Primary Sjögren's Syndrome Group Research Articles

The relationship of the prevalence and severity of restless legs syndrome in primary Sjögren syndrome with insomnia status, anxiety, depression, and neuropathic pain

Background and aimsIn this study, we aimed to compare the prevalence of restless legs syndrome (RLS) between primary Sjögren syndrome (PSS) patients and the healthy population and investigate the relationships between RLS and insomnia status, anxiety, depression, neuropathic pain, and lower extremity pain. Our case-control study, included 55 patients aged 18–65 who were diagnosed with PSS based on the 2016 ACR/EULAR criteria and 60 healthy controls aged 18–65. The pain levels of the participants were evaluated using the pain DETECT Questionnaire, the lower-extremity visual analog scale, and an algometer, all participants were screened for fibromyalgia syndrome, and their psychiatric parameters were evaluated with the Beck Depression Inventory and the Beck Anxiety Inventory. Insomnia status was assessed using the Insomnia Severity Index. The cases in the PSS group with and without restless legs syndrome were compared.ResultsWhile the rate of RLS in the PSS group was 26.7%, that in the control group was found as 9%, and the difference between the two groups was significant (p < 0.05). The severity of RLS in the PSS group was found to be significantly higher in comparison to that in the control group (p < 0.05). The PSS group had significantly higher lower-extremity pain, fibromyalgia, insomnia, depression, anxiety, and pain scores, as well as a significantly higher mean number of painful points, than the control group (p > 0.05). In the results of the multivariate regression analysis, depression and insomnia scores were identified as independent predictors for the presence of RLS in PSS cases (p < 0.05).ConclusionsWe found the prevalence and severity of restless legs syndrome higher in the primary Sjögren syndrome patients compared to the healthy participants in the control group. We identified depression and insomnia as independent predictors of the presence of restless legs syndrome in primary Sjögren syndrome cases.

Primary Sjögren's syndrome is not associated with poor outcomes after total hip arthroplasty: a retrospective case-control study with a matched cohort of osteoarthritis patients.

IntroductionThe number of patients with primary Sjögren’s syndrome (PSS) requiring total hip arthroplasty (THA) is expected to increase, but few studies have detailed their outcomes. The purpose of this study was to evaluate a THA cohort of patients with avascular necrosis of the femoral head (ANFH) who had PSS and to compare their outcomes with those of matched patients with osteoarthritis.MethodA case–control study using data from a single-institution arthroplasty registry was performed. Forty-two THAs in 32 patients undergoing THA with a diagnosis of PSS were identified and were matched with 84 THAs in 64 patients with osteoarthritis (1:2 ratio). Functional and health-related quality of life (QoL) evaluations were performed, and complications were recorded at the last follow-up. Logistic regression was used to determine factors associated with reaching the transfusion trigger of hemoglobin < 8 g/dL (TT8) in PSS patients.ResultsAfter a mean 5-year follow-up, both cohorts had similar hip function and health-related QoL outcomes. The incision complications and reaching TT8 were greater in the PSS group. No differences were observed in the rate of 90-day readmission, reoperation, or overall revision. By multivariate analysis, the influencing factors for reaching TT8 in PSS patients were lower preoperative hemoglobin (OR = 0.842, 95% CI [0.741–0.958], P < 0.05).ConclusionOur study demonstrated PSS patients who received THA due to ANFH could achieve clinical outcomes similar to those of non-PSS patients. Improving preoperative Hb level can reduce the risk of transfusion.Key Points• THA significantly improved hip function and health-related quality of life in PSS patients with osteonecrosis of the femoral head.• Patients with PSS were more likely to reach the transfusion trigger and higher rates of incision complications after THA.• Improving preoperative Hb level can reduce the risk of transfusion for PSS patients who underwent THA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10067-022-06256-2.

Investigation of the relationship between the pelvic floor and sexual dysfunction in women with Sjögren's syndrome.

