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Non-Infectious Pediatric Uveitis

An Update on Immunomodulatory Management

  • Review Article
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Abstract

Pediatric non-infectious uveitis remains a rare but potentially sight-threatening group of diseases. However, early screening and treatment can improve outcomes. No single agent has proven to be efficacious in all cases. A wide variety of long-term immunomodulatory treatments are available; these agents differ in both their potency and side effect profiles. Corticosteroids remain an extremely valuable form of treatment in the short-term management of uveitis. Other major groups of immunomodulatory treatments include the calcineurin inhibitors and antimetabolites such as methotrexate, which is frequently used as the first-line agent. The biologics, including anti-tumor necrosis factor agents and interferons, are newer and potentially very useful therapies although side effects limit their use. Successful outcomes may be achieved with appropriate immunosuppressant therapy given early in the disease, although clinical trials are required to define the true efficacy of this strategy.

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References

  1. Zierhut M, Michels H, Stubiger N, et al. Uveitis in children. Int Ophthalmol Clin 2005; 45: 135–56

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Cunningham Jr ET. Uveitis in children. Ocul Immunol Inflamm 2000; 8: 251–61

    Article  PubMed  Google Scholar 

  4. Sudharshan S, Biswas J, Ganesh SK. Analysis of juvenile idiopathic arthritis associated uveitis in India over the last 16 years. Indian J Ophthalmol 2007; 55: 199–202

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Edelsten C, Reddy MA, Stanford MR, et al. Visual loss associated with pediatric uveitis in english primary and referral centers. Am J Ophthalmol 2003; 135: 676–80

    Article  PubMed  Google Scholar 

  7. Kanski JJ, Shun-Shin GA. Systemic uveitis syndromes in childhood: an analysis of 340 cases. Ophthalmology 1984; 91: 1247–52

    PubMed  CAS  Google Scholar 

  8. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, et al. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 1996; 80: 332–6

    Article  PubMed  CAS  Google Scholar 

  9. Tugal-Tutkun I, Havrlikova K, Power WJ, et al. Changing patterns in uveitis of childhood. Ophthalmology 1996; 103: 375–83

    PubMed  CAS  Google Scholar 

  10. Wright T, Cron RQ. Pediatric rheumatology for the adult rheumatologist. II: uveitis in juvenile idiopathic arthritis. J Clin Rheumatol 2007; 13: 205–10

    Article  PubMed  Google Scholar 

  11. Smith JR. Management of uveitis in pediatric patients: special considerations. Paediatr Drugs 2002; 4: 183–9

    PubMed  Google Scholar 

  12. Jabs DA, Nussenblatt RB, Rosenbaum JT. 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 

  13. Yu EN, Meniconi ME, Tufail F, et al. Outcomes of treatment with immunomodulatory therapy in patients with corticosteroid-resistant juvenile idiopathic arthritis-associated chronic iridocyclitis. Ocul Immunol Inflamm 2005; 13: 353–60

    Article  PubMed  CAS  Google Scholar 

  14. Lacomba MS, Martin CM, Chamond RR, et al. Aqueous and serum interferon gamma, interleukin (IL) 2, IL-4, and IL-10 in patients with uveitis. Arch Ophthalmol 2000; 118: 768–72

    PubMed  CAS  Google Scholar 

  15. Chalom EC, Goldsmith DP, Koehler MA, et al. Prevalence and outcome of uveitis in a regional cohort of patients with juvenile rheumatoid arthritis. J Rheumatol 1997; 24: 2031–4

    PubMed  CAS  Google Scholar 

  16. Soylu M, Ozdemir G, Anli A. Pediatric uveitis in southern Turkey. Ocul Immunol Inflamm 1997; 5(3): 197–202

    Article  PubMed  CAS  Google Scholar 

  17. Kump LI, Cervantes-Castañeda RA, Androudi SN, et al. Analysis of pediatric uveitis cases at a tertiary referral center. Ophthalmology 2005 Jul; 112(7): 1287–92

