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Community-Acquired Pneumonia (CAP) is the first leading cause of death due to infection worldwide.Many gram-positive, gram-negative bacteria, funguses and viruses can cause the infectious pulmonary disease, and the severity of pneumonia depends on the balance between the microorganism charge, the body immunity defenses and the quality of the underlying pulmonary tissue. The microorganisms may reach the lower respiratory tract from inhaled air or from infected oropharyngeal secretions. The same organism may produce several different patterns that depend on the balance between the microorganism charge and the body immunity defenses.CAP is classified into three main groups: lobar pneumonia, bronchopneumonia and interstitial pneumonia.Lobar pneumonia is characterized by the filling of alveolar spaces by edema full of white and inflammatory cells. Necrotizing pneumonia consists of a fulminant process associated with focal areas of necrosis that results in abscesses. Bronchopneumonia or lobular pneumonia, is characterized by a peribronchiolar inflammation with thickening of peripheral bronchial wall, the diffusion of inflammation to the centrilobular alveolar spaces and development of nodules.The interstitial pneumonia represents with the destruction and esfoliation of the respiratory ciliated and mucous cells. The interstitial septa, the bronchial and bronchiolar walls become thickened for the inflammation process and lymphocytes interstitial infiltrates.Chest radiography represents an important initial examination in all patients suspected of having pulmonary infection and for monitoring response to therapy.Its role is to identify the pulmonary opacities, their internal characteristics and distribution, pleural effusion and presence of other complications as abscesses and pneumothorax.High spatial CT resolution allows accurate assessment of air space inflammation.The CT findings include nodules, interlobular septal thickening, intralobular reticular opacities, ground-glass opacities, tree-in-bud pattern, lobar-segmental consolidation, lobular consolidation, abscesses, pneumatocele, pleural effusion, pericardial effusion, mediastinal and hilar lymphoadenopaties, airway dilatation and emphysema.
KeywordsInfective Endocarditis Bronchial Artery Hemorrhagic Fever With Renal Syndrome Bronchial Wall Diffuse Alveolar Damage
1 Community-Acquired Pneumonia
Community-acquired pneumonia (CAP) is a frequent lower respiratory tract infection.
It is highly influenced by the geographic area and the population.
The microorganisms may reach the lower respiratory tract from inhaled air or from infected oropharyngeal secretions (Vincent et al. 1995). Droplet transmission from human to human is another usual mode of spread of the pulmonary infection, especially in immunocompetent patients and young children.
Clearance by mucociliary system can filter infective organisms 5–10 nm in diameter, so that microorganisms between 1 and 2 nm can reach the alveolar tissue. The alveolar infection depends on the balance between the virulence of the microorganism and body defenses due to cellular phagocytosis. There are several factors predisposing to the development of CAP as cardiovascular diseases, diabetes, uremia, immunodeficiency, obstructive pulmonary chronic disorders with mucociliary clearance insufficiency, and age.
Alcoholic patients and people with poor oral hygiene are particularly sensitive to develop pulmonary infections (Barlettand Finegold 1974).
The clinical presentation of pneumonia is frequently represented with sudden symptoms as high fever, cough, purulent expectoration, and deep chest pain. Neutrophilia is common.
CAP is classified into three main groups: lobar pneumonia, bronchopneumonia, and interstitial pneumonia (Bhalla and Mc Loud 1998).
Lobar pneumonia appears in the lung parenchyma periphery and then diffuses up to the hilum. It is generally limited to one pulmonary segment or lobe.
Bronchopneumonia occurs when infectious microorganisms produce acute bronchial mucosal inflammation and spread through the airway into the alveolar spaces determining pulmonary consolidation.
Interstitial pneumonia is determined by the infection of pulmonary interstitium and is mainly caused by viral organism.
The same organism may produce several different patterns that depend on the balance between the microorganism charge and the body immunity defenses.
The spectrum of bacteria responsible for CAP includes Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, and Klebsiella pneumoniae (American Thoracic Society 1995; Marom et al. 1999; De Paso 1991).
Among the types of CAP, S. pneumoniae is the most frequent causing bacteria, and it is associated with a high mortality rate in the elderly and childhood.
Haemophilus influenzae also is one of the most frequent bacteria causing CAP, because it frequently colonizes the human upper respiratory tract, especially the nasopharynx, and is considered to form part of the normal respiratory flora. It is also an important cause in the acute exacerbation of chronic obstructive pulmonary infectious disease (Kofteridis et al. 2009).
The viruses that most commonly cause pneumonia are respiratory syncytial virus, herpes simplex, parainfluenza virus, influenza virus, adenovirus, and cytomegalovirus.
The funguses that most commonly cause pneumonia are Pneumocystis, Aspergillus, and Candida.
1.2 Lobar Pneumonia
Lobar pneumonia is characterized by the filling of alveolar spaces by edema full of white and inflammatory cells. The inflammation generally begins at the lung mantle and then diffuses to the entire lobe through Kohn pores and peripheral small airways; usually it is limited by an interlobar fissure. The air bronchograms within the consolidation area are preserved (Fig. 2). Nodular pneumonia is frequently caused by fungal infections and is prevalent in young or immunocompromised patients.
A large solitary abscess or primary lung abscess can develop in a patient without underlying lung inflammation as a consequence of aspiration of oropharyngeal secretions in combination with impairment of systemic defense condition.
Necrotizing pneumonia, generally determined by Gram-negative bacteria, produces exfoliated pulmonary tissue within a cavity or diffuses microabscesses secondary to thrombosis of the vessel that supply the consolidation. Sometimes necrotizing pneumonia consists of a fulminant process associated with focal areas of necrosis that results in abscesses that can coalescence, resulting in large cavities that may exhibit thick fibrotic walls if they are chronic. There are large cavities with concomitant small cavities frequently associated with empyema (Winer-Muram et al. 1993). This feature is frequent in immunocompromised patients.
1.4 Interstitial Pneumonia
Interstitial pneumonia is frequently caused by virus.
The pneumonia can heal completely, but sometimes a chronic interstitial fibrosis can occur.
1.5 Radiographic Features
Chest radiography represents an important initial examination in all patients suspected of having pulmonary infection and for monitoring response to therapy.
Radiographic manifestations depend on the immune status of the patient and the presence of preexisting lung chronic alterations as emphysema, chronic bronchitis, and bronchiectasis and vary somewhat among the various species of causing microorganisms.
The most common radiographic findings include hazy ground-glass opacities, confluent or patchy airspace consolidations, cavitations, and poorly defined linear or reticular-nodular opacities (Chastre et al. 1998).
These alterations may involve mainly the perihilar regions, lower lung zones, or upper lung zones. They are usually unilateral but may involve both lungs. Other findings are pleural effusion and hilar adenopathy.
However, the bedside plain film, the projection effects, and the poor density resolution frequently limit the value of radiography as a diagnostic tool. Radiographic features are sometimes nonspecific, and the relatively low diagnostic accuracy of chest radiography can be improved with CT.
1.6 Computed Tomography Findings
CT has been shown to be more sensitive than x-ray plain film and provide additional information that affects diagnosis or management in up to 70 % critically ill patients (Heussel et al. 1997).
High resolution CT allows accurate assessment of airspace inflammation (Okada et al. 2012).
The distribution of parenchymal alterations is based on the evidence of their localization at CT scan. If the primary opacity is predominantly located in the inner third of the lungs, the pathology is classified as having a central distribution. A peripheral opacity is defined as a lesion localized in the outer third of the lungs. Zonal predominance is classified as either upper or lower. In the upper lung zone predominance, the alteration is located above the level of the tracheal carina, whereas in the lower zone predominance, it is located below the upper zone.
The CT findings include nodules, interlobular septal thickening, intralobular reticular opacities, ground-glass opacities, tree-in-bud pattern, lobar-segmental consolidation, lobular consolidation, abscesses, pneumatocele, pleural effusion, pericardial effusion, mediastinal and hilar lymphadenopathies, airway dilatation, and emphysema.
Nodules measure from 3 to 10 mm and are divided into three types: centrilobular nodules that are small nodules in centrilobular location, peribronchovascular nodules that are relatively larger nodules associated with the peribronchovascular bundle, and “random nodules” that are not associated with centrilobular structures or bronchovascular bundle.
