HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) CME Test (opens in a new window) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, E. A Articles by Han, J. Search for Related Content PubMed PubMed Citation Articles by Kim, E. A Articles by Han, J. Related Collections Chest Radiology Computed Tomography

Viral Pneumonias in Adults: Radiologic and Pathologic Findings¹

¹ From the Departments of Radiology (E.A.K., K.S.L., H.K.Y., H.S.B., T.S.K.), Medicine (G.Y.S., O.J.K.), and Diagnostic Pathology (J.H.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea; and the Department of Radiology, Oregon Health Sciences University, Portland (S.L.P.). Recipient of a Certificate of Merit award for an education exhibit at the 2001 RSNA scientific assembly. Received January 29, 2002; revision requested March 14 and received April 10; accepted April 26. Address correspondence to K.S.L. (e-mail: kslee@smc.samsung.co.kr).

	Abstract

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

 
Numerous viruses, including influenza virus, measles virus, Hantavirus, adenovirus, herpesviruses, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus, can cause lower respiratory tract infection in adults. Viral pneumonia in adults can be classified into two clinical groups: so-called atypical pneumonia in otherwise healthy hosts and viral pneumonia in immunocompromised hosts. Influenza virus types A and B cause most cases of viral pneumonia in immunocompetent adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus, herpesviruses, measles virus, and adenovirus. The radiographic findings, which consist mainly of patchy or diffuse ground-glass opacity with or without consolidation and reticular areas of increased opacity, are variable and overlapping. Computed tomographic findings, which are also overlapping, consist of poorly defined centrilobular nodules, ground-glass attenuation with a lobular distribution, segmental consolidation, or diffuse ground-glass attenuation with thickened interlobular septa. The radiologic findings reflect the variable extents of the histopathologic features: diffuse alveolar damage (intraalveolar edema, fibrin, and variable cellular infiltrates with a hyaline membrane), intraalveolar hemorrhage, and interstitial (intrapulmonary or airway) inflammatory cell infiltration. Clinical information such as patient age, immune status, community outbreaks, symptom onset and duration, and presence of a rash remain important aids in diagnosis of viral causes.

© RSNA, 2002

Index Terms: Lung, infection, 60.206 • Pneumonia, 60.21 • Viruses, 60.206, 60.2062, 60.2063, 60.2064, 60.2065, 60.2066, 60.2069

	LEARNING OBJECTIVES

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

 
After reading this article and taking the test, the reader will be able to:

• Recognize the radiographic and CT findings of various viral pneumonias in adults.
  
• Describe the correlations between the radiologic findings and the histopathologic findings.
  
• Discuss differentiation between various viral pneumonias on the basis of radiologic and clinical features.
  

	Introduction

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

 
Numerous viruses may cause lower respiratory tract infection in adults. The viruses include influenza virus, adenovirus, measles virus, Hantavirus, varicella-zoster virus, and cytomegalovirus (1).

Clinically, viral pneumonia in adults can be divided into two groups: so-called atypical pneumonia in otherwise normal hosts and viral pneumonia in immunocompromised hosts (2). Influenza virus types A and B account for the majority of viral pneumonias in immunocompetent adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus and herpesviruses, as well as measles virus and adenovirus (Table 1). In specific populations (recent military recruits and some immunocompromised patients), the prevalence and severity of these pneumonias are high. Adenovirus pneumonia was common in military recruits prior to the development of a live attenuated adenovirus vaccine (3). Therefore, recognition of the various radiologic manifestations of viral pneumonias in conjunction with patients’ clinical history is imperative for narrowing the differential diagnosis and determining appropriate management.

	Common Pathologic Findings

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

 
Viruses can result in several pathologic forms of lower respiratory tract infection including tracheobronchitis, bronchiolitis, and pneumonia. Because the organisms replicate within tissue cells, the most prominent histologic changes are seen in the epithelium and adjacent interstitial tissue. In tracheobronchitis, airway walls are congested and the lumen contains mononuclear cell infiltrates. Degeneration and desquamation of the epithelial cells are seen. Bronchiolitis, which is particularly important in children, appears with epithelial necrosis, neutrophilic exudate in the airway lumen, and predominantly mononuclear infiltrates in its wall (4,5).

Parenchymal involvement (pneumonia) initially involves the lung adjacent to the terminal and respiratory bronchioles; however, extension throughout the lobule may occur. Rapidly progressive pneumonia may be seen particularly in the elderly and in immunocompromised patients (6). In these circumstances, the lungs histologically show diffuse alveolar damage comprising interstitial lymphocyte infiltration, air-space hemorrhage, edema and fibrin, type 2 cell hyperplasia, and hyaline membrane formation (7,8) (Fig 1).

View larger version (181K): [in this window] [in a new window] [Download PPT slide]   Figure 1.  Photomicrograph (original magnification, x100; hematoxylin-eosin stain) of a lung biopsy specimen from a 36-year-old man with pneumonia due to herpes simplex virus type 1 shows a fibrous exudate (large arrows) along the alveolar walls. Note the interstitial thickening due to fibroblastic proliferation (small arrows).

