Distinguishing Polymorphonuclear Leukocyte-Predominant Tuberculous Pleural Effusion from Parapneumonic Effusion in Patients with Elevated Serum C-Reactive Protein

Background: Tuberculous pleural effusion (TPE) occasionally presents with polymorphonuclear leukocyte (PMN)-predominant pleural fluid (PF) and elevated serum C-reactive protein (CRP), mimicking parapneumonic effusion (PPE). We investigated factors distinguishing TPE from PPE in this diagnostically challenging setting. Methods: We retrospectively reviewed consecutive patients with confirmed TPE or PPE at a tertiary referral center (2010–2024). Patients with serum CRP ≥ 10 mg/dL were classified according to PF PMN-predominance. Independent discriminators between PMN-predominant TPE and PPE were identified using multivariable Firth logistic regression. Results: Among 414 patients with confirmed TPE, 108 (26%) had serum CRP ≥ 10 mg/dL, including 20 with PMN-predominance and 88 without. Anti-tuberculosis treatment was modestly delayed in the PMN-predominant group (p = 0.017). These 20 patients were compared with 335 PPE patients showing the same CRP/PMN profile. Pulmonary nodular lesions on chest computed tomography and PF adenosine deaminase (ADA) were independent discriminators. A composite two-tier rule—nodular lesions present or PF ADA > 80 IU/L if absent—achieved an AUROC of 0.925, 80.0% sensitivity, and 86.2% specificity. Conclusions: In patients with PMN-predominant pleural effusion and elevated serum CRP, this simple, readily available rule may help identify patients warranting early pleural biopsy and heightened suspicion for TPE before microbiological confirmation.