Reactive and Enteropathic Arthritis

  • Robert D. Inman


The role of infection as a triggering factor in the pathogenesis of the various forms of spondyloarthritis (SpA) is implicated with varying degrees of certainty among the SpA subcategories. The very definition of reactive arthritis (ReA)—a sterile synovitis following an extra-articular infection—clearly implicates infection in its defining features, and ReA occupies the conceptual ground somewhere between septic arthritis and the classic autoimmune rheumatic diseases, such as rheumatoid arthritis (RA). An etiologic classification has fueled the search for definitive links between particular pathogens and ReA. Many of these studies are based on guilt by association, in that the demonstration of a particular immune response profile by serology or cellular responses leads to identification of the causative pathogen even when there is no direct demonstration of the organism or its antigens in synovial tissues or fluid. The predictive power of a diagnostic microbiology test, however, critically depends on the prevalence of positives in the healthy population at large (1), and this is an important consideration in the case for causality in ReA.


Ulcerative Colitis Ankylose Spondylitis Septic Arthritis Pyoderma Gangrenosum Reactive Arthritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Sieper J, Rudwaleit M, Braun J, et al. Diagnosing reactive arthritis. Arthritis Rheum 2002;46:319–327.CrossRefPubMedGoogle Scholar
  2. 2.
    Fendler C, Laitko S, Sorensen H, et al. Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis. Ann Rheum Dis 2001;60:337–343.CrossRefPubMedGoogle Scholar
  3. 3.
    Nikkari S, Puolakkainen M, Narvanen A, et al. Use of a peptide based enzyme immunoassay in diagnosis of Chlamydia trachomatis triggered reactive arthritis. J Rheumatol 2001;28:2487–2493.PubMedGoogle Scholar
  4. 4.
    Soderlin MK, Borjesson O, Kautiainen H, et al. Annual incidence of inflammatory joint diseases in a population-based study in southern Sweden. Ann Rheum Dis 2002;61:911–915.CrossRefPubMedGoogle Scholar
  5. 5.
    Buxton JA, Fyfe M, Berger S, et al. Reactive arthritis and other sequelae following sporadic Salmonella typhimurium infection in British Columbia, Canada - a case control study. J Rheumatol 2002;29:2154–2158.PubMedGoogle Scholar
  6. 6.
    Hannu T, Mattila L, Siitonen A, Leirisalo-Repo M. Reactive arthritis following an outbreak of Salmonella typhimurium phage type 193 infection. Ann Rheum Dis 2002;61:264–266.CrossRefPubMedGoogle Scholar
  7. 7.
    Locht H, Molbak K, Krogfelt KA.High frequency of reactive arthritis symptoms after an outbreak of Salmonella enteritidis. J Rheumatol 2002:29:767–771.PubMedGoogle Scholar
  8. 8.
    Hannu T, Mattila L, Rautelin H, et al. Campylobacter-triggered reactive arthritis: a population-based study. Rheumatol 2002;41:312–318.CrossRefGoogle Scholar
  9. 9.
    Boyer GS, Templin DW, Bowler A, et al. Spondyloarthropathy in the community: clinical syndromes and disease manifestations in Alaskan Eskimo populations. J Rheumatol 1999;26:1537–1544.PubMedGoogle Scholar
  10. 10.
    Rudwaleit M, Richter S, Braun J, Sieper J. Low incidence of reactive arthritis in children following a salmonella outbreak. Ann Rheum Dis 2001;60:1055–1057.CrossRefPubMedGoogle Scholar
  11. 11.
    Colmegna I, Cuchacovich R, Espinoza LR. HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev 2004;17:348–369.CrossRefPubMedGoogle Scholar
  12. 12.
    Soderlin MK, Kautiainen H, Puolakkainen M, et al. Infections preceding early arthritis in southern Sweden: a prospective population-based study. J Rheumatol 2003;30:425–429.Google Scholar
  13. 13.
    Gerard HC, Branigan PJ, Schumacher HR Jr, et al. Synovial Chlamydia trachomatis in patients with reactive arthritis/Reiter’s syndrome are viable but show aberrant gene expression. J Rheumatol 1998;25:734–742.PubMedGoogle Scholar
  14. 14.
    Kuipers JG, Jurgens-Saathoff B, Bialowons A, et al. Detection of Chlamydia trachomatis in peripheral blood leukocytes of reactive arthritis patients by polymerase chain reaction. Arthritis Rheum 1998;41:1894–1895CrossRefPubMedGoogle Scholar
  15. 15.
    Jendro MC, Fingerle F, Deutsch T, et al. Chlamydia trachomatis-infected macrophages induce apoptosis of activated T cells by secretion of tumor necrosis factor-alpha in vitro. Med Microbiol Immunol 2004;193:45–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Tse SML, Mason D, Botelho RJ, et al. Accumulation of diacylglycerol in the Chlamydia inclusion vacuole. Possible role in the inhibition of host cell apoptosis. J Biol Chem 2005;280:25210–25215.CrossRefPubMedGoogle Scholar
  17. 17.
