The Core Curriculum: Cardiopulmonary Imaging, 1st Edition (2004)

Chapter 6. Infections in the Immunocompromised Host

Immunocompromised hosts have altered immune mechanisms, either cell mediated or humoral, and are predisposed to opportunistic infections. Pulmonary infections constitute an important category of major complications in the immunocompromised host. Almost all human immunodeficiency virus (HIV)-infected patients will suffer at least one respiratory illness over the course of their disease (1). The incidence of pulmonary infections in other forms of immune compromise varies. Approximately 50% of bone marrow transplant recipients (2) and 80% of acute leukemia patients will develop pneumonia (3).

The radiologist plays a critical role in the diagnosis and monitoring of pulmonary infections. This includes detection and analysis of abnormalities on the chest radiograph (CXR), generating an appropriate differential diagnosis, and monitoring disease progression, response to treatment, and complications. The radiologist should recommend further evaluation with computed tomography (CT) and high resolution CT (HRCT) when needed and should guide appropriate interventional procedures such as fiberoptic bronchoscopy, open lung biopsy, and CT-guided biopsy. The different pulmonary infections related to acquired immunodeficiency syndrome (AIDS) and to other forms of immune compromise are the subject of this chapter.

Pulmonary Manifestations of Acquired Immunodeficiency Syndrome

Approach

HIV-infected patients suffer from a variety of lung infections and neoplasms. Several factors are crucial in making the correct diagnosis. The CD4 count is a measure of a patient’s immune status and is predictive of which pulmonary manifestation will be encountered (Table 6.1). For example, cytomegalovirus (CMV) infections are encountered in patients with CD4 counts under 20 cells/mm3, whereas Nocardia pneumonia and Kaposi sarcoma are encountered when the count is less than 200 cells/mm3 (4).

The CD4 count is a measure of immune status that helps to predict which infections are likely.

Table 6.1: CD4 Counts in AIDS—Correlation with Associated Diseases

Disease

CD4 Count (cells/mm3)

Demographic Data

Bacterial infection

   Bacterial pneumonia

Any

i.v. drug users—S. aureus, S. epidermidis, gram negatives

   Nocardia

<200

 

   M. tuberculosis

Any

PPD+, i.v. drug users, African Americans, exposure toMycobacteria

<350

Reactivation of dormant bacteria; similar appearance to reactivation TB in immunocompetent hosts

<200

Similar appearance to primary TB in immunocompetent hosts

MAC

<50

 

Fungal infection

   Histoplasma

<100

Endemic area

   Aspergillus

<50

 

PCP

<200

 

CMV

<20

Infection with HIV through sexual contact

Neoplasms

   Kaposi sarcoma

200

Male homosexual/bisexual

   Lymphoma

<200

 

   Lung cancer

Any

Smoker, male

PPD+, tuberculin purified protein derivation; MAC, mycobacterium arium complex; TB, tuberculosis; PCP, pneumocystis carinii pneumonia; CMV, cytomegalovirus; HIV, human immunodeficiency virus.

Patient demographics also help to determine likely pulmonary manifestations (Table 6.1). Intravenous drug abusers are more likely to suffer infections such as Staphylococcus aureus pneumonia, septic emboli, and tuberculosis (5), whereas CMV infections are more frequent in patients infected by HIV through sexual contact (6).

Prophylactic antimicrobial therapy decreases the likelihood of infection with drug-susceptible organisms (4) but may delay diagnosis by interfering with blood and sputum culture results (7). Integration of the radiographic appearance with demographic data, laboratory results, and clinical presentation is necessary to reach a reasonable differential diagnosis (8).

Bacterial Infections

AIDS patients have altered B-cell function and are therefore susceptible to severe infections by encapsulated bacteria, such asStreptococcus pneumoniae and Hemophilus influenza, with any CD4 count (9). As the CD4 count falls, the susceptibility to bacterial infection increases (10). The introduction of Pneumocystis carinii pneumonia (PCP) prophylaxis has increased the incidence of bacterial pneumonia relative to that of PCP (10). Intravenous drug abusers are at greater risk to develop S. aureus pneumonia, septic emboli, and empyema (5).

Bacterial pneumonia typically presents with segmental or lobar airspace disease. In patients with AIDS there is a higher incidence of multilobar pneumonia (4) and of rapid progression and cavitation (7) (Fig. 6.1) than in non-immunocompromised hosts. Pyogenic airway disease with bronchitis, bronchiolitis, and bronchiectasis is common in HIV-infected patients with normal CD4 counts. The radiographic findings are subtle and include bronchial wall thickening on the CXR and tree-in-bud opacities, bronchiectasis, bronchial wall thickening, and mucoid impactions on HRCT (11).