	Common Radiologic Findings

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

Viral pneumonia manifests radiologically as poorly defined nodules (air-space nodules of 4–10 mm in diameter) and patchy areas of peribronchial ground-glass opacity and air-space consolidation. Because of the associated bronchiolitis, hyperinflation is commonly present (4,5). The progressive form of pneumonia shows the rapid confluence of consolidation leading to diffuse alveolar damage, consisting of homogeneous or patchy unilateral or bilateral air-space consolidation and ground-glass opacity or poorly defined centrilobular nodules (9) (Fig 2).

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Pneumonia due to influenza virus (type C) in a 46-year-old man with dyspnea. (a) Initial chest radiograph shows diffuse reticulonodular areas of increased opacity in both lungs. (b) Follow-up chest radiograph obtained 15 days after a shows progression of the extent of disease with diffuse consolidation throughout both lungs. (c) Thin-section (1-mm collimation) computed tomographic (CT) scan obtained 16 days after a at the level of the aortic arch shows diffuse ground-glass attenuation with some irregular linear areas of increased attenuation in both lungs. (Case courtesy of Dr Jung Hwa Hwang, Soonchunhyang University Seoul Hospital, Korea.)

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Pneumonia due to influenza virus (type C) in a 46-year-old man with dyspnea. (a) Initial chest radiograph shows diffuse reticulonodular areas of increased opacity in both lungs. (b) Follow-up chest radiograph obtained 15 days after a shows progression of the extent of disease with diffuse consolidation throughout both lungs. (c) Thin-section (1-mm collimation) computed tomographic (CT) scan obtained 16 days after a at the level of the aortic arch shows diffuse ground-glass attenuation with some irregular linear areas of increased attenuation in both lungs. (Case courtesy of Dr Jung Hwa Hwang, Soonchunhyang University Seoul Hospital, Korea.)

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 2c.  Pneumonia due to influenza virus (type C) in a 46-year-old man with dyspnea. (a) Initial chest radiograph shows diffuse reticulonodular areas of increased opacity in both lungs. (b) Follow-up chest radiograph obtained 15 days after a shows progression of the extent of disease with diffuse consolidation throughout both lungs. (c) Thin-section (1-mm collimation) computed tomographic (CT) scan obtained 16 days after a at the level of the aortic arch shows diffuse ground-glass attenuation with some irregular linear areas of increased attenuation in both lungs. (Case courtesy of Dr Jung Hwa Hwang, Soonchunhyang University Seoul Hospital, Korea.)

	Viruses

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

	Various Viral Pneumonias

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

 
Influenza Virus Pneumonia
Influenza virus infection usually involves the upper respiratory tract including the trachea and major bronchi in children and young adults. However, elderly and immunocompromised persons are at increased risk for development of fulminant pneumonia. Influenza viruses are divided into three groups (A, B, and C) according to internal membrane and nucleoprotein antigens. Of these three groups, type A and occasionally type B organisms cause influenza virus pneumonia (10). Although the pneumonia is usually mild, it can be overwhelming and fatal within 24 hours. Predisposing conditions for the infection include mitral stenosis, pregnancy, diabetes, old age, and immunosuppression (6,11).

Histologically, airway walls are congested and lumina contain mononuclear cell infiltrates. Degeneration and desquamation of the epithelial cells are seen. Parenchymal change shows typical features of diffuse alveolar damage (7,12).

Serial radiographs show poorly defined, patchy areas of air-space consolidation, 1–2 cm in diameter, that rapidly become confluent (Fig 2). Diffuse or patchy areas of ground-glass attenuation mixed with consolidation are frequently seen at CT (Fig 2). Small centrilobular nodules representing alveolar hemorrhage may be associated (Fig 3). Pleural effusion is rare. The radiologic abnormalities usually resolve in approximately 3 weeks (9). In one study, influenza virus pneumonia showed air-space consolidation or ground-glass attenuation with a lobular distribution at high-resolution CT. Hyaline membrane formation in the alveolar parenchyma around the bronchiole probably accounts for the predominant CT findings of air-space consolidation or ground-glass attenuation with a lobular distribution (13).

View larger version (153K): [in this window] [in a new window] [Download PPT slide]   Figure 3a.  Pneumonia due to influenza virus in a 21-year-old man with a cough. (a) Initial chest radiograph shows poorly defined nodules (arrows) and reticular areas of increased opacity in both lungs. (b, c) Thin-section (1-mm collimation) CT scans obtained at the levels of the aortic arch (b) and suprahepatic inferior vena cava (c) show multifocal peribronchovascular or subpleural consolidation and ground-glass attenuation in both lungs. Some lesions have a lobular distribution (arrows). Note the acinar nodules (arrowheads). (Case courtesy of Jin Mo Goo, MD, PhD, Seoul National University Hospital, Korea.)

