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Recent advances in reactive arthritis

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Abstract

Reactive arthritis (ReA), one of the spondyloarthropathies, is an infectious related disease that occurs in a genetically predisposed individual, characterized by an immunemediated synovitis with intra-articular persistence of viable nonculturable bacteria and/or immunogenic bacterial antigens. ReA long term prognosis is not as good as it was earlier believed. Two-thirds of patients develop prolonged joint discomfort, low back pain, or enthesopathies after acute ReA, and 15% to 30% of them develop chronic symptoms. The therapeutic options for patients with the more severe forms of the disease have been rather limited. The efficacy of tumor necrosis factor antagonists in other spondyloarthritis suggested that anticytokine therapy could also be effective for ReA. This paper reviews the latest concepts in urogenital and postenteric human leukocyte antigen-B27-associated ReA.

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References and Recommended Reading

  1. Toivanen A, Toivanen P: Reactive arthritis. Best Pract Res Clin Rheumatol 2004, 18:689–703. Detailed review of the clinical, pathogenetic, and therapeutic aspects of ReA.

    Article  PubMed  Google Scholar 

  2. Colmegna I, Cuchacovich R, Espinoza LR: HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev 2004, 17:348–369. Recent update on basic research and clinical manifestations of the HLA-B27 associated ReA.

    Article  PubMed  CAS  Google Scholar 

  3. Laasila K, Laasonen L, Leirisalo-Repo M: Antibiotic treatment and long term prognosis of reactive arthritis. Ann Rheum Dis 2003, 62:655–658. Assessment of outcome at 10 years of a small number of patients treated for 3 months with limecycline versus placebo in the acute phase of ReA.

    Article  PubMed  CAS  Google Scholar 

  4. Flores D, Marquez J, Garza M, Espinoza LR: Reactive arthritis: newer developments. Rheum Dis Clin North Am 2003, 29:37–59.

    Article  PubMed  Google Scholar 

  5. Zeidler H, Kuipers J, Kohler L: Chlamydia-induced arthritis. Curr Opin Rheumatol 2004, 16:380–392.

    Article  PubMed  Google Scholar 

  6. Carter JD, Valeriano J, Vasey FB: Doxycycline 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. Open-label trial of combined antimicrobials for the treatment of undifferentiated spondyloarthropathies.

    PubMed  CAS  Google Scholar 

  7. Inman RD, Whittum-Hudson JA, Schumacher HR, et al.: Chlamydia and associated arthritis. Curr Opin Rheumatol 2000, 12:254–262.

    Article  PubMed  CAS  Google Scholar 

  8. Kuipers JG, Zeidler H, Kohler L: How does chlamydia cause arthritis? Rheum Dis Clin North Am 2003, 29:613–629.

    Article  PubMed  Google Scholar 

  9. Rees JR, Pannier MA, McNees A, et al.: Persistent diarrhea, arthritis, and other complications of enteric infections: a pilot survey based on California FoodNet surveillance, 1998–1999. Clin Infect Dis 2004, 38(Suppl 3):S311-S317.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. Savolainen E, Kaipiainen-Seppanen O, Kroger L, et al.: Total incidence and distribution of inflammatory joint diseases in a defined population: results from the Kuopio 2000 arthritis survey. J Rheumatol 2003, 30:2460–2468.

    PubMed  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. Hannu T, Mattila L, Rautelin H, et al.: Campylobacter-triggered reactive arthritis: a population-based study. Rheumatology (Oxford) 2002, 41:312–318.

    Article  CAS  Google Scholar 

  14. Hannu T, Mattila L, Siitonen A, Leirisalo-Repo M: Reactive arthritis attributable to shigella infection: a clinical and epidemiological nation-wide study. Ann Rheum Dis 2005, 64:594–598. Population-based study of the incidence and clinical picture of Shigella-associated ReA.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. Hannu T, Kauppi M, Tuomala M, et al.: Reactive arthritis following an outbreak of campylobacter jejuni infection. J Rheumatol 2004, 31:528–530.

    PubMed  Google Scholar 

  17. Hannu T, Mattila L, Nuorti JP, et al.: Reactive arthritis after an outbreak of yersinia pseudotuberculosis serotype O:3 infection. Ann Rheum Dis 2003, 62:866–869.

    Article  PubMed  CAS  Google Scholar 

  18. Sieper J, Rudwaleit M, Braun J, van derHeijde D: Diagnosing reactive arthritis: role of clinical setting in the value of serologic and microbiologic assays. Arthritis Rheum 2002, 46:319–327. Diagnostic approach to urogenital and enteric ReA based on the analysis of pre- and post-test probabilities.

