Reactive arthritis, ankylosing spondylitis, juvenile arthritis

Role of chlamydiae

Reactive arthritis

The presence of C. trachomatis in the joint of patients with reactive arthritis secondary to a genital tract infection was first unambiguously demonstrated, after a number of inconclusive studies, by Taylor-Robinson et al., 1992. Subsequently Bas et al., 1995 in a remarkably thorough study found chlamydial DNA by PCR amplification in fluid from the joints of 22 patients with reactive arthritis or undifferentiated oligoarthritis. Wilkinson et al., 1998 confirmed these results, finding C. trachomatis DNA in the joint fluid of roughly a third of patients with undifferentiated oligoarthritis. However they were unable to demonstrate any association between the presence of chlamydial nucleic acid and the local antibody or T cell response. Moreover, they concluded, despite previous anecdotal reports, that C. pneumoniae probably did not play a major role in the pathogenesis of reactive arthritis [Wilkinson et al., 1998]. Other studies also concluded that C. pneumoniae, although a common respiratory bacterium, is probably not a major cause of reactive arthritis [Hannu et al., 1999; Schumacher et al., 1999]. A study in Finland [a country where C. pneumoniae is intensively studied], estimated that the organism was a triggering factor in approximately 10% of patients with acute reactive arthritis [Hannu et al., 1999].

Clinically, reactive arthritis often occurs following either a bout of gastroenteritis caused by enteric bacteria or following a sexually transmitted infection caused by C. trachomatis. There appears to be some geographic variation in the major organisms associated with reactive arthritis. In Berlin for example, a relatively high proportion of cases appear to be due to the enteric bacterium Yersinia enterocolitica. In approximately 50% of patients with reactive arthritis in the Berlin area it is possible to detect the presence of a known arthritogenic bacterium in the joint [Fendler et al., 2001].

A feature of reactive arthritis as opposed to septic or infectious arthritis is that it is often not possible to isolate a viable bacterium from the joint, even though, at least in the case of C. pneumoniae [Gerard et al., 2000] and C. trachomatis [Gerard _et al., 1998], there is evidence from turnover of nucleic acid that the organisms are metabolically active. Wilkinson et al., 1999 in the author's laboratory used a sensitive, broad-range, bacterial nucleic acid amplification technique capable of detecting most bacteria, found bacterial DNA in synovial fluid from a number of inflammatory forms of arthritis including rheumatoid arthritis. Some of the bacteria detected were childhood pathogens, including Haemophilus influenzae and Bordetella. It was suggested that these bacteria had been trapped in the joint for years. Thus the joint was thus seen as representing the cumulative history of exposure of the individual to blood-borne bacterial infection. In support of this Cox et al., 2003 found a wide range of bacterial nucleic acids in culture negative synovial fluid from various cases of arthritis whereas Chen et al., 2003 found bacterial DNA by broad spectrum PCR in only 5 of 15 cases of reactive arthritis. [This difference is most likely to arise as a result of methodological problems].

In Hamburg, using species or genus specific PCR, C. trachomatis DNA was found in the synovial fluid of 17% of 52 patients with undifferentiated oligoarthritis and Borrelia burgdorferi DNA was found in 12% [Schnarr et al., 2001]. However, the mere presence of the nucleic acid of a pathogenic bacterium in the joint, although certainly suggestive, does not prove that organism is responsible for the associated arthritic disease [Wilkinson et al., 1999]. This is one of the main stumbling blocks to understanding the role of infection in reactive arthritis and ankylosing spondylitis.

In a small study, Laasila et al., 2003 found that a three month course of lymecycline had little effect on the long term prognosis of reactive arthritis except among those cases which were thought to be triggered by C. trachomatis infection. [However this affect does not appear to be statistically significant].

Juvenile arthritis

The cause of juvenile chronic arthritis is unknown. So-called pauciarticular juvenile chronic arthritis is the most common subtype, divided into early (type I) and late (type II) onset forms, the latter clinically resembling reactive arthritis. A bacteria-specific synovial cellular immune response was found in two of three (67%) patients with reactive arthritis and 14 of 28 (50%) patients with pauciarticular juvenile chronic arthritis type II but only in one of 11 (9%) patients with pauciarticular juvenile chronic arthritis type I and in no patients with psoriatic arthritis. Six patients responded specifically to C. trachomatis and 11 to Yersinia enterocolitica, another bacterium associated with reactive arthritis. It was suggested that bacteria associated with reactive arthritis, notably C. trachomatis and Y. enterocolitica, may also have a a causative role in pauciarticular juvenile chronic arthritis type II but not type I [Sieper et al., 1992].

[MEW] July 2003

NEXT: Arthritis Pathogenesis

References

Bas, S., Griffais, R., Kvien, T. K., Glennas, A., Melby, K. & Vischer, T. L. (1995). Amplification of plasmid and chromosome Chlamydia DNA in synovial fluid of patients with reactive arthritis and undifferentiated seronegative oligoarthropathies. Arthritis & Rheumatism 38, 1005 - 1013.