They are defined as a dot-like opacities localized inside the center of a secondary pulmonary lobule. They are present around the peripheral pulmonary arterial branches or 3–5 mm from the pleura, interlobular septa, or pulmonary veins.
Hemorrhagic pulmonary nodules have a central area of soft tissue attenuation surrounded by a halo of ground-glass attenuation (Primack et al. 1994).
Pulmonary hemorrhage in association with nodules occurs in patients with herpes simplex virus, candidiasis, and cytomegalovirus pneumonia (Thurlbeck et al. 1991)
Interlobular septal thickening are defined as abnormal widening of the interlobular septa. Intralobular reticular opacity is considered to be present when interlacing line shadows are separated by a few millimeters (Fig. 9) (Austin et al. 1996).
The abscess can drain into a bronchus that leads to the classic air-fluid level, present in up to 72 % of cases (Fig. 3). The complete drainage of the cavity can lead to a pneumatocele.
Pneumatocele is a frequent consequence of an abscess drained in the lumen of a bronchus; it is a gas-filled area with a thin wall that may increase and can get ruptured into the pleural space, causing a pneumothorax. It can also heal completely, fading from the periphery to form a tiny thin-walled air-cyst or a linear scar.
Pleural effusion is better detected with CT than with radiography and is often associated with a high risk of empyema that requires prompt early drainage.
Mediastinal and hilar lymphadenopathies are evaluated when the minimal diameter of a lymph node is larger than 10 mm. Lymph node enlargement is very frequent in pneumonia and generally involves the paratracheal, tracheobronchial, and subcarinal mediastinal chains.
Airway dilatation predisposes to pneumonia and is considered to be present if the bronchial size exceeded that of the near pulmonary artery.
Pulmonary emphysema is frequently associated with pneumonia and is defined as scattered or diffuse areas of low attenuation without internal vascular structures in comparison with normal pulmonary parenchyma (Fig. 1).
Pneumonia is the first leading cause of death due to infection worldwide (Vilar et al. 2004a).
Many Gram-positive, Gram-negative bacteria, funguses, and viruses can cause the infectious pulmonary disease, and the severity of pneumonia depends on the balance between the microorganism charge, the body immunity defenses, and the quality of the underlying pulmonary tissue.
Among the types of CAP, S. pneumoniae is the most frequent causing bacteria, has a tendency to develop antibiotic resistance, and is associated with a high mortality rate in the elderly and childhood (Musher et al. 2002).
Radiographically pneumonia is divided into three patterns: lobar pneumonia, bronchopneumonia, and interstitial pneumonia (Muller et al. 2007).
Chest x-ray film is routinely performed for the initial evaluation of patients with suspect pulmonary infection, and it is considered the recommended tool for the diagnosis of CAP. However, chest x-ray film not always evidences all the findings of pneumonia, and it is limited by the interobserver variability in interpretation.
Especially in not clear or even negative chest radiography pattern, in patients with clinical symptoms, CT is recommended, for its high spatial resolution and the ability to evidence very early and minimal pulmonary alterations indicative of pneumonia.
2 Atypical Infections
Community-acquired pneumonias have been traditionally divided into “typical” and “atypical” pneumonias. The main aim of such a classification was to help the clinician narrow the differential diagnosis and choose an appropriate therapy based on the likely offending organism (Murray and Mason 2010).
Typical pneumonia is characterized by infection with bacteria such as Streptococcus pneumoniae, Klebsiella pneumoniae, and Haemophilus influenzae. It presents with symptoms such as acute onset of high grade fever with chills, cough with purulent expectoration, and pleuritic chest pain. Further evaluation of these patients reveals an elevated white blood cell count, elevated CRP, and lobar or segmental consolidation on imaging studies (Murray and Mason 2010).
Atypical pneumonia, as the name explains, does not show these typical features. An early use of this term in the literature dates back to 1938 when cases of patients who presented with milder symptoms and protracted course came to notice (Reimann 1938). These patients had more generalized symptoms like malaise, body pains, and low-grade fever with dry cough and flu-like symptoms. The causative organism could not be cultivated on regular media or stained with regular staining methods. Mycoplasma was first isolated in 1944 and was attributed as the etiology of primary atypical pneumonia (Eaton et al. 1944). However, several other organisms cause atypical symptoms.
Although originally used to signify any infection that was unusual in presentation, atypical pneumonia is now a broad term that includes infections caused by common organisms like Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila and viruses (Marrie et al. 1981). Atypical, however, does not mean that they are rare; they account for almost 15–20 % of the cases of CAP (Arnold et al. 2007). Mycoplasma pneumoniae is the most common cause of atypical pneumonia followed by Chlamydia pneumoniae and Legionella pneumophila (Arnold et al. 2007). Apart from these conventional pathogens, there are emerging infections with newer organisms like Hantavirus, human metapneumovirus that can also cause atypical pneumonia. In view of the current radiological discussion and similar radiological appearances shared by mycoplasma and various viruses, we will also be discussing some additional infections in this chapter, which, although not considered routinely under the heading of “atypical pneumonia,” are atypical enough to justify their inclusion here.
2.2 General Features
Infections with many, if not all, atypical organisms share some common features. Mycoplasma, chlamydia, and viruses have many similarities in their pathology, clinical, and radiological features. Grossly, these pathogens cause predominant histological changes in the respiratory epithelium and in the peribronchial interstitium (Müller et al. 2007; Müller 2003). The ensuing bronchiolitis and alveolitis are characterized by infiltration of the epithelium with mononuclear cells and presence of neutrophilic exudate in the lumen of the airways. These changes are predominantly seen in the terminal and respiratory bronchioles and manifest radiologically as peribronchial nodules (Müller et al. 2007; Müller 2003).
Bronchiolitis with exudate in the lumen of the airways is seen on radiographs as reticulonodular pattern and on CT as tree-in-bud nodules. As the nodules enlarge, they involve the entire secondary pulmonary lobule and are seen as “lobular” consolidation: these features are typical of bronchopneumonia pattern. Further extension into segmental and patchy lobar consolidation may be seen in advanced stages, and this may be difficult to distinguish from bacterial infection. Partial filling of the airways gives rise to ground-glass opacities (Müller et al. 2007).
Some infections like influenza and hantavirus cardiopulmonary syndrome, on the other hand, cause rapidly progressive pneumonia with diffuse alveolar damage (Kim et al. 2002).
The clinical course of atypical pneumonias is generally subacute, the WBC counts are generally normal, and the imaging features are heterogeneous and nonspecific.
2.3 Radiological Aspects
Diagnosis of pneumonia requires a combination of clinical, microbiological, and radiological features. Chest radiograph is usually sufficient to confirm the diagnosis. It also helps in follow-up of the patients and evaluation of the response to treatment. CT scans are not routinely recommended but are helpful in case of doubtful features on chest radiographs, when no adequate response to the treatment is noted and when complications or underlying pathology is suspected (Vilar et al. 2004b). CT scan can be further helpful in suggesting an etiological diagnosis. In indeterminate cases, CT-guided procedures come in as problem-solving tools for the correct diagnosis.
2.4.1 Mycoplasma Pneumonia
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, particularly in young children. It is the smallest free-living organism, measuring approximately 125–150 microns in size which is similar to that of myxovirus (Marrie et al. 2012). Lack of cell wall makes them highly pleomorphic.
Mycoplasma pneumoniae was first isolated from the sputum of a patient with “atypical pneumonia” by Eaton et al. and was initially considered to be a virus due to its ability to pass through bacterial filters. Subsequent studies led to its identification as bacteria (Cunha 2010).
Mycoplasma pneumonia is commonly seen in young children and adolescents and shows a declining incidence in adults (Meyer Sauteur et al. 2016). It spreads through droplet spread or direct contact. The incubation period is around 1–2 weeks (John et al. 2001).
Clinical symptoms resemble a viral infection and are characterized by mild symptoms like dry cough, headache, malaise, and low-grade fever (John et al. 2001). In view of these mild symptoms, it is also called as “walking pneumonia” (Meyer Sauteur et al. 2016). However, sometimes severe infection and extrapulmonary manifestations may also be seen. In one study by Marrie et al., common extrapulmonary manifestations were thrombocytosis, hemolysis, Guillain-Barré syndrome, and pulmonary hemorrhage (Marrie et al. 2012). In asthmatic patients, it can cause an acute exacerbation of asthma and present with acute dyspnea.
