Sjogren's syndrome (SS), the ideal model to study autoimmunity and lymphoid malignancy, is a common chronic disease which in the last 30 years has been studied extensively on clinical and pathophysiological grounds. Clinical studies regarding kidney disease in SS patients have shown that the predominate lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one-fourth of SS patients suffer from subclinical, interstitial lung disease. Reevaluation, however, of the pulmonary disease, using functional, radiologic (including CT-scan), and histopathologic studies, revealed that the lesion starts peribronchially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the majority of extraglandular manifestations of SS are due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the protooncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients, by in situ hybridization, revealed that the mRNA of the proinflammatory cytokines IL-1 and IL-6 also comes from the epithelial cells. Finally, proviral DNA is incorporated in the DNA of epithelial cells. On the basis of these clinical and basic observations, we suggest that the major suffering cell in SS patients is the epithelium and thus we propose this descriptive term "autoimmune epithelitis" instead of "Sjogren's syndrome.

Sjogren's Syndrome: Autoimmune Epithelitis

Objective

To determine the accuracy of salivary gland ultrasonography (SGUS) for diagnosing primary Sjogren's syndrome (SS) and to suggest modifications of the American–European Consensus Group (AECG) classification criteria.



Methods

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.



Results

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.



Conclusion

Modifications of the AECG criteria, including the addition of a SGUS score, notably improved diagnostic performance.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.37698

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

Sjogren’s syndrome (SS) is a systemic progressive autoimmune disease characterized by a complex pathogenesis requiring a predisposing genetic background and involving immune cell activation and autoantibody production. The immune response is directed to the exocrine glands, causing the typical ‘sicca syndrome’, but major organ involvement is also often seen. The etiology of the disease is unknown. Infections could play a pivotal role: compared to normal subjects, patients with SS displayed higher titers of anti-Epstein-Barr virus (EBV) early antigens, but lower titers of other infectious agent antibodies such as rubella and cytomegalovirus (CMV) suggest that some infections may have a protective role against the development of autoimmune disease. Recent findings seem to show that low vitamin D levels in patients with SS could be associated with severe complications such as lymphoma and peripheral neuropathy. This could open new insights into the disease etiology. The current treatments for SS range from symptomatic therapies to systemic immunosuppressive drugs, especially B cell-targeted drugs in cases of organ involvement. Vitamin D supplementation may be an additional tool for optimization of SS treatment.

https://link.springer.com/content/pdf/10.1186%2F1741-7015-11-93.pdf

Novel aspects of Sjögren’s syndrome in 2012

Background and overview Xerostomia, also known as "dry mouth," is a common but frequently overlooked condition that is typically associated with salivary gland hypofunction, which is the objective measurement of reduced salivary flow. Patients with dry mouth exhibit symptoms of variable severity that are commonly attributed to medication use, chronic disease and medical treatment, such as radiotherapy to the head and neck region. Chronic xerostomia significantly increases the risk of experiencing dental caries, demineralization, tooth sensitivity, candidiasis and other oral diseases that may affect quality of life negatively. This article presents a multidisciplinary approach to the clinical management of xerostomia, consistent with the findings of published systematic reviews on this key clinical issue. Conclusions and practice implications Initial evaluation of patients with dry mouth should include a detailed health history to facilitate early detection and identify underlying causes. Comprehensive evaluation, diagnostic testing and periodic assessment of salivary flow, followed by corrective actions, may help prevent significant oral disease. A systematic approach to xerostomia management can facilitate interdisciplinary patient care, including collaboration with physicians regarding systemic conditions and medication use. Comprehensive management of xerostomia and hyposalivation should emphasize patient education and lifestyle modifications. It also should focus on various palliative and preventive measures, including pharmacological treatment with salivary stimulants, topical fluoride interventions and the use of sugar-free chewing gum to relieve dry-mouth symptoms and improve the patient's quality of life.

https://jada.ada.org/article/S0002-8177(14)60200-2/pdf

Managing xerostomia and salivary gland hypofunction: Executive summary of a report from the American Dental Association Council on Scientific Affairs

Objective. Ultrasonography (US) is a sensitive tool in the diagnosis of major salivary gland abnormalities in primary Sjogren's syndrome (pSS). The aim of this systematic review was to assess the metric properties of this technique. Methods. PUBMED and EMBASE databases were searched. All publications between January 1988 and January 2013 were considered. Data were extracted from the articles meeting the inclusion criteria according to US definition of salivary gland scoring system and metric properties studied. The type and number of glands tested, study design and metric properties according to OMERACT filter (truth, discrimination, feasibility) were assessed. Results. Of 167 publications identified initially with PUBMED and EMBASE, 31 met the inclusion criteria. The number of pSS patients varied among the studies from 16 to 140. The diagnosis of pSS was in line in most of the cases with the American-European Consensus Group (AECG) classification criteria for Sjogren's syndrome. The US examination was performed in suspected pSS only in studies in which the sensitivity ranged from 45.8 to 91.6% and specificity from 73 to 98.1%. There was heterogeneity in regard to the definition of US in B-mode and few studies used US in colour Doppler. Few studies reported reliability of US and sensitivity to change in pSS. Conclusion. US is a valuable tool for detecting salivary gland abnormalities in pSS. Its reliability has been poorly investigated and there is considerable variation in the definition of US abnormalities. Further studies are required to validate and standardize the US definition of salivary gland in pSS.

Is salivary gland ultrasonography a useful tool in Sjögren’s syndrome? A systematic review

(AUC-ROC) was employed to evaluate the screening method’s performance. Results. Of the 77 patients with pSS, 66 had abnormal US findings. Mean US score in pSS patients was 9.0 (range from 3 to 16). Subjects without confirmed pSS had the mean US score 3.9 (range from 0 to 9) (P 6U S resulted in the best ratio of sensitivity (75.3%) to specificity (83.5%), with a likelihood ratio of 4.58. If a threshold >8.0 was applied the test gained specificity, at the cost of a serious loss of sensitivity (sensitivity 54.5%, specificity 97.5%, likelihood ratio 21.5). Conclusions. Salivary gland US is a useful method in visualizing glandular structural changes in patients suspected of having pSS and it may represent a good option as a first-line imaging tool in the diagnostics of the disease.

/pdf/ultrasonography-of-salivary-glands-in-primary-sjogren-s-58hnb3p0j4.pdf

M. Maggi

Papers

Ultrasonography of salivary glands in primary Sjögren's syndrome: a comparison with contrast sialography and scintigraphy