Potential involvement of subclinical Sjögren's syndrome in various lung diseases

Objectives: Sjögren's syndrome (SS) affects the respiratory system, but previous studies have not assessed the role of subclinical SS in lung disease. The aim of this investigation was to explore the potential role of subclinical SS as a factor in the pathogenesis of various diffuse lung diseases. Methodology: This single‐cohort prospective study was performed over a 5‐year period in 313 consecutive patients with diffuse lung disease, who had neither primary xerosis nor a diagnosis of SS. They were referred for the Saxon test and underwent additional tests for SS when decreased saliva production was detected. Results: The subjects included 109 patients with sarcoidosis, 77 with various interstitial pneumonias, 49 with bronchiectasis, and 78 with other diseases. The incidence of decreased saliva production was 17.3% (54 out of 313). A total of 40 of the 54 patients completed further examinations, and definite or probable SS was diagnosed in 29 (9.3% of the original 313). Definite SS was diagnosed in six patients with interstitial pneumonia, three with bronchiolitis, three with sarcoidosis, and five with other diseases. Conclusions: The prevalence of decreased saliva production and SS without obvious symptoms of dryness was high among patients with diffuse lung disease. In these patients, it is important to screen for SS, even if symptoms are not apparent.     

Case of HLA-DR8 positive sarcoidosis following polymyositis and Sj?gren's syndrome]

A 69-year-old woman had been found to have idiopathic interstitial pneumonia (fibrotic NSIP) in 1997. Proximal muscle weakness appeared in April 2005. Chest CT revealed hilar and mediastinal lymphadenopathy. Polymyositis and Sj?gren's syndrome were subsequently diagnosed. We assumed that the interstitial pneumonia had preceded polymyositis and Sj?gren's syndrome. A muscle biopsy and transbronchial needle aspiration biopsy demonstrated noncaseating epithelioid cell granulomas. A diagnosis of sarcoidosis complicated with polymyositis and Sj?gren's syndrome was made from these findings. Moreover, her HLA genotype contained DR8. HLA-DR8 is considered to be associated with polymyositis, Sj?gren's syndrome, and sarcoidosis in Japanese patients. This case suggests the possibility that there are common immunological and genetical pathogenetic mechanisms in autoimmune diseases and sarcoidosis.     

Evaluation of two quantitative tests for salivary secretion--the chewing gum test and the Saxon test in normal subjects and in patients with Sj?gren's syndrome

A cooperative multicenter study was performed to evaluate two salivary secretion methods-the chewing gum test and the Saxon test by a crossover method. Twenty healthy volunteers and 27 patients with Sj?gren's syndrome were examined. In healthy controls the amount of saliva collected per minute was larger in the Saxon test. Both tests revealed a significant decrease of salivary secretion in patients with Sj?gren's syndrome, but the amount of saliva per minute was also larger in Saxon test. By repeated trials of both tests a notable increase of saliva was always observed at the second trial. Since this phenomenon may be due to the learning effect of the tests, one should perform at least one practice before starting formal tests. Saxon test could be performed in a patient having dental prostheses who was unable to masticate chewing gum. The Saxon test, thus, may be an efficient method, to evaluate the salivary secretory function.     

Efficacy of low-dose prednisolone maintenance for saliva production and serological abnormalities in patients with primary Sjögren's syndrome

OBJECTIVE: To evaluate efficacy of low dose prednisolone maintenance in patients with primary Sj?gren's syndrome. METHODS: An open, prospective pilot study of prednisolone for the treatment of 20 patients with primary Sj?gren's syndrome was performed. Evaluations included the amount of whole saliva measured by the Saxon test, serological abnormalities and oral symptoms. RESULTS: Initial dosage of prednisolone was 15.0+/-1.5 (mean+/-SEM) mg/day. Maintenance dosage was 7.5-5.0 mg/day. Follow-up period was 26.3+/-3.8 months (range 3-48). The amount of whole saliva significantly increased after 1 month of prednisolone therapy and the increase continued up to 48 months by maintaining low-dose prednisolone. A mean percent increase of whole saliva from baseline ranged from +105.2+/-36.2% to +245.7+/-82.1%. Serum IgG, anti-SS-A/Ro, anti-SS-B/La antibodies and IgM rheumatoid factor levels significantly decreased throughout the study with partial decreases of IgA and IgM levels. The improvement of subjective oral symptoms was also confirmed. CONCLUSION: Low-dose prednisolone maintenance may have a worthwhile clinical benefit in patients with primary Sj?gren's syndrome that deserves further evaluation in a controlled trial.     

