Sepsis of a prosthetic joint and biological therapies

M. Fernández-Castro, J. L. Andreu, P. Muñoz and L. Silva

Department of Rheumatology, Hospital Universitario Puerta de Hierro, Madrid, Spain

Correspondence to: J. L. Andreu, Department of Rheumatology, Hospital Universitario Puerta de Hierro, C/ San Martín de Porres 4, 28035 Madrid, Spain. E-mail: jlandreu{at}arrakis.es

SIR, We read with interest the article of Ledingham and Deighton [1] updating the guidelines for prescribing TNF-{alpha} blockers in adults with rheumatoid arthritis. The guidelines establish that the sepsis of a prosthetic joint that remains in situ is an important exclusion criterion for anti-TNF therapy. As the authors admit in the article, this exclusion criterion is based on opinion, but there is no good evidence.

We report here a case of a 59-yr-old woman with long-lasting, severe, erosive and seropositive rheumatoid arthritis. Despite treatment with several DMARDs, including parenteral gold, methotrexate (up to 20 mg/week), chloroquine, sulphasalazine and cyclosporin, the disease remained active and structural damage progressed. A prosthetic joint was implanted in the right knee in August 2001. In November 2001, she was diagnosed with sepsis of the prosthetic joint, with penicillin-sensitive Staphylococcus aureus isolated from synovial fluid culture. She was treated with intravenous cefazolin for 3 weeks and extensive surgical debridement, without removing the prosthetic joint. An oral 6-month course of ciprofloxacin and rifampicin was completed.

In February 2002, despite the treatment with leflunomide, celecoxib and low-dose prednisone, the disease remained active, with a Disease Activity Score (DAS) of 7.28. After an in-depth discussion about the risk of reactivation of the sepsis of the prosthetic joint, the patient accepted the treatment with infliximab. Three years later, the activity of rheumatoid arthritis is well controlled with 3 mg/kg every 8 weeks of infliximab and 5 mg/day of prednisone, the DAS score being 2.70. The right knee is asymptomatic and gallium scintillography is not suggestive of infection (Fig. 1).



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FIG. 1. Gallium scintillography fails to show any data suggestive of periprosthetic infection.

 
The risk of severe infections appears to be increased by the use of biological therapies [2]. Therefore, clinicians should maximize caution, especially with respect to intracellular agents or infections in which the formation of granuloma is an essential mechanism of defence, including tuberculosis [3, 4], histoplasmosis [5], coccidiomycosis [6] and listeriosis [7].

The decision to treat this patient with infliximab was difficult, due to the high risk of reactivation of a putative latent infection in the prosthetic joint, since the synthetic material was not removed. On the other hand, the high activity of the disease, despite aggressive treatment with non-biological agents, required additional therapeutic options. We think that more information about the true risk of reactivation of a latent infection in the prosthetic material with anti-TNF therapy is essential. A formal exclusion criteria based on opinion and not on evidence will hinder the acquisition of robust data from randomized trials or well-designed observational studies. We think that the use of anti-TNF agents in these cases should be tailored, and that an in-depth discussion with the patient about the risks and benefits of anti-TNF therapy is essential.

The authors have declared no conflicts of interest.

References

  1. Ledingham J, Deighton C on behalf of the British Society for Rheumatology Standards, Guidelines and Audit Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNF{alpha} blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology 2005;44:157–63.[Free Full Text]
  2. Ellerin T, Rubin RH, Weinblatt ME. Infections and anti-tumor necrosis factor {alpha} therapy. Arthritis Rheum 2003;48:3013–22.[CrossRef][ISI][Medline]
  3. Keane J, Gershon S, Wise R et al. Tuberculosis associated with infliximab, a tumor necrosis factor {alpha}-neutralizing agent. N Engl J Med 2001;345:1098–104.[Abstract/Free Full Text]
  4. Gomez-Reino JJ, Carmona L, Rodríguez-Valverde V, Mola EM, Montero MD; BIOBADASER Group. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 2003;48:2122–7.[CrossRef][ISI][Medline]
  5. Lee J, Slifman N, Gershon S, Edwards E et al. Life-theatening histoplasmosis complicating immunotherapy with tumor necrosis factor antagonists infliximab and etanercept. Arthritis Rheum 2002;46:2565–70.[CrossRef][ISI][Medline]
  6. Bergstrom L, Yocum DE, Ampel NM et al. Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 2004;50:1959–66.[CrossRef][ISI][Medline]
  7. Slifman NR, Gershon SK, Lee JH, Edwards ET, Braun MM. Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents. Arthritis Rheum 2003;48:319–24.[CrossRef][ISI][Medline]
Accepted 18 March 2005





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