Figure 6.1 Cavitary Nocardia pneumonia in acquired immunodeficiency syndrome (AIDS). (A) Posteroanterior and (B) lateral chest radiographs: multifocal airspace disease with cavitation (C). C. Computed tomography 11 days later: extensive right upper lobe pneumonia with cavitation (C). Cavitary disease also present in the left upper lobe (arrows). (Courtesy of Dr. Rosita Shah, Philadelphia, Pennsylvania.)

Mycobacterial Infections

Tuberculosis

The estimated infection rate with Mycobacterium tuberculosis among HIV-infected patients is 5%. The rate is higher among specific groups such as Latinos, African Americans, and intravenous drug abusers (12). Because tuberculosis is a highly contagious and treatable disease, it needs to be recognized promptly (13).

A typical finding of tuberculosis in AIDS patients is low attenuation lymph nodes with enhancing rims.

The clinical presentation and radiographic appearance are influenced by immune status and CD4 level. With CD4 counts below 350 cells/mm3, reactivation of dormant M. tuberculosis may occur (8). Findings will be similar to reactivation tuberculosis in immune competent hosts, with upper lobe predominant exudative and cavitary disease. Pleural effusions in AIDS patients are more prevalent and tend to be bigger, with a higher inoculum of bacteria (14). When the CD4 counts drop below 200 cells/mm3, the radiographic appearance is more like primary tuberculosis, with randomly distributed focal airspace disease, diffuse infiltrates, miliary nodules, and/or multiple pulmonary nodules. Cavitation is rare in this setting (15). Bulky hilar and mediastinal lymph node enlargement are typical in HIV patients (Fig. 6.2), unlike in non-AIDS patients. On enhanced CTs lymph nodes may demonstrate low attenuation centers with enhancing rims (16) (Fig. 6.3).

Figure 6.2 Lymph node tuberculosis in AIDS. (A) Posteroanterior and (B) lateral chest radiograph 11-84: normal. (C) Posteroanterior and (D) lateral chest radiograph 5-85: interval development of mediastinal lymph node enlargement (N). (Courtesy of Dr. David Spizarny, Detroit, Michigan.)

Figure 6.3 Lymph node tuberculosis in AIDS. Computed tomography demonstrates low attenuation mediastinal lymph nodes (N) with rim enhancement (arrows).

Atypical Mycobacteria

Mycobacterium avium complex infection occurs in severely immunocompromised patients, with CD4 counts less than 50 cells/mm3. Disease is disseminated throughout the reticuloendothelial system and may involve the lungs as well. Disease tends to be subacute, with constitutional symptoms (4). The radiographic appearance ranges from a normal CXR to large pulmonary nodules that may cavitate, often with lymph node enlargement (17,18). On HRCT there is a tendency for bilateral lower lobe distribution and ground glass opacities (GGOs) (19). Other forms of atypical mycobacteria are rare (Fig. 6.4).

Figure 6.4 M. kansasii in AIDS (CD4 count = 23). (A) Posteroanterior and (B) lateral chest radiograph: cavitary upper lobe pneumonia (P), especially involving the right upper lobe.

Figure 6.5 Miliary histoplasmosis in AIDS (CD4 count = 160). (A) Posteroanterior chest radiograph and (B) computed tomography: miliary nodules.

Fungal Infection

Fungal pneumonia is uncommon in AIDS patients because neutrophil activity is preserved. Patients receiving antiviral therapy that induces granulocytopenia are susceptible to fungal infections (7) (Fig. 6.5). The common pathogens causing fungal pneumonia are Cryptococcus andAspergillusCryptococcus is a fungus that commonly causes meningitis. The radiographic features of Cryptococcus pneumonia include nodular interstitial infiltrates, solitary or multiple pulmonary nodules or masses that may cavitate, pleural effusions, and lymph node enlargement (20). The radiographic appearance of Aspergillus is discussed later in this chapter (Fig. 6.6).

Figure 6.6 Two diagnoses in a patient with AIDS. Computed tomography shows ground glass opacity bilaterally (G) and a cavitary right upper lobe mass (M). Percutaneous aspiration of the right upper lobe mass revealed Aspergillus. Because of continued fevers, bronchoscopy was subsequently performed and revealed Pneumocystis.

