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. 2001 Apr;60(4):337–343. doi: 10.1136/ard.60.4.337

Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis

C Fendler 1, S Laitko 1, H Sorensen 1, C Gripenberg-Lerche 1, A Groh 1, J Uksila 1, K Granfors 1, J Braun 1, J Sieper 1
PMCID: PMC1753604  PMID: 11247862

Abstract

OBJECTIVE—Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an important differential diagnosis in patients presenting with the clinical picture of an undifferentiated oligoarthritis (UOA). This study was undertaken to evaluate the best diagnostic approach.
PATIENTS AND METHODS—52 patients with ReA, defined by arthritis and a symptomatic preceding infection of the gut or the urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis without a preceding symptomatic infection and after exclusion of other diagnoses (UOA), were studied. The following diagnostic tests were applied for the identification of the triggering bacterium: for yersinia induced ReA—stool culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection of antibodies to yersinia; for salmonella or campylobacter induced ReA—stool culture, EIA for the detection of antibodies to salmonella and Campylobacter jejuni; for infections with shigella—stool culture; for infections with Chlamydia trachomatis—culture of the urogenital tract, microimmunofluorescence and immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis.
RESULTS—A causative pathogen was identified in 29/52 (56%) of all patients with ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia trachomatis was the causative pathogen in 12/19 (63%) of the patients with urogenic ReA. In patients with the clinical picture of UOA a specific triggering bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%), salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%).
CONCLUSIONS—Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.



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Figure 1  .

Figure 1  

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Frequency of all bacteria or single bacteria identified as responsible for enteric reactive arthritis (eReA), urogenic reactive arthritis (uReA), or undifferentiated oligoarthritis (UOA).

Figure 2  .

Figure 2  

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Percentage of symptoms or tests which were positive in patients with arthritis induced by chlamydia, yersinia, or salmonella (as defined in table 2). *Positive antibodies more than two or three standard deviations (SD) above the mean in a control population measured by a yersinia-specific or a salmonella-specific enzyme immunoassay (EIA). MIF = microimmunofluorescence test for the detection of Chlamydia trachomatis-specific antibodies; IPA = immunoperoxidase assay for the detection of Chlamydia trachomatis-specific antibodies; ND = not done.

Figure 3  .

