OMERACT International Consensus for Ultrasound Definitions of Tenosynovitis in Juvenile Idiopathic Arthritis: Systematic Literature Review and Delphi Process.

OBJECTIVE: Synovitis and tenosynovitis are present in juvenile idiopathic arthritis (JIA), both as joint pain and/or inflammation, making them difficult to detect on physical examination. Although ultrasonography (US) allows for discrimination of the 2 entities, only definitions and scoring of synovitis in children have been established. This study was undertaken to produce consensus-based US definitions of tenosynovitis in JIA. METHODS: A systematic literature search was performed. Selection criteria included studies focused on US definition and scoring systems for tenosynovitis in children, as well as US metric properties. Through a 2-step Delphi process, a panel of international US experts developed definitions for tenosynovitis components (step 1) and validated them by testing their applicability on US images of tenosynovitis in several age groups (step 2). A 5-point Likert scale was used to rate the level of agreement. RESULTS: A total of 14 studies were identified. Most used the US definitions developed for adults to define tenosynovitis in children. Construct validity was reported in 86% of articles using physical examination as a comparator. Few studies reported US reliability and responsiveness in JIA. In step 1, experts reached a strong group agreement (>86%) by applying adult definitions in children after one round. After 4 rounds of step 2, the final definitions were validated on all tendons and at all locations, except for biceps tenosynovitis in children <4 years old. CONCLUSION: The study shows that the definition of tenosynovitis used in adults is applicable to children with minimal modifications agreed upon through a Delphi process. Further studies are required to confirm our results.

Case report: Prader-Willi syndrome and inflammatory arthritis-An important consideration.

Background: Prader-Willi syndrome (PWS) is a multisystemic genetically determined disorder. Musculoskeletal manifestations are common in most patients. We report the cases of two children with PWS who developed inflammatory arthritis, complicated with chronic anterior bilateral uveitis in one case. To our knowledge, no previous reports of such an association exist. Case presentation: Case 1 was of a 3-year-old girl diagnosed with PWS who developed arthritis of the right knee with morning stiffness, joint swelling, and limited range of motion. Other causes of arthritis were ruled out. Increased inflammatory markers, antinuclear antibody (ANA) positivity, and hypertrophic synovitis on ultrasound confirmed the diagnosis of inflammatory arthritis compatible with juvenile idiopathic arthritis (JIA). Despite the treatment with methotrexate, arthritis progressed, and etanercept was added. The patient reached and maintained articular remission while on combined MTX and etanercept treatment during 9 years of follow-up. Case 2 was of a 6-year-old boy diagnosed with PWS who developed arthritis of the right knee. Laboratory investigations showed mildly increased acute phase reactants, microcytic anemia, and ANA positivity at high titer (titer 1:1,280). Infectious and other causes of arthritis were excluded. Ultrasound confirmed the presence of joint effusion and synovial thickening, and synovial fluid analysis was consistent with inflammatory arthrosynovitis (white blood cell count of 14,200/µl) compatible with JIA. Shortly after the diagnosis, the ophthalmologic evaluation revealed the presence of bilateral anterior uveitis. Despite MTX and topical corticosteroid, ocular inflammation persisted and adalimumab was added. At the last follow-up, 9 months later, the child experienced inactivity of arthritis and uveitis with normal growth. Conclusions: We aim to raise awareness of this possible association among pediatricians since arthritis might be underestimated due to high pain tolerance, behavioral disturbances, and other musculoskeletal abnormalities in PWS patients.

Prevalence of Sarcopenia in Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

An association between knee osteoarthritis (OA) and sarcopenia has been proposed, but the evidence is controversial, with the recent literature showing disparate results. Therefore, we aimed to perform a systematic review and meta-analysis to evaluate the prevalence of sarcopenia in knee OA patients compared to people not affected by this condition. We searched several databases until 22 February 2022. The data regarding prevalence were summarized using odds ratios (ORs) with their 95% confidence intervals (CIs). Among the 504 papers initially screened, 4 were included for a total of 7495 participants with a mean age of 68.4 years, who were mainly females (72.4%). The prevalence of sarcopenia in people with knee OA was 45.2%, whilst, in the controls, it was 31.2%. Pooling the data of the studies included that the prevalence of sarcopenia in knee OA was more than two times higher than in the control group (OR = 2.07; 95%CI: 1.43-3.00; I2 = 85%). This outcome did not suffer any publication bias. However, after removing an outlier study, the recalculated OR was 1.88. In conclusion, the presence of sarcopenia in knee OA patients was high, affecting one person in every two persons and was higher than in the control groups included.

