med 610 clinical respiratory diseases & critcare med

Pleural Effusions

Case 3 Answers

A 50 year-old woman who immigrated from Cambodia 15 years ago presents to the International Clinic complaining of left-sided chest pain and increasing difficulty breathing. She reports having intermittent fevers and decreased appetite. She recalls being treated for tuberculosis when she was a child after several family members became ill with the disease. She had a clear chest x-ray when she entered the country 15 years ago. A chest x-ray is performed and reveals a left pleural effusion occupying half of her chest. The fluid layers out on decubitus x-rays and a thoracentesis is performed. Pleural fluid studies reveal LDH 335 (serum value 250, upper limit of normal for serum 180), total protein 4.5 (serum value 6.8). The WBC differential includes 65% lymphocytes, 20% monocytes, 2% mesothelial cells. Gram’s stain and AFB stain are negative.

How would you interpret these pleural fluid studies?

The LDH is above the upper limit of normal for serum and the pleural fluid: serum LDH ratio is 1.34 with a pleural fluid: serum protein ratio of 0.66. This effusion should, therefore, be classified as an exudative process.

What is the differential diagnosis for this effusion?

The differential diagnosis for exudative effusions is much larger than for transudative processes and includes: parapneumonic effusions (most common), malignant effusions (second most common), tuberculous pleurisy, rheumatoid pleurisy, pancreatic disease, hypothyroidism, lupus pleuritis, chylothorax, drug-induced pleural effusion, pulmonary embolism, post-cardiac injury syndrome and esophageal perforation, Yellow Nail syndrome, benign asbestos effusions and scattered other causes.

What do you make of the 65% lymphocytes in the pleural fluid? Does this change your differential diagnosis at all?

This effusion would be classified as a lymphocyte-rich pleural effusion. This is a useful distinction as it helps narrow the differential diagnosis considerably. The leading causes of lymphocyte-predominant pleural effusions include tuberculous pleurisy, chylothorax, lymphoma, yellow nail syndrome, chronic rheumatoid pleurisy, sarcoidosis, trapped lung and post-CABG effusion. Given this patient’s history of immigration from a Tb-endemic area and prior Tb exposure you should be highly suspicious that her effusion is due to tuberculosis.

Are the mesothelial cells helpful in this case?

The mesothelial cells are helpful but not diagnostic. Mesothelial cells line the pleural surfaces and are present in normal pleural fluid. When there is an inflammatory process such as Tb or rheumatoid pleurisy, the mesothelial cells cannot move between the pleural surface and the fluid and the counts within the pleural fluid go down (< 5%). The presence of greater than 5% mesothelial cells in pleural fluid makes tuberculosis highly unlikely as the cause of the effusion. Values below 5% are consistent with but not specific for the diagnosis of tuberculous effusion since any inflammatory process coating the lining of the pleura can decrease mesothelial cell counts in the fluid.

What further tests can you order to confirm or rule out the diagnosis of tuberculosis?

You can order an adenosine deaminase level on the pleural fluid. Values > 40-60 mg/dL are supportive of the diagnosis. In the end, however, definitive diagnosis requires isolation of mycobacteria. Although we often send the pleural fluid for AFB stains and culture, the sensitivity of these tests is low. For the pleural fluid AFB smear, sensitivity is < 5% while for pleural fluid culture, sensitivities between 12 and 70% have been reported. The highest diagnostic yield comes from either histologic examination or culture of pleural biopsy specimens obtained either by closed pleural biopsy or a surgical procedure (video-assisted thoracoscopic surgery or thoracostomy).

Should you start her on anti-tuberculosis therapy while you finish your diagnostic testing?

Because the culture results can take a long time to come back and because the sensitivity of pleural biopsy histology or culture is still only 55-85%, you do not have to wait for positive results in order to start a patient on anti-tuberculosis therapy. Treatment can be started empirically if the suspicion for the diagnosis is sufficiently high.

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