Figure 3  

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Frequency of other positive variables in patients with chlamydia induced arthritis with urethritis (A), positive culture for chlamydia (B), or a positive microimmunofluorescence test (MIF) for the detection of chlamydia-specific antibodies (C). IPA = immunoperoxidase assay for the detection of Chlamydia trachomatis-specific antibodies.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amor B. Reiter's syndrome and reactive arthritis. Clin Rheumatol. 1983 Dec;2(4):315–319. doi: 10.1007/BF02041549. [DOI] [PubMed] [Google Scholar]
  2. Bas S., Cunningham T., Kvien T. K., Glennås A., Melby K., Vischer T. L. The value of isotype determination of serum antibodies against Chlamydia for the diagnosis of Chlamydia reactive arthritis. Br J Rheumatol. 1996 Jun;35(6):542–547. doi: 10.1093/rheumatology/35.6.542. [DOI] [PubMed] [Google Scholar]
  3. Bas S., Griffais R., Kvien T. K., Glennås A., Melby K., Vischer T. L. Amplification of plasmid and chromosome Chlamydia DNA in synovial fluid of patients with reactive arthritis and undifferentiated seronegative oligoarthropathies. Arthritis Rheum. 1995 Jul;38(7):1005–1013. doi: 10.1002/art.1780380718. [DOI] [PubMed] [Google Scholar]
  4. Bas S., Vischer T. L. Chlamydia trachomatis antibody detection and diagnosis of reactive arthritis. Br J Rheumatol. 1998 Oct;37(10):1054–1059. doi: 10.1093/rheumatology/37.10.1054. [DOI] [PubMed] [Google Scholar]
  5. Branigan P. J., Gérard H. C., Hudson A. P., Schumacher H. R., Jr, Pando J. Comparison of synovial tissue and synovial fluid as the source of nucleic acids for detection of Chlamydia trachomatis by polymerase chain reaction. Arthritis Rheum. 1996 Oct;39(10):1740–1746. doi: 10.1002/art.1780391018. [DOI] [PubMed] [Google Scholar]
  6. Braun J., Bollow M., Remlinger G., Eggens U., Rudwaleit M., Distler A., Sieper J. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum. 1998 Jan;41(1):58–67. doi: 10.1002/1529-0131(199801)41:1<58::AID-ART8>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  7. Braun J., Laitko S., Treharne J., Eggens U., Wu P., Distler A., Sieper J. Chlamydia pneumoniae--a new causative agent of reactive arthritis and undifferentiated oligoarthritis. Ann Rheum Dis. 1994 Feb;53(2):100–105. doi: 10.1136/ard.53.2.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cevenini R., Sarov I., Rumpianesi F., Donati M., Melega C., Varotti C., La Placa M. Serum specific IgA antibody to Chlamydia trachomatis in patients with chlamydial infections detected by ELISA and an immunofluorescence test. J Clin Pathol. 1984 Jun;37(6):686–691. doi: 10.1136/jcp.37.6.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dougados M., van der Linden S., Juhlin R., Huitfeldt B., Amor B., Calin A., Cats A., Dijkmans B., Olivieri I., Pasero G. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991 Oct;34(10):1218–1227. doi: 10.1002/art.1780341003. [DOI] [PubMed] [Google Scholar]
  10. El-Gabalawy H. S., Goldbach-Mansky R., Smith D., 2nd, Arayssi T., Bale S., Gulko P., Yarboro C., Wilder R. L., Klippel J. H., Schumacher H. R., Jr Association of HLA alleles and clinical features in patients with synovitis of recent onset. Arthritis Rheum. 1999 Aug;42(8):1696–1705. doi: 10.1002/1529-0131(199908)42:8<1696::AID-ANR19>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  11. Gaydos C. A., Howell M. R., Pare B., Clark K. L., Ellis D. A., Hendrix R. M., Gaydos J. C., McKee K. T., Jr, Quinn T. C. Chlamydia trachomatis infections in female military recruits. N Engl J Med. 1998 Sep 10;339(11):739–744. doi: 10.1056/NEJM199809103391105. [DOI] [PubMed] [Google Scholar]
  12. Granfors K., Toivanen A. ELISA and RIA for serologic diagnosis of yersiniosis. Rev Infect Dis. 1984 May-Jun;6(3):421–424. doi: 10.1093/clinids/6.3.421-a. [DOI] [PubMed] [Google Scholar]
  13. Granfors K., Viljanen M., Tiilikainen A., Toivanen A. Persistence of IgM, IgG, and IgA antibodies to Yersinia in yersinia arthritis. J Infect Dis. 1980 Apr;141(4):424–429. doi: 10.1093/infdis/141.4.424. [DOI] [PubMed] [Google Scholar]
