Hydrothorax Caused by Tuberculosis
Pleural effusion is more often a manifestation of primary tuberculosis than of reactivation tuberculosis. Tuberculous effusions occur more commonly in young adults than in children. Typically, the effusion develops 3 to 6 months after initial exposure to Mycobacterium tuberculosis. A tuberculin skin test is positive at the time of clinical presentation in 70% of patients; in the remaining 30% of patients, the skin test becomes positive within 6 weeks after an initial negative result. In many cases, pleural effusion is the only abnormality detected on chest radiograph. Tuberculous pleural effusions are thought to be caused by the rupture of a small subpleural focus of infection into the pleural space, with the discharge of tuberculoprotein and viable tubercle bacilli. Widespread granulomatous infection of the parietal and visceral pleurae ensues, as indicated by the high yield of closed pleural biopsy in this setting. In patients with primary tuberculosis, untreated pleural effusions resolve spontaneously in approximately 2 to 4 months. However, active tuberculosis develops in two thirds of such patients during the ensuing 5 years.
Diagnosis Tuberculous pleuritis in patients with primary tuberculosis may present acutely as a febrile illness accompanied by pleuritic chest pain or subacutely as anorexia, weight loss, and dyspnea on exertion. The pleural liquid is usually serous or serosanguineous. In most cases, the differential white cell count reveals a lymphocytosis. A finding of more than 10% eosinophils or more than 5% mesothelial cells suggests a diagnosis other than pleural tuberculosis. In approximately 20% of cases, the pleural liquid glucose level drops below 60 mg/dl and the pleural liquid pH below 7.3. Increased levels of adenosine deaminase and interferon gamma distinguish tuberculous effusions from those of other causes.38 Use of polymerase chain reaction techniques to analyze pleural liquid for detection of mycobacterial DNA may become the method of choice for identifying tuberculous effusions.
Acid-fast bacilli are rarely seen in pleural liquid, and cultures are positive in only 20% to 40% of patients. However, closed-needle biopsy of the pleura reveals caseating or noncaseating granulomas in approximately 70% of cases and provides material that is culture positive in approximately 75% of cases. Thus, the total diagnostic yield, based on histopathology and culture, is 90% to 95%.
Treatment Patients who have pleural effusions from primary tuberculosis should be treated with at least two antitubercu-lous drugs.40 Treatment schedules should be identical to those used for parenchymal pulmonary tuberculosis. Corticosteroids have not been found to be of benefit41 [see 7:VIII Infections Due to Mycobacteria]. Chest tube drainage is not necessary. On the other hand, in cases of reactivation tuberculosis, infection may spill directly into the pleural space, causing a thick, purulent effusion known as tuberculous empyema. In these cases, chest tube drainage is required, as it is for other forms of empyema.
Hydrothorax Caused by Pulmonary Embolism
Pleural effusion may develop in patients with pulmonary embolism, even though pulmonary infarction (as manifested by a parenchymal infiltrate on chest radiograph) may not be present. In a large series of patients with emboli documented by angiog-raphy, 28% of the patients had radiographic evidence of pleural effusion at presentation.42 Spiral CT scans used for the diagnosis of pulmonary embolism detect pleural effusions in 57% of cases.43 The precise pathogenetic mechanism for pleural liquid formation in the absence of lung infarction is not known, although increased capillary permeability in the lung and visceral pleura and systemic venous hypertension have been suggested as contributing factors.
Diagnosis In many cases of pleural effusion caused by pulmonary embolism, pleural liquid analysis reveals an exudative effusion that is serosanguineous in appearance (> 10,000 red cells/mm3). A differential white cell count typically reveals a predominance of polymorphonuclear leukocytes. However, the characteristics of such an effusion are highly variable. The pleural liquid may be serous, may have a low protein concentration and meet the diagnostic criteria for a transudate, and may contain more than 50% lymphocytes. In addition, the total white cell count may vary from less than 100/mm3 to more than 50,000/mm3. Thus, none of the findings on routine pleural liquid analysis can be used to exclude a diagnosis of pulmonary embolism.
