Pleural empyema overview

# Overview
An empyema is a collection of pus within a pre-existing body cavity. It must be differentiated from an abscess, which is a collection of necrotic and suppurated tissue located in the parenchyma of an organ. Empyema is most commonly used to refer to pus collection in the pleural cavity although several other organs can be affected example brain, gallbladder, joint and urinary bladder. Thoracic empyema arises from an infection within the lung, often associated with parapneumonic effusions. 
Parapneumonic effusions may be uncomplicated or complicated effusions. Complicated parapneumonic effusion results when bacteria invade the pleural space with a resultant formation of an empyema.

# Historical Perspective
Pleural infection was first described by Hippocrates as far back as 460-370 B.C.
During this time open chest drainage was the sole treatment modality and was associated with high mortality. In 1873, Playfair gave the first description of a water-seal chest drainage system in the treatment of a child with thoracic empyema. In 1875, Gotthard Bulau a German Internist described the use of closed water-seal chest drainage to treat an empyema, as an alternative to the standard rib resection and open tube drainage. He punctured the pleural membrane with trocar and introduced a rubber catheter into the pleural cavity. The free end of the catheter inserted in a bottle one-third full of solution allowing pus to flow freely from the chest into the bottle. Closed chest tube drainage was experimentally practiced during the influenza epidemic in 191719 when open surgical drainage was associated with a high mortality rate. This coincided with world war I and the resultant crisis of streptococcal pneumonia and empyema. Closed chest tube drainage became the standard of treatment from late 1950.

# Classification
Pleural empyema may be classified according to the etiology and pathological course of the disease. Primary thoracic empyema occurs most commonly as iatrogenic empyema without associated pneumonia whereas secondary empyema happens more commonly secondary to pneumonia. Empyema necessitans is a spontaneous  discharge of an empyema that has burrowed through the parietal pleura into the chest wall to form a subcutaneous abscess that may eventually rupture through the skin.  Tuberculous empyema is the most common cause of empyema necessitans with majority of affected patients being immunocompromised. There are 3 stages of empyema which are important in terms of the laboratory findings. These are exudative, fibrinopurulent and organizing.

# Pathophysiology
The process leading to the formation of empyema involves  migration of organisms into the pleural cavity.  Lung parenchymal infection stimulates local pleural immune activation, neutrophil migration and release of inflammatory cellular components and toxic oxygen species, such as IL-6, IL-8 and tumour necrosis factor (TNF)-.
These mediators promotes endothelial injury resulting in increased pleural membrane permeability and increased osmotic pressure. With persistent inflammation, increased permeability of vascular and mesothelial membranes results in increased plasma leakage into the pleural cavity. Coagulation cascade when activated within the pleural cavity contributes to the development of a fibrinopurulent or complicated parapneumonic effusion. Fibrin is deposited over the pleural surfaces with fibrinous septae producing loculated effusions.

# Causes
Streptococcus pneumoniae was the most common bacteria found in empyemas before the development of antibiotics.  More recently, however, anaerobes have become the predominant organism in culture positive empyemas (and therefore careful anaerobic cultures should always be sent when working up parapneumonic effusions).  Mixed aerobic and anaerobic infections are also common. In general any bacteria can cause an empyema, however different bacteria are associated with different rates of empyema formation. Some of the common bacteria causes include; bacteroides, fusobacterium, haemophilus influenzae, pneumococcal infections, staphylococcus aureus, streptococcus, and TB.

# Differentiating pleural empyema from other Diseases
Empyema must be diffrentiated from pneumonia, lung abscess, lung cancer and parapneumonic effusions on the basis of the presentation, physical examination findings, chest xray, ultrasound and CT scan findings. For instance on ultrasound, empyema is positive for suspended microbubble sign, air fluid level, curtains sign and loss of gliding sign but these are negative in a lung abscess.
Again empyema is differentiated from a lung abscess in that empyema on CT scan is seen as a lung mass whose cavity is regular with smooth well-defined boundary and shape changes with change in patient's position. Mass may resolve on antibiotics. The split pleura sign is present (most reliable sign to differentiate empyema from lung abscess).

# Epidemiology and Demographics
The incidence and prevalence of empyema has been increasing over the past 15 years. More than 40% of patients have preexisting comorbidities. There have been a 26% increase in age and sex-standardized incidence rate from 8.7 per 100,000 person-years in 1997 to 11.8 per 100,000 person in 2011. This increment is most notably among older people aged  80 years (87.3% ) compared with people aged 40 to 64 years (27.8% ). Men are more commonly affected with empyema than women. The male to female ratio is approximately 1.7- to 3.1-fold higher in men than in women. The rate of patients with empyema requiring hospitalization appear to be increasing in western populations, however updated population-based data are scanty. The few available data on adult empyema have reported increase between 30% and 97% over the past 15 years in the United States and Canada. There is however a decreasing trend in the median days of hospital stay from 22 days 17 days.

