Reply (2005)

To the Editor: We would like to thank Drs. Akkoc and Khan for their careful review of our 1998 study on the prevalence of AS and the whole group of spondylarthropathies. Their recalculation of our data suggests an overestimation of the prevalence of AS in our previous report and they propose a more conservative value of 0.66%. There are several factors of possible relevance for such calculations: 1) HLA–B27 association of the subset; 2) HLA–B27 background in the population; 3) structure of the target population; 4) sex distribution; 5) sample size (number of HLA–B27–negative subjects); 6) ascertainment of diagnosis. At the time we performed the study, we did not adjust for these factors because we thought that, with this type of study that includes blood donors, only rough estimates are possible and more detailed calculations may not be useful. In this regard, we agree that the calculation based on HLA–B27–negative donors is very risky. Nevertheless, since Drs. Akkoc and Khan have now analyzed our report in some detail, we have taken the challenge to recalculate the original numbers. In our study, which was performed in Berlin, SpA was diagnosed in 20 of 273 individuals: 19 of 140 B27-positive individuals (13.6%) and 1 of 133 B27-negative individuals (0.7%) (15 male, 5 female). AS was diagnosed in 9 individuals (7 male, 2 female; 45%), undifferentiated SpA in 7 (5 male, 2 female; 35%), psoriatic arthritis in 3 (2 male, 1 female; 15%), and chronic reactive arthritis in 1 (male; 5%). The relative risk of developing AS in B27-positive individuals was calculated to be 6.43%. Using the above results along with published data on the male:female ratio in the population (1) (Table 1), we calculated standardized prevalence rates with 95% confidence intervals (95% CIs) and standard errors (SE), as follows: AS = ([7/95] × 4.72) + ([2/45] × 4.58) + 0 + 0 = 0.55% (SE 0.19%, 95% CI 0.18–0.92%); SpA = ([14/95] × 4.72) + ([5/45] × 4.58) + ([1/88] × 46.05) + 0 = 1.73% (SE 0.6%, 95% CI 0.56–2.9%). Thus, we agree with Drs. Akkoc and Khan that the prevalence rates calculated in 1998 represented an overestimation. However, as already discussed, there are limitations to the approach of looking at “healthy” blood donors who are artificially enriched with HLA–B27. Nevertheless, the strength of that approach was that most patients were clinically examined and many underwent magnetic resonance imaging, which is now considered a useful tool, not only for the early diagnosis of SpA, but also for assessment of disease activity (2, 3). Despite the discovery in 1973 of a strong genetic link of HLA–B27 to AS and to the group of spondylarthropathies overall (4) we still do not know the nature of the obvious influence of HLA–B27 on these rheumatic diseases. The HLA–B27 background prevalence in a population is known to have some impact on the prevalence of AS. The history of prevalence studies in AS started in the 1960s. In 1975, the first blood donor study was published (5), in which an overall prevalence of AS of 1.0–1.5% was calculated. This high number was clearly not reproduced in a Dutch population-based study (6), which had an HLA–B27 background of ∼8%. Since definite AS was rarely found, it was calculated that 1.3% of the HLA–B27–positive population, in comparison with only 0.1% of the total population, had AS. In contrast, an epidemiologic survey in northern Norway (7) revealed a prevalence of definite AS of 1.1–1.4%, with an HLA–B27 background of ∼15%. It was calculated that 6.7% of the B27-positive individuals had AS. This proportion is consistent with our findings (Table 1). There are several other publications on the subject, but we have only mentioned some very recent studies for comparison. The age- and sex-adjusted prevalence of AS in Greece was found to be 0.3% (8). From France (9, 10), overall prevalence rates of SpA of 0.47% and 0.30% were reported, which are quite similar to the rates for rheumatoid arthritis. In another Greek study, an SpA prevalence of 0.49% was found (11). Taken together, the ranges of prevalence rates for AS and SpA show some variation in Europe, with some correlation with the HLA–B27 prevalence in the population. In addition, there are established geographic and ethnic influences. The recalculated standardized prevalence rate for AS from the Berlin study is 0.55%, and for SpA, the recalculated prevalence rate is 1.73%. Clearly, all available data indicate that the prevalence of AS has been underestimated for years. J. Braun MD*, J. Listing PhD , J. Sieper MD , * Herne and Ruhr-University, Bochum, Germany, Deutsches Rheumaforschungszentrum, Deutsches Rheumaforschungszentrum, Universitätsmedizin Charité, Berlin, Germany.