Characteristics and mortality in primary Sjögren syndrome-related interstitial lung disease.

ABSTRACT: Aim of the study was to determine the characteristics and prognosis, and to identify the risk factors for mortality in patients with primary Sjögren syndrome (pSS) with interstitial lung disease (pSS-ILD).A total of 1422 patients with SS were screened and 178 patients with pSS-ILD were recruited. The medical records and outcomes were retrospectively reviewed. Overall survival and case control study were performed to explore the predictors of death.Among 178 pSS-ILD patients, 87.1% were women. Mean age was 61.59 ±â€Š11.69-year-old. Median disease duration was 72.0 (24.0, 156.0) months. Nonspecific interstitial pneumonia was the predominant high-resolution computed tomography pattern (44.9%). Impairment in diffusion capacity was the most common abnormality of pulmonary function test (75.8%) and the most severe consequence. Type 1 respiratory failure and hypoxia were observed in 15.0% and 30.0% patients, respectively. Mean survival time after confirmation of pSS-ILD diagnosis was 9.0 (6.8, 13.0) years. The 10-year survival rate for all patients with pSS-ILD was 81.7%. Forty-four (24.7%) of 178 patients died during the follow-up period. The most predominant cause of death was respiratory failure (n = 27). Twenty-seven patients died of ILD and formed study group. The 78 patients who survived formed control group. Age and smoking were risk factors for mortality in patients with pSS-ILD. In addition, severity of ILD, as reflected by high-resolution computed tomography, pulmonary function test, and arterial blood gas, was an independent risk factor. However, inflammation status (erythrocyte sedimentation rate, C-reactive protein) and anti-Sjögren syndrome-related antigen A and anti-Sjögren syndrome-related antigen B were not.ILD is a severe complication of pSS. Age, smoking, and severity of lung involvement are more critical for prognosis rather than inflammation status and autoantibodies.

Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome.

OBJECTIVES: Clinical presentation of primary Sjögren's syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. METHODS: We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. RESULTS: We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10-62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. CONCLUSION: Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.

Burden of illness among subgroups of patients with primary Sjögren's syndrome and systemic involvement.

OBJECTIVES: To describe how patients with primary SS (pSS) and systemic organ involvement are classified and clustered in routine practice. METHODS: This multinational, cross-sectional survey of real-world quantitative data was conducted across Europe and the US. Rheumatologists who treated seven or more adult patients per month with pSS and current/past systemic manifestations undertook a survey before completing a patient record form capturing demographic, clinical and treatment information for their next six eligible patients. Patients with a completed patient record form were invited to complete a patient self-completion questionnaire capturing insights into their disease and treatment. Subgroups were defined by physicians' assessment of disease severity; clusters were derived based on key clinical characteristics using latent class analysis. RESULTS: Rheumatologists completed 316 physician surveys and 1879 patient record forms; 888 patients completed the patient self-completion questionnaire. pSS severity reflected organ involvement and symptomatology. Latent class analysis produced five clusters distinguished by the organ systems involved and the presence of pain and fatigue symptoms at the time of the survey. A minority of patients [n = 67 (4%)] were categorized with multiple organ involvement and the highest frequency of pain and fatigue. A total of 324 patients (17%) were categorized as 'low burden'. The remaining three clusters exhibited high frequencies of articular involvement but were distinguished by the extent of other organ system involvement. CONCLUSION: Cluster analysis using a real-world cohort of patients with pSS and systemic organ involvement highlights the heterogeneous presentation of patients with pSS and confirms the importance of pain and fatigue as well as organ involvement when determining disease burden.

Fibromyalgia, Sjogren's & depression: linked?

