II. Epidemiology

  1. Clinicians under-read PPDs
    1. Kendig (1998) Chest 113:1175-7 [PubMed]

III. Mechanism

  1. Immune Allergic Contact Dermatitis after prior Mycobacterium tuberculosis exposure
  2. Based on Type 4 Hypersensitivity Reaction (Cell-Mediated, Delayed)
  3. Detectable 2-12 weeks after Tuberculosis infection

IV. Efficacy: General

  1. Accurate results are highly dependent on the reader's proficiency in measuring skin induration
  2. Accuracy statistics are far more variable than these values indicate
  3. Test Sensitivity: 68.9%
  4. Test Specificity: 59%
  5. Positive Likelihood Ratio: 1.68
  6. Negative Likelihood Ratio: 0.595
  7. Kendig (1998) Chest 113(5): 1175-7 [PubMed]

V. Efficacy: False Negatives

  1. False Negative Rate: 10-20% in immunocompetent patients
  2. Immunocompromised state
    1. AIDS
    2. Immunosuppressant use
    3. Alcoholism
    4. Bariatric Surgery
    5. Malnutrition
    6. Chronic Kidney Disease
    7. Sarcoidosis
    8. Comorbid systemic infection
    9. Zinc Deficiency
  3. Lab errors and timing errors
    1. Testing too soon after exposure (within 6-8 weeks)
    2. Inaccurate reading of induration or incorrect placement of injection
    3. Improper handling of TST solution
    4. Live Vaccine (e.g. MMR Vaccine) within the 6 weeks prior to PPD

VI. Efficacy: False Positives

  1. Boosting reaction (baseline 2-step PPD will help avoid interpretation as conversion)
  2. Nontuberculous Mycobacterium (e.g. Mycobacterium Avium Complex in COPD patients)
  3. Prior BCG vaccine
  4. Inaccurate reading of induration (e.g. measuring erythema instead of induration)

VII. Indication: Testing for Latent Tuberculosis

  1. Mycobacterium tuberculosis testing
    1. Low risk patients
      1. Routine screening not recommended
      2. Screen only if symptoms suggest possible Tuberculosis
    2. High risk patients
      1. See Tuberculosis Risk Factors for Tuberculosis Screening Indications
  2. Cases in which TST is preferred over IGRA
    1. Children younger than 5 years old

VIII. Contraindications

  1. BCG vaccine within 1 year of testing
    1. PPD should otherwise be placed as if BCG not given

IX. Technique

  1. Inject 0.1 ml Purified Protein Derivative Intradermal
    1. Injection typically in volar Forearm
    2. Contains 5 tuberculin units
    3. Injection should raise initial wheal of 6-10 mm
  2. Read in 48 to 72 hours after injection
    1. Reaction is largest at 72 hours
    2. Reading after 72 hours carries risk of False Negative and should be repeated
    3. Reading at 72 hours reduces False Negative Rate
      1. Singh (2002) Chest 122:1299-301 [PubMed]
  3. Measure induration (palpable) across Forearm
    1. Perpendicular to long axis
    2. Pen Technique
      1. Draw with pen in from both lateral margins to edge
      2. Pen stops at induration
  4. Record result in millimeters (No induration: 0 mm)
  5. Additional factors
    1. Anergy testing is not recommended for HIV patients due to variability in results
    2. BCG vaccine will cause a False Positive (reaction wanes over time)
      1. However BCG Vaccination status should not be used to interpret the results
    3. Healthcare workers should have baseline distant exposure testing initially
      1. Two step performed with second test done at 1-3 weeks after negative result
      2. A negative on the second test suggests no prior exposure

X. Protocol

  1. Step 1: Tuberculin Skin Test
    1. Positive: Go to Step 2
    2. Negative: Go to Step 3
  2. Step 2: Obtain Chest XRay and examination
    1. Positive (cough, fever, abnormal Chest XRay): Treat as Active Tuberculosis
    2. Negative: Treat as Latent Tuberculosis
  3. Step 3: Does patient have exposure to Active Tuberculosis?
    1. Yes: Go to Step 4
    2. No: No treatment or further testing needed at this time
  4. Step 4: Repeat Tuberculin Skin Test at 12 weeks after Active Tuberculosis exposure
    1. Positive: Go to Step 2
    2. Negative: Treat as Latent Tuberculosis if patient high risk (HIV, Immunocompromised)

