Paediatr Oslo Nor. 1992;2004(93):30–6.

    Google Scholar 

  46. Nathan N, Marcelo P, Houdouin V, Epaud R, de Blic J, Valeyre D, et al. Lung sarcoidosis in children: update on disease expression and management. Thorax. 2015;70:537–42.

    Article  PubMed  Google Scholar 

  47. Fauroux B, Clément A. Paediatric sarcoidosis. Paediatr Respir Rev. 2005;6:128–33.

    Article  PubMed  Google Scholar 

  48. Chadelat K, Baculard A, Grimfeld A, Tournier G, Boule M, Boccon-Gibod L, et al. Pulmonary sarcoidosis in children: serial evaluation of bronchoalveolar lavage cells during corticosteroid treatment. Pediatr Pulmonol. 1993;16:41–7.

    Article  CAS  PubMed  Google Scholar 

  49. Blau EB. Familial granulomatous arthritis, iritis, and rash. J Pediatr. 1985;107:689–93.

    Article  CAS  PubMed  Google Scholar 

  50. Wouters CH, Maes A, Foley KP, Bertin J, Rose CD. Blau syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatr Rheumatol Online J. 2014;12:33.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Häfner R, et al. CARD15 mutations in Blau syndrome. Nat Genet. 2001;29:19–20.

    Article  CAS  PubMed  Google Scholar 

  52. Rosé CD, Pans S, Casteels I, Anton J, Bader-Meunier B, Brissaud P, et al. Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes. Rheumatol Oxf Engl. 2015;54:1008–16.

    Article  Google Scholar 

  53. Deiva K. Pediatric onset multiple sclerosis. Rev Neurol (Paris). 2020;176:30–6.

    Article  CAS  PubMed  Google Scholar 

  54. Brola W, Steinborn B. Pediatric multiple sclerosis—current status of epidemiology, diagnosis and treatment. Neurol Neurochir Pol. 2020;54:508–17.

    Article  PubMed  Google Scholar 

  55. Steinlin MI, Blaser SI, MacGregor DL, Raymond BJ. Eye problems in children with multiple sclerosis. Pediatr Neurol. 1995;12:207–12.

    Article  CAS  PubMed  Google Scholar 

  56. AlBloushi AF, Dheyab AM, Al-Swaina NF, Al-Obailan M, Daif A-K, Abu El-Asrar AM. Clinical findings and outcomes of uveitis associated with multiple sclerosis. Eur J Ophthalmol. 2021;31:482–90.

    Article  PubMed  Google Scholar 

  57. Casselman P, Cassiman C, Casteels I, Schauwvlieghe P-P. Insights into multiple sclerosis-associated uveitis: a scoping review. Acta Ophthalmol (Copenh). 2021;99:592–603.

    Article  Google Scholar 

  58. Clive DM, Vanguri VK. The syndrome of tubulointerstitial nephritis with uveitis (TINU). Am J Kidney Dis. 2018;72:118–28.

    Article  PubMed  Google Scholar 

  59. Nguyen AH, Mekonnen B, Kim E, Acharya NR. Clinical outcomes of pediatric macular edema associated with non-infectious uveitis. J Ophthalmic Inflamm Infect. 2021;11:8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Turk M, Hayworth J, Nevskaya T, Pope J. The frequency of uveitis in patients with adult versus childhood spondyloarthritis. RMD Open. 2020;6: e001196.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Angeles-Han ST, Ringold S, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. Arthritis Care Res. 2019;71:703–16.

