e positive for ANA. Eight of the 11 (72.7%) were positive when the interval from sampling to onset of first symptoms was ≤ 2 years and 2 of 5 cases (40%) were positive when the interval was > 3 years. Based on an incidence rate of lupus of 5/100,000/year, the authors calculated that lupus would develop in less than one percent of the ANA positive individuals. Cabral et al.  followed the course of 24 children who were considered clinically not to have an inflammatory disease despite being ANA positive and found that no patient developed an overt inflammatory disease during a follow-up period of 61 months (range 13 to 138 months).
Some studies have evaluated the outcome in patients with fibromyalgia. Fibromyalgia is a musculoskeletal pain condition not thought to be an autoimmune disease. Interestingly, some fibromyalgia patients are also ANA positive, but there has been no evidence that the occurrence of a positive ANA influences patient outcome. Al-Allaf et al.  found the ANA positivity rate (titers not given, a positive result was simply defined as "plus") in their adult patients with fibromyalgia was 8.8%. This rate was almost identical to the 8.9% ANA positivity rate in their control patients with osteoarthritis. The 12 individuals who had fibromyalgia and were ANA positive were matched for age and sex with 12 ANA negative patients. Over a 2-4 year follow-up period one patient in the ANA positive group fulfilled criteria for SLE, and one in the ANA negative group fulfilled criteria for Sjögren's syndrome. The authors concluded that the ANA test (at least in low titer) was not a good predictor of future connective tissue disease.
In a separate study of 59 pediatric patients with fibromyalgia, 17 (28.8%) were ANA positive (mean titer 1:160). Fifty patients were followed for a mean of 18.3 months and during that time no patient developed a connective tissue disease . We would conclude from these findings that only rarely is the presence of ANA the harbinger of occult SLE or another connective tissue disease.
ANA 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