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Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests for Evaluating Musculoskeletal Complaints in Children
Comparative Effectiveness Reviews, No. 50
Investigators: Kai O Wong, MSc, Kenneth Bond, BEd, MA, Joanne Homik, MD, MSc, Janet E Ellsworth, MD, Mohammad Karkhaneh, MD, Christine Ha, BSc, and Donna M Dryden, PhD.
Author Information and AffiliationsStructured Abstract
Objectives:
To assess the test performance of antinuclear antibody (ANA), rheumatoid factor (RF), and cyclic-citrullinated peptide (CCP) tests in children and adolescents with undiagnosed musculoskeletal (MSK) pain or joint swelling, compared with clinical diagnoses of pediatric systemic lupus erythematosus (pSLE) and juvenile idiopathic arthritis (JIA). To explore differences in test performance for accuracy modifiers including age, sex, race or ethnicity, comorbidities, and recent infections. To evaluate the impact of test results on clinical decisionmaking and clinically important outcomes such as referrals, ordering of additional tests, clinical management, and anxiety experienced by children and parents.
Data Sources:
We conducted comprehensive searches in nine electronic databases. We also hand searched reference lists and conference proceedings. There were no restrictions on language, year of publication, and study design.
Review Methods:
Study selection, quality assessment, data extraction, and grading the evidence were conducted independently by two reviewers. A combination of qualitative and quantitative approaches was used to synthesize the data. We calculated sensitivity (Sn) and specificity (Sp).
Results:
The search identified 11,695 citations; 28 were included in the review. Only one cohort study examined the test performance of RF to diagnose JIA among children with undiagnosed MSK pain. It demonstrated an Sn of 5 percent and an Sp of 98 percent. Fifteen case-control studies did not specifically address the test performance of RF among children with MSK pain. The strength of evidence is low for both Sn and Sp. The 12 case-control studies that examined other test-disease combinations did not specifically address the prevalence of positive tests for ANA or CCP among children presenting with undiagnosed MSK pain. The strength of evidence is insufficient to determine the test performance of ANA or CCP to diagnose JIA or pSLE in children with undiagnosed MSK pain. No studies addressed children with joint swelling. There was no evidence addressing the prespecified accuracy modifiers or clinically important outcomes.
Conclusions:
Most of the evidence from the 28 studies included in the review was not applicable to the population of interest as most studies examined children with known disease rather than with undiagnosed MSK pain. No studies provided a complete investigation on accuracy modifiers. No studies examined clinically important outcomes such as the impact of the test results on referrals, ordering of additional tests, patient management, and patient and parent anxiety levels. Because the Sn and Sp of these tests have yet to be verified, current evidence does not support their use as diagnostic tests for children with undiagnosed MSK pain. They have a potential application as an adjunct to a clinical assessment that suggests the presence of an inflammatory arthritis or connective tissue disease.
Contents
- Preface
- Acknowledgements
- Technical Expert Panel
- Peer Reviewers
- Executive Summary
- Introduction
- Methods
- Results: Part One
- Key Question 1.1 Incidence and Prevalence of Undiagnosed Musculoskeletal Complaints in Children
- Key Question 1.2: The Positivity of Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests in Healthy Children
- Key Question 2.1 Noninflammatory Causes of Pediatric Musculoskeletal Pain
- Key Question 2.2 Inflammatory Causes of Pediatric Musculoskeletal Pain
- Key Question 2.3 The Resolution or Recurrence of Pediatric Musculoskeletal Pain
- Results: Part Two
- Literature Search
- Characteristics of Included Studies
- Key Question 3.1 Antinuclear Antibody Test for Pediatric Systemic Lupus Erythematosus
- Key Question 3.2 Antinuclear Antibody Test for Juvenile Idiopathic Arthritis
- Key Question 3.3 Rheumatoid Factor Test for Pediatric Systemic Lupus Erythematosus
- Key Question 3.4 Rheumatoid Factor Test for Juvenile Idiopathic Arthritis
- Key Question 3.5 Cyclic-Citrullinated Peptide Test for Pediatric Systemic Lupus Erythematosus
- Key Question 3.6 Cyclic-Citrullinated Peptide Test for Juvenile Idiopathic Arthritis
- Key Question 4.1 Accuracy Modifiers of Antinuclear Antibody, Rheumatoid Factor, Cyclic-Citrullinated Peptide Test for Pediatric Systemic Lupus Erythematosus
- Key Question 4.2 Accuracy Modifiers of Antinuclear Antibody, Rheumatoid Factor, Cyclic-Citrullinated Peptide Test for Juvenile Idiopathic Arthritis
- Key Question 5 Clinical Impacts due to the Results of Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests
- Rating the Body of Evidence
- Summary and Discussion
- References and Included Studies
- Acronyms
- Appendixes
- Appendix A American College of Rheumatology Criteria for Classification of Systemic Lupus Erythematosus
- Appendix B Literature Search Strings
- Appendix C Forms
- Appendix D List of Excluded Studies
- Appendix E Methodological Quality of Included Studies
- Appendix F Evidence Tables
- Appendix G Subgroup Analyses by Onset Type of Juvenile Idiopathic Arthritis
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. HHSA 290 2007 10021 I, Prepared by: University of Alberta Evidence-based Practice Center, Edmonton, AB, Canada
Suggested citation:
Wong KO, Bond K, Homik J, Ellsworth JE, Karkhaneh M, Ha C, Dryden DM. Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests for Evaluating Musculoskeletal Complaints in Children. Comparative Effectiveness Review No. 50 (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. HHSA 290 2007 10021 I). AHRQ Publication No. 12-EHC015-EF. Rockville, MD: Agency for Healthcare Research and Quality. March 2012. Effectivehealthcare.ahrq.gov/reports/final.cfm.
This report is based on research conducted by the University of Alberta Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA 290 2007 10021 I). The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products or actions may not be stated or implied.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
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540 Gaither Road, Rockville, MD 20850; www
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