Imaging of Pleural Tuberculosis: A Narrative Review

Abstract

Pleural tuberculosis is the second most common type of extrapulmonary tuberculosis (TB) after TB lymphadenitis and presents secondary to pulmonary TB in most cases. TB pleuritis develops due to a delayed hypersensitivity response precipitated by the discharge of tubercular bacilli in the pleural space typically within 6 to 9 months of the initial TB infection. TB empyema on the other hand is multibacillary and purulent, often seen in cases of pulmonary TB. Longstanding pleural TB can also present as fibrothorax, chylothorax, or empyema necessitans. It shows features similar to pleural mesothelioma in later stages and is important to be considered as a differential, especially in endemic regions. This review article aims to provide an in-depth knowledge into the basic anatomy of pleural space, pathophysiology of pleural TB, and imaging features helpful in making a diagnosis.

 

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Keywords

tuberculosis - pulmonary - pleural - imaging

Introduction

Pleural tuberculosis (PTB) is the second most common type of extrapulmonary TB after TB lymphadenitis. It presents secondary to pulmonary TB in most cases. Rarely, it presents in the form of isolated pleural effusion, empyema, and their complications. This review article aims to provide an in-depth knowledge into the basic anatomy of pleural space, pathophysiology of PTB, and imaging features helpful in making a diagnosis.[1]

 

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Anatomy

The pleural space is a potential space between the visceral and parietal pleurae, filled with a thin layer of lubricating fluid which allows the two layers to glide smoothly against each other during respiration, preventing friction and ensuring effortless lung expansion and contraction. The parietal pleura covers the mediastinum, diaphragm, and inner surface of the thoracic cage and receives blood supply from systemic circulation (intercostal arteries). The thinner visceral pleura forms interlobar fissures by covering the lungs and receiving blood supply by branches of the pulmonary arteries, and smaller areas by bronchial arteries.[2] [3]

Pleural space fluid is circulated from the capillaries of the visceral pleura and reabsorbed primarily by parietal pleura lymphatic drainage connected to intercoastal, internal mammary, and mediastinal lymph node chains. Any interruption or changes in the capillary permeability, lymphatic function, or hydrostatic/oncotic pressure result in an imbalance in the formation or resorption of the pleural fluid.[4] Pleural effusion can be classified into either exudate (due to infection, inflammatory pathology, neoplasm) or transudate (due to congestive heart failure, low protein content, myxedema, cirrhosis, nephrotic syndrome, etc.). Based on modified Light's criteria, exudative pleural fluid has either a pleural fluid protein/serum protein ratio of > 0.5; and/or lactate dehydrogenase (LDH)/serum LDH ratio of more than 0.6; and/or LDH over two-thirds of the upper limits of normal laboratory value.[5]

 

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Pathophysiology of Pleural Tuberculosis

PTB manifests most commonly as TB pleuritis and occasionally as tubercular empyema or TB-associated lipid effusion. PTB develops from the subpleural lung focus discharged to the pleural space, and/or bronchopleural fistula, and occasionally direct extension from adjacent nodes. Rarely, tubercular pleural involvement is seen by hematogenous spread or iatrogenic interventions such as pneumonectomy or oleothorax.[6]

TB pleuritis develops due to a delayed hypersensitivity response precipitated by the discharge of tubercular bacilli in the pleural space typically within 6 to 9 months of the initial TB infection. An immune response follows as infiltration of neutrophils and monocytes in the early stage and influx of lymphocytes (memory T-lymphocytes) causing persistent fluid buildup (pleural effusion) in a later stage. Memory T-helper (Th) 1 cells, previously sensitized to mycobacterium TB (mTB), migrate to the infected pleural space and produce proinflammatory cytokines (interferon [IFN]-γ) and other Th1 cytokines that increase capillary permeability leading to fluid leak into the pleural space. Additionally, lymphocytic pleuritis and granuloma formation impair pleural fluid resorption.[1] [6] The inflammatory response led by activated CD3+ and CD4+ Th1 cells via INF-γ creates compartmentalization of pleural space and effects a highly efficient anti-TB response, thus explaining the paucibacillary nature of most tuberculous effusions.[6]

Typically, tubercular pleural effusion is yellow or straw-colored, occasionally blood-tinged, with protein 2 to 4 g/dL and glucose 20 to 40 mg/dL. The tubercular pleural fluid typically does not show Gram staining, however, may show growth in up to 50% of cases. Up to 90% of pleural biopsies show caseating granulomas, and culturing the tissue confirms TB in up to 70% of cases.[7] The pathophysiology of TB pleuritis is summarized in [Fig. 1].