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 3b.  Pneumonia due to influenza virus in a 21-year-old man with a cough. (a) Initial chest radiograph shows poorly defined nodules (arrows) and reticular areas of increased opacity in both lungs. (b, c) Thin-section (1-mm collimation) CT scans obtained at the levels of the aortic arch (b) and suprahepatic inferior vena cava (c) show multifocal peribronchovascular or subpleural consolidation and ground-glass attenuation in both lungs. Some lesions have a lobular distribution (arrows). Note the acinar nodules (arrowheads). (Case courtesy of Jin Mo Goo, MD, PhD, Seoul National University Hospital, Korea.)

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 3c.  Pneumonia due to influenza virus in a 21-year-old man with a cough. (a) Initial chest radiograph shows poorly defined nodules (arrows) and reticular areas of increased opacity in both lungs. (b, c) Thin-section (1-mm collimation) CT scans obtained at the levels of the aortic arch (b) and suprahepatic inferior vena cava (c) show multifocal peribronchovascular or subpleural consolidation and ground-glass attenuation in both lungs. Some lesions have a lobular distribution (arrows). Note the acinar nodules (arrowheads). (Case courtesy of Jin Mo Goo, MD, PhD, Seoul National University Hospital, Korea.)

Atypical measles develops when children who have been immunized with inactivated measles viruses are exposed again to measles virus or to live measles virus vaccine. Although not proved, an immune mechanism is regarded as the underlying pathophysiology because clinical and radiologic findings change rapidly (16).

The prevalence of measles virus pneumonia is higher in pregnant women and patients who are immunocompromised due to hematologic malignancy (leukemia or lymphoma), acquired immunodeficiency syndrome (AIDS), or immunosuppressive therapy (17–19).

Measles virus pneumonia without bacterial superinfection appears with epithelial hyperplasia and diffuse alveolar damage. Epithelial hyperplasia associated with many foci of squamous metaplasia is seen in bronchioles and peribronchial alveoli. It is also seen in the tracheobronchial epithelium with cystic dilatation of mucous glands. Histologically, measles virus pneumonia is characterized by multinucleated giant cells containing up to 50 nuclei in the alveolar air spaces and within the bronchiolar and tracheobronchial epithelium (18).

Chest radiographic findings of primary measles virus pneumonia are mixed reticular opacities and air-space consolidation (15) (Fig 4). In children, lymph node enlargement in the hilum may be associated. CT findings include ground-glass attenuation, air-space consolidation, and small centrilobular nodules (20). These findings represent the underlying pathologic mechanism of diffuse alveolar damage, producing both interstitial and air-space diseases. Atypical measles virus pneumonia appears with spherical or segmental consolidation, which clears rapidly. Hilar lymph node enlargement and pleural effusion are frequently associated (16).

View larger version (175K): [in this window] [in a new window] [Download PPT slide]   Figure 4.  Pneumonia due to measles virus in a 13-year-old boy with a fever, cough, and skin rash. The patient had an increased immunoglobulin M antibody titer to measles virus. Chest radiograph shows poorly defined nodules and patchy consolidation in the left middle and lower lung zones.

The natural reservoir of all Hantaviruses is wild rodents and deer mice, the latter being the most important animal harboring the Sin Nombre variant in the United States (21,23). The organism is believed to be transmitted to humans by inhalation of dried rodent excreta associated with outdoor activities in rural areas, such as cleaning barns, plowing with hand tools, and harvesting rice.

Hantavirus pulmonary syndrome characteristically presents as respiratory distress from noncardiogenic edema. After an incubation period of 9–35 days, the syndrome begins to progress through its three stages. The initial stage is the prodromal phase, which is followed by the cardiopulmonary and convalescent phases.

Histologically, interstitial and air-space edema, mild to moderate interstitial infiltrates of lymphocytes, epithelial necrosis, vascular thrombosis, and hyaline membranes are seen (24). The lung disease in the Hantavirus syndrome has some distinct pathologic differences from diffuse alveolar damage due to other causes. They are extensive cellular debris, destruction of type I cells, prominence of type II cells, neutrophil infiltrates, and fibrosing alveolitis (24).

Radiographically, Hantavirus pulmonary syndrome presents as interstitial edema with or without rapid progression to air-space disease. The air-space disease shows a central or bibasilar distribution. Also, pleural effusion is a common finding. The radiographic findings in Hantavirus pulmonary syndrome are consistent with a pulmonary capillary leak (Fig 5). However, pulmonary manifestations may occasionally be secondary to renal failure. In these cases, pulmonary edema and cardiomegaly with or without pleuropericardial effusion are the predominant findings in the oliguric phase of renal failure (25). However, in infection of the Sin Nombre organism, more severe findings with diffuse alveolar damage are usually seen (Fig 5). Recently, Boroja et al (23) identified two broad categories of Hantavirus pulmonary syndrome clinically and radiographically: (a) a rapidly progressive, fulminant, and often fatal clinical form with radiographic features of rapidly progressive alveolar pulmonary edema, air-space consolidation, and pleural effusions; and (b) a limited, less severe clinical form usually associated with mild interstitial edema and minimal air-space disease. All patients with the limited form of Hantavirus pulmonary syndrome survived the illness, whereas 46% of those with the fulminant form died.

