Microbiota and arthritis: cause or consequence?

The relationship between intestinal microbiota and arthritis has garnered significant attention, with emerging evidence suggesting a potential association between dysbiosis and various forms of inflammatory arthropathies. While observational studies have provided valuable insights into microbiota alterations in patients with arthritis, establishing causality remains challenging. Observational data, influenced by multiple confounders such as environmental factors, medication effects, and dietary habits, are insufficient to conclusively determine whether microbiota changes are somehow causally linked to arthritis. The heterogeneity of results across independent studies further complicates interpretation. To further support this hypothesis, interventional randomised trials are deemed necessary, yet their implementation in this area presents significant technical limitations. Experimental animal models offer insights into potential pathogenic mechanisms linking dysbiosis to arthritis, including compromised intestinal barrier function, the role of microbiota-derived metabolites and molecular mimicry. However, conflicting findings underscore the complexity of hostmicrobiota interactions and the challenges in establishing causality.Efforts to modulate the microbiota for arthritis treatment or prevention have shown promise, yet efficacy and applicability remains uncertain. Antibacterial drugs, dietary interventions, probiotics, and faecal microbiota transplantation have been explored, but their clinical utility awaits further validation. In conclusion, while the association between intestinal microbiota and arthritis is increasingly recognised, establishing causality remains elusive.

Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs.

OBJECTIVES: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Structured request form in musculoskeletal radiology examinations (CONCERTO): results of an expert Delphi consensus-structured radiology request form for correct classification of patients to undergo radiological examinations of the Italian Society of Medical and Interventional Radiology (SIRM), the Italian Society of Rheumatology (SIR) and the Italian Society of Orthopedics and Traumatology (SIOT).

PURPOSE: To describe a Delphi consensus for the realization of a structured radiology request form for patients undergoing musculoskeletal imaging. METHODS: A steering committee (four radiologists, a rheumatologist and an orthopedic surgeon) proposed a form to an expert panel (30 members, ten radiologists, ten rheumatologists and ten orthopedic surgeons). Through an online survey, the panelists voted on their level of agreement with the statements of the form using a 10-point Likert scale (1: no agreement; 10: total agreement) in a three-round process. A combination of two distinct criteria, a mean agreement level ≥ 8 and a percentage of at least 75% of responses with a value ≥ 8, was deemed as acceptable. RESULTS: The form achieved high median ratings in all the assessed key features. During the first round, all items met the threshold to be advanced as unmodified in the next round. Additional proposed items were considered and introduced in the next round (six items in Section 1, five items in Section 2, ten items in Section 3, 11 items in Section 4, six items in Section 5, eight items in Section 6, ten items in Section 7 and eight items in Section 8). Of these items, in round 3, only six reached the threshold to be integrated into the final form. CONCLUSIONS: Implementation of a structured radiology request form can improve appropriateness and collaboration between clinicians and radiologists in musculoskeletal imaging.

The measurement of fibromyalgia severity: converting scores between the FIQR, the PSD and the FASmod.

OBJECTIVES: The revised Fibromyalgia Impact Questionnaire (FIQR) is a widely used fibromyalgia severity assessment tool that was introduced in 2009 prior to the publication of the American College of Rheumatology (ACR) preliminary fibromyalgia criteria in 2010 and its revision in 2016. In 2020, the modified Fibromyalgia Assessment Scale (FASmod) was published. The Polysymptomatic Distress scale (PSD) of the fibromyalgia criteria and FASmod include assessments of pain location severity and can be used for diagnosis as well as in non-fibromyalgia patients. The aim of this study is to provide equations for the conversion of the FIQR scores to PSD and FASmod as an aid to understanding and sharing fibromyalgia severity information. METHODS: 3089 patients with fibromyalgia, diagnosed according to the ACR 2010/2011 criteria and belonging to the Italian Fibromyalgia Registry completed FIQR, FASmod and PSD questionnaires. Pearson's correlation coefficient was used to test the correlations between indices. The least square regression approach was used to produce predictive equations for each scale based on the remaining scales. RESULTS: FIQR was correlated with PSD (r=0.714) and FASmod (r=0.801); PSD and FASmod showed the highest correlation (r=0.897), expected since they assess the same constructs. Predictive equations showing a linear model were effective in producing mean cohort values, but individual predictions deviated substantially, precluding prediction in the individual patient. CONCLUSIONS: Conversion equations that allow for interconversion of multiple scales fibromyalgia severity assessment scales are produced. These can be useful in obtaining mean values for cohorts but are not accurate enough for use in individual patients.

