Long-lasting tuberculous pleurisy

From the authors:

We read with interest the correspondence from L. Ampollini and colleagues, in which they report the case of an immunocompetent patient who originally presented with pulmonary and extra-pulmonary tuberculosis (TB) at 33 years of age and which was thought to have persisted over many years. However, based on the clinical story described, we doubt that the patient had reactivation of TB at 65 years of age, when he presented with chest pain and dyspnoea and a computerised tomography (CT)-scan showed a calcifying pleurisy leading to a contralateral mediastinal shift and lung atelectasis. Mycobacterium tuberculosis was not isolated from the pleural effusion. Rather, a positive culture of Streptococcus was obtained and the patient was treated successfully with an anti-streptococcal therapy that was not TB-specific (amoxicillin/clavulanic acid for 3 weeks), with no sign of a TB relapse at follow up 2 years later. Therefore, it seems likely that L. Ampollini and colleagues are describing a case of bacterial pleuritis occurring in a patient with previous TB and calcified sequaele.

Evaluating the case, the clinicians correctly posed the question of reactivation of TB and performed bronchoscopy and microbiological evaluation of the pleural fluid. As a supporting assay, the Quantiferon-TB (Gold-in-Tube) test was also requested. Unfortunately, both of these laboratory tests have suboptimal sensitivity for the diagnosis of TB effusion [1, 2]; however, they are often performed initially because of their relatively low invasiveness. An additional option might have been the performance of interferon-γ release assay and molecular tests on the pleural fluid that may have increased the diagnostic accuracy [2, 3]. Following the negative laboratory tests for TB, the clinicians could have performed a pleural biopsy, which is the recommended investigation for confirmation of pleural TB [4], allowing histological evaluation in addition to microbiological and molecular tests.

L. Ampollini and colleagues question whether the biomarkers described as predictive for progression to active TB, the so-called “correlates of risk (COR) for TB progression” [5] may be useful in such clinical cases. In our review, we state that COR may predict progression from TB infection to active disease; however, the current COR tests are all blood-based and developed for microbiologically-confirmed pulmonary TB. To our knowledge, these assays have never been tested or validated in extra-pulmonary TB. It is therefore difficult to comment on the application of such biomarkers to the reported case without speculating on their utility in extra-pulmonary TB. Nevertheless, the described COR may have diagnostic potential, as described in Zak et al. [6]. Although biomarkers which are of specific interest to L. Ampollini and colleagues (for the prediction of TB reactivation) have not been described, this issue may yet be addressed by further transcript data mining [6] or by studying specific CD4/CD8 T-cell responses [7, 8] or variation in CD27 expression [8, 9]. Recently, positron emission tomography and CT-imaging, along with the demonstration of M. tuberculosis mRNA in clinical samples, have been described as promising research tools [10] to evaluate incomplete TB “cures”. Therefore, we agree with L. Ampollini and colleagues, the scientific community needs to strengthen and focus research to find better tools to predict and monitor TB-treatment outcomes and potential for reactivation.

Disclosures