Increased bronchial responsiveness in primary and secondary Sj?gren's syndrome

We examined one group of 33 patients with primary Sj?gren's syndrome, one group of 17 patients with secondary Sj?gren's syndrome, i.e. associated with other connective tissue diseases, and one group of 14 patients with connective tissue diseases but without Sj?gren's syndrome. In each patient we obtained chest radiographs and measured lung volumes, carbon monoxide diffusing capacity and airway responsiveness to methacholine. We observed no difference in chest radiograph abnormalities, in lung volumes and in carbon monoxide diffusing capacity among the three groups. However, we found a slight but significant increase of bronchial responsiveness in patients with primary and secondary Sj?gren's syndrome compared with patients with connective tissue disorders but without Sj?gren's syndrome. Thus PD20FEV1 methacholine was 1.07 mg (1.2) (geometric mean and GSEM) in primary Sj?gren's syndrome, 0.91 mg (1.4) in secondary Sj?gren's syndrome (NS), and 2.24 mg (1.09) in patients with connective tissue diseases but without Sj?gren's syndrome (t = 2.59 and t = 2.8, both p less than 0.05, vs primary and secondary Sj?gren's syndrome, respectively). These results show that some patients with Sj?gren's syndrome have mild bronchial hyperresponsiveness, which may be related to the specific airway abnormalities of this disease.     

A case of sarcoidosis complicated by primary Sj?gren's syndrome]

A 35-year-old woman had been suffering for 10 years from a dry mouth and dry eyes without being medically examined. When she finally saw a doctor in September 1996, a chest radiograph revealed bilateral hilar lymphadenopathy. Histopathological examination of the lung and scalene lymph nodes revealed non-specific lymphadenitis. She was followed thereafter without any therapy. In 1997, she was referred to our hospital because of a high titer of antinuclear antibody. A diagnosis of Sj?gren's syndrome was made on the basis of the results of sialography, lip biopsy, Schirmer's test, and the present of anti-SS-A antibody. Re-evaluation of the mediastinal lymph nodes and the lung by thoracoscopic biopsy revealed non-caseating epithelioid cell granulomas, which led to a diagnosis of sarcoidosis. Although the coexistence of Sj?gren's syndrome and sarcoidosis has been reported occasionally, cases with histological proof of sarcoidosis have been rare. In a survey of 27 reported cases, the majority of the patients were female and in roentgenological stage I. In most cases, Sj?gren's syndrome preceded sarcoidosis. The predominance of the Th 1 immune response at the site of each disease may be involved in the pathogenic mechanism by which these diseases coincide.     

The spectrum of lung involvement in collagen vascular-like diseases following allogeneic hematopoietic stem cell transplantation: report of 6 cases and review of the literature

Multisystem autoimmune diseases occurring after allogeneic hematopoietic stem cell transplantation are infrequent, late-onset manifestations that resemble well-defined collagen vascular disorders. Because the lung is frequently involved in the course of connective tissue disorders, we focused on lung manifestations occurring in autoimmune diseases following allogeneic stem cell transplantation. In the present series, we report 6 patients with systemic lupus erythematous, mixed connective tissue disease, Sj?gren syndrome, polymyositis, and ANCA-positive vasculitis who presented with a spectrum of pulmonary manifestations affecting the airways, lung parenchyma, and probably respiratory muscles. We identified 3 different histopathologic patterns of interstitial pneumonia consistent with the underlying autoimmune disorder: lymphocytic interstitial pneumonia and non-specific interstitial pneumonia in 2 patients with Sj?gren syndrome and diffuse alveolar damage in 1 patient with ANCA-positive vasculitis. These lung manifestations had poor prognoses. Further studies are needed to determine the optimal therapy for these complications.     

