Multicenter cross-sectional study on 97 patients with clinical sicca symptoms. The pSS (n = 22) met the American-European Consensus Group (AECG) classification criteria. The control patients (n = 36) with sicca symptoms did not fulfill the AECG criteria. Four scores were used to evaluate the 4 major salivary gland echostructure: the Salaffi score (0–16), Jousse-Joulin score (0–4), Hocevar score (0–48) and Milic score (0–12).
Results
The medians of ultrasonographic (US) scores were higher in the pSS and sSS groups than in the control group (P < 0.001). The receiver-operating characteristic (ROC) curves and the positive likelihood ratio (LR+) of the four scores showed a good diagnostic performance for the US diagnosis of pSS and sSS. Respectively, for pSS and sSS, the AUC were 0.891 (95%CI 0.812–0.970) and 0.824 (95%CI 0.695–0.954) for Hocevar score, 0.885 (95%CI 0.804–0.965) and 0.808 (95%CI 0.673–0.943) for Milic score, 0.915 (95%CI 0.848–0.982) and 0.844 (95%CI 0.724–0.965) for Salaffi score, 0.897 (95%CI 0.821–0.973) and 0.851 (95%CI 0.735–0.968) for Jousse-Joulin score. This study showed an interesting inter-observer reproducibility (kappa = 0.714 ± 0.131) of the US evaluation with 85.7% agreement between reader to determine the pathological character of the salivary glands.
Conclusion
Salivary gland US is a simple, non-invasive and performant imaging procedure for the diagnosis of pSS and sSS, with Salaffi, Milic and Jousse-Joulin scores.
Introduction
The primary Sjögren's Syndrome (pSS) is a chronic autoimmune disease. It is characterized by a lymphocytic infiltration and destruction of the salivary and lacrimal glands, which causes dryness of the eyes (xerophthalmia) and mouth (xerostomia) by loss of glandular functions. Asthenia, inflammatory arthralgia often complete this clinical background. Almost a third of patients have systemic involvement with pulmonary, renal, neurologic, rheumatologic, vascular or lymphatic disorders. The pSS is the systemic disease for which the incidence of non-Hodgkin's Lymphoma (NHL) is the highest [1], [2]. Biologically, anti-SSA/SSB antibodies are the most specific markers, but are present in only 50% to 75% of pSS diagnostics. The anti-nuclear antibodies present in 80% of pSS and the rheumatoid factors in 40% to 75% of pSS, are non-specific and can be found in other systemic autoimmune diseases [3], [4], [5]. The Sjögren's Syndrome is considered secondary (sSS) when associated with other connective tissue disease.
Like other systemic diseases, there is no single and specific diagnostic test. The diagnosis of the Sjögren's syndrome is based on a range of clinical, biological, morphological and histological symptoms. The most widely used classification criteria were proposed by the American-European Consensus Group (AECG) in 2002 [6]. They are used to define and standardize the diagnosis of primary and secondary SS. Among these criteria, parotid sialography and salivary gland scintigraphy are morphological examinations that are now rarely used in clinical practice, because of the radiating character of sialography and the low specificity of scintigraphy [7]. The ultrasonography (US) appears to be an attractive imaging approach by its non-invasive, inexpensive, non-irradiating and accessible technique. It allows also morphologic evaluation. Major salivary gland US (2 parotid and 2 submandibular glands) has been developed over the past 20 years. Several studies have shown that it provides similar information to sialography while being considerably less invasive [7], [8]. MRI showed a high diagnostic performance [9], [10], [11] with good correlation between parotid MRI and salivary gland US (kappa agreement = 0.87) [9]. However, its lack of availability and its high cost does not allow its use for diagnostic purpose, but rather for the exploration of a suspicious glandular lesion.
With US B mode, the most specific pathogenic characteristic in SS is the inhomogeneity of the glandular parenchyma. Since the first proposal of US score made in 1992 by De Vita et al. [12], several US scores have been proposed with different items: gland size, contour regularity, clearness of the posterior glandular border, presence of hypoechogenic zones, echogenic bands and size of the cysts. The lack of consensual score for SS diagnosis is therefore one of the first limits for the use of salivary gland US in clinical practice. In another hand, few studies have evaluated this imaging method for sSS diagnosis. Finally, the main disadvantage of US is its operator-dependent character, with currently little data on its inter- and intra-observer reproducibility.