  14. Hannu T., Puolakkainen M., Leirisalo-Repo M. Chlamydia pneumoniae as a triggering infection in reactive arthritis. Rheumatology (Oxford) 1999 May;38(5):411–414. doi: 10.1093/rheumatology/38.5.411. [DOI] [PubMed] [Google Scholar]
  15. Hülsemann J. L., Zeidler H. Undifferentiated arthritis in an early synovitis out-patient clinic. Clin Exp Rheumatol. 1995 Jan-Feb;13(1):37–43. [PubMed] [Google Scholar]
  16. Inman R. D., Johnston M. E., Hodge M., Falk J., Helewa A. Postdysenteric reactive arthritis. A clinical and immunogenetic study following an outbreak of salmonellosis. Arthritis Rheum. 1988 Nov;31(11):1377–1383. doi: 10.1002/art.1780311106. [DOI] [PubMed] [Google Scholar]
  17. Isomäki O., Vuento R., Granfors K. Serological diagnosis of salmonella infections by enzyme immunoassay. Lancet. 1989 Jun 24;1(8652):1411–1414. doi: 10.1016/s0140-6736(89)90124-4. [DOI] [PubMed] [Google Scholar]
  18. Keat A. C., Thomas B. J., Taylor-Robinson D., Pegrum G. D., Maini R. N., Scott J. T. Evidence of Chlamydia trachomatis infection in sexually acquired reactive arthritis. Ann Rheum Dis. 1980 Oct;39(5):431–437. doi: 10.1136/ard.39.5.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Khan M. A. An overview of clinical spectrum and heterogeneity of spondyloarthropathies. Rheum Dis Clin North Am. 1992 Feb;18(1):1–10. [PubMed] [Google Scholar]
  20. Kingsley G., Sieper J. Third International Workshop on Reactive Arthritis. 23-26 September 1995, Berlin, Germany. Report and abstracts. Ann Rheum Dis. 1996 Aug;55(8):564–584. doi: 10.1136/ard.55.8.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Konttinen Y., Nordström D., Bergroth V., Leirisalo-Repo M., Santavirta S. Occurrence of different ensuing triggering infections preceding reactive arthritis: a follow up study. Br Med J (Clin Res Ed) 1988 Jun 11;296(6637):1644–1645. doi: 10.1136/bmj.296.6637.1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kosunen T. U., Rautelin H., Pitkänen T., Pönkä A., Pettersson T. Antibodies against an acid extract from a single campylobacter strain in hospitalized campylobacter patients. Infection. 1983 Jul-Aug;11(4):189–191. doi: 10.1007/BF01641193. [DOI] [PubMed] [Google Scholar]
  23. Kuipers J. G., Nietfeld L., Dreses-Werringloer U., Koehler L., Wollenhaupt J., Zeidler H., Hammer M. Optimised sample preparation of synovial fluid for detection of Chlamydia trachomatis DNA by polymerase chain reaction. Ann Rheum Dis. 1999 Feb;58(2):103–108. doi: 10.1136/ard.58.2.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kvien T. K., Glennås A., Melby K., Granfors K., Andrup O., Karstensen B., Thoen J. E. Reactive arthritis: incidence, triggering agents and clinical presentation. J Rheumatol. 1994 Jan;21(1):115–122. [PubMed] [Google Scholar]
  25. Lauhio A., Leirisalo-Repo M., Lähdevirta J., Saikku P., Repo H. Double-blind, placebo-controlled study of three-month treatment with lymecycline in reactive arthritis, with special reference to Chlamydia arthritis. Arthritis Rheum. 1991 Jan;34(1):6–14. doi: 10.1002/art.1780340103. [DOI] [PubMed] [Google Scholar]
  26. Mäki-Ikola O., Granfors K. Salmonella-triggered reactive arthritis. Lancet. 1992 May 2;339(8801):1096–1098. doi: 10.1016/0140-6736(92)90675-s. [DOI] [PubMed] [Google Scholar]
  27. Mäki-Ikola O., Heesemann J., Toivanen A., Granfors K. High frequency of Yersinia antibodies in healthy populations in Finland and Germany. Rheumatol Int. 1997;16(6):227–229. doi: 10.1007/BF01375653. [DOI] [PubMed] [Google Scholar]
  28. Mäki-Ikola O., Lahesmaa R., Heesemann J., Merilahti-Palo R., Saario R., Toivanen A., Granfors K. Yersinia-specific antibodies in serum and synovial fluid in patients with Yersinia triggered reactive arthritis. Ann Rheum Dis. 1994 Aug;53(8):535–539. doi: 10.1136/ard.53.8.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mäki-Ikola O., Leirisalo-Repo M., Kantele A., Toivanen P., Granfors K. Salmonella-specific antibodies in reactive arthritis. J Infect Dis. 1991 Dec;164(6):1141–1148. doi: 10.1093/infdis/164.6.1141. [DOI] [PubMed] [Google Scholar]