Typically, the WBC counts remain in the normal range. A secondary bacterial infection is likely when they are elevated (John et al. 2001).
An attempt to suggest the offending organisms on radiology can be worthwhile for two main reasons: firstly, infection with these cell wall-deficient bacteria calls for treatment with antibiotics other than the usual cell wall synthesis inhibitors like penicillin, which are otherwise suitable for typical infections with pneumococcus. Laboratory tests take time, pending, which a radiological diagnosis can prove helpful in clinical decision making. Secondly, in appropriate settings, radiological features, although not highly specific, can be suggestive of the diagnosis in many cases.
The chief pathology is acute cellular bronchiolitis with bronchial wall inflammation, peribronchial infiltrates of lymphocytes and macrophage, and intraluminal exudative fluid (Pipavath et al. 2005; Muller and Miller 1995). This is seen radiologically as thickening of bronchial wall and centrilobular nodules.
2.4.2 Chlamydia pneumoniae
Chlamydias are obligate intracellular bacteria that possess a cell wall. They exist in two forms: a smaller extracellular elementary body and a larger intracellular form called the reticulate body (Webb et al. 2011). Three species of chlamydia area known:
Chlamydia trachomatis typically causes ocular infection (trachoma) and sexually transmitted disease but may cause pneumonia in infants who are born to infected mothers.
Chlamydia psittaci is a pathogen in birds (causing psittacosis) and may cause respiratory infections in humans. The mode of infection is through aerosols containing bacteria generated from infected birds (Knittler and Sachse 2015).
Chlamydia pneumoniae was the third species to be discovered, first isolated in 1968 during trachoma vaccine trail and accounts for an estimated 10 % of the CAP cases (Kuo et al. 1995). It is a common cause of atypical pneumonia.
Transmission of infection occurs through respiratory secretions. Incubation period is several weeks.
Symptoms tend to be protracted and are subacute in onset. Prolonged cough and low-grade fever are typical features. Initial prodromal phase of upper respiratory tract symptoms like pharyngitis and hoarseness of voice are not uncommon.
The infection is typically mild, and extrapulmonary symptoms are less common in comparison to mycoplasma infection. It has also been implicated in coronary artery disease.
CT features consist of bronchopneumonia with consolidation, GGO, peribronchial thickening, and nodules, similar to mycoplasma infection. However, pleural effusions are more common in patients with Chlamydia pneumoniae, bronchial wall thickening and centrilobular nodules more common in mycoplasma infection (Okada et al. 2005). Some studies described increased prevalence of emphysema and bronchial dilatation in Chlamydia pneumoniae pneumonia; COPD is an important risk factor for chlamydia (Hahn 1999; Karnak et al. 2001).
2.4.3 Legionella pneumophila
Legionella pneumonia is an atypical pneumonia, first discovered in 1976 due to an outbreak in a convention in Philadelphia (Fraser et al. 1977). The source of infection was later narrowed down to the cooling system of the air conditioner with circulating water which acts like a conducting medium for the bacteria.
It is a Gram-negative obligate intracellular bacterium that is a parasite of freshwater protozoans. It tends to colonize in various water facilities and causes outbreaks of infection when aerosols containing the bacteria are inhaled (Fields et al. 2002). In humans, it infects the macrophages, where it resides and multiplies.
Legionella pneumophila is described to cause two diseases: Legionnaires’ disease which is a severe multisystemic infection and pneumonia with a long incubation period from 2 to 10 days and Pontiac fever which is a mild clinical illness with flu-like symptoms and a short incubation period of 36 h. Legionella pneumophila serogroup 1 accounts for most of the cases (Fields et al. 2002).
Legionnaires’ disease varies from mild to severe disease requiring ICU care. It tends to cause electrolyte abnormalities, typically hyponatremia and hypophosphatemia, the presence of which must raise the suspicion of this infection. Presenting symptoms are usually constitutional like fever, myalgias, headache, confusion, and diarrhea which are seen early in the course of the disease, and then nonproductive cough appears later (Tsai et al. 1979).
Radiological features are usually nonspecific and resemble bacterial lobar pneumonia.
Radiographs show patchy peripheral consolidations initially. Airspace consolidation due to alveolitis is typical. Bilateral, multilobar, and multisegment consolidation and ground-glass opacities are the most common radiological features on CT (Yagyu et al. 2003). Centrilobular nodules and diffuse peribronchial thickening characteristic of mycoplasma and chlamydia are less commonly encountered in legionella (Kim et al. 2007). Cavitation may be seen occasionally in immunosuppressed individuals and patients on high steroids (Fairbank et al. 1991). Pleural effusions are seen in up to half of the patients and are usually mild or moderate. Delayed clearing up of the infiltrates and residual fibrosis may occasionally be seen.
Lower respiratory tract infections can be caused by various viruses, and it is estimated that approximately 10 % of infections in CAP are due to viral etiology (ref). Along with the various radiological features, knowledge of the clinical history can be invaluable in narrowing the differential diagnosis. For example, in immunocompetent host, influenza virus is commonly implicated as an offender. In immunosuppressed individuals, however, the usual inciting organisms are herpes, cytomegalovirus, and adenovirus (Kim et al. 2002).
Viruses can be divided into (a) RNA viruses, myxoviruses (influenza, RSV, measles), coronavirus, and hantavirus, and (b) DNA viruses, adenovirus and herpes group including CMV and varicella zoster.
2.5.1 Influenza Virus
Influenza virus belongs to the family Orthomyxoviridae and is a single-stranded RNA virus. It has three predominant serotypes: influenza A, B, and C. Influenza A is responsible for majority of the epidemics and pandemics. Influenza virus A and B may cause pneumonia, while C causes only sporadic mild infections (Webb et al. 2011).
Infection with influenza virus is usually self-limiting. It favors secondary bacterial infection through various mechanisms like altering the respiratory epithelium. Diabetes mellitus, pregnancy, extremes of age, immunosuppression, and underlying pulmonary or cardiac conditions are some of the factors that predispose to a fulminant infection and pneumonia, and death within 24 h may be seen in extreme cases (Oikonomou et al. 2003). Such an infection is characterized histologically by diffuse alveolar damage.
2.5.2 Respiratory Syncytial Virus
It is an RNA virus belonging to Paramyxoviridae family. Almost all infants are infected with RSV by 2 years of age (Drysdale et al. 2016). RSV typically causes upper respiratory tract infections, otitis media, bronchiolitis, asthma-/viral-induced wheezing, and pneumonia. Bronchiolitis may be seen in up to 80 % of the cases (Drysdale et al. 2016). In immunocompromised individuals, it can cause severe pneumonia with high mortality (Mayer et al. 2014).
In addition to bronchial wall thickening and peribronchial nodules, typical features of RSV infection on radiography are air-trapping and hyperinflation due to bronchiolitis (Müller et al. 2007). CT reflects the features of bronchopneumonia and bronchiolitis. Multifocal consolidations/GGO with tree-in-bud nodules may be seen interspersed with areas of air-trapping (Mayer et al. 2014).
It is a febrile illness with rash caused by an RNA virus belonging to Paramyxoviridae family. It spreads from one person to another through droplet spread. The clinical manifestations are more severe in adults and immunocompromised hosts.
Bronchial wall thickening, centrilobular nodules, GGO, and interlobular septal thickening are seen on CT, and the features are nonspecific (Franquet 2011).
Coronaviruses, commonly implicated in cold, are RNA viruses of Coronaviridae. In 2002, a new strain caused an outbreak in China which spread rapidly throughout the world (Peiris et al. 2003). This was called SARS-coronavirus (severe acute respiratory syndrome). Transmission occurs through droplet spread; incubation period varies from 2 to 14 days (Peiris et al. 2003).
Typical symptoms are fever with myalgia and cough. Characteristic early CT findings include focal ground-glass opacities and crazy-paving pattern which are scattered in distribution. Subsequent development of consolidations may be seen. Air leak syndromes with development of spontaneous mediastinum or pneumothorax have also been reported. Residual fibrosis and scarring may also be seen (Chan et al. 2004).
