What is the initial workup for a patient presenting with pleurisy?

Initial Workup for Pleurisy

Begin with chest radiography (PA and lateral views) or chest ultrasound as your initial imaging modality, followed by thoracentesis for diagnostic pleural fluid analysis when an effusion is present, and proceed to CT chest with IV contrast (acquired 60 seconds post-bolus) if imaging suggests complexity, malignancy, or when initial workup is non-diagnostic. 1

Clinical Assessment

History and Physical Examination

• Document detailed occupational history, particularly asbestos exposure, as this is vital for all pleural effusions 1
• Review complete medication history using resources like the Pneumotox app, as tyrosine kinase inhibitors are now the most common drugs causing exudative pleural effusions 1
• Assess for symptoms suggesting life-threatening causes: pulmonary embolism (found in 5-20% of emergency department presentations with pleuritic pain), pericarditis, pneumonia, myocardial infarction, and pneumothorax 2
• Recognize that physical examination findings have low positive likelihood ratios for detecting pleural effusions, supporting the need for imaging 1

Initial Imaging Strategy

Chest Radiography

• Obtain PA and lateral chest radiographs as first-line imaging, which can detect >75 mL of fluid on lateral view and >175 mL on frontal view 1, 3
• The lateral view has higher sensitivity (83.9%) versus PA alone (67.3%) for detecting pleural effusions 3

Thoracic Ultrasound

• Perform thoracic ultrasound on every patient at initial presentation, as it detects >20 mL of pleural fluid and has 93-96% sensitivity and specificity 1, 3
• Use ultrasound to assess safety for diagnostic aspiration and evaluate effusion size and character 1
• Look for signs of malignancy including nodularity of the diaphragm and parietal pleura, which streamline the diagnostic pathway 1
• Ultrasound serves as the gold standard for characterizing pleural fluid collections and guiding thoracentesis 3

Diagnostic Thoracentesis

When to Perform

• Perform thoracentesis for all new and unexplained pleural effusions 4
• Always use image-guided thoracentesis to reduce complications 1
• Parapneumonic effusions <2.5 cm in anteroposterior dimension can often be managed without thoracentesis 1, 3

Pleural Fluid Analysis

• Send 25-50 mL for cytological analysis in suspected malignant pleural effusion, though smaller volumes should be sent if this cannot be achieved (with awareness of reduced sensitivity) 1
• Measure protein and LDH to distinguish transudate from exudate 4, 5
• Perform cellular differential count and bacterial/mycobacterial culture systematically 5
• For suspected pleural infection, send fluid in both plain containers and inoculate 5-10 mL into aerobic and anaerobic blood culture bottles 1

Specific Biomarkers

• In high prevalence populations, consider pleural fluid adenosine deaminase (ADA) and/or interferon gamma for diagnosing tuberculous pleural effusion 1
• In low prevalence populations, use pleural fluid ADA as an exclusion test for tuberculosis 1
• Consider pleural fluid antinuclear antibody (ANA) to support lupus pleuritis diagnosis 1
• Pleural fluid NT-proBNP is useful for heart failure but not superior to serum NT-proBNP 1

Advanced Imaging

CT Chest with IV Contrast

• Obtain CT chest with IV contrast when initial aspiration is unsafe, when malignancy is suspected (include chest, abdomen, and pelvis), or for non-malignant cases requiring pleural characterization 1
• For suspected parapneumonic effusion or empyema, CT with IV contrast is recommended by the American Association for Thoracic Surgery (class IIa recommendation) 1
• Acquire images 60 seconds after IV contrast bolus to optimize pleural visualization 1
• Five key CT findings for empyema include: pleural enhancement (sensitivity 84%, specificity 83%), pleural thickening (sensitivity 68%, specificity 87%), loculation (sensitivity 52%, specificity 89%), extrapleural fat proliferation (sensitivity 53%, specificity 91%), and increased extrapleural fat attenuation (sensitivity 39%, specificity 97%) 1
• The combination of parietal pleural enhancement and pleural thickening is seen in 98.7% of patients with laboratory-proven pleural infection 1

CT Scoring for Malignancy

• A CT-based scoring system can differentiate malignant from benign effusions: any pleural lesion ≥1 cm (5 points), liver metastases/abdominal mass/lung mass ≥1 cm (3 points each), absence of loculations/pericardial effusion/cardiomegaly (2 points each); score ≥7 yields 88% sensitivity and 94% specificity 6

Tissue Sampling

When Pleural Biopsy is Needed

• Perform thoracoscopic pleural biopsy when pleural fluid cytology is negative but suspicion remains high, as it provides higher diagnostic yield 1
• Tissue sampling for culture and sensitivity is the preferred option for all patients with suspected tuberculous pleural effusion 1
• Percutaneous closed pleural biopsy is easiest to perform, least expensive, with minimal complications for evaluating tuberculosis or malignancy 4
• Consider direct biopsies for tumor subtypes with low cytological yield (especially mesothelioma) 1

Serum Testing

Serum NT-proBNP

• Order serum NT-proBNP to support heart failure diagnosis in unilateral pleural effusion, but do not use in isolation as multiple conditions may coexist 1
• Serum biomarkers should not be used to diagnose secondary pleural malignancy, pleural infection, or autoimmune pleuritis 1

When Diagnosis Remains Unclear

Watchful Waiting Strategy

• Reconsider diagnoses with specific treatments: tuberculosis, pulmonary embolism, lymphoma, IgG4 disease, and chronic heart failure 1
• Watchful waiting with interval CT scans is appropriate for persistent effusions too small to sample 1
• Despite thorough evaluation, approximately 20% of pleural effusions remain without clear etiology and require prolonged follow-up with sometimes repeated thoracentesis or biopsy 4, 5

Common Pitfalls

• Never proceed with thoracentesis without ultrasound guidance, as this significantly increases complication risk 1
• Do not use CT angiography for pleural evaluation, as contrast timing (<60 seconds) is too early for adequate pleural enhancement 1
• Avoid ordering pleural fluid biomarkers for diagnosing secondary pleural malignancy, as they lack diagnostic utility 1
• Remember that chest radiographs cannot reliably distinguish viral from bacterial pneumonia (sensitivity 72%, specificity 91%) 3
• For suspected empyema, do not rely on non-contrast CT alone, as pleural enhancement (the most accurate finding) requires IV contrast 1