Health care has become increasingly fragmented, partly due to advancing medical technology. Patients are often managed by various specialty teams when presenting with symptoms that could be manifestations of different diseases. Approximately one third of them are referred to specialists, at over half for outpatient appointments. Fatigue, pain, depression, dry mouth, headaches, and arthralgia are common complaints and frequently require referral to specialist physicians. Differential diagnoses include fibromyalgia (FM), Sjogren's syndrome (SS), and depression. Evaluations involve various sub-specialist especially physicians like those practicing pain management, rheumatology, and psychiatry. Thresholds for referring vary. Patients sometime feel lost in a 'medical maze'. Disagreement is frequent between specialties regarding management. Each discipline has its own diagnostic and treatment protocols and there is little consensus about shared decision-making. Communication between doctors could improve continuity. There are many differences and similarities in the pathophysiology, symptomatology, diagnosis, and treatment of fibromyalgia, Sjogren's syndrome, and depression. Understanding the associations between fibromyalgia, Sjogren's syndrome and depression should improve clinical outcome via a common holistic approach.

Analysis of ocular surface damage and visual impact in patients with primary and secondary Sjögren syndrome.

The objective of this study is to review the ocular surface changes and complications of patients with Sjögren syndrome and assess their visual impact. A retrospective, cross-sectional, observational, and descriptive study of patients with Sjögren syndrome diagnosed according to the American-European Consensus Group criteria was designed. Data including age, gender, the reason for consultation, associated systemic disease, visual acuity, and ocular complications were recorded. Dry eye tests including tear meniscus thickness; tear film break-up time; ocular surface staining (fluorescein and lissamine green); and Schirmer I test were performed. A total of 249 patients, 233 women (93.6%) and 16 men (6.4%) were studied. Meibomian gland dysfunction was found in 46% (n = 229 eyes) patients; shortened tear film break-up time in 44% (n = 220 eyes); decreased tear meniscus in 49% (n = 243 eyes); significant superficial punctate keratopathy in 49% (n = 242 eyes); a mean ocular surface staining score of 5.92 points; and a low score for Schirmer I test (mean = 5.4 mm). Eyes with a 4 + corneal fluorescein score showed the worst BCVA (mean = 0.63 ± 0.66 LogMAR, ≤ 20/80 Snellen eq., 95% CI 0.29-0.97), compared to 1 + to 3 + scores (mean = 0.211 ± 0.37 LogMAR, 20/32 Snellen eq., 95% CI 0.53-1.15). Ten eyes (4.0%) presented central corneal ulceration with a mean visual acuity of 20/500 (96% visual loss). Ocular surface alterations related to severe dry eye and complications from Sjögren syndrome may have a significant impact on visual acuity. Secondary Sjögren syndrome to rheumatoid arthritis had the worse dry eye prognosis, visual outcome, and ocular complications.

Unique Sjögren's syndrome patient subsets defined by molecular features.

OBJECTIVE: To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes. METHODS: pSS patients met American-European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of ⩾0.1 ml/min. Correlated transcriptional modules were derived from gene expression microarray data from blood (n = 47 with appropriate samples). Patients were clustered based on this molecular information using an unbiased random forest modelling approach. In addition, multiplex, bead-based assays and ELISAs were used to assess 30 serum cytokines, chemokines and soluble receptors. Eleven autoantibodies, including anti-Ro/SSA and anti-La/SSB, were measured by Bio-Rad Bioplex 2200. RESULTS: Transcriptional modules distinguished three clusters of pSS patients. Cluster 1 showed no significant elevation of IFN or inflammation modules. Cluster 2 showed strong IFN and inflammation modular network signatures, as well as high plasma protein levels of IP-10/CXCL10, MIG/CXCL9, BLyS (BAFF) and LIGHT. Cluster 3 samples exhibited moderately elevated IFN modules, but with suppressed inflammatory modules, increased IP-10/CXCL10 and B cell-attracting chemokine 1/CXCL13 and trends toward increased MIG/CXCL9, IL-1α, and IL-21. Anti-Ro/SSA and anti-La/SSB were present in all three clusters. CONCLUSION: Molecular profiles encompassing IFN, inflammation and other signatures can be used to separate patients with pSS into distinct clusters. In the future, such profiles may inform patient selection for clinical trials and guide treatment decisions.

Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren's syndrome.

