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Internal Medicine

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A 45-year-old married physician has been out of the work force for 15 years since her residency in New York City, while she raised her three children.

She is returning now to patient care.

She has Marfan syndrome, and is on warfarin anticoagulation for a mechanical aortic valve and prosthetic aortic graft. At her hospital orientation, she is found to have 12 mm of induration around her PPD (purified protein derivative) intradermal skin test at 48 hours after placement of the test.

Her chest X-ray is negative. She is asymptomatic.

Her last PPD when she was a resident was negative but since then she has volunteered as a care provider at a homeless shelter that serves a clientele of undocumented individuals many of whom are from Latin America. 


You should advise her to:

  • Repeat the PPD skin test in 1 to 3 weeks

  • Take a 6-month self-directed course of isoniazid

  • Take a 12-week course of weekly isoniazid and rifapentine

  • Perform an interferon-γ release assay

@Everyone


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This physician has obviously had potential exposures since her last PPD. Epidemiologically, she could have been infected with M. tuberculosis by one of her clients at the shelter.


There two major issues here: 1) is the patient really latently infected; 2) is a rifapentine containing preventive regimen the best option for this patient? The use of directly observed therapy (DOT) is also an issue, but is more controversial.

Tuberculosis skin tests are read at 48-72 hours; so, a 48-hour interval is acceptable. Tests may be repeated in 1-3 weeks if initially negative, to look for the "booster" phenomenon (an amnesic response), but this test is already positive and therefore does not need re-testing. Treating an individual for a positive PPD skin test is done based on the likelihood that the test represents latent tuberculosis infection.


If present, latent tuberculosis has about a 2-5% of reactivating during the individual's lifetime. The likelihood of a positive test representing latent disease is based on the amount of induration and pre-test probability of infection. In this case - a physician with plausible patient exposure -10 or more mm of induration would be considered a positive reaction.

Then the question is the appropriate preventive regimen; 6 months of isoniazid, unless there is concern for drug resistance based on exposure history, will reduce the risk of reactivation of tuberculosis by more than 90%.


Three months of daily isoniazid plus rifampin, or 12 weeks of once-weekly isoniazid plus rifapentine, or 4 months of daily rifampin are listed as preferred regimens in current US guidelines. However, and especially for this patient, rifapentine and rifampin have numerous drug interactions (warfarin, certain antidepressants, certain antihypertensives, oral contraceptives, methadone, etc.) and would be a poor choice for someone relying on warfarin for anticoagulation in the setting of a mechanical heart valve.

In some hospitals, when prior BCG vaccination is likely, employees would be screened with an interferon-gamma release assay. The Quantiferon assays and T-SPOT assay have encountered problems of false positives in hospital screening in the United States, but the same could be said of tuberculin skin tests.

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