Role of Ultrasound Evaluation of Temporomandibular Joint in Juvenile Idiopathic Arthritis: A Systematic Review.

Background: Juvenile idiopathic arthritis (JIA) is childhood's most frequent chronic rheumatic disease. JIA is a broad term that includes all arthritides starting before 16 years, lasting at least six weeks, and of unknown cause. The temporomandibular joint (TMJ) could be involved in JIA both at onset and during the disease course. The presence of TMJ synovitis might severely impair dentofacial maturation in pediatric patients. The ultrasound (US) application to detect early signs of TMJ synovitis in children with JIA has provided contradictory results. We sought to assess the current role of TMJ US in JIA through a systematic literature review. Methods: The systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Results: The literature search found 345 records. After duplicates removal, 253 records were screened, 20 full-text articles were reviewed to assess their eligibility, and 7 of them were included in the qualitative analysis. Joint effusion was the most recorded parameter, followed by bony condylar abnormalities. Compared to contrast enhancement MRI, the capability to detect signs of active synovitis of TMJ by US is low, especially at the early stages. Conclusion: Understanding how US may help diagnose and manage children with JIA is advisable for several reasons. MRI cannot be frequently repeated, may need sedation, and is expensive. The constant technical improvement of US will undoubtedly allow for better evaluation of what, in the past, was not clear or not even captured by sonography. So far, the role of US in the assessment of TMJ involvement in JIA is indubitably secondary to the MRI. Even so, we think that a baseline MRI of TMJ and the repetition of the sonography over time might both help the interpretation of US images and intercept significative changes.

Synovial Fluid-Derived Extracellular Vesicles of Patients with Arthritides Contribute to Hippocampal Synaptic Dysfunctions and Increase with Mood Disorders Severity in Humans.

Arthritides are a highly heterogeneous group of disorders that include two major clinical entities, localized joint disorders such as osteoarthritis (OA) and systemic autoimmune-driven diseases such as rheumatoid arthritis (RA). Arthritides are characterized by chronic debilitating musculoskeletal conditions and systemic chronic inflammation. Poor mental health is also one of the most common comorbidities of arthritides. Depressive symptoms which are most prevalent, negatively impact patient global assessment diminishing the probability of achieving the target of clinical remission. Here, we investigated new insights into mechanisms that link different joint disorders to poor mental health, and to this issue, we explored the action of the synovial fluid-derived extracellular vesicles (EVs) on neuronal function. Our data show that the exposure of neurons to different concentrations of EVs derived from both RA and OA synovial fluids (RA-EVs and OA-EVs) leads to increased excitatory synaptic transmission but acts on specific modifications on excitatory or inhibitory synapses, as evidenced by electrophysiological and confocal experiments carried out in hippocampal cultures. The treatment of neurons with EVs membrane is also responsible for generating similar effects to those found with intact EVs suggesting that changes in neuronal ability arise upon EVs membrane molecules' interactions with neurons. In humans with arthritides, we found that nearly half of patients (37.5%) showed clinically significant psychiatric symptoms (CGIs score ≥ 3), and at least mild anxiety (HAM-A ≥ 7) or depression (MADRS and HAM-D ≥ 7); interestingly, these individuals revealed an increased concentration of synovial EVs. In conclusion, our data showing opposite changes at the excitatory and inhibitory levels in neurons treated with OA- and RA-EVs, lay the scientific basis for personalized medicine in OA and RA patients, and identify EVs as new potential actionable biomarkers in patients with OA/RA with poor mental health.

Ultrasound versus physical examination in predicting disease flare in children with juvenile idiopathic arthritis: a systematic literature review and qualitative synthesis.

In this systematic review we analyzed the published articles related to the predictive value for flare of subclinical synovitis assessed by ultrasound (US) in juvenile idiopathic arthritis (JIA). Medline, Embase and Cochrane databases were searched from 1990 to 2020 by two authors, using PICO methodology. The study is built and reported according to PRISMA guidelines. Searches identified four articles comprising a total of 187 JIA patients in clinical remission from at least 3 months. Two of the articles found US subclinical signs of synovitis to be predictive for flare, with a five times higher risk (with Power Doppler signal as an important feature), while in the other two baseline US abnormalities did not predict a clinical flare. The articles differed for protocols, definitions, and length of follow-up. US has an expanding role in pediatric rheumatology, with interest-ing applications especially during the follow-up, potentially identifying subclinical inflammatory signs predictive of flare. However, the few studies available do not allow definite conclusions at this time.