Women with Sjögren's syndrome (SS) may have sexual dysfunctions due to vaginal dryness and may also have pelvic floor problems. The aim of this study was to examine the pelvic floor distress of women with SS with a self-reported questionnaire, to compare this group with healthy individuals, and to examine the relationship between pelvic floor problems and sexual dysfunction. The study included 94 women with SS, aged 47.26±7.56years, and 94 age-matched healthy women, aged 48.15±8.73years. The Pelvic Floor Disease Inventory (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7), and Female Sexual Function Scale (FSFI) were used for assessment. The PFDI-20, PFIQ-7, and FSFI scores of the healthy control group were found to be statistically significantly better than those of the primary SS group (Z=-2.69 to -8.03, P=.00). A moderate-high correlation was found between the total and sub-parameters of PFDI-20 and disease duration, the total and sub-parameters of the PFIQ-7 and the pain sub-parameter and total score of the FSFI (r=-0.66 to 0.78, P=.00-.04). According to the study results, as the disease duration increases, the distress increases and this distress has a negative effect on the health-related quality of life of these women. Pelvic floor distress was associated with poor sexual function and pain. From these results, it can be recommended that the methods of pharmacology, education, exercise, relaxation, lifestyle change, and so on for pelvic floor dysfunction and pain in women with SS should be applied together with a multidisciplinary approach.

Sjögren's Syndrome and Autoimmune Thyroid Disease: Two Sides of the Same Coin.

The coexistence of Sjögren's syndrome (SS) and autoimmune thyroid disease (AITD) has been documented. However, there is no consensus whether this coexistence should be considered as the same nosological condition or as polyautoimmunity. Thus, in this monocentric retrospective study, patients with SS alone (i.e., primary) were compared with patients with SS and AITD. In addition, a discussion of previous studies including those about genetic and environmental factors influencing the development of both conditions is presented. In our series, all patients with AITD had Hashimoto's thyroiditis (HT). No significant differences in age, gender, age of disease onset, and disease duration were found between the two groups. Lymphadenopathy and urticaria were more frequently registered in patients with SS-HT than in patients with SS alone (p < 0.05). Anti-Ro/SSA antibodies were more frequent in the primary SS group (p = 0.01). SS-HT patients were more likely to report a positive history of smoking (p = 0.03). The clinical expression of SS varies slightly when HT coexists. Although both entities share common physiopathological mechanisms as part of the autoimmune tautology, they are nosologically different and their coexistence should be interpreted as polyautoimmunity. Further studies based on polyautoimmunity would allow establishing a new taxonomy of autoimmune diseases.

Presence of enthesopathy in patients with primary Sjogren's syndrome: ultrasonographic study of a local cohort.

Musculoskeletal findings in Sjögren's syndrome are arthralgia, arthritis, myalgia, myositis, fibromyalgia, and chronic fatigue. Enthesis zones are important in the formation of pain in the musculoskeletal system. Musculoskeletal ultrasound (US) may show subclinical enthesitis in the synovial joints and in the axial skeleton before joint swelling in inflammatory diseases characterized by arthritis. In this study, we aimed to determine the presence of enthesopathy using the Madrid sonographic enthesitis index (MASEI) in patients with primary Sjögren's syndrome (PSS). Consecutive patients with PSS and age-matched healthy controls were included in this study. All the patients met the 2002 American College of Rheumatology/European League against Rheumatism classification criteria for PSS. The demographic characteristics of the patients were recorded. Six enthesis sites were evaluated using gray-scale and Doppler US with a linear transducer, and they were scored using the MASEI. They were assessed by the EULAR Sjögren's syndrome disease activity index (ESSDAI). We evaluated 40 patients with PSS (average age 48.67±11.23years) and 30 healthy controls (average age 45.40±8.24years). Patients with PSS had significantly higher MASEI scores than the healthy controls. Plantar fascia, Achilles tendon, and distal patellar tendons were significantly thicker in the PSS group than in the healthy controls. The MASEI total score had a positive correlation with age. There was no correlation between MASEI total score and BMI and ESSDAI. In this study, it was shown that the MASEI scores assessed by US were significantly higher in patients with PSS than in healthy controls. Plantar fascia, Achilles tendon, and distal patellar tendon were significantly thicker in the PSS group than in the healthy controls. This result suggests that PSS may be one of the causes of musculoskeletal pain that can be seen in patients with PSS. Our study was the first study to use an enthesis index ultrasonographically in patients with PSS. In addition, it is the first study to investigate the relationship between the presence of enthesopathy and disease activity by means of US.

