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(Chest. 2006;130:1489-1495.)
© 2006 American College of Chest Physicians

Interstitial Lung Disease in Primary Sjögren Syndrome*

Joseph G. Parambil, MD; Jeffrey L. Myers, MD, FCCP; Rebecca M. Lindell, MD; Eric L. Matteson, MD and Jay H. Ryu, MD, FCCP

* From the Divisions of Pulmonary and Critical Care Medicine (Drs. Parambil and Ryu) and Rheumatology (Dr. Matteson), and Department of Radiology (Dr. Lindell), Mayo Clinic, Rochester, MN; and Department of Pathology (Dr. Myers), University of Michigan, Ann Arbor, MI.

Correspondences to: Jay H. Ryu, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Desk East 18, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: ryu.jay{at}mayo.edu

Abstract

Background: Primary Sjögren syndrome (pSS) has been associated with various histologic patterns of interstitial lung disease (ILD).

Methods: We retrospectively identified 18 patients with pSS and suspected ILD who underwent lung biopsies (14 surgical biopsies and 9 bronchoscopic biopsies) at our institution during a 13-year period from 1992 through 2004. Histopathologic findings were analyzed and correlated with radiologic features and outcome.

Results: Median age was 62 years (range, 34 to 78 years), and 15 patients (83%) were women. Most patients presented with dyspnea and cough. Chest radiographs demonstrated bilateral infiltrates, and high-resolution CT revealed abnormalities of various types including ground-glass, consolidation, reticular, and nodular opacities. The major histopathologic patterns included nonspecific interstitial pneumonia (NSIP) [five patients], organizing pneumonia (OP) [four patients], usual interstitial pneumonia (UIP) [three patients], lymphocytic interstitial pneumonia (three patients), primary pulmonary lymphoma (two patients), and diffuse interstitial amyloidosis (one patient). In four patients (three with OP and one with amyloidosis), the diagnosis was established on transbronchial biopsy results. Treatment commonly included prednisone with or without another immunosuppressive agent. During the follow-up period (median, 38 months), most patients improved or remained stable except three patients with UIP, one patient with NSIP, and one patient with amyloidosis. Seven patients (39%) died, including three deaths from acute exacerbation of interstitial pneumonia.

Conclusions: A variety of histologic patterns can be seen in patients with pSS-associated ILD. Those with UIP tended to have progression of lung disease. Death from acute exacerbation of interstitial pneumonia may occur in patients with pSS-associated ILD.

Key Words: interstitial lung disease • interstitial pneumonia • lung biopsy • pulmonary fibrosis • Sjögren syndrome

Primary Sjögren syndrome (pSS) is a systemic inflammatory disorder that commonly affects exocrine glands.12 Although sicca features are the central clinical manifestations of the disease, pSS can cause systemic extraglandular manifestations. The reported frequency of pulmonary involvement in pSS varies widely, ranging from 9 to 75% depending on the detection method employed, and consists of various forms of small airways and interstitial lung diseases (ILDs).3456

Aside from a well-established association with lymphocytic interstitial pneumonia (LIP),3456 there is relatively little information regarding other ILD patterns occurring in patients with pSS. We characterized histologic patterns of ILD associated with pSS by examining a consecutive series of these patients seen at our institution. We also correlated these histologic findings with clinicoradiologic presentations and outcomes.

Materials and Methods

Patient Selection
A computer-aided search was conducted to retrospectively identify all adults (≥ 18 years old) seen at our institution during the 13-year period from January 1, 1992, to December 31, 2004, with pSS and either pulmonary fibrosis, interstitial pneumonia, or suspected ILD. We identified 32 patients with pSS and ILD who had no identifiable cause for their lung disease other than the underlying connective tissue disease. Eighteen of these 32 patients had lung biopsies performed for histopathologic diagnosis of persistent bilateral lung infiltrates and formed the final study group.

