What is the recommended management for a patient with a positive tuberculosis (TB) skin test, particularly those with compromised immune systems, such as human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) or those taking immunosuppressive medications?

Management of Positive Tuberculosis Skin Test

All patients with a positive tuberculin skin test must immediately undergo chest radiography to exclude active TB disease, followed by treatment for latent TB infection (LTBI) with a rifamycin-based short-course regimen unless contraindications exist. 1, 2

Step 1: Immediate Evaluation to Exclude Active TB Disease

Obtain a chest radiograph immediately for all persons with a positive tuberculin skin test, regardless of symptoms. 1, 3

• Assess for TB symptoms including cough, hemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, and fatigue 1
• If chest X-ray shows abnormalities (upper lobe infiltration, cavitation, patchy or nodular infiltrates) or symptoms are present, obtain three consecutive sputum samples for AFB smear and culture before initiating treatment 3
• Active TB disease must be ruled out through history, physical examination, chest radiography, and bacteriologic studies when indicated before starting LTBI treatment 2

Step 2: Interpret the Positive Test Based on Risk Category

The definition of "positive" depends on the patient's risk factors:

• ≥5 mm induration is positive for: HIV-infected persons, recent TB contacts, immunosuppressed patients (including those on corticosteroids or other immunosuppressive medications), and persons with chest radiographs showing fibrotic lesions suggestive of old TB 1, 4
• ≥10 mm induration is positive for: recent immigrants from high-prevalence countries, injection drug users, residents of congregate settings, healthcare workers, persons with diabetes mellitus, silicosis, end-stage renal disease, or hematologic malignancies 1, 4
• ≥15 mm induration is positive for: persons with no known risk factors 3

Step 3: Select Treatment Regimen for Latent TB Infection

For HIV-Negative Patients:

First-line preferred regimens:

• 3 months of once-weekly rifapentine plus isoniazid (3HP) is the preferred regimen, with highest adherence rates and equivalent efficacy to 9 months of isoniazid but with less hepatotoxicity 1, 2
• 4 months of daily rifampin (4R) is a strongly recommended alternative with clinically equivalent effectiveness and lower toxicity 1, 2

Alternative regimen:

• 9 months of daily isoniazid (9H) when rifamycin-based regimens are contraindicated, with 60-90% protective efficacy if completed 2

For HIV-Infected and Immunosuppressed Patients:

HIV-infected persons require special consideration:

• 3HP regimen is equally effective in HIV-positive and HIV-negative persons and is preferred 2
• If isoniazid is chosen, 9 months (not 6 months) is required for HIV-infected persons 5, 2
• HIV-infected persons should receive a minimum of 12 months of therapy if using isoniazid 4
• Candidates with fibrotic pulmonary lesions or pulmonary silicosis should receive 12 months of isoniazid or 4 months of isoniazid and rifampin concomitantly 4

For Pregnant Women:

• Treatment should not be delayed based on pregnancy alone for women at high risk (HIV-infected or recently infected), even in the first trimester 2
• Isoniazid (9 or 6 months) is recommended for HIV-negative pregnant women 2
• Rifampin is not recommended during pregnancy 2
• Chest radiographs with appropriate shielding should be obtained as soon as feasible, even during the first trimester 3

For Children:

• 9 months of isoniazid is the only recommended regimen for children, though short-course rifampin-based regimens appear superior 5, 2
• Children younger than 5 years should have both posterior-anterior and lateral chest radiographs 3

Step 4: Monitor During Treatment

Baseline and ongoing monitoring:

• Obtain baseline liver function tests for patients with suspected liver disorders, HIV infection, pregnancy or immediate postpartum period, or chronic conditions increasing liver disease risk 2
• Administer pyridoxine (vitamin B6) with all isoniazid-containing regimens to prevent peripheral neuropathy, especially in HIV-infected persons, pregnant women, diabetics, and alcoholics 1
• Conduct monthly clinical evaluations for all patients on isoniazid or rifampin monotherapy, assessing for hepatitis symptoms 2, 6
• For patients on rifampin plus pyrazinamide regimens, evaluate at 2,4, and 8 weeks 2
• Discontinue treatment immediately if evidence of liver injury occurs 2

Step 5: Special Circumstances for High-Risk Contacts

Primary prophylaxis for high-risk contacts with initial negative test:

• Children <5 years and HIV-infected persons exposed to infectious TB should receive immediate treatment even with negative initial skin test, after active TB is ruled out 5, 1
• Repeat tuberculin skin test 8-12 weeks after last exposure 5
• If second test is negative and patient is immunocompetent with no ongoing exposure, discontinue treatment 5
• If second test is negative but patient is immunocompromised (HIV-infected), complete full course of LTBI therapy 5

For drug-resistant TB exposure:

• Obtain drug susceptibility results from the index case before selecting a regimen 1
• For isoniazid-resistant, rifampin-susceptible TB: treat with rifampin plus pyrazinamide for 2 months, or rifampin alone for 4 months if pyrazinamide not tolerated 2
• For multidrug-resistant TB: treat with pyrazinamide plus ethambutol or pyrazinamide plus a fluoroquinolone for 6-12 months 2

Critical Pitfalls to Avoid

• Never use rifapentine as monotherapy 2
• Never use 2-month rifampin-pyrazinamide (2RZ) in HIV-negative adults due to unacceptably high hepatotoxicity risk 2
• Never add a single drug to a failing regimen—always add at least 2 drugs to which the organism is susceptible to prevent resistance 2
• Never use 6 months of isoniazid for HIV-infected persons or those with radiographic evidence of prior TB—9 months is required 2
• Intermittent (twice-weekly) isoniazid regimens should always be administered as directly observed therapy (DOT) 2
• Do not perform routine follow-up chest films for asymptomatic individuals with positive skin tests after initial evaluation unless symptoms develop 5, 3