Automated counting of white blood cells in synovial fluid: reply

R. de Jonge, R. Brouwer, M. Smit, M. de Frankrijker-Merkestijn, R. J. E. M. Dolhain1, J. M. W. Hazes1, A. W. van Toorenenbergen and J. Lindemans

Erasmus MC, Clinical Chemistry, 1 Erasmus MC, Rheumatology, Rotterdam, The Netherlands.

Correspondence to: R. de Jonge. E-mail: r.dejonge{at}erasmusmc.nl

We would like to thank Dieppe and Swan for their response to our recent article in this journal [1]. Before commenting on their experiment and conclusions, we would like to emphasize that the object of our study was to validate and to determine the reliability of automated white blood cell (WBC) counting in synovial fluid rather than to evaluate its diagnostic accuracy. Although, to date, there have been few studies on this subject, there is convincing evidence that WBC counting can distinguish inflammatory from non-inflammatory joint effusions [2, 3]. Furthermore, manual synovial fluid WBC counting is routinely performed by most diagnostic laboratories, despite its high analytical imprecision [4]. In our article [1], we showed that synovial fluid WBC counts can be reliably determined using the DIFF channel of the Sysmex XE-2100. Not unimportantly, we also demonstrated that automated counting offers more precise results when compared with manual counting.

The question put forward by Dieppe and Swan as to whether WBC counting really adds information to bedside examination of the existence of inflammation is very interesting and fits in with the multivariable approach of doing diagnostic research in contrast to the univariable approach [5]. Based on their interesting experiment, Dieppe and Swan conclude that (1) WBC counting does not add to clinical examination and gross appearance of the synovial fluid and (2) the differential WBC count is more informative than the total WBC count. However, we think that these conclusions cannot be substantiated by the presented data. Firstly, Dieppe and Swan looked at agreement between two tests by calculating Pearson correlation coefficients. However, for agreement between categorical data, kappa scores should be calculated instead of Pearson correlation coefficients. Secondly, the observed correlations are at best modest (r ≤ 0.58) and are only high between ‘after aspiration’ and ‘differential white cell count’ (r = 0.79). Thirdly, in our opinion, simply looking at correlations between determinants of inflammation does not solve the issue of whether WBC counting adds information to clinical examination. Instead, multivariate logistic regression analysis should be used in whichever clinical examination is put first into the model whereafter total (and differential) WBC counting is added. The classification of synovial fluids as being either inflammatory or non-inflammatory should be based on standard criteria (gold standard). The area under the curve of the receiver operating characteristic (ROC) curve of both models should then be compared to determine the added value of the synovial fluid WBC count. Using such an approach, Shmerling et al. [3] demonstrated that determination of the differential WBC count added diagnostic value beyond that of synovial fluid total WBC count alone.

Once the characteristics (diagnostic accuracy) of tests used to discriminate between inflammatory and non-inflammatory joint disease are known, as well as the added value of each test, then one still has to look at the individual test characteristics before a diagnostic decision model can be selected. If, for instance, it appears that clinical examination and total WBC counting show similar diagnostic accuracy (sensitivity, specificity) in univariate analysis and that WBC counting does not add information to clinical examination in multivariate logistic regression analysis, we are still left with the question of test reliability (imprecision). As we have shown in our article [1], automated WBC counting has the advantage of low imprecision (≤10%) but requires an invasive procedure to obtain synovial fluid. In contrast, clinical examination is not invasive but is probably very imprecise. In the study presented by Dieppe and Swan, there was only a high correlation between differential WBC counts and the clinical prediction rule based on observation of the appearance of the synovial fluid. If we assume similar diagnostic accuracy for both tests, then (differential) WBC counting is probably still a cheap, fast and precise assay. Since reliable and reproducible methods such as automated cell counting are available nowadays, we feel that simply looking at the appearance of the synovial fluid will put us back to the Middle Ages where uroscopy and ‘urine fortune telling’ were also practised by physicians.

The issue raised by Dieppe and Swan is important for clinical diagnosis. We would welcome a full publication on the four-point scoring system for the clinical assessment of knee joint inflammation and the appearance of synovial fluid describing the diagnostic accuracy of this test in conjunction with other tests such as (differential) WBC counting as suggested. This would be a valuable contribution to the scarce literature data on this subject.

The authors have declared no conflicts of interest.

References

  1. de Jonge R, Brouwer R, Smit M et al. Automated counting of white blood cells in synovial fluid. Rheumatology 2004;43:170–3.[Abstract/Free Full Text]
  2. Freemont AJ, Denton J, Chuck A, Holt PJ, Davies M. Diagnostic value of synovial fluid microscopy: a reassessment and rationalisation. Ann Rheum Dis 1991;50:101–7.[Abstract]
  3. Shmerling RH, Delbanco TL, Tosteson AN, Trentham DE. Synovial fluid tests. What should be ordered? J Am Med Assoc 1990;264:1009–14.[Abstract]
  4. Hasselbacher P. Variation in synovial fluid analysis by hospital laboratories. Arthritis Rheum 1987;30:637–42.[ISI][Medline]
  5. Moons KGM, Biesheuvel CJ, Grobbee DE. Test research versus diagnostic research. Clin Chem 2004;50:473–6.[Free Full Text]
Accepted 28 May 2004





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