Uveitis common in childhood Arthritis

In a Nordic population-based study it has been found that children with juvenile idiopathic arthritis have a high incidence of uveitis with the presence of autoantibodies being predictors of this complication. Uveitis is the most common extra-articular manifestation of JIA and it contributes significantly to the disease burden of JIA.The condition can be acute or chronic, insidious, and asymptomatic and therefore challenging to diagnose with varying prevalences according to ethnic and geographic factors. Among Caucasian children in Finland and the U.S., the prevalence ranged from 8% to 25%, while in studies conducted in Taiwan and Costa Rica the prevalence was lower, from 1% to 7%.

Nordal E, et al studied JIA cases from defined geographical areas in Denmark, Finland, Sweden and Norway with disease onset between January 1997 to June 2000 were followed for median 98 months in this prospective longitudinal cohort study. Potential clinical and immunological predictors of uveitis were identified with logistic regression analysis.

They found that during more than 8 years of follow-up, Uveitis occurred in 89 (20.5%) of the 435 children with regular ophtalmologic follow-up among the 500 included. Chronic asymptomatic uveitis developed in 80 and acute symptomatic uveitis in 9 children. Uveitis developed at a median interval of 0.8 (range − 4.7 to 9.4) years after the onset of arthritis. Predictors of uveitis were age < 7 years at JIA onset (Odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5), presence of antihistone antibodies (AHA) > 15 U/ml (OR 4.8 (1.8 to 13.4)) and antinuclear antibodies (ANA) (OR 2.4 (1.5 to 4.0)). Mean combined IgM/IgG AHA was significantly higher in the uveitis group (19.2 U/ml) than in the non-uveitis group (10.2 U/ml) (p = 0.002). Young age at JIA onset predicted uveitis in girls (p < 0.001), but not in boys (p = 0.390) as reported by the researchers online in Pediatric Rheumatology.

Children in the cohort underwent ophthalmologic screening every 2 to 3 months for the first 2 years after JIA diagnosis and then at longer intervals depending on disease duration and disease subcategory.

Among the 435 children included in the analysis, two-thirds were girls and median age at JIA onset was 5.5 years. Half had oligoarticular onset. Seropositivity for ANA was seen in 27.2%, AHA levels above 15 U/mL were detected in 17.2%, and AHA levels of 30 U/mL or higher were found in 7.5%.

Among the 89 children who developed uveitis, nine were acute cases, with eight of these having the enthesitis-related arthritis JIA subtype and seven being HLA-B27 positive. The other 80 affected patients had chronic insidious uveitis.

The highest incidence of uveitis was in the psoriatic arthritis subtype, at 35.7%, followed by the enthesitis-related arthritis subtype, at 25%. No cases of uveitis developed among children in the systemic or polyarticular rheumatoid factor-positive categories.

The uveitis occurred in the first year after arthritis onset in 48 children, but in four others, it developed more than 8 years after the arthritis onset. Uveitis was present before the arthritis in five.

The number of patients with uveitis occurring in the first year after JIA onset was six times the number with uveitis in the second year and 16 times the number during the fifth year.

When the analysis was stratified by gender, girls with uveitis were shown to have a significantly younger median age at arthritis onset (3.4 years) than those without uveitis (6.8 years, P<0.001). There was no difference among boys, however.

The presence of ANA was a significant predictor for both genders, but levels of AHA IgM/IgG were significantly higher in those with uveitis only among girls (14.2 versus 6.9 U/mL, P=0.003).

The disparity in predictors of uveitis between girls and boys "may reflect that different categories of JIA have different types of uveitis with different predicting factors," according to the authors.

The fact that four cases developed more than 8 years after diagnosis with two being asymptomatic emphasizes the importance of ongoing screening efforts. "Based on these data, long-term ophthalmologic follow-up into adulthood must be considered," they stated.

They also noted that despite the apparent association between ANA and AHA and uveitis, no specific ocular target has been identified for either autoantibody so a potential role in disease etiology or pathogenesis remains uncertain.

A limitation of the study was that the onset of JIA in this cohort was in the early days of the biologic era, so little is known about the potentially protective effects of current treatment.

It was concluded that Early-onset arthritis and presence of AHA in girls, as well as presence of ANA in both genders, were significant predictors of chronic uveitis. The high incidence of uveitis in this long-term Nordic JIA cohort may have severe implications in a lifelong perspective.