ommented on previously [8,9].
In our lab, no combination of ANA titer, or staining pattern was specific for any particular rheumatic disease. The test combinations with the best positive predictive values for a rheumatic disease were: a) a titer ≥1:640 with mitotic positive staining or b) a titer ≥1:640 with a homogenous and mitotic staining pattern. These tests had positive predictive values of 77% and 72% respectively. Yet these results were only slightly higher than the positive predictive value of 69% obtained with a titer of ≥1:640 alone, ignoring the pattern of staining. Although the addition of patterns somewhat increases the specificity and positive predictive value of the ANA test for a rheumatic disease, it does so at the expense of both the sensitivity and negative predictive value of the test using titers alone.
The pattern of staining also does not appear to be helpful in distinguishing between rheumatic diseases. For example, although high titer homogenous, mitotic positive staining was the most common combination seen in children with SLE, it was actually found in only 27.3% of ANA positive lupus patients. This combination was also found in 12.5% of ANA positive JRA and 5.4% of ANA positive JDM patients. This lack of specificity of the ANA immunofluorescent pattern has been recognized previously, both for adults and children [8,10,11]. A study by Parker et al.  evaluated the usefulness of combining ANA titer and pattern. Although they felt that knowledge of both titer and pattern was helpful, they did not calculate specific test characteristics, and in fact no combination was restricted to any single rheumatic disease. Our assessment of these data is that the addition of information about patterns of immunofluorescence does not appear to significantly improve the utility of the ANA test.
Practical Concerns about ANA Testing
Referrals for positive ANA titers
As part of a study exploring what precipitated a referral to a pediatric rheumatologist, McGhee et al.  found that children referred, at least in part, because of a positive ANA test were no more likely to have a chronic inflammatory disease than children with a negative test.
In another study from a pediatric rheumatology clinic, only 55% of all of the children with a positive ANA test had an inflammatory rheumatic disease. Positive antibodies to double-stranded DNA or to extractable nuclear antigens (Sm, RNP) indicating SLE or MCTD were strongly correlated with an ANA titer ≥1:640. The authors recommended therefore, that these more specific tests be performed only if the child had a positive ANA test at high titer .
McGhee and colleagues reviewed the ANA titer clinical utility in 2004 . One hundred and ten children were evaluated who had been referred for a positive ANA. Of the 110, 10 subsequently were found to have SLE, 18 had JRA, 1 had MCTD, and 1 had Raynaud's phenomenon. Neither a positive ANA neither titer nor the degree of positivity of the ANA helped pick out the children with SLE from the children without a chronic inflammatory disease. Tellingly, it wasn't the elevated ANA titer that distinguished the children with JRA from those with other musculoskeletal problems, but the history (e.g., morning stiffness) and the physical exam (e.g., presence of rash, swollen joints).
All these studies demonstrate that a positive ANA test is found frequently in a pediatric hospital population, and even in high titer has only a poor ability to determine whether a child has an inflammatory rheumatic disease.
Development of rheumatic diseases in ANA positive individuals
It could be argued that the finding of a positive ANA test indicates that the child has an occult disease that will become manifest later. Is there any evidence to support or refute this?
There is some evidence that ANA may sometimes precede the development of SLE by several years. Using Finland's Social Security Institution's population registry, Aho et al.  were able to trace 16 serum samples from apparently healthy subjects who later developed SLE or MCTD. Ten of the 16 (62.5%) samples wer