Risk of asthma in patients with primary Sjögren's syndrome: a retrospective cohort study.

BackgroundSjögren’s syndrome (SS) has been associated with bronchial hyperresponsiveness and asthma; however, no population-based cohort study has been performed. We evaluated the risk of asthma in patients with primary SS in a nationwide population.MethodsWe conducted a retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. The primary SS group included 4725 adult patients diagnosed between 2000 and 2006. Each patient was frequency-matched with four people without SS by sex, age and year of diagnosis. The occurrence and hazard ratio (HR) of asthma was monitored by the end of 2011.ResultsThe overall incidence density of asthma was 1.62-fold higher in the primary SS group than in the non-SS group (9.86 vs. 6.10 per 1000 person-years), with a multivariable Cox proportional hazards model measured adjusted HR of 1.38 [95% confidence interval (CI) = 1.21–1.58]. Stratified analyses by sex, age group, and presence of comorbidity revealed that asthma incidences were all higher in the primary SS group than in the non-SS group, and the relative HRs of asthma associated with primary SS were significant in all subgroups.ConclusionPatients with primary SS are associated with an increased risk of developing asthma. We should pay more attention to this group of individuals and provide them with appropriate support.

Primary Sjögren's syndrome is associated with significant cognitive dysfunction.

Cognitive dysfunction is a neurologic manifestation in primary Sjögren syndrome (PSS). On the other hand, several antibodies are related to cognitive dysfunction. The aim of this study is to assess the cognitive dysfunction of PSS patients via detailed neurologic tests. Moreover, its associations with antibodies were also evaluated. Twenty-eight female patients with PSS and 17 healthy controls comprised the study groups. Short-term memory, long-term memory, verbal learning, visual memory, visual spatial perception, attention, verbal frequency function, executive functions and information processing speed were evaluated with neurologic tests in both of the study groups. Furthermore, anti-N-methyl-D-aspartate (NMDA) type anti-glutamate-receptor antibody, anti-ribosomal-p and antiganglioside antibodies were assessed in the study groups. The attention, data processing speed, verbal learning, short-term verbal memory and visuo-spatial perception performances were lower in the patients with PSS when compared to the healthy controls. The difference reached statistical significance in Paced Auditory Serial Addition Test (P < 0.01), Serial Digit Learning Test (P < 0.01), clock drawing (P = 0.03), Auditory Verbal Learning Test immediate verbal memory (P = 0.01) and Benton Judgement of Line Orientation Test (P = 0.03). Even if antiganglioside antibodies were more likely to be present in the PSS group when compared to the healthy controls, no relationship was found between its positivity and cognitive dysfunction. Results of this study suggest that cognitive dysfunction is quite prevalent in PSS patients without being associated with studied antibodies.

Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results.

ObjectiveTo determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjögren's syndrome (SS) patients and to compare them to healthy controls.MethodsData on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group.ResultsPrimary SS patients had a higher prevalence of hypertension (28–50% versus 15.5–25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it.ConclusionPrimary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.

Elevated IgG4 serum levels among primary Sjögren's syndrome patients: do they unmask underlying IgG4-related disease?