Pneumocystis carinii Pneumonia

P. carinii is a unicellular organism that behaves like a protozoan but is classified as a fungus (21). The organism cannot be grown in cultures, and therefore the diagnosis is based on visualizing the organism (or its cyst) in special stains preformed on sputum or bronchoalveolar lavage fluid. PCP can occur at any level of immunosuppression, but it becomes common when CD4 counts are at or below 200 cells/mm3. Despite the use of effective prophylactic therapy and the resultant decline in PCP, it remains the most common opportunistic pulmonary infection in AIDS. Approximately 70% of AIDS patients will suffer at least one PCP infection during the course of their disease. It is more common in homosexual and male patients (21,22). PCP in AIDS patients is insidious and presents with nonproductive cough, dyspnea, low-grade fever, and malaise (8).

Pneumocystis remains the most common opportunistic pneumonia in AIDS, ultimately affecting roughly 70% of AIDS patients.

The radiologic manifestations of PCP are varied. In most cases it presents as bilateral, diffuse, symmetric parenchymal abnormality with a perihilar and basilar predominance (Fig. 6.7). Early findings are often subtle, and the CXR is normal or nearly normal in anywhere from 10% to as many as 39% of patients (8). Infection may appear as interstitial granular or reticular opacities or as airspace disease. Without treatment PCP often progresses to confluent airspace disease (22,23). Upper lobe disease is classically seen in patients receiving aerosolized prophylactic pentamidine therapy (23). Radiographic improvement is expected within 10 days of appropriate treatment, although there is usually initial radiographic worsening due to capillary leak. Atypical manifestations are encountered in approximately 5% and include isolated lobar disease, focal parenchymal opacities, nodules and masses, a miliary pattern, endobronchial lesions, and pleural effusions (23).

AIDS patients may present with cystic lesions (Fig. 6.8), thin or thick walled, regular or irregular in shape, that may be surrounded by GGOs (Fig. 6.9), indicating inflammatory pneumonitis. This form of disease is termed cystic PCP and is rare in non-AIDS patients (21,23). The cystic lesions show a predilection for the lung apices and subpleural areas, and patients present with spontaneous pneumothorax in 6% to 7% of cases (Fig. 6.10). The pneumothoraces are frequently bilateral, associated with a higher mortality rate of 33% to 57%, and not always responsive to standard chest tube placement (21).

Figure 6.7 Pneumocystis pneumonia in AIDS (CD4 count = 27). Widespread bilateral parenchymal abnormality with perihilar confluent airspace disease, left greater than right.

Figure 6.8 Pneumocystis pneumonia in AIDS. Two cysts in left upper lobe (arrows).

Figure 6.9 Pneumocystis pneumonia in AIDS (CD4 count = 169). A. Computed tomography at the level of the carina: ground glass opacity, especially in the left perihilar lung (G) and smaller cysts. B. Computed tomography more caudal than (A): left lower lobe pneumatocele (P).

Chest CT and HRCT are helpful for the patient with a nonspecific clinical presentation and normal or near normal CXR or when PCP relapse is suspected in the presence of an abnormal CXR from a previous episode of infection (21). At HRCT, PCP manifests as GGOs that may be diffuse and homogeneous or patchy and geographic in distribution, often in the perihilar lungs (7,21). GGO is attributed to accumulation of fluid, organisms, and debris within the alveoli and is considered highly suggestive of P. carinii infection in the setting of HIV infection (Figs. 6.66.9, and 6.10). HRCT may show thickening of interlobular septa secondary to edema and cellular infiltration and may delineate the extent and distribution of cyst formation and changes of interstitial fibrosis secondary to chronic PCP. CT findings may suggest an alternative diagnosis, an additional diagnosis along with PCP (Fig. 6.6), or another pathogen and may help to direct a biopsy.

Figure 6.10 Chronic Pneumocystis pneumonia in AIDS (CD4 count = 24). Computed tomography at two different levels (A and B)reveals numerous small cysts, larger cysts in the left lung anteriorly (arrows), ground glass opacity, and a large right pneumothorax (P).

Viral Infections

CMV is a common pathogen in AIDS patients with CD4 counts below 100 cells/mm3. It is more prevalent in patients who contracted AIDS through sexual contact (6). The lungs are infected with CMV in 50% to 90% of patients (4,8). The exact role of CMV as a pulmonary pathogen is not clear, and it is often not the cause of death. Chronic CMV pneumonitis is thought to be related to extrathoracic manifestations of CMV, including retinitis, colitis, esophagitis, and encephalitis.

The classic radiographic appearance includes diffuse GGO, patchy airspace disease, and pulmonary nodules (24). Airway disease such as bronchiectasis and bronchial wall thickening is commonly seen and may be the sole manifestation (25). Other viruses such as herpes simplex, varicella-zoster, and Epstein-Barr virus seldom cause pulmonary infection in AIDS patients (8).

