Risk of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. A prospective cohort study.

INTRODUCTION/AIMS: Laboratory and clinical data suggest a link between neurologically mediated inflammation and psoriasis, but the risk and features of peripheral neuropathy in psoriasis or psoriatic arthritis remain unknown. The aim of this exploratory study was to evaluate the risk and to describe the features of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. METHODS: One hundred patients with psoriasis and/or psoriatic arthritis and 100 control subjects were consecutively enrolled. Diagnostic confirmation included electrophysiological examination, skin biopsy, and nerve ultrasound for confirmed polyneuropathy. RESULTS: Nine patients were diagnosed with confirmed polyneuropathy, while none of the control subjects had the condition (relative risk [RR] = 19.00, 95% confidence interval [CI] = 1.12-322.11). Specific relative risks for polyneuropathy were 22.09 (95% CI = 1.17-416.43) in psoriasis patients and 18.75 (95% CI = 1.07-327.62) in psoriatic arthritis patients. The observed polyneuropathy in all nine patients was length-dependent, symmetrical, and predominantly sensory, with minimal or no disability. Comorbidities and exposure to therapies known to increase the risk of polyneuropathy were more frequent in psoriasis and/or psoriatic arthritis patients compared to controls (42% vs. 4%, p = .0001). Analyzing data after excluding possible contributory causes, the risk of polyneuropathy in patients with psoriasis and/or psoriatic arthritis was not significant. DISCUSSION: Psoriasis and psoriatic arthritis appear to be associated with an increased risk of polyneuropathy. This increased risk seems to be linked to the higher prevalence of contributing factors for polyneuropathy, rather than a direct increase in neuropathy risk specifically related to psoriasis and psoriatic arthritis.

Tumor Necrosis Factor Alpha Inhibitors and Cardiovascular Risk in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an increased risk of cardiovascular events, due to the complex interplay between traditional and disease-related risk factors. Chronic inflammation and persistent disease activity are the key determinants of this risk, but despite great improvement in the disease management and prognosis, cardiovascular events are still the main cause of morbidity and mortality in RA cohorts1. In the last decades, the advent of new biological and targeted-synthetic DMARDs was accompanied by an improvement in disease activity control, but the role of each class of drugs on CVD risk is still a matter a debate. Since their approval for RA treatment, tumor necrosis factor alpha (TNFα) inhibitors have been widely investigated to better understand their effects on cardiovascular outcomes. The hypothesis that the reduction of chronic inflammation with any treatment may reduce the cardiovascular risk has been recently confuted by the direct comparison of TNFα-inhibitors and JAK inhibitors in patients with RA and coexisting risk factors for cardiovascular disease. The aim of this literature review is to add to the available evidence to analyze the relationship between TNFα-inhibitors and CVD risk in patients with RA and also provide some clinical scenarios to better explain the treatment dilemmas. In particular, while data on major cardiovascular events and thromboembolism seem consistent with an inflammation-mediated benefit with TNFα-inhibitors, there remain concerns about the use of this class of bDMARDs in patients with chronic heart failure.

Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study.

BACKGROUND: Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. METHODS: One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. RESULTS: At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.  At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p < 0.001) for DAPSA and 1.21 ± 0.97 (p < 0.001) for ASDAS-CRP. Thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naïve to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24. CONCLUSIONS: This is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months.

Safety of Janus Kinase Inhibitors: A Real-World Multicenter Retrospective Cohort Study.

OBJECTIVE: Oral Janus kinase inhibitors (JAKis) represent an effective strategy for rheumatoid arthritis (RA) treatment. A previous study supported that tofacitinib (TOF) is associated with higher incidence of cardiovascular (CV) and neoplastic events compared to tumor necrosis factor inhibitors. Given the apparent discrepancy between these data and real-world experience, we aimed to investigate the safety and efficacy of the available JAKis in a multicenter cohort. METHODS: We retrospectively evaluated patients with RA who ever received 1 JAKi (TOF, baricitinib [BAR], upadactinib [UPA], filgotinib [FIL]) from 4 tertiary care centers in Milan, Italy. Outcomes related to JAKi safety were recorded, particularly major CV events as well as adverse events of special interest (AESIs), which included serious infections, opportunistic infections, venous thromboembolism, herpes zoster infections, liver injury, malignancies, and deaths; retention rates were also calculated. Further analyses included patients fulfilling the risk factors suggested to influence TOF safety. RESULTS: Six hundred eighty-five patients were included and received BAR (48%), TOF (31%), UPA (14%), or FIL (7%) as first-line innovative treatment prior to a biologic. Of a total of 1137 patient-years of observation, we recorded 1 stroke and 123 (18%) AESIs, including 3 deaths, all a result of severe infections. Among patients with a higher CV risk, we observed a higher frequency of AESIs (23%). CONCLUSION: Our real-world data confirm that JAKis are effective and carry a low risk of AESIs, especially in patients who do not display CV risk factors at baseline. Our study could not identify differences between JAKis. Different safety profiles should be defined in larger prospective cohorts.