Hantaviruses are a group of RNA viruses belonging to the family Bunyaviridae (Mattar et al. 2015). Unlike other infections of Bunyaviridae, infection with hantaviruses is a rodent-borne zoonosis that spreads through inhalation of rodent secretions (feces, urine, or saliva), and humans are accidental hosts (Manigold and Vial 2014). Each species of hantavirus is associated with a unique rodent host, and thus the epidemiology of hantavirus infections correlates closely with the geographical distribution of the respective rodents (Manigold and Vial 2014).
Infection with hantaviruses causes two distinct clinical pictures: hemorrhagic fever with renal syndrome (HFRS) which is more common in Europe and Asia, caused by the “old world” hantaviruses, and hantavirus cardiopulmonary syndrome (HCPS) which is more common in the Americas, caused by the “new world” hantaviruses (Mattar et al. 2015; Manigold and Vial 2014). Close to 150,000–200,000 cases occur every year, commonly in Asia (Manigold and Vial 2014). In Germany, a peak in 2012 with more than 2800 new cases was reported (Kruger et al. 2013).
Pathologically both these infections are characterized by breakdown of the endothelial barrier in blood vessels and marked vasodilatation.
HFRS is characterized by fever followed by hypotension and petechial hemorrhages due to vascular leakage, oliguric phase, polyuric phase, and convalescence. Oliguric phase is the most critical phase characterized by renal failure and pulmonary edema, and most of the case fatalities occur in this stage.
After an incubation period of 9–35 days, HCPS is characterized by abrupt onset of fever and other constitutional symptoms. In the next cardiopulmonary phase, cough, dyspnea, tachycardia, and hypotension occur due to extravasation of fluids as a result of increased capillary leakage. Rapidly progressive noncardiogenic pulmonary edema and cardiogenic shock may be seen with respiratory failure and need for ventilator support. Case fatality rate is high (Manigold and Vial 2014).
They are DNA viruses belonging to Adenoviridae family. Many serotypes exist.
Adenovirus is a common cause of upper respiratory tract infection in children. Severe infection is seen in immunocompromised patients. It causes sequelae such as bronchiectasis, obliterative bronchiolitis, and Swyer-James syndrome (unilateral hyperlucent lung).
Pathologically, severe adenovirus pneumonia is characterized by areas of hemorrhagic consolidation, interspersed with air-trapping, atelectasis, and diffuse alveolar damage (Becroft 1967). In mild cases, inflammatory cell infiltrate in the alveoli and interstitium is seen (Chong et al. 2006).
Radiographs show unilateral or bilateral parenchymal opacities. Especially in children, areas of overinflation and atelectasis may be seen (Kim et al. 2002). On CT, extensive GGO with or without consolidations are noted. GGO correlates with areas of diffuse alveolar damage. In a study by Chong et al. in five adults with adenovirus pneumonia, one patient had shown crazy-paving appearance (Chong et al. 2006).
2.5.7 Herpes Simplex Type 1
Herpes simplex type 1 is a DNA virus of the Herpesviridae, along with CMV and varicella zoster virus. Primary infection is usually asymptomatic, but can manifest as pharyngitis or gingivostomatitis. Following initial infection, it remains latent and can undergo reactivation at a later stage and manifest as esophagitis or tracheobronchitis.
Pneumonia due to HSV-1 occurs commonly due to contiguous spread from upper respiratory tract or aspiration and less commonly due to hematogenous spread (Graham and Snell 1983; Ramsey et al. 1982). HSV-1 pneumonia is almost exclusively seen in immunosuppressed individuals or in patients with squamous metaplasia of the airways due to intubation, burns, or chronic smoking (Ramsey et al. 1982).
Fever, dyspnea, chest pain, and productive cough are usual clinical features. Herpes labialis and extensive oropharyngeal lesions may also be seen (Simoons-Smit et al. 2006).
The epithelial lesions are characterized by ulceration and necrosis. Pneumonia shows alveolar necrosis and exudate with inflammation (Kim et al. 2002).
On radiography, patchy segmental or lobar consolidation is usually seen, and pleural effusions are common (Aquino et al. 1998). On CT multifocal areas of GGO and consolidation are seen (Kim et al. 2002).
Cytomegalovirus (CMV) is a member of herpes family and is a DNA virus. It is well known to cause opportunistic infections in immunosuppressed individuals especially in bone marrow or solid organ transplant recipients and AIDS patients.
Clinical features include fever, cough, and dyspnea.
The pathological features of CMV infection in transplant recipients are reported to be different from those seen in AIDS patients. In transplant recipients, predominant necrotizing pneumonia is seen due to immune-mediated mechanisms, and CMV pneumonia is seen in the first few months after transplantation. AIDS patients, on the other hand, have insufficient immune response and show effects primarily due to the cytopathic effect of the virus with diffuse alveolar damage (Kim et al. 2002).
Radiographic manifestations are nonspecific and consist of reticulonodular pattern and/or airspace consolidations. CT features consist of diffuse or focal ground-glass opacities (GGO), multiple nodules, and lobar consolidation. Nodular lesions with surrounding GGO (halo sign) may be occasionally seen, GGO representing hemorrhage or inflammation (Franquet et al. 2003). Dense consolidation or mass-like opacities may be seen in AIDS patients especially with Kaposi’s sarcoma (McGuinness et al. 1994).
2.5.9 Varicella Zoster
Varicella zoster is another virus belonging to Herpesviridae group. It causes two major manifestations: chickenpox (varicella) and herpes zoster. Pneumonia occurs most commonly in patients with chicken pox, although it may be seen in both forms (Müller et al. 2007).
Chickenpox is usually seen in children 2–8 years old; however, in recent times, the incidence in adults is increasing due to various factors (Mohsen and McKendrick 2003). While the common varicella infection in children is usually benign, infection in adults has a more fulminant course with a 25 times increased risk of pneumonia and consequent high mortality (Mohsen and McKendrick 2003).
Predisposing factors for the development of varicella pneumonia are immunosuppression, chronic lung diseases, pregnancy, or underlying malignancy like leukemia or lymphoma (Müller et al. 2007). Varicella pneumonia presents about 1–6 days after the onset of rash with cough, dyspnea, fever, and sometimes chest pain and hemoptysis (Mohsen and McKendrick 2003).
The pulmonary lesions in varicella seem to be due to hematogenous spread rather than airborne entry. The lesions are characterized by endothelial damage in pulmonary vessels with focal hemorrhagic necrosis, mononuclear infiltrates in the alveolar walls, and exudates in the alveoli (Mohsen and McKendrick 2003). Later small nodules are seen which are characterized by outer lamellated fibrous capsule and inner necrotic or hyalinized collagen with varying degrees of calcification (Kim et al. 1999).
Although radiography and CT can be helpful in excluding a CAP, they may not be accurate in suggesting an etiological diagnosis. In every case, careful attention to the clinical history and radiological findings may help to narrow down the etiology and suggest the diagnosis.
Tuberculosis is often a challenge to the clinicians and radiologists alike, particularly in areas where it is not endemic. As the clinical signs and symptoms are often nonspecific, extra attention and a high degree of suspicion are required to make the right diagnosis.
As the manifestations of tuberculosis are a result of the interaction between the offending bacteria and the host immune system, there is no definite radiological picture that defines or is typical for tuberculosis and a wide range of differential diagnoses exist. However, some features, particularly when seen in typical distributions and typical combinations, can be very helpful in suggesting the right diagnosis, as discussed below.
Tuberculosis (TB) or captain of all these men of death is one of the oldest diseases known to mankind. It is still a disease of global concern, affecting millions of people worldwide every year. It is a leading cause of death among infectious diseases. Together with HIV, TB accounted for a staggering 1.5 million deaths in 2014 (World Health Organization 2015). Ninety-five percent of these deaths were reported in low- to middle-income countries, where tuberculosis is highly prevalent (World Health Organization 2015).
Although the incidence of TB globally has been showing a declining trend for several years, still an estimated 9.6 million new cases were reported by WHO in 2014. Majority of these cases were reported in Southeast Asia, Western Pacific, and Africa with highest number of incident cases seen in India, Indonesia, and Nigeria. 12 % of these patients were HIV positive, and notably 75 % of HIV-positive people with tuberculosis lived in Africa (World Health Organization 2015).
