Infectious diseases
Pneumocystis jiroveci Pneumonia
Pneumocystis jiroveci (formerly P. carinii) is an organism that was previously thought to be a protozoan but, on the basis of genetic studies, is currently considered to be a fungus. Pneumocystis pneumonia (PCP) typically occurs in patients who are immuno-compromised, most commonly those with HIV/AIDS. Radi-ographically, PCP presents as multifocal infiltrates, usually hazy opacities in the perihilar regions.6 These infiltrates can become diffuse and associated with severe respiratory compromise. CT shows ground-glass attenuation that may be diffuse or in a mosaic pattern. Less commonly, PCP presents as solitary or multiple, solid or cavitary opacities. Cysts, often associated with pneu-mothorax, can also be seen.
Tuberculosis
Primary tuberculosis is often focal and often associated with ipsilateral hilar adenopathy, especially in children. Most diagnosed adult cases of tuberculosis, however, result from reactivation of latent infection. Reactivation tuberculosis is often multifo-cal [see 7:II Tuberculosis].7 Bilateral infiltrates in the upper lung zones are most characteristic. The upper lung zones are favored sites, because a higher ratio of ventilation to perfusion results in higher local oxygen tension, which enhances growth of Mycobac-terium tuberculosis. The apical and posterior segments of the upper lobes are most commonly involved, followed by the apical-posterior segments of the lower lobes. The lingula, the middle lobe, and the basal segments of the lower lobes can all be involved by bronchogenic spread. Concomitant pleural disease occurs in a minority of patients.
Cavitation is frequent, but even in the absence of cavitation, the diagnosis of tuberculosis should be considered when multi-focal infiltrates are present. Atypical radiographic patterns, including isolated lower lobe infiltrates, are particularly common in elderly, debilitated patients. These patterns can complicate and delay diagnosis. Atypical radiographic features, including midlung or lower lung field infiltrates, hilar adenopathy, and absence of cavitation, can be seen in immunocompromised patients, especially in patients with AIDS [see 7:XXXII HIV and AIDS].
Endemic Fungal Pneumonias
Endemic fungal pneumonias are acquired by inhalation of aerosolized particles (usually small respirable spores) rather than by microaspiration of pharyngeal organisms—the mechanism of infection for most pyogenic bacterial pneumonias. Severe cases of endemic fungal pneumonia usually involve multiple areas; blastomycosis and coccidioidomycosis often cause multiple dense alveolar infiltrates [see 7:XXXVIIMycotic Infections].
Melioidosis
Melioidosis is an indolent bacterial pneumonia caused by the gram-negative bacillus Burkholderia pseudomallei. It is most common in Southeast Asia and may appear in patients months or even years after they have migrated to nonendemic areas. Multi-focal infiltrates are characteristic. The clinical illness resembles tuberculosis except that upper lobe predominance is not as striking in melioidosis.
Invasive Aspergillosis
An opportunistic fungal infection that is also acquired by inhalation, invasive aspergillosis occurs in patients who experience a decrease in the number or function of phagocytes.8 Prolonged neutropenia from cytotoxic chemotherapy for acute leukemia is the most common predisposing factor. High-dose glucocorticoid therapy also predisposes to this infection, as do several immunosuppressive regimens used for solid-organ transplantation and, especially, for bone marrow transplantation. Clinical features include fever, dyspnea, pleuritic chest pain, hemoptysis, and hypoxemia. The chest radiograph shows characteristic multiple dense infiltrates, which may be nondescript, wedge shaped and peripheral, or even nodular. Individual lesions may cavitate, particularly as the number of neu-trophils begins to rebound after chemotherapy. During this recovery time, the patient is at the highest risk for major hemoptysis [see 7:XXXVIII Mycotic Infections in the Compromised Host]. CT shows a characteristic pattern of nodules surrounded by ground-glass attenuation (halo sign).
Diagnosis is difficult because actual tissue invasion must be determined. However, any positive culture for Aspergillus from sputum or bronchoscopic specimens has high predictive value in the patient with profound neutropenia. Such cultures are valuable but less specific in transplant recipients or other moderately immunosuppressed patients and are often not helpful in patients with chronic bronchitis, who are frequently colonized with this organism. Negative cultures never rule out the diagnosis of invasive aspergillosis.
Neoplastic diseases
Two neoplasms that present as focal infiltrates [see Focal Pulmonary Infiltrates, above] also commonly present as multifocal infiltrates: alveolar cell carcinoma2 [see Figure 2c] and Hodgkin disease. Hodgkin disease, however, almost always has associated hilar and mediastinal adenopathy, whereas alveolar cell carcinoma almost never does. Lymphomatoid granulomatosis, an angiocentric T cell lymphoma of variable grade, usually presents as multiple pulmonary nodules [see Multiple Nodules and Masses, below] but can also present as multifocal pulmonary infiltrates.