    Article  PubMed  Google Scholar 

  18. Ng JSK, Fan DSP, Young AL, et al. Ocular hypertensive response to topical dexamethasone in children: a dose-dependent phenomenon. Ophthalmology 2000; 107: 2097–100

    Article  PubMed  CAS  Google Scholar 

  19. Stanbury RM, Graham EM, Systemic corticosteroid therapy: side effects and their management. Br J Ophthalmol 1998 Jun; 82(6): 704–8

    Article  PubMed  CAS  Google Scholar 

  20. Smith JR, George RK, Rosenbaum JT. Lower eyelid herniation of orbital fat may complicate periocular corticosteroid injection. Am J Ophthalmol 2002; 133: 845–7

    Article  PubMed  Google Scholar 

  21. Sivaprasad S, McCluskey P, Lightman S. Intravitreal steroids in the management of macular oedema. Acta Ophthalmol Scand 2006; 84: 722–33

    Article  PubMed  CAS  Google Scholar 

  22. Chang J, McCluskey PJ, Grigg JR, et al. Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular oedema in children. Clin Experiment Ophthalmol 2006; 34: A59–68

    Article  Google Scholar 

  23. Zulian F, Martini G, Gobber D, et al. Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a double-blind trial. Rheumatology (Oxford) 2004; 43: 1288–91

    Article  CAS  Google Scholar 

  24. Eberhard BA, Sison MC, Gottlieb BS, et al. Comparison of the intraarticular effectiveness of triamcinolone hexacetonide and triamcinolone acetonide in treatment of juvenile rheumatoid arthritis. J Rheumatol 2004; 31: 2507–12

    PubMed  CAS  Google Scholar 

  25. Sijssens KM, Rothova A, Berendschot TTJM, et al. Ocular hypertension and secondary glaucoma in children with uveitis. Ophthalmology 2006; 113: 853–9

    Article  PubMed  Google Scholar 

  26. Jaffe GJ, Martin D, Callanan D, et al. Fluocinolone acetonide implant (retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology 2006; 113: 1020–7

    Article  PubMed  Google Scholar 

  27. Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2005; 32: 362–5

    PubMed  CAS  Google Scholar 

  28. Malik AR, Pavesio C. The use of low dose methotrexate in children with chronic anterior and intermediate uveitis. Br J Ophthalmol 2005; 89: 806–8

    Article  PubMed  CAS  Google Scholar 

  29. Berker N, Ozdamar Y, Soykan E, et al. Vogt-koyanagi-harada syndrome in children: report of a case and review of the literature. Ocul Immunol Inflamm 2007; 15: 351–7

    Article  PubMed  Google Scholar 

  30. Singsen BH, Goldbach-Mansky R. Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumatoid and nonrheumatic disorders. Rheum Dis Clin North Am 1997; 23: 811–40

    Article  PubMed  CAS  Google Scholar 

  31. Doycheva D, Deuter C, Stuebiger N, et al. Mycophenolate mofetil in the treatment of uveitis in children. Br J Ophthalmol 2007; 91: 180–4

    Article  PubMed  CAS  Google Scholar 

  32. Greiner K, Varikkara M, Santiago C, et al. Efficiency of mycophenolate mofetil in the treatment of intermediate and posterior uveitis [in German]. Ophthalmologe 2002; 99: 691–4

    Article  PubMed  CAS  Google Scholar 

  33. Dipchand AI, Benson L, McCrindle BW, et al. Mycophenolate mofetil in pediatric heart transplant recipients: a single-center experience. Pediatr Transplant 2001; 5: 112–8

    Article  PubMed  CAS  Google Scholar 

  34. Siepmann K, Huber M, Stübiger N, et al. Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis. Graefes Arch Clin Exp Ophthalmol 2006; 244: 788–94

    Article  PubMed  CAS  Google Scholar 

  35. Baltatzis S, Tufail F, Yu EN, et al. Mycophenolate mofetil as an immunomodulatory agent in the treatment of chronic ocular inflammatory disorders. Ophthalmology 2003; 110: 1061–5

