Tuberculin skin testing with tuberculin purified protein derivative (PPD) is used to screen persons for latent tuberculosis (TB) infection. However, it is not a perfect screening test, and anergy testing, performed along with PPD, has been proposed as a method of determining a person's ability to exhibit a delayed-type hypersensitivity response, and thus, to “verify” a negative tuberculin skin test result.

By the 1970s, anergy testing was routinely performed when a PPD was performed, despite the lack of data supporting this step. In 1991, the Centers for Disease Control and Prevention (CDC) issued guidelines recommending anergy testing as an adjunct to tuberculin testing when screening persons who were human immunodeficiency virus (HIV)-positive for latent tuberculosis. The CDC later revised these guidelines and withdrew this recommendation. It is known that some persons with TB exhibit specific anergy to tuberculin but still respond to other antigens, possibly because available T-cell receptors are saturated and unable to react to the administered tuberculin antigen. This result may be especially evident in persons with miliary TB. Slovis and colleagues review the history and use of the anergy panel.

Results from studies in HIV-positive persons (without acquired immune deficiency syndrome [AIDS]) have revealed that persons who had a positive PPD test result were just as likely as not to be anergic to mumps and Candida antigens. The lack of a standardized protocol for selection of the number and type of antigens to be used in an anergy panel, criteria for defining positive and negative reactions, and administration and interpretation techniques are issues in anergy testing. There are also geographic differences in reactivity, with reactions to Trichophyton species being common in some areas, and reactions to histoplasmin (rarely used) being common in others.

In summary, the lack of reactivity to an anergy panel does not aid in predicting the lack of occurrence or accuracy of tuberculin reactivity. Several special cases exist. Anergy testing in HIV-negative persons has not been shown to change the risk of developing tuberculosis in persons who have a negative tuberculin test result. Anergy panel results should not influence the decision to administer chemoprophylaxis to persons with latent tuberculosis. In persons who are HIV-positive and have latent TB, a high risk of reactivation of latent TB exists. This risk can be decreased with isoniazid chemoprophylaxis. However, anergy is more common in HIV-positive infected persons because CD4 counts decrease, making the tuberculin test less sensitive. In populations in whom the prevalence of latent TB is high and in a TB-endemic area, cutaneous anergy predicts development of active tuberculosis as well as a positive PPD test result. However, these anergic HIV-positive persons may not derive the same benefit from isoniazid chemoprophylaxis; thus, anergy panel testing is still not recommended. Persons who are suspected of having active TB should not have a tuberculin test or cutaneous anergy tests, because a negative tuberculin test does not exclude active tuberculosis and relying on positive control antigens may delay proper diagnosis and treatment.