Treatment Management of pulmonary embolism need not be modified because of the presence of a pleural effusion, even if the effusion is bloody. In this setting, pleural effusions are maximal at their onset and gradually resorb with time, although resolution often requires more than 7 days if the effusion is large and associated with pulmonary consolidation. An enlarging effusion or the subsequent development of a contralateral effusion should raise suspicion of recurrent embolization or another complication, such as empyema.
Hemothorax
Direct hemorrhage into the pleural space most commonly results from trauma to the thorax. The trauma may be either blunt (e.g., sustained in a motor vehicle accident), in which case rib fractures are usually present, or penetrating (e.g., a knife or bullet wound). In a majority of cases, air or alveolar gas enters the pleural space along with blood, causing a hemopneumothorax. Hemothorax may also complicate invasive diagnostic or therapeutic procedures that lacerate pleural or mediastinal blood vessels; such procedures include thoracentesis, pleural biopsy, and cannulation of the subclavian or internal jugular veins. In rare instances, abnormal vascular structures in the mediastinum or lung periphery rupture into the pleural space; examples include hemothorax associated with arteriovenous malformation, pleu-ral endometriosis,45 and thoracic aortic aneurysm. Rare causes of nontraumatic hemothorax include pleural metastasis and iatro-genic or disease-related coagulopathy.
Diagnosis
When hemothorax is suspected, the hematocrit of the pleural liquid should be measured. It is important to remember that the pleural liquid may appear bloody even when its hematocrit is less than 1%. However, in true hemothorax, the pleural liquid hematocrit exceeds 50% of the peripheral blood hematocrit. He-mothorax, even if it is sterile, may be a cause of transient fever.
Treatment
In a large or rapidly accumulating hemothorax, blood should be promptly drained from the pleural space with a wide-bore chest tube. If rapid bleeding (100 to 200 ml/hr) continues, a tho-racoscopy47 or thoracotomy will be necessary. After bleeding has stopped, intrapleural fibrinolytic therapy to lyse clots not removed by the chest tube may obviate thoracotomy.Potential adverse consequences of undrained pleural blood include em-pyema and fibrothorax. Empyema may develop because blood provides a rich culture medium for growth of bacteria. Fibrotho-rax is a late sequela of moderate or large hemothoraces and results from organization of clotted blood into a dense fibrous peel surrounding the lung. A small, self-limited hemothorax associated with minor trauma such as a rib fracture will resolve without drainage or surgery.
Chylothorax and pseudochylothorax
Chyle is the lipid-rich liquid transported from small intestinal villi—the so called lacteals—to systemic veins in the thorax via the thoracic duct. Disruption or compression of the thoracic duct may lead to leakage of chyle first into the posterior mediastinum and then into the pleural space. Alternatively, an atretic or obstructed thoracic duct may cause reversal of lymph flow through dilated collateral channels. Rupture of these lymphatic channels may also produce chylothorax.
The thoracic duct follows a variable course through the mediastinum. Commonly, it crosses the diaphragm to the right of the vertebral column, entering the chest cavity through the aortic hiatus. It then crosses to the left of the vertebral column between the seventh and fifth thoracic vertebrae, arches above the level of the clavicle, and enters the systemic venous circulation in the region of the left jugular and subclavian veins. Depending on the particular anatomy of a given patient and the level at which the thoracic duct is disrupted, chylous effusions may be left sided, right sided, or, occasionally, bilateral.
Chylothorax
Etiology Various conditions can cause chylothorax. Medi-astinal tumors are the most common cause, with lymphomas exceeding metastatic carcinomas in frequency.49 Trauma is the other major cause of chylothorax in adults. In some cases, major chest trauma has been sustained. In other cases, seemingly minor actions, such as hyperextension of the back, are the only identifiable antecedent events. Thoracic and cardiovascular surgery occasionally results in transection of the thoracic duct and the subsequent development of chylothorax. In addition, chylothorax frequently occurs as a complication of the rare disease lymphangiomyomatosis.50 Other conditions producing me-diastinal lymphatic disruption or obstruction may cause chy-lothorax. Such conditions include congenital lymphangiectasis, mediastinal irradiation, fibrosing mediastinitis, granulomatous mediastinitis, left subclavian vein thrombosis, and esophageal sclerotherapy.