Europe accounts for 4 % of TB burden in the world with close to 1000 new cases per day (European Centre for Disease Prevention and Control 2015). Within the EU/EEA (European Union/European economic area), an overall declining trend in TB reporting in the last 10 years has been observed. It is noteworthy that a significant 28 % of cases were of foreign origin. In some countries like Luxemburg, Malta, Norway, Sweden, and Switzerland, the TB cases of foreign origin accounted for >70 % cases, highlighting the increased prevalence in migrants, with an increased prevalence of MDR-TB in these groups of patients (European Centre for Disease Prevention and Control 2015; Odone et al. 2015).
The early diagnosis and treatment are further challenged by the development of multidrug-resistant and extensively drug-resistant tuberculosis. Multidrug-resistant tuberculosis (MDR-TB) is defined by resistance to the two most powerful first-line drugs, isoniazid and rifampin. WHO reported that in 2014, around 3.3 % of new cases and 20 % of previously treated cases had MDR-TB. Extensively drug-resistant tuberculosis (XDR-TB) is defined as MDR-TB with additional resistance to at least one fluoroquinolone and one of the second-line injectable drugs (World Health Organization 2015). It is estimated that around 9.7 % people with MDR-TB have XDR-TB (World Health Organization 2015).
These large numbers of TB prevalence and drug resistance signify the importance of early diagnosis and treatment. To understand imaging features in tuberculosis, an understanding of the epidemiology and pathophysiology is an important prerequisite so that a high index of suspicion in appropriate clinical settings can favor a timely diagnosis, avoid life-threatening complications, and prevent further spread of this dangerous disease.
TB is caused by bacteria of the group Mycobacterium tuberculosis complex. It comprises of various bacteria; common ones causing infection in humans are Mycobacterium tuberculosis and M. bovis. M. tuberculosis accounts for the majority of tuberculosis cases, whereas M. bovis is less commonly implicated due to routine pasteurization of milk.
M. tuberculosis is an obligate aerobic, non-sporing, nonmotile bacillus. Its cell wall is rich in mycolic acid, accounting for its staining properties. It resists staining by the usual Gram method, being neither Gram negative or positive. When stained with dyes such as Ziehl-Neelsen, it resists decolorization by the acid alcohol and is therefore called acid fast. It is a facultative intracellular parasite, which preferentially resides in the human macrophages. Many of these properties explain its pathogenicity and virulence.
Person-to-person transmission of infection occurs through inhalation of droplet nuclei which are expelled/discharged into the air when a patient with active pulmonary or laryngeal TB coughs, talks, or sings (Leung 1999). Patients with cavitation in the lungs, sputum culture-positive TB, and sputum smear-positive pulmonary TB who expectorate around 106–107 acid fast bacillus (AFB) per mL of sputum are more contagious than sputum-negative patients (as they expectorate usually less than 103 AFB per ml) (Sepkowitz 1996). Additional factors that favor the spread are an improper ventilation which promotes prolonged suspension of the droplet nuclei, crowded living conditions, and prolonged contact with an “open” case.
Open tuberculosis: Not all patients with pulmonary tuberculosis are infectious to others. Those patients who show sputum positivity for the acid fast bacilli are notably more contagious than sputum-negative cases (see above). The presence of cavitation and evidence of endobronchial spread (tree-in-bud) on radiological examination serves as an indication that there is a communication between the lung lesions and the airways, thereby increasing the risk of infectivity. These “open” cases must be isolated from others.
3.4 Pathogenesis, Clinical, and Radiological Features
Classical teaching explains the lesions of pulmonary tuberculosis based on the time since infection. It states that primary disease after a recent infection manifests itself in lower lobes, lymph nodes, or as pleural effusion, whereas reactivation of latent tuberculosis causes an upper lobe predominant disease with cavitation. Although this classical “dogma” of tuberculosis which classifies the lesions based on the time since infection is widely accepted since time immemorial, it has been challenged in the recent past (Rozenshtein et al. 2015).
Recent studies based on molecular epidemiology using restriction fragment length polymorphism suggest that radiological features of pulmonary tuberculosis do not depend on time since infection (Jones et al. 1997; Glynn et al. 1999). Rather, the lesion manifestations depend on the immune status of the host. Infected persons who are immunocompetent develop apical disease with cavitation. Patients who are immunodeficient, on the other hand, develop lower lobe predominant disease with consolidation and lymphadenopathy without evidence of cavitation. This group includes HIV-positive adults with low CD4 counts and also children, as their cellular immunity is relatively weak.
This concept is further supported by the fact that HIV-positive patients with TB who have CD4 counts >200/mm3 are more likely to develop apical predominant disease with cavitation (positive predictive value >78 %) and those patients with CD4 cell counts <200/mm3 are more likely to have a predominantly lower lobe disease (positive predictive value 84 %), irrespective of the time since infection (Post et al. 1995).
Further studies in the coming future can make this distinction clear. Though the ongoing debate about the pathophysiology of TB has been discussed above, the terms from classical teaching, i.e., primary and reactivation tuberculosis, will be used here for the sake of simplicity as most of the literature is based on this terminology.
Tuberculosis in a previously unexposed individual is described as primary tuberculosis. Once inhaled, the bacilli traverse the upper airways and reach the alveoli where they are phagocytosed by the pulmonary macrophages.
The subsequent outcome of infection depends on the interaction between the microbicidal capacity of the macrophage and the virulence of Mycobacterium tuberculosis bacillus (MTB). If the MTB are destroyed at this stage, no disease develops. But if the macrophage is not able to contain the infection or the bacillus is highly virulent, MTB multiplies multifold before the macrophage bursts. Release of various cytokines by the macrophages attracts further macrophages which phagocytose the released MTB (Knechel 2009). In the first 2–3 weeks, development of T cell-mediated immunity causes activation of macrophages which then destroy the MTB within them (van Crevel et al. 2002). This causes the formation of a typical granuloma with a caseation necrosis in the lungs and the draining lymph nodes. This attributes to the typical imaging features in primary TB. Thus, in tuberculosis destruction of the host tissue occurs as a part of the host immune response.
Once the infection is successfully brought under control, the patient becomes asymptomatic, although MTB may still lie inactive within the macrophages. Healing of the lesions occurs with fibrosis, and dystrophic calcification may also be seen (Pratt 1979).
In immunosuppressed hosts, extensive hematogenous spread of infection can manifest as a miliary TB, with multi-organ involvement.
Many years, typically 3–5 years later, commonly due to reactivation and less commonly due to reinfection, there is a resurgence of the disease (Leung 1999). This stage, in previously sensitized individuals, is known as postprimary TB.
The disease is typically seen in apical and posterior segments of the upper lobes and apical segments of the lower lobes, probably due high oxygen tension and impaired lymphatic drainage in these areas which favor the growth of this obligate aerobe (Leung 1999). As the infection proceeds, the area of necrosis increases in this area, under liquefaction, and then decompresses itself into an adjacent bronchus. As a result of the formation of this communication with airways, air enters the lung parenchyma in this area of consolidation, forming what is a typical lesion of the secondary TB, that is, a cavity. As the contents of the cavity are discharged into the bronchus, the patient develops cough with expectoration. Spread of these discharges into the airways may also give rise to typical imaging appearance of endobronchial spread. When there is no cavity, endobronchial spread of Tb may still be seen due to endobronchial rupture of a lymph node, hematogenous spread of infection (Leung 1999).
3.4.2 Clinical Features
Majority of the TB cases are pulmonary with around 1/3 cases being extrapulmonary.
The clinical symptoms of tuberculosis are to an extent dependent on patient’s age and immune status. At extremes of age, in children and elderly, the symptoms tend to be nonspecific and cause a delay in the diagnosis. Primary TB is most commonly seen in children, particularly in endemic areas. However, it is increasingly being seen in adults too.
The usual symptoms in pulmonary TB are cough with expectoration, low-grade fever with evening rise of temperature, malaise, and loss of weight (American Thoracic Society 1990). Hemoptysis and chest pain may also be seen.