Noninfectious Pulmonary Manifestations of Acquired Immunodeficiency Syndrome

AIDS patients are continuously exposed to viruses associated with malignancy, such as Epstein-Barr virus and human papilloma virus. AIDS patients are thus predisposed to neoplasms, including Kaposi sarcoma, lymphoma, lung cancer, and pulmonary metastases.

Kaposi Sarcoma

Among AIDS patients, Kaposi sarcoma almost exclusively affects homosexual or bisexual men and is thought to be related to human papilloma virus-8 (4). It initially manifests as purplish skin lesions, but as CD4 counts drop below 100 cells/mm3, disease often disseminates to abdominal organs and to the larynx, tracheobronchial tree, and lungs (26).

The radiographic findings are typical, often enabling the radiologist to reach a diagnosis without the need for invasive procedures. In fact, CT is reported to be more then 90% accurate (8). Kaposi sarcoma is characterized by nodularity along the bronchovascular bundles that spreads to the perihilar regions (Fig. 6.11). As disease progresses, lung nodules and septal lines develop. The nodules tend to be ill-defined and may obstruct airways, thereby causing postobstructive pneumonia. In advanced disease, pleural effusions and enlarged lymph nodes may appear. The lymph nodes are not markedly enlarged but typically are high in attenuation as a result of contrast enhancement (7,27).

Figure 6.11 Kaposi sarcoma in AIDS. A. Posteroanterior chest radiograph: linear and nodular opacities, predominantly in the perihilar lungs. B. Computed tomography: nodularity (arrows) extends along the bronchovascular bundles.

CT is reported to be more than 90% accurate for the diagnosis of Kaposi sarcoma.

Lymphoma

The most common lymphoma in AIDS patients is B-cell non-Hodgkin lymphoma. It is termed AIDS-related lymphoma and is thought to result from Epstein-Barr virus (28). AIDS-related lymphoma is an extranodal disease that primarily involves the central nervous system and gastrointestinal tract and occurs when CD4 counts are less than 55 cells/mm3. The chest is involved in only 10% to 50% of patients (4), either via spread from extrathoracic foci or rarely as primary pulmonary lymphoma.

Unilateral pleural effusion is the most common thoracic manifestation of extrapulmonary AIDS-related lymphoma (Fig. 6.12) and may be the only manifestation. Other findings include parenchymal nodules (Fig. 6.13), masses, and airspace disease. Enlarged mediastinal lymph nodes occur but are not the hallmark of disease (29).

There are few reports of primary pulmonary AIDS-related lymphoma. The disease is characterized by pulmonary nodules, often bilateral and basilar, sometimes with air bronchograms or cavitation. Enlarged thoracic lymph nodes are less typical, and pleural effusions are rare (30).

Lung Cancer

There is a known association between HIV infection and lung cancer. There is controversy about whether HIV infection is a risk factor for lung cancer or a coincidental disease (31). However, lung cancer deserves consideration in AIDS patients. HIV-infected patients with lung cancer are typically younger than the general population of lung cancer patients. There is a strong male predilection, and there is usually a history of smoking (32), identifying a subpopulation that is at particular risk. There is no correlation with CD4 counts. Adenocarcinoma is the usual cell type, but other cell types are reported as well. The diagnosis is typically only made late in the course of disease, and prognosis is grim. This is because the more common infections and neoplasms that AIDS patients develop are considered long before lung cancer, and the younger than expected age and sometimes confusing radiographic presentation in lung cancer patients with AIDS can be misleading. It is therefore suggested that transbronchial or percutaneous biopsy should be obtained whenever abnormality persists despite antibiotic therapy.

Figure 6.12 Two diagnoses in AIDS. Loculated left pleural effusion (E) results from large cell lymphoma. Underlying nodular lung disease represents Kaposi sarcoma.

Figure 6.13 Lymphoma in AIDS. (A) Posteroanterior chest radiograph and (B) computed tomography: enlarged hilar lymph nodes (L) and multiple lung nodules.

Lung cancer is known to be associated with HIV infection, and because its manifestations overlap with AIDS-related infections, diagnosis is frequently delayed and prognosis is grim.

The typical radiographic presentation is of a lung nodule or mass, peripheral or central, predominantly in the upper lobes (Fig. 6.14). Postobstructive airspace disease is also frequently seen. Lymph node enlargement and pleural effusion are common but are not specific and may be caused by many other AIDS-related diseases (32). Diffuse pleural thickening has been reported as a rare manifestation of lung cancer in AIDS. This situation presents particular diagnostic difficulty, because bacterial and mycobacterial infections, lymphoma, and Kaposi sarcoma may present in this exact way. CT demonstration of underlying pleural and lung masses and metastases may be helpful.