    Article  PubMed  Google Scholar 

  36. Imrie FR, Dick AD. Nonsteroidal drugs for the treatment of noninfectious posterior and intermediate uveitis. Curr Opin Ophthalmol 2007 May; 18(3): 212–9

    Article  PubMed  Google Scholar 

  37. Okada AA. Immunomodulatory therapy for ocular inflammatory disease: a basic manual and review of the literature. Ocul Immunol Inflamm 2005; 13(5): 335–51

    Article  PubMed  CAS  Google Scholar 

  38. Kilmartin DJ, Forrester JV, Dick AD. Cyclosporin A therapy in refractory non-infectious childhood uveitis. Br J Ophthalmol 1998: 82(7): 737–42

    Article  PubMed  CAS  Google Scholar 

  39. Tappeiner C, Roesel M, Heinz C, et al. Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis. Eye 2009; 23(5): 1192–8

    Article  PubMed  CAS  Google Scholar 

  40. Miserocchi E, Baltatzis S, Ekong A, et al. Efficacy and safety of chlorambucil in intractable noninfectious uveitis: the massachusetts eye and ear infirmary experience. Ophthalmology 2002; 109: 137–42

    Article  PubMed  Google Scholar 

  41. Allali F, Benomar A, Karim A, et al. Behcet’s disease in Moroccan children: a report of 12 cases. Scand J Rheumatol 2004; 33: 362–3

    Article  PubMed  CAS  Google Scholar 

  42. Mudun BA, Ergen A, Ipcioglu SU, et al. Short-term chlorambucil for refractory uveitis in Behcet’s disease. Ocul Immunol Inflamm 2001; 9: 219–29

    Article  PubMed  CAS  Google Scholar 

  43. Rosenbaum JT. Treatment of severe refractory uveitis with intravenous cyclophosphamide. J Rheumatol 1994; 21: 123–5

    PubMed  CAS  Google Scholar 

  44. Ardoin SP, Kredich D, Rabinovich E, et al. Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up. Am J Ophthalmol 2007; 144: 844–9

    Article  PubMed  CAS  Google Scholar 

  45. Foeldvari I, Nielsen S, Kummerle-Deschner J, et al. Tumor necrosis factor-alpha blocker in treatment of juvenile idiopathic arthritis-associated uveitis refractory to second-line agents: results of a multinational survey. J Rheumatol 2007; 34: 1146–50

    PubMed  CAS  Google Scholar 

  46. Gallagher M, Quinones K, Cervantes-Castaneda RA, et al. Biological response modifier therapy for refractory childhood uveitis. Br J Ophthalmol 2007; 91: 1341–4

    Article  PubMed  Google Scholar 

  47. Saurenmann RK, Levin AV, Rose JB, et al. Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology (Oxford) 2006; 45: 982–9

    Article  CAS  Google Scholar 

  48. Kahn P, Weiss M, Imundo LF, et al. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 2006; 113: 860–4

    Article  PubMed  Google Scholar 

  49. Biester S, Deuter C, Michels H, et al. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol 2007; 91: 319–24

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  51. Smith JA, Thompson DJ, Whitcup SM, et al. A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Rheum 2005; 53: 18–23

    Article  PubMed  CAS  Google Scholar 

  52. Cochrane S, Dick AD. Tumor necrosis factor-alpha-targeted therapies in uveitis. In: Pleyer U, Foster CS, Weinreb RN, et al., editors. Uveitis and immunological disorders. Berlin: Springer, 2006: 9–11

    Google Scholar 

  53. Smith JR, Levinson RD, Holland GN, et al. Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease. Arthritis Rheum 2001; 45: 252–7

    Article  PubMed  CAS  Google Scholar 

  54. Taban M, Dupps WJ, Mandell B, et al. Etanercept (enbrel)-associated inflammatory eye disease: case report and review of the literature. Ocul Immunol Inflamm 2006; 14: 145–50

