Skip to main content
Log in

Molekularpathologische Infektionsdiagnostik in der orthopädischen Pathologie

Molecular pathological diagnostics of infections in orthopedic pathology

  • Hauptreferate
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Die Infektionsdiagnostik bei Patienten mit Arthritis und/oder Gelenkprothesen erfordert eine interdisziplinäre Zusammenarbeit unter Einsatz modernster Methoden. Die histologische Untersuchung der Synovialmembran ermöglicht die Einteilung in akute, chronische und granulomatöse Synovialitiden. Die Anwendung der Polymerasekettenreaktion (PCR), welche auf die Detektion konservierter Regionen des mikrobiellen Genoms zielt, speziell 16S rRNA für Bakterien und 18S rRNA für Pilze, ist ein breiter Ansatz, um nichtkultivierbare Pathogene bei Infektionen schnell nachzuweisen. Infektiöse Arthritiden und periprothetische Infektionen teilen das Erregerspektrum mit der Sepsis. Deshalb können auch multiplex-PCR-basierte Sepsistests eingesetzt werden.

Die molekulare Diagnostik minimaler Infektionen in periprothetischen Geweben ist auch nach Antibiotikatherapie möglich. Reaktive Arthritiden können unter Kenntnis der Anamnese (enterale oder urogenitale Infektion), Klinik (Oligoarthritis) und weiterer Parameter (HLA-B27 etc.) von anderen Arthritiden abgegrenzt werden. Molekulare Methoden erlauben in zahlreichen Fällen den Nachweis der Erreger-DNA oder RNA in der Synovia/Synovialis. Die geringe Sensitivität histochemischer Verfahren bei der Differenzialdiagnose granulomatöser Synovialitiden kann durch die Anwendung der PCR kompensiert werden, speziell bei mykobakteriellen Infektionen. Molekulare Methoden in der Infektionsdiagnostik von Arthritiden können sowohl bei septischen als auch reaktiven Arthritiden eingesetzt werden. MicroRNA-Techniken kombiniert mit molekularer Keimdetektion können zur Unterscheidung der rheumatoiden Arthritis mit einer hohen entzündlichen Aktivität infektiöser Arthritiden beitragen. Proteomische Methoden könnten das Spektrum der molekularen Infektionsdiagnostik zukünftig ergänzen.

Abstract

The diagnosis of infections in patients with arthritis and/or in joint prostheses requires interdisciplinary cooperation and the application of up-to-date methods. The histological investigation of the synovial membrane allows the differentiation of acute, chronic and granulomatous synovialitis. Detection of conserved regions of the microbial genome by PCR, especially 16S rRNA for bacteria and 18S rRNA for fungi, is a broad approach for the classification of pathogens which cannot be cultured. Acute infectious arthritis and periprosthetic infections share the spectrum of pathogens with sepsis, therefore multiplex PCR-based methods for the detection of sepsis can be employed. Molecular diagnostics can detect minimal infections in periprosthetic tissues even after antibiotic therapy. The anamnesis (enteral or urogenital infection), clinical picture (oligoarthritis) and further parameters (e.g. HLA B27 status) are important for the diagnosis of reactive arthritis. In many cases of reactive arthritis, molecular methods allow the detection of bacterial DNA or RNA in synovial fluid or tissue samples. The low sensitivity of histopathological methods may be compensated by application of PCR techniques, especially in the differential diagnosis of granulomatous synovitis including mycobacterial infections. Molecular methods can be used to support the differential diagnosis of septic and reactive arthritis. MicroRNA techniques combined with PCR for detection of pathogens support the differential diagnosis of rheumatoid arthritis with severe inflammatory activity compared to infectious arthritis. Proteomic methods could expand the methodological spectrum for the diagnosis of infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581

    Article  PubMed  Google Scholar 

  2. Altman RD (1995) The classification of osteoarthritis. J Rheumatol Suppl 43:42–43

    CAS  PubMed  Google Scholar 

  3. Ammari M, Jorgensen C, Apparailly F (2013) Impact of microRNAs on the understanding and treatment of rheumatoid arthritis. Curr Opin Rheumatol 25:225–233

    Article  CAS  PubMed  Google Scholar 

  4. Birmingham P, Helm JM, Manner PA et al (2008) Simulated joint infection assessment by rapid detection of live bacteria with real-time reverse transcription polymerase chain reaction. J Bone Joint Surg [Am] 90:602–608

  5. Bowness P (2002) HLA B27 in health and disease: a double-edged sword? Rheumatology 41:857–868

    Article  CAS  PubMed  Google Scholar 

  6. Carter JD, Gerard HC, Whittum-Hudson JA et al (2012) The molecular basis for disease phenotype in chronic Chlamydia-induced arthritis. Int J Clin Rheumatol 7:627–640

    Article  CAS  Google Scholar 

  7. Casadonte R, Caprioli RM (2011) Proteomic analysis of formalin-fixed paraffin-embedded tissue by MALDI imaging mass spectrometry. Nat Protoc 6:1695–1709

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Cazanave C, Greenwood-Quaintance KE, Hanssen AD et al (2013) Rapid molecular microbiologic diagnosis of prosthetic joint infection. J Clin Microbiol 51:2280–2287

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Cazanave C, Greenwood-Quaintance KE, Hanssen AD et al (2012) Corynebacterium prosthetic joint infection. J Clin Microbiol 50:1518–1523

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Choe H, Inaba Y, Kobayashi N et al (2013) Use of real-time polymerase chain reaction for the diagnosis of infection and differentiation between gram-positive and gram-negative septic arthritis in children. J Pediatr Orthop 33:e28–e33

