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Pulmonary lesions associated with Sjögren's syndrome: radiographic and CT findings

¹ Department of Radiology, ² 2nd Department of Internal Medicine and ³ Institute of Tropical Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan

Correspondence: Dr Kazuto Ashizawa

	Abstract

Top Abstract Introduction Methods and patients Results Discussion References

 
The aim of this study was to analyse and compare the chest radiographic and CT findings in patients with primary and secondary Sjögren's syndrome. We retrospectively evaluated the frequency of abnormality and findings of both the chest radiography (n=107) and CT (n=59) in patients with Sjögren's syndrome. Abnormal cases were classified into five patterns based on predominant CT findings. Chest radiographic and CT abnormalities were seen in 24 (22%) and in 34 (58%) patients, respectively. Most frequently observed abnormal findings were linear and reticular opacities on chest radiograph, and ground-glass opacity, interlobular septal thickening and intralobular interstitial thickening on CT in both primary and secondary Sjögren's syndrome. Centrilobular abnormalities were significantly more common in patients with primary Sjögren's syndrome (p=0.018). According to our CT classification, interstitial pneumonia (IP) pattern was the most common in patients with both primary and secondary Sjögren's syndrome. Bronchiolitis pattern was more common in patients with primary Sjögren's syndrome and lymphoproliferative disorder (LPD) pattern was only observed in primary Sjögren's syndrome. In conclusion, although the most frequently observed pattern in our CT classification was IP pattern in both primary and secondary Sjögren's syndrome, centrilobular abnormalities and LPD pattern were relatively characteristic in patients with primary Sjögren's syndrome.

	Introduction

Top Abstract Introduction Methods and patients Results Discussion References

 
Sjögren's syndrome is an inflammatory connective tissue disorder of unknown aetiology, characterized as an autoimmune exocrinopathy. Sjögren's syndrome can be categorized as primary and secondary. The latter indicates the occurrence of the sicca syndrome with another autoimmune disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) [1]. Earlier studies have evaluated the prevalence of lung involvement in primary Sjögren's syndrome on the basis of lung function test and conventional chest radiography [2–5]. The reported prevalence of pulmonary abnormality varies widely from 9% to 75%, depending on the sensitivity of the variables studied and the criteria used to define abnormality. CT findings of lung lesions in patients with Sjögren's syndrome have been assessed in only a few reports [6–10]. Moreover, to our knowledge, there has been no comprehensive study that compared the imaging findings of lung involvement between primary and secondary Sjögren's syndrome.

The purpose of our study was to analyse the frequency of abnormality and findings of both the chest radiography and CT in patients with Sjögren's syndrome and to compare these between primary and secondary Sjögren's syndrome.

	Methods and patients

Top Abstract Introduction Methods and patients Results Discussion References

 
Patients
We retrospectively identified 107 consecutive patients with proven Sjögren's syndrome who underwent chest radiography at our hospital between June 1988 and March 2000. All 107 patients selected for this study fulfilled the criteria defined by Vitali et al for diagnosis of Sjögren's syndrome [11]. We retrospectively evaluated the patients diagnosed before 1993 and confirmed that they fulfilled these criteria. They consisted of 9 men and 98 women ranging in age from 18 years to 74 years (mean age 55 years). Sjögren's syndrome had been diagnosed 1 month to 17 years prior to chest radiographic examination in 102 patients, and chest radiographic examination preceded the diagnosis of Sjögren's syndrome by 1 month to 12 months in 5 patients with secondary Sjögren's syndrome. 79 (74%) of the 107 patients had no respiratory symptoms at the time of the study. 59 patients had primary Sjögren's syndrome without evidence of another autoimmune disease. 48 patients had secondary Sjögren's syndrome in association with other autoimmune diseases (RA 11, SLE 12, PSS 6, polymyositis/dermatomyositis (PM/DM) 2, calcinosed, Raynaud's phenomenon, oesophageal deformity, sclerodactyly and teleangiectasia (CREST) syndrome 2, mixed connective tissue disease (MCTD) 9, Felty's syndrome 1, polyarteritis nodosa (PN) 1, RA+PSS 2, RA+SLE 1 and RA+CREST 1).