Effectiveness of SB4 Transition from Originator Etanercept in Rheumatoid Arthritis and Axial Spondyloarthritis: A Subgroup Analysis from the BENEFIT Study.

Objectives: The pan-European BENEFIT study of patients with stable rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who transitioned from reference etanercept to SB4 found no clinically meaningful changes in disease control after transition. The analysis aims to illustrate the peculiarities of the Italian cohort of patients compared with the whole population to provide a more real-life approach to the data for the Italian rheumatologists, ruling out possible local confounding factors. Methods: A prospective study for up to 6 months following transition was conducted. Outcome measures of interest include clinical characteristics at time of transition and disease activity scores (Disease Activity Score-28 [DAS28] for RA, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] for axSpA) over time and safety. Results: One-hundred and eleven subjects (out of the 557 in total enrolled in the study) were derived from 8 Italian sites, including 79 with RA and 32 with axSpA. In both cohorts, the efficacy was maintained at 3 months and 6 months from the transition to the biosimilar with no significant change in mean DAS28 and BASDAI scores: at the end of the 6 months of observation the mean DAS28 and BASDAI was similar to baseline (confidence interval [CI] -0.22, 0.22), while the mean variation of the BASDAI was -0.14. Of note, 100.0% (95% CI 89.1, 100.0) in the axSpA and 90.8% (95% CI 81.5, 95.5) in the RA cohort of patients continued to receive SB4 at month 6 (binary variable with 95% Clopper-Pearson CI). Conclusions: Italian patients with stable RA or axSpA who transitioned from originator Etanercept to SB4 maintained clinical response at 6 months post-transition. Both the cohorts are representative of typical patients with long-standing established diagnoses. Most of the patients transitioned to the same dose regimen of biosimilar as that received for the originator, and the regimen remained unchanged at 6 months, supporting the effectiveness of the transition.

Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases.

The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p < 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of >1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80−98, p < 0.0001). Moreover, in the seroconverted patients, a daily dose of >1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of >1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease.

Lymphocyte modulation by tofacitinib in patients with rheumatoid arthritis.

Tofacitinib is an oral small molecule targeting the intracellular Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways approved for the treatment of active rheumatoid arthritis (RA). We investigated the effects of tofacitinib on the response of RA lymphocytes to B and T cell collagen epitopes in their native and post-translationally modified forms. In particular, peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy subjects were cultured with type II collagen peptides (T261-273, B359-369, carT261-273, citB359-369) or with phorbol myristate acetate (PMA)/ionomycin/CD40L in the presence or absence of 100 nM tofacitinib for 20 h and analyzed by fluorescence activated cell sorter (FACS). Cultures without brefeldin A were used for cytokine supernatant enzyme-linked immunosorbent assay (ELISA) analysis. Tofacitinib down-regulated inflammatory cytokines by stimulated B [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] and T [interferon (IFN)-γ, IL-17 or TNF-α] cells in the short term, while a significant reduction of IL-17 and IL-6 levels in peripheral blood mononuclear cell (PBMC) supernatant was also observed. IL-10 was significantly reduced in collagen-stimulated B cells from patients with RA and increased in controls, thus mirroring an altered response to collagen self-epitopes in RA. Tofacitinib partially prevented the IL-10 down-modulation in RA B cells stimulated with collagen epitopes. In conclusion, the use of tofacitinib exerts a rapid regulatory effect on B cells from patients with RA following stimulation with collagen epitopes while not reducing inflammatory cytokine production by lymphocytes.

Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study.

OBJECTIVES: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. METHODS: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). RESULTS: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. CONCLUSIONS: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Utilisation patterns and clinical impact of the introduction of infliximab-biosimilar in Tuscany, Italy: real world evidence following the recommendation of switching for non-medical reasons.

