Diagnosis Of pSS Research Articles

Neurological Involvement in Primary Sjögren Syndrome: A Focus on Central Nervous System

ObjectivesSjögren syndrome is an autoimmune disease involving mainly salivary and lacrimal glands. Beyond widely described PNS involvement, high variable prevalence of CNS manifestations ranging from 2.5 and 60% of all pSS patients has been reported, without specific syndrome definition. The aim of this cohort study was to evaluate the prevalence of CNS signs and symptoms in pSS patients and to identify possible biomarkers of CNS damage.Methods120 patients with pSS diagnosis according to the 2002 American-European Consensus Group criteria were enrolled after exclusion of secondary causes. All patients underwent to a wide neurological, neuropsychological, psychiatric, neuroradiological and ultrasonographic evaluation.ResultsCentral and peripheral nervous system involvement was observed in 81 patients with a prevalence of 67.5%. The prevalence of CNS involvement was significantly higher than PNS disease (p 0.001). 68 patients (84%) shown non-focal CNS symptoms and 64 (79%) focal CNS deficits with headache as the most common feature (46.9%), followed by cognitive (44.4%) and mood disorders (38.3%). Particularly, we observed a high prevalence of migraine without aura, subcortical frontal executive functions and verbal memory impairment and apathy/alexythimia. MR spectroscopy revealed a reduction of NAA levels or NAA/Cr ratio decrease in subcortical frontal and basal ganglia white matter, while ultrasonography showed an impairment of microvasculature response. At multivariate analysis, headache, cognitive disorders and psychiatric symptoms was significantly associated to serological markers (anti-SSA), MRS and ultrasonographic features.ConclusionsThe higher prevalence of MWO-mimic headache, cognitive dys-esecutive syndrome and mood disorders observed in this series confirmed previous evidences of a higher diffused CNS compromission rather than focal involvement such as SM-like clinical course or NMO-like syndrome. The association with immunological biomarkers, metabolic cerebral dysfunction and microvascular damage suggests a possible endothelial dysfunction of the cerebral microcirculation or a potential inflammation-mediated shift of the neurovascular coupling.

Pain in primary Sjögren’s syndrome: the role of catastrophizing and negative illness perceptions

Objectives: Pain is a major factor in health quality in Sjögren’s syndrome (SS), but little is known about the factors that contribute to pain severity. Because pain perception has been linked to catastrophizing in other diseases, we assessed subjects with primary SS (pSS) to explore a possible link between pain, illness appraisal, and catastrophizing.Method: A total of 92 subjects who met American–European consensus criteria for the diagnosis of pSS completed a questionnaire that included health history, medication use, illness perceptions, pain severity, mood, fatigue, pain anxiety, and pain catastrophizing. Linear regression was used to test the effect of each variable on pain severity. Multivariate models were constructed using backwards elimination to assess the significant predictors of pain severity.Results: From linear regression analysis, catastrophizing was more strongly predictive of pain severity than age, fatigue, depression, or anxiety in both seropositive and seronegative pSS patients. In the multivariate model identified using backwards selection, four variables (pain catastrophizing, fibromyalgia status, serological status, and the conviction that illness would have severe consequences) predicted 55% of the variance in pain severity.Conclusions: Pain catastrophizing was a significant predictor of pain severity in both seropositive and seronegative pSS patients. This study suggests that behavioural interventions designed to reduce pain catastrophizing and negative appraisal of illness could be of benefit in pSS patients. Research is needed to test the effect of psycho-educational therapies on key patient-reported outcomes, particularly pain, depression, and fatigue, in pSS.

A Meta-analysis of the Diagnostic Value of Minor Salivary Gland Biopsy for Primary Sjogren's Syndrome

Objective. The purpose of this study is to evaluate the diagnostic performance of minor salivary gland biopsy (MSGB) for patients with primary Sjogren’s syndrome (pSS). Methods. We have conducted a search from Medline, Embase, and Cochrane Library databases, and performed a meta-analysis on the diagnostic accuracy of MSGB in pSS patients. Results. A total of eight studies, including 583 pSS and 627 non-pSS patients, were available for the meta-analysis. The pooled sensitivity and specificity of MSGB were 75.7% (95% confidence interval [CI], 72.0∼79.1) and 90.7% (88.1∼92.9), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 9.475 (4.051∼22.16), 0.266 (0.208∼0.340), and 38.92 (19.12∼72.21), respectively. The area under the curve was 0.901 and the Q* index was 0.902, indicating a high diagnostic accuracy. Some between-study heterogeneity was found in the meta-analyses; however, there was no evidence of a threshold effect (Spearman correlation coefficient=0.419; p=0.301). Meta-regression showed that the study quality, sample size, study design, and diagnostic criteria were not sources of heterogeneity, and subgroup meta-analyses did not change the overall diagnostic accuracy. Conclusion. Our meta-analysis of published studies demonstrates that MSGB has a high diagnostic accuracy and may play an important role in the diagnosis of pSS.