Chest CT examination was performed in 59 patients from this group (30 patients with primary Sjögren's syndrome, 29 patients with secondary Sjögren's syndrome). The interval between CT and chest radiography was less than 3 months, but most of the patients underwent chest radiography and CT within 1 month. Out of them, 5 patients were current smokers, 6 were former smokers and 48 were non-smokers.

Biopsy samples were obtained in 11 patients (by open lung biopsy in 6 patients and by video-assisted thoracic surgery (VATS) in 5 patients). Six patients with secondary Sjögren's syndrome had evidence of PSS (n=2), SLE (n=1), PM/DM (n=1), Felty's syndrome (n=1) and MCTD (n=1).

Radiologic evaluation
A conventional CT scanner (a model 9800; General Electric Medical Systems, Milwaukee, WI), or helical scanners (Somaton Plus 32S; Siemens, Erlangen, Germany; and CT HiSpeed or CT HiSpeed Advantage; General Electric Medical Systems) were used in this study. For the acquisition of all images through whole lung, a conventional scan with 5–7 mm collimation at 7–10 mm intervals, or a helical scan with 5–7 mm collimation and a pitch (ratio of table speed to collimation) of 1–2 was done. High-resolution CT (HRCT) scans (1–2 mm collimation with a high-spiral-frequency algorithm) were also obtained. All CT scans were obtained at the suspended end-inspiratory volume. Window settings for the lung were a level of -900 HU to -600 HU and a width of 1000–2000 HU.

Chest radiographs and CT scans were interpreted independently and in random order by two chest radiologists (NM, KA) without knowledge of the clinical status of the patients. A decision was made by consensus if there were disagreements. The frequency and distribution of parenchymal abnormality of both the chest radiograph and CT were evaluated. Each of the following radiographic features was separately recorded as present or absent: (a) linear and reticular opacities; (b) ground-glass opacity; (c) consolidation; (d) honeycombing; (e) lung cysts; and (f) traction bronchiectasis. According to Webb's classification, the radiologists also recorded the following features seen on CT: (a) peribronchovascular interstitial thickening; (b) interlobular septal thickening; (c) intralobular interstitial thickening; (d) centrilobular abnormalities; (e) ground-glass opacity; (f) consolidation; (g) honeycombing; (h) lung cysts; (i) traction bronchiectasis; (j) mosaic perfusion; (k) small nodules; (l) large nodules; and (m) masses [12]. The distribution of lung abnormality was visually assessed and recorded for the following lung regions: apex to aortic arch; aortic arch to inferior pulmonary vein; and inferior pulmonary vein to lung base.

CT classification
Earlier studies reported several pulmonary abnormalities in Sjögren's syndrome including usual interstitial pneumonia (UIP), lymphoid interstitial pneumonia (LIP), follicular bronchiolitis, cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia (COP/BOOP) [7–10, 13–15]. Therefore we classified the cases into five patterns based on predominant CT findings:

Interstitial pneumonia (IP) pattern

Lymphoproliferative disorder (LPD) pattern

Bronchiolitis pattern

COP pattern and

Unclassified.

IP pattern was mainly composed of intralobular interstitial thickening, ground-glass opacity, honeycombing and traction bronchiectasis. LPD pattern was mainly composed of ground-glass opacity, peribronchovascular interstitial thickening and interlobular septal thickening. Bronchiolitis pattern was mainly composed of centrilobular abnormalities including branching opacity and small nodules. COP pattern was mainly composed of ground-glass opacity and/or consolidation.

Statistical analysis
Comparisons of chest radiographic and CT findings between primary and secondary Sjögren's syndrome were made using chi-square statistics. Probability values of less than 0.05 were considered significant.

