and other diseases
It should also be remembered that ANA are associated not only with the classical autoimmune diseases, but also with infection , malignancy [20,21] and drugs (Table 1) . To illustrate this point, a study of Jones et al in 2006 analyzed 71 children who presented to a rheumatologist and who eventually were diagnosed with acute lymphocytic leukemia. Of the 71 children, 47 were tested for the ANA titer performed upon referral. Of the 47 ALL children, 8 (17%) had an elevated ANA titer . Not only is the ANA test often positive in non-rheumatic diseases, it is often negative in many rheumatic diseases (Table 2).
Table 1. Diseases or syndromes that are frequently associated with an positive ANA test
Table 2. ANA positivity in rheumatic diseases in children
Environmental toxins may also predispose to ANA production. Although hopefully not relevant in pediatrics, there is evidence of an increased frequency of ANA in individuals with silicone breast implants , and at least two studies have suggested that rural populations have a higher frequency of ANA positivity than urban populations, perhaps due to toxin exposure [24,25]. Therefore the finding of a positive ANA test should not blind the physician to the possibility of a non-autoimmune diagnosis.
A situation where a positive ANA test may be of some value is in children diagnosed with idiopathic thrombocytopenic purpura (ITP). In a study of 87 children with ITP, it was found that 36% of those with a positive ANA (titer ≥1:40) developed further "autoimmune symptoms". Five children developed SLE, compared to none of those who were ANA negative (p < 0.001). 
ANA positivity as a risk factor for uveitis in children with JIA
There is little doubt that in children with JIA the ANA test is more frequently positive in those with uveitis than in children without uveitis. The American Academy of Pediatrics recommends performing the ANA test as part of the screen for uveitis . However, although there is a statistically significant difference between children with and without uveitis, we would argue that this difference itself is of little clinical significance.
In a recent study from Finland , for example, uveitis was found in 104 of 426 new cases of juvenile idiopathic arthritis. Antinuclear antibodies were found in 66% of those with uveitis compared to 37% of those without uveitis, a statistically significant difference. However if the presence or absence of a positive ANA test was used in determining the frequency of ophthalmologic examinations, it is possible that some of the 46/104 children with uveitis and negative ANA's might well have had a delayed diagnosis due to the partial reliance on the ANA positivity to determine the frequency of eye checkups. So there is risk for ANA negative children as well. This should not detract from the utility of a positive ANA in selecting out a population of children with arthritis who are at a higher risk for uveitis.
What should be done?
So what should be done with a positive ANA test? Our answer would be exemplified by the answer a local inhabitant gave when asked directions from place A to B by a foreign tourist: "I wouldn't be leaving from here!" In other words, it would be best if the ANA test had not been done in the first place! We would suggest that a positive ANA test can safely be ignored unless there are other suggestive clinical signs, and simple laboratory tests (such as a raised ESR or cytopenias) that point towards a diagnosis of lupus or similar connective tissue disease, particularly if the ANA titer is less than 1:640. Given the high false positive rate of ANA tests, a positive test cannot be used as confirmatory evidence that the child with a swollen joint has JIA, rather than some other serious condition such as septic arthritis, leukemia, or hemophilia. Similarly, symptoms such as fatigue and aches and pains in a child should not be ascribed to SLE simply because of a positive ANA test. It is much more likely that such a child has an idiopathic pain syndrome such as fibromyalgia or hypermobility. A negative ANA 