Hyaluronic Acid Therapy in Hip OA Does Not Perform Equally in Osteoarthritis Secondary to Juvenile Idiopathic Arthritis When Compared to Primary Osteoarthritis: A 2-Year Preliminary Evaluation.

OBJECTIVE: Hip involvement in juvenile idiopathic arthritis (JIA) is one of most important causes of pain and disability. Total hip arthroplasty (THA) is considered the standard when medical approaches fail to relieve pain. However, THA is problematic for many reasons. As current literature lacks studies valuating medical management of osteoarthritis (OA) secondary to JIA, we assessed the long-term pain relief effect of US-guided intra-articular viscosupplementation in hip osteoarthritis secondary to JIA versus primary OA under different etiological conditions. METHODS: Patients in both groups received intra-articular Hylan G-F 20 2 ml once a month for 3 consecutive months and every 6 months for 2 years as maintenance. Effectiveness (VAS and WOMAC), NSAID/analgesic consumption, tolerability, withdrawals and reason for discontinuation were collected at each time point. An inverse probability weighting was used to balance the two groups. RESULTS: We retrospectively retrieved data of 14 JIA patients and 26 primary OA. Weighting successfully accounted for differences between the disease groups supporting the results. Viscosupplementation led to an early and significant improvement of pain and function and concomitant decrease in NSAIDs consumption, while the response diverged over 1 year with loss of benefits in JIA. The worst outcome was observed in active JIA. CONCLUSIONS: Duration of symptom relief after intra-articular injection of hyaluronic acid depends on the nature of arthritis. Multiple courses of viscosupplementation are required to maintain low-dose NSAIDs consumption in patients responsive to treatment while shortening the time between consecutive injections might provide persistent positive results in patients suffering from JIA.

Predictors, Risk Factors, and Incidence Rates of Psoriatic Arthritis Development in Psoriasis Patients: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Agreement on how to identify psoriasis (PsO) patients at risk of developing psoriatic arthritis (PsA) is lacking. OBJECTIVE: To identify predictors, risk factors and incidence rate (IR) of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA). METHODS: MEDLINE, Embase, and Cochrane databases were searched. Cohort studies were used to assess the predictors, while case-control studies for PsA risk factor determination. RESULTS: We screened 4698 articles for eligibility, and 110 underwent a full reading and 26 were finally included. Among skin and nail phenotypes, PsO severity and nail pitting were selected as predictors of PsA development. Furthermore, PsO patients with arthralgia (pooled RR 2.15 [1.16; 3.99]) and/or with imaging-MSK inflammation (pooled RR 3.72 [2.12; 6.51]) were at high risk of PsA. Higher categories of BMI and a family history of PsA were other predictors. In outpatient-based cohort studies, the IR of PsA per 100 patient-years varied from 1.34 to 17.4. LIMITATIONS: Despite the strength of the overall results, the heterogeneity and the number of the cohort studies could be considered a limitation. CONCLUSIONS: This study provides a tentative profile of the PsO patient at risk of PsA and will help the design of PsA prevention trials.

Potential Short-Term Air Pollution Effects on Rheumatoid Arthritis Activity in Metropolitan Areas in the North of Italy: A Cross-Sectional Study.

Rheumatoid arthritis (RA) flare is related to increased joint damage, disability, and healthcare use. The impact of short-term air pollution exposure on RA disease activity is still a matter of debate. In this cross-sectional study, we investigated whether short-term exposure to particulate matter (PM)10, PM2.5, nitrogen dioxide (NO2), and ozone (O3) affected RA disease activity (DAS28 and SDAI) in 422 consecutive RA residents in Lombardy, North of Italy. Air pollutant concentrations, estimated by Regional Environmental Protection Agency (Lombardy-Italy) at the municipality level, were used to assign short-term exposure from the day of enrolment, back to seven days. Some significant negative associations emerged between RA disease activity, PM10, and NO2, whereas some positive associations were observed for O3. Patients were also stratified according to their ongoing Disease-Modifying anti-Rheumatic Drugs (DMARDs) treatment: no DMARDs (n = 25), conventional synthetic DMARDs (n = 108), and biological or targeted synthetic DMARDs (n = 289). Therapy interaction seemed partially able to influence the relationship between short-term air pollution exposure and RA disease activity (PM2.5 levels and DAS28 at the day of the visit-O3 levels and disease activity scores for the seven days before the evaluation). According to our results, the impact of short-term air pollution exposure (seven days) minimally impacts disease activity. Moreover, our study suggests therapy could alter the response to environmental factors. Further evidence is needed to elucidate determinants of RA flare and its management.