Primary pulmonary tuberculosis manifests itself radiologically variably as parenchymal opacities, lymphadenopathy, and/or pleural effusion. Chest radiography is usually the first imaging modality to suspect primary TB; however, the lesions are better appreciated on CT.
The granulomatous lesion in the pulmonary parenchyma is seen radiologically as an area of consolidation. It tends to be unilateral, in the middle or lower lobe, and is commonly observed on the right side (Leung et al. 1992). Multifocal involvement may also be seen in 12–24 % (Woodring et al. 1986). It is usually homogenous and dense, segmental, or lobar in distribution. The lesion can also be nodular or linear in appearance.
In two-thirds of the cases, the consolidation resolves without any sequelae (Leung 1999). In the remaining one-third cases, it heals with the formation of a linear scar or fibrosis, with calcification. This focus is called as Ghon’s focus (Leung 1999). Tuberculomas which are mass-like opacities and satellite calcifications may be also seen in 9 % of the cases.
The enlarged lymph nodes can cause extrinsic compression of the airways. Complete obstruction of the lumen manifests as segmental or lobar collapse of the distal lung (Andreu et al. 2004). Partial obstruction, on the other hand, can present with air-trapping and hyperinflation of the involved lobe due to ball-valve-like effect and subsequent trapping of air (Arora et al. 2013).
Healing of the granulomatous lesions with dystrophic calcification leads to the formation of calcified hilar lymph node with a calcified pulmonary Ghon’s lesion, also known as Ranke’s complex. It serves as a telltale sign of previous TB infection in the past.
Reactivation tuberculosis is characterized by parenchymal opacifications, predominantly in the posterior and apical segments of upper lobes and apical segment of lower lobes. Multisegmental involvement is often seen. Atypical distribution involving exclusively other segments is rare and is seen in approximately 5 % of the cases of postprimary TB (Woodring et al. 1986). Cavities are seen in 40–45 % of cases of postprimary disease. They may be single or multiple and have varied appearances ranging from thick walled to thin walled. Cavities usually occur in areas of consolidation. Cavities may mimic carcinoma; however, careful attention to adjacent bronchogenic spread with tree-in-bud lesions and satellite nodules may aid in the diagnosis.
When an area of caseous necrosis erodes into adjacent airways, bronchogenic spread is seen. It is an important hallmark of the activity of the disease. CT is more sensitive in demonstrating bronchogenic spread: in one study by Im et al., bronchogenic spread was notably seen in 95 % of patients with postprimary TB, while radiography showed these findings reliably only in 20 % patients (Im et al. 1993). Earliest markers of bronchogenic spread are sharp centrilobular nodules or linear branching opacities 2–4 mm in diameter. In extensive bronchogenic spread, a typical tree-in-bud appearance is described, the stalk represents the distal airways, and the bud represents alveolar ducts and bronchioles, which are filled with caseous material. Other signs of bronchogenic spread are bronchial wall thickening with or without bronchiectasis, poorly defined nodules 5–8 mm in diameter. Interlobular septal thickening may also be seen. These changes signify an active underlying disease and regress with effective treatment in 5–9 months (Im et al. 1993).
Complete regression of the parenchymal lesions may be seen when healing occurs before the development of caseous necrosis, which is however rare (Pratt 1979). In posttreatment changes with development of distortion of bronchovascular structure, fibrotic bands in areas of caseous necrosis are well established. Areas of paracicatricial emphysema may develop due to bronchostenosis and traction (Im et al. 1993). Marked fibrotic reaction with upward hilar retraction is typical and may be seen in one-third of the cases. Apical pleural thickening, usually less than 1 cm, may also be occasionally seen (Woodring et al. 1986).
When to Think of TB?
Patient features: Migratory background, poor immune status
Radiological features: Primary TB: Unilateral dense segmental or lobar consolidation in lower or middle lobes, lymphadenopathy with central hypodensity on CECT
Reactivation TB: Cavitation in apical segments, centrilobular tree-in-bud nodules, with or without sequelae of primary TB infection
Hilar and mediastinal lymphadenopathy is less likely in postprimary tuberculosis. Spontaneous pneumothorax may be seen in extensive cavitary disease, although rare.
At any stage, either after primary or postprimary, a fulminant infection can give rise to disseminated infection with multiple granulomas seen in various organs. These granulomas resemble millet seeds, and thus the term “miliary” tuberculosis was used to describe them. Various conditions that predispose to the development of miliary TB are HIV/AIDS, malnutrition, diabetes mellitus, underlying malignancy, immunosuppression, treatment with corticosteroids, and immunomodulators (anti-TNF alpha agents) (Sharma et al. 2012).
In some cases, military tuberculosis can progress to adult respiratory distress syndrome. Spontaneous pneumothorax due to rupture of subpleural nodules has also been reported (Sharma and Kumar 2002).
3.5 Pleural Involvement
Pleural effusion can be seen not only as a part of primary TB but also in patients with reactivation TB and is thus not specific for any stage of TB.
It occurs supposedly due to a delayed hypersensitivity reaction as a result of rupture of a caseating subpleural focus into the pleural cavity. The release of inflammatory mediators causes accumulation fluid in the pleural space, which is an exudate.
Tuberculous pleuritis often presents acutely with rapid onset of pleuritic chest pain that is worsened by deep breathing, fever, and cough. In HIV-positive patients, a more subacute course is described. It is usually unilateral, often seen on the same side of the parenchymal lesion. Isolated pleural effusions without any parenchymal lesion are not rare.
On ultrasound examination, it often shows septations which are usually not appreciated on CT (Cardinale et al. 2015). On contrast-enhanced CT, pleural fluid of fluid density with smooth peripheral pleural enhancement, “split pleura” is typical (Yilmaz et al. 1998). Presence of a changing air-fluid level in the pleural space mandates ruling out a bronchopleural fistula (Johnson et al. 1973).
3.6 Airway Involvement
The involvement of airways in tuberculosis is seen in 10–20 % of patients with pulmonary tuberculosis (Moon et al. 1997). Various mechanisms responsible for the involvement of airways are spread of infection from the parenchymal lesion along the peribronchial lymphatic channels, implantation from infected sputum, erosion of an adjacent lymph node, or hematogenous spread (Moon et al. 1997; Kim et al. 1997).
Acute tracheobronchitis with involvement of the distal trachea and the proximal bronchi may be seen (Kim et al. 1997). Tracheobronchial TB is characterized commonly by a long-segment thickening (>3 cm) (smooth or irregular), causing circumferential narrowing of the airways. Less common appearances are that of a granulomatous, polypoid ulcerated mass (Andreu et al. 2004).
Chronic inflammation of the airways may cause tracheal or bronchial stenosis. Traction bronchiectasis due to fibrosis is often seen as sequel of infection.
A calcified peribronchial node that usually erodes into the adjacent bronchus is a common cause of broncholithiasis. Common sites are the proximal right middle lobar bronchus and anterior segmental bronchus of the right upper lobe.
3.7 Pericardial Involvement
Tuberculous pericarditis is seen in around 1 % pulmonary TB patients; the incidence is rising due to HIV-TB coinfection (Mayosi et al. 2005). In HIV-infected groups, 85 % of the cases of pericardial effusion are due to TB (Ntsekhe and Hakim 2005). It may present as pericardial effusion, constrictive pericarditis, or a combination of both.
Via infected mediastinal lymph nodes: predominant in immunocompetent individuals, it is largely a hypersensitivity reaction with paucibacillary status.
Via hematogenous route: more often encountered in HIV-positive and other immunosuppressed individuals, where is it often a more florid infection with a multibacillary status (Ntsekhe and Mayosi 2013).
Less common mode of spread is via direct spread from an adjoining pulmonary infection.
Typically, an insidious onset, with complaints of fever, dyspnea, chest pain, and malaise, is described. Cardiac tamponade may be frequently seen and is a late feature. Acute presentation with dyspnea, fever, and retrosternal chest pain is also possible.
