Juvenile rheumatoid arthritis as defined by the American College of Rheumatology, is the presence of chronic (6 weeks duration), seronegative, peripheral arthritis before the age of 16 years, when other known causes have been excluded. It is the most common rheumatic disease of childhood.1 The current terminology used for this condition by the International league against rheumatism is juvenile idiopathic arthritis (JIA). The cumulative incidence of uveitis in JIA has been reported between 8.5% and 25% in series from referral centers around the world1 and is a common cause of visual morbidity in children. Arthritis, typically precedes the onset of uveitis.1
We describe the clinical profile, complications, management and visual outcome in patients with JIA associated uveitis in a major tertiary eye care hospital in India.
Materials and Methods
A retrospective chart review of all patients of JIA seen at a referral uveitis clinic, between January 1988 and March 2004 was done. Patients with JIA and with a minimum follow up of 3 months were included. Complete ophthalmic evaluation included a complete history, visual acuity, cycloplegic refraction, slit lamp examination applanation tonometry (with tonopen in younger children whenever Goldman applanation tonometry was not possible) and indirect ophthalmoscopy on each visit. Presence of ocular inflammation or reactivation of inflammation site and severity were recorded (based on Kimura Hogan's grading)2. Results of laboratory investigations, diagnostic and therapeutic procedures were analyzed. The systemic condition of the patient was managed by a rheumatologist.
Ocular complications due to JIA associated uveitis such as band shaped keratopathy (BSK), secondary glaucoma, peripheral anterior synechiae (PAS), reactivation of uveitis, complicated cataract were identified and recorded.
Forty patients (64 eyes) with JIA seen at our hospital between 1988 and 2004 were included in the study. Age at onset ranged between 2 to 16 years (mean of 9 years). The male: female ratio was 1.3:1. Twenty-six patients (65%) had a bilateral presentation and 12 patients (30%) had a unilateral presentation. Two patients did not have uveitis on presentation. The mean follow up was 2.5 years (range 3 months to 16 years). Presentations of JIA included pauciarticular type in 34 patients (85%) and polyarticular type in 6 patients (15%).
Knee joint was most commonly involved in 33 patients. Ankle joint was affected in 10 patients, wrist joint in 5 patients, small joints in 7 patients and shoulder and elbow joints in 2 patients each. Arthritis preceded the onset of uveitis in 38 (95%) patients while in 2 patients (5%) uveitis was the primary manifestation. Presentation of uveitis in our series included chronic uveitis in 39 eyes (61%), acute anterior uveitis in 10 eyes (16%) of which 2 eyes presented with uveitis with hypopyon, panuveitis in 7 eyes (11%) and intermediate uveitis in 4 eyes (6 %). In 4 eyes there was no active uveitis at presentation or during follow-up. Defective vision was the most common presenting complaint in 64 eyes. Other presenting symptoms included redness and mild pain in 35 eyes each and photophobia in 11 eyes.
Complicated cataract and BSK [Fig. 1] were the most common complications seen in 38 eyes (63%) and 37 eyes (62%) respectively. Other complications included secondary glaucoma in 6 eyes (9%), hypotonic maculopathy in 5 eyes (8%) and phthisis in 3 eyes (5%). Other posterior segment features included parsplanitis 4 eyes (6%), vitritis 10 eyes (16%), cystoid macular edema in 5 eyes (8%), disc edema and glaucomatous optic atrophy in 2 eyes each (3%). Fundus examination was normal in 32 eyes (50%).
Two patients (4 eyes) without uveitis, one with polyarticular and the other with pauciarticular type were followed up for 6 months and 2 years respectively and they did not develop uveitis till the last follow up.
All patients were investigated for rheumatoid arthritis (RA) factor and erythrocyte sedimentation rate (ESR). Raised ESR was found in 29 patients.
RA factor was positive in 2 patients. Anti nuclear antibodies (ANA) and C-reactive protein (CRP) tests were done in 12 patients and was found to be positive in 2 patients each. Human leucocyte antigen (HLA) B27 typing was done in 5 patients and was detected in one patient who was found to be a 14-year-old adolescent male.
Prednisolone acetate 1% eye drops were used in tapering dosage, the frequency of application was based on the severity of anterior chamber reaction. Topical medication alone was used in 10 eyes (17%). A combination of topical and periocular steroid injection was required in 2 eyes (3%). Fifty-two eyes (86%) were treated with a combination of topical, periocular and oral prednisolone (1 mg/kg body weight), which was the most common combination. Two patients with vision threatening panuveitis were treated with a pulse therapy of intravenous methyl prednisolone followed by systemic steroids and immunosuppressives (methotrexate or azathioprine). Thirty- three patients (58%) (16 bilateral and 7 unilateral) were treated with immunosuppressives in addition to topical, periocular and/or systemic steroids. Tab methotrexate was used in a majority (21 patients) in the dose of 7.5-15 mg/wk orally once per week in a single dose while 2 patients were treated with azathioprine (2.5 mg/kg body weight).