Figure 6.14 Small cell carcinoma of lung in AIDS. A. Posteroanterior chest radiograph: nodules (N) and hydropneumothorax. Arrowsmark lung edge. B. Computed tomography at soft tissue window settings: nodules (N) are pleural. C. Computed tomography at lung window settings: left lung volume loss despite left hydropneumothorax. E, effusion; P, pneumothorax. (Courtesy of Dr. Rosita Shah, Philadelphia, Pennsylvania.)

Pulmonary Manifestations in Non–Acquired Immunodeficiency Syndrome Immunocompromised Patients

Approach

In the last several decades there has been a steady increase in the number of patients with immune compromise as a result of advances in cancer therapy, more frequent organ transplantation, and aggressive immunosuppressive therapy for collagen vascular disorders and autoimmune diseases (33). There are four main categories of lung defense against infection: mechanical barriers, phagocytic defense, cell-mediated defense, and humoral immunity (34). Impairment of one or more defense mechanisms results in different forms of immune compromise and predisposes affected patients to specific organisms.

Defining the nature of immune defect and its severity helps to determine the organisms to which the patient is susceptible (33). For example, lymphoma patients or patients receiving corticosteroids have altered cell-mediated immunity and are susceptible to fungal infections such as CryptococcusHistoplasma, and Candida and to bacterial infections such as Legionella and Nocardia. Patients receiving chemotherapy or patients with myeloproliferative disorders have granulocyte dysfunction and are susceptible to infections with gram-negative bacteria, StaphylococcusAspergillus, and Candida (33,34).

Duration of immune compromise also influences the organisms that are likely to infect a patient. Cancer patients treated with cytotoxic drugs are prone to develop bacterial pneumonia with typical pathogens such as S. aureus in the first few days after therapy. Patients with severe neutropenia over a prolonged period of time are at greater risk of developing Aspergillus infections (35). After organ transplantation, patients are susceptible to infection with different organisms depending on the time interval since transplantation.

From 1 to 4 months after kidney transplantation, T-cell-mediated immunity is severely impaired, rendering patients at risk for infection withAspergillusCryptococcusMucoralesNocardia, PCP, CMV, and Mycobacteria. Later, as immunosuppression is tapered, the immune system recovers. Patients in this stage are more likely to develop community-acquired pneumonias, although the risk of PCP and Cryptococcuspersists (36).

After heart transplantation, in addition to the effects of potent immunosuppressive therapy, there is increased susceptibility to pulmonary infection as a result of prolonged intubation, pulmonary edema, and effects of thoracic surgery on lung mechanics. After lung transplantation there is added lung liability due to impaired mucociliary clearance, organ injury during transplantation, and the presence of recipient alveolar macrophages in transplanted lungs. Patients are therefore at risk for nosocomial pneumonias with gram-negative bacteria and Staphylococcus in the immediate postoperative period and later are susceptible to viral, PCP, and fungal infections (37).

Pre–bone marrow transplantation (BMT) induction includes high dose chemotherapy and whole body radiation, which cause severe neutropenia (38). Similarly, after BMT patients suffer from severe neutropenia and are at increased risk for lung infections by gram-negative bacteria, StaphylococcusStreptococcus, and Aspergillus. In the subacute phase (30 to 100 days after transplantation) granulocytes recover, but cell-mediated immunity and antibody production are impaired, leading to infection with CMV and PCP. From that point on, graft-versus-host disease may involve the lungs. In the chronic post-BMT phase, patients suffer from combined immunodeficiency as a result of immunosuppressive therapy, reduced antibody production, and graft-versus-host disease. At this stage there is increased susceptibility to infections with encapsulated organisms such as Streptococcus.

Radiographic Patterns

Radiographic features of opportunistic infections are nonspecific. However, there is some correlation between the radiologic pattern and the responsible pathogen. Some organisms have typical radiographic patterns of presentation. Correlating the radiographic pattern with clinical data helps to narrow the differential diagnosis (39,40).

The main radiographic patterns encountered in non-AIDS immunocompromised patients include airspace disease, nodules, and diffuse lung disease. The role of chest CT and HRCT is discussed later.

Normal Chest Radiograph

Chest radiography plays a major role in evaluating febrile immunocompromised patients. The CXR has limited sensitivity for detection of early infection, especially in neutropenic patients. A normal CXR does not exclude lung infection (Fig. 6.15). Neutropenic patients have an altered inflammatory response, with subtle and delayed radiographic findings (40). The CXR is normal in up to 78% of such patients with initial febrile episodes, recurrent fevers, or persistent fevers (41). HRCT may increase sensitivity for subtle abnormality in neutropenic patients, suggest the causative pathogen, help to guide diagnostic procedures, and allow early initiation of therapy to improve survival (42,43). In a febrile immunocompromised patient with a normal CXR or questionable findings, HRCT deserves serious consideration (41,42).

