Variability in the intradermal and in vitro lymphocyte responses to PPD in patients receiving isoniazid chemoprophylaxis.

Much attention has been focused on problems related to the interpretation of the tuberculin (Tb) skin test in terms of the "booster" phenomenon observed with repeated skin testing. However, relatively little attention has been given to the problem of the interpretation of repeat Tb skin tests in patients who have been given isoniazid (INH) chemoprophylaxis. Sixteen female hospital workers who were receiving INH for asymptomatic recent conversion of their Tb skin test, and 1 male physician under treatment with INH and rifampin for active tuberculosis as a result of a patient exposure, were studied over a 1-yr period. Intradermal skin tests with 5 tuberculin units purified protein derivative (PPD) and assessment of in vitro lymphocyte proliferation and production of leukocyte inhibitory factor on exposure to PPD were performed on 4 occasions at 3-month intervals-3 during therapy and 1 after completion of therapy. Four of 10 patients tested on all occasions showed at least 1 negative Tb skin test. In 2 of 4, the reversions were not stable. Considerable variability was observed between results of skin tests and in vitro lymphocyte responses, and no one in vitro lymphocyte response to PPD was adequate to identify the presence of delayed hypersensitivity to PPD. On the basis of these data, it is concluded that the presence of a single negative PPD skin test during or shortly after the completion of INH chemoprophylaxis does not constitute sufficient evidence to conclude that a patient has had a stable skin test reversion. Confirmation of the loss of tuberculin reactivity requires the in vitro assessment of lymphocyte responses to PPD both in terms of proliferation and the production of a lymphokine(s).