    Article  Google Scholar 

  62. Goirand M, Breton S, Chevallier F, Duong N-P, Uettwiller F, Melki I, et al. Clinical features of children with enthesitis-related juvenile idiopathic arthritis/juvenile spondyloarthritis followed in a French tertiary care pediatric rheumatology centre. Pediatr Rheumatol Online J. 2018;16:21.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Marino A, Weiss PF, Brandon TG, Lerman MA. Juvenile spondyloarthritis: focus on uveitis. Pediatr Rheumatol Online J. 2020;18:70.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Weiß A, Minden K, Listing J, Foeldvari I, Sieper J, Rudwaleit M. Course of patients with juvenile spondyloarthritis during 4 years of observation, juvenile part of GESPIC. RMD Open. 2017;3:e000366.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Żuber Z, Turowska-Heydel D, Sobczyk M, Chudek J. Prevalence of HLA-B27 antigen in patients with juvenile idiopathic arthritis. Reumatologia. 2015;53:125–30.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Chan NS-W, Choi J, Cheung CMG. Pediatric uveitis. Asia Pac J Ophthalmol Phila. 2018;7:192–9.

    PubMed  Google Scholar 

  67. Guex-Crosier Y. Uveitis masquerade syndrome and orbital lymphoma: two challenging diagnosis. Klin Monatsbl Augenheilkd. 2014;231:303.

    Article  CAS  PubMed  Google Scholar 

  68. Fardeau C, Alafaleq M, Dhaenens C-M, Dollfus H, Koné-Paut I, Grunewald O, et al. ROSAH syndrome mimicking chronic uveitis. Clin Genet. 2023;103:453–8.

    Article  CAS  PubMed  Google Scholar 

  69. Schüler A, Coupland SE, Krause L, Bornfeld N. Malignant and non-malignant uveitis-masquerade syndromes in childhood. Klin Monatsbl Augenheilkd. 2007;224:477–82.

    Article  PubMed  Google Scholar 

  70. Siiskonen M, Hirn I, Pesälä R, Hautala T, Ohtonen P, Hautala N. Prevalence, incidence and epidemiology of childhood uveitis. Acta Ophthalmol (Copenh). 2021;99:e160–3.

    Article  Google Scholar 

  71. Bishop JO, Madson EC. Retinoblastoma: review of the current status. Surv Ophthalmol. 1975;19:342–66.

    CAS  PubMed  Google Scholar 

  72. Balasubramanya R, Pushker N, Bajaj MS, Ghose S, Kashyap S, Rani A. Atypical presentations of retinoblastoma. J Pediatr Ophthalmol Strabismus. 2004;41:18–24.

    Article  PubMed  Google Scholar 

  73. Haute Aut. Santé. Uvéites chroniques non infectieuses de l’enfant et de l’adulte. 2023. https://www.has-sante.fr/jcms/p_3187246/fr/uveites-chroniques-non-infectieuses-de-l-enfant-et-de-l-adulte. Accessed 12 Feb 2023.

  74. Foeldvari I, Maccora I, Petrushkin H, Rahman N, Anton J, de Boer J, et al. New and updated recommendations for the treatment of juvenile idiopathic arthritis-associated uveitis and idiopathic chronic anterior uveitis. Arthritis Care Res. 2023;75:975–82.

    Article  Google Scholar 

  75. Thorne JE, Woreta FA, Dunn JP, Jabs DA. Risk of cataract development among children with juvenile idiopathic arthritis-related uveitis treated with topical corticosteroids. Ophthalmology. 2020;127:S21–6.

    Article  PubMed  Google Scholar 

  76. Heiligenhaus A, Minden K, Tappeiner C, Baus H, Bertram B, Deuter C, et al. Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Semin Arthritis Rheum. 2019;49:43–55.

    Article  CAS  PubMed  Google Scholar 

  77. Henderson LA, Zurakowski D, Angeles-Han ST, Lasky A, Rabinovich CE, Lo MS, et al. Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. Pediatr Rheumatol Online J. 2016;14:9.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Leal I, Steeples LR, Wong SW, Giuffre C, Pockar S, Sharma V, et al. Update on the systemic management of non-infectious uveitis in children and adolescents. Surv Ophthalmol. 2023;S0039–6257(23):00001–2.

    Google Scholar 

  79. Kim L, Li A, Angeles-Han S, Yeh S, Shantha J. Update on the management of uveitis in children: an overview for the clinician. Expert Rev Ophthalmol. 2019;14:211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ferrara G, Mastrangelo G, Barone P, La Torre F, Martino S, Pappagallo G, et al. Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting. Pediatr Rheumatol Online J. 2018;16:46.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Smith JR, Matthews JM, Conrad D, Hall AJ, Niederer RL, Singh-Grewal D, et al. Recommendations for the management of childhood juvenile idiopathic arthritis-type chronic anterior uveitis. Clin Experiment Ophthalmol. 2021;49:38–45.