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.

Polyangiitis overlap syndrome: a rare clinical entity.

Polyangiitis overlap syndrome is a rare clinical entity comprising patients with overlapping features of more than one vasculitis, usually eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis (GPA). Few cases of polyangiitis overlap syndrome have been described in the literature, mostly associated with c-ANCA, anti-proteinase (PR)-3 positivity, a protean clinical picture characterized by vasculitis, eosinophilia and eosinophilic infiltrates in tissues and a favorable response to steroids and immunosuppressant treatments. Herein, we present a case of a 66-year-old woman with nasal obstruction, external nose deformity, sensorineural hearing loss, peripheral blood eosinophilia, high titer anti-PR3 antibodies and lung involvement. Nasal septum biopsies showed inflammatory infiltrate with eosinophilic component; histopathology of the lung demonstrated necrotizing granulomas associated with inflammatory infiltrate composed of numerous neutrophils and some eosinophils. The patient was diagnosed with polyangiitis overlap syndrome and successfully treated with cyclophosphamide. Recognizing this entity is fundamental given the distinct clinical phenotype and outcomes to therapy in the complex scenario of ANCA-associated vasculitides.

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies.

OBJECTIVE: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. METHODS: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. RESULTS: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). CONCLUSION: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

Ultrasound scoring systems affect the distribution of sialadenitis scores in Sjögren's syndrome: an inter-system reproducibility study.

OBJECTIVES: Salivary gland ultrasonography (SGUS) is commonly employed in the diagnosis and follow-up of patients with Sjögren's syndrome (SS) and multiple scoring systems have been developed to quantify the grade of sialadenitis of major salivary glands (SG). Their diagnostic performance seems overall comparable, however, the parameters evaluated by the various systems are different. The objective of this study was to compare how four different scoring systems affect the distribution of sialadenitis grades. METHODS: One hundred and three SGUS images from 26 SS patients were blindly scored by two investigators according to the De Vita, Salaffi, Milic and OMERACT scoring systems in independent sessions. RESULTS: The distribution of SGUS images according to De Vita, Salaffi, Milic and OMERACT systems was significantly different. At post-hoc analysis, Milic system performed differently compared to the De Vita (p<0.0001), OMERACT (p<0.0001) and Salaffi (p<0.0001) systems, showing a relative overestimation of sialadenitis grade. CONCLUSIONS: Milic scoring system showed to relatively overestimate the grade of sialadenitis compared to De Vita, Salaffi and OMERACT systems. Although all scoring systems seem to be comparable in terms of diagnostic accuracy, in the prospect of selecting one system to be potentially included in future versions of SS classification criteria, it is important to compare their ability to classify SGUS images among the various degrees of sialadenitis.

Increased COVID-19 mortality in patients with rheumatic diseases: results from the CONTROL-19 study by the Italian Society for Rheumatology.