Noninfectious, nonneoplastic disorders
Several noninfectious, nonneoplastic pulmonary diseases may produce multiple areas of lung infiltration.
Drug Reactions
Multifocal infiltrates can occur as a manifestation of drug tox-icity, especially acute methotrexate, nitrofurantoin-related, and amiodarone-related pulmonary toxicity [see 14:V Chronic Diffuse Infiltrative Lung Disease]. With amiodarone-related lung disease, the infiltrates may be bilateral and more prominent in upper lung zones. The drug profile must be reviewed carefully in any patient with unexplained multifocal pulmonary infiltrates.
Simple Eosinophilic Pneumonia
Patients with simple eosinophilic pneumonia, often called Loffler syndrome, have nonproductive cough and fever [see 14:V Chronic Diffuse Infiltrative Lung Disease]. The chest radiograph shows patchy infiltrates, typically in the lower lung fields; the infiltrates resolve within 1 to 2 weeks. The main clue to the diagnosis is an increase in the number of peripheral eosinophils, often to 60% or more of the total white blood cell count. Bronchoalveo-lar lavage is seldom indicated, because patients are only mildly ill; when lavage is done, it reveals pulmonary eosinophilia. The main causes of this pneumonia are drugs and worms—usually nematodes such as Ascaris and Strongyloides, which migrate through the lung during one phase of infection [see 7:XXXV Helminthic Infections]. Drugs that cause the syndrome include but are not limited to carbamazepine, chlorpromazine, cocaine, imipramine, isoniazid, naproxen, nitrofurantoin, penicillins, sul-fonamides, and tetracycline.
Tropical Pulmonary Eosinophilia
Tropical pulmonary eosinophilia, which is caused by im-munologic hyperreactivity to microfilariae, is characterized by dyspnea, wheezing, and coughing, all of which are worse at night, as well as fever, weight loss, and fatigue [see 14:V Chronic Diffuse Infiltrative Lung Disease]. The chest radiograph reveals interstitial micronodular lesions that may be diffuse or multifo-cal. Peripheral blood eosinophilia is in excess of 3,000/mm3; the serum IgE levels are extremely high, and antibodies to microfi-lariae are present. Two filarial parasites, Wuchereria bancrofti and Brugia malayi, are causative agents [see 7:XXXV Helminthic Infections]. Blood eosinophilia is less prominent in patients with chronic forms of the disease. Patients who have lived in areas where tropical pulmonary eosinophilia is endemic can present with restrictive or obstructive lung disorders that are the residua of episodes of tropical eosinophilia that occurred earlier in life.
Chronic Eosinophilic Pneumonia
Chronic eosinophilic pneumonia is more serious than simple eosinophilic pneumonia9 [see 14:V Chronic Diffuse Infiltrative Lung Disease]. It primarily affects women between 20 and 40 years of age; however, it has been reported in patients of both sexes and of all ages. Most patients have moderate to severe illness lasting from 1 month to several months, with fever, night sweats, nonproductive cough, shortness of breath, and weight loss. About one third of patients have a history of asthma, and up to one half have some atopic history, including allergic rhinitis and nasal polyps. About one half of patients have wheezing as part of their clinical presentation, some for the first time. The chest radiograph may show dense peripheral infiltrates that are often referred to as reverse pulmonary edema or the photographic negative of pulmonary edema. When the clinical presentation and chest radiograph are highly typical, the diagnosis can be made clinically. About two thirds of patients have peripheral eosino-philia; a minority have an elevated serum IgE level. Broncho-alveolar lavage shows increased eosinophils and increased lymphocytes. Open lung biopsy, which is seldom required, shows lymphocytes and eosinophils in alveolar walls and spaces, as well as bronchiolitis obliterans in up to one third of specimens.
The etiology of chronic eosinophilic pneumonia is unknown. The disease may represent a hypersensitivity response to unknown antigens or may be an idiopathic immunologic activation.