Diagnostic accuracy of blood B-cell subset profiling and autoimmunity markers in Sjögren’s syndrome

IntroductionThe aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjögren’s syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) criteria.MethodsIn a single-center cohort of patients with suspected pSS, we tested the diagnostic performance of anti-SSA, antinuclear antibody (ANA), rheumatoid factor (RF), gammaglobulins, IgG titers, and B-cell ratio defined as (Bm2 + Bm2′)/(eBm5 + Bm5), determined using flow cytometry. The reference standard was a clinical diagnosis of pSS established by a panel of experts.ResultsOf 181 patients included in the study, 77 had pSS. By logistic regression analysis, only ANA ≥1:640 (sensitivity, 70.4%; specificity 83.2%) and B-cell ratio ≥5 (sensitivity, 52.1%; specificity, 83.2%) showed independent associations with pSS of similar strength. In anti-SSA-negative patients, presence of either of these two criteria had 71.0% sensitivity but only 67.3% specificity for pSS; whereas combining both criteria had 96.2% specificity but only 12.9% sensitivity. Adding either of these two criteria to the AECG criteria set increased sensitivity from 83.1% to 90.9% but decreased specificity from 97.1% to 85.6%, whereas adding both criteria in combination did not substantially modify the diagnostic performance of the criteria set. The adjunction of RF + ANA ≥1:320, as proposed in the new American College of Rheumatology (ACR) criteria, did not improve the diagnostic value of anti-SSA.ConclusionsBlood B-cell subset profiling is a simple test that has good diagnostic properties for pSS. However, adding this test, with or without ANA positivity, does not improve current classification criteria.

Diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjögren's syndrome

Objectives. To estimate the diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjögren's syndrome (pSS).Methods. Sixty-four pSS subjects and 108 non-pSS patients were prospectively enrolled in this study. Serum anti-alpha-fodrin IgA and IgG were detected by ELISA in a blind fashion. The diagnostic accuracy of anti-alpha-fodrin antibodies was assessed by receiver operating characteristic (ROC) curve analysis. Logistic regression was used to investigate whether anti-alpha-fodrin antibodies could improve the accuracy of pSS diagnosis if used in addition to anti-SSA and anti-SSB.Results. The areas under the ROC curves for anti-alpha-fodrin IgG and IgA were 0.69 (95% confidence interval (CI): 0.60–0.77) and 0.63 (95% CI: 0.54–0.72), respectively (P < 0.01 for both). The optimal diagnostic thresholds for anti-fodrin IgG and IgA were 11.75 U/ml and 9.75 U/ml, respectively, with a sensitivity of 0.59 and 0.55, and a specificity of 0.75 and 0.73, respectively. Anti-alpha-fodrin IgG and IgA antibodies were associated with pSS after adjustment for anti-SSA and anti-SSB.Conclusions. Anti-alpha-fodrin IgG and IgA antibodies are useful diagnostic markers which may improve the accuracy of pSS diagnosis.

Primary Sjögren's syndrome 1976–2005 and associated interstitial lung disease: a population-based study of incidence and mortality

ObjectiveA very few studies describe the epidemiology of primary Sjögren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists...

Increased Risk of Primary Sjögren's Syndrome in Female Patients with Thyroid Disorders: A Longitudinal Population-Based Study in Taiwan