    Article  PubMed  Google Scholar 

  55. Lim LL, Fraunfelder FW, Rosenbaum JT. Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 2007; 56: 3248–52

    Article  PubMed  CAS  Google Scholar 

  56. Reddy AR, Backhouse OC. Does etanercept induce uveitis? Br J Ophthalmol 2003; 87(7): 925

    Article  PubMed  CAS  Google Scholar 

  57. Schiff MH, Burmester GR, Kent JD, et al. Safety analyses of adalimumab (humira) in global clinical trials and us postmarketing surveillance of patients with rheumatoid arthritis. Ann Rheum Dis 2006; 65: 889–94

    Article  PubMed  CAS  Google Scholar 

  58. Spillane AP, Xia Y, Sniezek PJ. Drug-induced lupus erythematosus in a patient treated with adalumimab. J Am Acad Dermatol 2007; 56: S114–6

    Article  PubMed  Google Scholar 

  59. Lepore L, Marchetti F, Facchini S, et al. Drug-induced systemic lupus erythematosus associated with etanercept therapy in a child with juvenile idiopathic arthritis. Clin Exp Rheumatol 2003; 21: 276–7

    PubMed  CAS  Google Scholar 

  60. Sharma SM, Ramanan AV, Riley P, et al. Use of infliximab in juvenile onset rheumatological disease-associated refractory uveitis: efficacy in joint and ocular disease. Ann Rheum Dis 2007; 66: 840–1

    Article  PubMed  CAS  Google Scholar 

  61. Gerloni V, Pontikaki I, Gattinara M, et al. Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients. Ann Rheum Dis 2008; 67(8): 1145–52

    Article  PubMed  CAS  Google Scholar 

  62. Horneff G, Schmeling H, Biedermann T, et al. The german etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 2004; 63: 1638–44

    Article  PubMed  CAS  Google Scholar 

  63. Wallis RS. Tumour necrosis factor antagonists: structure, function, and tuberculosis risks. Lancet Infect Dis 2008; 8(10): 601–11

    Article  PubMed  CAS  Google Scholar 

  64. Malinowski SM, Pulido JS, Folk JC. Long-term visual outcome and complications associated with pars planitis. Ophthalmology 1993; 100: 818–24

    PubMed  CAS  Google Scholar 

  65. Burmester GR, Mease PJ, Dijkmans BA, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. Epub 2009 Jan 15

    Google Scholar 

  66. Balachandran C, McCluskey PJ, Champion GD, et al. Methotrexate-induced optic neuropathy. Clin Experiment Ophthalmol 2002 Dec; 30(6): 440–1

    Article  PubMed  Google Scholar 

  67. Nestorov I. Clinical pharmacokinetics of TNF antagonists: how do they differ? Semin Arthritis Rheum 2005; 34(5 Suppl.1): 12–8

    Article  PubMed  CAS  Google Scholar 

  68. Peyrin-Biroulet L, Desreumaux P, Sandborn WJ, et al. Crohn’s disease: beyond antagonists of tumour necrosis factor. Lancet 2008; 372: 67–81

    Article  PubMed  CAS  Google Scholar 

  69. Murphy CC, Ayliffe WH, Booth A, et al. Tumor necrosis factor (alpha) blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 2004; 111(2): 352–6

    Article  PubMed  Google Scholar 

  70. Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthamol 2005; 123(7): 903–12

    Article  CAS  Google Scholar 

  71. Ruperto N, Lovell DJ, Cuttica R, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticularcourse juvenile rheumatoid arthritis. Arthritis Rheum 2007; 56: 3096–106

    Article  PubMed  CAS  Google Scholar 

  72. Galor A, Perez VL, Hammel JP, et al. Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation. Ophthalmology 2006; 113: 2317–23

