By Ralph D. Levinson, MD
This retrospective study found a favorable outcome of anti-tuberculosis (TB) treatment in patients with uveitis and scleritis of unknown origin and positive QuantiFERON–TB Gold In-Tube testing (quantiferon).
What to do with a positive quantiferon test has become one of the most confusing issues in inflammatory eye disease. It is amazing how many patients turn out to be positive without any other evidence of tubercular disease. I highly recommend this article and the accompanying editorial for anyone who will ever see a patient with uveitis. Another question is if four-drug therapy is needed.
The authors reviewed the charts of 77 HIV-negative patients with uveitis and scleritis and positive quantiferon tests in the Netherlands, a country not endemic for TB. However, 60 of these patients had lived for at least six months in TB-endemic regions.
Their intraocular inflammation was characterized by a wide spectrum of ocular features with two distinct posterior segment entities: occlusive retinal vasculitis and serpiginoid choroiditis. One-third of the patients exhibited hilar and/or mediastinal adenopathy on radiologic and/or CT scan examinations, which was considered consistent with either sarcoidosis or TB or could be compatible with both.
Anti-TB treatment was associated with a decrease in inflammatory activity, few recurrences and increase in visual acuity, although only a small minority had documented (prior) M tuberculosis disease. The quantiferon levels were usually highly elevated, and 33 percent of patients exhibited lymphadenopathy, suggesting the diagnosis of sarcoidosis.
The authors conclude that future studies are required to elucidate the exact pathogenesis of quantiferon-associated intraocular inflammation and lymphadenopathy, and to show whether viable mycobacteria are present in affected tissues or whether the inflammation represents an immune reaction or a combination of both processes.
The authors of the accompanying editorial note that routine screening with quantiferon testing in nonendemic areas remains problematic due to the risk of false-positive results. They write that even with 99 specificity of quantiferon (and presumed sensitivity of 90 percent), the predictive value of the test is only about 78 percent, given 22 percent false positives, although the negative predictive value would be 99 percent. They say the study further adds to the complexity of quantiferon interpretation with the finding of false-positive tests in a number of patients with uveitis from underlying sarcoidosis.
They say the results of the study suggest that sarcoidosis should be suspected in uveitis cases with positive quantiferon and no evidence of TB infection. The implications for therapy are significant, as treatment of true TB with immunosuppression can be catastrophic.
Ultimately, the diagnosis of TB or sarcoidosis in challenging cases must rely on pathologic examination of tissue specimens and not solely on the result of the quantiferon assay, they say. Molecular studies, such as PCR testing of ocular fluids for M tuberculosis, may be useful in the diagnosis and treatment of these diagnostic dilemmas.