A febrile immunocompromised patient with a normal CXR may benefit from HRCT.

Airspace Disease

Bacteria are the most common organisms to cause pulmonary infections in the non-AIDS immunocompromised host. In a neutropenic patient, bacterial pneumonia typically develops in the acute neutropenic stage, whereas fungal pneumonia will develop in the subacute neutropenic phase (about 2 weeks later). The clinical presentation of bacterial pneumonia is of an acute rapidly progressive febrile illness.S. aureus is a frequent pathogen.

Gram-negative bacteria are common pathogens, because the organisms colonizing the oropharynx are altered in debilitated patients. Altered phagocytosis in neutropenic patients also increases the susceptibility to gram-negative infections. Legionella and Pseudomonas may develop in moist ventilation tubing (40).

Figure 6.15 Infection with nearly normal chest radiograph in patient with acute myelogenous leukemia and bone marrow transplant. A.Posteroanterior chest radiograph: questionable nodularity in lower lungs, left greater than right. B and C. Computed tomography 1 day after A: multiple bilateral lung nodules with a computed tomography halo sign (arrows) and several cavities (arrowheads) result from invasive pulmonary aspergillosis. P, pneumomediastinum.

The typical radiographic pattern caused by bacteria is airspace disease resulting from filling of alveoli with inflammatory exudate. It may occur in a lobar, segmental, subsegmental, or patchy distribution. Disease is characteristically confluent, and air bronchograms are common. Cavitation is also common, either solitary or in the form of multiple microabscesses. Large pleural effusions and empyemas are infrequent (39).

Airspace disease most commonly reflects bacterial infection, but infection with other organisms may manifest similarly. Fungi such asAspergillusHistoplasma, and Coccidioides and other species of bacteria such as Nocardia may manifest as indolent pneumonia clinically and may cause airspace disease, with or without cavitation (33). M. tuberculosis and M. avium complex infections are generally uncommon in non-AIDS immunocompromised hosts but are relatively more prevalent in patients after organ transplantation or in patients with lymphoproliferative diseases and primary neoplasms of lung, head, and neck. The most common radiographic picture is typical reactivation tuberculosis, with consolidation of the apical or posterior segments of the upper lobes, often with cavitation (33).

Nodules

Rapidly growing nodules are the hallmark of fungal infection. Nodules may be single or multiple, and cavitation is frequent. Several fungi cause nodules in the immunocompromised host. Aspergillus is the most frequent pathogen. Invasive pulmonary aspergillosis (IPA) is a form of Aspergillus infection in severely immunocompromised hosts, most frequently encountered in patients with acute leukemia who are receiving cytotoxic therapy. These patients typically have prolonged neutropenic fevers treated with broad-spectrum antibiotics (43).Aspergillus is also encountered in patients on prolonged corticosteroid therapy or other immunosuppressive therapy for collagen vascular disease and in AIDS. Definitive diagnosis of IPA is difficult, because the organism is seldom isolated in sputum and is isolated in bronchoalveolar lavage or transbronchial biopsy specimens in only 50% of patients (43). Therefore, the diagnosis is generally empirical, based on the presence of typical radiographic findings in immunocompromised patients not responding to broad-spectrum antibiotics. HRCT demonstrates increased sensitivity for early detection of disease and plays a major role in the diagnosis of IPA (42). Radiographic features of IPA vary. Classically there are multiple ill-defined nodules. A rim of GGO around nodules, termed the “CT halo sign,” provides a significant HRCT clue for early diagnosis (Fig. 6.15). The “halo sign” reflects areas of hemorrhagic infarction and/or edema (33), likely resulting from the angioinvasive nature of the infection (Fig. 6.16).

Rapidly growing nodules are the hallmark of fungal infection.

A rim of ground glass around nodules (“CT halo sign”) at HRCT suggests invasive pulmonary aspergillosis.

Cavitation occurs relatively late in the course of disease, usually as the white blood cell count recovers (Figs. 6.17 and 6.18). At this stage crescentic lucency may appear, termed the “air crescent sign.” This should not be confused with a mycetoma in an immune competent host (43). A mycetoma is usually single; IPA typically results in multiple cavities. A mycetoma arises in the setting of an old pulmonary cavity; IPA usually arises in previously normal lung. A mycetoma is typically freely mobile in its cavity; the central opacity in an IPA cavity is usually fixed, a finding that has been called “the mural nodule” (Figs. 6.19 and 6.20). Aspergillosis may even involve the tracheobronchial tree (Fig. 6.21).

