title: Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection.
abstract: BACKGROUND
  During screening for latent tuberculosis infection (LTBI), before anti-tumor-necrosis-factor-α treatment, most patients are already receiving immunosuppressive therapy. The objective was to evaluate the performance of the QuantiFERON Gold In-Tube (QFT-IT) and the Tuberculin Skin Test (TST).
  
  
  METHODS
  A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohn's disease (54), rheumatoid arthritis (111), and spondylo-arthropathy (44).
  
  
  RESULTS
  QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54/238 (23%) patients. Chest x-ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had ≥1 risk-factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment. During prednisolone treatment interferon gamma (IFN-γ) response to mitogen stimulation was impaired (median IFN-γ response 4.9 IU/mL; interquartile range [IQR] 0.8 to ≥10.0) compared to patients 1) not receiving corticosteroids (median ≥10.0; IQR 5.0 to ≥10.0; P = 0.0015) or 2) receiving long-acting corticosteroids (median >10.0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1-0.8; P = 0.018), and with an increased risk of indeterminate QFT-IT results AOR 16.1 (4.1-63.2; P < 0.001), whereas no negative effect was found for long-acting corticosteroids. Doses of ≥10 mg prednisolone were associated with a 27% risk of indeterminate results. Single use of azathioprine, methotrexate, or 5-aminosalicylate (5-ASA) did not affect the test results.
  
  
  CONCLUSIONS
  Oral prednisolone severely suppressed QFT-IT and TST performance, whereas the long-acting corticosteroids methotrexate, azathioprine, and 5-ASA did not have a similar detrimental effect. Patients should be screened for LTBI with QFT-IT or TST prior to initiation of prednisolone therapy and negative QFT-IT or TST results interpreted with caution in patients treated with any corticosteroid until further data are available.
authors.affiliation: Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Erika
authors.initials: E
authors.lastname: Bélard
authors.forename: Synne
authors.initials: S
authors.lastname: Semb
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Werlinrud
authors.forename: Bolette
authors.initials: B
authors.lastname: Soborg
authors.forename: Frank Krieger
authors.initials: FK
authors.lastname: Jensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Thomsen
authors.forename: Annette
authors.initials: A
authors.lastname: Brylov
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.forename: Inge
authors.initials: I
authors.lastname: Nordgaard-Lassen
authors.forename: Pernille
authors.initials: P
authors.lastname: Ravn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D055985:Latent Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000494:pharmacology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014374:Tuberculin Test / Q000295:instrumentation* / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D006046:Gold; D007371:Interferon-gamma; D011239:Prednisolone