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Nonmalignant pleural effusions develop as a consequence of diverse extrapleural conditions that secondarily affect the pleural space. These disorders include systemic diseases (e.g., lupus), disorders of individual organ systems (e.g., chronic pancreatitis, congestive heart failure [CHF]), trauma and surgery, and iatrogenic interventions (e.g., drug related). Pleural fluid (PF) collects by one or more mechanisms: (1) pleural injury that causes increased pleural membrane permeability and protein-rich exudates, (2) increased intravascular hydrostatic forces and/or decreased oncotic forces that cause protein-poor transudates, and (3) extravasation of fluid from lymphatic or vascular structures or from an adjacent body compartment into the pleural space.1

Determining the etiology of a pleural effusion requires a sequential approach that begins with a detailed history and physical examination. Exposures and past occupations (e.g., tuberculosis, asbestos), underlying known conditions (e.g., rheumatoid arthritis [RA], CHF, pneumonia), and subtle symptoms related to a disorder not yet diagnosed (e.g., muscle weakness from myositis) may suggest the probable cause of an effusion. A thorough physical examination may detect abnormal nails with lymphedema suggesting yellow nail syndrome (YNS) or a malar rash indicating lupus pleuritis. Often the history and physical examination provide more diagnostic information than PF analysis or pleural biopsy, which may be nondiagnostic.

A differential diagnosis formulated from the history and physical examination guides a focused evaluation with imaging studies. Initial studies may examine nonpleural structures rather than the pleural space itself. Echocardiography, for instance, may establish CHF or pericarditis as the cause of a pleural effusion. Abdominal computerized tomography (CT) may detect hydronephrosis that underlies urinothorax. Among pleuropulmonary imaging studies, ultrasonography (US) and chest CT with pleural phase contrast enhancement provide detailed examinations of the pleural space, lung, diaphragm, and mediastinal structures that surpass the diagnostic value of standard chest radiography.

Portable US is highly sensitive and accurate for detecting and measuring the volume of PF.2 It also gauges pleural thickness and defines pleural masses, loculations, and the viscosity of PF for diagnostic purposes, guiding thoracentesis and pleural biopsy. Chest CT allows imaging of interlobar and paramediastinal pleural surfaces beyond the reach of US in addition to associated lung abnormalities.3 Like US, CT imaging can guide pleural biopsy and interventions to drain the pleural space. CT angiography allows the diagnosis of pulmonary embolism, which is increasingly recognized as a cause of exudative effusions.4

Thoracentesis is indicated for all patients with an undiagnosed pleural effusion in the presence of >1 to 2 cm of layering fluid detected by imaging studies unless CHF is the probable cause. Categorization of the fluid as a transudate or exudate simplifies the differential diagnosis, because conditions associated with PF formation tend to cause effusions of one of these types. Light’s three-criteria rule has been the traditional approach for identifying exudative effusions (Table 76-1). Although the Light’s criteria rule has a high sensitivity; it requires blood tests, suffers from mathematical coupling with two ...

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