American-European Consensus Group Classification Research Articles

Ultrasonography as an additional item in the American College of Rheumatology classification of Sjögren's syndrome.

In this study we evaluated US as an additional classification item in the ACR classification of SS. Of 581 patients classified as either SS (n = 364) or non-SS (n = 217) based on the minimum requirements of the American-European Consensus Group (AECG) classification, 184 patients (102 SS and 82 non-SS) who had scored two or more positive or two or more negative results according to the ACR criteria were selected. The AECG classification was used as the gold standard. A parotid and/or submandibular gland that was assigned a score ≥G1 was designated as SS positive. We evaluated US alone or with varying combinations of the ACR classification items in the diagnosis of SS. The ACR criteria diagnosed the 184 patients with 91% sensitivity, 90% specificity and 91% accuracy. US alone diagnosed the 184 ACR patients with 79% sensitivity, 90% specificity and 83% accuracy, which was comparable to the results of US diagnosis in the AECG cohort (81%, 86% and 83%, respectively). Incorporating the US criteria as an alternative to one of the three ACR classification items achieved 89-91% sensitivity, 87-96% specificity and 89% or 92% accuracy, which was comparable to that of the original ACR classification. Furthermore, kappa analysis indicated that the results of the original ACR and US-replaced ACR classifications matched completely (κ = 0.960-0.974). These results suggest that US can be used as an alternative to any of the three ACR classification items.

AB0562 Male versus Female Patients with Primary SjÖGren's Syndrome: A Comparison of Ethnicity, Clinical Features, Serology and Outcome in 156 Patients – is There a Male SjÖGren's Phenotype?

BackgroundThere are conflicting data from previous studies as to whether a male Sjögren's phenotype really exists. We have taken advantage of our own Sjögren's cohort (n=156) followed up for 27...

SP0083 The Role of US for Diagnosing SjÖGren's Syndrome - Practical Aspects

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterized by lymphocytic infiltrates in the lachrymal and salivary glands. Dryness of the eyes (keratoconjunctivitis sicca) and mouth (xerostomia) are the...

FRI0435 Salivary Epidermal Growth Factor (EGF) in SjÖGren's Syndrome: Association between Salivary EGF Levels and the Severity of Intraoral Manifestations

BackgroundXerostomia accompanied in patients with Sjögren's syndrome (SS) relates to reduced salivary flow rate as a result of salivary gland dysfunction. Dry mouth causes various intraoral manifestations such as refractory...

FRI0373 Clinical Outcome of Dental Implant Therapy in Patients with SjÖGren's Syndrome

BackgroundPatients with Sjögren's syndrome are subject to loss of teeth related to the high caries risk. Dental implant therapy is often considered as a proper possibility for prosthodontic rehabilitation of...

Level of agreement between 2002 American-European Consensus Group and 2012 American College of Rheumatology classification criteria for Sjögren's syndrome and reasons for discrepancies.

IntroductionThe aims of this study were to assess agreement between the currently used 2002 American–European Consensus Group (AECG) classification criteria and the new 2012 American College of Rheumatology (ACR) criteria for Sjögren’s syndrome (SS) and to identify potential sources of disagreement.MethodsWe studied 105 patients between 2006 and 2013 from the Brittany cohort of patients with suspected SS. AECG criteria were applied using only Schimer’s test and unstimulated whole salivary flow (UWSF) to assess objective ocular and oral involvement, since these are the tests most physicians use in clinical practice. Agreement between the two sets of criteria was assessed using Cohen’s κ coefficient.ResultsOf those studied, 42 patients fulfilled AECG and 35 ACR criteria. Agreement between the two sets was moderate (κ = 0.53). Patients fulfilling ACR but not AECG criteria (n = 8) were significantly younger and had shorter symptom durations, but only three of them had SS in the opinion of the evaluating physician. Xerostomia and xerophthalmia (AECG set only) did not discriminate between patients with and without SS. The use of UWSF in the AECG but not the ACR criteria explained part of the disagreement. The serological item in the ACR set (positive rheumatoid factor and antinuclear antibody ≥1:320 or anti-SSA/SSB positivity) did not result in classification differences compared to anti-SSA/SSB antibody alone (AECG set). Agreement between ocular staining score ≥3 (ACR set) and Schirmer’s test ≤5 mm/5 min (AECG set) was very low (κ = 0.14).ConclusionsAgreement was only moderate between ACR and AECG criteria, suggesting these two sets would not select comparable patient populations. An international consensus about which classification criteria should be used in clinical studies is needed.