    Article  PubMed  Google Scholar 

  73. Mo JS, Matsukawa A, Ohkawara S, et al. Involvement of TNF alpha, IL-1 beta and IL-1 receptor antagonist in 1ps-induced rabbit uveitis. Exp Eye Res 1998; 66: 547–57

    Article  PubMed  CAS  Google Scholar 

  74. Shen DF, Buggage RR, Eng HC, et al. Cytokine gene expression in different strains of mice with endotoxin-induced uveitis (eiu). Ocul Immunol Inflamm 2000; 8: 221–5

    Article  PubMed  CAS  Google Scholar 

  75. Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 2005; 201: 1479–86

    Article  PubMed  CAS  Google Scholar 

  76. Verbsky JW, White AJ. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol 2004; 31(10): 2071–5

    PubMed  Google Scholar 

  77. Gattorno M, Piccini A, Lasigliè D, et al. The pattern of response to antiinterleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 1999; 58(5): 1505–15

    Article  CAS  Google Scholar 

  78. Teoh SC, Sharma S, Hogan A, et al. Tailoring biological treatment: anakinra treatment of posterior uveitis associated with the CINCA syndrome. Br J Ophthalmol 2007; 91: 263–4

    Article  PubMed  CAS  Google Scholar 

  79. Arostegui JI, Arnal C, Merino R, et al. Nod2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a spanish cohort. Arthritis Rheum 2007; 56: 3805–13

    Article  PubMed  CAS  Google Scholar 

  80. Hull KM, Shoham N, Chae JJ, et al. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol 2003; 15: 61–9

    Article  PubMed  CAS  Google Scholar 

  81. Matsubayashi T, Sugiura H, Arai T, et al. Anakinra therapy for CINCA syndrome with a novel mutation in exon 4 of the cias1 gene. Acta Paediatr 2006; 95: 246–9

    Article  PubMed  Google Scholar 

  82. Seitz M, Kamgang RK, Simon HU, et al. Therapeutic interleukin (IL) 1 blockade normalises increased IL1 beta and decreased tumour necrosis factor alpha and IL10 production in blood mononuclear cells of a patient with CINCA syndrome. Ann Rheum Dis 2005; 64: 1802–3

    Article  PubMed  CAS  Google Scholar 

  83. Matsubara T, Hasegawa M, Shiraishi M, et al. A severe case of chronic infantile neurologic, cutaneous, articular syndrome treated with biologic agents. Arthritis Rheum 2006; 54: 2314–20

    Article  PubMed  Google Scholar 

  84. Martin TM, Zhang Z, Kurz P, et al. The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. Arthritis Rheum 2009; 60(2): 611–8

    Article  PubMed  CAS  Google Scholar 

  85. Milman N, Andersen CB, Hansen A, et al. Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation. APMIS 2006; 114(12): 912–9

    Article  PubMed  Google Scholar 

  86. Hawkins PN, Lachmann HJ, Aganna E, et al. Spectrum of clinical features in muckle-wells syndrome and response to anakinra. Arthritis Rheum 2004; 50: 607–12

    Article  PubMed  CAS  Google Scholar 

  87. Nussenblatt RB, Fortin E, Schiffman R, et al. Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-tac mab: a phase I/II clinical trial. Proc Natl Acad Sci U S A 1999; 96: 7462–6

    Article  PubMed  CAS  Google Scholar 

  88. Guex-Crosier Y, Raber J, Chan CC, et al. Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases. J Immunol 1997; 158: 452–8

    PubMed  CAS  Google Scholar 

  89. Nussenblatt RB, Thompson DJS, Li Z, et al. Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration. J Autoimmun 2003; 21: 283–93

    Article  PubMed  CAS  Google Scholar 

  90. Yeh S, Wroblewski K, Buggage R, et al. High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, noninfectious uveitis. J Autoimmun 2008; 31(2): 91–7

    Article  PubMed  CAS  Google Scholar 

  91. Buggage RR, Levy-Clarke G, Sen HN, et al. A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to behcet’s disease. Ocul Immunol Inflamm 2007; 15: 63–70

