Multiple myeloma and AL amyloidosis mimicking Sj?gren''s syndrome

A 49-year-old white man had xerostomia, orthostatic hypotension, salivary gland enlargement, and a monoclonal gammopathy. Salivary gland biopsy revealed AL amyloidosis without histopathologic evidence of Sj?gren's syndrome; serologic evidence of Sj?gren's syndrome was also absent. Bone marrow biopsy revealed more than 30% plasma cells, and a diagnosis of multiple myeloma was made. The association of myeloma amyloidosis with salivary gland infiltration and xerostomia is rare. Unusual causes of xerostomia, such as myeloma amyloidosis, should be considered when histopathologic and serologic evidence of Sj?gren's syndrome are absent.     

Value of quantitative salivary gland scintigraphy in the early stage of Sj?gren's syndrome

The aim of this study was to test the impact of quantitative salivary gland scintigraphy in patients with suspected Sj?gren's syndrome. Thirteen patients with suspected Sj?gren's syndrome were investigated. During clinical work-up, three had severe and four had mild Sj?gren's syndrome, while six were normal. Quantitative salivary gland scintigraphy was performed using a standardized method. The normal data-base consisted of 172 patients without any evidence of salivary gland malfunction. Visual and quantitative comparisons of the patients' scintigrams were made. In the patients with severe Sj?gren's syndrome, uptake was 0.10 +/- 0.04% and 0.09 +/- 0.03% in the parotid and submandibular glands respectively, confirming the visual diagnosis. In the patients without Sj?gren's syndrome, concordance between the visual and quantitative evaluations could also be shown. In contrast, among the patients with mild Sj?gren's syndrome, uptake was diminished (P < 0.05), amounting to 0.21 +/- 0.05% and 0.16 +/- 0.02% in the parotid and submandibular glands respectively, while visual analysis indicated normal parenchymatous function. In conclusion, quantitative salivary gland scintigraphy is essential for the reliable detection of parenchymatous malfunction at an early stage of Sj?gren's syndrome, which may be missed by visual analysis alone.     

Biopsy of the accessory salivary glands. 5 years' experience

Biopsy of the minor salivary glands has become a routine examination ordered by physicians working in a wide range of disciplines in order to search for or eliminate the diagnosis of Gougerot Sj?gren's disease or another systemic disease. We emphasize the need to use this examinations as a part of a complete work-up of the buccal cavity and the salivary glands. We reviewed our experience with 1,500 biopsies. The glands biopsied were normal in 56% of the cases and led to the diagnosis of Gougerot Sj?gren's disease in 24%, chronic sialadenitis in 10% and diverse trophic problems in 5%. The clinical stage of Gougerot Sj?gren's disease is usually proposed according to the Chisholm classification which we propose to compare with the Chomette classification. Finally, we described the technique of minor salivary gland biopsy.     

Current concepts of autoimmune exocrinopathy: immunologic mechanisms in the salivary pathology of Sj?gren's syndrome

Sj?gren's syndrome is a systemic autoimmune disorder characterized by symptoms of oral and ocular dryness and a chronic, progressive loss of salivary and lacrimal function. The exocrine involvement is the result of a focal, peri-ductal mononuclear cell infiltrate and the subsequent loss of secretory epithelial cells. The mechanisms of this autoimmune exocrinopathy are not understood fully. Many recent investigations have described alterations in a number of immune mediators within the salivary glands. These studies provide new insights into the immune regulation of normal salivary gland functions and the mechanisms of gland damage in Sj?gren's syndrome.     

Immunolocalization of aromatase in human minor salivary glands of the lower lip with primary Sj?gren's syndrome

The enzyme aromatase is involved in the conversion of androgens to estrogens and in the modulation of various androgenic and estrogenic actions. Abnormalities of estrogen metabolism have been postulated to play roles in the development and/or pathophysiology of Sj?gren's syndrome. In the present study, aromatase was immunolocalized in 75 cases of inflammatory disorders of human minor salivary glands of the lower lip. These included cases of primary Sj?gren's syndrome (19 cases), of chronic sialadenitis (34 cases) and of mucous extravasation cysts (22 cases), in order to clarify the possible involvement of in situ estrogen production in primary Sj?gren's syndrome. Aromatase immunoreactivity was detected in myoepithelial cells of acini and in interstitial cells adjacent to acini and ducts in 13/19 (68%) cases of primary Sj?gren's syndrome. In contrast, aromatase expression was detected in only six of 34 (18%) cases of chronic sialadenitis and in seven of 22 (32%) cases of mucous extravasation cyst. These results suggest that increased aromatase expression in minor salivary glands with primary Sj?gren's syndrome in premenopausal women may be involved in the biological features of primary Sj?gren's syndrome through the production of estrogens in situ and possibly through the aggravation of the inflammatory reaction.     

