RHEUMATOLOGY: Evaluating potential rheumatic diseases

Laboratory tests are not very helpful when trying to determine whether a child with musculoskeletal complaints has any of the rheumatic diseases of childhood, and using adult models to evaluate these children is equally ineffective. This is the takeaway message from “What’s New in the Laboratory Evaluation of Potential Rheumatic Diseases?” by James N. Jarvis, MD.

According to Jarvis, the main aim of his presentation was to provide the busy clinician with 2 or 3 questions they can ask to quickly pinpoint whether or not they should be concerned about the potential for rheumatic disease. To that end, he said, the results of a history and physical examination should make a clinician think about rheumatoid disease, and he discussed what he called “very marginal context” in which to also use laboratory tests to make the diagnosis.

One context, he said, is for the child with suspected lupus. Laboratory tests for these children should include an antinuclear antibody (ANA) test. Also essential when ordering an ANA test is to test complement levels and do a urinary analysis. The only time these laboratory tests should be done is if the clinician is asking the question “Does this child have lupus?” For all other children, these tests are not worthwhile, and he emphasized that the ANA is commonly positive in many children.

A laboratory test that he said is useless in children as a diagnostic tool for rheumatoid disease is the measurement of rheumatoid factor. Although this autoantibody detects about 70% of adults with rheumatoid arthritis, it has a very low sensitivity in children. In addition, the test is not needed to make the diagnosis of juvenile idiopathic arthritis because the signs and symptoms of disease are sufficient for accurate diagnosis.

He ended the session with a brief discussion of future research, focusing on work being done in his lab on the development of a diagnostic test for rheumatoid arthritis based on patterns of gene expression.

James N. Jarvis, MD, FAAP, is clinical professor and chief, Allergy/Immunology and Rheumatology, University of Buffalo, New York.

Over the last decade, little has changed in the laboratory options available to physicians when screening children for potential rheumatologic conditions. A commercial assay for a novel autoantibody associated with inflammatory arthritis, anticyclic citrullinated peptide (anti-CCP), has been developed and is available for general use. Anti-CCP antibody is found in fewer than 10% of children with juvenile idiopathic arthritis (JIA), correlates highly with the presence of rheumatoid factor (RF), and portends a more aggressive disease course. Like RF, anti-CCP testing is not recommended as a screening tool for JIA but should rather be used as an indicator of prognosis following the diagnosis of arthritis. Serologic testing for antineutrophil cytoplasmic antibody (ANCA), associated with certain forms of chronic vasculitis, has become more widely available.

Interassay performance variation may limit the value of ANCA as a screening tool for children with suspected chronic vasculitis. Genetic testing for recurrent fever syndromes such as familial Mediterranean fever (FMF) syndrome is also commercially available in the United States and can be used to confirm the diagnosis in children with suspect phenotypes in addition to providing prognostic information regarding disease sequelae. However, clinicians should be aware of the carrier rates of these genetic mutations in the normal population as well as the possibility of normal gene sequences in patients with phenotypically classic recurrent fever syndromes.

Laboratory testing options in children with rheumatologic conditions, especially biomarkers for disease activity, genetics, and pharmacogenomics, will continue to expand. Yet, if history is our guide, the cost-efficient screening and diagnosis of children with suspected rheumatologic conditions will continue to rely on the consistent application of fundamental medicine (ie, a thorough history and physical examination) by the astute clinician.

Steven Spalding, MD, is director, Center for Pediatric Rheumatology, Cleveland Clinic Children’s, Ohio.