View larger version (173K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Pneumonia due to Hantavirus (Sin Nombre species) in a 39-year-old American woman with dyspnea. (a, b) Initial posteroanterior (a) and lateral (b) chest radiographs show bilateral perihilar and basilar ground-glass opacity. Fissures are accentuated on the lateral radiograph (b). The heart is of normal size. (c) Follow-up anteroposterior chest radiograph obtained 4 days after a shows progression to extensive bilateral consolidation in the middle and lower lung zones.

View larger version (153K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Pneumonia due to Hantavirus (Sin Nombre species) in a 39-year-old American woman with dyspnea. (a, b) Initial posteroanterior (a) and lateral (b) chest radiographs show bilateral perihilar and basilar ground-glass opacity. Fissures are accentuated on the lateral radiograph (b). The heart is of normal size. (c) Follow-up anteroposterior chest radiograph obtained 4 days after a shows progression to extensive bilateral consolidation in the middle and lower lung zones.

View larger version (145K): [in this window] [in a new window] [Download PPT slide]   Figure 5c.  Pneumonia due to Hantavirus (Sin Nombre species) in a 39-year-old American woman with dyspnea. (a, b) Initial posteroanterior (a) and lateral (b) chest radiographs show bilateral perihilar and basilar ground-glass opacity. Fissures are accentuated on the lateral radiograph (b). The heart is of normal size. (c) Follow-up anteroposterior chest radiograph obtained 4 days after a shows progression to extensive bilateral consolidation in the middle and lower lung zones.

Pathologically, the lungs in adenovirus pneumonia are large and heavy and show patchy areas of hemorrhagic consolidation, mixed with areas of overinflation or atelectasis. In the airways, mucopurulent or hemorrhagic materials are seen along with wall thickening caused by congestion. Microscopically, the lung parenchyma contains necrotic changes with diffuse alveolar damage. In mild forms, findings of interstitial inflammatory cell infiltration may predominate (28,29). Nuclear inclusion bodies, most prominent in alveolar lining cells but also found in the airway epithelium, may be identified in infected cells. Their presence in the expectorated sputum may provide evidence supportive of the diagnosis.

The most frequent radiographic findings of adenovirus pneumonia, especially in children, consist of diffuse bilateral bronchopneumonia and severe overinflation. Lobar atelectasis is also a frequent finding (Fig 6). Right upper lobe atelectasis occurs most commonly in infants, while left lower lobe atelectasis is more common in older children. In patients with uncomplicated pneumonia, the disease resolves within 2 weeks radiographically. Chronic disease is more common in children under 2 years of age at the time of the acute illness than in older patients (30). In a recent study by Han et al (4), adenovirus pneumonia in children mimicked bacterial pneumonia on chest radiographs in most patients. In their study, which included 21 pediatric patients with adenovirus pneumonia, chest radiographs showed typical lower respiratory infection with hyperaeration, bronchial wall thickening, and patchy areas of atelectasis in only two patients. In the remaining 19 patients, lobar or segmental air-space consolidation was seen. The consolidation was bilateral in 12 of 19 patients (63%). Pleural effusion was present in 13 of 21 patients (62%). The authors suggested that a normal or decreased white blood cell count associated with lymphocytosis and progression of disease despite extensive antibiotic therapy may help differentiate adenoviral from bacterial pneumonia.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Pneumonia due to adenovirus in a 15-year-old boy. Thin-section (1-mm collimation) CT scans obtained at the levels of the inferior pulmonary vein (a) and the dome of the liver (b) show complete atelectasis of the right middle lobe and multifocal air trapping (arrows), an appearance indicative of acute bronchiolitis.

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Pneumonia due to adenovirus in a 15-year-old boy. Thin-section (1-mm collimation) CT scans obtained at the levels of the inferior pulmonary vein (a) and the dome of the liver (b) show complete atelectasis of the right middle lobe and multifocal air trapping (arrows), an appearance indicative of acute bronchiolitis.

Pathologically, disease caused by herpes simplex virus type 1 manifests as focal or diffuse ulcers in the tracheobronchial epithelium with or without necrotizing bronchopneumonia (33,34). The airway lesion is characterized histologically by epithelial necrosis and ulceration. Pneumonia is usually characterized by alveolar necrosis and a proteinaceous exudate with a variable polymorphonuclear inflammatory response (35) (Fig 7).

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Pneumonia due to herpes simplex virus type 1 in a 36-year-old man with myelodysplastic syndrome. (a) Initial chest radiograph shows diffuse ground-glass opacity, poorly defined nodules, and patchy consolidation in both lungs. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the inferior pulmonary vein shows diffuse ground-glass attenuation and some air-space nodules (arrows) in both lungs. Note the small bilateral pleural effusions. (c) Photomicrograph (original magnification, x12; hematoxylin-eosin stain) shows diffuse alveolar wall thickening (large arrows) due to fibroblastic proliferation (diffuse alveolar damage, organizing stage). Note the intraalveolar exudate (small arrows). (d) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows eosinophilic inclusions (arrows) within large nuclei.