Diagnostic Criteria
The American-European classification criteria7 were used to make the diagnosis of pSS and included the following items: ocular symptoms of inadequate tear production, oral symptoms of decreased saliva production, ocular signs of corneal damage due to inadequate tearing, salivary gland histopathology demonstrating foci of lymphocytes, test results indicating impaired salivary gland function, and the presence of autoantibodies (anti-SS-A/Ro, anti-SS-B/La, or both). Definite diagnosis of pSS required the presence of four of the six items with histopathologic findings or autoantibodies being one of the four items. The diagnosis of ILD required the persistent presence of bilateral parenchymal lung infiltrates by chest radiography and/or CT. Patients with transient or focal infiltrates were excluded. We limited the analyses to patients with pSS by excluding those with underlying connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, polymyositis/dermatomyositis, scleroderma, and mixed connective tissue disease. We also excluded patients with preexisting lymphoma, sarcoidosis, infection with HIV or hepatitis C virus, prior head and/or neck irradiation, recent use of drugs with anticholinergic properties, and graft-vs-host disease.

Clinical, Laboratory, and Radiologic Data
Clinical data and diagnostic results were extracted from the medical records and included demographic data, clinical presentation, physical findings, laboratory results, radiologic findings, and echocardiographic data. Presenting signs and symptoms were recorded from the first encounter at our institution that led to a diagnosis of pSS-associated ILD. Pulmonary function data included plethysmographically determined total lung capacity and residual volume, along with FVC, FEV1, ratio of FEV1 to FVC, and diffusing capacity for carbon monoxide (DLCO). Spirometry and measurements of lung volumes and DLCO were performed in our pulmonary function laboratory and were expressed as percentage of predicted normal values, using previously described techniques.8 All expressed values are mean ± SD unless stated otherwise. Chest radiographs and CTs of the lungs were reviewed and interpreted without knowledge of biopsy results or clinical manifestations by a chest radiologist with a specific interest in ILD (R.M.L).

Surgical lung biopsy slides were retrieved and reviewed by a pulmonary pathologist (J.L.M.) without knowledge of clinical or radiologic information. The histopathologic diagnosis was made using terminology proposed in the American-European consensus statement on idiopathic interstitial pneumonias.9 The Mayo Foundation Institutional Review Board approved this study. Patients who did not authorize the use of their medical records for research were excluded from this study.

Results

Clinical Features
The median age of our 18 patients at the time of lung biopsy was 62 years (range, 34 to 78 years), and 15 patients (83%) were women. Four patients (22%) had a smoking history and included one current smoker. Four of the 18 patients (22%) had both pSS and ILD diagnosed within 1 month of their initial presentation. The remaining 14 patients (78%) had pSS diagnosed prior to diagnosis of lung disease (median interval, 6.3 years; range, 1.2 to 9.8 years). Clinical features at initial presentation are summarized in Table 1 . All patients had respiratory symptoms, most commonly exertional dyspnea. The duration of respiratory symptoms ranged from 3 to 12 months (median, 7 months) prior to lung biopsy.


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  		Table 1.. Presenting Symptoms and Signs

 
Laboratory Findings
Laboratory results are summarized in Table 2 and included the presence of anti-nuclear antibody and anti-SS-A/Ro antibody in nearly all patients tested. Polyclonal hypergammaglobulinemia, an elevated erythrocyte sedimentation rate, and elevated rheumatoid factor titers were also evident in most patients. Anti-SS-B/La antibody was detected in one half of patients. Labial salivary gland biopsies were performed in 10 patients (56%) and demonstrated multiple foci of lymphoid infiltrates in 7 patients (70%) and were nondiagnostic in the in the remaining 3 patients.


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  		Table 2.. Serologic Results*

 
Histopathologic Findings
Several distinct histopathologic lesions were seen in these patients and included nonspecific interstitial pneumonia (NSIP) [five patients], organizing pneumonia (OP) [four patients], usual interstitial pneumonia (UIP) [three patients], LIP (three patients), primary pulmonary lymphoma (two patients), and diffuse interstitial amyloidosis (one patient). Both patients with primary pulmonary lymphoma had extranodal B-cell lymphomas of mucosa-associated lymphoid tissue limited to the lungs at the time of presentation. Minor secondary changes were associated with a variety of underlying pathologic processes and included nodular deposits of amyloid and amyloid-like material in both patients with primary pulmonary lymphoma as well as follicular bronchiolitis in two other patients. Diagnoses were made in four patients using bronchoscopic (transbronchial) biopsy alone and included three patients with OP and the one patient with diffuse interstitial amyloidosis. In the patient with amyloidosis, immunofluorescence microscopy demonstrated marked positivity for monospecific anti-AA protein consistent with secondary AA amyloidosis (serum and urine studies did not reveal monoclonal Ig nor monoclonal light chains).

