What are the causes of pleural effusion in older adults with a history of cancer or heart failure?

Causes of Pleural Effusion in Older Adults with Cancer or Heart Failure History

In older adults with a history of cancer or heart failure, the most common causes of pleural effusion are heart failure (29% of all effusions), malignancy (26%), and pneumonia (16%), with heart failure accounting for over 80% of transudative effusions and lung cancer being the leading malignant cause. 1

Primary Causes by Mechanism

Transudative Effusions (Systemic Processes)

Heart failure dominates as the leading cause of bilateral pleural effusions, representing more than 80% of all transudates. 1, 2 In patients with known cardiac disease, this should be your first consideration, particularly when effusions are bilateral and the patient has other signs of volume overload.

• Cirrhosis accounts for approximately 10% of transudates and 3% of all pleural effusions, making it the second most common transudative cause. 1, 2
• End-stage renal failure causes effusions in 24.7% of ESRF patients, typically from fluid overload, heart failure, or uremic pleuritis. 1, 3
• Hypoalbuminemia and nephrotic syndrome produce transudates through decreased oncotic pressure. 1, 2

Exudative Effusions (Localized Pleural Processes)

Malignancy is the leading exudative cause in cancer patients, with lung cancer being the most common neoplasm (25-52% of malignant effusions), followed by breast cancer (3-27%). 4, 1 In your cancer patient population, this is the primary concern when an exudate is identified.

• Parapneumonic effusions from pneumonia represent 16% of all effusions and are the most common exudative cause overall. 1, 5
• Lymphoma accounts for approximately 10% of malignant effusions and may present bilaterally. 4, 1
• Pulmonary embolism associates with pleural effusions in up to 40% of cases, with 80% being exudates and 80% bloodstained. 3, 2
• Tuberculosis accounts for 6% of pleural effusions and must always be reconsidered in undiagnosed cases. 1, 3

Critical Diagnostic Distinctions

First, determine whether the effusion is a transudate or exudate using Light's criteria, which has 98% sensitivity but only 72% specificity for identifying exudates. 2 This distinction fundamentally changes your diagnostic approach.

When Heart Failure is Suspected but Light's Criteria Suggest Exudate:

• Apply the serum-effusion albumin gradient >1.2 g/dL to reclassify as transudate. 1, 2 This corrects the 25-30% misclassification rate of cardiac transudates as exudates. 1, 3
• NT-BNP levels >1500 μg/mL in serum or pleural fluid accurately diagnose heart failure as the cause. 1, 2

Specific Markers for Cancer Patients:

In malignant effusions, look for specific cancer markers including CDH1, MUC1/CA-15-3, THBS4, MSLN, HPX, SVEP1, SPINT1, CK-18, and CK-8 that discriminate cancerous effusions. 6 Lung cancer is the primary tumor in 25-52% of malignant effusions, breast cancer in 3-27%, and lymphoma in 12-22%. 4, 1

Special Considerations in This Population

Autoimmune Causes (Less Common but Important):

• Rheumatoid arthritis causes pleural effusions in 5% of patients, more commonly in men; suspect when pleural fluid glucose is <1.6 mmol/l (29 mg/dl). 4, 1
• Systemic lupus erythematosus causes pleural disease in up to 50% of patients during disease course. 4, 1 However, do not measure pleural fluid ANA levels as they mirror serum levels and are unhelpful. 4, 3

Infection-Related Causes:

Parapneumonic effusions require urgent assessment for pH <7.2, which indicates complicated effusion requiring drainage. 5 In tuberculosis, a positive tuberculin skin test with an exudative lymphocytic effusion may justify empirical antituberculous therapy, as pleural fluid smears are only positive in 10-20% of cases. 3

Approach to Persistent Undiagnosed Effusions

In persistently undiagnosed effusions, always reconsider pulmonary embolism and tuberculosis as they are amenable to specific treatment. 4, 1, 3 Approximately 15% of pleural effusions remain undiagnosed despite repeated cytology and pleural biopsy. 4, 3

Many "undiagnosed" effusions ultimately prove to be malignant with continued observation. 3, 2 If malignancy is suspected after routine tests fail, consider thoracoscopy for definitive diagnosis. 1, 2

Common Pitfalls to Avoid

• Do not perform diagnostic bronchoscopy unless the patient has hemoptysis or features of bronchial obstruction—it is not indicated for undiagnosed effusion workup alone. 4, 1
• Small bilateral effusions in patients with decompensated heart failure, cirrhosis, or kidney failure are likely transudative and do not require diagnostic thoracentesis. 5
• Always use point-of-care ultrasound to guide thoracentesis as it reduces complications and can detect effusions as small as 20 mL. 4, 5