OBJECTIVE: Major salivary gland ultrasonography (SGUS) is widely used for the diagnosis of primary Sjögren's syndrome (pSS). Our objective was to assess the contribution of SGUS compared to other items of the 2016 ACR/EULAR pSS classification criteria, based on expert opinion. METHODS: A secure web-based relational database was used by 24 experts from 14 countries to assess 512 realistic vignettes developed from data of patients with suspected pSS. Each vignette provided classification criteria items and information on history, clinical symptoms and SGUS findings. Each expert assessed 64 vignettes, and each vignette was assessed by 3 experts. A diagnosis of pSS was defined according to at least 2 of 3 experts. Validation was performed in the independent French DiapSS cohort of patients with suspected pSS. RESULTS: A criteria-based pSS diagnosis and SGUS findings were independently associated with an expert diagnosis of pSS (P < 0.001). The derived diagnostic weights of individual items in the 2016 ACR/EULAR criteria including SGUS were as follows: anti-SSA, 3; focus score ≥ 1, 3; SGUS score ≥ 2, 1; positive Schirmer's test, 1; dry mouth, 1; and salivary flow rate < 0.1 mL/min, 1. The corrected C statistic area under the curve for the new weighted score was 0.96. Adding SGUS improves the sensitivity from 90.2 % to 95.6% with a quite similar specificity 84.1% versus 82.6%. Results were similar in the DiapSS cohort: adding SGUS improves the sensitivity from 87% to 93%. CONCLUSION: SGUS had similar weight compared to minor items, and its addition improves the performance of the 2016 ACR/EULAR classification criteria.

Quantitative analysis for modified Schall's classification by stimulation test with dynamic scintigraphy in Sjögren's syndrome.

OBJECTIVES: To update Schall's classification for Sjögren's syndrome (SS) by the new quantitative stimulation test with dynamic salivary glands scintigraphy (qsDSGS) and to standardize quantitative salivary gland scintigraphy. METHODS: The histopathology, oral, ocular, serological examination and qsDSGS of 268 consecutive patients with suggestive SS were evaluated in this retrospective cohort study. The serological examination included 15 autoantibodies, antinuclear antibodies (ANA) and so on. The diagnostic thresholds of the functional parameters were set by the quantitative method, and the modified Schall's classification is well established and verified. RESULTS: Based on the quantitative analysis of qsDSGS, the peak uptake level (PUL) and stimulation excretion fraction (sEF) of each parotid gland were determined as the key imaging features, which had good diagnostic performance for SS. By the modified Schall's classification, all patients were classified into: Class 1 (normal; n = 44), Class 2 (mild to moderate involvement; n = 130), Class 3 (severe involvement; n = 56) and Class 4 (very severe involvement, non-function; n = 38). Using the threshold PUL ≤ 10 counts per sec/pixel as positivity, the modified Schall's classification could provide better diagnostic performance with 88.4% specificity, 71.3% sensitivity, 96.14% positive predictive value and 43.20% negative predictive value for SS (likelihood ratio 6.15). The trends of serologically positive frequencies against SSA/Ro, anti-SSB/La and ANA were significantly increased with the new classification. CONCLUSION: The modified Schall's classification by the new stimulation test with dynamic scintigraphy is eligible to standardize quantitative salivary gland scintigraphy for SS, and may be more convenient and suitable in daily practice for clinical research and management of SS.

Salivary rheumatoid factor in primary and secondary Sjögren's syndrome / Factor reumatoide salival en síndrome de Sjögren primario y secundario

Sjögren's syndrome is a chronic autoimmune disease, characterized by the presence of hyposalivation and xerophthalmia, which in addition to other factors is diagnosed by the presence of rheumatoid factor in blood. The objective of the present study is to evaluate the presence of rheumatoid factor (IgG-IgM) in the saliva of patients with primary and secondary Sjögren's syndrome. Materials and methods: Forty samples from patients with primary and secondary Sjögren's syndrome previously diagnosed by the Arthritis and Rheumatism Specialist Center of the Autonomous University of Nuevo Leon were analyzed. Samples were taken from the saliva using the Carlson-Crittenden device to evaluate the IgG-IgM immunocomplex using the ELISA method. Results: No significant difference was found between the presence of IgM in primary (0.099±0.016) and secondary Sjögren syndrome (0.098±0.017), however, a high presence of IgG was found in the group of patients with secondary Sjögren's syndrome (0.134±0.054). Conclusion: The search for diagnostic tools using salivary biomarkers has come with economic and clinical advantages, however, in the present study no significant changes were found in salivary rheumatoid factor between both groups.