Our objective was to compare the performance of four scoring methods for the diagnosis of pSS and sSS, and to evaluate inter and intra-observer reproducibility of salivary gland US.
Section snippets
Methods
This is a multicentre, cross-sectional observational study carried out in three French university hospitals (Rennes, Tours and Fort-de-France).
Characteristics of the studied population
Five patients were excluded (3 patients were not at US appointment, 1 patient did not have the questionnaire, 1 patient died). Ultimately, 97 patients were included for the analysis. Thirty-nine of them met the AECG criteria for the diagnosis of pSS and 22 patients met the AECG criteria for the diagnosis of sSS (9 patients with systemic lupus, 9 with rheumatoid arthritis, 2 with systemic scleroderma and 2 with Sharp syndrome). There were 36 control patients with sicca symptoms who did not
Discussion
Our study confirms the high diagnostic performance of salivary gland US to discriminate pSS, sSS and symptomatic control patients with 3 US scores (Milic, Salaffi, and Jousse-Joulin). The medians of the scores were significantly higher in the pSS and sSS groups than in the control group. The Milic, Salaffi and Jousse-Joulin scores were significant and clinically relevant (LR+ > 11.0) for the diagnosis of pSS. The LR + was also greater than 11 with the Milic and Salaffi scores for the diagnosis
Contributorship
All listed authors have had substantial contributions in the acquisition, analysis, and interpretation of data for the work; they were involved in revising it critically and give final approval for the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgments
The authors would like to thank the patients who participated in the study and the Doctor Christophe Boulnois for his proofreading and translation work in the English language.
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Patients with primary Sjögren's syndrome (pSS) take a higher risk of developing lymphoma, which is the most frequent cause of death in pSS. Based on this situation, the number of publications focusing on pSS-associated lymphoma has been growing. Nevertheless, the extent, range, and nature of available research in this field have not been systematically summarized. This study aimed to map the literature available on pSS-associated lymphoma and identify global hotspots and trends.
Papers on pSS and lymphoma published from 1991 to 2022 were searched from the Web of Science Core Collection. Microsoft Excel, SPSS Statistics, VOSviewer, and CiteSpace software were used to analyze and visualize the quantity and citations of publications, and the global research hotspots and trends of pSS-associated lymphoma.
629 publications from 50 countries/regions and 538 institutions were included in this study. From 1991 to 2022, the cumulative publications steadily increased. The USA ranked first in the number of publications (n = 118, 18.76 %), followed by Italy (n = 94, 14.94 %) and France (n = 73, 11.61 %). Udine University (n = 29) and Salvatore De Vita (n = 39) were the most prolific affiliation and author, respectively. Claudio Vitali was the most frequently cited author (n = 335). In total, the most frequently occurring keywords were clustered into four well-defined groups. The first group of keywords pointed to the clinical assessment and treatment of pSS-associated lymphoma. The second group highlighted the pathogenesis. The third group identified the predictors and prognosis of pSS-associated Lymphoma, while the fourth group focused on interstitial lung disease and pulmonary lymphoma in patients with pSS. Currently, the hot keywords include consensus, disease activity, and pathogenesis. Ultrasonography, mucosa-associated lymphoid tissue (MALT) lymphoma, and epidemiology are the emerging research trends in pSS-associated lymphoma.
Research on pSS-associated lymphoma is burgeoning. Despite clinical assessment, treatment and pathogenesis, researchers also showed great interest in the predictors, prognosis, and pulmonary manifestations of pSS-associated lymphoma. Current research of pSS-associated lymphoma mainly focuses on consensus, disease activity, and pathogenesis, while the emerging research trends in pSS are pointing to ultrasonography, MALT lymphoma and epidemiology.
Évaluer l’atteinte des glandes salivaires (GS) chez les patients atteints de sclérodermie systémique (ScS) par échographie des glandes salivaires (SGUS).
Des patients présentant une ScS (n = 62), un syndrome de Gougerot-Sjögren primitif (SGSp) (n = 59) et un syndrome sec idiopathique (n = 43) ont été évalués à l’aide du système de classification SGUS défini par l’OMERACT (Outcome Measures in Rheumatology Clinical Trial). Ont également été évalués les bandes hyperéchogènes par un système de notation de 0 à 3, le signal doppler Puissance (DP) intraglandulaire et le volume des GS.
