Diseases of Altered Immunologic Activity

Chapter 9 Diseases of Altered Immunologic Activity

Several pulmonary disorders are associated with systemic or local bronchopulmonary immunologic alterations. Some of these disorders primarily involve the lung, and in others, the pulmonary manifestations result from disease arising elsewhere. The choice of diseases included in this chapter is somewhat arbitrary. For example, asthma is addressed elsewhere with chronic obstructive pulmonary disease. Some of the infiltrative lung diseases such as sarcoidosis and occupational lung diseases such as silicosis and asbestosis are associated with multiple immunologic aberrations, but they are also discussed elsewhere.


There are four basic types of immunologic reaction, all of which may be responsible for diseases in the lung. These reactions are not mutually exclusive, and the development of one type may be accompanied by the simultaneous or subsequent development of another (Box 9-1).

Type I:

Type II:

Type III:

Type IV:



Goodpasture’s syndrome (Box 9-2) is a disorder of unknown origin that is characterized by repeated episodes of pulmonary hemorrhage, iron deficiency anemia, and glomerulonephritis. It is often rapidly progressive. The immunopathologic nature of the disease is apparent because of the linear deposits of immunoglobulins, which can be demonstrated in the glomerular basement membrane and alveolar septa.

Radiographic Features

The classic radiographic appearance of Goodpasture’s syndrome consists of diffuse, homogeneous consolidation or alveolar opacities distributed fairly uniformly throughout all lung zones (Fig. 9-1). These changes are characteristic of the early stages of the disease and the development of acute pulmonary hemorrhage. Although the radiographic pattern is similar to that of cardiogenic pulmonary edema, conspicuously absent features are cardiomegaly, Kerley B lines, and pleural effusions. In the later stages, the changes depend on the time sequence and the number of hemorrhages that have occurred in the past. The alveolar consolidation seen during the acute episode may resolve in 2 to 3 days. Irregular or linear opacities often persist for an extended period. If bleeding is continuous or repetitive, these linear and occasionally nodular opacities become permanent as increasing amounts of hemosiderin are deposited within the interstitial tissue. Goodpasture’s syndrome must be differentiated from pulmonary hemorrhage due to other causes, such as idiopathic pulmonary hemorrhage (i.e., hemosiderosis) and numerous causes of vasculitis. Hemorrhage may occur rarely in patients receiving systemic anticoagulants.


The connective tissue or collagen vascular diseases are a group of immunologically mediated disorders characterized by inflammation of joints, serosal membranes, connective tissue, and blood vessels in various organs. Pathologically, alterations occur in the connective tissue ground substance, which contains elastin, collagen, and reticulin. Edema, fibrinoid degeneration, and vascular lesions are characteristic.

Rheumatoid Disease

Rheumatoid Pleurisy

Pleural involvement is the most common thoracic manifestation of rheumatoid disease (Box 9-3). Clinical evidence of rheumatoid pleurisy appears in about 20% of patients, but only 5% have radiologic evidence of effusions. In contrast, pleural involvement may be found in 50% of autopsy series. Pleural disease occurs much more frequently in men than in women with rheumatoid disease. Rheumatoid pleurisy usually occurs in the sixth decade of life and is associated with moderate to severe arthritis. Rheumatoid factor is present in the serum and the pleural fluid in high titers. The pleural fluid is exudative and characterized by a low glucose concentration and low pH.

The chest radiograph usually shows a small- to medium-sized pleural effusion. It is typically unilateral, with a slight predominance on the right. Rheumatoid effusions tend to remain unchanged for many months or even years. Other manifestations of rheumatoid lung disease, such as interstitial fibrosis, are usually absent. The effusions may be recurrent and occasionally result in a diffusely thickened pleura or fibrothorax (Fig. 9-2).