OBJECTIVES: This study was aimed at assessing the impact of a non-medical recommendation on drug-utilisation patterns and clinical outcomes in a central Region of Italy (Tuscany). METHODS: We performed a pre-post study on data collected in Tuscan healthcare administrative databases. We included patients with diagnosis of rheumatoid arthritis, or psoriatic arthritis, or ankylosing spondylitis, or ulcerative colitis, or Crohn's disease, or psoriasis. The first analysis compared patients treated with infliximab on January 1st, 2013 (originator only available) to those on January 1st, 2016 (both originator and biosimilar available). The second analysis compared infliximab-originator users with infliximab-biosimilar ones. Adjusted odds ratios (OR) of persistence on treatment, Emergency Department (ED) admissions, hospitalisations and specialist visits were calculated. RESULTS: The first analysis included 606 patients and the second 434. In both analyses, we did not observe any significant difference in persistence. In the first analysis, the 2016 infliximab-originator cohort showed a significant association with the risk of having at least one ED admission (OR 1.54, 95% CI 1.02 to 2.31). A significant difference of accessing a specialist visit (more frequently rheumatologic) was observed in the 2016 cohort (OR 1.52, 95% CI 1.05 to 2.20). In the second analysis, the risk of having at least one hospitalisation decreased significantly in switchers to infliximab-biosimilar (OR 0.49, 95% CI 0.26 to 0.96). CONCLUSIONS: Our study showed no relevant changes in the clinical outcomes following the introduction of infliximab-biosimilar. The few observed differences observed can be explained mainly by a selective switching to infliximab-biosimilar in patients with lower burden of disease.

Advances in salivary gland ultrasonography in primary Sjögren's syndrome.

Salivary gland ultrasonography (US) has recently been re-discovered as a useful tool to assess salivary gland involvement in primary Sjögren's syndrome (SS). In this review, we discuss US of the major salivary glands in the diagnosis of primary SS and analyse the possible added value of inclusion in classification criteria. We review the literature concerning associations between US of the major salivary glands, salivary gland histology and serology, with the possibility that US may be of value in disease stratification. We also examine the possible utility for US to monitor patient response to therapy in both clinical research and standard clinical care.

Imaging in primary Sjögren's syndrome: the 'obsolete and the new'.

Primary Sjögren's syndrome (pSS) is a complex systemic autoimmune disease primarily characterised by a focal chronic inflammation of glandular parenchyma, with chronic and persistent involvement of major salivary gland remaining a key element of the disease. Indeed, classification criteria proposed for pSS have always included items for histological and/or imaging salivary gland assessment. Over time, the approach to the definition of glandular involvement in pSS is constantly evolving. In this review we will therefore illustrate the state of the art of imaging techniques in pSS, focusing on conventional and novel modalities and discussing their advantages, drawbacks and possible future developments.

Artificial neural networks help to identify disease subsets and to predict lymphoma in primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a complex chronic systemic disorder, for which specific and effective therapeutic interventions are still lacking. In this era of precision medicine, there is a clear need for a better definition of disease phenotypes to foster the research of novel specific biomarkers and new therapeutic targets. The main objectives of this work are: 1) to compare Auto Contractive Map (AutoCM), a data mining tool based on an artificial neural network (ANN) versus conventional Principal Component Analysis (PCA) in discriminating different pSS subsets and 2) to specifically focus on variables predictive of MALT-NHL development, assessing the previsional gain of the predictive models developed. METHODS: Out of a historic cohort of 850 patients, we selected 542 cases of pSS fulfilling the AECG criteria 2002. Thirty-seven variables were analysed including: patient demographics, glandular symptoms, systemic features, biological abnormalities and MALT-NHLs. AutoCM was used to compute the association of strength of each variable with all other variables in the dataset. PCA was applied to the same data set. RESULTS: Both PCA and AutoCM confirmed the associations between autoantibody positivity and several pSS clinical manifestations, highlighting the importance of serological biomarkers in pSS phenotyping. However, AutoCM allowed us to clearly distinguish pSS patients presenting with predominant glandular manifestations and no or mild extra-glandular features from those with a more severe clinical presentation. Out of 542 patients, we had 27 cases of MALT-NHLs. The AutoCM highlighted that, besides other traditional lymphoproliferative risk factors (i.e. salivary gland enlargement, low C4, leukocytopenia, cryoglobulins, monoclonal gammopathy, disease duration), rheumatoid factor was strongly associated to MALT-NHLs development. By applying data mining analysis, we obtained a predictive model characterised by a sensitivity of 92.5% and a specificity of 98%. If we restricted the analysis to the seven most significant variables, the sensitivity of the model was 96.2% and its specificity 96%. CONCLUSIONS: Our study has shed new light on the possibility of using novel tools to extract hidden, previously unknown and potentially useful information in complex diseases like pSS, facing the challenge of disease phenotyping as a prerequisite for discovering novel specific biomarkers and new therapeutic targets.

One year in review 2018: novelties in the treatment of rheumatoid arthritis.

The current approach to treatment of rheumatoid arthritis (RA) includes early and aggressive intervention aiming to reach early and persistent low disease activity and remission. New drugs have improved the therapeutic armamentarium of rheumatologists, providing new options for patients. Beyond these innovations, new evidence has improved the safety of therapies and provided tools for the optimisation of long-term management of RA. This paper reviews the most relevant studies published over the last year in the field of treatment of RA.