The presence of Sj?gren's syndrome is a major determinant of the pattern of interstitial lung disease in scleroderma and other connective tissue diseases

A number of patients with scleroderma, Sj?gren's syndrome and other connective tissue diseases (CTD) were assessed to ascertain the prevalence of respiratory abnormalities as defined by bronchoalveolar lavage (BAL), standard respiratory function studies and gallium scan of the lung, and the relationship of these abnormalities to the presence or absence of dyspnea. These results suggest that respiratory symptoms are very common in CTD and in scleroderma, particularly if Sj?gren's syndrome is also present. Our findings also suggest the presence of 2 patterns of interstitial lung involvement in scleroderma. In scleroderma alone this appears to be characterized by the presence of increased neutrophil proportions in the BAL, decreased DLCO, and no increase in gallium uptake within the lung. Where scleroderma is associated with Sj?gren's syndrome, there is an increase in the proportion of lymphocytes in the BAL and respiratory symptoms are very prominent, the latter associated with an increase in gallium uptake within the lung. This suggests that Sj?gren's is a major determinant of the pattern of interstitial lung disease seen in CTD.     

A case of primary Sj?gren's syndrome with interstitial pneumonia showing bronchiolitis obliterans organizing pneumonia pattern and lymphofollicular formation]

A 46-year-old woman with a 2-year history of xerostomia, who had had an episode of suspected Sj?gren's syndrome in 1995, was admitted to our hospital because of a dry cough. Chest radiography on admission showed ground-glass infiltrates and reticular shadows in both lower lung fields. Primary Sj?gren's syndrome was diagnosed by lip biopsy. Video-assisted thoracoscopic lung biopsies revealed the co-existence of interstitial pneumonia with the BOOP pattern and follicular bronchiolitis. Treatment with oral prednisolone improved the symptoms, and reduced the abnormal chest shadows. This was an interesting case of the BOOP pattern in a lung lesion associated with primary Sj?gren's syndrome.     

A case of systemic lupus erythematosus associated with Sj?gren's syndrome diagnosed by lung localization]

A 30-year-old female, diagnosed as having SLE and followed at our hospital while receiving oral prednisolone (5 mg/day) for about 6 months, was admitted because of fever and productive cough. Chest X-ray and CT scan showed a tumor-like homogeneous shadow in the right middle lobe. Antibiotic treatment was not effective. Specimens obtained by TBLB revealed massive infiltration of mature plasma cells and lymphocytes into the alveolar septa and interstitial tissues. These findings were considered compatible with lymphoid interstitial pneumonia. Associated conditions such as Sj?gren's syndrome were suggested, but the diagnostic criteria of Sj?gren's syndrome were not satisfied. Both the abnormal shadow on chest X-ray and the clinical symptoms markedly improved by increasing the dose of prednisolone (20 mg/day). After 3 months, however, bilateral BAL findings showed alveolar lymphocytosis, providing evidence that subclinical diffuse pulmonary involvement had continued. This case indicates that radiological appearance may vary depending on the extent of lung involvement, even if the histological features are identical. It is concluded that the present diagnostic criteria of Sj?gren's syndrome must be reconsidered so as not to overlook subclinical and asymptomatic cases of Sj?gren's syndrome.     

Sj?ren's syndrome with infiltrative lung disease showing upper lung field predominance]

We report two cases of Sj?ren's syndrome (SjS) with infiltrative lung disease showing upper lung field predominance. Case 1 was seen in a 68-year-old woman, who was admitted with dyspnea on exercise. Chest CT scanning demonstrated a central predominance of irregularly shaped consolidation with tractionectasis, distributed along the broncho-vascular bundles in both upper lobes. Case 2 occurred in a 70-year-old woman, who was admitted with cough. Chest CT scan showed a central predominance of irregularly shaped opacities with multiple small cystic structures in both upper lobes. Both cases were shown to be nonspecific interstitial pneumonia (NSIP) by video-assisted thoracoscopic lung biopsy, in which lung involvements were distributed around the bronchovascular sheath with relative sparing of the subpleural region. Although neither case complained of sicca symptoms, decreased saliva production was detected using the Saxon test, and further examinations revealed the presence of primary SjS. Pulmonary involvement in SjS is variable, and distribution along the broncho-bronchioles in the majority of the upper central lung field is a characteristic appearance of SjS lung disease. In patients with such patterns in chest radiography, further diagnostic differentiation should be conducted to confirm or rule out SjS.     