    Article  PubMed  Google Scholar 

  19. Mannoja A, Pekkola JM, Hamalainen MT, et al.: Lumbosacral radiographic signs in patients with previous entero- or uroarthritis. Ann Rheum Dis 2005, In press. A study showing that the radiologic findings in the lumbosacral spine of patients with uro or enteroarthritis are characteristically similar.

  20. Bas S, Genevay S, Schenkel MC, et al.: Importance of species-specific antigens in the serodiagnosis of chlamydia trachomatis reactive arthritis. Rheumatology (Oxford) 2002, 41:1017–1020.

    Article  CAS  Google Scholar 

  21. Zino E, Di Terlizzi S, Carugo C, et al.: Rapid detection of all HLA-B*27 alleles (B*2701-B*2725) by group-specific polymerase chain reaction. Tissue Antigens 2004, 63:88–92. Description of a rapid and reliable PCR protocol for the detection of all 28 B*27 allelles known to date.

    Article  PubMed  CAS  Google Scholar 

  22. Monack DM, Mueller A, Falkow S: Persistent bacterial infections: the interface of the pathogen and the host immune system. Nat Rev Microbiol 2004, 2:747–765. Review describing the strategies used by different bacteria, in particular Salmonella, during persistent infections that allow them to evade the immune surveillance.

    Article  PubMed  CAS  Google Scholar 

  23. Belland RJ, Nelson DE, Virok D, et al.: Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation. Proc Natl Acad Sci U S A 2003, 100:15971–15976. Study showing that an IFN-γ-inducible stimulus mediates C. trachomatis persistence, and that persistence is an alternative life cycle used by chlamydiae to avoid the host immune response.

    Article  PubMed  CAS  Google Scholar 

  24. Morrison RP: New insights into a persistent problem—chlamydial infections. J Clin Invest 2003, 111:1647–1649.

    PubMed  CAS  Google Scholar 

  25. Yu D, Kuipers JG: Role of bacteria and HLA-B27 in the pathogenesis of reactive arthritis. Rheum Dis Clin North Am 2003, 29:21–36. Review of ReA pathogenesis with particular emphasis on the role of HLA-B27.

    Article  PubMed  Google Scholar 

  26. Caldwell HD, Wood H, Crane D, et al.: Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates. J Clin Invest 2003, 111:1757–1769.

    PubMed  CAS  Google Scholar 

  27. 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.

    PubMed  CAS  Google Scholar 

  28. Gerard HC, Whittum-Hudson JA, Schumacher HR, Hudson AP: Differential expression of three Chlamydia trachomatis hsp60-encoding genes in active vs. persistent infections. Microb Pathog 2004, 36:35–39.

    Article  PubMed  CAS  Google Scholar 

  29. Bulut Y, Faure E, Thomas L, et al.: Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J Immunol 2002, 168:1435–1440.

    PubMed  CAS  Google Scholar 

  30. Butrimiene I, Jarmalaite S, Ranceva J, et al.: Different cytokine profiles in patients with chronic and acute reactive arthritis. Rheumatology (Oxford) 2004, 43:1300–1304. Analysis of the cytokine profile in patients with acute and chronic ReA. This study provides preliminary data that support the use of anti-TNF agents in the chronic phase of the disease.

    Article  CAS  Google Scholar 

  31. Gerard HC, Wang Z, Whittum-Hudson JA, et al.: Cytokine and chemokine mRNA produced in synovial tissue chronically infected with Chlamydia trachomatis and C. pneumoniae. J Rheumatol 2002, 29:1827–1835.

    PubMed  CAS  Google Scholar 

  32. Appel H, Neure L, Kuhne M, et al.: An elevated level of IL-10- and TGF beta-secreting T cells, B cells and macrophages in the synovial membrane of patients with reactive arthritis compared to rheumatoid arthritis. Clin Rheumatol 2004, 23:435–440.

    Article  PubMed  Google Scholar 

  33. Bas S, Kvien TK, Buchs N, et al.: Lower level of synovial fluid interferon-gamma in HLA-B27-positive than in HLA-B27-negative patients with Chlamydia trachomatis reactive arthritis. Rheumatology (Oxford) 2003, 42:461–467.

    Article  CAS  Google Scholar 

  34. Braun J, Yin Z, Spiller I, et al.: Low secretion of tumor necrosis factor alpha, but no other Th1 or Th2 cytokines, by peripheral blood mononuclear cells correlates with chronicity in reactive arthritis. Arthritis Rheum 1999, 42:2039–2044. Large prospective cohort analysis of the secretion of cytokines by peripheral blood mononuclear cells in patients with early ReA.