    Article  PubMed  Google Scholar 

  82. Simonini G, Cantarini L, Bresci C, Lorusso M, Galeazzi M, Cimaz R. Current therapeutic approaches to autoimmune chronic uveitis in children. Autoimmun Rev. 2010;9:674–83.

    Article  CAS  PubMed  Google Scholar 

  83. Wieringa WG, Armbrust W, Legger GE, Los LI. Efficacy of high-dose methotrexate in pediatric non-infectious uveitis. Ocul Immunol Inflamm. 2019;27:1305–13.

    Article  CAS  PubMed  Google Scholar 

  84. Simonini G, Paudyal P, Jones GT, Cimaz R, Macfarlane GJ. Current evidence of methotrexate efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach. Rheumatol Oxf Engl. 2013;52:825–31.

    Article  CAS  Google Scholar 

  85. Kalinina Ayuso V, van de Winkel EL, Rothova A, de Boer JH. Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis. Am J Ophthalmol. 2011;151:217–22.

    Article  PubMed  Google Scholar 

  86. Bou R, Adán A, Borrás F, Bravo B, Calvo I, De Inocencio J, et al. Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus. Rheumatol Int. 2015;35:777–85.

    Article  PubMed  Google Scholar 

  87. Little JA, Sen ES, Strike H, Hinchcliffe A, Guly CM, Lee RWJ, et al. The safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious uveitis in childhood. J Rheumatol. 2014;41:136–9.

    Article  CAS  PubMed  Google Scholar 

  88. Sood AB, Angeles-Han ST. An update on treatment of pediatric chronic non-infectious uveitis. Curr Treat Options Rheumatol. 2017;3:1–16.

    Article  Google Scholar 

  89. Cantarini L, Simonini G, Frediani B, Pagnini I, Galeazzi M, Cimaz R. Treatment strategies for childhood noninfectious chronic uveitis: an update. Expert Opin Investig Drugs. 2012;21:1–6.

    Article  CAS  PubMed  Google Scholar 

  90. Tappeiner C, Roesel M, Heinz C, Michels H, Ganser G, Heiligenhaus A. Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis. Eye. 2009;23:1192–8.

    Article  CAS  PubMed  Google Scholar 

  91. Feutren G, Mihatsch MJ. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. N Engl J Med. 1992;326:1654–60.

    Article  CAS  PubMed  Google Scholar 

  92. Vazquez-Cobian LB, Flynn T, Lehman TJA. Adalimumab therapy for childhood uveitis. J Pediatr. 2006;149:572–5.

    Article  CAS  PubMed  Google Scholar 

  93. Quartier P, Baptiste A, Despert V, Allain-Launay E, Koné-Paut I, Belot A, et al. ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. Ann Rheum Dis. 2018;77:1003–11.

    Article  CAS  PubMed  Google Scholar 

  94. Ramanan AV, Dick AD, Jones AP, McKay A, Williamson PR, Compeyrot-Lacassagne S, et al. Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis. N Engl J Med. 2017;376:1637–46.

    Article  CAS  PubMed  Google Scholar 

  95. Chia A, Lee V, Graham EM, Edelsten C. Factors related to severe uveitis at diagnosis in children with juvenile idiopathic arthritis in a screening program. Am J Ophthalmol. 2003;135:757–62.

    Article  PubMed  Google Scholar 

  96. Jani M, Barton A, Warren RB, Griffiths CEM, Chinoy H. The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases. Rheumatol (Oxf). 2014;53:213–22.

