Uses of Anti-CCP in Early Rheumatoid Arthritis

Uses of Anti-CCP in Early Rheumatoid Arthritis Posted By:
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A young woman presents for evaluation of joint pain in both wrists and hands and swelling of one knee. Her history and physical exam suggest rheumatoid arthritis (RA) and you reflexively order a rheumatoid factor (RF), antinuclear antibody, creatine kinase, c-reactive protein, and erythrocyte sedimentation rate, along with a complete blood count and comprehensive metabolic panel. The differential diagnosis includes psoriatic arthritis and/or autoimmune diseases such as systemic lupus erythematosus (SLE), scleroderma, polymyositis, viral arthritis (eg, EBV, parvovirus B-19, rubella, hepatitis B/C, Lyme arthritis), reactive arthritis, inflammatory bowel disease-associated spondyloarthritis, fibromyalgia, and possibly hypothyroidism.

Hopefully, when you suspect RA, you order anti-CCP. Anti-CCP is more sensitive in early RA and is more predictive of erosive disease than RF. The two tests, RF and anti-CCP, are similar in specificityranging from 60% to 80%. However, the sensitivity of anti-CCP is superior to RF in early RA and ranges between 90% and 95%—in contrast to RF, which is approximately 75%.

False positives are more common with RF than anti-CCP. There are many infections, connective tissue diseases, malignancies, and advancing age factors associated with false-positive RF tests.

The false-positive rate of anti-CCP is difficult to come by. In a systematic review from 2010, it was found that false positivity can also occur in chronic infections most often associated with tuberculosis. Connective tissue diseases other than RA can also have a very small false-positive rate, including scleroderma and SLE. When compared to RF, however, anti-CCP has a lesser rate of false positives.

In summary, anti-CCP should be ordered with RF; when both are positive, the likelihood of RA is 95% to 98%. If anti-CCP is positive, this will also predict radiographic progression. As always, patient history and a physical, along with the overall clinical picture, guides the diagnosis.

References
  • Forslind K, Ahlmen M, Eberhardt, Hafstrom KI, Svensson B, BARFOT study group. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis. 2004;63:1090-1095.
  • Lee DM, Schur PH. Clinical utility of the anti-CCP assay in patients with rheumatic diseases. Ann Rheum Dis. 2003;62:870-874.
  • Lima I, Santiago M. Antibodies against cyclic citrullinated peptides in infectious diseasesa systematic review. Clinical Rheumatology. 2010;29:1345-1351.
  • Van Boekel AM, Vossenaar ER, Van den Hoogen HJ, Van Venrooij WJ. Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res. 2002;4:87-93.
  • West SG, Kolfenbach J. Rheumatology secrets. 4th edition. Philadelphia PA: Elsevier; 2020.

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Filed under: Rheumatology

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