    Chen T, Rimpilainen M, Luukkainen R, et al. Bacterial components in the synovial tissue of patients with advanced RA or OA; analysis with gas chromatography-mass spectrometry and pan-bacterial polymerase chain reaction. Arthritis Rheum 2003;49: 328–334.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang X, Pacheco-Tena C, Inman RD. Microbe hunting in the joints. Arthritis Rheum 2003;49:479–482.CrossRefPubMedGoogle Scholar
  19. 19.
    Stone MA, Payne U, Schentag C, Rahman R, Pacheco-Tena C, Inman RD. Comparative immune responses to candidate arthritogenic bacteria do not confirm a role for Klebsiella pneumoniae in the patho-genesis of familial ankylosing spondylitis. Rheumatology 2004;43:148–155.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhang X, Aubin J, Kim TH, et al. Synovial fibroblasts infected with Salmonella enterica serovar typhimurium mediate osteoclast differentiation and activation. Infect Immun 2004;72:7183–7189.CrossRefPubMedGoogle Scholar
  21. 21.
    Ekman P, Saarinen M, He Q, et al. HLA-B27-transfected and HLA-A2-transfected human monocytic U937 cells differ in their production of cytokines. Infect Immun 2002;70:1609–1614.CrossRefPubMedGoogle Scholar
  22. 22.
    Pentinnen MA, Holmberg CI, Sistonen LM, Granfors K. HLA-B27 modulates NFkB activation in human monocytic cells exposed to lipopol/saccharide. Arthritis Rheum 2002;46:2172–2180.CrossRefGoogle Scholar
  23. 23.
    Pentinnen MA, Heiskanen KM, Mohaptra R, et al. Enhanced intracellular replication of Salmonella enteritidis in HLA B27-expressing human monocytic cells. Arthritis Rheum 2004;50:2225–2263.Google Scholar
  24. 24.
    Young JL, Smith L, Matyszak MK, Gaston JS. HLA-B27 expression does not modulate intracellular Chlamydia trachomatis infection of cell lines. Infect Immun 2001;69:6670–6675.CrossRefPubMedGoogle Scholar
  25. 25.
    Payne U, Inman RD. Determinants of synovocyte clearance of arthritogenic bacteria. J Rheumatol 2003;30:1291–1297.PubMedGoogle Scholar
  26. 26.
    Ringrose JH, Meiring HD, Spiejer D, et al. Major histocompatibility complex class I peptide presentation and Salmonella enterica serovar typhimurium infection assessed via a stable isotope tagging of the B27-presented peptide repertoire. Infect Immun 2004;72:5097–5105.CrossRefPubMedGoogle Scholar
  27. 27.
    Dulphy N, Rabian C, Douay C, et al. Functional modulation of expanded CD8+ synovial fluid T cells-NK cell receptor expression in HLA-B27-associated reactive arthritis Int Immunol 2002;14:471–479.CrossRefPubMedGoogle Scholar
  28. 28.
    Ugrinovic S, Mertz A, Wu P, et al. A single nonamer from the Yersinia 60-kDa heat shock protein is the target of HLA-B27-restricted CTL response in Yersinia-induced arthritis. J Immunol 1997;159:5715–5723.PubMedGoogle Scholar
  29. 29.
    Kuon W, Holzhutter HG, Appel H, et al. Identification of HLA-B27-restricted peptides from the Chlamydia trachomatis proteome with possible relevance to HLA-B27-associated diseases. J Immunol 2001;167:4738–4746.PubMedGoogle Scholar
  30. 30.
    Appel H, Kuon W, Wu P, et al. Use of HLA-B27 tetramers to identify low-frequency antigen-specifiv T cells in Chlamydia-triggered reactive arthritis. Arthritis Res Ther 2004;6:521–534.CrossRefGoogle Scholar
  31. 31.
    Lopez-Larrea C, Gonzalez S, Martinez-Borra J. The role of HLA-B27 polymorphism and molecular mimicry in spondyloarthropathy. Mol Med Today 1998;4:540–549.CrossRefPubMedGoogle Scholar
  32. 32.
    Lo WF, Woods AS, DeCloux A, et al. Molecular mimicry mediated by MHC class Ib molecules after infection with gram-negative pathogens. Nat Med 2000;6:215–218.CrossRefPubMedGoogle Scholar
  33. 33.
    Ramos M, Alvarez I, Sesma L, et al. Molecular mimicry of HLA-B27-derived peptide ligand of arthritis-linked subtypes with chlamydial proteins. J Biol Chem 2002;277:37573–37581.CrossRefPubMedGoogle Scholar
  34. 34.
    Popov I, Dela Cruz CS, Barber BH, Chiu B, Inman RD. Breakdown of CTL D, tolerance to self HLA-B*2705 induced by exposure to Chlamydia trachomatis. J Immunol 2002;169:4033–4038.PubMedGoogle Scholar
  35. 35.
