title: Comparison of a commercial interferon-gamma release assay and tuberculin skin test for the detection of latent tuberculosis infection in Hong Kong arthritis patients who are candidates for biologic agents.
abstract: BACKGROUND
  It is universally agreed that screening for latent tuberculosis infection prior to biologic therapy is necessary, especially in endemic areas such as Hong Kong. There are still, however, controversies regarding how best to accomplish this task. The tuberculin skin test has been the routine screening tool for latent tuberculosis infection in Hong Kong for the past decade although accuracy is far from perfect, especially in patients who have been vaccinated with Bacillus Calmette-Guérin, who are immunocompromised, or who have atypical mycobacterium infection. The new interferon-gamma release assays have been shown to improve specificity and probably sensitivity. This study aimed to evaluate agreement between the interferon-gamma release assay and the tuberculin skin test in the diagnosis of latent tuberculosis infection in patients with arthritic diseases scheduled to receive biologic agents.
  
  
  METHODS
  We reviewed 38 patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis at a local hospital in Hong Kong from August 2013 to April 2014. They were all considered candidates for biologic agents. The patients underwent both the interferon-gamma release assay (ASACIR.TB; A.TB) and the tuberculin skin test simultaneously. Concurrent medications were documented. Patients who tested positive for either test (ie A.TB+ or TST+) were prescribed treatment for latent tuberculosis if they were to be given biologic agents. All patients were followed up regularly for 1 year and the development of active tuberculosis infection was evaluated.
  
  
  RESULTS
  Based on an induration of 10 mm in diameter as the cut-off value, 13 (34.2%) of 38 patients had a positive tuberculin skin test. Of the 38 patients, 11 (28.9%) also had a positive interferon-gamma release assay. The agreement between interferon-gamma release assay and tuberculin skin test was 73.7% (kappa=0.39). Six patients were TST+/A.TB- and four were TST-/A.TB+. When positive tuberculin skin test was defined as an induration of 5-mm diameter, the agreement between the two tests improved with a kappa value of 0.47. In that case, half of the patients had a positive tuberculin skin test; among them, nine were TST+/A.TB-. Only one was TST-/A.TB+. Subgroup analysis showed that the agreement between both tests improved further (kappa=0.69) in patients not taking a concurrent systemic steroid. For patients prescribed systemic steroid, the agreement was only slight with a kappa value of 0.066. Finally, none of the 38 patients, of whom 32 had an exposure to biologic agents, developed active tuberculosis during the 1-year follow-up period.
  
  
  CONCLUSIONS
  In a tuberculosis-endemic population, although 10-mm diameter induration is the usual cut-off for a positive tuberculin skin test, the level of agreement between the interferon-gamma release assay and tuberculin skin test improved from fair to moderate when the cut-off was lowered to 5 mm. A dual testing strategy of tuberculin skin test and interferon-gamma release assays appeared to be effective and should be pursued especially in patients who are on systemic steroid therapy. Nonetheless, the issue of potential overtreatment is yet to be evaluated.
authors.affiliation: Department of Medicine and Geriatrics, Kwong Wah Hospital, Yaumatei, Hong Kong.
authors.forename: H
authors.initials: H
authors.lastname: So
authors.affiliation: Department of Medicine and Geriatrics, Kwong Wah Hospital, Yaumatei, Hong Kong.
authors.forename: C Sw
authors.initials: CS
authors.lastname: Yuen
authors.affiliation: Department of Medicine and Geriatrics, Kwong Wah Hospital, Yaumatei, Hong Kong.
authors.forename: R Ml
authors.initials: RM
authors.lastname: Yip
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001685:Biological Factors / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006723:Hong Kong; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013167:Spondylitis, Ankylosing / Q000188:drug therapy; D014374:Tuberculin Test / Q000379:methods*
chemical_list: D001685:Biological Factors
keywords: Arthritis, rheumatoid; Biological products; Interferon-gamma release tests; Latent tuberculosis; Tuberculin test