BackgroundA number of reports have indicated an association between thyroid diseases and primary Sjögren's syndrome (pSS). However, fewer studies have investigated whether the presence of thyroid diseases is associated with increased risk of developing pSS. Thus, the aim of our study was to use a nationwide health claims database to explore the prevalence and risk of pSS in female patients with thyroid diseases.MethodsFrom the Registry of Catastrophic Illness database in the National Health Insurance Research Database in Taiwan, we identified 389 female patients with a diagnosis of pSS from 2005 to 2010. We also obtained 1945 control subjects frequency-matched on sex, 10-year age interval, and year of index date from the Longitudinal Health Insurance Database (LHID2000). Both groups were retrospectively traced back to a period of eight years to obtain diagnosis of thyroid diseases prior to index date.ResultsA significantly higher risk of pSS was associated with the presence of thyroid diseases (adjusted odds ratio (AOR) = 2.1, 95% confidence interval (CI) = 1.6–2.9). Among the sub-categories of thyroid diseases, patients with thyroiditis (AOR = 3.6, 95% CI = 1.7–7.5), thyrotoxicosis (AOR = 2.5, 95% CI = 1.6–3.8), and unspecified hypothyroidism (AOR = 2.4, 95% CI = 1.2–4.6), and simple and unspecified goiter (AOR = 2.0, 95% CI = 1.3–3.3) were significantly associated with increased risk of pSS. The associations were generally stronger in the mid-forties to mid-sixties age group, except in patients with unspecified hypothyroidism.ConclusionsThe risk of pSS was significantly increased in female patients with thyroid diseases, particularly those in their mid-forties to mid-sixties. An increased awareness of the possibility of pSS in perimenopausal females with thyroid diseases is important to preserve their quality of life and to avoid comorbidity.

Sjögren Syndrome-Associated Small Fiber Neuropathy

We conducted the current study to analyze the clinical, immunologic, and neurophysiologic features of primary Sjögren syndrome (pSS)-associated sensory small fiber neuropathies (SFNs). Forty consecutive pSS patients with SFN were included. SFN was defined by the presence of suggestive sensory painful symptoms with normal nerve conduction studies and abnormal neurophysiologic tests for small nerve fibers or a low intraepidermal nerve fiber density at skin biopsy. Included patients were compared to 100 pSS patients without peripheral neuropathy.SFN patients were mainly female (92.5%). Age at pSS diagnosis was 55.3 ± 13.1 years, and at SFN diagnosis, 58.9 ± 11.8 years, with a median time to SFN diagnosis after symptom onset of 3.4 years. Clinical symptoms included burning pains (90%), numbness (87.5%), tingling (82.5%), pins and needles (72.5%), electric discharges (70%), and allodynia (55%). Dysautonomia included vasomotor symptoms (66%) and hyperhidrosis (47%). Abnormal neurophysiologic tests included laser evoked potentials (97.5%), thermal quantitative sensory testing (67.5%), and sympathetic skin reflex (40%). A skin biopsy revealed low intraepidermal nerve fiber density in 76% of the 17 tested patients.Compared to the 100 pSS patients without peripheral neuropathy, the 40 pSS-SFN patients were older at pSS diagnosis (55.3 ± 13.1 vs. 49.5 ± 14.9 yr; p = 0.03), and more often had xerostomia (97.5% vs. 81%; p = 0.01) and arthralgia (82.5% vs. 65.0%; p = 0.04). Immunologically, they were characterized by a lower prevalence of serum B-cell activation markers, that is, antinuclear antibodies (65% vs. 85%; p = 0.01), anti-SSA (42.5% vs. 71%; p = 0.002), and anti-SSB (17.5% vs. 39%; p = 0.017); rheumatoid factor (32.5% vs. 66%; p = 0.0005); and hypergammaglobulinemia (35% vs. 62%; p = 0.005).In conclusion, we report the main features of SFN in patients with pSS, the first such study to our knowledge. Our results show that patients with pSS-associated SFN are characterized by an older age at pSS diagnosis and a distinctive immunologic profile hallmarked by a lower frequency of serum B-cell activation markers.

Diagnostic model of saliva peptide finger print analysis of primary Sjögren's syndrome patients by using weak cation exchange magnetic beads

Saliva diagnostics has become an attractive field utilizing nanotechnology and molecular technologies for pSS (primary Sjögren's syndrome). However, no specific methods have been established. To refine the diagnostic power of the saliva peptide finger print for the early detection of pSS, we screened the expression spectrum of salivary peptides in pSS patients by using mass spectrometry MALDI-TOF-MS (matrix-assisted laser-desorption ionization-time-of-flight MS) combined with magnetic bead. The present study was comprised 12 pSS patients and 13 healthy controls and broken down to two different phases. In the initial ‘exploratory phase’, we enrolled seven pSS patients with eight age- and sex-matched healthy volunteers. Proteomics analysis of the unstimulated salivary samples was conducted to generate proportional peptide mass fingerprints. A diagnostic model was established. The testing cohort of the second ‘validation phase’ was represented by five pSS patients and five age- and sex-matched healthy controls. The diagnostic power of this diagnostic panel was then validated. The results showed seven m/z (mass-to-charge) ratio peaks with significant differences. Five peptides were up-regulated and two down-regulated in the pSS patients compared with matched healthy subjects. In the validation phase, four out of five pSS patients were diagnosed as pSS, and four of the five healthy controls were diagnosed as healthy controls, respectively. Potential biomarkers were also primarily predicted. The novel diagnostic proteomic model with m/z peaks 1068.1 Da, 1196.2 Da, 1738.4 Da, 3375.3 Da, 3429.3 Da, 3449.7 Da and 3490.6 Da is of certain value for early diagnosis of pSS.