El síndrome de Sjögren es una enfermedad autoinmune crónica, caracterizada por la presencia de hiposalivación y xeroftalmia, la cual además de otros factores es diagnosticada por la presencia del factor reumatoide en sangre. El objetivo del presente estudio es evaluar la presencia del factor reumatoide (IgG-IgM) en saliva parotídea de pacientes con síndrome de Sjögren primario y secundario. Materiales y métodos: Se analizaron 40 muestras de pacientes con síndrome de Sjögren primario y secundario previamente diagnosticados por el Centro de Especialistas en Artritis y Reumatismo de la Universidad Autónoma de Nuevo León, a los cuales se les tomó una muestra de saliva parotídea mediante el dispositivo Carlson-Crittenden para evaluar mediante el método ELISA el inmunocomplejo IgG-IgM. Resultados: No se encontró diferencia significativa entre la presencia de IgM en el síndrome de Sjögren primario (0.099±0.016) y secundario (0,098±0,017), sin embargo en cuanto a la presencia de la IgG se encontró elevada en el grupo de pacientes con síndrome de Sjögren secundario (0,134±0,054). Conclusión: La búsqueda de herramientas diagnósticas mediante biomarcadores salivales ha traído consigo ventajas económicas y clínicas, sin embargo en el presente estudio no se encontró un cambio significativo en el factor reumatoide salival entre ambos grupos.

[Sjögren's syndrome update: Clinical and therapeutic aspects]. / Actualités dans le syndrome de Sjögren primitif : aspects cliniques et thérapeutiques.

Sjögren's syndrome (SS) is a systemic orphan disease. It is characterized by the involvement of epithelial tissues leading to the term of autoimmune epithelitis. New classification criteria have been developed in 2016. New scores have also been developed: a patient-reported outcome called ESSPRI and a score assessing systemic activity of the disease called ESSDAI. These new tools are very helpful to better stratify patients and to customize the management of this very heterogeneous disease. Among the autoimmune diseases, SS is associated with the highest risk of lymphoma. Five to ten percent of the patients will have a B cell lymphoma mostly a low-grade lymphoma developing from mucosa-associated lymphoid tissue (MALT). Major advances have been made in this field: pathogeny is better understood, new predictors are available and progresses have been made in the management of this severe complication. Research in the field of SS is very dynamic as illustrated by the high number of therapeutic trials. There is hope that these innovations, reviewed in the present article, will have potential significant repercussions for the patients in the next few years.

Cytokine Profiles in Autoantibody Defined Subgroups of Systemic Lupus Erythematosus.

The aim of this study was to evaluate how the cytokine profiles differed between autoantibody based subgroups of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disease, characterized by periods of flares (active disease) and remission (inactive disease). The disease can affect many organ systems, e.g., skin, joints, kidneys, heart, and the central nervous system (CNS). SLE patients often have an overproduction of cytokines, e.g., interferons, chemokines, and interleukins. The high cytokine levels are part of the systemic inflammation, which can lead to tissue injury. In the present study, SLE patients were divided into five groups based on their autoantibody profiles. We thus defined these five groups: ANA negative, antiphospholipid (aPL) positive, anti-Sm/anti-RNP positive, Sjögren's syndrome (SS) antigen A and B positive, and patients positive for more than one type of autoantibodies (other SLE). Cytokines were measured using Mesoscale Discovery (MSD) multiplex analysis. On the basis of the cytokine data, ANA negative patients were the most deviating subgroup, with lower levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-12/IL-23p40, and interferon gamma-induced protein (IP)-10. Despite low cytokine levels in the ANA negative group, autoantibody profiles did not discriminate between different cytokine patterns.