Figure 6.16 Invasive pulmonary aspergillosis in multiple myeloma. Computed tomography at two different levels (A and B) reveals cavitary lung masses (M), one of which directly invades the right inferior pulmonary vein (arrows). Lytic skeletal lesions of multiple myeloma are also seen (arrowheads).

 

Other fungi manifesting with nodules include MucoralesCandidaCoccidioidesBlastomyces, and Cryptococcus. Zygomycosis, now the preferred term for the clinical manifestations of Mucorales infection, is quite similar, clinically and radiologically (Figs. 6.22 and 6.23), to IPA (39). Cryptococcus pneumonia is rare and often presents with associated meningitis. Radiographic features are of single or multiple nodules, sometimes with cavitation.

Candida is a common oropharyngeal commensal organism and may easily contaminate sputum cultures. A lung biopsy is therefore required for the diagnosis of Candida pneumonia.

Figure 6.17 Invasive pulmonary aspergillosis in acute myelogenous leukemia. A. Posteroanterior chest radiograph May 1st: mass-like left upper lobe opacity (M). B. Posteroanterior chest radiograph May 23rd: interval cavitation (arrows) with a large suspended mural nodule (N).

Figure 6.18 Invasive pulmonary aspergillosis in acute lymphocytic leukemia. A. Computed tomography January 25th: right lower lobe mass (M) with computed tomography halo sign (arrows)B. Computed tomography March 4th: smaller nodule with early cavitation (arrow). C. Computed tomography March 26th: nodule is almost entirely cavitary.

Figure 6.19 Invasive pulmonary aspergillosis in AML. Posteroanterior radiograph demonstrates multiple cavitary nodules, many with central suspended mural nodules (N).

Figure 6.20 Invasive pulmonary aspergillosis in acute myelogenous leukemia. Computed tomography at two different levels (A and B)demonstrates nondependent mural nodules (N).

Figure 6.21 Tracheobronchial invasive aspergillosis in leukemia. A. Posteroanterior chest radiograph February 7th: normal trachea. B.Posteroanterior chest radiograph February 18th: early tracheal narrowing (arrows)(C) Posteroanterior chest radiograph March 4th: more obvious tracheal narrowing (arrows), detected in part because of new onset of stridor.

Figure 6.22 Zygomycosis in systemic lupus erythematosus treated with steroids, with vascular invasion. A. Computed tomography: large low attenuation left lung lesion with amorphous central contrast (C). B. Left pulmonary arteriogram: lesion is a large pseudoaneurysm (P).

Figure 6.23 Tracheobronchial zygomycosis in diabetic with renal transplant on immunosuppressive therapy. A. Posteroanterior chest radiograph in 1993 is normal. B. Posteroanterior chest radiograph 1-2-95: mild narrowing of the left main bronchus (arrows)C.Posteroanterior chest radiograph 2-1-95: marked narrowing of the left main bronchus (arrows) with development of left upper lobe collapse (C) and pneumothorax (arrows mark lung edge). D. Computed tomography 2-2-95: confirmation of abnormality of left main bronchus (B), left upper lobe collapse (C), and pneumothorax (P).

Patients with decreased cellular immunity, especially patients on prolonged corticosteroid therapy, are susceptible to Nocardia pneumonia. Radiographically, there are single or multiple nodules that may cavitate (Fig. 6.24). Extension to the pleural cavity and chest wall invasion are suggestive of Nocardia.

Septic emboli are a nodular complication of indwelling catheters, commonly used in immunocompromised patients. S. aureus andStaphylococcus epidermidis are the most common pathogens. Radiographic features include multiple nodules (Fig. 6.25), often with indistinct margins, and frequent cavitation (Fig. 6.26).

Figure 6.24 Cavitary nocardiosis in multiple myeloma. Computed tomography at (A) soft tissue and (B) lung window settings: cavitary right lower lobe pneumonia (C) (arrows mark lesions of multiple myeloma).

Diffuse Lung Disease

Viral lung infections may result in diffuse bilateral lung disease. CMV is the most common such pathogen. Organ recipients are susceptible to CMV pneumonia, particularly through seropositive organ donors or blood transfusions (33). Infection is often asymptomatic.

Symptomatic disease is usually self-limited, but rapid deterioration may occur, typically in BMT recipients. Symptomatic CMV pneumonia may manifest with a normal chest radiograph or may produce diffuse bilateral linear, small nodular, ground glass, or airspace opacities (Fig. 6.27). A single nodule or lobar airspace disease occurs infrequently. Other viral causes of diffuse lung disease include herpes zoster, herpes simplex, and respiratory syncytial virus. Again, organ recipients are at risk. Viral pneumonias characteristically result in diffuse interstitial opacity, GGO, or a reticular or reticulonodular pattern and may progress to diffuse airspace disease.

