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Saliva is a complex oral fluid, and plays a major role in oral health. Primary Sjögren's syndrome (pSS), as an autoimmune disease that typically causes hyposalivation. In the present study, salivary metabolites were studied from stimulated saliva samples ( n = 15) of female patients with pSS in a group treated with low-dose doxycycline (LDD), saliva samples ( n = 10) of non-treated female patients with pSS, and saliva samples ( n = 14) of healthy age-matched females as controls. Saliva samples were analyzed with liquid chromatography mass spectrometry (LC-MS) based on the non-targeted metabolomics method. The saliva metabolite profile differed between pSS patients and the healthy control (HC). In the pSS patients, the LDD treatment normalized saliva levels of several metabolites, including tyrosine glutamine dipeptide, phenylalanine isoleucine dipeptide, valine leucine dipeptide, phenylalanine, pantothenic acid (vitamin B5), urocanic acid, and salivary lipid cholesteryl palmitic acid (CE 16:0), to levels seen in the saliva samples of the HC. In conclusion, the data showed that pSS is associated with an altered saliva metabolite profile compared to the HC and that the LLD treatment normalized levels of several metabolites associated with dysbiosis of oral microbiota in pSS patients. The role of the saliva metabolome in pSS pathology needs to be further studied to clarify if saliva metabolite levels can be used to predict or monitor the progress and treatment of pSS.

Purpose: To investigate inter- and intra-individual variation in the levels and outputs (concentration multiplied by salivary flow rate) of salivary metabolites in patients with primary Sjögren's syndrome (pSS)., Methods: A total of 56 samples of stimulated saliva were collected from 14 female pSS patients during four laboratory visits within 20 weeks and analyzed using proton nuclear magnetic resonance spectroscopy. Single saliva samples from each of 15 controls were also analyzed., Results: Among 21 quantified metabolites, choline was significantly elevated in the pSS patients at each time point (P ≤ 0.015), taurine at the last three time points (P ≤ 0.013), alanine at the last two time points (P ≤ 0.007) and glycine at the last time point (P = 0.005). Inter-individual variation in metabolite concentrations was generally larger among the patients than among the controls, and significantly large variations were observed for glycine (P ≤ 0.007, all time points), choline (P ≤ 0.033, three last time points) and alanine (P = 0.028, baseline). Metabolite output analysis showed that choline had the lowest intra-patient variation., Conclusion: In spite of considerable intra- and inter-individual variation, levels and outputs of specific metabolites in patients with pSS differ from those in controls, and may be potentially applicable as new biological markers for monitoring of the response to treatment.

Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS). Low-dose doxycycline (LDD) inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients. This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately., Results: Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p < 0.05). The differences may, however, reflect normal fluctuation of symptoms in SS patients., Conclusion: LDD may not be useful in reducing the primary SS symptoms.

Objectives: To investigate if disease assessment by contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative nanocolloid (NC) scintigraphy gives useful additional information in early rheumatoid arthritis (RA)., Methods: Twenty-seven patients with early RA (disease duration < or =12 months) were followed up for 1 yr and 24 of them for 2 yrs with contrast-enhanced MRI and NC scintigraphy of the wrist joint. Synovial inflammation was assessed by measuring time-dependent enhancement rates (E-rate) from dynamic MRI scans and technetium(99m)-labelled nanocolloid ((99m)Tc-NC) uptake from scintigraphy scans. Synovial membrane hypertrophy, bone oedema and erosions were semiquantitatively scored according to the Outcome Measures in Rheumatology Clinical Trials RA-MRI scoring system from static MR images. Response to the treatment was evaluated based on whether or not > or = 50% improvement was achieved in the tender and swollen joint scores and the Health Assessment Questionnaire score, with normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) levels. Progression of the erosion score on wrist MRI was evaluated as the outcome., Results: The baseline MRI bone oedema score (rho= 0.67), MRI synovitis score (rho= 0.57), ESR (rho= 0.56), CRP (rho= 0.48), E-rate (rho= 0.47) and (99m)Tc-NC uptake (rho= 0.45) were related with the change in the MRI erosion score from baseline to 2 yrs (rho= Spearman's correlation). In the multivariate logistic regression model, the bone marrow oedema score was the only baseline variable that predicted erosive progression at 2 yrs' follow-up (OR 4.2, 95% CI 1.3-13.8). The median (interquartile range) change in the erosion score from baseline to 2 yrs was 0 (0, 0) and 4 (2, 5) in the patients with (n= 9) and without (n= 15) a persistent clinical response over the 2 yrs, respectively (P= 0.001). The non-responders who presented with erosive progression from 1 yr to 2 yrs had higher MRI synovitis scores, bone oedema scores, E-rate and (99m)Tc-NC uptake at 1-yr follow-up than the non-responders without progressive bone damage., Conclusion: The degree of local synovial inflammation at baseline, evaluated by dynamic and static MRI and quantitative NC scintigraphy, is closely related to the progression of wrist joint erosions during the first 2 yrs of the disease. Furthermore, at follow-up, if no persistent clinical response is achieved, these imaging methods may help to predict future erosiveness and help in clinical therapeutic decision making.