Acute Eosinophilic Pneumonia
Idiopathic acute eosinophilic pneumonia (AEP) is another syndrome that presents as multifocal infiltrates10 [see 14:V Chronic Diffuse Infiltrative Lung Disease]. Blood eosinophilia is usually absent, and the onset is acute, generally within several days. Patients may have a fever and severe hypoxemia and may progress to respiratory failure. There is usually no history of atopy. There are rales on physical examination, but there is rarely any wheezing. The prime diagnostic consideration is severe community-acquired pneumonia. The chest radiograph shows bilateral infiltrates that may progress to diffuse infiltrates. Unlike the case with chronic eosinophilic pneumonia, there is no tendency for peripheral subpleural localization. CT shows multifocal air-space opacities, often with an interstitial component. Increased septal markings (Kerley B lines) are seen in about one third of cases. Diagnosis of AEP is usually made by bronchoalveolar lavage, which shows over 25% eosinophils (mean, 37 ± 2.5). Culture for respiratory pathogens is negative.
The etiology of this immune disorder is unknown. In addition to the increase in pulmonary eosinophils, pathobiologic features include an increase in the number of helper T cells and neu-trophils in the lung and elevated concentrations of interleukin-5 (IL-5) in lavage fluid.
Bronchiolitis Obliterans Organizing Pneumonia
Bronchiolitis obliterans alone is a distinct pathologic process in which distal airways are filled with plugs of loose connective tissue containing fibroblasts and inflammatory cells [see 14:III Chronic Obstructive Diseases of the Lung]. Clinical manifestations in patients with this pathology include severe airflow obstruction and poor response to bronchodilator therapy; chest radiographs show no infiltrates. Some cases are idiopathic, but others are associated with specific immunologic abnormalities, such as rheumatoid arthritis, graft versus host disease (GVHD) in bone marrow transplant recipients, and chronic rejection in lung transplant recipients.
Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity that is also (and perhaps more descriptively) called cryptogenic organizing pneumonia [see 14:V Chronic Diffuse Infiltrative Lung Disease]}1 The lung parenchyma is involved, and alveolar spaces are filled with loose connective tissue that contains fibroblasts and mixed inflammatory cells. The process also involves contiguous distal airways, so the characteristic plugs of bronchiolitis obliterans are also seen. The chest radiograph often shows multiple dense peripheral infiltrates.9 A less common pattern of idiopathic BOOP is a dense lobar infiltrate, which resembles bacterial pneumonia in radiographic appearance. Because of the long course of the illness, clinical suspicion often focuses on chronic pulmonary infections, such as blasto-mycosis or even alveolar cell carcinoma. The most common features on CT scanning, which shows the extent of disease better than a chest radiograph, include patchy bilateral air-space consolidation, small nodular opacities (sometimes with a reversed halo sign), and bronchial wall thickening and dilatation. In half of cases, these abnormalities are mainly subpleural; in the other half of cases, they are distributed throughout the affected lobes.12
The diagnosis of BOOP can often be made on transbronchial lung biopsy. In cases in which an open lung biopsy is needed, the video-assisted thoracoscopic technique has become the established procedure.
Allergic Granulomatosis and Angiitis
Also known as Churg-Strauss syndrome, allergic granulo-matosis and angiitis is rare [see 15:VIII Systemic Vasculitis Syndromes].13 Almost all patients with allergic granulomatosis and angiitis have a strong history of atopic allergy with preexisting bronchial asthma for an average of 5 to 10 years before diagnosis of the vasculitis. Patients present with fever, shortness of breath, and a variety of complaints related to skin and nerve involvement (e.g., purpura, painful skin nodules, skin infarction, footdrop, wristdrop, or painful neuropathy). Myocardial involvement occurs in a minority of patients but on occasion can dominate the clinical presentation. Wheezing is common. Clinically significant renal involvement is uncommon. In 25% of cases, the chest radiograph shows peripheral infiltrates or nodules that seldom cavitate. Pleural effusion, pericardial effusion, or both may occur with or without infiltrates. Churg-Strauss syndrome, though rare, most often occurs in patients with bronchial asthma. There is an association between Churg-Stauss syndrome and treatment of asthma with leukotriene inhibitors.14 Onset of the vasculitis usually occurs as glucocorti-coids are tapered during leukotriene inhibitor therapy, and it is possible that some of these cases represent occult Churg-Strauss disease that is initially suppressed with glucocorticoids and then flares with glucocorticoid withdrawal. However, at least one case has been reported in a patient with no recent glu-cocorticoid use.15
Other Noninfectious, Nonneoplastic Multifocal Disorders
Other immunologic lung diseases can produce multifocal infiltrates. Wegener granulomatosis is the most common lung vas-culitis. The radiographic spectrum of illness includes infiltrates and nodules that are usually multiple and often cavitate [see Cystic and Cavitary Infiltrates, below].
