Rheumatology Advance Access originally published online on January 29, 2008
Rheumatology 2008 47(3):375-376; doi:10.1093/rheumatology/kem367
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LETTERS TO THE EDITOR |
RF latex and anti-CCP antibodies: a combined strategy for diagnosing RA in primary care?
1Department of Rheumatology and 2Department of Immunology, Wexham Park Hospital, Slough, Berks SL2 4HL, UK.
Correspondence to: A. Steuer, Department of Rheumatology, Wexham Park Hospital, Slough, Berks SL2 4HL, UK. E-mail: alan.steuer{at}hwph-tr.nhs.uk
SIR, Deborah Symmons makes a strong case in your recent editorial that RF testing should not be abandoned but used in conjunction with anti-cyclic citrullinated peptide (CCP) antibodies in the diagnosis of early RA in secondary care [1]. Whilst combining RF with anti-CCP antibodies may add some additional diagnostic and prognostic information, there is a consensus view that measuring anti-CCP antibodies in patients who are already known to have clinically diagnosed RA adds little additional information in the presence of high-titre RF [2]. However, serological testing for RF is not diagnostic, being predictive of more severe disease in those with known RA. In secondary care, where the pre-test probability of a diagnosis of inflammatory arthritis in patients is high, one may argue that there is a need for CCP antibody testing only for those in whom the diagnosis of RA is not yet clear. However, in primary care, where currently patients are tested inappropriately for RF with a lower pre-test probability, there are many false positives, leading to inappropriate referrals to specialist clinics. The use of anti-CCP antibody testing in this setting may reduce false positive results, inappropriate referral and ultimately prove cost-saving to the health economy.
We undertook a prospective study to examine a new serological approach for the diagnosis of RA in primary care. We hypothesized that a rheumatoid latex test could be used as an initial screening tool, given its relatively high sensitivity and low specificity. Samples from primary care were screened by RF latex testing, and if positive, tested for anti-CCP antibodies. We compared this strategy with the conventional RF latex plus particle agglutination assay (RAPA) currently used for diagnosis of RA in primary care.
We collected 112 new referrals to the rheumatology outpatient department with joint pain who had previously been subjected to RF testing in primary care. Serum samples were tested for RF using a latex test (RF latex at a screening dilution of 1:120), particle agglutination assay (RAPA-positive if titre >1:80) and anti-CCP antibody (Diasorin, Reading, UK). Clinical diagnoses were recorded blindly by an experienced rheumatologist.
Out of 112 patients referred, 31 (27.6%) had a diagnosis of inflammatory arthritis, of whom 13 were diagnosed with definite RA. Fifteen patients were RF latex/RAPA positive of whom nine (60%) had inflammatory arthritis and eight (53%) definite RA. In contrast, nine patients were RF latex and anti-CCP positive, all of whom had inflammatory arthritis and eight out of nine (89%) had definite RA. One patient with an undifferentiated inflammatory arthritis had a negative RF latex and was positive for anti-CCP antibody. Ninety patients were negative for RF and anti-CCP, of whom five were diagnosed with RA (5.6%). Furthermore, of the 80 patients with non-inflammatory joint pain, 5 (6.25%) were latex/RAPA positive and 12 (15%) were latex-positive/CCP-negative, and referred to out patients on this basis; no patient was CCP antibody positive in this group.
This pilot study suggests that using RF latex as a screening test together with anti-CCP antibody (if the latex test is positive) is an effective strategy for screening for RA in primary care. The combination of RF latex testing and CCP antibody testing provides a highly specific screening test for RA, with comparable sensitivity to latex/RAPA. This approach will not pick up those RA patients who are latex negative and CCP antibody positive, although only one such patient was identified in this study. However, such patients would not be picked up anyway with the conventional approach to screening (latex/RAPA).
Whilst there is a cost implication to this screening strategy, we calculate that within a catchment population of around 400 000 people, we need to reduce inappropriate outpatient referrals by only 20 patients/yr to make this strategy cost-effective for the health economy, based on current outpatient tariffs. We believe this approach to serological testing for RA in primary care merits further study [3].
Disclosure statement: The authors have declared no conflicts of interest.
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- Symmons DPM. Classification criteria for rheumatoid arthritis – time to abandon rheumatoid factor? Rheumatology (2007) 46:725–6.
[Free Full Text] - Nell VP, Machold KP, Stamm TA, et al. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis (2005) 64:1731–6.
[Abstract/Free Full Text] - Watkins JA, Smith F, Day L, Demetriadi F, Steuer A, Chapel H. The end of rheumatoid factor in primary care? Rheumatology (2006) 45:i90.
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