Chest Radiography and CT
Chest radiography and high-resolution CT (HRCT) of the chest was performed in all 18 patients. The radiologic findings are summarized in Table 3 . Chest radiography demonstrated bilateral lung infiltrates in all patients. The character of these infiltrates varied on HRCT, which revealed bilateral areas of ground-glass, consolidative, reticular, and nodular opacities as well as cysts.


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  		Table 3.. Radiologic Findings (n = 18)

 
Areas of ground-glass attenuation and reticular opacities distributed peripherally in both lower lung zones were the dominant HRCT findings among patients with NSIP (Fig 1 ). HRCT in patients with OP revealed bilateral patchy, nonsegmental areas of consolidation distributed predominantly in the subpleural and peribronchovascular regions admixed with patchy areas of ground-glass attenuation (Fig 2 ). UIP was associated with reticular opacities and associated traction bronchiectasis with a basal and peripheral predominance (Fig 3 ). Subpleural honeycombing was seen in two of three patients. The main HRCT findings among patients with LIP as well as primary pulmonary lymphoma consisted of patchy areas of consolidations and nodules as well as ground-glass opacities (Fig 4 ). Multifocal cysts were seen in three patients (two with LIP and one with primary pulmonary lymphoma). Scattered areas of subpleural honeycombing were noted in one patient with LIP. Prominent interlobular septal thickening with small randomly distributed nodules in a basal distribution characterized the HRCT scan in the patient with diffuse interstitial amyloidosis.


Figure 1
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  		Figure 1.. HRCT scan of NSIP in a 41-year-old man with pSS. This image demonstrates bilateral ground-glass opacities and mild reticulation, more extensive in the left lung. There is associated mild traction bronchiectasis.

 

Figure 2
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  		Figure 2.. CT scan of OP in a 50-year-old woman with pSS. This image shows bilateral peripheral parenchymal consolidation with air bronchograms, more extensive in the right lung.

 

Figure 3
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  		Figure 3.. HRCT scan of UIP in a 63-year-old man with pSS. This image demonstrates coarse reticular opacities in both lungs with associated traction bronchiectasis and subpleural honeycombing.

 

Figure 4
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  		Figure 4.. HRCT scan of primary pulmonary lymphoma in a 63-year-old woman with pSS. This image demonstrates patchy, small, rounded areas of consolidation and ground-glass opacities as well as two cysts.

 
Echocardiography
Transthoracic echocardiography was performed in 13 patients (72%). The mean estimated pulmonary artery systolic pressure (PASP) was 42 ± 21.8 mm Hg. Eight patients (62%) had pulmonary hypertension, defined by a PASP ≥ 35 mm Hg at rest. Pulmonary hypertension was relatively mild (PASP, 35 to 50 mm Hg) in six of these eight patients. The remaining two patients with PASP > 50 mm Hg had UIP and exhibited evidence of right ventricular systolic dysfunction; one of these patients received vasodilator therapy with bosentan. Two patients (15%) had small pericardial effusions without evidence of cardiac tamponade.

Pulmonary Function
Fifteen patients (83%) underwent pulmonary function testing (PFT) at the time of their initial evaluation, and the results were abnormal in 13 patients (87%); 2 patients with normal PFT results both had primary pulmonary lymphoma. Ten patients (67%) had a restrictive defect with a mean total lung capacity of 55 ± 7% of predicted and a mean DLCO of 44 ± 5% of predicted. Two patients (13%) with preexisting smoking-related COPD had an obstructive defect with a mean FEV1 of 53 ± 2% of predicted and a FEV1/FVC ratio of 63 ± 4%. A reduced DLCO was found in 13 patients (87%) and was the only pulmonary function abnormality in 1 patient.