To determine IgG4 levels in a cohort of consecutive patients with primary Sjögren's syndrome (SS) and other autoimmune diseases and explore whether they associate with distinct clinical, serologic, and histopathologic features. Serum IgG4 levels were measured in 133 primary SS patients and 49 healthy donors (HDs). Seventy-four lupus and 54 rheumatoid arthritis (RA) patients served as disease controls. Immunohistochemical IgG4 analysis was performed in paraffin-embedded minor salivary gland (MSG) tissues. Raised IgG4 serum levels (>135 mg/dl) were detected in 10 (7.5%) of 133 primary SS patients (high-IgG4 group), in 8 (10.8%) of 74 lupus patients, in 7 (12.9%) of 54 RA patients, and in 1 (2%) of 49 HDs. Compared to the normal-IgG4 (<135 mg/dl) primary SS group, high-IgG4 patients exhibited increased prevalence of IgG4-related features (autoimmune cholangitis, autoimmune pancreatitis, and interstitial nephritis), lower rates of antinuclear antibody positivity, and higher IgG2 and IgE levels. Positive staining for IgG4+ plasma cells with an IgG4:IgG ratio ≥40% was detected in 3 of 6 available MSG tissues in the high-IgG4 group. Criteria of possible or definite IgG4-related disease (IgG4-RD) were fulfilled by 10 (7.5%) of 133 of our primary SS cohort. Raised IgG4 serum levels were detected in 7.5% of primary SS patients in association with IgG4RD-reminiscent clinical, serologic, and histopathologic features. Whether this high-IgG4 primary SS group represents a misclassified IgG4-RD group or a distinct primary SS subtype remains to be further explored in future studies.

Quantitative and visual evaluation of salivary and thyroid glands in patients with primary Sjögren's syndrome using salivary gland scintigraphy: relationship with clinicopathological features of salivary, lacrimal and thyroid glands

To evaluate quantitative and visual salivary gland scintigraphy in patients with primary Sjögren's syndrome (SS) and to compare the scintigraphic findings with clinicopathological features of the salivary, lacrimal and thyroid glands. Twenty-seven patients with primary SS and 10 healthy age-matched and sex-matched individuals as a control group were included in this study. The diagnosis of SS was made on the basis of the classification criteria of the American-European Consensus Group. The patients with primary SS were divided into two groups as early-stage and advanced-stage according the labial biposy scores (16 early-stage and 11 advanced-stage). After the administration of 370 MBq Tc-99m pertechnetate, static images were obtained at 20 min and also after lemon stimulation. Functional parameters for the parotid, submandibular, and thyroid glands were calculated. Schirmer-I, tear film break-up time and Rose Bengal tests were evaluated. Statistically significant differences existed for the functional parameters of the parotid and submandibular glands between the early-stage and advanced-stage groups. The submandibular glands were more frequently affected than the parotid glands. Asymmetric uptake pattern was more common in the parotid glands during the early-stages of primary SS. When compared with the control group, the thyroid uptake ratio of the early-stage primary SS and advanced-stage group was not significantly different. According to the results of the ophthalmological tests, there was a statistically significant difference between patients with advanced-stage and early-stage disease. There were no significant correlations between functional parameters of salivary gland and any of the ophthalmological tests. The results indicate that quantitative salivary gland scintigraphy may be a useful method for evaluating salivary gland dysfunction and also for determining disease severity in primary SS. Asymmetric activity pattern in the parotid glands commonly observed during the early stages of the disease may be a predictor of progression. In addition, the histopathological stage is related not only to the scintigraphic findings of the salivary glands but also to lacrimal gland function in primary SS. However, thyroid uptake seemed to be unaffected in patients with both early-stage and advanced-stage disease.

Quality of life in patients with Sjögren’s syndrome and sicca complex

To investigate the general and oral quality of life in patients with Sjögren's syndrome (SS) and sicca complex. Forty-four patients with SS were studied consecutively, 33 were primary SS and 11 secondary SS, classified in accordance with the Vitali European criteria. The Spanish version of the Medical Outcome Short Form (36) Health Survey questionnaire (SF-36) was used to evaluate general quality of life and the Oral Health Impact Profile (OHIP-49) Spanish version to study oral quality of life. Regarding general quality of life using the SF-36, when comparing the SS and the control groups, lower scores were obtained in the SS groups in all domains and on comparing primary and secondary SS, lower scores were found for primary SS in all the subscales. With respect to oral quality of life using the OHIP-49 (all items), we found lower scores for the primary SS group with respect to the control group. Patients with primary SS present lower scores for both oral and general quality of life.

