Persistently high plasma procalcitonin levels despite successful treatment of tuberculous pleuritis and tuberculous lymphadenitis patients

Abstract

In a prospective cohort study, we evaluated plasma PCT levels in 48 TB lymphadenitis (TBLN) and 41 TB pleuritis (TBPE) patients. Measurements of PCT were done in unstimulated plasma of microbiologically and clinically confirmed TBLN and TBPE patients registered for anti-TB treatment at a tertiary care hospital in Lahore, Pakistan. Plasma levels of PCT were found to be raised in 89% of the patients at baseline with a median of 1.5 ng/ml. Levels were higher (p = 0.001) in TBLN as compared to TBPE (2.69, 0.96 ng/ml). PCT levels were not related to the bacterial burden depicted by culture positivity in these patients. PCT showed a negative correlation with the severity of constitutional symptoms (rho = - 0.238, p = 0.034), and inflammatory biomarkers; ferritin (rho = - 0.43, p < 0.001), INF-γ (rho = - 0.314, p = 0.003), TNF-α (rho = - 0.220, p = 0.039), IL-6 (rho = - 0.224, p = 0.035), and several chemokines of CCL and CCXL group. Raised plasma levels of PCT did not decrease with anti-TB treatment, indicating it is not a good biomarker to monitor treatment response in TBLN and TBPE patients. More studies with a larger number of confirmed EPTB cases are needed to define the role of PCT and its interaction with other biomarkers in EPTB.

Keywords: Inflammatory biomarkers; Procalcitonin; Response to treatment; TB lymphadenitis; TB pleuritis.

Fig. 1

Flow chart showing patients included in the study and their demographic and clinical characteristics. EPTB: extra-pulmonary tuberculosis, TBLN: tuberculous lymphadenitis, TBPE: tuberculous pleuritis, HIV: human immunodeficiency virus.

Fig. 2

Box plots showing plasma levels of plasma procalcitonin in, a) all patients, tuberculous lymphadenitis, and pleuritis patients, and b) male and female patients. The Mann–Whitney U was used to compare procalcitonin levels among tuberculous lymphadenitis, and pleuritis patients, and male and female patients in each group. A p-value < 0.05 was considered significant. Boxes represent the median and interquartile range, and the whisker shows minimum/maximum values. PCT: procalcitonin, TBLN: tuberculous lymphadenitis, TBPE: tuberculous pleuritis, n = number of patients in each group.

Fig. 3

Box plots showing difference of plasma procalcitonin levels in culture-positive and culture-negative cases among all patients, TB lymphadenitis, and TB pleuritis patients. The Mann–Whitney U was used to compare procalcitonin levels among the culture-positive and culture-negative patients in each group. A p-value < 0.05 was considered significant. Boxes represent the median and interquartile range, and the whisker shows minimum/maximum values. PCT: procalcitonin, EPTB: extra-pulmonary tuberculosis, TBLN: tuberculous lymphadenitis, TBPE: tuberculous pleuritis, n = number of patients at different time points.

Fig. 4

Dot plots showing association of symptom burden with plasma concentration of PCT in all, TBLN, and TBPE patients. Each dot represents a patient’s plasma PCT concentration and the number of symptoms reported by the patients. The Spearman correlation test was used to see the association among PCT levels and number of symptoms. *Correlation is significant at the 0.05 level (2-tailed). A p-value < 0.05 was considered significant. PCT: procalcitonin, EPTB: extra-pulmonary tuberculosis, TBLN: tuberculous lymphadenitis, TBPE: tuberculous pleuritis, n = number of patients.

Fig. 5

Box plots showing difference in plasma levels of PCT in patients with different constitutional symptoms. The Mann–Whitney U was used to compare PCT levels in patients with or without the presence of constitutional symptoms. A p-value < 0.05 was considered significant. Boxes represent the median and interquartile range, and the whisker shows minimum/maximum values. PCT: procalcitonin, n = number of patients at different time points.

Fig. 6

Box plots showing all extra-pulmonary, TB lymphadenitis, and TB pleuritis patients with raised plasma levels of procalcitonin at baseline and changes in its levels at 2 and 6 months of treatment. The Wilcoxon signed rank test was used to compare biomarkers expression at different time points. A p-value < 0.05 was considered significant. Boxes represent the median and interquartile range, and the whisker shows minimum/maximum values. PCT: procalcitonin, EPTB: extra-pulmonary tuberculosis, TBLN: tuberculous lymphadenitis, TBPE: tuberculous pleuritis, n = number of patients at different time points. M: month of treatment.