Ocular Immunology & Inflammation, 2015; 23(1): 102–105 ! Informa Healthcare USA, Inc. ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2013.863941
LETTER TO THE EDITOR
Early Onset Bilateral Anterior Uveitis Preceding a Late Manifestation of Juvenile Idiopathic Arthritis: A Case Report Ocul Immunol Inflamm Downloaded from informahealthcare.com by University of Victoria on 04/25/15 For personal use only.
Fulvio Parentin, MD1, Lorenza Matarazzo, MD2, Loredana Lepore, Stefano Pensiero, MD1, and Alessandro Ventura, MD1,2 1
MD
1
,
Institute for Maternal and Child Health, IRCCS ‘‘Burlo Garofolo’’, Trieste, Italy and 2 University of Trieste, Trieste, Italy
CASE REPORT
Once inflammation had been controlled, she underwent bilateral cataract extraction with intraocular lenses implantation. Immunosuppressive therapy was then stopped. Visual acuity improved to 20/20 in both eyes. In the following 9 years the patient was examined every 4–6 months. During this period, only 10 episodes of mild recurrent iridocyclitis occurred, especially in the right eye (7 relapses), without any significant reduction of the visual acuity. We treated these episodes only with short-term topical steroids and cycloplegic eyedrops. At the age of 13 years when the patient developed arthritis at the right ankle and left knee, she was diagnosed with oligoarticular juvenile idiopathic arthritis (JIA) with good response to NSAID therapy alone. Blood exams showed positive ANA autoantibody (1:640, positive 41:80), with negative antidsDNA. A few months after the onset of the arthritis the patient showed recurrent relapses of bilateral iridocyclitis; she was diagnosed as a case of JIArelated anterior uveitis and treated with topical and systemic corticosteroids. A progressive decrease in the right visual acuity (20/80) was noticed at the age of 15 years, secondary to the presence of cystoid macular edema and confirmed by OCT (Figure 1). Considering this major complication, therapy with infliximab (7 infusions each of 350 mg every 2, 4, and 8 weeks) and methotrexate (MTX) was immediately started without any side effects. Visual acuity promptly rose to 20/20 and cystoid macular edema resolved. After 1 year, when she was 16 years old, a mild relapse of right
We report the case of a girl, aged 17 years, who was diagnosed at the age of 3 years with a chronic bilateral iridocyclitis. Visual acuity was light perception in the right eye and 20/80 in the left at presentation. The right eye showed a dense cataract as well as a band keratopathy in addition to diffuse posterior synechiae, with neovascular tufts at the pupillary margin. The left eye had a posterior subcapsular opacity, band keratopathy, and posterior synechiae. A 3þ cellular reaction and 2þ flare were found in the anterior chamber of both eyes. Intraocular pressure was within normal range in both eyes. While vitreoretinal structures of the right eye were not visible, those of the left eye showed no alteration. Blood test results did not show any systemic diseases (inflammatory markers and ANA autoantibody were negative); the condition was thus defined as a primary bilateral anterior uveitis. Topical treatment with dexamethasone 0.2%, atropine sulfate 0.5% and systemic therapy with prednisone 1 mg/kg was initiated. After 4 weeks the decrease of visual acuity in the left eye persisted with increased opacity of the lens. Cyclosporine A therapy was initiated (100 mg/ daily) with only slight reduction of intraocular inflammation. A dramatic decrease of uveitis and neovascularization was recorded after addition of thalidomide (50 mg/daily). The left eye regained a visual acuity of 20/50. The effectiveness of thalidomide in this patient was reported in a previous case report.1
Received 4 April 2013; revised 5 November 2013; accepted 5 November 2013; published online 18 December 2013 Correspondence: Fulvio Parentin, MD, Institute for Maternal and Child Health – IRCCS ‘‘Burlo Garofolo’’, Via dell’Istria 65/1, 34137, Trieste, Italy. Tel: 00390403785433. E-mail: [email protected]; [email protected]
102
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Uveitis and juvenile idiopathic arthritis
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FIGURE 1. OCT scan of the macular retina before and after the TNF-alfa therapy: resolution of macular edema.
iridocyclitis was detected and a shift toward adalimumab (40 mg subcutaneously every 2 weeks) was performed, without further relapse during 1-year follow-up.