    Article  PubMed  CAS  Google Scholar 

  35. Appel H, Kuon W, Kuhne M, et al.: Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in chlamydia-triggered reactive arthritis. Arthritis Res Ther 2004, 6:R521-R534.

    Article  PubMed  CAS  Google Scholar 

  36. Popov I, Dela Cruz CS, Barber BH, et al.: Breakdown of CTL tolerance to self HLA-B*2705 induced by exposure to chlamydia trachomatis. J Immunol 2002, 169:4033–4038.

    PubMed  CAS  Google Scholar 

  37. Ramos M, Alvarez I, Sesma L, et al.: Molecular mimicry of an HLA-B27-derived ligand of arthritis-linked subtypes with chlamydial proteins. J Biol Chem 2002, 277:37573–37581.

    Article  PubMed  CAS  Google Scholar 

  38. Sinha R, Aggarwal A, Prasad K, Misra R: Sporadic enteric reactive arthritis and undifferentiated spondyloarthropathy: evidence for involvement of salmonella typhimurium. J Rheumatol 2003, 30:105–113.

    PubMed  Google Scholar 

  39. Meyer-Bahlburg A, Brinkhoff J, Krenn V, et al.: Infection of synovial fibroblasts in culture by yersinia enterocolitica and salmonella enterica serovar enteritidis: ultrastructural investigation with respect to the pathogenesis of reactive arthritis. Infect Immun 2001, 69:7915–7921.

    Article  PubMed  CAS  Google Scholar 

  40. Zhao YX, Lajoie G, Zhang H, et al.: Tumor necrosis factor receptor p55-deficient mice respond to acute yersinia enterocolitica infection with less apoptosis and more effective host resistance. Infect Immun 2000, 68:1243–1251.

    Article  PubMed  CAS  Google Scholar 

  41. Meyer-Bahlburg A, Greil S, Kruse N, et al.: Yersinia enterocolitica leads to transient induction of TNF-alpha and activates NF-kappaB in synovial fibroblasts. Clin Exp Rheumatol 2004, 22:278–284.

    PubMed  CAS  Google Scholar 

  42. Penttinen MA, Heiskanen KM, Mohapatra R, et al.: Enhanced intracellular replication of salmonella enteritidis in HLA-B27-expressing human monocytic cells: dependency on glutamic acid at position 45 in the B pocket of HLA-B27. Arthritis Rheum 2004, 50:2255–2263. Study showing that HLA-B27 expression modulates the host-microbe interaction resulting in an impaired capacity of monocytes to resist intracellular replication of S. enteritidis.

    Article  PubMed  CAS  Google Scholar 

  43. Hill Gaston JS, Lillicrap MS: Arthritis associated with enteric infection. Best Pract Res Clin Rheumatol 2003, 17:219–239.

    Article  Google Scholar 

  44. 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. Analysis of the long term outcome of patients with ReA treated with a 3 month course of ciprofloxacin or placebo in the acute phase.

    Article  PubMed  CAS  Google Scholar 

  45. Kvien TK, Gaston JS, Bardin T, et al.: Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study. Ann Rheum Dis 2004, 63:1113–1139.

    Article  PubMed  CAS  Google Scholar 

  46. Braun J, Sieper J: Biological therapies in the spondyloarthritides—the current state. Rheumatology (Oxford) 2004, 43:1072–1084. Review of the role of biologic agents in the treatment of spondyloarthropaties.

    Article  CAS  Google Scholar 

  47. Kaipiainen-Seppanen O, Niinisalo H, Korpilahde T, Virolainen J: Treatment of reactive arthritis with infliximab. Scand J Rheumatol 2003, 32:122–124.

    Article  Google Scholar 

  48. Gaylis N: Infliximab in the treatment of an HIV positive patient with Reiter’s syndrome. J Rheumatol 2003, 30:407–411.

    PubMed  Google Scholar 

  49. Espinola RG, Uknis A, Sainz IM, et al.: A monoclonal antibody to high-molecular weight kininogen is therapeutic in a rodent model of reactive arthritis. Am J Pathol 2004, 165:969–976. Study in the Lewis rat model that postulates the modulation of the plasma kallikrein-kinin system activation as a potential therapeutic target in ReA.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. LSU Medical Center, 1542 Tulane Ave., 70112, New Orleans, LA, USA

    Luis R. Espinoza MD

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  1. Ines Colmegna MD
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  2. Luis R. Espinoza MD
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Colmegna, I., Espinoza, L.R. Recent advances in reactive arthritis. Curr Rheumatol Rep 7, 201–207 (2005). https://doi.org/10.1007/s11926-996-0040-4

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