Rheumatology Advance Access originally published online on June 12, 2006
Rheumatology 2006 45(8):1049-1050; doi:10.1093/rheumatology/kel196
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LETTER TO THE EDITOR |
Detection of tuberculosis by extensive screening in a patient with rheumatoid arthritis prior to anti-TNF-
therapy
Departments of Rheumatology, Kantonsspital Aarau, Aarau, 1 The Division of Infectious Diseases & Hospital Epidemiology and 2 The Department of Rheumatology, University Hospital Basel, Basel, Switzerland
Correspondence to: Paul Hasler, MD, Rheumaklinik, Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland. E-mail: paul.hasler{at}ksa.ch
SIR, TNF-
blocking agents have seen increasing use in the treatment of systemic inflammatory diseases such as rheumatoid arthritis (RA). An association of anti-TNF- agents with the occurrence of mycobacterial infections (MTBI), with a high proportion of extrapulmonary and disseminated cases, has been noted [1, 2]. The article by Horsburgh [3] highlights the public health consequences of MTBI in the setting of anti-TNF- therapy. It is recommended to exclude MTBI before anti-TNF- therapy and to give prophylactic isoniazid (INH) if latent MTBI (LMTBI) is suspected [4]. The use of INH in patients >50 yrs is associated with a considerable mortality of 2.3% [5]. In addition, the effectiveness of prophylactic INH therapy is in the range of 25–92%, depending on underlying disease, compliance and type of study [6]. Therefore, we decided to implement a more stringent pre-treatment screening protocol. This encompasses conventional radiographs of the chest in two planes and, if results were questionable, a CT scan. The tuberculin skin test (TST) was performed with two IU injected intracutaneously according to the standard procedure in Switzerland. A reading was taken 48–72 h later, an induration of 
5 mm was considered positive. If negative, the TST was repeated after 7–10 days, with identical criteria applied for reading. If the TST was positive, and/or imaging of the chest suspicious, bronchosopy with lavage and brushings for cultures and nucleic acid amplification tests (NAAT) for mycobacteria, and cultures and NAAT of the urine were performed.
From September 2002 until July 2004, 17 patients with the indication for anti-TNF- therapy were screened according to this procedure. Six had further examinations, of which three were based on the chest radiograph and three on a positive TST. Among the latter, the following case of LMTBI was detected.
A 76-year-old woman with RA of 14 years duration, who had persistent erosive disease despite various disease-modifying anti-rheumatic drugs (DMARDs), qualified for anti-TNF- treatment. Apart from her age, and the use of DMARDs and low-dose glucocorticosteroids, there were no apparent risk factors for tuberculosis, and clinical signs of an acute or chronic infection were absent. The chest X-ray (Fig. 1) showed no evidence of MTBI, but the TST provoked an induration of 10 mm in diameter. Bronchoscopy was unremarkable and fluorescence microscopy of the specimens and of the urine for mycobacteria were negative. However, cultures and NAATs (Cobas Amplicore MTB) of the tracheobronchial lavage and of the urine identified Mycobacterium africanum, which was sensitive to rifampicin (RIF), INH, ethambutol (ETB) and pyrazinamide (PZA). Possible active foci in the chest and abdomen could not be detected by a CT scan of the chest and abdominal ultrasonography. A tuberculostatic regimen with INH 50 mg, PZA 300 mg and RIF 120 mg daily for 2 months followed by INH 100 mg and RIF 150 mg daily for 7 months was given under continued weekly methotrexate and daily low-dose prednisone. Culture and PCR for mycobacteria in the urine turned negative.
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This case raises several questions relating to anti-TNF-
therapy. First, how adequate are the current recommendations for the detection of LMTBI? Second, how appropriate is prophylactic INH to prevent the possible activation of LMTBI under anti-TNF- therapy? Third, what is the cost–benefit ratio of INH prophylaxis in view of potential toxicity and drug resistance? Fourth, are there any differences between the available anti-TNF- agents? Fifth, will the introduction of T-cell stimulation test with MTB peptides improve the screening procedure for LMTBI [7, 8]? The answers will establish whether more extensive procedures to exclude LMTBI before anti-TNF- therapy and treatment as necessary are superior to prophylactic INH, with the exposure of patients not needing it, and the potential drawback of resistance. Until these questions are resolved, astute clinical assessment under consideration of the recommendations of national professional societies must guide the handling of this issue. The authors have declared no conflicts of interest.
References
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