Case Presentation: A 49 year-old Asian female with a history of multinodular thyroid, cervical stenosis, and latent tuberculosis infection (LTBI) presented to the emergency department with five-day history of nonproductive cough, pleuritic chest pain, and intermittent fevers and chills. During the previous year, she had completed three months of LTBI treatment with isoniazid and rifapentine (3HP) as a household contact of a patient with pulmonary TB. On admission, she had a fever of 38.4oC and was mildly tachycardic and tachypnic but oxygen saturation was 94% on room air. Physical exam findings included poor dentition and diminished breath sounds in the left lower lung field without rales. Chest radiography demonstrated a left lower lobe consolidation with a moderate pleural effusion. Laboratory studies were unremarkable including a normal white blood cell (WBC) count. Ceftriaxone and azithromycin were initiated for community-acquired pneumonia.

With continued fevers and chest pain, her antibiotic regimen was broadened to piperacillin/tazobactam and vancomycin. To evaluate her pleural effusion, a thoracentesis was performed and demonstrated an exudative pleural effusion with >7,000 WBCs (lymphocytic predominant) with an adenosine deaminase (ADA) of 8.3 U/L (normal). Three sputum samples were smear-negative for acid-fast bacilli (AFB). On day 25, pleural fluid culture yielded Mycobacterium tuberculosis, which was susceptible to all first-line agents. Sputum cultures remained negative at six weeks.

Discussion: Pleural TB is the most common form of extrapulmonary TB and occurs in approximately 4% of patients with TB. Since pleural TB is a paucibacillary infection, <10% of pleural fluid smears are positive for AFB. The most sensitive test is pleural biopsy with histopathological exam (90% sensitivity). Other tests performed on pleural fluid, such ADA level, interferon-gamma release assays, or TB polymerase chain reaction, may also facilitate diagnosis.

Recent guidelines for treatment of drug-susceptible TB recommend 6 months of standard TB treatment for patients with pleural TB. Pleural TB needs to be distinguished from TB empyema because this may require surgical intervention. Infection transmission was unlikely in our patient with pleural TB based on negative AFB sputum smears and cultures.

Approximately 90% of patients will successfully eradicate LTBI with treatment for latent infection, whether INH or 3HP. However, our patient developed pleural TB after completing treatment with the regimen of 3HP. The patient’s TB isolate was drug-susceptible indicating that drug-resistance was not a valid explanation for the failure.

Conclusions: We present this patient’s case to highlight unique aspects of diagnosing pleural TB and note that her infection occurred after LTBI treatment, despite a drug-susceptible isolate. This case also demonstrates an excellent example of anchoring bias: although this patient had findings that supported a diagnosis of TB, such as a lymphocytic pleural effusion, TB was considered unlikely based on the patient’s previous LTBI treatment.