 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 test is more useful than a positive one, as it does, for all practical purposes, exclude the diagnosis of SLE in a child.
What is needed is a cost-effectiveness study to evaluate whether the ANA test should be replaced by testing initially for anti-dsDNA and anti-ENA (anti-Sm, RNP, SSA and SSB) antibodies. Until that study is done, we would recommend that non-rheumatologists only do an ANA test if there is a fairly high probability (perhaps a 10+% chance) that a child's symptoms could be due to SLE or MCTD. If the test is positive at a titer of > 1:160 then it would be appropriate to order antibodies to dsDNA and ENA, with lower titers being ignored as well as complement levels.
We would strongly recommend that the ANA test is not ordered indiscriminately as part of "a rheumatologic work-up". This is not a new message. Other pediatric rheumatologists have pointed out in the literature that the ANA is a poor screening test and is being used inappropriately [7,9,12,14,16,29,30]. It is our hope that a continued demonstration of these facts will gradually decrease its inappropriate use. The cost of inappropriate referrals, extra venipuncture, unnecessary expense, and increased parental and child anxiety is a considerable problem that pediatric rheumatologists see every day.
The question why the ANA test is so frequently positive in populations without an autoimmune disease remains a fascinating one. It suggests that the breaking of immunological tolerance is really quite common, but that this tolerance breakdown only rarely leads to disease. It is possible that antinuclear antibodies have some useful function that is not yet fully understood.
However, the ANA test has such a high false-positivity rate that a positive test is of little, if any, clinical utility as a screening test and should not be ordered routinely to screen children with musculoskeletal complaints. Its use should be limited to the diagnosis of SLE, MCTD, and similar systemic illnesses. If the test is performed, low titer ANA results (< 1:640) in mos