Outcome assessment in patients with primary Sj?gren''s syndrome

PURPOSE: The authors describe a 68-year-old woman in whom ischemic choroidopathy and optic neuropathy developed in association with primary Sj?gren's syndrome with central nervous system involvement. METHODS: Diagnosis of primary Sj?gren's syndrome was made upon the association of keratoconjunctivitis sicca, minor salivary gland biopsy and serologic abnormalities. Fluorescein angiography showed signs highly suggestive of ischemic choroidopathy. The authors discuss differential diagnosis and pathophysiology of such choroidal manifestations. Treatment consisted in massive steroid therapy. Secondarily, an immunosuppressant agent (azathioprine) was successfully added because of neurological recurrences. CONCLUSION: Primary Sj?gren's syndrome should be considered in the differential diagnosis of ischemic choroidopathy.     

Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sj?gren's syndrome

Structures resembling germinal centers are seen in the salivary glands of patients with Sj?gren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sj?gren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters. The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants. These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sj?gren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune diseases, we propose that germinal center- type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases.     

Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation

A 91 year old woman with Sj?gren's syndrome who developed a lymphoepithelial lesion and showed an active state of the disease is described. Since June, 1990, the patient had been complaining of dry eyes and mouth and a left submandibular tumor (1.0 x 1.5 cm in diameter). A biopsy of the tumor revealed lymphoepithelial lesions in the salivary gland. Mild anemia (Hb 9.6 g/dl) and an elevated erythrocyte sedimentation rate (80 mm/hr) were noted. The gamma-globulin level was 2.7 g/dl, IgG 2789 mg/dl, IgA 469 mg/dl, RAHA x80, antinuclear antibody x20, anti-SS-A x256, thyroid test x400 and microsome test x102400. The Schirmer's test showed decreased tear secretion (Lt. 3mm, Rt. 9mm) and keratoconjunctivitis sicca were noticed by an ophthalmologist. Salivary scintigraphy revealed decreased uptake and slow excretion of the isotope (grade II). A biopsy of a minor salivary gland showed periductal lymphocytic infiltration and acinar cell destruction. Immunohistochemical analyses revealed the cross-reactive idiotype of a monoclonal rheumatoid factor which is associated with a patient with Sj?gren's syndrome, in the infiltrating lymphocytes and plasma cells of the minor salivary glands, but not in the lymphoepithelial lesions of the left submandibular gland. This was a rare case concerning a 91-year old patient with Sj?gren's syndrome who developed a lymphoepithelial lesion and showed high activity in the serum and gives us valuable information on the relationship between aging and autoimmunity.     

Interaction of alpha-interferon with chemotherapeutic agents: effects on cytotoxic drug metabolism and multiple drug resistance

Sj?gren's syndrome (SS) is an autoimmune exocrinopathy that primarily affects the salivary glands but can also involve almost any other part of the gut. The most distressing manifestation of SS is xerostomia secondary to destruction of the salivary glands. The lack of saliva also leads to difficulty with chewing and initial swallowing and an increased frequency of dental caries. Another major problem is dysphagia due to the lack of saliva as well as esophageal dysmotility and/or esophageal webs. Chronic atrophic gastritis probably accounts for the epigastric pain, nausea, and other dyspeptic symptoms seen in SS. Sj?gren's syndrome is also one of the most frequent extrahepatic diseases associated with primary biliary cirrhosis, suggesting that this entity may be a secondary form of SS. The degree to which SS affects the small and large bowel is unclear, whereas pancreatic involvement appears to lead to only subclinical exocrine insufficiency.     

Salivary gland scintigraphy in subjects with and without symptoms of dry mouth and/or eyes, and in patients with primary Sj?gren's syndrome

The major salivary glands were examined with 99m-Tc-pertechnetate scintigraphy in randomly selected subjects with (n = 30) and without (n = 12) symptoms of dry mouth and/or eyes, and in patients with primary Sj?gren's syndrome (1 degree SS, n = 17). The scans were quantitatively evaluated and compared to other objective tests used to diagnose 1 degree SS. As compared with those for asymptomatic subjects, most values for the scintigraphic variables were non-significantly lower for symptomatic subjects and the time-activity curves were slightly flatter for all major salivary glands. In patients with 1 degree SS most values for the scintigraphic variables were significantly lowered and the submandibular glands were the glands most affected, as reflected in a flat time-activity curve, while the parotid glands were mainly affected during stimulated secretion. The scintigraphic variables correlated with the self-rated dryness of mouth in symptomatic subjects and with the abnormality of sialometry results in patients with 1 degree SS. We conclude that salivary gland scintigraphy is a sensitive and valid method to measure salivary gland function and abnormalities.     