Current concepts on Sjögren's syndrome - classification criteria and biomarkers.

Sjögren's syndrome is a lymphoproliferative disease with autoimmune features characterized by mononuclear cell infiltration of exocrine glands, notably the lacrimal and salivary glands. These lymphoid infiltrations lead to dryness of the eyes (keratoconjunctivitis sicca), dryness of the mouth (xerostomia), and, frequently, dryness of other surfaces connected to exocrine glands. Sjögren's syndrome is associated with the production of autoantibodies because B-cell activation is a consistent immunoregulatory abnormality. The spectrum of the disease extends from an organ-specific autoimmune disorder to a systemic process and is also associated with an increased risk of B-cell lymphoma. Current treatments are mainly symptomatic. As a result of the diverse presentation of the syndrome, a major challenge remains to improve diagnosis and therapy. For this purpose an international set of classification criteria for primary Sjögren's syndrome has recently been developed and validated and seems well suited for enrolment in clinical trials. Salivary gland biopsies have been examined and histopathology standards have been developed, to be used in clinical trials and patient stratification. Finally, ultrasonography and saliva meet the need of non-invasive imaging and sampling methods for discovery and validation of disease biomarkers in Sjögren's syndrome.

Performance of the 2016 ACR-EULAR classification criteria for primary Sjogren's syndrome in a Korean cohort.

This study compared the performance of the newly proposed 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria to the 2002 American-European Consensus Group (AECG) and 2012 ACR classification criteria for primary Sjogren's syndrome (pSS) in well-characterized Korean patients. Patients with pSS from 12 university-affiliated hospitals in Korea were enrolled from October 2013 to January 2017. Clinical and laboratory data were reviewed. For the validation set, patients who underwent evaluation tests to rule out pSS at Seoul St. Mary's hospital from November 2016 to December 2017 were analyzed. Baseline registry data were available in 458 patients, and 328 patients had sufficient data to determine the fulfillment of each criteria set. All three sets of criteria were met by 307 patients (93.6%). The newly proposed 2016 ACR/EULAR criteria were met by 325 patients (99.1%). The 2002 AECG and 2012 ACR criteria were met by 325 (99.1%) and 310 patients (94.5%), respectively. In a validation cohort consisting of 161 patients with pSS-related symptoms/signs, the sensitivity and specificity of the 2016 ACR/EULAR criteria were 100% [95% confidence interval (CI), 96.11-100.00] and 81.8% [95% CI, 76.15-94.26], respectively. Agreement between the 2016 criteria and 2012 or 2002 criteria was high (Cohen's kappa 0.736 and 0.769, respectively). The newly proposed 2016 ACR/EULAR criteria were met by most patients diagnosed with pSS according to previous criteria and showed higher sensitivity and lower specificity compared with both previous criteria sets.

Validation of the ACR-EULAR criteria for primary Sjögren's syndrome in a Dutch prospective diagnostic cohort.

Objectives: To validate the ACR-EULAR classification criteria for primary SS (pSS), and compare them to the American-European Consensus Group (AECG) and ACR criteria in a Dutch prospective diagnostic cohort. Methods: Consecutive patients (n = 129) referred for suspicion of pSS underwent a multidisciplinary evaluation, including a labial and/or parotid gland biopsy. Patients with an incomplete work-up (n = 8) or associated systemic auto-immune disease (n = 7) were excluded. The ACR-EULAR classification was compared with expert classification, AECG and ACR classification. Additionally, the accuracy of individual ACR-EULAR items in discriminating pSS from non-pSS was evaluated. The validity of criteria sets was described separately using parotid or labial gland biopsy results for classification. Results: Of the 114 evaluated patients, the expert panel classified 34 (30%) as pSS and 80 (70%) as non-pSS. Using labial gland biopsy results, ACR-EULAR classification showed 87% absolute agreement (κ = 0.73) with expert classification, with a sensitivity of 97% and specificity of 83%. Using the parotid gland biopsy results, the ACR-EULAR criteria performed excellently as well. Focus score, anti-SSA titre and ocular staining score showed good to excellent accuracy, whereas unstimulated whole saliva and Schirmer's test had poor accuracy. The ACR-EULAR and AECG criteria had equal validity. Compared with ACR classification, ACR-EULAR classification showed higher sensitivity but lower specificity. Conclusion: The ACR-EULAR criteria showed good agreement with expert classification, but some patients may be misclassified as pSS. Unstimulated whole saliva and Schirmer's test showed poor discriminative value. The ACR-EULAR criteria performed equally to the AECG criteria, and had higher sensitivity but lower specificity than the ACR criteria.