  30. Pacheco-Tena C., Burgos-Vargas R., Vázquez-Mellado J., Cazarín J., Pérez-Díaz J. A. A proposal for the classification of patients for clinical and experimental studies on reactive arthritis. J Rheumatol. 1999 Jun;26(6):1338–1346. [PubMed] [Google Scholar]
  31. Rabenau H., Berger A., Doerr H. W., Weber B. Testing for Chlamydia trachomatis in urine. Lancet. 1997 Apr 5;349(9057):1024–1025. doi: 10.1016/S0140-6736(05)62923-6. [DOI] [PubMed] [Google Scholar]
  32. Rich E., Hook E. W., 3rd, Alarcón G. S., Moreland L. W. Reactive arthritis in patients attending an urban sexually transmitted diseases clinic. Arthritis Rheum. 1996 Jul;39(7):1172–1177. doi: 10.1002/art.1780390715. [DOI] [PubMed] [Google Scholar]
  33. Schumacher H. R., Jr, Arayssi T., Crane M., Lee J., Gerard H., Hudson A. P., Klippel J. Chlamydia trachomatis nucleic acids can be found in the synovium of some asymptomatic subjects. Arthritis Rheum. 1999 Jun;42(6):1281–1284. doi: 10.1002/1529-0131(199906)42:6<1281::AID-ANR27>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  34. Schumacher H. R., Jr, Gérard H. C., Arayssi T. K., Pando J. A., Branigan P. J., Saaibi D. L., Hudson A. P. Lower prevalence of Chlamydia pneumoniae DNA compared with Chlamydia trachomatis DNA in synovial tissue of arthritis patients. Arthritis Rheum. 1999 Sep;42(9):1889–1893. doi: 10.1002/1529-0131(199909)42:9<1889::AID-ANR13>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  35. Sieper J., Braun J., Brandt J., Miksits K., Heesemann J., Laitko S., Sörensen H., Distler A., Kingsley G. Pathogenetic role of Chlamydia, Yersinia and Borrelia in undifferentiated oligoarthritis. J Rheumatol. 1992 Aug;19(8):1236–1242. [PubMed] [Google Scholar]
  36. Sieper J., Braun J. Problems and advances in the diagnosis of reactive arthritis. J Rheumatol. 1999 Jun;26(6):1222–1224. [PubMed] [Google Scholar]
  37. Sieper J., Braun J. Reactive arthritis. Curr Opin Rheumatol. 1999 Jul;11(4):238–243. doi: 10.1097/00002281-199907000-00003. [DOI] [PubMed] [Google Scholar]
  38. Sieper J., Fendler C., Laitko S., Sörensen H., Gripenberg-Lerche C., Hiepe F., Alten R., Keitel W., Groh A., Uksila J. 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 Rheum. 1999 Jul;42(7):1386–1396. doi: 10.1002/1529-0131(199907)42:7<1386::AID-ANR12>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  39. Sieper J., Kingsley G. H., Märker-Hermann E. Aetiological agents and immune mechanisms in enterogenic reactive arthritis. Baillieres Clin Rheumatol. 1996 Feb;10(1):105–121. doi: 10.1016/s0950-3579(96)80008-2. [DOI] [PubMed] [Google Scholar]
  40. Thomson G. T., DeRubeis D. A., Hodge M. A., Rajanayagam C., Inman R. D. Post-Salmonella reactive arthritis: late clinical sequelae in a point source cohort. Am J Med. 1995 Jan;98(1):13–21. doi: 10.1016/S0002-9343(99)80076-X. [DOI] [PubMed] [Google Scholar]
  41. Wang S. P., Grayston J. T. Human serology in Chlamydia trachomatis infection with microimmunofluorescence. J Infect Dis. 1974 Oct;130(4):388–397. doi: 10.1093/infdis/130.4.388. [DOI] [PubMed] [Google Scholar]
  42. Wilkinson N. Z., Kingsley G. H., Sieper J., Braun J., Ward M. E. 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 Rheum. 1998 May;41(5):845–854. doi: 10.1002/1529-0131(199805)41:5<845::AID-ART11>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  43. Wilkinson P. C. Immunoglobulin patterns of antibodies against Brucella in man and animals. J Immunol. 1966 Mar;96(3):457–463. [PubMed] [Google Scholar]
  44. Willkens R. F., Arnett F. C., Bitter T., Calin A., Fisher L., Ford D. K., Good A. E., Masi A. T. Reiter's syndrome. Evaluation of preliminary criteria for definite disease. Arthritis Rheum. 1981 Jun;24(6):844–849. doi: 10.1002/art.1780240612. [DOI] [PubMed] [Google Scholar]

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