Psychosomatic obstetrics and gynecology in the next millennium: some thoughts and observations

Diagnostic pitfalls exist when benign salivary gland diseases are mistakenly classified as malignant, with consequences for treatment and prognosis. Examples are necrotizing sialometaplasia, metaplastic Warthin tumour and sclerosing polycystic sialadenopathy. The proper diagnosis is of eminent importance to distinguish cases of primary tumours that have developed in salivary glands or their lymph nodes from cases of extraglandular tumours with metastases in these glands or their nodes. In these cases clinical data and additional immunocytochemical methods are necessary to clarify the exact diagnosis, especially when the primary salivary gland tumours have a structure largely identical to the metastases (e.g. squamous cell carcinoma). Nasopharyngeal or cervical chordomas can be mistaken for pleomorphic adenoma or mucinous adenocarcinoma. The initial stage of malignant MALT lymphomas in association with Sj?gren's syndrome demands identification of clonal rearrangement for therapeutic implication. The diagnostic criteria for proper classification are analysed in detail.     

Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sj?gren's syndrome

The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sj?gren's syndrome. NOD.Igmu null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Igmu null mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab')2 fragments from parental NOD mice or human primary Sj?gren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors. Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [3H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sj?gren's syndrome.     

Lymphomatoid granulomatosis of the lung, associated with a long history of benign lymphoepithelial lesions of the salivary glands and lymphoid interstitial pneumonitis. Report of a case

A case of a man who had bilateral benign lymphoepithelial lesions of major salivary glands, subsequently had lymphoid interstitial pneumonitis at the age of 26 years, and progressed to lymphomatoid granulomatosis of the lung at the age of 42 years is reported, A labial gland biopsy was consistent with Sj?gren's syndrome, which the patient was clinically suspected of having although his disease lacked many of the classic clinical features of that disorder. There was no evidence of malignant lymphoma of lymph nodes. Immunoglobulin distribances were minor, limited to slightly elevated IgG.     

Sj?gren's syndrome in progressive systemic sclerosis

Thirty-five consecutive patients with progressive systemic sclerosis were prospectively evaluated for evidence of Sj?gren's syndrome. Six of the 35 (17%) were judged to have the disorder. This is a higher prevalence than in most reports, but much lower than that recently reportedly by Alarcón-Segovia and associates (7). An additional 17 of the 35 patients (48%) had significant fibrosis in the absence of sufficient mononuclear cell infiltrates to confirm the diagnosis of Sj?gren's syndrome. This group had particularly aggressive scleroderma with serious visceral features, and five died after a short duration of illness. No significant abnormalities were found in biopsies from six patients with the mixed connective tissue disease syndrome, five with Raynaud's phenomenon alone, or in 29 autopsy control subjects who had no evidence of connective tissue disease. Fibrosis in the absence of mononuclear infiltration in minor salivary glands of patients with progressive systemic sclerosis indicates a poor prognosis.     

Minor salivary gland biopsies in patients investigated for primary Sj?gren's syndrome. A review of 187 patients

OBJECTIVE: To correlate presenting features and indication for biopsy with results in patients undergoing minor salivary gland biopsy for the diagnosis of primary Sj?gren's syndrome (SS). METHODS: The charts of 187 patients undergoing minor salivary gland biopsy for primary SS over a 9-year period were reviewed. RESULTS: 76 patients had a focus score > 1, 111 had a focus score < or = 1. No difference between the 2 groups was noted in most features, including frequency of symptomatic dry eyes or mouth, or Schirmer test results. Patients with focus score > 1 had significant increases in frequency of salivary gland swelling (25 vs 9%), antinuclear antibodies > 1:100 (68 vs 32%), rheumatoid factor > 1:160 (63 vs 22%), anti-SSA (46 vs 9%), anti-SSB (32 vs 4%), or any serologic marker (87 vs 46%). Abnormal biopsies were more frequent in those biopsied for serologic abnormalities (53%) than for sicca symptoms (33%) or systemic illness (29%). CONCLUSION: Serologic markers are better predictors of results than clinical features in patients undergoing minor salivary gland biopsy for primary SS. The frequency of a positive biopsy is increased in patients in whom unexplained serologic markers are being evaluated.     