Serum calprotectin (S100A8/9), clinical and ultrasound assessment in patients with juvenile idiopathic arthritis.

OBJECTIVES: To explore the association between serum S100A8/9 (calprotectin), clinical and ultrasound (US) assessment in juvenile idiopathic arthritis (JIA) patients. METHODS: A total of 30 well-characterised consecutive patients (18 female) with non-systemic JIA and 20 age-matched healthy controls were included. Serum and plasma samples obtained the same day of the clinical and sonographical assessment were tested for calprotectin levels by ELISA. Clinical status was defined using Wallace criteria. Ultrasonographic B-mode and power Doppler (PD) assessment of 44 joints for each subject was performed. RESULTS: Clinically active disease was present in 14 patients, while 16 patients were active according to US evaluation. We found no differences in the serum/plasma calprotectin levels in clinically active disease group [29.6 (5.4-198.1) ng/ml; 12.6 (2.8-65.8) ng/ml] as compared with inactive disease group [24.8 (14.1-204.3); 12.7 (3.4-65.1)] (p=0.73; p=0.29). There was also no difference between US active disease [29.8 (5.4-204.3); 12.9 (2.8-65.8)] and US inactive disease [24.8 (12.1-197.1); 11.7 (3.4-44.2)] with regard to the serum/plasma calprotectin levels (p=0.83; p=1.0). Serum/plasma calprotectin levels correlated moderately with C-reactive protein (CRP) (Spearman r=0.44, p=0.01; Spearman r=0.56, p=0.0021). CONCLUSIONS: To our knowledge, this is the first study to simultaneously examine the correlation between serum/plasma calprotectin levels, clinical and US assessment in JIA. Calprotectin was not associated with the disease status in JIA patients with low number of active joints and its levels were moderately correlated with CRP. Our preliminary study needs to be extended with a larger number of patients.

One-year efficacy and safety of single or one to three weekly injections of hylan G-F 20 for knee osteoarthritis: a systematic literature review and meta-analysis.

The aim of this study was to evaluate the long-term efficacy and safety of single or 1-3 weekly injections of hylan G-F 20 at 1 year following the first injection for knee osteoarthritis (OA). Searches were conducted in PubMed/MEDLINE, Embase, and CENTRAL and included relevant conference proceedings (January 1, 1995-August 17, 2020). Randomized controlled trials (RCTs), non-randomized trials, and observational studies investigating 1-year efficacy and safety of 1-3 weekly injections or single hylan G-F 20 injection for knee OA were included. Primary outcomes were WOMAC pain, physical function, and stiffness. Meta-analyses of RCTs and non-randomized studies were conducted separately. Our search identified 24 eligible studies. Hylan G-F 20, in the meta-analyses of RCTs, showed statistically significant improvement in WOMAC pain (SMCC - 0.98, 95% CI - 1.50, - 0.46), physical function (SMCC - 1.05, 95% CI - 1.28, - 0.83), and stiffness (SMCC - 1.07, 95% CI -1.28, -0.86). Improvement was also seen for VAS pain, SF-36 MCS (mental component summary), and SF-36 PCS (physical component summary). Analyses of non-randomized studies showed similar efficacy estimates. There were no significant differences in efficacy based on injection schedule, nor between RCT and non-randomized studies. Rates of adverse events (AEs) were low for most types of AEs. Hylan G-F 20 (either as single or 1-3 weekly injections) showed improvement in 1-year efficacy outcomes in comparison to baseline and was generally well tolerated. While further research will inform the medical field regarding viscosupplementation treatment options for knee OA, these findings show that hylan G-F 20 at both frequencies/dosages are efficacious and generally well tolerated for long-term use.

Deep learning segmentation of Primary Sjögren's syndrome affected salivary glands from ultrasonography images.

