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 most cases should be ignored unless the child is systemically ill and shows signs of SLE or a similar systemic disease.
ANA: antinuclear antibody titer; SLE or lupus: systemic lupus erythematosus; HEp-2 cells: human epithelial cells used as ANA substrate; ENA: extranuclear antigens; MCTD: mixed connective tissue disease; JRA: juvenile rheumatoid arthritis; [(JIA): also known as juvenile idiopathic arthritis]; JDM: juvenile dermatomyositis; dsDNA: double stranded DNA antibodies; Sm: Smith antigen (one of the extractable nuclear antigens); RNP: ribonuclear protein antigen; (another of the extractable nuclear antigens): SSA: Sjögren's syndrome A antigen; (Ro): (one more of the extractable nuclear antigens); SSB: Sjögren's syndrome B antigen; (La): (another of the extractable nuclear antigens); ITP: idiopathic thrombocytopenic purpura; (JRA): juvenile rheumatoid arthritis; (JIA): and juvenile idiopathic arthritis are the old and new classification terms for chronic arthritis diseases in children. JRA is used preferentially here as the data collection began before the term JIA was more universally accepted.
The authors declare that they have no competing interests.
PM conceived the project, acquired the data, and reviewed the results; MM did the statistical analyses. PM, MSH, and CHS were responsible for the interpretation of the data and literature as well as preparation of the manuscript. The final manuscript was approved by the authors.
We would like to acknowledge the help of Louis Wadsworth MBBS, FRCPC, Director, Hematopathology Program British Columbia's Children's Hospital who provided generous help with acquiring the ANA data presented here.
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