Treatment
The initial treatment in 15 of the 18 patients (83%) included corticosteroids, most commonly in the form of oral prednisone at 1 mg/kg/d (Table 4 ). Other agents were often added later in the clinical course when there appeared to be no improvement, and included hydroxychloroquine (five patients), azathioprine (two patients), and cyclophosphamide (two patients). One of two patients with primary pulmonary lymphoma was treated with a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone. Three patients (17%), one with UIP, one with primary pulmonary lymphoma, and one with LIP, were expectantly observed without specific treatment.


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  		Table 4.. Treatment and Outcome Data

 
Follow-up Clinical Course
All 18 patients had follow-up data available over a median duration of 38 months (range, 7 to 164 months) [Table 4]. During this period, there was evidence of improvement in pulmonary function as judged by a ≥ 10% increase in FVC or a ≥ 15% increase in DLCO from pretreatment baseline values in nine patients (50%).10 These nine patients included all four patients with OP, three of five patients with NSIP, and two of three patients with LIP. There was deterioration in PFT results as judged by a ≥ 10% decrease in FVC or a ≥ 15% decrease in DLCO from pretreatment baseline values despite treatment in five patients (28%).10 These five patients included all three patients with UIP, one patient with NSIP, and one patient with diffuse interstitial amyloidosis. The remaining four patients (22%) maintained stable pulmonary function during the follow-up period and included both patients with primary pulmonary lymphoma, one patient with LIP, and one patient with NSIP.

Seven patients (39%) died during the follow-up period after a median interval of 67 months (range, 7 to 105 months) following the diagnosis of ILD. The causes of death included acute exacerbation of interstitial pneumonia with an illness described as ARDS with no identifiable cause in three patients (two with NSIP and one with UIP). One patient with LIP died from non-small cell lung cancer (an ex-smoker). The patient with diffuse interstitial amyloidosis died from progression of the underlying disease. The causes of death in the two remain patients included non-Hodgkin lymphoma in the brain (the patient with NSIP) and septic shock related to acute pyelonephritis (the patient with UIP receiving prednisone treatment).

Discussion

Sjögren syndrome is an inflammatory disorder targeting exocrine glands often accompanied by various systemic manifestations including lung involvement.12345611 Diffuse ILD is the most serious form of lung involvement due to its potentially progressive nature and the concomitant risk of respiratory failure.

Patients with pSS are at risk for several different types of ILD, including NSIP, OP, UIP, LIP, and diffuse interstitial amyloidosis as demonstrated in our study population. Earlier studies3456 emphasized LIP and primary pulmonary lymphoma as dominant forms of pSS-associated parenchymal lung diseases, but these were seen in less than one third of our patients. Differences in the spectrum of histologic diagnoses associated with ILD in pSS may, in part, reflect revisions in recent criteria for separating idiopathic interstitial pneumonias.9 For example, some cases previously classified as LIP may be now categorized as NSIP depending on the degree of lymphocytic infiltration. Interestingly, Ito and colleagues12 recently examined 33 patients with pSS-associated ILD and reported NSIP as the most common histopathologic pattern of disease, occurring in 61% of their patients. The patients included in their study were "biopsied in deteriorating phases of disease," and the histologic features may have been modified by previous medical therapy. In our study, lung biopsies were performed during the initial phase of evaluation for ILD and may more accurately reflect the presenting histopathologic patterns of ILD in patients with pSS. Prior to lung biopsy, three of our patients (17%) were receiving hydroxychloroquine therapy for the management of arthralgias, but none had been on immunosuppressive therapy. Patients with pSS have accounted for 0 to 8% of patients with histologically proven NSIP.131415

The HRCT findings in our pSS patients demonstrated a relationship to specific histopathologic patterns analogous to the radiologic-pathologic correlations seen in patients with idiopathic interstitial pneumonias. HRCT findings in patients with Sjögren syndrome-related pulmonary disease have been described in several previous reports,161718192021 which found small airways disease and ILD to be the most common abnormalities but without detail concerning variations in the histopathologic types of underlying ILD. Overall, the HRCT features appeared to correlate relatively well with the underlying histopathologic pattern of ILD in our patients with pSS.