DISCUSSION Juvenile idiopathic arthritis is defined as an arthritis lasting at least 6 weeks occurring before the age of 16 years when other causes of arthritis have been excluded. There are 3 major types of JIA: oligoarticular (up to 4 joints affected), either persistent or extended (more than 4 joints affected after the first 6 months); polyarticular (more than 4 joints affected); and systemic arthritis.2 Uveitis is the most frequent extraarticular manifestation of JIA and it usually has an anterior localization. It can be chronic, recurrent, acute, or associated with vitreous involvement. Uveitis occurs in 12–13% of patients with all types of JIA3 and in 16–40% of oligoarticular JIA.4 According to different studies, the onset of uveitis and arthritis may change. Recently Zannin et al.,5 in a multicenter Italian study, highlighted a mean age at arthritis onset of 4.4 years !
2015 Informa Healthcare USA, Inc.
(range 1.2–15.8 years) and a mean interval time between arthritis and uveitis onset of 1.8 years (range: 0.0–14.2 years). In this cohort study the same author shows that the time interval resulted as the main predictor of severe course uveitis. The most common form of uveitis is the chronic anterior uveitis followed by acute anterior and recurrent uveitis. Patients at risk of developing uveitis are especially girls under the age of 6 years, with ANA autoantibody positivity and oligoarticular involvement.6–11 Some 65–90% of children with chronic uveitis present ANA autoantibodies, which are the major risk factor. Most cases of uveitis are bilateral (70–80%) but unilateral disease may progress into bilateral.2 Guidelines provide that children with ANA-positive oligoarticular and polyarticular JIA with onset before the age of 7 years should have an eye examination every 3–4 months, reduced to every 6 months in case of ANA-negative oligo- or polyarticular JIA.9 Uveitis can usually be found at diagnosis of JIA with a period of higher risk in the first 4 years of JIA development even if these children may develop uveitis throughout their life.2,3,6 Although JIA is associated with uveitis, there is no correlation
Ocul Immunol Inflamm Downloaded from informahealthcare.com by University of Victoria on 04/25/15 For personal use only.
104 F. Parentin et al. between arthritis activity and uveitis.10 Uveitis usually appears later than arthritis but in some cases can precede JIA.6 In fact, eye involvement precedes joint involvement in approximately 5–10% of cases,2,4 usually a few months before the onset of arthritis. Kotaniemi et al.6 describe a population of 426 children, 51 of whom (12%) received a diagnosis of uveitis made before the joint involvement (6 patients) or no more than 3 months after the onset of arthritis (45 patients). Saurenmann et al.7 also describe 18 patients out of 142 (12.7%) who developed uveitis before the appearance of JIA. Therefore, uveitis occurs early in the development of arthritis and in some cases may precede it. The onset of uveitis may be asymptomatic, and symptoms (redness, pain, photophobia, reduced/ blurry vision) may occur only once complications have already taken place.7,9,10 Therapy is based initially on the use of topical steroids followed by mydriatic and NSAIDs. For the systemic treatment there are NSAIDs, corticosteroids, and immunosuppressive agents (MTX, cyclosporine, mycophenolate). Among the possible ocular complications, cataract is the most common, followed by synechiae, glaucoma, band keratopathy, and cystoid macular edema.2,6,10 Although most patients have a good outcome, there may be impaired vision or blindness for some.6,7 More recently Kalinina Ayuso12 highlighted that male gender and uveitis as initial manifestation of JIA were independently associated with a complicated course of JIA–associated uveitis. In this large study up to 25% of children aged less than 7 years developed uveitis prior to arthritis. Particularly, development of cystoid macular edema, early cataract surgery, and papillitis were all associated with male gender; furthermore, children with uveitis prior to arthritis had more complications at various time points during follow-up. Probably the higher rate of complications could be explained with a delayed diagnosis and a delay in effective therapy. Even in this large study no patient had a long-term interval between uveitis and arthritis, as reported in our case. The efficiency of anti TNF-a therapy in the JIA-related uveitis is well known. TNF-a