Comparative analysis of the 2016 ACR-EULAR and the 2002 AECG classification criteria for Sjögren's syndrome: Findings from the NIH cohort.

INTRODUCTION: The introduction of new classification criteria for Sjögren's syndrome, known as the 2016 American College of Rheumatology/European League against Rheumatism Classification Criteria (ACR-EULAR), created a need for the evaluation of its performance in an external cohort. The purpose of this study was to compare the performance of the 2016 ACR-EULAR classification set with the widely used American-European Consensus Group Classification criteria (AECG) in the cohort at the National Institutes of Health, USA, and to compare the performance of the sets in classifying both primary and secondary Sjögren's syndrome (pSS and sSS). METHODS: The study cohort at the NIH (N = 1,303) was enrolled for clinical suspicion of SS. Participants were classified as SS, pSS, and sSS according to both classification sets. Performance of 2016 ACR-EULAR and AECG sets was compared holding each as gold standard to the other. Statistical analysis of test diagnostics and agreement between the two sets were undertaken. RESULTS: By the AECG set, 701 were classified as having SS (627 pSS, 74 sSS) and 714 were classified with SS (647 pSS, 67 sSS) by the 2016 ACR-EULAR set. Sensitivity and specificity of the two sets were comparable in classifying SS, pSS, and sSS. There was high agreement between the two sets for classifying SS (κ = 0.79), pSS (κ = 0.81), and sSS (κ = 0.87). The specificity of the 2016 ACR-EULAR set was significantly higher for classifying sSS than pSS, while the sensitivity was similar for the two disease groups. However, this pattern was also exhibited by the AECG set. CONCLUSION: There was high agreement between the two classification sets with comparable performance diagnostics. There was no evidence of superior performance value by the new 2016 ACR-EULAR set over the AECG set, and the two sets were found to be equivalent. Findings from our cohort indicate that 2016 ACR-EULAR classification could be extended to classification of sSS.

Comparison of 2002 AECG and 2016 ACR/EULAR classification criteria and added value of salivary gland ultrasonography in a patient cohort with suspected primary Sjögren's syndrome.

BACKGROUND: The objective was to evaluate concordance between 2002 American-European Consensus Group (AECG) and 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's syndrome (pSS) and to assess how salivary gland ultrasonography (SGUS) might improve the classification of patients. METHODS: Patients with suspected pSS underwent a standardised evaluation, including SGUS, at inclusion into the single-centre Brittany DIApSS cohort. Agreement between the two criteria sets was assessed using Cohen's κ coefficient. Characteristics of discordantly categorised patients were detailed. RESULTS: We prospectively included 290 patients between 2006 and 2016, among whom 125 (43%) met ACR/EULAR criteria and 114 (39%) also met AECG criteria; thus, 11 (4%) patients fulfilled only ACR/EULAR, no patients AECG only, and 165 (57%) patients neither criteria set. Concordance was excellent (κ = 0.92). Compared to patients fulfilling both criteria sets, the 11 patients fulfilling only ACR/EULAR criteria had similar age and symptom duration but lower frequencies of xerophthalmia and xerostomia (p < 0.01 for each) and salivary gland dysfunction (p < 0.01); most had systemic involvement (91%), including three (27%) with no sicca symptoms; 91% had abnormal salivary gland biopsy and 46% anti-Sjögren's-syndrome-related antigen A (anti-SSA); 64% were diagnosed with pSS by the physician. SGUS was abnormal in 12% of the 165 patients fulfilling no criteria set. Including SGUS among the ACR/EULAR criteria increased sensitivity from 87.4% to 91.1% when physician diagnosis was the reference standard. CONCLUSIONS: Agreement between AECG and ACR/EULAR criteria sets is excellent. ACR/EULAR criteria are slightly more sensitive and classified some patients without sicca symptoms as having pSS. Including SGUS in the ACR/EULAR criteria may further improve their sensitivity.