View larger version (138K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Pneumonia due to herpes simplex virus type 1 in a 36-year-old man with myelodysplastic syndrome. (a) Initial chest radiograph shows diffuse ground-glass opacity, poorly defined nodules, and patchy consolidation in both lungs. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the inferior pulmonary vein shows diffuse ground-glass attenuation and some air-space nodules (arrows) in both lungs. Note the small bilateral pleural effusions. (c) Photomicrograph (original magnification, x12; hematoxylin-eosin stain) shows diffuse alveolar wall thickening (large arrows) due to fibroblastic proliferation (diffuse alveolar damage, organizing stage). Note the intraalveolar exudate (small arrows). (d) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows eosinophilic inclusions (arrows) within large nuclei.

View larger version (182K): [in this window] [in a new window] [Download PPT slide]   Figure 7c.  Pneumonia due to herpes simplex virus type 1 in a 36-year-old man with myelodysplastic syndrome. (a) Initial chest radiograph shows diffuse ground-glass opacity, poorly defined nodules, and patchy consolidation in both lungs. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the inferior pulmonary vein shows diffuse ground-glass attenuation and some air-space nodules (arrows) in both lungs. Note the small bilateral pleural effusions. (c) Photomicrograph (original magnification, x12; hematoxylin-eosin stain) shows diffuse alveolar wall thickening (large arrows) due to fibroblastic proliferation (diffuse alveolar damage, organizing stage). Note the intraalveolar exudate (small arrows). (d) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows eosinophilic inclusions (arrows) within large nuclei.

View larger version (172K): [in this window] [in a new window] [Download PPT slide]   Figure 7d.  Pneumonia due to herpes simplex virus type 1 in a 36-year-old man with myelodysplastic syndrome. (a) Initial chest radiograph shows diffuse ground-glass opacity, poorly defined nodules, and patchy consolidation in both lungs. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the inferior pulmonary vein shows diffuse ground-glass attenuation and some air-space nodules (arrows) in both lungs. Note the small bilateral pleural effusions. (c) Photomicrograph (original magnification, x12; hematoxylin-eosin stain) shows diffuse alveolar wall thickening (large arrows) due to fibroblastic proliferation (diffuse alveolar damage, organizing stage). Note the intraalveolar exudate (small arrows). (d) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows eosinophilic inclusions (arrows) within large nuclei.

Varicella-Zoster Virus Pneumonia
Varicella-zoster virus pneumonia is the most serious complication of disseminated varicella-zoster virus infection with mortality rates of 9%–50% (37). Reported prevalences of varicella-zoster virus pneumonia have varied from less than 5% to up to 50% of all varicella infections in adults (38). Varicella-zoster virus most commonly causes self-limited benign disease (chickenpox) in children. However, in adults it tends to cause significant complications such as varicella-zoster virus pneumonia. More than 90% of cases of varicella-zoster virus pneumonia in adults occur in patients with lymphoma and immunocompromised patients (39).

Histologic features of varicella-zoster virus pneumonia are those of diffuse alveolar damage. With recovery from the initial disease, spherical nodules are seen, scattered randomly throughout the lung parenchyma. Histologically, the nodules are composed of an outer, often lamellated fibrous capsule frequently enclosing areas of hyalinized collagen or necrotic tissue. Calcification varies in intensity (40).

Chest radiographic findings of varicella-zoster virus pneumonia consist of multiple 5–10-mm ill-defined nodules that may be confluent and fleeting. Hilar lymphadenopathy and pleural effusion are unusual. The small, round nodules usually resolve within a week after the disappearance of the skin lesions but may persist for months. Usually resolving in 3–5 days in milder disease, the small nodules may persist for several weeks in widespread disease. The lesions calcify and can persist as numerous, well-defined, randomly scattered, 2–3-mm dense calcifications (40,41).

High-resolution CT usually shows 1–10-mm well-defined and ill-defined nodules diffusely throughout both lungs (Fig 8). Nodules with a surrounding halo of ground-glass opacity, patchy ground-glass opacity, and coalescence of nodules are also seen. These findings disappear concurrently with healing of skin lesions after antiviral chemotherapy (40).

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 8.  Pneumonia due to varicella-zoster virus in a 30-year-old man with a fever and skin rash. Thin-section (1-mm collimation) CT scan obtained at the level of the bronchus intermedius shows multiple 1-2-mm-diameter nodules scattered throughout both lungs. (Courtesy of Dong Wook Sung, MD, Kyung Hee University Hospital, Seoul, Korea.)