One year in review 2017: novelties in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic disease characterised by inflammation of the synovial tissue in joints, which can lead to joint destruction. The primary goal of the treatment is to control pain and inflammation, reduce joint damage and disability, and maintain or improve physical function and quality of life. The present review is aimed at providing a critical analysis of the recent literature on the novelties in the treatment of RA, with a particular focus on the most relevant studies published over the last year.

Salivary gland ultrasound abnormalities in primary Sjögren's syndrome: consensual US-SG core items definition and reliability.

OBJECTIVES: Ultrasonography (US) is sensitive for detecting echostructural abnormalities of the major salivary glands (SGs) in primary Sjögren's syndrome (pSS). Our objectives were to define selected US-SG echostructural abnormalities in pSS, set up a preliminary atlas of these definitions and evaluate the consensual definitions reliability in both static and acquisition US-SG images. METHODS: International experts in SG US in pSS participated in consensus meetings to select and define echostructural abnormalities in pSS. The US reliability of detecting these abnormalities was assessed using a two-step method. First 12 experts used a web-based standardised form to evaluate 60 static US-SG images. Intra observer and interobserver reliabilities were expressed in κ values. Second, five experts, who participated all throughout the study, evaluated US-SG acquisition interobserver reliability in pSS patients. RESULTS: Parotid glands (PGs) and submandibular glands (SMGs) intra observer US reliability on static images was substantial (κ > 0.60) for the two main reliable items (echogenicity and homogeneity) and for the advised pSS diagnosis. PG inter observer reliability was substantial for homogeneity. SMGs interobserver reliability was moderate for homogeneity (κ = 0.46) and fair for echogenicity (κ = 0.38). On acquisition images, PGs interobserver reliability was substantial (κ = 0.62) for echogenicity and moderate (κ = 0.52) for homogeneity. The advised pSS diagnosis reliability was substantial (κ = 0.66). SMGs interobserver reliability was fair (0.20< κ ≤ 0.40) for echogenicity and homogeneity and either slight or poor for all other US core items. CONCLUSION: This work identified two most reliable US-SG items (echogenicity and homogeneity) to be used by US-SG trained experts. US-PG interobserver reliability result for echogenicity is in line with diagnosis of pSS.

Cystatin S-a candidate biomarker for severity of submandibular gland involvement in Sjögren's syndrome.

Objectives: Salivary cystatin S is a defence protein mainly produced by submandibular glands and involved in innate oral immunity. This study aimed to verify whether cystatin S was diversely expressed in different disease subsets of primary Sjogren's syndrome (pSS) patients, defined on the basis of salivary flow [unstimulated salivary flow rate (USFR)], minor salivary gland (MSG) focus score and submandibular gland ultrasonography abnormalities. We also evaluated miR-126 and miR-335-5p expression in MSG biopsies to verify whether an aberrant regulation of cystatin S at the glandular level may influence its salivary expression. Methods: Forty pSS patients and 20 sex- and age-matched healthy volunteers were included. Salivary cystatin S levels were assessed by western blot analysis using a stain-free technology. The expression of miR-126, miR-335-5p and cystatin S was assessed by quantitative PCR in 15 MSG biopsies differing for USFR and MSG focus score. Results: We found that salivary cystatin S was significantly decreased in pSS patients vs healthy volunteers ( P = 0.000), especially in those with hyposalivation. A positive correlation was observed between cystatin S and USFR ( r = 0.75, P = 0.01). Salivary cystatin S was also significantly reduced in patients with a submandibular gland ultrasonography score ⩾2. The expression levels of miR-126 and miR-335-5P increased in inverse proportion with USFR. The mRNA of cystatin S did not change significantly, suggesting post-transcriptional regulation. Conclusion: Cystatin S emerged as a promising biomarker for pSS, strongly correlated with glandular dysfunction. An upregulation of miR-126 and miR-335-5P might be implicated in its expression.

Salivary Gland Ultrasonography in Sjögren's Syndrome: Clinical Usefulness and Future Perspectives.

In recent years, salivary gland ultrasonography (SGUS) has emerged as a promising tool for the diagnosis and prognostic stratification of patients with primary and secondary Sjögren's syndrome. Several studies have emphasized that salivary ultrasonography could be a highly specific tool for the diagnosis of the disease. However, before it can be used in daily clinical practice the SGUS procedure needs standardization and validation in larger disease-control groups. In this review we provide an update on the role of SGUS in the diagnostic algorithm of primary Sjögren's syndrome.

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

OBJECTIVE: Ultrasonography (US) is a sensitive tool in the diagnosis of major salivary gland abnormalities in primary Sjögren'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 Sjögren'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.