AB0823 Scleroderma and silica: Erasmus syndrome in west north spain

BackgroundProgressive systemic sclerosis (PSS) is a complex multisystem connective tissue disease whith unknown aetiology, but environmental and genetic factors may play a role. Since the first association of silica exposure...

OP0145 Salivary Gland Ultrasonography Improves the Diagnostic Performance of ACR 2012 Classification Criteria for Sjögren’s Syndrome

BackgroundRecently published ACR classification criteria for primary Sjögren’s syndrome (pSS) include only 3 objective tests: 1) a serological item: anti-SSA/SSB antibodies or [antinuclear antibody (ANA) titer ≥1:320 and rheumatoid factor...

SAT0232 Lymphoma in patients with primary sjögren’s syndrome: A population-based study of lymphoma subtypes, risk factors and survival

BackgroundPatients with primary Sjögren’s syndrome (pSS) have an increased risk for lymphoma, typically of the indolent mucosa-associated lymphoid tissue (MALT) type. Recent studies also indicate an increased risk of the...

AB0663 Neurological involvement in primary sjÖgren syndrome

BackgroundPrimary Sjögren Syndrome (pSS) is an autoimmune disorder characterized by a chronic lymphocytic and plasmacellular infiltration of exocrine glands and extraglandular features including both peripheral nervous system and central nervous...

THU0436 Usefulness of salivary glands ultrasonography in the non invasive early detection of subclinical glandular involvement in PSS

ObjectivesTo evaluate ultrasonographic (US) changes in major salivary glands associated with primary Sjogren’s syndrome (pSS) and to determine the usefulness of US in pSS assessment at the diagnosis and during...

THU0304 Gross Cystic Disease Fluid Protein-15(GCDFP-15)/Prolactin-Inducible Protein (PIP): A Functional Salivary Biomarker for Primary SjöGren’s Syndrome?

BackgroundGross cystic disease fluid protein-15(GCDFP-15)/prolactin-inducible protein (PIP) is a secretory acinar glycoprotein of 14KDa which has been recently described as significantly lower in salivary samples of patients with primary Sjögren’s...

AB0686 Association between the immunological profile of the patients with primary sjÖgren syndrome and occurrence of the extraglandular manifestations

BackgroundPrimary Sjogren’s syndrome (pSS) is a chronic inflammatory disease characterized by lymphocytes and plazmocytes infiltration of exocrine glands. Typical clinical manifestations of pSS are symptoms of dry mouth and dry...

OP0148 Peripheral Neuropathy (PN) in Primary Sjögren’s Syndrome: Implications of Clinical Assessment, Time of Diagnosis and Treatment

BackgroundClinical evidence of Primary Sjögren’s Syndrome (pSS) includes sicca symptoms, autoantibodies, physical exam evidence of keratoconjunctivitis sicca, and reduced salivary output. Patients with pSS may also present with peripheral neuropathy...

FRI0307 Vitamin d (VD) levels are associated with inflammation in minor salivary glands (MSG) and westergren sedimentation rate (W-ESR) in patients with sjögren’s syndrome

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune exocrinopathy, manifested by a wide spectrum of clinical sequelae ranging from sicca to severe extra-glandular features. A hallmark of the pathogenesis of SS...

THU0192 Myositis in primary sjægren’s syndrome: Data from a multicenter cohort

BackgroundAlthough muscle pain is relatively frequent in primary Sjogren Syndrome (pSS), a frank myositis is rare and reported only in 2.5-11% of patients. The most frequent symptoms are muscular weakness...

AB0654 Diagnostic value of blood B-cell subset profiling for primary sjÖgren’s syndrome

BackgroundPrimary Sjögren’s syndrome (pSS) is a systemic auto-immune disease, characterised by abnormalities of B cell homeostasis. Several studies demonstrated that the repartition of blood B cell subsets is altered during...