How do you interpret a tuberculin (Purified Protein Derivative) test result in patients with varying risk factors and medical histories, such as immunocompromised (e.g. Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome) individuals?

How to Read a Tuberculin (PPD) Test

The tuberculin skin test must be read by trained healthcare personnel between 48-72 hours after injection by measuring only the transverse diameter of induration (not erythema) in millimeters, with interpretation based on risk-stratified cutoff values: ≥5 mm for high-risk patients (HIV-positive, recent TB contacts, immunosuppressed), ≥10 mm for moderate-risk patients (recent immigrants, injection drug users, healthcare workers), and ≥15 mm for low-risk individuals. 1

Administration Technique

• Inject 0.1 mL of 5 tuberculin units (TU) PPD intradermally into the volar or dorsal surface of the forearm using the Mantoux technique 1, 2
• A proper injection produces a discrete, pale wheal measuring 6-10 mm in diameter 1, 2
• If significant leakage occurs or the injection is subcutaneous, repeat immediately at a different site several centimeters away 1, 3

Reading the Test

Timing

• Read between 48-72 hours after injection when induration is maximum 1, 2
• Tests read after 72 hours tend to underestimate true induration size 1
• Reading at 24 hours, while predictive, should not be used for final clinical decisions 4

Measurement Technique

• Measure only induration (palpable, raised, hardened area), NOT erythema (redness) 1, 2
• Measure the transverse diameter perpendicular to the long axis of the forearm 1
• Record in millimeters; document "0 mm" for no induration, never write "negative" 1
• Use good lighting and inspect from a side view against light as well as direct light 1
• The ball-point pen method of Sokal can decrease interobserver variability 1

Critical Caveat

Patient self-reading is highly inaccurate and should never be accepted for clinical decisions 1, 2, 4, 5. Studies show only 1 of 18 patients correctly identified their positive PPD result 5, and even with training, errors occur in 12% of cases 6.

Interpretation Based on Risk Stratification

≥5 mm Induration is Positive for:

• HIV-infected persons (most critical group due to high progression risk) 1
• Recent close contacts of active TB cases 1
• Persons with fibrotic changes on chest X-ray consistent with prior TB 1
• Organ transplant recipients and immunosuppressed patients (equivalent of >15 mg/day prednisone for ≥1 month) 1
• Children <4 years old 1

≥10 mm Induration is Positive for:

• Recent immigrants (<5 years) from high-prevalence countries 1
• Injection drug users 1
• Residents and employees of high-risk congregate settings (prisons, nursing homes, hospitals, homeless shelters) 1
• Mycobacteriology laboratory personnel 1
• Persons with high-risk clinical conditions: silicosis, diabetes mellitus, chronic renal failure, hematologic disorders (leukemias, lymphomas), head/neck/lung malignancies, >10% weight loss, gastrectomy, jejunoileal bypass 1

≥15 mm Induration is Positive for:

• Persons with no risk factors for TB 1
• Low-risk individuals tested at employment entry where longitudinal testing programs exist 1

Special Considerations for Immunocompromised Patients

HIV-Infected Individuals

• Use the ≥5 mm cutoff, but recognize that PPD has a 25% false-negative rate in active TB and even higher rates in HIV patients 1
• The sensitivity of PPD decreases as CD4+ counts decline 7
• A negative PPD cannot rule out TB infection or active disease in HIV-positive patients 1
• Consider lowering the cutoff to ≥2 mm in HIV-positive patients to reduce misclassification, though this is not standard practice 7
• Anergy testing is often unreliable and should not be used to guide TB diagnosis 1

Other Immunosuppressed States

• Patients on corticosteroids (>15 mg/day prednisone for >1 month), chemotherapy, or other immunosuppressive agents may have false-negative results 1
• Patients with malignancies (Hodgkin's disease, lymphoma, leukemia) or sarcoidosis have impaired responses 1

Factors Causing False-Negative Results

Patient-Related Factors:

• Viral infections (measles, mumps, chickenpox, HIV) 1
• Bacterial infections (typhoid, brucellosis, pertussis, overwhelming TB) 1
• Recent live virus vaccination (measles, mumps, rubella, varicella, yellow fever, BCG, oral polio) - test either same day as vaccination or wait 4-6 weeks 1
• Metabolic derangements (chronic renal failure) 1
• Severe protein depletion 1
• Age extremes (newborns, elderly with waned sensitivity) 1
• Acute stress (surgery, burns, severe illness) 1

Technical Factors:

• Improper storage (exposure to light/heat) 1
• Subcutaneous rather than intradermal injection 1
• Injection of insufficient antigen 1
• Delayed administration after drawing into syringe 1

BCG Vaccination Considerations

Do not assume a positive PPD is due to BCG vaccination - interpret as indicating M. tuberculosis infection, especially in persons from high-prevalence countries 1. Reasons include:

• BCG conversion rates are often <100% 1
• Mean reaction size after BCG is often <10 mm 1
• BCG-induced tuberculin sensitivity wanes over time 1
• Most BCG-vaccinated persons are from high TB prevalence areas where true infection is more likely 1

Skin Test Conversion

For persons undergoing serial testing (e.g., healthcare workers), an increase of ≥10 mm within 2 years indicates conversion and recent infection 1, 2. This definition applies regardless of baseline induration size and accounts for test variability 1.

Two-Step Testing for Baseline Screening

Perform two-step testing for newly employed healthcare workers without documented negative PPD in the preceding 12 months 2:

• If first test is negative, repeat in 1-3 weeks 2
• This detects the "booster phenomenon" where waned TB sensitivity is restored by initial testing 2
• Without two-step testing, a boosted reaction on subsequent annual testing may be misinterpreted as new infection 2
• Particularly important in older adults, BCG-vaccinated persons, and those from high TB prevalence countries 2

Common Pitfalls to Avoid

• Never accept patient self-reading - accuracy is poor even with training 1, 2, 4, 5
• Never measure or record erythema - only induration matters 1, 2
• Never read tests outside the 48-72 hour window - accuracy decreases 1, 2
• Never use multiple puncture tests (Tine, Heaf) - unreliable and should be repeated with Mantoux method 1
• Never dismiss BCG vaccination as the cause of positivity without considering true infection 1
• Never rely on PPD alone to rule out active TB in symptomatic or high-risk patients - always obtain chest X-ray and sputum studies 1, 8
• Never use 1 TU or 250 TU PPD strengths - only 5 TU is sufficiently accurate 1