Tuberculin Skin Test

Definition

Tuberculosis (TB) is an airborne infectious disease caused by the bacteria Mycobacterium tuberculosis. Besides culturing in the laboratory, the two most common types of tests to screen for exposure to this disease are the Mantoux PPD tuberculin skin test, which is generally considered more reliable, and the older TB tine test, which is now rarely used. These tests are designed to help identify individuals who may have been infected by the tuberculosis bacteria. A diagnosis of active, infectious tuberculosis is never made solely based on the results of a TB skin test, but requires further testing, including a sputum culture and a chest x-ray.

Purpose

Because TB is spread through the air, especially in poorly ventilated areas, it is more commonly found among people living in crowded conditions, such as jails, nursing homes, and homeless shelters. Often, a TB skin test will be given as part of a physical examination when a person is hiring a new employee, particularly for those individuals seeking employment in the health care or food service professions.

People can be exposed to or infected with TB without showing any symptoms or necessarily developing the disease. Individuals with normally functioning immune systems generally prevent the spread of the bacteria by "walling off" or encysting the bacteria within the body. To be at risk for infection a person must have or had close contact with someone who has active tuberculosis (such as a friend or family member). Persons who are more at risk for developing the TB infection overtly include those with a weakened immune system (immunocompromised), either from a chronic disease, such as HIV infection; or as a result of a tissue or organ transplant or other medical treatment designed to suppress the immune system. In addition, persons who are heavy users of crack cocaine or alcohol are more susceptible to TB than those who do not abuse these substances. Symptoms of tuberculosis include a persistent cough, fever, weight loss, night sweats, fatigue, and loss of appetite.

Precautions

Although the test is generally considered safe, it is important to inform the person conducting the test if the patient may be pregnant, has had a positive TB test in the past, or has had tuberculosis in the past. People who have had a positive TB test in the past will probably always have a positive test and should not be tested again.

There are several situations when the TB test results might not be accurate. These include situations involving people who:

• have had vaccinations (such as those for measles, polio, rubella or mumps ) within the last four weeks
• are taking steroids
• have severe malnutrition

Description

TB skin tests are usually given at a clinic, hospital, or doctor's office. Sometimes the tests are given at schools or workplaces and may be a pre-employment requirement. Many cities provide free TB skin tests and followup care. The Mantoux PPD tuberculin skin test involves injecting a very small amount of a substance called PPD tuberculin just under the top layer of the skin (intracutaneously). Tuberculin is a mixture of antigens obtained from the culture of M. tuberculosis. Antigens are foreign particles or proteins that stimulate the immune system to produce antibodies. Two different tuberculin preparations are available, Old Tuberculin (OT) and Purified Protein Derivative (PPD). The latter is the preferred testing substance. The test is usually given on the inside of the forearm about halfway between the wrist and the elbow, where a small bubble will form as the tuberculin is injected. The skin test takes just a minute to administer.

After 48-72 hours, the test site will be examined by a trained person for evidence of swelling. People who have been exposed to tuberculosis will develop an immune response, causing a slight swelling at the injection site. If there is a lump or swelling, the health care provider will use a ruler to measure the size of the reaction. Some public health physicians recommend using a 72-hour waiting period as a general practice on the grounds that a 48-hour waiting period yields a higher percentage of false negative test results.

The other method of TB skin test is called the multiple puncture test or tine test because the small test instrument has several small tines that lightly prick the skin. The small points of the instrument are either coated with dried tuberculin or are used to puncture through a film of liquid tuberculin. The test is read by measuring the size of the largest papule. Because it is not possible to precisely control the amount of tuberculin used in the tine test, a positive test should be verified using the Mantoux test. For this reason, the tine test is not as widely used as the Mantoux test and is considered to be less reliable; as of 2000, it is no longer recommended for general use.

Preparation

There is no special preparation needed before a TB skin test. A brief personal history will be taken to determine whether the person has had tuberculosis or a TB test before, has been in close contact with anyone with TB, or has any significant risk factors. Directly before the test, the skin on the arm at the injection site is usually cleaned with an alcohol swab and allowed to air dry.

Aftercare

After having a TB skin test, it is extremely important to make sure that the patient keeps the appointment to have the test reaction read. The patient is instructed to keep the test site clean, uncovered, and to not scratch or rub the area. Should severe swelling, itching, or pain occur, or if the patient has trouble breathing, the clinic or health care provider should be contacted immediately.

Risks

The risk of an adverse reaction is very low. Occasionally, an individual who has been exposed to the TB bacteria will develop a large reaction in which the arm swells and is uncomfortable. This reaction should disappear in two weeks. A sore might develop where the injection was given, or a fever could occur, but these are extremely rare reactions.

It is possible that a person who has TB may receive a negative test result (called a "false negative") or a person who does not have TB may receive a positive test result (called a "false positive"). If there is some doubt, the test may be repeated or the person may be given a diagnostic test using a chest x ray and/or sputum sample culture test to determine whether the disease is present and/or active in the lungs.

Normal results

In people who have not been exposed to TB, there will be little or no swelling at the test site after 48-72 hours. This is a negative test result. Negative test results can be interpreted to mean that the person has not been infected with the tuberculosis bacteria or that the person has been infected recently and not enough time has elapsed for the body to react to the skin test. Persons become sensitive between two and ten weeks after the initial infection. As a result, if the person has been in contact with someone with tuberculosis, the test should be repeated in three months. Also, because it may take longer than 72 hours for an elderly individual to develop a reaction, it may be useful to repeat the TB skin test after one week to adequately screen these individuals. Immunocompromised persons may be unable to react sufficiently to the Mantoux test, and either a chest x ray or sputum sample may be required.