Ultrasonography of major salivary glands compared with parotid and labial gland biopsy and classification criteria in patients with clinically suspected primary Sjögren's syndrome.

OBJECTIVE: To assess the validity of ultrasound of major salivary glands (sUS) compared with parotid and labial gland biopsies, sialometry, anti-SSA/Ro antibody status and classification criteria in patients clinically suspected with primary Sjögren's syndrome (pSS). METHODS: 103 consecutive outpatients with clinically suspected pSS underwent sUS. Parenchymal echogenicity, homogeneity, hypoechogenic areas, hyperechogenic reflections and clearness of salivary gland border were scored according to the Hocevar scoring system. Total ultrasound score was calculated as the sum of these domains (range 0-48). RESULTS: Absolute agreement between sUS and parotid (83%) and labial (79%) gland biopsy outcome was good. Negative sUS predicts negative parotid gland biopsy, and positive sUS predicts positive labial gland biopsy. Compared with the American European Consensus Group (AECG) classification, sUS showed an absolute agreement of 82%, sensitivity of 71% and specificity of 92%. Compared with the American College of Rheumatology (ACR) classification, absolute agreement was 86%, sensitivity was 77% and specificity was 92%. Compared with the ACR-European League Against Rheumatism (EULAR) classification, absolute agreement was 80%, sensitivity was 67% and specificity was 94%. Positive sUS predicts classification, but negative sUS does not exclude classification. The combination of positive sUS with presence of anti-SSA/Ro antibodies or negative sUS with absence of anti-SSA/Ro antibodies showed a high predictive value for classification as pSS or non-pSS. CONCLUSION: In our prospective inception cohort study derived from daily clinical practice, absolute agreement between sUS and salivary gland biopsies was slightly higher for parotid compared with labial gland biopsies. The combination of positive sUS and presence of anti-SSA/Ro antibodies highly predicts classification according to the AECG, ACR and ACR-EULAR classification criteria.

[Ultrasound diagnostics in Sjögren's syndrome]. / Ultraschalldiagnostik beim Sjögren-Syndrom.

Ultrasound of the salivary glands is a specific examination for detecting pathology of salivary glands in the diagnosis of Sjögren's syndrome. It is easy to learn, rapidly performed, non-invasive and inexpensive. Other imaging techniques, such as sialography and scintigraphy, are currently only rarely performed. For the examination, linear ultrasound probes with frequencies between 7 and 12 MHz are recommended. Such probes are already widely available to the rheumatologist performing musculoskeletal ultrasound. The parotid and submandibular glands are bilaterally scanned both in longitudinal and transverse planes as a standard.Normal salivary glands have uniformly hyperechoic and homogeneous tissue. They can be clearly delineated from the surrounding muscles and soft tissue and appear similar to the thyroid gland. The salivary glands are typically hypoechoic and inhomogeneous in Sjögren's syndrome. Focal or diffuse hypoechoic or anechoic foci are found in the glands. The submandibular glands may become atrophic (sagittal diameter <8 mm). Particularly in disease flares, the parotid glands may become enlarged (sagittal diameter >20 mm). The sensitivity for the diagnosis is 60 to 90% and the specificity is over 90%.Doppler sonography does not further improve the diagnostic accuracy. Sonography has thus become an important tool in the diagnosis of Sjögren's syndrome.