Direct healthcare costs and predictors of costs in patients with primary Sjogren's syndrome

To analyse the healthcare usage, direct healthcare costs and predictors of cost in primary Sjögren's syndrome (PSS) in the UK and to compare the findings with the data from healthy control groups and rheumatoid arthritis (RA) patients. A total of 129 patients with PSS (American-European criteria), 91 with RA and 92 controls, were included in the study. All groups were age-matched females and all completed questionnaires on health status (SF-36) and healthcare utilization (economic component of the Stanford Health Assessment Questionnaire). Annual direct healthcare costs were calculated (and expressed in 2004 UK pound sterling) and predictors of costs for each patient group were determined by regression analyses. Age, health status, disease duration and anti-Ro/La antibody positivity were used as potential predictor variables. Mean age was similar in the PSS (59.2 yrs, S.D. 11.6), RA (60.3 yrs, S.D. 10.5) and control groups (57.7 yrs, S.D. 12.5). The mean disease duration was 5.4 yrs (S.D. 4.8) in the PSS group and 13.4 yrs (S.D. 11.4) in the RA group. The mean annual total direct cost per patient [95% confidence interval (CI)] was 2188 pounds sterling (1831 and 2546 pounds sterling) in the PSS group, 2693 pounds sterling(2069 and 3428 pounds sterling) in the RA group and 949 pounds sterling (741 and 1156 pounds sterling) in the control group. The costs in the PSS group were greater than for the RA and control groups for visits to all healthcare professionals (total) as well as visits to the dentist, dental hospital and ophthalmologist. The costs in the PSS and RA groups were higher than in controls for diagnostic tests and visits to hospital and the accident and emergency (A&E) department. The PSS group also incurred higher costs than controls, but lower costs than the RA group, for visits to a rheumatologist, urine and blood tests, assistive devices and drug therapy. Regression analysis identified the SF-36 physical function subscale as the best predictor of costs in PSS patients as well as controls and the mental health subscale in RA patients. This is the first study to evaluate direct healthcare costs in patients with PSS. PSS has a significant impact on the healthcare system, similar to that of RA, by more than doubling costs compared with control patients.

Diagnostic Potential of Tear Proteomic Patterns in Sjögren's Syndrome

Histological and functional changes of the lacrimal gland might be reflected in proteomic patterns in tear fluids. In this study, we carried out a determination of the disease biomarkers in tear fluid for Sjögren's syndrome (SS) and a performance of noninvasive diagnostic test based on the proteomic patterns. Thirty-one SS patients and 57 control subjects were enrolled to this study. Their details were 23 cases with primary SS, 8 with secondary SS, 14 with dry eyes, 22 with miscellaneous ocular diseases, and 21 of healthy volunteers. Protein profiling in tear fluids was identified by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Multiple protein changes were reproducibly detected in the primary SS group, including 10 potential novel biomarkers. Seven of the biomarkers (2094, 2743, 14191, 14702, 16429, 17453, 17792 m/z) were down-regulated and 3 biomarkers (3483, 4972, 10860 m/z) were up-regulated in primary SS group, comparing to the protein profiles of control subjects. When cutoff value of SS down-score was set less than 0.5, this result yielded 87% sensitivity and 100% specificity. The positive predictive value for this sample set was 100%. There was a significant inverse correlation between SS down-scores and epithelial damages of the ocular surface in primary SS patients. These findings support the potential of proteomic pattern technology in tear fluids as the noninvasive diagnostic test for primary SS.

An In Vivo Confocal Masked Study on Corneal Epithelium and Subbasal Nerves in Patients with Dry Eye

