An indeterminate result of QuantiFERON-TB Gold In-Tube for miliary tuberculosis due to a high level of IFN-γ production

The QuantiFERON-TB Gold In-Tube^® test has excellent specificity for Mycobacterium tuberculosis. However, diagnosis of miliary tuberculosis remains challenging, and the interpretation of QuantiFERON^® results in immunocompromised individuals has not been fully established. Here, we present a patient with military tuberculosis who showed an indeterminate QuantiFERON^® result. A 76-year-old male presented with fever and pancytopenia. Radiological tests did not show the classical miliary pattern. Acid-fast staining and polymerase chain reaction of several specimens were negative for M. tuberculosis. The QuantiFERON^® responses were indeterminate on two separate tests, as interferon-γ (IFN-γ) concentration was high in the negative control. The patient did not respond to anti-microbiological therapy, and developed sepsis and disseminated intravascular coagulation, leading to lethal intracranial hemorrhage. An autopsy showed miliary tuberculosis and aplastic anemia. A literature review suggests a tendency towards indeterminate or false-negative QuantiFERON^® results in immunocompromised individuals or patients with miliary tuberculosis due to low production of IFN-γ. Our patient, however, showed substantial amounts of IFN-γ despite lymphocytopenia, which has not been reported in the literature. The present case suggests that indeterminate results of QuantiFERON^® should be interpreted with caution, as IFN-γ production in patients with miliary tuberculosis can vary significantly, even with sustained lymphocytopenia.