Salivary gland ultrasonography (SGUS) has proven to be a promising tool for diagnosing various diseases manifesting with abnormalities in salivary glands (SGs), including primary Sjögren's syndrome (pSS). At present, the major obstacle for establishing SUGS as a standardized tool for pSS diagnosis is its low inter/intra observer reliability. The aim of this study was to address this problem by proposing a robust deep learning-based solution for the automated segmentation of SGUS images. For these purposes, four architectures were considered: a fully convolutional neural network, fully convolutional "DenseNets" (FCN-DenseNet) network, U-Net, and LinkNet. During the course of the study, the growing HarmonicSS cohort included 1184 annotated SGUS images. Accordingly, the algorithms were trained using a transfer learning approach. With regard to the intersection-over-union (IoU), the top-performing FCN-DenseNet (IoU = 0.85) network showed a considerable margin above the inter-observer agreement (IoU = 0.76) and slightly above the intra-observer agreement (IoU = 0.84) between clinical experts. Considering its accuracy and speed (24.5 frames per second), it was concluded that the FCN-DenseNet could have wider applications in clinical practice. Further work on the topic will consider the integration of methods for pSS scoring, with the end goal of establishing SGUS as an effective noninvasive pSS diagnostic tool. To aid this progress, we created inference (frozen models) files for the developed models, and made them publicly available.

Sensitivity to change and clinical correlations of the novel DACtylitis glObal Sonographic (DACTOS) score in psoriatic arthritis.

OBJECTIVE: The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a PsA dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders. METHODS: Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, 1 month (T1) and 3 months (T3). RESULTS: We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (P < 0.001) and between clinical remission and non-remission groups (P < 0.001). CONCLUSION: The DACTOS score performs well in real-life clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

A Posteriori Dietary Patterns and Rheumatoid Arthritis Disease Activity: A Beneficial Role of Vegetable and Animal Unsaturated Fatty Acids.

To our knowledge, no studies have investigated the relationship between a posteriori dietary patterns (DPs)-representing current dietary behavior-and disease activity in patients with rheumatoid arthritis (RA). We analyzed data from a recent Italian cross-sectional study including 365 RA patients (median age: 58.46 years, 78.63% females). Prevalent DPs were identified through principal component factor analysis on 33 nutrients. RA activity was measured according to the Disease Activity Score on 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI). Single DPs were related to disease activity through linear and logistic regression models, adjusted for the remaining DPs and confounders. We identified five DPs (~80% variance explained). Among them, Vegetable unsaturated fatty acids (VUFA) and Animal unsaturated fatty acids (AUFA) DPs were inversely related to DAS28 in the overall analysis, and in the more severe or long-standing RA subgroups; the highest score reductions (VUFA: 0.81, AUFA: 0.71) were reached for the long-standing RA. The SDAI was inversely related with these DPs in subgroups only. This Italian study shows that scoring high on DPs based on unsaturated fats from either source provides independent beneficial effects of clinical relevance on RA disease activity, thus strengthening evidence on the topic.

Salivary Gland Ultrasonography in Sjögren's Syndrome: A European Multicenter Reliability Exercise for the HarmonicSS Project.

Objectives: Salivary gland ultrasonography (SGUS) is increasingly applied for the management of primary Sjögren's syndrome (pSS). This study aims to: (i) compare the reliability between two SGUS scores; (ii) test the reliability among sonographers with different levels of experience. Methods: In the reliability exercise, two four-grade semi-quantitative SGUS scoring systems, namely De Vita et al. and OMERACT, were tested. The sonographers involved in work-package 7 of the HarmonicSS project from nine countries in Europe were invited to participate. Different levels of sonographers were identified on the basis of their SGUS experience and of the knowledge of the tested scores. A dedicated atlas was used as support for SGUS scoring. Results: Twenty sonographers participated in the two rounds of the reliability exercise. The intra-rater reliability for both scores was almost perfect, with a Light's kappa of 0.86 for the De Vita et al. score and 0.87 for the OMERACT score. The inter-rater reliability for the De Vita et al. and the OMERACT score was substantial with Light's Kappa of 0.75 and 0.77, respectively. Furthermore, no significant difference was noticed among sonographers with different levels of experience. Conclusion: The two tested SGUS scores are reliable for the evaluation of major salivary glands in pSS, and even less-expert sonographers could be reliable if adequately instructed.

Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis.

BACKGROUND: Prevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis. METHODS: The study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated. RESULTS: The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04-1.44] to 3.20 [1.97-5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18-1.21] to 0.47 [0.46-0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed. CONCLUSIONS: During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection. TRIAL REGISTRATION: Retrospectively registered. Not applicable.

Ultrasound assessment of lacrimal glands: a cross-sectional study in healthy subjects and a preliminary study in primary Sjögren's syndrome patients.

