Subgroups of primary Sjögren's syndrome. Sjögren's syndrome in male and paediatric Greek patients

OBJECTIVES—To describe the clinical and serological findings in male and paediatric Sjögren's syndrome (SS) patients.
PATIENTS AND METHODS—Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.
RESULTS—The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p<0.01) and with female patients (p<0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p<0.05) and Raynaud's phenomenon (p<0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p<0.025) and antibodies to Ro(SSA) nuclear antigens (p<0.025) compared with women.
CONCLUSION—Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.

     

Salivary and serum hyaluronic acid concentrations in patients with Sjögren's syndrome

OBJECTIVE—To evaluate salivary hyaluronic acid (HA) concentration in patients with primary Sjögren's syndrome (SS).
METHODS—Salivary and serum HA concentrations were evaluated using a radiometric assay. Thirty nine patients with SS served as the study group and their results were compared with 19 patients having clinical symptoms and signs of dry mouth and with 10 normal controls.
RESULTS—Salivary HA concentrations were significantly increased (p < 0.05) in the 39 patients with SS compared with the 19 patients with dry mouth and the 10 normal controls (240.7 (38.5) v 99.8 (14.6) and 91.3 (7.9) ng/ml, respectively) (mean (SEM)). No significant differences were noted in the serum HA concentrations between the three groups (42 (3.9) v 36.3 (4.1) and 32 (4.3) ng/ml, respectively) (mean (SEM)). No correlation could be found between salivary HA concentrations and the focus score of lip biopsies, nor between salivary HA concentrations and erythrocyte sedimentation rate or other serological tests.
CONCLUSION—Increased salivary HA concentrations can serve as a marker of local inflammation and may be of value in the diagnosis of SS.

Keywords: saliva; hyaluronic acid; Sjögren's syndrome     

Serial analysis of Ro/SSA and La/SSB antibody levels and correlation with clinical disease activity in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the temporal correlation between anti-Ro/SSA and anti-La/SSB antibody levels and compare them with variation in clinical disease activity in patients with systemic lupus erythematosus (SLE). METHODS: Sequential serum samples collected over 18-44 months from 18 anti-Ro/SSA positive patients with systemic lupus erythematosus were analysed by ELISA with recombinant Ro60, Ro52 and La antigens. Disease activity was assessed by the BILAG index. RESULTS: Limited antibody level variation over time was found in most patients, but a subset displayed more changes and a co-variation between the levels of separate specificities was found in 40% of patients. In two patients antibody levels fluctuated with the global score. Antibodies also correlated with separate organ/systems involvement in individual patients. CONCLUSION: The Ro60, Ro52 and La antibody profile is fixed at an early stage of disease and in most patients hardly changes. Patients with fluctuating levels tend to have a co-ordinated expression of these autoantibodies.     

Fatigue in primary Sjögren's syndrome

OBJECTIVE—To assess fatigue in relation to depression, blood pressure, and plasma catecholamines in patients with primary Sjögren's syndrome (SS), in comparison with healthy controls and patients with rheumatoid arthritis.
METHODS—For the assessment of fatigue the Multidimensional Fatigue Inventory (MFI) was used, a 20 item questionnaire, covering the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Furthermore, the Zung depression scale was used to quantify aspects of depression. Forty nine female primary SS patients, 44 female patients with rheumatoid arthritis (RA), and 32 healthy women filled in both questionnaires. In addition, supine values of blood pressure and plasma catecholamines were measured in the patients with primary SS.
RESULTS—Primary SS patients were more fatigued compared with the healthy controls on all the five dimensions of the MFI. When the analyses were repeated using depression as a covariate, group differences disappeared for the dimensions of reduced motivation and mental fatigue. In the primary SS patients, significant positive correlations between depression and the dimensions of reduced motivation and mental fatigue were found. Comparing patients with primary SS with those with RA, using depression as covariate, no statistically significant differences were found between these groups. No relation between fatigue and blood pressure was found, but a negative correlation was observed between the general fatigue subscale of the MFI and plasma noradrenaline.
CONCLUSION—Patients with primary SS report more fatigue than healthy controls on all the dimensions of the MFI and when controlling for depression significant differences remain on the dimensions of general fatigue, physical fatigue, and reduced activity. The negative correlations between levels of noradrenaline and general fatigue in patients with primary SS may imply the involvement of the autonomic nervous system in chronic fatigue.

Keywords: Sjögren's syndrome; fatigue     

Collagenase in Sjögren's syndrome.

OBJECTIVE--To study collagenase production in labial salivary glands in patients with Sjögren's syndrome (SS). METHODS--Collagenases were localised in labial salivary glands by immunohistochemistry. Collagenase activity against triple helical type I collagen monomers in stimulated saliva was measured using sodium dodecyl sulphate polyacrylamide gel electrophoresis and laser densitometry; tissue inhibitor metalloproteinase (TIMP) was measured by enzyme linked immunosorbent assay. RESULTS--Cells containing collagenase of matrix metalloproteinase (MMP)-1 type were more frequent and more intensely staining in SS than in healthy glands. Only SS saliva contained functional enzyme (11.7 (6.8) x 10(-6) IU/1). Cells containing MMP-8 type neutrophil collagenase were not found in situ, which was in accordance with sialochemical findings/doxycycline inhibition studies. TIMP was found in both SS and normal saliva. CONCLUSIONS--Fibroblast, but not neutrophil type, collagenase is synthesised, secreted, and subsequently activated, but is not inhibited by TIMP in labial salivary glands or saliva in SS. Collagenase may destroy glandular and salivary duct tissue and perturb factors influencing the morphogenetic extracellular matrix.     