Fig. 1 Pathophysiology of tuberculosis (TB) pleuritis.

Contrary to TB pleuritis, TB empyema is the purulent fluid that contains abundant mTB, and neutrophils and typically progresses from primary tubercular effusion. Empyema may develop from the larger discharge of mTB from postprimary cavitary disease via the rupture of a cavity or through the bronchopleural fistula.[8] This chronic infection manifests as a thickened pleura and may be associated with calcification and rib thickening. Complications of TB empyema include “fibrothorax” due to severe scarring and chest cavity deformity and empyema necessitates due to decompression through the chest wall and forming fistulas.[1] The pathophysiology of development of pleural empyema is summarized in [Fig. 2].

Fig. 2 Pathophysiology of pleural empyema development.

Sometimes, PTB is associated with the presence of high levels of lipid in pleural fluid (TB-associated lipid effusions). Effusion with predominantly high cholesterol levels, presumably secondary to releasing cholesterol and other lipids from degenerating cells within the pleural space in a chronic tuberculous effusion is generally called pseudochylothorax. The pleural fluid in this case has high levels of triglycerides and chylomicrons, and it usually looks milky.[1]

 

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Imaging Diagnosis of Pleural TB

PTB is one of the most common forms of extrapulmonary TB. It is a challenge for clinicians and radiologists alike to differentiate PTB from other granulomatous disorders and malignancies, especially in endemic countries.[9] Even with the availability of microbiological testing systems for acid-fast bacilli and rapid polymerase chain reaction testing, in many of the developing countries, early and correct diagnosis of pulmonary and extrapulmonary TB can be challenging.[9]

Tuberculous pleural effusion is most often unilateral and occupies less than two-thirds of the hemithorax.[1] Diagnosis is made using several radiological modalities such as chest radiograph, high-resolution computed tomography (HRCT) chest, and B-mode ultrasound. Chest X-ray is the primary imaging modality used in most settings for screening and diagnosis. Several studies reveal that TB effusion is the cause of approximately 12% of all massive pleural effusions ([Fig. 3]). Often, concomitant pulmonary and extrapulmonary features are seen on chest X-ray. However, CT is a superior modality for evaluation. Recent studies have suggested that PTB is more common in drug-resistant forms of TB. Longstanding TB presents as pleural thickening on the chest X-ray. However, it can be difficult to differentiate it from effusion-based merely on X-ray and further imaging is often sought.[10]

Fig. 3 A 27-year-old patient came to the hospital with cough and evening rise of fever since 2 weeks. Chest radiograph shows right-sided moderate pleural effusion (marked by asterisk).

Thoracic ultrasound is a useful modality to visualize the pleural effusion in TB.[1] It is a cost-effective and readily available method in most developing countries. Even in resource-poor settings, with the advent of battery-powered and handheld ultrasound devices, it is now possible to diagnose even in remote and rural areas.[11]