Collagen vascular disease can be associated with multifocal lung involvement.16 Pneumonitis associated with systemic lupus erythematosus (SLE) may be diffuse but may also appear as dense lower lobe infiltrates. Other clinical and serodiagnostic features of SLE are present. Systemic sclerosis and mixed connective tissue disease usually present as diffuse interstitial infiltrates, often with basilar predominance [see 14:V Chronic Diffuse Infiltrative Lung Disease and 15:IV Systemic Lupus Erythematosus].
Lung disease associated with rheumatoid arthritis takes many forms, including pulmonary fibrosis, pleural effusions, and ne-crobiotic pulmonary nodules, the pathologic appearance of which is similar to that of subcutaneous rheumatoid nodules [see 14:V Chronic Diffuse Infiltrative Lung Disease and 15:II Rheumatoid Arthritis]. Peripheral dense, masslike infiltrates may also occur. Some lesions may cavitate; such lesions are most common in men with high-titer rheumatoid factor and subcutaneous rheumatoid nodules.
Other noninfectious, nonmalignant disorders that can cause multifocal infiltrates include silicosis and other diseases caused by inorganic dust inhalation.17 With extensive disease, progressive massive fibrosis may develop, producing large opacities. These opacities begin in peripheral areas of the lung and migrate centrally as lung volume is lost. The chest radiograph almost always shows a background of small nodules that are most prominent in the upper lobe. Patients have productive cough and dyspnea on exertion. The physiologic findings are typical of restrictive disease, but many patients also have airflow obstruction resulting from cigarette smoking or from airway damage caused by massive dust overload.
Table 3 Major Causes of True Segmental Infiltrates
|
Cause |
Examples |
|
Infectious |
Bacterial pneumonia Tuberculosis |
|
Invasive aspergillosis, Mucor pneumonia, Pseudomonas pneumonia |
|
|
Bronchiectasis |
|
|
Neoplastic |
Primary lung cancer |
|
Carcinoid tumors |
|
|
Cylindromas, mucoepidermoid carcinomas |
|
|
Noninfectious, nonneoplastic |
Foreign body |
|
Amyloidosis and sarcoidosis |
|
|
Asthma with mucous plugging |
|
|
Allergic bronchopulmonary aspergillosis |
|
|
Pulmonary infarction |
|
|
Bronchial fracture |
|
|
Postoperative atelectasis |
Caplan syndrome occurs in patients with rheumatoid arthritis who have been occupationally exposed to coal dust or other par-ticulates, such as silica, asbestos, aluminum dust, and iron dust. The tendency to form large, masslike infiltrates is more pronounced in these patients than it is in other patients with rheumatoid arthritis. The infiltrates are multiple and may be more than 5 cm in diameter. They are often somewhat nodular and may cavitate and even calcify. Histologically, they resemble other rheumatoid ne-crobiotic nodules except that the foreign particulate matter can be easily demonstrated. The occupational history and the nodules and fibrosis evident on the chest radiograph are diagnostic clues.
In ankylosing spondylitis, a spondyloarthritis that leads to a stiff spine, calcification of spinal ligaments results in a characteristic radiographic appearance, the so-called bamboo spine [see 15:III Seronegative Spondyloarthritis]. Chest wall expansion is impaired, and lung volumes are somewhat reduced. Patients may develop characteristic dense fibrous or fibrobullous infiltrates that are often limited to the upper lung zones. These chest radiographic findings mimic those of tuberculosis, and cavitation may occur. Once cavities have developed, abnormal air spaces may become colonized with Aspergillus species, causing fungus balls and even a locally invasive disease termed chronic necrotizing aspergillo-sis. CT studies of groups of patients with ankylosing spondylitis have found interstitial lung disease that is more diffuse and not confined to the apexes of the lung.18 The lung disease associated with ankylosing spondylitis does not progress to respiratory insufficiency. Dyspnea on exertion and nonproductive cough are the usual symptoms. Once Aspergillus colonization or infection has occurred, symptoms from the local fungal infection may predominate; such symptoms include hemoptysis, productive cough, and mild to moderate constitutional symptoms. Locally invasive Aspergillus infection may extend directly to the pleura but almost never spreads hematogenously to distant sites.
Exogenous lipoid pneumonia may also cause multifocal infiltrates. These infiltrates are dense and are usually seen in both lower lobes.