The role of a labial salivary gland biopsy in the diagnostic procedure for Sjögren's syndrome; a study of 94 cases.

Objectives: The purpose of the present study is to examine the role of the outcome of the labial salivary gland biopsy (LSGB) in the diagnostic procedure of patients suspected of suffering from Sjögren’s syndrome (SS). Material and Methods: In a retrospective study the result of histopathological assessment of 94 consecutively taken labial salivary gland biopsies has been examined. For the diagnosis of SS the American-European Consensus Group classification (AECG, 2002) have been used. The outcome of the assessment has been discussed in relation to a recently reported classification provided by the American College of Rheumatology (ACR, 2012). Results: In the 94 LSGBs support for a diagnosis of SS has been encountered in 24 out of 26 patients with SS. In the 68 patients with a negative diagnosis of SS only six positive LSGBs were observed. The sensitivity of the labial biopsy amounted 0.92; the specificity was 0.91, while the positive predictive value and the negative predictive value amounted 0.80 and 0.97 respectively. LSGBs taken by or on the request of the departments of Rheumatology or Internal Medicine had a significant higher yield compared to LSGBs taken in other clinical departments. Conclusions: The LSGB may play a role in the diagnostic procedure of Sjögren’s syndrome when using either the AECG classification or the ACR classification. A LSGB should preferably taken after counseling for the possible presence of SS by a department of Rheumatology or Internal Medicine since the yield of such biopsies is much higher than in patients who have not been counseled by these departments prior to the taking of a LSGB. When using the ACR classification, a positive serologic result and a positive ocular test make the taking of a LSGB redundant. Only in case of a negative serologic outcome or a negative result of the ocular test a LSGB is indicated. Since both the serologic test and the ocular test carry hardly any morbidity, these tests should, indeed, be performed first before considering to take a LSGB. Key words:Labial salivary gland biopsy, Sjögren’s syndrome.

Primary and secondary surveys on epidemiology of Sjögren's syndrome in Japan

Objective. To characterize the epidemiology of Sjögren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan.Methods. The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments.Results. The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 ± 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American–European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%).Conclusion. The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan.

FRI0448 Evaluating health status of 620 patients with primary sjÖgren’s syndrome using EQ-5D

BackgroundEQ-5D is a standardised tool for measurement of health status and is an increasingly popular health-related quality of life instrument but has not been applied to patients with primary Sjögren’s...

SP0113 Primary SjöGren’s Syndrome: What is New in 2012 to 2013? (Win)

The last year, significant progress has been made in the diagnostics, evaluation and treatment of primary Sjögren’s syndrome (pSS). The progress in the various areas will be discussed in detail.With...

CXC ligand 13 in rheumatoid arthritis and its relation to secondary Sjögren’s syndrome

Aim of the workThe aim of the present study was to measure the level of the chemokine CXC ligand 13 protein (CXCL13) in the plasma and unstimulated saliva of rheumatoid arthritis (RA) patients in order to find out its role in the disease activity and its relation to secondary Sjögren’s syndrome (sSS). Patients and methodsThe study was conducted on thirty rheumatoid arthritis patients attending the Outpatient Clinic of Rheumatology and Rehabilitation department of Ain shams University Hospitals. The patients’ group had been classified into group (1) which included fifteen RA patients associated with sSS diagnosed according to the American–European Consensus Group Classification Criteria and group (2) which included fifteen RA patients not associated with sSS. Ten healthy subjects were included as a control group. Patients were subjected to full history taking, clinical examination, and laboratory detection of CXCL13 level in the plasma and saliva of patients as well as the control groups using ELISA technique. Assessment of disease activity in RA patients was done using the disease activity score (DAS28). ResultsPlasma levels of CXCL13 were significantly higher in RA patients than control group (p<0.001). Plasma levels of CXCL13 were significantly correlated with the RA disease activity (r=0.677, p<0.001) and disease duration (r=0.406, p<0.05), while the salivary levels were higher in those with sSS and correlated with sSS disease duration (r=0.536, p<0.05). A highly significant correlation was found between salivary CXCL13 and severity of sSS (r=0.816, p<0.001). Salivary levels of CXCL13 above 110pg/ml may diagnose sSS with sensitivity 80% and specificity 84%. ConclusionThe results of this preliminary study point out the importance of CXCL13 as a marker for RA disease activity, its role in diagnosing sSS, and estimation of sSS severity.