    Article  CAS  Google Scholar 

  97. Ducourau E, Rispens T, Samain M, Dernis E, Le Guilchard F, Andras L, et al. Methotrexate effect on immunogenicity and long-term maintenance of adalimumab in axial spondyloarthritis: a multicentric randomised trial. RMD Open. 2020;6:e001047.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Yang S, Huang Z, Hu Y, Zhang J, Liu X, Li H, et al. The efficacy of adalimumab as an initial treatment in patients with Behçet’s retinal vasculitis. Front Pharmacol.; 12. 2021. https://www.frontiersin.org/articles/https://doi.org/10.3389/fphar.2021.609148. Accessed 9 Aug 2023.

  99. Vitale A, Casa FD, Guerriero S, Ragab G, Mauro A, Caggiano V, et al. Efficacy and safety of adalimumab in pediatric non-infectious non-anterior uveitis: real-life experience from the International AIDA Network Uveitis Registry. Ophthalmol Ther. 2023;12:1957–71.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Richards JC, Tay-Kearney M-L, Murray K, Manners P. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Exp Ophthalmol. 2005;33:461–8.

    Article  PubMed  Google Scholar 

  101. Sukumaran S, Marzan K, Shaham B, Reiff A. High dose infliximab in the treatment of refractory uveitis: does dose matter? ISRN Rheumatol. 2012;2012:765380.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Lacomba MS, Martín CM, Galera JMG, Vidal MAG, Estévez EC, Chamond RR, et al. Aqueous humor and serum tumor necrosis factor-α in clinical uveitis. Ophthalmic Res. 2001;33:251–5.

    Article  Google Scholar 

  103. Li Y, Mao X, Tang X, Mao H. Efficacy and safety of anti-TNFα therapy for uveitis associated with juvenile idiopathic arthritis: a systematic review and meta-Analysis. Rheumatol Ther. 2021;8:711–27.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Lanz S, Seidel G, Skrabl-Baumgartner A. Golimumab in juvenile idiopathic arthritis-associated uveitis unresponsive to adalimumab. Pediatr Rheumatol Online J. 2021;19:132.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Tosi GM, Sota J, Vitale A, Rigante D, Emmi G, Lopalco G, et al. Efficacy and safety of certolizumab pegol and golimumab in the treatment of non-infectious uveitis. Clin Exp Rheumatol. 2019;37:680–3.

    PubMed  Google Scholar 

  106. Ramanan AV, Dick AD, Jones AP, Guly C, Hardwick B, Hickey H, et al. A phase II trial protocol of tocilizumab in anti-TNF refractory patients with JIA-associated uveitis (the APTITUDE trial). BMC Rheumatol. 2018;2:4.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Maleki A, Manhapra A, Asgari S, Chang PY, Foster CS, Anesi SD. Tocilizumab employment in the treatment of resistant juvenile idiopathic arthritis associated uveitis. Ocul Immunol Inflamm. 2021;29:14–20.

    Article  CAS  PubMed  Google Scholar 

  108. Iannone C, Marelli L, Costi S, Pellico MR, La Franca L, Caporali R, et al. Tocilizumab in juvenile idiopathic arthritis associated uveitis, a narrative review. Child Basel Switz. 2023;10:434.

    Google Scholar 

  109. Ramanan AV, Dick AD, Guly C, McKay A, Jones AP, Hardwick B, et al. Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial. Lancet Rheumatol. 2020;2:e135–41.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Wennink RAW, Ayuso VK, de Vries LA, Vastert SJ, de Boer JH. Tocilizumab as an effective treatment option in children with refractory intermediate and panuveitis. Ocul Immunol Inflamm. 2021;29:21–5.

    Article  CAS  PubMed  Google Scholar 

  111. Miraldi Utz V, Angeles-Han ST, Mwase N, Cassedy A, Hennard T, Lovell DJ, et al. Alternative biologic therapy in children failing conventional TNFα inhibitors for refractory, noninfectious, chronic anterior uveitis. Am J Ophthalmol. 2022;244:183–95.

    Article  CAS  PubMed  Google Scholar 

  112. De Simone L, Sangiovanni A, Aldigeri R, Mastrofilippo V, Bolletta E, Invernizzi A, et al. Interferon alpha-2a treatment for post-uveitic refractory macular edema. Ocul Immunol Inflamm. 2020;28:322–8.