La proportion de patients ayant un score OMERACT maximal (≥ 2) parmi les quatre GS était significativement plus importante dans les groupes ScS (51,6 %) et SGSp (62,7 %) que dans le groupe syndrome sec idiopathique (4,7 %). Les patients présentant une ScS ou un SGSp avaient des scores totaux de fibrose plus élevés que les témoins. Aucune différence n’a été observée entre les groupes ScS et SGSp concernant les scores de fibrose. Les scores DP des GS étaient plus élevés dans le groupe ScS que dans le groupe syndrome sec idiopathique. Il n’y avait pas de différence de volume des GS entre les groupes. Chez les patients atteints de ScS, les anticorps anti-centromères (ACA) étaient plus fréquents lorsque les scores SGUS étaient ≥ 2 que pour les scores de 0 et 1 (65,6 % contre 30,0 %). De même, les symptômes secs étaient plus fréquents chez les patients atteints de ScS ayant un score de fibrose ≥ 2 que lorsque le score de fibrose était de 0 ou 1. L’hétérogénéité et les bandes hyperéchogènes dans les GS n’ont pas été associées à l’atteinte d’organes dans la ScS.
Une atteinte des GS a été observée chez plus de la moitié des patients présentant une ScS, en particulier avec ACA. La fibrose des GS était plus marquée dans la ScS que dans le syndrome sec idiopathique et a été associée à des symptômes secs subjectifs. Toutefois, la présence de bandes hyperéchogènes dans les GS ne permet pas de différencier la ScS du SGSp.
Évaluer les caractéristiques échographiques des glandes salivaires (EGS), cliniques et biologiques dans le syndrome de Gougerot-Sjögren primitif (SGSp) du sujet âgé.
Nous avons inclus pendant une période de plus de 4 ans, des patients porteurs d’un SGSp issus de deux hôpitaux universitaires. Le score EGS (0–48) et le volume des GS ont été évalués. Les données cliniques, biologiques et EGS ont été comparées selon l’âge de début de la maladie : SGSp du sujet âgé (≥65 ans), SGSp du sujet adulte (≥40 et < 65 ans) et SGSp du sujet jeune (<40 ans).
Cette étude transversale incluait un total de 221 patients, parmi lesquels 43 (19,5 %) étaient porteurs d’un SGSp du sujet âgé. Les symptômes subjectifs de sécheresse, les résultats du test de Schirmer et le débit salivaire non stimulé n’ont pas révélé de différences significatives entre les groupes. Les pneumopathies interstitielles diffuses (PID) étaient plus fréquentes dans le groupe SGSp du sujet âgé (SGSp sujet âgé : 51,2 % vs. SGSp du sujet adulte : 13,5 % vs. SGSp du sujet jeune : 8,7 %, p < 0,001) et l’arthrite moins fréquente dans ce même groupe (7 % vs. 22,6 % vs. 39,1 %, p < 0,01). Le groupe SGSp du sujet âgé a rapporté une positivité des anticorps anti-SSA/Ro (51,2 %) et anti-SSB/La (7,0 %) significativement plus faible et des taux de facteur rhumatoïde, de C4, et d’IgG inférieurs. Nous avons également retrouvé dans le groupe SGSp du sujet âgé une plus faible positivité de l’EGS (définie par un score total ≥ 14) (44,2 % vs. 64,5 % vs. 78,3 %, p < 0,05), des scores EGS plus bas et un plus petit volume des glandes salivaires submandibulaires.
Nous rapportons un phénotype spécifique de SGSp du sujet âgé caractérisé par une forte prévalence de PID, une atteinte moins marquée des articulations périphériques et une faible activité biologique. L’évaluation EGS a mis en évidence un nombre moins élevé d’anomalies du parenchyme glandulaire mais des modifications atrophiques plus marquées des GS majeures chez les patients du groupe SGSp du sujet âgé. Si l’on considère la faible positivité des anticorps anti-SSA/Ro et de l’EGS dans le groupe SGSp du sujet âgé, la biopsie des GS reste la seule méthode efficace pour confirmer le diagnostic de SGSp, en particulier chez les patients âgés.
