Clinical and histological features of patients with primary Sjögren's syndrome and autoimmune thyroiditis: a national multicentre cross-sectional study.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is frequently associated with autoimmune thyroiditis (AT). The aim of this study was to evaluate the prevalence of AT in a national cohort of pSS and to describe the clinical and histological phenotype of patients with pSS and associated AT. METHODS: In this multicentre cross-sectional study, data from 2546 pSS were collected and the presence of AT was reported. In a subgroup, the histology of minor salivary glands was evaluated. Differences between pSS with and without AT were evaluated. RESULTS: A concomitant pSS and AT was detected in 19.6% of cases. Patients with pSS and AT displayed a lower prevalence of lymphoma, male sex and disease-modifying anti-rheumatic drugs (DMARDs) use and a higher prevalence of fibromyalgia, coeliac disease and hypergammaglobulinaemia. Multivariable analysis confirmed a higher prevalence of fibromyalgia and coeliac disease and lower use of DMARDs. In a subgroup of patients (n=232), a significantly higher focus score and number of foci was detected in pSS without AT (n=169) as compared to pSS with AT (n=54). CONCLUSIONS: This is the largest study evaluating the coexistence of pSS and AT. We confirm a high association between pSS and AT and describe the presence of a different phenotype characterized by a higher rate of celiac disease and fibromyalgia. Although not significant, the lower prevalence of both lymphoma and intake of DMARDs, along with a significantly lower focus score and number of foci, possibly suggest a more favourable outcome in concomitant pSS and AT which further deserve future investigations.

Determining the PASS cut-off points for the FIQR, FASmod and PSD in patients with fibromyalgia: a registry-based study.

OBJECTIVES: To determine the cut-off values of Patient Acceptable Symptom State (PASS) for the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Scale (FASmod), and the Polysymptomatic Distress scale (PSD) and to determine the predictors of PASS in patients with fibromyalgia (FM). METHODS: FM patients belonging to the Italian Fibromyalgia Registry (IFR) completed the FIQR, the FASmod and the PSD. The PASS was assessed using a dichotomous answer. The cut-off values were obtained through the receiver operating characteristic curve (ROC) analyses. A multivariate logistic regression analysis was performed to determine predictors of achieving the PASS. RESULTS: 5545 women (93.7%) and 369 males (6.3%) were included in the study. The 27.8% of patients reported an acceptable symptom state. Patients in PASS differed in all patient-reported outcome measures (p <0.001). The FIQR PASS threshold was ≤58 (area under the ROC curve [AUC] = 0.819). The FASmod PASS threshold was ≤23 (AUC = 0.805) and the PSD PASS threshold was ≤16 (AUC = 0.773). In the pairwise AUC comparison, the discriminatory power of the FIQR PASS outperforms both FASmod PASS (p = 0.0124) and PSD PASS (p <0.0001). Multivariate logistic analysis showed that FIQR items related to memory and pain were the only predictors of PASS. CONCLUSIONS: The FIQR, FASmod, and PSD PASS cut-off points for FM patients have never been determined before. This study provides additional information to facilitate interpretation of the severity assessment scales in daily practice and clinical research related to FM patients.

Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis.

OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.

Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome.

OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

EULAR points to consider for minimal reporting requirements in synovial tissue research in rheumatology.