Diagnosis Chylothorax is usually not suspected until tho-racentesis reveals a milky-white pleural liquid. Identification of chylomicrons by lipoprotein analysis establishes the diagnosis of chylothorax and distinguishes it from other causes of an opalescent pleural liquid. However, several less expensive screening tests also may be useful. For example, a chylous effusion remains opaque after centrifugation, whereas the supernatant in empye-ma is clear. Furthermore, if a chylous effusion sample is allowed to remain undisturbed for 12 to 24 hours, a creamy layer of chy-lomicrons floats to the top, and the addition of a few drops of ethyl ether rapidly causes the liquid to clear. In most cases of chylothorax, the triglyceride concentration exceeds 110 mg/dl; exceptions usually are limited to patients in whom feedings have been withheld, such as postoperative patients.49 A CT scan of the chest is indicated in most patients with chylothorax to determine if the etiology is carcinoma, and pleural liquid cytology in these patients occasionally yields malignant cells.
Table 2 Classification and Treatment of Parapneumonic Effusions and Empyema
|
Type of Effusion |
Radiographic and Laboratory Findings |
Treatment |
|
Typical parapneumonic pleural effusion |
> 10 mm maximum thickness on lateral decubitus chest radiograph; glucose level and pH are normal; Gram stain and culture are negative |
Antibiotics alone |
|
Complicated parapneumonic pleural effusion |
May be nonloculated or multiloculated; no obvious pus; glucose level and pH are low and/or Gram stain and culture are positive |
Tube thoracostomy plus antibiotics; if loculated, use intrapleural fibrinolytics; surgery rarely required |
|
Empyema |
Free-flowing single loculus or multiloculated; obvious pus present |
Tube thoracostomy plus antibiotics; if loculated, use intrapleural fibrinolytics; may require thoracoscopy or decortication |
Chylous effusions elicit little pleural inflammation and are only very rarely complicated by empyema because of the bacte-riostatic properties of chyle. The major consequence of chylous effusions is the rapid and recurrent accumulation of liquid in the pleural space. Normally, the thoracic duct transports chyle at a rate of 1.5 to 2.5 L/day. In patients with chylothorax, much or all of this liquid may enter the pleural space.
Treatment Repeated thoracenteses or chest tube drainage can avert lung compression caused by pleural liquid buildup. However, these procedures may result in large losses of protein, fat, and circulating lymphocytes, rapidly leading to malnutrition and possible immunosuppression.
Definitive treatment of chylothorax varies with the specific etiology. Radiation therapy, with or without chemotherapy, is frequently effective for patients with mediastinal malignant disease, especially lymphomas. Thoracotomy, with oversewing of the thoracic duct leak or ligation of the duct below the leak, is curative in cases of accidental or intraoperative trauma. Pleurodesis [see Hydrothorax Caused by Malignant Disease, above] may prevent reaccumulation of chyle in patients with unresponsive malignant disease or in other poor operative candidates.
Pseudochylothorax
Occasionally, in patients with long-standing pleural effusions, cholesterol crystals collect in the pleural liquid, causing a milky-white appearance that is indistinguishable from chylothorax on gross inspection.51 Such pseudochylous, or chyliform, effusions can usually be readily differentiated from true chylothorax on the basis of the clinical setting. Pseudochylous effusions typically occur as a complication of rheumatoid or tuberculous effusions that have been present for several years and are associated with extensive pleural thickening. Chyliform effusions have been reported with paragonimiasis. These effusions should be drained and the underlying process treated.
