10th January 2024

Differential Diagnosis

The aetiology of pleural effusion is wide, with over 50 aetiologies possible spanning multiple medical specialities. A thorough clinical history, examination and diagnostic approach helps narrow the differential diagnosis. The table below is by no means exhaustive but incorporates important differentials to know for the MRCP exams.

Table 2: Differential diagnosis of pleural effusion with key points relating to pleural effusion and clinical presentation characteristics. 

Table adapted from – Bhatnagar R, Maskell N. The modern diagnosis and management of pleural effusions. BMJ. 2015;351(September). Saguil A, Wyrick K, Hallgren J. Diagnostic approach to pleural effusion. Am Fam Physician. 2014;90(2):99–104. UpToDate. Diagnostic evaluation of a pleural effusion in adults: Initial testing [Internet]. 2022 [cited 2022 May 17]. Available from: https://www.uptodate.com/contents/diagnostic-evaluation-of-a-pleural-effusion-in-adults-initial-testing

Empyema

An important differential diagnosis of pleural effusion is an empyema, meaning infection of the pleural fluid. The gold standard diagnostic test for empyema is the growth of an organism from the aspirated pleural fluid, but it can also be suggested by a low pleural fluid pH <7.2. Pleural infections are seen more commonly at the extremes of age: in the very young and the very old, and as such, has a high associated mortality of 20% in the UK.

The causative organisms vary depending on whether the pleural infection was community-acquired or hospital-acquired in origin. In the community, gram-positive aerobic organisms such as Streptococcus and Staphylococci are the most commonly seen organisms, but the incidence of gram-negative isolates from these patients is increasing. In the hospital setting, the most common organism seen is Staphylococcal aureus (S aureus), with a high proportion of patients growing methicillin-resistant staphylococcal aureus (MRSA). Gram-negative organisms such as E coli, Enterobacter and Pseudomonas species are seen in higher proportion in hospital-acquired cases when compared to the community.

Table 3: Common causative organisms of empyema. 

Table adapted from – Maskell N. British Thoracic Society pleural disease guidelines – 2010 update. Thorax. 2010;65(8):667–9.  

Strange C. Management and prognosis of parapneumonic pleural effusion and empyema in adults [Internet]. UpToDate. 2021 [cited 2022 May 30]. Available from: https://www.uptodate.com/contents/management-and-prognosis-of-parapneumonic-pleural-effusion-and-empyema-in-adults

Empyema, or pleural infection, should be suspected in any patient who has remained persistently unwell with high inflammatory markers and temperatures despite appropriate antimicrobial treatment. Signs and symptoms consistent with sepsis can develop if a pleural infection remains untreated. The gold standard diagnostic test for pleural infection is pleural fluid culture, and would be the main way to differentiate from the other causes of pleural effusion detailed above, alongside a pleural pH level.

Haemothorax

Haemothorax refers to the presence of frank blood in the pleural space most commonly secondary to thoracic trauma. Its appearance on a plain chest x-ray is identical to a standard pleural effusion, but clinical history, pleural ultrasound features and diagnostic aspiration can help differentiate it.

Haemothorax tends to develop in the context of polytrauma, both in the young and old, and these patients may have evidence of haemodynamic instability from bleeding: hypotension or tachycardia. In addition to radiological features, a haemothorax may be suggested by a significant serum haemoglobin drop. Radiologically, it appears identical to all other causes of pleural effusion on chest x-ray, but on pleural ultrasound, it is a cause of a loculated pleural effusion (other causes being malignancy and pleural infection). The key to diagnosis, though, is on diagnostic aspiration with identification of pleural fluid: blood haematocrit ratio >50%.

If identified, haemothorax should be managed urgently (see management).