Surgical intervention was required in 41 eyes (64%). Lensectomy and vitrectomy in 18 eyes (30%), phacoemulsification with intraocular lens (IOL) implantation in 9 eyes (3 bilateral and 3 unilateral- 15%), penetrating keratoplasty in 3 eyes (5%) preceded by a trial of chelation with ethylenediaminetetraacetic acid (EDTA) for BSK, 3 patients with BSK were treated with EDTA chelation alone. Other associated procedures included belt buckle, vitrectomy alone, secondary IOL implantation in 1 patient each. Trabeculectomy was done in 3 eyes (5%) due to failure of maximal medical therapy. Maximum medical therapy used in our patients included a topical beta blocker twice daily, brimonidine tartarate three times daily along with maximum tolerated oral acetazolamide dose. IOL removal was done in 2 eyes (3%) due to severe post operative reactivation of uveitis and IOL intolerance after surgery.
There was recurrence of inflammation in 31 eyes (48%). However, recurrences could be controlled with medication.
None of the patients with unilateral disease, who were on immunosuppressives developed uveitis in the other eye. On analysis of the pre and post treatment visual acuity [Fig. 2], we found that 23 eyes (38%) had 2 Snellen's lines or more of improvement in visual acuity post treatment while in 27 eyes (45%), the vision remained stable and in 10 eyes (17%), vision deteriorated despite treatment due to complications of JIA uveitis
JIA associated uveitis, is reported to occur most commonly in young girls seropositive for ANA with pauciarticular-onset arthritis.34 Though several studies56 have noted that 30-40% of patients with JIA-associated uveitis experience severe loss of vision, overall vision improved or remained stable in 83% in our series. Prognosis of JIA associated uveitis has been reported to vary in different series.178
Males outnumbered females in our study, in contrast to data from western population where females were predominantly affected.134 In our study, the youngest patient was 2 years old while the oldest was 16 years.
In our series, pauciarticular type of JIA was seen in 80% of our patients. Pauciarticular type accounted for about 45-60% in studies by Foster et al.3 and Kanski1 while in an Indian study9 it was 47.3%. Increased incidence of pauciarticular type of JIA in our study is probably because pauciarticular type is commonly associated with uveitis1 and that most of our patients were referred to us with ocular symptoms.
In our study, arthritis was the first presentation in 38 patients while in 2 patients ocular disease preceded arthritis. Poor prognosis has been noted in patients with uveitis preceding arthritis6710 which was the case in both of our patients who had severe panuveitis leading to phthisis bulbi in one of them. Two patients with JIA in our series did not have uveitis at presentation as well as during follow up in our study.
In our series, chronic anterior uveitis was the most common presentation as in other studies.1 Similar to other studies, our study also showed complicated cataract (63%) and BSK (61%), as the most common complications.1
We found ANA positivity in only 2 of the 12 patients tested for the same. Western studies34 have noted a higher incidence and the risk of development of severe disease in females with ANA positivity. Agarwal et al.11 have, however, noted the rarity of ANA positivity in Indian population. Five patients in the adolescent age group, with a history of backache, were subjected to HLA B 27 typing and one 14-year-old boy tested positive for the same.
There was good control of inflammation with immunosuppressives, especially methotrexate in 19 out of 22 patients. None of the patients with unilateral disease on immunosuppressives developed uveitis in the other eye. Most common immunosuppressive agent used in our study was methotrexate and like other studies showed good efficacy.12131415 We found methotrexate as an effective steroid sparing agent especially as a long term option. Liver function tests and blood counts of the patients on methotrexate have to be monitored periodically (atleast every month) in association with an internist. Recurrence of inflammation occurred in 31 eyes (48%) of patients inspite of treatment with systemic steroids and/or immunosuppressives. This could be due to the natural course of the disease which remained unchanged inspite of systemic therapy.
BSK was initially managed with EDTA chelation alone in all patients. As BSK removal alone was not effective, penetrating keratoplasty was done in 3 eyes with good visual recovery. Kanski1 had noted good results after lensectomy for cataracts in patients with JIA.116 In our study, cataract was the most common cause for which patients underwent surgery. Most of the patients who underwent lensectomy were rehabilitated with aphakic correction with spectacles or contact lenses. Phacoemulsification with IOL implantation was done (in 9 eyes) mostly in older patients in whom the disease went into remission. In 2 patients who were referred to us with severe IOL related postoperative uveitis and was unresponsive to systemic steroids and immunosuppressive therapy, underwent IOL explantation.
The most common causes of irreversible vision loss in our series of patients were glaucomatous optic atrophy, hypotony and phthisis bulbi.
Our study indicates, that in India, JIA associated uveitis commonly presents as pauciarticular type and is more common in males. Investigations for RA and ANA, were probably not of much help in diagnosis or prognosis in those patients in whom they were tested in our study. Complications such as BSK and complicated cataract need prompt treatment for helping speedy visual recovery. As long-term treatment options, immunosuppressives are a better choice than steroids. These patients need to be followed up for long periods as recurrence of uveitis, development of complications like glaucomatous optic atrophy and hypotony can occur in such patients.
Source of Support:
Vision research foundation, Chennai, India.
Conflict of Interest:
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