The objective of the present study was to determine whether dry eye (DE) associated with primary Sjögren's syndrome (PSDE) and DE not associated with Sjögren's syndrome (NSDE) are related to an alteration of corneal innervation. Eleven healthy volunteers younger than 60 years (normal [N] < 60 group), 10 healthy volunteers 60 years of age or older (N > or = 60 group), 11 patients with PSDE, and 10 patients with NSDE were studied. Epithelial and stromal density and subbasal and stromal nerves were investigated by confocal microscopy. The density of the superficial epithelial cells was 741 +/- 306 cells/mm2 in the PSDE group; 1022 +/- 331 cells/mm2 in the NSDE group; 1523 +/- 294 cells/mm2 in the N > or = 60 group, and 1529 +/- 341 cells/mm2 in the N < 60 group (P < 0.0001, ANOVA). The number of subbasal nerves was 2.8 +/- 1.2 in the PSDE group, 3.3 +/- 0.7 in the NSDE group, 3.1 +/- 0.9 in the N > or = 60 group, and 4.6 +/- 0.8 in the N < 60 group (P < 0.0001, ANOVA). The number of beadlike formations observed in the different groups was 387 +/- 62/mm in the PSDE group, 323 +/- 64/mm in the NSDE group, 182 +/- 63/mm in the N > or = 60 group, and 198 +/- 66/mm in the N < 60 group (P < 0.0001, ANOVA). A correlation was found between the number of subbasal nerves and age (P < 0.01) and between the number of subbasal nerves and Schirmer's test (P < 0.001, Spearman rho). Patients with DE show alteration in the corneal innervations. The demonstration of such alterations introduces new strategies for treatment of this frequent disease.

Oral health condition and saliva flow in southern Chinese with Sjögren’s syndrome

To investigate the oral health condition and saliva flow of southern Chinese patients with Sjögren's syndrome (SS). 51 SS patients (26 primary and 25 secondary cases) and 29 controls took part in this cross-sectional study. Stimulated whole and parotid saliva flow rates, pH, and buffer capacity, and xerostomia, oral mucosal lesions, oral hygiene status, dental and periodontal conditions, prosthetic status were assessed and compared between groups. Stimulated whole saliva (SWS) flow was reduced in primary and secondary SS cases (p<0.001), pH and buffer capacity were also reduced in the primary SS group (p<0.05). SS patients had a greater prevalence of xerostomia than controls (p<0.001). Primary SS patients had a higher mean DMFT, more missing teeth, and more prostheses than secondary SS cases and controls (p<0.05). SWS flow correlated negatively with the number of filled teeth in both SS groups (p<0.05) and the number of decayed teeth in the primary SS group (p<0.05). Despite good oral hygiene and regular dental check-ups, the oral health of southern Chinese with primary SS was significantly compromised compared with secondary SS cases and controls, most probably due to the combined effect of impaired salivary gland function and poorer saliva buffer capacity.

Sjögren's syndrome associated with systemic lupus erythematosus: clinical and laboratory profiles and comparison with primary Sjögren's syndrome.

To address the clinical, serologic, pathologic, and immunogenetic features of sicca syndrome that occurs in systemic lupus erythematosus (SLE), as well as its similarities to, and differences from, sicca syndrome that occurs in primary Sjögren's syndrome (SS). A cohort of 283 consecutive unselected SLE patients was evaluated for the presence of associated SS using the American-European classification criteria. Clinical and laboratory parameters in SLE patients with SS (SLE-SS) were compared with those in SLE patients without SS (SLE-no SS) and with a group of 86 unselected patients with primary SS. SS was identified in 26 SLE patients (9.2%); the SS preceded the development of lupus in 18 of them (69.2%). Compared with the SLE-no SS group, patients with SLE-SS were significantly older, had a higher frequency of Raynaud's phenomenon, anti-Ro/SSA, anti-La/SSB, and rheumatoid factor, but had a significantly lower frequency of renal involvement, lymphadenopathy, and thrombocytopenia. Compared with the primary SS group, SLE-SS patients displayed a clinically similar sicca syndrome, but were significantly younger and had an increased frequency of perivascular infiltrates in the salivary glands associated with anticardiolipin antibodies in the serum. SLE-SS patients had a high frequency of the DRB1*0301 allele. This HLA profile distinguished the SLE-SS group from the SLE-no SS group, who had an increased frequency of DRB1*1501 and DQB1*0602 alleles, but was similar to the HLA profile of the primary SS group, who had an increased frequency of DRB1*0301. SLE-SS appears to constitute a subgroup of patients with distinct clinical, serologic, pathologic, and immunogenetic features, in whom SS is expressed as an overlapping entity and is largely similar to primary SS.