Chapter 4 Pulmonary Diseases in the Immunocompromised Host with or without Acquired Immunodeficiency Syndrome
PULMONARY INFECTIONS IN THE IMMUNOCOMPROMISED PATIENT WITHOUT HUMAN IMMUNODEFICIENCY VIRUS INFECTION
The immunocompromised host is an individual with altered defense mechanisms or immunity. Immunocompromised hosts without human immunodeficiency virus (HIV) infection include patients with hematologic malignancies such as lymphoma and leukemia, recipients of organ transplants, patients treated aggressively with cytotoxic drugs for solid tumors, and those receiving high-dose corticosteroid therapy for collagen vascular disease and other disorders.
The lung is a frequent target of infection in the immunocompromised host, and mortality rates associated with pulmonary disease often are as high as 40% to 50%. Infection is the most frequent cause of the radiographic abnormality; however, conditions such as extension of malignancy (e.g., lymphoma, metastases), drug reactions, or other noninfectious processes may be diagnostic possibilities (Table 4-1). Unfortunately, noninvasive diagnostic methods such as sputum smears and cultures that are used for evaluation of pneumonia are less useful in the immunocompromised host. The clinician must therefore choose between using invasive techniques to determine the exact cause of the pneumonia or employing empirically chosen therapy. The former choice is not without hazard in debilitated patients; the latter is complicated by the broad range of possible causes and appropriate therapies.
|Lobar or Segmental Consolidation||Nodules with Rapid Growth ± Cavitation||Diffuse Lung Disease|
|Radiographic features||Aspergillus||Pneumocystis jiroveci pneumonia|
BAL, bronchoalveolar lavage; TBB, transbronchial biopsy; TNB, transthoracic needle biopsy.
The radiologist plays an important role, which involves detection of an abnormality on the chest radiograph, analysis of the radiographic features with regard to diagnosis and choice of an appropriate interventional technique, performance of percutaneous needle biopsy of focal lesions when appropriate, and monitoring response to therapy and the development of complications. Although the radiographic features in most opportunistic infections are relatively nonspecific, there is a general correlation between the type of radiographic pattern and the microorganism producing the pneumonia. Three major patterns are used for classification: lobar or segmental consolidation, nodules with rapid growth or cavitation, and diffuse lung disease.
Table 4-1 summarizes the radiographic patterns for HIV-negative immunocompromised patients with pulmonary disease.
Lobar or Segmental Consolidation: Bacterial Pneumonia
Bacteria are the most common infectious agents invading the lungs of immunocompromised hosts. Colonization of the oral pharynx by altered flora in the presence of reduced lung defense mechanisms leads to a preponderance of gram-negative bacillary pneumonias. Organisms include Klebsiella, Enterobacter, Pseudomonas, Escherichia coli, Proteus, and Serratia. Among gram-positive organisms, staphylococci are the most common.
The radiographic features include localized dense consolidation, which may be lobar or segmental. Cavitation is a common feature. Cavities may be solitary, but many small microabscesses often are identified. Patchy, multilobar pneumonia may also occur. Effusions are typically small, and empyemas are unusual. Occasionally, the chest roentgenogram may be normal, especially in the setting of neutropenia. Bacterial pneumonia can be diagnosed by isolation and culture of the organisms from sputum samples or by observing a clinical response to empirically chosen antibiotics.
The Legionnaires’ disease bacterium (Legionella pneumophila) and Pittsburgh pneumonia agent are causes of acute bronchopneumonia in the immunocompromised host, particularly in renal transplant recipients. The clinical and radiographic appearance of Legionella pneumophila in these patients is usually identical to that seen in the normal host. Multilobar consolidation is common. However, the Pittsburgh agent (Legionella micdadei) typically produces circumscribed areas of pneumonia, creating a nodular appearance on the chest radiograph (Fig. 4-1).
Figure 4-1 Legionella micdadei pneumonia. A posteroanterior chest radiograph shows multiple nodules in both lungs (arrows).
Tuberculosis occurs with increased frequency in certain subgroups of immunosuppressed patients. However, in most reported series of pneumonias, the presence of mycobacterial disease in immunocompromised hosts is low. Tuberculosis, when it occurs in this setting, does carry a high fatality rate. The typical radiologic features of pulmonary tuberculosis consist of apical and posterior segmental disease in the upper lobes, with or without the development of cavitation. The differential diagnosis should include infection with atypical mycobacteria.
The differential diagnosis of lobar or segmental consolidation in the immunosuppressed patient is limited. Lymphoma involving the lung parenchyma may appear as a localized airspace or alveolar consolidation with prominent air bronchograms. This appearance may signal relapse after treatment, and hilar and mediastinal adenopathy may not be present.
Nodules with Rapid Growth or Cavitation: Fungal Pneumonias
Multiple nodules with rapid growth or cavitation are common features of fungal infection in the compromised host. This group includes pneumonias produced by Nocardia, although Nocardia asteroides is a higher transitional form of bacterium. The fungi most frequently isolated include the commensals, such as Aspergillus, Candida, Mucor, and true pathogenetic fungi, such as Cryptococcus. Fungal pneumonia characteristically develops in patients with hematologic malignancies who are neutropenic from cytotoxic drugs or who are receiving or have just completed a course of broad-spectrum antibiotics for fever of unknown cause.