The optimal treatment for patients with pSS-associated ILD is not known but likely depends on the specific underlying pathology. In our series, prednisone therapy in the range of 0.5 to 1 mg/kg/d was favored as the initial treatment. The majority of treated patients appeared to show subjective response with improvement in their respiratory symptoms within several weeks. Objective measures of lung disease including pulmonary function measurements and radiologic findings were slower to respond, occurring over a course of few to several months. Incomplete resolution of pulmonary infiltrates with residual infiltrates was commonly observed. Some of these patients required addition of another immunosuppressive agent such as azathioprine or cyclophosphamide later in the clinical course. Although favorable response to therapy was seen in some of our patients, it is not clear that all patients with pSS-associated ILD need immunosuppressive therapy. For those patients with mild and indolent ILD, as seen in some cases of LIP, an initial period of observation may be a reasonable alternative.

Theander and colleagues21 did not find an increase in all-cause mortality for patients with pSS compared with the general population, but there was excess mortality due to lymphoproliferative malignancy. In our series, seven patients (39%) died during the follow-up period, one patient due to lymphoproliferative malignancy, and one patient (ex-smoker) due to non-small cell lung cancer. Three patients died due to an acute exacerbation of chronic interstitial pneumonia. Few cases of acute exacerbation of interstitial pneumonia in patients with connective tissue disorders-related ILD have been previously reported.222324 The remaining two patients died from progression of associated amyloidosis and septic shock. Long-term corticosteroid therapy may have contributed to the fulminant infection in the latter patient.

In summary, ILDs seen in patients with pSS are associated with a variety of histopathologic patterns that appeared to have therapeutic and prognostic implications. Although corticosteroid therapy was commonly employed with a favorable response seen in the majority of patients, those with UIP and diffuse interstitial amyloidosis fared poorly with progressive deterioration in their lung disease. Several deaths occurred in this cohort of pSS patients, including three patients who died from acute deterioration of their ILD. Optimal treatment for patients with pSS-associated ILD remains to be defined.

Footnotes

Abbreviations: DLCO = diffusing capacity of the lung for carbon monoxide; HRCT = high-resolution CT; ILD = interstitial lung disease; LIP = lymphocytic interstitial pneumonia; NSIP = nonspecific interstitial pneumonia; OP = organizing pneumonia; PASP = pulmonary artery systolic pressure; PFT = pulmonary function testing; pSS = primary Sjögren syndrome; UIP = usual interstitial pneumonia

Funding was provided by the Mayo Foundation.

None of the authors have any conflicts of interest to disclose.

Received for publication March 13, 2006. Accepted for publication May 8, 2006.

