Rheumatoid arthritis is a chronic inflammatory
rheumatic disease which has a complex heterogeneous
phenotype and genotype.
5 Due to the heterogeneity of
the disease, during the diagnosis, the medical history
of the patient along with the opinion of the clinician
is very important, as is the case with other rheumatic
diseases. To reduce false diagnoses and to follow-up
the patients in a uniform manner, some classification
and diagnostic criteria were developed. Laboratory
tests, which are considered to be more objective, were
later added to these criteria lists along with pain and
joint swelling and radiological findings based on the
clinician's interpretation. Rheumatoid factor was first
mentioned in 1958 in the Association of American
Rheumatism (ARA) evaluation criteria. Anti-CCP and
RF were added to the ACR/EULAR classification
criteria in 2010. The anti-CCP is a test used to measure
the level of autoantibodies that are growing against
CCP structures.
4,6
Acute phase response develops through RA due
to tissue damage that forms in connection with
inflammation and as the result of metabolic stress
exposure of the cells. The most common test uses
ESR for the purpose of indirectly measuring the acute
phase response.7 However, the ESR was not to be evaluated as the only decisive test for disease diagnosis,
and it was not to be considered in the diagnostic or
classification criteria. The ESR has a low sensitivity
and specificity for RA diagnosis; however, although
it is elevated in many diseases, it may not be elevated
in some patients diagnosed with RA. It only remains
among the ACR criteria when considering remission.8
An ESR rate of 55% was reported for patients who
had been diagnosed with RA in a multicenter study
conducted in Finland and the United States,6 and
this rate was above the threshold value. In our study,
among the patients who were referred to clinics with
rheumatic complaints, only 39.6% had high ESR
values. Additionally, we calculated that there was a
low level of positive correlation between RA diagnosis
and ESR (Φ=0.236). Our results were not in harmony
with the data in the literature since only 50% of our
RA patients had elevated ESR. Our hospital, being
a third-level health organization, accepts patients
from neighboring hospitals. Furthermore, our PMR
rheumatic diseases clinic accepts patients to verify a
prediagnosis of RA and to perform anti-CCP testing
on them. The treatment of the patients in our study
began at other locations, which probably accounts for
the lack of dominant disease activity, and this may
be the cause for the lower than expected correlation
levels between the RA diagnosis and level of ESR.
Some existing data has shown that CRP may reflect
radiological damage in RA when it is used as the
monitoring agent for disease activity instead of ESR.8,9
It has been reported that 56% of the patients diagnosed
with RA had high CRP levels in the multicenter study
by Pincus et al.8 In our study, among the patients who
were referred to clinics with rheumatic complaints,
44.4% of the CRP values were found to be high, and
a statistically significant positive correlation level was
calculated between RA and the CRP results (Φ=0.289,
p<0.05). Although this result is close to the previous
data in the literature and was found to be statistically
significant, this rate had a lower than expected value.
This could be due to RA patients whose disease
activities were suppressed.
In the beginning, RF was seen as a specific sign for
RA, but it was later put forth that RF was observed with
positive rates of 60-80% among RA patients and that
it was also found to be positive in a number of other
diseases.10,11 In addition, it is known that RF positivity
is an indication of poor prognosis and that long-term
RF positivity is a risk factor for RA which stems from
the patients with no complaints.1 In another study
in our country, an RF positivity rate of 90% for RA
patients was reported, which is similar to our study
results.12 The RF was positive for 28.9% (77/270) of
the patients in our study. This ratio was calculated as
89.6% (60/67) for the patients diagnosed with RA, and
a statistically significant correlation level was observed
between RF and RA (Φ=0.782, p=0.000).
In a review that examined anti-CCP diagnostic
values, it was reported that the sensitivity was 0.53±0.10
and the specificity was 0.96±0.03.3 In the same study,
it was also emphasized that second-generation anti-
CCP tests had higher sensitivity levels while the
specificity values remained similar.1 Pincus et al.8
evaluated 37 different samples and found an anti-CCP
sensitivity of 0.67 and a specificity of 0.95 for RA. In
our study, the anti-CCP was positive for 21.5% of the
patients who came to our PMR clinic with rheumatic
complaints and findings. The anti-CCP positivity rate
was 86.6% (58/67) for the patients diagnosed with RA,
and there was a statistically significant correlation
level calculated between RA and anti-CCP (Φ=0.920,
p=0.000). Moreover, it was seen that the sensitivity,
specificity, positive productivity, and accuracy ratios of
anti-CCP were considerably higher than for the other
investigated tests for RA.
Anti-CCP positivity in patients with non-defined
arthritis, when examined independently from the
other factors, has been suggested as an indicator for
the development of RA.13 In another study, it was
reported that anti-CCP autoantibodies had a stronger
relationship with joint erosion but a weaker relationship
with extra-articular symptoms when compared with
RF.14 It should be noted that although the diagnosis
value of anti-CCP is high for early RA, it can also be
positive for other rheumatic diseases as well as for 5%
of the normal population.8,15,16 On the other hand, RA
development has been reported in 25% of patients with
early polyarthritis who originally tested negative for
anti-CCP.
In conclusion, for patients with rheumatic
complaints and findings, the diagnosis of RA should
be specified after an evaluation of their history,
clinical examinations, and laboratory and radiological findings. Although RF positivity may not be a single
factor for specifying a diagnosis, it should be included
among the evaluation criteria. Performing anti-CCP
testing on a daily basis would be beneficial since it has
high sensitivity and specificity values and it was the
latest proposed classification criteria for the diagnosis
of RA.
Declaration of conflicting interests
The authors declared no conflicts of interest with
respect to the authorship and/or publication of this
article.
Funding
The authors received no financial support for the
research and/or authorship of this article.
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