It has been suggested that cytomegalovirus pneumonitis in allogenic transplant recipients is caused by immune mechanisms mediated by a T cell response to virally induced antigens expressed in the lungs. Severe necrotizing pneumonitis may occur despite suppression of virus replication during ganciclovir therapy. AIDS patients, with more profound immune deficiency than transplant recipients, may be unable to begin the immune response necessary to cause cytomegalovirus pneumonitis by this mechanism. In AIDS patients, the lung damage may be due directly to cytopathogenic effects of cytomegalovirus, related to the extent of active virus replication. These differences in pathogenic mechanisms of pulmonary cytomegalovirus infection result in different histopathologic features between AIDS patients and transplant recipients. In transplant recipients with cytomegalovirus pneumonia, necrotizing inflammation is predominant with relatively few cytomegalovirus-infected cells at histopathologic examination. In AIDS patients with cytomegalovirus pneumonia, a high density of cytomegalovirus inclusion bodies is present and they are responsible for severe, symptomatic pneumonitis. The cytopathogenic effect of cytomegalovirus probably causes diffuse alveolar damage more frequently in AIDS patients than in patients without AIDS.

The CT findings of cytomegalovirus pneumonia are diverse and have been described without distinction between AIDS patients and patients without AIDS. Common findings are mixed alveolar-interstitial infiltrates such as ground-glass attenuation, consolidation, nodules, poorly defined small centrilobular nodules, bronchial dilatation, and thickened interlobular septa (42–45) (Figs 9, 10). Kang et al (42) reported CT findings of cytomegalovirus pneumonia in 10 transplant recipients. Abnormal findings were seen in nine patients including nodules (n = 6), consolidation (n = 4), ground-glass attenuation (n = 4), and irregular linear attenuation (n = 1). Moon et al (43) reported that poorly defined centrilobular small nodules (90%) and areas of consolidation (70%) are also common. In the study by Kim and Lee (44) of high-resolution CT findings in 11 immunocompromised patients, ground-glass attenuation (n = 11), irregular linear attenuation (n = 10), consolidation (n = 7), multiple small nodules or a mass (n = 6), and bronchial dilatation or wall thickening (n = 5) were seen.

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Pneumonia due to cytomegalovirus in a 28-year-old man with acute myeloid leukemia. (a) Thin-section (1-mm collimation) CT scan obtained at the level of the bronchus intermedius shows multifocal patchy ground-glass attenuation and poorly defined centrilobular nodules (arrows) in both lungs. (b) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows diffuse interstitial and intraalveolar fibroblastic proliferation (arrows) with some mononuclear cell infiltration (diffuse alveolar damage, organizing stage). (c) Photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows three large nuclei containing eosinophilic inclusion bodies (arrows) within hyperplastic pneumocytes. (d) Photomicrograph (original magnification, x400; immunohistochemical marker for cytomegalovirus) shows positive intranuclear inclusion bodies (arrows).

View larger version (207K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Pneumonia due to cytomegalovirus in a 28-year-old man with acute myeloid leukemia. (a) Thin-section (1-mm collimation) CT scan obtained at the level of the bronchus intermedius shows multifocal patchy ground-glass attenuation and poorly defined centrilobular nodules (arrows) in both lungs. (b) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows diffuse interstitial and intraalveolar fibroblastic proliferation (arrows) with some mononuclear cell infiltration (diffuse alveolar damage, organizing stage). (c) Photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows three large nuclei containing eosinophilic inclusion bodies (arrows) within hyperplastic pneumocytes. (d) Photomicrograph (original magnification, x400; immunohistochemical marker for cytomegalovirus) shows positive intranuclear inclusion bodies (arrows).

View larger version (143K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  Pneumonia due to cytomegalovirus in a 28-year-old man with acute myeloid leukemia. (a) Thin-section (1-mm collimation) CT scan obtained at the level of the bronchus intermedius shows multifocal patchy ground-glass attenuation and poorly defined centrilobular nodules (arrows) in both lungs. (b) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows diffuse interstitial and intraalveolar fibroblastic proliferation (arrows) with some mononuclear cell infiltration (diffuse alveolar damage, organizing stage). (c) Photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows three large nuclei containing eosinophilic inclusion bodies (arrows) within hyperplastic pneumocytes. (d) Photomicrograph (original magnification, x400; immunohistochemical marker for cytomegalovirus) shows positive intranuclear inclusion bodies (arrows).

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  Pneumonia due to cytomegalovirus in a 28-year-old man with acute myeloid leukemia. (a) Thin-section (1-mm collimation) CT scan obtained at the level of the bronchus intermedius shows multifocal patchy ground-glass attenuation and poorly defined centrilobular nodules (arrows) in both lungs. (b) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows diffuse interstitial and intraalveolar fibroblastic proliferation (arrows) with some mononuclear cell infiltration (diffuse alveolar damage, organizing stage). (c) Photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows three large nuclei containing eosinophilic inclusion bodies (arrows) within hyperplastic pneumocytes. (d) Photomicrograph (original magnification, x400; immunohistochemical marker for cytomegalovirus) shows positive intranuclear inclusion bodies (arrows).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Pneumonia due to cytomegalovirus in a 45-year-old man who underwent liver transplantation. (a) Chest radiograph obtained 4 weeks after liver transplantation shows patchy air-space consolidation in both lungs. An endotracheal intubation tube, a pigtail drainage catheter in the right pleural space, a chest tube in the left pleural space, and a central venous catheter are seen. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the right upper lobe bronchus 2 days before a shows multifocal patchy ground-glass attenuation in both lungs. Note the consolidation (white arrow) and the small, poorly defined nodules (black arrows). There are associated bilateral pleural effusions.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Pneumonia due to cytomegalovirus in a 45-year-old man who underwent liver transplantation. (a) Chest radiograph obtained 4 weeks after liver transplantation shows patchy air-space consolidation in both lungs. An endotracheal intubation tube, a pigtail drainage catheter in the right pleural space, a chest tube in the left pleural space, and a central venous catheter are seen. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the right upper lobe bronchus 2 days before a shows multifocal patchy ground-glass attenuation in both lungs. Note the consolidation (white arrow) and the small, poorly defined nodules (black arrows). There are associated bilateral pleural effusions.