Braun, J., Tuszewski, M., Ehlers, S., Haberle, J., Bollow, M., Eggens, U., Distler, A. & Sieper, J. (1997). Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multiple bacterial species in inflammatory joint diseases. II. Examination of sacroiliac and knee joint biopsies of patients with spondyloarthropathies and other arthritides. Journal of Rheumatology24, 1101 - 1105.

Chen, T., Rimpilainen, M., Luukkainen, R., Mottonen, T., Yli-Jama, T., Jalava, J., Vainio, O. & Toivanen, P. (2003). Bacterial components in the synovial tissue of patients with advanced rheumatoid arthritis or osteoarthritis: analysis with gas chromatography-mass spectrometry and pan-bacterial polymerase chain reaction. Arthritis and Rheumatism 49, 328 - 334.

Cox, C. J., Kempsell, K. E. & Gaston, J. S. (2002). Investigation of infectious agents associated with arthritis by reverse transcription PCR of bacterial rRNA. Arthritis Research and Therapy 5, R1-8. Full article [Acrobat] .

Fendler, C., Laitko, S., Sorensen, H., Gripenberg-Lerche, C., Groh, A., Uksila, J., Granfors, K., Braun, J. & Sieper, J. (2001). Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis. Annals of Rheumatic Diseases 60, 337 - 343.

Gerard, H. C., Branigan, P. J., Schumacher, H. R. Jr. & Hudson, A. P. (1998). Synovial Chlamydia trachomatis in patients with reactive arthritis/Reiter's syndrome are viable but show aberrant gene expression. Journal of Rheumatology 25, 734 - 742.

Gerard, H. C., Schumacher, H. R., el-Gabalawy, H., Goldbach-Mansky, R. & Hudson, A. P. (1999). Chlamydia pneumoniae present in the human synovium are viable and metabolically active. Microbial Pathogenesis 29, 17-24.

Hannu, T., Puolakkainen, M. & Leirisalo-Repo, M. (1999). Chlamydia pneumoniae as a triggering infection in reactive arthritis. Rheumatology (Oxford) 38, 411 - 414.

Laasila, K., Laasonen, L. & Leirisalo-Repo, M. (2003). Antibiotic treatment and long term prognosis of reactive arthritis. Annals of Rheumatic Disease 62, 655 - 658.

Schnarr, S., Putschky, N., Jendro, M. C., Zeidler, H., Hammer, M., Kuipers, J. G. & Wollenhaupt, J. (2001). Chlamydia_ and Borrelia DNA in synovial fluid of patients with early undifferentiated oligoarthritis: results of a prospective study. Arthritis and Rheumatism 44, 2679 - 2685 [see also editorial comment]

Schumacher, H. R. Jr., Gerard, H. C., Arayssi, T. K., Pando, J. A., Branigan, P. J., Saaibi, D. L. & Hudson, A. P. (1999). Lower prevalence of Chlamydia pneumoniae DNA compared with Chlamydia trachomatis DNA in synovial tissue of arthritis patients. Arthritis & Rheumatism 42 , 1889 - 1893.

Sieper, J., Braun, J., Doring, E., Wu, P., Heesemann, J., Treharne, J. & Kingsley, G. (1992). Aetiological role of bacteria associated with reactive arthritis in pauciarticular juvenile chronic arthritis. Annals of Rheumatic Disease 51, 1208 - 1214.

Sieper, J., Fendler, C., Laitko, S., Sorensen, H., Gripenberg-Lerche, C., Hiepe, F., Alten, R., Keitel, W., Groh, A., Uksila, J., Eggens, U., Granfors, K. & Braun, J. (1999). No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study. Arthritis & Rheumatism, 1386 - 1396. 42

Taylor-Robinson, D., Gilroy, C. B., Thomas, B. J. & Keat, A. C. (1992). Detection of Chlamydia trachomatis DNA in joints of reactive arthritis patients by polymerase chain reaction. Lancet 340, 81 - 82.

Wilkinson, N. Z., Kingsley, G. H., Jones, H. W., Sieper, J., Braun, J. & Ward, M. E. (1999). The detection of DNA from a range of bacterial species in the joints of patients with a variety of arthritides using a nested, broad-range polymerase chain reaction. Rheumatology (Oxford). 38, 260 - 266.

Wilkinson, N. Z., Kingsley, G. H., Sieper, J., Braun, J. & Ward, M. E. (1998). Lack of correlation between the detection of Chlamydia trachomatis DNA in synovial fluid from patients with a range of rheumatic diseases and the presence of an antichlamydial immune response. Arthritis & Rheumatism 41, 845 - 854.

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Topic revision: r6 - 2011-03-31 - SanderO
 
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