Sicca symptoms and secondary Sjögren's syndrome in systemic lupus erythematosus: comparison with rheumatoid arthritis and correlation with disease variables

OBJECTIVE—Firstly, to study the prevalence of ocular and oral sicca symptoms, reduced tear and saliva production, and the minimum frequency of secondary Sjögren''s syndrome (sSS) in systemic lupus erythematosus (SLE). Secondly, to compare sicca symptoms and findings with those of matched patients with rheumatoid arthritis (RA), and sicca symptoms with those in healthy controls. Finally, to study possible associations of clinical variables with sicca symptoms and sSS in SLE.
METHODS—Self reported sicca symptoms were recorded in 81 patients with SLE aged ⩽70, 81 matched patients with RA, and 81 matched healthy controls. Other study variables included Schirmer-I test (S1T), unstimulated whole saliva, health status measures (in SLE and RA), disease activity, accumulated organ damage, and serological markers (in SLE).
RESULTS—A significantly higher proportion of patients with SLE reported sicca symptoms than healthy controls. Further, a significantly higher proportion reported ocular sicca symptoms (43 and 21%, respectively) and had pathologically reduced S1T compared with RA (46 and 21%, respectively). No difference was seen in oral sicca symptoms and saliva production. In SLE, sicca symptoms were associated with fatigue, and sSS with anti-SSB or anti-SSA antibodies, or both.
CONCLUSIONS—An increased prevalence of sicca symptoms was found in patients with SLE compared with controls, and a higher prevalence of ocular sicca symptoms and reduced tear production in SLE compared with RA. Sicca problems should be considered in the care of patients with SLE, especially those with anti-SSB and/or anti-SSA antibodies who have sicca symptoms and fatigue.

     

Oesophageal dysfunction in patients with primary Sjögren's syndrome.

Oesophageal motility was studied in 22 patients with primary Sjögren''s syndrome and 20 normal volunteers. Oesophageal dysfunction was detected in eight of the 22 patients (36.4%) with primary Sjögren''s syndrome. No abnormalities were detected in the normal subjects. Individual analysis of the oesophageal motility studies showed different patterns of oesophageal dysfunction; aperistalsis (three patients), triphasic tertiary contractions (two patients), frequent non-peristaltic contractions (two patients), and low contractions (one patient). These oesophageal abnormalities did not correlate with the parotid flow rate, the degree of inflammatory infiltrate of the minor salivary glands, the extraglandular manifestations, or the presence of autoantibodies.     

Concomitant diagnosis of primary Sjögren's syndrome and systemic AL amyloidosis

A 48 year old woman was referred to hospital for buccal discomfort. Physical examination showed a macroglossia and features of xerostomia. She was diagnosed as having primary Sjögren''s syndrome according to the criteria proposed by the European Community study group in 1993. Furthermore, a lower lip salivary gland biopsy showed amyloid deposits that were also seen in the stomach and in the bone marrow. Echocardiography was consistent with cardiac amyloidosis. Serum immunofixation identified a monoclonal IgGλ. As far as is known, this is the first report of systemic primary amyloidosis associated with Sjögren''s syndrome. The relation between these two disorders is discussed.

     

Assessment of anti-endothelial cell antibodies in systemic sclerosis and Sjögren's syndrome

OBJECTIVES—Anti-endothelial cell antibodies (AECA) have been detected in 19 to 30% of patients with systemic sclerosis (SSc). The objective of this study was first to assess the role of a secondary Sjögren's syndrome (SS) in the occurrence of AECA in SSc. Secondly, we researched AECA in patients with primary SS, and investigated whether AECA were associated with vascular manifestations (Raynaud's phenomenon and vasculitis).
METHODS—IgG-AECA were tested by an ELISA method in serum samples from 50 patients with SSc (16 of them had also a secondary SS), 50 patients with primary SS, and 50 healthy controls.
RESULTS—AECA levels were significantly higher in patients with SSc or primary SS than in healthy controls (p < 0.01 and p < 0.01, respectively). In patients with SSc, AECA values were significantly higher in patients with secondary SS (p < 10⁻⁵). In patients with primary SS, AECA levels were significantly higher in patients with Raynaud's phenomenon (p < 0.01), but not in patients with vasculitis.
CONCLUSION—In patients with SSc, AECA are associated with a secondary SS. In patients with primary SS, AECA are associated with Raynaud's phenomenon, but not with vasculitis.

     

Bronchial hyperreactivity in systemic sclerosis patients: influence of associated Sjögren's syndrome.

OBJECTIVE--To determine the frequency and relative risk of bronchial hyperreactivity to methacholine in systemic sclerosis patients with or without associated Sjögren's syndrome. METHODS--A prospective study of 56 patients with systemic sclerosis (42 with the diffuse and 14 with the limited variant; 24 with associated Sjögren's syndrome), 57 with primary Sjögren's syndrome, and 61 healthy controls. RESULTS--Bronchial hyperreactivity (BH) was present in 6.5% of the healthy controls, 25% of the systemic sclerosis patients without associated Sjögren's syndrome, 42.2% of those with primary Sjögren's syndrome, and in 50% of those with systemic sclerosis with associated Sjögren's syndrome. The presence of BH did not correlate with age, disease duration, chest radiograph abnormalities, respiratory, and immunological data. The subgroup of subjects with the limited variant of systemic sclerosis more frequently had associated BH than did those with the diffuse variant of the disease; coexisting Sjögren's syndrome further increased this frequency. CONCLUSIONS--In agreement with previous studies, we have confirmed the high prevalence of bronchial hyperreactivity in primary Sjögren's syndrome; systemic sclerosis likewise appears to be associated with an increased frequency of bronchial hyperreactivity compared with healthy control subjects. There is evidence also that the coexistence of Sjögren's syndrome and systemic sclerosis further increases the frequency and the calculated relative risk of developing bronchial hyperreactivity.