Ultrasound is a superior modality to chest radiographs to diagnose very small amounts of pleural effusion and is also useful in distinguishing the different basal lung pathologies. A low-frequency phased array probe placed in the lower intercostal space provides good penetration to look for small amounts of fluid accumulated in dependent position.[12] Pleural fluid can be classified as simple or complex based on echogenicity and presence or absence of septations. In case, the pleural fluid is clear and mobile, it is considered as simple pleural effusion and is readily picked up on routine bedside ultrasonography.[13] As empyema starts to set in, small mobile internal echoes can be visualized in the pleural fluid and the underlying basal segments of lung demonstrate air bronchograms which are indicative of basal atelectasis. This kind of pattern is characterized as complex nonseptate pleural effusion. The movement of hyperechoic debris is often referred to as the plankton sign. With the disease progression, septations and locules begin to form and pleural fluid compresses over the lung parenchyma causing further collapse. It can be classified as a complex septated fixed effusion or complex septate mobile effusion based on mobility of septae[13] ([Fig. 4]). A predominantly hyperechoic pleural fluid is indicative of high cellular count. This hyperechoic cellular content creates layering by gravity and is called hematocrit sign.[13] Echogenicity of the lung starts to appear like the liver in progressive disease due to collapse.[12] Color Doppler can be utilized to look for the movement of pleural fluid. Lack of color uptake is indicative of thickened dense pleural fluid seen in advanced disease and empyema. M-mode ultrasonography is a helpful tool to look for the lung movement within the pleural fluid (also referred to as the sinusoid sign).[12]

Fig. 4 A 35-year-old patient, known case of old pulmonary tuberculosis, posttreatment, came to hospital with pain abdomen and breathlessness since 4 days. Routine ultrasonography showed right-sided mild pleural effusion (demonstrated with asterisk) with multiple thick septae (demonstrated via straight arrow). A differential diagnosis of pleural tuberculosis was made.

However, B-mode ultrasound has a few setbacks. It is not a reliable tool to diagnose pleural thickening and subtle pericardial effusions. HRCT chest is still the higher modality and investigation of choice to look for the same.[11] It is difficult to diagnose TB based solely on ultrasound findings. Clinical history, previous history of exposure, immunosuppression, human immunodeficiency virus status, endemicity, signs, and symptoms are all taken into account along with the microbiological and imaging features to arrive at a diagnosis. Even with all this information, sometimes, it can be challenging to differentiate PTB from other benign and malignant causes. Hence, higher modalities like contrast-enhanced CT (CECT) chest are often used to characterize pulmonary and extrapulmonary lesions and guide diagnosis.

The CT findings of PTB most commonly include circumferential pleural thickening followed by mediastinal pleural involvement, and pleural thickening > 1 cm. Nodular pleural thickening is seldom associated with PTB and is more indicative of a malignant pathology[9] ([Fig. 5]). However, pleural masses and nodules in an endemic setting with history of exposure should raise a suspicion of TB. PTB can present in this form with or without parenchymal and mediastinal involvement owing to lymphatic and blood spread of the mycobacterium.[14]

Fig. 5 Axial short tau inversion recovery (STIR) image in upper thoracic cavity showing STIR, hyperintense nodular thickening along the posterior chest wall of the right thoracic cavity (demonstrated by asterisk). Initial diagnosis of tuberculosis was made, however, on further investigations, patient was diagnosed with malignant mesothelioma.

A pictorial essay, written by Choi et al, documents the various complications of longstanding tuberculous pleural effusion. In chronic phase, tuberculous pleural effusion can become purulent and transform into an empyema. This is seen on CT as having the classical split pleura sign ([Figs. 6] and [7]). It can also present as a well-defined loculated pleural collection[15] ([Fig. 8]).

Fig. 6 Computed tomography (CT) done to evaluate a patient with pleuritic chest pain shows pleural effusion with enhancing walls indicative of empyema (demonstrated by asterisk) with adjacent consolidation (demonstrated by arrow). Acid-fast bacillus (AFB) analysis was done to confirm the initial suspicion of pleural tuberculosis.

Fig. 7 A 25-year-old lady with loss to follow-up for pulmonary tuberculosis visited the hospital with complaints of chest pain, fever, and cough. High-resolution computed tomography (HRCT) chest revealed mild right-sided pleural effusion with enhancing walls, consistent with diagnosis of pleural spread of pulmonary infection. Centrilobular nodules and fibrocavitatory changes were noted in bilateral lungs.

Fig. 8 A 30-year-old smoker visited the hospital with complaints of cough with expectoration. Acid-fast bacilli analysis came positive for pulmonary tuberculosis (TB). High-resolution computed tomography (HRCT) chest revealed well-defined peripherally enhancing loculated right-sided pleural effusion (locules demonstrated by asterisk).

