What is the recommended management for a 38-year-old female with a positive Tuberculin (TB) skin test and a negative Chest X-ray (CXR), who has a history of Bacillus Calmette-Guérin (BCG) vaccination?

Management of Latent Tuberculosis Infection in a BCG-Vaccinated Adult

A 38-year-old female with a positive TB skin test, negative chest X-ray, and history of BCG vaccination should be offered treatment for latent tuberculosis infection (LTBI) if she has additional risk factors for TB or if her skin test induration is ≥15mm. 1, 2

Diagnostic Interpretation

Interpreting the Positive TB Skin Test in BCG-Vaccinated Individuals

• BCG vaccination can cause false-positive tuberculin skin test (TST) results, but this does not contraindicate TST testing 1
• No reliable method exists to distinguish between TB reactions caused by BCG vaccination versus natural M. tuberculosis infection 1
• A positive TST in a BCG-vaccinated person should be considered indicative of TB infection when:
  • The person has risk factors for recent TB infection
  • The person has medical conditions that increase risk for TB disease
  • The TST induration is large (≥15mm) 1, 3

Risk Assessment Algorithm

1. Determine induration size threshold for positivity:

   • ≥5mm: HIV-infected persons, recent TB contacts, persons with fibrotic changes on CXR, immunosuppressed patients
   • ≥10mm: Recent immigrants from high-prevalence countries, injection drug users, residents of congregate settings, persons with certain medical conditions
   • ≥15mm: Persons with no known risk factors 4, 2

2. Consider additional factors that increase likelihood of true LTBI:

   • Birth in a high TB-prevalence country
   • Recent arrival to the US
   • Larger TST induration size (≥16mm)
   • Abnormal chest radiograph even if not active TB 3

Management Approach

For Patients with Likely True LTBI:

• Offer treatment with one of the following regimens:
  • Isoniazid 300mg daily for 9 months (standard regimen) 4, 2
  • Rifampin 600mg daily for 4 months (alternative regimen) 4
  • Isoniazid plus rifampin for 3-4 months 4

For Patients with Low Likelihood of True LTBI:

• Consider IGRA testing (QuantiFERON-TB Gold) as a confirmatory test 1
• IGRAs have higher specificity in BCG-vaccinated individuals 5, 6
• A two-step procedure (TST followed by IGRA) is recommended for BCG-vaccinated persons with positive TST 5
• Only 30% of BCG-vaccinated adults with positive TST will have a positive IGRA result 3

Monitoring and Follow-up

• If treatment is initiated:

  • Monitor for hepatotoxicity with liver function tests every 2-4 weeks 4
  • Educate patient about symptoms of hepatotoxicity
  • Complete the full course of therapy for maximum effectiveness 4

• If treatment is deferred:

  • Document the decision-making process
  • Educate patient about TB symptoms
  • No routine follow-up chest X-rays needed for asymptomatic patients with negative initial chest X-ray 4

Important Considerations

• Active TB must be ruled out before starting LTBI treatment 1, 2
• The negative chest X-ray in this case helps exclude active pulmonary TB 1
• Single-drug treatment is appropriate for LTBI but inadequate for active TB 2
• The risk of hepatotoxicity increases with age, pre-existing liver disease, and alcohol use 4
• Patients should be educated about symptoms of active TB and when to seek medical attention 4

Special Circumstances

• If the patient has fibrotic lesions on chest X-ray consistent with healed TB, a longer treatment duration (12 months of isoniazid or 4 months of isoniazid plus rifampin) is recommended 2
• For patients who will be starting immunosuppressive therapy (especially anti-TNF agents), LTBI treatment should be initiated at least 3 weeks before starting immunosuppression 1