A 65-year-old female, with a known medical history of rheumatoid arthritis, and a left mastectomy for breast cancer treated with radiotherapy 7 years ago, presents with respiratory failure requiring intubation and mechanical ventilation. Chest X-ray reveals a large left-sided pleural effusion, into which  an intercostal catheter is placed.

With regard to this patient, discuss how examination of the pleural fluid may assist in identifying the cause of this effusion.
 


 


 

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College answer

Appearance                                                                                                              (1.5 marks)

Clear, straw-coloured – more likely transudate (although still may be exudate) Blood-stained – malignancy, pulmonary infarction

Yellow/green – rheumatoid Pus – empyema

Turbid – inflammatory exudate

Transudate vs exudate                                                                                           (3 marks)

Clearly some overlap, but in general terms Transudate – cardiac failure,

Exudate – malignancy, empyema, parapneumonic, , connective tissue disease (e.g. rheumatoid), pulmonary infarction, TB

Based on biochemical analysis

Different diagnostic criteria for distinguishing e.g. Light’s Criteria Rule

Light’s Criteria

Exudate if at least one of the following; Pleural fluid protein / serum protein ratio > 0.5

Pleural fluid LDH / serum protein LDH ratio > 0.6

Pleural fluid LDH > 2/3 of the upper limit of the lab’s normal serum LDH

Pleural fluid pH < 7.30 - exudate, with following differentials more likely; Malignant effusion

Complicated parapneumonic effusion or empyema Rheumatoid pleural disease

(SLE, TB)

pH < 7.2 is predictive of empyema, and is the best marker of a complicated parapneumonic effusion

(1.5 marks)

Glucose – low concentration (< 3.3 mmol/L) or pleural fluid / serum glucose ratio < 0.5 not only supports exudate, but makes following differentials more likely;

 

Malignant effusion

Complicated parapneumonic effusion or empyema

Rheumatoid pleural disease (glucose can be particularly low)                        (1.5 marks)

Microscopy                                                                                                                (1.5 marks)

Nucleated cell counts rarely diagnostic but may be supportive (e.g. >50,000/ml usually only complicated parapneumonic effusion/empyema)

Lymphocytosis – very high lymphocyte ratio (85-95% of total nucleated cells) suggests rheumatoid, TB,

Cytology                                                                                                                     (0.5 marks)

Malignant cells – overall sensitivity of only 60% in malignant effusions. Varies with type of malignancy.

Culture/Sensitivity                                                                                                    (0.5 marks)

Empyema

To achieve high marks candidates needed to demonstrate an understanding of how individual results point to specific diagnoses, rather than simply listing test options.

Examiners Comments:

This question was not answered well. Those who provided a good diagnostic approach to the evaluation of pleural effusion in the clinical context scored higher compared to those who provided only a list of differential diagnoses. Many candidates did not know Light's criteria differentiating exudate from transudate.

Discussion

Biochemistry and cytology are the main things one can order. 

Biochemistry:

  • Pleural fluid protein and LDH;  Serum protein and LDH. Light's own 1972 paper about his criteria is available online. Of course at that stage he never actually called them "Light's criteria". However, 30 years later in his article on pleural effusions for NEJM Richard W Light does refer to his own criteria as "Light's criteria".
    • In short, your effusion is exudative if:
      • The fluid to serum protein ratio is greater than 0.5
      • The fluid LDH is over 200 IU/L
      • the fluid LDH to serum LDH ratio os greater than 0.6
  • Glucose:  an extremely low pleural fluid glucose suggests that something is consuming it. Low pleural fluid glucose suggests TB, pneumonia or malignancy.
  • pH: this is a weird one. Everybody orders pleural fluid pH, and few understand what significance it has. According to the 2000 guidelines from CHEST, pH can determine the need for therapeutic drainage. Anormal pleural pH is about 7.60; a pH of <7.20 is equivalent to a positive gram stain in terms of identifying an effusion which requires drainage. Oesophageal rupture can also cause a low pleural pH.
  • Amylase:  this is elevated in pancreatitis-related effusion and in oesophageal rupture
  • Cholesterol: this reveals the effusion as a chylothorax

Cytology from the cell count:

  • Lymphocytosis = malignancy or tuberculosis. This cell count clue comes from another paper by Light. In his case series, of 31 exudative effusions with a lymphocytic predominance, 30 were due either to tuberculosis or neoplasm.
  • Neutrophilia = parapneumonic effusion or PE.
  • Eosinophilia (more than 10% eosinophils)  usually means there has recently been blood or air in the pleural space; however weird causes include drugs  and environmental toxins (dantrolene, bromocriptine, nitrofurantoin, exposure to asbestos) or autoimmune causes eg.  Churg–Strauss syndrome.
  • Malignant cells, obviously.

 Other tests:

  • Culture. The presence of bugs will identify the effusion as an empyema
  •  Direct visual inspection: although it appears to be highly unreliable (Villena et al, 2004), and one really cannot list it among diagnostic tests (i.e. it may do nothing to "assist in identifying the cause of this effusion").

References

Light, Richard W., et al. "Pleural effusions: the diagnostic separation of transudates and exudates." Annals of Internal Medicine 77.4 (1972): 507-513.

Light, Richard W. "Pleural effusion." New England Journal of Medicine 346.25 (2002): 1971-1977.

Shinto, Richard A., and Richard W. Light. "Effects of diuresis on the characteristics of pleural fluid in patients with congestive heart failure." The American journal of medicine 88.3 (1990): 230-234.

Light, Richard W., Yener S. Erozan, and Wilmot C. Ball. "Cells in pleural fluid: their value in differential diagnosis." Archives of Internal Medicine 132.6 (1973): 854-860.

Colice, Gene L., et al. "Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline." CHEST Journal 118.4 (2000): 1158-1171.

Villena, Victoria, et al. "Clinical implications of appearance of pleural fluid at thoracentesis." Chest 125.1 (2004): 156-159.