When is a PPD (Purified Protein Derivative) skin test recommended, particularly for individuals with compromised immune systems, such as HIV-positive individuals?

PPD Skin Testing: Indications and Recommendations

All HIV-infected persons should receive PPD tuberculin skin testing to screen for tuberculosis infection, with a positive result defined as ≥5 mm induration, regardless of their immune status or CD4 count. 1

Primary Screening Recommendations for HIV-Infected Individuals

HIV-infected persons must be screened for tuberculin infection because they are at elevated risk for active TB disease through either reactivation of latent infection or rapid progression of newly acquired infection. 1

Key Testing Parameters

• Administer 5 TU PPD using the Mantoux intradermal injection technique on the volar or dorsal forearm 2
• Read the test between 48-72 hours after injection, measuring only induration (not erythema) in millimeters 2
• For HIV-infected persons, ≥5 mm induration is considered positive and indicates TB infection 1, 3

Critical Limitation: Anergy in HIV Infection

HIV-infected persons have compromised ability to react to PPD testing due to elevated risk for cutaneous anergy, which increases as CD4+ T-lymphocyte counts decline. 1

Revised Anergy Testing Recommendations (1997 Update)

Routine anergy testing in conjunction with PPD testing is no longer recommended for screening programs among HIV-infected persons in the United States. 1

This represents a major reversal from 1991 guidelines due to:

• Problems with standardization and reproducibility of anergy testing 1
• Low risk for TB associated with a diagnosis of anergy 1
• Lack of demonstrated benefit of preventive therapy for groups of anergic HIV-infected persons 1
• Variability in available anergy testing methods and their lack of reproducibility 1

When Anergy Testing May Still Be Considered

Anergy testing may assist in guiding individual decisions regarding preventive therapy in selected situations, specifically: 1

• HIV-infected persons with ongoing high risk for exposure to M. tuberculosis (e.g., prison inmates where TB prevalence is high) 1
• Settings where exposure is likely but PPD conversion has not occurred and primary prophylaxis is being considered 1

If anergy testing is performed, use two FDA-approved Mantoux-method tests (mumps and Candida) together, with cut-off diameters of ≥5 mm induration. 1

Management Based on PPD Results in HIV-Infected Persons

PPD-Positive (≥5 mm induration)

HIV-positive persons with ≥5 mm induration who have not been treated for TB infection and whose evaluation excludes active TB should receive 12 months of isoniazid preventive therapy. 1, 3

• Evaluate to exclude active TB with chest radiography and clinical assessment 2
• This recommendation applies even if the date of PPD conversion cannot be determined 1

PPD-Negative

The most important factors in considering TB preventive therapy for HIV-infected persons with negative PPD results are the likelihood of exposure to transmissible active TB and the likelihood of latent M. tuberculosis infection. 1

Preventive therapy should be considered for: 1

• HIV-infected persons with recent contact with patients who have infectious pulmonary TB (complete 12-month course of isoniazid) 1
• HIV-infected children born to HIV-infected women who are close contacts of infectious TB cases 1
• HIV-infected adults who reside or work in institutions with continual unavoidable exposure to infectious TB patients 1

Special Populations and Considerations

Children with HIV Infection

• HIV-infected children should begin annual Mantoux tuberculin skin testing at age 3-12 months using 5 TU PPD 4
• Among HIV-infected children, >5 mm induration is considered positive 4
• False-negative reactions occur more frequently in young children, particularly those <2 years or with HIV infection 4

Healthcare Workers

• Baseline PPD testing should be performed during pre-employment physical examinations 2
• Two-step testing is recommended for those without documented negative PPD in the preceding 12 months 2
• For HIV-infected healthcare workers, use ≥5 mm cutoff for positive results 1

Common Pitfalls and Critical Caveats

• Never use multiple puncture tests (e.g., Tine tests) - only the Mantoux intradermal method is acceptable 4
• A negative PPD does not rule out TB in HIV-infected persons due to high rates of anergy 1
• Approximately 55% of HIV-positive TB patients may have PPD anergy, especially those with lower CD4 counts 1
• Reading the test outside the 48-72 hour window reduces accuracy 2
• Measuring erythema instead of induration leads to incorrect interpretation 2
• Previous BCG vaccination can cause false-positive results but should not prevent PPD testing in individuals who need screening 2
• Improper administration technique (failure to produce 6-10 mm wheal) can lead to false-negative results 2