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Determination of anti-CCP antibodies in patients with suspected rheumatoid arthritis: does it help to predict the diagnosis before referral to a rheumatologist?
  1. I K Gao1,
  2. A Haas-Wöhrle1,
  3. K G Mueller2,
  4. H-M Lorenz3,
  5. C Fiehn3
  1. 1Rheumatology Practice, Heidelberg, Germany
  2. 2Department of Internal Medicine II, University of Heidelberg, Germany
  3. 3Department of Internal Medicine V, University of Heidelberg and Centre for Rheumatic Diseases, Baden-Baden, Germany
  1. Correspondence to:
    PD Dr C Fiehn
    Centre for Rheumatic Diseases Baden-Baden, Rotenbachtalstr. 5, 76530 Baden-Baden, Germany;

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Prognosis in rheumatoid arthritis (RA) depends critically on early diagnosis and timely treatment with immune modulating drugs. As a consequence, early referral and access of patients with suspected RA to rheumatologists is mandatory for the establishment of diagnosis and initiation of treatment.

Measurement of antibodies to cyclic citrullinated peptide (CCP) is a new and highly specific test for the diagnosis of RA. Detection of anti-CCP antibodies—in particular, if the second generation of anti-CCP2 tests is used—has been shown to be of prognostic significance and to be helpful in early diagnosis of RA.1–9

The goal of this work was to investigate whether the measurement of anti-CCP antibodies alone or in combination with easily determinable parameters of a patient’s complaints and routine laboratory tests might help to identify prospectively patients with a high probability for RA.

For this study 102 patients from a routine rheumatology clinic were examined. All were referred by general practitioners, orthopaedic surgeons, or other non-rheumatological subspecialties because of suspected RA. In all patients the value of the anti-CCP antibody (second generation anti-CCP2-test; Euroimmun, Lübeck, Germany), IgM rheumatoid factor (RF, as determined by nephelometry; Beckman Coulter, Krefeld, Germany), C reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured, and physical, laboratory, and radiological examinations were performed. RA was diagnosed according to the American College of Rheumatology (ACR) criteria revised in 1987.10 All patients were questioned about the presence of morning stiffness of the joints and or muscles and about the presence of polyarticular pain, which was interpreted as positive if at least four tender joints were reported.

Sensitivity and specificity and—to obtain better information about the diagnostic value with a low pretest probability—the positive and negative predictive values (PPV and NPV) of the tests were calculated. For the latter, the following formulae were used:

PPV = a/(a+b); NPV = d/(c+d)

where a = test positive, disease positive; b = test positive, disease negative; c =  test negative, disease positive; d = test negative, disease negative.

Moreover, the relative risk of fulfilling the ACR criteria for RA, whether or not the test criteria were present, was determined.

Twenty eight of the 102 patients fulfilled the diagnosis of RA according to the ACR criteria (pretest probability of 27%).10 The other patients were classified as having unclassified monarthritis, polyarthritis, or oligoarthritis (n = 21), arthralgias of unknown origin (n = 20), osteoarthritis of the fingers (n = 20), psoriatic arthritis (n = 4), fibromyalgia (n = 3), polymyalgia rheumatica (n = 2), cervicobrachialgia (n = 2), periostitis (n = 1), and reactive arthritis (n = 1).

If a patient was positive for anti-CCP, the PPV, or in other words the probability of fulfilling the ACR criteria for RA, increased to 55% (table 1).

Table 1

 Values of the anti-CCP and the rheumatoid factor (RF) test alone or in combination with different laboratory parameters and patient’s complaints for the diagnosis of RA

This relatively low predictive value of the anti-CCP test was increased when it was combined with easily obtainable information about the patient’s complaints: if a patient had a positive anti-CCP test and at the same time morning stiffness of at least 60 min the PPV was 89%. In fact, the only patient who was positive for both measures without fulfilling the ACR criteria for RA was thought by the examining rheumatologist to have early RA. Polyarticular pain is a symptom which was present in all patients with RA and, additionally, in the patients with arthralgias, undifferentiated polyarthritis, fibromyalgia and polymyalgia rheumatica. If anti-CCP positive patients had polyarticular pain, a PPV of 78% and a NPV of 81% was obtained. In contrast, the combination of anti-CCP and RF, as was suggested by other reports,2,9 did not result in a similar increase of the PPV or NPV (59% and 79%, respectively). The rather low sensitivity and specificity of the anti-CCP test (table 1) was in accordance with other reports with similar results obtained in unselected rheumatological patients who were not subjected to a prolonged follow up.11

In conclusion, if information about morning stiffness of the joints or polyarticular pain is added, anti-CCP gives us a tool which more accurately predicts the presence of RA. This tool might be important to identify patients with early RA and facilitate a more precise selection of patients for rapid access to rheumatologists.


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