	Results

Top Abstract Introduction Methods and patients Results Discussion References

 
The frequency of abnormality on chest radiograph and CT is summarized in Table 1. Abnormality on chest radiograph was present in 24 (22%) of a total of 107 patients with both primary and secondary Sjögren's syndrome. The frequency of abnormality was 12 (20%) of 59 patients with primary Sjögren's syndrome and 12 (25%) of 48 patients with secondary Sjögren's syndrome. The abnormal findings on chest radiographs are summarized in Table 2. In primary Sjögren's syndrome linear and reticular opacities were present in 10 (83%) of 12 patients and ground-glass opacity were present in 3 patients (25%) (Figure 1). In secondary Sjögren's syndrome linear and reticular opacities were present in 11 (92%) of 12 patients and ground-glass opacity was present in 5 patients (42%) (Figure 2). We found no statistically significant difference between primary and secondary Sjögren's syndrome for the frequency of radiographic abnormalities. Radiographic abnormalities were predominantly seen in lower lung zones in both primary and secondary Sjögren's syndrome.

View larger version (95K): [in this window] [in a new window]   Figure 1. 49-year-old woman with primary Sjögren's syndrome. (a) Chest radiograph shows bilateral linear and reticular opacities, ground-glass opacity as well as lung cysts. These opacities are dominant in lower lung field. (b, c) Thin-section CT scans obtained at two levels. Peribronchovascular interstitial thickening, interlobular septal thickening, centrilobular abnormalities and ground-glass opacity are seen. In addition, multiple lung cysts are demonstrated. This case was classified as lymphoproliferative disorder pattern. Pathological diagnosis of lymphoid interstitial pneumonia was obtained.

View larger version (64K): [in this window] [in a new window]   Figure 2. 63-year-old woman with secondary Sjögren's syndrome (polymyositis/dermatomyositis). (a) Chest radiograph shows bilateral linear and reticular opacities and ground-glass opacity predominantly in both lower lung fields. (b) Thin-section CT scan obtained at lung base. Intralobular interstitial thickening, ground-glass opacity, honeycombing and traction bronchiectasis are demonstrated. This case was classified as IP pattern. Pathological diagnosis of usual interstitial pneumonia was obtained.

View larger version (110K): [in this window] [in a new window]   Figure 3. 71-year-old woman with secondary Sjögren's syndrome (progressive systemic sclerosis). Thin-section CT scan obtained at lung base. Interlobular septal thickening, intralobular interstitial thickening and traction bronchiectasis are seen. In addition to these findings, multiple lung cysts are demonstrated. This case was classified as interstitial pneumonia pattern and pathological diagnosis of usual interstitial pneumonia was made.

View larger version (105K): [in this window] [in a new window]   Figure 4. 70-year-old woman with primary Sjögren's syndrome. Thin-section CT scan obtained at the level of aortic arch. Centrilobular abnormalities and bronchiolectasis are seen. This case was classified as bronchiolitis pattern.

Biopsy samples were obtained in 5 patients with primary Sjögren's syndrome and in 6 patients with secondary Sjögren's syndrome. In patients with primary Sjögren's syndrome, pathological diagnosis of UIP and LIP was made in 3 and 2 patients, respectively. In patients with secondary Sjögren's syndrome, UIP was diagnosed in 4 patients and COP and desquamative interstitial pneumonia (DIP) was identified in one patient each. In these patients a pattern classification based on CT findings gave good agreement with pathological diagnosis.

	Discussion

Top Abstract Introduction Methods and patients Results Discussion References

 
There have been only a few reports on diagnostic imaging of lung involvement in Sjögren's syndrome. In particular, the reports describing the CT findings in patients with Sjögren's syndrome have been scant [6–10]. The reported prevalence of pulmonary abnormality varies widely from 9% to 75%, depending on the sensitivity of the variables studied and the criteria used to define abnormality [2–5]. In our study chest radiographic and CT abnormalities in patients with Sjögren's syndrome were seen in 22% and 58%, respectively. However, actual frequency might be lower because some patients without respiratory symptom might not have undergone chest radiography and/or CT examination.

Owing to superior contrast resolution and decreased superimposition, lung abnormalities with Sjögren's syndrome were more frequently seen on CT than on radiograph. Moreover the abnormalities were better shown on CT. Traction bronchiectasis was depicted in 16 patients on CT but in none on radiograph.