XI. Interpretation: PPD under 5 mm

  1. Negative
  2. Observe Patient

XII. Interpretation: PPD 5 mm or greater

  1. Positive if
    1. HIV Infection
    2. Recent close Tuberculosis contact
    3. Clinical findings suggestive of prior or current Tb
    4. Apical fibronodular changes on Chest XRay (old Tb scarring) or other findings on Chest XRay
    5. Immunosuppressed
      1. HIV Infection
      2. Prednisone >15 mg/day for >1 month (or equivalent other Corticosteroid)
      3. Immunosuppressants
      4. Organ transplant
  2. Management
    1. Chest XRay and exam for disseminated disease
    2. Refer to Public Health or Infectious Disease
    3. See Tuberculosis Prophylaxis

XIII. Interpretation: PPD 10 mm or greater

  1. Positive if
    1. Health care workers
    2. New Immigrant within last 5 years from developing nations
    3. Intravenous Drug Abuse
    4. Children under age 5 years old, or children/teens exposed to high risk adults
    5. Malnutrition
    6. Diabetes Mellitus
    7. Cancer
    8. Chronic Kidney Disease
    9. Body weight >10% below Ideal Weight
    10. Silicosis
    11. Tuberculosis endemic to region
    12. High risk living environments (prison, Nursing Homes, hospitals, homeless shelter)
  2. Management
    1. Chest XRay and exam for disseminated disease
    2. Refer to Public Health or Infectious Disease
    3. See Tuberculosis Prophylaxis

XIV. Interpretation: PPD 15 mm or greater

  1. Positive in all persons (regardless of risk factors)
  2. Management
    1. Chest XRay and exam for disseminated disease
    2. Refer to Public Health or Infectious Disease
    3. Isolate organism for drug susceptibility testing
    4. See multi-drug Tuberculosis treatment regimen

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Related Studies

Ontology: Purified Protein Derivative of Tuberculin (C0034131)

Definition (NCI) A purified protein extract derived from the bacterium Mycobacterium tuberculosis. Intradermally-administered, PPD stimulates preprimed CD4 T cells in immunologically competent subjects previously exposed to the bacterium Mycobacterium tuberculosis; these activated CD4 T cells secrete various cytokines that attract granulocytes, monocytes, and macrophages in an inflammatory response known as delayed hypersensitivity. (NCI04)
Concepts Indicator, Reagent, or Diagnostic Aid (T130) , Immunologic Factor (T129) , Amino Acid, Peptide, or Protein (T116)
MSH D014373
SnomedCT 423321003, 108731003, 300902008, 20669006, 256229009
English Purified protein derivative, PPD, PPD-S, PPD-Purif protein derivative-S, Purified protein derivative-S, Tuberculin PPD, Tuberculin purified protein derivative (product), Tuberculin, Purified Protein Derivative of Tuberculin, PPD - Purified protein derivative - S, Purified protein derivative - S, tuberculin purified protein derivative, Purified Protein Derivative of Tuberculin [Chemical/Ingredient], ppd's, ppds, derivative protein purified, purified protein derivative, Tuberculin Purified Protein Derivative, Purified protein derivative (product), Purified protein derivative - S (substance), Purified protein derivative (substance), tuberculin,purif.prot.deriv., Tuberculin purified protein derivative (substance), Tuberculin purified protein derivative, Purified Protein Derivative, TUBERCULIN,PURIFIED PROTEIN DERIVATIVE
Spanish derivado proteico purificado de la tuberculina (producto), PPD tuberculina, derivado proteico purificado de la tuberculina, PPD - derivado proteico purificado - S, derivado proteico purificado - S (sustancia), PPD, derivado proteico purificado, derivado proteico purificado (producto), tuberculina, derivado proteico purificado - S, derivado proteico purificado (sustancia), derivado proteico purificado de tuberculina (sustancia), derivado proteico purificado de tuberculina, reacción de Mantoux
French Dérivé protéique purifié de tuberculine, Dérivé protéique purifié de la tuberculine, Tuberculine PPD