Validation of different sets of criteria for the diagnosis of Sjögren’s syndrome in Japanese patients

Objective: To validate the revised Japanese Ministry of Health criteria for the diagnosis of Sjögren’s syndrome (SS) (JPN) (1999), The American-European Consensus Group classification criteria for SS (AECG) (2002), and American College of Rheumatology classification criteria for SS (ACR) (2012).Methods: The study subjects were 694 patients with SS or suspected SS who were followed-up in June 2012 at ten hospitals that form part of the Research Team for Autoimmune Diseases, The Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW). All patients had been checked for all four criteria of the JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). We studied the clinical diagnosis made by the physician in charge and the satisfaction of the above criteria.Results: Of the 694 patients, 499 patients did not have other connective tissue diseases (CTDs). SS was diagnosed in 476 patients (primary SS in 302, secondary SS in 174), whereas non-SS was diagnosed in 218 patients (without other CTDs in 197, with other CTDs in 21) by the physician in charge. The sensitivities of JPN, AECG, and ACR in the diagnosis of all forms of SS (both primary and secondary SS) were 79.6, 78.6, and 77.5 %, respectively, with respective specificities of 90.4, 90.4, and 83.5 %. The sensitivities of the same systems in the diagnosis of primary SS were 82.1, 83.1, and 79.1 %, respectively, with specificities of 90.9, 90.9, and 84.8 %, respectively. The sensitivities of the same systems in the diagnosis of secondary SS were 75.3, 70.7, and 74.7 %, respectively, with specificities of 85.7, 85.7, and 71.4 %, respectively.Conclusion: The sensitivity of JPN to all forms of SS and secondary SS, the sensitivity of AECG to primary SS, and the specificities of JPN and AECG for all forms of SS, primary SS, and secondary SS were highest in the diagnosis of SS in Japanese patients. These results indicate that the JPN criteria for the diagnosis of SS in Japanese patients are superior to ACR and AECG.

Sjögren’s Syndrome in Older Patients

Sjögren's syndrome (SS) is a systemic autoimmune disease, characterized by chronic inflammation of exocrine glands that results in development of xerostomia and keratoconjunctivitis sicca. The disease activity of SS is not restricted to exocrine glands, and many other organs and organ systems can be involved. Diagnosis of SS in the elderly population can be challenging because xerostomia, dry eyes, symptoms of fatigue, weight loss and muscle pain are also common features of old age. Delay between clinical onset and diagnosis of SS in the elderly may be due to the shared features of SS and old age. The 2002 revised American-European Consensus Group (AECG) classification criteria for SS are the preferred tool used to confirm diagnosis of SS, but recently alternative criteria have been put forward by the American College of Rheumatology (ACR). The AECG criteria set combines subjective symptoms of dry eyes and dry mouth with objective signs of keratoconjunctivitis sicca, salivary gland dysfunction and histopathological (salivary gland biopsy) and serological (autoantibodies against SSA/Ro and SSB/La antigens) features. Treatment of SS in the elderly does not differ from that in younger patients. The aims of the treatment of SS are to control glandular and extraglandular manifestations, to prevent damage to organ systems and loss of function, and to decrease morbidity and mortality. Treatment of the elderly can be complicated by co-morbidities, an increased rate of adverse events related to therapeutic agents, and polypharmacy. Therefore, careful follow-up of the treatment is required.

Validation of different sets of criteria for the diagnosis of Sjögren’s syndrome in Japanese patients

