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Positive Tuberculin Skin Test (PPD)
POSITIVE TUBERCULIN SKIN TEST (PPD) Ashwin Dharmadhikari, MD
Tuberculosis (TB) infection remains a leading cause of morbidity worldwide, making it an important area for public health prevention and treatment efforts. In the United States, its impact is seen in the 10–15 million individuals who are infected. Although annual rates of TB infection in the United States are declining, there are still cases in every state, and drug-resistant TB looms as the next hurdle in the care of patients with TB. One of the most important decision points in evaluating and treating patients for TB is to determine whether they have active TB disease or latent TB infection (LTBI). As part of that diagnostic evaluation, the tuberculin skin test (purified protein derivative; PPD) has historically been and continues to be an important tool. A. Testing for TB or LTBI using the PPD is most useful when applied carefully in targeted populations. Random testing is of little utility and may unnecessarily expose patients to unneeded medications or health care evaluations. Knowledge of disease prevalence and patient risk are important factors in deciding who to test. The overall goals of PPD testing are to find people with LTBI who would benefit from prophylactic treatment and to find people with TB disease who would benefit from treatment. Individuals at low risk should not be routinely tested. PPD testing is safe in pregnancy. B. Certain conditions place people into high-risk groups for exposure to TB. These conditions include close contact with a known or suspected case of TB, foreignborn individuals from endemic areas, residents of highrisk settings such as jails or nursing homes, health care workers, individuals who are medically underserved, injection drug users, or people in high-risk racial or ethnic populations. Once infected (i.e., patient has LTBI), individuals with HIV, substance abuse, diabetes, silicosis, prolonged immunosuppression, head and neck cancer, end-stage renal disease, hematologic malignancies, low body weight, gastrectomy or intestinal bypass, or malabsorption syndromes are at higher risk for progression to active disease. C. The PPD skin test is a combination of low molecular weight proteins and carbohydrate components of the tubercle bacillus. It is administered intradermally on the volar forearm as 5 thousand units (TU) of PPD. Results are interpreted 48–72 hours later based
502
D.
E.
F.
G.
H.
on millimeters of skin induration, with predetermined thresholds for positivity based on patient demographics and risk factors to determine further treatment. It is important that PPD results be read by health care professionals rather than by patients. The presence of induration meeting threshold criteria is termed positive PPD and generally represents infection with TB. False-positive PPD results may arise from nontuberculous mycobacterial infection or BCG (Bacille Calmette-Guérin) vaccination. False-negative PPD results may occur in the setting of anergy, recent TB infection, recent vaccination with live viruses, or overwhelming TB disease. Nonetheless, in immunocompetent individuals with latent TB infection, the PPD test approaches 100% sensitivity. On average, there is a 10% lifetime risk of developing TB disease from LTBI with a normal immune system. In patients who are HIV positive, this risk increases to a 7%–10% annual risk of developing TB disease. The greatest risk in all people occurs within the first 2 years after initial exposure to TB. A result of 0–5 mm in any patient is read as “negative.” Although there is a small risk of a false-negative result in patients who are anergic (usually as a result of immunosuppression), the current American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America (ATS/CDC/ ISDA) guidelines do not recommend routinely planting controls to test for anergy. A PPD result is positive at ⱖ5 mm for patients who are HIV positive, recent contacts of those with TB, persons with chest radiographic findings of fibrotic changes, or patients who have received organ transplants or are immunosuppressed. A threshold of ⱖ10 mm is used for people who have recently arrived from high prevalence areas, injection drug users, residents of nursing homes or jails, people who work with tuberculosis in a laboratory setting, health care workers, or children/adolescents exposed to adults at high risk. A threshold of ⱖ15 mm is considered positive for people with no known risk factors for TB. As previously stated, for the most part, these patients should not have a PPD placed because LTBI testing should be targeted to those with increased risk of infection.
503 Patient with POSITIVE TUBERCULIN SKIN TEST
A
B Individual identified as needing testing for tuberculosis based on medical history, demographics, or exposure
C PPD placed by health care professional D Patient returns to have PPD read by health care professional at 48–72 hr
E 0–5 mm
Negative
Potentially anergic if no induration Consider whether patient is immune suppressed
F ⱖ5 mm
G ⱖ10 mm
Positive if patient is: HIV positive Recent contact of a TB case Has radiograph consistent with old TB Immunosuppressed or organ transplant recipient
Positive if patient is: Injection drug user Resident of highrisk setting (jail/nursing home) Health care worker TB laboratory employee Recent immigrant from high prevalence area
H ⱖ15 mm Positive for patients with no known risk factors
Evaluate for active TB disease
I If no evidence for active TB disease, determine risk/benefit of treatment choices for LTBI and begin therapy
I. Once a patient is established as having a positive PPD, the next step involves using clinical and radiographic information to determine whether he or she has LTBI or active TB disease. For LTBI, the current ATS/CDC/ ISDA guidelines recommend a course of isoniazid (also called INH) 300 mg daily for 9 months’ duration, regardless of whether the patient is immunocompromised. Because patient compliance is often a challenge, there are three alternative regimens of one or two drugs of shorter duration.
References American Thoracic Society Statement: Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:5221–5247. Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603. Core curriculum on tuberculosis: What the clinician should know, 4th ed. Washington, DC: U.S. Department of Health and Human Services, Center for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention, Division of Tuberculosis Elimination, 2000.
