What are the next steps after a positive Tuberculin (TB) titer?

Management of Positive Tuberculin (TB) Titer

After a positive tuberculin skin test (TST), patients should undergo chest radiography and clinical evaluation to rule out active TB disease, followed by treatment for latent TB infection if active disease is excluded.

Initial Evaluation After Positive TST

• All individuals with a positive TST result (≥5 mm induration) should undergo chest radiography and clinical evaluation to exclude active TB disease 1
• Patients with symptoms suggestive of TB should promptly undergo chest radiography and clinical evaluation regardless of their TST status 1
• Collection of specimens for mycobacteriologic testing (e.g., sputum) should be considered on a case-by-case basis and is not routinely recommended for healthy contacts with normal chest radiographs 1

Interpretation of Positive TST Results

• A positive TST is defined as ≥5 mm induration for:
  • HIV-infected persons
  • Recent contacts of TB cases
  • Persons with fibrotic changes on chest radiograph
  • Patients with organ transplants or immunosuppression 1, 2
• A positive TST is defined as ≥10 mm induration for:
  • Recent immigrants from high-prevalence countries
  • Injection drug users
  • Residents of high-risk congregate settings
  • Persons with certain medical conditions (diabetes, silicosis, end-stage renal disease) 3
• A positive TST is defined as ≥15 mm induration for persons with no known risk factors 3

Treatment for Latent TB Infection

• All HIV-infected persons with a positive TST but no evidence of active TB should receive treatment for latent TB infection 1
• Treatment options for latent TB infection include:
  • Isoniazid daily or twice weekly for 9 months (preferred regimen) 1, 3
  • Rifampin daily for 4 months 1, 4
  • Rifabutin daily for 4 months (alternative when rifampin cannot be used) 1
  • Rifampin and pyrazinamide daily for 2 months (caution due to hepatotoxicity risk) 1

Special Considerations for Specific Populations

Immunocompromised Patients

• Patients on immunosuppressive therapy (including biologics) should receive treatment for latent TB infection before continuing or initiating biologic therapy 1, 2
• Treatment with biologics can be resumed after 1 month of latent TB treatment 2
• Annual TB screening should be considered for patients with ongoing risk factors for TB exposure 1, 2

Children Under 5 Years

• Children under 5 years are more susceptible to TB disease and more vulnerable to invasive, fatal forms of TB 1
• All children under 5 years with positive TST should receive a full diagnostic medical evaluation, including chest radiography 1

Close Contacts of TB Cases

• Close contacts of persons with infectious TB should be treated for latent TB infection, regardless of their TST results, after active TB has been excluded 1
• For contacts exposed to drug-resistant TB, treatment decisions should be made in consultation with public health authorities 1

Monitoring During Treatment

• Patients receiving isoniazid should also receive pyridoxine (vitamin B6) to prevent peripheral neuropathy, especially HIV-infected persons 1
• Directly observed therapy should be used with intermittent dosing regimens and when otherwise operationally feasible 1
• Liver function tests should be monitored every 2-4 weeks during treatment 1
• Patients should be educated about symptoms of hepatotoxicity (nausea, vomiting, jaundice) 1, 5

Common Pitfalls and Considerations

• False-negative TST results can occur in immunocompromised individuals, so clinical judgment is important 6
• Interferon-gamma release assays (IGRAs) like QuantiFERON-TB Gold and T-SPOT.TB may be preferred over TST in BCG-vaccinated populations due to higher specificity 1, 7
• The positive predictive value of TST for development of active TB is generally poor, while the negative predictive value is high 1, 8
• Clinical presentation of TB disease can differ according to TST result, with negative TST more likely associated with disseminated disease 9

By following this systematic approach to managing patients with positive TB titers, clinicians can effectively identify and treat latent TB infection, preventing progression to active disease and reducing TB transmission in the community.