OBJECTIVES: To investigate differences in coronavirus disease 2019 (COVID-19) mortality between patients with rheumatic musculoskeletal diseases (RMD) and the general population in Italy. METHODS: We analysed the data from the national surveillance study promoted by the Italian Society for Rheumatology (CONTROL-19 database) including patients with RMD and COVID-19 between 26 March 2020 and 29 November 2020, compared with official data from the Italian population (within the same period) adjusted for age, sex and geographic location. The main outcome of the analyses was mortality. The relationship between RMD and mortality was analysed using adjusted logistic models and sensitivity analyses were conducted to support the robustness of our results. RESULTS: We included 668 RMD patients (62.7% with inflammatory arthritis, 28.6% with systemic autoimmune diseases), who had a mean age of 58.4 years and of which 66% were female. Compared to the general population, the RMD population showed an increased risk of death (OR 3.10 (95% CI 2.29-4.12)), independently from the differences in age and sex distribution. Even after considering the potential influence of surveillance bias, the OR was 2.08 (95% CI: 1.55-2.73). Such excess of risk was more evident in the subgroup of younger patients, and more consistent in women. Subjects with systemic autoimmune diseases showed a higher risk of death than patients with any other RMDs. CONCLUSIONS: Patients with RMD and COVID-19 infection evidenced a significant increase in mortality during the first pandemic phases in Italy. These findings support the need for strong SARS-CoV-2 prevention in patients with rheumatic diseases.

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.

Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort.

BACKGROUND: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN). AIM: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life. PATIENTS AND METHODS: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria <0.5 g/24 h, eGFR≥90 ml/min/1.73 m2) was considered as secondary outcome. Prevalence and predictors of PERR were evaluated at 6, 12, 24 months by multivariate logistic regression. RESULTS: Among the 466 SLE patients of BeRLiSS, 91 fulfilled the inclusion criteria, 79 females, median age 41.0 (33.0-47.0) years, median follow-up 22.0 (12.0-36.0) months. Sixty-four (70.3%) achieved PERR, of whom 38.4% reached CRR. Among patients achieving PERR at 6 months, 86.7% maintained response throughout the follow-up. At multivariable analysis, hypertension (OR [95%CI]: 0.28 [0.09-0.89], p = 0.032), high baseline serum creatinine (0.97 [0.95-0.99], p = 0.01) and high baseline proteinuria (0.37, [0.19-0.74], p = 0.005) negatively predicted PERR. Positive predictors of PERR at 12 and 24 months were baseline anti-Sm positivity (OR [95%CI]: 6.2 [1.21-31.7], p = 0.029; 19.8 [2.01-186.7], p = 0.009, respectively) and having achieved PERR at 6 months (14.4 [3.28-63.6]; 11.7 [2.7-48.7], p = 0.001 for both). CONCLUSIONS: Add-on therapy with belimumab led to durable renal response in patients with LN in a real-life setting.

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.

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19.

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk. Coronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome. Several efforts are currently made to find a treatment for COVID-19 patients. So far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series. In COVID-19 patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-α has been demonstrated. Moreover, high levels of IL-6 and TNF-α have been observed in patients requiring intensive-care-unit hospitalization. This provided rationale for the use of anti-rheumatic drugs as potential treatments for this severe viral infection. Other agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect. The anti-viral aspect of immunosuppressants towards a variety of viruses has been known since long time and it is herein discussed in the view of searching for a potential treatment for SARS-CoV-2 infection.

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome.

OBJECTIVE: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. METHODS: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents. RESULTS: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). CONCLUSION: The systemic phenotype of primary Sjögren's syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Characterisation of articular manifestations in primary Sjögren's syndrome: clinical and imaging features.

OBJECTIVES: Articular manifestations (AMs) are observed in a large proportion of patients with primary Sjögren's syndrome (pSS) and can occur at the time of pSS diagnosis or during the disease course. Although in the majority of cases AMs are mild and self-limiting, some patients may experience chronic polyarthritis requiring treatment with DMARDs. Ultrasonography (US) and magnetic resonance imaging (MRI) can help assessing the extent of articular involvement and guide the treatment. The aim of this study was to describe clinical, serological, and histological picture of a cohort of pSS patients with AMs. METHODS: Clinical and serological records were retrospectively evaluated and either US or MRI were performed to evaluate AMs and their features were described according to the OMERACT scoring systems. RESULTS: One hundred and thirty-three pSS patients were enrolled, of whom 115 (86%) with articular involvement. In particular, 91 patients (68%) displayed AMs at the time of pSS diagnosis while 24 patients (32%) during the course of the disease. Patients with AMs during the disease course were diagnosed with pSS at a younger age and reported a higher VAS dryness compared to patients displaying AMs at pSS onset. Hands and wrists were the most frequently involved sites followed by knees, shoulders and ankles. Overall, a consistent number of abnormalities were detected, more by MRI than US. Hands and wrists were the most frequently evaluated sites and the prevalence of all MRI abnormalities was similar between the different sites and comparable between the groups. CONCLUSIONS: pSS AMs encompass a wide disease spectrum ranging from arthralgia to erosive arthritis resembling RA and therefore represent an important determinant of patients' quality of life. Imaging techniques such as US and MRI may be useful in the follow-up of pSS patients for prompt identification of AMs, for the quantification of their extent and ultimately for providing guidance on treatment and improving patient care.

