The antinuclear antibody test (ANA) is a much overused test in pediatrics. The ANA does have a role in serologic testing but it should be a very limited one. It is often ordered as a screening test for rheumatic illnesses in a primary care setting. However, since it has low specificity and sensitivity for most rheumatic and musculoskeletal illnesses in children, it should not be ordered as a screening test for non-specific complaints such as musculoskeletal pain. It should only be used as a diagnostic test for children with probable Systemic Lupus Erythematosus (SLE) or Mixed Connective Tissue Disease, (MCTD) and other possible overlap-like illnesses. Such children should have developed definite signs and symptoms of a disease before the ANA is ordered. This review presents data supporting these conclusions and a review of the ANA literature in adults and children.
By limiting ANA testing, primary care providers can avoid needless venipuncture pain, unnecessary referrals, extra medical expenses, and most importantly, significant parental anxieties. It is best not to do the ANA test in most children but if it ordered and is positive in a low titer (<1:640), the results can be ignored if the child is otherwise well and does not have other features of a systemic illness.
Since the introduction of the indirect immunofluorescence (IF) test for antinuclear antibodies (ANA) by Friou in 1957 , ordering an ANA appears to have become a reflexive response to the question "could this patient have a rheumatic disease?" What is the evidence that ordering such tests is of any value, and what should be done with a positive test?
The ANA test in health and disease
In diagnosing children with rheumatic disease, there are no markers as of now that identify a risk factor for a disease. Risk factors might allow primary prevention (e.g., screening for high serum cholesterol) or secondary prevention (e.g., detecting an illness before there are signs and symptoms e.g. pap smears for cervical cancer). In rheumatology only tertiary prevention is possible as illness may be detected as early in the disease course as possible in an effort to try and prevent the disease worsening and causing significant complications. Ideally there should be a screening test for children with arthritis or other positive rheumatic physical findings with a high specificity (test normal when someone does not have the disease) and high sensitivity (test abnormal when someone has the illness). A screening test should allow early diagnosis compatible with primary or secondary prevention.
For children with arthritis, only a few diagnostic tests are available (e.g., Lyme titer) and the ANA in particular has very limited usefulness as a diagnostic test. To put it another way, ideally a test should always be positive in those with a disease, and always negative in those without a disease. This situation rarely if ever occurs, but to be useful a test generally needs to have sensitivity and specificity of at least 90%. That is, at least 9 out of 10 individuals with the disease will have a positive test, a "true positive", and 9 out of 10 individuals without the disease will have a negative test. Unfortunately the ANA test, whether performed by IF or by an enzyme linked immunosorbent method (ELISA), fails to demonstrate these test characteristics . The ELISA particularly has its problem with false positives.
Part of the problem is that the test is being used indiscriminately as part of "a rheumatologic work-up" or "rheumatology panel". No test can sensibly be expected to be accurate in the diagnoses of diseases as different as juvenile idiopathic arthritis (JIA), rheumatoid arthritis, SLE, MCTD, scleroderma, or the vasculitis diseases. Yet, in practice, this is what often seems to be asked of the ANA test. However, even if the test is used more sensibly to address specific questions such as: "does this child with a rash and fever have lupus?" or "does this child with a swollen knee have juvenile idiopathic arthritis (JIA)?", or "is this child with JIA going to develop uveitis?" w