BACKGROUND: Synovial tissue research has become widely developed in several rheumatology centres, however, large discrepancies exist in the way synovial tissue is handled and, more specifically, how data pertaining to biopsy procedure, quality check and experimental results are reported in the literature. This heterogeneity hampers the progress of research in this rapidly expanding field. In that context, under the umbrella of European Alliance of Associations for Rheumatology, we aimed at proposing points to consider (PtC) for minimal reporting requirements in synovial tissue research. METHODS: Twenty-five members from 10 countries across Europe and USA met virtually to define the key areas needing evaluation and formulating the research questions to inform a systematic literature review (SLR). The results were presented during a second virtual meeting where PtC were formulated and agreed. RESULTS: Study design, biopsy procedures, tissue handling, tissue quality control and tissue outcomes (imaging, DNA/RNA analysis and disaggregation) were identified as important aspects for the quality of synovial tissue research. The SLR interrogated four databases, retrieved 7654 abstracts and included 26 manuscripts. Three OPs and nine PtC were formulated covering the following areas: description of biopsy procedure, overarching clinical design, patient characteristics, tissue handling and processing, quality control, histopathology, transcriptomic analyses and single-cell technologies. CONCLUSIONS: These PtC provide guidance on how research involving synovial tissue should be reported to ensure a better evaluation of results by readers, reviewers and the broader scientific community. We anticipate that these PtC will enable the field to progress in a robust and transparent manner over the coming years.

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19.

OBJECTIVES: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. METHODS: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. RESULTS: We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.

EULAR points to consider for the use of imaging to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs).

OBJECTIVES: To develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: European Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: A total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel. CONCLUSION: These are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs.

Safety and efficacy of SARS-CoV-2 vaccination in 1237 patients with primary Sjögren syndrome.

OBJECTIVES: To investigate the safety and efficacy of SARS-Cov-2 vaccination in patients with primary Sjögren syndrome (pSS) due to scarcity of data in this population. METHODS: By the first week of May 2021, all Big Data SS Consortium centres patients who had received at least one dose of any SARS-CoV-2 vaccine were included in the study. The in-charge physician asked patients about local and systemic reactogenicity to collect SARS-CoV-2 vaccination data. RESULTS: The vaccination data of 1237 patients were received. A total of 835 patients (67%) reported any adverse events (AEs), including local (53%) and systemic (50%) AEs. Subjective symptoms (63%) were the most common local AEs, followed by objective signs at the injection site (16%), and general symptoms were the most commonly reported systemic AEs (46%), followed by musculoskeletal (25%), gastrointestinal (9%), cardiopulmonary (3%), and neurological (2%). In addition, 141 (11%) patients reported a significant worsening/exacerbation of their pre-vaccination sicca symptoms and fifteen (1.2%) patients reported active involvement in the glandular (n=7), articular (n=7), cutaneous (n=6), pulmonary (n=2), and peripheral nervous system (n=1) domains due to post-vaccination SS flares. In terms of vaccination efficacy, breakthrough SARS-CoV-2 infection was confirmed after vaccination in three (0.24 %) patients, and positive anti-SARS-Cov-2 antibodies were detected in approximately 95% of vaccinated SS patients, according to data available. CONCLUSIONS: Our data suggest that patients with pSS develop adequate humoral response and no severe AEs after SARS-CoV-2 vaccination and therefore raise no concerns about the vaccine's efficacy or safety profile in this population.

Characterisation of the coexistence between sarcoidosis and Sjögren's syndrome. Analysis of 43 patients.

OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

Sociodemographic factors in fibromyalgia: results from the Italian Fibromyalgia Registry.

OBJECTIVES: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/clinical factors and symptom severity measures using a web-based registry of patients with FM. METHODS: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)). RESULTS: Data relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared (F 3.321, p<0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p<0.0001). CONCLUSIONS: Our results indicated that being male and separated/divorced is associated to higher severity of FM symptoms, as rated with FIQR. Furthermore, a relationship between educational level and FIQR scores has been detected. This study supports the importance of collecting simple SES measures to identify environmental risk factors for FM severity.

Fibromyalgia severity according to age categories: results of a cross-sectional study from a large national database.

OBJECTIVES: The role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database. METHODS: This cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41-50 years, between 51-60 years, between 61-70 years, and ≥71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA). RESULTS: The study included 2889 patients (199 males and 2690 females), mean age of 52.58 (±11.82) years, with a mean FIQR score of 59.22 (±22.98) and a mean FAS 2019mod of 25.50 (±8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the ≥71 years category showed significantly higher scores (p<0.05) compared the 18-40 years category. CONCLUSIONS: The severity of FM has a significant level of stationarity according to age categories. Patients between 60-70 years have a lower disease burden. Physical function is the health domain with the most significant difference between the groups.

EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19.

OBJECTIVES: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. METHODS: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. RESULTS: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. CONCLUSIONS: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.

SARS-CoV-2 infection in patients with primary Sjögren syndrome: characterization and outcomes of 51 patients.

OBJECTIVE: To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. METHODS: We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. RESULTS: A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. CONCLUSION: Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities.

Childhood-onset of primary Sjögren's syndrome: phenotypic characterization at diagnosis of 158 children.

OBJECTIVES: To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria. RESULTS: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease. CONCLUSIONS: Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

Definition of fibromyalgia severity: findings from a cross-sectional survey of 2339 Italian patients.

OBJECTIVE: To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. METHODS: Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: 'In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?'-which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. RESULTS: The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th-75th percentiles) were respectively 61.16 (41.16-77.00), 27.00 (19.00-32.00) and 19.0 (13.00-24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0-23 for remission, 24-40 for mild disease, 41-63 for moderate disease, 64-82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0-12 for remission, 13-20 for mild disease, 21-28 for moderate disease, 29-33 for severe disease and >33 for very severe disease; PDS: 0-5 for remission, 6-15 for mild disease, 16-20 for moderate disease, 21-25 for severe disease and >25 for very severe disease. CONCLUSIONS: Disease severity cut-offs can represent an important improvement in interpreting FM.

Traditional and disease-related non-computed variables affect algorithms for cardiovascular risk estimation in Sjögren's syndrome and rheumatoid arthritis.

OBJECTIVES: Several cardiovascular (CV) risk algorithms are available to predict CV events in the general population. Their performance and validity in rheumatic disease patients is suboptimal as some disease-specific variables which strongly contribute to the pathogenesis of CV disease are not included in these CV algorithms. We aimed to evaluate the performance of two CV algorithms and investigate which variables not included in the score contribute to CV risk score in a cohort of rheumatoid arthritis (RA) and Sjögren's syndrome (SS) patients. METHODS: A consecutive cohort of 77 RA and 68 SS patients without prior CV events was included. Clinical and serological features and traditional CV risk factors were collected. The 10-year CV risk was assessed by Reynold Risk Score (RSS) and "Progetto Cuore" algorithms. RESULTS: Prevalence of traditional CV risk factors and 10-year risk of fatal and non-fatal CV events assessed by RSS and "Progetto Cuore" were similar between the two cohorts. Multiple linear regression model showed that, among variables not included in both algorithms, body mass index (BMI) and disease activity were predictors of "Progetto Cuore" while BMI and bone erosions of RSS in RA. In SS, C-reactive protein was predictor of "Progetto Cuore" while hypertension, ESSDAI and LDL-cholesterol of RSS. CONCLUSIONS: The 10-year risk of fatal and non-fatal CV events is similar in RA and SS. Traditional CV risk factors, as hypertension, strongly contribute to CV risk in these patients. Inflammatory parameters and disease activity are two disease-specific variables which should be included in CV algorithm assessment in rheumatic disease patients.

Adherence to the Mediterranean diet and the impact on clinical features in primary Sjögren's syndrome.