Parapneumonic Effusions and Empyema
Thoracic empyema most often results from contiguous spread of infection from an underlying region of pneumonia and occasionally from a lung abscess or bronchiectasia. Bacteria are the most common pathogens, although any microorganism capable of causing pneumonia may also cause empyema. In a report from an inner-city municipal hospital, as many as 7% of patients admitted with acute pneumonia had empyema on presentation.52
The pleural space may also become infected as a result of seeding of pathogens after thoracic surgery, penetrating trauma, thoracentesis, or tube thoracostomy. Direct spread of infection from a subdiaphragmatic site, hematogenous spread of infection during septicemia, and embolic spread during septic thrombophlebitis are other mechanisms by which the pleural space may become infected. Finally, empyema may occur as a complication of spontaneous pneumothorax, mediastinitis, or esoph-ageal rupture.
Etiology Microorganisms causing empyema have changed considerably during the past 50 years, largely because of the introduction and increasingly widespread use of potent broad-spectrum antibiotics. In the 1930s and 1940s, Streptococcus pneumoniae (pneumococcus) and hemolytic streptococci were the pathogens most frequently isolated from empyemas. In the 1950s and 1960s, Staphylococcus aureus and gram-negative bacilli (e.g., Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa) became the predominant pathogens found in empyemas. Some series, employing modern techniques for culturing anaerobic bacteria, have found a preponderance of anaerobes, either alone or in combination with aerobic bacteria.53 Fungi have been isolated from empye-mas more frequently in recent years, particularly in hospitalized patients with significant comorbidities who are immuno-compromised.
Diagnosis The most common presenting symptoms of empyema are fever, chest pain, cough, and dyspnea. These symptoms, however, are not specific enough to distinguish patients who have pneumonia and empyema from those who have pneumonia alone. Patients with anaerobic empyema are more likely to have an indolent presentation, characterized by low-grade fever, anorexia, weight loss, or anemia. Between 10% and 15% of patients with empyema do not have fever or an elevated white cell count.
In patients with pneumonia and pleural effusion, it is important to determine whether the effusion is a typical parapneu-monic effusion (formerly known as a sympathetic effusion), a complicated parapneumonic effusion, or an empyema. These three types of effusion can be distinguished on the basis of the radiographic appearance and characteristics of the pleural liquid obtained at thoracentesis [see Table 2].
Treatment In general, very small pleural effusions (maximum thickness < 10 mm as measured on lateral decubitus chest radiograph) in the setting of acute pneumonia will resolve with appropriate antibiotic treatment of the pneumonia and do not require further investigation by thoracentesis. However, most larger effusions require thoracentesis. Loculations on radi-ographic studies, low pleural liquid pH and glucose concentrations, high LDH, or positive Gram stain and cultures indicate the presence of a complicated parapneumonic effusion (in cases in which there is no obvious presence of pus) or empyema (in cases in which there is obvious presence of pus). A pleural liquid pH of 7.2 or higher favors the diagnosis of typical parapneumonic effusion. Pleural liquid pH values between 7.0 and 7.2 are considered to be indeterminate (borderline complicated pleural effusion) and necessitate repeated thoracenteses, often from different sites, to determine whether a parapneumonic effusion is typical or complicated.
Systemic antibiotic therapy and prompt drainage of the pleu-ral space are key.55 In general, antibiotics penetrate the pleural space well and should be given systemically rather than in-trapleurally. The choice of antibiotics should be guided by the results of a Gram stain and culture of pleural samples, blood samples, sputum samples, or a combination of these. For anaerobic empyema, clindamycin is the drug of choice because as many as 10% to 15% of the anaerobic isolates are penicillin-resistant Bac-teroides fragilis.