    Article  PubMed  CAS  Google Scholar 

  92. Smith JM, Nemeth TL, McDonald RA. Current immunosuppressive agents in pediatric renal transplantation: efficacy, side-effects and utilization. Pediatr Transplant 2004; 8: 445–53

    Article  PubMed  CAS  Google Scholar 

  93. Patten SB. Psychiatric side effects of interferon treatment. Curr Drug Saf 2006; 1(2): 143–50

    Article  PubMed  CAS  Google Scholar 

  94. Plskova J, Greiner K, Muckersie E, et al. Interferon-alpha: a key factor in autoimmune disease? Invest Ophthalmol Vis Sci 2006; 47: 3946–50

    Article  PubMed  Google Scholar 

  95. Okada AA, Keino H, Fukai T, et al. Effect of type I interferon on experimental autoimmune uveoretinitis in rats. Ocul Immunol Inflamm 1998; 6: 215–26

    Article  PubMed  CAS  Google Scholar 

  96. Selmi C, Lleo A, Zuin M, et al. Interferon alpha and its contribution to autoimmunity. Curr Opin Investig Drugs 2006; 7: 451–6

    PubMed  CAS  Google Scholar 

  97. Pivetti-Pezzi P, Accorinti M, Pirraglia MP, et al. Interferon alpha for ocular behcet’s disease. Acta Ophthalmol Scand 1997; 75: 720–2

    Article  PubMed  CAS  Google Scholar 

  98. Alpsoy E, Durusoy C, Yilmaz E, et al. Interferon alfa-2a in the treatment of behcet disease: a randomized placebo-controlled and double-blind study. Arch Dermatol 2002; 138: 467–71

    Article  PubMed  CAS  Google Scholar 

  99. Wechsler B, Bodaghi B, Huong DL, et al. Efficacy of interferon alfa-2a in severe and refractory uveitis associated with Behcet’s disease. Ocul Immunol Inflamm 2000; 8(4): 293–301

    Article  PubMed  CAS  Google Scholar 

  100. Krause L, Turnbull JR, Torun N, et al. Interferon alfa-2a in the treatment of ocular Adamantiades-Behcet’s disease. Adv Exp Med Biol 2003; 528: 511–9

    Article  PubMed  CAS  Google Scholar 

  101. Krause L, Altenburg A, Pleyer U, et al. Long-term visual prognosis of patients with ocular Adamantiades-Behcet’s disease treated with interferon-alpha-2a. J Rheumatol 2008; 35(5): 896–903

    PubMed  CAS  Google Scholar 

  102. Guillaume-Czitrom S, Berger C, Pajot C, et al. Efficacy and safety of interferon-alpha in the treatment of corticodependent uveitis of paediatric Behcet’s disease. Rheumatology (Oxford) 2007; 46: 1570–3

    Article  CAS  Google Scholar 

  103. Iorio R, Pensati P, Botta S, et al. Side effects of alpha-interferon therapy and impact on health-related quality of life in children with chronic viral hepatitis. Pediatr Infect Dis J 1997; 16(10): 984–90

    Article  PubMed  CAS  Google Scholar 

  104. Ballauff A, Schneider T, Gerner P, et al. Safety and efficacy of interferon retreatment in children with chronic hepatitis B. Eur J Pediatr 1998; 157: 382–5

    Article  PubMed  CAS  Google Scholar 

  105. Heiligenhaus A, Niewerth M, Mingels A, et al. Epidemiology of uveitis in juvenile idiopathic arthritis from a national paediatric rheumatologic and ophthalmologic database [in German]. Klin Monatsbl Augenheilkd 2005; 222: 993–1001

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  107. Menezo V, Lau C, Comer M, et al. Clinical outcome of chronic immunosuppression in patients with non-infectious uveitis. Clin Experiment Ophthalmol 2005; 33: 16–21

