TB SKIN TESTING

Tuberculosis is a bacterial infection, classically of the lungs, caused by the bacteria Mycobacterium tuberculosis.  The illness is primarily spread through expectoration of respiratory droplets from a sick individual, and subsequent inhalation of said particles by exposed people.  The organism then grows in the lungs in two main stages, depending on the immune status of the infected individual: latent infection and active disease.   Latent TB occurs when the tuberculin skin test (TST) is positive, but the chest radiograph is normal and /or the patient is asymptomatic.  Active disease occurs when there are clinical signs and symptoms of infection (pulmonary or extrapulmonary), and/or the CXR is abnormal  Typical fings on a CXR of a patient with TB include hilar lymphadenopathy or Gohn complexes generally in the upper apices of the lungs.

The most well known non-invasive method to identify TB in high-risk patients with possible latent infection is the placement of the Tuberculin Skin Test (TST).  The TST examines the body's immune response to tuberculin antigen, which is a T cell mediated delayed hypersensitivity reaction.  It is usuallay postitve 2-6 weeks after onset of infection, and in all those with symptomatic illness.  The most utilized test is the PPD.  0.1cc of 5 units of Purified Protein Derivative is injected intradermally on the volar surface of the arm.  A 6-10 mm. wheal should be produced at the time of injection. 

Indications for Testing
1. Routine skin testing is not recommended for children in areas of low TB prevalence 
2. Children in areas with high prevalence of TB but with no other risk factors should be tested between the ages of  4-6 and 11-16 
3. Immediate testing should be performed 
   a. Contact with individuals suspected of having TB or has an infiltrate consistent with TB on chest radiograph 
   b. Radiograph suspicious of TB 
   c. Children who have come from endemic countries (Asia, the Middle East, Africa, and Latin America)
   d. Travel recently to a country where TB is endemic 
4. Annual Testing
   a. Child is HIV + or an HIV + individual lives in the house 
   b. Incarcerated adolescent 
5. Testing every 2-3 years
   a. On-going exposure to HIV + individuals, migrant workers, incarcerated individuals, nursing home residents, IV drug users, and homeless individuals.
6. Testing at 4-6 and 11-16 years of age
    a. Children whose parents emigrated with unknown TST status from endemic areas
    b. Children who have continued exposure by ravel to endemic areas, or household contact with people from endemic areas.

Interpretation of PPD
1. The test must be interpreted between 48-72 hours by an individual trained in evaluating PPD's.  Studies have shown that parental interpretation of PPD's have been inaccurate and almost 60% of PPD's placed are never read. 
2. The interpretation is based on the size of induration, not redness. 
3. A thorough history of the child,  family members, other household members, and prevalence in the community is important in the interpretation of the test. 

Positive Tests

> 5 mm
1.  Children in close contact with a known or suspected person with active TB. 
2. Children suspected to have TB 
   a. + chest radiograph consistent with active disease or previously active disease 
   b. Clinically picture consistent with TB, i.e. meningitis, pleural effusion, TB pericarditis, lymphadenopathy/scrofula, Potts disease. 
3, Immunocompromised individuals i.e. children on immunosuppresive drugs including high doses of steroids,  HIV + patients, , or those with other immunosuppressed states 

> 10 mm
1. < 4 years old 
2. Diabetics, chronic renal disease, malnourished individuals, lymphoma, and Hodgkin's disease 
3. Child or their parents are born in endemic areas 
4. Exposure to HIV+ individuals, incarcerated or institutionalized persons, IV drug users, nursing home residents,  healthcare workers, and migrant workers. 
5. Travel to endemic areas ( Africa, Southeast Asia, Western Pacific)

> 15 mm
1. > 4 years old without any risk factors 

False Positives
1. Improper application of the test 
2. Cross reactivity with non-tuberculosis mycobacterium 

False Negatives
1. Within the incubation period of developing TB, 2-12 weeks 
2. Incorrect interpretation 
3. Disseminated disease 
4. Viral illness- measles, chicken pox, influenza, HIV 
5. T cell disease 
6. Steroids 
7. Malnutrition 
8. Chronic illnesses 
9. 5% of culture proven TB will have negative PPD. A negative PPD never excludes TB 

Interpretation of PPD Following BCG Administration
1.The Bacille Calmett-Guerin Vaccine (BCG) is used in more than 100 countries and usually given at birth or shortly after.  It is derived from Mycobacterium bovis and is 50-80% protective against life threatening TB such as miliary and TB meningitis. It does not prevent infection with the bacteria. 
2. Some children who are administered BCG never have a positive PPD 
3. If PPD is positive, usually less than 10 mm 
4. + test usually persists 3-5 years after administration 
5. PPD should be administered to individuals with the same indications of non-BCG recipients.  Try to verify that the child had the BCG or check for the typical  scar that the administration of the vaccine produces. 
6. If greater than 10 mm of induration, a chest radiograph should be performed, and the necessity for chemotherapy evaluated.  A consultation with a TB specialist is recommended to decide whether to initiate anti-tuberculosis medications.

Reference
1. The 2009 Redbook 
2. Abernathy RS. Tuberculosis: An Update. Pediatrics in Review. 1997; 18:50-58.
3. Committee on Infectious Diseases. Update on Tuberculosis Skin Testing of Children.  Pediatrics Vol.97 No. 2 February 1996.
4. Correa AG. Unique Aspects of Tuberculosis in the Pediatric Population. Clinics in Chest Medicine. 1997. 18(1):89-98.
5. Santiago E. A ProspectiveStudy of Bacillus Calmette-Guerin Scar Formation and Tuberculin skin Testist Reactivity in Infants in Lima, Peru.  Pediatrics. Vol 112 No. 4. October 2003
6. Nelson LJ. Epidemiology of Childhood Tuberculosis in the United States, 1993-2001: The Need for Continued Vigilance.  Pediatrics August 2004
7. Mayers M. Tuberculosis. Pediatrics in Review April 2008 
8. Lighter J. et al. Latent Tuberculosis Diagnosis in Children by Using the QuantiFERON Gold in-Tube Test. Pediatrics Jan 2009
9. Bianchi L, et al. Interferon-Gamma Release Assay and Improving the Diagnosis of Tuberculosis in Children.  Ped Inf Disease Journal  2009 ;28:510.
10. Word Health Organization Fact Sheets: Tuberculosis.  http://www.who.int/mediacentre/factsheets/fs104/en/
11. Cruz A, Starke J. Pediatric Tuberculosis.  Pediatric I Review, Jan 2010
12, MMWR Updated guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis- United States 2010 June 25, 2010
13. Horsburgh CR. Latent Tubderculosis Infection in the Unitied States.  NEJM April 14, 2011.