Nailfold capillaroscopy in Sjögren's syndrome: a systematic literature review and standardised interpretation.

OBJECTIVES: To identify the role of nailfold capillaroscopy (NC) in Sjögren's syndrome (SS). METHODS: The literature was systematically reviewed in three databases. All published original studies which assess patients with SS by NC were revised. A quality assessment was applied to all studies based on population description, presence of a control group, presence of instrumental specifications and/or standardly applied NC methodology, presence of clear descriptions of capillaroscopic characteristics and based on the used statistical analysis. The capillaroscopic findings per study were described in a EULAR consented standardised way. Significant associations of capillaroscopic characteristics in SS patients with clinical and laboratory variables were summarised. RESULTS: The search resulted in 869 hits. Based on title and abstract screening 29 original studies were identified and of these, 14 full texts described an assessment by NC in SS. Seven studies were retained after performing a critical quality assessment. One study compared NC in SS with healthy controls and attested a lower capillary density in SS. Concerning clinical associations, capillary density was associated with Raynaud's phenomenon in two studies and with interstitial lung disease or systemic manifestations in one study each. No association between serologic features (anti-nuclear antibodies, anti-SSA, anti-SSB and anti-RF) and NC characteristics were found. CONCLUSIONS: A small number of studies have investigated the role of NC in SS. More studies, including prospective follow up studies with standard NC evaluation in SS are needed.

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19).

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments.

Significance of anti-La/SSB antibodies in primary Sjögren's syndrome patients with combined positivity for anti-Ro/SSA and salivary gland biopsy.

OBJECTIVES: Immunological parameters exert a relevant diagnostic and prognostic role in primary Sjögren's syndrome (pSS) and may identify specific disease phenotypes. Among disease-associated immunological features, anti-La/SSB are rarely found without concomitant anti-Ro/SSA and their clinical significance in patients with pSS has been poorly investigated. Thus, we aimed to characterise the value of anti-La/SSB analysing clinical and serologic features of a wide cohort of pSS patients with both circulating anti-Ro/SSA and positive salivary gland biopsy (SGB). METHODS: Clinical and serological data of 600 pSS patients with both anti-Ro/SSA and SGB positivity and categorised according to anti-La/SSB status were retrospectively analysed. Comparisons between patients with and without circulating anti-La/SSB were performed. RESULTS: Among the whole cohort, 319 (53%) of patients were anti-La/SSB negative and 281 (47%) were anti-La/SSB positive. Anti-La/SSB positive patients were younger at disease diagnosis and had a longer disease duration. Moreover, anti-La/SSB positive patients had a higher prevalence of hypergammaglobulinaemia and circulating rheumatoid factor and of lymphoproliferative disorders in comparison to seronegative group. At multivariate analysis, hypergammaglobulinaemia (OR=1,7; 95% CI 1.17, 2.43), rheumatoid factor (OR=2.3; 95% CI 1.6, 3.3) and lymphoma (OR=2.6; 95% CI 1.12, 5.96) were identified as independent variables significantly associated with anti-La/SSB positivity. CONCLUSIONS: In patients with pSS and concomitant anti-Ro/SSA and SGB positivity, the presence of anti-La/SSB may help in identifying a disease subset with distinct prognostic features, especially in terms of higher risk of lymphoproliferative complications.