OBJECTIVES: This study aimed to: i) perform an ultrasonographic (US) evaluation of the lacrimal glands (LGs) in healthy subjects in order to define the sonographic elementary lesions which could be identified in the LGs and describe their frequencies in healthy subjects; ii) test the intra and inter-rater agreement between four rheumatologists; iii) preliminary assess whether the elementary lesions of the LGs let us differentiate healthy subjects from primary Sjögren's syndrome (pSS) patients. METHODS: A consensus meeting was held to define the sonographic lesions to be evaluated. Healthy subjects and pSS patients underwent lacrimal glands ultrasound (LGUS) examinations in two Italian Rheumatology Clinics. A web-based reliability exercise was performed on healthy subjects' images by four rheumatologists. Afterward, images of pSS patients were evaluated for the presence of the sonographic lesions previously defined and compared to the US findings in healthy subjects. RESULTS: Fifty-seven healthy subjects and 17 pSS patients were evaluated. The intra and inter-rater reliability score was good-excellent for almost all the agreed US features assessed (glandular parenchyma visibility, size, homogeneity, hypoechoic areas, hyperechoic spots, fibrous gland appearance, fatty deposition). Among the LGUS elementary lesions in pSS patients compared with healthy subjects, we detected a significantly difference in glandular inhomogeneity [13/33 (39.4%) vs. 9/63 (14.3%), p=0.01], and in fibrous gland appearance [3/33 (9.1%) vs. 0/63 (0%), p=0.04]. CONCLUSIONS: In this preliminary study, LGUS proved to have a good-excellent intra and inter-rater reliability. The glandular parenchyma inhomogeneity and the fibrous gland appearance could help differentiate pSS patients from healthy subjects.

The burden of air pollution and temperature on Raynaud's phenomenon secondary to systemic sclerosis.

OBJECTIVES: to evaluate the effect of air pollution (ozone - O3 and particulate matter <=10 µm and <=2.5 µm - PM10 and PM2.5) on the severity of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). DESIGN: cross-sectional, observational, and single centre study. SETTING AND PARTICIPANTS: all consecutive SSc patients residing in Lombardy (Northern Italy) were enrolled. PM10, PM2.5, and O3 concentrations were calculated for each patient at municipality resolution in the week before the evaluation. Similar considerations were made for meteorological variables (temperature and humidity). MAIN OUTCOME MEASURES: patients were asked to assess RP severity during the week before the evaluation according to a visual analogue scale (VAS). Ordinal logistic regression models were fitted to evaluate the short-term effect of temperature and air pollution with respect to RP. A univariate linear regression model was created to consider the association between temperature and pollutants. RESULTS: in this study, 87 SSc patients were enrolled. Temperature was confirmed to strongly influence RP severity. PM10 and PM.5 were found to significantly worsen RP severity for the first four days before the evaluation, including the day of the visit, and as mean up to six days before the evaluation. O3 seemed to exert a protective effect on RP severity that was significant for the first four days before the evaluation, including the day of the visit, and as mean up to seven days before the evaluation. CONCLUSIONS: since the overwhelming effect of temperature on RP, final conclusions about the exact contribution of pollutants on RP severity cannot be drawn because of the strong inter-correlation between air pollution and temperature.

Adherence to Mediterranean diet and patient perception of rheumatoid arthritis.

OBJECTIVE: To evaluate the association between the adherence to Mediterranean diet (MD) and disease impact, activity, and comorbidities in patients with rheumatoid arthritis (RA). DESIGN: Consecutive patients with RA were enrolled in this cross-sectional study. For each patient, Disease Activity Score on 28 joints (DAS28), Simple Disease Activity Index (SDAI), RA Impact of Disease (RAID), Health Assessment Questionnaire (HAQ), patient global assessment (PGA) and general health (GH) and a self-reported questionnaire called MD score were recorded. RESULTS: 205 RA patients (median age 53 years, female 80.49 %) were enrolled. An association between MD score and HAQ (p-value = 0.033), PGA and GH (p-value 0.023 both) was observed. RAID total score had a statistically significant negative relationship with MD score (p-value = 0.016). A statistically significant negative association was found for pain (p-value = 0.025), functional disability (p-value<0.001), sleep (p-value = 0.041), physical well-being (p-value = 0.027) and coping (p-value = 0.008). Multiple regression analysis to evaluate the relationship between significant RAID items and MD score did not show any statistical significance as all items are strongly related to each other. A negative trend, although not statistically significant was found for DAS28 and SDAI. The only comorbidity associated with MD score was arterial hypertension (OR = 0.94). CONCLUSIONS: In this Italian RA cohort, the adherence to MD was significantly associated with a better RAID, PGA and GH, but higher MD score was not significantly associated with lower disease activity. Our study suggests an overall potential beneficial effect of MD in RA patients.