is produced by monocytes and macrophages and it acts on the permeability of cell membrane as well as on the recruitment of inflammation cells and adhesion molecules.11 TNF-a is implicated in the pathogenesis of uveitis and it is detectable in the vitreous humor of these patients.13 Several studies in the literature report the effectiveness of infliximab (IgG1 murine–human chimeric antibody that binds to the membrane-bound and soluble TNF-a) in uveitis JIA correlated with poor control of intraocular inflammation during steroids or immunosuppressive therapy and with reduction of intraocular inflammation and improvement in visual acuity during infliximab therapy.11,13,14
Therapy with a dose of 5–10 mg/kg intravenously every 0, 2, 4, and then 6–8 weeks is administered usually with maintenance of immunosuppressive agents.14 In particular, simultaneous use of MTX increases the efficacy and duration of infliximab treatment not only because the latter alone has a greater risk of developing autoantibodies, but also because it can be an insufficient therapy for JIA-associated uveitis.11 Adalimimab (a fully human monoclonal TNF-a antibody), at a dose of 24 mg/m2 subcutaneously every 2 weeks, seems to be an alternative valid option with a superior activity in maintaining remission for a longer period and with a higher rate than infliximab.15 We believe that this case is of great interest due to the appearance of JIA a long time after uveitis (10 years). To our knowledge, there are no other reports in literature describing the onset of uveitis more than 10 years before the emergence of JIA. Therefore, in childhood uveitis always suspect the concomitant presence of systemic autoimmune illness, first of all JIA, with possible onset even after many years.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Parentin F, Da Pozzo S, Lepore L, et al. Thalidomide effectiveness for bilateral chronic idiopathic anterior uveitis in a three-year-old child. Ophthalmologica. 2001;215: 70–73. 2. Cassidy J, Kivlin J, Lindsley C, et al. Ophthalmologic examinations in children with juvenile rheumatoid arthritis. Pediatrics. 2006;117:1843–1845. 3. Hoeve M, Kalinina Ayuso V, Schalij-Delfos NE, et al. The clinical course of juvenile idiopathic arthritis-associated uveitis in childhood and puberty. Br J Ophtalmol. 2012;96: 852–856. doi: 10.1136/bjophthalmol-2011-301023. Epub 2012 Mar 7. 4. Abdwani R. Challenges of childhood uveitis. Sultan Qaboos Univ Med J. 2009;9:247–256. Epub 2009 Dec 19. 5. Zannin ME, Buscain I, Vittadello F, et al. Timing of uveitis onset in oligoarticular juvenile idiopathic arthritis (JIA) is the main predictor of severe course uveitis. Acta Ophthalmol. 2012;90:91–95. 6. Kotaniemi K, Kautiainen H, Karma A, et al. Occurrence of uveitis in recently diagnosed juvenile chronic arthritis: a prospective study. Ophthalmology. 2001;108:2071–2075. 7. Saurenmann RK, Levin AV, Feldman BM, et al. Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study. Arthritis Rheum. 2007; 56:647–657. 8. Akduman L, Kaplan HJ, Tychsen L. Prevalence of uveitis in an outpatient juvenile arthritis clinic: onset of uveitis Ocular Immunology & Inflammation
Uveitis and juvenile idiopathic arthritis
9.
10.
11.
Ocul Immunol Inflamm Downloaded from informahealthcare.com by University of Victoria on 04/25/15 For personal use only.
12.
more than a decade after onset of arthritis. J Ophthalmic Nurs Technol. 1997;16:177–182. Oren B, Sehgal A, Simon JW, et al. The prevalence of uveitis in juvenile rheumatoid arthritis. J AAPOS. 2001;5: 2–4. Kodsi SR, Rubin SE, Milojevic D, et al. Time of onset of uveitis in children with juvenile rheumatoid arthritis. J AAPOS. 2002;6:373–376. Richards JC, Tay-Kearney ML, Murray K, et al. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Exp Ophthalmol. 2005;33:461–468. Kalinina Ayuso V, Ten Cate HA, van der Does P, et al. Male gender as a risk factor for complications in uveitis
!
2015 Informa Healthcare USA, Inc.
105
associated with juvenile idiopathic arthritis. Am J Ophthalmol. 2010;149:994–999. 13. Kahn P, Weiss M, Imundo LF, et al. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology. 2006;113:860–864.e2. Epub 2006 Mar 20. 14. Tugal-Tutkun I, Ayranci O, Kasapcopur O, et al. Retrospective analysis of children with uveitis treated with infliximab. J AAPOS. 2008;12:611–613. Epub 2008 Oct 19. 15. Simonini G, Taddio A, Cattalini M, et al. Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res (Hoboken). 2011;63:612–618.
