Low CD4 count is predictor of TB in patients with HIV
Low CD4 count is predictor of TB in patients with HIV
Study confirms link to abnormal X-rays
A recent study of chest X-rays from HIV-positive patients confirms the importance of knowing a person’s level of immunosuppression when evaluating him or her for pulmonary tuberculosis. The lower the patient’s CD4 count, the more likely the patient will have atypical presentations of pulmonary TB, the study concludes.
"The message here is that you see less cavitation in HIV-positive patients, and you particularly see less of it in patients with low CD4 counts, and therefore don’t ever rule out TB if you are smart," says Richard Hafner, MD, medical officer for the National Institute of Allergy and Infectious Diseases in Bethesda, MD, and an author in the study, published in the September issue of Clinical Infectious Diseases.1
The need for better reading of X-rays for diagnosing TB in HIV-positive patients comes at a time when fewer facilities are performing routine anergy testing. (See article on anergy testing on p. 141.)
David Perlman, MD, director of inpatient AIDS services at Beth Israel Medical Center in New York City, explains that this study reaffirms prior observations that the radiographic manifestations of HIV TB may be "atypical" that is, atypical for the adult reactivation TB seen in HIV-uninfected people. The study also strengthens conclusions from other studies that the frequency of "atypical" manifestations (adenopathy, infiltrates) varies by CD4 count. Specifically, "typical" manifestations (cavitation) are seen more at higher CD4 counts, while "atypical" features are seen at lower CD4 counts.
"In assessing the likelihood of TB in HIV-infected patients, the CXR [chest X-ray] pattern [often used to raise or lower the index of suspicion of TB] should be interpreted in the context of the patient’s CD4 count," he explains. "The other implication is that the pathophysiology of TB in HIV-infected persons differs as a function of the degree of immunosuppression. The CXR findings at higher CD4s resemble those of reactivation TB in HIV-negative adults, perhaps suggesting that TB in HIV-infected persons is likely to be reactivation TB among those with higher CD4s."
In patients with lower CD4s, the patterns are atypical for reactivation, due possibly to reactivation of TB in a different manner than seen in HIV-negative patients. However, the patterns are actually "typical" for the CXR patterns seen in primary TB in children, he explains, adding that the finding implies that more of the TB seen among those patients may be due to recent transmission.
Exploring reasons for abnormal X-rays
HIV-positive TB patients have been known to have cavitations in their lungs less frequently than HIV-negative patients, and a higher frequency of adenopathy on chest X-rays. The reason for these differences has not been well-established. Primary and reactivated TB also differ in radiologic presentations, and some researchers have argued that the atypical features of chest radiographs in HIV-positive patients may be attributed to the higher rate of primary TB among them.
To clarify the reasons, the study evaluated chest radiographic findings in a prospective multicenter treatment trail of HIV-related pulmonary TB. Baseline radiographs and CD4 counts were compared among 135 patients with culture-confirmed HIV-related TB. The study found that most of the patients 118 of 128 had abnormal radiographs that varied in manifestation dependent on their level of immunosuppression. Only seven patients with CD4 counts less than 200 had cavities, compared to 20 for those with CD4 counts greater than 200. The difference was statistically significant, Hafner says.
"The study showed that you were about three times less likely to see a cavitation if you have a patient who has CD4 counts less than 200," he added.
The differences make sense when considering the normal course of TB infection, Hafner explains. In normal patients who have reactivated TB, their immune system usually is strong enough to fight the bugs, resulting in the inflammation and the formation of granulomas that appear as a cavity in the lungs. With immunocompromised patients, the inability to initiate an adequate response often results in abnormal radiographs.
Indeed, 10 of 128 patients had X-rays that showed no signs whatsoever of TB neither adenopathy or infiltrates even though their sputum grew TB, Hafner notes. "This is a striking finding," he explains. "It means that in HIV-positive patients, you can have very unimpressive to negative X-rays and still have pulmonary TB." The number of patients with normal X-rays was too small to detect a statistically significant relationship to their level of CD4 counts, he adds.
Typically, lymphadenopathy is unusual in patients with reactive TB. However, the study found that lymphadenopathy was found more frequently in HIV-positive patients than in HIV-negative patients, indicating that without a strong immune response, TB can spread more rapidly into the lungs and lymph nodes. Patients with CD4 counts less than 200 also experienced more cases of hilar/mediastinal lymphadenopathy evident in their X-rays (30%) than those whose had CD4 counts greater than 200 (7%).
"This means that if you see a lymphadenopathy in a patient with low CD4 count, think TB," Hafner adds.
With the advance of viral-load testing, the question is raised whether a patient’s viral load could be a predictor of abnormal X-rays in the same way CD4 counts are. Because CD4s and HIV RNAs are correlated, Perlman notes, one might predict that cavitary disease would be seen at lower HIV RNA levels and adenopathy and infiltrates at higher HIV RNA levels.
Reference
1. Perlman D, El-Sadr W, Nelson E, et al. Variation of chest radiographic patterns in pulmonary tuberculosis by degree of HIV-related immunosuppression. Clin Infect Dis 1997; 25:242-246.
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