CMV is an important pathogen in organ transplant recipients.

Figure 6.25 Septic emboli in esophageal carcinoma patient receiving chemotherapy. A and B. Computed tomography at lung window settings: multiple peripheral lung nodules (N), several recognizably wedge-shaped (arrows)C. Computed tomography at soft tissue window settings: thrombus (arrows) in left axillary vein.

PCP is the most common protozoan to cause diffuse lung disease. Although it is closely linked to AIDS, PCP infection also occurs after corticosteroid withdrawal or completion of chemotherapy. The clinical presentation is often fulminant, with rapidly progressive tachypnea and hypoxemia. Diffuse lung disease is often seen (Fig. 6.28), as detailed in the section on AIDS.

Diffuse small nodular disease, the so-called miliary pattern, may be a manifestation of overwhelming M. tuberculosis infection (Figs. 6.29and 6.30). It is not commonly seen in atypical mycobacterial infections. Disseminated fungal infections, including histoplasmosis, coccidioidomycosis, and blastomycosis, may all present radiographically with miliary nodules (33).

Figure 6.26 Septic emboli in systemic lupus erythematosus patient on steroids with indwelling catheter. A and B. Computed tomography at two different levels: bilateral cavitary nodules (arrows).

 

Noninfectious Lung Disease

Many noninfectious processes occur in the non-AIDS immunocompromised host. The radiologist should be aware of these diseases and should suggest them in the appropriate clinical and radiographic setting. For example, the lungs may be infiltrated with the patient’s primary disease, such as leukemic (Fig. 6.31) or lymphomatous infiltration, creating airspace disease, nodules, and, rarely, diffuse lung disease. Metastatic carcinoma usually presents with lung nodules, but lymphangitic carcinomatosis presents with small irregular opacities (reticulonodular pattern), in some patients resembling miliary nodules or other interstitial patterns.

Figure 6.27 Cytomegalovirus pneumonia after renal transplant. A. Posteroanterior chest radiograph September 14th: early diffuse parenchymal abnormality with septal lines, nodularity, and ground glass opacity. B. Posteroanterior chest radiograph September 17th: diffuse bilateral airspace disease.

Figure 6.28 Pneumocystis pneumonia in patient with T-cell defect. Bilateral airspace disease, predominantly in the central upper lungs.

Figure 6.29 Miliary tuberculosis in patient receiving steroids. Chest radiograph reveals miliary nodules.

Figure 6.30 Miliary tuberculosis in rheumatoid arthritis patient receiving cytotoxic therapy. Computed tomography at two different levels (A and B) demonstrates disseminated small nodules.

Figure 6.31 Leukemic infiltration of lung in acute myelogenous leukemia. Posteroanterior chest radiograph shows bilateral airspace disease, greatest in the right perihilar lung and left lower lobe.

Intrathoracic lymphoproliferative disorders are more common in AIDS patients but are also well documented in organ transplant recipients. Radiographic findings vary and include multiple nodules, diffuse GGO, and airspace disease. Pleural effusions and lymph node enlargement may or may not occur (42,44) (Fig. 6.32). Posttransplant lymphoproliferative disorder may regress as immunosuppression is withdrawn. Immunocompromised patients also develop complications of therapy.

Intrathoracic lymphoproliferative disease deserves special consideration in AIDS patients and in organ transplant recipients.

Figure 6.32 Posttransplant lymphoproliferative disorder 12 years after heart transplant for transposition of the great vessels with a single ventricle. A and B. Computed tomography at two different levels: extensive lymph node mass (M) throughout the mediastinum with loculated right pleural effusion (E). Patient presented with 2- to 3-day history of dry cough on October 7th and died on October 21st.

Pulmonary hemorrhage may complicate chemotherapy-induced thrombocytopenia and usually manifests as airspace disease. Cytotoxic therapy, especially with Adriamycin (Doxorubicin), is potentially cardiotoxic. It may cause heart failure and resultant pulmonary edema. Pulmonary edema may also develop after excessive hydration. Other chemotherapeutic agents such as bleomycin and busulfan are known to cause pulmonary fibrosis. Radiation pneumonitis may follow radiation therapy, usually conforming to the radiation port. Rejection of transplanted lung and pulmonary graft-versus-host disease in BMT patients both result in bronchiolitis obliterans. HRCT features of bronchiolitis obliterans include air trapping, centrilobular nodules, and bronchiectasis.

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