LETTER TO THE EDITOR
Early Onset Bilateral Anterior Uveitis Preceding a Late Manifestation of Juvenile Idiopathic Arthritis: A Case Report Ocul Immunol Inflamm Downloaded from informahealthcare.com by University of Victoria on 04/25/15 For personal use only.
Fulvio Parentin, MD1, Lorenza Matarazzo, MD2, Loredana Lepore, Stefano Pensiero, MD1, and Alessandro Ventura, MD1,2 1
MD
1
,
Institute for Maternal and Child Health, IRCCS ‘‘Burlo Garofolo’’, Trieste, Italy and 2 University of Trieste, Trieste, Italy
CASE REPORT
Once inflammation had been controlled, she underwent bilateral cataract extraction with intraocular lenses implantation. Immunosuppressive therapy was then stopped. Visual acuity improved to 20/20 in both eyes. In the following 9 years the patient was examined every 4–6 months. During this period, only 10 episodes of mild recurrent iridocyclitis occurred, especially in the right eye (7 relapses), without any significant reduction of the visual acuity. We treated these episodes only with short-term topical steroids and cycloplegic eyedrops. At the age of 13 years when the patient developed arthritis at the right ankle and left knee, she was diagnosed with oligoarticular juvenile idiopathic arthritis (JIA) with good response to NSAID therapy alone. Blood exams showed positive ANA autoantibody (1:640, positive 41:80), with negative antidsDNA. A few months after the onset of the arthritis the patient showed recurrent relapses of bilateral iridocyclitis; she was diagnosed as a case of JIArelated anterior uveitis and treated with topical and systemic corticosteroids. A progressive decrease in the right visual acuity (20/80) was noticed at the age of 15 years, secondary to the presence of cystoid macular edema and confirmed by OCT (Figure 1). Considering this major complication, therapy with infliximab (7 infusions each of 350 mg every 2, 4, and 8 weeks) and methotrexate (MTX) was immediately started without any side effects. Visual acuity promptly rose to 20/20 and cystoid macular edema resolved. After 1 year, when she was 16 years old, a mild relapse of right
We report the case of a girl, aged 17 years, who was diagnosed at the age of 3 years with a chronic bilateral iridocyclitis. Visual acuity was light perception in the right eye and 20/80 in the left at presentation. The right eye showed a dense cataract as well as a band keratopathy in addition to diffuse posterior synechiae, with neovascular tufts at the pupillary margin. The left eye had a posterior subcapsular opacity, band keratopathy, and posterior synechiae. A 3þ cellular reaction and 2þ flare were found in the anterior chamber of both eyes. Intraocular pressure was within normal range in both eyes. While vitreoretinal structures of the right eye were not visible, those of the left eye showed no alteration. Blood test results did not show any systemic diseases (inflammatory markers and ANA autoantibody were negative); the condition was thus defined as a primary bilateral anterior uveitis. Topical treatment with dexamethasone 0.2%, atropine sulfate 0.5% and systemic therapy with prednisone 1 mg/kg was initiated. After 4 weeks the decrease of visual acuity in the left eye persisted with increased opacity of the lens. Cyclosporine A therapy was initiated (100 mg/ daily) with only slight reduction of intraocular inflammation. A dramatic decrease of uveitis and neovascularization was recorded after addition of thalidomide (50 mg/daily). The left eye regained a visual acuity of 20/50. The effectiveness of thalidomide in this patient was reported in a previous case report.1
Received 4 April 2013; revised 5 November 2013; accepted 5 November 2013; published online 18 December 2013 Correspondence: Fulvio Parentin, MD, Institute for Maternal and Child Health – IRCCS ‘‘Burlo Garofolo’’, Via dell’Istria 65/1, 34137, Trieste, Italy. Tel: 00390403785433. E-mail: [email protected]; [email protected]
102
Ocul Immunol Inflamm Downloaded from informahealthcare.com by University of Victoria on 04/25/15 For personal use only.
Uveitis and juvenile idiopathic arthritis
103
FIGURE 1. OCT scan of the macular retina before and after the TNF-alfa therapy: resolution of macular edema.
iridocyclitis was detected and a shift toward adalimumab (40 mg subcutaneously every 2 weeks) was performed, without further relapse during 1-year follow-up.