Epstein-Barr Virus Pneumonia
Pulmonary involvement associated with Epstein-Barr virus infection is a rare but potential complication of infectious mononucleosis (46).

Infectious mononucleosis usually occurs in young adults aged 15–30 years. Infectious mononucleosis caused by Epstein-Barr virus usually resolves over a period of weeks or months without sequelae but may occasionally be complicated by a wide variety of neurologic, hematologic, hepatic, respiratory, and psychologic complications.

Pathologically, mononuclear inflammatory cells are apparent along bronchovascular bundles and interlobular septa in interstitial pulmonary infiltrates. These mononuclear cells are also present, in lesser numbers, in the alveolar exudates (47).

Intrathoracic involvement by infectious mononucleosis is uncommon. The most common radiologic abnormalities are mediastinal lymphadenopathy and rarely interstitial infiltrates (Fig 11). Pulmonary consolidation in infectious mononucleosis associated with interstitial pulmonaryinfiltrates is very rare (48). Splenomegaly is common and may be seen in up to 47% of chest radiographic examinations (49).

View larger version (156K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.  Pneumonia due to Epstein-Barr virus in a 25-year-old man with a fever, chills, and palpable lymph nodes. (a) Chest radiograph shows ground-glass opacity and multiple small nodules in both lungs, especially in the middle and lower lung zones, along with small bilateral pleural effusions. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the left inferior pulmonary vein shows numerous small nodules (arrows) and diffuse ground-glass attenuation.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.  Pneumonia due to Epstein-Barr virus in a 25-year-old man with a fever, chills, and palpable lymph nodes. (a) Chest radiograph shows ground-glass opacity and multiple small nodules in both lungs, especially in the middle and lower lung zones, along with small bilateral pleural effusions. (b) Thin-section (1-mm collimation) CT scan obtained at the level of the left inferior pulmonary vein shows numerous small nodules (arrows) and diffuse ground-glass attenuation.

	Conclusions

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

 
The radiologic findings of adult viral pneumonias are variable and overlapping (Table 2). Specific-organism diagnosis of a viral pneumonia cannot be made on the basis of imaging features alone. Clinical features such as patient age; immune status; time of year; illness in other family members; community outbreaks; onset, severity, and duration of symptoms; and the presence of a rash remain important aids in diagnosing viral causes of both atypical pneumonia and pneumonia in immunocompromised patients.

	Footnotes

 
Abbreviation: AIDS = acquired immunodeficiency syndrome

	References

Top Abstract LEARNING OBJECTIVES Introduction Common Pathologic Findings Common Radiologic Findings Viruses Various Viral Pneumonias Conclusions References

 