Interstitial Fibrosis and Pneumonitis

Interstitial lung disease (Box 9-4) may be seen in a variety of collagen vascular diseases. Histopathologically, the abnormalities may take the form of any of the various idiopathic interstitial pneumonias, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonitis (NSIP), cryptogenic organizing pneumonia (COP), and lymphocytic interstitial pneumonia (LIP). Whereas NSIP is the most common histopathologic pattern in most collagen vascular disorders, UIP predominates in patients with rheumatoid arthritis. The prevalence may be as high as 30%. Immunologically mediated injury most likely plays a central role in this interstitial pneumonitis, and immune complexes (i.e., type III reaction) containing rheumatoid factor have been identified in alveolar walls and pulmonary capillaries by immunofluorescence.

The interstitial lung disease may occur before, after, or with the onset of arthritis. The classic symptom is progressive dyspnea, and pulmonary function tests show evidence of restrictive ventilatory impairment.

The radiologic features of rheumatoid interstitial disease are usually identical to those seen in UIP (Fig. 9-3) and NSIP. In the early stages, a pattern of fine linear or irregular opacities can be identified predominantly in the bases, which may progress to coarse reticulation with end-stage cystic changes and honeycombing. CT findings include reticular opacities located predominantly in the subpleural regions in the lung bases; ground-glass attenuation (especially in NSIP) (Fig. 9-4); irregular pleural and mediastinal interfaces; thickened interlobular septa; and honeycomb cysts (especially in UIP). Progressive loss of volume (“shrinking lungs”) may be observed on serial studies. Pleural effusion or thickening may be present. Occasionally, other features of rheumatoid disease may be observed in the bony thorax, including typical arthritic changes in the shoulder, joints, and tapering of the distal clavicles.

Airways Disease

Bronchiectasis has been reported in up to 30% of patients with rheumatoid arthritis. In most cases, it is not clinically significant. Obliterative bronchiolitis may be caused by rheumatoid arthritis or several drugs used to treat this condition, including d-penicillamine, gold, and sulfasalazine. This disorder is discussed separately in Chapter 13. Patients with rheumatoid arthritis may also develop follicular bronchiolitis, a benign condition characterized by lymphoid hyperplasia of bronchus-associated lymphoid tissue (BALT). This entity is discussed separately at the end of this chapter.

Progressive Systemic Sclerosis: Scleroderma


Progressive systemic sclerosis or scleroderma (Box 9-5) is a connective tissue disease characterized by fibrosis and atrophy of the skin, lungs, gastrointestinal tract, heart, and kidneys. Patients are usually affected in the fourth to sixth decade of life, and the disease is three times more common in women than in men.

After the esophagus, the lung is the second most frequently involved visceral organ. Chest radiographic abnormalities have been reported in up to 25% of cases. The pulmonary manifestations of scleroderma may take one of three forms; interstitial fibrosis is the most common, but pulmonary vascular disease and pleural changes may also occur. Although the pathogenesis of interstitial lung disease is unknown, an immunologic mechanism is likely. Vascular disease involving the arterioles and capillary bed frequently occurs in the lungs of scleroderma patients. These changes appear to be unrelated to the interstitial fibrosis and may occur independently. Pulmonary hypertension may develop as a consequence of these lesions.

Radiographic Features

The radiographic pattern is usually identical to that seen in NSIP or UIP and may be indistinguishable from rheumatoid lung. NSIP is the most common histopathologic pattern in patients with systemic sclerosis. A fine linear pattern of small, irregular opacities can be identified, with predominant involvement at the bases and often accompanied by ground-glass attenuation. As the disease progresses, the opacities become coarser, and eventually, traction bronchiectasis and honeycomb cysts develop. The latter pattern is a typical feature of UIP. Progressive loss of volume occurs over several years. Pleural involvement, however, is uncommon. On high-resolution CT (Fig. 9-6), findings are similar to those described in rheumatoid lung disease. In patients with systemic sclerosis, interstitial lung disease is frequently accompanied by thoracic lymphadenopathy, which tends to increase as the profusion of lung disease worsens.