True Segmental Infiltrates
A chest radiograph that shows nearly complete involvement of a single lung segment, especially if associated with volume loss, should raise suspicion that there is disease in the bronchus or in the pulmonary artery supplying that segment [see Table 3].19
Infectious diseases
Common bacterial pneumonias caused by S. pneumoniae and H. influenzae are usually not truly segmental unless an entire lobe is involved. In contrast, involvement of one or more discrete segments, often at the lung bases, is common in Mycoplasma pneumonia [see Figure 3a].1
Three types of pneumonia exhibit a strong tendency for an-gioinvasion and cause dense, wedge-shaped peripheral infiltrates resulting from combined infection and infarction of a lung segment. Patients may have fever and purulent sputum from the infection, and they may have hemoptysis and pleural pain from lung infarction. Aspergillus and Mucor species are important causes of this syndrome in immunosuppressed patients, particularly patients with neutropenia or those receiving high-dose glucocor-ticoid therapy [see 7:XXXVIII Mycotic Infections in the Compromised Host], and Pseudomonas pneumonia is an important cause of this syndrome in debilitated patients [see 7:X Infections Due to Haemophilus, Moraxella, Legionella, Bordetella, and Pseudomonas].
Bronchiectasis is a disease of the airways that can present as a peripheral segmental infiltrate, from dilated bronchi filled with mucus and infiltrate, and as an associated volume loss. Air-fluid levels may be seen in dilated saccular airways. Because CT scanning is more sensitive and specific than chest radiography in documenting bronchiectasis, it has replaced bronchography in the diagnosis of this process. The usual clinical presentation is a chronic cough that produces purulent sputum [see 14:III Chronic Obstructive Diseases of the Lung].
Tuberculosis is a parenchymal lung disease but may also involve the airways heavily. Bronchiectasis is a common late sequela. Because it occurs most often in bronchi of the upper lobes, it is well drained; hence, little or no sputum is produced (so-called dry bronchiectasis). Hemoptysis, often massive, can occur in patients who have no history of chronic cough and sputum. True segmental infiltrates may be seen early or late in the course of this chronic infection.
Pulmonary aspergillosis is an uncommon and, usually, very late complication of AIDS. Endobronchial aspergillosis is one manifestation of AIDS that often presents as true segmental infiltrates of the involved segment or segments. Pulmonary as-pergillosis in AIDS may also present as multiple nodules and single or multiple infiltrates.
Neoplastic diseases
Lung tumors that arise in the lung parenchyma present as nodules or masses. Tumors that arise in central airways block a segment of the lung, leading to distal infection, atelectasis, or both; the infection or atelectasis conforms perfectly to the obstructed segment, lobe, or lung. Symptoms include cough and hemoptysis or purulent sputum, as well as fever from the post-obstructive pneumonia.
Carcinoid Lung Tumors
Carcinoid tumors of the lung are low-grade adenocarcinomas [see 12:VIIILung Cancer].20 Most carcinoid tumors arise in central airways, so they present as segmental infiltrate or atelectasis more often than do primary lung cancers [see Figure 3b]. Carci-noid tumors grow more slowly and metastasize less often than primary lung cancers, and they are not related to cigarette smoking. Although the mean age of incidence is 55 years, carcinoid tumors are almost evenly distributed across adulthood; in contrast, the incidence of primary lung cancer increases markedly with age. Despite their relative infrequency, carcinoid tumors account for a high percentage of lung tumors in patients in their third and fourth decades but only a tiny percentage of tumors in patients of advanced age.
Other Lung Tumors
Several other lung tumors typically grow in central airways and also present as segmental infiltrate, atelectasis, or both. Adenoid cystic carcinomas, known as cylindromas, and mucoepidermoid carcinomas are low-grade cancers of the mucous glands that usually occur in the trachea or central bronchi. The clinical presentation is similar to that of carci-noid tumors, but mucous gland tumors occur less than one tenth as often as carcinoid tumors. The histopathologies of cylindromas, mucoepidermoid carcinomas, and carcinoid tumors differ.
Figure 3 (a) Unlike common bacterial pneumonias, Mycoplasma pneumonia frequently involves one or more specific segments. In this chest radiograph of a 42-year-old man, Mycoplasma pneumonia involves the anterior basal segment of the right lower lobe. (b) This chest radiograph of a 24-year-old man demonstrates a carcinoid tumor obstructing the medial basal segment of the right lower lobe. (c) Allergic bronchopulmonary aspergillosis may cause a segmental infiltrate or segmental atelectasis. In this chest radiograph of a 40-year-old man, the infiltrate revealed in the medial basal segment of the right lower lobe is the result of allergic bronchopulmonary aspergillosis.
Benign lung tumors are uncommon. Most are hamartomas, which present peripherally as nodules [see Single Small Nodules, below]. Benign tumors presenting in the central airways are extremely rare; most are fibromas or lipomas.