    Article  PubMed  Google Scholar 

  113. Tugal-Tutkun I. Uveitis in Behçet disease: an update. Curr Opin Rheumatol. 2023;35:17–24.

    Article  PubMed  Google Scholar 

  114. Qian Y, Qu Y, Gao F, Pei M, Liang A, Xiao J, et al. Comparison of the safety and efficacy of interferon alpha-2a and cyclosporine-A when combined with glucocorticoid in the treatment of refractory Behçet’s uveitis: a randomized controlled prospective study. Front Pharmacol. 2021;12:699903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. De Simone L, Invernizzi A, Aldigeri R, Mastrofilippo V, Marvisi C, Gozzi F, et al. Effectiveness of infliximab and interferon alpha-2a for the treatment of Behçet’s uveitis: customizing therapy according to the clinical features. Ocul Immunol Inflamm. 2022;30:506–14.

    Article  PubMed  Google Scholar 

  116. Sag E, Bilginer Y, Ozen S. Autoinflammatory diseases with periodic fevers. Curr Rheumatol Rep. 2017;19:41.

    Article  PubMed  Google Scholar 

  117. Fabiani C, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S, et al. Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol. 2017;36:191–7.

    Article  PubMed  Google Scholar 

  118. Maccora I, Land P, Miraldi Utz V, Angeles-Han ST. Therapeutic potential of JAK inhibitors in juvenile idiopathic arthritis-associated uveitis. Expert Rev Clin Immunol. 2023;19:689–92.

    Article  CAS  PubMed  Google Scholar 

  119. Wen J, Hu H, Chen M, Yang H, Zhao Y, Liu Y. Role of janus kinase (JAK) inhibitor in autoimmune ocular inflammation: a systematic review. J Immunol Res. 2021;2021:2324400.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Ramanan AV, Guly CM, Keller SY, Schlichting DE, de Bono S, Liao R, et al. Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT). Trials. 2021;22:689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Baquet-Walscheid K, Heinz C, Rath T, Scheel M, Heiligenhaus A. Beneficial effect of upadacitinib in an adult patient with juvenile idiopathic arthritis-associated uveitis after unsatisfactory response to tofacitinib: a case report. Ocul Immunol Inflamm. 2023;31:1079–80.

    Article  PubMed  Google Scholar 

  122. Bauermann P, Heiligenhaus A, Heinz C. Effect of Janus kinase inhibitor treatment on anterior uveitis and associated macular edema in an adult patient with juvenile idiopathic arthritis. Ocul Immunol Inflamm. 2019;27:1232–4.

    Article  CAS  PubMed  Google Scholar 

  123. Miserocchi E, Giuffrè C, Cornalba M, Pontikaki I, Cimaz R. JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis. Clin Rheumatol. 2020;39:847–51.

    Article  PubMed  Google Scholar 

  124. Quiñones K, Cervantes-Castañeda RA, Hynes AY, Daoud YJ, Foster CS. Outcomes of cataract surgery in children with chronic uveitis. J Cataract Refract Surg. 2009;35:725–31.

    Article  PubMed  Google Scholar 

  125. van Meerwijk CLLI, Jansonius NM, Los LI. Uveitic glaucoma in children: a systematic review on surgical outcomes. J Ophthalmic Inflamm Infect. 2022;12:35.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Cheung CSY, Mireskandari K, Ali A, Silverman E, Tehrani N. Earlier use of systemic immunosuppression is associated with fewer ophthalmic surgeries in paediatric non-infectious uveitis. Br J Ophthalmol. 2020;104:938–42.

    Article  PubMed  Google Scholar 

  127. Haasnoot AM, Kuiper JJ, Hiddingh S, Schellekens PA, de Jager W, Imhof SM, et al. Ocular fluid analysis in children reveals interleukin-29/interferon-λ1 as a biomarker for juvenile idiopathic arthritis-associated uveitis. Arthritis Rheumatol. 2016;68:1769–79.

