College of American Pathologists
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Anergy testing in conjunction with tuberculin skin testing

August 2001

CAP TODAY published an article in November 2000 about Nancy Cornish, MD, director of microbiology, Methodist Hospital and Children's Hospital, Omaha, who is working to improve physician test-ordering. She teaches Methodist's physicians about lab tests through periodic clinical briefs, which she writes and distributes. The response of CAP TODAY readers to Dr. Cornish's work was so enthusiastic and the requests for copies of her briefs so numerous that we asked her to share the clinical briefs she writes as they become available. Here, this month, is her word on anergy testing in conjunction with tuberculin skin testing.

Anergy testing is no longer recommended when tuberculin skin testing is performed. The laboratory will no longer be routinely placing anergy testing panels (controls) when tuberculin skin testing is requested. The effective date for this change: June 1, 2001. This decision is based on guidelines published recently by the American Thoracic Society and Centers for Disease Control and Prevention.

In the 1970s, anergy testing became common practice as a theoretical way to improve the reliability of negative tuberculin test results, despite lack of data to support this practice. Since then, studies have shown that the validity of the practice is questionable and may be misleading for the following reasons:

  • Selective nonreactivity to purified protein derivative (PPD) antigen: five to 10 percent of patients with active tuberculosis have negative tuberculin test results but a positive response to another antigen.
  • Mumps reactivity may remain after loss of PPD reactivity.
  • Patients with loss of PPD reactivity but positive reactions to control antigens can be boosted with a second tuberculin test seven to 10 days later and may convert from a negative to a positive response.

Because of these findings, reactivity to control antigens with a negative response to PPD is not proof that the patient is not infected with tuberculosis. In addition, failure to respond to anergy tests does not mean the patient will not respond to PPD.

Furthermore, anergy panels suffer from:

  • Lack of standardized protocols for antigen selection, including types and numbers of antigens that need to be placed.
  • Variability between lots of antigen available for purchase.
  • Lack of uniform criteria for defining cutaneous reactivity.
  • Regional variability in skin reactivity.
  • Inability of anergy testing to predict the risk of progression to active tuberculosis.

In conclusion, a negative tuberculin test does not exclude active or latent tuberculosis in the presence of a reaction to other antigens placed as controls. The only useful result from the intracutaneous tuberculin test (PPD) is a positive result.

1. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med. 2000;161: 1376-1395.
2. Slovis BS, Plitman JD, Haas DW. The case against anergy testing as a routine adjunct to tuberculin skin testing. JAMA. 2000;283(15):2003-2007.
3.  American Academy of Pediatrics. Tuberculosis. In: Pickering LK, ed. Red Book: Report of the Committee on Infectious Diseases. 25th ed. 2000:593.
4. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR. 2000;49(RR06):1-54. Available at