From the Guidelines
The best initial screening markers for rheumatoid arthritis are rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), as they are predictive of RA diagnosis and prognosis. When evaluating patients with undifferentiated peripheral inflammatory arthritis (UPIA), testing for RF and/or ACPA should be performed, as these factors are predictive of RA diagnosis and prognosis 1. The presence of ACPA or RF increases the probability of developing persistent synovitis or a worse radiographic outcome.
Key Markers
- Rheumatoid factor (RF)
- Anti-citrullinated protein antibodies (ACPA)
- Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should also be considered
Additional Tests
Additional autoantibody tests should be considered if a connective tissue disease/systemic inflammatory disorder is suspected, as recommended by a broad international panel of rheumatologists in the 3e initiative 1. The use of imaging, such as ultrasound or MRI, can also be used to predict the progression to clinical RA from undifferentiated inflammatory arthritis, with the presence of inflammation seen with ultrasound or MRI being a strong predictor 1.
Clinical Context
These laboratory tests should always be interpreted in the context of clinical findings, including joint examination for swelling, tenderness, and limited range of motion, particularly in small joints of hands and feet in a symmetric pattern. X-rays of hands and feet are also important to check for early erosive changes. A complete blood count may show anemia of chronic disease, and basic metabolic and liver function tests should be included to establish baseline values before starting medications.
From the Research
Best Markers for Initial Screen of Rheumatoid Arthritis
The best markers for the initial screen of rheumatoid arthritis include:
- Anti-cyclic citrullinated peptide (anti-CCP) antibody
- Rheumatoid factor (RF)
- C-reactive protein (CRP)
- Erythrocyte sedimentation rate (ESR)
Diagnostic Performance of Markers
The diagnostic performance of these markers is as follows:
- Anti-CCP antibody: high sensitivity and specificity, with a sensitivity of 88.0% and specificity of 90.4% 2
- RF: sensitivity of 91.0% and specificity of 74.4% 2
- Combination of RF and anti-CCP antibody: sensitivity of 90.2% and specificity of 83.3% 2
- Anti-CCP2 assay: diagnostic specificity and positive predictive value of 94.9% and 87.8%, respectively 3
Combination of Markers
The combination of markers can improve the diagnostic accuracy of rheumatoid arthritis:
- Combination of anti-CCP2 assay and RF: diagnostic specificity and positive predictive value of 96.9% and 90.9%, respectively 3
- Combination of anti-CCP2 assay, RF, and CRP: diagnostic specificity and positive predictive value of 98.7% and 95.5%, respectively 3
- Combination of ACPA test and IgM and IgA RF: best combination for early RA screening 4
Clinical Implications
The combined presence of ACPAs and RF is associated with a more rapid progression to RA, suggesting that anti-CCP+/RF+ individuals have a more advanced preclinical disease state and that the onset of RA may be imminent 5