References

Fig. 27.5 Iressa (gefitinib)-associated lung disease of acute interstitial pneumonia (diffuse alveolar damage) pattern in a 40-year-old man with lung adenocarcinoma (primary tumor in left lung, lung-to-lung and extrathoracic metastases). (a, b) Lung window images of CT scans (5.0-mm section thickness) obtained at levels of aortic arch (a) and cardiac ventricle (b), respectively, show patchy, extensive, and mixed areas of parenchymal consolidation and ground-glass opacity in both lungs. Also note primary cancer (open arrows) and lung-to-lung metastatic nodules (arrowheads). Patient took Iressa for 3 months

References

1. Min JH, Lee HY, Lim H, et al. Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non-small cell lung cancer: a review on current insight. Cancer Chemother Pharmacol. 2011;68:1099–109.

2. Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 2000;20:1245–59.

3. Pietra GG. Pathologic mechanisms of drug-induced lung disorders. J Thorac Imaging. 1991;6:1–7.

4. Padley SP, Adler B, Hansell DM, Muller NL. High-resolution computed tomography of drug-induced lung disease. Clin Radiol. 1992;46:232–6.

5. Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS). Semin Cutan Med Surg. 1996;15:250–7.

Fig. 27.6 Iressa (gefitinib)-induced hypersensitivity pneumonia in a 53-year-old woman with lung adenocarcinoma and lung-to-lung metastases. (a, b) Lung window images of CT scans (5.0-mm section thickness) obtained at levels of inferior pulmonary veins (a) and liver dome (b), respectively, show patchy areas of parenchymal ground-glass opacity (arrows) in both lungs. The lesions disappeared spontaneously without any treatment

6. Cooper Jr JA, White DA, Matthay RA. Drug-induced pulmonary disease. Part 2: noncytotoxic drugs. Am Rev Respir Dis. 1986;133:488–505.

7. Searles G, McKendry RJ. Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol. 1987;14:1164–71.

8. Rosenow 3rd EC, Myers JL, Swensen SJ, Pisani RJ. Drug-induced pulmonary disease. An update. Chest. 1992;102:239–50.

9. Ellis SJ, Cleverley JR, Muller NL. Drug-induced lung disease: high-resolution CT findings. AJR Am J Roentgenol. 2000;175:1019–24.

10. Silva CI, Muller NL. Drug-induced lung diseases: most common reaction patterns and corresponding high-resolution CT manifestations. Semin Ultrasound CT MR. 2006;27:111–6.

Collagen vascular diseases (CVDs) showing features of interstitial lung disease (ILD) pattern include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjögren’s syndrome, and mixed connective tissue disease (MCTD). Histopathologically, interstitial lung diseases associated with CVD are diverse and include nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), cryptogenic organizing pneumonia (COP), apical fibrosis, diffuse alveolar damage (DAD), and lymphoid interstitial pneumonia (LIP) patterns (Tables 28.1 and 28.2). NSIP accounts for large proportion, especially in PSS, DM and PM, and MCTD. More favorable prognosis in interstitial pneumonia associated with CVDs than in idiopathic interstitial pneumonias (IIPs) may be explained by the larger proportion of NSIP pattern than UIP pattern. Thin-section CT (TSCT) seems to help characterize and determine the extent of ILD in CVDs [1].

associated with an interstitial pneumonitis, have been well documented, although this is an unusual feature of acute lupus pneumonitis [3].

Diffuse interstitial pneumonitis and fibrosis is uncommon; in one series of 120 patients, only 5 (4 %) showed the interstitial lung disease [4]. Pathologic findings in these cases are those of UIP or NSIP pattern (Fig. 28.2). A few cases of COP pattern have been reported [1].

Radiographic evidence of interstitial fibrosis, consisting of a reticular pattern involving mainly the lower lung zones, is seen in only about 3 % of patients who have SLE. By contrast, interstitial abnormalities are seen in approximately 30 % of patients on TSCT [5, 6]. These include interlobular septal thickening (33 %), irregular linear opacity (33 %), and architectural distortion (22 %). Such abnormalities are usually mild and focal; diffuse disease occurs in only 4 % of patients [4]. Honeycombing (HC) is uncommon. Groundglass opacity (GGO) and consolidation on TSCT may reflect the presence of interstitial pneumonitis and fibrosis, acute lupus pneumonitis, hemorrhage or, occasionally, COP pattern of lung abnormality.