    Article  CAS  PubMed  Google Scholar 

  128. Kalinina Ayuso V, de Boer JH, Byers HL, Coulton GR, Dekkers J, de Visser L, et al. Intraocular biomarker identification in uveitis associated with juvenile idiopathic arthritis. Invest Ophthalmol Vis Sci. 2013;54:3709–20.

    Article  PubMed  Google Scholar 

  129. Angeles-Han ST, Utz VM, Thornton S, Schulert G, Rodriguez-Smith J, Kauffman A, et al. S100 proteins, cytokines, and chemokines as tear biomarkers in children with juvenile idiopathic arthritis-associated uveitis. Ocul Immunol Inflamm. 2021;29:1616–20.

    Article  CAS  PubMed  Google Scholar 

  130. Angeles-Han ST, Yeh S, Patel P, Duong D, Jenkins K, Rouster-Stevens KA, et al. Discovery of tear biomarkers in children with chronic non-infectious anterior uveitis: a pilot study. J Ophthalmic Inflamm Infect. 2018;8:17.

    Article  PubMed  PubMed Central  Google Scholar 

  131. van Straalen JW, Kearsley-Fleet L, Klotsche J, de Roock S, Minden K, Heiligenhaus A, et al. Development and external validation of a model predicting new-onset chronic uveitis at different disease durations in juvenile idiopathic arthritis. Arthritis Rheumatol. 2023;75:318–27.

    Article  PubMed  Google Scholar 

  132. Acharya NR, Ebert CD, Kelly NK, Porco TC, Ramanan AV, Arnold BF, et al. Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST-Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial. Trials. 2020;21:887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Papasavvas I, Gehrig B, Herbort CP. Clinical course and treatment paradigms for JIA-related uveitis and pars planitis uveitis using precise ocular investigational methods. Klin Monatsbl Augenheilkd. 2021;238:458–68.

    Article  PubMed  Google Scholar 

  134. Angeles-Han ST, Yeh S, McCracken C, Jenkins K, Stryker D, Myoung E, et al. Using the effects of youngsters’ eyesight on quality of life questionnaire to measure visual outcomes in children with uveitis. Arthritis Care Res. 2015;67:1513–20.

    Article  Google Scholar 

  135. McDonald J, Cassedy A, Altaye M, Andringa J, Cooper AM, Drews-Botsch C, et al. Comprehensive assessment of quality of life, functioning, and mental health in children with juvenile idiopathic arthritis and noninfectious uveitis. Arthritis Care Res. 2022;74:1311–20.

    Article  Google Scholar 

  136. Rosenberg KD, Feuer WJ, Davis JL. Ocular complications of pediatric uveitis. Ophthalmology. 2004;111:2299–306.

    Article  PubMed  Google Scholar 

  137. Ferrara M, Eggenschwiler L, Stephenson A, Montieth A, Nakhoul N, Araùjo-Miranda R, et al. The challenge of pediatric uveitis: tertiary referral center experience in the United States. Ocul Immunol Inflamm. 2019;27:410–7.

    Article  PubMed  Google Scholar 

  138. Angeles-Han ST, Rabinovich CE. Uveitis in children. Curr Opin Rheumatol. 2016;28:544–9.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Choi J, Hawley DP, Ashworth J, Edelsten C, Bossuyt ASAM. An update on the modern management of paediatric uveitis. Br J Ophthalmol. 2019;103:1685–9.

    PubMed  Google Scholar 

  140. Carlsson E, Beresford MW, Ramanan AV, Dick AD, Hedrich CM. Juvenile idiopathic arthritis associated uveitis. Children. 2021;8:646.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Yildiz M, Haslak F, Adrovic A, Sahin S, Koker O, Barut K, et al. Pediatric Behçet’s disease. Front Med. 2021;8:627192.

    Article  Google Scholar 

  142. Regusci A, Lava SAG, Milani GP, Bianchetti MG, Simonetti GD, Vanoni F. Tubulointerstitial nephritis and uveitis syndrome: a systematic review. Nephrol Dial Transplant. 2022;37:876–86.