# Risk Factors
Common risk factors in the development of empyema include: Bacterial pneumonia, thoracic surgery NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, Lung abscess, chest trauma, and post-thoracostomy drainage.

# Screening
There is no established screening modality for empyema however, lateral chest x-ray is the initial imaging of choice in patients with pneumonia. It is superior in detecting parapneumonic effusions compared to anteroposterior chest x ray.

# Natural History, Complications, and Prognosis
If left untreated 40% of complicated pneumonia results in effusion with 60% resulting in the formation of empyema. 
Empyema may result in the following complications; empyema necessitans,
imparired perfusion and ventilation of lungs as a result of pleural thickening and reduced lung function,
necrotizing fasciitis of the chest wall,
bronchopulmonary fistula or alveolar-pleural fistula, 
The prognosis of empyema after treatment is good however, the risk of permanent lung damage and mortality increase when empyema complicates pneumonia.
Advanced age and comorbidity are strong prognostic factors. Thirty-day mortality rate ranges from 1.2% in patients aged 15 to 39 years to 20.2% in those aged  80 years. Mortality also varies substantially according to level of comorbidity.

# Diagnosis

## History and Symptoms
Symptoms of empyema may vary in severity. Most patients with empyema may prersent with fever and chills, cough, shortness of breath, pleuritic chest pain, anaerobic infections however, can be more indolent, with up to 70% of patients having symptoms for more than 1 week. Additionally, these patients tend to have more constitutional symptoms including; excessive night sweating, weight loss

## Physical Examination
On examination, the following findings may be seen: lateral chest wall swelling and tenderness, clubbing of the fingernails, dull percussion note, reduced breath sounds on the affected side of the chest, egophony, coarse crackles, increased fremitus, mediastinal shift to opposite side with large empyema

## Laboratory Findings
Diagnosis is confirmed by thoracentesis. Aspiration of the purulent fluid is necessary especially when condition is not resolving on antibiotics. The pleural fluid typically has a low pH (<7.20), low glucose (<60 mg/dL), and contains infectious organisms. Although the presence of pus or organisms on gram stain is extremely helpful in making a diagnosis of empyema, a positive bacteria culture from pleural fluid is not needed  before diagnosis of empyema is comfirmed.

## Imaging Findings
Chest radiography is the initial imaging modality in evaluation of pleural disease. Lateral view is superior in detecting parapneumonic effusions and empyema compared to anteroposterior chest x ray. Chest X ray of empyema shows air-fluid level with continuous homogenous pattern from the mediastinum to the chest wall forming and obtuse angle with the lung parenchyma.
Thoracic ultrasound have greater sensitivity in detecting pleural effusions than clinical examination or chest radiographs (AP or lateral). Thoraxic ultrasound is the next prefered imaging test after chest xray. Ultrasound in empyema is positive for suspended microbubble sign, air fluid level, curtains sign and loss of gliding sign.
Thoracic MRI may show an internally septated, thick wall, and heterogeneous mass especially in empyema necessitans
On Computed tomographic scan, empyema is seen as a lung mass whose cavity is regular with smooth and regular lumen and well-defined boundary. The shape changes with change in patient's position. Mass on CT scan may resolve on antibiotics. The split pleura sign on CT scan is present (most reliable sign to differentiate empyema from lung abscess where it is absent).

## Other Diagnostic Studies
Leucocytosis as well as increased levels of pleural adenosine deaminase and pleural lactate dehydrogenase (usually above 1000) may provide additional diagnostic feature for empyema.

# Treatment

## Medical Therapy
The mainstay of therapy for empyema includes: controlling the infectious focus, drainage of fluid and pus, re-expansion of the lung. This involves the use of antimicrobial agents, thrombolytics, and drainage of the pleural space.  Pharmacologic therapies for acute empyema include either Ceftriaxone, Nafcillin or Oxacillin, Vancomycin or Linezolid, or TMP-SMX.  The preferred regimen for subacute and chronic empyema is a combination of Clindamycin and Ceftriaxone.

## Surgery
Definitive surgical treatment for empyema entails drainage of the infected pleural fluid.  A chest tube may be inserted, often using ultrasound guidance. Intravenous antibiotics are given. If this is insufficient, surgical debridement of the pleural space may be required. Management strategies of empyema necessitans with pulmonary involvement and lung abscess may involve  thoracotomy with pulmonary resection in addition to extended duration antimicrobial therapy.

## Prevention
Early and efficient treatment of pleural effection have been found to prevent the development of empyema.