Aspergillus pneumonia is the most common fungal pulmonary infection in immunosuppressed patients. Aspergillus causes an invasive necrotizing pneumonia resulting from invasion of blood vessels with accompanying pulmonary infarction. The roentgenographic features consist of multiple nodular areas of consolidation that often abut the pleural surfaces (Fig. 4-2). These areas frequently cavitate and may show crescentic radiolucencies around the parenchymal opacities (i.e., air crescent sign) that may mimic mycetoma. This sign also can be identified on CT studies (Fig. 4-3). Another characteristic finding is a pulmonary mass surrounded by a zone of lower attenuation with ground-glass opacification (i.e., halo sign), probably produced by adjacent hemorrhage. The diagnosis of Aspergillus pneumonia usually requires invasive procedures, such as needle aspiration or open lung biopsy.
Figure 4-2 Invasive aspergillosis. There are multiple, bilateral nodules (arrows), and blood vessels leading to the nodules can be identified in some instances.
Figure 4-3 Invasive aspergillosis in an immunocompromised patient. CR shows a rim of air in the periphery; the air crescent (open arrows) separates the central amorphous infarcted lung (asterisk) from the rim of inflamed viable lung (black arrows). This appearance is often seen as the patient’s white cell count is recovering.
Pulmonary disease caused by Mucor is clinically and radiographically indistinguishable from that caused by Aspergillus. It is frequently seen in patients with lymphoproliferative disease, leukopenia, and diabetes, and it is detected in patients after antibiotic use. The organism likewise has a predilection for blood vessel invasion and pulmonary infarction (Fig. 4-4).
Figure 4-4 Mucormycosis. A, Standard posteroanterior chest radiograph demonstrates a wedge-shaped area of consolidation in the right upper lobe. B, Coronal reformation CT image (lung window setting) shows a halo of ground glass surrounding the right upper lobe consolidation.
Primary candidal pneumonias are rare in immunosuppressed patients; the lung is more likely to be involved by disseminated fungemia. Invasive biopsy is usually required for diagnosis. The radiologic appearance is nonspecific, and there may be areas of airspace consolidation or nodular opacities.
Cryptococcal pneumonia, much less common than Aspergillus pneumonia, usually occurs in patients with defective cellular immunity rather than in neutropenic hosts. Disseminated disease with central nervous system involvement is the rule, and neurologic symptoms may first call attention to the presence of cryptococcal disease. The radiographic manifestations consist of single or multiple nodules with or without cavitation. Well-defined lobar or segmental consolidation is uncommon. Cryptococcus may be isolated from the sputum or, more frequently, from the cerebrospinal fluid on lumbar puncture. In some cases, a lung biopsy is required.
Nocardia asteroides is an opportunistic bacterium that causes pneumonia in the compromised host with diseases or conditions in which cellular immunity is depressed. Antecedent corticosteroid therapy is a common history, but white blood cell counts are often normal. Nocardia usually does not cause a fulminant, rapidly progressive pulmonary infection. The usual radiologic appearance is that of single or multiple nodules with or without cavitation (Fig. 4-5). They may extend to the pleural surface with associated pleural effusion or chest-wall invasion. The diagnosis can occasionally be made on sputum smears or cultures, but invasive procedures are usually required.
The differential diagnosis for the radiographic appearance of multiple nodules in the immunocompromised host is rather limited. The appearance may be produced by metastatic disease or occasionally by lymphoma involving the lung parenchyma. In both instances, rapid growth is usually not a feature. Transplant recipients who receive cyclosporine as a principal immunosuppressive agent may develop an unusual lymphoproliferative disorder in the lung (PTLD). It usually manifests 4 to 6 months after transplantation, although its appearance may be delayed as long as 2 years. The pulmonary manifestations include a solitary mass or multiple pulmonary nodules that are often associated with hilar adenopathy. Multiple organs are frequently involved. The radiographic abnormalities often regress after the reduction of immunosuppression.
Diffuse Lung Disease
A radiologic pattern of diffuse infiltration of the lungs in the immunocompromised host can be produced by a number of microorganisms, the most common of which are the fungus Pneumocystis jiroveci (formerly called P. carinii) and a variety of viral agents, including herpes zoster, cytomegalovirus (CMV), and respiratory syncytial virus (RSV). A diffuse interstitial pattern can be seen as a result of nonspecific interstitial pneumonitis, cytotoxic drug reactions, radiation pneumonitis, or lymphangitic spread of tumor.
The prevalence of pneumonia caused by Pneumocystis jiroveci has decreased because of widespread prophylaxis in immunocompromised patients with or without HIV infection, but it remains a major cause of morbidity and mortality. Once classified as a protozoan, the organism is now considered to be a fungus. The pneumonia it produces is acute and fulminating. The classic radiographic manifestation is initially a bilateral, perihilar or diffuse, symmetric interstitial pattern, which may have a finely granular, reticular, or ground-glass appearance. If left untreated, it may progress over 3 to 5 days to a homogeneous, diffuse alveolar consolidation (Fig. 4-6). Hilar adenopathy and pleural effusion are distinctly unusual. Computed tomography (CT), particularly high-resolution CT (HRCT), may show areas of disease due to Pneumocystis pneumonia when the appearance on a standard chest radiograph is normal. Involved areas of the lung show ground-glass opacification without obliteration of normal pulmonary vessels. Because it is not possible to culture these organisms, the diagnosis depends on morphologic identification of Pneumocystis