Objective: To assess whether the addition of salivary gland ultrasonography (SGUS) or replacement of current criteria items by SGUS influences the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for primary Sjögren's syndrome.Methods: Included were consecutive patients with complete data on all ACR/EULAR items (n = 243) who underwent SGUS in our primary Sjögren's syndrome expertise center. Clinical diagnosis by the treating physician was used as the gold standard. Separate analyses were performed for patients who underwent labial or parotid gland biopsies. The average score for hypoechogenic areas in 1 parotid and 1 submandibular gland was determined (range 0–3). Next, performance of the ACR/EULAR criteria was evaluated after addition of SGUS or replacement of current items by SGUS.Results: Receiver operating characteristic analysis showed an optimal cutoff value of ≥1.5 for SGUS. The optimal weight for SGUS positivity was 1. Cutoff for ACR/EULAR fulfilment remained ≥4. In patients who underwent a labial gland biopsy (n = 124), the original criteria showed an area under the curve (AUC) of 0.965, sensitivity of 95.9%, and specificity of 92.2%. After the addition of SGUS, the AUC was 0.966, with a sensitivity of 97.3% and specificity of 90.2%. In patients who underwent a parotid gland biopsy (n = 198), similar results were found. Sensitivity of the criteria decreased substantially when SGUS replaced salivary gland biopsy or anti‐SSA antibodies, while performance remained equal when SGUS replaced the ocular staining score, Schirmer's test, or unstimulated whole saliva flow.Conclusion: Validity of the ACR/EULAR criteria remains high after incorporation of SGUS. With SGUS, clinicians are offered a larger array of tests to evaluate fulfillment of the ACR/EULAR criteria.

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction and lymphocytic infiltration of the salivary and lacrimal glands. Besides the characteristic sicca complaints, pSS patients can present a spectrum of signs and symptoms, which challenges the diagnostic process. Various imaging techniques can be used to assist in the diagnostic work-up and follow-up of pSS patients. Developments in imaging techniques provide new opportunities and perspectives. In this descriptive review, we discuss imaging techniques that are used in pSS with a focus on the salivary glands. The emphasis is on the contribution of these techniques to the diagnosis of pSS, their potential in assessing disease activity and disease progression in pSS, and their contribution to diagnosing and staging of pSS-associated lymphomas. Imaging findings of the salivary glands will be linked to histopathological changes in the salivary glands of pSS patients.

The involvement of salivary glands in primary SS (pSS) can be assessed in different ways: histopathology, salivary flow and ultrasonography. To understand the relative value of these different approaches, it is crucial to understand the relationship between them. As we routinely perform these three modalities in the parotid gland for disease evaluation, our aim was to investigate the construct validity between these modalities in one and the same gland. Consecutive sicca patients underwent a multidisciplinary diagnostic workup including parotid gland biopsy, collection of parotid gland–specific saliva and parotid gland ultrasonography. Patients who were classified as pSS according to the ACR-EULAR criteria were included. Construct validity was assessed using Spearman’s correlation coefficients. The 41 included pSS patients completed a full workup within a mean time interval of 2.6 months. Correlations between histopathological features and stimulated parotid salivary flow were fair (ρ = −0.123 for focus score and ρ = −0.259 for percentage of CD45⁺ infiltrate). Likewise, poor correlations were observed between stimulated parotid salivary flow and parotid ultrasonography (ρ = −0.196). Moderate to good associations were found between the histopathological items focus score and the percentage of CD45⁺ infiltrate, with parotid US scores (total US score: ρ = 0.510 and ρ = 0.560; highest for homogeneity: ρ = 0.574 and ρ = 0.633). Although pSS-associated ultrasonographic findings did correlate with histopathological features, the three modalities that evaluate salivary gland involvement assess different (or at best partly related) constructs. Therefore histopathology, salivary flow and ultrasonography are complementary measurements and cannot directly replace each other in the workup of pSS.

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. 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. 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. 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.

Objective: The aim of this study was to evaluate the diagnostic accuracy of the labial salivary gland biopsy based on multiple histopathological features in patients with suspected primary Sjögren syndrome (pSS).Methods: Patients from a diagnostic sicca cohort with clinically suspected pSS who underwent a labial gland biopsy were included. Patients were categorized as having pSS or non‐Sjögren syndrome sicca (non‐SS sicca) based on vignettes scored by an expert panel. Labial gland biopsies were analyzed for the presence of four histopathological features: focus score (FS) ≥1, prelymphoepithelial and lymphoepithelial lesions, immunoglobulin G plasma cell shift, and germinal centers. Sensitivity and specificity of histologic features were calculated, and the optimal cutoff value for the number of histopathological features needed to diagnose pSS was determined with receiver operating curve analysis.Results: A total of 38 patients were categorized as having pSS and 65 as having non‐SS sicca. In labial gland biopsies of patients with pSS, the prevalence of FS ≥1 was 82%, followed by 68% for pre‐lymphoepithelial and lymphoepithelial lesions, 63% for plasma cell shift, and 24% for germinal centers. Although FS ≥1 showed the highest sensitivity for patients with pSS (82%), specificity was higher for the other three features (98%–100%). The presence of two or more (of four) histopathological features had almost comparable sensitivity to FS alone, but specificity increased with 12% to 100%. For fulfillment of American College of Rheumatology/EULAR criteria, specificity increased from 84% to 95% when an abnormal biopsy was defined by the presence of two or more histopathological features instead of FS ≥1 only.Conclusion: The diagnostic accuracy of the labial gland biopsy increases when other histopathological features besides FS are taken into account, by reducing the number of false‐positive biopsies.

To assess the usefulness of [¹⁸F]-fluorodeoxyglucose (FDG)-PET/CT (i) to discriminate between primary SS (pSS) patients with and without lymphomas and (ii) to evaluate systemic disease activity in pSS. ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. Receiver operating characteristic curve analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma. Of the 70 included patients, 26 were diagnosed with a pSS-associated lymphoma, mostly of the mucosa-associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax > 3.1 and submandibular SUVmax > 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs. FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.