It can further undergo fibrosis and calcification causing pleural thickening, pleural calcification, and fibrothorax. These features are easily identified in an HRCT chest as a soft tissue density filling the space between the chest wall and the lung parenchyma with or without calcific densities within. Sometimes, longstanding empyema can rupture through the parietal pleural and percolate along the anterior chest wall, most commonly in the subcutaneous tissue. This is called empyema necessitates. Pleural fluid can also communicate with the bronchial tree and form a bronchopleural fistula. This is seen in chest CT as air–fluid levels in the pleural space, communicating with the lung parenchyma. Finally, longstanding chronic inflammation of the pleural can have malignant transformation. Some of these malignancies are lymphoma, squamous cell carcinoma, histiocytoma, sarcoma, etc. CT features are enhancing soft tissue density mass lesions seen around the empyema.[15]

It is important to keep the differentials of tuberculous empyema in mind when diagnosing a case of complex pleural effusion. Malignant pleural effusions are most commonly confused with tuberculous pleurisy. Smooth pleural thickening is seen most commonly in tubercular effusions, while nodular pleural thickening should raise a suspicion for malignant etiology. However, in TB endemic areas, any form of pleural thickening with or without lung findings should raise a primary suspicion for TB.[9] Furthermore, other features that suggest a malignant etiology are soft tissue mass adjacent to the empyema, medialization of pleura, new onset of air–fluid levels in the empyema cavity, and chronic longstanding empyema.[15]

18F-fluorodeoxyglucose-positron emission tomography-CT can also be used for TB diagnosis. The degree and intensity of uptake by the pleura can help in the differentiation of benign and malignant effusions as well as active and inactive disease. It is further also used to monitor patient response to antitubercular treatment. However, it is a costly investigation and is seldom found in resource-poor settings.[10]

As per national guidelines, antitubercular therapy is recommended for 6 months for cases of PTB. Clinical improvement starts 2 weeks after initiation of treatment. Follow-up radiograph is recommended after 8 weeks to monitor treatment. Although the use of corticosteroids is seen to decrease the residual pleural fluid as well as reduce the pleural thickening, however, the complications of steroid therapy are far more and therefore steroid therapy should be avoided as per current guidelines.[10] Pleural fluid drainage forms the mainstay of diagnosis and treatment of tuberculous empyema. Ultrasound-guided thoracocentesis is the most widely used method with high success rates. Ultrasound guidance ensures correct site for tube placement as well as allows the physician to judge the type and length of needle required for the procedure. For most simple pleural effusions, straight needles are preferred. For complex septate empyemas, therapeutic drainage is done by keeping a catheter in situ. In recent literature, it is found that small bore catheters with thrombolytic cover is as good as large bore catheters and provide the same efficiency of treatment to patient with less pain and discomfort.[12] Medical thoracoscopy can be performed for thick purulent empyemas with septations within. A thoracoscope is introduced into the correct intercostal space followed by suctioning and irrigation of the pleural cavity. The septae are thoroughly broken down with the help of forceps and drain is placed in situ at the end of the procedure. Video-assisted thoracoscopy is another therapeutic option for patients with complex septate empyemas.[13] The drained fluid should be sent for biochemical and microbiological analysis and appropriate medicines should be started timely based on the bacteriological report.

 

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Conclusion

TB is a common communicable disease in most developing countries. In the spectrum of extrapulmonary TB, PTB is one of the most common presentations following TB lymphadenitis, often secondary to pulmonary TB. It most commonly presents as TB pleurisy but can progress to pleural thickening, empyema, pleural nodules, fibrothorax, and even undergo malignant transformation. Radiological modalities are often used for diagnosis and monitoring of patients. Chest X-ray is the primary screening modality used; however, several studies show that ultrasound can also be useful for raising suspicion of PTB. However, CECT thorax and HRCT thorax are more commonly used for diagnosis and are highly sensitive modalities. Confirmation is done based on pleural fluid analysis and biopsy.

 

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Conflicting Interest

None declared.

• References

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Publikationsverlauf

Artikel online veröffentlicht:
06. Dezember 2024