Pleural drainage usually requires prompt placement of a chest tube because complicated parapneumonic effusions and empyema liquid reaccumulate rapidly after thoracentesis. In addition, continuous drainage is required to sterilize the pleural space, and drainage prevents the formation of loculi. In some patients with complicated parapneumonic effusions and empyema that do not resolve radiographically after placement of a chest tube, intrapleural streptokinase or urokinase56 may allow adequate drainage and obviate the use of multiple chest tubes or surgical drainage, although the evidence for this approach is not strong.57 Urokinase may be preferred over streptokinase because urokinase is associated with less frequent febrile reactions.58 Use of intrapleural fibrinolytic agents may also allow small-bore pigtail catheters to be placed into loculi with CT or fluoroscopic guidance.59 This approach may be unsuccessful with thick pleura, multiple loculi, or both.60 Early thoracoscopic therapy may be more cost-effective than attempts at drainage and the use of fi-brinolytic agents in such cases.61
With appropriate treatment, most patients will become afebrile within 4 days, and peripheral white cell counts will return to normal within a week. In a minority of cases, adequate pleural drainage cannot be achieved, and fever and leukocytosis persist; in such cases, a surgical procedure, either video-assisted thoracoscopy (early stage) or thoracotomy (late stage), is usually required.62 Stripping the adherent inflammatory peel from the pleural surfaces and removing the purulent exudate from the pleural cavity (i.e., decortication and empyemectomy) is a demanding surgical procedure. In elderly or severely debilitated patients, a more conservative surgical procedure may be used in which a partial rib resection is performed to create an open pleu-rocutaneous tract.63 The chronic empyema cavity that is formed can then be managed in the same way as any other chronic open wound and eventually may close spontaneously or can be closed by reconstructive surgery.
If left untreated, empyema can lead to septic shock. Other complications of untreated empyema include localized dissection of infection and consequent rupture through the skin (empyema necessitatis) or into the bronchial tree (bronchopleu-ral fistula).
Pleural Plaques, Diffuse Pleural Thickening, and Pleural Calcification
Pleural plaques
Pleural plaques are asymptomatic collections of collagenous connective tissue that form on the parietal pleura. They usually occur as a consequence of heavy exposure to asbestos fibers. In rare cases, plaques may form in response to inhalation of inorganic fibers other than asbestos, or they may arise in association with hyaloserositis or other conditions. Pleural plaques are discrete lesions that are covered by a layer of normal mesothelium and are clearly demarcated from normal surrounding pleura. They vary in diameter from a few millimeters to several centimeters and have an average thickness of approximately 0.5 cm. They typically form on the lateral and posterior pleural surfaces and the central (aponeurotic) portion of the diaphragm, sparing both the costophrenic sulci and the upper third of the thorax. They are often difficult to identify on chest radiograph unless their orientation is tangential to the x-ray beam, and only a small percentage of noncalcified pleural plaques identified at surgery or postmortem examination are recognized radiographically. CT scanning is more sensitive than plain films of the chest for detection of plaques. After several years, pleural plaques calcify, causing a radiographically distinct image [see Figure 7].
Figure 7 (a) Dense, white linear opacity along the left diaphragm (arrow) represents calcification of the parietal pleura in a patient with long-standing asbestos exposure. (b) CT scan shows area of dense calcification along the central dome of the diaphragm (arrow).
Figure 8 Radiograph reveals a so-called trapped lung, which was caused by marked thickening of the visceral pleura from a chronic empyema. Despite the application of a highly negative pressure to the pleural space, the right lung does not expand. A pyopneumothorax is present in the right thorax because evacuated pus has been replaced by air. There is no bronchopleural fistula (air leak from the lung). Obstruction of the mainstem bronchus may also cause a trapped lung.
Pleural plaques develop slowly over a period of many years, and they usually do not become apparent until 20 years after initial asbestos exposure. After 40 years, as many as 50% of persons who had occupational exposure to asbestos have pleural plaques. These hyaline plaques do not degenerate into neoplas-tic disease, but minimal changes in lung function may be associated with their presence.64 Their main significance is as a marker of probable asbestos exposure.
Other processes that resemble plaques include metastases, callus formation surrounding rib fractures, and normal areas of muscle insertion or fat accumulation. The distinction can usually be made easily by overpenetrated oblique views on radiograph or, if necessary, by CT scanning.