On routine chest radiography, enlarged cardiac silhouette is seen in tuberculous effusion. Concomitant evidence of active pulmonary tuberculosis may be seen in 30 % of the individuals, and 30–50 % may show pleural effusions (Reuter et al. 2005). Another interesting feature to note is that the hilar lymph nodes are not usually involved; mediastinal nodes not detected with PA radiographs and therefore the lymphadenopathy in tuberculous pericarditis are not seen on routine frontal radiographs (Reuter et al. 2005). On echocardiography, pericardial thickening with evidence of strands in the fluid is commonly seen in around 60 % cases and is not specific for TB pericarditis (Mayosi et al. 2005).
Imaging features on CT may point to the tuberculous origin of the effusion. Thickened enhancing pericardium is seen; however, it may be difficult to distinguish between small effusions and thickening on CT, where ultrasound may prove more helpful. In one study, enlarged mediastinal lymph nodes were described in all patients with tuberculous pericarditis (Cherian 2004). These lymph nodes usually regress with treatment. On the contrary, other causes of effusion with mediastinal lymphadenopathy, like lymphoma, malignancy, or sarcoidosis, show hilar lymphadenopathy in addition
In constrictive pericarditis, fibrous or calcific thickening of the pericardium is seen, with or without effusion. Pericardial thickening of more than 3 mm with supporting findings of dilated inferior vena cava and deviated interventricular septum can help in accurate diagnosis, in appropriate clinical settings. Calcification of the visceral pericardium in the atrioventricular groove, interventricular groove, and crux of the heart is uncommon but may be seen (Suchet and Horwitz 1992).
3.8 Acute Complications: Tuberculosis in the Emergency Room
Tuberculosis, although as described above, has an insidious onset and progress, can also present acutely, in a previously healthy person. Common symptoms with which the patients present to the emergency room are dyspnea, fever, hemoptysis, or chest pain. It may be a challenge to diagnose tuberculosis in acute settings, especially in countries where it is less endemic and a wide other close differential diagnoses exist. However, an awareness of the migratory background and immune and HIV status of the patient, compounded by a high index of suspicion of the treating physician and the radiologist, may expedite the diagnostic process.
Hemoptysis, or expectoration of blood, is an acute life-threatening complication of tuberculosis. Incidence of hemoptysis in TB may be up to 7 %, depending upon the regional prevalence of tuberculosis, with a high mortality rate ranging from 9 to 18 % (Krishnan et al. 2009; Johnston and Reisz 1989; Alkhuja and Miller 2001). Hemoptysis in TB does not always signify an underlying active disease (Prasad et al. 2009).
Massive hemoptysis is defined variably in the literature, with the volume of blood ranging from 100 to 1000 mL in 24 h, although any amount of bleeding that causes hemodynamic instability should be considered significant (Corder 2003; Jean-Baptiste 2000). Almost 90 % of causes of massive hemoptysis in general originate from bronchial vessels, while 10 % originate from pulmonary vessels, understandably because the bronchial vessels are at systemic pressure (Yoon et al. 2002). Notable among the common causes are chronic inflammatory conditions like bronchiectasis, tuberculosis, and lung abscess and malignancies like bronchogenic carcinoma, which account for a vast majority of cases of massive hemoptysis.
The first step in managing any patient with massive hemoptysis is stabilization of the patient, resuscitation, and protection of the lower airways, as the risk of death due to asphyxiation overweighs that due to exsanguination (Marshall and Jackson 1997).
The next step is to identify the site and cause of bleeding and treat it accordingly. Various procedures form a part of the diagnostic algorithm for further evaluation, with MDCT angiography followed by bronchoscopy standing at the forefront. If the patient is clinically stable, the first logical step will be a MDCT angiography to locate the site of bleeding. CT has many advantages as it enables not only the identification of the site of bleeding but also facilitates the evaluation of the lungs to recognize the underlying cause of bleeding (Yoon et al. 2002).
On the other hand, patients who are not stable are taken up directly for rigid/flexible fiber-optic bronchoscopy. Many studies nevertheless recommend using CT angiography prior to bronchoscopy routinely in all patients with hemoptysis, as CT aids in a comprehensive evaluation with a better diagnosis of the cause of hemoptysis compared to bronchoscopy (Revel et al. 2002; Bruzzi et al. 2006).
Causes of Hemoptysis in Tuberculosis
Several underlying pathologies in tuberculosis can cause hemoptysis. Bronchial vessels are a more common source than pulmonary vessels and, when involved, tend to cause severe hemoptysis which is difficult to control.
Tuberculous bronchitis and bronchiectasis tend to cause bronchial arterial bleeding. Tuberculosis cavities can erode into adjacent structures, for example, into pleura and chest wall, and cause hemoptysis due to the involvement of intercostal, internal mammary, or subclavian vessels. Furthermore, colonization of preexisting cavities with fungus – aspergilloma – can also present as hemoptysis. Inflammation of pulmonary artery branches adjoining the cavities of TB, with consequent formation of “Rasmussen” aneurysm, can precipitate fatal hemoptysis. Erosion of the involved lymph nodes into adjacent tracheobronchial tree or vessels may also cause hemoptysis (Chatterjee et al. 2015; Halezeroglu and Okur 2014).
Bronchiectasis and Dilatation of Bronchial Arteries
Bronchial arteries are the primary source of nourishment to the bronchial tree and have microvascular connections with pulmonary circulation. These connections become functional in patients with bronchiectasis and chronic inflammation like TB.
In various chronic inflammatory conditions like tuberculosis and bronchiectasis (which can itself be as a result of tuberculosis), there is associated vasculitis and thrombosis of pulmonary vessels that cause local hypoxia. This stimulates the release of angiogenetic growth factors such as vascular endothelial growth factor, thereby promoting neovascularity, collateral formation, and enlarged bronchial arteries. This accounts for flow of blood from bronchial arteries at systemic pressure into the pulmonary vessels and hemoptysis (Bruzzi et al. 2006).
Special attention should be given to CT appearances in these patients. Presence of nodular or tubular soft tissue attenuation structures in the mediastinum, particularly around the airways, which are atypical for lymph nodes, should be viewed with suspicion. These structures may point toward hypertrophied bronchial arteries (Song et al. 1998).
Hemoptysis in aspergilloma is often associated with vasculitis in the cavity wall and extensive collateral formation from axillary and subclavian vessels (Uflacker et al. 1983; Remy et al. 1977). Hypertrophied bronchial arteries may also be seen as the cause of hemoptysis, and these should be actively searched for on CT.
The diagnosis can be challenging when the air crescent is not clearly appreciated due to obliteration of the cavity. Other differential diagnoses for intracavitary lesions are angioinvasive aspergillosis, echinococcal cysts, Rasmussen aneurysm in a cavity, lung abscess, bronchogenic carcinoma, intracavitary clot or hematoma, and P. carinii pneumonia (Franquet et al. 2001)
Treatment: Spontaneous resolution may be seen in 10 % of the patients (Hammerman et al. 1973). Palliative bronchial artery embolization is undertaken for acute management of hemoptysis, although a significantly high rate of recurrent hemoptysis in aspergillosis has been reported (Uflacker et al. 1983; Remy et al. 1977). Definitive treatment is thus surgical resection with perioperative antifungal treatment.
Rasmussen’s aneurysm is another rare cause of life-threatening hemorrhage in tuberculosis. A prevalence of 4 % in autopsy studies in patients who died of tuberculosis has been described.
Rasmussen’s aneurysm is a pseudoaneurysm which arises due to erosion of a cavity into an adjacent pulmonary artery. As the inflammation of the cavity involves an adjoining pulmonary artery branch, there is progressive weakening and thinning of the arterial wall as a result of necrotizing granulomatous inflammation, giving rise to a pseudoaneurysm months or years later (Santelli et al. 1994; Kim et al. 2001). Eventual rupture can cause fatal hemoptysis.
MDCT angiography plays an important role in not only identifying the aneurysm but also in correctly characterizing it as arising from pulmonary artery, distinguishing it from bronchial artery aneurysms which are more frequent. Careful attention to the cavity on post-contrast images may exhibit a focal enhancing lesion, thereby clinching the diagnosis.
Emergency endovascular management technique like percutaneous catheter embolization of the aneurysm is the treatment of choice (Remy et al. 1980).
Hemoptysis Due to Lymph Nodes
Although extremely rare, reports of tuberculous lymph nodes causing erosion of mediastinal vessels like aorta or pulmonary artery with subsequent formation of trachea/bronchovascular fistula and fatal hemorrhage do exist (Krishnan et al. 2009; Fatimi et al. 2006).