In our series, linear and reticular opacities were the most common chest radiographic abnormality in patients with both primary and secondary Sjögren's syndrome. In earlier studies, the most common radiographic findings in patients with primary Sjögren's syndrome have been described as reticular and reticulonodular abnormality [2, 3]. Our results were similar to those previously reported. Ground-glass opacity, interlobular septal thickening, intralobular interstitial thickening and centrilobular abnormalities were the frequently observed CT findings in patients with primary Sjögren's syndrome. Franquet et al also reported that the most common CT findings were parenchymal linear opacities and bronchiolar abnormalities [7]. In patients with secondary Sjögren's syndrome centrilobular abnormalities were less frequently seen in our study. In previous studies, centrilobular nodules indicating peripheral airway abnormalities are frequently seen in patients with primary Sjögren's syndrome and RA [7, 16, 17]. It is not clear why peripheral airway abnormalities are less frequently seen in secondary Sjögren's syndrome than in primary Sjögren's syndrome.

In our study LPD pattern was only seen in patients with primary Sjögren's syndrome. Although the number of patients with LPD pattern was small, LIP is thought to be characteristic in patients with primary Sjögren's syndrome. To our knowledge, LIP has been reported in patients with primary Sjögren's syndrome but not in patients with other collagen diseases. It is speculated that lung abnormalities in secondary Sjögren's syndrome may be dominated more by associated collagen disease than by Sjögren's syndrome itself. Lung cysts seen in LIP and amyloidosis have been reported as the characteristic findings in Sjögren's syndrome [14, 15]. In our study, lung cysts were seen in 1 of 2 patients with LPD pattern (Figure 1). Ichikawa et al reported that several bronchioles were either stenotic or obstructed by peribronchiolar lymphocytic infiltration and resulted in cyst formation through secondary bronchiolectasis in LIP [18].

Lung cysts were present in four patients with primary Sjögren's syndrome. Centrilobular abnormalities were seen in all of these four patients (Figure 1) and mosaic perfusion was seen in three of them. Webb et al described that mosaic perfusion is most frequent in patients with airway diseases that result in focal air-trapping or poor ventilation of lung parenchyma [12]. Mayer et al reported that the lung cyst formation was thought to be caused by check-valve phenomenon in peripheral airway [15]. Lung cyst formation in our study seems to be due to peripheral airway disease although the number of cases with lung cysts is small. Traction may also be the cause of lung cyst formation.

Our study has two limitations. Firstly, expiratory HRCT scan was not performed in our study. Mayer et al reported that expiratory HRCT scan was useful to reveal the structural and functional changes caused by small airways disease. If expiratory HRCT scans had been performed, small airway disease and concomitant air trapping would have been more clearly demonstrated. Secondly, histopathological evidence was not available in all patients. Biopsy samples were obtained in 11 (32%) of 34 patients having abnormality on chest CT. However, this was similar to other reports [7, 8]. Franquet et al stated the lack of histopathological data was a limitation in their study [7]. Koyama et al reported that histological confirmation was obtained in only 10 (17%) of 60 patients [8]. One plausible reason for small number of cases with correlation between CT and pathological findings in published studies could be the fact that in routine clinical practice lung biopsy is not necessarily performed in the presence of characteristic CT findings for specific diffuse lung diseases. However, in patients with biopsy samples a pattern classification based on CT findings gave good agreement with pathological diagnosis. Therefore even in patients without biopsy samples, a pattern classification based on CT findings was thought to be useful.

In summary, chest radiographic and CT abnormalities in patients with Sjögren's syndrome were seen in 22% and 58%, respectively. Most frequently observed pattern in our CT classification was IP pattern in both primary and secondary Sjögren's syndrome. Centrilobular abnormalities and LPD pattern were characteristic in patients with primary Sjögren's syndrome.

Received for publication August 12, 2002. Revision received July 31, 2003. Accepted for publication September 10, 2003.