A newer test that appears to be preferable to the tuberculin skin test in evaluating patients who are HIV-positive is the enzyme-linked immunospot (ELISPOT) assay. A group of researchers in the United Kingdom found that the ELISPOT assay was more accurate than the PPD test in detecting active as well as latent tuberculosis in HIV-positive patients.

Abnormal results

A reaction of 5 mm of induration (swelling) is considered positive for the following groups:

• household contacts of persons with active tuberculosis
• AIDS patients
• persons with old healed tuberculosis on chest x ray

• organ transplant recipients.
• persons receiving immunosuppressive medications

A reaction of 10 mm of induration is considered positive in individuals with one or more of the following risk factors which are either reasons to have a higher exposure to TB and/or a condition that increases the risk for progression to active TB:

• foreign-born immigrants from Asia, Africa, or Latin America
• injection drug users and persons who abuse alcohol
• residents and employees of such high-risk congregate settings as hospitals, homeless shelters, and jails
• medically under-served low income populations
• TB laboratory personnel
• children younger than four years of age or infants, children or adolescents exposed to adults in high risk categories
• residents of long-term care facilities
• individuals with certain medical conditions that increase the risk of developing tuberculosis; these medical conditions include being 10% or more below ideal body weight, silicosis, chronic renal failure, diabetes mellitus, high dose corticosteroid or other immunosuppressive therapy, some blood disorders like leukemia and lymphomas, and other cancer

Finally, a reaction of 15 mm of induration or greater is considered positive in those with no risk factors and are therefore at the lowest risk of developing TB.

A TB skin conversion is defined as an increase of 10 mm or greater of induration within a two year period, regardless of age.

A positive reaction to tuberculin may be the result of a previous natural infection with M. tuberculosis, infection with a variety of non-tuberculosis mycobacteria (cross-reaction), or tuberculosis vaccination with a live, but weakened (attenuated) mycobacterial strain. TB vacination is not done in the US. Crossreactions are positive reactions that occur as a result of a person's exposure to other non-tuberculosis bacteria. These tend to be smaller than those caused by M. tuberculosis. There is no reliable way of distinguishing whether a positive TB skin test is due to a previous vaccination against tuberculosis. Generally, however, positive results are not due to vaccination exposure because reactions in vaccinated people tend to be less than 10 mm, and an individual's sensitivity to tuberculin steadily declines after vaccination. If the skin test is interpreted as positive, a chest x ray will be performed to determine whether the person has active tuberculosis or whether the body has sufficiently handled the infection.

KEY TERMS

Antibody— A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen.

Antigen— Any foreign particle or protein that causes an immune response.

Attenuated— Alive but weakened; an attenuated microorganism can no longer produce disease.

Cross-reaction— A positive reaction that occurs as a result of a person's exposure to other non-tuberculosis bacteria.

Immunocompromised— A state in which the immune system is suppressed or not functioning properly.

Induration— An abnormally hard spot or area on the skin. The tuberculin skin test produces an induration at the test site in persons who have been exposed to TB.

Intracutaneous— Into the skin, in this case directly under the top layer of skin.

Mantoux or PPD test— Other names for a tuberculin skin test. PPD stands for purified protein derivative.

Tuberculin— A mixture of antigens obtained from the cultured bacteria that cause tuberculosis, Mycobacterium tuberculosis.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Infectious Diseases Caused by Mycobacteria." In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

PERIODICALS

Centers for Disease Control (CDC). "Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection." Morbidity and Mortality Weekly Report 49, RR-6 (2000): 3-4.

Chapman, A. L., M. Munkanta, K. A. Wilkinson, et al. "Rapid Detection of Active and Latent Tuberculosis Infection in HIV-Positive Individuals by Enumeration of Mycobacterium tuberculosis -Specific T Cells." AIDS 16 (November 22, 2002): 2285-2293.

Howard, A. A., R. S. Klein, E. E. Schoenbaum, and M. N. Gourevitch. "Crack Cocaine Use and Other Risk Factors for Tuberculin Positivity in Drug Users." Clinical Infectious Diseases 35 (November 15, 2002): 1183-1190.

Kong, P. M., J. Tapy, P. Calixto, et al. "Skin-Test Screening and Tuberculosis Transmission Among the Homeless." Emerging Infectious Diseases 8 (November 2002): 1280-1284.

Singh, D., C. Sutton, and A. Woodcock. "Tuberculin Test Measurement: Variability Due to the Time of Reading." Chest 122 (October 2002): 1299-1301.

ORGANIZATIONS

American Lung Association. (800) LUNG-USA.

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. 〈http://www.cdc.gov〉.

National Heart, Lung, and Blood Institute (NHLBI). P. O. Box 30105, Bethesda, MD 20824-0105. (301) 592-8573. 〈www.nhlbi.nih.gov〉.

National Tuberculosis Center. University of Medicine and Dentistry of New Jersey. Executive Office, Suite GB1, 65 Bergen Street, Newark, NJ 07107-3268. (800) 4TB-DOCS. ∼ntbcweb/ntbchome.htm">〈http://www.umdnj.edu/∼ntbcweb/ntbchome.htm〉.

OTHER

American Academy of Family Physicians. "Positive Skin Tests for Tuberculosis." 〈http://www.aafp.org/healthinfo〉.

"Diagnostic Standards and Classification of Tuberculosis." 〈http://aepo-xdv-www.epo.cdc.gov/wonder/prevguid/p0000425/body006.htm〉.

U.S. Department of Health and Human Services Public Health Service, Centers for Disease Control and Prevention. "Questions and Answers About TB." 〈http://www.cdc.gov/nchstp/tb/faq.htm〉.