OBJECTIVES: The relationship between dietary patterns, including the Mediterranean diet, and rheumatic and musculoskeletal diseases (RMDs) has been increasingly assessed but data on patients with established primary Sjögren's syndrome (pSS) is lacking. The aim of the study was to explore the adherence to the Mediterranean diet and its relationship with metabolic and inflammatory features in a cohort of patients with pSS. METHODS: Demographic, clinical and serological data, including anthropometric parameters and cardiovascular (CV) disease risk factors/events among others were collected from 91 pSS patients. Adherence to the Mediterranean diet over the previous 12 months was assessed with the 14-item PREvencion con DIeta MEDiterranea (PREDIMED) tool and the 28-item Mediterranean Lifestyle (MEDLIFE) index. RESULTS: According to the PREDIMED score 29 (31%) patients had a good adherence to the Mediterranean Diet, 57 (61%) a medium adherence and only 7 (8%) a poor adherence. No difference could be identified across groups with regard to demographic data, disease activity, CV risk factors or other parameters. With regard to the MEDLIFE, the total of blocks 1 and 2, that are related to Mediterranean foods and dietary habits, did not correlate with the total of block 3 (related to other healthy habits such as physical activity), meaning that the patients adhering the most to the Mediterranean Diet not necessarily had an overall healthy lifestyle. The PREDIMED score was inversely correlated with disease activity, as measured by ESSDAI (Spearman's rho=-0.27, p=0.009) and ClinESSDAI (Spearman's rho=-0.26, p=0.01). Fish consumption was associated with lower prevalence of hypertension. CONCLUSIONS: Adherence to the Mediterranean diet, with particular attention to fish consumption, may be beneficial on various domains in pSS, such as the CV system and the inflammatory environment, and as such should be recommended to patients with this disease.

Psychosocial burden in young patients with primary anti-phospholipid syndrome: an Italian nationwide survey (The AQUEOUS study).

OBJECTIVES: The AQUEOUS (Anti-phospholipid syndrome: a QUEstionnaire for yOUng patientS) study aimed to assess how the diagnosis of primary anti-phospholipid syndrome (PAPS) affects the psychosocial status of young patients. METHODS: Subjects with PAPS aged 18-45 years were invited to compile an ad hoc designed questionnaire and the Short Form-12 to assess quality of life (QoL). RESULTS: Ninety-two patients (83.7% females) were recruited in 10 Italian centres. Vascular and obstetric manifestations were equally represented. Nearly half of the patients perceived the need for psychological support, 89.2% when considering women after pregnancy complications. Social activities and working efficiency were reduced in APS patients, also intimacy was threatened. In all cases, fatigue appeared to be the main determinant. PAPS affected family planning, due to fears of treatment side-effects, disease hereditariness, inability to care for the newborn child. Fertility appeared to be conserved: the median time to pregnancy was 2 months; assisted reproduction techniques were pursued by 5 women. Our survey documented significantly lower rates of hospitalisation and learning disabilities in 51 children born after APS diagnosis as compared to 48 children born before. PAPS patients displayed lower QoL in physical and, to a greater extent, mental scores compared to the general Italian population. Both components were significantly lower in women and in patients with fatigue. CONCLUSIONS: The AQUEOUS study assessed for the first time the unmet needs of young PAPS patients, enabling the development of a future "youth-focused" strategy to reduce disease burden.

Post-COVID-19 syndrome in patients with primary Sjögren's syndrome after acute SARS-CoV-2 infection.

OBJECTIVES: To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. METHODS: By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). RESULTS: We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. CONCLUSIONS: This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.

Advancing frontiers in rheumatic and musculoskeletal imaging.

In recent years, technological improvements allowed imaging modalities to become increasingly essential in achieving early and precise diagnoses in the field of rheumatic and musculoskeletal diseases (RMDs). To date, imaging examinations are routinely used in all steps of diagnostic and therapeutic care pathways of patients affected by RMDs. The articles published in this Article Collection clearly show the efforts of researchers to find innovative applications of musculoskeletal imaging in clinical practice and to face the crucial challenges that remain in the interpretation and quality control of images. Highly performing diagnostic technologies are currently available to early diagnose and accurately monitor several musculoskeletal disorders, but also to guide personalized interventional therapeutic procedures tailored to the individual patients in the emerging process of precision medicine. Among these new modalities, some are particularly promising and thereby subject to several lines of research in RMDs, including SPECT-CT and dual-energy CT, MRI sequences, high and ultra-high frequency ultrasound with effective tools like shear wave elastography.