Objectives: To evaluate ultrasonography (US) of salivary glands in primary Sjögren's syndrome (SS) and to compare US with parotid magnetic resonance (MR) imaging and MR sialography., Methods: US examination of parotid, submandibular and sublingual glands was performed on 27 patients with primary SS, 27 healthy controls and 27 symptomatic controls without SS. The results were compared with parotid MR imaging and MR sialography and the clinical features of the patients., Results: Salivary gland abnormalities, parenchymal inhomogeneity or adipose degeneration, were visualized in 21 (78%) SS patients, in one healthy control and in two symptomatic controls by US. Eighteen (67%) patients had changes in the parotid and submandibular glands and 8 (30%) changes in the sublingual glands. In the comparison, MR sialography was found to be the most sensitive method (96%), followed by MR imaging (81%) and US (78%), in detecting glandular changes. The specificity of US was 94%. The US and MR results were related to anti-Ro/SSA positivity but not to saliva secretion. The focus scores were related only to parotid MR imaging findings., Conclusions: US, MR imaging and MR sialography with modern technology have reached such a good accuracy in visualizing glandular structural changes that they are promising alternatives to the conventional invasive examinations in the diagnostics of SS.

Objective: Autonomic neuropathy is associated with increased mortality. Autonomic nervous system disorders have been described in patients with primary Sjögren's syndrome (SS), but the results in controlled studies have been contradictory, varying from normal to sympathetic or parasympathetic dysfunction. Since the earlier studies employed varying methodologies, which may have led to the discrepancy, we conducted a comprehensive study on autonomic function in patients with primary SS and compared our findings to healthy, carefully matched population based controls., Methods: A conventional cardiovascular reflex test battery (Valsalva maneuver, deep breathing test, active orthostatic test) and measurements of baroreflex sensitivity with phenylephrine and 24 hour heart rate variability were performed on 30 patients with primary SS and 30 healthy age and sex matched population based controls., Results: There were no significant differences between the SS patients and the healthy controls in any of the tests., Conclusions: The prevalence of autonomic dysfunction is not increased in patients with primary SS compared to the general population.

Objective: To look for structural parotid gland changes on magnetic resonance (MR) imaging and MR sialography of primary Sjögren's syndrome (SS) patients and healthy control subjects and to compare these methods with each other., Methods: MR imaging and MR sialography of both parotid glands were performed on 26 patients and 7 healthy controls. Bilateral surface coils were used to obtain high spatial resolution., Results: Twenty-two of the 26 patients had abnormalities on MR imaging. Twenty-one had a nodular or dendritic parenchymal pattern, 5 had cavities, and 6 had duct dilatations. On MR sialography, 25 of the 26 patients had abnormalities of the ducts, and 16 of them also had cavities. One patient and all 7 controls had normal results with both methods. The structural appearance of the parotid glands on MR images had marginal linear association with the duct system changes but no correlation with the cavitary changes seen on MR sialography. Furthermore, duct system abnormalities did not correlate with cavitary changes. Both parenchymal and sialographic abnormalities were associated with the presence of Ro/SSA antibodies but not with age of the patient, disease duration, salivary flow rate, or the presence of hypergammaglobulinemia or extraglandular manifestations., Conclusion: MR imaging and MR sialography are noninvasive methods that provide definitive information of morphologic changes in parotid glands and can be used as diagnostic indicators of primary SS. Because these methods give information on different aspects of glandular pathology, both should be performed when evaluating parotid glands of SS patients. MR sialography is more sensitive, but conventional MR imaging gives complementary information on the progressive pathologic changes of glandular parenchyma.

Objective: Autonomic neuropathy is associated with increased mortality. In patients with primary Sjögren's syndrome (SS), disturbances in the autonomic nervous system have been described using conventional cardiovascular reflex tests. Heart rate variability (HRV) measured from Holter recording has proved to be a reliable and sensitive method in assessing autonomic function and prognosis. We evaluated cardiovascular autonomic function based on HRV in patients with primary SS compared to the general population., Methods: We analyzed HRV from 24 h electrocardiography recordings in 28 patients with primary SS and 28 healthy age and sex-matched population-based controls., Results: There were no significant differences in time or frequency domains or nonlinear measures of HRV between the groups., Conclusion: The prevalence of autonomic disturbances is not increased in patients with primary SS compared to the general population.

Objective: Central nervous system (CNS) involvement in primary Sjögren's syndrome (pSS) is controversial with regard to frequency, significance, and etiology., Methods: We describe a young woman with pSS and severe CNS disease and review the literature on the pathophysiology, clinical significance, symptoms, diagnostic examinations, and treatment of CNS disease with concomitant pSS (CNS-SS)., Results: Our patient with pSS had a 5-month history of benign lymphadenopathy and myositis, after which she developed severe CNS disease, vasculitic lesions on her hands, and a neurogenic bladder attributable to spinal cord involvement. The diagnosis was based on the clinical picture and the results of a brain magnetic resonance imaging (MRI) scan, electroencephalography (EEG), and cerebrospinal fluid (CSF) analysis. The disease did not respond to corticosteroids, but the administration of cyclophosphamide resulted in recovery. In the literature, the incidence of CNS-SS varies widely, from rare to incidence rates of 20% to 25%. The clinical picture is diverse, ranging from mild cognitive symptoms to fatal cerebrovascular accidents. The pathophysiology of CNS-SS is unclear, specific diagnostic methods are not available, and diagnosis is based on the clinical picture and a combination of examinations. MRI is the most sensitive test and cerebral angiography the most specific. CSF reflects involvement of the leptomeninges, and EEG is nonspecific. There are no controlled studies of the treatment of CNS-SS. Regimens for vasculitis are commonly used., Conclusions: CNS-SS is uncommonly recognized and difficult to diagnose. Increasingly accurate and available diagnostic examinations will yield more information about the association of CNS disease with pSS.