	References

Top Abstract Introduction Methods and patients Results Discussion References

 

1. Moutsopoulos HM, Chused TM, Mann DL, et al. Sjögren's syndrome (Sicca syndrome): current issues. Ann Intern Med 1980;92:212–26.
2. Constantopoulos SH, Papadimitriou CS, Moutsopoulos HM. Respiratory manifestations in primary Sjögren's syndrome: a clinical, functional, and histologic study. Chest 1985;88:226–9.[Abstract/Free Full Text]
3. Strimlan CV, Rosenow EC, Divertie MB, Harrison EG. Pulmonary manifestation of Sjögren's syndrome. Chest 1976;70:354–95.[Abstract/Free Full Text]
4. Lahdensuo A, Korpela M. Pulmonary findings in patients with primary Sjögren's syndrome. Chest 1995;108:316–9.[Abstract/Free Full Text]
5. Gardiner P, Ward C, Allison A, et al. Pleuropulmonary abnormalities in primary Sjögren's syndrome. J Rheumatol 1993;20:831–7.[Medline]
6. Franquet T, Diaz C, Domingo P, Gimenez A, Geli C. Air trapping in primary Sjögren's syndrome: correlation of expiratory CT with pulmonary function tests. J Comput Assist Tomogr 1999;23:169–73.[CrossRef][Medline]
7. Franquet T, Gimenez A, Monill JM, Diaz C, Geli C. Primary Sjögren's syndrome and associated lung disease: CT findings in 50 patients. AJR Am J Roentgenol 1997;169:655–8.[Abstract/Free Full Text]
8. Koyama M, Johkoh T, Honda O, et al. Pulmonary involvement in primary Sjögren's syndrome: spectrum of pulmonary abnormalities and computed tomography findings in 60 patients. J Thoracic Imaging 2001;16:290–6.[CrossRef][Medline]
9. Ogura T, Iwazawa T, Itou T, et al. Bronchopulmonary involvement in primary Sjögren's syndrome; evaluation with HRCT findings in 12 patients [Japanese]. Rinshou houshasen 2000;45:101–8.
10. Bachir T, Michel WB, Isabelle M, et al. Thin-section chest CT findings of primary Sjögren's syndrome: correlation with pulmonary function. Eur Radiol 2002;12:1504–11.[CrossRef][Medline]
11. Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjögren's syndrome. Results of prospective concerted action supported by European Community. Arthritis Rheum 1993;36:340–7.[Medline]
12. Webb WR, Muller NL, Naidich DP. High-resolution CT of the lung. Philadelphia, PA: Lippincott-Raven, 1996:41–90.
13. Kobayashi H, Matsuoka R, Kitamura S, Tsunoda N, Saito K. Sjögren's syndrome with multiple bullae and pulmonary nodular amyloidosis. Chest 1988;94:438–40.[Abstract/Free Full Text]
14. Hayasaka S, Fujino N, Yoshinaga T, Kiyama T, Maemoto H, Outsuka Y. Primary Sjögren's syndrome with lymphocytic interstitial pneumonia and pulmonary multiple cystic lesions [Japanese]. Nihon Kokyuki Gakkai Zasshi 1999;37:802–6.[Medline]
15. Meyer CA, Pina JS, Taillon D, Godwin JD. Inspiratory and expiratory high-resolution CT findings in a patient with Sjögren's syndrome and cystic lung disease. AJR Am J Roentgenol 1997;168:101–3.[Free Full Text]
16. Akira M, Sakatani M, Hara H. Thin-section CT findings in rheumatoid arthritis-associated lung disease: CT patterns and their courses. J Comput Assist Tomogr 1999;23:941–7.[CrossRef][Medline]
17. Remy-Jardin M, Remy J, Cortet B, Mauri F, Delcambre B. Lung changes in rheumatoid arthritis: CT findings. Radiology 1994;193:375–82.[Abstract/Free Full Text]
18. Ichikawa Y, Kinoshita M, Koga T, Oizumi K, Fujimoto K, Hayabuchi N. Lung cyst formation in lymphocytic interstitial pneumonia: CT features. J Comput Assist Tomogr 1994;18:745–8.[Medline]

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