3.8.2 Chest Pain/Dyspnea
Acute onset chest pain and difficulty in breathing in tuberculosis can be due to a variety of underlying causes: acute respiratory distress syndrome (ARDS), pleuritis, pneumothorax, pericarditis, chest wall abscess to name a few.
Pneumothorax: Secondary Spontaneous Pneumothorax
Pneumothorax can complicate the course of roughly 1 % of tuberculosis, more often in severe cavitary tuberculosis. Underlying pathology is rupture of pleural caseous nodules which undergo necrosis. It must be suspected when apical abnormality is seen after re-expansion of the lung (Kim et al. 2001).
Pneumothorax, which may also be bilateral, has been reported in patients with miliary tuberculosis, who present with acute onset of breathlessness during the course of treatment with antituberculous drugs (Sharma and Kumar 2002; Arya et al. 2011; Khan et al. 2011; Singh et al. 2014). Caseation of the subpleural miliary nodules with subsequent rupture into the pleural space has been attributed as the triggering factor. On imaging, miliary shadows may not be discernible initially and may be evident only when the lung re-expands.
4 Hematogenous Spread of Pulmonary Infection
Hematogenous origin of pulmonary infection depends on septic pulmonary embolism (SPE). This is an uncommon syndrome characterized by pulmonary embolization of infected thrombi containing microorganisms admixed with fibrin. It depends on a primary infectious site spread out into the venous circulation, with implantation into peripheral pulmonary arterial vessels, resulting in alveolar infective infiltrates.
The most common causative Gram-positive bacteria are Staphylococcus aureus and Streptococcus pneumoniae, whereas the most frequent Gram-negative bacterium is Pseudomonas aeruginosa (Angus and van der Poll 2013).
Historically SPE was most commonly associated with Lemierre’s syndrome, postpartum septic pelvic thrombophlebitis, and right-sided infective endocarditis (Mac Millan et al. 1978; Goldenberg et al. 2005).
In the last decade, attention has been made to changes in the epidemiology, including thrombophlebitis due to contiguous deep soft tissue or bone infection or for infected endovascular catheters and implantable devices (Brenes et al. 2012a; Cook et al. 2005a).
In fact, like all foreign bodies, venous catheters, cardiac pacemaker, implantable cardioverter defibrillator, and joint prosthesis could carry a risk of infection. Due to increase in the number of that devices, the risk of infections have become a common problem in clinical practice (Baddour et al. 2003).
The incidence of infections is 1.9 per 1000 devices per year, and the cumulative probability of device infections is higher among patients with defibrillators compared with those with pacemaker and central venous catheters or joint prosthesis (Uslan et al. 2007).
Septic embolism also occurs in 22–50 % of patients with infective endocarditis. The predictors of embolism are vegetation size greater than 10 mm, mitral location, and infection of S. aureus.
The brain, the spleen, and lungs are the most frequent sites of embolism in left- and right-sided infective endocarditis (Takin et al. 2012).
4.1.1 Clinical Characteristics
Frequently the patients with SPE have an infective endocarditis (IE) that primarily involves the cardiac valve leaflets and can spread septic emboli into the pulmonary arterial circulation. Patients with large cardiac valve-infective vegetations (>10 mm) are at high risk of pulmonary embolism. The mitral valve is the most frequent infected valve (50 %) followed by the aortic valve (40 %) and tricuspid valve (10 %). Multiple valves, usually the mitral and aortic valves, are involved in 20 % of cases (Moriera et al. 2012; Nucifora et al. 2007).
The mortality of IE is about 30–60 % and is due to septic embolism involving mitral valve, lungs, and cerebrovascular sites (Nucifora et al. 2007).
4.2 Pathophysiologic Sequence
A local infection can cause extravasation of microorganisms into the venous system. Depending on the extent of the infection, edema could result in venous compression and stasis (Nourse et al. 2007) (Fig. 40).
The venous endothelium could be damaged by inflammatory mediators and production of thrombogenic toxins by the microorganism, leading to venous thrombosis. The fibrin and platelet matrix serves as an ideal nidus for proliferation of the microorganism with potential for propagation and allows for distant metastatic infection as its contents are drained into the pulmonary circulation through the venous system.
Specifically, it is known that S. aureus has a tendency to promote venous thrombosis. The bacterium produces an extracellular heat stable leukocidin that exhibits thrombogenic effects, through indirect inflammatory mechanism, including the development of reactive oxygen species and release of secondary inflammatory mediators from dying granulocytes, causing intense endothelial dysfunction (Boyle-Vavra and Daum 2007). S. aureus produces coagulase too, which specifically interacts with fibrinogen and causes coagulation (Gorenstem et al. 2000).
The predominance of S. aureus as the causative agent is related to its intrinsic thrombogenic and pro-inflammatory potential, rather than just its expected relation to the type of primary focus (Vinder Have et al. 2009; Hota et al. 2001). Once in the blood flow, the bacterium can damage directly the pulmonary parenchyma through the toxins (Boyle-Vavra and Daum 2006) and indirectly through inflammatory mediators (Holm et al. 2011) that may occasionally promote local thrombosis which serves as an additional nidus for proliferation of the bacterium. Embolization of these thrombi, inside the pulmonary arterial circulation (Fig. 41), allows for multiple infection infiltrates of the lungs, even in the absence of heart valvular involvement.
The endothelial cells of the capillaries and arterioles as well as the venules of the lungs are highly susceptible to hypoxia. Therefore, mild transient ischemia of lung tissue may result in marked vessel dilatation as well as increased vascular permeability with fluid and erythrocyte leakage inside the alveolar sacs (Wagenwoort 1995).
4.3 Radiographic Features
The microembolism is not generally observed directly on CT scan. Indirect findings of microembolism are pulmonary edema, pulmonary infarctions, and pulmonary hypertension findings with enlargement of arterial vessels.
The presence of parenchymal consolidation in pulmonary infarction is mainly caused by pulmonary hemorrhage (Balakrishnan et al. 1989).
Unusual presentations of SPE include pneumomediastinum and subcutaneous emphysema (Wang et al. 2004) as well as the evidence of septic emboli in the subsegmental pulmonary arteries. Pleural effusion is also observed in 70 % of patients (Fig. 42).
The chest CT findings typically lead to cardiac imaging because of the association with right-sided infective endocarditis. The absence of obvious cardiac valvular lesions should prompt careful consideration of other potential sources of infections, including venous devices (Fig. 51), or thrombophlebitis due to soft tissue infections (Fig. 40). Additional imaging modalities including ultrasound help in delineating the root cause of infection (Gadcowski and Stout 2008).
Echocardiographic examination of all cardiac valves, including right-sided valves, should be carried out in all patients with suspecting infective endocarditis, especially when the patient has a risk factor (Chua et al. 2000). In the absence of signs of endocarditis, further evaluation to identify the infectious source is indicated (Vos et al. 2012).
Sepsis is a syndrome caused by the inefficiency of the mechanism of control and containment of the infection. It is characterized by symptoms and signs of systemic inflammatory reaction to infection and manifestations of organ dysfunction, resulting from alterations in the microcirculation. It is the second common cause of death with a mortality rate between 15 and 50 % (Ferrari and Barletta 2012).
SPE has manifestations ranging from an insidious illness with fever and respiratory symptoms to acute generalized sepsis with disseminated intravascular coagulopathy or acute renal failure.
The diagnosis of SPE is based on clinical manifestations, culture data, and radiographic evidence of peripheral thrombosis and pulmonary infection. Respiratory impairment with high grade fever and marked increase of serum inflammatory markers differentiate septic pulmonary embolism from nonseptic pulmonary embolism (Melina et al. 2010).
The concurrence of an extrapulmonary source of infection with contiguous septic thrombophlebitis complicated by septic pulmonary embolism seems to affect particularly the adult populations. A high index suspicion of thrombosis is present in patients where the manifestations of the soft tissue infection (erythema, pain, and swelling) can overlap those of SPE (Fred and Harle 1969).
Chest x-ray film could be rather nonspecific, whereas chest CT scan provides the earliest and most easily identifiable indication of SPE and systemic embolization of infection.
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