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Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease

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Zsuzsanna Kurti1, Barbara Dorottya Lovasz1, Krisztina Barbara Gecse1, Anita Balint2, Klaudia Farkas2, Agnes Morocza-Szabo1, Andras Gyurcsanyi1, Katalin Kristof3, Zsuzsanna Vegh1,4, Lorant Gonczi1, Lajos Sandor Kiss1, Petra Anna Golovics1, Laszlo Lakatos4, Tamas Molnar2, Peter Laszlo Lakatos1

1) 1st Department of Medicine, Semmelweis University, Budapest,
2) 1st Department of Medicine, Szeged University, Szeged,
3) Institute of Medical Microbiology, Semmelweis University, Budapest,
4) Department of Medicine, Csolnoky F. Province Hospital, Veszprem, Hungary

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.244.bcg

Background & Aims: There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort.

Methods: 166 consecutive moderate-to-severe IBD patients (122 Crohn’s disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed.

Results: TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p<0.001). In addition, a cut-off of 14 and 17mm for TST was defined to identify IGRA positivity in a ROC analysis (AUC: 0.76, p=0.03). TST and/or IGRA positivity was not influenced by medical therapy or disease phenotype. Importantly, smoking was identified as a risk factor for TST but not IGRA positivity (OR: 2.70-5.02, p<0.01, for TSTcut-offs=5-20mm).

Conclusion: TST and IGRA tests are partly complimentary methods, and additional testing by TST (with a cut-off of >15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

Key words: IBD – tuberculosis – tuberculin skin test – interferon gamma release assay test – immunosuppressive – biological treatment.

Abbreviations: AZA: azathioprine; BCG: Bacille Calmette-Guérin; CD: Crohn’s disease; CRP: C-reactive protein; HBI: Harvey–Bradshaw Index; IBD: inflammatory bowel diseases; IGRA: interferon-gamma release assay; IST: immunosuppressive therapy; LTB: latent tuberculosis; UC: ulcerative colitis; TB: tuberculosis; TNF: tumor necrosis factor; TST: tuberculin skin test/ Mantoux skin test