Second Department of Medicine, Lainz Hospital and Department of Rheumatology, University of Vienna, Vienna, Austria
The diagnosis of rheumatoid arthritis (RA) is hampered by the fact that the currently most accepted serological feature, rheumatoid factor (RF), is not very specific for RA nor very sensitive in early RA, even if it is part of the RA classification criteria [1, 2]. Therefore, the search for additional tests which improve the differentiation of RA from non-RA conditions is ongoing and any additional such test, particularly when more specific, will then be helpful. It will particularly be helpful in RF-negative patients, but may also be confirmatory in RF-positive ones. Nevertheless, every advance has to be looked at critically, and, therefore, we are grateful for the comments of Dr Jobanputra and particularly for the attempts to help interpret our data. However, we would like to clarify certain aspects of these interpretations which appear to be related to a misunderstanding of our methods and results.
The 1987 American Rheumatism Association (ARA) criteria [1] have been regarded by us to replace points A, B and C of the 1958 ARA classification criteria [3], since they clearly state that a distinction between classical, definite and probable RA should no longer be made. However, the 1958 criteria, under point E, also contain exclusion criteria which we did not regard to be invalid after the revision of the classification criteria for RA. Among these exclusions is the existence of a defined connective tissue disease. [It is unlikely that the ARA intended to classify patients as suffering from RA merely on the basis of e.g. symmetric joint swelling of the hands and fingers for many weeks, morning stiffness, and RF, if they also satisfied classification criteria for systemic lupus erythematosus (SLE) or other connective tissue diseases, since symmetric arthritis is a common feature of these disorders. However, this is an aspect which may have to be clarified elsewhere.] In fact, many patients with connective tissue diseases would otherwise fulfil RA classification criteria [4]. To prevent such contradiction and on the basis of the above exclusion criterion, we have excluded all patients with defined connective tissue diseases from classification as RA. Therefore, the 2 x 2 table designed by Dr Jobanputra does not reflect our approach.
On the other hand, Dr Jobanputra is correct in that we did not show data on patients who had a clinical diagnosis of RA and did not fulfil ARA criteria. However, in our cohort of patients, 1 yr after their first visit all patients with early RA fulfilled ARA criteria and we did not discern patients who could not be classified as RA initially from those who could, because there did not appear to be a difference in results, although their numbers were not equal. It is this notion which led us to suggest that the hypothesis put forward in our study needed to be supported by additional studies.
Interestingly, such an additional study has been performed in parallel to our study by another group, and they have arrived at quite similar conclusions [5], indicating that, in fact and in contrast to the opinion of Dr Jobanputra, anti-Sa is a very useful marker which may have diagnostic importance for RA and particularly also for RA in its early stages. On the basis of these as well as our own data, we do have difficulty in following Dr Jobanputra's conclusions on the usefulness of anti-Sa: if a marker serves to identify five of a total of 19 (26%) of those patients who tested negative by other assays and, in addition, supports another serological test in 16 of a total of 48 patients (33%), why should such a marker not be considered helpful as a diagnostic test? We say: it will be up to further studies to support or refute such consideration, and a third such study (led by Drs El Gabalawy, Schumacher and Klippel) is on its way in a large NIH cohort of early arthritis patients in whom we have tested blindly anti-Sa and anti-RA33 autoantibodies.
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