Rheumatologic Tests: A Primer for Family Physicians

 

Patients with a suspected connective tissue disorder should undergo serologic testing to confirm the diagnosis and, in some cases, to monitor disease activity and predict flares. Patients with suspected systemic lupus erythematosus should be tested for antinuclear antibodies. However, antinuclear antibodies are not specific and may be present in many other connective tissue disorders and nonrheumatologic diseases. Thus, patients with suspected systemic lupus erythematosus should undergo further testing to confirm the diagnosis. Patients with Sjögren syndrome may have a positive antinuclear antibody titer, but often also have positive anti-Sjögren antigen A or B results. Similarly, antinuclear antibodies can be present in patients with scleroderma, mixed connective tissue disease, and dermatomyositis or polymyositis. Additional tests are needed to help confirm the diagnosis. In patients with findings of rheumatoid arthritis, a positive rheumatoid factor titer suggests the diagnosis, but as with antinuclear antibodies, it is not specific and can occur in other conditions. Rheumatoid factor can also be negative in patients with rheumatoid arthritis. A positive anticyclic citrullinated peptide antibody titer is more specific for rheumatoid arthritis and can help confirm the diagnosis. Physicians should order these serologic tests only when patients have a high pretest probability of a specific connective tissue disorder.

This article gives a framework for laboratory testing in patients with a suspected connective tissue disease. Common diseases are presented with typical symptoms, and an overview of appropriate testing is provided.

 Enlarge     Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

In patients with a suspected connective tissue disorder and a positive ANA titer, further testing (e.g., anti–double-stranded DNA antibodies, anti-Smith antibodies, Sjögren antibodies) should be performed based on clinical findings that raise suspicion for specific disorders.

C

9

Testing for antineutrophil cytoplasmic antibodies is not indicated in the evaluation of patients with sinusitis who have no other features of vasculitis.

C

29, 30


ANA = antinuclear antibodies.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

In patients with a suspected connective tissue disorder and a positive ANA titer, further testing (e.g., anti–double-stranded DNA antibodies, anti-Smith antibodies, Sjögren antibodies) should be performed based on clinical findings that raise suspicion for specific disorders.

C

9

Testing for antineutrophil cytoplasmic antibodies is not indicated in the evaluation of patients with sinusitis who have no other features of vasculitis.

C

29, 30


ANA = antinuclear antibodies.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

 Enlarge     Print

BEST PRACTICES IN RHEUMATOLOGY

Recommendations from the Choosing Wisely Campaign

RecommendationSponsoring organization

Do not order autoantibody panels unless ANA test is positive and there is evidence of rheumatic disease.

American College of Rheumatology-Pediatric Rheumatology

Do not test ANA subserologies without a positive ANA test result and clinical suspicion of immune-mediated disease.

American College of Rheumatology


ANA = antinuclear antibodies.

For more information on the Choosing Wisely Campaign, see http://www.choosingwisely.org. For supporting citations and to search Choosing Wisely recommendations relevant to primary care, see https://www.aafp.org/afp/recommendations/search.htm.

BEST PRACTICES IN RHEUMATOLOGY

Recommendations from the Choosing Wisely Campaign

RecommendationSponsoring organization

Do not order autoantibody panels unless ANA test is positive and there is evidence of rheumatic disease.

American College of Rheumatology-Pediatric Rheumatology

Do not test ANA subserologies without a positive ANA test result and clinical suspicion of immune-mediated disease.

American College of Rheumatology


ANA = antinuclear antibodies.

For more information on the Choosing Wisely Campaign, see http://www.choosingwisely.org. For supporting citations and to search Choosing Wisely recommendations relevant to primary care, see https://www.aafp.org/afp/recommendations/search.htm.

Clinical Scenario

Jump to section +

The Author

YOUSAF ALI, MD, is an associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, NY.

Address correspondence to Yousaf Ali, MD, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1118, New York, NY 10029 (e-mail: yousaf.ali@mountsinai.org). Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Stinton LM, Fritzler MJ. A clinical approach to autoantibody testing in systemic autoimmune rheumatic disorders. Autoimmun Rev. 2007;7(1):77–84....

2. Goldenberg DL. Guide to laboratory testing in patients with suspected rheumatic disease. September 27, 2017. https://www.practicalpainmanagement.com/resources/diagnostic-tests/guide-laboratory-testing-patients-suspected-rheumatic-disease. Accessed April 19, 2018.

3. Slater CA, Davis RB, Shmerling RH. Antinuclear antibody testing. A study of clinical utility. Arch Intern Med. 1996;156(13):1421–1425.

4. Emlen W, O'Neill L. Clinical significance of antinuclear antibodies: comparison of detection with immunofluorescence and enzyme-linked immunosorbent assays. Arthritis Rheum. 1997;40(9):1612–1618.

5. Solomon DH, Kavanaugh AJ, Schur PH; American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum. 2002;47(4):434–444.

6. Meroni PL, Schur PH. ANA screening: an old test with new recommendations. Ann Rheum Dis. 2010;69(8):1420–1422.

7. Verizhnikova Z, Aleksandrova E, Novikov A, et al. Diagnostic accuracy of automated determination of antinuclear antibodies by indirect reaction of immunofluorescence on human hep-2 cells and enzyme-linked immunosorbent assay (ELISA) for diagnosis of systemic lupus erythematosus [abstract]. Ann Rheum Dis. 2014;73(suppl 2):1140.

8. Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA; American College of Pathologists. Guidelines for clinical use of the anti-nuclear antibody test and tests for specific autoantibodies to nuclear antigens. Arch Pathol Lab Med. 2000;124(1):71–81.