DISCUSSION Juvenile idiopathic arthritis is defined as an arthritis lasting at least 6 weeks occurring before the age of 16 years when other causes of arthritis have been excluded. There are 3 major types of JIA: oligoarticular (up to 4 joints affected), either persistent or extended (more than 4 joints affected after the first 6 months); polyarticular (more than 4 joints affected); and systemic arthritis.2 Uveitis is the most frequent extraarticular manifestation of JIA and it usually has an anterior localization. It can be chronic, recurrent, acute, or associated with vitreous involvement. Uveitis occurs in 12–13% of patients with all types of JIA3 and in 16–40% of oligoarticular JIA.4 According to different studies, the onset of uveitis and arthritis may change. Recently Zannin et al.,5 in a multicenter Italian study, highlighted a mean age at arthritis onset of 4.4 years !
2015 Informa Healthcare USA, Inc.
(range 1.2–15.8 years) and a mean interval time between arthritis and uveitis onset of 1.8 years (range: 0.0–14.2 years). In this cohort study the same author shows that the time interval resulted as the main predictor of severe course uveitis. The most common form of uveitis is the chronic anterior uveitis followed by acute anterior and recurrent uveitis. Patients at risk of developing uveitis are especially girls under the age of 6 years, with ANA autoantibody positivity and oligoarticular involvement.6–11 Some 65–90% of children with chronic uveitis present ANA autoantibodies, which are the major risk factor. Most cases of uveitis are bilateral (70–80%) but unilateral disease may progress into bilateral.2 Guidelines provide that children with ANA-positive oligoarticular and polyarticular JIA with onset before the age of 7 years should have an eye examination every 3–4 months, reduced to every 6 months in case of ANA-negative oligo- or polyarticular JIA.9 Uveitis can usually be found at diagnosis of JIA with a period of higher risk in the first 4 years of JIA development even if these children may develop uveitis throughout their life.2,3,6 Although JIA is associated with uveitis, there is no correlation
Ocul Immunol Inflamm Downloaded from informahealthcare.com by University of Victoria on 04/25/15 For personal use only.
104 F. Parentin et al. between arthritis activity and uveitis.10 Uveitis usually appears later than arthritis but in some cases can precede JIA.6 In fact, eye involvement precedes joint involvement in approximately 5–10% of cases,2,4 usually a few months before the onset of arthritis. Kotaniemi et al.6 describe a population of 426 children, 51 of whom (12%) received a diagnosis of uveitis made before the joint involvement (6 patients) or no more than 3 months after the onset of arthritis (45 patients). Saurenmann et al.7 also describe 18 patients out of 142 (12.7%) who developed uveitis before the appearance of JIA. Therefore, uveitis occurs early in the development of arthritis and in some cases may precede it. The onset of uveitis may be asymptomatic, and symptoms (redness, pain, photophobia, reduced/ blurry vision) may occur only once complications have already taken place.7,9,10 Therapy is based initially on the use of topical steroids followed by mydriatic and NSAIDs. For the systemic treatment there are NSAIDs, corticosteroids, and immunosuppressive agents (MTX, cyclosporine, mycophenolate). Among the possible ocular complications, cataract is the most common, followed by synechiae, glaucoma, band keratopathy, and cystoid macular edema.2,6,10 Although most patients have a good outcome, there may be impaired vision or blindness for some.6,7 More recently Kalinina Ayuso12 highlighted that male gender and uveitis as initial manifestation of JIA were independently associated with a complicated course of JIA–associated uveitis. In this large study up to 25% of children aged less than 7 years developed uveitis prior to arthritis. Particularly, development of cystoid macular edema, early cataract surgery, and papillitis were all associated with male gender; furthermore, children with uveitis prior to arthritis had more complications at various time points during follow-up. Probably the higher rate of complications could be explained with a delayed diagnosis and a delay in effective therapy. Even in this large study no patient had a long-term interval between uveitis and arthritis, as reported in our case. The efficiency of anti TNF-a therapy in the JIA-related uveitis is well known. TNF-a