To validate the revised Japanese Ministry of Health criteria for the diagnosis of Sjögren's syndrome (SS) (JPN) (1999), The American-European Consensus Group classification criteria for SS (AECG) (2002), and American College of Rheumatology classification criteria for SS (ACR) (2012). The study subjects were 694 patients with SS or suspected SS who were followed-up in June 2012 at ten hospitals that form part of the Research Team for Autoimmune Diseases, The Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW). All patients had been checked for all four criteria of the JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). We studied the clinical diagnosis made by the physician in charge and the satisfaction of the above criteria. Of the 694 patients, 499 patients did not have other connective tissue diseases (CTDs). SS was diagnosed in 476 patients (primary SS in 302, secondary SS in 174), whereas non-SS was diagnosed in 218 patients (without other CTDs in 197, with other CTDs in 21) by the physician in charge. The sensitivities of JPN, AECG, and ACR in the diagnosis of all forms of SS (both primary and secondary SS) were 79.6, 78.6, and 77.5%, respectively, with respective specificities of 90.4, 90.4, and 83.5%. The sensitivities of the same systems in the diagnosis of primary SS were 82.1, 83.1, and 79.1%, respectively, with specificities of 90.9, 90.9, and 84.8%, respectively. The sensitivities of the same systems in the diagnosis of secondary SS were 75.3, 70.7, and 74.7%, respectively, with specificities of 85.7, 85.7, and 71.4%, respectively. The sensitivity of JPN to all forms of SS and secondary SS, the sensitivity of AECG to primary SS, and the specificities of JPN and AECG for all forms of SS, primary SS, and secondary SS were highest in the diagnosis of SS in Japanese patients. These results indicate that the JPN criteria for the diagnosis of SS in Japanese patients are superior to ACR and AECG.

Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: Toward new diagnostic criteria?

To determine the accuracy of salivary gland ultrasonography (SGUS) for diagnosing primary Sjögren's syndrome (SS) and to suggest modifications of the American-European Consensus Group (AECG) classification criteria. We conducted a cross-sectional study in a prospective cohort of patients with suspected primary SS that was established between 2006 and 2011. The echostructure of the bilateral parotid and submandibular glands was graded from 0 to 4, and the gland size was measured; blood flow to the parotid gland was assessed using Doppler waveform analysis. The reference standard was a clinical diagnosis of primary SS as determined by a group of experts blinded to the results of SGUS. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic value of the 0-4-point echostructure grade for each of the 4 major salivary glands, the sum of the grades for the 4 glands, and the highest grade among the 4 glands. Of the 158 patients in the study, 78 had a diagnosis of primary SS according to the experts, including 61 patients (78.2%) who met the AECG criteria. Doppler waveform analysis and gland size measurement showed poor diagnostic performance. The results of ROC curve analysis showed that the highest grade among the 4 glands provided the best diagnostic value. The optimal grade cutoff was 2 (62.8% sensitivity and 95.0% specificity). A weighted score was constructed using scores for the 5 variables selected by logistic regression analysis, as follows: (salivary flow×1.5)+(Schirmer's test×1.5)+(salivary gland biopsy×3)+(SSA/SSB×4.5)+(SGUS×2). According to ROC curve analysis, a score of ≥5 of 12.5 had 85.7% sensitivity and 94.9% specificity, compared with 77.9% sensitivity and 98.7% specificity for the AECG criteria. The addition of SGUS to the AECG criteria increased sensitivity to 87.0% but did not change specificity. Modifications of the AECG criteria, including the addition of a SGUS score, notably improved diagnostic performance.

American College of Rheumatology classification criteria for Sjögren's syndrome: A data‐driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance Cohort

We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American–European Consensus Group (AECG) criteria, a model-based “gold standard”obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Clinical efficacy of the smartplug™ in the treatment of primary Sjogren’s syndrome with keratoconjunctivitis SICCA: one-year follow-up study

To evaluate the efficacy of a thermo-sensitive punctum plug, (SmartPlug™) in Primary Sjogren's Syndrome (pSS) patients with dry eyes, whose symptoms persist despite preservative-free artificial tear treatment. In this study, 22 Primary Sjögren's Syndrome (pSS), as defined by American-European Consensus Group Classification Criteria. All patients being followed up by Ege University Departments of Rheumatology and Ophthalmology. The patients had positive Schirmer test results (<5 mm without anesthesia). SmartPlug™ (Medennium, Irvine, California, USA) was inserted into the inferior lacrimal canaliculi of both eyes. Visual acuity measurements, Schirmer I test measurements, lissamine green staining scores, and tear-film breakup times (BUT) were noted before plug insertion and at the 1st, 6th, and 12th months following the procedure. Minimum follow-up period was 6 months for 19 patients and 12 months for 16 patients. Significant improvements were seen in the Schirmer I test scores (before insertion: 1.98 ± 2.67; 1st month: 5.68 ± 6.69; 6th month: 5.35 ± 5.38; 12th month 6.43 ± 5.14 P = 0.006), tear-film BUT in seconds (before insertion: 4.64 ± 3.7; 1st month: 5.80 ± 2.36; 6th month: 7.53 ± 2.92; 12th month 7.50 ± 2.52, P < 0.0001), respectively. Thermodynamic punctum plug insertion only in inferior canaliculus is a simple, effective, and comfortable option for treatment of severe aqueous tear deficiency that cannot be controlled using preservative-free tears.