Tuberculosis (TB) infection remains a leading cause of morbidity worldwide, making it an important area for public health prevention and treatment efforts. In the United States, its impact is seen in the 10–15 million individuals who are infected. Although annual rates of TB infection in the United States are declining, there are still cases in every state, and drug-resistant TB looms as the next hurdle in the care of patients with TB. One of the most important decision points in evaluating and treating patients for TB is to determine whether they have active TB disease or latent TB infection (LTBI). As part of that diagnostic evaluation, the tuberculin skin test (purified protein derivative; PPD) has historically been and continues to be an important tool. A. Testing for TB or LTBI using the PPD is most useful when applied carefully in targeted populations. Random testing is of little utility and may unnecessarily expose patients to unneeded medications or health care evaluations. Knowledge of disease prevalence and patient risk are important factors in deciding who to test. The overall goals of PPD testing are to find people with LTBI who would benefit from prophylactic treatment and to find people with TB disease who would benefit from treatment. Individuals at low risk should not be routinely tested. PPD testing is safe in pregnancy. B. Certain conditions place people into high-risk groups for exposure to TB. These conditions include close contact with a known or suspected case of TB, foreignborn individuals from endemic areas, residents of highrisk settings such as jails or nursing homes, health care workers, individuals who are medically underserved, injection drug users, or people in high-risk racial or ethnic populations. Once infected (i.e., patient has LTBI), individuals with HIV, substance abuse, diabetes, silicosis, prolonged immunosuppression, head and neck cancer, end-stage renal disease, hematologic malignancies, low body weight, gastrectomy or intestinal bypass, or malabsorption syndromes are at higher risk for progression to active disease. C. The PPD skin test is a combination of low molecular weight proteins and carbohydrate components of the tubercle bacillus. It is administered intradermally on the volar forearm as 5 thousand units (TU) of PPD. Results are interpreted 48–72 hours later based
502
D.
E.
F.
G.
H.
on millimeters of skin induration, with predetermined thresholds for positivity based on patient demographics and risk factors to determine further treatment. It is important that PPD results be read by health care professionals rather than by patients. The presence of induration meeting threshold criteria is termed positive PPD and generally represents infection with TB. False-positive PPD results may arise from nontuberculous mycobacterial infection or BCG (Bacille Calmette-Guérin) vaccination. False-negative PPD results may occur in the setting of anergy, recent TB infection, recent vaccination with live viruses, or overwhelming TB disease. Nonetheless, in immunocompetent individuals with latent TB infection, the PPD test approaches 100% sensitivity. On average, there is a 10% lifetime risk of developing TB disease from LTBI with a normal immune system. In patients who are HIV positive, this risk increases to a 7%–10% annual risk of developing TB disease. The greatest risk in all people occurs within the first 2 years after initial exposure to TB. A result of 0–5 mm in any patient is read as “negative.” Although there is a small risk of a false-negative result in patients who are anergic (usually as a result of immunosuppression), the current American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America (ATS/CDC/ ISDA) guidelines do not recommend routinely planting controls to test for anergy. A PPD result is positive at ⱖ5 mm for patients who are HIV positive, recent contacts of those with TB, persons with chest radiographic findings of fibrotic changes, or patients who have received organ transplants or are immunosuppressed. A threshold of ⱖ10 mm is used for people who have recently arrived from high prevalence areas, injection drug users, residents of nursing homes or jails, people who work with tuberculosis in a laboratory setting, health care workers, or children/adolescents exposed to adults at high risk. A threshold of ⱖ15 mm is considered positive for people with no known risk factors for TB. As previously stated, for the most part, these patients should not have a PPD placed because LTBI testing should be targeted to those with increased risk of infection.
503 Patient with POSITIVE TUBERCULIN SKIN TEST
A
B Individual identified as needing testing for tuberculosis based on medical history, demographics, or exposure
C PPD placed by health care professional D Patient returns to have PPD read by health care professional at 48–72 hr
E 0–5 mm
Negative
Potentially anergic if no induration Consider whether patient is immune suppressed
F ⱖ5 mm
G ⱖ10 mm
Positive if patient is: HIV positive Recent contact of a TB case Has radiograph consistent with old TB Immunosuppressed or organ transplant recipient
Positive if patient is: Injection drug user Resident of highrisk setting (jail/nursing home) Health care worker TB laboratory employee Recent immigrant from high prevalence area
H ⱖ15 mm Positive for patients with no known risk factors
Evaluate for active TB disease
I If no evidence for active TB disease, determine risk/benefit of treatment choices for LTBI and begin therapy
I. Once a patient is established as having a positive PPD, the next step involves using clinical and radiographic information to determine whether he or she has LTBI or active TB disease. For LTBI, the current ATS/CDC/ ISDA guidelines recommend a course of isoniazid (also called INH) 300 mg daily for 9 months’ duration, regardless of whether the patient is immunocompromised. Because patient compliance is often a challenge, there are three alternative regimens of one or two drugs of shorter duration.
References American Thoracic Society Statement: Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:5221–5247. Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603. Core curriculum on tuberculosis: What the clinician should know, 4th ed. Washington, DC: U.S. Department of Health and Human Services, Center for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention, Division of Tuberculosis Elimination, 2000.