1. Greenberg SB. Viral pneumonia. Infect Dis Clin North Am 1991; 5:603-621.[Medline]
2. Sullivan CJ, Jordan MC. Diagnosis of viral pneumonia. Semin Respir Infect 1988; 3:148-161.[Medline]
3. Retails P, Strange C, Harley R. The spectrum of adult adenovirus pneumonia. Chest 1996; 109:1656-1657.[Abstract/Free Full Text]
4. Han BK, Son JA, Yoon HK, Lee SI. Epidemic adenoviral lower respiratory tract infection in pediatric patients: radiographic and clinical characteristics. AJR Am J Roentgenol 1998; 170:1077- 1080.[Abstract/Free Full Text]
5. Palmer SM, Jr, Henshaw NG, Howell DN, Miller SE, Davis RD, Tapson VF. Community respiratory viral infection in adult lung transplant recipients. Chest 1998; 113:944-950.[Abstract/Free Full Text]
6. Tillett HE, Smith JW, Clifford RE. Excess morbidity and mortality associated with influenza in England and Wales. Lancet 1980; 1:793-795.[Medline]
7. Feldman PS, Cohan MA, Hierholzer WJ, Jr. Fatal Hong Kong influenza: a clinical microbiological and pathological analysis of nine cases. Yale J Biol Med 1972; 45:49-63.[Medline]
8. Yeldandi AV, Colby TV. Pathologic features of lung biopsy specimens from influenza pneumonia cases. Hum Pathol 1994; 25:47-53.[CrossRef][Medline]
9. Galloway RW, Miller RS. Lung changes in the recent influenza epidemic. Br J Radiol 1959; 32:28-32.
10. Nolan TF, Jr, Goodman RA, Hinman AR, et al. Morbidity and mortality associated with influenza B in the United States, 1979–1980: a report from the Centers for Disease Control. J Infect Dis 1980; 142:360-362.[Medline]
11. Mullooly JP, Barker WH, Nolan TF. Risk of acute respiratory disease among pregnant women during influenza A epidemics. Public Health Rep 1986; 101:205-211.[Medline]
12. Soto PJ, Broun GO, Wyatt JP. Asian influenzal pneumonitis: a structural and virologic analysis. Am J Med 1959; 27:18-21.[CrossRef][Medline]
13. Tanaka N, Matsumoto T, Kuramitsu T, et al. High resolution CT findings in community-acquired pneumonia. J Comput Assist Tomogr 1996; 20:600-608.[CrossRef][Medline]
14. Hinman AR, Orenstein WA, Block AB, et al. Impact of measles in the United States. Rev Infect Dis 1983; 5:439-444.[Medline]
15. Gremillion DH, Crawford GE. Measles pneumonia in young adults: an analysis of 106 cases. Am J Med 1981; 71:539-542.[CrossRef][Medline]
16. Margolin FR, Gandy TK. Pneumonia of atypical measles. Radiology 1979; 131:653-655.[Abstract]
17. Atmar RL, Englund JA, Hammill H. Complications of measles during pregnancy. Clin Infect Dis 1992; 14:217-226.[Medline]
18. Becroft DM, Osborne DR. The lungs in fatal measles infection in childhood: pathological, radiological and immunological correlations. Histopathology 1980; 4:401-412.[Medline]
19. Kaplan LJ, Daum RS, Smaron M, McCarthy CA. Severe measles in immunocompromised patients. JAMA 1992; 267:1237-1241.[Abstract]
20. Tanaka H, Honma S, Yamagishi M, et al. Clinical features of measles pneumonia in adults: usefulness of computed tomography. Nihon Kyobu Shikkan Gakkai Zasshi 1993; 31:1129-1133[Japanese].[Medline]
21. Butler JC, Peters CJ. Hantaviruses and Hantavirus pulmonary syndrome. Clin Infect Dis 1994; 19:387-394.[Medline]
22. Moolenaar RL, Breiman RF, Peters CJ. Hantavirus pulmonary syndrome. Semin Respir Infect 1997; 12:31-39.[Medline]
23. Boroja M, Barrie JR, Raymond GS. Radiographic findings in 20 patients with Hantavirus pulmonary syndrome correlated with clinical outcome. AJR Am J Roentgenol 2002; 178:159-163.[Abstract/Free Full Text]
24. Ketai LH, Williamson MR, Telepak RJ, et al. Hantavirus pulmonary syndrome: radiographic findings in 16 patients. Radiology 1994; 191:665-668.[Abstract/Free Full Text]
25. Lee KS, Kim HJ, Chun YH, Choi HS, Lee DS, Moon JS. Thoracic manifestations in hemorrhagic fever with renal syndrome. J Korean Radiol Soc 1988; 24:541-545[Korean].
26. Brandt CD, Kim HW, Vargosko AJ, et al. Infections in 18,000 infants and children in a controlled study of respiratory tract disease. I. Adenovirus pathogenicity in relation to serologic type and illness syndrome. Am J Epidemiol 1969; 90:484-500.
27. Bateman ED, Hayashi S, Kuwano K, Wilke TA, Hogg JC. Latent adenoviral infection in follicular bronchiectasis. Am J Respir Crit Care Med 1995; 151:170-176.[Abstract]
28. Becroft DM. Histopathology of fatal adenovirus infection of the respiratory tract in young children. J Clin Pathol 1967; 24:561-569.
29. Kawai T, Fujiwara T, Aoyama Y, et al. Diffuse interstitial fibrosing pneumonitis and adenovirus infection. Chest 1976; 69:692-694.[Abstract/Free Full Text]
30. Wenman WM, Pagtakhan RD, Reed MH, Chernick V, Albritton W. Adenovirus bronchiolitis in Manitoba: epidemiologic, clinical, and radiologic features. Chest 1982; 81:605-609.[Abstract/Free Full Text]
31. Graham BS, Snell JD, Jr. Herpes simplex virus infection of the adult lower respiratory tract. Medicine 1983; 62:384-393.[Medline]
32. Ramsey PG, Fife KH, Hackman RC, Meyers JD, Corey L. Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients. Ann Intern Med 1982; 97:813-820.
33. Herout V, Vortel V, Vondrackova A. Herpes simplex involvement of the lower respiratory tract. Am J Clin Pathol 1966; 46:411-419.[Medline]
34. Byers RJ, Hasleton PS, Quigley A. Pulmonary herpes simplex in burn patients. Eur Respir J 1996; 9:2313-2317.