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• LTBI, hepatotoxicity and the anti TNF patient
  Dean D Creer
  Published on: 14 November 2005

• Published on: 14 November 2005

  LTBI, hepatotoxicity and the anti TNF patient

  • Dean D Creer, Consultant Physician
  • Other Contributors:
    • Devish J Dhasmana, Julian Nash, Jane C Bradley

  Dear Editor

  We read with interest the letter by Provenzano et al (1) on TB screening and anti-TNF treatment and wish to comment on this highly topical subject.

  Latent TB infection (LTBI) was diagnosed in 24.6% of the 69 rheumatological patients undergoing evaluation for anti-TNF treatment (n=17) of which 6 received anti-TNF therapy and TB chemoprophylaxis. The ethnicity and place of birth was not commen...

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  Dear Editor

  We read with interest the letter by Provenzano et al (1) on TB screening and anti-TNF treatment and wish to comment on this highly topical subject.

  Latent TB infection (LTBI) was diagnosed in 24.6% of the 69 rheumatological patients undergoing evaluation for anti-TNF treatment (n=17) of which 6 received anti-TNF therapy and TB chemoprophylaxis. The ethnicity and place of birth was not commented on which may have had some bearing on this apparently high incidence of LTBI. Previous BCG vaccination was not reported in the cohort, particularly those (8.7%) with a positive Mantoux test, which could give rise to false positive results. Prior to Mantoux testing steroids were stopped (for one week) but no comment is made regarding other immunosuppressive therapies which might interfere with the accuracy of tuberculin skin testing (2) and would account for the poor sensitivity of the Mantoux test in this cohort (sensitivity 35%). It is also unclear whether the two patients with a previous history of TB had received appropriate treatment at the time of initial diagnosis or whether they were subsequently included in the six patients who received chemoprophylaxis. Recent BTS guidelines recommend that previously adequately treated patients are monitored rather than receive chemoprophylaxis (2). Four of the six patients who received isoniazid chemoprophylaxis were required to stop the drug due to hepatotoxicity. The authors did not comment on whether these patients had abnormal liver function tests prior to receiving isoniazid nor on the degree of hepatotoxicity required to discontinue isoniazid.

  Our experience is with similarly small numbers. Nine out of 50 (18%) rheumatological patients screened for anti-TNF treatment were referred to our TB clinic after they were found to have either risk factors for TB (ethnicity and place of birth, n=7), positive TB skin tests after recent TB exposure (n=1) a history of previous adequately treated TB (n=1). Our patients had a mean age of 55, identical to that reported by the authors although they did not report whether the mean age of those receiving isoniazid was similar to that of the entire cohort. All nine of our patients were on immunosuppressive therapy including steroid therapy at the time of screening, one of which had abnormal liver function tests thought to be secondary to methotrexate. TB chemoprophylaxis has been deferred in the patient with abnormal liver function whilst Methotrexate has been withdrawn awaiting normalisation of the liver function tests. Six patients with normal liver function tests patients have commenced six months isoniazid chemoprophylaxis prior to anti-TNF treatment after a risk assessment according to BTS guidelines. One patient with rheumatoid arthritis on hydroxychloroquine and prednisolone developed an isolated raised ALT (>200) with no symptoms and discontinued isoniazid in accordance with previously published recommendations (3).

  Whilst these numbers are small they suggest the high level of hepatotoxicity reported by Provenzano et al is not universal. We agree that the additive effects of concurrent therapy for active rheumatological disease and rheumatological disease per se might increase the rates of liver toxicity in patients treated with TB chemoprophylaxis. We suggest that further studies are needed in this patient population to assess whether the incidence of significant hepatotoxicity related to TB chemoprophylaxis is associated with identifiable risk factors such as age, ethnicity, co-morbidity or medications such as immunosuppressive therapy. In addition further research is required to determine the value of interferon-g assays for the diagnosis of LTBI in this patient population given the limitations of TB skin tests and risk assessments.

  References 1 Provenzano G, Ferrante MC, Simon G. TB screening and anti-TNFa treatment. Thorax 2005;60:613.

  2 British Thoracic Society Standards of Care Committee. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-a treatment. Thorax 2005;60:800-15.

  3 Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998 Thorax 1998;53:536-45.

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  Conflict of Interest:
  None declared.

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