A single centre retrospective analysis of AECG classification criteria for primary Sjogren's syndrome based on 112 minor salivary gland biopsies in a Japanese population

To assess the usefulness and performance of the American European Consensus Group (AECG) criteria based on minor salivary gland biopsy (MSGB) in Japanese patients with primary SS. Among 208 MSGB cases, we retrospectively selected 112 subjects who satisfied the complete set of AECG classification criteria. Of the 112 subjects studied, 63 primary SS patients and 49 non-SS group subjects were classified according to the AECG criteria. The contribution of subjective and objective components was statistically analysed. Sex, dry eye, Saxon test, Schirmer's test, anti-SSA/Ro antibody, MSGB grading and sialography statistically contributed to the diagnosis. Multiple logistic regression analysis showed that positive MSGB [odds ratio (OR) 105; 95% CI 13, 849), positive anti-SSA/Ro antibody (OR 96; 95% CI 10, 923), a positive Saxon test (OR 46; 95% CI, 6, 340) and the existence of dry eye (OR 8, 95% CI 2, 43) were associated with the diagnosis of primary SS. Among the components of the AECG criteria, MSGB and anti-SSA/Ro antibody were very strong contributors. Furthermore, the abnormal-finding positive rate in sialography significantly correlated with MSGB grading (P-value for trend = 0.0006), although other subjective and objective components were not associated with MSGB grading. The usefulness of the AECG criteria for Japanese primary SS patients was confirmed.

Diagnostic evaluation and classification criteria in Sjögren's Syndrome

Objectives Our objective is to carry out a clinical study of the performance of the preliminary European classification criteria for Sjögren Syndrome and that of the criteria proposed by the American European Consensus Group. Methods Eighty-eight patients who had undergone a biopsy of the salivary gland on suspicion that they were suffering from Sjögren Syndrome were studied by two independent rheumatologists. Two pathologists independently revised the biopsies without knowing the diagnosis. With all of this information, the clinicians established, or did not establish, a diagnosis of primary Sjögren Syndrome or secondary Sjögren Syndrome. Finally, it was analysed whether or not the patients met the American European Consensus Group classification criteria and the preliminary European criteria for primary Sjögren Syndrome and secondary Sjögren Syndrome, and their sensitivity and specificity with respect to the clinical diagnosis were determined. Results Clinicians estimated that 35 cases (39.8%) had primary Sjögren Syndrome (kappa 0.718) and 17 cases (19.3%) had secondary Sjögren Syndrome (kappa 0.761). The specificity and sensitivity of American European Consensus Group criteria, with regard to the clinical diagnosis, for primary Sjögren Syndrome were 97.2% and 48.6%, respectively. For secondary Sjögren Syndrome, the specificity was 97.2% and the sensitivity 64.7%. The preliminary European criteria for primary Sjögren Syndrome demonstrated a lesser specificity (75%), but a higher sensitivity (65.7%). In secondary Sjögren Syndrome the specificity reached 97.2% with sensitivity at 70.6%. Conclusions These results underline the difficulty in applying the Sjögren Syndrome classification criteria from the American European Consensus Group and the preliminary European criteria, in the diagnosis of individual patients.

Multilevel examination of minor salivary gland biopsy for Sjögren's syndrome significantly improves diagnostic performance of AECG classification criteria

The recently observed low reproducibility of focus score (FS) assessment at different section depths in a series of single minor salivary gland biopsies highlighted the need for a standardized protocol of extensive histopathological examination of such biopsies in Sjögren's syndrome. For this purpose, a cumulative focus score (cFS) was evaluated on three slides cut at 200-μm intervals from each of a series of 120 salivary biopsies. The cFS was substituted for the baseline FS in the American–European Consensus Group (AECG) criteria set for Sjögren's syndrome classification, and then test specificity and sensitivity were assessed against clinical patient re-evaluation. Test performances of the AECG classification with the original FS and the score obtained after multilevel examination were statistically compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance of AECG classification significantly improved when the cFS was entered in the AECG classification; the improvement was mostly due to increased specificity in biopsies with a baseline FS ≥ 1 but <2. The assessment of a cFS obtained at three different section levels on minor salivary gland biopsies can be useful especially in biopsies with baseline FSs between 1 and 2.