is produced by monocytes and macrophages and it acts on the permeability of cell membrane as well as on the recruitment of inflammation cells and adhesion molecules.11 TNF-a is implicated in the pathogenesis of uveitis and it is detectable in the vitreous humor of these patients.13 Several studies in the literature report the effectiveness of infliximab (IgG1 murine–human chimeric antibody that binds to the membrane-bound and soluble TNF-a) in uveitis JIA correlated with poor control of intraocular inflammation during steroids or immunosuppressive therapy and with reduction of intraocular inflammation and improvement in visual acuity during infliximab therapy.11,13,14
Therapy with a dose of 5–10 mg/kg intravenously every 0, 2, 4, and then 6–8 weeks is administered usually with maintenance of immunosuppressive agents.14 In particular, simultaneous use of MTX increases the efficacy and duration of infliximab treatment not only because the latter alone has a greater risk of developing autoantibodies, but also because it can be an insufficient therapy for JIA-associated uveitis.11 Adalimimab (a fully human monoclonal TNF-a antibody), at a dose of 24 mg/m2 subcutaneously every 2 weeks, seems to be an alternative valid option with a superior activity in maintaining remission for a longer period and with a higher rate than infliximab.15 We believe that this case is of great interest due to the appearance of JIA a long time after uveitis (10 years). To our knowledge, there are no other reports in literature describing the onset of uveitis more than 10 years before the emergence of JIA. Therefore, in childhood uveitis always suspect the concomitant presence of systemic autoimmune illness, first of all JIA, with possible onset even after many years.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Parentin F, Da Pozzo S, Lepore L, et al. Thalidomide effectiveness for bilateral chronic idiopathic anterior uveitis in a three-year-old child. Ophthalmologica. 2001;215: 70–73. 2. Cassidy J, Kivlin J, Lindsley C, et al. Ophthalmologic examinations in children with juvenile rheumatoid arthritis. Pediatrics. 2006;117:1843–1845. 3. Hoeve M, Kalinina Ayuso V, Schalij-Delfos NE, et al. The clinical course of juvenile idiopathic arthritis-associated uveitis in childhood and puberty. Br J Ophtalmol. 2012;96: 852–856. doi: 10.1136/bjophthalmol-2011-301023. Epub 2012 Mar 7. 4. Abdwani R. Challenges of childhood uveitis. Sultan Qaboos Univ Med J. 2009;9:247–256. Epub 2009 Dec 19. 5. Zannin ME, Buscain I, Vittadello F, et al. Timing of uveitis onset in oligoarticular juvenile idiopathic arthritis (JIA) is the main predictor of severe course uveitis. Acta Ophthalmol. 2012;90:91–95. 6. Kotaniemi K, Kautiainen H, Karma A, et al. Occurrence of uveitis in recently diagnosed juvenile chronic arthritis: a prospective study. Ophthalmology. 2001;108:2071–2075. 7. Saurenmann RK, Levin AV, Feldman BM, et al. Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study. Arthritis Rheum. 2007; 56:647–657. 8. Akduman L, Kaplan HJ, Tychsen L. Prevalence of uveitis in an outpatient juvenile arthritis clinic: onset of uveitis Ocular Immunology & Inflammation
Uveitis and juvenile idiopathic arthritis
9.
10.
11.
Ocul Immunol Inflamm Downloaded from informahealthcare.com by University of Victoria on 04/25/15 For personal use only.
12.
more than a decade after onset of arthritis. J Ophthalmic Nurs Technol. 1997;16:177–182. Oren B, Sehgal A, Simon JW, et al. The prevalence of uveitis in juvenile rheumatoid arthritis. J AAPOS. 2001;5: 2–4. Kodsi SR, Rubin SE, Milojevic D, et al. Time of onset of uveitis in children with juvenile rheumatoid arthritis. J AAPOS. 2002;6:373–376. Richards JC, Tay-Kearney ML, Murray K, et al. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Exp Ophthalmol. 2005;33:461–468. Kalinina Ayuso V, Ten Cate HA, van der Does P, et al. Male gender as a risk factor for complications in uveitis
!
2015 Informa Healthcare USA, Inc.
105
associated with juvenile idiopathic arthritis. Am J Ophthalmol. 2010;149:994–999. 13. Kahn P, Weiss M, Imundo LF, et al. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology. 2006;113:860–864.e2. Epub 2006 Mar 20. 14. Tugal-Tutkun I, Ayranci O, Kasapcopur O, et al. Retrospective analysis of children with uveitis treated with infliximab. J AAPOS. 2008;12:611–613. Epub 2008 Oct 19. 15. Simonini G, Taddio A, Cattalini M, et al. Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res (Hoboken). 2011;63:612–618.