Other nonpulmonary manifestations of scleroderma may be identified on the chest radiograph. Calcinosis may be present in the skin and subcutaneous tissue of the thorax, particularly about the shoulders. Atrophy and atony of the esophagus that results in absent peristalsis may also lead to dilation of the esophagus. On chest radiography and CT, this is manifested by the presence of gas without an air-fluid level in a distended esophagus, the so-called air esophagram (see Fig. 9-6). Dilation of the central pulmonary arteries with rapid tapering of peripheral vessels is characteristic of pulmonary arterial hypertension (Fig. 9-7).

Systemic Lupus Erythematosus

SLE is a chronic disease of unknown origin that affects the components of connective tissue of many organs, including the lungs. The vascular system, the epidermis, and serous and synovial membranes are the most commonly involved sites. The diagnosis of SLE is established by clinical and laboratory phenomena, including a positive antinuclear antibody test result and the lupus cell (i.e., LE cell phenomenon). SLE is the prototype of disease caused by a type III immunologic reaction.

Young women are affected four times as often as men. Renal and central nervous system involvement and various infections are common determinants of survival. The lungs and pleura are involved more frequently in SLE than in any other collagen vascular disease, with the prevalence ranging from 30% to 70% in several series.

The clinical manifestations of pleural pulmonary lupus vary. Symptoms include pleuritis and cough with or without dyspnea. Pleuritis occurs in 35% to 40% of patients and is often painful and accompanied by fever. Patients occasionally have hemoptysis associated with pulmonary hemorrhage. The radiographic manifestations may be classified in six categories (Box 9-6), and patient may have more than one of these entities.

Acute Lupus Pneumonitis

Acute lupus pneumonitis is an uncommon but well-recognized manifestation of SLE. It is characterized by severe dyspnea, nonproductive cough, fever, and hypoxia. The radiographic features (Fig. 9-9) consist of poorly defined focal areas of increased opacity at the bases or widespread, extensive, unilateral or bilateral consolidation. These pulmonary opacities usually respond to steroids or cytotoxic drugs. The pathogenesis of this disorder is unclear, but histologic alterations include vasculitis and hemorrhage.

Polymyositis or Dermatomyositis


Polymyositis and dermatomyositis (Box 9-7) include a group of autoimmune disorders characterized by diffuse inflammatory and degenerative changes in striated muscle. Fewer cases are associated with underlying malignancy. Symptoms include dyspnea on exertion and nonproductive cough. There is evidence of restriction on pulmonary function testing, and there may be a profound weakness of the muscles of respiration. The cause is unknown, and unlike other collagen vascular diseases, there are no circulating immune complexes.

Three types of pulmonary disease can be identified in this disorder: chronic interstitial pneumonitis, aspiration pneumonia due to a hypotonic esophagus, and hypostatic pneumonia due to chest wall involvement with resultant hypoventilation. The prevalence of interstitial pneumonitis is low, estimated to be about 5%.

Dermatomyositis or polymyositis is twice as common in women as in men. A peak incidence occurs in the first decade and in the fifth and sixth decades.



Any disease characterized pathologically by an inflammatory response within blood vessels may be considered a vasculitis. If the inflammation produces destruction of vessel walls, the process is called a necrotizing vasculitis. Most vascular diseases are systemic, although there often is a target organ. The lungs commonly are involved by several types of vasculitis. Box 9-8 provides a classification that divides these disorders into four groups. This section deals with diseases in category 1, those that histopathologically have a granulomatous appearance and have been characterized by Liebow as pulmonary angiitis and granulomatosis. In all these diseases, the lung is the major site of involvement. These granulomatous vasculitides include classic and limited Wegener’s granulomatosis, lymphomatoid granulomatosis, allergic granulomatosis (i.e., Churg-Strauss syndrome), necrotizing sarcoid angiitis and granulomatosis, and bronchocentric granulomatosis.

Feb 28, 2016 | Posted by in RESPIRATORY IMAGING | Comments Off on Diseases of Altered Immunologic Activity

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