SGUS has been proposed as an addition to or replacement for other diagnostic tests in the most recent SD criteria.54 Although most studies on SGUS involve primary SD, SGUS also has been used successfully in diagnosis of nonprimary SD51 and pedSD.13,15 Salivary scintigraphy, a radiolabeled functional test, can show delayed or absent isotope uptake and secretion in SD.55
Salivary gland ultrasonography (SGUS) has been proven to be an effective imaging tool for visualising structural abnormalities in major salivary glands. The investigation of the severity of salivary glandular involvement is now feasible using SGUS [11,12]. In addition, SGUS can provide volumetric information and intra-glandular vascularisation [13–15].
To assess the clinical, laboratory, and salivary gland ultrasound (SGUS) characteristics of elderly-onset of primary Sjögren's syndrome (EopSS).
We included pSS patient from two referral hospitals over a 4-year period. The SGUS scores (0–48) and SG volumes were assessed. Clinical, laboratory, and SGUS data were compared according to age at onset: EopSS (≥ 65 years), adult-onset (AopSS) (≥ 40 and < 65 years), and young-onset (YopSS) (< 40 years).
This cross-sectional study included a total of 221 patients, 43 (19.5%) of which had EopSS. Subjective sicca symptoms, results of the Schirmer's test, and unstimulated salivary flow rate revealed no significant differences between the groups. EopSS patients presented a significantly higher frequency of interstitial lung disease (ILD) (EopSS: 51.2% vs. AopSS: 13.5% vs. YopSS: 8.7%, P < 0.001) and lower frequency of arthritis (7% vs. 22.6% vs. 39.1%, P < 0.01). They also had significantly lower positivity of anti-Ro/SSA (51.2%) and anti-La/SSB (7.0%) and lower levels of rheumatoid factor, C4, and IgG. The EopSS group had significantly lower SGUS positivity (defined as total scores ≥ 14) (44.2% vs. 64.5% vs. 78.3%, P < 0.05), lower SGUS scores, and smaller submandibular gland volume.
We report a specific phenotype of EopSS, characterised by high prevalence of ILD, less involvement of the peripheral joint, and low biological activity. SGUS evaluation showed less parenchymal abnormalities but more atrophic changes in major SGs in EopSS patients. Considering the low positivity of anti-Ro/SSA and SGUS in EopSS, SG biopsy remains the only way to confirm the diagnosis of pSS, especially in elderly patients.
La ecografía es una técnica de imagen no invasiva, inocua, reproducible y coste-eficiente, que aporta información inmediata al poder realizarla en nuestras consultas. El buen perfil de la técnica y los avances tecnológicos acontecidos en los últimos años, que han permitido una mejora sustancial en la resolución de la imagen hasta hacerla casi anatómica, han impulsado la investigación sobre su aplicación al estudio integral de las enfermedades inflamatorias sistémicas. En la actualidad, se ha traspasado el umbral de utilizar la ecografía para investigar exclusivamente las manifestaciones músculo-esqueléticas, para aplicarla también al estudio de las manifestaciones extraarticulares y las comorbilidades asociadas a las enfermedades reumáticas. En la presente revisión repasaremos su utilidad para el diagnóstico de la afectación glandular en el síndrome de Sjögren, la enfermedad pulmonar intersticial o la arteritis de células gigantes y para la estratificación del riesgo cardiovascular en pacientes con enfermedades reumáticas inflamatorias crónicas.
Ultrasound is a non-invasive, innocuous, reproducible, cost-efficient imaging technique that provides immediate information, as it can be performed in our consultations. The good profile of ultrasound and the technological advances that have taken place in recent years, which have allowed a substantial improvement in the resolution of the image to make it almost anatomical, have promoted research on its application in the comprehensive study of systemic inflammatory diseases. At present, the threshold of using ultrasound to exclusively investigate musculoskeletal manifestations has been crossed, to also apply it to the study of extra-articular manifestations and comorbidities associated with rheumatic diseases. In this review we will revise its usefulness for the diagnosis of glandular involvement in Sjögren's syndrome, interstitial lung disease or giant cell arteritis and for stratification of cardiovascular risk in patients with chronic inflammatory rheumatic diseases.