Infective endocarditis associated with Sjogren's syndrome

Sj?gren's syndrome is one of the major autoimmune diseases, however infective endocarditis associated with Sj?gren's syndrome has not previously been reported. A patient with Sj?gren's syndrome associated with aortic valve regurgitation due to infective endocarditis, underwent successful aortic valve replacement. Patients with Sj?gren's syndrome tend to be at a higher risk of intraoral infections due to diminished secretion of saliva. Particular care must be taken of Sj?gren's syndrome patients as they can also be at an increased risk of infective endocarditis.     

Sj?gren's syndrome with pseudolymphoma 13 years after Hodgkin's disease

A patient who had Hodgkin's disease at age 11 that was cured by radiation therapy, had nonspecific adenopathy at age 20. When he was 24 years old, the symptoms of Sj?gren's syndrome developed, and this diagnosis was confirmed by biopsy of the lip. The patient subsequently had dyspnea and a diffuse pulmonary infiltrate which, at open lung biopsy, was diagnosed as pseudolymphoma and has responded to cytotoxic chemotherapy. This is the first reported case of Sj?gren's syndrome and pseudolymphoma following the cure of a malignant lymphoma. The interrelationship between lymphoid malignancies, autoimmune diseases, and pseudolymphoma is herein discussed.     

Ear-nose-throat manifestations of autoimmune rheumatic diseases

Ear-nose-throat (ENT) manifestations of connective tissue disorders represent a diagnostic challenge for clinicians as they often constitute the initial sign of an otherwise asymptomatic autoimmune disease. Moreover, in patients with known autoimmune rheumatic diseases, ENT manifestations can be overlooked. Hearing disturbances may be seen in patients with systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis, polyarteritis nodosa, Cogan's syndrome, Sj?gren's syndrome, and less frequently in Churg-Strauss syndrome and Adamantiades-Beh?et's disease. Nose and paranasal sinuses are variably affected during the course of Wegener's granulomatosis, Churg-Strauss syndrome, relapsing polychondritis and sarcoidosis. Recurrent mucosal ulcerations are common in systemic lupus erythematosus and Adamantiades-Beh?et's disease. Xerostomia is a common feature of primary and secondary Sj?gren's syndrome; salivary gland enlargement may be also seen in these patients, as well as in patients with sarcoidosis. The cricoarytenoid joint can be involved during the course of rheumatoid arthritis, ankylosing spondylitis and gout; osteoarthritic changes have also been described. Motility disorders of the upper and/or the lower portions of the esophagus have been reported in patients with dermatomyositis/polymyositis, systemic sclerosis and systemic lupus erythematosus. Trigeminal nerve dysfunction may occur in patients with Sj?gren's syndrome, systemic sclerosis, systemic lupus erythematosus and mixed connective tissue disease. Peripheral facial nerve palsy has been described to complicate the course of Sj?gren's syndrome and sarcoidosis.     

Cancer and interstitial lung disease

PURPOSE OF REVIEW: This review assesses the contribution of various conditions that cause interstitial lung disease to the development of cancer. RECENT FINDINGS: Interstitial lung diseases for which the available evidence suggests an increased risk of lung cancer include idiopathic pulmonary fibrosis, systemic sclerosis, and certain forms of pneumoconioses. The pathogenesis of lung cancer remains unclear, and the available data on inflammation-induced pulmonary fibrosis as a risk factor for lung cancer are summarized. There is inadequate evidence for any conclusions about the risk of solid tumors and hematologic malignancies in patients with sarcoidosis, rheumatoid arthritis, and systemic lupus erythematosus. An increased incidence of lymphoma is detected in Sj?gren's syndrome. For patients with dermatomyositis and polymyositis, there is a well-documented association with a wide range of cancers. SUMMARY: Further studies are needed to clarify the cause(s) and the mechanisms that link various interstitial lung diseases and cancer.     