9. Agmon-Levin N, Damoiseaux J, Kallenberg C, et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis. 2014;73(1):17–23.

10. Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA; American College of Pathologists. Guidelines for clinical use of the anti-nuclear antibody test and tests for specific autoantibodies to nuclear antigens. Arch Pathol Lab Med. 2000;124(1):71–81.

11. Pisetsky DS. Anti-DNA antibodies—quintessential biomarkers of SLE. Nat Rev Rheumatol. 2016;12(2):102–110.

12. Linnik MD, Hu JZ, Heilbrunn KR, Strand V, Hurley FL, Joh T; LJP 394 Investigator Consortium. Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus. Arthritis Rheum. 2005;52(4):1129–1137.

13. Pan LT, Tin SK, Boey ML, Fong KY. The sensitivity and specificity of auto-antibodies to the Sm antigen in the diagnosis of systemic lupus erythematosus. Ann Acad Med Singapore. 1998;27(1):21–23.

14. Antonov D, Kazandjieva J, Etugov D, Gospodinov D, Tsankov N. Drug-induced lupus erythematosus. Clin Dermatol. 2004;22(2):157–166.

15. Burlingame RW, Rubin RL. Drug-induced anti-histone autoantibodies display two patterns of reactivity with substructures of chromatin. J Clin Invest. 1991;88(2):680–690.

16. Fayyaz A, Kurien BT, Scofield RH. Autoantibodies in Sjögren's syndrome. Rheum Dis Clin North Am. 2016;42(3):419–434.

17. Izmirly PM, Buyon JP, Saxena A. Neonatal lupus: advances in understanding pathogenesis and identifying treatments of cardiac disease. Curr Opin Rheumatol. 2012;24(5):466–472.

18. Benito-Garcia E, Schur PH, Lahita R; American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Guidelines for immunologic laboratory testing in the rheumatic diseases: anti-Sm and anti-RNP antibody tests. Arthritis Rheum. 2004;51(6):1030–1044.

19. Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther. 2003;5(2):80–93.

20. Reveille JD, Solomon DH; American College of Rheumatology Ad Hoc Committee of Immunologic Testing Guidelines. Evidence-based guidelines for the use of immunologic tests: anticentromere, Scl-70, and nucleolar antibodies. Arthritis Rheum. 2003;49(3):399–412.

21. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362(9388):971–982.

22. Albrecht K, Zink A. Poor prognostic factors guiding treatment decisions in rheumatoid arthritis patients: a review of data from randomized clinical trials and cohort studies. Arthritis Res Ther. 2017;19(1):68.

23. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007;146(11):797–808.

24. Shojania K. Rheumatology: 2. What laboratory tests are needed?. CMAJ. 2000;162(8):1157–1163.

25. Shmerling RH, Delbanco TL. The rheumatoid factor: an analysis of clinical utility. Am J Med. 1991;91(5):528–534.

26. Barra L, Pope J, Bessette L, Haraoui B, Bykerk V. Lack of seroconversion of rheumatoid factor and anti-cyclic citrullinated peptide in patients with early inflammatory arthritis: a systematic literature review. Rheumatology (Oxford). 2011;50(2):311–316.

27. Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum. 2002;46(2):357–365.

28. Rao JK, Weinberger M, Oddone EZ, Allen NB, Landsman P, Feussner JR. The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener granulomatosis. A literature review and meta-analysis. Ann Intern Med. 1995;123(12):925–932.

29. Vassilopoulos D, Hoffman GS. Clinical utility of testing for antineutrophil cytoplasmic antibodies. Clin Diagn Lab Immunol. 1999;6(5):645–651.

30. Damoiseaux J, Csernok E, Rasmussen N, et al. Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis. 2017;76(4):647–653.

31. Bodis G, Toth V, Schwarting A. Role of human leukocyte antigens (HLA) in autoimmune disease [published online ahead of print March 7, 2018]. Rheumatol Ther. https://link.springer.com/article/10.1007/s40744-018-0100-z. Accessed April 16, 2018.

32. Reveille JD, Hirsch R, Dillon CF, Carroll MD, Weisman MH. The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum. 2012;64(5):1407–1411.

33. Dasgupta B, Cimmino MA, Maradit-Kremers H, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71(4):484–492.

34. Sox HC Jr, Liang MH. The erythrocyte sedimentation rate. Guidelines for rational use. Ann Intern Med. 1986;104(4):515–523.

35. Brigden ML. Clinical utility of the erythrocyte sedimentation rate. Am Fam Physician. 1999;60(5):1443–1450.

36. Osei-Bimpong A, Meek JH, Lewis SM. ESR or CRP? A comparison of their clinical utility. Hematology. 2007;12(4):353–357.

37. Bray C, Bell LN, Liang H, et al. Erythrocyte sedimentation rate and C-reactive protein measurements and their relevance in clinical medicine. WMJ. 2016;115(6):317–321.

38. Saito M, Ishimitsu T, Minami J, Ono H, Ohrui M, Matsuoka H. Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors. Atherosclerosis. 2003;167(1):73–79.

39. Healthcare Bluebook. http://www.healthcarebluebook.com. Accessed February 21, 2018.

40. Lane SK, Gravel JW Jr. Clinical utility of common serum rheumatologic tests. Am Fam Physician. 2002;65(6):1073–1080.

 

 

Copyright © 2018 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP


Editor's Collections


Related Content


More in Pubmed

MOST RECENT ISSUE


Dec 15, 2018

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article