    Sieper J, Fendler C, Laitko S, et al. 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;42:1386–1396.CrossRefPubMedGoogle Scholar
  36. 36.
    Laasila K, Lassonen L, Leirisalo-Repo M. Antibiotic treatment and long term prognosis of reactive arthritis. Ann Rheum Dis 2003;62:655–658CrossRefPubMedGoogle Scholar
  37. 37.
    Smieja M, MacPherson DW, Kean W, et al. Randomised, blinded, placebo-controlled trial of doxycycline in chronic seronegative arthritis. Ann Rheum Dis 2001;60:1088–1094.CrossRefPubMedGoogle Scholar
  38. 38.
    Carter JD, Valeriano J, Vasey FB. Doxcycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to Chlamydia-induced arthritis. A prospective, randomized 9-month comparison. J Rheumatol 2004;31:1973–1980.PubMedGoogle Scholar
  39. 39.
    Yli-Kerttula T, Luukkainen R, Yli-Kerttula U, et al. Effect of a three-month course of ciprofloxacin on the late prognosis of reactive arthritis. Ann Rheum Dis 2003;62:880–884.CrossRefPubMedGoogle Scholar
  40. 40.
    Kvien TK, Gaston JSH, Bardin T, et al. Three month treatment of reactive arthritis with azithromycin: a EULAR double-blind, placebo-controlled study. Ann Rheum Dis 2004;63:1113–1119.CrossRefPubMedGoogle Scholar
  41. 41.
    Mielants H, Veys EM, Cuvelier C, De Vos M, Botelberghe L. HLA-related arthritis and bowel inflammation. Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis. J Rheumatol 1985;12:294–298.PubMedGoogle Scholar
  42. 42.
    Veloso FT, Carvalho J, Magro F. Immune-related manifestations of inflammatory bowel disease—a pros-pective study of 792. J Clin Gastroenterol 1988;83:703–709.Google Scholar
  43. 43.
    Steer S, Jones H, Hibbert J, et al. Low back pain, sacroiliitis and the relationship with HLA-B27 in Crohn’s disease. J Rheumatol 2003;30:518–522.PubMedGoogle Scholar
  44. 44.
    Turkcapar N, Toruner M, Soykan I, et al. The prevalence of extraintestinal manifestations and HLA association in patients with inflammatory bowel disease. Rheum Int 2005;34:387–391.Google Scholar
  45. 45.
    Mielants H, Veys EM, Cuvelier C, et al. The evolution of spondyloarthropathies in relation to gut histology. Relation between gut and joint. J Rheumatol 1995;22:2279–2284.PubMedGoogle Scholar
  46. 46.
    Palm O, Moum B, Jahnsen J, Gran JT. The prevalence and incidence of peripheral arthritis in patients with inflammatory bowel disease: a prospective population study. Rheumatology 2001;40:1256–1261.CrossRefPubMedGoogle Scholar
  47. 47.
    Brophy S, Pavy S, Lewis P, et al. Inflammatory eye, skin and bowel disease in spondyloarthritis: genetic, phenotypic and environmental factors. J Rheumatol 2001;28:2667–2673.PubMedGoogle Scholar
  48. 48.
    Helliwell PS, Hickling P, Wright V. Do the radiologic changes of classic ankylosing spondylitis differ from the changes found in spondylitis associated with inflammatory bowel disease, psoriasis and reactive arthritis. Ann Rheum Dis 1998;57:135–140.CrossRefPubMedGoogle Scholar
  49. 49.
    Peeters H, Van der Cruyssen B, Laukens D, et al. Radiologic sacroiliitis, a hallmark of spondylitis is linked with CARD15 gene polymorphisms in patients with Crohn’s disease. Ann Rheum Dis 2004;63:1131–1134.CrossRefPubMedGoogle Scholar
  50. 50.
    Kirwan JR, Hallgren R, Mielants H, et al. A randomized, placebo-controlled 12-week trial of budesonide and prednisolone in rheumatoid arthritis. Ann Rheum Dis 2004;63:688–695.CrossRefPubMedGoogle Scholar
  51. 51.
    Marzo-Ortega H, McGonagle D, O’Connor P, Emery P. Efficacy of etanercept for treatment of Crohn’s-related spondyloarthroarthritis but not colitis. Ann Rheum Dis 2003;62:74–76.CrossRefPubMedGoogle Scholar
  52. 52.
    Rispo A, Scarpa R, Di Girolamo E, et al. Infliximab in the treatment of extra-intestinal manifestations of Crohn’s disease. Scand J Rheumatol 2005;34:387–391.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Robert D. Inman
    • 1
  1. 1.Department of Medicine, Division of Rheuma-tologyUniversity of Toronto, Toronto Western HospitalTorontoCanada

Personalised recommendations