Sj?gren's syndrome with pulmonary fibrosis. A case report (author's transl)

The case is pointing to two remarkable facts: 1. Sj?gren's syndrome may also be proceeding--without demonstrating any inflammatory rheumatic symptoms--with an isolated pulmonary fibrosis, as it had been evident in another case mentioned. 2. In certain circumstances, it may be considerably difficult to differentiate, with reliable certainty, the morphological changes in the salivary gland from those of a malignant lymphoma. Besides, also in literature there are reports concerning malignant degeneration turning into malignant lymphomata [1,8] in cases of Sj?gren's syndrome.     

The social consequences of surgical complications for patients with proximal femoral fractures

OBJECTIVES: In 1985 and 1988 a positive effect of treatment of primary Sj?gren's syndrome with hydroxychloroquine was reported in two small open studies. To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sj?gren's syndrome a two year study was performed. METHODS: The design of the study included a prospective, placebo controlled, two year double blind crossover trial in 19 patients. RESULTS: A significant decrease in IgG and IgM and a tendency for a decrease in the erythrocyte sedimentation rate (ESR) during treatment with hydroxychloroquine compared with treatment with placebo were found. No beneficial clinical effect of the use of hydroxychloroquine as expressed in preference for treatment with hydroxychloroquine or placebo with regard to symptoms and signs of primary Sj?gren's syndrome could be shown, however, nor any relevant change in tear gland activity and sequelae of peripheral tear function deficiency, nor salivary gland scintigraphy. CONCLUSIONS: The use of hydroxychloroquine at a dose of 400 mg daily taken over a 12 month period does not have a worthwhile clinical benefit in patients with primary Sj?gren's syndrome despite an improvement of hyperglobulinaemia and slight changes in the ESR and IgM.     

Case report: sicca syndrome due to primary amyloidosis

Sicca syndrome consists of two major clinical findings: keratoconjunctivitis sicca and xerostomia due to destruction of the lacrimal and salivary gland parenchyma. Although it is most often due to Sj?gren's syndrome, a variety of other diseases causes sicca syndrome. We report the rare case of a patient with gland infiltration in primary amyloidosis. Sonographic, computed tomographic and magnetic resonance findings are presented.     

Effect of cyclic AMP level reduction on human neutrophil responses to formylated peptides

In an attempt to elucidate the mechanism of development of organ-specific autoimmune lesions resembling human Sj?gren's syndrome of MRL/lpr mice, we have analyzed local cytokine gene expressions and organ-specific autoantibody production in vivo. We have demonstrated that a major proportion of T cells bearing CD4 and V(beta)8 molecules are essentially responsible for triggering the autoimmunity in the salivary glands of MRL/lpr mice. The local cytokine gene expressions including interferon(IFN)-gamma, IL-12(p40) mRNAs were observed during the course of murine Sjogren's syndrome in MRL/lpr autoimmune strain. In particular, a high level of local expressions of IL-12 mRNA was detected earlier in the proinflammatory stage of autoimmune lesions. A significant level of local expression of MHC class-II(I-Ak) mRNA was detected before the onset of inflammatory lesions in the salivary glands, and I-Ak-positive epithelial duct cells were frequently observed in the salivary glands of MRL/lpr mice. In addition, we found the salivary gland-specific autoantibody in sera from MRL/lpr mice with early phase of autoimmune lesions by immunoblot analysis. These results suggest that cytokine gene stimulation and autoantibody production are essentially involved in the development of organ-specific autoimmune lesions in Sj?gren's syndrome of MRL/lpr mice.     

A case of an old woman with Sj?gren's syndrome associated with insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is thought to result from the autoimmune destruction of the insulin-dependent beta cells of the pancreas. Sj?gren's syndrome is also an autoimmune disease characterized by the destruction of the lacrimal and salivary glands that leads to keratoconjunctivitis sicca and xerostomia. But it is a very rare case that a patient with Sj?gren's syndrome developed IDDM. We present a case of a 65-year old woman with Sj?gren's syndrome who developed diabetic ketoacidosis due to IDDM. Recent studies have revealed that there was molecular mimicry between glutamic acid decarboxylase (GAD) and coxsackievirus. Furthermore, some reports have shown that sialadenitis was represented in IDDM model mice. This case shows the possibility that a causal relationship between IDDM and Sj?gren's syndrome may exist.