Systemic Lupus Erythematosus (SLE)

Pleuropulmonary involvement occurs in approximately 50–60 % of SLE patients [1]. Most involvements are pleural diseases. In one prospective study including 1,000 patients, lung involvement was identified only in 3 % at the onset of the disease; an additional 7 % developed lung disease over the period of observation [2]. Pulmonary manifestations of SLE comprise both acute and chronic lesions. Acute disease includes pulmonary hemorrhage, acute lupus pneumonitis (Fig. 28.1), and pulmonary edema. Chronic disease such as interstitial pneumonitis and fibrosis is less common in SLE than in other connective tissue disorders [3].

Acute lupus pneumonitis occurs in 1–4 % of patients. Histopathologic findings of acute lupus pneumonitis include alveolar wall damage and necrosis leading to inflammatory cell infiltration, hemorrhage, edema, and hyaline membrane formation. Thrombi in small vessels,

Table 28.1 Frequency of involvement of interstitial pneumonia and other pulmonary diseases in various collagen vascular diseases

Reprinted from Kim et al. [1] with permission

Note: UIP usual interstitial pneumonia, NSIP nonspecific interstitial pneumonia, DAD diffuse alveolar damage, BOOP bronchiolitis obliterans organizing pneumonia, LIP lymphocytic interstitial pneumonia, SLE systemic lupus erythematosus, RA rheumatoid arthritis, PSS progressive systemic sclerosis, DM dermatomyositis, PM polymyositis, MCTD mixed connective tissue disease

Fig. 28.1 Acute lupus pneumonitis in a 47-year-old woman with systemic lupus erythematosus. Lung window image of CT scan (2.5-mm section thickness) obtained at level of azygos arch shows patchy and extensive areas of parenchymal opacity in upper lung zones. Also note mild and smooth thickening of interlobular septa (arrows)

Rheumatoid Arthritis (RA)

Pleuropulmonary complications in rheumatoid arthritis (RA) are common and include interstitial pneumonitis and fibrosis, rheumatoid (necrobiotic) nodules, COP pattern of lung abnormality (Fig. 28.3), bronchiectasis, bronchiolitis

obliterans, follicular bronchiolitis, and pleural effusion or thickening [1]. Interstitial pneumonitis and fibrosis are the most common pulmonary manifestation of RA (Fig. 28.4). Evidence of interstitial fibrosis is seen on chest radiographs in approximately 5 % of patients with RA [7] and on TSCT in 30–40 % [8]. The complication is seen most frequently in men between 50 and 60 years of age [9].

The majority of patients who have interstitial fibrosis associated with RA have UIP pattern of lung abnormality (Fig. 28.4); a small percentage has histologic findings of NSIP pattern [1]. Nodular aggregates of lymphocytes may be prominent in both the parenchymal interstitium and in the interstitial tissue in bronchiolar walls and interlobular septa (follicular bronchiolitis). According to a report, a wide variety of histopathologic features were seen in open lung biopsy from patients with rheumatoid lung disease [10]. Five different groups based on histologic patterns were identified: pulmonary rheumatoid nodules, UIP pattern, COP pattern, lymphoid hyperplasia, and cellular interstitial infiltrates (NSIP pattern). Few cases of DAD have been reported [11].

The predominant abnormality on TSCT consists of reticulation caused by a combination of intralobular lines and irregular thickening of interlobular septa [12]. HC is seen, most markedly near the diaphragm. According to a study [13], three predominant CT patterns were identified in 29 patients: reticulation with or without HC (n = 19),

Fig. 28.2 Pulmonary fibrosis of nonspecific interstitial pneumonia pattern in a 37-year-old woman with systemic lupus erythematosus. (a, b) Lung window of CT scans (2.5-mm section thickness) obtained at levels of inferior pulmonary veins (a) and liver dome (b), respectively,

show patchy areas of ground-glass opacity and reticulation in subpleural lungs and along bronchovascular bundles in both lungs. Also note traction bronchiectasis (open arrows)

Fig. 28.3 Interstitial pneumonia of cryptogenic organizing pneumonia pattern in a 48-year-old woman with rheumatoid arthritis. (a, b) Lung window of CT scans (2.5-mm section thickness) obtained at levels of

inferior pulmonary veins (a) and liver dome (b), respectively, show patchy areas of consolidation in both lungs, distributed along bronchovascular bundles or along subpleural lungs

Fig. 28.4 Interstitial fibrosis of usual interstitial pneumonia pattern in a 35-year-old woman with rheumatoid arthritis. (a, b) Lung window of CT scans (2.5-mm section thickness) obtained at levels of inferior

pulmonary veins (a) and liver dome (b), respectively, show patchy areas of reticulation in both lungs. Also note honeycomb cysts (arrows)