    Article  PubMed  Google Scholar 

  11. Chopra N, Kirschenbaum AE, Widman D (2002) Mycobacterium marinum tenosynovitis in a patient on etanercept therapy for rheumatoid arthritis. J Clin Rheumatol 8:265–268

    Article  PubMed  Google Scholar 

  12. Deanehan JK, Kimia AA, Tan Tanny SP et al (2013) Distinguishing Lyme from septic knee monoarthritis in Lyme disease-endemic areas. Pediatrics 131:e695–e701

    Article  PubMed  Google Scholar 

  13. Gallo J, Kolar M, Dendis M et al (2008) Culture and PCR analysis of joint fluid in the diagnosis of prosthetic joint infection. New Microbiol 31:97–104

    PubMed  Google Scholar 

  14. Gaubitz M, Dressler F, Huppertz HI et al (2014) Diagnosis and treatment of Lyme arthritis: recommendations of the pharmacotherapy commission of the Deutsche Gesellschaft fur Rheumatologie (German Society for Rheumatology). Z Rheumat 73:469–474

    Article  CAS  Google Scholar 

  15. Grif K, Heller I, Prodinger WM et al (2012) Improvement of detection of bacterial pathogens in normally sterile body sites with a focus on orthopedic samples by use of a commercial 16S rRNA broad-range PCR and sequence analysis. J Clin Microbiol 50:2250–2254

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Gupta MN, Sturrock RD, Field M (2003) Prospective comparative study of patients with culture proven and high suspicion of adult onset septic arthritis. Ann Rheum Dis 62:327–331

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Hamilton H, Jamieson J (2008) Deep infection in total hip arthroplasty. Can J Surg 51:111–117

    PubMed Central  PubMed  Google Scholar 

  18. Kostrzewa M, Sparbier K, Maier T et al (2013) MALDI-TOF MS: an upcoming tool for rapid detection of antibiotic resistance in microorganisms. Proteomics Clin Appl 7:767–778

    Article  CAS  PubMed  Google Scholar 

  19. Krenn V, Morawietz L, Konig B et al (2006) Low-grade-/high-grade-synovitis: synovitis-score as a gold standard? Orthopade 35:853–859

    Article  CAS  PubMed  Google Scholar 

  20. Kriegsmann J, Hopf T, Jacobs D et al (2009) Applications of molecular pathology in the diagnosis of joint infections. Orthopade 38:531–538

    Article  CAS  PubMed  Google Scholar 

  21. Kriegsmann M, Casadonte R, Randau T et al (2014) MALDI imaging of predictive ferritin, fibrinogen and proteases in haemophilic arthropathy. Haemophilia 20:446–453

    Article  CAS  PubMed  Google Scholar 

  22. Kriegsmann M, Seeley EH, Schwarting A et al (2012) MALDI MS imaging as a powerful tool for investigating synovial tissue. Scand J Rheumatol 41:305–309

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Levy O, Iyer S, Atoun E et al (2013) Propionibacterium acnes: an underestimated etiology in the pathogenesis of osteoarthritis? J Shoulder Elbow Surg 22:505–511

    Article  PubMed  Google Scholar 

  24. Lu MC, Yu CL, Chen HC et al (2014) Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased IGF-1 mediated IL-10 production. Clin Exp Immunol, in press

  25. Mathews CJ, Weston VC, Jones A et al (2010) Bacterial septic arthritis in adults. Lancet 375:846–855

    Article  PubMed  Google Scholar 

  26. Nocton JJ, Dressler F, Rutledge BJ et al (1994) Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 330:229–234

    Article  CAS  PubMed  Google Scholar 

  27. Peluso R, Di Minno MN, Iervolino S et al (2013) Enteropathic spondyloarthritis: from diagnosis to treatment. Clin Dev Immunol 2013:631408

    Article  PubMed Central  PubMed  Google Scholar 

  28. Rosey AL, Abachin E, Quesnes G et al (2007) Development of a broad-range 16S rDNA real-time PCR for the diagnosis of septic arthritis in children. J Microbiol Meth 68:88–93

    Article  CAS  Google Scholar 

  29. Smith JW, Chalupa P, Shabaz Hasan M (2006) Infectious arthritis: clinical features, laboratory findings and treatment. Clin Microbiol Infect 12:309–314

    Article  CAS  PubMed  Google Scholar 

  30. Tarkin IS, Henry TJ, Fey PI et al (2003) PCR rapidly detects methicillin-resistant staphylococci periprosthetic infection. Clin Orthop Relat Res 414:89–94

    Article  PubMed  Google Scholar 

  31. Townes JM (2010) Reactive arthritis after enteric infections in the United States: the problem of definition. Clin Infect Dis 50:247–254

    Article  PubMed  Google Scholar 

  32. Zeidler H, Hudson AP (2014) New insights into chlamydia and arthritis. Promise of a cure? Ann Rheum Dis 73:637–644

    Article  CAS  PubMed  Google Scholar 

  33. Zmistowski B, Della Valle C, Bauer TW et al (2014) Diagnosis of periprosthetic joint infection. J Orthop Res 32(Suppl 1):S98–S107

    Article  PubMed  Google Scholar 

Download references

Einhaltung ethischer Richtlinien

Interessenkonflikt. J. Kriegsmann und R. Casadonte weisen auf folgende Beziehung hin: Technische Unterstützung von Bruker Daltonik GmbH. N. Arens, C. Altmann, M. Kriegsmann, M. Otto geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Kriegsmann.

Additional information

The supplement this article is part of is not sponsored by the industry.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kriegsmann, J., Arens, N., Altmann, C. et al. Molekularpathologische Infektionsdiagnostik in der orthopädischen Pathologie. Pathologe 35 (Suppl 2), 225–231 (2014). https://doi.org/10.1007/s00292-014-1983-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-014-1983-2

Schlüsselwörter

Keywords

Navigation