    Article  PubMed  Google Scholar 

  143. Hintzen RQ, Dale RC, Neuteboom RF, Mar S, Banwell B. Pediatric acquired CNS demyelinating syndromes: features associated with multiple sclerosis. Neurology. 2016;87:S67-73.

    Article  PubMed  Google Scholar 

  144. Kaza H, Tyagi M, Agarwal K, Behera S, Pappuru RR, Mohan S, et al. Vogt Koyanagi Harada disease in paediatric age group: clinical characteristics, remission, recurrences and complications in Asian Indian population. Semin Ophthalmol. 2022;37:187–92.

    Article  PubMed  Google Scholar 

  145. Gallagher K, Viswanathan A, Okhravi N. Association of systemic lupus erythematosus with uveitis. JAMA Ophthalmol. 2015;133:1190–3.

    Article  PubMed  Google Scholar 

  146. Guillo L, Abreu M, Panaccione R, Sandborn WJ, Azevedo VF, Gensler L, et al. Endpoints for extraintestinal manifestations in inflammatory bowel disease trials: the EXTRA consensus from the International Organization for the Study of Inflammatory Bowel Diseases. Lancet Gastroenterol Hepatol. 2022;7:254–61.

    Article  PubMed  Google Scholar 

  147. Heiligenhaus A, Mingels A, Heinz C, Ganser G. Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication. Eur J Ophthalmol. 2007;17:743–8.

    Article  CAS  PubMed  Google Scholar 

  148. Simonini G, Taddio A, Cattalini M, Caputo R, de Libero C, Parentin F, et al. Superior efficacy of adalimumab in treating childhood refractory chronic uveitis when used as first biologic modifier drug: adalimumab as starting anti-TNF-α therapy in childhood chronic uveitis. Pediatr Rheumatol Online J. 2013;11:16.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Zannin ME, Birolo C, Gerloni VM, Miserocchi E, Pontikaki I, Paroli MP, et al. Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: 1-year followup data from the Italian Registry. J Rheumatol. 2013;40:74–9.

    Article  CAS  PubMed  Google Scholar 

  150. Miserocchi E, Modorati G, Pontikaki I, Meroni PL, Gerloni V. Long-term treatment with golimumab for severe uveitis. Ocul Immunol Inflamm. 2014;22:90–5.

    Article  CAS  PubMed  Google Scholar 

  151. Dev S, McCallum RM, Jaffe GJ. Methotrexate treatment for sarcoid-associated panuveitis. Ophthalmology. 1999;106:111–8.

    Article  CAS  PubMed  Google Scholar 

  152. Jamilloux Y, Cohen-Aubart F, Chapelon-Abric C, Maucort-Boulch D, Marquet A, Pérard L, et al. Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: a multicenter study of 132 patients. Semin Arthritis Rheum. 2017;47:288–94.

    Article  CAS  PubMed  Google Scholar 

  153. Alpsoy E, Leccese P, Emmi G, Ohno S. Treatment of Behçet’s disease: an algorithmic multidisciplinary approach. Front Med. 2021;8. 2023. https://www.frontiersin.org/articles/https://doi.org/10.3389/fmed.2021.624795. Accessed 11 Mar 2023.

  154. Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis. 2018;77:808–18.

    PubMed  Google Scholar 

  155. Saadoun D, Wechsler B, Terrada C, Hajage D, Le Thi HD, Resche-Rigon M, et al. Azathioprine in severe uveitis of Behçet’s disease. Arthritis Care Res. 2010;62:1733–8.

    Article  CAS  Google Scholar 

  156. Constantin T, Foeldvari I, Anton J, de Boer J, Czitrom-Guillaume S, Edelsten C, et al. Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative. Ann Rheum Dis. 2018;77:1107–17.

    PubMed  Google Scholar 

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Nguyen, A.T., Koné-Paut, I. & Dusser, P. Diagnosis and Management of Non-Infectious Uveitis in Pediatric Patients. Pediatr Drugs 26, 31–47 (2024). https://doi.org/10.1007/s40272-023-00596-5

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