References

  1. Hansen, A, Lipsky, PE, Dorner, T (2003) New concepts in the pathogenesis of Sjögren’s syndrome: many questions, fewer answers. Curr Opin Rheumatol 15,563-570[CrossRef][ISI][Medline]
  2. Kassan, SS, Moutsopoulos, HM Clinical manifestations and early diagnosis of Sjögren’s syndrome. Arch Intern Med 2004;164,1275-1284[Abstract/Free Full Text]
  3. Gardiner, P, Ward, C, Allison, A, et al Pleuropulmonary abnormalities in primary Sjögren’s syndrome. J Rheumatol 1993;20,831-837[ISI][Medline]
  4. Deheinzelin, D, Capelozzi, VL, Kairalla, RA, et al Interstitial lung disease in primary Sjögren’s syndrome: clinical-pathological evaluation and response to treatment. Am J Respir Crit Care Med 1996;154,794-799[Abstract]
  5. Cain, HC, Noble, PW, Matthay, RA Pulmonary manifestations of Sjögren’s syndrome. Clin Chest Med 1998;19,687-699[CrossRef][ISI][Medline]
  6. Davidson, BKS, Kelly, CA, Griffiths, ID Ten-year follow up of pulmonary function in patients with primary Sjögren’s syndrome. Thorax 2000;59,709-712
  7. Vitali, C, Bombardieri, S, Jonsson, R, et al Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61,554-558[Abstract/Free Full Text]
  8. Douglas, WW, Ryu, JH, Schroeder, DR Idiopathic pulmonary fibrosis: impact of oxygen and colchicine, prednisone or no therapy on survival. Am J Respir Crit Care Med 2000;161,1172-1178[Abstract/Free Full Text]
  9. American Thoracic Society/European Respiratory Society International multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165,277-304[Free Full Text]
  10. American Thoracic Society/European Respiratory Society.. Idiopathic pulmonary fibrosis: diagnosis and treatment; international consensus statement. Am J Respir Crit Care Med 2000;161,646-664[Free Full Text]
  11. Papiris, SA, Maniati, M, Constantopoulos, SH, et al Lung involvement in primary Sjögren’s syndrome is mainly related to the small airway disease Ann Rheum Dis 1999;58,61-64[Abstract/Free Full Text]
  12. Ito, I, Nagai, S, Kitaichi, M, et al Pulmonary manifestations of primary Sjögren’s syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med 2005;171,632-638[Abstract/Free Full Text]
  13. Cottin, V, Donsbeck, A-V, Revel, D, et al Nonspecific interstitial pneumonia: individualization of a clinicopathologic entity in a series of 12 patients. Am J Respir Crit Care Med 1998;158,1286-1293[Abstract/Free Full Text]
  14. Screaton, NJ, Hiorns, MP, Lee, KS, et al Serial high-resolution CT in non-specific interstitial pneumonia: prognostic value of the initial pattern. Clin Radiol 2005;60,96-104[CrossRef][ISI][Medline]
  15. Fujita, J, Ohtsuki, Y, Yoshinouchi, T, et al Idiopathic non-specific interstitial pneumonia: as an "autoimmune interstitial pneumonia. Respir Med 2005;99,234-240[CrossRef][ISI][Medline]
  16. Franquet, T, Gimenez, A, Monill, JM, et al Primary Sjögren’s syndrome and associated lung disease: CT findings in 50 patients. AJR Am J Roentgenol 1997;169,655-658[Abstract/Free Full Text]
  17. 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 Thorac Imaging 2001;16,290-296[CrossRef][ISI][Medline]
  18. Uffmann, M, Kiener, HP, Bankier, AA, et al Lung manifestation in asymptomatic patients with primary Sjögren’s syndrome: assessment with high resolution CT and pulmonary function tests. J Thorac Imaging 2001;16,282-289[CrossRef][ISI][Medline]
  19. Taouli, B, Brauner, MW, Mourey, I, et al Thin-section chest CT findings of primary Sjögren’s syndrome: correlation with pulmonary function. Eur Radiol 2002;12,1504-1511[CrossRef][ISI][Medline]
  20. Matsuyama, N, Ashizawa, K, Okimoto, T, et al Pulmonary lesions associated with Sjögren’s syndrome: radiographic and CT findings. Br J Radiol 2003;76,880-884[Abstract/Free Full Text]
  21. Theander, E, Manthorpe, R, Jacobsson, LT Mortality and causes of death in primary Sjogren’s syndrome: a prospective cohort study. Arthritis Rheum 2004;50,1262-1269[CrossRef][ISI][Medline]
  22. Mitsushima, H, Kawazoe, K, Takahashi, A, et al Secondary bronchiolitis obliterans organizing pneumonia with primary Sjogren’s syndrome resulting in acute respiratory distress syndrome: a case report. Nihon Kokyuki Gakkai Zasshi 2004;42,261-265[Medline]
  23. Hollingsworth, HM, Mark, EJ Case 32–2001: a 77-year-old man with rheumatoid arthritis and acute dyspnea and renal failure. N Engl J Med 2001;345,1193-1200[Free Full Text]
  24. Parambil, JG, Myers, JL, Ryu, JH Diffuse alveolar damage: uncommon manifestation of pulmonary involvement in patients with connective tissue diseases. Chest 2006;2,553-558



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