Celiac disease and markers of celiac disease latency in patients with primary Sjögren's syndrome

OBJECTIVE: Many autoimmune diseases occur concomitantly with celiac disease. We investigated prospectively the occurrence of celiac disease and small-bowel mucosal inflammation in patients with primary Sj?gren's syndrome. METHODS: A total of 34 patients with primary Sj?gren's syndrome and 28 controls underwent small bowel biopsy. Villous morphology, jejunal intraepithelial lymphocytes, and mucosal HLA-DR were evaluated and DQA and DQB alleles, serum antiendomysial, and antigliadin antibodies were examined. RESULTS: Five (14.7%) of 34 Sj?gren's syndrome patients were found to have celiac disease. The density of jejunal intraepithelial gammadelta+ T cells was increased in all celiac and in four nonceliac patients. All celiac patients, 69% of nonceliac Sj?gren's syndrome patients, and 11% of control subjects showed enhanced HLA-DR expression (p < 0.001). HLA DQ2 was present in 19 (56%) patients with Sj?gren's syndrome, including all five with celiac disease. CONCLUSIONS: The findings show a close association between Sj?gren's syndrome and celiac disease. Even among nonceliac patients with primary Sj?gren's syndrome, an ongoing inflammation is often present in the small bowel mucosa.     

The forgotten cause of sicca complex; sarcoidosis

Sarcoidosis is a chronic systemic disease of unknown cause with prominent symptoms from the respiratory system. It can occasionally affect the exocrine glands presenting with xerophthalmia and xerostomia similar to Sj?gren's syndrome. We present 5 such patients who visited our rheumatology clinic complaining of dry eyes and mouth. Investigation for xerophthalmia and xerostomia showed positive rose bengal tests in all patients, positive Schirmer's I tests in 4 and decreased parotid flow rate in 3. Minor salivary gland biopsy showed noncaseating granulomas compatible with sarcoidosis in 3. In the other 2 patients the diagnosis was obtained with transbronchial lung biopsy that revealed noncaseating granulomas. Transbronchial lung biopsy also showed granulomas in 2 patients with positive minor salivary gland biopsy. Our results suggest that sarcoidosis can present with initial symptoms of dry eyes and dry mouth. When this happens, transbronchial and minor salivary gland biopsy are very valuable in differentiating sarcoidosis from Sj?gren's syndrome.     

Follicular bronchiolitis in surgical lung biopsies: clinical implications in 12 patients

BACKGROUND: Follicular bronchiolitis is a histopathologic finding that occurs in diverse clinical contexts. The current study was conducted to characterize clinico-radiologic features, and assess outcomes associated with follicular bronchiolitis. SUBJECTS AND METHODS: Twelve subjects with follicular bronchiolitis on lung biopsy were seen over a 9-year period, between 1996 and 2005. Medical records, biopsy and radiographic findings, and details of outcome at the time of last follow-up were recorded. RESULTS: The study population included 4 men and 8 women; the median age at diagnosis was 54 years (range, 33-81 years). Four patients had underlying systemic diseases that included: 2 with common variable immunodeficiency, 1 Sj?gren's syndrome and 1 undifferentiated connective tissue disease. The diagnosis was obtained by surgical lung biopsy in all cases. Follicular bronchiolitis was the major histologic pattern in 9 patients; organizing pneumonia, nonspecific interstitial pneumonia and usual interstitial pneumonia was seen in 1 patient each with follicular bronchiolitis being an associated secondary histopathologic component. Computed tomographic findings included reticular opacities, small nodules and ground-glass opacities. Clinical course was characterized by relative stability with partial response to immunosuppressive agents. During a median follow-up period of 47 months, only one death occurred--out of 9 patients where the outcome information was available--and was unrelated to lung disease. CONCLUSIONS: The histologic lesion of follicular bronchiolitis may be seen as the predominant finding or a relatively minor feature in interstitial pneumonias. The clinical course and prognosis for most patients with follicular bronchiolitis is relatively good, and progressive lung disease is uncommon.     

Cystic lung disease associated with Sjögren's syndrome: 2 cases

INTRODUCTION: Cystic lung disease is characterised on chest iconography by foci of decreased lung density with definable and thinned walls (wall thickness<4 mm) and with length's diameter superior at 1 cm. Cystic lung disease is exceptionally associated with the Sj?gren's syndrome; very few cases have been described. EXEGESIS: We report two cases of cystic lung disease associated with Sj?gren's syndrome, one occurring in a Lupus-Sj?gren's overlapping syndrome, and another revealing primary Sj?gren's syndrome. CONCLUSION: The Sj?gren's syndrome should be recognised as could be associated with Cystic lung disease; and latent Sj?gren's syndrome should be researched in presence of cystic lung lesions.