    Article  PubMed  Google Scholar 

  108. Zerkak D, Dougados M. Benefit/risk of combination therapies. Clin Exp Rheumatol 2004; 22: S71–6

    PubMed  CAS  Google Scholar 

  109. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The premier study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006; 54: 26–37

    Article  PubMed  CAS  Google Scholar 

  110. Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary sjogren’s syndrome: an open-label phase II study. Arthritis Rheum 2005; 52: 2740–50

    Article  PubMed  CAS  Google Scholar 

  111. El Fassi D, Nielsen CH, Bonnema SJ, et al. B lymphocyte depletion with the monoclonal antibody rituximab in Graves’ disease: a controlled pilot study. J Clin Endocrinol Metab 2007; 92: 1769–72

    Article  PubMed  CAS  Google Scholar 

  112. Kuek A, Hazleman BL, Gaston JH, et al. Successful treatment of refractory polyarticular juvenile idiopathic arthritis with rituximab. Rheumatology (Oxford) 2006; 45: 1448–9

    Article  CAS  Google Scholar 

  113. Ishikawa H. Mizoribine and mycophenolate mofetil. Ishikawa H. Curr Med Chem 1999; 6(7): 575–97

    CAS  Google Scholar 

  114. Yoshioka K, Ohashi Y, Sakai T, et al. A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome. Kidney Int 2000; 58: 317–24

    Article  PubMed  CAS  Google Scholar 

  115. Ito S, Harada T, Nakamura T, et al. Mizoribine for renal sarcoidosis: effective steroid tapering and prevention of recurrence. Pediatr Nephrol 2009 Feb; 24(2): 411–4

    Article  PubMed  Google Scholar 

  116. Tanaka H, Oki ES, Tsugawa K, et al. Long-term intermittent pulse therapy with mizoribine attenuates histologic progression in young patients with severe lupus nephritis: report of two patients. Nephrology (Carlton) 2007; 12(4): 376–9

    Article  CAS  Google Scholar 

  117. Hayashi A, Hanada T, Kohda T, et al. Mizoribine oral pulse therapy for a patient with polyarticular juvenile idiopathic arthritis. Pediatr Int 2006; 48: 638–40

    Article  PubMed  CAS  Google Scholar 

  118. De Kozak Y, Omri B, Smith JR, et al. Protein kinase Czeta (PKCzeta) regulates ocular inflammation and apoptosis in endotoxin-induced uveitis (EIU): signaling molecules involved in EIU resolution by PKCzeta inhibitor and interleukin-13. Am J Pathol 2007 Apr; 170(4): 1241–57

    Article  PubMed  CAS  Google Scholar 

  119. Houslay MD, Schafer P, Zhang KY. Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 2005 Nov; 10(22): 1503–19

    Article  PubMed  CAS  Google Scholar 

  120. Rapoff MA, Lindsley CB. Improving adherence to medical regimens for juvenile rheumatoid arthritis. Pediatr Rheumatol Online J 2007; 5: 10

    Article  PubMed  Google Scholar 

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Acknowledgments

Dr Srilakshmi M. Sharma is supported by The Keeler Foundation scholarship. There were no other sources of funding for this study. Professor Andrew D. Dick has received consultancies from Pfizer and Novartis. The other authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Bristol Eye Hospital, Lower Maudlin Street, Bristol, BS1 2LX, UK

    Srilakshmi M. Sharma

  2. Department of Clinical Sciences South Bristol, University of Bristol, Bristol, UK

    Andrew D. Dick

  3. Bristol Royal Hospital for Children & Royal National Hospital for Rheumatic Diseases, Bath, UK

    Athimalaipet V. Ramanan

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  1. Srilakshmi M. Sharma
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  2. Andrew D. Dick
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  3. Athimalaipet V. Ramanan
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Correspondence to Srilakshmi M. Sharma.

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Sharma, S.M., Dick, A.D. & Ramanan, A.V. Non-Infectious Pediatric Uveitis. Pediatr-Drugs 11, 229–241 (2009). https://doi.org/10.2165/00148581-200911040-00002

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